Article Text

Download PDFPDF

2020 Western Medical Research Conference

Statistics from Altmetric.com

Western association of physicians

Western society for clinical investigation

Plenary session

9:30 AM
Thursday, January 23, 2020
1 Predictive value of CT for endoscopically refractory uncontrolled variceal bleeding in cirrhotic patients requiring portal venous intervention

J Pham*

J Kalantari

C Ji

J Chang

SC Kiang

UE Oyoyo

D Jin

RT Tomihama

Loma Linda University, Loma Linda, CA

Purpose of study

The objective of this study was to identify features on abdominal CT imaging associated endoscopically refractory uncontrolled variceal hemorrhage requiring portal venous intervention.

Methods used

Between January 2009 to January 2018, CT scans from 64 patients who experienced endoscopically refractory variceal hemorrhage requiring intervention such as transjugular intrahepatic portosystemic shunt (TIPS) placement or retrograde transvenous obliteration (RTO) and 67 patients without variceal hemorrhage but with severe symptomatic pressure gradient proven portal hypertension were analyzed. Two blinded radiologists reviewed the scans for the following parameters: size of varices, degree of variceal intraluminal protrusion, liver and splenic volumes, and portal vein diameter.

Summary of results

Gastric intraluminal variceal protrusion was found to be a strong CT parameter associated with refractory variceal hemorrhage (0.75 mm vs -2.91 mm, p=0.001). Regarding size, the hemorrhage group had larger gastric varices compared to the control group (8.03 mm vs 6.51 mm, respectively, p=0.001). However, this trend was not demonstrated in the sizes of the esophageal varices (6.28 mm vs 6.43 mm, p=0.370). Larger splenic volume (1312 cc vs 1152 cc, p=0.029) and liver volume (1514 cc vs 1143 cc, p=0.004) were also found to be predictors of endoscopically refractory variceal hemorrhage.

Conclusions

Imaging parameters on abdominal CT, such as intraluminal protrusion of gastric varices, gastric variceal size, larger splenic and liver volumes were predictive of portal venous intervention while esophageal variceal size was not.

Adolescent medicine and general pediatrics I

Concurrent session

12:45 PM

Thursday, January 23, 2020
2 Racial/ethnic differences in prenatal and postnatal counseling about maternal and infant health promoting practices among adolescent mothers

P Shah*

S Tong

S Hwang

SL Bourque

University of Colorado, Aurora, CO

Purpose of study

Racial/ethnic disparities in teen birth rates persist. In 2017, the teen birth rate was 27.5 per 1000 for non-Hispanic black (NHB) teens and 28.9 per 1000 for Hispanic teens, compared with 13.2 per 1000 for non-Hispanic white (NHW) teens. Despite this difference, data describing racial/ethnic differences in counseling is lacking. This study evaluates racial/ethnic differences in 1) prenatal counseling and 2) postnatal counseling of teen mothers.

Methods used

Pregnancy Risk Assessment Monitoring System (PRAMS) 2012–2016 data, a national perinatal surveillance system was analyzed. Prenatal counseling topics included substance use (tobacco, alcohol and illicit drug use), medical care (HIV testing, influenza vaccination and recommended weight gain), and breastfeeding. Postnatal counseling topics included infant safe sleep, postpartum depression, and contraception. Bivariate associations of maternal/infant characteristics and receipt of counseling were estimated using chi-square tests. Multivariable logistic regression was used to assess the independent relationship between race/ethnicity and receipt of pre-/postnatal counseling, controlling for maternal and infant demographic and clinical factors.

Summary of results

11805 teen mothers surveyed represent a weighted sample of 544,930, including 20.4% NHB, 29.5% Hispanic and 42.1% NHW teens. Compared to NHW teens, NHB teens were more likely to receive any prenatal substance use [AOR 8.42, 95%CI (3.47, 20.42)] and breastfeeding counseling [AOR 2.51, 95%CI (1.12, 5.65)]. Compared to NHW teens, Hispanic teens were more likely to receive postpartum birth control counseling [AOR 9.99, 95%CI (1.81, 55.22)].

Conclusions

This study demonstrates racial/ethnic differences in substance use and postpartum family planning counseling with minority teens being more likely to receive this counseling compared to their NHW counterparts. Ongoing investigation is needed to better understand the drivers of these differences including additional factors that vary by region.

3 Evaluating the predictive validity of the MyHEARTSMAP psychosocial self-assessment tool in youth presenting to the emergency department with mental health concerns

B Li1,*

Q Doan1,2

1University of British Columbia, Vancouver, BC, Canada

2BC Children’s Hospital Research Institute, Vancouver, BC, Canada

Purpose of study

The number of youth visiting the pediatric emergency department (PED) for mental health care is increasing. The use of digital self-assessment tools is an efficient method of evaluating mental health due to ease of administration without a clinician. We quantified the predictive validity of a psychosocial self-assessment tool, MyHEARTSMAP, in youth presenting to the PED with mental health concerns.

Methods used

We conducted a prospective cohort study in two tertiary PEDs from December 2017-June 2019. Youth 10–17 years old triaged for a mental health concern were screened and enrolled to complete MyHEARTSMAP on a mobile device. A blinded clinician conducted a HEARTSMAP assessment, which was the reference standard. Both tools collect information about ten sections: Home, Education and activities, Alcohol and drugs, Relationships and bullying, Thoughts and anxiety, Safety, Sexual health, Mood and behavior, Abuse, and Professional resources. Based on scoring from 0–3 (no concern, mild, moderate, or severe), a score for psychosocial domains (psychiatry, social, youth health, and function) is computed and resources are recommended based on need. Sensitivity and specificity were measured for youth and guardian MyHEARTSMAP assessments in detecting severe psychiatric concerns and any other domain concerns.

Summary of results

We screened 510 youth and 167 families enrolled. Concerns included suicidality or safety concerns (49.7%) and mood (25.7%) and behavioral disorders (12.6%). The remaining were substance use, social issues, and eating and thought disorders. Youth and guardian’s sensitivity for detecting a severe psychiatric concern was 70.5% (95% CI: 54.8%, 83.2%) and 80% (65.4%, 90.4%) respectively. Specificity was 34% (24.6%, 44.5%) and 41.2% (31.5%, 51.4%). The sensitivity for detecting any domain concern in youth and guardians were 93.9% (87.3%, 97.7%) and 93.3% (86.8%, 97.3%) for social, 88.2% (80.4%, 93.8%) and 90% (82.8%, 94.9%) for youth health, and 96.8% (91.9%, 99.1%) and 97% (92.4%, 99.2%) for function.

Conclusions

Assessment by families using MyHEARTSMAP is sensitive for detecting psychosocial concerns requiring mental health follow-up beyond PED evaluation.

4 Treating streptococcal pharyngitis with penicillin versus broad spectrum antibiotics

T Sumibcay1,2,*

L Yamamoto1,2

J Lee-Jayaram1,2

1Kapi’olani Medical Center for Women and Children, Honolulu, HI

2Hawai’i Pacific Health, Honolulu, HI

Purpose of study

Dysbiosis of the human microbiome, caused especially by a decline in its microorganism diversity, can play a role in the development of harmful, long-term conditions that impact human health. A major contributor to this dysbiosis is the use of antibiotics to treat bacterial infections. Antibiotics can be divided into two groups: narrow spectrum antibiotics, which are effective against a specific group of bacteria, and broad spectrum antibiotics (BSA), which are effective over a wider range of bacteria and can pose a risk of disrupting the microbiome. Antibiotic treatment of Group A strep (GAS) infection, which causes strep throat and scarlet fever, serves as area where microbiome harm can be reduced via treatment with penicillin (PCN), a narrow spectrum drug that GAS are 100% sensitive to. Antibiotics commonly used for treatment, however, include amoxicillin, a moderate BSA, along with other broader spectrum antibiotics. We sought to characterize the antibiotics used to treat strep throat and scarlet fever and to further describe the extent to which BSA are used for treatment.

Methods used

We performed retrospective data extraction and analyses of 3,169 patients who were less than 22 years old, received a diagnosis of strep throat or scarlet fever, and were seen in an outpatient setting. Patients were further excluded if they had a PCN allergy or had any diagnoses of co-infections or comorbidities that would require the use of BSA. We then used descriptive statistics as our primary mode of data analysis.

Summary of results

In summary, 2,208 patients were determined to have simple strep throat or scarlet fever. Of these patients, 65% were treated with various BSA, mainly amoxicillin; 27% were treated with PCN; and 8% were given no antibiotics. With subjects divided by age group (0–3, 4–12, 13+), the trend of BSA being used more often for treatment continues, though a greater proportion of patients aged 13 and above were found to be treated with PCN.

Conclusions

Our findings highlight opportunities for clinicians to reflect on their use of antibiotics in treating strep throat and scarlet fever. It is important for providers to prioritize the reduction of harm to the microbiome, which is essential in maintaining human health, by reducing their use of BSA whenever possible.

5 Integrating technology into patient education to empower pediatric endocrinology patients to improve their health through a patient-centered care approach

K Piri*

V Wang

R Kinman

UCSF Fresno, Fresno, CA

Purpose of study

In a patient-centered care approach, one of the roles of the healthcare professional is to act as their patient/family’s health coach. It is thus imperative that medical professionals be able to educate their patients and to have that education easily accessible, easy to understand and retain, and actively engaging. This is particularly true in a chronic disease model. The use of technology with its ability to access information 24/7 can be especially advantageous in providing information in a multimedia format, and as such can serve as a supplement to the more traditional forms of education in order to improve self-efficacy in patients and their families.

Methods used

Two high school students enrolled in the UCSF Fresno Medical Education Program Summer Biomedical Research Internship Program were charged with the creation of the websites. 34 diabetes patients and 47 patients with other endocrine disorders were surveyed, along with their parents. Websites were built using Google Sites given its easy accessibility, with all content either original or with Creative Commons licensing. Videos were created using iMovie and housed in a YouTube site.

Summary of results

77% of diabetes patients/parents and 64% of other endocrine patients/parents were interested in the development of educational websites. Two separate websites were created: one for diabetes and for patients with other endocrine disorders. Both websites contain easy-to-understand information written for those even with lower literacy levels. Brief educational videos were created to reinforce concepts taught in the clinic, and diabetes videos such as ‘My Diabetes Monster’ were created by our patients and parents to empower them and show them that they are not alone in their struggles with diabetes.

Conclusions

The majority of patients and parents surveyed expressed interest in the development of easily accessible educational websites, which can be easily accessed by both inpatients and outpatients even outside normal business hours. Such sites can be built by high school students interested in health careers under the guidance of the physician, thus providing medical pipelines as well as patient education. These sites should help patients and their families improve their self-efficacy in providing care for their disease.

6 The effectiveness of an adolescent reproductive health symposium on interprofessional perceptions of providing comprehensive care for adolescents in california’s central valley

C Vargas1,*

RR Filbrandt1

K Zografos2

L Khang2

J Limon1

1Valley Children’s Hospital, Madera, CA

2California State University, Fresno, Fresno, CA

Purpose of study

In California’s Central Valley, the teen birth rate is almost double the national average and sexually transmitted infection (STI) rates are disproportionately higher amongst minority populations. In this study we assessed the effectiveness of an adolescent reproductive health symposium for interprofessionals in offering comprehensive reproductive services to adolescents in this region.

Methods used

The sample consisted of interprofessionals, including pediatricians, pediatric residents, nurses, and community healthcare educators. Participants were recruited from a one-day, lecture style symposium where education was provided on national and local current trends in STI and pregnancy rates amongst adolescents, effective contraceptive methods, community resources, and referral options to provide comprehensive reproductive healthcare services to adolescents. A pre and post survey instrument and a 3-month post survey were utilized to assess provider perceptions of providing comprehensive care for adolescents.

Summary of results

Participant perceptions of their clinical competencies in offering comprehensive adolescent reproductive health services improved after the symposium (n=64). Statistically significant differences were noted in the perceptions of having adequate training (p<0.001) and feeling comfort taking a psychosocial and sexual history (p=0.001). There were also statistically significant differences in the perceptions of being adequately prepared to counsel adolescent patients on contraceptive methods (p<0.001), including options for long acting reversible contraceptives (p=0.003) and local referral options (p<0.001). There were no statistically significant differences found 3 months after the initial education; however, participants showed maintenance of perceptions.

Conclusions

A symposium based intervention demonstrates the positive impact that interprofessional education has on adolescent reproductive health by increasing provider competency in offering comprehensive adolescent reproductive health services.

7 Longitudinal evaluation of pediatric residency didactics transition from noon conference to an academic half day

K Montano

R Craig

L Lopez

A Greene

A Belmonte

A Staples

CP Chow

W Dehority

C Zeorlin*

T Ford

Y Zhu

University of New Mexico, Albuquerque, NM

Purpose of study

In 2009, the University of New Mexico (UNM) Pediatric Residency transitioned program didactics from noon conference to an academic half day. Immediate evaluation of resident and faculty satisfaction, resident attendance, board exam pass rate and In-Training-Exam (ITE) scores showed improvements with this change. These results by Dr. Walter Dehority were published in 2012. The primary aim of this study was to investigate the longitudinal impact of the academic half day at UNM on resident and faculty satisfaction, resident attendance and clinical knowledge in the form of standardized exam results. In addition, use self-determination theory to explore effects of the academic half day on autonomy, competence and relatedness in pediatric residents.

Methods used

In this mixed methods study, surveys regarding satisfaction were conducted of current pediatric residents (n=32) and faculty (n=32) at UNM. To assess clinical knowledge, quantitative measures such as pediatric board exam pass rate were evaluated. Finally, focus groups were conducted with pediatric residents and faculty separately to evaluate concepts related to resident autonomy, competence and engagement with the academic half day.

Summary of results

Resident and faculty satisfaction was sustained with significance at 88% and 67% (p-value of 0.02 and 0.009), respectively. Resident attendance was also sustained at 88.4% (p=0.005). Board exam pass rates are increased since 2009, with unclear significance. Focus groups identify overall satisfaction from residents and faculty and identified a need for addressing resident engagement with didactics secondary to clinical pressures and interactivity of didactics.

Conclusions

The academic half day shows continued success in terms of faculty and resident satisfaction and resident attendance. More research is needed to investigate other factors related to the board pass rate. Further intervention and research will be needed to improve resident engagement in the academic half day.

8 Pediatric communication: big words aren’t for little patients

S Leung1,*

ME Brown2

S Jackson3

P McBurney3

1University of California, San Diego, San Diego, CA

2Tufts Medical Center, Boston, MA and

3Medical University of South Carolina, Charleston, SC

Purpose of study

Current curriculums teach medical trainees how to talk with patients and families though online videos, simulated patients, small groups, and clinical encounters, with or without feedback given by trained providers. Few pediatric curriculums address communication fundamentals: semantics, phrasing, and developmental milestones. The purpose of this curriculum is for pediatric residents to learn effective semantic and phrase usage as well as understand developmental milestones to improve their communication knowledge and skill confidence.

Methods used

Pediatric residents of all training levels at one academic institution participated in a one-time 45-minute workshop. The curriculum included three exercises covering semantics, phrasing and milestones via small group discussions and self-assessments of communication/milestone knowledge. Pre-, post-, and 7-month intervention surveys that evaluated knowledge and confidence about their communication skills with pediatric patients were collected. Qualitative feedback was acquired for curriculum improvement.

Summary of results

Forty-one pediatric residents participated in the workshop: 71% female, 88% categorical pediatrics, and 17% with children. Residents included 1st, 2nd, 3rd, and 4th years: 34%, 44%, 20%, 2%, respectively. Survey participation (3 surveys) averaged at 68%. Significant improvement occurred following the workshop: knowledge about speaking with patients increased from 9% to 44% (p≤0.01, Z-score=-3.1), knowledge in developmental stages increased from 28% to 72% (p≤0.01, Z-score=-3.5), confidence while speaking with patients increased from 16% to 53% (p≤0.01, Z-score=-3.2). At 7-month follow up, 91% of participants stated that they used at least one piece of knowledge or skill gained from this workshop.

Conclusions

This workshop increases communication knowledge and confidence immediately after as well as 7 months after the session by focusing on the semantics, phrasing, and developmental milestones. It provides pediatric trainees with the fundamentals for communicating with pediatric patients, which are applicable for all patients, compared to learning through experience in feedback, which may be patient-specific.

9 Improving support of breastfeeding at a baby-friendly™ designated large urban hospital in albuquerque, new mexico

T Hatfield*

P Mendoza

C Zeorlin

J Martinez

C Peceny

MM Ramos

E Sebesta

University of New Mexico, Albuquerque, NM

Purpose of study

Breastfeeding has conclusively proven to be the healthiest feeding option for infants. Baby-Friendly™designated hospitals and birthing centers follow the Ten Steps to Successful Breastfeeding, which are considered to be the gold standard for supporting mothers who wish to breastfeed. However, even a Baby-Friendly™designated hospital may have room for improvement. The University of New Mexico Hospital (UNMH) is an urban hospital serving a predominantly Hispanic and Native American population, and the majority of pediatric patients are covered by Medicaid. Despite its Baby-Friendly™ designation, UNMH had low rates of physician documentation of discussing the health impacts of breastfeeding in the postpartum setting and discussion of home visitation prior to discharge. We aimed to improve these measures using the Plan-Do-Study-Act (PDSA) model.

Methods used

We conducted this study from August 2018 to August 2019 in the UNMH Mother Baby Unit. Providers reviewed 61 to 86 charts for each of four medical record reviews (MRR). Based on the results of the first two MRRs, providers decided to focus on increasing home visitation referrals. After the third MRR, providers worked to increase discussion and documentation of the health impacts of breastfeeding. Changes made included creation of a discharge planning checklist, modifying admission and discharge templates, educating attending and resident physicians via emails, meetings, chart reviews, and bulletin boards in the team room, and adding home visitation referral forms to all patient charts.

Summary of results

Over the one year study period, rates of discussing home visitation status increased from 49.2% to 89.2%. The rates of discussing health impacts of breastfeeding increased from 31.1% to 86.5%.

Conclusions

Implementation of these quality improvement measures resulted in substantial gains in several key breastfeeding metrics, despite having already earned the designation Baby-Friendly™. We propose that all hospitals, including those that are designated Baby-Friendly™, can better support breastfeeding through ongoing quality improvement initiatives.

10 Buckle fracture treatment with removable wrist orthosis achieving clinical excellence

C Wang*

D Kephart

HB Leshikar

J Magana

UC Davis, Sacramento, CA

Purpose of study

Distal radius and ulna buckle fractures are a frequent reason for pediatric emergency department (ED) visits. Previously, providers used immobilization in a short arm cast. Studies have shown equivalent outcomes in using a removable splint over a cast, with reduced costs, increased efficiency, and improved patient/family satisfaction. Our baseline data demonstrated that nearly all children with distal radius/ulna buckle fractures were being casted at our ED. We planned to increase the use of removable splints in children 2–18 years old with these fractures from 17% to >90% and to reduce orthopedic consultations in the ED from 88% to <10% over a 12 month period.

Methods used

We performed a retrospective chart review to obtain baseline data. In collaboration with orthopedics, a standardized protocol was created and implemented in January 2019. Treatment involved placing splints for patients ages 2–18 with distal forearm buckle fractures seen on x-ray without consulting or following up with orthopedics. Emergency medicine, pediatric, and orthopedic physicians were educated on the protocol. Standardized instructions for caregivers and primary care providers were made. We reviewed monthly data on the number of splint placements, orthopedic consults and follow-ups, x-rays, and length of stay.

Summary of results

In the first seven months of implementation there have been 11 patients that fit the inclusion criteria. The proportion of removal splints increased from 17% (n=9) to 63% (n=7) (p=0.01). Orthopedic and plastic surgery consults decreased from 88% (n=46) to 36% (n=4) (p=0.02), and surgical clinic follow up decreased from 86% (n=45) to 36% (n=4) (p=0.008). Average x-rays done decreased from 1.3 to 1.0 (p=0.02), and length of stay decreased from 202.9 to 154.3 minutes (p=0.0001).

Conclusions

Initiation of a protocol for distal forearm buckle fractures in our pediatric ED has increased the use of removal splints and reduced orthopedic consults, clinic follow up, number of x-rays, and length of stay. We plan to increase the duration of data collection to achieve adequate sampling. Next steps include educating plastic and trauma surgery services about the protocol and further partnering with caregivers to prevent unnecessary orthopedic referrals.

Cardiovascular I

Concurrent session

12:45 PM

Thursday, January 23, 2020
11 Electronic cigarettes together with a high fat diet induces cardiac dysfunction and cardiac structural changes

MM Razipour1,*

M Parveen1

J Espinoza-Derout1

F Bautista1

X Shao1,2

MC Jordan2

K Roos2

S Mahata3

A Sinha-Hikim1,2

T Friedman1,2

K Hasan1

1Charles R Drew University of Medicine and Science, Los Angeles, CA

2University of California, Los Angeles, Los Angeles, CA

3University of California, San Diego, La Jolla, CA

Purpose of study

The disturbing trend of youth electronic cigarette (EC) use has been classified as an urgent, unpredicted public health epidemic. Similarly, high fat diets (HFDs) have been shown to be addictive and common in present day youth. This translational model investigates the cardiovascular effects of ECs in mice exposed to a HFD.

Methods used

Male C57BL/6J mice were exposed to chronic, intermittent EC aerosol for twelve weeks with ad lib access to a HFD. Mice were exposed to ECs in the presence (2.4%) or absence (0%) of nicotine and saline. Echocardiography, histology, and western blot analysis were used to determine the cardiovascular effects of EC aerosol exposure.

Summary of results

Echocardiographic data revealed mice exposed to 2.4% ECs had a decreased left ventricular fractional shortening, left ventricular ejection fraction, and velocity of circumferential fiber shortening compared to mice exposed to 0% ECs or saline. Transmission electron microscopy revealed that cardiomyocytes of mice treated with 2.4% ECs exhibited left ventricular abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy. The detrimental effects of 2.4% ECs on cardiac structure and function were associated with significantly greater oxidative stress, increased plasma free fatty acid levels, cardiomyocyte apoptosis, and inactivation of AMP-activated protein kinase as well as activation of its downstream target, acetyl-CoA carboxylase.

Conclusions

This study suggests adverse effects of 2.4% EC use in conjunction with a HFD on cardiac function and biochemistry. Chronic EC use may cause cardiomyopathy, potentially leading to significant morbidity and mortality. These results support limiting EC use with nicotine to prevent the renormalization and glamorization of nicotine and tobacco products, particularly in adolescents and those consuming a HFD.

12 T-cell deficient mice demonstrate reduced atherosclerotic plaque burden

AJ Shepherd*

MG Yussman

DH Wagner

University of Colorado School of Medicine, Aurora, CO

Purpose of study

Atherosclerosis is characterized by arterial plaque deposition. The CD40-CD154 inflammatory dyad is a major driver of the auto-inflammation seen in atherosclerosis and type 1 diabetes (T1D). A sub-type of CD4+ T cells that express CD40 (Th40 cells) is increased in T1D, but has not been defined in atherosclerosis. Thus, this study seeks to explore the role of this pathogenic T-cell on plaque formation.

Methods used

ApoE-/- transgenic mice represent a model of atherosclerotic disease. We have generated a novel TCRα-/- ApoE-/- mouse model to investigate the role of Th40 cells. Baseline and ‘add back’ T cell experiments have been conducted. Mice are sacrificed at 8 months of age and then dissected to obtain the aortas and hearts. The aorta is used for en-face Sirius Red stain analysis while serial aortic valve cross sections are used to characterize the lesion in terms of area, volume, necrosis, and cellular content.

Summary of results

Trichrome-stained aortic valve cross sections show a significant reduction in overall plaque as well as ability to form advanced plaque (as determined by macrophage content) in the ApoE-/- TCRα-/- mouse model (shown in image B) as compared to its ApoE-/- counterpart (A). This reduction in plaque deposition is also shown in the Sirius Red analysis of the whole aorta. Representative samples of double KO mice show 16% plaque deposition (C) compared to 33% within ApoE-/- mice (D).

Conclusions

T-cell deficient ApoE-/- mouse models demonstrate a decreased plaque burden in comparison to the ApoE-/- counterparts illustrating that T-cells are implicated in atherosclerosis pathogenesis. Future studies will characterize the cell populations within the plaques.

13 Warfarin anticoagulation following pediatric heart surgery: comparing home versus traditional lab monitoring

A Ligsay1,*

D Griffin2

J Frazer3,4

S Sah1,2

1University of California San Diego, San Diego, CA

2Rady Children’s Hospital, San Diego, CA

3University of California Los Angeles, Los Angeles, CA

4Santa Barbara Cottage Hospital, Santa Barbara, CA

Purpose of study

Warfarin is commonly used following placement of mechanical heart valves or an extracardiac conduit in the Fontan procedure in order to minimize risk of thrombotic events. The degree of anticoagulation is monitored by the patient’s international normalized ratio (INR), which is traditionally done by serial outpatient blood draws. The goal of this pilot study is to determine if anticoagulation can be better managed using a home INR monitoring system compared to traditional laboratory monitoring.

Methods used

Patients who underwent artificial mechanical valve placement and/or an extracardiac Fontan procedure were consented and randomized to one of two 3-month arms: INR testing via 1) traditional laboratory monitoring (venipuncture), or 2) a home INR monitor (finger stick test). After 3 months, patients were crossed-over to the other arm (6 months total in the study). Frequency of INR checks was determined per cardiologists’ clinical judgement. A questionnaire was completed after each arm of the study. Eleven subjects have been enrolled into the study thus far: 10 have completed at least one arm of the study, 5 have completed both arms, and 1 patient was withdrawn after the first arm due to non-compliance. Student t-tests were performed to compare time and cost differences between the two arms.

Summary of results

The ease of obtaining INR value between home and laboratory monitoring was rated as similar (3.4/5 vs 3.8/5), with similar pain rating experience by the subject (2/5 vs 2.4/5). However, parents were more satisfied with using the home INR system (4/5 vs 2.9/5) and were more likely to recommend to others (4.2/5 vs 2.5/5). The average time it took to use the home INR monitor versus lab monitoring was also significant (3.8 minutes vs 53.3 minutes; p<0.0001). The percentage of INR in therapeutic range for subjects was also similar between arms (home 46.9% vs lab 43.4%; p=0.6396).

Conclusions

Overall, preliminary data show similar outcomes between home vs lab INR monitoring, with the former showing improved patient satisfaction and time saved. Ongoing cost-effective analysis is being conducted as the pilot study continues.

14 Active smoking is associated with decreased rates of wound healing after endovascular treatment of critical limb ischemia

A Sarkar*

T Jordan

M Haider

D Kokkinidis

University of California, Davis, Sacramento, CA

Purpose of study

To examine whether active smoking is associated with worse complete wound healing rates in patients with CLI undergoing endovascular interventions.

Methods used

A single center observational study was conducted. Consecutive patients with CLI who underwent endovascular interventions were included. Smoking status was assessed at the time of the intervention and active smoking was compared to no active smoking at the time of the intervention. Cox and logistic regression analyses were conducted to compare the complete wound healing rates of the two groups during follow-up.

Summary of results

In total, 264 patients (active smokers: n=41; not active smokers: n=223) and 553 lesions were included. Active smoking was associated with decreased rates of complete wound healing in the 6-month univariate cox regression analysis (HR: 0.22; 95% CI: 0.07 - 0.71; p=0.012). The 6-month KM estimates for complete wound healing were 8.9% for the active smoking group vs 34% for the no current smoking group. Active smoking was also associated with decreased rates of complete wound healing in the 9-month univariate (HR: 0.43; 95% CI: 0.21- 0.90; p=0.026) and multivariate analysis (HR: 0.11; 95% CI: 0.01 – 0.94; p=0.044). The 9-month KM estimates for complete wound healing were 25.2% in the active smoking group vs 46% in the no active smoking group. No difference was found between the two groups in the 9-month major amputation rates. The time to complete wound healing was longer in the active smoking group (269.7±187.5 days vs. 208.3±115.7 days; p=0.009).

Conclusions

Active smoking status at the time of intervention in CLI patients is associated with lower rates of complete wound healing during 6- and 9-month follow-up. Active smoking was associated with a two-month delay in the median time to wound healing. These findings emphasize the importance of smoking cessation for patients with CLI.

15 Hospital reporting of critical congenital heart disease screening

H Siefkes1,*

M Jocson2

S Lakshminrusimha1

J Schulman2

1University of California, Davis, Sacramento, CA

2California Children’s Services, Integrated Systems of Care Division, Department of Health Care Services, Sacramento, CA

Purpose of study

California passed legislation in 2013 mandating oxygen saturation (SpO2)-based screening for critical congenital heart disease (CCHD) screening and annual data submission to the Department of Health Care Services (DHCS). We conducted a retrospective review of CCHD screening data reported to California DHCS to describe reporting compliance and assess data accuracy.

Methods used

This was a retrospective review of hospital CCHD screening reports provided to California DHCS from January 2015 to December 2016. We compared the reported birth data to California’s Office of Statewide Health Planning and Development (OSHPD) for accuracy of live births reported and to determine frequency of reporting from hospitals meeting the CCHD reporting requirement criteria. We also evaluated the data for other potential markers of accuracy using proxies such as number of report revisions required and accurate summation of variable cells (i.e. all screen results accounted for, or all eligible newborns undergoing screening).

Summary of results

Thirty-four percent of hospitals did not comply to mandated CCHD screen reporting. When hospitals comply to reporting, 45.8% in 2015 and 44.2% in 2016 submitted reports in which the number of completed screens did not match the number of screen results. Only 21.8% in 2015 and 21.1% in 2016 of hospitals submitted live births that matched their respective live births reported to a second database. In 2015, the submitted data represented 375,283 live births, which was 80% of the 468,936 live births reported to OSHPD that year. In 2016, the submitted data represented 318,424 live births, or 56% of the 570,786 live births reported to OSHPD that year. For the two years combined, up to 623 newborns with CCHD could have been missed or unaccounted for due to non-reporting.

Conclusions

A third of hospitals do not comply to reporting guidelines and over half of the submitted reports are inaccurate. A large number of newborns with CCHD may potentially be missed due to under/inaccurate reporting.

16 Age-specific cardiac remodeling outcomes induced by isoproterenol

J Zumo1,*

RF Cook2

BD McNair2

J Schlatter2

EE Schmitt1,2

KC Woulfe3

DR Bruns1,2

1University of Washington, Seattle, WA

2University of Wyoming, Laramie, WY

3University of Colorado- Denver, Aurora, CO

Purpose of study

Heart failure (HF) impacts patients of all ages and is an enormous public health problem. Historically, HF has been treated with a single, multi-purpose approach, despite the observation that biological differences such as age influence the pathogenesis and thus treatment of this disease. We hypothesized that molecular mechanisms of HF pathogenesis differ across the life-course, a hypothesis which we tested with a mouse model of cardiac dysfunction at three distinct stages of life.

Methods used

C57BL/6 mice at pediatric (5 weeks; n=12), adult (3–5 months; n=12), and old (18 months, n=10) ages were treated with a subcutaneous mini-osmotic pump that eluted isoproterenol (ISO; 30 mg/kg/hour), a non-selective β-adrenergic receptor agonist commonly used to induce acute cardiomyopathy in mice. Following 6 days, we performed echocardiography, biochemical assessments, and RNA sequencing of the left ventricle (LV).

Summary of results

Both the pediatric and adult groups underwent hypertrophic remodeling in response to ISO, as evident by higher LV weight relative to tibia length (TL). However, ISO exposure did not increase LV/TL in old mice. Echocardiographic imaging demonstrated thickening of the ventricular wall in ISO mice compared to control. Expression of pro-fibrotic mediators also differed across the life-course in response to ISO, with adults inducing a pro-fibrotic transcriptional program (α-smooth muscle actin, fibronectin, collagen, periostin) that was attenuated in old and absent in pediatric animals. RNA-sequencing identified that 119, 1515, and 33 genes were significantly differentially expressed in pediatric, adult, and old mice exposed to ISO, respectively (p<0.05). Of these genes, only 2 transcripts were differentially expressed across all three ages.

Conclusions

Biological age significantly impacts the molecular mechanisms of ISO-induced cardiac remodeling. Ongoing analysis of these molecular targets will inform HF therapies using age as a biological variable.

17 Variability of end-tidal carbon dixoide in out-of-hospital cardiac arrest

B Grabman1,*

NE Bulger1

BM Harrington1

RG Walker2

AJ Latimer1

M Sayre1,3

C Maynard4

NJ Johnson1

CR Counts1,3

1University of Washington School of Medicine, Seattle, WA

2Stryker Emergency Care, Redmond, WA

3Seattle Fire Department, Seattle, WA

4University of Washington School of Public Health, Seattle, WA

Purpose of study

End-tidal carbon dioxide (ETCO2) guides decision-making during out-of-hospital cardiac arrest (OHCA), but its prognostic value is poorly understood. We investigated the relationship between ETCO2, return of spontaneous circulation (ROSC), and outcome in OHCA patients.

Methods used

This retrospective study included adult OHCA patients treated by Seattle Fire Department (SFD) in 2018. Those who were not intubated, had advance directives, or received prior advanced life support interventions were excluded. Median peak ETCO2 was evaluated for the following intervals: the first and last minute (initial [non-intubated] and final, respectively), the entire pre-intubation period, 30 seconds post-intubation, 90 seconds pre- and post-ROSC, and 90 seconds pre- and post-defibrillation. ETCO2 during each interval was compared to cardiac rhythm and outcome. ETCO2 changes were observed after defibrillation based on identification of ROSC on the subsequent pulse-check. Reported values are medians with quartiles [25%/75%].

Summary of results

Of 353 included patients, initial ETCO2 were 24 mmHg [11/34] and 10 mmHg [2/22] for shockable and non-shockable rhythms, respectively. Pre-intubation values for these cohorts were 27 mmHg [4/40] and 10 mmHg [3/27] and post-intubation values were 43 mmHg [33/59] and 46 mmHg [25/64]. Post-defibrillation, ETCO2 increased from 38 mmHg [30/53] to 54 mmHg [41/60] among patients who achieved ROSC and 41 mmHg [25/57] to 42 mmHg [27/56] among those without ROSC. With initial VF/VT, higher post-intubation and post-ROSC ETCO2 were associated with worse cerebral performance categorization (CPC) among survivors (post-intubation CPC 1/2: 35 mmHg [28/44], CPC 3/4: 59 mmHg [48/71]; post-ROSC CPC 1/2: 50 mmHg [45/59], CPC 3/4: 64 mmHg [57/67]).

Conclusions

Patients with ROSC after defibrillation had larger rises in ETCO2 than patients without ROSC. Pre-intubation ETCO2 values appear clinically unreliable. Our finding that higher ETCO2 is associated with worse neurologic outcomes for patients who survive to hospital discharge warrants further investigation.

18 Kencor remote monitoring system optimizes blood pressure control and improves serum creatinine levels in hypertensive patients

K Dhond1,2,*

Y Gill2

M Villalon2

S Lahsaei2

MJ Dhond2

C Mancherje2

J Breneisen2

M Dhond2,3

1UC Santa Cruz, Santa Cruz, CA

2Northbay Healthcare, Fairfield, CA and

3UC Davis, Davis, CA

Purpose of study

Hypertension(HTN) costs the US $48.6 billion per year, it occurs in one third of the US population with only 54% reaching guideline values. We used KenCor Remote Monitoring System (KRMS) to evaluate its utility in optimizing blood pressure control.

Methods used

43 clinic patients with HTN were enrolled in KRMS. Patients were oriented into KRMS software which was downloaded onto their smartphones. Patients were provided with a Bluetooth-enabled blood pressure (BP) cuff and weigh scale. Patients completed a daily questionnaire and recorded their vitals, with uploading of that data to the clinic nurse. KRMS then stratified the patients into low (green), medium (yellow), or high (red) risk vitals. Patients with red alerts were contacted by the nurse. Patients at high risk for more than 1 day were seen in the clinic for medication adjustment. We collected data for one year pre and post KRMS enrollment on blood pressure (BP), weight, serum creatinine (Cr), brain natriuretic peptide (BNP), and ejection fraction (EF).

Summary of results

40/43 patients were compliant with KRMS. The majority of patients uploaded data between two to seven times per week. The patients (20 women) were aged 39–96 years (average 64.5 years). 19/40 patients were diabetic with an average weight of 102.3 kg. The average EF was 41.5%. Data was analyzed for twelve months pre and post KRMS enrollment. The average Cr pre and post was 1.49 and 1.25 (p=0.0180). The average BNP pre and post was 6572.7 to 5339.4 (p=NS). The average systolic/diastolic BPs pre and post were 139.8/84.0 and 119.4/69.0 (p=0.0035 and 0.0001 respectively).

Conclusions

1/In hypertensive patients, KRMS led to a significant reduction in BP levels with the majority of patients reaching guideline values.

2/Serum Cr was significantly reduced in patients on KRMS.

3/KRMS appears to be an effective tool to aid in the chronic care management of HTN and its related complications.

19 NSTEMI and HFrEF due to Methamphetamine

JA Coleman*

D Aguirre

Kern Medical, Bakersfield, CA

Purpose of study

To discuss the diagnosis, evaluation, and management of methamphetamine-induced acute myocardial infarction in the presence of methamphetamine induced cardiomyopathy.

Methods used

Retrospective Chart Review.

Summary of results

A 35-year-old male with no pmh who has a social history significant for tobacco, alcohol, methamphetamine, cocaine, and PCP abuse presented to the emergency department 3 days h/o dyspnea and acute onset of new onset of pressure-like pain in his chest, which was constant, 7/10, and non-radiating, wth no aleviating or aggrevating factors. Upon presentation he was hemodynamically stable, and admitted to using methampheamine hours prior. Chest x-ray was unremarkable. EKG showing no ST segment elevations or depressions. Initial serum troponin was elevated at 0.63 and urine toxicology was positive for methamphetamine and PCP. NSTEMI was diagnosed. He was admitted and started on ACS protocol, and TTE ordered. Repeat troponin was 2.45, and TTE revealed a LVEF of 25–30%. Patient subsequently underwent a left heart catheterization which found the proximal left anterior descending (LAD) artery to have a lesion of 80% with the left ventriculography estimating a LV EF of 20%. Patient was transferred to MICU while pending transfer to tertiary institution for PCI. Patient underwent revascularization and bare metal stenting of proximal LAD baring no complications and closely followed up in cardiology clinic.

Medications on discharge were aspirin, clopidogrel, carvedilol, lisinopril, furosemide, atorvastatin, and spironolactone. Eight months later, the repeated TTE resulted in significant improvement of the LV EF of 40–45% from 20–25%. The dual antiplatelet therapy with aspirin and clopidogrel was given for a duration of 12 months. Patient is now 14 months post PCI and is remaining clinically asymptomatic.

Conclusions

Amphetamine associated acute myocardial infarction may become more common if the rate of amphetamine abuse continues to increase. Methamphetamine associated cardiomyopathy appears to be potentially reversible upon cessation of methamphetamine and guideline directed management for heart failure.

Endocrinology and metabolism I

Concurrent session

12:45 PM

Thursday, January 23, 2020
20 Unmasking of Pneumocystis jiroveci pneumonia triggered by treatment of cushing’s syndrome

SC Fernandes

C Schmid*

AM Mansoor

E Varlamov

Oregon Health and Sciences University, Portland, OR

Case report

Case: A previously healthy 29 year old man presented with new onset hypertension, diabetes mellitus (DM), easy bruising, 70-lbs weight gain and painful purple stretch marks. Physical examination was notable for blood pressure of 156/91 mmHg, moon facies, facial plethora, acne, dorsocervical and supraclavicular fat pads, violaceous striae, abdominal bruising and thin skin. Labs showed hypokalemia (3.1 mmol/L), markedly elevated adrenocorticotropic hormone (ACTH 480 pg/mL; Nl <45) and 24 hour urine free cortisol (UFC 7950 ug/day; Nl <60), consistent with an ACTH-dependent Cushing’s syndrome (CS). Pituitary MRI showed a possible 4 mm lesion, however inferior petrosal sinus sampling confirmed ectopic ACTH CS. CT and nuclear imaging were negative. Escalating doses of ketoconazole were started with UFC reduction to 73.3 ug/day. He developed transaminitis, as well as respiratory distress with hypoxemia. Chest imaging demonstrated bilateral ground glass opacities concerning for Pneumocystis jiroveci pneumonia (PJP). Serum 1,3 beta-D glucan was elevated (188 pg/mL; NL <80) increasing suspicion for PJP. Patient declined bronchoscopy to confirm diagnosis and was empirically treated with trimethoprim-sulfamethoxazole and prednisone, resulting in rapid improvement of respiratory symptoms. The patient underwent bilateral adrenalectomy for CS and started on replacement hydrocortisone and fludrocortisone. He had 30 pound weight loss and diabetes and hypertension resolved in 3 weeks.

Conclusions

Patients with CS are at high risk for opportunistic infections. Cortisol excess depresses immune function allowing PJP to colonize the lungs. Treatment with cortisol decrease results in T cells recovery, which can cause an inflammatory reaction to PJP, analogous to immune reconstitution syndrome in HIV patients. Ectopic CS and higher cortisol levels increase PJP risk. Thus, PJP prophylaxis should be considered in patients with severe CS prior to initiation of any cortisol lowering therapies.

21 Evaluation of the immune system in pediatric cushing disease

M Rescigno1,2,*

C Tatsi2

C Lyssikatos2

E Belyavskaya2

M Keil2

G Papadakis2

C Stratakis2

1Universtiy of Nevada, Reno School of Medicine, Reno, NV

2National Institute of Health, Bethesda, MD

Purpose of study

Cushing Disease (CD) is a rare pediatric endocrine disorder that results from adrenocorticotropic hormone (ACTH) secreting pituitary adenomas. CD should be recognized as early as possible in the pediatric population due to the significant morbidity and mortality associated with late diagnosis and treatment. In the present study, we sought to describe the relationship between complete blood count (CBC) values, serum cortisol level, and size of the thymus. We also studied the association of the neutrophil to lymphocyte ratio (NLR), recently identified as a diagnostic and prognostic factor in cancer, with markers of hypercortisolemia.

Methods used

The inclusion criteria for the study included diagnosis of CD before age 18 years, diagnosis between 1997 and 2019, and previous imaging study that included visualization of the thymus (obtained prior to transsphenoidal surgery). CBC and serum cortisol levels at diagnosis were retrieved from medical records via retrospective chart review. Neutrophil and lymphocyte z-scores were calculated based on age and sex specific reference ranges. NLR was calculated using absolute levels among patients 6–12yo and >12yo. All studies were approved by the NIH Institutional Review Board.

Summary of results

Among 48 patients that met our inclusion criteria, no significant correlation was found between Hemoglobin (Hb) and cortisol. A significant correlation was found between cortisol levels and neutrophil (β=0.07, R2=0.1978, p<0.01) and lymphocyte (β=0.04, R2=0.1524, p<0.01) z-scores. Midnight cortisol was significantly correlated with the NLR in patients >12 years old (β=0.14, R2=0.6958, p<0.0001). Results of NLR for patients ≤12 years old did not reach statistical significance (p=0.096). Thymic data are pending complete analysis.

Conclusions

Immune dysregulation in CD can be used as supportive evidence of its diagnosis. NLR can be easily calculated from CBC and correlates with cortisol with a stronger coefficient of determination than solely using neutrophil or lymphocyte values. Further investigation is needed to establish a cutoff for NLR that can potentially differentiate patients with CD from eucortisolemic obese patients.

22 Testosterone and cortisol modulate the metabolic effects of sleep restriction

PY Liu1,*

D Sidebottom2

H Van Dongen2

1Harbor-UCLA Medical Center and LABioMed, Torrance, CA

2Washington State University Spokane, Spokane, WA

Purpose of study

Sleep restriction is highly prevalent and increases the risk of type 2 diabetes mellitus. The mechanisms by which sleep restriction causes insulin resistance (IR) are not known. Understanding these mechanisms would allow targeted interventions beyond requiring more sleep. Sleep restriction decreases testosterone, and increases cortisol, which are the main anabolic and catabolic hormones, respectively. Through a dual hormonal clamp intervention, we investigated whether testosterone and cortisol affect IR due to sleep restriction.

Methods used

34 healthy men aged 33.3±6.4y with BMI of 25.4±2.5 kg/m2 completed the study. Subjects were admitted to the Clinical and Translational Research Center. They had one night with a 10h opportunity (22:00–08:00) for baseline sleep and were then restricted to 4h sleep (01:00–05:00) for 4 consecutive nights. This pattern was repeated on two separate occasions with different treatment conditions, in randomized order: dual testosterone/cortisol clamp (ketoconazole + transdermal testosterone gel + oral hydrocortisone at mid-physiological doses) during all sleep restriction days, or no clamp (matching placebo). A 3-hour intensively sampled (23 samples) oral glucose tolerance test was performed after the baseline night, and after the fourth sleep-restricted night, to calculate IR by Matsuda Index (Mi) and by minimal model (Si). Effects of condition and measurement day and their interaction were determined by mixed-model.

Summary of results

Following sleep restriction, Mi showed greater IR in both conditions, but the increase was dampened in the dual clamp condition (F=4.90, p=0.029 for interaction). A composite sensitivity index that combined all glucose metabolic indices (Si, HOMA-IR, Matsuda Inex) confirmed this finding (F=4.81, p=0.029 for interaction).

Conclusions

A dual hormonal clamp intervention of testosterone and cortisol in a sample of healthy, young adult men dampened the negative effects of sleep restriction on glucose metabolism. Our results show that testosterone and cortisol modulate the effects of sustained sleep restriction on insulin resistance.

23 Changes in metabolic parameters after administration of novel oral androgens with progestational activity for 28 days

F Yuen1,*

A Thirumalai2

R Swerdloff1

PY Liu1

Y Pak1

L Hull1

S Page1

C Wang1

1Los Angeles Biomedical Research Institute, Torrance, CA

2University of Washington, Seattle, WA

Purpose of study

While the metabolic effects of testosterone have been well studied, the effects of co-administration of an androgen and progestin are less established. Two novel compounds being investigated for male hormonal contraception, dimethandrolone undecanoate (DMAU) and 11β-methyl-19-nortestosterone dodecylcarbonate (11b-MNTDC), have both androgenic and progestational activity. Preliminary data suggest that these androgens decrease HDL-C and increase weight.

Aim: Characterize the effects of DMAU and 11β-MNTDC on metabolic parameters including weight, lipid parameters, insulin resistance, and adiponectin.

Methods used

Two randomized, double-blind, placebo-controlled studies in healthy men were previously performed to assess the safety and tolerability of DMAU and 11β-MNTDC taken orally for 28 days. Insulin and adiponectin assays were performed on banked samples. Changes in weight, LDL-C, HDL-C, fasting glucose, HOMA-IR, and adiponectin were assessed. Log transformations were performed as needed. Two way ANOVA with post hoc Tukey HSD was performed to assess for dosage (0, 200, or 400 mg) and drug (DMAU or 11β-MNTDC) effects.

Summary of results

A total of 85 subjects were included in this analysis. Overall, there was a significant decrease in HDL-C and increase in weight and LDL-C (all p<0.001). For weight and HDL-C, both the 200 mg and 400 mg groups were significantly different from placebo, but there was no significant difference between the 200 mg and 400 mg groups. For LDL-C, the 200 mg groups were not significantly different from placebo (p=0.059) but the 400 mg groups were significantly different from placebo (p<0.001); there was no significant difference between the 200 mg and 400 mg groups (p=0.11) nor differences between the two novel androgens. There was no difference in fasting glucose, adiponectin or HOMA-IR.

Conclusions

DMAU and 11β-MNTDC reduced HDL-C and increased weight and LDL-C in these analyses. Changes in metabolic parameters may be considered during further development of male hormonal contraception.

24 A case of pheochromocytoma presenting as right basal ganglia infarct

R Hall1,2

H Saab1,*

L Moosavi1

RD Polineni1

E Cobos1

1Kern Medical-UCLA, Bakersfield, CA

2Ross University School of Medicine, Bridgetown, Barbados

Purpose of study

Pheochromocytoma is a rare tumor originating in chromaffin cells of the adrenal gland with an incidence rate estimated at 0.8 per 100,000 individuals per year. There have been few documented cases of the tumor and its consequences when not recognized in time.

Methods used

Retrospective case report.

Summary of results

A 45-year-old male with unknown past medical history presented via emergency medical services (EMS) to the emergency department (ED) after patient was found down by the railroad with reported right facial droop, dysarthria, and weakness. EMS reported that a friend on scene disclosed that patient had recently smoked methamphetamine. On arrival to the ED, patient was noted to have a blood pressure of 265/131, with a National Institutes of Health Stroke Scale (NIHSS) of 10 and a Glasgow Coma Scale (GCS)14. He was started on intravenous blood pressure medications and later switched to oral regimen. CT brain found hypodensities in basal ganglia, periventricular centrum semiovale, regions worse on left, suggestive of lacunar infarctions. Hospital course was complicated by uncontrolled hypertension, right sided paresis, aphasia and dysphagia. Given high risk for aspiration, the decision was made to place a percutaneous gastronomy tube for nutrition and medication management. CT abdomen and pelvis performed prior to procedure revealed an incidental finding of a 6 cm heterogeneous adrenal mass likely pheochromocytoma confirmed by serum metanephrine assays greater than 1000 pg/mL. The patient was treated with appropriate antihypertensive medication based on guidelines set forth by Endocrine Society, with planned laparoscopic resection of adrenal mass scheduled for two weeks later.

Conclusions

Given how rare the diagnosis of pheochromocytoma is, the differences in presentation and the need for early diagnosis and management, a clinician’s index of suspicion should be higher in individuals with no risk factors presenting with neurological manifestations and uncontrolled hypertension.

25 Intrauterine growth restriction and supplemental DHA alter rat hepatic histone methylation

R Kaddu*

S Kasera

H Wang

L Joss-Moore

University of Utah, Salt Lake City, UT

Purpose of study

Intrauterine growth restriction (IUGR) dysregulates circulating docosahexaenoic acid (DHA) in the fetus and neonate. Low DHA is associated with the development of postnatal morbidities including increased hepatic lipid accumulation. Recent studies suggest that sequestration of methyl groups for hepatic histone methylation, particularly H3K36me3 and H3K79me3, contributes to increased hepatic lipid accumulation. We previously demonstrated that IUGR increases hepatic dysfunction in male, but not female, rat pups. However, the effects of IUGR and DHA supplementation on hepatic histone methylation and associated lipid droplet accumulation are unknown. We hypothesize that IUGR and DHA supplementation cause sex-divergent changes in hepatic histone methylation and hepatic lipid droplet accumulation in the rat.

Methods used

IUGR was induced by uterine artery ligation in the rat. Control and IUGR rats received a regular diet or DHA diet (0.01%-Low or 0.1%-High) throughout pregnancy and lactation. At postnatal day 21 (d21) rat pup liver was collected. Global levels of histone modifications (H3K36me3, H3K79me3) were measured using western blotting of acid-extracted histones. Lipid droplet accumulation was detected using Oil-Red-O staining.

Summary of results

In female rats, IUGR with and without DHA increased H3K36me3 (209±11%-no DHA, 154 ±10%-low; 136±6%-high), and H3K79me3 (159±9%-no DHA, 212±15%-high). In male rats, IUGR without DHA did not affect H3K26me3. The combination of IUGR and High DHA decreased H3K36me3 (80±8%). In male rats, IUGR with and without DHA increased H3K79me3 (153±3%-no DHA,156±6%-low;144±16%-high). Qualitative assessment of hepatic lipid droplet accumulation suggests that IUGR increases lipid droplet accumulation in both male and female IUGR liver, while DHA supplementation normalizes lipid droplets dependent on dose and sex with improved resolution in female liver.

Conclusions

We conclude that IUGR and DHA supplementation cause sex-divergent changes in hepatic histone methylation in the rat and normalization with DHA depends on DHA dose and fetal sex at day 21 of development. We speculate that IUGR affects the capacity for hepatic histone methylation in male rat pups, thus potentially increasing hepatic lipid droplet accumulation. Ongoing studies are identifying specific H3K36me3 and H3K79me3 hepatic target genes.

26 Low K is not okay

M Cai*

R Hashemzadeh-Gargari

R Vohra

UCSF Fresno, Fresno, CA

Case report

A 15 year old hispanic male was in his usual state of health until morning of presentation. He awoke to go to the bathroom, but found himself unable to move his extremities well. He then proceeded to crawl to the bathroom where he vomited twelve times. In ED, vitals were normal, but exam remarkable for flaccid weakness of upper and lower extremities, and mild proptosis. Pertinent labs revealed potassium 1.4, glucose 169, magnesium 1.6, pH 7.41. EKG illustrated prolonged QT interval, ST depression and U waves. He was given IV potassium over four hours with repeat potassium 4.8. Repeat EKG normalized with paralysis slightly improved. Toxicology initially consulted for possible ingestion cause, but no substance found in urine or blood. Thyroid studies revealed TSH of <0.01, and elevated free T4 of 3.83, confirming the diagnosis of thyrotoxic periodic paralysis (TPP). Propranolol was started, along with supplemental magnesium and potassium. Within 24 hours of presentation, patient’s paralysis completely resolved. Patient was found to have Graves’ disease with elevated TSI at 133, and diffuse uptake in radionuclide thyroid scan. He was subsequently started on methimazole. The pathophysiology of TPP is unclear but is theorized to rapid intracellular shifts of potassium via the Na/K ATPase. Thyroid hormone increases the activity of Na/K ATPase at the level of skeletal muscle and is increasingly stimulated in the thyrotoxic state.The underlying increased activity of Na/K ATPase in skeletal muscle are hit by a further insult such as large, carbohydrate rich meals (which signals for insulin release and further intracellular shift of potassium), or catecholamine release from stress, exercise, or alkalosis as the case in our patient from the vomiting.

Conclusion

The patient in this case demonstrates a departure from the usual cases of TPP. He was a Hispanic male, whereas there is normally a higher incidence amongst Asians. The patient was also 15 years old, which is younger than the cited peak ages of 20–40. Sometimes there can be a genetic predisposition, as paternal grandmother possibly had the same symptoms. More often, these children have no preceding disease, as in this case. It is important for ED providers and pediatricians alike to keep this in mind as it can be easily remedied, but fatal if not recognized.

Healthcare delivery research I

Concurrent session

12:45 PM

Thursday, January 23, 2020
27 Lights, camera, surgery: video resources enhancing healthcare communication

K Nguyen1,*

C Binda1

P Mangat1

D Duffy2

K Mulpuri3,2

1University of British Columbia, Vancouver, BC, Canada

2BC Children’s Hospital, Vancouver, BC, Canada

3University of British Columbia, Vancouver, BC, Canada

Purpose of study

Effectively communicating medical information to patients and their caregivers can help improve patient understanding, adherence to treatment and health outcomes. Despite the importance of communication, physicians often do not communicate satisfactorily with their patients. Our purpose is to create interdisciplinary educational video resources for caregivers who are accessing surgical services at BC Children’s Hospital (BCCH). These videos, supplementing regular clinical practice, will help patients and caregivers understand their child’s condition, improve surgical outcomes, reduce stress as well as the financial burden of unnecessary emergency room visits.

Methods used

Surgical team members and research staff from three departments, orthopaedics, urology and general surgery at BCCH, identified suitable video topics and learning objectives. Existing patient resources were combined with further research and expert opinion to draft video scripts. Patients and caregivers were voluntarily asked for their participation and consented through signing a media release form. Videos were then created and edited using software such as Powtoons, WireWax and Adobe After Effects. Completed videos were made available on the Office of Paediatric Surgery Evaluation and Innovation (OPSEI) YouTube channel and on clinic websites. URLs and QR codes were also used to connect viewers to the video resources.

Summary of results

62 videos were created in collaboration with 31 families, 7 surgeons, 3 physiotherapists, 2 occupational therapists, 5 nurses, and 5 researchers. Video topics for each series included hip dysplasia, clubfoot, limb reconstructions, ACL reconstructions, ostomies, circumcisions and hypospadias repairs. Within each series, videos ranged from pre and post-operative care instructions, screening methods, caregiver testimonials, treatment options to post-operative exercise tutorials.

Conclusions

Video educational resources show promise as a tool that may enhance the exchange of knowledge from healthcare providers to their patients. The creation of video resources engages interdisciplinary team members, patients and caregivers in patient centric communication.

28 Impact assessment of the transition of a co-management perioperative hospitalists model to a consultation model towards patient outcome markers

J Shen*

L Gad

D Ramsingh

D Nurkse

B Austin

G Stier

Loma Linda University, Loma Linda, CA

Purpose of study

Perioperative care has wide variability in quality with conflicting models. In 2015, the Departments of Anesthesiology and Urology implemented a perioperative hospitalist service (PHS), consisting of anesthesiology-trained physicians, to co-manage patients during their perioperative period. From 2015 to 2016, the PHS team demonstrated improvements in patient recovery markers, decrease in hospital length of stay, and a reduction in total patient costs. In 2017, the PHS was phased out, but the patient care protocols remained active for the urology service. This study sought to evaluate if the improvement in patient care remained with the transition of PHS from a daily rounding co-management structure to a consultation service.

Methods used

PHS was formed of selected anesthesiologists who received training on the core competencies for hospitalist medicine and were to medically manage patients undergoing major urologic procedures (prostatectomy, cystectomy, and nephrectomy). Impact was assessed by comparisons of patient outcome markers between the last year of the co-management structure service to the year of the consultation only service. The primary outcome marker was a reduction in length of stay. Secondary outcome markers included complication rate, return of bowel function, number of consultations, reduction in total direct patient costs, and bed days saved.

Summary of results

Patient outcome markers showed no negative results from the transition of co-management to a consultation service. Reductions in length of stay were seen for cystectomy cases, along with reductions in complication rates and ileus for nephrectomy cases over the year of the consultation service.

Conclusions

Our previous study showed that anesthesiologists can function as perioperative hospitalists who provide appropriate medical management while improving patient recovery. With this study, the impact of PHS remained up to one year after the transition of the co-management daily rounding service to a consultation only service. Infact, some patient categories showed further improvement in post-operative outcomes. These findings suggest that the transition of a daily rounding co-management PHS to a consultation only service is feasible without negatively impacting patient care.

29 Benefits of a community hospital – academic university pediatric partnership

M Hamline1,*

K Forman1

K Tran-Viet1

B McCollough2

L Donati2

H McKnight1

S Lakshminrusimha1

DA Lubarsky1

1University of California Davis Health, Sacramento, CA

2Adventist Health Lodi Memorial, Lodi, CA

Purpose of study

Academic children’s hospitals increasingly partner with community hospitals to provide inpatient neonatal and pediatric care in the patient’s own community. Although some academic hospitals are hesitant to form these partnerships due to concern for decreasing incoming transfers, few studies report the true effect of such collaboration. We hypothesized that such partnership would increase community inpatient pediatric volume and reduce transfers but increase case mix index (CMI) of transferred patients.

Methods used

In July 2018, we established a partnership between an urban tertiary care academic medical center and a not-for-profit 194-bed community hospital, located 37 miles away. The partnership involved 1) staffing the community inpatient unit with academic-affiliated pediatric hospitalists, 2) obtaining level-II NICU certification and initiating neonatal rounds via telemedicine, 3) providing training for existing nurses and staff at the community site, and 4) developing pediatric protocols and policies. We utilized two-sample t-tests to compare one-year pre- and post-partnership time periods (July 2017-June 2018 versus July 2018-June 2019) to analyze the community hospital’s pediatric average daily census, average length of stay (LOS), CMI of patient transfers, and payor mix.

Summary of results

Data regarding the community hospital inpatient pediatric population and pediatric transfers to the academic medical center are shown below. The academic center’s contribution margin increased by 123% from pre- to post-partnership. The partnership was cost-neutral at the departmental level.

Conclusions

Our data suggest that the community-academic partnership successfully increased admissions and reduced LOS and inter-facility transfers while increasing acuity of transfers. These partnerships promote appropriate pediatric patient care and are cost-effective to both partners.

30 Frequent flyers: stellar strategies for emergency department superutilizers

LC Epperson*

S Shipman

Integris Southwest Medical Center, Oklahoma City, OK

Purpose of study

Determine cost avoidance and utilization rates (Emergency department (ED) visits and hospital admissions) of a group of highest utilizers post-intervention by a Community Care Coordination Team (CCCT).

Methods used

Superutilizers comprise a small portion of patients who account for a high percentage of costs. They have social determinants that prevent successful outpatient management of chronic conditions. Less than 5% of our patients accounted for more than 50% of healthcare costs. We subsequently developed the 5/50 Program to reduce reliance on the ED for non-emergent care and saved our institution $2.5 million. Candidates were identified through lists of 3+ ED visits/90 days, EMR alerts for multiple visits, and physician referrals. Our CCCT consisted of 2 nurses, 2 social workers, 2 bilingual team members, and 1 nurse practitioner that followed patients up to 6 months post-discharge to address social and medical needs. The CCCT worked with community partners, homeless outreach teams, mental health services, paramedics, nursing homes, low-cost clinics, food banks, and the health department. Interventions included extensive outreach and frequent face-to-face communication with patients to assist with primary care and medication management. The CCCT reassessed patients, established care plans, and provided education for self-management of chronic conditions.

Summary of results

Our program shows successful outcomes with decreased acute-care service utilization. ED visits were reduced over a 3.5-year period by 58%, from 1510 visits pre-enrollment to 882 post-enrollment. Total admissions decreased by 58% from 986 admissions pre-enrollment to 573 post-enrollment. Participants averaged 6.3 ED visits pre-enrollment, reduced to 2.7 visits with a mean difference of -3.6 (95% CI -4.9 to -2.4, p<0.0001). Participants averaged 1.6 admissions pre-enrollment, reduced to 0.6 admissions with a mean difference of -1.1 (95% CI -1.4 to -0.7, p<0.0001). Cost-benefit estimation showed our institution spent $5,418,628 to manage superutilizers. The program cost $1,294,500 over a 3-year period, reduced to $1,615,2289 post-enrollment, yielding a cost avoidance of $2,508,899 (46% reduction).

Conclusions

Our program reduced resource-intensive services and provides information to fix the national burden superutilizers imposes on the healthcare system.

31 Patient and provider perspectives on access to medical nutrition therapy for patients with non-dialysis dependent (NDD) chronic kidney disease (CKD)

JM Maloney1,*

K Kelley2

H Kramer3

D Brommage3

M Schofield2

E Jimenez2,4

1University of New Mexico School of Medicine, Albuquerque, NM

2Academy of Nutrition and Dietetics(Academy), Chicago, IL

3National Kidney Foundation (NKF), Chicago, IL

4UNM, Albuquerque, NM

Purpose of study

CKD affects approximately 30 million U.S. adults. Nutrition management can slow CKD progression and delay or prevent end-stage renal disease, but only 10% of patients with CKD receive any medical nutrition therapy (MNT) before initiating dialysis. This study aimed to identify factors that influence timely access to MNT for patients with NDD CKD from the perspective of patients and providers.

Methods used

Three anonymous surveys were distributed to adults with NDD CKD, registered dietitian nutritionists (RDNs) and medical providers via REDCap. Surveys were distributed via the NKF 2019 Spring Clinical Meeting app, via Academy email listservs for RDNs and NKF email listservs for patients and medical providers. Descriptive analyses and Fisher’s exact tests were conducted with R (version 3.5.3).

Summary of results

348 patients, 66 RDNs and 30 medical providers responded. Patients were more optimistic than providers that they could make lifestyle changes to reduce CKD complications, with 44% of patients strongly agreeing with this statement vs. 29% of RDNs and 13% of medical providers. There was strong concordance regarding patient interest, with about two-thirds of medical providers, RDNs and patients feeling that patients would be interested in an RDN referral. However, there were feasibility concerns. Two-thirds of RDNs and medical providers felt that there are not enough RDNs with expertise in renal nutrition available for referrals. Around 40–50% of RDNs and medical providers felt that the EMR was not set-up to make RDNs referrals easy, and that there was not adequate insurance coverage. About half of RDNs were aware of Medicare coverage for MNT, but few medical providers or patients were familiar with the coverage.

Conclusions

Many patients with NDD CKD are interested in MNT and confident that it can help them with disease management. Perceived referral and reimbursement barriers should be further explored.

32 iPACK block associated with similar length of stay and opioid consumption in total knee arthroplasty

RC Jensen1,2,*

1University of Washington School of Medicine, Seattle, WA

2Providence Sacred Heart Medical Center, Spokane, WA

Purpose of study

Effective analgesic modalities improve outcomes in patients undergoing total knee arthroplasty (TKA). We hypothesized implementation of a relatively new nerve block method, the iPACK block would be associated with decreased length of stay and 24-hour opioid consumption in TKA.

Methods used

This retrospective cohort studies outcomes of interest were postoperative length of stay (LOS) and postoperative 24-hour oral morphine equivalent (OME) consumption. All patients received a single shot adductor canal block (ACB) and local infiltration analgesia (LIA) and were grouped based on whether they received an iPACK block. Potentially confounding variables such as age, gender, BMI, presence of comorbid conditions, operation room time, and current chronic steroid or opioid medication therapy were recorded. Descriptive statistics characterized patients in our sample. Categorical demographic and clinical group differences were examined using Chi-square analysis. Continuous group differences were explored using 2 sample t-tests for symmetrical distributions and Mann-Whitney U for skewed distributions. Linear regression models were performed to detect differences in study outcomes between the two groups, controlling for confounding variables.

Summary of results

Incorporation of the iPACK block was not associated with reduced LOS unadjusted (p=0.11) or in fully controlled models (p=0.21). Potentially modifiable factors that were found to increase length of stay included chronic opioid consumption (p=0.04) and case duration (p=0.01). Use of the iPACK block was not associated with a change in 24-hour OME consumption unadjusted (p=0.52) or in fully controlled models (p=0.34). Potentially modifiable factors that significantly increased opioid consumption were a history of chronic opioid therapy (p=0.002) or corticosteroid therapy (p=0.003).

Conclusions

As only the second study performed investigating incorporation of an iPACK into a pathway already including LIA and ACB we have contributed to a small body of evidence suggesting the iPACK block may not add significant benefit alongside these methods. To date no prospective study has investigated outcomes associated with lone addition of iPACK block into a pathway including ACB and LIA. Further randomized research is warranted.

33 Improving medical student documentation: can the RED checklist assist with teaching documentation?

J Evans

M Kim*

N Chan

C Daum

A Hayton

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of study

With the new CMS guidelines and a desire by many medical educators to better prepare medical trainees for residency, we sought to determine if using the Responsible Electronic Documentation Checklist (RED Checklist) would improve the quality of medical student inpatient progress notes.

Methods used

At Week 5 of the 10-week Internal Medicine Clerkship, 163 third year medical students had progress notes scored using the RED checklist by a core group of faculty members. Students then received 15–20 minutes of targeted note feedback. At Week 10, students had a new set of progress notes scored by note evaluators without any in-person feedback. Data was analyzed using Paired-sample t-tests and Cohen’s d to evaluate change in the quality of notes as measured by the RED checklist after the intervention. Hierarchical linear regressions analysis was performed to determine whether changes in RED Checklist scores could predict subjective clinical performance, NBME, and OSCE scores.

Summary of results

We found significantly higher objective note score (t=5.64, p<0.001), assessment/plan (A/P) score (t=5.75, p<0.001), and total note score (t=7.67, p<0.001) post-intervention compared to at baseline. Post-intervention A/P scores significantly predicted OSCE scores, such that a one standard deviation increase in post-intervention RED A/P scores was associated with a 0.24 standard deviation increase in OSCE scores (β=0.24, sr2=0.04, p=0.015). Our model also indicated that baseline RED Objective scores significantly predicted OSCE scores, such that a one standard deviation increase in baseline RED Objective scores was associated with a 0.24 standard deviation increase in OSCE scores (β=0.24, sr2=0.04, p=0.015). The changes in Objective and A/P Scores were not associated with NBME and Clinical evaluation scores.

Conclusions

After implementation of the RED Checklist with structured feedback, student note quality improved. Our study also found that an improved A/P score and baseline Objective scores correlated with higher OSCE scores. As many physicians struggle to find enough time and lack the tools to provide structured quality feedback to trainees, physicians can implement the RED Checklist, a time efficient tool, to improve quality of student note writing and prepare students for residency.

34 Development and evaluation of a free online point of care ultrasound training curriculum

M Buell1,*

K Cook1

B Lew2

P Vu3

J Hinson4

M Martinez4

M Alschuler4

M Holsclaw4

D Ramsingh4

1Loma Linda University School of Medicine, Loma Linda, CA

2Western University of Health Sciences, Pomona, CA

3Kansas City University of Medicine and Biosciences, Kansas City, MO

4Loma Linda University Medical Center, Loma Linda, CA

Purpose of study

Point-of-care ultrasound (POCUS) has rapidly emerged as a modality to improve bedside assessment. The driving force for this adoption is that clinical decision-making can be improved over traditional physical examination with the application of POCUS. Since the limiting factor for the adoption of POCUS is education, the authors launched a free open access educational platform. We present our initial data from our online users on improving content knowledge.

Methods used

Over a two-year period a validated educational POCUS curriculum, the FORESIGHT Examination, was transitioned to an online platform (www.foresightultrasound.com). The curriculum was developed to educate and evaluate: cardiovascular function, volume status, pulmonary function, presence of abdominal fluid, gastric content, position of the endotracheal tube, and presence of increased intracranial pressure. Performance of the website was evaluated via surveys on the content and content multiple choice testing. The primary outcome marker was improvement in content testing scores after reviewing the online curriculum. Analysis was performed via student t-test, a p value of significance equal to 0.05.

Summary of results

To date 530 users have accessed the website. Survey results on the website content to improve POCUS knowledge showed that 83% reported to strongly agree, 10% to agree, and 7% were neutral. Review of content testing showed a statistically significant (p<0.05) improvement in scores from pre to post training for each testing category: 1. ultrasound physics, 2. mechanisms of hypotension/volume status, 3. cardiac, 4. pulmonary, and 5. abdominal/vascular access/neuro.

Conclusions

While there is still much to be developed, the concept of P-POCUS (perioperative POCUS) has shown dramatic growth in recent years. Further innovation and integration of this tool have tremendous potential for impacting the quality of care we can provide at the bedside. This study highlights one successful platform to improve knowledge on this topic.

35 What matters most: an intervention for learners

SD Andersen*

H Lokos

A Hayton

Loma Linda University, Loma Linda, CA

Purpose of study

Inquiring about what matters most has been deemed a powerful tool to support greater patient wellbeing. The purpose of this study was to better equip junior medical students to offer whole person care (WPC). We expect that perceived value, confidence and frequency of students asking patients what matters most to them will increase after the intervention. We hope as a result of students being more engaged with their patients, they will feel more involved on the team.

Methods used

A pre-baseline survey was administered to junior medical students at the beginning of their Internal Medicine clerkship. A workshop was conducted early in the clerkship. Students were given a pocket guide with questions aiding connection with patients. Students were told to ask each patient they saw about what matters to them and present this information on rounds. Attendings and residents were encouraged by email to encourage students to present. A post-baseline survey was issued to each group at the end of the clerkship. At the end of the academic year, a survey will be issued to the entire junior class to assess potential long-term impact.

Summary of results

Perceived importance of, and confidence in providing WPC was rated on the following scale; 1=not at all, 2=slightly, 3=moderately, 4=very, 5=extremely. The average perceived value increased from 3.64 to 4.21 (p<0.05) and perceived confidence from 2.85 to 3.07 (p=0.3491). The post-baseline survey of the first clerkship found that 80% of students asked patients about what matters most at least weekly. 57% reported this to faculty weekly. The main barriers selected by students were time constraints, workload, and lack of support. Students reported that the intervention increased sense of meaning. Students perceived a need for more role models and earlier training in their pre-clinical years to enhance the effectiveness of this intervention.

Conclusions

Preliminary results show that students express a significant increase in the value they place on WPC after undergoing the intervention. We anticipate that as the study’s power increases with more student responses, we will see a statistically significant difference in student confidence in ability to provide WPC. As students engage on this level with their patients we expect they will find more meaning in their practice.

Immunology and rheumatology I

Concurrent session

12:45 PM

Thursday, January 23, 2020
36 Secukinumab and incident inflammatory bowel disease in ankylosing spondylitis

PD Nilsson1,*

H Sawhney2

M Castillo2

L Gensler2

1University of Nevada, Reno School of Medicine, Reno, NV

2University of California, San Francisco, San Francisco, CA

Purpose of study

Secukinumab is a fully human monoclonal antibody against interleukin-17A for use in treating active ankylosing spondylitis (AS). Inflammatory bowel disease (IBD) is increased in AS and subclinical gut inflammation is found in 50–60 percent of AS patients. Incident IBD and exacerbation of established IBD was reported as an adverse event in secukinumab clinical trials, though these were rare events (<1%) and not significantly different compared to the placebo population. There have been 60 reported cases of IBD, including ulcerative colitis, and Crohn’s disease in the FDA Adverse Events Reporting System (FAERS) in AS patients treated with secukinumab, with 2 cases listed as exacerbation of preexisting disease. We evaluated the incidence of IBD in AS patients after initiation of secukinumab.

Methods used

Data was extracted from a prospective axial spondyloarthritis (axSpA) cohort followed by a tertiary care center in a subspecialty spondyloarthritis clinic at the University of California, San Francisco. We describe a case-series of three AS patients who developed incident IBD after treatment with secukinumab. The patient demographics, treatment exposures, medication use and disease course since initial presentation at the clinic are reported.

Summary of results

In our axSpA cohort, 22 patients with AS were treated with secukinumab. Three patients (13.6%) developed incident IBD (2 Crohn’s disease and 1 ulcerative colitis). The patients experienced symptoms of IBD within seven months (1.5–7) after starting secukinumab and were referred to a gastroenterologist in the setting of new diarrhea. IBD diagnoses were confirmed by a gastroenterologist in the setting of a clinical evaluation, colonoscopy and histopathology.

Conclusions

Our findings suggest that IBD incidence may occur more frequently with secukinumab exposure than has been reported. There are limitations to this study as it is uncontrolled, and the patient population may have more severe disease at a tertiary care center. We recommend that providers treating AS patients with secukinumab take a detailed gastrointestinal history and have a low threshold for further evaluation in those with new gastrointestinal symptoms.

37 Secondary efficacy failure is the predominant etiology for discontinuation of tumor necrosis factor inhibitor in psoriasis/psoriatic arthritis

S Wolfe1,2,*

E Cheng2

K Brees2

L Caplan1,2

1University of Colorado School of Medicine, Aurora, CO

2Rocky Mountain Regional VA Medical Center, Aurora, CO

Purpose of study

Psoriatic arthritis is a chronic inflammatory disease of the joints and skin that affects 1/1000 people in the US. Tumor necrosis factor inhibitors (TNFi) are used when symptoms are severe. However, current research describing TNFi persistence rates, defined as time from initiation to discontinuation of the drug, is inconsistent and incomplete. This study examined characteristics associated with persistence of TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) and reasons for discontinuation.

Methods used

US veterans enrolled in the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) from 2007 – 2017 who 1) were diagnosed with psoriatic arthritis or psoriasis and 2) had been treated with a TNFi were included in the study. Stata was used to conduct Student’s t-tests, Pearson Chi2 tests, time-to-event analyses, and multivariate analyses.

Summary of results

321 individuals with 931 TNFi courses were included in the study. The mean age was 55.4 years, and 83.8% of the cohort continued at least one TNFi course at one year. Course order was correlated with persistence on a TNFi at one year (HR 1.09, p<0.01). Baseline Bath Ankylosing Spondylitis Functional Index (BASFI) and baseline pain scores were correlated with response to a TNFi (HR 1.12, p=0.018 and HR 0.689, p<0.01, respectively). Other demographics were not independent predictors of response or persistence. Infliximab (79.31%) was associated with improved persistence at 24 months when compared to adalimumab (66.40%, p=0.019) and certolizumab (54.17%, p=0.013). The most commonly cited reason for discontinuing TNFi treatment was secondary failure (33%), defined as a loss of prior efficacy after >6 months of treatment, followed by adverse events (25%).

Conclusions

This study found that most clinical characteristics, other than course order, did not affect persistence on a TNFi, suggesting that persistence is difficult to anticipate. Since persistence is suboptimal, further research should study possible mechanisms to explain loss of efficacy, including the immunogenicity of TNFi, in an effort to increase persistence and improve treatment outcomes.

38 Correlation between clinical and in vitro response to methotrexate in rheumatoid arthritis

M Yu*

N Goel

D Siringoringo

W Langridge

KD Torralba

Loma Linda University, Loma Linda, CA

Purpose of study

Rheumatoid arthritis (RA) is a systemic autoimmune disease that decreases quality of life and can lead to disability. Methotrexate (MTX), which targets activated T cells, is the first-line of therapy for RA. Unfortunately, 30 to 50% of RA patients do not experience adequate reduction of symptoms while on MTX. Predicting MTX response would be helpful for guiding treatment decisions and improving the lives of RA patients. The purpose of this pilot study was to explore a possible association between clinical response to MTX and in vitro effects of MTX on leukocyte secretion of IL-17 and IFN-g, pro-inflammatory cytokines associated with the activated Th17 and Th1 cells.

Methods used

Peripheral blood samples were collected from 16 RA patients prescribed MTX but prior to initiation of MTX treatment. Leukocytes were isolated from the blood samples, activated with anti-CD3 and anti-CD28 antibodies, and treated with several concentrations of MTX (0 to 1 uM). Supernatant was harvested at 72 hours, and concentrations of IL-17 and IFN-g were assessed by ELISA. The RA patients’ charts were reviewed to assess the clinical effects of MTX after 3 months of MTX treatment, as described by changes in clinical disease activity index (CDAI) and any side effects.

Summary of results

In most blood samples, 1 uM of MTX decreased secretion of IL-17 and IFN-g. Maximal decrease was -28 - 87% for IL-17, and 15 – 92% for IFN-g. The concentration of MTX required to achieve half-maximal decrease (IC50) also varied for both IL-17 (0.02 – 0.3 uM) and IFN-g (0.01 – 0.3 uM). Based on samples from 9 patients, there is greater variation in the IL17 IC50s of those with side effects vs those without (p<0.05), with absence of side effects associated with IL17 IC50 0.03 – 0.05 uM.

Conclusions

There is large person-to-person variation in the in vitro effects of MTX on IL-17. Increased sample size is needed to assess whether this variation could be of clinical significance.

40 Hair repigmentation after rituximab use in a patient with systemic sclerosis

AN Kiani1,*

K Reiter2

D Cisneros1

K Konstantinov2

1UNM Hospital, Albuquerque, NM

2VA Medical Center Albuquerque, NM

Purpose of study

Repigmentation of gray/white hair is rarely reported in the literature. There are several etiologies contributing to this, and autoimmune diseases have been considered one of them. An overactive immune response could result in sudden graying of hair in mouse models through inducible expression of melanogenesis associated transcription factor (MITF), which controls the production and life cycle of melanocytes and acts as an off-switch to innate immune target genes at the same time. Similarly, change of hair color have been associated with a multitude of drugs including corticosteroids, cyclosporine and most recently targeted anticancer therapies targeting immune system. However, very little is known of the effects of biologics used in autoimmune diseases and their role in hair repigmentation.

Methods used

A 70 year old male with systemic sclerosis was started on Rituximab therapy in 09/2017, now s/p 5 cycles of Rituximab given every 6 months. Initially presented with Raynaud’s, shortness of breath, weight loss, arthralgias and skin findings. On presentation, physical examination revealed achromotrichia (silver hair) of normal aging, without hair loss or thinning. After 6–9 months into Rituximab therapy, patient had repigmentation of hair to black. Now he has over 60% of repigmentation and is into third year of rituximab therapy with stable disease.

Summary of results

Graying of hair usually begins in the third and fourth decade of life after melanocyte depletion unless there are other causes including nutritional deficiencies, stress, and smoking among others. In those instances, hair changes can be seen earlier. Rituximab among other biologics has been used in several autoimmune conditions including SLE, rheumatoid arthritis and systemic sclerosis. Alopecia is considered a side effect commonly seen, but hair repigmentation is not reported. To our knowledge this is the first ever reported case of repigmentation in a patient on Rituximab for systemic sclerosis. Hair darkening after use of biologics might be reversible but the exact mechanism remains elusive.

Conclusions

To our knowledge this is the first ever reported case of repigmentation in a patient on Rituximab for systemic sclerosis. Hair darkening after use of biologics might be reversible but the exact mechanism remains elusive.

41 Identification of unique molecular markers of diabetogenic T-cells

D Woodruff*

University of Utah, Salt Lake City, UT

Purpose of study

Type 1 diabetes is a complex autoimmune disorder in which the pancreas’s insulin-producing-cells are destroyed. Previous research has indicated that pancreatic -cells autoantigen recognition both initiates and perpetuates the disease and that CD4+ and CD8+ T cells play a major role in those processes. Yet, the unique markers of these T cells and how they overcome tolerance to B-cell autoantigens remains unclear. Using single-cell RNA sequencing, we have identified significant changes in gene expression values in diabetic mouse models. Here we seek to validate the RNA sequencing data using qPCR and flow cytometry.

Methods used

Flow Cytometry: Single cell suspension of mouse splenocytes was achieved by physical disruption of spleen and filtering through 100 mm nylon cell strainer. Cells were enriched for CD8+ T cells using the MACS CD8a+ T Cell Isolation kit according to manufacturer’s instructions. Antibodies for CD127, CX3CR1, CD44, CD4, CD3, CD8a, CD11b, CD11c, CD19, 7AAD, TCR b, KLRG1, and PD-1 were purchased from Bio-legend.

qPCR: Splenocytes from prediabetic and diabetic non-obese diabetic (NOD) mice and G9 were harvested and enriched for CD8+ T-cells using the MACS CD8a+ T Cell Isolation Kit according to manufacturer’s instructions. Total RNA was extracted using the QIAGEN RNeasy kit (with optional on-column DNase digestion) and reverse transcribed using Quantabio’s qScript cDNA SuperMix following manufactures instructions.

Klrk1, CCl5, Gzmb, Ctla2a, Cx3cr1, Lgals1, Myo1F-1, HopX, CXCR6, Gimap7, Ahnak, S100a6, Rgs1, Anxa2, Itgb1, Gzma, Gzmk, Fasl, and Tbx21, and B-actin primers were ordered from Sigma-Aldrich. The sequences of primers are available upon request. PCR product with the PowerUp SYBR Green Master Mix.

Summary of results

There is an increased mRNA expression in expression of CCl5, Ctla2a, Cx3cr1, HopX, Anxa2, Fasl, and Gzmk transcripts in diabetic mice. We also find there is a unique subpopulation of CD8+ T-cells in splenocytes that co-express Cx3cr1 and Klrg1 in diabetic mice.

Conclusions

Ultimately, our goal is to identify molecular markers specific to diabetogenic T-cells that can predict changes in T-cell functionality as can be detected by the Evavold lab’s ultrasensitive two-dimensional affinity and force-based single cell assays. This project is the first step in identifying those potential molecular markers.

42 An unusual case of systemic lupus erythematosus induced pericarditis in a young hispanic male

L Moosavi

J Bowen

M Afridi

C Donath

F Joolhar

T Win*

Kern Medical Center, Bakersfield, CA

Purpose of study

Emphasize to the medical community the importance of keeping a broad differential and eliminating bias when evaluating patients to reduce the chance of misdiagnosis in males who present with SLE symptoms.

Methods used

Evaluation of patient.

Summary of results

Systemic Lupus Erythematosus, SLE, is an autoimmune disease of an unknown and multifactorial etiology. There is a higher prevalence among females in particular African-American and Hispanic women. Cardiovascular diseases, such as, thrombosis, HTN and heat failure have become the leading causes of mortality and morbidity among SLE patients. Cardiovascular manifestations develop in the majority of SLE patients at some time during their illnesses, the most common being acute pericarditis and pericardial effusion.however, pericarditis as the first manifestation of SLE is less common.

An 22-year-old Hispanic male with no prior significant medical history presented to the emergency department with 48 hours of progressive dyspnea and constant sharp substernal chest pain exacerbated by lying flat. He also had a bilateral wrist pain and swelling that had led to limited range of motion. On examination, patient was febrile, tachycardic, tachypneic with normal oxygen saturation. EKG revealed diffuse concave upward ST segment elevation with PR depression in leads I &II. CXR demonstrated a left sided pleural effusion. Patient‘s initial laboratory tests results were significant for leukocytosis without bands, elevated C-reactive protein, and erythrocyte sedimentation rate. IV fluids and broad spectrum antibiotics were started. Blood cultures and infectious workup was unremarkable for viral or bacterial sources of infection; however, following autoimmune workup lead to the diagnosis of SLE. The patient was subsequently started on oral Colchicine, Indomethacin, and Prednisone. patient’s vital signs, pleuritic chest pain, bilateral wrist pain resolved.

Conclusions

Medical bias can increase the difficulty in distinguishing between sepsis and an acute episode of SLE can be challenging in a patient without prior history of medical illness.Therefore, clinicians should have a high degree of suspicion for autoimmune diseases (i.e.SLE) when a patient presents with a life-threatening and multiorgan condition.

Infectious diseases I

Concurrent session

12:45 PM

Thursday, January 23, 2020
43 Effect of extracorporeal shockwave on rhizopus oryzae biofilm

KH Anderson1,*

P Slezak2

K Olga3

T Hillock3

1University of Utah, Salt Lake City, UT

2Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria

3Utah Valley University, Orem, UT

Purpose of study

Fungal biofilms are communities of adherent cells surrounded by an extracellular matrix. Clinically, biofilm associated infections can be extremely difficult to eradicate due to their resistance to antifungals and host defense mechanisms. In this study we investigate the effect of extracorporeal shock wave treatment (ESWT) on Rhizopus oryzae biofilm. ESWT is an effective treatment for soft tissue wounds including severe burns and vascular ulcers. ESWT acts through mechanotransduction and complex biological pathways. However, the exact biological effects of ESWT on human, fungal and bacterial cells is not completely understood. While many reports suggest that extracorporeal shock wave is effective at inducing neovascularization and tissue regeneration in the host and causing damage to bacterial biofilm in vitro the effect of shock waves on fungal biofilm has been largely ignored. Our study focuses on fungal extracellular matrix production, cellular respiration and morphological hyphal alteration following the application of ESWT.

Methods used

Biofilms were treated under four main conditions: Shock only, Shock + Amp B, Amp B control and Biofilm control. Shocks were applied to pre-biofilm, 12, and 24 hours post plating (mature biofilm). Tubes were exposed to 300 pulses using an energy density of 0.55 mJ/mm2 at 3 Hz. Shock wave treatment was performed using a water bath setup.

Summary of results

Results indicate that shockwave application in combination with antifungal treatment increases fungal cellular respiration, extracellular matrix production and hyphal width compared to antifungal treatment alone. Shockwave when applied in isolation, (without antifungal treatment) revealed no difference in respiration or matrix production.

Conclusions

It is suggested that shockwaves disrupt biofilm structure allowing antifungal drugs to penetrate and interact with the underlying cells causing an increase in cellular respiration, hyphal growth and extracellular matrix production. This could allow the host system to recognize pathogen proteins and increase pathogen clearing by the immune system. However, further reserach will need to be done to confirm this hypothesis.

44 Congenital syphilis: a qualitative retrospective longitudinal study on characteristics of mothers and newborns in a tertiary care hospital

R Kaushal*

H Chow

R Jain

C Nelson

C Rongkavilit

UCSF Fresno, Fresno, CA

Purpose of study

  1. To determine maternal factors leading to increased prevalence of congenital syphilis in our community and state.

  2. To study the effects in newborns of in utero exposure to untreated or partially treated maternal syphilis.

Methods used

ICD-9 and 10 codes were used to identify newborns born to mothers with a diagnosis of syphilis at the time of delivery at a tertiary care hospital in Fresno, California from 01/2010 -12/2018. 231 newborns and mother dyads were included in analysis.

Summary of results

Maternal characteristics:

The mean age was 27 years old (range 16–42 years). 57(24.7%) were Caucasian and 167(75.3%) were ethnic minorities.205(88.7%) were unmarried, 207(89.6%) were unemployed.17 (7.4%) were incarcerated,18 (7.8%) moms were homeless,11 (4.8%) were victims of domestic violence.136(58.9%) admitted to drug use, of which 112 (48.5%) used methamphetamines, 57(24.7%) used marijuana, and 15(6.5%) used opiates. 78(33.8%) smoked tobacco,14 (6.1%) drank alcohol during pregnancy. 61(26.4%) positive for HSV by serology. 35(15.2%) positive for Chlamydia,11(4.8%) positive for Gonorrhea, 6(2.6%) positive for HIV. 75(32.5%) were treated adequately for syphilis during pregnancy,119(51.5%) treated inadequately, and 34(14.7%) received no treatment.

Newborn characteristics:

Of 231,67 were born from 2010–14(20.4%) and 184 born from 2015–18(79.6%). At delivery,19(8.2%) newborns were a gestational age≤32 weeks, 57 (24.7%) 33–37 weeks, and 155(67.1%) >37 weeks.15(6.5%) had a positive CSF VDRL,36(15.6%) had an abnormal bone survey, 5(2.2%) had an abnormal eye examination. 220(95.2%) received treatment for syphilis, and 7(3.0%) did not receive treatment. Of those treated, 56(24.2%) received IM Penicillin, 139(60.2%) received IV Penicillin, and 28(12.1%) received both IM and IV Penicillin.

Conclusions

We identified that ethnic minorities, unemployment, illicit drug use, STDs were prevalent among pregnant women with syphilis. High rates of inadequate/no treatment during pregnancy is concerning and have led to prolonged hospitalization of newborns for IV therapy. Strengthening public health infrastructures to test and care for these high-risk pregnant women is urgently needed.

45 Comparison of procalcitonin and C-reactive protein (CRP) in neonatal bacterial sepsis

A Bilg1,2,*

M Choi1

S Tewari1

B Chan1

S Anis1

J Luu1

B Afghani1,3

1UC Irvine School of Medicine, Irvine, CA

2UC Riverside School of Medicine, Riverside, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Blood culture, the gold standard for the confirmation of bacterial sepsis, has significant limitations including time delay in obtaining results. Biomarkers such as serum procalcitonin (PCT) and CRP are commonly used to predict sepsis in adult patients. The purpose of this study is to evaluate the use of PCT and CRP in predicting early-onset bacterial sepsis in neonates.

Methods used

A comprehensive literature review was utilized through multiple search engines, such as PubMed, Google Scholar, and Cochrane using keywords, ‘neonate’, ‘sepsis’, ‘procalcitonin’ and ‘CRP’. Studies in our final analysis have included measurement of both PCT and CPR. Only studies of term and premature neonates which included bacteriologically proven early onset sepsis with control groups were included in the analysis.

Summary of results

Of 20 studies, 6 satisfied our inclusion criteria. The main reasons for excluding studies were lack of a control group (no sepsis) or late onset sepsis (>3 days of life). Sensitivity of PCT ranged from 48.7% to 87% and CRP ranged from 44.5% to 91.1%. The specificity of PCT ranged from 48% to 90% and CRP ranged from 59.4% to 100%. Although most studies took into account the confounding variables such as gestational age, maternal factors and intrapartum complications, it was difficult to make firm conclusions when comparing PCT and CRP in predicting neonatal sepsis. Among different studies, there was heterogeneity of cut-off values, variable times to differentiate early onset sepsis, lack of uniformity in the control groups and differing sampling times.

Conclusions

Our review suggests that the sensitivities and specificities of PCT and CRP are comparable in predicting bacterial infection in premature and term neonates. More data are needed to determine the optimal cut-off values. Interpretation of test results has to be individualized based on clinical circumstances.

46 Characterization of HIV quasispecies via particle-templated emulsification

WY Shin*

M Hatori

UCSF, San Francisco, CA

Purpose of study

RNA retroviruses can form ‘similar-but-different’ variants (quasispecies). These variants are found through next-generation sequencing to track shifts in quasispecies during early infection. A disadvantage is that it may be expensive to sequence a long stretch of RNA if needed. Droplet microfluidic devices create micron size water-in-oil droplets, where rare cells or novel genes can be trapped into one droplet and analyzed. The advantages are that it is high-throughput and uses less reagents. Barriers to microfluidics are the hardware, expertise, and cost needed to fabricate the devices. The goal of this project is to see whether the method particle templated emulsification (PTE) can be used to track rare HIV RNA variants. This method creates droplets simply by vortexing polyacrylamide beads with your sample. We also want to show that we can do Splicing by Overlap Extension (SOE) PCR in PTE, which fuses two separate pieces of DNA to reduce the size of the amplicon.

Methods used

Droplet microfluidic devices are made via standard photolithography. Polyacrylamide beads for PTE are made via an air-triggering device that splits the flow of acrylamide into micron size beads. We mix the PCR reagents with the polyacrylamide beads and allow them to incubate. For PTE, we vortex the mixed beads in a solution of surfactant. This process creates an emulsion encapsulating each bead with the PCR reagents. The beads are transferred to PCR tubes and run through a standard PCR program. The amplified products in the beads are viewed under a microscope.

Summary of results

After PCR amplification, we see that the control group and SOE PCR reaction have amplified product. However, we get the incorrect size product for the SOE PCR reaction, meaning SOE PCR did not work in PTE.

Conclusions

Further optimization is needed for SOE PCR to work in PTE. We will use a different test plasmid that encodes the HIV gag gene. We would repeat the PTE experiments again with the new plasmid and further optimize the protocols. If there is no progress, one alternative to the project is to use primer studded beads as the template for PTE with unique molecular identifiers.

47 Interferon beta increased Siglec-1 expression on human gut macrophages

SM Lada*

CM Purba

SM Dillon

ML Santiago

CC Wilson

University of Colorado Anschutz Medical Campus, Aurora, CO

Purpose of study

A breakdown in gut homeostasis is a key feature of HIV-1 infection, in part due to the high levels of HIV-1 replication that occur in early in the gut. Type 1 Interferons (IFN-1s) are innate cytokines that play critical roles in controlling viral replication. Siglec-1 (CD169) expression, induced by IFN-1s on myeloid dendritic cells (mDC) and macrophages (MΦ), binds HIV and has been implicated in HIV trans-infection of CD4 T cells. Increased CD169 in response to gram-negative (GN) bacterial cell wall component lipopolysaccharide (LPS) has also been reported. We previously showed elevated levels of the IFN-1 interferon beta (IFNβ) as well as LPS in gut tissue of people living HIV. CD169 is expressed on murine gut MΦ, but few studies have investigated expression in human gut tissues or its regulation. We hypothesized that exposure to IFNβ or GN bacterial products would increase CD169 expression on human gut MΦ.

Methods used

Human jejunum lamina propria mononuclear cells (LPMC), obtained from healthy discarded surgical tissue (N=4), were cultured for 18 hrs with IFNβ (1000–1 pg/mL; 10-fold dilutions), enteric commensal GN Escherichia coli lysate (10μg/mL), or were unstimulated. Flow cytometry was used to evaluate expression of CD169 on MΦ or mDC pre (baseline) and post in vitro culture.

Summary of results

MΦ were identified as HLA-DR+CD64+CD11c± cells within viable CD45+CD3-CD19- LPMC. At baseline MΦ constituted 0.16±0.03% (Mean±SEM); of these MΦ 7.95±4.1% expressed CD169. HLA-DR+CD64-CD11c+ mDC within viable CD45+CD3-CD19- LPMC, constituted 0.11±0.02% of baseline; there were few mDC expressing CD169 0.95±0.59%. In the presence of 1000 pg/mL IFNβ, 27±4% of MΦ expressed CD169, a 6.2-fold increase over unstimulated. With 100 pg/mL IFNβ, 20±5% of MΦ were CD169+, a 4.2-fold increase over unstimulated. At lower doses of IFNβ, CD169 expression by MΦ only increased by 1.5-fold versus unstimulated. Exposure to E. coli lysates increased CD169 expression on MΦ by 2.3-fold.

Conclusions

IFNβ induced CD169 expression on human gut MΦ in vitro in a dose dependent manner. Additionally, GN commensal bacteria lysates increased expression, although to a lesser degree than high doses of IFNβ. Future studies will investigate the role of CD169+ gut MΦ in T cell HIV infection.

48 Implementing a pediatric antibiotic stewardship program in a multidisciplinary primary care clinic

CH Kim*

S Goggin

y Garcia E Fernandez

N Nakra

U Shaikh

UC Davis Health, Sacramento, CA

Purpose of study

Family practitioners, nurse practitioners, and physician assistants prescribe higher rates of antibiotics for acute respiratory infections (Agiro 2018). We established a pediatric resident teaching clinic within a local primary care center where pediatric care had previously been delivered by clinicians without pediatric training. Guided by the CDC’s ‘Core elements of outpatient antibiotic stewardship,’ we identified guideline-based pediatric antibiotic prescribing as an area for quality improvement (QI). We aimed to reduce unnecessary antibiotic prescriptions (Rx’s) for viral diagnoses by 15% and inappropriate Rx’s (based on drug choice, dose, or duration) by 25% for patients ≤11 years old over an 18-month intervention period.

Methods used

We implemented regular feedback sessions on Rx rates, as well as treatment guideline review sessions. We used 3-month PDSA cycles to identify ongoing opportunities for improvement. Pediatric residents performed chart reviews for systemic antibiotic Rx’s identified in the EMR. We determined the proportion of antibiotic Rx’s that were unnecessary or inappropriate. We compared data from the intervention period to a 10-month baseline period.

Summary of results

During the first 8 months thus far, compared to baseline, the proportion of unnecessary Rx’s decreased by 10% (27% vs 17%) and inappropriate Rx’s by 47% (82% vs 35%). Interventions performed included a baseline session at month 0, review of acute otitis media guidelines at month 1, and feedback session and review of streptococcal pharyngitis guidelines at month 4. From month 5 through month 8, an EMR change led to a delay in obtaining charts for abstraction, inability to provide feedback, and a rise in inappropriate Rx’s (24% mo. 4 vs 35% mo. 8), though unnecessary Rx’s continued to decline during this period (21% mo. 4 vs 17% mo. 8).

Conclusions

Utilizing QI techniques in the outpatient setting to improve adherence to pediatric antibiotic prescribing guidelines has yielded promising early results, though technical challenges have reinforced that ongoing interventions are needed to sustain these results. We identified streamlining of data collection and providing individualized, real-time feedback with behavioral nudges (Meeker 2016, Linder 2017) to clinicians as areas for future improvement.

49 Macrophage suppression during the acute phase of congenital cytomegalovirus infection does not change hearing outcomes in a mouse model

C Nielson*

K Shi

M Firpo

A Park

University of Utah, Salt Lake City, UT

Purpose of study

To determine whether treatment with clodronate-containing liposomes reduces sensorineural hearing loss (SNHL) in cytomegalovirus-infected mice and to evaluate the effect of clodronate-containing liposomes on systemic macrophage count.

Methods used

BALB/c mice were inoculated intracranially with murine-CMV (mCMV) or saline on postnatal day 3. The mice were treated with intraperitoneal injections of clodronate-containing or control liposomes over 14 days. Auditory thresholds were assessed using Distortion Product Otoacoustic Emission (DPOAE) and Auditory Brainstem Response (ABR) testing at three weeks of age. Spleens were harvested at 9 days post-infection and evaluated using flow cytometry to confirm global knockdown of monocyte macrophages by clodronate-containing liposomes.

Summary of results

MCMV-infected mice treated with clodronate-containing liposomes did not show significant reduction in ABR (P>0.5 by Kruskal-Wallis test) and DPOAE (P>0.5) thresholds compared to mCMV-infected mice treated with control liposomes. Significant differences were observed in ABR and DPOAE thresholds of mCMV-infected mice compared to non-infected mice (P<0.001). MCMV-infected mice treated with clodronate-containing liposomes showed significant reduction of splenic monocyte macrophages compared to mCMV-infected mice treated with control liposomes (P<0.01 by t-test).

Conclusions

Treatment with clodronate-containing liposomes did not change hearing thresholds in mCMV-infected mice at three weeks of age although clodronate treatment did cause a global knockdown of monocyte macrophages. These results warrant further investigation into the role of specific subpopulations of cochlear macrophages in the development of progressive SNHL in congenital CMV infection.

50 Tyrosine kinase inhibition to reduce the HIV-1 reservoir

M Szaniawski*

A Spivak

University of Utah, Salt Lake City, UT

Purpose of study

To validate the efficacy of tyrosine kinase inhibitors (TKI) as anti-proliferative and anti-HIV-1 agents in CD4+ T cells and myeloid cells, respectively. Ultimately, these data will inform the design of a clinical trial focused on the use of TKI as an HIV-1 cure strategy.

Methods used

Whole blood was obtained by peripheral phlebotomy from healthy donors, and peripheral blood mononuclear cells (PBMC) were isolated followed by purification of CD14+ monocytes and CD4+ memory T cells. Monocytes were differentiated over 7 days in autologous serum to generate monocyte-derived macrophages (MDM).

Summary of results

TKIs inhibit proliferation induced by IL-2, IL-7, or IL-15 in memory CD4+T cells in vitro, preventing the major mechanism responsible for expansion and persistence of the viral reservoir. We find that HIV-1 infection induces a senescent phenotype in macrophages, which is further counteracted by the use of dasatinib. Finally, TKIs are potent inhibitors of HIV-1 in myeloid cells through activation of the host restriction factor SAMHD1, which prevents new infection through direct inhibition of reverse transcription.

Conclusions

We conclude that dasatinib possess two major immunomodulatory qualities that make them attractive candidates for HIV-1 cure. As an anti-proliferative, dasatinib interrupts homeostatic proliferation, the major mechanism underlying HIV-1 persistence in CD4+ T cells. In macrophages, dasatinib both directly inhibits HIV-1 reverse transcription through the activation of SAMHD1 and counteracts the pro-inflammatory effect of HIV-1 infection in myeloid cells, a process that may underlie HIV-1 comorbidities including cardiovascular disease (CVD) and HIV-associated neurocognitive disease (HAND).

51 Pathogen and antimicrobial resistance surveillance in ugandan HIV positive adults with pneumonia

JD Bloomstein1,*

S Caldera2

L Huang2

W Worodria3

P Byanyima3

E Musisi3

S Kaswabuli3

J Zawedde3

J Moore2

S Lynch2

M Shenoy2

C Langelier2

1University of California, Davis, Sacramento, CA

2University of California, San Francisco, San Francisco, CA

3Makarere University, Kampala, Uganda

Purpose of study

Preliminary analyses using machine learning algorithms developed to predict phenotypic antimicrobial resistance from high dimensional genomic data demonstrate 85–100% concordance between culture-determined resistance and detection of antimicrobial-specific resistance genes from cultured isolates. To further evaluate the algorithms, Next Generation Sequencing (NGS) data from Ugandan HIV positive adults with pneumonia was analyzed to identify the type of infection- bacterial pneumonia, viral pneumonia, presence of TB, and disease correlations with CD4 count.

Methods used

We implemented the Rules-Based Method to identify individual or multiple pathogens implicated in each pneumonia case for 218 patients. Using RNA-seq analysis of patient samples, we first analyzed the landscape of the patient virome and determined which patients had active CMV or EBV infections. Next we evaluated for the presence of Pneumocystis jirovecci infection. Subsequently we identified patients with Mycobacterium tuberculosis infections by finding an optimal threshold of sequencing reads that maximized sensitivity.

Summary of results

Preliminary bacterial results show that the most common pathogen were Haemophilus influenzae, Pseudomonas aeruginosa, and Pneumocystis jirovecii. Preliminary viral results show that the most common secondary viruses were Rhinovirus and Influenza. While all 8 patients positive for Pneumocystis jirovecii bronchoalveolar Giemsa stain were positive by NGS, 2 patients had high read numbers by NGS.

Conclusions

The RBM showed high sensitivity for detection of bacterial, viral, and fungal pathogens in pneumonia patients. NGS showed high sensitivity for Pneumocystis jirovecii in particular. Preliminary correlations between infection with CMV, and other viruses, with CD4 count <200 suggest that there could be a potential connection between immunosuppression due to AIDS and certain viruses that has not been previously appreciated. The potentially high prevalence of Pseudomonas aeruginosa could have important consequences for clinical care. Current empirical treatment at the hospital is Ceftriaxone, which does not cover Pseudomonas aeruginosa.

Neonatology general I

Concurrent session

12:45 PM

Thursday, January 23, 2020
52 Effect of contact precautions on staphylococcus aureus and clinical outcomes of colonized patients in the neonatal intensive care unit

S Shahbaz*

M Garg

A de St Maurice

M Sim

UCLA, Los Angeles, CA

Purpose of study

The primary objective is to assess the incidence of S. aureus colonization and invasive disease during and after contact precautions. The secondary objective is to evaluate clinical outcomes of colonized patients versus noncolonized controls.

Methods used

A retrospective chart review of all infants at two UCLA NICUs who screened positive for S. aureus (n=83). Information was also collected was for controls with negative screens (n=151). Of note, from Aug 2014 to Aug 2016 contact precautions were mandated; they were universally discontinued from Sept 2016 to November 2018.

Summary of results

There was a lower incidence of S. aureus colonization when contact precautions were utilized (28.6% vs 44.6%, p=0.01). Of the positively colonized patients, 20.5% were colonized with MRSA and 79.5% with MSSA. There were twice as many positive invasive MSSA cultures than MRSA. Most invasive cultures occurred in previously colonized infants (100% for MRSA, 73.9% for MSSA). There was a higher rate of invasion with MRSA (41.2%) than MSSA (16.7%). There were no differences in measured clinical outcomes in colonized patients before and after contact precautions (e.g., duration invasive mechanical ventilation, incidence of chronic lung disease and necrotizing enterocolitis, NICU length of stay and in-hospital mortality). Colonized patients were 38.5 more likey to be associated with a soft tissue infection (p=0.0005) and have an average 27 day longer NICU length of stay (p<0.0001) when compared to noncolonized patients (when controlling for gestational age and surgical status).

Conclusions

There was a lower incidence of S. aureus colonization when contact precautions were utilized. Most invasive cultures occurred in colonized patients, with a higher rate of invasion for MRSA. There was a higher incidence of MSSA colonization and invasive cultures. There were no differences in clinical outcomes among colonized patients during and after contact precautions. Colonization was more likely to be associated with soft tissue infection and longer NICU length of stay.

53 Associations between maternal pre-pregnancy obesity and neonatal neurobehavior in infants born before 30 weeks gestation

N Nosavan*

L Smith

J Hofheimer

E McGowan

T O’Shea

S Pastyrnak

C Neal

B Carter

J Helderman

J Check

A Soliman

M Roberts

L Dansereau

S DellaGrotta

B Lester

The NOVI Research Network, Providence, RI

Purpose of study

The rate of pre-pregnancy obesity has steadily increased, increasing the risk for preterm delivery, gestational diabetes, pregnancy-induced hypertension, and cesarean sections. Elevated pre-pregnancy weight has also been linked to poor long-term child neurodevelopmental outcomes such as decreased cognitive performance, behavioral and emotional difficulties, and ADHD symptoms. The purpose of our study is to examine the relationship between maternal pre-pregnancy obesity and short-term neonatal neurobehavior in infants born <30 weeks post-menstrual age.

Methods used

The Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study recruited at 9 NICUs affiliated with 6 universities participating in the Vermont-Oxford Network. The NICU Network Neurobehavioral Scale (NNNS) was used to assess neurobehavior at discharge.

Summary of results

709 infants enrolled in NOVI and 664 had completed neurobehavioral assessments and medical data. Of those 227 (34.2%) infants were born to mothers with pre-pregnancy obesity (BMI >30). In unadjusted analyses, stress abstinence and non-optimal reflexes on the NNNS were higher in infants born to mother with pre-pregnancy obesity. Generalized estimating equations examined the associations of pre-pregnancy obesity with NNNS summary scores adjusting for maternal minority race or ethnicity, gestational diabetes, maternal hypertension (chronic or pregnancy-induced), pregnancy weight change, PMA at birth, and PMA at NNNS exam. Pre-pregnancy obesity was associated with an increase in non-optimal reflexes (B=0.41, SE=0.17, Adjusted Means: Pre-pregnancy obesity=5.64, No pre-pregnancy obesity=5.23).

Conclusions

Infants of mothers who were obese prior to pregnancy showed an increase in non-optimal reflexes on the NNNS. The association between maternal pre-pregnancy obesity and atypical child neurodevelopment may be ascertained as early as infancy.

54 Long-term neurodevelopmental outcomes among preterm infants exposed to gestational diabetes mellitus

J Sugar1,2,*

T Lum1,2

D Poeltler2

A Katheria2

1Western University of Health Sciences, Pomona, CA

2Sharp Mary Birch Hospital for Women and Newborns, San Diego, CA

Purpose of study

Gestational Diabetes Mellitus (GDM) is associated with adverse pregnancy outcomes. Current evidence suggests the potential adverse effects GDM has on fetal brain development and neurodevelopmental delays. The purpose of this study is to investigate the relationship between infants born to mothers diagnosed with GDM and neurodevelopmental outcomes at two-year follow-ups.

Methods used

This is a retrospective, multicenter cohort study from May 2007 to July 2019 of preterm infants. Infants were assessed using the Bayley Scales of Infant and Toddler Development (Bayley-III), which screens for cognitive, language, and motor delays in early childhood. Multivariable regression analyses were used to determine an association between GDM exposure and Bayley scores. Independent variables considered for inclusion in multivariable modeling included gestational age, maternal age, length of stay in the NICU, Apgar score at 5 minutes, days of ventilation, birth weight, intraventricular hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia.

Summary of results

748 infants with 130 (17%) born to mothers diagnosed with GDM were assessed. Multivariable regression analysis showed a significant decrease in two-year cognitive, language, and motor composite scores when infants where exposed to GDM (unstandardized-β [95% CI]: -4.312[-7.587 to -1.036], P=0.01; -6.347 [-10.693 to -2.0], P=0.004; -3.582 [-7.084 to –0.079], P=0.045, respectively).

Conclusions

This study found infants exposed to GDM during pregnancy had an increased risk of poorer cognitive, language, and motor outcomes at two-year follow-ups. Larger prospective studies are needed to confirm this association and ascertain whether neurodevelopmental delays persist from two years of age into later childhood.

55 Fatty acids and growth and development in critically ill neonates

A Sivanandam*

S Govardhan

N Li

KL Calkins

UCLA, Los Angeles, CA

Purpose of study

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are essential for development. Infants in the neonatal intensive care unit (NICU) are at risk for ARA and DHA deficiencies secondary to premature delivery and prolonged parenteral nutrition (PN). This study’s purpose is to determine the correlation between DHA and ARA and growth and neurodevelopment.

Methods used

Inclusion criteria for this prospective study 1) <14 days of age, 2) PN-dependence and 3) follow-up in the High-Risk Infant Follow-Up (FU) Clinic. Blood samples were collected at enrollment and weekly on PN. Gas chromatography/mass spectrometry was used to measure DHA and ARA% in the red blood cell membrane. Neurodevelopment was assessed using the Bayley Scales of Infant Development (BSID-III).

Summary of results

In this cohort (n=42), the mean (±SD) gestational age was 29±4 weeks, and 17% had an intestinal disorder. Subjects received 27±22 days of PN. Length of stay was 71±29 days, and the mean corrected gestational age at follow-up was 7±2 months. When compared to birth, weight z-scores were significantly less at 1 week and 30 days of age, discharge and FU (p<0.001 for all). When compared to birth, length z-scores were significantly less at 30 days and discharge (p<0.01 for both). Both ARA and DHA were significantly less at study weeks 2 and 3 when compared to study week 1 (p<0.0001 for all). The ARA change (week 2 – week 1) demonstrated a non-significant correlation with language BSID-III scores (figure 1).

Conclusions

In this study, ARA and DHA decreased after birth, and a larger postnatal ARA decline was associated with a lower language BSID-III score. Studies are needed to determine how fatty acids alter development, and how clinicians can mitigate this deficiency.

56 Associations between chronic lung disease, cry acoustics, and neonatal neurobehavior in infants born before 30 weeks gestation

M Martin*

L Smith

S Sheinkopf

J Hofheimer

E McGowan

T O’Shea

S Pastyrnak

C Neal

B Carter

J Helderman

J Check

A Soliman

M Roberts

L Dansereau

S DellaGrotta

B Lester

The NOVI Research Network, Providence, RI

Purpose of study

Chronic lung disease (CLD) is a known risk factor for developmental delays in infants born preterm. Most studies have focused on neurodevelopmental exams performed at or after 12 months of age, with no known studies in patients prior to discharge from the NICU. Our aim is to examine whether the presence of CLD at or near the time of hospital discharge is associated with short-term neurobehavioral outcomes.

Methods used

The Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study recruited from 9 NICUs affiliated with 6 universities participating in the Vermont-Oxford Network. The NICU Network Neurobehavioral Scale (NNNS) and cry acoustics were used to assess neurobehavior at discharge. Maximum likelihood factor analysis was performed on cry acoustics. Generalized estimating equations examined the associations of CLD with NNNS summary scores and cry factors adjusting for maternal medical risks, severe ROP, brain injuries, infant sepsis, outborn status, antenatal steroid use, post menstrual age (PMA) at birth and PMA at NNNS exam.

Summary of results

709 infants enrolled in NOVI; 418 had complete medical, NNNS, and cry data and were analyzed. Of those, 197 (47.1%) infants had CLD. Factor analysis of cry data revealed two factors that explained the greatest proportion of variation: frequency/energy (loudness) and hyperphonation (high pitch). Cry factors were not associated with CLD. CLD was associated with a decrease in the NNNS attention summary score (B=-0.34, SE=0.16, Adjusted Means: CLD=4.63, No CLD=4.98).

Conclusions

The presence of CLD at the time of NICU discharge was associated with a decrease in attention scores on the NNNS. CLD has been shown to have long-term adverse effects on behavior including attentional skills. Earlier identification of these at risk infants may lead to earlier initiation of therapeutic interventions.

57 Procalcitonin in neonates undergoing early onset sepsis work up

A Zepeda-Tiscareno*

MG Dominguez Garcia

FB Wertheimer

A Chambliss

M Cielo

R Ramanathan

M Durand

LAC + USC Medical Center, Keck School of Medicine, University of Southern California, Los Angeles, CA

Purpose of study

Obtain serum procalcitonin (PCT) reference values for neonates undergoing early onset sepsis (EOS) work up at LAC+USC Medical Center. Evaluate the utility of PCT when compared to high sensitivity C-reactive protein (hsCRP) in those who are pending blood culture results.

Methods used

Demographic and laboratory values (blood culture, CBC, PCT, hsCRP) of neonates undergoing EOS work up admitted to the nursery over a 6 month period were analyzed. Data were retrospectively collected from our electronic medical records. PCT values were obtained by electrochemiluminescence immunoassay and hsCRP by immunoturbidimetric assay.

Summary of results

There were 50 patients ≥35 weeks (gestational age 38.5±1.8 weeks, birth weight 3313±614 g, mean ± SD). Paired hsCRP and PCT values were obtained prior to 6 hours, 6 to 24 hours, and greater than 24 hours of life. There were 44 healthy infants (negative work up) and 6 treated with antibiotics for presumed sepsis (one positive blood culture). The median (IQR) reference values for the healthy infants are shown in table 1; their hsCRP and PCT values are correlated with each other at <6 hours (Pearson correlation coefficient, r=0.36, P=0.04), but are more highly correlated at 6–24 hours (r=0.60, P=0.0001) and at >24 hours (r=0.47, P=0.0036). The hsCRP median values for the 6 infected newborns were 2.40, 17.30, and 20.60 mg/L and the PCT median values were 1.47, 24.59, and 17.89 ng/mL, respectively.

Conclusions

PCT reference values for healthy newborns with negative EOS work up are presented. PCT and hsCRP values are highly correlated at 6–24 hours and at greater than 24 hours. Studies with a larger number of healthy and sick newborns are needed, especially in very preterm infants.

58 Effects of clinical and histologic chorioamnionitis on outcomes of very low birth weight preterm infants

S Sakhamuru*

A Hisey

L Barton

R Ramanathan

M Biniwale

LAC+USC Medical Center, Los Angeles, CA

Purpose of study

Clinical and histologic chorioamnionitis complicate many preterm births with preterm labor or premature rupture of membranes, and has been shown to be a risk factor of adverse neonatal outcomes, including earlier gestational age at delivery and neonatal brain and lung injuries. The goal of this study is to evaluate clinical and histologic chorioamnionitis as risk factors for short and long term neonatal morbidities.

Methods used

This is a retrospective observational study with data gathered for very low birth weight (VLBW) infants, defined as less than 1500 grams, born at LAC+USC Medical Center between 2009–2018. Clinical chorioamnionitis data was obtained based on maternal clinical symptoms diagnosed by the obstetrician. Histologic chorioamnionitis was derived from certified placenta pathology reports. Delivery resuscitation efforts and the most common neonatal morbidities and mortality were collected.

Summary of results

Of the 308 infants, 95.1% had clinical chorioamnionitis and 64% had histologic chorioamnionitis. Infants with histologic chorioamnionitis had increased risk for intubation at the time of delivery (61.5% vs. 42.5%, P=0.003) and were likely to remain intubated at 24 hours of age (54.7% vs. 39.3%, P=0.020). There was also an increased risk of intraventricular hemorrhage (IVH) in this group (47.3% vs. 32.5%, P=0.021). The infants with clinical chorioamnionitis had a significant risk of having severe IVH (14.1% vs. 2.5%, P=0.001). Finally, those with histologic chorioamnionitis had a higher risk of mortality (17.6% vs. 7.7%, P=0.024).

Conclusions

VLBW infants with exposure to either clinical or histologic chorioamnionitis are at a higher risk for intraventricular hemorrhage. In addition, infants with histologic chorioamnionitis require increased intubations and are at an increased risk for mortality.

59 Practices & attitudes toward compassionate extubation in the neonatal intensive care unit

KE Goodman1,2,*

M Fossa3

S Dabagh3

M Caliboso3

S Nair2

D Lotstein3

1LAC+USC Medical Center, Keck School of Medicine of USC, LA, CA

2Fetal and Neonatal Institute, Children’s Hospital Los Angeles, Keck School of Medicine of USC, LA, CA

3Children’s Hospital Los Angeles, Keck School of Medicine of USC, LA, CA

Purpose of study

Compassionate Extubation (CE) in the Neonatal Intensive Care Unit (NICU) may be pursued when long-term survival with acceptable quality of life is not possible, yet little medical literature exists to guide best practice. A multidisciplinary quality improvement (QI) project assessed baseline practices and attitudes among NICU providers and created an intervention to improve quality and standardization of CE in a Level 4 freestanding children’s hospital.

Methods used

12 months of retrospective analysis and chart review assessed practices, attitudes and symptom management among NICU providers towards CE. Staff who cared for a patient who underwent CE were surveyed on their comfort and team communication. A standardized CE checklist and debrief were then created to address common factors in CE management. After provider education, this intervention is being prospectively evaluated.

Summary of results

In our NICU, 60% (30 of 50) of deaths in a 12 month period occurred after CE. Provider survey analysis found consistency in choices for PRN and standing pain medications, but high variability in other symptom management. Nursing survey analysis found 80% of nurses who cared for a patient who underwent CE (n=44) found the medical plan for CE adequate. 79% (n=28) found it easy to maintain the patient’s comfort. Only 12% of nurses debriefed with the medical team after CE, and 57% rated the communication with the medical team as ‘good’. Analysis after checklist and debrief implementation is ongoing, with 8 CE events pending chart review and post-implementation survey.

Conclusions

While retrospective analysis found consistency regarding pain management, there was variation in other management aspects of CE. A notable minority of nurses showed concern over maintenance of patients’ comfort, and debriefings were not routine. We will use feedback from checklist and debrief testing to modify tools for NICU practice.

60 Experiences withdrawing artificial nutrition and hydration: a survey of regional children’s hospital neonatal intensive care units

RE Williams1,2,*

D Locke3

KM Sullivan4,5

A Shah2,6

1Harbor UCLA Medical Center, Torrance, CA

2Children’s Hospital Orange County, Orange, CA

3Thomas Jefferson/AI DuPont Hospital for Children, Philadelphia, PA

4Nemours/AI duPont Hospital for Children, Wilmington, DE

5Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, PA

6University of California Irvine, Orange, CA

Purpose of study

To explore the practice of withdrawal of artificial nutrition and hydration (ANH) occurring in level IV NICUs within the Children’s Hospital Neonatal Consortium (CHNC).

Methods used

A survey of nine questions was created using REDCap to investigate the withdrawal of ANH for neonates not requiring intensive respiratory support (i.e. mechanical ventilation). This survey was sent to each site within the CHNC, with subsequent quantitative analysis of the data. Open-ended questions were not qualitatively analyzed but will be used to inform further research.

Summary of results

From 34 CHNC sites, there was a 76% response rate. 14 of 26 (54%) respondents defined the withdrawal of ANH as the ‘removal of total parenteral nutrition (TPN), gavage feeds, and nutritive oral (PO) feeds with continuation of non-nutritive suckling for those unsafe to PO feed.’ 16 of the 26 responding sites offered withdrawal of ANH in the last 5 years for a total of 41 infants, with 15 of those ultimately dying at home with hospice care. Common care practices included the continuation of colostrum for oral care (16/23, 70%) and comfort breastfeeding (17/23, 74%), as well as the discontinuation of an IV for sedation assistance (15/22, 68%). Most units did not engage an ethics consultant in the withdrawal of ANH (18/24, 75%); however most did involve a Palliative Care consultant (22/24, 92%).

Conclusions

Withdrawal of ANH is rare in level IV NICUs, increasing the value of collaborative survey work. Across the US, the withdrawal of ANH is primarily characterized by the removal of TPN, gavage and PO feeding with comfort feeding being continued. Survey responses generally reflected that this rare and difficult process is individualized, often with the help of palliative care consultations.

Neonatology pulmonary I

Concurrent session

12:45 PM

Thursday, January 23, 2020
61 Potential role of fox family transcription factors in the pathogenesis of bronchopulmonary dysplasia

A Rashed*

F Gao

S Bellusci

R Ramanathan

P Minoo

LAC+USC Medical Center and Children’s Hospital Los Angeles, Los Angeles, CA

Purpose of study

Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in preterm infants as a result of long-term mechanical ventilation and oxygen exposure. The pathogenesis resulting in BPD is not completely understood. Studies using postmortem BPD lung tissue have shown that there is altered expression of a number of developmentally important genes.

Methods used

We generated three independent genetic models of BPD-like phenotype by disrupting the signaling pathways of TGFb, PDGFα, and IGF-1 in neonatal lung in mice. The mutations to disrupt the pathways were induced in secondary crest myofibroblasts (SCMF) whose role is critical for normal alveologenesis. RNAseq analysis was performed which identified a cluster of differentially expressed genes that were common amongst the three BPD-like phenotypes. To assess the physiologic relevance of a specific subset of the identified genes, we examined their expression in a well-established hyperoxia-induced hypoalveolization mouse model. We analyzed gene expression using a total of ten mice exposed to hyperoxia compared to eight combined controls at three different points during neonatal life. mRNA expression was assessed by quantitative RT-PCR.

Summary of results

Expression of Foxq1, Foxd1, Foxc2 were decreased in the mouse BPD lungs suggesting a role for the selected genes in the pathogenesis of BPD. We further demonstrate that Foxd1 is expressed in SCMF and ablation of SCMF during alveologenesis via Foxd1-cre arrests alveolar formation leading to a BPD-like phenotype. To validate our findings in the mouse model, we show that Foxd1 is also reduced in human BPD lung tissue.

Conclusions

Collectively, these observations support the notion that disruption of Foxd1 and FOX family transcription factors may play a major role in the pathogenesis of BPD in preterm infants. This study was supported by NHLBI and The Hastings Foundation.

62 Antenatal exosome treatment preserves lung structure and vascular growth in an experimental model of bronchopulmonary dysplasia due to chorioamnionitis

AN Abele1,*

N Wilson2

A Abikoye2

G Seedorf1

A Brooks1

S Kourembanas3

SH Abman1

1Pediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, CO

2University of Notre Dame, Notre Dame, IN

3Boston Children’s Hospital, Harvard University, Cambridge, MA

Purpose of study

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, results in many complications that significantly alter quality of life and decrease life expectancy. Prenatal stresses such as chorioamnionitis (CA) increase the risk for BPD in infants independent of postnatal lung injury. Past studies have shown that antenatal endotoxin (ETX) exposure as a model of CA causes sustained disruption of lung alveolar and vascular growth, hallmark findings in BPD. Recent research has shown promising results for postnatal treatment of BPD with mesenchymal stem cell-derived exosomes (MEx), however, the antenatal efficacy of MEx for the prevention of BPD is unknown. Thus, we hypothesized that antenatal treatment with MEx in an experimental rat model of CA will be sufficient to prevent the development of BPD.

Methods used

Effects of antenatal MEx injections were studied using an established rat model of CA as induced by ETX. At E20, rat litters were treated with intra-amniotic injections of saline control, ETX only (100uL/sac), or ETX plus MEx. Pups were delivered near term (E22) via cesarean section. Morphometric studies to assess airspace growth (by mean linear intercept; MLI), vascular growth (vessel density; VD), and lung function (FlexiVent) were performed at 2 weeks postnatal age.

Summary of results

When compared with controls, intra-amniotic injections of ETX reduced alveolar growth as reflected by increased MLI by 23.2% and reduced vascular growth (decreased VD) by 44.4% at 2 weeks postnatal age (p<0.05). In infant rats treated with antenatal MEx and ETX, MLI and VD were not different from control rats. Lung resistance and compliance also improved with antenatal MEx treatment in comparison with the effects of ETX alone.

Conclusions

Antenatal treatment with MEx preserves lung structure and function in rats with experimental BPD induced by ETX. We speculate that early MEx treatment may be sufficient to prevent the development of BPD in premature infants, especially in the clinical setting of CA.

63 Intranasal and intraperitoneal lipopolysaccharide administration activates distinct gene networks in lung macrophage subsets

E Sajti*

N Spann

O Zhengyu

L Prince

C Glass

University of California San Diego, San Diego, CA

Purpose of study

Microbial pathogens attack the lung via the airspace or pulmonary circulation. The lung immune system contains distinct myeloid cell populations resident in the alveolar space, interstitium, and pulmonary capillary bed. How the anatomic site of the initial inflammatory signal might lead to differences in immune response is not fully understood.

Methods used

We administered LPS intraperitineally (i.p) or intranasally (i.n.) to C57BL/6J mice and examined transcriptomic changes in lung macrophages and monocytes. Alveolar macrophages (AM), interstitial macrophages (IM), and inflammatory Ly6c+ monocytes (iMo) were sorted by FACS 2 h, 6 h and 22 h after LPS. Gene expression was measured in sorted cells by RNA-seq and chromatin accessibility by ATAC-seq. Informatic analysis included ingenuity pathway analysis (IPA) and HOMER for transcription factor binding prediction.

Summary of results

Following i.p. LPS, IM and iMo showed robust, largely overlapping changes in gene expression. AM showed modest changes. IPA of enriched pathways for iMo and IM showed substantial quantitative differences. After i.n. LPS, AM were most responsive, with few changes in gene expression in IM and iMo. Comparing genes induced at the time of maximal response in IM (2h, i.p. LPS) to genes in AM (6h, i.n. LPS) we found minimal overlap. Remarkably, LPS caused opposite changes in the most enriched gene expression pathways in AM and IM. For example, LPS stimulated expression of oxidative phosphorylation genes in AM but repressed them in IM. ATAC-seq analysis identified a distinct group of genes whose genomic accessibility correlated with cell-specific transcriptional responses.

Conclusions

Different routes of LPS administration in vivo lead to very distinct transcriptional responses within lung myeloid populations. Remarkably, the direct responses of IM to i.p. LPS and AM to i.n. LPS are mostly divergent, in many cases leading to predictions of opposite biological outcomes. Differences in the chromatin landscapes of genes with divergent responses may lead to distinct enhancers available for binding signal dependent transcription factors, including NF-kB.

64 Antenatal vitamin D attenuates lung injury in a preeclampsia model of bronchopulmonary dysplasia

M Cookson*

T Gonzalez

G Seedorf

B Smith

SH Abman

E Mandell

University of Colorado, Aurora, CO

Purpose of study

Preeclampsia (PE) is a major risk factor for preterm birth and is strongly associated with the subsequent development of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity. We have previously shown that antenatal (AN) exposure to soluble fms-like tyrosine kinase 1 (s-FLT), an endogenous VEGF antagonist that is markedly increased in maternal blood and amniotic fluid in PE, causes abnormal lung structure and function in infant rats. Clinical studies suggest that maternal vitamin D deficiency is a risk factor for severe PE, however, whether AN vitamin D (VD) treatment can restore lung structure and function after exposure to AN s-Flt is unknown. We aimed to determine if early VD (1,25-(OH)2D3) treatment will preserve lung structure and function in infant rats after antenatal exposure to s-Flt.

Methods used

Fetal rats were exposed to recombinant human sFlt-1 (1μg), recombinant human s-Flt (1μg) + 1,25-(OH)2D3 (1ng/ml), or saline via intra-amniotic (IA) injection at E20 and delivered two days later. At 14 days of age, lung function including total respiratory system compliance (Crs) and resistance (Rrs) was determined by Flexivent and lung structure was assessed for radial alveolar counts (RAC) and pulmonary vessel density (PVD) by standard morphometric analysis. Infant hearts were assessed for right ventricle hypertrophy (RVH) by the ratio of RV/LV+S (Fulton’s Index).

Summary of results

IA s-Flt decreased RAC and PVD by 28% and 43%, respectively, and increased RVH by 32% as compared to controls (p<0.001). IA s-Flt increased lung resistance by 30% and decreased compliance by 30% compared to controls (p<0.01). IA 1,25-(OH)2D3 treatment in s-Flt exposed animals restored lung structure, function, and prevented RVH when compared to controls (p=ns).

Conclusions

IA VD improved infant lung structure and function and prevented right ventricular hypertrophy after s-Flt exposure in vivo. We speculate that 1,25-(OH)2D3 may preserve lung growth and function through enhanced angiogenesis in experimental PE.

65 Perinatal vitamin D deficiency alters expression of asthma-related genes in rat lung mesenchymal stromal stem cells: a proteomic analysis

A Vaid*

A Rehan

R Sakurai

Y Wang

Y Liu

V Rehan

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA

Purpose of study

Genome Wide Association Studies (GWAS) have identified several asthma-related genes. High variability in the expression of the asthma phenotype in families implies a significant effect of environmental exposures, including vitamin D (VD) status during lung development. Although the effects of perinatal VD deficiency on alveolar type II cells and lipofibroblasts are well-characterized, its effect on lung mesenchymal stromal cells (LMSCs), critical regulators of lung injury repair, is largely unknown. Here in a rat model of perinatal VD deficiency associated asthma, we study the expression of asthma-related genes identified by GWAS.

Methods used

4 weeks before pregnancy, Sprague-Dawley rats were put on no cholecalciferol (D3) or 250, 500, or 1000 IU/kg D3 added diet, which was continued through pregnancy and lactation. At postnatal day 21, pups were sacrificed, and lungs collected for LMSC isolation using standard methods. Cells were characterized based on surface characteristics (expression of CD90, CD105, CD45, CD31, Stro1) and their multi-lineage potential. Cell lysates were processed for proteomics analysis using Easy nLC Q-Exactive orbitrap, and quantified by mass spectrometry on the basis of the peak area metric. Gene homology information was derived from the Ensembl Compara database, and resultant data was analyzed using the Python programming language.

Summary of results

Mass spectrometry of LMSC identified 3965 proteins. 21 proteins of homologous genes identified from GWAS were found to have differential expression in accordance with VD status. The up- or down- regulation of these genes in VD deficient rats (no dietary D3) in comparison to their expression in VD supplemented groups is as shown in the table 1.

Conclusions

Perinatal VD status determines the expression of several asthma-related genes as identified by GWAS. Functional network data mining places VD as a key determinant of several lung development pathways that determine lung homeostatic vs. asthmatic phenotypes.

66 Vitamin D stimulates pulmonary endothelial cell growth through enhanced pparγ signaling

T Gonzalez1,*

G Seedorf1

J Fleet2

SH Abman1

E Mandell1

1University of Colorado Denver, Aurora, CO

2Purdue University, West Lafayette, IN

Purpose of study

Maternal vitamin D deficiency (VDD) in pregnancy increases risk for childhood lung disease. Past studies have shown offspring of VDD dams have impaired lung function, airway hyperreactivity, and decreased lung vascular growth at two weeks. We further found vitamin D (VD) stimulates fetal pulmonary artery endothelial cell (PAEC) growth and distal lung structure in vivo, but mechanisms through which VD enhances angiogenesis are uncertain. Peroxisome proliferator-activated receptor (PPARg) regulates alveolar development and PPARg expression is decreased in lungs of rats with VDD. The purpose of this study is to determine whether VD stimulates PAEC growth through enhanced PPARγ signaling or upregulation of vascular endothelial cell growth factor (VEGF), a pro-angiogenic agonist.

Methods used

PAEC were isolated from proximal pulmonary arteries of late gestation fetal sheep. Three-day growth assays were performed on PAEC treated with either VEGF or VD (1,25-(OH) D) in the presence or absence of T007 (a specific PPARg antagonist), Pioglitazone (Pio; a PPARg agonist), or Axitinib (Ax; a VEGF receptor inhibitor). PAEC lysates from these experiments were collected for assays of VEGF and PPARg protein.

Summary of results

Treatment with either VD, VEGF or Pio alone increased cell growth above basal conditions by over 30% (p<0.0001). PAEC exposed to either T007 or Ax alone did not change cell growth compared to controls. PPARg inhibition of PAEC prevented VD and Pio enhancement of PAEC growth. Conversely, PAEC exposed to T007 and treated with VEGF demonstrated a 20% increase in cell growth (p<0.001). However, VD stimulated PAEC growth during VEGF inhibition by 20% growth compared to controls (p<0.0001). VD treatment of PAEC increased PPARg and VEGF expression by 80% compared to controls (p<0.001).

Conclusions

We conclude that the mechanism of VD treatment on PAEC growth cannot be explained by increased VEGF expression alone; this VEGF-independent component of VD induced PAEC growth is likely due to the independent effects of VD on PPARg signaling.

67 DHA supplementation of growth restricted rats increases airway hyperresponsiveness in association with decreased nuclear FABP4

N Jessen*

B Ringham

B Zhao

A Kharkar

H Wang

L Joss-Moore

University Of Utah, SLC, UT

Purpose of study

Preterm infants often experience postnatal growth restriction (PGR). PGR increases the severity and incidence of sex-divergent lung outcomes including bronchopulmonary dysplasia (BPD) and airway hyperresponsiveness (AHR). Docosahexaenoic acid (DHA) is important for lung development and inflammation control. A molecular mediator of DHA in the lung is fatty acid binding protein 4 (FABP4). FABP4 and DHA are decreased in BPD and in AHR. However, outcomes from clinical studies examining the effects of DHA supplementation on lung outcomes are conflicting. As a result, consensus on dose and sex effects of DHA supplementation in human PGR infants is lacking. We previously showed in a rat model, that PGR causes sex-divergent 1) baseline deficits in lung function, 2) changes in whole cell FABP4 protein, and 3) altered circulating DHA. We hypothesize that in PGR rats, postnatal DHA supplementation causes dose and sex-dependent changes in response to methacholine challenge in association with changes in nuclear FABP4.

Methods used

We induced PGR by randomizing newborn rat pups into litters of 8 (control) or litters of 16 (PGR). Each litter was randomized to receive diets with DHA at 0%, 0.01%, or 0.1%. At d24 of life, methacholine challenge was performed using the FlexiVent. Lung nuclear and cytoplasmic FABP4 protein levels were determined using western blot.

Summary of results

Rat pups in the PGR group weighed less than control through d21 on all DHA diets. In male PGR rats, DHA at 0.1% worsened response to methacholine (increased airway resistance and decreased lung compliance) relative to male control and male PGR rats not receiving DHA. In addition, nuclear FABP4 was reduced in male PGR rats receiving the 0.1% DHA diet. Female PGR rats with or without DHA did not differ in response to methacholine or in nuclear FABP4.

Conclusions

We conclude that in PGR rats, postnatal DHA supplementation causes dose and sex-dependent changes in response to methacholine challenge in association with decreased nuclear localization of FABP4. These data highlight the importance of dose and sex considerations in DHA supplementation. We speculate that sex-divergent fatty acid metabolism in the lung may contribute to sex-divergent effects of DHA supplementation.

Surgery I

Concurrent session

12:45 PM

Thursday, January 23, 2020
68 Castile soap, chlorhexidine and tri-antibiotic as a prophylactic rinse to reduce breast implant infections in the setting of biofilms

C Drew*

C Lee

L Tobing

S Roddick

S Gupta

Loma Linda, Loma Linda, CA

Purpose of study

Infection is a major complication estimated to affect 2% of breast implant procedures. The best established prophylactic method is the use of an antibiotic rinse of cefazolin, bacitracin, and gentamicin in saline. The implant and surgical field are rinsed in this solution of antibiotics prior to implantation. Recently, orthopaedic surgeons have used castile soap as an irrigation solution in knee and hip replacement surgeries and endodontics have used chlorhexidine solution for root canal irrigation. The replacement of the antibiotic rinse with these irrigants or addition of these irrigants to the antibiotic rinse may better protect from bacterial infection in the setting of biofilms. This study aims to evaluate the efficacy of castile soap, chlorhexidine, and tri-antibiotic as pre-operative rinses for prevention of biofilm growth on tissue expanders and breast implants.

Methods used

Two experiments were carried out: Kerby-Bauer disc diffusion assay to establish antibiotic efficacy by zone of inhibition and trypticase soy broth(TSB) incubation to simulate efficacy against biofilm growth. Each type of implant or tissue expander was rinsed in the corresponding solution and then plated on lawn streaked Mueller Hinton agar plates in the case of the Kerby-Bauer disc diffusion assay or incubated in a 0.5 McFarland standard TSB broth.

Summary of results

Disc diffusion assay supported that castile soap, chlorhexidine,and tri-antibiotic significantly inhibited bacterial growth on all tissue expanders and breast implants used in comparison to saline.Trypticase soy broth incubation demonstrated that chlorhexidine and tri-antibiotic solutions inhibited biofilm growth on all breast implants and Allergan tissue expanders significantly more than saline. Mentor tissue expanders rinsed in chlorhexidine did not significantly inhibit biofilm growth although significant inhibition was found when rinsed in tri-antibiotic. Castile soap, did not inhibit the growth of biofilm significantly more than saline.

Conclusions

Chlorhexidine shows promise as a prophylactic measure against biofilm growth on breast implants and expanders. Tri-antibiotic did prevent against bacterial growth and biofilm growth in these in vitro studies. Dosing and toxicity studies will now need to be performed.

69 Use of full-coverage dressing with closed incision negative pressure therapy for bilateral mastectomy in breast cancer patients

RM Gold1,*

E O’Rorke1

M Pfaffenberger2

L Eldenburg2

A Gabriel3

1Elson S. Floyd College of Medicine, Spokane, WA

2Private Practice Allen Gabriel MD, Vancouver, WA

3Loma Linda University Medical Center, Loma Linda, CA

Purpose of study

Bilateral mastectomy with immediate reconstruction, a complex surgery undertaken to prevent or treat breast cancer, resultis in incisions at risk for post-surgical complications. Incisions created during mastectomy often face challenges with wound healing due to well-documented negative impacts of certain cancer therapies. These incisions may benefit from closed incision negative pressure therapy (ciNPT)—a wound dressing that holds incisions together, facilitates removal of fluid and infectious materials, and creates a barrier to external contaminants, supporting tissue healing and repair. A two-piece, full-coverage dressing designed to give negative pressure to incisions and surrounding tissues is available for use with commercial ciNPT systems. This case series reports our initial experience using this dressing with ciNPT in 3 breast cancer patients who underwent bilateral mastectomies with immediate reconstruction.

Methods used

Full-coverage dressings were placed over the breast once bilateral mastectomy, reconstruction, and closure was complete. ciNPT was initiated on postoperative day (POD) 0 and left in place for 5–6 days. Oral antibiotics were administered post-surgery per best practice.

Summary of results

The 3 patients in our case series underwent bilateral mastectomy with immediate reconstruction. Patient 1, a 59-year-old female with type 2 diabetes, hypertension, and obesity, had bilateral vertical incisions. Patient 2 and 3 were 58- and 50-year-old females with no notable medical histories. Patient 2 had bilateral inverted ‘T’ incisions. Patient 3 had bilateral inframammary incisions. After application of ciNPT, all patients were discharged POD 1 and returned POD 5–6 to remove dressings. Follow-up at POD 30 showed closed incisions in all patients. There were no incidences of seromas, dehiscences, or site infections. At follow-up 4–5 weeks post-surgery no adverse events were reported.

Conclusions

In this patient group at risk for poor wound healing due to cancer therapy, full-coverage dressings with ciNPT supported incision healing and soft tissue repair after bilateral mastectomy and reconstruction for breast cancer.

70 Analysis of differential enigma gene expression in thyroid cancer vs benign nodules

SK Choi*

K Roberts

E Frank

D Foulad

S Mirshahidi

M Perez

A Firek

A Simental

S Khan

Loma Linda University, Loma Linda, CA

Purpose of study

Thyroid cancer incidence is rising worldwide. Although fine-needle aspiration biopsy (FNAB) is an accurate modality for evaluating thyroid nodules, up to 25% of FNABs still yield indeterminate results. There is an increasing number of thyroidectomies due to indeterminate nodules by FNAB alone. Therefore, there is a need for a more accurate and time-efficient diagnostic approach for analyzing indeterminate thyroid nodules. Recently, the osteogenic protein Enigma has been associated with different cancer types, including thyroid cancer progression and calcification through its interaction with bone morphogenic protein-1 (BMP-1), and tyrosine kinases linked to mitogenic signaling pathways. Our published data on Enigma protein analysis with immunohistochemistry showed promising results in discriminating between malignant versus benign thyroid nodules, and demonstrated correlation with thyroid cancer staging. In this study, we are investigating Enigma at a gene expression level by RT-qPCR, which is a quantitative and more time-efficient method that requires smaller samples (FNA) than immunohistochemistry.

Methods used

We extracted mRNA/DNA/proteins from fresh malignant and benign thyroid nodules using a QIAGEN DNA/RNA/Protein Kit. We prepared cDNA from isolated pure mRNA and ran through Enigma-qPCR assay using primers.

Summary of results

The results showed that the Enigma-mRNA expression level was 3-fold higher in malignant as compared to benign thyroid tissue, which is statistically significant. This finding supports our previous Enigma immunohistochemistry data and shows a relative quantitative difference in Enigma-mRNA expression level between malignant and benign thyroid nodules.

Conclusions

We conclude that Enigma-RT-qPCR can be used to effectively determine malignancies in FNAB samples derived from thyroid nodules. This method could potentially enhance the diagnostic accuracy of indeterminate nodules and decrease diagnostic thyroidectomies and subsequent morbidity.

71 Peripapillary retinal nerve fiber layer microcirculation in glaucoma patients of african and european descent using optical coherence tomography angiography

L Taylor*

KD Bojikian

J Wen

Z Chu

X Zhou

Q Zhang

RC Mudumbai

MA Johnstone

RK Wang

PP Chen

H Jung

University of Washington, Seattle, WA

Purpose of study

To investigate the differences in peripapillary retinal nerve fiber layer (RNFL) microcirculation in open angle glaucoma (OAG) patients of African descent (AD) and European descent (ED) using optical coherence tomography-angiography (OCTA).

Methods used

Twenty-three OAG eyes of AD and 27 OAG eyes of ED were scanned using AngioPlex OCTA system (Zeiss Meditec Inc., Dublin, CA) covering a 6 × 6 mm scanning area centered at the optic nerve head (ONH). Peripapillary RNFL microcirculation was measured by calculating the overall blood flux (BF) and vessel area density (VAD) within an annulus centered at the ONH (2.5-mm and 3.7-mm as inner and outer diameters) with the exclusion of big retinal vessels. Two-sample, independent t-tests were used to compare the peripapillary RNFL blood flow metrics between AD and ED eyes. Linear regression models were used to investigate the correlation between peripapillary RNFL blood flow metrics and structural and functional parameters.

Summary of results

There was no significant difference in age, sex, systolic blood pressure (BP), diastolic BP, mean ocular perfusion pressure, RNFL thickness, visual field (VF) mean deviation (MD) and VF pattern standard deviation (PSD) between AD and ED glaucomatous eyes included (p ≥ 0.062). Eyes of AD and ED had similar peripapillary RNFL blood flow metrics (p≥0.380). Peripapillary RNFL blood flow metrics were significantly correlated with VF MD, VF PSD and RNFL thickness (p≤0.026).

Conclusions

Peripapillary RNFL blood flow metrics were significantly correlated with disease severity in AD and ED glaucomatous eyes. Peripapillary RNFL microcirculation detected by OCTA was similar between AD and ED glaucomatous eyes.

72 Tissue plasminogen activator protocol for frostbite in alaska: improved access in rural and remote areas

J Jarrell1,*

C Stadler2

J Capo2

EG Brownson1,2

1University of Washington School of Medicine, Anchorage, AK

2Alaska Native Medical Center, Anchorage, AK

Purpose of study

Use of tissue plasminogen activator (tPA) for treatment of severe frostbite has facilitated limb salvage when previously amputation was inevitable. To address Alaska’s rural and remote areas, a protocol for systemic tPA in patients with grade 3 or 4 frostbite extremity injuries was adopted. This study evaluated the efficacy of this protocol and identified barriers to its success.

Methods used

We compiled all patients treated for frostbite at this institution from October 2012 – May 2019 using data from inpatient admissions, outpatient clinic visits, Emergency Department consult notes, and pharmacy records of tPA infusions. This established a pre-treatment cohort from October 2012 – September 2017 and a tPA eligible cohort from October 2017 – May 2019. Chart review determined key variables including injury grade, timing and location (of injury, first evaluation, and tPA administration), distance from treating facility, amputation level, and tPA candidacy. Descriptive statistics were gathered, and chi squared test was used to compare the two groups.

Summary of results

Clinical characteristics were similar in both groups. A pre-protocol group who were retrospectively determined to be tPA candidates consisted of 13 men (76%) with an average age of 36.3 [25 (26–51)]. Post-protocol tPA recipients consisted of 7 men (78%) with an average age of 37.2 [20 (25–45)]. Amputation of grade 3 and 4 frostbite injuries decreased from 82% (pre-treatment) to 22% (post-treatment). Average time from rewarming to tPA administration was 5.1 hours [3.9 (3.4–7.3)]. There were no adverse events of tPA treatment. Of the two amputations after tPA, one was complicated by infection, and one received amputation after a second re-freezing injury. Many patients were not considered for tPA based on time from rewarming to evaluation.

Conclusions

Systemic tPA administration is shown to be effective in decreasing amputation among patients with grade 3 and 4 frostbite injuries while providing means of accessible treatment in rural and remote settings. Education of frostbite as a time-critical injury may increase patient identification for treatment and improve outcomes.

73 Necrotizing enterocolitis in a rat animal model

GV Perrier1,*

YS Mendez2

FA Khan2

A Radulescu2

1Loma Linda University, Loma Linda, CA

2Loma Linda University Health, Loma Linda, CA

Purpose of study

Necrotizing Enterocolitis (NEC) is one of the leading causes of death in premature infants. The purpose of this research endeavor was to reproduce and develop an animal model of NEC that can be used for possible therapeutic interventions.

Methods used

Sprague Dawley rat pups were delivered prematurely by C-section at 21 days gestation. Newborn rat pups were fed by an orogastric tube with 15 g Similac & 75cc of Esbilac 200kcal/kg every 4 h, receiving 0.1 ml on day 1 of life advancing to 0.4 ml by day 4 of life. Pups were exposed to 100% N x 60 sec followed by 40C x 10 min beginning 10 min after birth three times a day. The pups received LPS (2 mg/kg) via OG tube 8h after birth. Pups were monitored closely for clinical signs of NEC (bloody stools, abdominal distention, lethargy, respiratory distress) and were sacrificed if any above symptoms were observed. On day 5, all surviving pups were sacrificed and intestines were harvested. Samples of duodenum, jejunum, ileum and colon were fixed in 10% formalin. Histological changes in the intestines were graded: grade 0, normal, no damage; grade 1, epithelial cell lifting or separation; grade 2, sloughing of epithelial cells to mid villus level; grade 3, necrosis of entire villus; and grade 4, transmural necrosis. Tissues with histological scores 2 or higher were designated as positive for NEC.

Summary of results

The incidence of NEC found in our experiement using preterm rat pups was 62.9%.

Conclusions

The rat animal model of NEC is a useful tool in the study of NEC as well as in developing therapeutic interventions. Currently, our laboratory is investigating the role of Heparin-binding EGF-like growth factor (HB-EGF) in prevention and treatment of NEC using this animal model.

74 Surgical capacity and trauma system functionality in rural uganda

I Zivkovic1,*

M Ajiko2

Y Yousef3

D Duffy4

R Baird4

1UBC, Vancouver, BC, Canada

2Soroti Regional Referral Hospital, Soroti, Uganda

3Montreal Children’s Hospital, Montreal, QC, Canada

4BC Children’s Hospital, Vancouver, BC, Canada

Purpose of study

Surgical capacity assessment in combination with an evaluation of the trauma system and services at Soroti Regional Referral Hospital (SRRH), Soroti, Uganda, are key factors to identifying priorities in care and growth in partnership together with BC Children’s Hospital. As such, study objectives include assessing surgical capacity at SRRH and evaluating functionality of the Soroti trauma system and services.

Methods used

The Global Assessment in Pediatric Surgery (GAPS) checklist, a novel capacity assessment tool, was implemented at SRRH, administered via interview with a senior surgical faculty member. To evaluate the trauma system, a 26-item environmental scan was implemented via three structured interviews with a general surgeon, medical officer, and intern, in addition to a focus group with four interns. This project took place during July 2019.

Summary of results

GAPS highlights strengths in surgical capacity at SRRH, including ability to perform surgery 24-hr/day; consistent access to 2 equipped operating rooms; and availability of a surgical and anesthesia team with experience in pediatric care. Over 50% of health care practitioners involved in pediatric care attend 1–2 CME sessions annually. Areas for growth in capacity include improving timely access to surgical care (currently, <50% of patients reach definitive care in <2 hrs) and formalized tracking of patient outcomes. Key identifications of the environmental scan include the need for establishment of EMS in the community, and significant trainee interest (consensus amongst 2/2 trainee interviewees, and 4/4 trainees in focus group) in the development of trauma care provider education during internship, such as ATLS and simulation training.

Conclusions

This study demonstrates insight into the current scope of surgical capacity and trauma services at SRRH. Potential partnership priorities include a focus on integrated pre-hospital care and educational resources for trainees at the institution.

75 Comparison of SVF viability from fat harvested via ultrasound assisted liposuction versus standard assisted liposuction: a preliminary volumetric analysis

L Tobing*

C Lee

S Roddick

CS Drew

S Gupta

Loma Linda University, Loma Linda, CA

Purpose of study

Interest in the stromal vascular fraction (SVF) of adipose tissue has grown because of its potential to be a source of therapeutic progenitor cells due to its multipotency and ease of harvest via liposuction. The gold standard method of suction-assisted liposuction (SAL) has been established but alternative methods are gaining popularity such as ultrasound-assisted liposuction (UAL). Studies have not yet directly compared these two methods regarding the quantity of adipose-derived mesenchymal stem cells preserved. This study evaluated if ultrasound collection of fat allows for larger amounts of viable stromal vascular fraction after the isolation process compared to standard suction technique of fat collection in patients undergoing autologous fat transfer.

Methods used

Autologous lipoaspirates were harvested from a total of eight female patients. In our study, our UAL was specifically Vibration Amplification of Sound Energy at Resonance (VASER). Lipoaspirates were cooled and stored in a freezer until processing, centrifuged in 10 mL tubes at 3000 revolutions per minute. Then, SVF was preserved by extracting and discarding the fat and plasma layer and measured for viability using trypan blue solution staining and microscopic high power field counts to determine the number of cells preserved from each method.

Summary of results

Table 1 summarizes the findings of this experiment. The average mass of SVF harvested via SAL was 0.75 g versus an average of 1.64 g for the SVF harvested via UAL. A two tailed t-test revealed a p value of <0.002. Viable cell counts per high power field yielded a value of 23.2 for SAL versus 40.2 for UAL. The p value for the two tailed t-test was 0.03.

Conclusions

The fat collected by the VASER method resulted in a higher volume of SVF with a greater density of viable cells. This suggests that UAL is a more efficient method of collection which also was reported to be less physically taxing for surgeons.

76 The utilization of extended criteria donors in liver transplantation does not affect patient and graft surivival

L Hysa1,*

JD Perkins1

MI Montenovo2

1University of Washington, Seattle, WA

2Vanderbilt University Medical Center, Nashville, TN

Purpose of study

Increasing organ scarcity has motivated transplant centers to relax restrictions to donation creating the term ‘‘extended-criteria donor’ (ECD). ECD include organs that carry increased risk of impaired allograft function and/or donor-transmitted disease. Due to a better understanding in the utilization of these grafts, we hypothesize that both patient and graft survival associated with utilization of liver grafts from ECD will be similar to standard criteria donors (SCD).

Methods used

Retrospective cohort analysis of adult patients who received a liver transplant at the University of Washington (UW) between January 1, 2014 and December 31, 2016. Clinical data was obtained from transplant database at UW. Analysis was limited to transplant recipients who received primary liver transplant. Patients with re-transplantation, multi-organ transplants and living donor liver recipients were excluded. Demographic data was analyzed using a t-test for continuous variables and a Fischer’s Exact test for categorical variables. Survival curves were calculated with Kaplan-Meier analyses and compared with a log-rank test. Cox proportional hazards model was performed to determine the contribution of the recipient and donor variables on allograft and patient survival.

Summary of results

We identified 104 ECD and 135 SCD recipients. Mean age for ECD donor is 37.6±14.2 years old and SCD donor is 32.5±13.5 years old (p=0.002). ECD livers have shorter cold ischemia time (7.1±2.0 hours vs. 8.0±2.5; p=0.003). The rate of primary non-function, re-transplantation, length of hospital stay and liver enzymes post-op are not different between groups. Kaplan Meier patient and graft survival show no difference between recipient groups. Cox proportional hazards model showed no statistical significance between graft or patient outcomes.

Conclusions

The utilization of ECD in liver transplantation does not have any impact in both patient and graft survival. These findings suggest that ECD should be considered more in an era of scarce organ availability and high wait list mortality.

Cardiovascular II

Concurrent session

3:15 PM

Thursday, January 23, 2020
77 Use of hepatitis B donors in heart transplantation: are there consequences?

T Megerdichian*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Cedars-Sinai Medical Center, Los Angeles, CA

Purpose of study

In the past, Hepatitis B donors have been declined in patients who have not been vaccinated by the Hepatitis B vaccine. There is concern that these donors would transmit Hepatitis B to the recipient if they are not vaccinated. There is treatment available for these Hepatitis B infections, however, it has not been established as to its efficacy in patients on immunosuppression. In addition, hepatitis viruses have been reported to affect the endothelium of vital organs. Hepatitis B may injure the endothelium of the coronary vascular tree and could potentially result in a greater development of cardiac allograft vasculopathy (CAV) after heart transplantation. Therefore, we sought to assess this possibility by examining our patients who received Hepatitis B donors.

Methods used

Between 2010 and 2016 we assessed 24 heart transplant patients who received a Hepatitis B donor. All of the recipients had received a Hepatitis B vaccine prior to transplantation. Endpoints include 3-year survival, 3-year freedom from CAV, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE), and freedom from first year rejection, including any treated rejection, acute cellular rejection (ACR), and antibody-mediated rejection (AMR). These study patients were compared with 600[KJ1] [SA2] [SA3] patients without Hepatitis B donors in a contemporaneous era.

Summary of results

3-year survival, freedom from NF-MACE, and freedom from first year rejection were similar between the Hepatitis B and Control groups. There is numerically a lower incidence of freedom from CAV in the Hepatitis B group compared to the control, but this was not statistically significant.

Conclusions

Hepatitis B donors appear to have acceptable outcome compared to non-Hepatitis B donors after heart transplantation. Larger numbers of Hepatitis B donors will be needed to confirm these findings.

78 Family attitudes toward genomic sequencing in children with cardiac disease

D Gal1,*

N Deuitch2

R Tang1

D Magnus2

D Char1

1Stanford Medicine, Palo Alto, CA

2Stanford Center for Biomedical Ethics, Palo Alto, CA

Purpose of study

Care for children with cardiac disease often involves difficult decisions and clinical uncertainty. Genomic Sequencing (GS) promises to improve clinical prognostics and could impact how difficult decisions are made. We sought to determine how GS results might alter family attitudes towards bedside care choices.

Methods used

We conducted semi-structured interviews of 35 families at a high-volume pediatric heart center. We discussed previous experience with and understanding of GS, perceptions toward GS in real and hypothetical scenarios, and support needed for implementing GS in clinical care. Responses were analyzed using grounded theory and a codebook was developed. Researchers discussed interpretation of codes and identified and described emerging themes. Interrater reliability was 0.91.

Summary of results

Three themes emerged: 1) Is knowledge beneficial? Families saw benefits in GS—the ability to provide specific and/or earlier diagnoses, clarify prognosis, change family planning, and avoid unnecessary/additional testing—but also struggled with the sense that GS results did not translate into meaningful changes in clinical care. 2) Should GS guide life limiting decisions and resource allocation? Some parents felt using GS to justify withdrawal of care or allocation of scarce resources (like organs for transplantation) could represent genetic discrimination; other parents felt GS should be used when allocating resources, even if it meant limitation of treatment options for their child. 3) Is giving GS results to the healthcare system safe? All families indicated mistrust of at least one facet of the medical system including insurance companies, maintenance of confidentiality, and the incentive structure in healthcare. Some also expressed distrust of direct to consumer GS testing.

Conclusions

In families of children with cardiac disease, trust is lacking in perceptions of the clinical utility of GS results, in using GS results to inform difficult decisions and in clinical protections for privacy or handling of GS results. Further efforts to improve the trustworthiness of clinical GS are needed to engage family support in implementation of GS to clinical care.

79 Engineered cardiac graft reduces heart failure-mediated ventricular tachycardia

I Chinyere*

J Lancaster

JW Koevary

E Juneman

S Goldman

University of Arizona, Tucson, AZ

Purpose of study

Patients with Heart Failure with reduced Ejection Fraction (HFrEF) have a high incidence of ventricular tachycardia (VT). Though pharmacologic and invasive therapies exist for HFrEF-mediated VT, none restore the electrical stability of the infarcted myocardium. Fibroblasts are the principle component of cardiac stroma and we hypothesize that they can be utilized surgically to modulate susceptibility to ventricular tachyarrhythmia.

Methods used

We performed a proof-of-concept study by surgically implanting engineered cardiac grafts epicardially in a rodent model of chronic ischemic heart failure (HF). A single graft formulation was utilized as the experimental therapy: human dermal fibroblasts cultured into a bioabsorbable polyglactin-910 woven scaffold. The specific aims of this study were to 1) compare susceptibility to induced VT via programmed electrical stimulation in SHAM, HF, and HF+graft rats and 2) to compare two-dimensional epicardial electroanatomic map findings between the three groups.

Summary of results

HF rats (n=29) exhibited no change (1.0±0.1 versus 0.7±0.2, p=0.1430) in capture threshold, a prolongation (68±3 versus 53±4, p=0.0191) of effective refractory period (ERP), and an increase (72% versus 0%, p=0.0394) in the incidence of inducible VT compared to SHAM rats (n=7). Graft-treated rats (n=12) exhibited no change (0.8±0.1 versus 1.0±0.1, p=0.3220) in capture threshold, a prolongation (88±7 versus 68±3, p=0.0029) of ERP and a non-significant decrease (42% versus 72%, p=0.08) in the incidence of inducible VT compared to HF rats. Epicardial electroanatomic mapping revealed lower (p<0.05) monophasic action potential amplitudes in the left ventricle of HF and graft-treated HF rats compared to SHAM rats.

Conclusions

An engineered cardiac graft composed of human dermal fibroblasts on a scaffold was implanted onto the epicardium of rodents with HFrEF and altered the effective refractory period of the infarcted left ventricle. This graft may also influence susceptibility to HFrEF-mediated VT via impeding the successful conversion of R-on-T phenomena to ventricular tachyarrhythmia. This proof-of-concept study confirmed the model and methods necessary to evaluate the therapeutic potential of this cell-based therapy and other novel cell-based therapies for HFrEF.

80 Does the type of explosive brain-death correlate with outcome after heart transplantation?

T Hage*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Cedars-Sinai Medical Center, Los Angeles, CA

Purpose of study

In heart transplantation, the origin of brain death may have an impact on outcome after heart transplantation. It has been reported that explosive brain death, including head trauma, gunshot to the head, and subarachnoid hemorrhage (SAH), may lead to increased catecholamine surge with damage to the donor heart as well as upregulation of inflammatory markers. Other forms of brain death such as hanging, drowning, and drug overdose may also impact outcome, but this has not been firmly established. Therefore, we sought to evaluate explosive brain death and its relationship to outcomes in the current era.

Methods used

Between 2010 and 2018, we assessed 823 heart transplant patients and divided them into two groups based on whether the heart donor underwent explosive or non-explosive brain death. Endpoints included 1-year survival, freedom from the development of cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR), donor specific antibodies (DSA), and severe primary graft dysfunction (PGD).

Summary of results

Patients from both explosive and non-explosive brain death mechanisms have comparable outcomes in terms of survival and freedom from severe PGD, CAV, NF-MACE, and rejection.

Conclusions

Explosive brain death does not appear to be associated with less than optimal outcomes after heart transplantation.

81 Pre-transplant collagen vascular disease is associated with an increase in cardiac allograft vasculopathy after heart transplantation

G Harris*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA

Purpose of study

Collagen vascular disease, including disease states such as systemic lupus erythematosus, rheumatoid arthritis, and scleroderma, have auto-antibodies in common as their etiology. These patients (pts) develop an inflammatory disease state and are known to be triggered by IgG and IgM antibodies against self. It is not clear whether pts with underlying collagen vascular disease face an increased risk of developing donor specific antibodies (DSA), rejection, and cardiac allograft vasculopathy (CAV).

Methods used

Between 2010–2018, we assessed 22 heart transplant pts who had pre-transplant diagnoses of collagen vascular disease specified as lupus (n=7), rheumatoid arthritis (n=9), scleroderma (n=3), and mixed connective tissue disease (n=3). Pre-transplant immunotherapy, first-year post-transplant survival, and freedom from CAV (as defined by stenosis ≥30% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), acute cellular rejection (ACR), antibody-mediated rejection (AMR), DSA, and left ventricular dysfunction (as defined by left ventricular ejection fraction <40%) were recorded.

Summary of results

Pts with pre-transplant underlying collagen vascular disease have significantly lower freedom from CAV. First year freedom from NF-MACE, rejection, and DSA appear to be similar between study and control groups. Collagen vascular disease pts who were treated with pre-transplant disease-modifying agents were then compared as a subgroup to those pts who did not have a disease-modifying agent.

Conclusions

Pts with pre-transplant collagen vascular disease appear to have increased risk of CAV. Heightened immunosuppression may be warranted in this group of patients undergoing heart transplantation.

82 The outcome of right ventricular primary graft dysfunction after heart transplantation: is it bad?

D Melamed*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Cedars-Sinai Medical Center, Los Angeles, CA

Purpose of study

Primary graft dysfunction (PGD) is observed in approximately 7% of all heart transplant (HTx) patients (pts). According to the International Society for Heart and Lung Transplantation (ISHLT), a new PGD scale includes left ventricular (PGD-LV), or right ventricular (PGD-RV) PGD. PGD-LV when severe is noted to have increased mortality. PGD-RV has been described as hemodynamics with RAP >15 mmHg, PCWP <15 mmHg, CI <2.0 L/min/m^2, or need for RV temporary support. PGD-RV has not been well studied.

Methods used

Between 2013 and 2018, we assessed 13 HTx pts who developed PGD-RV within 24 hours after HTx and compared them to pts without PGD. Endpoints included 1-year survival, need for temporary kidney dialysis, need for RV unloading with sildenafil, first-year any treated rejection (ATR), 1-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), and 1-year freedom from non-fatal major adverse cardiac events (NF-MACE, defined as myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke).

Summary of results

Pts with PGD-RV appear to have comparable outcomes to pts without PGD for survival, freedom from CAV, freedom from NF-MACE, and rejection. Pts with PGD-RV required RV unloading therapy which may have affected outcome. There was a trend for decrease in the freedom from temporary kidney dialysis in the PGD-RV group.

Conclusions

Right ventricular primary graft dysfunction after HTx appears to have comparable outcome with good recovery. RV unloading therapy may be helpful. However, there was an associated increased need for temporary kidney dialysis within the first year after HTx. Larger numbers are warranted to confirm these findings.

83 The use of cardiac magnetic resonance imaging (MRI) to predict outcome after heart transplantation

B Zarrabi*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA

Purpose of study

Heart transplant patients are known to develop cardiac rejection and cardiac allograft vasculopathy (CAV) after heart surgery. The severity of these rejection episodes and the detection of rejection has not been adequate with the endomyocardial biopsy. In fact, biopsy negative rejection is seen in approximately 5% of this patient population. The use of cardiac MRI has been increasing to demonstrate myocardial edema or fibrosis. However, it has not been established what these cardiac MRI abnormalities represent and whether they can predict the development of CAV by angiography or clinical outcomes.

Methods used

Between 2011 and 2018, we assessed 26 heart transplant patients who underwent clinically indicated cardiac MRI imaging. In most cases, cardiac function was decreased or endomyocardial biopsy was either negative or ambiguous for rejection. Patients with abnormal cardiac MRI findings of myocardial edema or fibrosis were compared to patients without findings of myocardial edema or fibrosis. These patients were followed for 1 year after the imaging study was performed. Patients from each group were assessed for 1-year subsequent (from MRI scan) survival, 1-year subsequent freedom from CAV, 1-year subsequent freedom from NF-MACE, and the presence of left ventricular dysfunction defined as left ventricular ejection fraction (LVEF) <40%.

Summary of results

Although the numbers are small (no p-values done), there is a numerically lower survival in patients with myocardial edema or fibrosis on cardiac MRI. Cardiac dysfunction with LVEF <40% was more prevalent in the abnormal cardiac MRI group compared to the control.

Conclusions

Cardiac MRI findings of myocardial edema or fibrosis appear to be associated with lower outcome compared to controls. Larger studies are needed to confirm the use of cardiac MRI in this patient population.

84 Does the dose of mycophenolate mofetil impact outcome after heart transplantation?

S Mersola*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA

Purpose of study

Mycophenolate mofetil (MMF) is an anti-proliferative agent that is used in heart transplantation (HTx). The multicenter randomized trial of mycophenolate published in Transplantation in 1998 demonstrated that MMF conferred a survival benefit. The average dose of MMF was 2.8 g/day. It is not clear whether lower doses of MMF also have benefit in terms of control of rejection as well as other outcomes.

Methods used

Between 2010 and 2018, we assessed 240 HTx patients and divided them into categories of MMF dosing in the first year after HTx. The average daily dose of MMF was obtained for all patients in the first year, with an average of 10 MMF dose levels over the first year. Patients were divided into groups based on receiving an average daily dose of <500 mg MMF/day, 500–1000 mg/day, 1001–1500 mg/day, 1501–2000 mg/day, and >2000 mg/day. Endpoints included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR)).

Summary of results

Patients treated with <500 mg MMF/day and >2000 mg MMF/day had a trend toward decreased freedom from ATR. There was no difference in outcome between all groups in terms of 1-year survival, freedom from CAV, freedom from NF-MACE, and freedom from ACR and AMR.

Conclusions

The average daily dose of MMF in the first year after HTx does not appear to have an impact on outcome. Longer follow-up will be necessary to assess whether MMF dosing correlates to long-term complications such as CAV.

85 Correlation of complement binding donor specific antibody and subsequent outcome

A Shen*

K Nishihara

R Levine

M Hamilton

J Kobashigawa

Smidt Heart Institute, Los Angeles, CA

Purpose of study

It has been reported that the development of donor specific antibody (DSA) is correlated to the subsequent development of cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography) following heart transplantation. We now have the ability to assess whether DSA can bind complement (C1q+ assay) which suggests that these DSA are potentially cytotoxic to the donor heart and can result in CAV. We sought to assess if C1q+ DSA leads to the development of CAV in heart transplant patients.

Methods used

Between 2010 and 2014, we assessed 50 heart transplant patients who developed DSA after heart transplantation. Patients were divided into groups that developed C1q+ DSA (n=21) and those that did not have this ability (n=29). Endpoints included the following 5-year outcomes subsequent to the development of DSA: survival, freedom from CAV, freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR)).

Summary of results

Patients with C1q+ DSA had decreased survival and freedom from NF-MACE in the 5-years following the development of DSA. These patients also had a numerical lower freedom from CAV.

Conclusions

The development of C1q+ DSA appears to be correlated with poor clinical outcome. It is not clear if treating C1q+ DSA with desensitization therapy can improve outcomes.

86 Cardiovascular disease risk begins early in males with klinefelter syndrome

N Morelli*

J Kaar

K Moreau

S Davis

University of Colorado Anschutz Medical Campus, Aurora, CO

Purpose of study

Klinefelter Syndrome (XXY) has an incidence of 1 in 600 births each year. Men with XXY have higher morbidity and mortality from cardiovascular disease (CVD). Increased carotid intima-media thickness (cIMT) is associated with CVD risk and has been shown to be higher in men with XXY. cIMT has not been assessed in adolescents with XXY. The objective of this study was to investigate CVD risk in adolescents with XXY with the hypothesis that elevated cIMT would be observed in youth with XXY.

Methods used

This was a cross-sectional pilot study in adolescents with karyotype 47,XXY. cIMT was measured using ultrasound in the supine position by standard protocol. A one-sample t-test was used to compare cIMT in our sample to published norms for adolescent males (0.45±0.04 mm). A two-sample t-test was used to compare cIMT between boys treated with testosterone to those untreated. Correlation was used to assess relations between cIMT and clinical biomarkers of metabolic function, including seated systolic and diastolic blood pressure (SBP, DBP), pulse pressure (PP), BMI percentile (BMIp), waist circumference (WC), fasting blood glucose (FBG) and lipid profile (total cholesterol, LDL, HDL, and triglycerides).

Summary of results

cIMT in 25 males with XXY (mean age 14.5±1.5yrs, BMI percentile 55.3±32.6) was 0.55±0.07 mm, significantly greater than expected for this age (p<0.0001). There was no difference in cIMT in males on testosterone treatment (n=11, 0.56±0.07) compared to those without treatment (0.54±0.07 mm, p=0.53). cIMT was correlated with FBG (r=0.51, p=0.009) and PP (r=0.61, p=0.001). cIMT was not correlated with BMIp, WC, SBP, DBP, or lipid profile components (p>0.1 for all).

Conclusions

This sample of normal-weight adolescents with XXY had a higher cIMT than would be expected for healthy males their age, suggesting their risk for CVD begins early despite the absence of obesity, hypertension, or diabetes. cIMT did not consistently correlate with common markers of cardiometabolic health; however, this pilot study was underpowered for these analyses. Future studies with larger sample sizes, controls, and longitudinal assessments will help determine the pathogenesis and ultimately lead to earlier prevention and intervention for CVD in XXY.

Global health I

Concurrent session

3:15 PM

Thursday, January 23, 2020
87 Outcomes of low-birthweight infants following implementation of a community-based health surveillance intervention in rural india

MA Budge*

LN Donovan

K Maves

A Patil

A Beckstead

S Hourston

K Vlasic

M Indart

B Fassl

A Judkins

University of Utah, Salt Lake City, UT

Purpose of study

Low birthweight (LBW) babies (<2500 g) have 20-fold higher mortality in their first year of life and account for 30% of neonatal deaths. In the Indian state of Gujarat, over 43% of infants are LBW. The purpose of this study is to determine the impact of a health surveillance intervention on growth and mortality in LBW infants in a rural area of Gujarat.

Methods used

A pre-intervention assessment of LBW infants was conducted from January 6 to February 12, 2016. Infants were born at the Mota Fofalia Pediatric Center (MFPC) and discharged to villages in the Garudeshwar taluka. Families were not given newborn counseling or education. Assessment included weight and length.

A health surveillance intervention implemented in April 2016 provided pre-discharge counseling at the MFPC on infant warming and breastfeeding. Six follow-up household visits were made in the first year of life. Assessment included weight, length, temperature, and ECEB criteria for signs of infection. Families received counseling on infant care at each assessment.

Summary of results

On baseline assessment, 72 of 86 identified infants were found for follow up (53% female; mean [range] age at follow-up, 4.7 [1–12] months). In the intervention phase, 330 LBW infants’ families received pre-discharge counseling and 254 (77%) completed follow-up (56% female). There was no significant difference in weight gain between baseline (19.5 g/day) and intervention groups (19.0 g/day, t(360)=0.49, p=0.62). One-year infant mortality was lower in the intervention group (n=14, 4%) compared to baseline (n=8, 11%), as was neonatal mortality (intervention, n=3, 1%, baseline, n=3, 4%), though neither were significant (intervention, p=0.096, baseline, p=0.097).

Conclusions

A health surveillance intervention in Garudeshwar with counseling on best feeding and care practices decreased LBW infant mortality. Future iterations of this study should address methods for increasing participant retention.

88 Sustainable improvement in maternal-neonatal health services delivery in rural nepal

J Doane1,*

JW Thomas2

D Levy2

A Chambers2

B Fassl2

1University Of Utah School of Medicine, Salt Lake City, UT

2University of Utah, Salt Lake City, UT

Purpose of study

Pregnancy and childbirth-related maternal and neonatal mortality in rural areas of Nepal remains high. The purpose of this study is to describe the features and characteristics of an effective and sustainable multifaceted maternal-neonatal health intervention in rural Nepal.

Methods used

Between 2015–2019, a public-private-academic partnership team implemented a multifaceted MCH intervention to build care capacity in the Humla and Solukhumbu districts of Nepal. Fourteen birthing center facilities were established at health posts, engaging the local government health system, local administrators, and the ministry of health to develop a sustainable model for improved MCH services delivery in existing rural clinics. We describe administrative, educational, and management interventions which led to self-sustaining improvements in service delivery for women and children. Fifteen skilled birthing attendants were provided with training, as well as 95 community-based providers for community liaison work and 75 health facility staff for basic perinatal care. Measures of care quality were measured using a standardized WHO survey before and after intervention.

Summary of results

Deliveries at health facilities improved from 37% (before intervention) to 49% (after), deliveries attended by trained professionals increased from 27% to 46%. Women receiving postpartum hemorrhage chemoprophylaxis increased from 31% to 43%, delivery planning increased from 76% to 95%, and newborns receiving most or all essential elements of newborn care increased from 32% to 58%.

Conclusions

Key features of the public private academic partnership intervention included: 1) Local ownership, fingerprinting and accountability, local input into design, and local financial contributions to staff salaries and performance monitoring; 2) Improvement of case management capacity of staff through problem-focused hands on training experiences and government certification programs; 3) One-time investment in necessary equipment upgrades; 4) Integration of birthing centers within the government health system to access governmental supply chain for consumable materials; 5) Building local capacity for monitoring service delivery, care quality and outcomes through data systems and feedback loops.

89 Educating dhulikhel hospital emergency department patients and family members about the risk factors of cardiovascular disease

S Spooner*

University of Washington School of Medicine, Seattle, WA

Purpose of study

The World Health Organization estimates that deaths due to noncommunicable diseases (NCDs) in Nepal have risen from 51% in 2010 to 60% in 2014, with 22% attributed to cardiovascular disease (CVD). Within the Nepali population there is limited education about CVD and its risk factors. In the absence of primary care, the first contact for patients and family members is often the Emergency Department (ED). A 2013 WHO cross-sectional study identified insufficient fruit and vegetable intake, obesity and overweight, hypertension, and hyperlipidemia as the main risk factors within the Nepali population.

Methods used

A partnering Dhulikhel Hospital ED physician identified the need for CVD educational materials in the ED. A literature review of CVD in Nepal was conducted to identify the main risk factors locally. With the assistance of ED physicians and a research assistant, a poster was created featuring Nepali individuals and culturally relevant displays of risk factors. After feedback from ED staff and patients, the poster was revised to include common symptoms of CVD along with the Dhulikhel Emergency Medical Services (DEMS) contact information. The posters will be mounted and displayed on the walls in the ED and waiting room.

Summary of results

Before printing, feedback from 10 ED patients or family members confirmed that the translation and grammar were correct, and the pictures depicting risk factors were clear. After printing, the poster was evaluated by the 13 ED staff for effectiveness using a short survey. On a scale of 1–5, with 5 being easy and 1 being very difficult to understand, 7 staff rated the poster at 4/5 with the remaining 6 rating it as 5/5. All 13 staff members thought a patient without a health background would be able to comprehend the poster’s meaning and stated that they would use it to educate their patients about CVD.

Conclusions

The project succeeded in creating a culturally relevant educational platform for ED patients and their family members to learn more about the risk factors for CVD in Nepal. It also provides a description of symptoms associated with CVD, a visual of the DEMS contact information, and a reminder encouraging patients to seek care immediately. More work is needed to create materials educating patients about CVD risk-reducing behaviors.

90 Engaging traditional mexican midwives in the use of bag valve masks to treat asphyxiated neonates

PF Draper*

University of Utah School of Medicine, Salt Lake City, UT

Purpose of study

This project launched a collaborative partnership between an American medical school and a traditional midwifery school in Oaxaca, laying the groundwork for future neonatal health endeavors in partnership with traditional midwives (‘Parteras’’) in the region.

Methods used

In March 2019, two certified Helping Babies Breath master trainers–a neonatologist and a medical student—taught an 8-hour course for eighteen Parteras involving didactic content and several hours of hands-on practice with neonatal mannequins and bag valve masks.

Summary of results

Participating Parteras clarifed their ability identify neonatal asphyxiation, gained insight into the strengths and weaknesses of their current interventions and learned to effectively utilize a bag valve mask to treat asphyxiated neonates.

Conclusions

Parteras from across Oaxaca gained a tangible skill to address neonatal asphyxiation in low-resource settings. Several neonatal mannequins and bag valve masks were donated to the school to ensure ongoing training on this topic. As training is sustained by the midwifery school, traditional midwifes will be equipped with the skills, resources, and confidence to identify areas of local need and implement their own training programs for other traditional birth attendants. This Training Of The Trainer model opens up long-term potential for reduced neonatal mortality due to asphyxiation in the rural communities of Oaxaca.

91 Rapid baseline assessment of emergency department utilization and triage in rural india

L Donovan*

K Maves

A Patil

A Beckstead

MA Budge

K Vlasic

C Indart

JW Thomas

B Fassl

A Judkins

University of Utah, Salt Lake City, UT

Purpose of study

Establish baseline data for a rural hospital in Gujarat, India, quantifying intake vital sign assessment and qualitative information regarding care in the Emergency Department.

Methods used

This direct observational assessment took place at Shree Chhotubhai A. Patel Hospital, a rural hospital in Gujarat, India. In January – July of 2019, medical students trained in data collection directly observed Emergency Care delivery and triage assessment using a standardized evaluation tool. The data collected is descriptive.

Summary of results

A total of 43 patient encounters were assessed during the data collection period. Heart rate and peripheral capillary oxygen saturation (SpO2) were the most frequently assessed vital signs, measured in 30% (13/43) and 27% (12/43) of patient encounters, respectively. Blood pressure was measured for 25% (11/43) of patients. Least frequently measured was patient temperature at 7% (3/43) and respiratory rate at 2% (1/43).

The presenting symptoms for 47% (20/43) patients seen were seen for trauma, 12% (5/43) for obstetrics care, 7% (3/43) with concern for stroke, 5% (2/43) with chest pain. In terms of Emergency room staff availability, 70% patients were seen by nursing within 5 minutes of arrival to the emergency department, with maximum wait time of 20 minutes until a nurse was able to assess the patient. 70% (30/43) patients were seen by the medical officer on duty within 30 minutes of arrival.

Conclusions

WHO guidelines recommend triage systems based on presenting signs and vitals. Staff are available to assess patients rapidly upon arrival to the emergency department. There is a need to improve the measurement of vital signs. One key element contributing to the challenge of a triage assessment is the limited availability of equipment needed for accurate assessment. Availability of pulse oximeters and mobile blood pressure cuffs led to a relative increase of vital sign measurement. There was not a working thermometer in the hospital. This baseline analysis helps initiate an effort to understand the current practices in the ED and informs the creation of plans to improve appropriate patient care delivery.

92 Rapid baseline assessment of peripartum care delivery by skilled birth attendants in rural india

K Maves*

LN Donovan

A Patil

A Beckstead

MA Budge

JW Thomas

B Fassl

A Judkins

University of Utah School of Medicine, Salt Lake City, UT

Purpose of study

Perinatal mortality remains a global public health issue. In 2015, about 303,000 women died from complications related to pregnancy and childbirth; 60% were related to untreated maternal conditions. India alone is currently responsible for 20% of global maternal deaths. Improving maternal and child health are central to the realization of National Health Goals outlined in the National Rural Health Mission (NRHM). Key interventions include increased support of deliveries by skilled birth attendants (SBAs). This study provides a descriptive assessment of current maternal care delivery by SBAs in the peripartum period.

Methods used

This assessment took place at Shree Chhotubhai A. Patel Hospital in rural Gujarat, India. In July, 2019, medical students trained in data collection directly observed perinatal care delivery to estimate SBA proficiency. SBA competency was assessed by medical students via a standardized evaluation tool, the components of which were adapted from the World Health Organization’s (WHO) top priority quality indicators.

Summary of results

A total of 26 partial or complete care encounters were assessed during this data collection period. Of the 9 observed admissions, maternal blood pressure, temperature, and heart rate were assessed 44%, 0%, and 33% of the time, respectively. In these women, fetal heart rate was assessed 100% of the time, but was never documented. A total of 9 cesarean sections (C/S) and 16 vaginal deliveries were observed. Of the 16 vaginal deliveries, 11 (69%) women experienced inappropriate fundal pressure applied by SBAs. Of the 25 deliveries (16 vaginal, 9 C/S), 19 women (76%) received oxytocin at some point after delivery; only 6 women (24%) appropriately received oxytocin within 1 minute of birth.

Conclusions

This evaluation found variation and deficiencies in perinatal care services provided by SBAs. There is a need to refine provider training and protocols to improve the quality of perinatal care.

93 Screening for depression and anxiety among adolescents in himachal pradesh, india

E Loy*

J Johnston

A Hooper

M Cornett

S Sachdeva

J Tan

V Kapoor

University of British Columbia, Vancouver, BC, Canada

Purpose of study

The WHO ranks depression and anxiety as the two largest contributors to disability globally, with over 80% of affected people living in low- and middle-income countries. However, these conditions often remain undiagnosed and undertreated in developing countries due to stigma, sociocultural variance in perceptions of mental health, and limited regionally-specific knowledge. A greater effort to describe and study mental illness beyond a Western context is much-needed. The University of British Columbia’s Global Health Initiative (GHI) has a longstanding partnership with Munsel’ling Boarding School in northern India. After hearing anecdotal reports of high stress levels among students, the GHI team developed a preliminary study to screen for depression and anxiety among adolescent students. The rationale for the study is supported by Parik et al.’s findings that students in Goa and Delhi experience high levels of stress due to academic pressure and other factors, and that stress is often associated with anxiety and depression (2019).

Methods used

This cross-sectional study was carried out at Munsel’ling School in Himachal Pradesh, India. Students aged 12 or older (N=222; mean age 13.8±1.4 years and maximum age 18, 53.6% female) were assessed using the PHQ-2 and GAD-2 screening tools for depression and anxiety. PHQ-2 positive students were given the option to complete a PHQ-9.

Summary of results

Of the 222 students screened, 12.2% (N=27) screened positive for GAD-2, and 6.3% of students (N=14) screened positive for PHQ-2. All 14 PHQ-2 positive students chose to complete the PHQ-9 questionnaire with a mean score of 9.6 (SD=4.3): 1 scored between 0–4, 6 scored between 5–9, 5 scored between 10–14, and 2 scored between 15–19. Male students reported anxiety more often than depression, and female students reported anxiety and depression equally, while the number of male and female students affected overall was even.

Conclusions

This preliminary study suggests that depression and anxiety are experienced by students in this region. While prevalence is low, there are currently no resources available to help students manage mental health. Our team identified several areas for future research and program development, with the most important next-step being to develop more culturally-specific screening tools.

94 An anthropometric assessment of children under 5 in rural kenya

JB Creelman1,*

J Jacob1

SM Gunn1

C Pang1

P Mbullo2

V Kapoor1

1University of British Columbia, Vancouver, BC, Canada

2Northwestern University, Evanston, IL

Purpose of study

Globally, 1 in 9 people face hunger. 52 million children are wasted and 155 million have stunted growth. Pamoja, a community-based organization in the Kisumu district of rural Kenya, has programs to improve health, income and food security of its residents. In order to identify how best to design and deliver programs, Pamoja identified a need to do a baseline assessment of nutrition and food security of community households. This collaboration is a continuation of a decade-long partnership between Pamoja and the University of British Columbia Global Health Initiative.

Methods used

Pamoja identified 434 children under age 5. Height-for-age (HAZ), weight-for-age (WAZ), and height-for-weight (HWZ) were measured to gauge stunting, underweight, and wasting, respectively. Mid-upper arm circumference (MUAC) was measured as an indicator of acute malnutrition. With written informed consent from the household head, community health workers collected anthropometric data. Supervision and the WHO training course on Child Growth Assessment were provided. Ethical approval was granted by UBC BREB and AMREF. WHO Anthro Analyzer software was utilized to calculate age-adjusted Z-scores, comparing to WHO Child Growth Reference data. Stunted, underweight, and wasted children were identified by Z-score values of ≤-2SD (moderate) and ≤-3SD (severe) based on HAZ, WAZ, and HWZ, respectively.

Summary of results

62 (14.3%) children had moderately stunted growth and 40 (9.2%) had severely stunted growth. 24 (5.5%) children were moderately underweight and 24 (5.5%) were severely underweight. 20 (4.6%) children had moderately wasted growth and 13 (2.9%) had severely wasted growth. 7 children (1.6%) had MUAC measurements in the moderate to severe malnourishment range and were referred to acute medical care.

Conclusions

The most prevalent form of malnutrition in this study population is stunting, which is typically indicative of chronic nutrient deficiency. This baseline data enables Pamoja to effectively target nutrient-deficient families and track their service delivery and impact. It is important to note that all children included in this study are beneficiaries of Pamoja. Therefore, this study population was not randomly sampled, which presents selection bias and a limitation to interpretation.

95 A survey-based method of assessing food insecurity and dietary diversity in rural west kenya

SM Gunn1,*

C Pang1

J Jacob1

JB Creelman1

P Mbullo2

V Kapoor1

1University of British Columbia, Vancouver, BC, Canada

2Partners in Community Transformation, Kisumu, Kenya

Purpose of study

The United Nations identifies the right to food as a basic human right. However, the Kenyan government reports that 47% of their citizens are food insecure. To gain more insight into this issue, the UBC Global Health Initiative partnered with a local NGO, Pamoja, that provides community education and nutritional support to the Kisumu region of Kenya. The aim was to gather baseline assessments of household food insecurity and dietary diversity of families with children under 5 receiving nutritional support from Pamoja. The purpose was to identify families who require additional support and refer them to the appropriate Pamoja programs.

Methods used

Community Health Workers (CHW’s) identified households registered with Pamoja with children under 5 and a household head with a minimum age of 18 and fluent in Luo. Using a survey adapted from the Household Food Insecurity and Access Scale (HFIAS) and the Household Dietary Diversity Scale (HDDS), data was collected by Pamoja field officers and our team.

Summary of results

CHW’s identified and recruited 358 households. On average, household heads were 38.5 (SD 11.1) years old and 91.3% female. Analyzing the HFIAS with the Food and Agriculture Organization analysis scale indicated that 299 (83.3%) households were classified as severely food insecure in terms of food quantity. The mean score was 16.8 (±5.0) out of a maximum 27. The HDDS indicated that 15 households were severely food insecure in terms of food diversity with 15 under the score of 4 out of a maximum 15. The average score was 6.58 (±1.61).

Conclusions

Although the HDDS suggests that many of these households are getting a decent variety of foods, the HFIAS indicates that most households are not able to access a sufficient amount of food. These results will better enable Pamoja in the allocation of funding and programs to improve the access to sufficient nutrition, and modify the food support to vulnerable families. The study is limited due to the reporting period of the HFIAS and HDDS. HFIAS captures data from the past month and HDDS from the past day. Thus, the average longitudinal consumption of a family might not be represented. Households will be followed with surveys and growth monitoring for 5 years.

96 The utility of teledermatology to enhance follow-up care and information distribution in Lima, Peru

S Briggs*

A Kalus

University of Washington, Seattle, WA

Purpose of study

With the increasing use of WhatsApp among physicians and patients, this form of communication is being adapted to improve clinical practice. The purpose of this project was to identify ways to overcome barriers to care among patients in a dermatology clinic in Lima, Peru.

Methods used

Fifty patient interviews were conducted to better understand healthcare barriers at the Hospital Nacional Daniel Alcides Carrión in Lima, Peru. The interviews also assessed WhatsApp use and if patients would be comfortable using it to for follow-up care. In a pilot study, 10 patients were selected to receive follow-up care via WhatsApp. Over 8 weeks, patients sent in photos and concerns to a smartphone for this project. Responses were given by the chief dermatologist (EQ). To use WhatsApp for information distribution, educational materials were developed on three topics (self-medication, antibacterial soaps, and recommendations for skin products). Patients were asked about the readability and understanding of these messages. The 10 patients who completed WhatsApp follow-up care were asked about their comfort receiving dermatologic care via WhatsApp and whether they would do it again.

Summary of results

From the patient interviews, common barriers included high cost, long travel times, and difficulty getting free time away from work or school. Seven (14%) of the 50 patients reported disabilities impacting travel. The majority (76%) of patients had smartphones capable of taking photos. From the pilot study, nine (90%) of the ten patients said they would do it again and all ranked their comfort as a 9–10 of 10. One patient did not give feedback. The response was overall positive, including comments like, ‘I want to thank you and Dr. Quijano for caring about my health. This means of communication is very useful.’

Conclusions

In this pilot study, WhatsApp was a powerful tool that improved communication between physicians and patients, especially those who had difficulty attending in-person appointments. The hospital plans to continue using this method. In the future, we plan to compare outcomes in patients who receive follow-up via routine clinic visit or via WhatsApp. If outcomes are similar, WhatsApp could potentially provide a method to improve care for more patients.

Global health II

Concurrent session

3:15 PM

Thursday, January 23, 2020
97 Improving understanding of the burden of traumatic injuries through trauma registries in Lima, Peru

T Jordan*

University of Washington School of Medicine, Seattle, WA

Purpose of study

Trauma registries are databases that can be used to better understand the burden of trauma within a population. Data can be used to implement quality improvement projects, inform local policies, and develop targeted preventative health measures. Staff at Hospital de Vitarte in Lima have spent 13 months using a trauma registry, though much of their data is missing or incomplete. The goal of this project was to examine the process of data collection and entry and propose solutions to improve data quality.

Methods used

Preliminary data were presented to hospital staff to illustrate current gaps. Meetings were held to gather feedback on how to improve data entry processes. Inclusion criteria were defined and will be posted on the wall of the department. A new paper intake form was created and a schedule was developed for interns to digitize intake forms. A training workshop was developed for and delivered to residents and interns. Training materials were left with staff for future workshops. Finally, a patient education pamphlet on pedestrian, bicycle, and automobile safety was developed for distribution after data analysis identified a high burden of traffic accident-related trauma.

Summary of results

A total of 19 residents and interns were trained in the use of trauma registries and the new paper intake form. In a post-workshop survey, 90% of respondents indicated agreement that trauma registries are important tools for improving outcomes in trauma patients. Additionally, 84% of participants agreed that the new paper entry form would improve data quality and 79% thought that the new form would ease the process of online data entry. The Director of the Trauma Quality Committee of the Society of General Surgeons of Peru is seeking approval through that society and the Panamerican Trauma Society to distribute the patient education pamphlet as part of a larger public health campaign.

Conclusions

This project led to the implementation of specific strategies for data quality improvement, including changes to the paper intake form, well-defined inclusion criteria, and weekly data upload and revisions. Additional funding and resources including dedicated administrative staff are needed to improve data entry and inform injury prevention strategies to reduce morbidity and mortality in trauma patients.

98 Improving hand hygiene in the pediatrics department of the regional hospital of Loreto, Peru

K Chaffee*

University of Washington School of Medicine, Seattle, WA

Purpose of study

The pediatrics department of the Regional Hospital of Loreto has had 163 nosocomial infections reported in the last 5 years, and hand hygiene is an effective and inexpensive intervention to decrease interpersonal spread of microbes. This project aimed to improve hand hygiene through increased access to resources, reminders, and educational materials.

Methods used

An initial assessment of the availability of hand hygiene resources and of staff and family hand hygiene compliance was performed. Together with quality control and pediatrics department staff, I worked to increase access to hand hygiene materials; place WHO reminders and education materials for hand hygiene in patient rooms, bathrooms, and sinks; and evaluate technique, compliance, and barriers to proper hand hygiene among staff and families an provide performance feedback. We provided a final written report of the department’s hand hygiene compliance status and recommendations for improvement to the office of quality control.

Summary of results

The initial assessment identified a lack of hand hygiene resources throughout the department and low sanitation standards among personnel and patient families. Barriers to hand hygiene voiced by hospital staff included lack of resources, inconvenience from washing or dislike of hand sanitizer, and preferring to simply wear gloves. By the project’s end, all rooms were equipped with WHO hand hygiene educational materials and hand sanitizer, and bathrooms and sinks were equipped with soap and WHO educational materials. Most personnel demonstrated proper knowledge of technique, but few knew the WHO 5 moments when hand hygiene is indicated. Staff that were in the habit of cleaning their hands appreciated and utilized the increased access to hand hygiene materials and reported that they now more frequently clean their hands. Most families evaluated utilized the hygiene resources but there was large variability in hygiene knowledge and habits.

Conclusions

Improving hand hygiene of personnel in the pediatrics department of HRL will be dependent on maintaining hygiene resources and overseeing hand hygiene compliance. Families of patients should be educated on proper hand hygiene (instructional posters on walls and in bathrooms or direct teaching) and provided with enough resources and functioning bathroom sinks.

99 Growth assessment of infants admitted to a government hospital newborn unit in Nakuru, Kenya

A Morozov1

M Van Ormer1

M Thoene1

N Switchenko2,*

E Kibaru3

C Hanson1

A Anderson-Berry1

1University of Nebraska Medical Center, Omaha, NE

2University of Utah, Salt Lake City, UT

3Egerton University, Nakuru, Kenya

Purpose of study

Inadequate nutrition remains a leading cause of growth failure in neonates, especially those born preterm or critically ill. Previously, members of this research team implemented a respiratory intervention in the newborn unit in a government hospital in Nakuru, Kenya. Infant growth failure in the unit was suspected based on clinical observation. The purpose of this study is to quantify growth velocity and weight z-score changes for infants in a Kenyan newborn unit from birth to hospital discharge.

Methods used

After ethical approval, data was collected from the hospital charts of Kenyan infants (n=704) admitted to a newborn unit between June 2016 to December 2018. Collected information included birth gestational age (GA), birth weight, discharge weight, length of hospital stay (LOS) in days, and z-scores for weight on the INTERGROWTH 21st growth chart. Infant growth velocity was calculated as follows:1,000xln(discharge weight/birth weight)/LOS. Averages are reported in means. A t-test compared growth velocity and z-score changes from birth to discharge between infants with LOS <14 days vs. >14 days. Regression analysis predicted weight z-score change based on LOS. A p-value <0.05 was statistically significant.

Summary of results

283/704 (40.1%) infants were born <36 weeks GA. Mean birth GA was 36^6 weeks with weight 2.61 kilograms (kg) (z-score -0.024). Mean LOS was 7.4 days with discharge weight 2.54 kg (z-score -0.855). Infants with LOS >14 days (mean 24 days) experienced more growth failure than infants with LOS <14 days (mean 4 days) with change in z-score -1.66 vs. -0.64 (p<0.001). Growth velocity of infants with LOS >14 days was low at 4.7 grams/kg/day, with each day of hospitalization predicting a -0.044 decrease in weight z-score (p<0.001).

Conclusions

Infants admitted to a newborn unit in a government hospital in Nakuru, Kenya experience growth rates that are inadequate to meet recommended growth velocities by the World Health Organization. Longer lengths of hospital stay contribute to decreases in weight z-score and an increased risk of malnutrition. Additional assessment and intervention is needed to promote improved nutrition provision and growth rates of these infants.

100 Addressing pneumonia misconceptions and prevention in children under five in karagita, kenya

R Wollman1,2,*

1University of Washington School of Medicine

2University of Washington, Seattle, WA

Purpose of study

Pneumonia rates in Naivasha sub-county have doubled in the last 5 years, with a large percentage of cases admitted to Naivasha Community District Hospital (NCDH) coming from the Karigita community. Current research reports the changing nature of pneumonia to predominantly viral causes in response to effective bacterial vaccination and lack of attention placed on primary prevention. Professional Community Health Education Workers (CHEW) proposed training Community Health Volunteers (CHV) to educate households during work for ongoing projects.

Methods used

Building on ongoing local research, public health projects, and based on Kenyan and international guidelines, a training was developed to cover pneumonia-related misconceptions and preventative methods. Ongoing public health interventions already address immunization, indoor pollution, and hygiene to prevent diarrheal diseases, so emphasis was placed on incorporating cough hygiene, addressing misconceptions about pneumonia, educating about prompt care-seeking, avoiding antibiotic misuse, and promoting exclusive breastfeeding for 6 months. CHVs participated in a 1-hour educational session with facilitated discussion and pre/post-knowledge-based assessments. A 2-month follow up and data tracking of pneumonia cases will be used to assess the quality of the training and its impact on the community.

Summary of results

Thirty CHVs participated in this educational session, with the assistance of the Ministry of Health Public Health Branch, NCDH, and NIH funded research. The pre to post-test knowledge assessment score increased over 80% from 4/30 to 29/30. Continued education on pneumonia prevention is ongoing within Karigita and neighboring communities as a direct result of a successful educational session. A digital media for more efficient sharing, storage, and access was suggested and a readily accepted alternative to printed educational material.

Conclusions

Participating CHVs benefited from an increase in knowledge-base and were actively engaged in discussions to address methods of sensitizing the community and implementing change in cultural practices. The integrative scope of the project and the session’s engaging atmosphere generated opportunities to collaborate with ongoing research and set-up additional workshops addressing community needs.

101 Assessing the impact of newborn care training in rural india

A Beckstead*

LN Donovan

K Maves

A Patil

MA Budge

JW Thomas

B Fassl

A Judkins

School of Medicine, University of Utah, Salt Lake City, UT

Purpose of study

Newborn mortality in low resource settings shows only modest improvement despite investments in newborn health programs. In India, newborn mortality is reported as 32 per 1000 live births, with the majority of deaths due to birth asphyxia, low birth weight, and infections. These conditions are treatable if identified and managed early. The purpose of this study is to report on the quality of newborn care by healthcare providers in a community hospital in rural India following educational and QI interventions and to identify barriers to care delivery.

Methods used

The study took place at Mota Fofalia Community Health Center in rural Gujarat, India. Between 2015–2018, educational and QI interventions were provided to the staff. This study reports on changes in care quality over time. We measured the quality of healthcare delivery through direct observation of care by local providers, using a standardized, validated checklist, which was based on WHO best practice guidelines for newborn care. The checklist includes care practices for routine neonatal care, care for low birth weight infants, and the appropriate discharge of infants. We also performed a qualitative analysis of care delivery to identify barriers to the delivery of care and areas for improvement regarding personnel, equipment, and health system structure.

Summary of results

At baseline (2014), healthcare providers did not appropriately identify neonates as low birth weight (LBW) (0%, n26) and did not regularly provide appropriate inpatient monitoring (daily check of temperature, heart rate, respiratory rate) (0%, n138).

Postintervention analysis (2019) data show that training gradually impacted obtaining and recording regular weight values. 67% of neonates (14/21) were appropriately identified as high-risk LBW infants at birth, and 48% of LBW patients were appropriately discharged (>1800 g, feeding well, 10/21); appropriateness of daily newborn assessment, including vital signs, improved to only 20% (9/44). Significant barriers to care quality include a lack of adequate personnel and the availability of functional equipment staff feels confident using.

Conclusions

Despite educational and QI interventions, improvement in newborn care quality remains modest. Additional system strengthening interventions are needed.

102 Improving knowledge acquisition of rural healthcare providers in essential newborn care in nepal

J Vaughan*

B Fassl

A Chambers

A Sherpa

JW Thomas

A Judkins

University of Utah, Salt Lake City, UT

Purpose of study

Nepal ranks 148th out of 193 countries for neonatal mortality. Limited access to birthing facilities and training for healthcare providers pose barriers to improving outcomes. Many mountain villages rely on healthcare assistants (HA’s) for medical care, including child-birth. HA’s are lay-people with approximately 3 months of formal education and little to no emphasis on neonatal care, providing opportunity for educational intervention. With this study we sought to measure knowledge acquisition of health providers in the mountainous Humla district of North West Nepal in core tenets of newborn care, following standardized training interventions designed for low resource settings.

Methods used

To improve fundamental knowledge in newborn care, HA’s were trained by Nepali public health workers using the AAP’s Helping Babies Breathe (HBB) and Essential Care for Small Babies (ECSB) curricula in Fall, 2018. To evaluate content acquisition, knowledge tests for each curriculum (HBB and ECSB) were given before and after the 3 day training sessions. Scores from pre and post tests were compared for improvement using one-tailed paired t-test of means with alpha of 0.05.

Summary of results

For HBB, 11 HA‘s and 1 physician completed training and evaluation (n=12). There was a significant improvement in average scores before (M=0.715, SD=0.247) and after (M=0.938, SD=0.064) training (paired t(11)=-3.4, p<0.003). For the ECEB and ECSB, 10 HA‘s completed the course and evaluations (n=10). There was a significant improvement in scores from before (M=0.676, SD=0.081) to after training (M=0.773, SD=0.088) (paired t(9)=-2.2, p=0.03).

Conclusions

Our study demonstrates educational interventions with HBB, ECSB curricula for healthcare assistants in Nepal significantly increases knowledge acquisition of essential neonatal care. This study is limited by a small sample size from a single center and does not assess neonatal outcomes based on the educational intervention. Further studies will be required to assess retention of knowledge and clinical translation to neonatal outcomes following educational interventions with HBB, ECSB curricula.

103 Vector host preference of schistosome parasites in Kenya

C Ingram1,*

S Gay1

A Gleichsner2

M Mutuku3

E Reinhardt4

G Mkoji3

E Loker5

M Laidemitt5

M Steinauer1

1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Oregon, USA, Lebanon, OR

2State University of New York, Plattsburgh, NY

3Kenya Medical Research Institute, Nairobi, Kenya

4Purdue University, Chicago, IL

5University of New Mexico, Albuquerque, NM

Purpose of study

Schistosome parasites cause a chronic inflammatory disease in humans. Past evidence suggests that these parasites can detect macromolecules of their snail vector hosts; however, it is unclear if they can differentiate among potential hosts. Understanding host seeking behavior could lead to novel control strategies to prevent human infection.

Methods used

Using wild strains of African snails and parasites, we tested the hypothesis that parasites are attracted to the most susceptible host. We tested attraction to three snail species: Biomphalaria sudanica (BS), B. choanomphala (BC), and B. pfeifferi (BP) using choice chamber experiments in which parasites could orient toward a given snail stimulus. Attractiveness was assessed visually via microscopy by counting parasites that moved into each chamber toward stimuli.

Summary of results

Analysis indicated that miracidia were significantly more attracted to snail-incubated chambers compared to empty control chambers, indicating an attraction to all three snail species. In pairwise comparisons, we found that in some cases, the parasites were significantly attracted to the more susceptible species (BC v. BS), but in others, there was no significant difference (BS v. BP). Finally, we found a significant aversion of parasites to snails already infected with a parasite that preys on schistosome larvae within the snail, suggesting that the schistosome parasites can actively detect and avoid these predators.

Conclusions

The results of these experiments indicate that schistosomes use chemical signals to find hosts, and in some cases can differentiate signals to orient toward a host that will maximize their chance of successful establishment.

Hematology and oncology I

Concurrent session

3:15 PM

Thursday, January 23, 2020
104 Comparison of pseudoprogression in glioma patients following proton versus photon therapy

R Ritterbusch1,*

J Graber2

1University of Washington School of Medicine, Seattle, WA

2University of Washington, Seattle, WA

Purpose of study

Following radiation for glioma, new enhancements on MRI present a challenge in differentiating recurrent tumor and radiation-induced lesions, termed pseudoprogression (Ps). Criteria have been outlined to diagnose Ps after photon radiation by the Radiologic Assessment in Neuro-Oncology (RANO) group based on time and location of occurrence. Some patients receiving protons manifest changes that seem subjectively different in appearance, location and timing from photon Ps, and would be identified as recurrence. We retrospectively review post-treatment MRI changes of proton patients and compare the Ps seen after photon radiation. We propose a criterion to characterize proton pseudoprogression (PRoPs) distinct from photon.

Methods used

Post-treatment imaging of patients with gliomas were reviewed, along with clinical and pathological data. 74 proton patients were reviewed for the presence of PRoPs, and then 64 photon patients were reviewed for any matching imaging changes. Data collected included the location, timing, and morphology of the imaging change, tumor grade, molecular subtyping and chemotherapy received.

Summary of results

Thirteen patients (16%) received protons and had imaging changes unique to treatment with protons, which we term PRoPs (PRoton Pseudoprogression). We established the following criteria to characterize PRoPs: located not immediately in or adjacent to the resection cavity or residual tumor; located ~ 2 cm from target opposite proton beam entry; asymptomatic (unless simultaneous disease progression is also occurring); resolves without treatment, and some combination of subjectively multifocal, patchy, small (<1 cm). In the comparison group receiving photon, 0 had changes that met our criteria for PRoPs (p=0.001). The mean time when PRoPs occurred was 16.2 months after radiation.

Conclusions

Patients who receive protons are subject to a unique subtype of Ps that can mimic tumor progression. ProPs can possibly be explained by the increased Relative Biological Effectiveness (RBE) of protons and beam angle selection. Current RANO guidelines would inaccurately characterize ProPs as tumor progression. Using the radiation oncology treatment plan can help confirm the nature of the enhancement and prevent unnecessary treatment for mistaken tumor progression.

105 CRISPR-CAS9-based reactivation of a dormant tumor suppressor gene CDKN2A inhibits proliferation of skin cancer cells

DD Walker*

JW Lee

D Rokunohe

K Bradwisch

O Denisenko

K Bomsztyk

M Kawasumi

University of Washington, Seattle, WA

Purpose of study

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States and is often lethal with no reliable treatment when metastasized. It frequently manifests with inactivation of tumor suppressor gene CDKN2A, which encodes key cell cycle regulator p16INK4A. In cSCC, loss of p16INK4A expression is often due to epigenetic changes rather than genetic changes and may lead to progression and metastasis of this cancer. We investigated whether p16INK4A transcriptional suppression can be reversed by CRISPR-Cas9-based methods and whether targeted transcriptional reactivation of p16INK4A can inhibit cell proliferation in cSCC.

Methods used

We transduced cSCC cell line A431 with lentivirus containing nuclease-deactivated Cas9 (dCas9) fused to the catalytic domain of histone acetyltransferase p300 (dCas9-p300), which catalyzes acetylation of histone H3 at lysine 27 (H3K27ac). Alternatively, we transduced A431 with lentivirus containing dCas9 fused to transcriptional activator VP64 (dCas9-VP64). After drug selection to enrich transduced cells, we performed a second lentiviral transduction to introduce guide RNA (gRNA) directing dCas9 fusion proteins to the p16INK4A promoter within the CDKN2A locus. After one week of further drug selection, we collected these cells and measured p16INK4A mRNA expression (RT-qPCR) and cell proliferation (Cell Counting Kit-8).

Summary of results

RT-qPCR revealed that dCas9-p300 and dCas9-VP64, each with gRNA targeting the p16INK4A promoter within the CDKN2A locus, increased p16INK4A mRNA expression in A431 cells ~30–40-fold relative to untransduced cells. Both dCas9-p300 and dCas9-VP64 targeting the p16INK4A promoter reduced cell proliferation by ~20–30%. Increased p16INK4A expression correlated with decreased cell proliferation in these modified cells.

Conclusions

This study demonstrates that CDKN2A can be upregulated by targeted epigenetic modification or transcriptional activation, leading to inhibited cell proliferation. Future investigation will determine the kinetics, robustness, and off-target effects of targeted transcriptional reactivation tools. Targeted epigenome editing of cancer-relevant genes will be a versatile basis for precision anticancer therapies.

106 Identification of targetable vulnerabilities induced by type I interferon signaling in pancreatic ductal adenocarcinoma

AC Yu*

ER Abt

L Li

S Xu

CG Radu

T Donahue

University of California, Los Angeles, Los Angeles, CA

Purpose of study

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and intractable form of pancreatic cancer, due both to poor detection strategies and resistance to available therapies. One characteristic feature of PDAC is a pro-inflammatory tumor microenvironment with high levels of type I interferons (IFN), such as IFNβ. This study aimed to determine the effects of type I IFNs on PDAC cell signaling and metabolism and also aimed to identify novel targetable vulnerabilities within these pathways.

Methods used

Global and targeted metabolic profiling assays were performed via nLC-MS to comprehensively characterize the effects of IFNβ on PDAC cell metabolism. Targetable dependencies of IFN signaling were determined via integrated analysis of global phosphoproteomic changes and a high-throughput viability screen of protein kinase inhibitors. A panel of cell lines representative of the phenotypic heterogeneity of PDAC was used to confirm metabolomic and phosphoproteomic findings as well as the observed therapeutic synergy between high-scoring protein kinase inhibitors and IFNβ. A novel genetic PDAC model with inducible autocrine type I IFN signaling was developed for in vivo studies.

Summary of results

Type I IFN signaling induced the replication stress response via activation of the kinase Ataxia Telangiectasia and Rad3-related protein (ATR) and its downstream substrate, checkpoint kinase 1 (CHEK1). Type I IFN exposure also resulted in nucleotide insufficiency, a well-established trigger for the replication stress response. PDAC cell lines with high type I IFN signaling were more sensitive to ATR inhibition (ATRi), as IFNβ and ATRi were synergistic in causing S-phase arrest, inhibition of cell proliferation, and nucleotide insufficiency. These effects were replicated in vivo, as ATRi was effective in reducing the growth of orthotopic PDAC tumors with high type I IFN signaling.

Conclusions

Our findings show ATR inhibition, which is intensively studied in phase I/II clinical trials for cancer treatment, is a promising therapeutic approach for PDAC tumors with high type I IFN signaling.

107 Delivery of adjuvants with C3-targeting liposomes leads to myeloid cell activation for cancer immunotherapy

D Heald*

M Kullberg

H Martinson

University of Washington, Anchorage, AK

Purpose of study

Cancer immunotherapy treatments have gained much popularity recently, with many different pathways being targeted, including toll-like receptors (TLRs). These receptors have been implicated in tumor suppression via cytokine stimulation and as such, TLR agonists have shown promise in promoting tumor reduction in several cancer models. One such successful model is by use of liposomes to deliver these agonists. There is a lack of data, however, on what the exact mechanism is by which these TLR agonists are affecting tumors, which is important for understanding their safety and efficacy.

Methods used

In healthy C57BL/6 mice, bone marrow cells were treated in vitro and then underwent qPCR to determine gene expression for specific cytokines. Treatments included PBS, naked control and C3 liposomes, and control and C3 liposomes with TLR agonists encapsulated. In BALB/c mice with breast cancer, an identical method was used for obtaining PCR data, but treatments differed. These treatments were PBS, control and C3 liposomes with free TLR agonists, and control and C3 liposomes with TLR agonists encapsulated. The TLR agonists utilized were MPLA, CpG, and R848, and the genes examined included IL-1β, IL-6, TGF-β1, IP-10, and IRF-7.

Summary of results

In the C57BL/6 mouse, there was a significant increase in expression in the C3 with TLR agonist group for IL-1β, IL-6, IP-10, and IRF-7. Also, TGF-β1 expression was significantly reduced in TLR agonist encapsulated groups when compared to PBS. In the BALB/c mouse, the control and C3 with encapsulated agonist did show increased IL-6 expression, and these two groups along with the C3 and free agonist group showed increased IRF-7 expression. For IL-1β and IP-10, the four treatment groups did show increased expression compared to PBS.

Conclusions

In the C57BL/6 mouse, delivering TLR agonists via a C3 liposome showed increased expression of anti-tumor cytokines, as well as decreased expression of TGF-β1, a pro-tumor cytokine, elucidating how these agonists work. In the BALB/c mouse, each treatment group showed increased expression for anti-tumor cytokines. The C3 liposome may not have been as effective in this environment due to cytokine saturation; more research is needed.

108 Radiogenomic model for detecting prostate cancer

N Oune1,*

MT Nguyentat2

A Sasani1

P Bhatter1

C Chahine1

PA Kohanteb1

J Glavis-Bloom1

E Uchio1

R Houshyar1

1University of California Irvine Medical Center, Orange, CA

2University of Colorado Anschutz Medical Campus, Aurora, CO

Purpose of study

Multiparametric MRI (mpMRI) utilizing Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) can accurately detect prostate cancer (PCa). Genomic data shows overexpression of Prostate Cancer Gene 3 (PCA3) in patients with PCa. However, no studies integrate these 2 indices. We propose a radiogenomic model amalgamating PCa mpMRI and PCA3 to predict clinically significant PCa (csPCa).

Methods used

147 consecutive patients who underwent digital rectal exam, PCA3 testing, prostate mpMRI, and MRI/TRUS Fusion Biopsy were included. PI-RADSv2 criteria was utilized for mpMRI. csPCa was defined as Gleason Score ≥ 7. Logistic regression, odds ratio (OR), and Area Under the Curve (AUC) were performed for correlation and accuracy.

Summary of results

For a total of 266 lesions we included 3 independent predictors of csPCA: PIRADSv2 (OR 3.9, 95% CI 2.5–6.0), DRE (OR 2.6, 95% CI 1.2–5.5), and PCA3 (OR 1.0, 95% CI 1.0–1.0). The specificity, negative predictive value (PV), sensitivity, and positive PV achieved were 91%, 82%, 50%, and 31%, respectively. Our model’s AUC (0.81, 95% CI 0.75–0.87) was greater than that of PIRADSv2 (0.77, 95% CI 0.71–0.84), PCA3 (0.69, 95% CI 0.61–0.76), and DRE (0.56, 95% CI 0.48–0.64) alone.

Conclusions

A combined PCA3 and mpMRI radiogenomic model demonstrates improved AUC for predicting csPCa. Applying this model in clinical practice may decrease unnecessary biopsies and reduce cost and morbidity.

109 Activation of proteasome by inhibiting autophagy in corneal epithelia cells with limbal stem cell deficiency

D Cortez1,2,*

F Bardag-Gorce1,2

Y Niihara1

1The Lundquist Institute Harbor-UCLA, Torrance, CA

2Charles R. Drew University of Medicine and Science, Los Angeles, CA

Purpose of study

Previously, failure of UPP (Ubiquitin Proteasome Pathway) was found associated with an activation of autophagy in corneal epithelial cells with limbal stem cell deficiency (LSCD). However, autophagy activation does not remove damaged, aggregated proteins such as keratins (K4 and K13). The present hypothesis proposes that UPP activation might increase the clearance of misfolded proteins including K4 and K13, improving corneal epithelial cell function.

Methods used

Rabbits with surgically-induced LSCD were used to quantify the elements of both pathways in corneal epithelial cells (CEC). Rabbit oral mucosa epithelial cells (OMECS) as, similar to conjunctival epithelial cells, are rich in K4 and K13. OMECS were isolated, cultured and treated with proteasome inhibitors and chloroquine to inhibit autophagy. Morphologic analysis of corneal tissue sections showed that both pathways stained positive in normal corneal epithelium.

Summary of results

While constitutive proteasome beta subunits B1, B2 and B5 were decreased, autophagy biomarkers – ATG5 and MAPLC3B, were significantly increased in LSCD-CEC. However, despite autophagy up regulation, modified K4 and K13 still deposited and accumulated in LSCD-CEC without clearance. Proteasome inhibition in OMECS also showed a significant increase in ATG12, ATG5 and MAPLC3, confirming our observation that when UPP is defective, autophagy is stimulated. Additionally, when autophagy was inhibited in OMECS using chloroquine, our results showed not only an increase in proteasome chymotrypsin-like activity, but also a significant decrease in unmodified K4 and K13 levels with no keratin high molecular weight deposition.

Conclusions

Proteasome activation in the ocular surface could be used to alleviate corneal epithelial cell dysfunction associated with LSCD.

110 Deep learning for prostate segmentation: case volume and performance

J Carbone*

M Bardis

A Sasani

C Chahine

P Bhatter

H Liu

P Chang

R Houshyar

University of California Irvine Medical Center, Orange, CA

Purpose of study

Deep learning analysis of medical images is a data hungry challenge. However, few studies have systematically calculated the ideal number needed to balance training and performance. Here, we examine this question through quantifying the neural network (NN) performance of prostate organ segmentation against the number of samples.

Methods used

This IRB approved retrospective review includes patients who had a prostate mpMRI between 9/2014 and 8/2018 and a MR-guided transrectal biopsy. A board-certified abdominal radiologist manually segmented each prostate organ on the T2 weighted images (T2WI). This study used our customized Hybrid 3D/2D U-Net architecture and kept the same hyperparameters across the different NN runs. A total of 400 patients were available for training and validation. This study only changed the number of accessions fed into the NN and overall dice score was calculated with these patient numbers: 8, 16, 24, 32, 40, 80, 120, 160, 200, 240, 280, 320. During validation, the maximum number of available patients was used for the overall dice score calculation i.e. when the NN trained in 40 patients, the validation was completed on 360 patients.

Summary of results

This study used 400 patients’ T2WI. The overall dice score varied from 0.424 with 8 patients to 0.867 with 320 patients with 0.800 reached at 80 patients (figure 1).

Conclusions

The Hybrid 3D/2D U-Net for prostate segmentation produced the highest overall dice score of 0.867 at 320 patients. The performance improved most significantly when the patient number changed from 8 to 16, and it started to plateau at 160 patients. The performance only improved by 0.09 from 160 to 320 patients.

111 Vetting the quality of available online information for patients with glioma

S Kipfer1,*

P Ingledew2

1University of British Columbia, Vancouver, BC, Canada

2BC Cancer, Vancouver, BC, Canada

Purpose of study

The internet has become an invaluable source of information, both easily accessible and widely used. However, the quality of information online cannot be guaranteed. Glioma is the most common of all CNS neoplasms, yet little work has been done to explore the extent and quality of information online. Physicians must be aware of available online information to identify errors and gaps to better guide their patients‘ self-directed glioma research.

Methods used

The term ‘glioma’ was searched in Google and the meta-search engines Dogpile and Yippy, resulting in over 12.5 million hits. The top 100 websites averaged from these three search engines relating to patient information were analyzed using a structured rating tool. The websites were assessed based on affiliations, accountability, interactivity, site organization, readability, and content quality.

Summary of results

In assessing the top 100 websites on glioma, it was found that 53% of the websites were commercial, and 7% of the websites were affiliated with an academic institute. Less than half of the websites provided authorship (40%) and cited sources (48%). About half (52%) stated the date of website creation, but only 38% of the websites identified dates of modification to content. A total of 26% of the websites had been updated within the last two years, with 66% of the websites last updated over four years ago. The majority of websites provided users with an in-site search engine as an interactive tool (86%), however, only 12% provided a discussion board or forum. In assessing readability, only 5% of the websites were readable at a level below grade 8 (elementary level). Almost all websites covered definition (91%) and treatment (92%), but very few of the websites covered prevention (4%). A total of 4% of the websites covering definition, and 4% covering treatment, provided inaccurate information.

Conclusions

Analysis of the top 100 websites relating to glioma revealed there is a lack of current and understandable information available to patients online. A lot of the information available is not reliable due to a lack of cited author(s) and sources. Although the majority of sites covered definition and treatment of glioma, many other topics were poorly covered, including etiology/risk factors, prevention, and prognosis.

112 Cutaneous metastasis of urothelial carcinoma resulting in vascular occlusion and livedo racemosa

A Savell1,*

B Morris1

M Heaphy2

1University of Nevada, Reno School of Medicine, Reno, NV

2Skin Cancer and Dermatology Institute, Reno, NV

Introduction

A skin metastasis can be the first sign of an underlying visceral neoplasm and clinical presentation can be highly variable, making clinical diagnosis of these metastases challenging. Follow up investigations are often required to establish the location of the primary. Cutaneous metastases are a known but uncommon manifestation of urothelial carcinoma.

Livedo reticularis is physical sign of the skin which presents as a net-like pattern consisting of macular, violaceous rings. Livedo racemosa is a pathologic form of livedo reticularis which is often associated with vaso-occlusive disorders. Both livedo reticularis and livedo racemosa arise secondary to dilation of the skin’s venous plexus which may be due to vasospasm, vasculopathy, or coagulopathy. Few cases of livedo reticularis or racemosa related to malignancy have been reported in literature and none describe vascular obstruction by tumor thrombus as the source of livedoid pattern.

Case report

In this report, we describe an 82-year-old male with a history of urothelial carcinoma who presented to clinic with multiple, erythematous nodules in his right groin and a livedo-reticularis-like rash covering the anterior surface of his right thigh. Biopsies were taken from nodules in the right groin and livedoid patches on the right thigh. Those taken from nodules in the right groin were positive for cytokeratin 7 (CK7) and cytokeratin 20 (CK20), consistent with the original pathology report that diagnosed urothelial carcinoma and metastatic deposits in a right-groin lymph node. Biopsies taken from livedoid patches on the right thigh were also CK7+/CK20+; but more remarkably, microscopic investigation of the tissue and staining with endothelial cell markers CD31 and CD34 showed intravascular tumor thrombus as the source of vascular occlusion causing the livedoid pattern.

Implications

This case report discusses the rare occurrence of cutaneous metastases of urothelial carcinoma and the novel finding of intravascular occlusion by metastatic carcinoma as the cause of livedo racemosa.

113 Two cases of locus minoris resistentiae in cancer metastasis

J West1,2,*

H Saab1

E Cobos1

1Kern Medical Center, Bakersfield, CA

2American University of the Caribbean, Cupecoy, Sint Maarten (Dutch part)

Purpose of study

Locus Minoris Resistentiae is a phenomenon in which previously damaged tissue is less resistant to microorganisms. This is noted to occur in infectious processes but has not been well documented in the setting of cancer metastasis. These cases demonstrate the potential of metastatic preference in cancer to previous areas of tissue compromise with less resistance than other healthier locations in the body.

Methods used

Retrospective case reports.

Summary of results

Case 1: Patient is a 63-year-old female diagnosed with Stage IVA serous carcinoma of the ovary with a history significant for prior breast augmentation. Initial diagnosis was made after presenting to the emergency department complaining of shortness of breath. A CT of the chest demonstrated a 16 × 14 × 16 cm pelvic mass and right sided pleural effusion. Thoracentesis identified malignant ovarian cancer cells. The patient underwent surgical debulking and completed eight cycles of chemotherapy. On physical exam after surgical debridement, it was noted the scar on the right breast from the breast implant procedure was distorted and hard. Further evaluation showed metastatic ovarian cancer in the surgical scar. After chemotherapy completion, she was started on maintenance therapy with Avastin due to increased tracer uptake was noted.

Case 2: Patient is a 56-year-old male initially diagnosed with prostate adenocarcinoma Stage II and history significant for a previous back injury to the L4 vertebrae. Initial treatment included 15 cycles of radiation along with Lupron Depot and Casodex for 3 months. Due to the side effects on the Lupron, the patient discontinued the Lupron with close follow up of PSA levels to monitor for recurrence. Nine months after stopping the Lupron, his PSA levels began to increase and the patient began to experience worsening back pain. An MRI of the spine was obtained due to the back pain which demonstrated potential prostate cancer recurrence with metastatic lesions noted at the L4 vertebrae.

Conclusions

Locus Minoris Resistentiae is important to understand in the setting of metastatic cancer. Identifying areas of previous tissue compromise might lead to earlier identification of metastatic disease. This could potentially lead to earlier and more effective treatment and management of such cases.

Neonatology general II

Concurrent session

3:15 PM

Thursday, January 23, 2020
114 Implementaion of eat, sleep, console as primary treatment for neonatal abstinence syndrome (NAS) in a level iv nicu

C Egesdal*

P Joe

J Kuller

B Flushman

K Ponder

UCSF Benioff Children’s Hospital Oakland, Oakland, CA

Purpose of study

The aim of our project was to implement the Eat-Sleep-Console (ESC) approach for infants admitted with NAS to our Level 4 NICU, and improve outcomes defined as a reduction of average length of stay (LOS) by at least 50% and a reduction in morphine exposure by 50%.

Methods used

ESC training was provided to NICU nursing staff. NAS babies were assessed for their ability to coordinate or sustain feeding, sleep for > than 1 hour, and be consoled within 10 minutes. Infants abilities to accomplish these physiologic outcomes guided pharmacologic and non-pharmacologic interventions. Non-pharmacologic interventions were prioritized and pharmacologic treatment using morphine or clonidine was provided when necessary.

Medical records for NAS babies born 2019–2020 were reviewed for type of in utero drug exposure, length of hospital stay, opioid treatment days, hours held by volunteers, discharge disposition, and readmission rates. Our NICU baseline retrospective data from 2015–2018 was obtained from the Children’s Hospitals Neonatal Consortium database for comparison. Infants who were premature (<33w GA), on iNO, or on HFOV were excluded. All data was de-identified and was compared using a two-sample t test.

Summary of results

A total of 12 infants were enrolled in our study from January to August of 2019. A total of 29 infants were used for comparison using our retrospective data from 2015–2018. The mean length of stay at our institution for babies with a primary diagnosis of NAS decreased from 29.8 days to 10.3 days, a reduction of 65%, with a p value of 0.002. Morphine exposure days, defined as a 24 hour period during which an infant received morphine, decreased from a mean of 24.2 days to 0.42 days, a reduction of 98%. We recorded an average of 27.7 hours per infant of volunteer cuddling. 11/12 of our infants were placed in foster care following discharge.

Conclusions

Our project displays that the Eat, Sleep, Console approach is an effective option even for patients admitted to a high acuity level IV NICU without a mother present to provide care. With the use of ESC in addition to adjunctive approaches such as volunteer cuddlers and automated smart sleeper beds, we were able to significantly decrease the length of stay and morphine exposure of patients in our unit admitted with NAS.

115 Utilization of functional echocardiography and near-infrared spectroscopy to characterize ductal hemodynamics in the premature neonate

M Ringle*

VY Chock

K Stauffer

L Lopez

R Punn

S Bhombal

Stanford University, Palo Alto, CA

Purpose of study

Echo is used for determining a hemodynamically significant duct (hsPDA) in the preterm neonate. Near-infrared-spectroscopy (NIRS), a noninvasive modality provides continuous feedback of organ perfusion. Historically, echo is used to diagnose ductal patency, and NIRS used for perfusion monitoring; rarely have they been used together to assess the duct. We aim to use the combined technology of echo and NIRS to identify patients with a hsPDA, as well as explore the possibility of solely using NIRS to identify and continuously monitor patients with a hsPDA.

Methods used

Infants born <30 weeks at the Packard Children’s Hospital NICU are enrolled for echoes on DOL 3, 5, 7, 14, and 30. Cerebral and renal NIRS are obtained with each echo. A hsPDA is based on measurements of ductal characteristics, markers of pulmonary overcirculation, and systemic perfusion.

Summary of results

We have 12 patients and 51 echoes with NIRS correlates; 18% show a hsPDA. The mean renal NIRS for infants with a hsPDA was 54 compared with 68 (p=0.001) for infants without a hsPDA. Cerebral NIRS for infants with a hsPDA was 60 vs 72 (p=0.0005) without. All infants with hsPDAs were born <27 weeks gestation and with a birth weight <1000 grams. We did not find any significant difference in mode of respiratory support or enteral feeding patterns.

Conclusions

When correlated with echo, we conclude that NIRS may be an adequate surrogate for a hsPDA, with renal NIRS showing greater variability, and should be utilized in neonates who are at high risk for a hsPDA.

116 Randomized trial comparing effect of different epinephrine doses and flush volumes in a perinatal model of asphyxial arrest

D Sankaran1,*

P Chandrasekharan2

S Gugino2

C Koenigsknecht2

J Helman2

J Nair2

B Mathew2

M Rawat2

P Vali1

L Nielsen2

S Lakshminrusimha1

1UC Davis, Sacramento, CA

2University at Buffalo, Buffalo, NY

Purpose of study

Current NRP guidelines recommend administration of 0.5–1 ml flush following epinephrine dose (0.01–0.03 mg/kg) via low umbilical venous catheter (UVC). This flush volume may not be adequate for epinephrine to reach right atrium and there are no pharmacokinetic/efficacy/safety studies comparing 0.01 vs. 0.03 mg/kg of epinephrine via low UVC.

Methods used

Asystole was induced by umbilical cord occlusion and resuscitation was initiated after 5 min of asystole. After 5 min of resuscitation per NRP guidelines, lambs were randomized to receive either 0.01 mg/kg (low dose) or 0.03 mg/kg (high dose) of epinephrine followed by either low flush (1 ml) or high flush (10 ml) of saline.

Summary of results

Out of 37 lambs, 9 had ROSC before epinephrine administration. Among lambs that received epinephrine,33% in low dose-low flush, 50% in low dose-high flush, 71% in high dose-low flush and 100% in high dose-high flush achieved ROSC. Time to ROSC was shorter with high dose-high flush compared to low dose-low flush (p=0.01). Higher peak plasma epinephrine levels were achieved with high dose-high flush at 1 min after epinephrine and flush (1086±503 ng/ml) compared to other groups (figure 1). After ROSC, lambs that received high dose epinephrine had higher heart rates.

Conclusions

Use of high dose-high flush led to higher peak plasma epinephrine levels resulting in higher and earlier occurrence of ROSC. Recommendation of 0.03 mg/kg of epinephrine followed by high flush of 3 ml/kg by NRP may simplify the algorithm, reduce errors and expedite ROSC.

117 Revision of tracheal suction guidelines for infants born through meconium stained amniotic fluid (MSAF): changing clinical significance of ‘non-vigorous’ state

AJ Leegwater1,*

P Vadlaputi2

S Lakshminrusimha1

VK Kalra1

1UC Davis Medical School, Sacramento, CA

2UC Davis Health Services, Sacramento, CA

Purpose of study

In 2016, the Neonatal Resuscitation Program (NRP) recommended that resuscitation of non-vigorous infants with MSAF follow the same principles as for those with clear fluid. Studies have shown increased respiratory morbidity among these infants after implementation of new guidelines. We hypothesize that babies who remain non-vigorous despite stimulation represent a sicker cohort of infants compared to non-vigorous babies immediately after birth undergoing routine tracheal suctioning.

Methods used

Detailed review of the hospital course of all infants born with MSAF at UC Davis Medical Center between Dec 2013- Feb 2014 (Era-1) was compared to infants born between Jan-April 2014 (Era-2).

Summary of results

Records of 428 and 461 consecutively born neonates before and after implementation of new NRP guidelines were screened. Incidence of MSAF (10.3% vs 10.2%) and characteristics were similar (table 1). In era-1, 8 babies were labeled non-vigorous and all underwent tracheal suction. Only one infant (29 week gestation) required admission and respiratory support. In era-2, 4 babies were non-vigorous despite stimulation and all required NICU admission and respiratory support.

Conclusions

‘Non-vigorous’ infants born through MSAF in the routine-suction era were less sick compared to persistently non-vigorous infants despite stimulation in era-2. Future studies should use MSAF as the denominator (and not non-vigorous) while comparing the outcomes.

118 Lack of utility of tracheal aspirates in intubated neonates

S Langston*

N Pithia

M Sim

M Garg

A de St Maurice

A Chu

University of California Los Angeles, Los Angeles, CA

Purpose of study

To evaluate the utility of tracheal aspirate (TA) cultures in suspected pneumonia in intubated neonates and measure the burden of antibiotic use associated with a positive TA culture.

Methods used

A single-site, retrospective chart review was conducted on patients in the NICU between January 2016 and December 2017. Infants who were intubated and had a tracheal aspirate culture sent for suspected infection were eligible. Exclusion criteria included infants with ureaplasma/mycoplasma infections or infants with a tracheostomy. Infants were identified by electronic medical record review by the UCLA Microbiology lab showing the presence of a TA culture. At the time the culture was sent and within 24 hours, clinical findings, laboratory, and radiographic study results were recorded. Patient demographic information, including gestational age (GA), sex, birth weight (BW), route of delivery, Apgar scores at 1 and 5 minutes, diagnosis of chronic lung disease (CLD), and death before hospital discharge, was collected.

Summary of results

84 infants were included in our analysis. 46% of infants (39/84) had a positive TA. Patients with a positive TA culture had smaller BWs (p<0.0001) and lower GAs at birth (p<0.0001) than their negative culture counterparts. They were more likely to require mechanical ventilation for greater than 7 days (p=0.002) and carry a diagnosis of CLD or BPD by time of discharge from the NICU. Presence of white blood cells (WBCs) on gram stain, abnormal changes from baseline CXR, serum WBC values, or abnormal CRP were not associated with having a positive TA. A normal I:T ratio was more likely to be associated with a positive TA culture (p=0.005). 85% of patients with a positive TA received prolonged antibiotics (>72 hours) compared to 56% of patients with a negative TA (p=0.004). Out of those patients with prolonged antibiotic courses, 81% received broad-spectrum antibiotics if they had a positive TA culture versus 48% that did not have a positive culture (p=0.001).

Conclusions

Positive TA cultures are not associated with commonly used laboratory or radiographic biomarkers of infection or the need for increased respiratory requirements, yet do increase risk of exposure to prolonged antibiotic courses with broad-spectrum agents.

119 Factors associated with adverse events and success during neonatal endotracheal intubation

LE Yaeger1,*

H Muniraman2

R Ramanathan1

M Biniwale1

1LAC+USC Medical Center, Los Angeles, CA

2Neonatology Association Limited, Obstetrix Medical Group of Phoenix, Mednax, Phoenix, AZ

Purpose of study

Endotracheal intubation is a commonly performed procedure in the neonatal intensive care unit (NICU) but is technically difficult and has a high risk of complications. The aim of this study is to evaluate the frequency with which adverse events occur during intubation in our institution and evaluate the characteristics of a successful intubation.

Methods used

This was a prospective, observational study of infants who were admitted to the NICU at LAC+USC Medical Center between July 2016 and June 2019. IRB authorization was obtained prior to the start of the study. All infants requiring intubation during admission in the NICU or delivery room setting were included in the study. Factors related to infant, procedure and provider for each encounter were collected immediately following the procedure.

Summary of results

There were 193 intubation encounters with 398 attempts performed that met inclusion criteria.The mean gestational age was 31 weeks with a mean birth weight 1751 g. Adverse events occurred in 19.6% of intubation encounters and bradycardia was the most common complication (36.8%). Intubations performed outside the NICU were more likely to have adverse events (35% vs. 15%, p=0.005). Multiple intubation attempts were not associated with increased risk of complications (p=0.100).There was a correlation between training level and the likelihood of success on the first attempt, with an attending neonatologist obtaining success 73% of the time compared to a neonatology fellow at any training level successful 54% of the time (p=0.012). A lower birth weight increased the likelihood of requiring more attempts (p=0.046). Pre-medication was not associated with successful intubation on the first attempt (p=0.315) or decreased likelihood of complications (p=0.72).

Conclusions

Adverse events occur frequently during intubation and success of intubation on the first attempt depends on the experience level of the provider. An increase in the incidence of adverse events is associated with intubation occurring outside the NICU but not with a higher number of intubation attempts. Premedication does not improve success of intubation on the first attempt or decrease complications.

120 Variations in caffeine use for apnea of prematurity in preterm infants in the united states

E Sander1,*

J Shepherd2

1LAC+USC Medical Center, LA, CA

2CHLA, LA, CA

Purpose of study

The Caffeine for Apnea of Prematurity trial demonstrated that caffeine administration within the first ten days of life in extremely premature infants to treat apnea led to decreased rates of bronchopulmonary dysplasia, death, and neurodevelopmental disability. Recent retrospective studies have suggested that caffeine used prophylactically can lead to similar improved outcomes; however, there are no known large prospective studies proving the effectiveness and safety of prophylactic caffeine and no consensus that prophylactic caffeine should be used. We surveyed NICU medical directors in the United States to delineate variations in usage of caffeine in order to identify potential focuses for future research and guidelines development.

Methods used

An online survey with questions regarding various aspects of caffeine use was emailed to all NICU medical directors in the United States.

Summary of results

127/532 (24%) of medical directors completed the survey. The majority are at level III or IV NICU’s (95%) and are academically affiliated (67%). The most common reasons for initiation of caffeine include treatment of apnea (87%), prophylaxis for apnea (73%), and facilitation of extubation (59%). While 69% start caffeine soon after birth, only 34% discuss caffeine during the prenatal consult. Of those, only a third discuss potential side effects. Post menstrual age (PMA) (53%) is the most important factor in the decision to discontinue caffeine, followed by cessation of apneic episodes (42%). 34 weeks is the most common PMA to discontinue caffeine (62%). Neonates are monitored for an average of 6 days following cessation of caffeine prior to discharge. Most (70%) do not send infants home on caffeine. Of those who do, 61% send those infants home with an apnea monitor.

Conclusions

Caffeine is widely used in preterm neonates both early and prophylactically in the US, despite the lack of strong evidence. Often, parents receive little information about use and side effects of caffeine prenatally. There is variation in clinical indication for stopping caffeine and use of caffeine following discharge. Prospective studies should be aimed at determining optimal timing for initiation and discontinuation of caffeine, as well as to direct development of national guidelines.

121 Invasive ventilation decreases renal capillary surface density more than noninvasive respiratory support in term lambs

K Albertine*

E Staub

M Dahl

University of Utah, Salt Lake City, UT

Purpose of study

Ventilation, regardless of mode, decreases glomerular capillary surface density (SVgc) in the renal cortex of preterm lambs (Staub et al. 2017). We hypothesized that ventilation itself, not just renal immaturity, reduces SVgc. We compared SVgc of unventilated term lambs with two groups of ventilated term lambs: mechanical ventilation (MV) versus noninvasive respiratory support (NRS).

Methods used

Unventilated term lambs were euthanized 1d after birth (n=8). Ventilated term lambs were intubated after CS and ventilated by MV or weaned in 2–3h to NRS for 3d (n=5 each). Kidney sections were immunostained with endothelial surface marker CD31 and SVgc calculated by stereological techniques. Physiological data were compared for the two ventilated groups. Statistical differences were tested by t-test for parametrical data and Mann-Whitney-test for non-parametrical data.

Summary of results

After 3d of MV, SVgc was significantly smaller in the renal cortex of term lambs compared to non-ventilated 1d lambs. In contrast, NRS did not reduce SVgc compared to non-ventilated 1d lambs (figure 1). Mean airway pressure was significantly higher in MV lambs compared to NRS lambs throughout the 3d studies. Other ventilation and physiological parameters were similar in both groups.

Conclusions

Our results show that MV is associated with lower SVgc in the renal cortex compared to no ventilation or NRS. Our findings suggest that higher mean airway pressure is associated with lower glomerular filtration capacity even after nephrogenesis is complete. This may lead to poor renal function later in life. (HL110002, HL062875; Bangerter-Foundation).

Neonatology pulmonary II

Concurrent session

3:15 PM

Thursday, January 23, 2020
122 Folic acid treatment recouples endothelial nitric oxide synthase and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets

M Douglass*

Y Zhang

M Kaplowitz

C Fike

University of Utah, Salt Lake City, UT

Purpose of study

Hypoxia contributes to the development of pulmonary hypertension (PH) by promoting an uncoupled state of the enzyme endothelial nitric oxide synthase (eNOS) that produces superoxide instead of nitric oxide (NO). Folic acid has been shown to recouple eNOS and prevent the development of several hypoxia-induced markers of PH in a murine model. The impact of folic acid on recoupling eNOS in a piglet model of chronic hypoxia-induced PH is unknown. We tested the hypotheses that treatment with folic acid will increase eNOS recoupling in hypoxic piglet pulmonary artery endothelial cells (PAECs) and that treatment with folic acid will decrease pulmonary vascular resistance (PVR) in an in vivo piglet model of chronic hypoxia-induced PH.

Methods used

Piglet PAECs were cultured under hypoxic conditions (4% oxygen) for 48 hours with no folic acid or 1.0 µM folic acid. eNOS dimer-to-monomer ratios were measured by western blot. NO concentrations were quantified by chemiluminescence. Newborn piglets were obtained on DOL 2 and placed in a normobaric hypoxic chamber (10–11% oxygen) for 10 days. Some hypoxic piglets received 5 mg/kg/day of folic acid from days 3–10 of hypoxia while other hypoxic piglets received no folic acid. On DOL 10 hemodynamic measurements of pulmonary artery pressure, left ventricle end diastolic pressure, and cardiac output were obtained to calculate PVR.

Summary of results

Hypoxic PAECs treated with 1.0 µM folic acid (n=9) demonstrated increased eNOS dimer-monomer ratios compared to untreated hypoxic PAECs (n=9)(p<0.05). Hypoxic piglet PAECs treated with 1.0 µM folic acid (n=13) demonstrated a 16% increase in NO production compared to untreated hypoxic PAECs (n=13)(p<0.05). PVR was lower in hypoxic piglets treated with 5 mg/kg/day folic acid (n=5) compared to untreated hypoxic piglets (n=9)(p<0.05).

Conclusions

Folic acid increases NO production by improving eNOS recoupling in hypoxic piglet PAECs. In an in vivo piglet model, treatment with folic acid ameliorates chronic hypoxia-induced PH. These findings suggest that folic acid has therapeutic potential to treat PH in human infants suffering from cardiopulmonary conditions associated with chronic hypoxia.

123 Pulmonary function tests in very low birth weight infants screened for pulmonary hypertension

JD Adair*

B Kelly

D Schilling

K Parkhotyuk

A Kim

B Scottoline

L Gievers

C McEvoy

Oregon Health and Sciences University, Portland, OR

Purpose of study

Compare pulmonary function tests (PFTs) in very low birth weight (VLBW) infants with and without pulmonary hypertension (PH). We hypothesized that infants with PH would have an increased passive respiratory resistance (Rrs).

Methods used

Infants with PFTs at 34 to 38 weeks post menstrual age (PMA) as part of a PH screening guideline for infants born at ≤ 1500 grams with respiratory support at >34 weeks PMA were included. One pediatric cardiologist reviews the echocardiograms and estimates the right ventricular pressure. Rrs and passive compliance (Crs) were measured with the single breath occlusion and functional residual capacity (FRC) with the nitrogen washout method as per standardized criteria. Based on previous data, about 22 infants were needed per group to show a 25% difference in Rrs with a α of 0.05 and power of 80%.

Summary of results

22 VLBW infants with and 26 without PH were studied. Those with PH had a significantly lower birth weight. There were no other demographic differences between groups. The infants with PH had a significantly increased Rrs and decreased Crs.

Conclusions

In this pilot study of VLBW infants screened for PH at 34–38 weeks PMA, those with PH had a significantly increased Rrs and decreased Crs compared to those without PH. Additional studies are needed to further phenotype infants with evolving BPD and PH.

124 Longitudinal B-type natriuretic peptide measurement as prognostic marker for outcomes in congenital diaphragmatic hernia

E Guslits*

M Steurer

H Nawaytou

R Keller

UCSF, San Francisco, CA

Purpose of study

To evaluate B-type Natriuretic Peptide (BNP) as a longitudinal biomarker for clinical outcome in Congenital Diaphragmatic Hernia (CDH). We hypothesize that persistent elevation of BNP (>2 wks of age) is associated with mortality or need for prolonged respiratory support at 56 days (Steurer et al, 2014).

Methods used

Retrospective cohort study. Detailed clinical information and BNP levels (pg/ml) were collected for the duration of hospitalization. At 56d, infants were classified as Poor Outcome if deceased or receiving ongoing respiratory support or Good Outcome if alive off support. Infants with congenital heart disease other than ASD, VSD, or PDA were excluded. BNP levels were available at week of life 1 (n=35), 3 (n=43), 4 (n=37) and 5 (n=38); week 2 data were insufficient for analysis. At each time point, we generated receiver operator characteristic curves using log transformed BNP and defined the BNP cut-off that maximized correct classification.

Summary of results

Of 49 infants, 29 had Poor Outcome and 20 had Good Outcome. There were no differences between groups in median gestational age (Poor: 39.1wk, IQR 38.1–39.3 vs. Good: 39wk, IQR 38.3–39.3; p=0.81) or laterality (Left-sided, Poor: 76% vs. Good: 85%; p=0.44). Liver herniation into the thorax was more common in Poor (90%) than Good (50%) Outcome (p=0.002). All infants with ECMO support had Poor Outcome (n=7/29, 24%; p=0.018). Median age at extubation was significantly longer in Poor vs. Good Outcome (19d, IQR 14–23 vs. 8d, IQR 4–11; p<0.001).

Median BNP at 1wk was lower in Poor Outcome (480, IQR 259–1020 vs. 1009, IQR 551–1540; p=0.08). At wks 3, 4 and 5, median BNP was higher in Poor Outcome: (3wks: 666, IQR 466–1040 vs. 111.5, IQR 76.5–227.5; p=0.0004); (4wks: 281, IQR 135–448 vs. 37.5, IQR 33–75.5; p=0.0018); and (5wks: 96, IQR 70–301 vs. 29, IQR 17–58; p=0.0025).

Conclusions

Higher BNP at week 3–5 of life is associated with Poor Outcome in CDH. BNP cut-off points to predict Poor Outcome decline over this time frame.

125 Noninvasive respiratory support of preterm lambs leads to appropriate alveolar capillary growth

A Rebentisch1,*

MJ Dahl1

A Lavizzari2

E Dawson1

O johnson1

C Bradford1

C Veneroni3

Z Wang1

B Yoder1

D Null4

R Dellaca3

K Albertine1

1U of Utah, Salt Lake City, UT

2Ospedale Maggoire Policlinico, Milan, Italy

3Politecnico di Milano, Milan, Italy and

4UC Davis, Davis, CA

Purpose of study

We reported that long-term outcomes for former-preterm lambs that were mechanically ventilated (MV) for 6–7d during the first week of postnatal life had persistent structural simplification of alveoli at 5 months corrected postnatal age (cPNA) compared to postnatal age-matched control term lambs. Five months cPNA is equivalent to ~6 yr PNA in humans (Dahl 2018). Most recently, we reported that noninvasive respiratory support (NRS) used for resuscitation and continuing management led to structural indices of alveolar formation that were comparable to the same indices in the lung of control term lambs (Rebentisch, WSPR 2019; J Invest Med 67:91, 2019). However, the latter report did not assess alveolar capillary growth. Therefore, our aim was to quantify alveolar capillary growth in the lungs of the same former preterm lambs that were managed by NRS and control term lambs.

Methods used

Preterm lambs (~128d gestation; term ~150d; equivalent to lung development at ~28w gestation in humans) were resuscitated by NRS and continued with NRS for 6–7d (n=5; Rebentisch, J Invest Med 67:91, 2019). This NRS group was weaned from all respiratory support and lived for 5 months cPNA. Control term lambs lived for 5 months PNA (equivalent to ~6 yr postnatal ages in humans). Quantitative histology was used to compared alveolar capillary surface density between the NRS group of preterm lambs and control term lambs.

Summary of results

Former preterm lambs that were managed by NRS during the first week of postnatal life had the same alveolar capillary surface density (1,040±264 cm-1; mean±SD; n=5) as control term lambs (918±61 cm-1; n=5; not significant). Epithelial surface density, the reference space, was not different between the NRS group (4,274±843 cm-1; n=5) and the control term group (3,938±447 cm-1; n=5).

Conclusions

NRS management, including resuscitation, of preterm lambs is associated with equivalent long-term growth of alveolar capillaries compared to control term lambs. These results, combined with our recent results, suggest that NRS management leads to appropriate capillary growth and structural formation of alveoli. Supported by R01 HL110002 and Division of Neonatology

126 Gentle ventilation with permissive hypercapnia in HIE with PPHN: hemodynamic effects

A Lesneski*

M Hardie

P Vali

S Lakshminrusimha

UC Davis, Davis, CA

Purpose of study

Therapeutic hypothermia and permissive hypercapnia are strategies to manage hypoxic-ischemic encephalopathy (HIE) and persistent pulmonary hypertension of the newborn (PPHN). The objective of this study was to evaluate the effect of PaCO2 on pulmonary and carotid blood flow in lambs with severe HIE and PPHN under normothermia (36.5–37.5°C) and hypothermia (32–34°C).

Methods used

25 near-term gestation lambs were asphyxiated by umbilical cord occlusion. Meconium aspiration syndrome (MAS) was induced by instilling meconium into the lungs during gasping leading to PPHN. Lambs were ventilated with normocapnia (temperature corrected PaCO238–48 mmHg) or hypercapnia (50–60 mmHg). Analysis was performed adjusting for hemoglobin (Hgb) level (high: 13–15 g/dL or low: 9–12 g/dL) and temperature.

Summary of results

For pulmonary blood flow, high vs. low PaCO2 resulted in a non-significant decrease in geometric mean blood flow of 3% (95% CI for relative change:-4 to 12%, p=0.41). For carotid blood flow (figure 1), high vs. low PaCO2 resulted in a statistically significant increased geometric mean blood flow of 16% (95% CI for relative change 0.1% to 34%, p<0.05).

Conclusions

Within a clinically relevant PaCO2 range of 38 to 60 mmHg, there is no significant alteration in pulmonary blood flow in lambs with HIE and PPHN. In contrast, hypercapnia is associated with an increase in carotid flow and possibly increased O2 delivery to the brain. Clinical trials evaluating long-term effects of permissive hypercapnia (PaCO250–60 mmHg) are warranted in HIE with PPHN.

127 Nasal high frequency jet ventilation versus nasal intermittent positive pressure ventilation as a mean of post extubation respiratory support

T De Beritto

JJ Keel*

R Ramanathan

M Biniwale

R CAYABYAB

Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center, Keck School of Medicine, University of Southern California, Los Angeles, CA

Purpose of study

To describe our experience of successfully using nHFJV superimposed on to nasal intermittent positive pressure ventilation (NIPPV) after extubation or when NIPPV mode is failing to maintain blood gases in an acceptable range in ELBW infants.

Methods used

All ELBW infants who received nHFJV while in the NICU were included in this study. IRB approval was obtained. Data was collected using NICU database and electronic medical records. The Bunnell Life Pulse HFJV was used to provide settings of: Jet PIP 30- 35 cmH2O, Jet Rate 240–300 bpm, Inspiratory time (IT) of 0.03 s. NIPPV rate on the conventional ventilator was set at 40 bpm, PIP at 30 cmH2O, PEEP 8–10 cmH2O, and IT at 0.5 s.

Summary of results

Fourteen ELBW patients met the criteria for inclusion. Mean birth weight was 642 g and mean gestational age was 24.5 weeks. In 9 patients, nHFJV was used as a primary mode of extubation along with NIPPV after invasive HFJV treatment while in 5 patients it was used as a rescue mode when NIPPV settings were maximized with hypoxia and carbon dioxide retention. Twelve patients (86%) remained successfully extubated by 72 hours of treatment. Mean duration of invasive and non-invasive ventilation was 36 days and 45 days respectively. Duration of nHFJV was a mean of 9 days before discontinuing nHFJV. Twelve of 14 patients were on room air at the time of discharge.

Conclusions

This is the first reported case series of the successful use of rescue nHFJV in conjunction with NIPPV to avoid reintubation in ELBW infants. Additional studies are needed to evaluate this mode of support in ELBW infants failing non-invasive modes of respiratory support.

128 Neurobehavioral outcomes of former preterm lambs are better when respiratory management is noninvasive compared to invasive

E Dawson1,*

S Bowen1

E Voll1

A Havlicak1

J Beachy2

MJ Dahl1

C Veneroni3

A Lavizzari4

D Null5

R Dellaca3

K Albertine1

1U of Utah, Salt Lake City, UT

2Cohen Children’s Med Ctr, New York, NY

3Politecnico di Milano, Milan, Italy

4Ospedale Maggoire Policlinico, Milan, Italy

5UC Davis, Davis, CA

Purpose of study

Neurobehavioral impairments may be a long-term outcome for survivors of premature birth and invasive mechanical ventilation (MV). Former preterm (FPT) lambs develop diffuse brain damage, evident as increased apoptosis, and decreased proliferation, of neurons and glia compared to other premature lambs managed by noninvasive respiratory support (NRS) or term lambs that are not ventilated. We developed neurobehavioral tests of learning and memory for normal term lambs (Bowen, J Invest Med 64:294, 2016). We used these tests to assess the hypothesis that neurobehavioral outcomes will be better when management is by NRS compared to MV.

Methods used

Three groups of FPT lambs were studied: (1) MV for 6–7d, n=6, (2) NRS, including for resuscitation, for 6–7d, n=5, (3) MV for ~3h followed by NRS for 6–7d, n=5. The FPT lambs lived for 6 months (5 months corrected postnatal age, cPNA; equivalent to ~6 years for humans). Control term lambs were the fourth group (n=8). Tests were repeated at 2 and 5 months. Lambs were habituated to the tests before having two 10-min trials/test (one test/d). Tests were separated by 30-min of rest. The routine was repeated the next day. Different tests were separated by a rest day. One test used a mirror and a non-reflective surface to test socialization. Another test used a maze, for which the reward was ewe’s milk, to test memory and problem solving.

Summary of results

For the 5-month test, 6–7d MV FPT lambs spent significantly more time at the non-reflective surface (8 (24) sec; median (IQR) than NRS FPT lambs (1 (8) sec; p<0.05). No differences were detected between the NRS FPT, MV for ~3h then NRS FPT, and control term groups. For the 5-month maze test, no differences in time to find the reward were detected between the 6–7d MV FPT lambs (7 (134) sec) and NRS FPT group (5 (2) sec).

Conclusions

Our results suggest that FPT lambs that were managed by MV during the first week of postnatal life have worse long-term neurobehavioral outcomes than NRS FPTs lambs. The range for the MV FPT lambs implies variability that may provide opportunity to identify underlying mechanisms. (HL110002 and Division of Neonatology).

129 Exposure to cannabidiol (CBD) results in myogenic differentiation and altered function in fetal rat lung fibroblasts

A Harb*

Y Liu

R Sakurai

Y Wang

V Rehan

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA

Purpose of study

Previously, we have demonstrated that perinatal nicotine exposure disrupts specific epithelial-mesenchymal paracrine signaling pathways, resulting in pulmonary interstitial fibroblast transdifferentiation to a myogenic phenotype. Recently, cannabidiol (CBD) has been implicated as one of the emerging contributors to the recent teen lung disease crisis in the US. However, it is unknown how CBD affects lung fibroblast differentiation and the developing lung.

Since a balance between Wnt and PPARγ signaling is a key determinant of lung interstitial fibroblast phenotype, i.e., lipogenic vs. myogenic, using a well-established in vitro model, we tested the hypothesis that CBD exposure would up-regulate Wnt and down-regulate PPARγ pathways in fetal rat lung fibroblasts.

Methods used

Using established methods, embryonic day 19 Sprague-Dawley rat lung fibroblasts were treated for 24 or 72 h with CBD (10-9, 10-8, 10-7, 10-6 M). Rate of triglyceride uptake, a key indicator of lipofibroblast function, was assessed through [3H]-triolein uptake assay. Mesenchymal markers of differentiation were determined by western analysis and qRT-PCR.

Summary of results

As assessed by differentiation and functional assays, CBD treatment affected fibroblast phenotype dose- and time-dependently. However, contrary of our hypothesis, both lipogenic and myogenic markers increased significantly at both time-points examined with more profound changes following 72 h exposure. In particular, Wnt signaling/myogenic markers (LEF-1, β-catenin, Fibronectin, Calponin, and α-SMA) demonstrated more robust changes, indicating CBD-induced myogenic differentiation of pulmonary interstitial fibroblasts, which was corroborated by triolein uptake assay (p<0.05).

Conclusions

We conclude that in line with the previously known effects of nicotine on the developing lung fibroblasts, CBD also induces myogenesis. However, unlike nicotine’s effects on lung fibroblasts, CBD’s effects seem to be more complex, i.e., concomitant up-regulation of both lipogenic and myogenic markers, possibly reflecting a compensatory response to CBD-induced dyshomeostasis. The implications of our data in an intact system are unclear and are being studied using well-established in vivo rodent models.

130 Evidence for pulmonary group 2 innate lymphoid type II cell involvement in perinatal nicotine-induced asthma

M Martin1,*

J Liu1

R Sakurai1

Y Wang1

Y Liu1

PS Jahani2

O Akbari2

V Rehan1

1Lundquist Institute at Harbor-UCLA, Torrance, CA

2University of Southern California, Los Angeles, CA

Purpose of study

Exposure of the developing lung to nicotine is a significant contributor to offspring asthma and other allergic diseases. Though the mechanisms underlying perinatal nicotine-mediated pulmonary structural effects are well studied, the mechanisms underlying allergic predisposition remain unknown. Group 2 innate lymphoid type II cells (ILC2s), relatively new players in asthma pathogenesis, produce Th2 cytokines in response to a number of environmental signals; however, their involvement in perinatal nicotine-induced asthma is unknown. We tested the hypothesis that ILC2s are involved in perinatal nicotine-induced asthma.

Methods used

Using a well-established perinatal nicotine exposure mouse model, pregnant C57BL6/J mouse dams received nicotine (2 mg/kg, s.c.) or diluent once daily from e6 to postnatal day (PND) 21. Starting 3 days before sacrifice on PND21, pups were administered recombinant murine (rm) IL-33 (0.5µg intranasally) or PBS once daily under brief isoflurane anesthesia, and sacrificed 24h after the last rmIL-33 dose for ILC2s collection using Aria III cell sorter. ILC2s were characterized based on the lack (CD3ε, CD45R, Gr-1, CD11c, CD11b, Ter119, TCRγδ, and FCεRI) and the expression of (CD45, ST2, and CD117) classical lineage markers. Cultured (5 × 103 cells/well) ILC2s from control and nicotine exposed pups were treated with rmIL-33 (10 ng/ml) for 48h and the supernatant was analyzed for Th2 cytokines IL-5 and IL-13. Lastly, the effect short chain fatty acid butyrate on IL-33-induced production of Th2 cytokines by ILC2s was determined.

Summary of results

Nicotine treatment resulted in a greater yields of ILC2s (ILC2s/lung/mouse- 2770±72 vs 1790±89; nicotine vs control; N=4; p<0.001). IL-33 treatment of nicotine exposed ILC2s resulted in a higher Th2 cytokine production compared with ILC2s isolated from controls (N=4; p<0.001). Sodium butyrate (20 mM) decreased IL-5 production by 61% and IL-13 production by 88% (vs. IL-33 treated group).

Conclusions

We for the first time implicate the involvement of ILC2s in perinatal nicotine-induced asthma and suggest a novel novel, safer, and effective mechanism-based (ILC2 negative regulators) therapy for perinatal smoke/nicotine-induced asthma.

131 Common vape flavors are detrimental to lung fibroblast differentiation

Y Liu

R Sakurai

Y Wang

A Harb*

V Rehan

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA

Purpose of study

A significant strategy of electronic cigarette (e-cig) marketing focuses on the variety of vape flavors available, which often mimic the taste of fruits to more elaborate aromas. Manufacturers of e-liquids, the fluid used in e-cigs, argue that their flavored products are ‘food grade’ and are ‘generally recognized as safe’ (GRAS). However, the GRAS certification pertains only to ingestion and does not take into account inhalation nor the heat-induced changes in flavorings’ compositions of vapes. The flavoring chemical concentrations, 1–4% range (10–40 mg/mL) in e-liquids are high enough to raise concern for toxicity, particularly, with chronic exposure. Since interstitial fibroblasts are the primary determinants of lung phenotype, we examined the effect of select commonly used e-cig flavorings on cultured fetal rat lung fibroblast toxicity and differentiation.

Methods used

Using well established methods, embryonic day 19 Sprague-Dawley rat lung fibroblasts were isolated and were treated for 24 h with nicotine (1 × 10-9M), vanilla, cherry, and menthol (1 × 10-9 and 1 × 10-6M) either alone or nicotine + each flavoring combination. Fibroblast toxicity [lactate dehydrogenase assay (lDH)] and differentiation (protein levels of key lipogenic (PPARγ) and myogenic proteins (α-SMA and fibronectin) via western analysis and immunofluorescence staining) were determined.

Summary of results

Based on the LDH assay, there was no overt effect on fibroblast toxicity among any of the flavorings examined at either tested doses (1 × 10-9 and 1 × 10-6M). However, with the exception of menthol and menthol+nicotine, there were marked effects on fibroblast differentiation in all other groups as evidenced by significantly decreased PPARγ and increased α-SMA and fibronectin protein levels as well as positive staining for these markers.

Conclusions

Based on our data, common e-liquid flavorings demonstrated significantly detrimental, albeit, differential effects on lung fibroblast differentiation as demonstrated by reduced lipogenic but increased myogenic markers, which are key characteristics of myofibroblasts. These findings, in general, contradict the claims of e-liquid manufacturers. However, more extensive and in vivo studies need to be performed to determine the clinical significance of our data.

Neuroscience I

Concurrent session

3:15 PM

Thursday, January 23, 2020
132 Duration of american football play and chronic traumatic encephalopathy

DH Daneshvar1,2,*

J Mez2

AC McKee2

1Stanford, Palo Alto, CA

2Boston University, Boston, MA

Purpose of study

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose-response relationship between duration of football played and CTE risk and severity.

Methods used

In a convenience sample of 266 deceased American football players from the Veterans Affairs-Boston University-Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. We evaluated the ability of years played to classify CTE status using receiver operating characteristic curve analysis. Simulation analyses quantified conditions that might lead to selection bias.

Summary of results

223 of 266 participants met neuropathological diagnostic criteria for CTE. More years of football played was associated with having CTE (odds ratio [OR]=1.30 per year played, 95%CI, 1.19–1.41; P=3.8 × 10-9) and with CTE severity (severe vs. mild; OR=1.14 per year played, 95%CI, 1.07–1.22; P=3.1 × 10-4). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio [LR]=0.102, 95%CI, 0.100–0.105) and were 10X as likely to have played >14.5 years (positive LR=10.2, 95%CI, 9.8–10.7) compared with participants without CTE. Sensitivity and specificity were maximized at 11 years played. Simulation demonstrated that years played remained adversely associated with CTE status when years played and CTE status were both related to brain bank selection across widely ranging scenarios.

Conclusions

The odds of CTE double every 2.6 years of football played. After accounting for brain bank selection, the magnitude of the relationship between years played and CTE status remained consistent.

133 Longitudinal functional magnetic resonance imaging (FMRI) findings in adolescents

K Nikroo1,2,*

A Hawkins2

D Singhania2

S Chitoori2

P Wiederkehr2

P Otero2

B Afghani2,3

1University of Southern California, Los Angeles, CA

2UC Irvine School of Medicine, Irvine, CA and

3CHOC Hospital, Orange, CA

Purpose of study

Studies that have evaluated functional MRI of adolescent cannabis (marijuana) users at a single time point have shown alteration in brain connectivity, especially in the orbitofrontal/temporal areas. However, longitudinal studies of fMRI at two different time points is limited. The objective of this study was to evaluate the fMRI changes in adolescent cannabis users over time.

Methods used

A comprehensive literature review was performed through multiple search engines, such as PubMed, Google Scholar, and Cochrane using keywords, ‘fMRI’, ‘cannabis’, ‘marijuana’, and ‘longitudinal’. Only studies that involved 2 or more fMRIs at least 18 months apart in adolescent cannabis users and a non-user group were included in our analysis.

Summary of results

Of 20 studies, 4 satisfied our inclusion criteria (table 1). Adolescent cannabis users had thinner cortices pre-initiation of cannabis but compared to non-users thicker cortices at follow-up (after cannabis use). Although cause and effect can’t be proven, thinner brain cortex in frontal and orbitofrontal volume may predict cannabis use later in life. In addition, there was a decrease in functional connectivity and impact on executive planning in cannabis users over time. The studies accounted for some, but not all of the confounding variable. There was variation in chronicity, age at onset, and amount of cannabis used.

Conclusions

Longitudinal fMRI studies in cannabis users are limited but there is some evidence that cannabis causes alterations in certain areas of the brain that may lead to deleterious effects. However, it is not clear if the alteration is due to use of cannabis or other confounding variables such as stage of adolescent maturation, use of other substances or preexisting differences. Prospective, longitudinal studies are needed to evaluate the association between chronicity of cannabis use and fMRI findings, taking into account other confounding variables.

134 Bdnf augmentation by ampakines expression rescues synaptic dysfunction after global cerebral ischemia in the developing brain

N Chalmers

JE Orfila

PS Herson

RM Dietz*

Univ of Colorado, Aurora, CO

Purpose of study

Global ischemia in the developing brain often leads to poor neurologic outcomes, including learning and memory deficits. Using a novel murine model of juvenile cardiac arrest (CA), we investigate mechanisms of cognitive deficits and recovery. Brain-derived neurotrophic factor (BDNF)-tyrosine kinase (Trk) B signaling is a required pathway for memory formation and hippocampal synaptic plasticity. We recently demonstrated that enhanced BDNF-TrkB signaling contributes to recovery of cognitive function after global ischemia. AMPAkines are allosteric modulators of AMPA receptors and some have been shown to augment BDNF levels. We hypothesize AMPAkines that augment BDNF will reverse synaptic dysfunction following CA.

Methods used

Male juvenile mice (PND 20–25; equivalent to 2–3 year old human) were subjected to 8 min CA and resuscitated. Memory function was measured using contextual fear conditioning, a hippocampal-dependent memory task. Hippocampal CA1 long-term potentiation (LTP), a well-accepted cellular model for learning and memory, was measured in acute brain slices following a theta-burst stimulation (TBS, 40 pulses 100Hz). Increase in field excitatory post-synaptic potential (fEPSP) slope 60 min after TBS was analyzed to quantify LTP. BDNF ELISA from hippocampal tissue was performed per manufacturer’s instructions. Results reported as mean±SD.

Summary of results

Memory is impaired 7d after CA (52±15% sham, n=8, vs 24±19% CA, n=9, p<0.05) and recovers 30d after CA (52±14%, n=7). Hippocampal LTP correlates with this neurobehavioral recovery. In controls, LTP was 153±15% (n=8) of baseline (100%). In contrast, 7d after CA, LTP was impaired (110±16%, n=8, p<0.05 vs sham), followed by recovery at 30d (157±16%, n=8, p<0.05). Using ELISA, BDNF levels decreased after CA compared to sham animals (n=4, p<0.05). Injection of the BDNF-inducing AMPAkine LY404187 7d after CA or sham increased BDNF (n=4 each, p<0.05). In paired studies 7 days after CA, LY404187 applied to hippocampal slices 7d after CA rescues impaired LTP (111±12 [n=4] vs. 155±13 [n=4], p<0.05, paired t-test).

Conclusions

These data provide unique new data that BDNF enhancing drugs are capable of enhancing recovery from global cerebral ischemia in the young brain during critical school ages.

135 Effects of GSK3B & mtor on microtubule stability & neurite length

H Kornblum1

K Ludwig1

S Ravaei2,*

1UCLA, Los Angeles, CA

2Tulane University, New Orleans, LA

Purpose of study

In our study, we hypothesized that modifying GSK3B or mTOR will ultimately result in increased microtubule stability and increased neurite length, which could lend insights into potential avenues for treating Glioblastoma (GBM). Therefore, we investigated whether altering GSK3B or mTOR could promote microtubule stability and increase neurite length in mouse neuronal cells in vitro.

Methods used

Mouse neurons were treated with DMSO (control and a strong dissociator), CHIR (inhibits GSK3B), Rapa (inhibits mTOR), Epothilone (stabilizes microtubules), and ST401 (destabilizes microtubules). The mouse neurons were derived from mouse stem cells. The differentiation process was straightforward. We took mouse neurospheres, plated them, and then withdrew growth factors from their media and waited approximately one week.

Summary of results

The average neurite lengths of mouse neurons placed in DMSO was roughly 174um, 347um in EPO, 177um in ST, 257um in CHIR, and 141um in rapamycin. We observed that the mouse neurons treated with EPO and CHIR appeared more pronounced, clear, and longer, compared to those treated with rapamycin and ST.

Conclusions

We concluded that inhibiting GSK3B promotes microtubule stability and increases neurite length, and inhibiting mTOR promotes microtubule stability, but decreases neurite length. Future directions include evaluating the molecular response and resistance to mTOR inhibition to improve options for GBM treatment by exploiting vulnerabilities in mTOR targeting and microtubule stabilization.

136 Identification of PLK1 and NUSAP1 as markers for fate-restricted oligodendrocyte-lineage progenitor cells

J Chauhan1,2,*

B Appel1

1University of Colorado Anschutz Medical Campus, Aurora, CO

2Children’s Hospital Colorado, Aurora, CO

Purpose of study

This study’s purpose was to identify whether a fate-restricted progenitor cell differentiates into oligodendrocyte-lineage cells and, if it does, to characterize the progenitor cell. In addition, we analyzed whether there are differences in the progenitor cell population when comparing wildtype zebrafish to Boc-/- and Fbxw7-/- mutants, both of which produce abnormal amounts of oligodendrocytes.

Methods used

We began experimentation by sequencing the mRNAs expressed by single pMN progenitors. This identified plk1 and nusap1 as candidates for markers of fate-restricted oligodendrocyte-lineage progenitor cells. To test this hypothesis, we used fluorescent in situ RNA hybridization to detect expression of plk1, nusap1, and olig2 (a marker of all pMN progenitors) in wildtype zebrafish. The fluorescent in situ RNA hybridization was then repeated on Boc-/- and Fbxw7-/- mutants.

Summary of results

Plk1 and nusap1 expression were restricted to a subset of olig2 cells located in the progenitor domain, consistent with the possibility that they mark progenitors fate-restricted to specify into oligodendrocyte-lineage cells. In addition, outside the progenitor domain, plk1 was colocalized with olig2 positive cells but there was little colocalization between nusap1 and olig2. Based on the experimentation on mutant zebrafish, oligodendrocyte development seems to be delayed in the absence of Boc receptors for Sonic Hedgehog (Shh) and premature in the absence of Fbxw7-dependent degradation of Notch.

Conclusions

The results provide insight into how the Shh and Notch signalling pathways regulate oligodendrocyte development. In addition, our work supports the theory that a fate-restricted progenitor cell differentiates into oligodendrocyte-lineage cells. We suggest that colocalization between only plk1 and olig2 marks oligodendrocyte precursor cells. Furthermore, our work indicates that inducing the expression of plk1, nusap1, and olig2 in pluripotent neural stem cells can ultimately create oligodendrocytes that remyelinate damaged axons and restore normal function. Therefore, this research has significance in helping to create a therapy for patients whose myelin has been damaged by disorders such as multiple sclerosis.

137 Assessing the repeatability of measurements obtained using the VIP-200 pupillometer

K Li1,*

M Kong2

S Fuchs1

P Davey3

1Western University of Health Sciences – COMP, Pomona, CA

2The People’s Hospital of Guangxi Nanning, Zhuang Autonomous Region, China

3Western University of Health Sciences, Pomona, CA

Purpose of study

Pupil measurements are an important eye examination that has clinical usage in neuro-ophthalmology, refractive surgery, and neuro critical care. Therefore, it is clinically important for accurate and repeatable measurements when assessing pupil measurements. We assessed the repeatability of pupil measurements with NeurOptics® VIP™-200 pupillometer.

Methods used

Fifty individuals in the age range of 22 to 35 were examined for this study. Both eyes were measured for each individual after undergoing an ocular examination. Pupillary measurements were obtained using the NeurOptics® VIP™-200 Pupillometer at scotopic (0 lux), low mesopic (0.3 lux), high mesopic (3 lux), and photopic (675 lux) lighting conditions. Trained users obtained two measurements with a time interval of 30 minutes between each measurement. A time interval of 2 minutes was allowed for subjects to dark adapt prior to any measurements performed.

Summary of results

The mean difference between pupillary measurements is 0.42 mm, 0.62 mm, 0.79 mm, and 0.73 mm for scotopic, low mesopic, high mesopic and photopic conditions, respectively. The paired samples t-test is p<0.001 for all comparisons. The 95% limits of agreement for measurements is -1.75 to +0.91 mm, -2.02 to +0.78 mm, -2.36 to +0.79 mm, and -1.84 to +0.38 mm for scotopic, low mesopic, high mesopic, and photopic conditions, respectively. Out of 100 sets of measurements, 68, 57, 71, 76 measurement differences are equal to or greater than the clinically significant 0.5 mm for scotopic, low mesopic, high mesopic, and photopic conditions, respectively.

Conclusions

In assessing the repeatability of NeurOptics VIP-200 infrared pupillometer, we found on average there were small but significant differences in pupil measurements during repeated measurements. On average, each lighting conditions were in the range of 0.50 mm, which is clinically significant and may have significant clinical consequences. Users of the NeurOptics VIP-200 pupillometer should consider taking multiple measurements at different times and averaging their values for more accurate pupil measurements.

138 Targeting glycogen synthase (GYS1) with antisense oligonucleotide treatment in a mouse model of pompe disease

V Kimonis1,*

L Weiss1

L Ta1

M Carrer2

T Grossman2

1UC Irvine, Irvine, CA

2Ionis Pharmaceuticals, Inc, Carlsbad, CA

Purpose of study

Pompe disease is a progressive myopathy resulting from the deficiency of acid a-glucosidase (GAA). ERT with recombinant human (rh) GAA works well in alleviating the cardiomyopathy; however, many patients continue to have progressive muscle weakness from muscle glycogen accumulation produced by muscle glycogen synthase (GYS1). Previous studies have provided proof of principle that knockdown of GYS1 mRNA by phosphorodiamidate morpholino oligonucleotide conjugated with a cell penetrating peptide reduced glycogen, however was nephrotoxic. Antisense Oligonucleotides (ASO) technology has emerged as a powerful therapeutic alternative for the treatment of genetic disorders by targeting RNA. Most recently, therapy for spinal muscular atrophy has been successful using ASOs, and our hope is that ASO technology will be successful in Pompe disease. We propose that knocking down GYS1 with ASOs may prove to be a useful therapeutic target in Pompe disease.

Methods used

In order to impart specificity for the muscle glycogen synthase (GYS1), we used ASO-mediated gene silencing through the RNaseH1 dependent degradation mechanism.

Summary of results

Over 150 ASOs were designed and screened in vitro to identify the most efficacious ASO for testing in wild type mice. The lead from the screen were validated in a dose response study and the top 10 ASOs were screened in vivo. Three ASOs (GYS1 ASO#1, ASO#2 and ASO#3) showed the best tolerability and efficacy profile leading to knock down of GYS1 mRNA by approximately 50% of control. We performed a pilot study of the efficacy of three GYS1 ASOs in Pompe mice as monotherapy. We were able to see reduced muscle GYS1 mRNA levels and glycogen with the ASOs versus PBS or a mismatch ASO. ASO#2 however resulted in weight loss of the mice. Overall GYS1 ASOs #1 and possibly #3 seemed the most promising in reducing muscle GYS1 levels and glycogen content.

Conclusions

These preliminary studies provide proof of principle that GYS ASOs might be a potentially promising adjunct treatment for Pompe disease in reducing GYS1 and glycogen in muscle.

139 Presumed conversion disorder in a patient found to have new onset multiple sclerosis: challenges in diagnosis and treatment

S Lam1,2,*

E Laboy-Gonzalez1,2

N Kotsyubko1,3

S Thara1

S Abdijadid1

1Kern Medical Center, Bakersfield, CA

2Ross University School of Medicine, Bridgetown, Barbados

3American

Introduction

Conversion Disorder, referred to as Functional Neurological Symptom Disorder under DSM-5, is often a diagnosis of exclusion after primary organic/neurological causes are ruled out, and when clinical findings do not correlate with recognized disease states. The following case report highlights the diagnostic and treatment challenges in a patient initially thought to have conversion disorder but later diagnosed with severe relapsing-remitting multiple sclerosis (MS).

Case report

45-year-old Caucasian female with a history of schizoaffective disorder and mild cognitive delay who was admitted to our facility after reported inability to move her limbs or walk for a month. She underwent extensive testing including neuroimaging of the head, neck, and spine and lumbar puncture in prior hospitalizations. Results revealed an abnormal signal at C5 level of MRI thoracic spine, however further testing was limited due to anxiety and refusal of additional analysis.

On admission, patient was unable to move her body, requiring a sitter to reposition, feed, and bathe her. Neurology was consulted and patient was found to have weakness/rigidity in her extremities as well as sensory/positional deficits below the neck. Labs revealed low vitamin B12 levels and she was started on replacement therapy in addition to her psychiatric medications. T2-weighted brain MRI with and without contrast with fluid-attenuated inversion recovery showed multiple periventricular hyperintense areas. Cerebrospinal fluid analysis revealed elevated IgG, IgG synthesis rate, and oligoclonal bands, further supporting a diagnosis of MS. Patient was treated with oral prednisone, aggressive plasmapheresis and physical therapy, with subsequent improvement in movement/ambulation.

Discussion

Clinicians should maintain a high level of suspicion and broad differential diagnosis in patients with established psychiatric illness and new neurologic symptoms. A thorough workup should be done to rule out underlying medical conditions before considering a diagnosis of conversion disorder. This is imperative to prevent misdiagnosis or delay in timely treatment and care.

140 The selective serotonin reuptake inhibitor fluoxetine reverses androgen deprivation therapy-induced disruption of hippocampal neurogenesis

R Shota1

D Oh1,*

A Alquisola1

J Jo2

T Alkam1

R Pechnick1

1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA

2University of California, Santa Barbara, Santa Barbara, CA

Purpose of study

Cognitive impairment (CI) is an important side effect of androgen deprivation therapy (ADT), a widely used treatment for prostate cancer. Previous studies show androgen deprivation reduces adult hippocampal neurogenesis (AHN), whereas selective serotonin reuptake inhibitors (SSRIs) stimulate it. Therefore, SSRIs may be a potential therapeutic approach to preventing and/or treating disruption of AHN and the subsequent CI. This investigation sought to test the hypothesis that the SSRI, fluoxetine, can reduce or block androgen deprivation-induced reduction of AHN.

Methods used

Mice were randomly divided into four groups: sham/vehicle, sham/fluoxetine, castration/vehicle, and castration/fluoxetine. They underwent castration or sham surgery and were then given fluoxetine in their drinking water or plain drinking water. The mice were sacrificed five weeks post-surgery and their brains harvested for Western blot analyses of Ki-67 (marker for neuron proliferation), doublecortin (DCX, protein expressed in immature neurons and neuron precursors), and NeuN (protein expressed in mature neurons). GAPDH (a housekeeping protein) was used as a loading control.

Summary of results

Our investigation showed decreased Ki-67 protein levels in castration/vehicle compared to the sham/vehicle group. The decrease in Ki-67 in the castration/vehicle groups was prevented in the castration/fluoxetine group. Furthermore, there were no differences between sham/vehicle and castration/fluoxetine groups. There were no differences in NeuN and DCX levels among the four treatment groups.

Conclusions

The results suggest that treatment with fluoxetine reduced the effects of ADT on AHN. It will be important to test whether other drugs that stimulate AHN also are effective in reducing the effects of ADT and whether they can reverse the effects once they develop. This approach may be useful in preventing and/or treating ADT-induced CI in patients with prostate cancer.

141 UBE3A overexpression reduces hippocampal SK2 channel levels in mice

V Ramirez1,2,*

J Sun1

X Hao1

X Bi1,2

1Western University of Health Sciences, Pomona, CA

2College of Osteopathic Medicine of the Pacific, Pomona, CA

Purpose of study

Angelman syndrome (AS) is characterized by severe developmental delay and cognitive and motor impairments. AS and autism spectrum disorder (ASD) are linked to abnormal neuronal levels of the E3 ligase, UBE3A. UBE3A is an imprinted gene with the maternal allele being expressed and paternal allele silenced. AS is caused by reduced maternal UBE3A gene expression which results in UBE3A protein deficiency. UBE3A overexpression is associated with increased risk for ASD. Our previous studies showed that UBE3A ubiquitinates small conductance potassium (SK2) channels and targets them for degradation. UBE3A deficiency in AS mice results in increased SK2 levels and impairments in synaptic plasticity and learning and memory. We hypothesized that UBE3A overexpression in transgenic (TG) mice would result in decreased SK2 levels, thereby affecting synaptic plasticity and learning and memory in ASD.

Methods used

Coronal brain sections from TG and wild-type (WT) mice were processed for immunohistochemical staining. After blocking, brain sections were incubated with primary antibody at 4°C overnight. Sections were then washed and incubated with secondary antibodies for 2 hours at RT. After further washes, sections were mounted and imaged with a Zeiss LSM 880 confocal microscope with a 20x objective. ImageJ software was used to evaluate average fluorescence intensity (AFI) of SK2 immunoreactivity (ir) in the hippocampus. Data were analyzed using a two-tailed, unpaired Student t-test.

Summary of results

The AFI of SK2-ir in the hippocampus of TG mice was 38±9.24% of the AFI of SK2-ir in the hippocampus of WT mice (set as 100%) (p=0.0068; n=12 sections from 3 TG and 3 WT mice).

Conclusions

Our preliminary results showed that mice with UBE3A overexpression exhibited decreased SK2 channel levels in the hippocampus as compared to WT mice. These results align with our hypothesis that SK2 is a substrate of UBE3A whose overexpression results in SK2 ubiquitination and degradation. Further experiments will need to test whether decreased SK2 levels affect synaptic plasticity and learning and memory in TG mice.

Pulmonary and critical care I

Concurrent session

3:15 PM

Thursday, January 23, 2020
142 Emergency department airway management for asthma

HT Godwin1,*

M Fix1

O Baker2

T Madsen1

RM Walls2

C Brown2

1University of Utah, School of Medicine, Salt Lake City, UT

2Brigham and Women’s Hospital, Boston, MA

Purpose of study

Data are limited regarding current practice and outcomes for emergency department airway management in asthma. Our goal was to describe the methods, equipment used, medications, techniques, adverse events and outcomes for emergency airway management in asthmatic patients through multi-center surveillance.

Methods used

We analyzed all intubations with a primary indication of asthma over a three-year period (January 1, 2016- December 31, 2018) using the National Emergency Airway Registry (NEAR), a 25-center prospective observational registry of ED intubations. We report the incidence of intubations for asthma, methods and medications used, device, peri-intubation adverse events, as well as intubation success and failure using univariate descriptive statistics and cluster-adjusted 95% Confidence Intervals (CI).

Summary of results

A total of 19,071 encounters were recorded during the study period with 14,517 intubated for medical indications. Of those, 173 (1.2%, CI 0.9–1.6%) were intubated for asthma. Nearly two-thirds (n=56, 62.9%) were pre-oxygenated with bi-level positive airway pressure. Rapid sequence intubation (RSI) was used in 96.5% of cases. For these, more than half (n=85, 50.9%, CI 30.1–71.4%) were induced with ketamine, followed by etomidate at 48.5% (n=81, CI 27.8–69.7%). There was an overall adverse event rate of 12.14%. First attempt success was 90.8%. Overall intubation success was 100%. There was no difference in first-attempt success between ketamine and etomidate intubations. Compared to the registry as a whole, asthma patients were more likely to undergo RSI (96.5% versus 80.8%), pre-oxygenation with bi-level positive airway pressure (62.9% versus 6.2%), and induction with ketamine (50.9% versus 12.8%).

Conclusions

In our registry, intubation for asthma is uncommon. When required, the majority of patients are intubated using rapid sequence intubation after preoxygenation with bi-level positive airway pressure and induction with ketamine, a practice unique to asthma. It is unclear whether the high rate of Bi-PAP use is reflective of initial treatment or simply the most popular means of pre-oxygenation. Videolaryngoscopy use and first-attempt success are high and similar to the registry as a whole.

143 Post-operative delirium is associated with poorer health-related quality of life and mortality after lung transplantation

CL DeBolt1,*

Y Gao1

N Sutter1

N Kolaitis1

J Greenland1

s hays1

J Kukreja1

V Douglas1

J Diamond2

P Smith3

JP Singer1

1UC San Francisco, San Francisco, CA

2University of Pennsylvania, Philadelphia, PA

3Duke University Medical Center, Durham, NC

Purpose of study

Post-operative delirium after lung transplantation (LT) is common. Its association with health-related quality of life (HRQL), depression, and mortality is unclear.

Methods used

In 236 LT recipients, HRQL and depressive symptoms were measured before and through the first year after LT. Surveys included the Geriatric Depressive Scale (GDS), with lower scores indicating fewer symptoms, and Survey Short Form 12-Physical Component Score (SF12-PCS), with higher scores indicating better HRQL. Delirium was assessed twice daily with the Confusion Assessment Method (Intensive Care Units version). Delirium and mortality data were extracted from the electronic medical record. We examined the association between delirium and depressive symptoms/HRQL with linear mixed effects models and the association between delirium and mortality with cox proportional hazard models. Models were adjusted for age, sex, native disease, and lung allocation score (LAS).

Summary of results

ICU delirium occurred in 34 subjects (14%). Delirium was associated with worse generic physical HRQL but not significantly poorer depressive symptoms (table 1). Those who experienced delirium had a nearly 16-fold increased risk of mortality (table 2).

Conclusions

Delirium after LT identifies a group at high risk for worse outcomes and is associated with poorer HRQL and increased mortality. Implementing strategies to prevent and/or treat delirium may improve both HRQL and mortality risk after LT.

144 Management of severe pulmonary hypertension in pregnancy with epoprostenol

E Davtyan1,*

T Bajaj2

M Edmundson3

N Kiai4

BA Mocan4

J Chandrasekhar2

1AUC School of Medicine, Pembroke Pines, FL

2Kern Medical, Bakersfield, CA

3Kern Medical, Bakersfield, CA

4ROSS School of Medicine, Miramar, FL

Case Report

Pulmonary arterial hypertension in pregnancy has a limited set of treatment options and we present a rare case in which Epoprostenol lead to a preterm delivery and a protracted hospital course.

Pulmonary arterial hypertension (PAH) is caused by increase in pulmonary vascular resistance secondary to vasoconstriction, remodeling, and thrombosis of small pulmonary arteries and arterioles. In pregnancy, physiologic changes occur which may contribute to increased complications.

We present a 31-year-old African American female, G13P1A11 with multiple comorbidities presenting with sudden onset dyspnea at rest. Right heart catheterization demonstrated mean pulmonary arterial pressure of 43.3 mmHg. Patient was started on intravenous Epoprostenol in the intensive care unit at 27 weeks and 5 days gestation. The initial dose was 2ng/kg/min with increasing dose by increments of 1–2ng/kg/min every fifteen minutes until the side effects of flushing, jaw pain, nausea, or hypotension occurred. Epoprostenol discontinued due to extreme lethargy. Patient continued to endorse shortness of breath and lethargy, requiring transfer to a higher level of care. After arrival and prior to Epoprostenol being restarted, the fetal heart tracing showed decelerations prompting emergent cesarean at 28 weeks gestation. Postpartum, patient underwent second course of treatment with Epoprostenol and discharged with Sildenafil and Macitentan. Postpartum echocardiography did not demonstrate improvement or worsening of PAH. Within the first postpartum week patient experienced multiple pulmonary embolisms requiring treatment with heparin later transitioning to apixaban. The neonate was delivered via cesarean and transferred to NICU.

Therapeutic agents include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs. Based on limited data, risk of fetal harm and maternal side effects remains uncertain. There are few case reports describing successful treatment with Epoprostenol in pregnant women with PAH. Endothelin receptor antagonists not used due to teratogenic effects. Further investigation is needed to formulate a safe and efficacious treatment plan.

145 Worse sleep quality is associated with increased risk of chronic obstructive pulmonary disease exacerbation

AD Baugh*

P Woodruff

N Thakur

University of California San Francisco, San Francisco, CA

Purpose of study

Sleep disturbance is recognized as a symptom component in chronic obstructive pulmonary disease.[i] One study demonstrated that poor sleep quality as defined by Pittsburgh Sleep Quality Index (PSQI) score >5 is associated with increased risk of COPD exacerbations.[ii] However, limited sample sizes and confounders have impeded the ability to replicate or quantify this association.

Methods used

A cross-sectional study of 1,137 participants with COPD from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) were included for this analysis. SPIROMICS is a multi-center prospective cohort of subjects with and without COPD. The Pittsburgh Sleep Quality Index (PSQI) is an instrument with 19 scored responses to assess sleep quality. Participants with an index of 5 or higher were considered to have poor sleep. Exacerbations were defined as events that led to some contact with the healthcare system with use of systemic corticosteroids or antibiotics. We used negative binomial regression to examine the association between COPD exacerbations and the PSQI. The model was adjusted for age, gender, race, FEV1%predicted, GOLD severity, diagnosis of asthma, ischemic heart disease, apnea, depressive and anxiety symptoms, pneumococcal and influenza vaccination status, history of malignancy, income, and educational attainment.

Summary of results

609 (53%) subjects had poor sleep. Compared with those with good sleep quality, poor sleepers were on average younger, more often African-American, of lower income and lower educational attainment, but with less smoking history. Even after adjusting for covariates, each unit increase in PSQI score (range 0–20) was associated with a 2.9% increase in the risk for exacerbation (IRR 95% CI 1.00 – 1.05) and a 4.2% increased risk for severe exacerbations (95%CI 1.00–1.08).

Conclusions

PSQI score is positively correlated with annual rate of acute COPD exacerbations. Sleep may be an important target for assessment in the treatment of this disease.

References

  1. Jones PW et al. ‘Development and first validation of the COPD Assessment Test.’ Eur Respir J 2009;34(3):648–54.

  2. Shorofsky M, et al. ’Impaired Sleep Quality in COPD Is Associated With Exacerbations: The CanCOLD Cohort Study.’ Chest 2019.

146 Recurrent syncope as a presentation of pulmonary embolism – a case report

K Suwanwongse*

N Shabarek

Lincoln Medical and Mental Health Center, Bronx, NY

Case Report

The diagnosis of pulmonary embolism (PE) is challenging especially when patients present with vague symptoms. Early diagnosis and management of PE is crucial to prevent life-threatening sequels.

A 60-year-old woman bought by EMS after having syncope while walking. She reported shortness of breath (SOB) before syncope. She has hypertension, type 2 DM, osteoporosis and multiple syncopes (>10) in past year. Her investigation in another hospital includes EKG, 24-hour telemetry, echocardiogram and stress-test were normal but did not have chest CT. Her vital signs and exam were normal. Blood tests and EKG were unremarkable except mild anemia (Hb10.9) and elevation of troponin T (0.015). She was advised to admit but signed out against advice. On way out, she had another syncope that recovered spontaneously but had worsening SOB. She had tachypnea, respiratory distress and hypoxemia, oxygen saturation in 60s. Chest CTA showed prominent bilateral PE. She received heparin and thrombolysis (EKOS). Doppler sonography found occlusive thrombosis left popliteal vein with partially occlusive distal left superficial femoral vein. She was discharged on apixaban. Her SOB improved and no recurrent syncope was reported.

PE is a differential diagnosis for syncope in most textbooks, but when patients came due to syncope, PE, a potentially fatal disease requiring urgent attention, is rarely considered. This case is interesting as a patient had multiple syncopes without suspicious of PE until developing severe hypoxemia. PE should be considered in all patients experience syncope particularly with SOB, respiratory distress and hypoxemia.

147 Comparison of lung inflammation in a house dust mite- and aspergillus fumigatus extract- induced allergic asthma mouse model

J Sumsion1,*

A Pulsipher1

C Pollard1

A Benally2

J Alt1

1University of Utah School of Medicine, Salt Lake City, UT

2Fort Lewis College, Durango, CO

Purpose of study

Asthma affects 8.3% of the U.S. population with rising prevalence and no cure. Current investigations have demonstrated that asthma is multifactorial. Due to these etiological complexities, animal models have been developed to further our understanding of the underlying pathogenesis and pathophysiology of different asthma phenotypes. The most well-characterized mouse model of allergic asthma is the ovalbumin model. However, asthma models induced by house dust mite (HDM) invasion have been recently considered to be more relevant to human asthma. We propose a new Aspergillus fumigatus (AF) extract-induced asthma model that may also be relevant to human asthma. Herein, we characterized and compared lung inflammatory responses induced by HDMs and AF extracts in two different mouse models of asthma.

Methods used

BALB/c mice were challenged with (1) intraperitoneal and intranasal HDMs over 16 days or (2) three times weekly intranasal AF extracts for 8 weeks. Bronchoalveolar lavage (BAL) fluid samples were collected and subjected to differential leukocyte analysis using flow cytometry. Data are represented as the mean of detected CD45+ macrophages, CD11b+ lymphocytes, Ly-6G+ neutrophils and Siglec F+/MHCII+ eosinophils as percentages of total counted viable leukocytes.

Summary of results

The models produced unique distributions of leukocytes in the BAL fluid. While the control group was almost exclusively characterized by CD11c+ alveolar macrophages (99.95%), the HDM-induced disease group demonstrated a significant neutrophil (39.06%) response. Contrastingly, the AF extract-induced disease group had significant increases in eosinophil (28.51%) and lymphocyte (14.52%) populations compared to controls (0.37% and 5.00%, respectively).

Conclusions

Differential leukocyte analysis of the BAL fluid collected from HDM-induced asthma suggested a severe, acute invasive response, marked by increased neutrophil infiltration. In contrast, the AF extract asthma model produced a Th2-mediated chronic allergic response, as marked by increased eosinophil and lymphocyte infiltration.

148 Sarcopenia is associated with frailty in lung transplant candidates

J Maheshwari1,*

J Diamond2

M Anderson3

Y Gao1

N Sutter1

G Tietje-Ulrich1

L Benevuto3

s hays1

J Greenland1

J Kukreja1

J Christie2

JP Singer1

1UCSF, San Francisco, CA

2UPenn, Philadelphia, PA

3Columbia University, New York, NY

Purpose of study

Frailty is associated with mortality in lung transplantation (LT). Sarcopenia is considered a part of frailty; this relationship has not been confirmed in lung disease.

Methods used

In 367 LT candidates, we used three sarcopenia definitions: European Working Group on Sarcopenia in Older People (EWGSOP); FNIH Sarcopenia Project (FNIH); and lowest quartile of appendicular skeletal muscle mass (ASMI). ASMI was measured by bioelectrical impedance analysis. Frailty was measured by Short Physical Performance Battery (SPPB; SPPB ≤7=frail) and Fried Frailty Phenotype (FFP; FFP ≥3=frail). Associations between sarcopenia definitions and frailty were tested by logistic regression adjusting for age, sex, diagnosis. Non-linear associations between ASMI and frailty were tested using generalized additive models (GAMs), adjusting for age, sex.

Summary of results

Sarcopenia was associated with increased risk of frailty by EWGSOP and lowest quartile definitions (table 1). By GAMs, the relationship between ASMI and frailty risk was linear (figure 1).

Conclusions

Sarcopenia is associated with frailty in LT candidates by EWGSOP and distribution-based definitions. Studies are needed to optimize sarcopenia definitions and determine if reducing sarcopenia improves LT outcomes.

Methods used

An analysis of adult patients who underwent wide excision or flap repair of facial skin cancer defects were recruited and provided consent for this study. The automated facial analysis program Emotrics automatically displays the facial image with 68 facial landmarks used to locate the perimeter of the face, interpupillary distance, and a central vertical axis of the face. These landmarks on preoperative and postoperative photographs were used to quantify facial symmetry. Measurements of facial features: brow, nasal ala, and nasal base excursion were calculated from preoperative and immediate postoperative photos and preoperative and three-month postoperative photos for analysis.

Summary of results

Photographic results will be presented and demonstrate a time scale for the improvement in facial skin distortion over the healing period. Brow deviation measured at 0.84 cm immediately postoperatively compared to preoperative baseline symmetry, measured at 0.22 cm of deviation from baseline at three-months postoperatively. Decay charts for the various facial regions measured demonstrate a similar phenomenon of improvement towards baseline appearance at three months.

Conclusions

Measurements of the skin’s compliance and the degree to which facial surgical site skin deviation returns to preoperative baseline measurements was captured using a machine learning technology. Further data gathered may help providers tailor counseling for different time points in the perioperative periods of facial surgery and better prepare patients for healing timeframe expectations.

Surgery II

Concurrent session

3:15 PM

Thursday, January 23, 2020
149 Automated facial measurements provide empirical data of skin compliance

S Roddick*

C Lee

L Tobing

cs drew

S Gupta

Loma Linda University, Loma Linda, CA

Purpose of study

A recent study found that concerns about social interactions and physical appearance did not improve until three months after facial reconstructive surgery and may correlate with improved healing and the appearance of skin over time. There is no empirical data and measurements of the skin’s compliance and the degree to which facial surgical site skin deviation returns to preoperative baseline measurements. Emotrics, a machine learning technology, provides an objective tool for facial analysis. The data from this study may help providers anticipate patient concerns and tailor counseling for different time points in the preoperative and postoperative periods.

Methods used

An analysis of adult patients who underwent wide excision or flap repair of facial skin cancer defects were recruited and provided consent for this study. The automated facial analysis program Emotrics automatically displays the facial image with 68 facial landmarks used to locate the perimeter of the face, interpupillary distance, and a central vertical axis of the face. These landmarks on preoperative and postoperative photographs were used to quantify facial symmetry. Measurements of facial features: brow, nasal ala, and nasal base excursion were calculated from preoperative and immediate postoperative photos and preoperative and three-month postoperative photos for analysis.

Summary of results

Photographic results will be presented and demonstrate a time scale for the improvement in facial skin distortion over the healing period. Brow deviation measured at 0.84 cm immediately postoperatively compared to preoperative baseline symmetry, measured at 0.22 cm of deviation from baseline at three-months postoperatively. Decay charts for the various facial regions measured demonstrate a similar phenomenon of improvement towards baseline appearance at three months.

Conclusions

Measurements of the skin’s compliance and the degree to which facial surgical site skin deviation returns to preoperative baseline measurements was captured using a machine learning technology. Further data gathered may help providers tailor counseling for different time points in the perioperative periods of facial surgery and better prepare patients for healing timeframe expectations.

150 Efficacy of intra-articular injections with corticosteroids versus ketorolac in the hip and knee

K Jurgensmeier1,*

P Fuerst1

D Jurgensmeier2

D Kunz2

S Daines2

1University of Washington School of Medicine, Seattle, WA

2Saint Alphonsus, Boise, ID

Purpose of study

Intra-articular steroid injections have become a mainstay of treating moderate to advanced arthritis. However, concern exists regarding associated risks and adverse effects. Non-steroidal anti-inflammatory injections, such as Ketorolac, may offer similar benefits as steroids without a similar risk profile. There is, however, a paucity of direct comparison between these two injection types. This study evaluates the effectiveness of Triamcinolone, a corticosteroid, and Ketorolac, an anti-inflammatory, in treating symptoms of moderate to advanced osteoarthritis of the hip and knee.

Methods used

110 patients (52 hips, 58 knees) with documented moderate to advanced degeneration of the hip or knee were randomized in a double-blinded study. Baseline measurements were obtained via the Visual Analogue Scale (VAS), Knee injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.) or Hip dysfunction and Osteoarthritis Outcome Score Jr. (HOOS Jr.), and PROMIS Global Health Score. Patients were randomly assigned to receive Ketorolac or Triamcinolone injections given via ultrasound guidance. Follow up surveys were collected 1 week, 1 month, and 3 months after the injection date. Data was compared by two-way repeated measures ANOVA with a Bonferroni posthoc test of means comparison.

Summary of results

No significant differences were noted in comparing the effectiveness of Triamcinolone or Ketorolac for KOOS Jr., HOOS Jr., and VAS (p>0.66). HOOS Jr. and VAS scores for hip injections were significantly lower comparing pre-injection to all time points (p<0.001). Knee injections showed identical results, except comparison of drug-time interactions revealed significant decreases in scores for both drugs with Triamcinolone effect occasionally being significant at a greater number of time points. No significant differences in Global Health score were noted due to injections.

Conclusions

Ketorolac is non-inferior compared to Triamcinolone in providing improved functionality and pain relief to degenerative joint disease in the hip and knee. This allows providers an additional low-cost medication to offer patients with contraindications to steroid injections. Further studies will be beneficial to assess if Ketorolac has a similar risk profile when compared to steroid injections.

151 Effect of pain medication regimen on hospital length of stay after cleft palate surgery

SN Ahmed*

R Courtemanche

N Almuqaimi

E Henkelman

University of British Columbia, Vancouver, BC, Canada

Purpose of study

Optimal post-operative length of stay (LOS) for patients having cleft palate surgery is unclear. This study aims to understand how pain medication regimen affects post-operative LOS following primary cleft palate repair.

Methods used

A retrospective chart review was performed on 200 consecutive patients who had cleft palate repair from June 2011 to May 2018 at BC Children’s Hospital. Data collection included: patient demographics, post-operative pain medication regimens (e.g. dose, frequency, regularity), and post-operative LOS.

Summary of results

The cohort of 200 patients (108 male : 92 female) had a median age of 11.0 months (IQR 9.5 – 12.4) at the time of surgery, and a median post-operative LOS of 43.1 hours (IQR 26.1 – 50.1). Regularly dosed acetaminophen (n=77) was associated with a shorter median LOS of 28.6 hours compared to 45.5 hours for PRN dosed acetaminophen (n=122), (p=0.02). Regularly dosed ibuprofen (n=20) was also associated with a shorter median length of stay of 26.1 hours as compared to 43 hours for PRN dosed ibuprofen (n=75) and 43.9 hours for no ibuprofen (n=105), (p=0.03). Length of stay was not associated with patients receiving only acetaminophen (n=104) or both acetaminophen and ibuprofen (n=95) (p=0.26). LOS was not associated with the type of opioid analgesia prescribed: codeine (n=66), morphine (n=65), or codeine and morphine (n=58), (p=0.95).

Conclusions

Patients receiving regularly dosed acetaminophen or ibuprofen have shorter LOS following cleft palate repair. Opioid analgesia is not associated with post-operative LOS.

152 Development of a model to recruit T-regulatory cells to vascularized composite aloograft tissue

AC Johnson1,*

B Li2

Y Wang2

C Owens2

CA Huang2

N Navarro-Alvarez2

A Su2

K Washington2

CB Verchere3

DW Mathes2

1University of Arizona, Tucson, AZ

2University of Colorado, Aurora, CO

3University of British Columbia, Vancouver, BC, Canada

Purpose of study

Regulatory T lymphocytes (T-regs), play a key role in immune homeostasis due to their ability to suppress effector T lymphocytes. Cancer immunology studies have shown that recruitment of T-regs enables tumors to evade the immune system using C-C motif chemokine ligand 22, or CCL22, to recruit T-regs. This concept has been extrapolated to transplant immunology. The known immunomodulatory potential of mesenchymal stem cells (MSCs) within bone marrow (BM) makes an attractive cell vector for expression of CCL22 in vascularized composite allograft tissue. We aim to assess the fate of the locally injected BM-MSCs expressing CCL22, and their ability to recruit T-regs.

Methods used

BM cells were isolated from rat hindlimb bones and cultured under standard protocol. After 3 passages, the percentage of MSCs was evaluated by flow cytometry based on CD45-, CD54+, and CD90+ markers. Cultured cells were then transfected with double stranded adenovirus encoding CCL22 and GFP (green fluorescent protein). Images of cultured cells were taken with a fluorescent microscope to confirm GFP expression. These cells were injected into the wound bed of rats recieving syngeneic skin grafts and in a non-surgical area of skin on the same animal. Tissue samples were collected from the skin graft, non-surgical injection site, and native skin on post-operative days 1 and 5. GFP expression was assessed by paraffin embedded tissue examination under fluorescence microscope. T-reg cell recruitment was evaluated by immunohistochemistry of FoxP3 expression.

Summary of results

We found 73.8% of our cultured BM to have the characteristic markers of MSCs. Transduction efficiency of cultured cells was 99%. Unstained paraffin sections showed no difference in fluorescence when compared to untreated controls. FoxP3 immunohistochemistry was negative for T-regulatory cells in the skin graft tissue and non-surgical tissue with injected cells.

Conclusions

Though the cultured BM-MSCs were able to robustly express GFP, the cells were not identified in vivo, nor were T-regs recruited to the areas examined. There are many variables involved in this experiment and the model requires continued optimization.

153 Resuscitative thoracotomy in the emergency department: factors and survival

J Lam1,2,*

E Lebby1,2

S Mohammed1,2

F Dong2

R Vara2

B Woodward2

M Neeki2

1California University of Science and Medicine, Colton, CA

2Arrowhead Regional Medical Center, Colton, CA

Purpose of study

The use of resuscitative thoracotomy in trauma patients remains a controversial topic. Previous investigations have reported that patients with blunt injuries have a higher rate of mortality than patients with penetrating injuries. The current retrospective study aimed to further explore the specific mechanisms of injury and factors that may increase survival of the patient undergoing the procedure.

Methods used

All patients with thoracotomies performed at Arrowhead Regional Medical Center (ARMC) from 2011–2019 were extracted from Electronic Medical Record (EMR). Patients were excluded from the analysis if they were less than 18 years old. Parameters of interest included mortality, age, time of thoracotomy compared to time of arrival, and mechanism of injury (blunt versus penetrating). Data was extracted from nurse notes, paramedic notes, discharge summaries, and EMR.

Summary of results

Among the 40 patients included in the original database, four patients were excluded due to age <18 years. As a result, 36 patients were included in the final analysis. The average age was 38.2 (SD=15.1) years, 75% (n=27) were males, 55.6% (n=20) were Hispanic, 41.7%, 69.4% (n=25) sustained penetrating trauma, and the average Injury Severity Score (ISS) was 27.6 (SD=17.2). The overall mortality was 77.8% (n=28). Blunt trauma was associated with 100% mortality (n=11 of 11), while penetrating trauma was associated with a 68% mortality (n=17 of 25), however the difference failed to reach statistical significance due to small sample size (p=0.0757). Factors such as age, gender, and ISS were not statistically significantly associated with mortality.

Conclusions

The primary aim of the study, which was to analyze thoracotomy survival rates at a regional trauma center based on a number of demographic and other factors, was met. The knowledge provided by this study highlights the need for continual revisiting of thoracotomy guidelines in order to decrease utilization of the procedure based on circumstance. Further multicenter studies are needed to illuminate how mortality is impacted by the many external factors listed previously.

154 The impact of intraoperative indocyanine green angiography (SPY-PHI) for patients with facial defects on operative time and number of procedures

C Lee*

S Roddick

L Tobing

CS Drew

S Gupta

Loma Linda University, Loma Linda, CA

Purpose of study

Basal and squamous cell skin cancers present a multiplex problem because of the risks of major disfigurement and muscle or nerve injury, especially in fragile areas such as the face. This causes an increase in operative time and trips to the operating room for patients with these facial defects. However, SPY Portable Handheld Imager (SPY-PHI) is a tool that uses indocyanine green fluorescence imaging technology that could aid in reducing operation time and trips. SPY-PHI enhances the surgeon’s ability to assess tissue viability by intraoperatively evaluating blood flow and tissue perfusion; thus, providing a more efficient method.

Methods used

This is a case series using intraoperative SPY-PHI angiography to evaluate patients with facial defects such as basal and squamous cell skin cancers. SPY-PHI was used to assess blood flow, examine the extent of vascular injury, and assist in flap tailoring. Angiography with SPY-PHI is performed at the beginning of the case to demarcate non-viable tissue and affected areas are marked for excision. It is subsequently used after flap elevation to ensure perfusion of transported tissue. Total operative minutes and trips to the operating room are compared to historical cases where SPY-PHI technology was not used.

Summary of results

Out of 30 patients, 4 have been assessed with intraoperative SPY-PHI angiography. With SPY-PHI, the average number of trips to the OR was 2.75 and the average operation time was 577.5 minutes. For the 26 patients that did not undergo SPY-PHI, the average number of trips to the OR was 1.35 and the average operation time was 202.08 minutes.

Conclusions

The previous hypothesis stated that SPY-PHI technology would decrease the time spent in the OR as well as trips to the OR. However, this was rejected as the results revealed that using SPY-PHI intraoperatively took more operating time and trips for patients with basal and squamous cell skin cancers. A possible reason for this outcome is that the cases which had used SPY-PHI were more complicated compared to those that had not used intraoperative angiography. Nonetheless, although SPY-PHI is highly useful in aiding surgeons to accurately assess tissue injury and viability, it does not reduce operative minutes and trips to the OR.

155 Evaluation of cohort progressing from first to second stage sacral neuromodulation and indications for unplanned device removal

A Feldkamp*

AS Amasyali

J Groegler

F Jellison

R Belay

A Staack

Loma Linda University, Loma Linda, CA

Purpose of study

Sacral neuromodulation (SNM) is indicated for the treatment of overactive bladder, urinary retention, and bowel disorders, and is typically implanted in two procedures. Patient selection criteria that predict progression from the first to second Stage of implantation is not well defined. The purpose of this study is to determine whether symptoms, comorbidities, and demographics influence progression to second Stage implantation or future unplanned SNM removal or revision. This study seeks to provide additional clinical guidance for deciding between staged or direct full (single) Stage procedures.

Methods used

A retrospective review was conducted in patients who underwent staged SNM at a single hospital by five different providers between 2012 and 2019. Outcome was measured as (1) progression from Stage 1 to 2, and (2) indications for unplanned SNM removal or revision. Chi Square analysis, Mann-Whitney U, and Fisher’s exact tests were used for data evaluation.

Summary of results

A total of 153 patients underwent SNM therapy for symptoms of overactive bladder (n=129), urinary retention (n=42), neurogenic bladder dysfunction (n=18), fecal incontinence (n=18), and constipation (n=5). 92.2% (n=118/128) of patients progressed to Stage 2. Diagnoses of urinary retention and neurogenic bladder dysfunction were associated with lower progression to Stage 2 (p=0.034, p=0.017, respectively). Non-obese patients (BMI <30 mg/kg2) were more likely to have SNM removal or surgical revision within 4 years (17.5%) than obese (BMI ≥ 30 mg/kg2) patients (9.5%) (p=0.041). Other demographic characteristics and medical parameters were not associated with SNM outcome.

Conclusions

The high progression rate to Stage 2 supports the concept that direct full Stage SNM can be performed in order to save time, costs, and potentially reduce morbidity related to an additional surgery. However, staged procedures should be discussed with patients with urinary retention and neurogenic bladder dysfunction due to their lower progression rates. BMI may also be an important selection criterion since a lower BMI is associated with a higher rate of SNM removal or revision. Future prospective studies are needed to further explore direct full Stage SNM implantation and parameters that predict SNM outcome.

156 The importance of preoperative nutrition in plastic surgery patients: a meta-analysis of key nutrients

L Tobing*

C Lee

CS Drew

S Roddick

S Gupta

Loma Linda University, Loma Linda, CA

Purpose of study

Patients and surgeons have long wondered if significantly increasing specific nutritional supplements such as vitamins, proteins, and minerals will influence the surgical outcomes (would healing time, infection rates) of plastic surgery patients compared to patients on a normal diet with no increase before and after surgery.

Malnutrition is a modifiable risk factor for increased morbidity and mortality in patients undergoing any type of surgery. Postoperatively, they are at risk for delayed healing being in an increased catabolic state in addition to commonly suffering from marginal nutritional deficiencies at baseline before their procedure. Preoperative nutritional interventions for plastic surgery patients have been proven to result in enhanced recoveries by preventing postoperative dietary deficiencies, and improving wound healing.

This article presents a meta-analysis on research that has been done regarding the postsurgical effects of key nutrients such as vitamin A, vitamin C, zinc, arginine, glutamine, hydrolyzed collagen, vitamin B complex, and protein. It aims to further the strength behind the necessity of optimal perioperative nutrition.

Methods used

The meta-analysis was conducted via searches run through Pubmed, Medline, and Google Scholar using one key nutrient at a time as the search terms. Boolean Operators were utilized to narrow down articles to exclusively surgical cases, especially plastic surgery cases. Extraction of data along with the framing/plotting of summary estimates and examination of publication bias was done on each individual study. A total of 4 articles were initially found, and a final tally of 20 articles were used for this analysis.

Summary of results

Each nutrient listed above improved at least one postsurgical outcome: reducing inflammation/bruising, tissue healing, effective collagen production, and overall skin health. A common trend discovered was that postbariatric patients were most at risk for not having enough primary nutrients for wound healing following surgery.

Conclusions

Appropriate nutritional supplementation with nutrients listed above is an effective means for correcting these nutritional deficiencies and it will also reduce surgical complications associated with the surgery.

157 Trial of a virtual reality tool to teach surgical technique for tibial shaft fracture intramedullary nailing

B Zukotynski1,*

G Blumstein1

N Cevallos1

C Ishmael1

SD Zoller1

Z Burke1

S Clarkson1

HY Park1

KR Hori1

N Bernthal1

JH Barad2

N SooHoo1

1UCLA David Geffen School of Medicine, Los Angeles, CA

2Osso VR, Palo Alto, CA

Purpose of study

The aim of this study was to compare the transferability of skills gained in a VR training program of a simulated intramedullary nailing (IMN) of a tibia by comparing performance of VR trained and standard guide (SG) trained novice medical students when performing a SawBones simulation of intramedullary nail fixation.

Methods used

20 first- and second-year novice medical students were recruited and randomized into VR (n=10) and SG (n=10) groups. Students with prior knowledge of the procedure were excluded. All 20 participants completed the first phase and 17 completed the second phase of the study. Participants were randomized to SG or VR training. After training, participants were then observed performing the tibial IMN procedure with SawBones and evaluated by a blinded attending surgeon using procedure-specific checklist and 5-point global assessment scale. Participants returned after 2-weeks for repeat training and evaluation.

Summary of results

Aggregate global assessment scores were significantly higher for VR than SG group (17.5 vs. 7.5, p<0.001), as were scores in all individual categories. The percentage of steps completed correctly was significantly higher in the VR group compared to the SG group (63% vs. 25%, p<0.002). The average improvement between the first and second phases of the study were higher in the VR group compared to SG group across all 5-categories of the global assessment scale, and significantly higher for knowledge of instruments (50% vs. 11%, p <0.01).

Conclusions

Virtual reality training was more effective than standard training in our model of simulated tibia IMN for novice medical students. Virtual reality training may be a useful and cost-effective method to reduce the initial learning curve and augment orthopaedic surgery training.

158 The effectiveness of intramedullary nailing of distal fibula fractures and dynamic fixation of syndesmosis with suture buttons

A Arora1,*

S Bhatti1

C Delman2

AM Saiz2

MR Haffner2

1University of California, Davis, Sacramento, CA

2UC Davis, Sacramento, CA

Purpose of study

Ankle fractures are a common presentation to the emergency department constituting 9% of all fractures. Unstable ankle fractures are treated with open reduction and internal fixation (ORIF) using plate and screw fixation, however, wound healing complications, infection, and hardware prominence are potential negative sequalae. Intramedullary fixation provides an alternative approach that obviates the need for an extensive incision. Our study assessed the efficacy of intramedullary fixation in the treatment of distal fibula fractures with concomitant use of syndesmotic screw fixation or suture button fixation for the syndesmosis.

Methods used

We performed an IRB approved retrospective chart review of patients with ankle fractures treated at UC Davis Medical center from 2017 to 2019. Inclusion criteria included patients with ankle fractures and/or syndesmosis injuries treated with an ORIF using a fibular intramedullary nail and suture-button device. Post-operative results such time to union and complications were analyzed, in addition to radiographic changes including tibiofibular overlap and medial clear space. Data was analyzed using the Student’s t-test for numerical data and a chi-squared test for categorical data.

Summary of results

22 patients with an average age of 52 were included. Most injuries were inversion/eversion injuries or rotational ankle fractures due to falls. Radiographic results demonstrated a mean increase in tibiofibular overlap by 2.4 mm when comparing pre-operative to post-operative patients (0.4 mm vs 3 mm, p<0.05). The mean decrease in medial clear space was 2.8 mm (5.6 mm vs 2.8 mm, p<0.05) and the mean decrease in tibiofibular clear space was 2.3 mm (5.2 mm vs 2.9 mm, p<0.05). Additionally, the decrease in mean displacement was 1.89 mm (3.5 mm vs 0.91 mm, p<0.05).

Conclusions

Fixation with nail and suture button is effective for syndesmotic injuries; there was an improvement in most parameters when comparing pre-operative to post-operative patients. Additionally, there was less hardware removal required due to the intra-osseous nature of the nail, and there were no complications. Limitations included small sample size and inability to compare these patients to standard ORIF patients.

Poster session

Adolescent medicine and general pediatrics

6:00 PM

Thursday, January 23, 2020
159 Hydrocarbon aspiration pneumonitis

C Bishara*

J Budiaman

B Wong

University of Nevada, Las Vegas (UNLV), Las Vegas, NV

Background

Mineral oil, in the form of baby oil, is a common household product when there are young children in the home. It is often overlooked as a potential source of harmful ingestion. This case is presented to raise awareness that everyday items in the home can cause significant injury to young children.

Case

This is a previously healthy 16 month old female who presented to the pediatric emergency department (PED) with fevers and increased work of breathing after ingesting an unknown amount of baby oil. The night prior to arrival, parents witnessed the child drink an opened bottle of baby oil. Overnight, she had a continuous cough, and the next day noted to have increased respirations and fever. She was taken to the PED, and was found to be febrile to 101.8 F and tachycardic, but with a benign lung exam. Her heart rate soon normalized and her lungs remained clear. Labs showed leukocytosis, elevated AST, and CRP. Chest XR demonstrated scattered airspace disease bilaterally more extensive on the right. Poison control recommended 24 hour observation and antibiotics. The patient was admitted for observation and continued on IV clindamycin. She remained afebrile and hemodynamically stable on room air. She continued to improve clinically and was discharged the next day without antibiotics.

Discussion

Hydrocarbon ingestion primarily exerts its effects on the respiratory and central nervous systems. Most concerning and most often seen are the respiratory complications that result from aspiration because of the organic properties of hydrocarbons. Pulmonary symptoms occur within 30 minutes of ingestion and include coughing, choking, tachypnea, dyspnea, rales, and/or grunting. Aspiration into the lung parenchyma leads to chemical pneumonitis and direct injury to the lung tissue. The prognosis for children who have ingested a hydrocarbon is dependent on the amount and specific agent involved. While most children survive without any complications, some can quickly progress to respiratory failure and death. The importance of this case is to remember that simple, common household products can cause major injuries to children. As a result, pediatricians need to include these products in their anticipatory guidance about poisonings, in addition to the more routinely discussed substances.

160 Neonatal diabetes mellitus

S Chen*

UCSF-Fresno, Fresno, CA

Introduction

Neonatal diabetes mellitus is characterized by persistent hyperglycemia typically within the first 6 months of life due to impaired insulin function. Etiology of neonatal diabetes is mostly monogenic and is an extremely rare condition world wide with an estimated incidence of 1:300k to 1:500k individuals. We present a case of neonatal diabetes mellitus that was able to respond to dietary regulation without insulin therapy.

Case presentation

An ex-37 6/7 wk newborn presented with recurrent episodes of hyperglycemia. Patient was first noted to have hyperglycemia on DOL 1. Glucose at birth was 159 but 24 hours later had quickly risen to 230. Patient was also noted to be hypotonic and having some temperature instability. Patient was transferred to the NICU at that time and placed on antibiotics for possible sepsis. However, given the negative blood cultures and re-assuring WBC count, patient was stopped on antibiotics. However blood sugars continue to rise peaking at >300. Patient had no iatrogenic source of glucose or exposure to any medications that may cause hyperglycemia.

Management and outcome

Endocrinology was consulted. Patient was found to have low/undetectable levels of insulin. Patient was suspected to have neonatal diabetes mellitus. Genetics was consulted as monogenic diabetes is the most common cause of neonatal diabetes. Patient remained in the NICU for glucose monitoring. Insulin therapy was not initiated as patient does occasionally dip to the 100’s and risks of hypoglycemia with insulin therapy outweighed risks associated with hyperglycemia. Patient feeding frequency was increased to Q2 hr to help stimulate pancreas to keep up with carbohydrate intake. Patient’s blood glucose began improving to the 130’s to 170’s. Although blood glucose remains elevated, patient was stable enough for discharge home on DOL 18. Patient scheduled to have close follow up with genetics and endocrine following discharge.

Discussion

The decision to start insulin therapy always requires careful consideration as risk of hypoglycemia in neonates can lead to poor neurocognitive development in the future. This case demonstrated an interesting presentation of neonatal diabetes mellitus which responded to non-pharmacologic management and dietary regulation alone. This case will add to the understanding of neonatal DM and aid in the decision for initiation of insulin therapy in future cases.

161 Establishing guidelines for pediatric fever in a community hospital

A Johnston*

R Azhir

A Panesar

E Schmitt

C Rongkavilit

UCSF Fresno, Fresno, CA

Purpose of study

Fever is one of the most common complaints for pediatric emergency department (ED) visits. As many pediatricians know, serious bacterial infections (SBI) can be difficult to diagnose as infants may only present with fever. Multiple studies have shown that prompt identification and administration of appropriate empiric antibiotic therapy prevents significant morbidity and mortality and improves outcomes. Working in a large, level 1 trauma community hospital with an annual ED volume of 110,000 patients, often pediatric patients are alongside acutely decompensating adult patients resulting in delay of care. This study aims to establish a pathway to aid in appropriate management of these patients.

Methods used

A needs assessment among physicians and nurses in the ED and department of pediatrics led to the creation of a new ‘Pediatric Fever’ pathway. The primary outcomes for analysis include (1) appropriate identification of high risk pediatric patients with a fever (2) administration of empiric antibiotics within an hour of identification of a fever in the ED and (3) time to admission from the ED. The algorithm includes transition of care from the ED to inpatient setting. The study also involves retrospective chart review of patients age 72 hours to 2 years presenting with fever, and use of the above measures to compare before and after implementation of the pathway for 3 months.

Summary of results

The implementation of the Pediatric Fever Pathway in our level one trauma ED and pediatric inpatient setting will provide insight on the percentage of febrile pediatric patients that were appropriately given antibiotics within one hour of identification of fever. The data will also reflect whether the appropriate antibiotic was initiated in the ED.

Conclusions

Many children’s hospitals have various pathways that aid healthcare providers. As a community hospital now caring for more children, it is imperative we collaborate with ED physicians to optimize care. This pathway hopes to address errors in identification and management of pediatric SBI. It promotes antimicrobial stewardship by avoiding inappropriate use of broad spectrum antibiotics to minimize bacterial resistance. This pathway also allows for education of resident doctors and a collaborative approach among emergency medicine and pediatrics.

162 The prepared first responder: engaging youth advocates at school, home and in the community

D Manzo1,2,*

E Picart1,2

1University of California San Francisco, Fresno, Fresno, CA

2University of California Davis, Sacramento, CA

Purpose of study

With youth empowerment at the core of this project and to engage with our surrounding community we found an opportunity to actively work with at-risk Fresno youth on their terms. We partnered with a local high school, Design Science Middle College High School, to develop interactive educational modules in educational areas that the youth found interesting, attributable to their daily living and where they felt they could genuinely advocate for change as advocates at school, home and in their community.

Methods used

A PhotoVoice project was implemented as a needs assessment tool into the tenth-grade class at DSMCHS to better understand their needs. Three modules were created focusing on topics our students found important; first aid, nutrition, and youth engagement. Surveys were administered before and after the modules using Qualtrics.

Summary of results

Twenty-seven percent of students reported being concerned about gang violence, drugs/alcohol, and/or poverty within their communities. ‘[l]ife after college’ and ‘[h]aving a place to belong and feel safe’ were their two largest stressors. Sixty-nine percent reported consumption of sodas or sugar-sweetened beverages 1–2 times a day. Seventy percent reported feeling more confident in writing a policy that can positively impact their community

Conclusions

During the educational modules, students acquired first aid skills to be able to respond to acute injuries they might encounter in everyday life learned how to read food labels to make healthier choices and prepared health presentations to improve their public speaking skills.

163 Altered expression of thioredoxins, peroxiredoxins, and thioredoxin reductases in CBS-deficient homocystinuria in the presence and absence of homocysteine-lowering treatment: possible implications for redox mediated pathology

MM Nguyen*

H Jiang

K Maclean

University of Colorado School of Medicine, Aurora, CO

Purpose of study

Cystathionine β-synthase-deficient homocystinuria (HCU) is a poorly understood, life-threatening, inborn error of sulfur metabolism. If left untreated, it can lead to cognitive impairment, connective tissue disturbances, and thromboembolic complications. Multiple lines of evidence from both the transgenic HO mouse model of HCU and human HCU patients indicate oxidative stress as a major pathogenic factor in this disease. Previous work has shown that impaired antioxidant defense may contribute to the generation of oxidative stress in HCU.

Methods used

We investigated the hepatic expression of the antioxidant proteins thioredoxin (TRX) 1, thioredoxin reductases (TRD) 1 and 2, and peroxiredoxins (PRDX) 1,2 and 3 in the presence and absence of the homocysteine-lowering therapy betaine in the HO mouse model of HCU.

Summary of results

Western blotting analysis revealed significant repression of TRDX, TRD1 and TRD2 in untreated HCU mouse livers. These effects were not ameliorated by betaine treatment. PRDX 1, 2 and 3 were all induced in HCU livers. Betaine treatment normalized PRDX 1 and 2 expression levels but induced a further induction of PRDX3.

Conclusions

Our data suggests that impaired expression of thioredoxin 1 and thioredoxin reductases has the potential to contribute to oxidative stress in HCU and that the induction of multiple peroxiredoxin isoforms may constitute a redox-sensitive homeostatic response in this disease.

164 Clinical pathway development for children with a solitary functioning kidney

T Po White*

E Chan

M Catapang

E Matsell

D Cojocaru

R Humphreys

C Mammen

D Matsell

University of British Columbia, Vancouver, BC, Canada

Purpose of study

Congenital anomalies of the kidney, including a solitary functioning kidney (SFK), are frequent causes of childhood chronic kidney disease (CKD). Those at high risk of developing CKD likely require a different standard of long-term care. We hypothesized that long-term SFK outcomes are not uniformly favorable, extensive local practice variation exists for length of follow-up and extent of surveillance, and risk stratification may improve care efficiency.

Methods used

This was a retrospective cohort study. All patients identified with a SFK from 2000–2017, due to either renal agenesis (RA) or multicystic dysplastic kidney disease (MCDK), were included. Relevant data was extracted from clinical charts. Outcomes highlighting local care patterns and resource use included length of follow-up, and number of clinic visits and renal ultrasounds over total follow-up. To assess the utility of risk-stratification, SFK patients were stratified into high (HR) and low risk (LR) groups based on an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73m2 or ≥90 at last follow-up, respectively. Between-group differences were analyzed by Mann-Whitney U test.

Summary of results

A total of 229 SFK patients (71 RA, 158 MCDK) were included. Median age at initial visit was 0.3 (IQR 0.6) years with a median follow-up of 4.3 (4.8) years. The mean eGFR at last follow-up was 89±28 ml/min/1.73m2. After stratification based on last eGFR, 53 patients (23%) were classified as HR and 176 (77%) as LR. With regards to practice variation, median number of clinic visits over total follow-up was 4 (2) ranging from 1–47, while median number of ultrasounds was 4 (4) with a range of 0–28. When practice patterns were stratified according to risk, there were no significant differences between HR and LR groups for length of follow-up (3.9 years vs 5.8, p=0.07), number of clinic visits (5 vs 6, p=0.26), or number of ultrasounds (5 vs 5, p=0.57).

Conclusions

Significant practice variation exists in the management of children with a SFK. Moreover, despite differences in long-term kidney function, the care of LR and HR patients is similar, suggesting that current care patterns warrant standardization and risk-based allocation of resources.

Poster session

Behavior and development

6:00 PM

Thursday, January 23, 2020
165 Third year resiliency days: fortifying students against burnout

J Sheehy*

E Yim

A Hayton

Loma Linda University, Loma Linda, CA

Purpose of study

Medical student mental health is an area of growing interest, with research demonstrating an increase in burnout and decline in empathy in the clinical years (Neumann et al, 2011). While many programs have introduced wellness curricula in the pre-clinical years of medical school (Slavin et al, 2014; Wasson et al, 2016), few have focused on designing resources for the clinical years. In the 2018–19 academic year, this institution implemented a wellness curriculum for third-year medical students, aiming to equip them for the challenges they face on the wards, help them develop skills to bounce back from difficulties, make them feel less alone, and improve their overall sense of wellbeing.

Methods used

Critical issues for students were identified through faculty brainstorming, student focus groups, and literature review. Faculty developed five 90-minute workshops to build coping skills and grapple with crucial areas: Gender Inequity, Anxiety, Non-accidental Trauma, Assertiveness, and Dealing with Death. In collaboration with key stakeholders, space was made in the curriculum for five required ‘Resiliency Days,’ with topics corresponding to clinical rotations and time split between workshops, team bonding, and leisure.

Students responded to confidential surveys midway through and at the end of the academic year that assessed their mental health using the Brief Resilience Scale (BRS), perceptions of the impact of the days, and suggested improvements. The results were tabulated.

Summary of results

Of the class of 160 students, 80% filled out the final survey. Of the responders, 62% experienced a direct positive effect on their mental health from the program, 68% learned new skills, and 61% felt less alone.

There were no significant differences in the BRS scores of the aggregated students in December 2018 (3.00, n=147) or June 2019 (2.99, n=133), nor were there differences in score between gender: female (2.94, n=57) and male (3.02, n=74). These scores indicate that students at the end of their third-year have borderline low to normal resilience.

Conclusions

Students reacted positively to the addition of Resiliency Days and felt that they had a beneficial impact on their mental health. They gained tools that may help them face future challenges and felt less alone. Impact on BRS scores was not seen likely because of the many factors that contribute to one’s resilience.

166 Stress, mindfulness disposition, and heart rate variability among smokers: a laboratory study

I Shull1,*

G Christodoulou2

N Salami2

M Kirkpatrick2

D Black2

1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA

2University of Southern California, Los Angeles, CA

Purpose of study

The purpose of the project is to (1) describe Heart Rate Variability (HRV) profiles of current smokers during a stress task; and (2) correlate HRV with self-report measures of perceived stress and mindfulness disposition. We hypothesize that HRV scores in response to stress will be anticorrelated with perceived stress and correlated with mindfulness disposition.

Methods used

In a pilot phase of a randomized controlled trial, participants (n=12) completed resting HRV assessment with the Firstbeat Bodyguard 2 device, self-report measures of stress (Perceived Stress Scale, PSS) and mindfulness disposition (Five Facet Mindfulness Questionnaire, FFMQ) during a baseline visit 1. During visit 2, participants were in smoking withdrawal (i.e., not smoked for 12 hrs prior) and completed HRV assessment during a stressor task (i.e., Trier Social Stress Test, TSST). Pearson correlations tested associations between visit 1 PSS and FFMQ and visit HRV parameters (RMSSD; time-domain measure of root mean square of standard deviation and HF-HRV; frequency-domain measure of high frequency range) during rest and the TSST. HRV reactivity (HF-HRV) was calculated by taking the mean difference between HRV at rest and during the TSST.

Summary of results

At visit 1, PSS scores were anticorrelated with FFMQ domains: non-judgement (r=-.88) and acting with awareness (r=-.88). These FFMQ domains were anticorrelated with HRV RMSSD during the TSST; non-judgement: (r=-.70); acting with awareness: (r=-.82). Acting with awareness domain was anticorrelated with HF-HRV reactivity during the TSST (r=-.92).

Conclusions

Since increased parasympathetic control relates to increased HF-HRV reactivity, higher mindfulness disposition may indicate greater self-regulation in response to stress. Cultivating mindfulness disposition may be beneficial for improving physiological profiles among smokers in withdrawal. This finding has value for future studies that incorporate mindfulness as a behavioral intervention for smokers attempting to improve their stress response and reduce their urge to smoke. Limitations include a small sample size; we aim to retest our analyses in a larger sample.

Poster session

Cardiology

6:00 PM

Thursday, January 23, 2020
167 Evaluation of dynamic monitors for the prediction of volume responsiveness in patients with and without diastolic dysfunction

A Zhelokhovtseva1,*

D Li1

O Badakhsh1

S Reddy2

E Lal3

N Fleming1

1University of California, Davis, Sacramento, CA

2University of Texas, Austin, Austin, TX

3University of California, San Diego, San Diego, CA

Purpose of study

Patients with diastolic dysfunction (DD) comprise more than 28% of patients aged 60 and older. Left ventricular DD is known to predict adverse outcomes such as major adverse cardiac events, and in-hospital mortality. Intra-operative optimization of cardiac function, in particular that of intravascular volume, can decrease incidence of complications. Current gold standard of measurement of cardiac function in response to intravenous fluids in patients under general anesthesia is the change in arterial waveform (PPV – Pulse Pressure Variation, SVV – Stroke Volume Variation) associated with respiration. The SVV values predictive of fluid responsiveness have been characterized in a general patient population. Thresholds haven’t been specifically validated for patients with DD. Identification and management of these patients can improve perioperative outcomes. Our research aims to evaluate and characterize the potential impact of DD on SVV, and SVV’s ability to predict volume responsiveness as measured by EV1000 device.

Methods used

Assessment of left ventricular DD via transthoracic echocardiogram was measured prior to induction of anesthesia. As hemodynamic parameters necessitated, a 200 ml of crystalloid or colloid was infused via Belmont Rapid Infuser. Patient’s response to each fluid bolus was automatically recorded by the monitor, and comparisons were made between patients with and without DD.

Summary of results

To date, 35 patients have been recruited. ROC curve analysis was produced to compare fluid responsiveness in those with or without DD.

Conclusions

The total sample size is currently too small for conclusions. Additional data is necessary to fully characterize the relationships.

Poster session

Clinical epidemiology and health disparities

6:00 PM

Thursday, January 23, 2020
168 Epidemiology of injuries in acrobatic dunking athletes

S Gay*

E Guenther

Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Oregon, USA, Lebanon, OR

Purpose of study

Injuries in professional athletes are common. However, to our knowledge, the injuries seen in acrobatic dunking athletes have not been studied. Our objective is to determine the most common self-reported injuries sustained by current professional acrobatic dunking athletes and their etiologies.

Methods used

Eligible participants were invited to complete the anonymous survey via the AD Facebook site with approximately 400 members. The survey instrument contained 21 questions covering demographics, history of injuries and additional questions specific to AD. Inclusion criteria: self-identified Dunkers. Exclusion criteria: age <18 years.

Summary of results

There were 65 total respondents, 96.9% were males, with 56.9% between 23 and 32 years of age. 83.1% were Caucasian. When asked, 83% were associated with a Dunk Team, while only 10.8% were affiliated with a university. Only 26.2% reported having a trainer on the team. Among respondents, there was approximately 9.2 years of experience with dunking (median 7 years) and an average of 1.2 days (median 1.0 days) or 3.7 hours (median 2 hours) of practice per week. There was an average of 22.6 injuries reported over the career of dunking. The most common area of injury was the ankle (51.3%), knee (12.8%), Head or neck (10.3%), and Upper leg (7.7%). These injuries occurred primarily during the landing phase of the dunk (70%) and dunking the ball (13.3%) while at practice (52.2%) and performance (41.8%). The majority of the respondents sought care from a physician (70.6%), followed by a paramedic or EMT (11.8%) and trainer (11.8%). An average of 19 days were missed due to this injury (median 4 days).

Conclusions

Acrobatic dunking is associated with significant injuries, most of which are musculoskeletal. Further study is needed.

169 Impact of caffeine on skin cancer prevention: a meta-analysis

S Joseph*

D Rokunohe

JW Lee

P Nghiem

M Kawasumi

University of Washington School of Medicine, Seattle, WA

Purpose of study

Skin cancer has an annual incidence of 5.5 million in the U.S., more than all other cancers combined. Epidemiological studies show that caffeinated beverage intake is associated with decreased risks of several skin cancer types: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Due to the high incidence of skin cancer and the popularity of caffeinated drinks, caffeine may have an appreciable impact on skin cancer incidence. We performed a systematic review and meta-analysis to estimate the annual reduction in skin cancer incidence and treatment cost by caffeinated beverage intake.

Methods used

We searched PubMed, Embase, and Scopus for observational studies that assessed the relative risk of skin cancer with coffee or tea intake up to June 30, 2019. High-quality studies were selected by the Newcastle-Ottawa Quality Assessment Scale for further analysis. Summary relative risk (SRR) was determined by the DerSimonian and Laird random effects model.

Summary of results

A database search yielded 22 high-quality studies covering 47,593 cases of skin cancer, mostly in the U.S. and Europe. For all skin cancer types combined, caffeinated coffee had the largest effect with SRR (95% confidence interval) of 0.78 (0.68–0.87). Tea had less effect (0.85 (0.77–0.93)), and decaffeinated coffee had no effect (0.98 (0.91–1.06)). Combining coffee and tea intake, SRRs were 0.88 (0.81–0.95) for BCC, 0.81 (0.69–0.93) for melanoma, 0.77 (0.59–0.94) for SCC, and 0.77 (0.59–0.95) for unspecified nonmelanoma skin cancer (BCC or SCC). These effects were dose-dependent. Based on SRR, dose dependency, and proportion of coffee drinkers, we estimate that current coffee consumption leads to 196,344 skin cancers prevented and 289 million dollars saved in treatment cost annually in the U.S.

Conclusions

Current caffeinated beverage intake significantly lowers the burden of skin cancer in incidence and treatment cost. This meta-analysis has limitations including varying caffeine content in coffee consumed. Future studies should clarify how to optimize skin cancer prevention by determining the ideal timing of caffeine intake relative to sunlight exposure.

170 A survey of primary care physicians on hyperhidrosis training and experience

JH Nelson1,*

O Pipitone2

W Lear3

E Guenther1

1Western University of Health Sciences COMP-NW, Lebanon, OR

2Samaritan Health Services, Corvallis, OR

3Silver Falls Dermatology, Corvallis, OR

Purpose of study

Data on hyperhidrosis education among physicians is lacking. Hyperhidrosis is defined as excessive sweating beyond the body’s needs for temperature regulation. The cause of primary focal hyperhidrosis is not well understood. Palmar and axillary primary focal hyperhidrosis are ranked as having the highest impact on quality of life when compared to 40 other dermatologic conditions. The aim of this project was to collect information on the nature and quality of training and knowledge related to hyperhidrosis within family medicine and internal medicine residency programs. In a recent study approximately 70% of hyperhidrosis patients reported seeing a primary care physician about their condition. This statistic highlights the need for adequate training of primary care physicians to manage patients with hyperhidrosis.

Methods used

An 8-question survey was administered to Family Medicine (FM) and Internal Medicine (IM) residents and attending physicians within the Samaritan Health Services FM and IM programs via paper copy and Survey Monkey. The survey was sent to 32 residents and 47 attending physicians. 32 residents and 13 attending physicians responded to the survey.

Summary of results

We recorded a 57% response rate. 92% of attending physicians and 53% of residents indicated that they had encountered a patient with either generalized or focal hyperhidrosis. Approximately 35% of attendings and 75% of residents reported feeling less than reasonably comfortable with diagnosing and managing a patient with hyperhidrosis. Only 7% of all respondents indicated that they were familiar with iontophoresis as a treatment option. It also appears that physicians may tend to underestimate the effect that hyperhidrosis has on an average patient‘s quality of life. 89% of all respondents reported having no specific training on hyperhidrosis diagnosis or management.

Conclusions

There appears to be a need for increased awareness and training for primary care physicians on understanding and managing patients with hyperhidrosis. Further work is required in expanding the survey to improve the generalizability of our results.

171 Identifying factors associated with loss to follow-up in patients with adult congenital heart disease

A Zehri*

J Andrews

S Klewer

University of Arizona, Tucson, AZ

Purpose of study

Congenital heart disease (CHD) is the most common form of birth defect affecting around 12 out of every 1000 children. Recent advances in pediatric cardiac care and more effective interventions has reduced mortality rates in children with moderate to severe CHD, which has led to a significant increase in the population of middle-aged and geriatric aged adults with CHDs (ACHD). Continued management of their condition is imperative and identifying risk factors associated with lost to follow up in ACHD may be a significant factor in improving outcomes in the overall population.

Methods used

For the research subjects, the population was surveyed using The Arizona Birth Defect Monitoring Program (ABDMP). Through the CH-STRONG (Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG) project, subjects were contacted by mail and asked to complete a questionnaire about their CHD and non-clinical questions. Patients were deemed lost to follow up if they had not been seen within the past year by a CHD specialist and if no address was on file. For travel time analyses, the Google Maps APIs were used to map the address to closest major specialty care facility sites in Arizona.

Summary of results

Out of the 2441 subjects identified with CHD, 1676 of them addresses were confirmed and 450 of them responded of these responded to the survey. According to our analysis based on this sample size, drive time but not distance in miles was significant, no insurance vs. commercial and public was trending towards significance, and Hispanic ethnicity was not significant for lost to specialist follow up.

Conclusions

The key findings demonstrate that neither distance nor insurance type were significantly associated with lost to follow up in ACHD at specialty treatment sites. For future, we would like to determine if our findings are consistent in other states. With this information, we can improve our understanding of the ACHD population and work to develop a system to reduce loss of care in the ACHD population.

Poster session

Community health and global health

6:00 PM

Thursday, January 23, 2020
172 Pilot study: using centering diabetes for adult patients with type ii diabetes at a free clinic

A Asmussen1,*

E Hepner1,2

C Paiva1

M McCarroll1

1Pacific Northwest University of Health Sciences, Yakima, WA

2Yakima Union Gospel Mission, Yakima, WA

Purpose of study

Diabetes is a multisystem disease, disproportionately affecting minorities, that can lead to complications such as heart disease, stroke, kidney failure, lower limb amputation, and adult-onset blindness if not adequately controlled using the standard of care guidelines. The objective was to examine the use of diabetes group appointments using a Centering model in a free clinic setting. Patients attending Yakima Union Gospel Mission are often inadequately treated for their diabetes due to resource limitations. Centering appointments have been efficacious in treating culturally diverse and low socioeconomic populations for pregnancy and pelvic pain, but limited studies are available for diabetes.

Methods used

A single group of adult patients with uncontrolled diabetes regularly participated in Centering Diabetes group appointments (n=3).The Centering group met bi-weekly for six sessions related to diabetes care. HbA1c and blood pressure were measured before and after the study. Additionally, pre- and post-study surveys were provided regarding self-efficacy. The curriculum originally included 6 sessions with topics such as: What is Diabetes?, Family Relationship and Stress, Glucose Monitoring, Exercise and Weight, Medications, and Foot and Eye Care.

Summary of results

Three patients consistently participated in Centering Diabetes appointments: a 44 y.o female with a 10 pack-year history of smoking; 49 y.o. male with difficulty maintaining weight due to insulin use; and a 47 y.o female with significant work and spouse stress. Pre- to post-Centering HbA1c were 12.1 to 11.2, 12.3 to 11.9 and 9.6 to 8.4, while pre- and post-Centering blood pressures were 154/96 to 120/70, 150/100 to 145/100, and 143/80 to 130/76 respectively.

Conclusions

The curriculum topics addressed the standard of care model and enabled a small group of patients to meet diabetes care guidelines. Challenges were met due to patient availability and difficulty recruiting patients. Patients were satisfied with the group appointments and agreed to continue attending centering appointments based on survey data. While statistically significant differences to blood pressure and HbA1c cannot be drawn from the data, community acceptance of the centering model has opened doors to further studies.

173 Systematic review: evaluation of interventions addressing timely access to surgical care as outlined by the lancet commission 2030 global surgery goals

C Binda1,*

I Zivkovic1

D Duffy2

G Blair1

R Baird2

1University of British Columbia, Vancouver, BC, Canada

2British Columbia Children’s Hospital, Vancouver, BC, Canada

Purpose of study

In 2015, the Lancet Commission on Global Surgery published 6 surgery goals, one of which is to provide 80% of the world’s population with timely access to Bellwether Surgical Procedures by 2030. Little research has been done to identify novel interventions implemented in Low and Middle Income Countries (LMICs) to help reach this goal since 2015. This systematic literature review addresses that gap.

Methods used

With oversight from a health librarian, we conducted a systematic review of articles and grey literature published in PubMed, Cochrane, MEDLINE, Web of Science, Scopus, and CINAHL databases in accordance with PRISMA guidelines. Independent reviewers evaluated captured abstracts to assess for inclusion and exclusion criteria. (inclusion criteria: LMIC interventions, Bellwether Procedures, exclusion criteria: non-surgical interventions, High Income Country (HIC) interventions, non-English papers, publication before August 8th, 2015). Entirety of selected manuscripts were read by 2 reviewers who completed data extraction and risk of bias assessment.

Summary of results

1923 articles were collected from the databases; 11 met inclusion criteria and were analysed. Innovations centered around task sharing, development of orthopaedic devices, and the evaluation of disparities in access to care. Quantitative and qualitative outcomes were assessed. 8 papers focused on caesarean sections, 3 on open fracture reduction, and 3 on laparotomy. 5 papers focused on West Africa, 2 on East Africa, 2 on South Asia, and 1 on Southeast Asia.

Conclusions

Multiple innovative interventions have been implemented since the publication of the 2015 Lancet Commission on Global Surgery goals that have or will increase the availability of timely surgical access in LMIC. The changing views on the validity of task-sharing in surgery with non-clinician surgeons and the scaling-up of innovations addressed in the literature will help realize timely access to Bellwether procedures.

174 Mitigating alcohol abuse in the boomtown economy of douglas, wyoming

A Blaine*

University of Washington School of Medicine, Seattle, WA

Purpose of study

As a community that revolves around the energy industry, Douglas, WY is home to transient employees. The Douglas community maintains an above average excessive drinking rate and a high rate of alcohol impaired driving deaths. Community conversations and further evaluation of community assets informed that Douglas needs support services to reduce alcohol consumption among transient energy industry employees.

Methods used

County health data proved a significant increase in excess drinking as well as an increase in the rate of alcohol impaired driving deaths in Douglas. Solutions for Life (SFL) a state subsidized mental health clinic and local physicians were interviewed regarding the local public health concern. An evidence based literature review outlined primary and secondary factors influencing alcohol abuse. Interviews with various stakeholders in the community and clinical observations provided further insight about energy industry employees perception of how much alcohol consumption is normal. Community conversations also considered the social environment and living conditions of transient employees.

Summary of results

Evidence based literature identified alcohol abuse interventions that focused on rural communities, transient employees of the energy industry, cultural alcohol misconceptions, social services, and collaborations with energy corporations. The director of SFL confirmed an excessive number court ordered patients in treatment were from the energy industry. Physicians and SFL professionals confirmed that energy employees were living in hotels and temporary housing with poor social networks. Considering the demographic of alcohol abuse reported by the community, evidence based literature determined that a targeted community health campaign towards energy industry employees in collaboration with energy corporations would be the most effective intervention to reduce alcohol consumption in rural communities.

Conclusions

Support through a strength-based approach from community assets such as SLF provided an understanding of the social background in Douglas. Next steps would include the development of collaboration between SLF and energy corporations to target energy industry employees. The collaboration would facilitate a community health campaign with the intention to decrease alcohol abuse in Douglas.

175 Multidisciplinary support for buprenorphine-naloxone treatment of opioid use disorder

A Hall*

University of Washington School of Medicine, Seattle, WA

Purpose of study

Opioid use disorder (OUD) is a significant concern within the population served by the Confluence Health system in Wenatchee, Washington with an average of 17.6 associated deaths annually. This project utilized an asset-based approach to examine fundamental resources, obstacles, and potential improvements in the prescription of buprenorphine-naloxone for OUD in the community.

Methods used

Discussion with a buprenorphine-naloxone prescriber outlined pharmacological therapy for OUD available in Wenatchee. OUD patients receiving buprenorphine-naloxone treatment were interviewed regarding craving control, use of addiction sponsors, therapy and support groups. The clinical director of an addiction treatment center detailed outpatient services for OUD and an addiction group therapy session was attended. Meeting with a team responsible for a buprenorphine prescriber incentive program validated administrative support for OUD.

Summary of results

Effective pharmacotherapy for OUD was determined to focus on harm-reduction and compliance. Observation of group therapy demonstrated limitations of medical management without psychological and social support. Dialogue with involved professionals allowed for distribution of other providers’ viewpoints. A poster integrating these findings was shared with buprenorphine prescribers. In assessing next steps, literature review revealed buprenorphine implants to be an effective alternative route of administration. Availability of buprenorphine implants in Wenatchee could improve medical management of OUD in patients with accessibility and diversion issues. Collaboration between mental health professionals and buprenorphine prescribers to determine the best method of administration would be necessary. The existing professional relationships in Wenatchee would foster this collaboration and improve patient-centered care.

Conclusions

This evaluation integrates expertise of physicians and addiction professionals while providing a testament of the patient experience in OUD pharmacotherapy. It highlights importance of an interdisciplinary treatment plan for patients undergoing treatment for OUD. It identifies an option of buprenorphine implantation as an attainable advancement in OUD treatment given the present infrastructure in Wenatchee.

176 Unintentional ingestion of marijuana in adults: a case series

A Hsueh1,*

K Fong1

K Kendric1

N Siddiqi2

J Georgiadis3

T Phan1

ET Reibling1

B Wolk4

1Loma Linda University School of Medicine, Loma Linda, CA

2Nova Southeastern University, Fort Lauderdale, FL

3South Baldwin Regional Medical Center, Foley, AL

4Loma Linda University, Loma Linda, CA

Purpose of study

Marijuana use has become increasingly popular as more US states legalize the substance. A greater number of people are admitted to the ED due to marijuana toxicity. Our study reviews a case of adults who were unintentionally exposed. This is novel because most of the current literature focuses on marijuana poisoning in pediatric patients.

Methods used

We conducted a retrospective analysis of twelve subjects. Subjects were evaluated in the Emergency Department and referred to Medical Toxicology Service after ingesting marijuana from food at a family event. Six of the subjects consented to be interviewed about their experiences which were qualitatively analyzed and grouped into common themes. The study was approved by the Institutional Review Board.

Summary of results

Three subjects required observation due to persistent symptoms. Eleven subjects tested positive for tetrahydrocannabinol (THC) via urine drug immunoassay. Two subjects tested positive for ethanol in their blood. Common symptoms experienced included confusion, difficulty speaking, weakness, nausea, tremors, and hallucinations. All subjects reported sleepiness. Subjects also reported multiple emotions, including anger, confusion, disbelief, and helplessness. Three of the interviewed subjects reported a negative impact on work.

Conclusions

This case series illuminates adverse effects after unintentional marijuana exposure in adults. More incidents of unintentional marijuana intoxications are expected as legal availability increases. Public education of marijuana’s effects should be widely disseminated to improve individual awareness and encourage policy implementation and regulation. This may minimize future unintentional intoxication cases.

177 Supporting california’s medical therapy program serving children with disabilities through telemedicine

A Favila*

L Davidson

A Bares

B Yoo

J Mouzoon

I Sigal

SC Haynes

M Lieng

JP Marcin

UC Davis Health, Sacramento, CA

Purpose of study

California’s Medical Therapy Program (MTP) provides physical therapy (PT), occupational therapy (OT), and medical oversight to children with qualifying disabilities, generally due to neuromuscular and musculoskeletal conditions. The MTP serves nearly 23,000 children at school-based clinics called Medical Therapy Units (MTUs). While every county is required to have a MTP, not every county has a MTU, creating difficulties for children in those counties to access care. Therefore, the School-Based Tele-Physiatry Assistance for Rehabilitative and Therapeutic Services (STARS) program was developed at UC Davis Health. STARS is an innovative program that uses telemedicine to provide medical direction at the MTUs.

Methods used

A needs assessment of the MTP was performed in all 58 counties through an e-mail questionnaire sent to the MTP’s Supervising Therapists. Data were collected on the counties’ resources, such as the number of MTUs. Telemedicine services began in San Joaquin and Butte Counties at the beginning of 2019. To evaluate its potential to address the shortcomings of the MTP, parent, physician and therapist satisfaction surveys were administered at the end of each monthly clinic.

Summary of results

Of California’s 58 counties, 14 do not have MTUs, forcing approximately 105 children to travel to other counties for MTP services. In counties with at least one MTU, approximately 690 children travel to receive PT and OT services because their county does not have these services. The average roundtrip driving distance for physicians traveling to provide care at MTUs, was 175 miles. Furthermore, only 45% of counties have access to a pediatric physiatrist, the specialist who provides medical direction for this patient population. Preliminary satisfaction data were collected from 64 patient-therapist-physician triads. Parents (84%), therapists (91%), and physicians (100%) reported that the quality of care provided by telemedicine was equal to in-person care.

Conclusions

California’s MTP is maldistributed, causing many patients and physicians to travel sometimes long distances for care. The results of the preliminary satisfaction analysis support the STARS program as a means of increasing ease of access to care and reducing burdens on families and providers.

178 3D image generation for translation of text-based medical questionnaires

B Stothers*

A Macnab

University of British Columbia, Vancouver, BC, Canada

Purpose of study

Globally those with limited language comprehension or literacy, face problems completing validated written questionnaires related to their health/treatment, hence the importance of developing picture-based scores e.g. facial images to quantify pain. Since health care providers world-wide need software to generate images for such scales, and must choose from several options we reviewed programs suitable for first time users.

Methods used

We evaluated 3 software programs (Poser version 11.0, Blender version 2.8 and Cheetah3D version 7.0) in order to select one to use to generate lifelike figures for a picture-based version of the 10-item assessment of limitations of activities (LoA) section of the SF-36 questionnaire, a validated written patient self-assessment tool. All 3 provide development tools and templates for creating figures with defined postures, facial expressions and clothing suitable for use in medical symptom scoring scales and picture-based questionnaires.

Summary of results

Poser software lets users who are beginners produce figures that are more realistic and lifelike than the other programs. In particular, the ‘Smooth Translation of Joints’ feature allows more accurate rendering of human anatomy. Images can also be animated and exported in BMP, JPEG and TIFF formats. In comparison, Blender is a free high-end open source product but has a steep learning curve and while Cheetah3D is versatile, aimed at amateur artists and easy to use it is specifically written in Cocoa for MacOS users. Limitations of Poser include its cost; the inability to import artwork from other programs; and some illustration tools found in comparable software are lacking, but it does have pencils, markers, airbrushes and shading tools.

Conclusions

Choices exist for those creating images for picture-based scales and questionnaires. Poser software enabled first-time users to generate lifelike images for a visual version of the 10 item LoA section of the SF 36 mobility self-assessment score, and then allowed for refinement of these images based on patient feedback to ensure that what the images were deemed to represent matched the content of the written questions. We suggest this software for picture based scale/questionnaire development to aid delivery of care equitably in a global context.

179 Does snacking help curb childhood obesity?

G Suarez*

J Moon

R Denny

G Brown

D Wagner

E Medina

M Baum

Loma Linda University, Loma Linda, CA

Purpose of study

According to the California Department of Education, students who are in Grade levels 5, 7, and 9, are near 48% overweight or obese. This is more than double what the national prevalence according to the Center for Disease Control. Unhealthy weight for this study is defined as overweight >85% BMI and obesity >95%BMI and is a serious problem that can lead to poor health, starting earlier in children. This study aims to assess a possible correlation between boredom and snacking to overweight and obesity using Body Mass Index (BMI).

Methods used

Children between the ages of 9–15 years were referred by a physician from a local federally qualified health center in San Bernardino to ‘Operation Fit’, a weeklong day camp, based on their unhealthy weight (BMI>85th percentile). In this program, 113 children participated in a group that was taught with interactive nutrition and physical activity lessons. Parents participated in a survey for lifestyle practices, including a question about boredom and snacking, with a parent education session at the end of the camp. These answers were then compared to their child’s BMI using logistic regression models.

Summary of results

In response to the statement ‘If I am bored, I will snack more’ there was a statistical significance for those that responded they do not snack.

Conclusions

Those that agree with snacking when bored are 0.401 times more likely to have children that are overweight than those who disagree. These results can be used in school systems to teach parents that the use of snacks in the correct way—as opposed to when bored—can help reduce the risk of gaining weight in children. This may also lead to the conclusion that healthy snacking habits can be used to help lower overweight and obese children, helping with reducing the additional risks with being overweight.

Poster session

Endocrinology and metabolism

6:00 PM

Thursday, January 23, 2020
180 A unique case of undiagnosed graves’ disease presenting as acute transient paralysis

G Petersen1,2

N Karapetians1,2,*

C Anderson1

D Farmand1

1Kern Medical, Bakersfield, CA

2UCLA, Los Angeles, CA

Purpose of study

Thyrotoxic Periodic Paralysis (TPP) is an unusual complication of hyperthyroidism, and is most commonly seen in Asian males. We are describing a case of a young Hispanic male presenting with acute onset lower extremity paralysis after strenuous physical activity who was found to have severe hypokalemia secondary to underlying undiagnosed Graves’ disease.

Methods used

Retrospective case report.

Summary of results

A 33-year-old Hispanic male with no significant past medical history presented with a two-day history of sudden onset bilateral lower extremity weakness leading to inability to ambulate. Symptoms started after patient performed strenuous activity in the setting of a sedentary lifestyle. Upon presentation to the ED, patient’s vitals were within normal limits and physical exam showed predominantly proximal bilateral lower extremity weakness, hyperreflexia in bilateral knees and 2 beats of clonus in bilateral ankles, action and postural tremors in bilateral hands. Laboratory assessment revealed severe hypokalemia, hypomagnesemia, mild elevation of creatinine phosphokinase, mild transaminitis, suppressed thyroid stimulating hormone and elevated free thyroxine. Urine potassium/creatinine ratio was less than 1 indicating transcellular shift as the cause of severe symptomatic hypokalemia. ECG 12-lead showed diffuse flattened T-waves. After normalization of potassium and magnesium, the paralysis and ECG abnormalities resolved within the first day of hospitalization. Treatment for hyperthyroidism with methimazole and propranolol was started during hospitalization and patient was discharged with outpatient follow up in endocrinology clinic.

Conclusions

This is a rare and interesting case of Thyrotoxic Periodic Paralysis in a young Hispanic male as the first manifestation of undiagnosed Graves’ disease. Thyrotoxic Periodic Paralysis often goes unrecognized at first attack due to low prevalence of disease and because patients usually exhibit mild symptoms of hyperthyroidism. TPP should always be considered in young patients presenting with acute onset muscle weakness and hypokalemia.

Poster session

Gastroenterology

6:00 PM

Thursday, January 23, 2020
181 A case of acute pancreatitis with refractory electrolyte imbalance

J Bhandohal*

J Bhaika

R Jariwal

R Gupta

S Allday

C Anderson

Kern Medical, Bakersfield, CA

Purpose of study

Pancreatitis secondary hypertriglyceridemia occurs in 1–14% of all acute pancreatitis cases. There have been no large randomized trials that have evaluated the effect of triglyceride lowering for primary prevention in patients with mild-to-moderate hypertriglyceridemia. It is important to recognize in order to provide appropriate therapy.

Methods used

Retrospective case report.

Summary of results

A 36-year-old male presented to the emergency department with epigastric pain with associated N/V x 1 week. Patient had a hx of alcohol abuse of 16 12-ounce beers/day x 1 yr. On physical examination, patient was in significant distress due to epigastric pain with guarding on abdominal palpation. Due to his hx and symptoms, a diagnosis of acute pancreatitis was suspected and patient was admitted for management of abdominal pain and intractable N/V. Initial lab testing did not result as patient’s blood sample was found to be grossly lipemic. This provoked a lipid panel to be drawn. Lipid panel was remarkable for triglycerides of 5700 mg/dl and total cholesterol of 658 mg/dl. Of all familial hypercholesterolemia’s, Type V dyslipidemia typically presents in adulthood with high risk of acute pancreatitis. Treatment was initiated with IV Insulin and dextrose, similar to the management of diabetic ketoacidosis, although our patient was not diabetic. Blood glucose checks were done Q1 hr to adjust insulin infusion accordingly. Triglyceride levels were checked Q12 hr. Insulin enhances the activity of VLDL and Hormone-Sensitive Lipase to promote the breakdown of FFA and triglycerides in the circulation. Gemfibrozil was added to increase HDL production thus further removing triglycerides from the circulation. Outpatient management includes atorvastatin, fenofibrate, niacin, and fish oil. Lifestyle components play a major role such as alcohol cessation, avoiding complex carbohydrates, initiating an aerobic exercise plan, and increased consumption of fish containing high amounts of omega-3 fatty acids.

Conclusions

There is limited data regarding which patients with hypertriglyceridemia require treatment and which therapies provide the best outcomes. This patient with pancreatitis secondary to an elevated triglyceride level of 5700 mg/dl was started on an insulin drip therapy for 3 days which lowered the level to 173 mg/dl.

Poster session

Healthcare delivery research

6:00 PM

Thursday, January 23, 2020
182 Acculturational affects reproductive health knowledge and perception of armenian americans

A Boodaghian*

A Hovssepian

AL Nelson

F Dong

Western University of Health Sciences College of Osteopathic Medicine of the Pacific, Pomona, CA

Purpose of study

The purpose of this study was to assess the perceptions about and knowledge of birth control amongst first and second generation Armenian men and women. A secondary objective was to investigate a possible association between education level and knowledge about birth control between the two groups.

Methods used

An anonymous online survey was administered to men and women who were first and second generation Armenians from ages 18–60. The questions included information about the demographics, self-assessment (perceptions) of their knowledge about birth control and test questions designed to objectively assess their factual knowledge about contraceptive efficacy and safety. The survey was conducted in private at an Armenian community center in Burbank, CA, from 6/10/19 to 7/26/19. Chi-square tests were conducted to assess the associations between knowledge (yes vs. no) and demographic variables collected.

Summary of results

Of the 147 individuals we approached, 135 participated in our study (response rate=92.8%). Overall, 61.6% were female, 33.3% were age 18–25 and 37.7% were age 26–35; 41.6% had been born in the U.S.

We analyzed the relationship between prior education and perceived and tested knowledge scores by birthplace and age of immigration. Perception of knowledge was higher than actual knowledge (p=0.04). Of those who believed they had been educated on birth control, only 33.3% answered the knowledge questions correctly, while those who believed they were not educated on the topic, 29.4% answered correctly. Higher education level correlated with higher actual knowledge (p=0.01), although those with less education perceived more knowledge on the topic.

Conclusions

Overall, only a minority of respondents correctly answered questions about contraceptive efficacy. Correct test scores (knowledge) were statistically significantly associated with both higher education level and birthplace. However, perceptions of contraceptive use had no significant relationship to age, education level or acculturation, either in unmarried or married couples.

183 The impact of medical student research as a discussion topic during the residency interview

K Daus*

M McEchron

University of Arizona College of Medicine – Phoenix, Phoenix, AZ

Purpose of study

The University of Arizona College of Medicine-Phoenix (UACOM-P) requires students to complete a longitudinal scholarly project. The present study surveyed fourth year medical students two weeks prior to the NRMP match. The goal of the study was to determine if medical student research was an important topic of discussion during the residency interview process.

Methods used

62 UACOM-P students from the class of 2019 completed a 16-question survey. The survey showed that 36 of the 62 students (58%) took on other research projects in addition to their SP. 32 students (48%) interviewed in primary care and 30 students (52%) interviewed for non-primary care specialties. The survey examined the student’s SP, volunteer experiences, work experiences, and non-SP research. The survey also determined if students published or presented research at a conference, and whether the research topics related to the specialty sought by the medical student.

Summary of results

Students reported that 29% of interviewers asked about their SP. Students interviewing in primary care were more likely to be asked about their SP if their research topic related to their specialty (42% vs 21%, p=0.0047). This relationship was not significant for students interviewing in non-primary care specialties (26% vs. 30%, p=0.6251). Students in non-primary care specialties were more likely to be asked about research if they had completed other research projects outside of their SP (56% vs 34%, p=0.0076). Interviewers were more likely to ask about the SP if the student had published their work or presented at a conference (35% vs 24%, p=0.0426).

Conclusions

Nearly 1/3 of residency interviewers ask students about their SPs. Students interviewing for primary care may expect more questions about their SP if their project is related to their specialty. Alternatively, if students are interviewing for a non-primary care specialty they may be more likely to receive questions about their research if they have completed other research projects in addition to their SP. Students who publish their SP or present their SP at a conference may be more likely to receive questions about their SP compared to those who do not. These findings suggest that scholarly research can provide medical students with an important vehicle of discussion during the residency interview process.

184 Decreasing medicare reimbursement for dermatological procedures 2000–2019

A Dorius1,*

M Kropelnicki1

JR Pollock2

JM Haglin2

G Hanson3

S Ochoa3

AR Mangold3

1Brigham Young University, Provo, UT

2Mayo Clinic Alix School of Medicine, Scottsdale, AZ

3Mayo Clinic, Phoenix, AZ

Purpose of study

With our aging population, patients covered by Medicare will continue to grow. For this reason, understanding Medicare reimbursement within dermatology will be increasingly important. In this study, we examine reimbursement trends for common Dermatology procedures from 2000 to 2019.

Methods used

The most commonly utilized dermatology procedures were found by searching for integumentary procedures in the CPY 2017 PUF data file. National reimbursement averages were then calculated and analyzed from 2000 and 2019 using The Physician Fee Schedule Look-Up Tool. Using the consumer price index, the averages were adjusted for inflation.

Summary of results

Medicare reimbursement for included procedures from 2000 to 2019 decreased substantially (-21.44% or 1.07%/year). The largest decreases were found in ‘Destruction of 2–14 skin growths’ (-79.43%), ‘Destruction of 15 or more skin growths’ (-52.94%), and ‘Removal of tissue from 1 to 5 finger or toe nails’ (-42.55%).

Conclusions

According to our data, Medicare reimbursement in dermatology has consistently declined when adjusted for inflation. As reimbursement continually decreases, Medicare patients may experience a decrease in accessibility to dermatologists and a reduced quality of care. A comprehension of these trends is essential as continued progress is made to achieve agreeable Medicare reimbursement in dermatology.

185 Learning with literature: how arts and humanities can be used in medical education

H Drake*

C Courneya

University of British Columbia, Vancouver, BC, Canada

Purpose of study

Empathy is the ability to understand the feelings of another and can be used by a physician to understand a patient’s values, feelings and perspective of their experience. This is an essential component of the doctor-patient relationship. Research demonstrates that students who engage in humanities develop higher levels of empathy and emotional intelligence; however, arts can be a challenge to incorporate in to traditional curricula of medical education.

Methods used

A student pilot project was developed to explore empathy through reading patients’ memoirs and creating reflections. Memoirs were selected based on two criteria: that they were written from the patients’ voice and secondly, that a variety of illnesses were captured. The student then depicted the patient’s story as a visual art piece, including themes from the book and representation of their illness. This was followed by a written reflection to combine, compare and contrast all of the lessons that were learned through the readings.

Summary of results

Through analyzing what the authors shared, a better understanding of what patients’ experience was developed. This led to the student having more confidence with patients, integrating tools learned from the authors, and understanding patient experiences.

Conclusions

This model could be adapted to a larger number of students, each reflecting in their own artistic way on the same memoir. A group experience provides different perspectives of the book and results in a deeper analysis.

186 Pocketophtho: development of a smartphone-based educational tool for learning ophthalmic knowledge

N Fong1,*

C Bacorn1

J Lee-Coomes2

G Yiu1

1University of California Davis, Sacramento, CA

2California Northstate University College of Medicine, Elk Grove, CA

Purpose of study

To create a high-quality smartphone app for educating ophthalmic knowledge developed under supervision of U.S. board-certified ophthalmologists.

Methods used

Ophthalmic content was curated from a team of board-certified ophthalmologists at the UC Davis Eye Center. De-identified ophthalmic images were obtained from these ophthalmologists and copyright-free online sources. Educational content and images were reviewed, verified, and updated by at least two independent ophthalmologists. The app was built in XCode, an integrated development environment for building apps compatible with Mac OS-X and iOS Apple operating systems, using the programming language Swift in collaboration with students from the UC Davis Computer Science Department.

Summary of results

The alpha prototype was built and reviewed with a panel of ophthalmic trainees including residents and fellows for functionality and usability to improve the prototype. The app name was selected based on survey responses. Survey questions include ‘Which app evokes reliability,’ ‘Which app sounds the most user-friendly,’ and ‘Which app sounds most reputable.’ Additional educational content has been included for development of a beta prototype.

Conclusions

PocketOphtho is a high-quality smartphone app for teaching ophthalmic knowledge developed in conjunction with U.S. board-certified ophthalmologists, which can be useful for residents and fellows in ophthalmology training or in preparation for the Ophthalmic Knowledge Assessment Program (OKAP) or Written Qualifying Exam (WQE).

187 Transitioning to adulthood with hydrocephalus: a patient’s perspective

S Fouladirad*

A Cheong

P McDonald

University of British Columbia, North Vancouver, BC, Canada

Purpose of study

Hydrocephalus is a chronic neurological condition that affects around 6 in 10 000 live births and is one of the most common indications for pediatric brain surgery. The condition is fatal if left untreated, however the introduction of new operative procedures such as shunt placements has led to most pediatric patients surviving and transitioning to adulthood. However, unlike other chronic conditions such as cystic fibrosis, congenital heart disease, type I diabetes, etc., the transition of adolescents with hydrocephalus from pediatric to adult care is often fragmented and disjointed given the lack of attention and research in establishing appropriate guidelines and models of transfer. This is particularly concerning not only due to the prevalence of hydrocephalus among the pediatric population, but the significant increase in morbidity and mortality associated post-transition with poorly handled transfers.

Methods used

The study consisted of two phases that used a series of interview and survey questions to collect qualitative and quantitative data to identify factors that challenge young adults with hydrocephalus who are transitioning/transitioned from B.C Children’s Hosptial in Vancouver into adult care at Vancouver General Hosptial.

Summary of results

Emerging themes from the data highlighted the difficulty patients and their family members have in forgoing strong and familiar relationships that have been formed over the years at B.C Children’s Hospital, adapting to the new cultural environment in an adult clinic and becoming self-reliant.

Conclusions

Understanding the expectations, concerns and overall input of patients is one of the many important steps that must be taken take in order to build a foundation for a transition model of care that can carefully attend to the needs of patients with hydrocephalus.

188 Oral self-emulsifying drug delivery system for detection of beta amyloid plaques in the retina of ad mice

N Hashem*

AC Bakshi

S Fuchs

M Issar

Western University of Health Sciences College of Osteopathic Medicine of the Pacific, Ontario, CA

Purpose of study

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive deterioration and is characterized by the accumulation of amyloid plaques found in neuronal tissue. Aß plaques can form in retinal tissue, allowing for early detection of AD. The objective of this project was to develop a self-emulsifying drug delivery system (SEDDS) for oral administration to enhance systemic absorption of curcumin via lymphatic route. Higher blood levels of curcumin equilibrate within the eye allowing binding to Aß plaques in retinal tissue. The intrinsic fluorescence of curcuminoids bound to Aß plaques would be quantified by imaging.

Methods used

SEDDS were developed using medium-length chain triglycerides (MCT), polyoxyl castor oil (emulsifying agent), and Transcutol to solubilize curcumin. These formulations were observed for stability, diluted, and incubated at 37°C for 24 hrs. Before testing in vivo, formulations were selected based on particle size and triglyceride ratio and the dialysis membrane method was used to test drug release in vitro. SEDDS were diluted and 0.2 ml were added into a dialysis bag which was immersed into 19 ml of citrate buffer containing 0.5% SDS. Samples were withdrawn at different time intervals until 48 hours and were analyzed for curcumin released into the medium by HPLC.

Summary of results

Addition of Oleic acid (OA) to MCT containing formulation dramatically decreased the release of curcumin from the micelles by 60%. Absolute values for drug release at 37°C for formulation #S407/10 (with OA) and #S407/9 (without OA) were 18.7% and 84.1% respectively at 48 hour. Whereas, addition of poloxamer 124 (another emulsifying agent) to polyoxyl castor oil containing formulation (#S507/8) increased drug release by approximately 80%.

Conclusions

A decrease in drug release for formulation #S49_7/10 could be due to greater lipophilicity of oleic acid, which is a long chain fatty acid. On the contrary, incorporation of a hydrophilic surfactant poloxamer 124 to polyoxyl castor oil possibly allowed greater release due to higher dissolution medium penetration within the micelles. Oral delivery of SEDDS formulations will be tested in vivo in mice to determine oral bioavailability of curcumin as a future diagnostic tool for AD.

189 Empowering nurses: using knowledge to screen & identify victims of human trafficking

P Khanna*

F Dong

R Trudgeon

IC Tuason

Western University of Health Sciences, Pomona, CA

Purpose of study

Nursing professionals are indispensable to the care team when serving victims of human trafficking. Knowledge & trauma informed training are pivotal for developing & implementig screening tools for potential victims. Purpose is to assess the effectiveness of an educational intervention to increase the knowledge of current graduate nursing students about resources and federal laws for victims of human trafficking

Methods used

Pre-licensure students & licensed nursing students at Western University of Health Sciences were invited to participate in an educational activity about human trafficking. Participants were asked to fill out a pre seminar questionnaire. A 30- minute presentation was delivered. After the presentation, participants completed a post seminar questionnaire that consisted of the same ten questions from pre seminar questionnaire.

Summary of results

Final analysis incuded 65 students. There was significant increase in awareness about human trafficking (84.9% vs 97.8%, p=0.0082). 7% corrected rank order of at risk victims before lecture and 15.2% post lecture (p=0.1025). Statistically significant change to correct response to questions was noted; which standard did US meet to eliminate human trafficking (64.8% vs 93.5%, p=0.0002), number of different types of human trafficking (16.3% vs 76.1%, p<0.0001), & what are the hotspot of human trafficking (20.4% vs 76.1%, p<0.0001).

Conclusions

Study suggeted increased information and awareness about human trafficking. The project aim, to empower nurses with knowledge so that they are informed agents of change was met. Equipping nurses with information is paramount for providing trauma informed care. Doing so by focusing on nurse edu. solidifies the importance of nurses’ knowledge about the growing public health concern.

190 Decreasing medicare reimbursement for ophthalmological procedures 2000–2019

M Kropelnicki1,*

DA Dorius1

J Pollock2

J Haglin2

D Patel2

1Brigham Young University, Provo, UT

2Mayo Clinic Alix School of Medicine, Scottsdale, AZ

Purpose of study

A large portion of ophthalmological patients are elderly, therefore, Medicare policy may disproportionately affect this field. In this paper, we analyze the change in Medicare reimbursement rates for common ophthalmological procedures from 2000 to 2019.

Methods used

Using the Centers for Medicare and Medicaid Services website, the most utilized ophthalmology procedures and treatments (65000–68000) were selected using the CPY 2017 PUF data file. The 2000 and 2019 national reimbursement averages for each procedure were gathered using the Physician Fee Schedule Look-Up Tool, and the data was analyzed. Each average was adjusted for inflation using the consumer price index.

Summary of results

When adjusted for inflation, the average reimbursement for the procedures analyzed in this study has decreased dramatically since 2000 (-20.82%). Rates for the majority of procedures have decreased by sizeable amounts. The largest decreases were seen in ‘laser destruction of leaking retinal blood vessels’ (-69.30%) and ‘injection of drug into eye’ (-59.14%).

Conclusions

These results demonstrate that Medicare reimbursement rates for ophthalmology procedures have declined over the last 20 years. As the number of patients covered by Medicare continues to increase, a growing portion of a physician’s patients will be covered by Medicare. If ophthalmology procedure reimbursement rates continue to fall, access to quality care for millions of Americans with Medicare may suffer.

191 Impact of waiting room art intervention on pediatric patients’ anxiety and cooperation with physician

P Matus*

A Belikova

F Dong

S Fuchs

Western University of Health Sciences, Pomona, CA

Purpose of study

To determine whether the implementation of an art activity decreases pediatric patients’ anxiety in the waiting room and increases cooperation with their healthcare provider. This is a longitudinal pilot study that will expand on existing pediatric anxiety studies. The relationship between art therapy and pediatric stress levels has not been evaluated in detail in this specific circumstance.

Methods used

Research is being conducted in the Patient Care Center at Western University of Health Sciences, Pomona, CA, and is approved by the Institutional Review Board. A randomized controlled study design is done with pre-and-post intervention evaluations of both the intervention and control groups. The subjects in the experimental group perform a creative art activity while control subjects choose their own activity. Anxiety is evaluated when the subjects enter the waiting room and before the physician encounter using a modified SCARED questionnaire. The physician assesses the quality of the encounter by completing a questionnaire. Data will be analyzed using the SAS software for Windows version 9.3. Descriptive statistics will be presented as means and standard deviations for continuous variables, along with frequencies and proportions for categorical variables. The change in the anxiety score will be calculated as the summation of the five key items. The change will be assessed by the general linear model with the group (control vs intervention) as the categorical variable. All statistical analyses will be two-sided. P-value<0.05 will be considered to be statistically significant.

Summary of results

We are currently completing data collection. We hypothesize that an art intervention will reduce pediatric patients’ anxiety. This will result in better cooperation with the physician during the medical encounter. Data analysis will focus on quantifying subjects’ daily anxiety and situational anxiety in the PCC waiting room.

Conclusions

Conclusions are pending until an appropriate amount of data is collected. If our hypothesis is supported by this pilot study, we will expand this research to a larger number of subjects and facilities to obtain confirmation. This can yield recommendations for pediatric waiting room settings. *AB and PM have contributed equally to this work.

192 Analysis of medicare reimbursement trends for medical office visits 2000–2019

JR Pollock1,*

JM Haglin1

DG Deckey2

1Mayo Clinic Alix School of Medicine, Scottsdale, AZ

2Mayo Clinic, Phoenix, AZ

Purpose of study

This study examines Medicare reimbursement trends from 2000 to 2019 for medical office visits for new and existing patients. These codes are commonly used in most medical specialties.

Methods used

The Physician Fee Schedule Look-Up Tool from CMS website was utilized to calculate national reimbursement averages from included codes (codes 99201–99205 and 99211–99215). Averages were then adjusted for inflation using the consumer price index.

Summary of results

From 2000–2019, Medicare reimbursement rates for the longest new patient visits of 45 and 60 minutes have increased by 64.7% and 110.3% respectively. Meanwhile, the shortest new patient visits of 10 and 20 minutes have decreased by 64.7% and 35.8% respectively. From 2000 to 2019, there was a 13.3% increase in reimbursement for new patient office visits (99201–99205), with a 32.1% decrease in reimbursement for existing patient office visits (99211–99215). Patient office visits codes 99201–99205 and 99211–99215 have seen a 9.4% overall decrease.

Conclusions

According to our results, Medicare reimbursements have increased for longer patient visits and decreased for shorter patient visits. Additionally, Medicare reimbursement has increased for new patient visits and decreased for existing patient visits. Healthcare quality and access could be impacted by these trends as physicians are incentivized to accept new Medicare patients rather than follow-up visits. Future studies should be done to futher examine reimbursement trends.

193 20 years of medicare reimbursement trends in transplant surgery

JR Pollock1,*

JM Haglin1

HE Vargas2

1Mayo Clinic Alix School of Medicine, Scottsdale, AZ

2Mayo Clinic, Phoenix, AZ

Purpose of study

As the elderly population of the United States grows, so does the Medicare population and the need for transplant surgery. This study examines the Medicare reimbursement trends for transplant surgeries from 2000 and 2019.

Methods used

The Centers for Medicare and Medicaid Services website was utilized to find the most commonly utilized transplant procedures using the CPY 2017 PUF data file and searching for the term ‘transplant’ in the HCPCS description. Using The Physician Fee Schedule Look-Up Tool, national reimbursement averages were calculated from 2000–2019 and data was analyzed. Averages were adjusted for inflation using the consumer price index.

Summary of results

Medicare reimbursement for included procedures decreased from 2000 to 2019 (-19.85% or 0.99%/year). The largest decreases were seen in ‘Harvest of donor bone marrow for transplantation’ (-45.75%), ‘Transplant of tendon and muscle rerouting at lower leg or ankle’ (-43.19%), and ‘Removal of bladder and lymph nodes on both sides of pelvis with transplantation of ureters to small or large bowel with creation of urinary opening’ (-34.46%).There were only 3 procedures with increased reimbursement.

Conclusions

Medicare is continually decreasing physician reimbursement rates for most transplant surgeries. Unfortunately, this potentially creates barriers to access these life-saving procedures for Medicare patients. This trend could also present many difficulties for surgeons and hospitals.

194 Onsite clinic care of work injuries in healthcare workers

LW Raymond1,2,*

1Atrium Health, Charlotte, NC

2Unversity of North Carolina, Chapel Hill, NC

Purpose of study

Onsite clinics (OSCs) render care for minor illnesses and uncomplicated hypertension, diabetes and other conditions. The aim of this pilot study was an analysis of OSC care by Advanced Practice Providers (APPs) -- Nurse Practitioners or Physician Assistants -- of healthcare workers (HCW) with workers compensation (WC) injuries.

Methods used

We compared the incidence of injuries and lengths of restricted duty (RD) among 18,000 hospital-based HCW, versus those expected from data of the US Bureau of Labor Statistics (USBLS) and a database associated with the American College of Occupational and Environmental Medicine (ACOEM).

Summary of results

HCW reported 68 injuries over 6 months for an incidence rate of 0.76 RD cases/100 workers per year, compared to 1.0 for all US HCW. RD days differed according to type of care (table 1). OSC care was associated with fewer RD days than expected. HCW who were prescribed physical therapy (PT) had 6-fold as many RD days, while those referred for specialty care (usually orthopedic) had over 5-times as many RD days, some results pending post-operative recovery. Causes included lifting and other direct patient care (35%), slips or trips (19%), and assaults (7%). Resulting effects included sprains or strains (40%), low back pain (25%) and abrasions or contusions (19%).

Conclusions

Reported injuries were fewer than expected by USBLS criteria. So were RD days according to an ACOEM-affiliated database, unless PT or specialty referral were prescribed. Whether these differences in RD days reflects severity of the injuries or other factors will require additional analysis. Care of hospital-based healthcare workers rendered in OSCs staffed by Advanced Practice Providers generally yielded very good results.

Abbreviations

OSCs, onsite clinics; PT, physical therapy; RDD, restricted duty days.

195 Health coaching: biometrics were better after a year

L Raymond1,2,*

M Slomba1

C Ford1

1Atrium Health, Charlotte, NC

2University of North Carolina, Chapel Hill, NC

Purpose of study

To compare glycemic control and other biometrics over 1 year in 2 groups of wellness program participants (WPP) at a rural North Carolina workplace. Group A WPP had high-risk biometrics and were provided health coaching. Group B WPP had lower risks and got no coaching.

Methods used

Glycated hemoglobin (HbA1c) was measured by high performance liquid chromatography. Fasting blood glucose (FBG), total cholesterol (TC), low- and high-density lipoproteins (LDL, HDL) and triglycerides (TG) were measured by autoanalyzer in 94 Group A WPP (age 48 ± 10 SD, 62% male) and 390 Group B WPP (age 45 ± 12 SD, 41% male). A certified health and wellness coach provided 2 to 4 counseling sessions to Group A WPP depending on risk factors: prediabetic and diabetic HbA1c >5.6 and >6.4, respectively, and improved diet, exercise, and weight control. WPP in both groups got letters with their blood test results requesting they share them with their physicians.

Summary of results

By group definitions, initial values of FBG, lipoproteins and blood pressures (table 1) were all much less salubrious in Group A than B (p=0.02–0.0001). A year later, between-group differences remained except for TC and LDL. HbA1c improved in Group A but glycemic control by FBG waned in Group B. TC and LDL also worsened in Group B. HDL and TG improved in both groups, with small but significant falls in diastolic blood pressure (BP).

Conclusions

Health coaching was accompanied by improved glycemic control not found in uncoached WPP. HDL and TG improved in both coached and non-coached groups, as did diastolic BP. The durability of these improvements requires further investigation.

Poster session

Infectious diseases

6:00 PM

Thursday, January 23, 2020
196 Evaluation of three cytomegalovirus IGG lateral flow assays for determination of cytomegalovirus serostatus

F Ali1,*

L Joncas-Schronce1

G Pepper1

RD Stapleton2

GD Rubenfeld3

M Boeckh1

A Limaye1

1University of Washington School of Medicine, Seattle, WA

2University of Vermont, Burlington, VT

3Sunnybrook Health Sciences Center, Toronto, ON, Canada

Purpose of study

Cytomegalovirus (CMV) serostatus is a major determinant of CMV reactivation risk. Current clinical serology assays are limited by slow turnaround time and need for either trained personnel and/or specialized equipment.

Methods used

We assessed the performance of three rapid lateral flow assays (LFA) for detection of CMV IgG antibodies compared to a primary reference CMV enzyme-linked immunoassay (ELISA) (Zeus ELISA™ CMV IgG), in serum from 200 consecutive adults, performed clinically. A subset (N=60) of samples for which there was discordance between the primary reference assay and one or more of the LFAs was also tested by a second reference method: LIAISON DiaSorin CMV IgG. LFA testing was done by a single blinded research technician and followed by inter-operator agreement assessment in three independent, blinded, non-laboratory-trained personnel, using the LFA with the best performance characteristics.

Summary of results

By the primary reference ELISA, 93 patients (46.5%) were seropositive, and 107 (53.5%) were seronegative, and there was 100% agreement (60/60) with the subset tested by the second reference assay. The sensitivity and specificity of the three LFAs (Healgen, Qoolabs read with Automated Reader, and nanoComposix), compared to the ELISA reference assay, were: 86%/83%, 99%/93%, and 57%/97%, respectively. For the QNow assay, the sensitivity and specificity were similar when interpreted by visual inspection with a UV wavelength flashlight (97%/97%). There was inter-operator agreement for 29/30 (97%) observations (10 samples; 4 positive, 6 negative).

Conclusions

All three LFAs were rapid, easy to perform and interpret, but showed variability in performance. The ease of performance and rapid turnaround time provide the rationale to further evaluate these assays in clinical settings where these attributes would be advantageous.

197 Coccidioidal meningitis and cirrhosis: is the game over?

C D’Assumpcao1,*

FC Venter1

K Sabetian1

A Heidari1,2

1Kern Medical – UCLA, Bakersfield, CA

2Valley Fever Institute, Bakersfield, CA

Introduction

Coccidioidal meningitis requires lifelong, potentially hepatotoxic, triazole therapy. Complicated cases might need neurosurgical shunt or reservoir for intrathecal treatment. Cirrhosis complicates treatment options due to impaired hepatic function, coagulopathy and thrombocytopenia. We share a challenging case of coccidioidal meningitis in a cirrhotic patient with thrombocytopenia.

Case report

62 year old Hispanic male with alcoholic cirrhosis, portal hypertension requiring transjugular intrahepatic portosystemic shunt (TIPS), thrombocytopenia with splenic embolization, protein S deficiency with thrombosis of portal vein and left cephalic vein now off warfarin for two years, prediabetes and pulmonary coccidioidomycosis for two years off fluconazole for two months due to insurance presented with six weeks of progressive persistent occipital headaches, photophobia, nausea, vertigo, tinnitus, decrease hearing, blurry vision and short term memory lapses. Initial CT neuroimaging found 8 mm hyperdense focus in the posterior left cerebellum. Platelets were 51,000/uL. Presenting cirrhosis prognostic scores were Child Pugh A and MELD 10. TIPS was non-functional by ultrasound. MRI brain found mild hydrocephalus and abnormal periventricular signal in midbrain structures with severe leptomeningeal enhancements. Lumbar puncture had normal opening and closing pressures, lymphocytic pleocytosis, hypoglycorrhachia, and elevated protein. Serum and CSF coccidioidal antibody immunodiffusion were reactive with severely elevated complement immunofixation titers. Due to thrombocytopenia intrathecal amphotericin was deferred. Because of fluconazole failure and voriconazole hepatotoxicity, isavuconazole was started. Dexamethasone taper was added due to hearing and short term memory loss. Outpatient audiogram and liver function monitoring was arranged with plan for lumbar puncture in four weeks. The pharmacokinetic and pharmacodynamic impact on his lifelong azole therapy from TIPS recanalization and impaired cytochrome P450 3A4 and 3A5 is unknown.

Conclusions

Coccidioidal meningitis is fatal if not treated. Hepatic impairment complicates management due to therapeutic limitations. Prognostic impact needs to be studied further but, in our experience, it is diminished.

198 Lyme disease: diversity of borrelia species in california and mexico based on a novel immunoblot assay

MC Fesler1,*

JS Shah2

MJ Middelveen3

JJ Burrascano2

RB Stricker1

1Union Square Medical Associates, San Francisco, CA

2IGeneX Laboratories, Milpitas, CA

3Atkins Veterinary Services, Calgary, AB, Canada

Purpose of study

Lyme disease is a growing tickborne epidemic with more than 400,000 new cases reported each year in the USA. If left undiagnosed and untreated, many of these cases progress to chronic Lyme disease, as recently defined (Stricker & Fesler, Am J Infect Dis 2018;14:1–44). Although Borrelia burgdorferi sensu stricto is considered the primary agent of Lyme disease in North America, recognition of previously undetected species of Borrelia burgdorferi sensu lato (Bbsl) and Relapsing Fever Borrelia (RFB) has complicated the diagnosis and treatment of Lyme disease. We report preliminary results of a serological survey of Bbsl and RFB in California and Mexico using a novel immunoblot technique.

Methods used

The immunoblot method was designed to detect seroreactivity with specific species of Bbsl and RFB based on recombinant Borrelia membrane proteins, as previously described (Liu et al, Healthcare 2018;6:99; Shah et al, Healthcare 2019, in press). Patients were considered seropositive if they reacted with at least two proteins from a specific Borrelia species.

Summary of results

Sixty-seven patients who resided in California or Mexico met the clinical definition of chronic Lyme disease. Immunoblot testing revealed that 30 patients were seropositive for Bbsl (Group 1), while 44 patients were seropositive for RFB (Group 2). Group 1 included patients who were seropositive for B. californiensis (6), B. spielmanii (8), B. afzelii/B. garinii (8), and mixed infections that included B. mayonii (3). Group 2 included patients who were seropositive for B. hermsii (5), B. miyamotoi (7), B. turicatae (7) and B. turcica (2). Seven patients were seropositive for both Bbsl and RFB species. In addition, four patients in Group 1 were seropositive for two species of Bbsl, while two patients in Group 2 were seropositive for two species of RFB. In the remaining Group 1 and Group 2 patients, the exact Borrelia species could not be identified using the immunoblot technique.

Conclusions

Lyme disease is associated with a diversity of Borrelia species in California and Mexico. The clinical significance of this diversity in terms of missed diagnosis and response to antibiotic therapy requires further study.

199 Osteomyelitis with infected hardware due to streptococcus dysgalactiae subspecies equisimilis

R Hall1,*

S Choi2

D Holt1

A Govindarajan3

A Heidari3

1Ross University School of Medicine, Miramar, FL

2Arizona College of Osteopathic Medicine (AZCOM) at Midwestern University, Glendale, AZ

3Kern Medical – UCLA, Bakersfield, CA

Purpose of study

Group C streptococci (GCS), specifically Streptococcus dysgalactiae subspecies equisimilis, are gram-positive, ß-hemolytic bacteria frequently isolated in the gastrointestinal tract, urogenital tract and occasionally as a part of the normal skin flora. We are presenting a complicated case of hip arthroplasty infection with Streptococcus dysgalactiae subspecies equisimilis.

Methods used

Retrospective chart review.

Summary of results

An 80-year-old female with a right total hip arthroplasty over 10 years ago was transferred to our hospital for fever, right hip swelling and pain. She stated that her hip dislocates every 6 to 8 months. Imagine showed underlying greater trochanter fracture and absent of hip abductors resulting in trochanteric escape and instability with hip dislocations. Imaging also revealed thick walled collection lateral to the hip extending to left iliacus muscle. She underwent incision and drainage and culture grew Streptococcus dysgalactiae subspecies equisimilis (SDSE). Sensitivity showed benzylpenicllin 0.32 mcg/mL and ceftriaxone 0.064 mcg. After 2 incision and drainage, She underwent 2 stage total hip revision. She continued on ceftriraxone 2 gram for 6 weeks.

Conclusion

Streptococcus dysgalactiae subspecies equisimilis is an emerging bacterial infection to humans. Infection of Total Hip Arthroplasty with this pathogen is rare and has not been published.

Streptococcus dysgalactiae, virulence, skin and soft tissue, infection, osteomyelitis, management.

References

  1. Bradley S.F., Gordon J.J., Baumgartner D.D., Marasco W.A., Kauffman C.A. Group C streptococcal bacteremia: analysis of 88 cases. Rev Infect Dis 1991;13(2):270–280. [PubMed] [Google Scholar]

  2. Broyles L.N., Van beneden C., Beall B. Population-based study of invasive disease due to beta-hemolytic streptococci of groups other than A and B. Clin Infect Dis 2009;48(6):706–712. [PubMed] [Google Scholar]

200 Disseminated coccidioidomycosis to the chest wall: flesh-eating fungus

N Raza

A Heidari*

S Dhital

Kern Medical, Bakersfield, CA

Purpose of study

Coccidioidomycosis is an infection caused by Coccidioides endemic to southwestern United States.1 The incidence of coccidioidomycosis has risen substantially: in California, the annual incidence increased from 2.5 to 8 per 100,000 during 1995–2006.2 The rates increased to 14 during 2010–11,3,4 and after a decline, jumped back to 13.7 in 2016 with the highest annual number to date.5 Although manifestations of coccidioidomycosis infection are well-described and typically resemble flu-like symptoms,6,7 presentation and treatment of disseminated coccidioidomycosis of chest wall is not well-studied.8

Methods used

Retrospective study.

Summary of results

A 33-year-old Hispanic male presented to regional hospital with complain of chest swelling, which increased over 6 weeks and eventually became painful with mild shortness of breath. He denied having a fever, cough, night sweats, or chills but reported generalized weakness and fatigue for 6 months, which started after a cold-like illness that lasted a week. He developed painful maculo-papulovesicular rash on his upper anterior chest wall. He was evaluated by several providers prior to the ER visit and was diagnosed with dermatomal varicella zoster infection. CT scan revealed multiple loculated fluid collections in the mid portion and right side of the anterior chest wall, suggesting abscesses. These measured approximately as big as 14.5 × 9.2 × 3.2 cm. CT guided drainage was done which revealed coccidioidomycosis immitis. Extensive incision and drainage were done which left bilateral large open wounds on both sides of the upper chest wall. He underwent several weeks of amphotericin IV with aggressive wound care which eventually allowed secondary closure. His treatment changed to high dose oral fluconazole. After a year, patient’s cocci titers were 1:256 with Cocci IgM and IgG reactive. After 2 more years of fluconazole, his treatment was tapered and stopped by outside providers.

He presented to us with reactivation of his serology back up to 1:32 and was restarted on his treatment. During this time, he only complains of generalized weakness and is undergoing investigation of other foci of infection.

Conclusions

A diagnosis of disseminated coccidioidomycosis should be considered in any unusual presentations in endemic areas for coccidioidomycosis.

201 A common illness masquerading as pyelonephritis

C Kien1,*

K Ganta2

1ASU, Tempe, AZ

2NMVAHCS, ABQ, NM

Case report

A 20 year old, otherwise healthy student, presented to the Emergency Room with 5 days of intermittent fevers, shaking chills, dry cough and a non tender neck mass. She had been seen 48 hours prior in urgent care where a mono spot and strep screen were negative. In the ER she denied sore throat and dysuria, however she did note abdominal pain. Exam was remarkable for a temperature of 38.90 C. She had fullness in her neck but no discreet lymph nodes; pharynx and lungs were normal. Bilateral upper abdominal and left CVA tenderness were noted. Lab studies showed a WBC of 7,300 (41% neuts, 47% lymphs, 10% monos), hematocrit 42 and platelets 107,000. Urinalysis showed protein >500 mg/dL, 6–10 WBCs and 11–20 RBCs/HPF. Nitrite and leukocyte esterase were negative with moderate bacteria. Renal function was normal. She was admitted with the diagnosis of pyelonephritis and started on Ceftriaxone. CT of the neck/chest/abd/pelvis revealed bilateral enlarged anterior cervical lymph nodes and an enlarged spleen. Her temperature reached 40.20 C with worsening abdominal pain. On day 2 she developed a significant anemia with a mild elevation in LDH, urine culture was no growth and Epstein Barr virus (EBV) infection was confirmed. Antibiotics were stopped. Because of the severity of her fever and an unrelenting cough she received solumedrol. Acyclovir was considered but not given. She was discharged on day 4 with a prednisone taper only to develop urticaria within 48 hours. The urticaria, felt to be associated with EBV, resolved 2 weeks after onset. In summary we present a case of initial mono spot negative EBV infection without pharyngitis but with lymphadenopathy, splenomegaly, abdominal pain and unusually high fevers on presentation. The urine abnormalities were consistent with interstitial nephritis, a rare, under recognized complication of EBV; sometimes mistaken for a UTI. Renal involvement is usually self limited as in our case. Additionally she experienced anemia, and urticaria which have been reported with EBV. In conclusion EBV, one of the most common viruses worldwide, and asymptomatic in many, can present with a confusing constellation of findings and without the hallmark pharyngitis leading to misdiagnosis, as in our patient. Our patient recovered, however rare reports of acute renal failure, encephalitis, and splenic rupture have been linked to EBV infection.

202 Pediatric coccidioidomycosis meningitis

C Sugirtharaj1,2,*

S Lam1,2

J Uy3

V Marquez3

R Gavilan3

J Ihejirika3

G Fernandez1,3

L Manzanares3

1Kern Medical Center, Bakersfield, CA

2Ross University School of Medicine, Bridgetown, Barbados

3Rio Bravo Family Medicine, Bakersfield, CA

Background

Coccidioidomycosis is a fungal infection that can manifest as flu like symptoms to more severe symptoms such as pneumonia or meningitis. However, coccidioidomycosis in the pediatric populations is not frequently studied with few studies on the management of pediatric coccidioidomycosis.

Case Report

A 7-year-old male presented to the ED with a cough and fever for 2 days. Chest x-ray indicated a right upper lobe and lingular pneumonia. Patient arrived 2 days after with persistent fevers, fatigue, nausea, emesis and meningeal symptoms with a positive Kernig and Brudzinski sign. He was afebrile and tachycardic on admission. Patient was admitted to the pediatric floor where he was given Dexamethasone, Acyclovir 200 mg, Ceftriaxone 2g and Vancomycin 320 mg. A lumbar puncture showed WBCs of 720, glucose of 27 and proteins of 128. CSF gram stain noted no organisms but with many PNMs. Patient continued to have nausea, emesis and fevers for 48 hours with temperatures up to 103. On day 3 of admission, serum coccidioidomycosis results indicated no IgM but a positive IgG with titers of 1:4 whereas the CSF results were negative. The patient was started on oral Fluconazole 200 mg and then transferred to a pediatric higher level of care. During transfer the patient suffered a grand-mal seizure for 1.5 minutes. He was then treated at the facility with Fluconazole 12 mg/kg/day and Keppra 30 mg/kg/day. Patient was discharged one week later with oral Fluconazole 100 mg twice a day and told to follow up for repeat LP and serum titers. An EEG conducted during his stay indicated mild encephalopathy. Patient would require Fluconazaole as a lifetime treatment.

Conclusion

In the course of a coccidioidomycosis infection less than 50% have IgM present a week after symptom onset indicating a high false negative during the early stage of infection. The stated patient had no antibodies in the CSF. As a result, following up with a repeat LP is crucial to confirm the etiology of his meningitis. Very few cases of pediatric cocci meningitis have been reported. As a result, establishing a standard of care when encountering such cases is imperative.

203 Bacterial two-component systems as antimicrobial targets

N Yamamoto1,*

M Rosales-Hurtado2

M Ogawa-Okada1

Z Benfodda2

P Meffre2

H Szurmant1

1Western University of Health Sciences, Pomona, CA

2Université de Nîmes, Nîmes, France

Purpose of study

Two-component systems (TCS) comprising sensor histidine kinase (HK) and response regulator proteins are ubiquitous bacterial signal transduction mechanisms with regulatory functions in virulence, antibiotic resistance, toxin expression, cell differentiation and others. Some TCS are essential for bacterial viability yet no similar mechanisms are found in the animal kingdom. TCS are thus considered attractive antimicrobial targets. Previous efforts have identified lead compounds that inhibit multiple HK proteins and feature promising broad spectrum antimicrobial activities. Medicinal chemistry efforts resulting in a series of 50 novel compounds were probed for improved antimicrobial activities of the initial lead compounds.

Methods used

Antimicrobial activities of 50 novel compounds against Staphylococcus aureus were assessed by Kirby-Bauer disk diffusion assays following Clinical & Laboratory Standards Institute guidelines. Minimal inhibitory concentrations (MICs) for the most promising compounds were assessed against a variety of Gram-negative and Gram-positive bacterial pathogens by serial dilution. All compounds were assayed for in vitro HK inhibitory activities and off-target inhibition of structurally related DNA-gyrase and structurally unrelated serine/threonine kinases were determined.

Summary of results

Antimicrobial assays of the compound series singled out three with MICs in the µg/mL range against all tested bacterial pathogens. The compound series revealed inhibitors with varying specificities for a set of three HK in vitro, as assayed by autoradiography. None of the compounds showed off-target inhibition of DNA-gyrase, which shares a structurally related ATP-binding domain with HK proteins. Similarly, structurally unrelated serine/threonine kinases were not inhibited by any of the compounds.

Conclusions

Novel compounds with promising antimicrobial activities were identified. TCS continue to be attractive targets and our efforts contribute towards a body of research with the ultimate goal of identifying effective inhibitors that can serve as new antibiotic agents.

Poster session

Morphogenesis and malformations

6:00 PM

Thursday, January 23, 2020
204 Bilateral agensis of the internal carotid arteries

TS Matern

A Shinagawa*

R Rangaswamy

University of Nevada, Reno, Reno, NV

Introduction

Bilateral internal carotid artery agenesis (BLICAA) is a rare anomaly with minimal reporting in the literature. This case of BLICAA, consistent with previous case reports, presented with neurological symptoms.

Case description

This case outlines an instance of bilateral ICA agenesis in a 59 year old male. The patient was hospitalized for acute onset left arm numbness. On admission, imaging revealed bilateral agenesis of the ICA. The intracranial vertebral arteries demonstrated atherosclerotic plaque with ~50% occlusion. MRI C-Spine also revealed severe left neuroforaminal stenosis at C6-7. The patient continued to experience left arm weakness and numbness, in a non-dermatomal distribution, with decreased bicep deep tendon reflexes. He denied associated radicular pain. The patient was discharged and instructed to follow-up with neurosurgery as an outpatient. Follow-up MRI revealed multiple lacunar infarcts. These imaging findings, in conjunction with an absence of radicular pain, were determined to be the cause of the patient’s left arm weakness and numbness.

Discussion

This case is classified as an instance of BLICAA (delineated from aplasia by the absence of carotid canal on CT), of which only 32 cases were found to be previously reported in the literature. Furthermore, this patient presented with two additional vascular variations; first, a common origin of the right vertebral artery and common carotid artery, and second, an aberrant right subclavian artery. It is unclear exactly how this patient’s vascular anomalies contributed to his presentation, but in the context of previous cases, the absence of both ICA’s was presumably a significant factor in the development of his cerebrovascular symptoms.

Poster session

Neonatal pulmonary

6:00 PM

Thursday, January 23, 2020
205 Does cesarean section increase the risk of lower respiratoy tract infections in infants?

HV Dayag1,2,*

B Myint2

K Ok2

V Sampath2

J Hockman2

A Yan2

P Lyu2

B Afghani2,3

1University of California, Irvine, Irvine, CA

2UC Irvine School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

There has been some suggestion that infants born by C-section may be at higher risk of lower respiratory tract infections (LRTI) but the evidence is not clear. The objective of this study is determine if c-section is associated with increased risk of LRTI in infants.

Methods used

A literature review was conducted using Google Scholar and PubMed using key terms such as: lower respiratory tract infection (LRTI), c-section bronchiolitis, and pneumonia. Only studies that included infants born via c-section and a control group (vaginal delivery) with one or more LRTIs during the first 36 months of age were included in our analysis.

Summary of results

We found 28 studies and of those, 5 met our inclusion criteria (see Table). Three of 4 studies that looked at the incidence of respiratory syncytial virus (RSV) showed a correlation between c-section and hospitalization due to RSV bronchiolitis. The correlation may be stronger in infants delivered by elective c-section vs emergent c-section (Shang et al). One study (Hendaus et al) did not find a correlation between c-section and recurrent LRTIs but this study did not take into account confounding variables, such as maternal age, pregnancy complications, maternal smoking and asthma.

Conclusions

Our review suggests a possible link between C-section and increased risk of hospitalization due to RSV bronchiolitis. Large prospective studies that take into account various confounding variables are needed to confirm this association.

206 Precision care for alveolar capillary dysplasia

CE Yost*

AR Putnam

L Jorgensen

RW Day

University of Utah, Salt Lake City, UT

Purpose of study

The majority of patients with alveolar capillary dysplasia and misalignment of the pulmonary veins (ACD) die in early infancy from respiratory failure and pulmonary hypertension (PH). Here we report a patient with ACD who has survived for more than four years with precision care.

Methods used

With IRB approval, we reviewed the medical records of a patient with ACD.

Summary of results

Timeline: 0–3 months: The patient developed respiratory failure and pulmonary hypertension on the first day of life. He was refractory to treatment with high frequency ventilation, surfactant and inhaled nitric oxide (iNO); and was supported with ECMO from days of life 1–6. His inpatient therapy also included, epoprostenol, sildenafil and bosentan. Tests for genetic variants associated with surfactant deficiency were negative.

3–10 months: He was treated with sildenafil, bosentan, a diuretic and oxygen (O2). The severity of PH decreased and bosentan was stopped after 5 months.

11–24 months: He developed evidence of severe PH, right heart failure with an increase in B-type natriuretic peptide (BNP) and an increased O2 requirement with a respiratory infection. A CT angiogram raised concern for pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. A lung biopsy showed evidence of a mild form of ACD. Genetic testing revealed a c.246C>G (p.F82L) heterozygous, novel and de novo variant in the FOXF1 gene. He was treated with bosentan, sildenafil, digoxin, aspirin and additional diuretics. His BNP normalized unless he experienced subsequent respiratory infections.

25–50 months: Heart catheterization and acute vasodilator testing (AVT) were performed to explore options for treatment with additional medications. His response to O2 with iNO satisfied the Sitbon criteria for an acute responder. AVT with nicardipine confirmed that outpatient treatment with a calcium channel blocker would be appropriate. Amlodipine was added. Estimates of systolic pulmonary arterial pressure remain high; however, his BNP has been normal despite occasional respiratory infections and a decrease in diuretics.

Conclusions

This case describes a patient with ACD who has survived for more than 4 years with medical therapy. His acute response to nicardipine and his long-term response to amlodipine suggests that AVT can be used to guide precision care, even in a patient with right heart failure.

Poster session

Neonatology general

6:00 PM

Thursday, January 23, 2020
207 Improving resident confidence at neonatal resuscitation through increased exposure

M Cai*

E Gastelum

UCSF Fresno, Fresno, CA

Purpose of study

Deterioration of resuscitation skills is seen with 39% of residents failing neonatal resuscitation program (NRP) skills shortly after completing training despite mandatory NRP training and adherence to ACGME requirements for newborn and NICU rotations. One study showed that pediatric residents were present at less than 50% of deliveries, declining to as low as 5%. The residents at our program attend very high risk resuscitations with a neonatologist, but are not required to attend normal term deliveries or lead resuscitations. This project hopes to advocate for increased exposure and a more deliberate curriculum toward resuscitative skills which has been shown to improve retention of NRP skills.

Methods used

An initial anonymous survey was sent to all residents at our program (n=36) about their resuscitation experience. Normal newborn resuscitations (NNR) defined as a term newborn born via vaginal delivery with no pre-determined risk. A high risk delivery defined as any change from normal delivery, such as cesarean section but no neonatologist need be present. Responses (n=24) gave insight on (1)exposure to NNR (2) interest towards attending resuscitations (3) confidence in running resuscitations. Survey results were presented to program leadership advocating for increased exposure to NNR. This led to a new requirement to attend an additional 15 deliveries of normal newborn and high risk deliveries over the 3 year residency. The first resident class affected was surveyed before the implementation was set, and re-surveyed at the end of the year post intervention.

Summary of results

The initial survey demonstrated that 92% of respondents requested more exposure to NNR in residency, which then led to a change in requirements. After implementing this change, there was an improvement in the number of residents who felt increased comfort at running resuscitations on their own from 21% to 58%. There was also improvement in knowledge regarding the type of equipment used at resuscitations.

Conclusions

By increasing the number and variety of newborn resuscitations our residents are required to attend, our program has made their first steps in improving resident confidence and comfort in applying their NRP skills at neonatal resuscitations. This study implies that more exposure will continue to improve confidence in leading newborn resuscitations, and retention of NRP skills.

208 Evaluating and improving continuous morphine weaning practice in the neonatal intensive care unit

A Iacob1,2,*

R Meyer1

A Hayes1

1Miller Children’s and Women’s Hospital Long Beach, Long Beach, CA

2Univ of California – Irvine, Orange, CA

Purpose of study

In the Neonatal Intensive Care Unit (NICU), some critically ill infants require intravenous continuous morphine (ICM) for pain control, sedation, or comfort care. Exposure to ICM can lead to increased central line days, feeding intolerance, poor tone and motor function, and prolonged hospitalization. In our institution no protocol exists for weaning ICM which could contribute to longer morphine exposure than necessary. The goal of this Quality Improvement (QI) project is to shorten the ICM wean duration in our Level 3 NICU by 25% by Feb 2020 by creating a standardized protocol for weaning and discontinuation of ICM.

Methods used

The first step was to analyze our current practice trends. All infants who received ICM for at least three consecutive days between Nov 2018 and Feb 2019 were evaluated for inclusion. Exclusion criteria were transfer to another facility or death while on ICM. The following data was collected for each patient: gestational age at birth (BGA), birth weight (BW), gender, gestational age (CGA) and primary diagnosis at initiation of ICM, duration of ICM, highest dose of ICM, duration of ICM wean, and duration and method of wean off ICM.

Summary of results

Data collection identified a total of 23 infants who met inclusion criteria, 13 infants were excluded, leaving 10 infants for analysis. Patient demographics included average BGA of 32w5d (23w4d–40w6d), 60% males, average BW of 2602 grams (565–4645 grams), and average CGA at time of initiation of ICM of 35w3d (25w1d–43w4d). Common primary diagnoses during ICM included pulmonary hypertension and hypoxic ischemic encephalopathy (HIE). Average exposure to ICM was 9.6 days (4–18.3 days). Average duration of the wean was 11.8 days (0–29 days). Infants weaned off directly from ICM compared to weaned off on a scheduled regimen had a shorter wean by 14.6 days (1.6 days versus 16.2 days).

Conclusions

Our opioid weaning protocol has been approved by the NICU physicians and pharmacists. and is now in the trial phase. The protocol will be implemented for infants on ICM, with the first cycle running from Novr-Dec 2019, and the second cycle Dec 2019-Jan 2020. After each cycle, we will assess not only duration of ICM weaning, but also adherence to the weaning protocol by practitioners and barriers to adherence.

209 Short-term outcomes of veno arterial -ECMO for HIE and severe PPHN

VK Kalra1,*

SN Mateev1

L Kenny2

S Lakshminrusimha1

1UC Davis Children’s Hospital, Sacramento, CA

2UC Davis Medical Center, Sacramento, CA

Purpose of study

To evaluate in-hospital outcomes of infants with Hypoxic Ischemic Encephalopathy (HIE) and severe Persistent Pulmonary Hypertension (PPHN) requiring therapeutic hypothermia (TH) and Veno- Arterial Extra Corporeal Membrane Oxygenation (VA-ECMO).

Methods used

Single center retrospective evaluation of neonates with HIE on TH requiring VA-ECMO from 2011–2019.

Summary of results

Among infants with HIE, meconium aspiration was the commonest cause of PPHN. All infants had echocardiographic evidence of PPHN and had received inhaled Nitric Oxide before ECMO. All except one infant tolerated complete course of TH for 72 h. Close monitoring of coagulation profile with prompt correction of abnormal values was performed during ECMO. All subjects were discharged home and 56% had normal MRI and only one patient had intracranial hemorrhage.

Conclusions

Among patients with HIE, severe PPHN observed during TH can be effectively treated with VA-ECMO with overall good results. In patients with HIE and PPHN, TH through ECMO is an effective strategy.

210 Independent evaluation of the neonatal sequential organ failure assessment score with direct comparison to hero technology

B Barnette1

JL Wynn2

S Lawrence1,*

1UCSD, San Diego, CA

2University of Florida, Gainesville, FL

Purpose of study

An operational definition neonatal sepsis is lacking. Technological tools and biomarkers that can accurately predict infection mortality outcomes, especially risks for multi-organ dysfunction syndrome, are constantly being sought. The neonatal sequential organ failure assessment (nSOFA) score, recently published by Dr. Wynn and Dr. Polin in Pediatric Research, provides an objective, electronic health record-automated score. Conversely, HeRO incorporates proprietary algorithms to calculate a sepsis score based upon variations in the patient’s heart rate. This study will independently validate the nSOFA score and directly compare the efficacy of nSOFA and HeRO scoring systems in predicting mortality related to neonatal sepsis.

Methods used

A retrospective chart review of infants born <33 weeks’ gestational age between 2012 and 2015 at UCSD Medical Center with positive blood cultures and/or necrotizing enterocolitis (NEC) were included. The electronic health records of these infants were reviewed to ascertain and document components of the nSOFA score (range 0–15) including: (a) need for mechanical ventilation and oxygen requirement (score range 0–8); (b) administration of vasoactive drugs including corticosteroids (score range 0–4); and (c) presence and degree of thrombocytopenia (score range 0–3). Scores were calculated for each infant at nine time points, including −48, −24, −12, −6, time 0 (sepsis evaluation), +6, +12, +24, and +48 hours. nSOFA data was directly compared to HeRO scores at similar time point to determine efficacy in predicting neonatal mortality associated with sepsis and/or NEC.

Summary of results

Seventy-five patients born <33 weeks’ gestational age were identified to have one or more positive blood cultures during the study period and were included for analysis. In addition, seventeen patients diagnosed with necrotizing enterocolitis during this time period have been identified. Chart review is nearly completed with final statistical analysis expected in November 2019.

Conclusions

Complete results with conclusion will be available by the WSPR conference date.

211 Effect of low-dose high-frequency multimedia refresher materials on helping babies breathe skills retention in tanzania

J Mascari*

UC San Diego, San Diego, CA

Purpose of study

Helping Babies Breathe (HBB) is an educational module created by the American Academy of Pediatrics that teaches the knowledge and skills required to care for babies in the first few minutes of life after birth. Since its creation in 2010, HBB has been implemented in 80 countries and has been taught to over 450,000 birth attendants resulting in a reduction of neonatal mortality by as high as 50%. The program relies on in-person trainings that cover both the knowledge and skills required to care for newborns. However, recent studies have shown that low-dose high-frequency refresher trainings are an effective means of accomplishing this, but to date these trainings have not incorporated multimedia tools. While multimedia materials have already been created to aid in teaching HBB, their effectiveness has never been studied. This project aims to study the effectiveness of targeted low-dose high-frequency refresher videos of HBB material in one hospital in Tanzania.

Methods used

Previously trained birth attendants and health care providers at Muhimbili National Hospital in Dar es Salaam, Tanzania will be recruited to participate in this study. Participants will be randomized to either a cohort that only views a refresher video, or a cohort that receives the standard in-person refresher teachings. Skills over time will be measured using the already established HBB bag and mask ventilation skills checklist. To establish a baseline, all participants will be scored by this checklist at the beginning of the study. Before the interventions are implemented, skills will be checked after 2 months to examine how skills change over time. Then, either a short refresher video or a hands-on person-to-person skills refresher will be presented to the respective cohorts. Skills stations will be set up in the labor and delivery area and all participants will self-practice bag and mask ventilation weekly for 5 minutes. The video cohort will be required to re-watch the skills video twice a month. The bag and mask ventilation skills checklist will be administered again after 2 months and the performance of the two cohorts will be compared.

Summary of results

Pending

Conclusions

It is hypothesized that the two cohorts will perform similarly which may suggest that self-study videos can replace in-person refresher trainings when trainers are not available.

212 Does continuous positive airway pressure alter the fecal microbiota of very low birth weight infants?

RD Robertson*

K Kuhn-Riordon

M Underwood

University of California Davis, Sacramento, CA

Purpose of study

The gut microbiota influences host innate and adaptive immune responses, and alterations in the microbiota appear to play a role in necrotizing enterocolitis and sepsis. Continuous positive airway pressure (CPAP) is commonly required in very preterm infants with gaseous abdominal distention a common side effect. The impact of swallowed air on the fecal microbiota is unknown. We hypothesize that distention of the distal small bowel and colon with swallowed air leads to dominance of pathogenic facultative anaerobes as opposed to the commensal obligate anaerobic population in a healthy gut.

Methods used

In a single center cohort study of infants with gestational age less than 33 weeks, we collected fecal samples twice weekly. We performed 16S ribosomal RNA gene sequencing of serial fecal samples from 22 infants who received CPAP for 5 or more days (94 samples) and from 19 infants not receiving CPAP therapy (129 samples). Measures of alpha diversity (Shannon) and beta diversity (non-metric multidimensional scaling (NMDS) based on weighted and unweighted UniFrac distances) will be compared between groups and in the subset of CPAP infants before and after cessation of CPAP.

Summary of results

Demographic details for the infants included in the analysis are summarized in the table. The sequencing of the samples has been completed and the bioinformatics analysis is in process.

Conclusions

The infants receiving >5 days of CPAP were more preterm, smaller, and had more BPD and longer hospital stays than the infants not receiving CPAP. Thus, differences in the microbiota will be heavily influenced by these confounders. Three comparisons will be most valuable in addressing our hypothesis: samples at matched gestational ages, samples in the same infants during and after CPAP, and samples from intubated infants compared to matched CPAP infants.

Poster session

Nephrology and hypertension – adult

6:00 PM

Thursday, January 23, 2020
213 Atypical presentation of severe non-traumatic rhabdomyolysis resulting in multi-organ failure

A Shah1,*

D Aguirre1

P Shrestha2

1Kern Medical-UCLA, Bakersfield, CA

2Ross University School of Medicine, Miramar, FL

Purpose of study

To bring awareness about the different presentation of acute kidney injury with a significant increase in creatinine from baseline with acute tubular necrosis and non-traumatic rhabdomyolysis.

Methods used

Retrospective Study.

Summary of results

Patient is a 37-year female with no past medical history who presented to the emergency department complaining of a four-day history of constant epigastric pain 10/10 in severity associated with nausea headache, non-bloody vomiting, productive cough with yellow sputum, and chest pain on inspiration. Results from an outside hospital showed CT of the abdomen was negative for pancreatitis and US of the abdomen showed fatty liver. Notable labs were lipase: 8120, AST/ALT: 3079/789, BUN 85, and creatinine 11.40. The urinalysis was notable for RBC>50 and protein 300 mg/dl. Chest x-ray was notable for bilateral multilobar patchy infiltrates. The patient was hemodynamically stable, not requiring oxygen despite the diffuse bilateral pulmonary infiltrates, and her pain was controlled with medication. Given the severe multiorgan disease process in a previously healthy person, autoimmune etiology was likely. Pulmonary service was consulted and performed a diagnostic bronchoscopy on the patient. However, the pathology was negative for malignancy or infection. Nephrology service was consulted and started dialysis. Both specialties agreed with an autoimmune etiology and high dose steroids was started. ANA, double stranded DNA, Smith Ab, Sjogren Ab, P-ANCA, C-ANCA, cardiolipin, and beta2 glycoprotein were negative. Parvo B19 and anti-streptolysin was negative. IGG subclass 4 was negative. Salicylate, acetaminophen, HIV, and hepatitis panel were negative. C3 was borderline low at 80. Given the negative workup, a renal biopsy was performed for definitive diagnosis, which showed ATN secondary to rhabdomyolysis and mild arteriosclerosis. The patient was continued on dialysis and prednisone and showed improvement in her multiorgan dysfunction. Her abdominal pain and pulmonary infiltrates had resolved. Her creatinine improved to 5.12. She was discharged with prednisone and outpatient dialysis.

Conclusions

Acute kidney injury from non-traumatic rhabdomyolysis and diffuse pulmonary infiltrates requiring steroids and hemodialysis is a rare phenomenon.

214 Spontaneous bilateral subcapsular renal hematoma

S Eppanapally

T Bajaj

N Trang*

F Nasrawi

Kern Medical Center, Bakersfield, CA

Spontaneous bilateral subcapsular hematoma is a rare condition.Upon literature review,only two case reports have elucidated possible etiologies for such a presentation.Similarly, we present a 52 year old female with PMH of DM type II,HTN,decreased cognitive function s/p TBI from MVAx2 last one in 2011,who developed spontaneous bilateral renal subcapsular hematoma on admission for management of DKA and pyelonephritis.Typically,subcapsular hematoma achieves spontaneous resolution with conservative management,however our patient was having active bleed with hypotensive shock needing left renal artery embolization and eventually left nephrectomy.Her condition was further complicated with total left lung collapse secondary to mucous plug and septic shock.

Purpose of study

Report a rare case of Bilateral sponatneous subcapsular hematoma.

Methods used

Chart review.

Summary of results

Our patient has multiple factors that are believed to set the stage for bilateral subcapsular hematoma.Uncontrolled DM predisposes her to diabetic nephropathy and pyelonephritis,bilateral ureteral stents and remote history of laceration of the right kidney.

Conclusions

The main interest of this case report lies in bilateral spontaneous subcapsular hematoma in a patient who has multiple factors that could have played a role in this condition.Our patient was treated with embolization,bilateral nephrostomy tubes,and nephrectomy of the left kidney.We present the first case of spontaneous bilateral subcapsular hematoma in the setting of no major risk factors that could possibly affect both kidneys simultaneously.

Poster session

Surgery

6:00 PM
Thursday, January 23, 2020
215 Something stinks! finding ways to manage noxious odours in the operating room: a randomized controlled trial

L Bjornson1,*

A Van Slyke1

M Bucevska1

R Courtemanche1

J Bone1

A Knox2

C Verchere1

J Boyle1

1University of British Columbia, Vancouver, BC, Canada

2University of Alberta, Edmonton, AB, Canada

Purpose of study

The operating room can be saturated with noxious smells. Anecdotally, medical staff apply products to surgical masks to lessen the impact of these smells. This study aimed to determine the odour-masking ability of four inexpensive and convenient products.

Methods used

This study was a randomized, single-blinded crossover study. Individuals between ages 19 and 30 years were included. Exclusion criteria included active allergies, upper respiratory tract infection, alteration to sense of smell, or failure of olfactory screen. Eighty-one individuals were recruited; one was excluded following a failed olfactory function test. Participants were exposed to an experimental odour in lieu of a noxious surgical odour. After smelling the experimental odour without barriers, participants were re-exposed to the odour using five surgical masks in randomized order. Each mask was lined with a test product (cherry lip balm, tincture of benzoin, Mastisol®, mint toothpaste, and control (plain mask)). Participants rated the effectiveness of products at masking the experimental odour from 0–100 (0 = completely ineffective, 100 = completely effective). Participants also rated the pleasantness of the products, recorded if the products made them feel unwell, and identified their preferred product overall. The main outcome measure was the odour-masking effectiveness of the four products.

Summary of results

Eighty participants were included in the study (33 male, 47 female), averaging 24.2 years of age. Mean odour-masking effectiveness for cherry lip balm was 66.5 (±24.6), tincture of benzoin: 62.6 (±25.0), Mastisol®: 61.3 (±23.9), mint toothpaste: 57.5 (±27.4), and control: 21.9 (±21.8). All products performed better than the control (p-value: <0.001), but there was no significant difference in performance between products. Cherry lip balm was the most preferred odour-masking product (29 participants), followed by mint toothpaste (22), Mastisol® (14), tincture of benzoin (10), and control (5).

Conclusions

All tested products demonstrated odour-masking abilities. We recommend that healthcare professionals find the odour-masking product that works best for them, starting with cherry lip balm.

216 Point of care ultrasound evaluation of airspace disease before and after prolonged surgery

K Cook*

M Buell

B Lew

P Vu

J Hinson

M Martinez

M Alschuler

M Holsclaw

D Ramsingh

Loma Linda University, Loma Linda, CA

Purpose of study

Point-of-care ultrasound (POCUS) has rapidly emerged as a modality to improve bedside assessment of pulmonary air-space disease. Indeed, POCUS has demonstrated to be superior for the assessment of air-space disease in comparison to both Chest x-ray and stethoscope auscultation. Given that patients undergoing a long surgical procedure requiring general anesthesia are at risk for pulmonary complications the ability to assess air-space disease perioperatively is of interest. The authors designed a feasibility study to evaluate the utility of point of care ultrasound to evaluate the development of air-space in this patient population.

Methods used

Adult patients were screened for those undergoing a surgical procedure scheduled for more than 3 hours of surgical time. Patients were then scanned using a validated POCUS examination to detect both the presence and severity of air-space disease across 5 lung fields for each side (total of 10 views). POCUS exams were performed immediately before and after their surgical procedure. Airspace disease was defined by the presence of B-lines, as previously validated. Before-to-after comparisons in air-space disease was performed by Chi-Square Analysis in the frequency of B-Lines in each lung quadrant and in total. A p value of less than 0.05 was identified as significant.

Summary of results

Preliminary data on 15 patients with 150 ultrasound images demonstrates significantly higher number of B lines post-surgery (17%) compared to pre-surgery (10%), p<0.05. The dependent lung zones were the most frequent areas to develop B lines both in the pre-op and post-op settings. All patients were able to have ultrasound images of the lung parenchyma across all lung fields.

Conclusions

POCUS examination of the lungs fields can be successful performed in the perioperative setting. Our preliminary data supports this tool be useful in the assessment of the change in the aeration of lung tissue from pre to post surgery. Specifically, for patients undergoing long surgical procedures, this modality may be useful to detect the development of new areas of airspace disease.

217 Comparison of patient outcomes following ankle fracture fixation with or without arthroscopy trend toward improved outcomes with the use of arthroscopy

K Drexelius*

K Smith

S Challa

D Moon

J Metzl

KJ Hunt

University of Colorado, Aurora, CO

Purpose of study

Rotational ankle fractures are among the most commonly treated orthopedic injuries, yet there is no consensus on the role of arthroscopy in the management of acute ankle fractures. The purpose of this study is to investigate the rate of chondral pathology and other intra-articular injuries in ankle fracture patients and compare the clinical and radiographic outcomes of the patients who underwent arthroscopy at the time of ankle fracture open reduction internal fixation (ORIF) with those patients who did not. Our hypothesis was that patients who underwent arthroscopy at the time of ankle fracture ORIF would have better patient reported outcomes scores compared to ORIF without arthroscopy.

Methods used

We recorded each patient’s demographic data, injury characteristics, surgical details, and follow-up radiographs to determine the degree of osteoarthritis and to assess the final outcome of the fracture. We then contacted the study patients via an email or telephonic survey. We utilized the PROMIS Global Health Short Form and the two question PASS scale as our selected patient reported outcome scores.

Summary of results

Among patients who received ORIF with arthroscopy, there was a 47.9% rate of arthroscopic intervention beyond the standard debridement of synovitis and fracture hematoma. The mean PROMIS physical function score was higher in the ORIF plus arthroscopy group compared to the traditional ORIF group (p value 0.064). 78% of the traditional ORIF group is satisfied with the function of their ankle compared to 89% satisfaction in the ORIF plus arthroscopy group. Patients with Weber B fibula fractures or tibiotalar joint dislocations that underwent arthroscopy plus ORIF had a statistically significant higher PROMIS physical function score at final follow up (p value 0.01).

Conclusions

We found that patients treated with ankle arthroscopy in addition to ORIF for a rotational ankle fracture had superior patient reported outcomes for all tested metrics and across all specific fracture mechanisms and characteristics. Ankle arthroscopy is a useful adjunct to traditional ORIF and can improve outcomes without a significant increase in operative time and no change in complication rate.

218 Adult mesenchymal hamartoma of the liver: case report and literature review

M Gross1,*

N Wilkinson2

1University of Washington School of Medicine, Seattle, WA

2Kalispell Regional Healthcare Surgical Specialists, Kalispell, MT

Case report

A 39-year-old woman presented to the emergency department for acute onset epigastric pain. Imaging demonstrated a 5 × 6 cm lesion in segment 4 of the liver. A left hepatic resection was performed and the patient did well post operatively. Final microscopic diagnosis demonstrated mesenchymal hamartoma. Mesenchymal hamartoma of the liver (MHL) is a benign lesion, commonly seen in children younger than five years. MHL rarely occurs in adults, with only 31 cases reported worldwide as of 2010. The pathogenesis of MHL is not completely understood, though it is believed to relate to aberrant development of the bile ducts. Despite a typically benign course, malignant transformation may occur. Recent cytogenic analysis has identified chromosomal rearrangements nearly identical to those observed in undifferentiated embryonal carcinoma (UEC), an aggressive lesion with a median survival of less than 1.5 years. UEC has arisen from MHL in multiple instances, while hepatic angiosarcoma has also been reported. Additionally, MHL may grow to massive proportions. Due to the potential for such complications, aggressive surgical management with complete resection is mandated when feasible. Herein we discuss the aforementioned case as well as the epidemiology, clinical presentation, histopathology, cytogenetics, and treatment of this rare adult neoplasm.

219 Utility of EEG in predicting hemispheric surgery outcome

K Hanjani1,*

M Connolly1,2

1University of British Columbia, Vancouver, BC, Canada

2BC Children’s Hospital, Vancouver, BC, Canada

Purpose of study

Treatment resistant epilepsy is a major health burden. Recurrent seizures can result in negative sequelae which include seizure related injury, cognitive and memory impairment, and increased healthcare utilization. Hemispheric surgery is an excellent and potentially curative option for carefully selected patients and is currently underutilized. One of the important modalities used to assess patient suitability for the surgery is the electroencephalogram (EEG), which can non-invasively study brain activity. The goal of this project was to evaluate the role of EEG in predicting surgery outcome.

Methods used

We hypothesized that generalized or bilateral epileptic abnormalities captured on EEG would be associated with risk of ongoing seizures and ongoing need for antiepileptic drugs (AEDs) post-surgery. To test this hypothesis, the medical records of all patients who had undergone hemispheric surgery at BC Children’s Hospital were evaluated. Data was gathered on clinical history, neuroimaging, EEG reports, seizure types, seizure frequency pre- and post-surgery and AED use.

Summary of results

We observed that over 90% of patients had very good outcomes in terms of seizure freedom with surgery but 43% percent of patients were still using AEDs post-operatively despite seizure freedom. Analysis of the data showed trends towards increased seizure recurrence and AED use with bilateral or generalized brain abnormalities on EEG, as hypothesized. However, these results were not significant, likely due to small sample size (n=40).

Conclusions

Given the high success rate of hemispheric surgery, when seizure freedom is the metric, any modest prediction capability confered by EEG analysis would be of limited clinical use. However, there may be a role for using pre-operative EEGs to inform medical care after surgery with regards to AED requirements and weaning.

220 Racial differences in the prostate cancer microenvironment

A Jarjour1,*

Y Zhang2

B Knudsen2

K Wawrowski2

CG Drake3

S Freedland2,4

A Vidal2

1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA

2Cedars-Sinai Medical Center, Los Angeles, CA

3Columbia University Medical Center, New York, NY

4Durham VA Medical Center, Durham, NC

Purpose of study

African-American men (AAM) are more likely to be diagnosed with prostate cancer (PC), and have more aggressive PC at diagnosis, than any other ethnic group. Differences in inflammatory cell types among races may account for this imbalance. We previously found that AAM have more T-cells in their PC as compared to European American men (EAM). Herein, we developed a panel to quantify myeloid cells in the same tissue samples. We hypothesize there are racial differences in myeloid-derived suppressor cell (MDSC) counts in the prostate cancer microenvironment.

Methods used

Using 5-plex immunofluorescence (IF) on prostate biopsy formalin-fixed paraffin-embedded (FFPE) slides of AAM and EAM matched controls and PC cases, we quantified granulocytic (G) and monocytic (M) MDSCs. The panel includes antibodies for CXCR2, CD14, CD11b, HLA-DR, and cytokeratin, enabling us to quantify the recruitment and density of M-MDSCs and G-MDSCs to the tumor microenvironment. M-MDSCs are defined as CD14+ and HLA-DR low/-, whereas G-MDSCs are defined as CD14-, HLA-DR low/-, and CD11b+. Each cell type was counted in PC regions as well as in biopsy negative controls. Data were then compared using unpaired t-tests with a=0.05/n, where n is the number of markers used, to accommodate multiple testing.

Summary of results

Among all men with PC, we found higher M-MDSC density in cancers vs. controls, though these differences were not statistically significant (p=0.076). AAM PCs had significantly more M-MDSCs (p<0.017) and G-MDSCs (p>0.19) than AAM non-PCs, though the latter was not statistically significant. There was a trend for higher G-MDSCs in EAM non-PC tissue as compared to AAM non-PCs (p<0.055). AAM PCs had significantly more CXCR2+ cells than EAM PCs (p<0.008).

Conclusions

We found racial differences in MDSC counts both in PC and non-PC prostate tissues. These preliminary results require further validation. Limitations of the study include potential selection bias, since sections were manually chosen for analysis, as well as imperfect multiplex staining of tissue.

221 Comparative assessment of patient surgical risk by surgeons vs. a universal, parsimonious statistical risk system

N Mason*

P Rozeboom

MR Bronsert

W Henderson

N Pradhan

A Lambert-Kerzner

K Hammermeister

R Meguid

University of Colorado School of Medicine, Aurora, CO

Purpose of study

The literature lacks evidence on accurate preoperative prediction of postoperative surgical outcomes by surgeons. The Surgical Risk Preoperative Assessment System (SURPAS) provides individual patients with accurate procedure-specific preoperative risk prediction of 30-day postoperative adverse outcomes including mortality, overall morbidity, & 9 other surgical complications. To predict these values, SURPAS uses 8 variables including procedural complexity & procedure-specific risk (both derived from the current procedural terminology code), functional health status, American Society of Anesthesiologists Physical Status Classification (ASA class), patient age, emergency status of the operation, in-/outpatient procedure, & surgeon specialty. These risk algorithms were developed from American College of Surgeons National Surgery Quality Improvement Program (NSQIP) data, which include the independent variables entered into SURPAS & the postoperative adverse outcomes.

Methods used

We compared the accuracy of surgeons’ ability to predict overall morbidity & mortality for a variety of surgical procedures within their specialty to the outcomes predicted by SURPAS, & to the known postoperative outcomes. 30 patients’ NSQIP data was presented to surgeons in standardized vignette formats, including the procedure performed & each patient’s comorbidities. Vignettes of 6 patients in each of ASA class I-V were randomly presented to the participants. Surgeons were asked to predict each patient’s likelihood of 30-day postoperative mortality & overall morbidity.

Summary of results

Preliminary results from general surgery residents show that surgeons were able to accurately & precisely predict both the morbidity & mortality risk amongst low risk patients (ASA class 1–2). In high risk patients (ASA class 3–5) the agreement amongst surgeons on both mortality & morbidity was variable. Surgeons were also less accurate at predicting risk in the high risk patients.

Conclusions

The data supports continuing the study in attending surgeons of different specialties. Each specialty will be administered a survey using the same standardized vignette format that includes common procedures from within their field of expertise. We will measure surgeon accuracy.

222 Effects of delayed ICU admission from the post-anesthesia care unit vs. direct admission to the surgical intensive care unit in post-operative patients

M Moran*

S Hendrix

T Cruz

R Raval

I Dorotta

Loma Linda University, Loma Linda, CA

Purpose of study

The post-anesthesia care unit (PACU) was established to minimize complications immediately after anesthesia and surgery. Often patients are held up in PACU due to bed availability or lack of appropriate staffing. This study was conducted with the hypothesis that PACU admission of a critically ill patient increases ICU length of stay (LOS). Secondarily we also looked at hospital LOS and mortality.

Methods used

A retrospective chart review was conducted at a tertiary academic medical center between 2/1/13–6/1/19. We identified all surgical patients admitted to the SICU, a total of 5365 patients. We separated these patients into two groups: (1) direct SICU admission and (2) PACU then SICU admission. We collected the following data: (1) demographic characteristics; (2) the American Society of Anesthesiologists (ASA) score; (5) PACU LOS; (6) SICU LOS; (7) Hospital LOS and (8) mortality.

Summary of results

Preliminary results of demographic data showed no statistically significant difference between the two groups. (Table 1) Outcomes data showed a statistically significant increase in SICU and hospital LOS for PACU admitted patients. Mortality was also statistically significant but was higher for SICU admitted patients. (Table 2)

Conclusions

We saw a median PACU LOS of 103 mins yet the PACU to SICU group’s SICU LOS was 844 mins longer than the PACU group. When it came to hospital LOS the PACU to SICU group had a 4229 mins longer stay. Delay in ICU care leads to increased LOS in the SICU and the hospital. The mortality was significantly higher in the directly admitted SICU patients which from our preliminary analysis appears to be from patients who had high ASA and APACHE II scores and died soon after ICU admission.

223 Surgical outcomes of supravalvular aortic stenosis repair techniques in pediatric patients: a systematic review

D Rodriguez1,*

B McCormick1

J Arbon1

J Jahanyar2

1Mayo Clinic Alix School of Medicine, Scottsdale, AZ

2Mayo Clinic, Pheonix, AZ

Purpose of study

Supravalvular aortic stenosis (SVAS) is a congenital anomaly arising from familial or sporadic mutations in the elastin gene. This mutation results in severe constriction of the sinotubular junction. SVAS is most commonly seen as a feature of Williams Syndrome. One, two, and three patch aortoplasty techniques are the most frequently performed corrective procedures for SVAS worldwide and have shown efficacious outcomes in the repair of SVAS. However, data comparing the outcomes and survival rates between these techniques are limited.

Methods used

A systematic literature review using PubMed and EMBASE identified 15 papers for data extraction related to pediatric SVAS surgical outcomes and survival. Papers were selected through systematic use of search terms and were manually assessed for relevance and inclusion of pertinent data. These data included re-operation rates, pre/post-operative Doppler gradients, mortality, and significant comorbidities. Review and meta-analysis were conducted according to PRISMA guidelines.

Summary of results

The average age of pediatric patients assessed was 7.8 years ± 3.2 with 44% of patients presenting with Williams syndrome. The pre/post-operative Doppler gradients showed no significant difference between the one, two, and three patch aortoplasty techniques. Similarly, early and late mortality was not significantly different between techniques. However, reoperation rates due to restenosis varied with an incidence of reoperation of 13.8%, 4.8%, and 0% in patients with one, two, and three patch aortoplasties, respectively.

Conclusions

In pediatric SVAS patients, one, two, and three patch aortoplasty techniques show no significant differences in pre/post-operative gradients and survival rates, while three patch aortoplasty reveals decreased incidence of reoperation. Further studies are needed to better delineate the best surgical approach.

224 Obstructive sleep apnea and early weight loss among adolescents that undergo bariatric surgery at children’s hospital colorado

SP Russell1,*

I Talker1

JM Moore1

TH Inge1

SM Hawkins1

MS Alioa2

J Kaar1

S Simon1

1University of Colorado Anschutz Medical Campus, Aurora, CO

2National Jewish Health, Denver, CO

Purpose of study

Adult literature demonstrates impressive results regarding the effect of bariatric surgery in ameliorating obstructive sleep apnea (OSA) however data are scarce in pediatric literature. As morbid obesity and OSA become increasingly common in adolescents, it is important to quantify the prevalence of OSA and the effects of surgical intervention in this unique, growing population.

Methods used

Retrospective chart review of adolescents enrolled in the Bariatric Surgery Center at Children’s Hospital Colorado (CHCO) with pre- and post-surgical polysomnography (PSG) between 06/17–08/19 (70/83 total patients). Inclusion criteria was based on availability of presurgical PSG results. Variables including age, gender, race, comorbidities, PSG results, and weight were collected. Pediatric OSA criteria were applied to PSG results to determine presence of OSA. Tests for nonparametric data were used to compare baseline characteristics and surgical outcomes between patients with and without preoperative OSA.

Summary of results

The prevalence of OSA among those with preoperative PSG, defined as apnea hypopnea index ≥1, was 77% pre-surgery, with 44% demonstrating severe OSA by OAHI ≥10. There were no significant differences in race, gender, BMI, or comorbidities according to diagnosis of OSA. Of 12 patients with preoperative OSA and a postoperative sleep study, 58% resolved their OSA an average of 4.92 months post-surgery. Average preoperative BMI for resolving patients was 45.46 versus 56.76 in those who did not have resolution of OSA (p=0.03). Average change in BMI from pre- to post-operative sleep study was -21.9% in the resolved group and -13.5% in the unresolved group (p=0.12).

Conclusions

The prevalence of OSA in the population of adolescents seen in the Bariatric Surgery Center at CHCO was more similar to the estimated prevalence in adults seeking bariatric surgery (74%) than the general population of adolescent with obesity (43%). Resolution of OSA after surgery correlated with lower preoperative BMI, but sample size limited further analysis.

225 Clinical outcome differences between single and multi-staged transtibial amputations

AF Shu*

DK Moon

KS Smith

S Challa

KJ Hunt

University of Colorado, Aurora, CO

Purpose of study

Transtibial amputations are currently performed as single guillotine amputations or multi-staged amputations with primary and formalization amputations. This study assessed if multi-staged amputations provide improved clinical outcomes over single stage transtibial amputations and what patient groups it may benefit.

Methods used

We queried 207 records of patients receiving transtibial amputations from January 2015 through December 2018. Patient demographics, comorbidities, preoperative factors, surgical factors, and complications were recorded. Regression modeling was utilized to compare functional outcomes and influential perioperative variables between single and multi-staged amputation groups. After accounting for exclusion criteria, 148 patient records were analyzed.

Summary of results

From the records analyzed, 49 patients (37%) underwent multi-stage amputation. Patients with multi-stage amputations had a hazard ratio of 0.60 for complication risk (P=0.04). The most common complications, often requiring readmission, were infection (n=30) and wound dehiscence (n=21). This was the case for both single and multi-staged amputations. For patients who were readmitted, 72% required amputation revision. Of the patients who experienced complications, 56% of patients were independently ambulatory with a prosthesis and 31% were ambulatory with additional assistive devices (e.g., cane, front wheel walker) after one-year post-surgery. Approximately half of the patients from each amputation group were independently ambulatory with a prosthesis (51% for single stage and 49% for multi-stage). Similarly, 27% of patients in both amputation groups were ambulatory with additional assistive devices.

Conclusions

Based on these preliminary results, single stage and multi-stage amputation groups demonstrate similar complication rates and recovery. However, multi-stage transtibial amputations may provide a protective effect against complication risk compared to single-stage amputations.

226 Sleep behaviors in adolescents undergoing bariatric surgery evaluation

I Talker1,*

SP Russell1

JM Moore1

TH Inge1

SM Hawkins1

MS Alioa2

S Simon1

J Kaar1

1University of Colorado Anschutz Medical Campus, Aurora, CO

2National Jewish Health, Denver, CO

Purpose of study

Poor sleep behaviors has been associated with increased risk of obesity and insulin resistance. Sleep health has not been examined in adolescents with obesity undergoing bariatric surgery.

Methods used

A chart review was performed and all patients receiving care at the Children’s Hospital Colorado (CHCO) Bariatric Surgery Center between 06/17–08/19 were included. Demographic, medical history, sleep behaviors, and laboratory measures were abstracted. T-tests were used to examine the differences between sleep variables and baseline weight and comorbidity status.

Summary of results

Data from 85 patients, aged 16.8 years, were identified. The majority of patients were female (71%) and Hispanic (52%). The majority of patients reported a family history of obesity (69%) and T2D (80%). Over half (52%) reported receiving mental health counseling previously. Pre-surgery, 24% of the patients were diagnosed with hypertension and 20% with Type 2 Diabetes. A total of 29% screened positively for anxiety and 41% were diagnosed with depression. Over half of the patients (60%) stated they did not have a regular sleep schedule. A typical total time in bed of 9 hours was reported with as much as 86 minutes of variability. A total of 36% of patients reported a bedtime of midnight or later and 78% were documented to have a mobile device with them in their bed. Patients who reported variability in their sleep schedule of at least 60 minutes were found to have significantly higher weights (139.1kg vs 131.1kg; p=0.02) and BMI (48.8 vs 44.9; p=0.04) at baseline. Similarly, patients who reported less than 8.5 hours of time in bed each night had significantly higher weights (144.7kg vs 131.7kg; p=0.002), BMI (50.3 vs 45.9; p=0.02), and HbA1c levels (6.18 vs 5.85; p<0.001), compared to patients that had greater than 8.5 hours of time in bed each night.

Conclusions

In a population of adolescents seen in the bariatric surgery center at CHCO, sleep behaviors preoperatively were related to baseline weight, BMI, and HbA1c levels. Insufficient sleep and unhealthy sleep behaviors may adversely impact adolescents’ overall health. Interventions to improve sleep health should be evaluated as part of efforts to improve health outcomes in patients undergoing bariatric surgery.

227 Optimal nail diameter to medullary canal ratio in diaphyseal tibia fractures treated with intramedullary nailing

AA Trizno1,*

Y Peng1,2

PM Carry1,2

JW Stoneback1

1University of Colorado School of Medicine, Aurora, CO

2Children’s Hospital Colorado, Aurora, CO

Purpose of study

Up to 17% of diaphyseal tibia fractures result in delayed union. Most patients achieve excellent outcomes with intramedullary nailing and it is unknown why some experience delayed healing. The goal of our study was to assess potential risk factors that may influence fracture healing in these patients with an emphasis on the nail dimeter to medullary canal (ND/MCD) ratio.

Methods used

Adult patients that underwent intramedullary nailing of tibia fractures over a 10-year period were retrospectively reviewed. Exclusion criteria were inadequate follow-up (<12 months), additional lower extremity fractures, additional hardware, non-diaphyseal and pathologic fractures. Post-operative anteroposterior (AP) and lateral radiographs were used to calculate the ND/MCD ratio. Multi-variable logistic regression analyses were used to identify demographic and clinical variables associated with complications. A receiver operating curve analysis was used to identify the ND/MCD ratio that best differentiated between subjects who developed a nonunion and those who did not.

Summary of results

The average age among the 95 individuals included in the study was 44.2 years (±16.1). The cumulative incidence of complications was 29% [95% CI: 20.3 to 39.7%]. The presence of an open fracture was the only variable significantly related to the risk of a complication. The odds of a complication among open fractures were 10.1 times [95% CI: 3.2 to 32.1, p<0.0001] times the odds of a complication among closed fractures. Nonunion was noted in 18 patients [19.0%, 95% CI: 11.1 to 26.8%]. Age, sex, ND/MCD ratio, and presence of an open fracture were used to build a logistic model to predict nonunion (AUC=0.83; 95% CI: 0.71 to 0.96]. ND/MCD ratio cutoff of 85% was associated with the highest AUC value (sensitivity=44%, specificity=79%) in an exploratory analysis differentiating between the subjects that developed nonunion and the ones that did not.

Conclusions

Presence of an open fracture is strongly associated with increased complication rates among patients undergoing intramedullary nailing of tibia fractures. Canal fill of <85% should be avoided as it may lead to nonunion development.

227A Understanding techniques of and attitudes towards preoperative risk assessment

N Pradhan1,*

MR Bronsert1

A Lambert-Kerzner1

N Mason1

W Henderson1,2

K Hammermeister1

H Qiu1

R Meguid1

1University of Colorado School of Medicine, Aurora, CO

2Colorado School of Public Health, Aurora, CO

Purpose of study

In the era of big electronic health data, formal surgical risk assessment tools have been developed to predict risk of adverse postoperative outcomes. Patients desire to understand their risks and report improved shared decision-making with use of such tools. However, these risk assessment tools are underutilized. We surveyed surgeons’ techniques of and attitudes towards preoperative risk assessment.

Methods used

108 surgical faculty and 95 surgical residents at the University of Colorado were emailed a 16-question survey between 8-9/2019. Surveys were excluded if the respondent was no longer practicing or did not complete the survey.

Summary of results

Of 203 surveys disseminated, 51 faculty and 41 residents responded. Of surgical faculty, median years in practice was 11, 42% were general surgeons, and 94% practiced at a large academic hospital. 55% of residents sometimes rely on online risk calculators, while 58% of faculty never or rarely use them (p<0.001). 82.0% of faculty and 35.5% of residents rely on prior experience to estimate risk most or all of the time (p<0.0001). 70.0% of faculty rely on current literature for risk estimates most or all of the time vs 75.0% of residents who rely on it some or most of the time (p=0.02). Surgical faculty and residents were equally likely to discuss risk with patients >65 years of age, when patients ask about risk, when they were perceived to have significant risk factors, and to dissuade patients/families from surgery. Faculty were more likely than residents to discuss risk with patients prior to an emergency operation. Barriers to use of a formal risk assessment tool include the amount of time needed to use the tool (40.0% report this is a moderate barrier), lack of integration into the electronic health record (33.3%: moderate barrier), and inaccessibility of the risk tool during the patient visit (38.9%: moderate barrier).

Conclusions

Surgeons rely heavily on prior experience and current literature to guide assessment of surgical risk. Surgical faculty communicate surgical risk directly rather than relying on residents. Time constraints and lack of accessibility are moderate barriers to using an objective, evidence-based risk assessment tool.

Adolescent medicine and general pediatrics II

Concurrent session

8:00 AM
Friday, January 24, 2020
228 Vascular anomalies, thromboembolism, and oral contraceptives: a retrospective study

J Wang1,2,*

J Teng1

1Stanford University School of Medicine, Palo Alto, CA

2Western University of Health Sciences, Pomona, CA

Purpose of study

Vascular anomalies, specifically venous and venolymphatic malformations, are rare disorders that are associated with increased risk of coagulopathy. In addition, hormonal contraceptives have been associated with increased risk of venous thromboembolism in the general population. There is limited literature on the relationship between oral contraceptives and risk of coagulopathy in patients with vascular malformations.

Methods used

In this study, we evaluated patients registered in the Stanford Children Vascular Anomalies Clinic database. In this database, the total number of patients was 432. The upper limit (<49 years old) and lower limit (>25 years old) of the age inclusion criterion were based on the childbearing age provided by the CDC. The gender criterion for this study was female. Furthermore, we restricted our study to the diagnosis of ‘venous malformation’ or ‘mixed lymphatic venous malformation.’ Patient data were collected from the past 3 years (2017–2019), which included 40 female patients of childbearing age with venous malformations.

Summary of results

Three of the seven (43%) patients using oral contraceptives developed clotting complications, as compared to 13 of 28 (40%) patients who did not use oral contraceptives. The majority of our participants were using third-generation progestin pills, including norgestimate, etonogestrel, and desogestrel. Only one participant used a second-generation progestin, known as levonorgestrel. This suggests that newer generations of oral contraceptives present less risk than earlier generations.

Conclusions

In our retrospective cohort study, we found that female patients with venous malformations who use oral contraceptives showed a similar propensity for developing clotting complications as those who did not use oral contraceptives. While previous literature suggests that female patients who are prescribed oral contraceptives should undergo additional monitoring for potential coagulation disorders, our study found minimal differences in risk.

229 Dietary supplement use among college students and athletes: a literature review

R Granados1,2,*

K Xu2

A Dihingia2

A Woo2

K Ajjarapu2

M Lai2

B Afghani2,3

1California State University, Fullerton, Fullerton, CA

2UC Irvine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Recent reports have suggested that 15–30% of dietary supplements do not list the ingredients or the amounts posing a risk of adverse health events to the users. Therefore, gaining an understanding about the patterns of dietary supplement use among youth is very important. The purpose of this study was to investigate the characteristics associated with supplement use among college students and athletes.

Methods used

A literature review using Pubmed and Google Scholar with the keywords ‘Use of Dietary Supplements among College Student’, ‘Dietary Supplements College Athletes’, ‘College Student Supplement Use’ was conducted. Only studies published after 2003 that incorporated questionnaires that categorized the frequency of supplement use in otherwise healthy college students were included in our analysis.

Summary of results

Of the 17 articles, only 10 satisfied our inclusion criteria with 6 studies involving college students and 4 involving college athletes exclusively. Prevalence of supplement use ranged from 26.5%-86.9% among college students and 76.8%-89.0% among college athletes. The most dietary supplement used were energy or caffeine containing drinks (48–80%), vitamins/mineral (18–80%) and protein supplements (17–42%). The reasons given for use of supplements were: to promote and maintain good health (14–73%), increase energy (29–50%), and improve strength and muscle (20–43%). The most popular source of information or influence for supplements among women was their families and for men was the internet. One limitation noted among the studies was the wide variation in the frequencies mainly due to the differences in reporting of short-term vs. long-term or recurrent use.

Conclusions

Supplement use is prevalent among college students and college athletes. With the increasing availability and access to these supplements, it is critical that healthcare professionals inquire about their use and serve as an important resource to provide education and awareness. Students should be educated to consume healthy diets consistent with accepted nutritional requirements and discouraged from using supplements to substitute for other healthy nutrition or behaviors.

230 The impact of scoliosis brace type on satisfaction and performance as assessed by the scoliosis research society-24

BC Yang*

Valencia High School, Valencia, CA

Purpose of study

Scoliosis often requires the wearing of a back brace. There are a variety of braces that are used, and there is no data one brace is superior in terms of efficacy. The quality of life is negatively affected by the wearing of a scoliosis brace but little data is available on how different types of scoliosis braces affect the quality of life. We hypothesized that the type of scoliosis brace used in treatment impacted the quality of life of patients with scoliosis.

Methods used

An online survey was conducted to gather data on patients with scoliosis; all participants granted informed consent. Collected data included demographic data, clinical information, treatments administered, compliance, patient experience including friendships, teasing, attitude towards scoliosis back brace, and involvement in choice of the brace used in their treatment. In addition, the Scoliosis Research Society-24 (SRS-24) questionnaire was used to determine subject satisfaction and performance. The SRS-24 instrument is a validated instrument used in adolescents with idiopathic scoliosis to determine satisfaction and performance after treatment. The SRS-24 measures pain, self-image, function, level of activity, and satisfaction.

Summary of results

Data collection is ongoing; to date 32 scoliosis patients have responded. Almost all respondents (96.9%) wore a brace as part of their treatment, 43.8% of patients had surgery, and 38.7% were prescribed exercises as part of their treatment. Among respondents, 59% wore a Boston Brace, 19% Rigo Cheneau, 13% Providence, 3% Charleston Brace, and 6% did not know their type of brace. Doctors chose the brace used in treatment for most patients (77%); parent(s) or guardian(s) chose the brace in 19.4% of patients. Satisfaction with wearing a scoliosis brace was low with 28.1% of respondents reporting they ‘hate’ their brace, and 43.8% stating they ‘dislike’ their brace. The total mean SRS-24 score was 3.6. We did not find a correlation between type of brace and SRS-24 scores.

Conclusions

Scoliosis and the use of a back brace has an impact in the quality of life of adolescent females. Despite this most girls do not have a say in the choice of their scoliosis back brace. There was no correlation between the type of brace worn and attitudes towards wearing the brace on the SRS-24 score.

231 Obesity-related comorbidities and outcomes in a multidisciplinary pediatric weight management clinic

H Kim1,*

D Markovic2

A Guerrero1,3

C Garell1,3

1UCLA David Geffen School of Medicine, Los Angeles, CA

2UCLA Division of General Internal Medicine and Health Services Research, Los Angeles, CA

3UCLA Mattel Children’s Hospital, Los Angeles, CA

Purpose of study

The purpose of this study was to identify the demographic characteristics, analyze obesity related comorbidities, and identify weight outcomes of patients seen in the UCLA Fit for Healthy Weight Program (Fit Clinic), a multidisciplinary pediatric weight management clinic.

Methods used

A retrospective chart review was conducted of 153 pediatric patients in the Fit Clinic between August 2014 and September 2016. The mean changes in BMI z-scores over time was evaluated using a mixed effects linear regression model allowing for random intercepts and slopes.

Summary of results

The average baseline BMI was 31.94 kg/m2 ± 7.97. In the sample, 11% (n=17) were overweight and 89% (n=136) were obese, including 56% (n=85) who were morbidly obese. The patients had an average of 4 to 5 problem diagnoses per visit. The prevalence of comorbidities was higher in the older age group (figure 1). The most common comorbidities for both older and younger age groups included dyslipidemia (50.0% vs. 45.3%), prediabetes (35.9% vs. 21.3%), and obstructive sleep apnea (10.3% vs. 4.0%). The mean BMI z-score tended to decrease over time, mean slope = -0.05 over 6 months (p=0.05).

Conclusions

Many Fit Clinic patients manifest obesity-related comorbidities and are at risk of adverse health outcomes related to cardiometabolic morbidity. The number of comorbidities increased with age, highlighting that early treatment may be imperative in preventing obesity-related comorbidities in older adolescents and adults. Fit Clinic patients’ overall mean BMI z-score tended to decrease over time, demonstrating a promising effect of a multidisciplinary approach to managing pediatric obesity.

232 Quality improvement in the outpatient management of pediatric asthma in the central valley

K Hockett1,*

C Nguyen1

D Corpus1

OC Dogan1

M Jasinto1

V Vidales1

N Bardach2

C Faulkenberry1

1UCSF Fresno, Fresno, CA

2UCSF, San Francisco, CA

Purpose of study

Fresno County has had higher rates of pediatric emergency department visits for asthma exacerbations compared to the rest of California. Written Asthma Action Plans have been shown to reduce emergency room visits and the need for oral steroids. We aim to use written personalized Asthma Action Plans to reduce asthma-related morbidity and mortality by improving pediatric asthma control in our ambulatory pediatric clinic, as a subset of the multi-site IMPLEMENT Asthma Collaborative study based out of The University of California, San Francisco.

Methods used

Retrospective chart reviews of randomized ambulatory clinic pediatric patients with a diagnosis of asthma or reactive airway disease before interventions and after interventions will be used to compare the rates of personalized electronic medical record (EMR)-based Asthma Action Plan provision. This will assess the efficacy of our interventions, which focus on resident-directed education. A portion of the data is included in the IMPLEMENT Collaborative study, however a larger population of patients is included in our dataset. We will also administer pre- and post-surveys to assess for resident awareness and comfort level with outpatient asthma management and to assess for potential areas of ongoing improvement.

Summary of results

We have seen an overall increase in the provision of personalized Asthma Action Plans compared to prior to the implementation of an EMR-based system. This study began in March 2018. Asthma Action Plans were provided at an average rate of approximately 20% as of June 2018; this has increased to approximately 35% as of August 2019.

Conclusions

Continuing resident physician education and implementation of a standardized EMR-based system for provision of personalized written Asthma Action Plans has led to an increased rate of utilization of this intervention. With further interventions, we expect to see further increase in the frequency of provision of a personalized Asthma Action Plan.

233 Correction of neonatal auricular deformities with DuoDERM®: a simple technique

I Manji1,*

K Durlacher1,2

C Verchere1,2

1University of British Columbia, Vancouver, BC, Canada

2BC Children’s Hospital, Vancouver, BC, Canada

Case report

Ear molding in neonates has been shown to successfully correct congenital auricular deformities. There are several currently available molding techniques. However, commercially available molding devices (e.g. EarWell and Ear Buddy) can be costly, and their alternatives have limited customizability. We selected illustrative cases seen in the BC Children’s Hospital plastic surgery clinic in the past 5 years to present the outcomes of a molding technique using cost-effective and customizable materials for common deformations (Stahl’s ear, constricted ear, and prominent ear). DuoDERM® Extra-thin, Steri-strips®, and 3M™ Kind Removal Silicone tape are used to splint the ear in a preferred position. The DuoDERM® is rolled into a putty, placed in the ear, and secured with tapes. This treatment is initiated in the clinic, with weekly splint changes carried out at home by caregivers, and intermittent follow-up appointments. Primary physicians/pediatricians can start this treatment as early as possible in the neonatal period, potentially reducing the need for future surgery. DuoDERM® molding is a safe, inexpensive, highly customizable, and simple way to correct auricular deformities.

Cardiovascular III

Concurrent session

8:00 AM
Friday, January 24, 2020
234 A rare presentation of eosinophilic thrombotic myocarditis

VF Civelli1,2

A Heidari1,*

J Kim3

P Sharma3,4

S Singh2,5

N Doctor2

1UCLA Kern Medical Center, Bakersfield, CA

2Central Cardiology Medical Clinic, Bakersfield, CA

3Touro University California, Bakersfield, CA

4Golden State Providers, Bakersfield, CA

5Cedars-Sinai, Los Angeles, CA

Purpose of study

A 62-year-old very healthy gentleman with a history of seasonal allergies presented to the hospital with stroke symptoms. Initial complete blood count showed an eosinophilic count of 44 thousand. The patient’s transesophageal echocardiogram showed a left atrial appendage with thrombus. For initial concern of cardiac embolic phenomenon, anticoagulation therapy was started but a subarachnoid hemorrhage soon developed. His course complicated quickly to include renal failure. The patient was transferred to a tertiary center where he was dialyzed and improved significantly. Despite improvements and steroid treatment, he remained in critical condition.

Methods used

Patient chart and literature review of ‘Eosinophilic Myocarditis with Thrombosis’.

Summary of results

His cardiac magnetic resonance imaging (MRI) and biopsy both suggested confirmatory diagnosis of eosinophilic myocarditis with left ventricular ejection fraction of 35% with acute congestive heart failure symptoms. He received a dose of cyclophosphamide and heart failure medications. Eosinophilic myocarditis with thrombotic phenomena is a very rare condition and presents as a stroke phenomenon and often found to have a left atrial appendage clot. There are 3 stages of eosinophilic myocarditis progression: inflammatory, thrombotic and fibrotic.

Conclusions

The patient is doing very well on cyclophosphamide to date.

235 The heart as a spring, the measurement of myocardial bounce to assess left ventricular diastolic function on cardiac MR

E Qiao*

TJ Dubinsky

D Hippe

University of Washington, Seattle, WA

Purpose of study

It is difficult to evaluate diastolic dysfunction on cardiac MR since to date this has required the performance of phase contrast imaging across the mitral valve to generate data similar to echocardiography. The purpose of this study is to determine if the myocardial bounce seen during atrial contraction at end diastole corresponds to diastolic and systolic function, and if loss of the bounce could be predictive of both diastolic and systolic heart failure.

Methods used

146 consecutive cardiac MR exams between Sept. and Dec. 2017 were selected for analysis. The bounce was graded by two blinded observers, and the change in LV diameter pre and post bounce was measured. The bounce was defined as the rapid change in LV volume that occurs at the end of diastole during atrial contraction just prior to systolic ejection. Inter-reader agreement was summarized using Cohen’s kappa. Spearman’s rank correlation coefficient was used to evaluate associations between bounce grade and cardiac physiology parameters.

Summary of results

Overall agreement was good with unweighted kappa =0.69 (95% CI: 0.60–0.79). Bounce grade was significantly correlated with the average change in LV diameter before and after the bounce (Spearman’s rho =0.76, p<0.001). Median diameter changes were 0.0, 1.9, and 4.2 mm in grades 0 (no bounce), 1 (small bounce), and 2 (normal), respectively. Bounce grade was significantly correlated with LV EF (Spearman’s rho =0.43, p<0.001). Median EF was 44%, 51%, and 58% in grades 0, 1, and 2, respectively. Of the 88–89 patients who had E/A ratio or E/e’ ratio measured, bounce grade was also significantly correlated with E/A ratio (r= -0.24, p=0.034) and E/e’ ratio (r= -0.24, p=0.022), with lower grades having higher ratio values on average.

Conclusions

The simple observation of a myocardial bounce during cine loop review of cardiac MR exams was predictive of diastolic and systolic cardiac function. Lack of myocardial bounce was highly associated with both systolic and diastolic dysfunction. The subpopulation of patients with loss of myocardial bounce and normal EF appear to represent patients with early diastolic dysfunction, but further evaluation will be needed with more patients with known diastolic heart failure.

236 Mitraclip in the setting of cardiogenic shock: beyond coapt

JM Deen*

T Lev

J Ebinger

Cedars-Sinai Medical Center, Los Angeles, CA

Purpose of study

To assess the short- and long-term outcomes of patients undergoing MitraClip for severe MR in the setting of cardiogenic shock.

Methods used

This was a retrospective observational cohort study of patients who underwent MitraClip at large academic institution between 2013 and 2019. Patients charts were reviewed to identify patients with pre-procedure cardiogenic shock. Patients were considered as having cardiogenic shock if at least 1 of the following were present: 1) documentation of ongoing cardiogenic shock by a provider, 2) hemodynamic monitoring data (cardiac index <2.2) or 3) use of inotropes (Dobutamine, Milrinone or Dopamine) or vasopressors (Norepinephrine, Epinephrine or Vasopressin) within 24 hours of the procedure. Patients were excluded if they lacked a pre- or post-procedure echocardiogram.

Summary of results

Out of 448 MitraClip patients, 29 (6.5%) were identified as having pre-procedure cardiogenic shock. Compared to patients undergoing MitraClip without cardiogenic shock, those with cardiogenic shock were younger (66.5±16.4vs 77.0±12.0, p=0.001), more frequently male (79.3% vs 57.3%, p=0.02) and had a lower left ventricular ejection fraction (35.8% vs 48.1%, p=0.004). Of those in cardiogenic shock prior to MitraClip, 26 (90%) were on inotropes and 16 (55%) were on vasopressors. This decreased to 22 (76%) and 15 (52%) post-procedure, respectively, though did not reach statistical significance (p=0.80). On pre-procedure echocardiography, MR severity was graded as severe or very severe in 21 (72.4%) of those with cardiogenic shock and 301 (71.8%) of those without shock. Of these patients, MR severity was reduced to moderate or less in 26 (89.7%) of those with shock and 400 (95.5%) of those without shock following the procedure (p=0.80). Mortality at 30 days was 20.7% (6 patients) for shock patients, compared with 0% of those without shock.

Conclusions

Use of MitralClip for the treatment of MR in the setting of cardiogenic shock is feasibility, with noted reductions in the severity of MR and inotropic requirements. Readmissions and mortality rates, however remain high. Prospective studies are needed to determine if MitraClip in the setting of cardiogenic shock offers a benefit over medical therapy alone.

237 The black cloud of severe left ventricular primary graft dysfunction after heart transplantation

A Patel*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Cedars-Sinai Medical Center, Los Angeles, CA

Purpose of study

Severe primary graft dysfunction (PGD) is seen in approximately 7% of all heart transplant recipients per the International Society for Heart and Lung Transplantation (ISHLT) PGD grading scale. These patients suffer endothelial cell damage and are known to have increased risk of early mortality. It is not known whether the survivors of severe PGD develop more donor specific antibody (DSA), have more treated rejections, have increased risk of the development of cardiac allograft vasculopathy (CAV), and have increased mortality at 3 years post transplantation. We sought to assess this potential association.

Methods used

Between 2010–16 we assessed 24 heart transplant patients who developed severe PGD per the ISHLT PGD grading scale. These patients who developed severe PGD were compared to those without severe PGD in a contemporaneous era. Patients were then followed for 3 years and assessed for the following endpoints: 3-year survival, 3-year freedom from CAV, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE, defined as myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and 1-year freedom from rejection, including any treated rejection (ATR), acute cellular rejection (ACR), and antibody mediated rejection (AMR).

Summary of results

Patients with severe PGD had decreased 3-year survival, 1-year freedom from any treated rejection, and 3-year freedom from NF-MACE compared to those patients who did not have severe PGD. There were no significant differences between the two groups in terms of 3-year freedom from CAV and freedom from DSA.

Conclusions

Severe PGD appears to have increased mortality and morbidity with more rejection and more NF-MACE. More intense therapies to offset the inflammatory response from severe PGD should be investigated.

238 Is lower low-density lipoprotein cholesterol after heart transplantation associated with optimal outcome?

J Thein*

K Nishihara

A Shen

R Levine

M Hamilton

J Kobashigawa

Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA

Purpose of study

Low-density lipoprotein (LDL) cholesterol has been demonstrated to adversely affect patients with underlying coronary artery disease. In heart transplantation (HTx), LDL cholesterol rises due to the use of corticosteroids and calcineurin inhibitors. From two randomized trials in HTx, it has been demonstrated that statins can lower LDL but also have an immunomodulatory effect by decreasing severe rejection and cardiac allograft vasculopathy (CAV) thus improving survival. It is not been established whether lowing LDL cholesterol to <70 mg/dL can result in improved HTx outcomes.

Methods used

Between 2010–2016, we assessed 109 HTx patients and assessed their LDL cholesterol at 1-year post-transplant. All patients were on statin therapy and patients were divided into quintiles based on their cholesterol levels. The groups were then compared for subsequent 3-year outcomes, including survival, freedom from CAV (as defined by stenosis ≥30%), freedom from non-fatal major adverse cardiac events (NF-MACE, defined as myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and 1-year subsequent rejection including any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). PCSK9 was not used in this study.

Summary of results

Patients in the lowest quintile of LDL cholesterol did not appear to have significantly improved outcomes compared to the other quintiles.

Conclusions

Lower levels of LDL cholesterol at 1-year post-transplant do not appear to have beneficial outcomes although all patients were on statin therapy. Aggressively lowering cholesterol levels may not be indicated in this patient population. Larger studies are warranted to confirm these results.

239 The effectiveness of anti-thymocyte globulin for sensitized patients undergoing heart transplantation

K Nishihara*

A Shen

R Levine

M Hamilton

J Kobashigawa

Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA

Purpose of study

Anti-thymocyte globulin (ATG), has been used as an induction agent in heart transplant (HTx). Early studies suggest that ATG can decrease de novo donor specific antibody (DSA) production after HTx. It has not been established as to the efficacy of ATG in various levels of sensitized pts undergoing HTx.

Methods used

Between 2010–2018, we assessed 370 sensitized pts who were divided into panel reactive antibody (PRA) groups: Group A: 0% (control); Group B: 1–25%; Group C: 26–50%; and Group D: >50%. Pts received ATG immediately post-transplant x5 days. Blood was drawn for antibody detection at baseline, 1, 3, 6, and 12 months after HTx. Groups were assessed for freedom from 1-year survival, rejection (any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR)), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and freedom from cardiac allograft vasculopathy (CAV).

Summary of results

Pts in Groups C and D had decreased freedom from DSA compared to the Control. Furthermore, there was lower freedom from AMR in pts in Group D compared to Control. There were no differences in outcome between each Group and the Control in 1-year survival, freedom from CAV, freedom from NF-MACE, freedom from any treated rejection, and freedom from ACR (see table 1).

Conclusions

ATG induction did not appear to decrease the development of AMR and DSA in those pts with PRA >50% compared to control. Larger studies and longer follow-up will need to be performed to assess ATG’s impact on antibodies and the development of chronic rejection (CAV).

240 Is desensitization therapy safe in mechanical circulatory support patients with existing driveline infection?

S Rajkumar*

K Nishihara

A Shen

R Levine

E Passano

M Hamilton

J Kobashigawa

Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA

Purpose of study

Mechanical circulatory support (MCS) is increasing for patients with advanced heart disease. A common complication is a driveline infection. It is also known that approximately 30% of MCS patients develop circulating antibodies (known as sensitization) due to blood transfusions. Becoming sensitized narrows the donor pool due to incompatible donors. For these patients, desensitization therapy is important to allow transplantation to occur with a compatible donor. There is concern that the use of desensitization therapy might worsen infection in MCS patients with an existing driveline infection.

Methods used

Between 2007 and 2018, we assessed 45 MCS patients who developed a driveline infection. These patients were divided into those who were sensitized (PRA ≥ 10%, n=22) and those who were not sensitized (n=23). The sensitized patients were further divided into those that received desensitization therapy (n=7) and those that did not (n=15). The groups were monitored for the ensuing 1 year after the driveline infection for survival, freedom from readmission, freedom from new driveline infection, and freedom from any infection.

Summary of results

There was no significant difference between sensitized and non-sensitized MCS patients with a driveline infection in terms of 1-year survival, freedom from hospital readmissions, and freedom from any infection subsequent to the initial driveline infection. Additionally, when comparing the subgroup of sensitized patients who received desensitization therapy and those that did not, there was no difference in outcome.

Conclusions

Desensitization appears to be safe in MCS patients with an existing driveline infection to potentially expand the compatible donor pool.

241 Effectiveness of intravenous immunoglobulin versus inlfiximab in patients with refractory kawasaki disease

K Ghasemian1,2,*

W Pan2

W Pan2

S Anand2

N Ton2

I Kane Gomez2

A Lu2

B Afghani2,3

1University of California, Irvine, Irvine, CA

2UC Irvine School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

It is unclear whether the use of Infliximab (IFX) or a second dose of intravenous immunoglobulin (IVIG) is more effective in treating patients with IVIG-resistant Kawasaki Disease (KD). The purpose of this study is to investigate whether retreatment with IFX or IVIG is associated with a greater and more rapid resolution of fever and fewer adverse coronary outcomes in patients with refractory KD.

Methods used

A literature review using Pubmed and Google Scholar with the keywords Infliximab, IVIG-resistant Kawasaki Disease, and Refractory Kawasaki Disease was conducted. Only studies that directly compared retreatment with IVIG versus IFX were used. Of these studies, only those that evaluated coronary outcomes, response rates, and febrile periods for each retreatment were used.

Summary of results

Of the 16 articles that we found, only 4 satisfied our inclusion criteria (see table 1 below). Our study was limited due to most studies focusing on treatment for patients with non-refractory KD. Additionally, many studies combined different treatment options together and were thus excluded from this study. All studies that tested IFX found a correlation between Infliximab administration and greater resolution of fever along with shorter febrile periods. The correlation between coronary abnormalities and the administration of IFX or IVIG remains inconclusive.

Conclusions

Our review suggests that IFX could be more successful in alleviating fevers versus retreatment with IVIG in refractory KD patients. The occurrence of coronary abnormalities and adverse events in retreatment with both drugs was not significant. Further research with larger sample sizes and longer follow up periods must be conducted to fully confirm these results.

Case reports I

Concurrent session

8:00 AM
Friday, January 24, 2020
242 Colon cancer presenting as a splenic abscess with associated fusobacterium mortiferum bacteremia

E Fitzsimmons1,*

T Torrico1

C Donath1

S Ragland2

1Ross University School of Medicine, Bridgetown, Barbados and

2Kern Medical Center, Bakersfield, CA

Case report

Streptococcus bovis bacteremia is a well-known classic association for an underlying colorectal carcinoma. However, more rarely, Gram-negative bacteremia’s can also be associated with colorectal cancer. This case report documents an underlying colorectal carcinoma with a previously undescribed Fusobacterium mortiferum bacteremia. In addition to the bacteremia, this patient presented with a splenic abscess, whose formation generally requires seeding from another primary source of infection. Cultures of the splenic abscess in this case did not grow Fusobacterium mortiferum but did grow Escherichia coli and Streptococcus group C beta. Surgical intervention later confirmed suspicion of direct contact of the distal transverse colon to the spleen due to an expanding colorectal carcinoma as no other primary sources of infection were found. To the best of our knowledge, there are no documented cases of Fusobacterium mortiferum bacteremia’s associated with colorectal carcinoma in the literature. Additionally, the formation of a splenic abscess by direct contact, rather than by seeding, remains incredibly rare.

243 A rare case of coccidioidal otomycosis

HK Sandhu*

G Petersen

A Heidari

Kern Medical, Bakersfield, CA

Purpose of study

Coccidioidomycosis(cocci) Immitis is found abundantly in soil in the Central Valley of California, southern Arizona, west Texas, and southern New Mexico. Around 40% of infections due to coccidioides are asymptomatic with vast majority being self-limited pulmonary infection. 12% of cases show dissemination beyond the lungs, most commonly to bones, ymph nodes, joints, and meninges. We here present the only case of coccidioidomycosis dissemination to the mastoid process that we experienced in our data base of over three thousand cases.

Methods used

Retrospective case study.

Summary of results

A 22 year old Hispanic male with uncontrolled Diabetes Mellitus type I was diagnosed with pulmonary coccidioidomycosis prior. Cocci complement fixing titer was 1:32. He was placed on fluconazole 800 mg daily. One year later he experienced gradual onset left ear pain with radiation to left jaw and left eye and purulent drainage. He was diagnosed with left otitis externa and was treated medically.

Subsequently, he presented with left sided progressive hearing loss and diffuse pounding headache, nausea and vomiting of 1 month duration. On otoscopic examination, tympanic membrane was erythematous, bulging with middle ear effusion. 512 tuning fork conclusive of conductive hearing loss on the left side. CT of the head showed complete opacification of mastoid air cell system on the left side with fluid in the middle ear. MRI showed left mastoiditis with an extradural collection. He was admitted and started on I.V. antibiotics.

Upon ENT consultation operative management was conducted for left mastoiditis and otitis media with left myringotomy with insertion of tympanostomy tube. Patient remained symptomatic 10 days postoperatively therefore, left mastoidectomy and tympanoplasty was performed for chronic mastoiditis. Mastoid tissue biopsy on culture grew Coccidioides Immitis after 28 days. The tympanic membrane healed well and there was a gradual increase of hearing in his left ear. Patient subsequently completed 12 week course of Liposomal amphotericin B and his treatment was changed to oral posaconazole he improved and followed up in the outpatient setting.

Conclusions

Clinicians should be aware that coccidioidomycosis could hematogenously disseminate to any foci of body particularly in the immunocompromised host.

244 A case of ocular syphilis as the initial presenting symptom in a patient with HIV

J Bhandohal*

J Bhaika

R Jariwal

R Gupta

J West

S Allday

C Anderson

B Oftedal

Kern Medical, Bakersfield, CA

Purpose of study

Syphilis is a bacterial infection from Treponema pallidum that is most commonly transmitted sexually. The disease progresses through many stages and has a broad spectrum of clinical manifestations. All stages are curable with the use of penicillin with route of administration and length of treatment based on stage at diagnosis. Syphilis is more commonly seen in individuals with human immunodeficiency virus (HIV) and ocular syphilis is an uncommon initial presentation of the infection.

Methods used

Retrospective case report.

Summary of results

A 58-year-old Hispanic male with a history significant for HIV presented to his ophthalmologist with complaints of seeing floaters in the previous three months. The floaters were associated with vision changes but no complete loss of vision or pain. Due to the patient’s HIV status and the recent vision changes, laboratory studies were performed to assess for a variety of diagnoses. The initial diagnosis of syphilis was confirmed and the patient was sent to the hospital for further management and treatment. On admission, physical exam demonstrated extraocular movements intact, pupils equal and reactive to light and accommodation with no reduction in peripheral vision. Cranial nerves II-XII were tested and intact and sensation to light touch was intact throughout. A lumbar puncture with differential and VDRL along with a serum qualitative syphilis antibody were obtained. The cerebral spinal fluid returned positive for syphilis and the patient was given a PICC line and was treated for 14 days with 4 million units of Penicillin G IV.

Conclusions

This case demonstrates an uncommon initial manifestation of syphilis that requires high suspicion for diagnosis and further workup to determine how invasive the infection for proper treatment protocol. Syphilis in general is more commonly seen in patients diagnosed with HIV and therefore any patient with HIV presenting with vision changes should undergo initial syphilis diagnostic testing as a delay in treatment may cause a worsening of symptoms. Finally, if ocular syphilis is the initial symptom at diagnosis, a CSF analysis should be done to determine if the patient also has neurosyphilis as this needs more aggressive treatment.

245 A case of acute liver injury in the setting of anti-tuberculosis therapy for presumptive ocular tuberculosis

D Lichtenfeld1,2,*

A Govindarajan2

D Learned3

A Heidari2

1Ross University School of Medicine, Miramar, FL

2Kern Medical – UCLA, Bakersfield, CA

3California Retina Institute, Bakersfield, CA

Purpose of study

Mycobacterium tuberculosis (MTB) is an obligate aerobic bacteria, and is the causative agent in ocular tuberculosis (TB); the oxygen tension of the choroid of the eye is one of the highest oxygen tensions in the body and is attractive for the bacillus to be seeded via hemagenous spread. Ocular TB is more common in the uveal tract, retina, and optic nerve respectively. The diagnosis is essentially clinical as the pulmonary disease is missing.

Summary of results

A 31-year-old Hispanic female who previously worked in a hospital in Mexico referred from her ophthalmologist with the diagnosis of ocular TB. The patient had been suffering for about 1 year with bilateral panuveitis with bilateral granulomatous inflammation. Her Quantiferon-Gold TB test, was positive with negative chest x-ray. She was initiated with rifampin, isoniazid, pyrazinamide and moxifloxacin. After about 4 months of therapy with clinical improvement with serial ophthalmological examination she was found to have epigastric pain, nausea, vomiting, and non-bloody diarrhea; her AST/ALT were 1,424/1,584 U/L, and Bili T of 4.4 mg/dl. All anti-TB medications were stopped, and the patient was admitted. Her liver injury continued to worsen to levels as high as 19/1957/2363 (Bili/AST/ALT). MELD as high as 23 and INR as high as 2.

She underwent liver biopsy complicated with intra-abdominal hemorrhage and embolization. Pathology showed periventricular necrosis, ballooning degeneration of hepatocytes, and mild bridging fibrosis, consistent with drug induced necrosis. Her ANA came back 1:160 suggestive of underlying autoimmune process as well. She was transferred to liver transplant center but fortunately, spontaneously start to improve with slow drop in liver injury markers. Plan is to restart her treatment only with 2 least hepatotoxic medications to finish her course of treatment.

Conclusion

Clinicians should be aware of the potential acute and severe liver injury when treating patients with ant-tuberculosis medications. Due to nature of clinical diagnosis and lacking microbiological data to deescalate treatment the risk of toxicity is higher.

246 Recurrent hospitalization for cannabinoid hyperemesis syndrome in an adolescent

K De Leon*

J Pham

TJ Chinnock

Loma Linda University, Loma Linda, CA

Case report

A 16 year-old male with history of major depressive disorder and attention deficit hyperactivity disorder presented to an outside ED with four days of recurrent episodes of nausea and vomiting associated with weight loss and decreased appetite. He was transferred due to chest pain and shortness of breath attributed to pneumomediastinum identified on chest radiograph. The patient reported at least 2 years of daily use of ‘wax’ marijuana which he smoked to maintain a constant ‘high’.

On admission the patient continued with nausea and non-bilious, non-bloody vomiting. Vital signs were reassuring with normal oxygen saturation. Physical exam was notable for crepitus over his upper left anterior chest wall but normal breath sounds and work of breathing. The abdomen was soft and non-distended but generally tender to palpation. Lab values were normal except for white blood cell count of 23.5 bil/L and slightly low sodium and chloride. Chest x-ray showed mediastinal air and CT scan of the chest, abdomen, and pelvis confirmed pneumomediastinum with subcutaneous air, and ruled out intestinal obstruction. His symptoms were unresponsive to typical antiemetics such as ondansetron and promethazine, but he reported significant relief with hot water bathing. Based on his chronic cannabis use and symptoms he was diagnosed with CHS. Due to persistent symptoms, he was started on haloperidol after which he experienced relief. He was discharged home, but would go on to have multiple further encounters.

Over the course of approximately 18 months he presented eight times to various EDs reporting the same symptoms. Five of these eight ED visits resulted in hospital admission for a total of 23 hospital days. Recurring clinical findings were: pneumomediastinum, leukocytosis (as high as 30.5 bil/L), hypertension, hypokalemia, and hypochloremia. He was treated with ondansetron and promethazine with negligible benefit. He did not tolerate a trial of topical capsaicin. He was given haloperidol on three visits with reported improvement each time. He underwent a total of three abdominal CT scans, two ultrasounds, and numerous x-rays. He received intravenous antibiotics on two occasions. Upon phone interview with the patient’s legal guardian, he has been symptom free for 8 months since he quit using cannabis.

247 Once but not twice: RIPE before snip

VF Civelli*

M Valdez

V Narang

A Heidari

R Johnson

Kern Medical, Bakersfield, CA

Purpose of study

Orcheictomy in the presence of unilateral mass is common practice in Urology; however, histopathology post-resection may be consistent with infectious etiology, such as tuberculosis (TB) or endemic fungal sources. Here we describe a case of presumptive TB of the testicles in a patient who underwent unilateral right orchiectomy followed by spread of symptoms to the contralateral testicle post-procedure.

Methods used

Retrospective single-patient case report.

Summary of results

The patient is a 41-year-old Hispanic male who underwent right-orchiectomy, to rule out malignancy, at an outside facility two years prior after he presented with right sided testicular enlargement. He subsequently presented to our facility with new left testicular pain and swelling, which started approximately 6–10 months after the right orchiectomy. Examination revealed a chronic wound with exudative material at the base of an erythematous and edematous scrotum. A firm mass and scrotal tenderness were appreciated. A course of doxycycline was completed due to concern for epididymitis, which provided no relief. The pathology report from the right orchiectomy was obtained and revealed necrotizing granulomatous inflammation with a rare, questionably AFB-stained organism. Additional work-up for coccidioidomycosis, granulomatosis with polyangiitis, sarcoidosis, histoplasmosis, and brucellosis were negative. Urine AFB stains and cultures were also negative. Regardless, empiric therapy with the standard 4-drug anti-tuberculosis medication regimen (RIPE), including rifampin, isoniazid, pyrazinamide, and ethambutol was initiated. The patient completed a 6 month course of RIPE therapy and experienced complete resolution of all symptoms, including left testicular pain, swelling, and erythema.

Conclusions

Clinicians should be mindful to include infectious etiologies, specifically TB, in the differential diagnosis for orchitis, epididymitis, and solid testicular masses, even in the setting of negative work-up. Although the urology literature describes that orchiectomies occur per standard guidelines for malignancy, in the case of spread of symptoms to the remaining testicle a comprehensive work-up for infectious etiologies and perhaps empiric therapy should be considered prior to resection.

248 A case of hepatitis B immune escape variant: is my spouse safe?

A Shah*

A Heidari

V Bali

M Valdez

Kern Medical-UCLA, Bakersfield, CA

Purpose of study

Immune escape variance in hepatitis B is a rare phenomenon seen particularly in the Asian population. Antigenic escape occurs when the immune system is unable to respond properly to an infectious agent. In the case of Hepatitis B (HBV), this presents as a possibility when the patient has the coexistence of HBsAg and HBsAb. The risk for malignancy, transmission rate, and other clinical significance of immune escape variance in hepatitis B is not well studied.

Methods used

Retrospective Study

Summary of results

50 year old Phillipinio male with a diagnosis of previously treated hepatitis B presented to our clinic for further evaluation after he had a positive hepatitis screening test. He reports no clinical symptoms including weight loss, abdominal pain, jaundice, pruritus. His laboratory result showed hepatitis B viral load of 36, HBsAg reactive, HBsAb 590, reactive HBcAb, nonreactive HBeAg and HBeAb without any clinical symptoms and had elevated liver enzymes (ALT 68, AST 39). Given the contradictory nature of the results, a repeat lab test was requested from the patient, which again showed HBeAg and HBeAb non-reactive, HBsAg reactive, HBsAb 706, Hep B DNA 73 and reactive HBcAb. Liver ultrasound showed coarse echogenicity of the live suggest of cirrhotic liver. The coexistence of HBsAg and HBsAb indicates possible immune escape variants. Additional Hepatitis B genotype study was ordered, however was not able to be performed because the patient had a viral load <600. Since patient showed evidence of cirrhosis by ultrasound based on AASLD guideline he was started on Entecavir 1 mg daily and continued with unknown duration. After being on the medication for 6 months, repeat serology showed HBsAg reactive, HBsAb 726, Hep B DNA not detected.

Conclusions

A diagnosis of immune escape variant of hepatitis B should be considered when the patient has serological findings of both the surface antigen and antibody. The family screening should be considered and immunization should be done in non-immunized at risk. However, risk of transmission of this variant even to individuals with adequate immunity is unknown and precautions are still warranted.

249 A case of escherchia coli vulneris necrotizing fascitis

R Hall1,2,*

S Choi2,3

A Govindarajan2

A Heidari2

1Ross University School Of Medicine, Miramar, FL

2Kern Medical – UCLA, Bakersfield, CA

3Arizona College of Osteopathic Medicine At Midwestern University, Glendale, AZ

Purpose of study

Escherichia vulneris is a gram-negative, oxidase-negative, fermentative, motile rod in the family of Enterobacteriaceae based on DNA relatedness studies and biochemical reactions. Most isolates of E. vulneris have been recovered from wounds and few case studies are available characterizing its pathogenic characteristic. We are presenting a rare case of type I polymicrobial necrotizing fasciitis with of Escherichia vulneris, streptococcus anginosus and eikenella corrodens.

Methods used

Retrospective case report.

Summary of results

A 26 year old African American female with schizoaffective disorder, intravenous drug abuse with methamphetamine and hepatitis C presented with right arm redness and swelling for one week, the physical exam revealed a significant area of skin erythema and induration; in addition, the central area of eschar and necrosis noted on the proximal medial aspect of the right upper extremity. CT showed scattered gas bubbles in the right arm. She underwent emergent debridement and was diagnosed with necrotizing fasciitis of right chest wall and right upper arm. Her course got complicated with pneumothorax. She was started on broad spectrum antibiotics with vancomycin and pipercillin/tazobactam. Her intraoperative cultures repeatedly grew E. vulneris, streptococcus anginosus and eikenella corrodens.

E. vulneris was only resistant to ampicillin but sensitive to ampicillin/sulbactam. She underwent multiple debridements and her antibiotic regimen was deescalated to ampicillin/sulbactam. After clinical improvement she underwent successful skin graft.

Conclusions

Even though Escherichia vulneris has been reported to colonize chronic wounds in this case it was isolated from intraoperative deep tissue source and was considered pathogenic. We only found one other case report of fatal E. vulneris necrotizing fasciitis.

Endocrinology and metabolism II

Concurrent session

8:00 AM
Friday, January 24, 2020
250 High prevalence of metabolic syndrome in adolescents with klinefelter syndrome

SI DeKlotz*

N Tartaglia

M Kelsey

KJ Nadeau

S Davis

University of Colorado, Aurora, CO

Purpose of study

Klinefelter Syndrome (KS) occurs in 1:600 males and is associated with high morbidity and mortality due to cardiovascular disease and diabetes. Metabolic syndrome (MetS) describes a set of features which confer an elevated risk for cardiovascular disease and diabetes. Previous studies have found that up to 50% of men with KS have MetS, but MetS has not been studied in adolescents with KS. We compared features of MetS in adolescents with KS to controls matched for sex, age and BMI-z score.

Methods used

This is a matched case-control cross-sectional study in 50 males with karyotype 47,XXY who were 10–17 years of age. Cases were matched 1:1 on age and BMI-z score with healthy male controls. Waist circumference, seated systolic blood pressure (SBP), fasting blood glucose (FBG) and lipid panel were measured. MetS was defined as meeting 3 or more of the following criteria: fasting triglycerides (Tg)≥100 mg/dL; HDL cholesterol <50 mg/dL if <15 years old or <45 mg/dL if >15 ; FBG ≥110 mg/dL; waist circumference >75th percentile for age and sex; and SBP >90th percentile for sex, age and height. The proportion of participants meeting MetS criteria was compared using a Fisher exact test. Continuous variables were compared using a paired t-test or Wilcoxon matched-pairs signed rank test.

Summary of results

Participants with KS (n=50) were well matched with controls (n=50) for age (14±1.7 vs. 14±1.5 years) and BMI-z score (0.31±1.3 vs. 0.36±1.2). MetS was present in 32% of adolescents with KS compared to only 12% of controls (p=0.028), correlating to an odds ratio of 3.5 (95% CI 1.3, 9.8). The KS group had significantly lower HDL (40±8 vs. 47±11 mg/dL, p=0.006), higher Tg (120±67 vs. 83±40 mg/dL, p<0.001) and larger waist circumference percentile (63±29 vs. 53±33%, p<0.001). FBG and SBP were similar (p>0.05).

Conclusions

Despite a normal BMI, the prevalence of MetS was strikingly high in adolescents with KS compared to controls, particularly for features of abdominal adiposity and dyslipidemia. Reinforcing healthy lifestyle choices and routine screening for MetS features should begin early for boys with KS. The pathophysiology of this unhealthy metabolic profile in the absence of obesity needs further investigation to facilitate prevention of the high morbidity of cardiovascular disease and diabetes in this population.

251 Muscle mitochondrial function in klinefelter syndrome

S Cung*

KJ Nadeau

D Dabelea

M Cree-Green

S Davis

University of Colorado, Aurora, CO

Purpose of study

Klinefelter Syndrome (XXY) occurs in 1 in 600 males, resulting in testosterone deficiency and a high prevalence of type 2 diabetes. Testosterone deficiency in men is known to cause insulin resistance and mitochondrial dysfunction is hypothesized to mediate this relationship, however mitochondrial function has not been assessed in XXY. The aim of this cross-sectional study was to evaluate mitochondrial function in adolescents with XXY and the relationship with insulin resistance.

Methods used

Twenty-seven adolescent males with XXY (age 14.7±1.8 yrs) were compared to 75 controls (age 16.7±1.3 yrs). A subset of n=13 XXY boys were receiving testosterone replacement. In-vivo muscle mitochondrial function was assessed via phosphorus MR spectroscopy (31P-MRS) of the dominant-leg soleus muscle following 90 seconds of exercise. Fasting serum was analyzed for glucose and insulin to calculate HOMA-IR. Multiple linear regression was used to compare 31P-MRS outcomes (ADP and Phosphocreatine (PCr) time constants, rate of oxidative phosphorylation (Oxphos), and maximal mitochondrial function relative to mitochondrial density [Qmax]) between groups after adjusting for age differences. Within the XXY group, linear regression was used to assess the relationship of mitochondrial function variables with HOMA-IR and testosterone treatment status.

Summary of results

There were no statistically significant differences in mitochondrial function outcomes between the two groups (ADP p=0.95, Oxphos p=0.19, PCr p=0.98, Qmaxp=0.56). HOMA-IR did not have a linear relationship with any of the mitochondrial variables. There were also no differences within the XXY group by testosterone treatment status (ADP p=1.00, Oxphos p=0.20, PCr p=0.23, Qmaxp=0.99).

Conclusions

In-vivo post-exercise muscle mitochondrial function is not impaired in adolescents with XXY compared to controls and treatment with testosterone does not significantly relate to muscle mitochondrial function in XXY. The insulin resistance associated with XXY does not appear to be mediated by muscle mitochondrial dysfunction.

252 Increased de novo lipogenesis in hepatics steatosis regardless of polycystic ovary syndrome status

JJ Stuppy1,2,*

C Severn1

EJ Parks3

A Carreau1

Y garcia-reyes1

H Rahat1,2

DH Wagner4

KJ Nadeau1

L Pyle1

M Cree-Green1

1University of Colorado Anschutz, Aurora, CO

2Rocky Vista University, Parker, CO

3University of Missouri, Columbia, MO

4Metabolic Solutions, Nashua, NH

Purpose of study

PCOS affects up to 15% of women and is associated with obesity and the metabolic syndrome. Adolescents with PCOS and obesity are more likely to have hepatic steatosis (HS) relative to girls with normal menses of similar age, race/ethnicity and adiposity. Serum markers for de novo lipogenesis (DNL) are increased in PCOS, but it is unknown if DNL was increased in girls with PCOS when controlling for HS status, or how DNL relates to HS in adolescents with obesity.

Methods used

Adolescents with obesity were selected for similar HS status and then either PCOS (N=11, 5 with HS, 6 without) or Controls with normal menses (N=9, 5 with HS, 4 without) were enrolled. Hepatic fat was measured with MRI utilizing the Dixon method, and ≈50% of each group had HS, defined as >5.5% fat. DNL was measured fasting and during an oral sugar tolerance test (OSTT; 76–78 g glucose +25 g fructose) using an intravenous stable isotope 13C2 acetate infusion with subsequent measurements of incorporation of the tracer into VLDL-triglyceride palmitate. Fasting hormones, lipid and inflammatory markers and OSTT-derived glucose and insulin were measured.

Summary of results

Percent liver fat was similar regardless of PCOS status (PCOS no HS 3.5±0.6%; Control no HS 2.7±0.4; PCOS HS 8.2±1.9; Control HS 8.8±3.1). The amount of OSTT stimulated VLDL-triglyceride DNL was also similar between PCOS and Controls without HS, and PCOS and Controls with HS (PCOS no HS 3.5±1.6 mg/dL; Control no HS 8.2±5.3; PCOS HS 9.8±4.1; Control HS 13.5±3.8). In the combined PCOS and Controls, OSTT DNL increased as the hepatic fat content increased (r=0.19, p=0.05). Within the PCOS cohort, OSTT DNL was significantly related to free testosterone (r=0.50, p=0.02).

Conclusions

In girls with obesity, PCOS status per se does not increase DNL relative to adolescents with normal menses. However, free testosterone related significantly to DNL within the PCOS group. The 3-fold higher prevalence of HS in girls with PCOS and obesity could perhaps be explained by excess testosterone driving higher rates of DNL in a larger percentage of girls with PCOS, and further work is needed to confirm this hypothesis.

253 Metabolomic characterization of hepatic steatosis in polycystic ovary syndrome

H Rahat*

K Alexander

J Reisz

Y Garcia-Reyes

A Carreau

KJ Nadeau

A D’Alessandro

M Cree-Green

Univ. of CO Anschutz, Aurora, CO

Purpose of study

Polycystic ovary syndrome (PCOS) affects 6–10% of women and is associated with hepatic steatosis (HS). HS is the best predictor of future diabetes and cardiovascular disease, yet the cause of HS in PCOS is unknown, difficult to diagnose, and treatments are limited. We sought to identify unique serum markers for HS in obese PCOS adolescents.

Methods used

All participants underwent fasting hormone and metabolic measures and abdominal MRI for hepatic fat, with HS defined as hepatic fat fraction ≥5.5%. Participants were divided into 4 cohorts of obese adolescents: 1) A development cohort of treatment-naïve girls with PCOS and HS (N=11) or PCOS without HS (N=9); 2) a validation cohort similar to cohort 1 (PCOS nonHS N=7, PCOS HS N=7); 3) a non-PCOS cohort with HS (N=6) and without HS (N=14); 4) a PCOS cohort treated with at least 6 months of estrogen therapy with HS (N=3) and without HS (N=7). Serum samples underwent polar metabolite liquid/liquid extraction then global metabolite profiling by ultra-HPLC-MS. Samples from cohort 1 underwent untargeted analysis to determine metabolites that distinguished HS, which were confirmed with targeted analysis. Metabolites in the targeted panel were then assessed in samples from the other 3 cohorts.

Summary of results

Significant differences in the serum metabolome of cohort 1 HS vs. non-HS were noted in amino acids, lipids, glycolytic, purine and heme metabolites (p<0.05). The most notably different compounds notable amino acids (notably glutamate), long chain fatty acids, biliverdin and sphingosine 1-phosphate (S1P) were confirmed in the targeted panel. In samples from cohort 2, hierachical clustering analysis of the top 25 metabolites by t-test confirmed results from cohort 1 with S1P, acylcarnitines, free fatty acids. Several amino acids confirmed as specific markers with ~71% accuracy. These markers were not different by HS status in cohort 3. In cohort 4, estrogen therapy normalizedonly S1P, but did not resolve the excess long chain fatty acids and glutamate in HS.

Conclusions

We determined that S1P, glutamate and several long chain fatty acids are uniquely elevated in HS+PCOS and S1P was lower in girls on estrogen therapy. These metabolites may be used as biomarkers to identify HS in girls with PCOS.

254 Employing metabolomics and microbiome data to build algorithms for interrogating host-microbe interactions

K Thurimella*

M Shaffer

C Lozupone

University of Colorado School of Medicine, Aurora, CO

Purpose of study

The microbiome has been linked to the pathogenesis and salubrious states in the human body. However, recent research has been driven by correlative studies, linking an unfavorable disease state to certain microbes. Untargeted metabolomics approaches have yielded an abundance of datasets but the complexity of the data interpretation remains. We introduce AMON: Annotation of Metabolite Origins via Networks and SCNIC: Sparse Cooccurence Network Investigation for Compositional data as tools to help address these issues. Both are open source software tools used to label compound origins of certain metabolites, from microbe to host or both, to then build a higher level groups of microbes that co-exist together.

Methods used

We illustrate the utility of AMON and SCNIC using a dataset (16s rRNA) from the gut microbiome and blood metabolome (LC/MS) of HIV positive individuals. This validation was part of a larger study of differences in fecal microbiomes in HIV and non-HIV populations. AMON uses KEGG Orthology to generate pathway enrichment and a hypergeometric test to verify the prediction of metabolites and their origin. SCNIC uses a microbiome table to build a correlation network to and groups of microbes are clustered together and collapsed into a smaller microbiome table.

Summary of results

After benchmarking SCNIC, the optimal parameter values were an R-value above 0.5 for the SMD algorithm and for a gamma value above 0.1 for the LMM algorithm. With AMON applied to the data, 40 compounds were produced by bacteria alone, 58 by the host alone and 91 by both. Together, these analyses show that AMON can be used to predict the putative origin of compounds detected in a complex metabolome and SCNIC can help understand microbial dynamics.

Conclusions

The limitations of integrating metabolomics and metagenomics are stark for complex microbial communities, where there are fewer genes of known function. With these tools, researchers can build a general framework to understand the specific interactions between certain microbes and the host, at a chemical level. Ultimately the understanding of microbiome interactions can influence many aspects of human health and disease through its metabolic activities, and with an understanding we can begin to develop more targeted therapies to mitigate human disease.

255 Recognition of distinct facial morphology in youth with congenital adrenal hyperplasia via machine learning techniques

H Mirzaalian1

X Guo1

L Randolph2

V Tanawattanacharoen2

H Ross2

M Geffner2

W Abd-Almageed1

M Kim2,*

1Information Sciences Institute, Marina Del Rey, CA

2Children’s Hospital Los Angeles, Los Angeles, CA

Purpose of study

Classical Congenital Adrenal Hyperplasia (CAH) affects 1:15,000 newborns and involves adrenal (cortisol) insufficiency and androgen excess. These hormonal abnormalities are evident as early as week 7 of gestation and persist throughout the pregnancy. Structural brain abnormalities also are known to occur in CAH youth and adults, with abnormalities of brain and facial structure occurring together in other conditions such as fetal alcohol syndrome and holoprosencephaly. We therefore sought to study facial features using machine learning for the first time in youth with CAH.

Methods used

We examined frontal images of the face in 63 youth with severe, salt-wasting classical CAH due to 21-hydroxylase deficiency (58.7% female; 11.5±7.1 yr; range 0.02–17.7 yr) and 37 unaffected controls (56.8% female; 11.1±6.2 yr; range 0.06–17.3 yr; p=NS). Images were acquired using an iPad v12.1. We started by automatically detecting face-bounding boxes, which were used to train a neural network to differentiate between CAH and control youth. Due to the small size of our dataset, we employed K-fold cross validation to obtain reliable statistical results. At each of the K-9 folds, 88% of data was used to train the neural network (including 216 control and 513 CAH images) and the rest was used to evaluate the trained neural network model (including 70 CAH and 29 control images). Test results of the nine folds were validated in terms of the area under the curve (AUC) of the receiver operating characteristic curves (ROCs).

Summary of results

The AUC of the averaged ROCs over nine folds was 0.88±0.07, representing strong predictive power as a proxy to correlating facial dysmorphology with CAH. We also produced heat (i.e., saliency) maps showing the effect of CAH on facial features, and 2D visualization of facial features showing well-defined separation between CAH and control group clusters.

Conclusions

Utilizing machine learning, we have shown that CAH youth have facial features that can reliably distinguish these youth from controls. Further study is merited in regard to the etiology of affected facial morphology in CAH, and associations with other brain and/or behavior abnormalities.

256 Early adiposity rebound in youth with congenital adrenal hyperplasia is associated with increased adiposity and bone age in adolescence

G Bhullar1

V Tanawattanacharoen1

M Yeh1

S Vartany1

W Kim1

A Vidmar1

M Geffner1

D Hwang2

M Kim1,*

1Children’s Hospital LA, Los Angeles, CA

2University of Southern California, Los Angeles, CA

Purpose of study

Youth with Congenital Adrenal Hyperplasia (CAH) have an increased prevalence of obesity. Adiposity rebound (AR) is a rise in body mass index (BMI) that corresponds to an increase in number and size of adipocytes. In the U.K., CAH youth exhibited an earlier mean AR by 3 years (1.7 yr) compared to the general population (~5 yr). Among healthy, unaffected youth, an earlier age at AR is predictive of future obesity and associated with advanced bone age. Our objective was to examine associations among AR, bone age, and adiposity in youth with CAH at our U.S. center.

Methods used

Data from 19 CAH patients were studied from the first clinic visit (prior to 2 yr), and every 6 months thereafter, until the last clinic visit. BMI (kg/m2) was calculated from length/standing height and weight at each visit. Visual inspection (VI) and cubic polynomial (CP) methods were used to determine age at AR. By VI, AR age was located at the point preceding the second rise of BMI after 1 year of age. By CP, AR age was located at the nadir before the second rise in the cubic model. Total fat and lean mass in adolescence were measured by DEXA. Waist circumference (WC), abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by single-slice CT or 3-Tesla MRI at the umbilicus. Bone age x-ray near the time of imaging was studied for advancement beyond chronological age.

Summary of results

Average age at AR for CAH youth was 3.3±0.3 yr by VI, and 3.2±1.2 yr by CP (p=0.9). Age at AR (by CP alone) was negatively correlated with total fat mass (r= -0.59, p=0.01), WC (r= -0.52, p=0.05), and SAT (r= -0.58, p=0.02), but not with lean mass or VAT. Age at AR was negatively correlated with bone age advancement by VI (r= -0.63, p=0.01) and CP (r= -0.45, p=0.03).

Conclusions

CAH youth at our center exhibited an earlier AR by 2 years compared to the general U.S. population, and those with earlier AR had increased adiposity in adolescence. AR and bone age advancement could be causally related in CAH or explained by other factors such as glucocorticoid treatment that merit further study.

257 A case of thyrotoxic periodic paralysis

P De Mola

G Renganathan

N Hasan*

D Aguirre

Kern Medical, Bakersfield, CA

Purpose of study

Thyrotoxic periodic paralysis (TPP) is a rare condition caused by untreated hyperthyroid disease. Patients typically present with lower extremity paralysis and associated hypokalemia. After IV KCl administration, lower extremity strength rapidly resolves, and the patient is often discharged without the causal hyperthyroid state exposed. Incidence of TPP is reported in 2% of patients with underlying thyrotoxicosis.

Methods used

Retrospective case report

Summary of results

32 y.o. Hispanic male with no significant PMH presented to ED with complaints of lower extremity paralysis x 4 hours. Patient endorsed 4 similar episodes over the past 6 years, however, disease was not worked up as the paralysis rapidly resolved with IV KCl in the ER. ROS notable for 10lbs weight loss, exophthalmos, heat intolerance, diaphoresis, tremors and anxiety. His only home medication was 40mEq of KCl daily. He denied any family members sharing similar episodes. Physical exam demonstrated sinus tachycardia and mild exophthalmos.

In the ED, K+ was 2.7 and 40 mEq of IV KCl was administered, followed by another 40 mEq given orally. After three hours, his lower extremity strength recovered completely. Repeat labs showed a rapid response to KCl with K+ rising to 5.8. The working diagnosis was hypokalemic periodic paralysis (hypoKPP), however, with no family history and symptomology consistent with a hyperthyroid picture, a thyroid panel was ordered. Labs were significant for TSH <0.008, with a free T4 of 3.24. Thyroid U/S demonstrated no masses or nodules; but the gland was diffusely enlarged with increased vascularity. Case was discussed with endocrinologist, who concurred with the diagnosis of TPP. Patient was started on methimazole and propranolol with plans to see endocrinology outpatient. Unfortunately, patient was lost to follow-up.

Conclusions

TPP is characterized by sudden onset of hypokalemia and subsequent lower extremity paralysis due to thyroid hormone sensitization of Na+/K+-ATPase channels. Clues that distinguish TPP from familial hypoKPP include a lack of family history of paralytic episodes, male sex, late presentation and signs of thyrotoxicosis. Treatment consists of nonselective beta-blockers, correction of hyperthyroid state and careful potassium supplementation. It is important for physicians to make the correct diagnosis as TPP is curable once euthyroid state is achieved.

Gastroenterology

Concurrent session

8:00 AM
Friday, January 24, 2020
258 Medical therapy and clinical outcomes in ulcerative colitis patients in a community gastroenterology practice

Z Herbert1,*

CM Gonzales2,3

1Weber State University, Ogden, UT

2Ogden Clinic, Ogden, UT

3McKay Dee Hospital, Ogden, UT

Purpose of study

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease characterized by inflammation of the colon and rectum. Medical therapy is recommended to prevent complications and eventual surgery. The aim of this study was to understand the clinical course, medical treatment, and clinical outcomes of UC patients to identify gaps in treatment and plan for future outcome studies.

Methods used

Over a one year period (1/2017 to 1/2018), 119 UC patients were seen in an outpatient gastroenterology clinic. A retrospective chart review was conducted for demographic information as well as surgical and treatment history, including biologic and corticosteroid use and outcomes.

Summary of results

A total of 119 patients were reviewed with a mean age of 45 years and mean UC duration of 9.8 years. The majority of patients had pancolitis phenotype (62%). Ten patients (8.4%) had colectomy/j-pouch surgery at an average 75 mo. from diagnosis of UC. Extraintestinal manifestations (EIMs) occurred in 13 patients (11%). UC patients were treated with mesalamine (45.4%), azathioprine/mercaptopurine (30.2%), and biologic (40.3%) therapies. Thirty patients (25.2%) were treated with at least 1 course of prednisone. Six patients (5%) became corticosteroid dependent (prednisone >10 mg per day for >60 days). Biologic treated patients (41.6%) were more likely to receive treatment with prednisone than patients not treated with biologics (14.1%, p=0.001). Ten patients (8.4%) were hospitalized for UC related flaring (mean LOS 8 days, range 4–20). Remission of symptoms was achieved in 88.8% of patients.

Conclusions

This cohort of UC patients in a community gastroenterology practice were older with more extensive disease phenotype (pancolitis) and had disease with durations longer than expected. Extraintestinal manifestations of UC occurred in 11% of patients and were likely underreported. Forty percent of UC patients were treated with biologic therapy. Corticosteroid use was common with 1 in 4 patients receiving at least 1 course of treatment. Corticosteroid dependent patients were uncommon. Remission was achieved in 89% of patients. No conclusions can be made comparing the effectiveness of different medical therapies due to small patient sample size.

259 Effectiveness of fecal microbiota transplant in patients with ulcerative colitis: a literature review

A Nguyen1,2,*

J Bustami2

S Adcook2

H Samiullah2

J Woo2

A Le2

M Shi2

B Afghani2,3

1University of California, Irvine, Irvine, CA

2UC Irvine School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Research suggests that alteration in gut bacterial colonies may play a role in the development of ulcerative colitis and/or its progression. The purpose of this study was to compile the literature regarding the effectiveness of Fecal Microbiota Transplant (FMT) in the management of ulcerative colitis (UC).

Methods used

A comprehensive search using keywords such as: ulcerative colitis, FMT, and microbiota transplant was performed via Pubmed, Cochrane and checking the references of published articles. Inclusion criteria included prospective studies of adult patients diagnosed with active UC with at least 10 subjects that measured clinical outcome.

Summary of results

Of 16 studies found, 8 met our inclusion criteria (table 1 below). Based on the limited data, FMT via enemas and colonoscopies demonstrated significant positive effects, whereas FMT via a nasoduodenal tube yielded insignificant improvement. The timing of data collection was very variable and ranged from 4 weeks to 18 months, and some studies lacked long follow-up periods. Common adverse effects include nausea, borborygmus and discomfort, while less than 10% of participants experienced more serious adverse effects such as intolerance to the FMT procedure and severe worsening of symptoms.

Conclusions

Our review suggests a possible role in FMT in certain patients who don’t respond to conventional therapy. Limitations of this review included variation in the type and frequency of FMTs delivered as well as the timing of assessment in different studies. Future controlled studies with a standard method of FMT and longer follow-up periods are warranted.

260 Prevalence and clinical significance of occult HCV infection

T Saito*

University of Southern California, Los Angeles, CA

Purpose of study

HCV infection is one of the major causes of end-stage liver diseases, which account for over 15,000 deaths annually in the US. The eradication of pathogen is the only definitive medical intervention. Currently, the successful clearance of HCV is determined by the undetectable viral genome in serum 12 weeks after the completion of the antiviral therapy, referred to as sustained virological response (SVR). Recently, anti-HCV therapy has revolutionized due to the development of direct-acting antivirals (DAA). DAA therapy offers SVR in nearly all patient with negligible toxicities. In contrast, the previous standard regimen, interferon is associated with intolerable toxicity and offers SVR only 60% of patients. Given this significant improvement, the number of patients who attained SVR is exponentially increased worldwide.

It is known that HCV could maintain dormant lifecycle in the liver tissue or PBMC after achieving SVR. This condition is called ‘occult HCV infection’ (OCI). The incidence of OCI is extremely rare in patients who achieved SVR with IFN, however, the prevalence of OCI in the population who attained SVR with DAA remain unexplored. Therefore, this study aimed to delineate the prevalence and clinical significance of OCI among patients who attained SVR with DAA.

Methods used

Total 50 subjects who developed abnormal liver function test, liver cancer, or liver failure after achieving SVR were enrolled. Liver tissue and PBMC were collected and subjected to the detection of HCV genome via RT-qPCR. In addition, histopathological and electron microscopic (EM) analysis of the liver tissue were performed.

Summary of results

6 subjects (12%) had detectable HCV genome in the liver tissue. HCV-RNA was also detected in PBMC of 3 subjects (6%). 2 subjects (4%) had detectable HCV genome in both liver tissue and PBMC. The histopathological analysis did not demonstrate any specific findings associated with the presence or absence of OCI. In contrast, EM analysis of OCI liver tissue showed unique features of cell injury and HCV replication.

Conclusions

Our study revealed a high prevalence of OCI among patients who achieved SVR with DAA. In addition, EM analysis of the liver tissue indicated that the presence of OCI might lead to the further progression of liver disease, suggesting the potential benefit of reinitiating antiviral therapy in those with evidence of OCI.

261 Examination of Wnt signaling as a therapeutic target for pancreatic ductal adenocarcinoma using a pancreatic tumor organoid library

HJ Hawkins*

BW Yacob

CD Brindley

WA Messersmith

PJ Dempsey

TM Pitts

University of Colorado, Aurora, CO

Purpose of study

Pancreatic ductal adenocarcinoma (PDAC) commonly presents at advanced stages and is refractory to most treatment modalities, making it one of the most lethal cancers. Although the low tumor cellularity and high desmoplastic response convolutes the relationship between genotype and biological phenotypes, gene mutations associated with PDACs have been identified. Wnt pathway mutations are rarely detected in PDAC, but Wnt signaling is activated by pancreatic duct ligation injury and plays a critical role in the proliferation and chemotherapeutic resistance in other cancers. Patient derived pancreatic tumor organoid libraries (PTOL) allow for more accurate investigation of the biological phenotypes that might lead to therapies that further improve survival. This study aims to subclassify PDAC organoids based on Wnt dependency to determine if combinatory treatment with Wnt inhibitors and chemotherapy would serve as a feasible treatment.

Methods used

Nine PDAC organoids were grown in Human Pancreatic Stem Cell medium. Minimal media conditions required to maintain growth was assessed with depletions of various niche factors. For confirmation of Wnt inhibition, organoids grown in minimal media were treated with three Wnt inhibitors. Growth was assessed with CellTiter Glo 3D.

Summary of results

Minimal media conditions, growth factor dependency, and Wnt dependency determined via Wnt inhibition were determined as described above. Five organoids demonstrated Wnt dependency. Two organoids demonstrated a Wnt independent phenotype. Minimal growth media was determined for two additional organoids, but Wnt dependency has yet to be assessed.

Conclusions

Based on the results obtained, each pancreatic organoid demonstrated different niche factor dependencies providing an avenue for targeted therapy, particularly with Wnt inhibition. WES and gene expression analysis of each organoid will allow for correlation between genotype and Wnt (in)dependency observed in vitro. Combinatory treatment with Wnt inhibition and chemotherapy will be assessed in vitro and confirmed in patient-derived xenograft models.

262 Association of cannabinoid use and hyperemesis syndrome

J Hong1,2,*

P Desagani3

S Narayanan2

V Muruhathasan2

I Prasad2

M Tanios2

B Afghani2,3

1Saint Bonaventure University, Saint Bonaventure, NY

2University of California School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Cannabinoid (marijuana) usage has increased significantly in recent years, especially after its recent legalization. The objective of the study is to determine the association between Cannabinoid use with hyperemesis or cyclic vomiting syndrome (CVS).

Methods used

A literature-based review of articles was performed through PubMed, Cochrane, and Google Scholar database using key words such as ‘Cannabinoid’ ‘Hyperemesis Syndrome’, and’ Cyclical Vomiting Syndrome’. The studies included took into account the confounding variables or excluded patients with other illnesses that could lead to hyperemesis.

Summary of results

We found 6 studies that matched our inclusion criteria (See table 1). Duration of cannabinoid use was variable among the studies. Studies showed that cannabinoid use has increased in recent years. In addition, cannabinoid users were more likely to be hospitalized or visit Emergency Department (ED) due to hyperemesis in comparison to non-users. Some studies noted that patients with cannabinoid associated vomiting reported compulsive hot showering to relieve vomiting. The reports suggested that the symptoms of hyperemesis stopped after discontinuation of cannbinoids.

Conclusions

Our literature review suggests that cannabinoid use is associated with hyperemesis syndrome. As the workup for diagnosis of hyperemesis syndrome could be very costly, healthcare professionals should have a high index of suspicion for cannabinoid use in patients who present with hyperemesis.

Genetics I

Concurrent session

8:00 AM
Friday, January 24, 2020
263 Characterization of CTCF as a rare cause of intellectual disability

F Velez-Bartolomei1,*

S Schelley1

A Hanson-Kahn1

LK Walsh2

E Smith1

L Hudgins1

M Manning1

1Stanford University, School of Medicine, Stanford, CA

2UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA

Purpose of study

Pathogenic variants in the CTCF gene have been recently associated with autosomal dominant mental retardation type 21 (MRD21). The main features of patients with MRD21 are intellectual disability, short stature, acquired microcephaly, hypermetropia/strabismus and mild dysmorphic facial features. We aim to further describe the phenotype of patients with MRD21 by presenting two patients with pathogenic variants in the CTCF gene found on whole exome sequencing (WES).

Methods used

We performed a retrospective chart review and a literature review.

Summary of results

We describe two patients with MRD21. Patient 1 is a male with mild intellectual disability, ptosis, hyperopic astigmatism, macrocephaly, hammertoes, pes planus, arrhythmogenic right ventricular cardiomyopathy and anxiety. He had mild dysmorphic facial features such as long palpebral fissures and low set ears. WES detected a de novo pathogenic variant in the CTCF gene (c.1094A>G). Patient 2 is a female with global developmental delay, esotropia, hypermetropia, hearing loss, decelerating head circumference, FTT, umbilical hernia, 5th finger clinodactyly, fragile nails and skin. Her dysmorphic features include epicanthal folds, blue sclera, mild synophrys, flat nasal bridge, downturned corners of the mouth and low set posteriorly rotated ears. WES detected a de novo likely pathogenic variant in the CTCF gene (c.1079G>A).

Conclusions

MRD21 should be considered in the differential diagnosis of any patient with intellectual disability. There is a wide spectrum of additional manifestations in this disorder. Features that were noted in our patients but not in previously reported cases include hearing loss, nail and skin fragility, macrocephaly, preauricular tags and arrhythmogenic right ventricular cardiomyopathy, further expanding the phenotype.

264 A large cohort of CNKSR2-related disease providing insights into natural history and the mutational spectrum

L Higa1

S Singh2

E Massiello1

T Foster3

JJ Shen3,*

1Community Regional Medical Center, Fresno, CA

2CNKSR2 Family Support Group, Reedley, CA

3UCSF Fresno, Fresno, CA

Purpose of study

A pathogenic variant in CNKSR2 (connector enhancer of kinase suppressor of Ras-2) was uncovered in a boy with a seizure disorder and delays especially in language. We have subsequently recruited the largest known cohort that doubles the number of affected individuals, and triples the number of suspected pathogenic variants, with the aim of improving our understanding of the neurodevelopmental and seizure characteristics of CNKSR2-related disease and its mutational spectrum.

Methods used

The proband was analyzed by clinical whole exome through a commercial laboratory. Clinical and molecular information from additional cases were provided through parents active in a CNKSR2 family support group.

Summary of results

CNKSR2-related disease is an X-linked disorder that results in a neurobehavioral phenotype consisting of intellectual disability and seizures. The delay in developmental progression can be severe, particularly so in language skills. There are characteristic EEG patterns during sleep that categorize this disease as part of the electrical status epilepticus during slow-wave sleep/epileptic encephalopathy with continuous spike-waves in sleep/epilepsy-aphasia spectrum. Since its initial recognition and characterization in 2011, there have been 13 affected males published in the medical literature representing 7 families. We have recruited an additional 14 affected males, each from a different family. The phenotypic spectrum is slightly broader than that previously reported, but there is still at least a moderate degree of developmental delay primarily affecting speech, and the seizures are poorly controlled. Continuing the trend of published cases, the presumed pathogenic variants are almost always loss-of-function (small out-of-frame deletions, splice site variants, nonsense mutations, whole gene deletions).

Conclusions

CNKSR2-related disease is a severe epileptic encephalopathic syndrome with characteristic EEG patterns, poorly controlled seizures, and a developmental delay profile significantly affecting speech. The responsible molecular mechanisms continue to be almost exclusively loss-of-function variants.

265 Documentation of IFT172 as the nineteenth gene causative of oral-facial-digital syndrome underscores the importance of ciliary trafficking in its pathogenesis

M Yamada*

K Kosaki

Keio University School of Medicine, Tokyo, Japan

Case report

Oral-facial-digital syndrome [OFD] is a part of ciliopathy-related disorder and is characterized by multiple frenula, hamartoma of the tongue, and digital defects. Mutations in 18 genes cause OFD. Currently, ciliopathy-related disorders including Joubert syndrome, Bardet-Biedl syndrome, isolated retinal degeneration, and short-rib thoracic dysplasia are ascribed to biallelic variants in IFT172, which plays critical roles in intraflagellar transport. Here we report a male 3-year-old male with a unique combination of ciliopathy-associated features including post-axial polydactyly, laterality defects of the heart tube, and multiple oral frenula that were highly suggestive of OFD. An exome analysis of the patient and his parents showed compound heterozygous variants of the IFT172 gene: Chr2(GRCh37):g.27712477C>T, c.39+5G>A and Chr2(GRCh37):g.27695163A>C, c.1478T>G (NM_01566.2) p.(Leu493Arg). RNA-seq of the peripheral blood indicated that only the c.1478T>G variant was observed at the transcriptome level. Since the patient was heterozygous for the c.1478T>G allele, the apparent monoallelic expression indicated that the transcript derived from the c.39+5G>A allele was subject to nonsense-mediated mRNA decay. The other variant, p.(Leu493Arg) was located within the 8th WD-40 repeats domain which is highly conserved. The amino acid residues surrounding variants VDWLELN is conserved down to Chlamydomonas with the CADD score of 29.2. We suggest that the IFT172 gene represents a 19th ciliopathy-related gene that causes the OFD phenotype. Ciliopathy-related genes have been classified into several categories: genes required for i) ciliogenesis, ii) ciliary compartmentalization, and iii) ciliary trafficking. Most of the genes causative of OFD have been classified as genes responsible for ciliogenesis or ciliary compartmentalization. The recognition of IFT172, which plays a critical role in ciliary trafficking as the causative gene of OFD, underscores the importance of ciliary trafficking in the pathogenesis of OFD.

266RAF1 duplications

M Palma1,*

J Lores2

D Stevenson1

J Bernstein1

L Calderwood1

H Pachajoa2

C Prada3

1Stanford University, Palo Alto, CA

2Universidad ICESI – Fundación Valle del Lili, Cali, Colombia

3Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

Purpose of study

Disruption of genes involved in the RAS/MAPK pathway is associated with well described conditions, including Noonan syndrome. However, phenotypes associated with a duplication of RAF1 are incompletely described and a unifying phenotype has not emerged. We describe two cases with duplications of RAF1. The underpinning mechanisms of this phenotype will be further explored in functional studies involving a zebrafish model.

Methods used

Review of medical records and literature; overexpression of raf1 in a zebrafish model.

Summary of results

The first individual is a 4yo female who presented in infancy with hypertonia, developmental delay, small PFO, pseudostrabismus, hypertelorism, mild ptosis, mild pectus excavatum, and plagiocephaly. Over time, gross motor delay improved but speech delay persisted. Chromosomal microarray showed a 921 kb duplication resulting in a trisomy of 3p25.2, which included RAF1 in addition to SYN2, TIMP4, PPARG, TSEN2, MKRN2OS, MKRN2, TMEM40, CAND2, RPL32, SNORA7A and IQSEC1. The second individual is a 13mo male with neonatal feeding issues and respiratory difficulties requiring mechanical ventilation. CT-angiogram with 3D reconstruction identified an aberrant subclavian artery. He underwent surgery and g-tube placement. Clinical features included short stature (<3rd centile), short neck, low hairline, right facial palsy, and minor facial anomalies. Chromosomal microarray identified a small duplication (180kb) including only the RAF1 and TMEM40 genes. Overexpression of wild type raf1 in a zebrafish model is underway and results will be presented.

Conclusions

We present two patients with microduplications that include RAF1, but neither exhibited a typical Noonan syndrome phenotype. The findings of these two patients suggest that increased gene dosage of RAF1 results in phenotypes that do not completely exhibit all of the classic Noonan syndrome features. To date, no functional studies have been performed to determine the impact of a duplication of RAF1 and whether there is a reproducible constellation of clinical findings. Results of the effects of raf1 overexpression in zebrafish from pending studies will help provide additional information.

267 Characterization of fractures and their etiology in pre and early ambulatory children

P Patel*

K Hollenbach

C Kuelbs

K Wigby

M Kaufhold

LM Bird

V Upasani

University of California, San Diego, San Diego, CA

Purpose of study

As children become ambulatory, the incomplete development of motor and balance skills may predispose them to injury. These injuries are less likely to present in pre-ambulatory children and may indicate a genetic condition, metabolic disorder, or non-accidental trauma. The purpose of this study was to idenitify fracture etiology and determine the incidence of metabolic and genetic disorders that predispose to fractures in these patients.

Methods used

A retrospective chart review was completed of patients presenting to Rady Children’s Hospital San Diego and its affiliated providers between July 2011 and December 2012. Encounters for fractures in EPIC for all children ages 18 months and younger were analyzed by a team of reviewers and revised with specialty faculty if required. Etiologies were classified as Accidental, Inflicted, Genetic/Metabolic Disorder, Other Predisposing Factor, and Undetermined. Exclusion criteria included dental fractures, imaging without evidence of fracture, or imaging not associated with an encounter. Statistical analysis was completed using Stata 16 (College Station, TX). Fisher’s Exact Test was used for comparisons of demographic and clinical factors among etiologic groups. Cases of Undetermined etiology were excluded from group-wise comparisons.

Summary of results

606 encounters were analyzed with a mean presenting age of 10.6 months (range: 3 days to 18 months). Etiologies of fractures by research team review were as follows: 516 cases (85.1%) of Accidental injury; 30 (5.0%) of Inflicted injury; 5 (0.8%) due to a Predisposing Factor; 4 (0.7%) due to a Genetic Disorder known to predispose to fracturing; and 51 (8.4%) of Undetermined cause. The Genetic Disorders included hypophosphatasia, osteopetrosis, osteogenesis imperfecta, and hereditary sensory and autonomic neuropathy. Interestingly, in 86 cases (14.2%), there was discrepancy between the initial clinical impression and the research team review of fracture etiology.

Conclusions

Though the number was small, there were children with genetic disorders who presented with fractures in early age. The discrepancy between initial and review team etiologies requires further analysis into factors that may have affected these conclusions.

268TANGO2 deficiency: a case series highlighting intrafamilial variability and review of the literature

J Schymick1,*

D Bonner2

P Leahy1

T Cowan1

M Ruzhnikov1

J Kohler2

C McCormack2

L Fernandez2

UD N3

D Matalon1

V Yarlagadda1

P Fisher1,2

E Ashley1,2

M Wheeler1,2

G Enns2

J Bernstein1,2

C Lee1

1Stanford University School of Medicine, Stanford, CA

2Stanford Center for Undiagnosed Diseases, Stanford, CA

3NIH Undiagnosed Diseases Network, Bethesda, MD

Purpose of study

Bi-allelic pathogenic variants in TANGO2 (transport and Golgi organization 2 homolog) have been recently identified as causing a rare metabolic disorder characterized by susceptibility to recurrent rhabdomyolysis, hypoglycemia, lactic acidosis, hyperammonemia, hypoglycemia, seizures, and life-threatening cardiac tachyarrhythmias. To date, 49 cases have been reported in the literature (Kramer 2016, Lalani 2016, Dines 2018, Nadja 2019, Jennions 2019). TANGO2 deficiency is proposed to affect mitochondrial fatty acid oxidation, OXPHOS, and ER-Golgi function, including the processing of secreted and plasma membrane proteins (Nadja 2019).

Methods used

We report 4 individuals from 2 families with bi-allelic pathogenic variants in the TANGO2 gene identified by whole exome sequencing.

Summary of results

In our first family, a homozygous deletion affecting exons 3–9 (coding exons 2–8) was identified in 3 siblings with clinical presentations ranging from mild intellectual disability to recurrent metabolic decompensation with arrhythmias and transient paraplegia. In our second family, compound heterozygous variants (c.460G>A [p.G154R]; exon 3–9 deletion) were identified in a child with global developmental delay who initially presented at 15 months of age with metabolic decompensation characterized by encephalopathy, ketotic hypoglycemia, and lactic acidosis during a febrile illness.

Conclusions

In this study we review the current literature on TANGO2-related disease and further define the phenotype of this life-threatening disorder. Our case series highlights a striking array of clinical variability ranging from mild intellectual disability to life threatening metabolic decompensation, arrhythmias, and variable neurologic symptoms. Furthermore, our family provides additional evidence for intrafamilial variability and offers a case example of a milder phenotype that may be underreported within this syndrome.

269 Clinical genomics and rapid targeted mouse modeling: a novel program to elucidate variants and genes of uncertain significance and advance translational research

S Shankar1,*

K Grimsrud2

K Lloyd2

KA Rauen1

1UC Davis, Sacramento, CA

2UC Davis, Davis, CA

Purpose of study

Whole Genome Sequencing (WGS) has revolutionized gene discovery for many inherited disorders, yet majority remains elusive. We report of a novel program using whole genome sequencing and rapid targeted mouse modeling to perform invivo functional analysis and accelerate precision medicine.

Methods used

Comprehensive clinical workup including WGS in 70 individuals with Diagnostic Odysseys. Development of a novel interdisciplinary approach to in vivo modeling and functional analysis of: 1) variants of unknown significance and 2) pathogenic variants in known disease-causing genes, to advance translational research, understand disease mechanisms and develop therapeutic interventions.

11 variants (4 pathogenic and 7 VUS) were selected for rapid and precise modeling in mice using CRISPR/Cas9 genome editing and targeted phenotyping.

Summary of results

45 of 70 WGS test results were reported: 15 positive, 23 VUS and 7 negative. Of the 11 variants chosen for mouse models, 10 have been successfully recapitulated in mice, 4 are being phenotyped, and 1 (CHAMP1) completed. The CHAMP1 variant mouse model exhibits a number of structural and behavioral abnormalities similar to the patient’s presentation, including dysmorphic craniofacial features, delayed growth, increased startle response, anxiety, and, social/object novelty.

Conclusions

WGS provided a definitive genetic diagnosis in 28–33% of patients, >50% of patients were reported as VUS, warranting expedited mouse modeling. Findings from in vivo functional analysis as for CHAMP1 will achieve a definitive diagnosis, contribute to clinical decision-making, and potentially accelerate implementation of an effective management plan. The UC Davis Precision Genomic Program and Mouse Biology Program have together successfully established a process for clinicians and researchers to nominate variants for expedited production of mice, recapitulating genetic variants and, catalyzed targeted phenotyping to accelerate disease diagnosis. These small animal avatars enable rapid determination of variant pathogenicity and inform clinical case management serving to advance precision medicine.

270 A new male case of kagami-ogata syndrome caused by paternal unipaternal disomy 14 resulting from robertsonian translocation

H Wang1,*

X Wang2

H Peng3

B Shah3

H Gu3

L Zhang2

1Loma Linda University School of Medicine, Loma Linda, CA

2The First Hospital of China Medical University, Shenyang, China

3The University of Oklahoma Health Science Center, Oklahoma City, OK

Introduction

Kagami–Ogata syndrome (KOS) is a rare imprinting disorder characterized by skeletal abnormalities, dysmorphic facial features, growth retardation and developmental delay. More than 60% of the cases are caused by uniparental parental disomy 14 [upd(14)pat]. Of about sixty reported cases of KOS, only 6 have upd(14)pat from a Robertsonian translocation (ROB) and all are female. We report a newly identified male case.

Case description

This naturally conceived male infant was born at 36 weeks by a cesarean section due to congenital anomalies and polyhydramnios. Mother had a history of miscarriage. Family history was negative without consanguinity. BW and HC were >97th percentile with length <10th percentile. He had narrow forehead, frontal bossing, short palpebral fissures, depressed nasal bridge, anteverted nares, elongated philtrum, low-set posteriorly rotated ears, and micrognathia. Omphalocele, short neck, bell-shaped chest, elongated fifth finger with flexion contractures, deep sacral dimple, bilateral undescended testes, right hydrocele, PDA, left-sided mild hydronephrosis, 11 pairs of ribs and bell-shaped thoracic cavity with coat hunger looking ribs were identified. Chromosome analysis revealed male karyotype with a balanced ROB:45,XY,der(13;14)(q10;q10). Parental karyotyping indicated that this ROB was inherited from his father. Concern for KOS caused by upd(14)pat was raised. The subsequent microsatellite analysis demonstrated that the patient inherited two homologous chromosome 14 from his father, confirming a paternal uniparental heterodisomy of 14q. SNP array revealed two ROH and no CVN. The results are consistent with the diagnosis of KOS caused by upd(14)pat.

Discussion/Conclusion

The potential mechanisms leading to UPD are multiple. Our case is considered to be trisomy rescue as the consequence of ROB. In the clinical setting, for neonates with characteristics features and ROB, further parental study and molecular analysis for UPD should be considered.

Neonatology general III

Concurrent session

8:00 AM
Friday, January 24, 2020
271 Neonatal hemolysis risk assessment in the era of universal bilirubin screening

A Ligsay*

EM Hubbard

J Koola

C Longhurst

University of California San Diego, San Diego, CA

Purpose of study

Umbilical cord Direct Coombs’ testing (DCT) is commonly used to screen for risk of hemolytic disease of the newborn (HDN) and development of hyperbilirubinemia, particularly when there is concern for ABO or Rh incompatibility between mother and neonate, or if mother is known to be antibody positive. Since 2001, our institutional policy has been to complete DCT in these scenarios and, if positive, screen the neonates’ total bilirubin (TB), complete blood count, and reticulocyte count at 12 hours of life (HOL). In 2004, our institution also started universal serum TB testing in all neonates at 18–24 HOL. The aim of this study was to analyze the utility of early testing in at risk neonates in the era of universal TB screening.

Methods used

We queried the electronic health record (Epic Systems, Madison Wisconsin) for all late-preterm and term newborns discharged from the newborn nursery at University of California, San Diego Health between May 14, 2011 and May 15, 2018. Data was analyzed for presence and result of DCT, TB levels and if phototherapy was started during admission.

Summary of results

We identified 14,764 newborns, of whom 1,051 (7.1%) received phototherapy. A total of 6,622 (44.9%) subjects had DCT and 781 had a positive result (25.0%). Of subjects with DCT, 592 (8.9%) received phototherapy (OR: 1.64, 95% CI: 1.45–1.86). Of subjects with positive DCT, 195 (25.0%) received phototherapy (OR: 4.53, 95% CI: 3.73–5.49; positive predictive value: 24.97%, 95% CI: 22.47–27.65%). In subjects who eventually required phototherapy during admission, the average TB level at 24 HOL was 7.4 mg/dL (SD 1.5) compared to 5.2 (SD 1.2) in subjects who did not receive phototherapy.

Conclusions

In patients who qualified for DCT, there was a small, increased need for phototherapy overall, and as expected, a positive DCT resulted in an even greater likelihood for phototherapy treatment. However, the average TB level for both phototherapy and non-phototherapy groups at 24 hours of life did not meet treatment thresholds based on the American Academy of Pediatrics guidelines. Therefore, 24 HOL screening was acceptable to help risk stratify patients, and escalated screening of TB at 12 HOL may not be essential in the setting of universal TB screening.

272 Early hyperbilirubinemia in neonates with down syndrome

TM Bahr1,*

ER Henry2

W Hulse1

V Baer2

JT Prchal3

VK Bhutani4

RD Christensen1,2

1University of Utah, Salt Lake City, UT

2Intermountain Healthcare, Murray, UT

3University of Utah and Salt Lake City VA Hospital, Salt Lake City, UT

4Stanford University, Stanford, CA

Purpose of study

To compare total serum bilirubin levels, phototherapy usage, and hospital readmission for jaundice treatment, among neonates with Down syndrome vs. controls.

Methods used

We collected first total serum bilirubin (TSB) values, phototherapy administration, and readmission for jaundice on neonates ≥35 weeks gestation born at Intermountain Healthcare hospitals from 2004 through 2018. We created reference intervals for TSB during the first 48 hours after birth, from control neonates who did not have Down syndrome, a positive DAT, an eventual diagnosis of G6PD deficiency, or hereditary spherocytosis. We then determined the proportion of neonates with Down syndrome whose TSB exceeded the 95th percentile control interval, the percentage receiving phototherapy in each group, and the rate of readmission to the hospital for jaundice treatment in each group.

Summary of results

We compared 357 neonates with Down syndrome with 377,368 controls. Those with Down syndrome had 4.7 times the risk (95% CI: 3.9–5.7; p<0.0001) of an initial TSB exceeding the 95th percentile control interval, 8.9 times (95% CI: 8.1–9.8; p<0.0001) the phototherapy usage, and 3.6 times (95% CI: 1.6–8.2; p=0.0009) the readmission rate for jaundice treatment.

Conclusions

Neonates with Down syndrome have increased risk of early hyperbilirubinemia and need for phototherapy when compared to controls. Clinicians caring for neonates with Down syndrome are advised by the AAP to obtain an early screening CBC. We submit that simultaneously obtaining a TSB is also advisable.

273 Impact of a parent video viewing program in the neonatal intensive care unit

J Weber1,*

H Sauers-Ford1

K Sohn2

A Hanhauser3

JP Marcin1

D Tancredi1

K Hoffman1

1UC Davis Health, Sacramento, CA

2University of Nevada, Reno School of Medicine, Reno, NV

3University of California, Davis, Davis, CA

Purpose of study

Parents of neonates in the NICU report high levels of stress and anxiety and feelings of lack of control and involvement. To address this, many NICUs have begun using bedside video cameras to facilitate virtual visits by family members. This study aimed to examine parents’ self-reported perceptions regarding various aspects of the NICU experience.

Methods used

Using a prospective study design, families were enrolled following informed consent and were asked to complete two identical surveys, the first survey at enrollment (S1) and the second survey at discharge from the NICU (S2). The survey consisted of 14 questions each with a scale of 1 (strongly disagree) to 7 (strongly agree). In addition to parent surveys, demographic data were collected on subjects, including breastmilk at discharge and use of video visits. The Welch-Sattherthwaite T-test was used to compare for each survey item the mean changes from survey 1 to survey 2 between those who used the video camera and those who did not. This test was chosen because of unequal variance between groups.

Summary of results

One hundred respondents who completed the set of both initial and follow up surveys were included for analysis. 30% of parents utilized video visits. Of the 14 questions, 2 differed between parents using video (N=30) and parents not using video (70). The median responses to these two questions are summarized in the table. Babies were also more likely to receive breastmilk at discharge in the group of parents using video visits, χ2 (2, N=87) =4.2, p<0.05.

Conclusions

Participation by parents in video viewing of their infant in the NICU was associated with sustained intention to breastfeed over the time of the NICU stay, higher likelihood of breastmilk at discharge, and perhaps improved self-perception of involvement in care. These findings justify further study of video viewing in this high-risk population.

274 Teaching in the NICU: can we do better?

S Langston*

A Relan

VP Walker

J Enciso

J Lloyd

M Nguyen

UCLA, Los Angeles, CA

Purpose of study

A needs assessment revealed pediatrics interns received variable teaching on core neonatology topics. We proposed a flipped classroom (FC) approach to promote active learning through engagement in case-based discussions. FC may improve knowledge acquisition and increase pediatric trainee competency with management of critically ill neonates.

Methods used

The intervention involves pediatric interns rotating through one Level III NICU. Interns complete pre-surveys of self-reported competency and knowledge in FC and non-FC topics prior to the rotation as they serve as their own matched control.Competency is scored on a scale of one to five, with five being the most competent. During their two-week rotation, interns review six brief, online digital presentations addressing core NICU topics. All six topics are discussed in the form of case-based learning in the NICU. Interns are assessed on other critical NICU topics not included in the FC curriculum to compare the impact of FC knowledge acquisition and competency with traditional teaching. Instruction of these additional subjects is at the discretion of the attending neonatologist. At the end of the rotation, interns complete the same surveys of competency and knowledge to assess change. A general evaluation to assess satisfaction with the FC curriculum is completed.

Summary of results

Scores are reported as means ± standard deviation. 13/14 interns agreed the FC approach improved decision-making, but 11/14 reported no preference for the FC curriculum over didactics. Matched-pairs T-Test showed average change in self-reported competency was greater for FC (10.8±2.93) than non-FC topics (5.4±4.21) (p<0.01). Knowledge scores showed an increase from start (58.91±16.56) to end (86.27±6.82) of the rotation for all topics (p<0.01). At the end of the rotation, the number of FC questions missed was lower than non-FC topics missed (p<0.01). Non-FC topics were inconsistently taught in the NICU. Overall, residents reported positive satisfaction levels with FC.

Conclusions

Our study demonstrates potential efficacy of a FC approach to promote knowledge and competency among physicians-in-training. Pediatric interns reported positive satisfaction levels. Use of FC throughout other training programs may enhance graduate medical education.

275 Hidden costs of time: a cost comparison of creating versus updating educational materials in neonatology fellowship

A Arias-Shah1,*

MM Carbajal1

H Karpen2

C Gisondo3

M Gray4

H French5

S Izatt6

L Johnston7

P Chess8

R Dadiz8

1Baylor College of Medicine, Houston, TX

2Emory School of Medicine, Atlanta, GA

3University of Michigan, Ann Arbor, MI

4University of Washington School of Medicine, Seattle, WA

5University of Pennsylvania, Philadelphia, PA

6Duke, Durham, NC

7Yale School of Medicine, New Haven, CT

8University of Rochester, Rochester, NY

Purpose of study

The flipped classroom (FC), compared to traditional didactics (TD), is an increasingly popular educational method. The Organization of Neonatal-Perinatal Medicine Training Program Directors (ONTPD) National Neonatology Curriculum (NNC) consists of peer-reviewed educational materials for FC learning of neonatal physiology and is free to fellows and educators. Potential cost savings of shared national resources for education materials is largely unstudied. We aim to: (1) define the costs of creating versus updating existing TD materials (data presented below) and (2) perform a cost comparison of TD and FC methodologies (data collection in process).

Methods used

As part of a randomized controlled trial comparing the effectiveness of TD versus FC methods, an IRB-approved survey was sent to faculty querying the time required to create versus update pre-existing TD materials and costs were calculated accordingly. A follow-up survey querying the time required to develop FC materials will be evaluated similarly and compared with TD data.

Summary of results

Ninety-six percent (298/309) of educators responded. The time spent creating new TD materials was significantly different from updating pre-existing materials (6 hrs vs 1 hr, P >0.0001). There was a four-fold difference in the cost to develop versus update TD materials ($692.28 vs. $115.38), with a higher cost per learner in smaller fellowships. Similar calculations will be conducted for developing FC material.

Conclusions

There is a greater cost associated with creating TD materials compared to updating existing materials, and the observed difference is highest in smaller-sized fellowships. A detailed analysis of how time is spent on developing FC materials for the NNC can provide insight as to how nationally shared peer-reviewed educational materials can potentially decrease the overall cost of education amongst fellowship programs.

276 Reducing length of stay in neonatal abstinence syndrome through quality improvement

R Carter*

K Weiss

R Manrique

C Le

S Fleming

G Romanowski

D Golembeski

R Song

L Moyer

Rady Children’s Hospital, San Diego, CA

Purpose of study

Neonatal abstinence syndrome (NAS) is characterized by abrupt drug withdrawal at birth in infants exposed to chronic in-utero opioids, and its frequency over the past decade has tripled due to rising opioid use and misuse. The use of standardized protocols for treatment of NAS can optimize outcomes, reduce opioid exposure, and reduce length of stay (LOS). Our current setting is a hospital system with seven Level II-IV NICUs caring for for patients with NAS. There is significant variability and lack of standardization in treatment for our NAS population with an elevated length of stay. Our specific aim is to reduce LOS in infants with NAS from 22 days to 18 days by June 2020.

Methods used

A multidisciplinary taskforce was established and monthly meetings with nursing, physicians, pharmacy, and ancillary staff were held. Baseline data on LOS for infants with NAS requiring pharmacologic treatment were collected from all sites. LOS for infants requiring pharmacologic treatment are tracked as a primary outcome measure.

PDSA cycles:

  1. Implementation of a standardized pharmacologic guideline with transition from morphine to methadone, and phenobarbital to clonidine. Creation of an electronic order set.

  2. Establishing NAS care champions at each site to facilitate nursing re-education through training videos and learning modules.

  3. Creation of a non-pharmacologic care bundle and testing of individual components at different sites.

  4. Prenatal consultation for at-risk mothers.

Summary of results

Baseline length of stay for 108 infants in the pre-intervention period (January 2015 – February 2019) was 22 days. Length of stay for 7 infants in the post-intervention period (March 2019 - present) is 18 days. Post-intervention data collection is ongoing. PDSA cycles have been implemented for a pharmacologic treatment protocol, staff education on NAS, and a non-pharmacologic care bundle.

Conclusions

We have successfully established a multidisciplinary team focused on improving care for infants with NAS, implemented a standard treatment protocol, established NAS care champions for our units, and created learning modules for re-education. We have applied QI methodology to improve care and reduce LOS in infants with NAS by 15% from baseline.

Neonatology – perinatal biology I

Concurrent session

8:00 AM
Friday, January 24, 2020
277 Role of alpha-1 receptors in the cerebral blood flow response to acute hypoxemia in fetal sheep

J Bierwirth1,*

T Liu1

B Mendez1

S Bragg1

G Power2

A Blood1,2

1Loma Linda University School of Medicine, Loma Linda, CA

2Longo Center for Per. Bio., Loma Linda, CA

Purpose of study

Acute hypoxemia is a common fetal stressor during gestation and labor. In response, the fetus increases cerebral blood flow (CBF) and decreases flow to the periphery. During systemic hypoxemia, peripheral vasoconstriction is mediated by catecholamines acting on alpha-1 receptors (a1R). a1R are also present in cerebral arteries where they mediate vasoconstriction. We hypothesized that a1R in the fetal brain counteract increases in CBF during acute hypoxemia.

Methods used

Near term fetal sheep (0.9 gestation) were chronically instrumented with central arterial and venous catheters and a composite laser doppler flow/tissue PO2 (tPO2) probe in the parietal cortex. After 4 days of recovery, by lowering the ewe’s FiO2, fetuses underwent 40-min of isocapnic hypoxia (PaO210 to 12 mmHg) while receiving an intravenous infusion of prazosin (a1R antagonist) dissolved in methanol or methanol alone (vehicle controls). Mean arterial pressure (MAP), heart rate (HR), CBF, cerebral vascular resistance (CVR) and tPO2 were continuously recorded and arterial blood gas samples collected.

Summary of results

13 experiments were conducted in 10 lambs (5 prazosin and 8 vehicle controls). Baseline tPO2 was similar between the control and prazosin groups (7.5±1.4 and 8.5±2.6 mmHg) and fell during hypoxemia to a nadir of 1.7±0.8 and 2.1±1.0 mmHg, respectively (mean ± SEM). Prazosin infusion resulted in a downward trend in MAP (from 50±1 to 40±1 mmHg) and CBF (by 13±4%) with no effect on CVR. In response to hypoxemia, CBF increased as much as 34±8% above baseline in the controls and 17±7% above the pre-prazosin baseline in the prazosin group. During hypoxemia, MAP increased and HR decreased in both groups, although the decrease in HR was attenuated by prazosin. Following hypoxemia, CBF decreased due to an increase in CVR in both groups. 2-way ANOVA determined that prazosin treatment resulted in significantly altered CBF, MAP, CVR, and HR, but post-hoc analyses did not identify timepoints when differences existed.

Conclusions

Blocking a1R during acute hypoxemia did not result in increased CBF or decreased CVR, suggesting that a1R do not counteract increased CBF during hypoxemia. CVR is elevated following hypoxemia and this is not mediated by a1R.

278 IUGR, development, and DHA supplementation alter rat hepatic pemt expression

S Kasera*

B Zhao

H Wang

L Joss-Moore

University of Utah, Salt Lake City, UT

Purpose of study

Intrauterine growth restriction (IUGR) reduces neonatal circulating docosahexaenoic acid (DHA), an ω-3 fatty acid essential for organogenesis and favorable neonatal outcomes. Mechanisms by which IUGR decreases circulating DHA are not completely understood. However, one potential mechanism involves hepatic metabolism of DHA and other long-chain fatty acids by the phosphatidylethanolamine methyltransferase (PEMT) phospholipid methylation pathway. Impaired PEMT activity reduces circulating DHA by increasing hepatic DHA accumulation in the form of phosphatidylethanolamine (PE) containing lipid droplets. We previously demonstrated that IUGR increases hepatic lipid droplet accumulation in weaning male, but not female, rat pups. However, the temporal changes in hepatic PEMT expression and the effects of IUGR and DHA supplementation on hepatic PEMT are unknown.

We hypothesized that hepatic PEMT expression varies with neonatal hepatic development and that at weaning, IUGR causes sex-divergent changes in hepatic PEMT expression.

Methods used

We measured mRNA in control rat liver at birth and day 4, 7, 10, 12, 14, and 21 after birth, using real-time RT PCR. IUGR was induced by bilateral uterine artery ligation. Control and IUGR rats received a regular diet or a 0.1% DHA diet throughout pregnancy and lactation. At postnatal day 21 (D21), hepatic PEMT mRNA and protein were measured using real-time RT PCR and western blot.

Summary of results

Both male and female IUGR rat pups weighed less than sex-matched control pups at birth and at D21. Hepatic PEMT mRNA levels were detectable from birth to D21, with expression peaking at D12 for both sexes. IUGR did not alter hepatic PEMT mRNA levels in either sex. However, IUGR increased hepatic PEMT protein levels in both female and male rats. DHA supplementation normalized female hepatic PEMT protein levels, but not male hepatic PEMT protein levels.

Conclusions

We conclude that IUGR increases PEMT protein levels in female and male rats. However, DHA supplementation normalizes PEMT levels only in female rats. As PEMT expression rises early in development, PEMT-driven DHA export from the liver may be occurring earlier than D21. Ongoing studies are evaluating the effect of IUGR on PEMT and hepatic PE-lipid droplets at earlier developmental time points.

279 Prediction of bronchopulmonary dysplasia on postnatal day one by gradient boosting, an ensemble machine learning algorithm

A Vaid*

L Padilla

V Rehan

Lundquist Institute at Harbor-UCLA, Torrance, CA

Purpose of study

Bronchopulmonary dysplasia (BPD) continues to be a significant contributor to morbidity and mortality in premature infants. Despite improvements in neonatal care, the ability to reliably predict BPD development remains limited, especially early in clinical course.

Machine learning can be used to build predictive models that outperform traditional predictive approaches. Here we use Gradient Boosting (GB), a powerful ensemble machine learning algorithm, to predict BPD development on postnatal day one of life.

Methods used

This is a single center [Harbor-UCLA Medical Center Neonatal Intensive Care Unit (NICU)]) study. 60 variables available within the first 24 hours of life in the California Perinatal Quality Care Collaborative database were extracted on all admissions to Harbor-UCLA NICU from 2005–2018. Variables missing data for more than 25% subjects were excluded. Infants with a major congenital anomaly (n=325) were also excluded. A total of 1832 infants were included for analysis.

A GB model was developed using the pandas, scikit-learn and XGBoost libraries in the Python programming language. Hyperparameter optimization to increase model performance was done using Exhaustive Grid Searching. Stratified K Fold (K=20) cross-validation was performed to train and test the model. Model performance was evaluated from the resultant confusion matrix.

Summary of results

For the trained and cross-validated model, accuracy was 91.1%. Sensitivity was 70.3%, and specificity was 93.4%. Area Under Receiver Operating Curve (AUROC) was 0.944. The accuracy and AUROC of our model exceeded that of a logistic regression by around 4.5% and 0.082, respectively. According to the model, variables that contributed most towards the final prediction (maximal information gain) were surfactant administration, post-delivery room high frequency ventilation, and postnatal steroids.

Conclusions

Our GB model yielded a high specificity for prediction of BPD in a heterogenous population of infants. These data can be utilized for risk stratification and prognostication even on postnatal day one of life.

280 Placental proteins: a new approach to prematurity

C Schreiner*

T Powell

T Jansson

University of Colorado, Aurora, CO

Purpose of study

Extreme prematurity continues to be a leading cause of infant morbidity and mortality and increases the risk of significant long-term sequelae such as cerebral palsy, respiratory, and neurodevelopmental disease. Emerging evidence from animal experiments indicate that factors secreted by the placenta are critical for normal fetal organ development. One fundamental difference between fetal and postnatal life is the instantaneous discontinuation of the umbilical circulation, depriving the premature infant of placental factors potentially critical for fetal organ development. We recently reported that 341 proteins are secreted by the term human placenta into the fetal circulation, however, it is currently unknown if they are secreted by the placenta earlier in gestation. Our objective was to identify proteins secreted by the premature placenta by determining the proteome of umbilical venous blood and neonatal blood to uncover proteins that rapidly decrease after birth given these are likely to be of placental origin and may be important for organ development in the premature baby.

Methods used

Venous cord blood was collected at delivery and neonatal blood at 48–72 hours of life from preterm infants (range 24.2 to 31.6 weeks; N=10) after informed consent. Plasma was collected and stored at -80°C until quantification of proteins was performed using the SomaLogic platform which uses modified aptamer-protein complexes which quantify protein abundance by florescence. Paired t-test was used to determine significant differences between cord blood and neonatal blood from the same infant.

Summary of results

The plasma concentrations of 70 proteins were higher and 92 were lower in the neonate as compared to umbilical circulation (p<0.05). Bioinformatics approaches (Reactome) demonstrated that the proteins that decreased significantly are involved in the immune system, angiogenesis, and developmental processes including axon guidance.

Conclusions

Our findings suggest that the late second trimester human placenta secretes proteins that are predicted to be involved in vital developmental processes such as neurogenesis and angiogenesis which are not produced by the neonate. We speculate that the loss of placenta-derived factors that participate in development of fetal organs contributes to poor outcomes in premature infants.

281 Hepatic postnatal induction of selenium and zinc associated antioxidant enzymes

L Sherlock*

K Sjostrom

M Zarate

L Nguyen

E Nozik-Grayck

C Wright

University of Colorado, Aurora, CO

Purpose of study

Oxidative stress is central to the etiology of many diseases of prematurity. Lower antioxidant defenses render premature infants vulnerable to oxidative damage secondary to infection and oxygen therapy. Antioxidant enzymes (AOE) increase perinatally in the blood and lungs. Many AOE require a micronutrient such as selenium (Se) or zinc (Zn) to function at maximum efficacy. These trace elements are low in neonates compared to adults.

The liver is an important immune surveillance organ where antioxidant defense is critical for host response. It also plays a major role in micronutrient processing. However, the developmental regulation and expression of AOE in the liver is uncompletely described. We hypothesized the neonatal liver would have decreased Se and Zn associated AOE.

Methods used

C57BL/6 mice were sacrificed at P0, P7, P21 and 8–12 weeks. mRNA and protein expression for key AOE (SOD1, SOD2, SOD3, Gpx1, Gpx4, Msrb1, TrxR1) and factors for Se processing (Sephs2/Sps2, Scly) were measured by qPCR and Western blot. Activity level pending.

Summary of results

Hepatic selenoenzymes Gpx1 and Msrb1 were developmental regulated, with mRNA low at P0 and increased by adult (p<0.05, n=5-6). Gpx1 protein increased 9-fold and Msrb1 protein increased 6-fold from P0 to adult (p<0.0001, n=2-4). Gene expression of Zn related SOD1 and SOD2 increased postnatally, low at P0 and increased in adult (p<0.01, n=5-6). Protein expression for each increased 3-fold from P0 to adult (p<0.001, n=4). The mRNA and protein expression for Gpx4, TrxR1, TrxR2 and SOD3 remained constant postnatally.

As the greatest induction was observed in selenoenzymes, factors for Se processing were evaluated. Sephs2 and Scly mRNA increased from P0 compared to P21 and adult (p<0.05, n=4-6). Protein expression for Sps2 and Scly increased postnatally (p<0.01, n=4).

Conclusions

The liver experiences a postnatal induction in essential Se and Zn associated AOE. Additionally, the hepatic machinery for Se processing is low in neonatal mice. We speculate that the neonatal liver is vulnerable to oxidative stress secondary to low AOE defense. We also speculate states that decrease neonatal micronutrient status may further impair the hepatic redox state.

282 Dysruption of calcium homoestasis amplifies TLR9 mediated IL-1 expression: implication for sterile inflammation

R de Dios*

L Nguyen

S McKenna

J Sandoval

C Wright

University of Colorado Anschutz Medical Campus, Aurora, CO

Purpose of study

Sterile inflammation and IL1 expression is central to the pathogenesis of ischemia reperfusion injury. Mitochondrial stress is thought to be involved in initiating sterile inflammation. With injury, CPG rich mitochondrial DNA leaves the mitochondria and acts as a TLR9 ligand initiating pro-inflammatory signaling. Studies have used synthetic CpG oligodeoxynucleotides to study this process; however, mitochondrial stress also disrupts calcium homeostasis. How this affects CPG-mediated TLR9 activation is unknown. Understanding the relationship between calcium and CPG-mediated TLR9 activation could identify therapeutic targets to reduce tissue injury linked to sterile inflammation.

Methods used

RAW 264.7 macrophages were exposed to CpG DNA (3 µM 0–4 hours) to interrogate innate immune signaling. To assess intracellular calcium effects on CpG mediated innate immune signaling, RAW 264.7 were exposed to CpG DNA (3 µM 0–4 hours) and a) calcium ionophore A23187 (10 µM) b) calcium chelator EGTA/AM (250 µM) or c) calcineurin inhibitor FK-506 (10 µM). TLR9 mediated NFkB activation was assessed by cytosolic degradation of NFkB inhibitory proteins and NFkB subunit nuclear translocation by Western blot. IL1α and IL1β expression was assessed by qPCR.

Summary of results

Exposing RAW 264.7 to CPG led to cytosolic degradation of IkB NFkB inhibitory proteins, NFkB subunit nuclear translocation, and increased IL1α and IL1β expression. Exposure to calcium ionophore significantly increased CPG-induced IL1α and IL1β expression which was associated with enhanced degradation of NFkB inhibitory proteins. In contrast, both EGTA/AM and FK-506 with CpG DNA led to decreased expression of CPG-induced IL1α and IL1β and was associated with attenuated CPG-mediated degradation of IkB NFkB inhibitory proteins.

Conclusions

A combination of CpG DNA release and increased intracellular calcium accelerates TLR9 signaling which synergistically increases IL1α and IL1β expression causing an increased inflammatory response. Based on these results, the targeting of disrupted calcium homeostasis in addition to CpG DNA poses an interesting opportunity for synergistic therapies to reduce tissue injury linked to sterile inflammation.

Surgery III

Concurrent session

8:00 AM
Friday, January 24, 2020
283 Risk factor assessment analysis for patients undergoing breast cancer reconstruction to enhance recovery

CS Drew*

C Lee

L Tobing

S Roddick

S Gupta

Loma Linda, Loma Linda, CA

Purpose of study

Rates of mastectomy followed by breast reconstruction as a treatment plan for breast cancer have risen significantly in the past few years. However, patients undergoing immediate reconstruction at the time of mastectomy tend to have a much higher rate of complications. Variables such as history of hypertension, depression, anxiety, diabetes mellitus, obesity, asthma and anemia have multiple systemic consequences and could potentially contribute to a higher risk of complications in this population. This study aims to better identify possible risk factors that may predispose a patient to complications post breast reconstruction.

Methods used

This is a retrospective study that collected data from July 2014 to June 2019 of patients who underwent breast reconstruction in a single institution. Comorbidities were gathered and statistical analysis was performed to analyze commonalities shared between patients predisposing them to higher rates of complications.

Summary of results

The results of this study are summarized in the table 1 below. Those with complications had a much higher incidence of anemia and asthma compared to the general population of patients undergoing reconstruction. In those with complications hypertension and obesity occurred at a similar incidence, while diabetes occurred at a lower incidence to the overall population undergoing this procedure.

Conclusions

Patients undergoing breast cancer reconstruction who also had asthma and anemia had relative risks of 3.36 and 3.58 to suffer complications. In patients with complications, hypertension and obesity were observed in the same proportion as those without complications. However, diabetes mellitus was observed less often than expected in patients with surgical morbidities. This data provides additional guidance in the development of enhanced recovery after surgery protocols for the population of breast cancer reconstruction patients.

284 Etiology of chronic exertional compartment syndrome and a non-surgical treatment

TA Thompson1,*

S Ficken2

J White2

J McGinley1,2,3

1University of Washington, Seattle, WA

2Casper Medical Imaging and Outpatient Radiology, Casper, WY

3McGinley Education Innovations, Casper, WY

Purpose of study

Chronic exertional compartment syndrome (CECS) occurs when increased intramuscular pressure produces severe, sometimes debilitating pain and neurologic complications. Due to incomplete understanding of the pathophysiology, both diagnostic criteria and treatments options for CECS are lacking in reliability and efficacy.

The purpose of this study is two-fold. First, to investigate the theory that CECS results from functional venous outflow obstruction due to muscular compression. Second, to investigate the treatment of CECS through an image guided botulinum toxin injection targeted at the site of functional muscular compression.

Methods used

Retrospective case study of 284 patients (age 15–77, mean: 27) with exertional lower leg pain. Patients were assessed for CECS and areas of functional venous outflow obstruction using lower extremity MRI at rest and after exertion and CT Angiography at rest and with plantar flexions against resistance using the MVP Flex device.

Using both ultrasound and CT imaging guidance, a targeted injection of botulinum toxin was administered into the muscles at the site of venous compression. Patients were followed up at fixed time points over several years to track their treatment response.

Summary of results

260 of the 284 patients demonstrated both CECS and functional venous outflow obstruction on pre-treatment stress imaging. Active plantar flection caused venous obstruction, in the absence of active CECS symptoms.

Following botulinum toxin treatment, venous compression diminished with most patients demonstrating symptom resolution and normal imaging studies. Return of symptoms occurred at an average of 6.9±2.4 months (range 2–24 months). Repeat treatments were performed in 167 patients.

Conclusions

91.5% of patients displayed both CECS and functional venous obstruction. The results of this study suggest CECS results from functional venous outflow obstruction due to muscular compression.

Targeted botulinum toxin injections at the site of venous outflow obstruction resulted in significant symptom improvement, with a short recovery period. This treatment provides a viable non-surgical alternative to treat CECS by improving venous outflow.

285 Metaphyseal clamshell osteotomy for long bone deformity

DA Bravin1

M Rice2,*

MA Lee1

1UC Davis Health, Sacramento, CA

2UC Davis, Sacramento, CA

Purpose of study

Metaphyseal malunions and nonunions pose a challenge especially in the setting of complex deformity. Common options have significant limitations, especially in poor quality bone and when deformity centers are near the joint. The clamshell osteotomy has been described as treatment for complex diaphyseal malunions and provides efficient acute multiplanar correction and allows for early weight bearing. The purpose of this study is to report union and complication rates of metaphyseal and meta-diaphyseal clamshell osteotomies.

Methods used

After obtaining IRB approval, patients were identified using CPT codes from 01/01/2010 to 09/30/2018. Inclusion criteria were age >18 and a metaphyseal or meta-diaphyseal clamshell osteotomy of the tibia or femur, indicated by malunion or nonunion. Exclusion criteria were <6 mos of follow up. Chart and radiograph review was used to determine time to union and complications.

Summary of results

15 patients met inclusion criteria. 12 of 15 patients achieved union by 16 mos (union rate of 80%). 10 of 15 (66.7%) patients healed after the primary procedure, at an average of 8.75 mos. 4 of 15 (26.7%) patients required a secondary procedure (exchange intramedullary nailing). 2 of these 4 patients went on to union, while the other 2 did not have union at final follow up. 1 of 15 (6.7%) patients was lost to follow up at 8 mos without union. 2 patients had a post-op PE, 1 had a draining wound that required a sinus tract excision, and 1 developed a non-displaced fracture from the RIA.

Conclusions

The clamshell osteotomy is one potential tool for treating complex multiplanar deformities in the meta-diaphyseal and metaphyseal portion of lower extremity long bones. A high union rate can be seen using modern nail designs and atraumatic technique; however, union times can be long and some patients will require secondary procedures.

286 Determinants of caregiver satisfaction in pediatric orthopedics

IM Singleton1,*

R Garfinkel2

H Temkit3

MV Belthur3

1University of Arizona College of Medicine – Phoenix, Phoenix, AZ

2Henry Ford, Detroit, MI

3Phoenix Children’s Hospital, Phoenix, AZ

Purpose of study

With healthcare transitioning from volume-based to value-based, patient satisfaction is becoming increasingly tied to physician reimbursement as well as publicly reported. Aside from its use as a quality metric, it is also a key component of patient-centered care. This study investigates determinants of pediatric orthopedic patients’ parent or guardian (caregiver) satisfaction with the provider as measured by the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS).

Methods used

This was a prospective cross-sectional study of 200 English-speaking caregivers of pediatric patients that checked into the Phoenix Children’s Hospital orthopedic clinic from March 1, 2017 to November 1, 2018. All patients saw the same attending physician. Questionnaires given in clinic included the Newest Vital Sign (NVS) and the Literacy in Musculoskeletal Problems (LiMP) survey to measure general and musculoskeletal health literacy, respectively, demographic information, wait time, Consultation and Relational Empathy Measure (CARE) to measure perceived physician empathy, and CG-CAHPS.

Summary of results

Of the factors measured, perceived physician empathy correlated the strongest with the caregiver’s overall physician satisfaction. Pearson correlation coefficient yielded an r of 0.740 and a p-value of <0.0001. Using multivariable modeling, physician empathy alone accounted for 53% of the variation in satisfaction scores. Other factors such as health literacy as measured by the NVS (r=0.004; p=0.964), LiMP (r=0.013; p=0.879), wait time (r= -0.003; p=0.974), and time spent with the physician (r=0.016; p=0.866) did not independently affect satisfaction.

Conclusions

The main determinant of caregiver satisfaction with the provider in a pediatric orthopedic setting is perceived physician empathy, accounting for over half of the variation in satisfaction. Health literacy, wait time, and time spent with the physician do not significantly affect satisfaction. This highlights the importance of quality over quantity patient-physician interactions. This is the first study, to our knowledge, that directly correlates pediatric caregivers’ perceived physician empathy with provider satisfaction.

287 Does ultrasound-guided osteotomy improve the aesthetic outcome of patients undergoing rhinoplasty surgery?

C Lee*

CS Drew

L Tobing

S Roddick

S Gupta

Loma Linda University, Loma Linda, CA

Purpose of study

General ultrasound imaging is a widely available, easy-to-use, and cheaper alternative to other advanced imaging methods. Furthermore, it is noninvasive, painless, and safe as it does not have harmful radiation. However, ultrasound is not frequently used intraoperatively because of its inability to penetrate bone and large amounts of tissue to produce a clear image. In thin areas such as the nose where these restrictions can be eliminated though, this method could be highly beneficial intraoperatively by guiding nasal osteotomies during rhinoplasty to improve patients’ aesthetic outcome with enhanced visualization of symmetry.

Methods used

This is a case series using ultrasound to assist osteotomies for patients undergoing nasal surgery. A SonoSite ultrasound is specifically used with the L25 13–6 probe and under the musculoskeletal exam. The nose is seen superficially at a depth of 2.0 cm and examined longitudinally for optimal view. Gain may be adjusted for a more advantageous assessment. Ultrasound gel is placed on the patient’s nose as well as on the probe underneath the sterile wrap to provide a clear image. After confirming the bony landmarks, the plastic surgeon performs the closed osteotomy with visualization, and the ultrasound is continuously utilized to check correction and symmetry.

Summary of results

Ultrasound-assisted osteotomy was used for 5 patients undergoing nasal surgery. No complications arose during the surgery. Cartilage was clearly demarcated. Seven plastic surgeons and plastic surgery residents were surveyed regarding the potential for this technology to enhance their rhinoplasty outcomes. Comments were collected from the users and observers to guide further implementation.

Conclusions

Intraoperative ultrasound imaging for patients undergoing nasal surgery has so far been successful in ensuring symmetry compared to the naked eye alone. Furthermore, it has enabled surgeons to visually confirm precision and accuracy beyond the skin surface and has accordingly provided a stronger outlook on the aesthetic result for the patients. Thus, with sufficient learning and skill, intraoperative ultrasound can be a highly advantageous tool in aesthetic and reconstructive plastic surgery.

288 Self-reported health measures in burn survivors undergoing burn surgery following acute hospitalization

DE Luna1,*

C Sheckter2

G Carrougher1

B Stewart1

J Schneider3

C Ryan3

R Holavanahalli4

D Amtmann1

N Gibran1

1University of Washington, Seattle, WA

2Stanford, Stanford, CA

3Harvard, Boston, MA

4UT Southwestern, Dallas, TX

Purpose of study

Perception of mental and physical function in adult burn survivors is decreased following injury. Individuals who undergo post hospitalization reconstructive surgery may have lower Health Related Quality of Life (HRQoL) that is influenced by the severity of their burns. We sought to characterize self-reported health perceptions in burn survivors undergoing surgery post-hospitalization within 24 months of injury.

Methods used

Patient Reported Outcomes Measurement Information System (PROMIS)-29 Profile v2.0 data were collected from participants from a multi-center longitudinal study at 6, 12, and 24 months post-injury. Surgical operations performed within the 24-month follow-up period were classified as: wound closure, contracture release or scar revision. PROMIS-29 domain scores were compared for those undergoing surgery (surgical participants) versus those who did not (non-surgical participants) using linear regression, adjusting for age, burn size, range of motion limitation, number of operations during acute treatment, and insurance/payer.

Summary of results

727 participants provided complete PROMIS-29 data, of which 227 (31.2%) underwent >1 operative procedure within 24 months post-injury (Table). PROMIS-29 anxiety and depression scores were worse at 6 months post-injury for participants who underwent contracture release and scar revision compared to non-surgical peers (p<0.05). At 12 months after injury, individuals who underwent wound closure at any time post initial hospitalization reported worse anxiety, depression, and pain interference (p<0.05). Participants in the contracture release and scar revision categories reported lower PROMIS-29 scores in all domains 24 months after injury (p<0.05), even after adjusting for confounders.

Conclusions

Burn-related reconstructive surgery has the potential to improve the lives of patients including promoting functional recovery and improving cosmetic appearance. Our data suggest that participants who undergo reconstruction surgery after hospital discharge, report worse self-reported indicators of health compared to participants who do not undergo surgery after adjusting for known confounders.

289 C-reactive protein level at time of discharge is not predictive of risk of reoperation or readmission in children with septic arthritis

M Bouchard1,2

L Shefelbine3,*

V Bompadre4

1The Hospital for Sick Children, Toronto, ON, Canada

2University of Toronto, Toronto, ON, Canada

3University of Washington School of Medicine

4Seattle Children’s Hospital, Seattle, WA

Purpose of study

C-reactive protein (CRP) level is used at our tertiary pediatric hospital in the diagnosis, management, and discharge evaluation of patients with septic arthritis. The purpose of this study was to evaluate the efficacy of a discharge criterion of CRP <2.0 mg/dL for patients with septic arthritis in preventing reoperation and readmission. We also aimed to identify other risk factors of treatment failure.

Methods used

Patients diagnosed with septic arthritis between January 1, 2007 and December 31, 2017 were identified with ICD 9/10 and related CPT codes. Systematic chart reviews were performed to obtain demographic data, infection characteristics, and treatment details. Bivariate tests of associations between potential risk factors and readmission and reoperation were performed. Quantitative variables were analyzed using Mann-Whitney tests and categorical variables were analyzed using Chi-square tests.

Summary of results

One hundred and eighty-three children with septic arthritis were included in the study. Seven (3.8%) were readmitted after hospital discharge for further management, including six who required reoperation. Mean CRP at discharge for single-admission patients was 1.71 mg/dL (±1.07) and 1.96 mg/dL (±1.19) for the readmission group (p=0.664). Forty-eight children (25.9%) had CRP values greater than the recommended 2.0 mg/dL at discharge. Only three of these patients (6.2%) were later readmitted. The only common variable of the readmitted children was an antibiotic-resistant or atypical causative bacteria.

Conclusions

CRP levels are useful in monitoring treatment efficacy of septic arthritis in children but are not reliable as a discharge criterion to prevent readmission or reoperation. We recommend determining discharge readiness on the basis of clinical improvement and down-trending CRP values. There was a higher risk of readmission in children with an antibiotic-resistant or atypical causative bacteria. Close monitoring of these patients and those with negative cultures at time of discharge is suggested to identify signs of persistent infection.

290 Elements of 0% leak rate in sleeve gastrectomy

J Gevorkian*

K Sasse

UNR School of Medicine, Reno, NV

Purpose of study

Laparoscopic sleeve gastrectomy is a widely utilized and effective surgical procedure for weight loss and diabetes reversal in obese patients. Reducing complications is critical to enabling greater acceptance of metabolic surgery. Leak at the sleeve staple line remains the most serious complication of this procedure, occurring in <1–3% of cases. Techniques to minimize the risk of sleeve gastrectomy leaks have been published, although no universally agreed upon set of techniques exists. This report describes a single-surgeon experience with a specific 10-point approach to sleeve leak prevention resulting in a progressive decrease in leak rate over 8 years.

Methods used

2,139 consecutive sleeve gastrectomy cases between 2016–2019 were reviewed retrospectively. The 10 technical steps include:

  • Use of 40–French calibration tube.

  • Allowing generous volume around calibration tube at curve of incisura.

  • Avoiding disruption of cardiotuberosity branch arteries serving as the blood supply to posterior proximal stomach in cardia region.

  • Angling linear stapler to left and >15 mm away from true GE junction.

  • Use of blue or 3.5 mm tissue stapler cartridges in proximal stomach without staple line reinforcement.

  • Fibrin glue sealant application to staple line.

  • Hand–sewn, interrupted sutures to invert staple line at proximal 4 cm of sleeve.

  • Apposition of omentum to rest in proximity to completed staple line.

  • Suturing omentum back to mid and lower staple line to prevent a potentially obstructing ‘windsock’ deformity.

  • Avoidance of 1–stage revisional sleeves concomitant with band removal.

  • Patient characteristics, sleeve leaks, staple line hemorrhage, and percent body weight loss at 6 months were reported for each year.

Summary of results

Implementing the described techniques of the sleeve gastrectomy, rate of sleeve leaks fell from 4% (2012) to 0% (2015) and have remained at 0% (2016–2019) without a significant change in weight loss, as depicted by 6 month change in body weight and percent excess BMI lost.

Conclusions

In this single-surgeon experience, sleeve gastrectomy leak rate has fallen to 0% since the implementation of 10 specific technical modifications in the procedure. It is plausible that these specific 10 points, or a similar specific technique for each step, could be taught to surgical trainees to reduce the incidence of leaks at earlier stages of the experience learning curve.

Behavior and development I

Concurrent session

10:15 AM
Friday, January 24, 2020
291 Speech and language development, autism spectrum disorders and seizures: would whole genome sequencing provide a connecting link?

SL Cole1,*

M Hegde2

S Shankar1

1UC Davis, Sacramento, CA

2PerkinElmer, Atlanta, GA

Purpose of study

Many studies have shown a correlation between autism spectrum disorders (ASD), neurodevelopmental disorders and epilepsy/seizure disorders. We evaluated whole genome sequencing (WGS) results in a subset of patients with limited speech/nonverbal, with or without ASD, neurodevelopmental disorders and seizures to find common genetic variants/network.

Methods used

Clinical whole genome sequencing was performed and relevant genetic variants were analyzed to identify recurring pathways or genes.

Summary of results

We found 15 individuals in our cohort with this combination of phenotypic characteristics. Four had pathogenic or likely pathogenic variants in SLC16A2, PHF6, ERCC8 (relevant to phenotype), and MME (incidental finding), 10 patients had one or more variants of unknown significance (VUS) and 1 had a negative test result reported. VUSs included autosomal dominant inheritance in genes consistent with the phenotypes in our cohort. Additionally, some patients had multiple VUSs in causative genes suggesting oligogenic gene effects.

Conclusions

WGS provides an opportunity to evaluate regions of the genome that are not picked up by traditional genetic testing. Overall, we identified many changes that have been reported as VUS. Some of these variants are likely contributing to these patients’ phenotypic findings. However, given the novelty of WGS, a direct correlation requires additional patients with WGS testing and phenotypic correlation to determine significance.

292 Controlled trial of lovastatin and language intervention in children with fragile x syndrome

RJ Hagerman1,*

A Thurman2

K Kim2

L Abbeduto2

1University of California Davis, Sacramento, CA

2UC Davis, Sacramento, CA

Purpose of study

To carry out a controlled trial of lovastatin (10 to 40 mg per day), a targeted treatment for Fragile X Syndrome (FXS), in children with FXS ages 10 to 18 combined with an open label of Parent Implemented Language Intervention (PILI) to both groups delivered by Skype into the families’ homes.

Methods used

The randomized-double blind controlled trial lasted 4 months and our primary outcome measure was the number of different words (NDW) used during a parent-child narrative task. Our secondary outcome measures included total utterances, the ADAMS, the Abberant Behavior Checklist, VAS and the CGI-I.

Summary of results

There was no significant difference in age or sex between groups (n=14 on lovastatin vs n=16 on placebo). IQ (44.00 vs 43.13), ADOS-2 comparison score and parent education were not significantly different between groups. Baseline and outcome verbalizations were 38.61 (±35.24) and 118.75 (±66.86) on lovastatin and 50.02 (±32.91) and 108.94 (±56.22) on placebo so both groups had significant improvements (P<0.0001), but there was no significant difference between groups (p=0.54). Significant improvements occurred in the secondary outcome measures including the CGI-I and the VAS for spoken language and social impairment for both groups but no significant difference between groups. Adverse events were not significantly different between the groups, but both cholesterol and low-density lipoprotein dropped significantly lower on lovastatin vs. placebo (134.67 to 104.75 vs 132.27 to 134.13; p<0.001; and 73.75 to 47.33 vs. 70.47 to 73.87; p<0.0002, respectively). Interestingly, although improvements in parental use of the PILI-targeted strategies utilization was observed in both the groups, parental use of PILI-targeted strategies was correlated with the child’s improvement in NDW, in the placebo group and not in the lovastatin group.

Conclusions

Children treated with placebo or lovastatin made significant language gains when also give PILI intervention over a 4 month period. Lovastatin did not add significantly to the language gains compared to placebo but lovastatin may have compensated for the variation in the parent’s use of PILI-targeted strategies to enhance the child’s improvement in NDW.

293 Developmental delay and psychiatric issues in an under-stimulated deaf child

NM Shah*

Loma Linda University, Loma Linda, CA

Introduction

In the United States, about 10,000 infants are born with sensorineural hearing loss, 95% of which have hearing parents. These children experience barriers to communication with their families. The lack of proper communication and stimulation in the first years of life can be detrimental to mental development. This leads to a lack of abstract thinking and problem-solving skills, ability to form peer relationships, and healthy self-esteem. 9% of deaf children have learning disabilities and 5% have severe developmental delays. Emotional and behavioral problems are twice as prevalent.

Case description

A 15-year-old female born deaf and mute was brought in to the Behavioral Medicine Center (BMC) after recovering from an overdose on ibuprofen, famotidine, and ranitidine. The parents did not understand the patient’s actions and could not communicate effectively with her. They knew very little sign language and spoke mainly Spanish. The patient attends a school for deaf children and can communicate in American Sign Language (ASL) while at school. However, her interaction with family is severely limited due to both a Spanish/English communication barrier and the lack of knowledge of sign language.

Her social skills were minimal both with staff and other patients on the unit. She consistently presented as indifferent and guarded. She responded to most questions with a shrug or nod whether or not the question warranted it.

The patient showed symptoms of depression including suicidality, hypersomnia, anhedonia, low energy, decreased appetite, poor mood, and psychomotor retardation. Social workers were able to connect the family and patient to helpful mental health resources in the community. The patient was placed on Fluoxetine (40 mg) for long-term management of depression.

Discussion

The importance of awareness campaigns for developmental health of deaf children cannot be ignored. In this case of the 15-year-old female, we see what the unfortunate effects are of lack of proper care for deaf children. Educating parents about these long-term effects may motivate them to be more proactive in caring for their deaf children. Furthermore, the support community for deaf people should be connected with the mental health community. These individuals have unique needs and life experiences that deserve careful attention in all healthcare settings.

294 Crossfit KAMP: an intervention to improve peer relationships and exercise capacity in children with autism spectrum disorder

P Kaluzhny*

University of California Davis, Sacramento, CA

Purpose of study

Peer relationships and social skills (SS) are core challenges for those with autism spectrum disorders (ASD). Exercise is a modality that has been examined as a means to improve some core symptoms of ASD. CrossFit Kids provides a scalable structured group exercise program that could potentially improve the core challenges for children with ASD; however, it has not been previously studied.

Methods used

CrossFit KAMP (Kids with Autism Making Pals) is a pilot waitlist randomized control trial.19 children (17 boys/2 girls) ages 8–11 years with ASD participated in a 14-week twice weekly CrossFit Kids exercise program. Parent and child social & behavioral functioning rating scales were administered at baseline, after each 14-week session, and 8 weeks post-intervention.The same workout was video recorded at week 1 & 14 of intervention to assess exercise capacity. Treatment effects evaluated by Wilcoxon signed rank test and rank sum test.

Summary of results

Group 1 (n=10) attendance rate was 85% and group 2 (n=5) was 81%.Group 1 had significant improvements in peer relationship on the Promis Parent Proxy Peer Relationship Measure (PPPRM) (p=0.004) and SS on the SRS Communication subscale t-score (p=0.03). Compared to the group 2 waitlist, group 1 had better parent and child rated Peer Relationship Measures (p=0.04 and p=0.05 respectively) at the end of the first 14 weeks.The 8 week follow up from group 1 showed significance of SRS total t-score (p=0.04) and SRS Restricted and Repetitive Behaviors (RRB) t-score (p=0.02). Qualitatively, 11/15 participants wanted to do another exercise group like KAMP and 12/15 made a friend.Parent report shows 12/15 children verbally conveyed that they enjoyed participating in KAMP, and 11/15 made a friend. Overall both groups increased exercise capacity by an average of 23 seconds.

Conclusions

Results of this pilot study demonstrate that CrossFit KAMP is feasible, can help improve peer relationships/SS, possibly reduce RRB, and improve exercise capacity. Qualitatively, both parents and children reported enjoyment in participating, wanting to continue exercising in a group like KAMP, along with making a friend. CF KAMP may be a promising intervention to help improve peer relationships, SS, and stereotypical behaviors for children with ASD while also providing improved health through exercise.

295 A gender bias curriculum: empowering our learners in the #MeToo Era

K Roberts*

N Yim

A Hayton

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of study

The incidence of gender bias (GB) and sexual harassment (SH) is prevalent among medical students and residents. Challenges such as unfair treatment due to gender, discomfort while listening to sexual humor, and unwanted sexual advances are common, especially to female learners. These negative encounters are experienced as early as the preclinical years for many medical students and can lead to avoidance, withdrawal, ethical/moral distress, and burnout. Though some interventions involving educational workshops that focused on issues of GB/SH in medicine have shown to decrease GB/SH in various settings (including clinical and academic), there has yet to be data on effects of such methods in the earlier years of training.

Methods used

In this study, we conducted a 120-minute workshop with third year medical students that focused on promoting awareness of GB and SH including a gender privilege walk and a discussion of the root causes of gender bias and sexual harassment. Students were also introduced to the bystander approach and the reality that gender bias, harassment and violence are everyone’s problem to solve. Students then broke into small groups to discuss cases from actual learner experiences. Our workshop concluded by providing the medical students with strategies to empower all genders to respond to inequities that they observe. A survey was issued to the students immediately following the workshop, as well as at the end of the year to assess long-term impact.

Summary of results

Third year medical students who participated in our curriculum showed a significant and sustainable improvement, compared to before the workshop, in their knowledge of gender bias and sexual harassment (p=0.001) as well as their ability to confront these issues in the learning environment when they personally experience GB/SH themselves (p=0.001) or when they witness GB/SH (p=<0.0001). Students also reported feelings of validation, awareness and empowerment as well as appreciation for the process of information sharing, faculty facilitation, and practical techniques gained from the workshop.

Conclusions

Our study suggests that students exposed to a 120-minute workshop are better equipped to recognize and respond to GB/SH. This workshop is the first step in empowering our learners.

296 Simulation training with standardized patient versus high-fidelity manikin increases active learning for medical students

SS Kwon*

R Krause

A Hayton

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of study

Clinical case simulations using standardized patients (SP) or high-fidelity manikins (HFM) are implemented into medical school curriculums in order to cultivate clinical competence in aspiring physicians. It is unclear whether SP or HFM are superior in creating a realistic simulation. The purpose of our study is to evaluate active participation when interacting with SP vs HFM.

Methods used

We conducted a non-blinded randomized control trial with year-3 medical students on the internal medicine clerkship at Loma Linda University. The study period was from February 2017 to February 2018. During pulmonary simulation training, randomized students interacted with SP versus HFM voiced by an SP. A post-training survey using a 5-point Likert scale assessed perceived participation. The SP reported interpersonal communication skills (ICS) demonstrated by participants during simulation using a modified SEGUE scoring system. Statistical analysis was performed using Stat12.1 statistical software. Differences were analyzed via the Mann-Whitney U test.

Summary of results

Of the 130 students (75 in SP arm, 65 in HFM arm), the SP arm showed significantly greater participation when compared to the HFM arm with 98% agreeing/strongly agreeing to have ‘actively participated’ vs. 88% (p<0.05) Additionally, students in the SP arm reported greater levels of confidence in their ability to transfer the knowledge gained into a real clinical situation with 97% vs. 89% agreeing/strongly agreeing (p<0.05). They also reported greater confidence in performing physical exams practiced during the simulation on an actual patient, with 88% vs. 80% agreeing/strongly agreeing (p<0.05). Post-simulation surveys completed by the SPs with results of the modified SEGUE showed higher ICS in the SP arm. (p<0.05).

Conclusions

Our study demonstrates that during simulation training, year-3 internal medicine clerkship students felt they were more active participants, had greater levels of confidence in their ability to transfer knowledge gained into a real clinical situation, and demonstrated improved ICS when interacting with SP versus HFM. We believe this study suggests that directly interacting with SP creates a more realistic simulation experience than interacting with HFM, which leads to an improved learning environment.

297 The association between social media use and the development of disordered eating: a closer look at the literature

CM Hidalgo1,2,*

V Simhambhatla2

F Afzal2

P Raj2

A Patel2

A Saha2

B Afghani2,3

1University of San Diego, San Diego, CA

2UC Irvine School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

The prevalence of social media is widespread and its effect on the etiology of eating disorders is unclear. The objective of this study is to investigate the effects of social media use on eating pathology.

Methods used

A literature review utilizing PubMed and Google Scholar with the keywords Social Media Use, Instagram, Facebook, Eating Disorders, and Disordered Eating was conducted. Only studies published after 2012 were included and studies that did not focus on eating pathology were excluded.

Summary of results

Of the 15 articles, only 5 satisfied our inclusion criteria. Each of the articles summarized in the table 1 below incorporated a self-report survey design. Of the 5 articles, each one found a significant association between social media use and disordered eating. Three of the articles found that body dissatisfaction plays a role in the relationship between social media usage and disordered eating outcomes. Limitations of some of the studies included the self-report nature and lack of control for confounding variables leading to disordered eating.

Conclusions

This review suggests a correlation between social media use and disordered eating outcomes but a causal relationship cannot be determined. Prospective controlled studies that account for confounding variables are warranted in order to make causal inferences regarding social media usage and its effects on the development of eating disorders.

Community health

Concurrent session

10:15 AM
Friday, January 24, 2020
298 Adverse childhood experiences and poverty: collaborative partnerships to improve self-efficacy and resilience in impoverished minority youth

M Cabada1,*

D Lee1

C Casillas1

M Chavez1

K Colwell1

R Kinman2

1Fresno High School, Fresno, CA

2UCSF Fresno, Fresno, CA

Purpose of study

Children growing up in poverty can face a variety of adverse childhood experiences (ACES) which can negatively impact their ability to succeed in life. According to the American Psychological Association, resilience ‘is the process of adapting well in the face of adversity, trauma, tragedy, threats, or significant sources of stress’. Although impoverished adolescents want to become healthy and successful adults, they may need assistance to develop their own self-efficacy and resilience. High-risk impoverished minority adolescents thus partnered with UCSF Fresno Pediatrics and the Fresno Community Health Improvement Partnership (FCHIP) to increase self-efficacy and resilience in their fellow youth.

Methods used

Students explored the effect of poverty on ACES and anonymously surveyed 155 fellow high school students about their ACES exposures. They collaborated with FCHIP’s Trauma and Resilience Network to educate themselves on how to build self-efficacy and resilience within their own community, and used the information they had gathered to educate their fellow students.

Summary of results

42% of high school students surveyed had been the victim of violence, 54% had experienced violence within their own families, 35% reported food insecurity, 57% had divorced or separated parents, 49% had a household member with substance abuse issues, 46% had a household member who had been in prison, and 15% had experienced homelessness or foster care. Students collaborated with FCHIP and UCSF Fresno to create an annual Health Careers Job Shadow Day to educate students on how to develop their own community action research partnerships, were the closing speakers for the 2nd annual FCHIP breakfast, and developed an interactive lunchtime session at their school to educate their fellow students on how to build resilience and decrease stress.

Conclusions

Although impoverished minority youth have significant exposure to ACES, they can successfully develop community partnerships to help them identify and address issues of concern within their own communities, while helping them build resilience to mitigate the effects of these ACES on their own lives.

299 Homeless to housed: how does stable housing affect healthcare utilization and perceptions in residents of the forget-me-not manor, a housing first program in juneau alaska

N Ord*

R Urata

University of Washington, Seattle, AK

Purpose of study

Housing first (HF) is a solution to chronic homelessness demonstrated to reduce public service utilization in urban populations but less is known about rural areas. In October of 2017 Juneau Alaska, a town of 32,000 opened the Forget-Me-Not Manor to house Juneau’s most vulnerable. In five months after opening, 22 of the 32 residents experienced impressive reductions in ER visits (73% reduction), recovery center sleep off visits (99% reduction), and contacts with police officers (77% reduction) compared with 6 months prior (Heidi Brocious, UAF). However, little is known about why residents use less services and the reasons residents seek healthcare. This study examines resident’s relationship to healthcare services before and after joining HF through qualitative interviews and healthcare records analysis.

Methods used

Two qualitative 30-minute interviews were conducted 3 months apart exploring resident’s definition of health, barriers to improving health, and role housing first plays in their health. Additionally, resident’s healthcare records were collected from three of the most frequently visited healthcare organizations during the period of December 1st, 2015 – December 1st, 2018. The modality of each interaction (clinic, hospital, etc.), diagnosis codes, and summary category (acute illness, maintenance of chronic disease, etc.) associated with each healthcare is recorded.

Summary of results

Total participants are 17. Interviews were recorded with 17 and 15 residents respectively. Participant responses to standardized interview questions are summarized and compared in pre-defined categories. 636 Medical records are collected from 17 of 17 participants and three healthcare organizations. The data is analyzed for usage patterns by location, diagnosis codes, and summary category relative to the date residents joined housing first.

Conclusions

The combination of quantitative and qualitative data is used to discuss the relationship between healthcare services and the study participants before and after joining HF. Resident’s most common diagnoses are compared with the general population and HF programs in urban populations. Differences between HF in rural and urban regions are discussed. Limitations of this study and avenues for future research are proposed.

300 A novel program at the science museum to increase the interest and knowledge of a diverse population of youth towards healthcare

JS Chang1,2,*

D Leung2

C Stockford2

M Ly2

A Shin2

B Afghani2,3

1University of Southern California, Los Angeles, CA

2UC Irvine School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Increasing the number of underrepresented individuals in healthcare fields is critical to meeting the needs of an increasingly diverse society. The purpose of this study is to evaluate the effectiveness of an interactive health exhibit in enhancing the knowledge of youth towards healthy habits and garnering their interest towards healthcare.

Methods used

Through a partnership between the UC Irvine School of Medicine and the Discovery Cube in Santa Ana, CA, we have established an interactive exhibit where trained volunteers teach the young visitors about the hazards of smoking using models, introduce them to basic life support, and teach them intubation using a simulator. A feedback survey is distributed to the visitors for any qualitative feedback.

Summary of results

526 feedback surveys were collected since 2016. When visitors were asked if their interest in healthcare had increased, 378 (72%) responded and 28% left it blank or said they ‘don’t know’. Of 378, 279 (74%) gave a positive response. When asked what they liked most about the exhibit, 103 (61%) of the 170 underrepresented (UR) and 181 (55%) of the 327 non-underrepresented (NUR) provided comments (Table). Of 284 respondents, 33% liked the hands-on nature, 28% liked the knowledge gained, and 27% liked the interaction with knowledgeable mentors. Interestingly, the underrepresented were more likely to comment that their knowledge had increased (UR=39% vs NUR=23%) and the non-underrepresented were more likely to enjoy the interactive nature of the exhibit (NUR=37% vs UR=25%).

Conclusions

Our interactive exhibit was effective in garnering the interest of a diverse population of youth towards healthcare. Such interactive models can be used to enhance the knowledge and stimulate the interest of youth in school and non-school settings.

301 Prenatal vaccine awareness among pregnant women and partners

YY Razi1

KE Patapoff1,*

AF Schiller1

M Mellon2

AL Nelson1,2

H Stohl3,4

1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA

2Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, OR

3Harbor-UCLA Medical Center, Torrance, CA

4David Geffen School of Medicine at UCLA, Los Angeles, CA

Purpose of study

Whooping cough and influenza viruses disproportionally affect babies under 6 months of age given that they cannot be fully immunized. Thus, vaccination is recommended for all contacts of a newborn. This study sought to estimate Tdap and flu vaccine awareness of pregnant women and their partners.

Methods used

After oral consent was obtained, a survey of vaccine knowledge was administered on a one-to-one basis in English and Spanish at Harbor-UCLA Prenatal Clinic. A Chi square analysis of possible associations was used to calculate statistical significance with p<0.05. The study was IRB approved.

Summary of results

Of 293 respondents, 40% and 81% were aware of the need in pregnancy for Tdap and flu vaccines, respectively. Both gender and language were associated with Tdap awareness, whereas only gender was predictive of flu awareness. Age, previous pregnancies, gestational age, and education were not associated. The table 1 displays awareness percentages of subgroups.

Conclusions

Overall, vaccine awareness was low, driven mostly by ignorance of the Tdap vaccine, as more participants knew of the flu than Tdap vaccine. More women than men were aware of the Tdap vaccine, whereas men were slightly more aware of the flu vaccine. Nearly double the number of women were aware of both vaccines than men. Additionally, Spanish speakers were less aware of the Tdap vaccine than English speakers and awareness of both vaccines by Spanish speakers was less than a third of that of English speakers. To increase vaccine awareness and decrease infection, recommendations for pregnant women to encourage their partners and baby’s contacts to receive both vaccines should be made. Also, vaccine education initiatives should be enhanced for Spanish-only speaking populations.

302 An assessment to reduce smoking during pregnancy in park county, wyoming

A Golden*

University of Washington School of Medicine, Seattle, WA

Purpose of study

Powell, Wyoming is an agricultural community with a mean household income and education level below the national average. Through interviews with local physicians and community organizations, a lack of education and resources for mothers were found to be public health concerns. Specifically, smoking during pregnancy was identified. Data collected found that 16.1% of women in the county smoked during their pregnancy, which is above the national average.

Methods used

An asset-based approach was used to determine available resources for mothers in Powell. The Serenity Pregnancy Resource Center and the Public Health Office were identified as organizations providing education and services for mothers. Using information gathered from community-based interviews, a literature review was conducted to identify possible ways to reduce smoking in pregnant women using the resources available within the town.

Summary of results

Five literature review articles that proposed interventions to help with smoking cessation during pregnancy were evaluated for their potential efficacy in Powell. One of the most promising interventions proposed initiating a text-message based support group for mothers. An additional study evaluated the use of smoking cessation therapy in pregnancy. Both of these studies have realistic uses in a rural setting and are able to use resources and assets that already exist in Powell. The Serenity Pregnancy Resource Center provides education for mothers and already has a database that could be used for the text messaging program. The Public Health office provides many services to pregnant and new mothers and could potentially implement a medication cessation service.

Conclusions

The assessment to help pregnant women quit smoking was aided through the use of a strength-based framework. Available resources within the community were identified and information about this public health concern were shared with local providers and community organizations. Next steps include establishing a Mother Child Health Coalition with the Public Health Office. The development of this coalition has been initiated and is pending input from providers in Park County who treat pregnant women and new mothers. Maternal smoking will be one area of focus and evidence-based interventions from this research will be assessed to decide which is most applicable for the Powell community.

303 Supporting safe and sustainable employment among residents in protected homes for people with serious mental illness in iquitos, peru

A Larson*

University of Washington, Seattle, WA

Purpose of study

As part of a national reform towards community-based mental health services, a network of protected homes for people with serious mental illness were introduced in Iquitos, Peru starting in 2012. While these homes are intended to serve a transitional role, challenges in obtaining employment and independent living for the residents have persisted since the protected homes were first established. Staff in one home proposed the introduction of an employment program in the form of a self-maintaining shop within one of the homes. However, there was initially no evaluation tool specifically for monitoring residents’ progress in occupational capacities, and tools to promote workplace health and safety as well as best practices were also missing.

Methods used

A survey focused on occupational development was developed, using a variety of existing tools, for ongoing evaluation of residents participating in the employment program. An informal health and safety checklist for use by staff was developed based on tools from PAHO and the Peruvian government and piloted with staff and residents in the shop location. In addition, a team-based best practices checklist for administration of occupational programs for people with serious mental illness was developed, based on existing literature.

Summary of results

After feedback from staff and residents, the evaluation survey was streamlined into 5 short domains including Employment Functioning, Role and Identity, Self-Efficacy, Skills, and Quality of Life. The survey used a consistent numerical scoring system throughout, with optional prompts for further discussion between the evaluator and resident. The Health and Safety checklist was successfully employed with staff at the planned project site and used to inform the introduction of safety infrastructure in the home. The Best Practices checklist was reviewed and approved by staff on multiple levels.

Conclusions

The employment program is equipped with tools to evaluate progress of individual residents, conduct ongoing internal reviews of workplace health and safety, and promote best practices through team discussion. These tools should be employed before and during official implementation of the program.

304 Community-based strategies to reduce diabetes incidence through educational gardening in grand coulee, washington

E Kershaw*

University of Washington, Spokane, WA

Purpose of study

Grand Coulee, WA is a rural community located in a USDA food desert. It is home to Coulee Medical Center (CMC), a critical access hospital that serves 7,000 patients from surrounding counties including Lincoln, Douglas, Grant, and Okanogan and has a 21% Native American patient population. These counties have obesity rates 2-7% higher than the state average. Community conversations revealed a concern for obesity in young people. Health care providers cited diabetes management adherence concerns, which includes lifestyle modifications such as obesity. One primary factor contributing to obesity is unhealthy food choices, with selected secondary risk factors including lack of healthy food access and limited healthy food knowledge.

Methods used

Using an asset-based approach, community resources working to address secondary risk factors were evaluated. The Care and Share food bank and the local Senior Center Meals program identified less nutritious food choices in a free food setting. For example, the selection of white bread rather than multigrain bread. Local individuals cited high food prices in general as a concern. Food education is currently addressed at CMC and the local senior center by CMC staff. The Chamber of Commerce has established a plot of land which can be utilized for a community garden. Therefore, community gardening strategies and their efficacy in improving obesity risk was the literature review focus.

Summary of results

A successful clinic-based community gardening program includes provider encouragement, nutritional and gardening-based educational components, and utilization of volunteers. Such programs have been shown to be a strong educational addition to communities, with increases in quantity of purchased produce, regardless of income. Community gardening itself will not alleviate food insecurity, but can serve to strengthen awareness of the local food bank and senior center, which aim to meet this need.

Conclusions

This project highlights how a community’s concerns can be addressed by utilizing its strengths. Next steps include lease of land by CMC, gardening expert-informed establishment of layout and rules, garden promotion, and securing funding for supplies via food desert-based grant funding and/or local business donations.

305 Correlation between parental meal planning habits and childhood obesity

J Moon1,*

G Suarez1

G Browne1

D Wagner1

R Denny1

E Medina2

M Baum1

1Loma Linda University, Loma Linda, CA

2Loma Linda University Health, Loma Linda, CA

Purpose of study

Childhood overweight (BMI>85%) and obesity (BMI>95%) status is a serious health epidemic crisis in the United States. In San Bernardino County, childhood obesity rates more than double the national rate of 18.5%. Because obesity can lead to serious health concerns, it is important to address and understand the complexity of environment, behavior, and parental attitudes influencing unhealthy weight in children. This study aims to determine if a correlation exists between parental meal planning habits and children’s BMI.

Methods used

At-risk San Bernardino County children ages 9-15 years participated in Operation Fit, a week-long day camp focused on healthy lifestyle, nutrition, and physical exercise. Primary care physicians from a university associated federally qualified health center referred 115 pediatric patients for their unhealthy weight (BMI>85%). At the beginning and end of camp, parents and children completed surveys for lifestyle practices. One survey question asked parents to disagree or agree with the statement: ‘I take time to plan meals for the coming week.’

Summary of results

A logistic regression with N=115 showed a statistically significant (p<0.0144) relationship exists between parental meal planning habits and elevated BMI in their children. Parents who disagreed with taking time to plan meals were 0.35 times as likely to have overweight children than parents who did take time to plan meals, with a confidence interval of 0.151-0.811.

Conclusions

It appears that there is a correlation between a non-habit of parental meal planning and childhood obesity. This outcome is reasonable because parents who do not plan meals ahead of time may not shop for groceries beforehand or thoughtfully address healthy food choices containing necessary nutrients. Further exploration is needed to determine exactly what aspect of not taking time to plan meals earlier is correlated to increased childrens’ BMI.

306 Barriers to healthcare in students on an individualized education plan in rural oregon

HR Cannon1

B Winfield1,*

A Sainz1

JH Nelson1

RB Cannon2

E Guenther1

1Western University of Health Sciences, Lebanon, OR

2Lebanon Community School District, Lebanon, OR

Purpose of study

According to a 2013 report, the number of Oregon children on Medicaid who received an annual wellness exam by their pediatrician was 41%. We suspect that the number of adolescents who visit their primary care provider annually may be lower in rural Oregon for students who are on an Individualized Education Plan (IEP, indicating some form of learning disability). Previously published literature specifically linking students on an IEP and annual wellness exams was not found. The purpose of our project was to determine what barriers, if any, exist to healthcare for students on an IEP in rural Oregon.

Methods used

Parents of students ages 14-18 who qualified for an IEP per district guidelines were given an 8-question survey to complete during an annual IEP meeting. Results were analyzed with a Chi-Square test after all surveys had been completed.

Summary of results

46 out of 140 parents filled out the survey (33%). 82% of respondents indicated that they had seen a provider in the past year. There was no significant difference in male vs. female students (p=0.6131) or in age groups (p=0.9761). 40% responded that they had sought mental health resources for their child. Of those that had sought mental health resources, 77.7% were able to see a mental health provider. There was no significant difference between male vs. female in seeking mental health resources (p=0.3295) or being able to see a provider (p=0.2521).

Conclusions

We found that IEP students in this rural Oregon population were receiving annual wellness checks at a higher rate than the state Medicaid average of 41%. We suspect that our study had significant selection and non-response bias. Further study is needed to determine if these findings are generalizable.

Healthcare delivery research II

Concurrent session

10:15 AM
Friday, January 24, 2020
307 Sustained impact of a bronchiolitis home oxygen therapy care process model

T Ohlsen1

A Knudson2,*

K Korgenski1

M Hoffman1

DR Sandweiss1

T Glasgow1

E Coon1

1University of Utah, Salt Lake City, UT

2University of Utah School of Medicine, Salt Lake City, UT

Purpose of study

Beginning with the winter 2010-11 season, we implemented a care process model (CPM) to encourage hospital discharge with oxygen therapy for patients with bronchiolitis and mild hypoxemia without other indication for continued hospitalization. A previous study suggested initial reductions in length of stay and cost of hospitalization in the first year after implementation.

Methods used

We conducted a retrospective cohort study of children aged 2-24 months old discharged from 17 hospitals within the Intermountain healthcare system with a diagnosis of bronchiolitis. Patients with diagnosis codes for chronic lung disease, tracheostomy dependence, or pulmonary hypertension were excluded, as were encounters that occurred outside of winter respiratory season (May-October). The primary outcome was mean length of stay. Balancing measures included 7-day readmission rate and mean cost per episode of care, defined as the total cost of all hospital visits within 7 days of initial hospital discharge. Costs were adjusted for inflation to 2017 dollars. Outcomes were compared before and after CPM implementation using linear regression models in an annual interrupted time series approach, adjusted for patient age, gender, race, ethnicity, and insurance type.

Summary of results

A total of 9,887 patients met inclusion criteria (3,033 pre-implementation; 6,854 post-implementation). Implementation of a home oxygen therapy CPM was associated with immediate decreases in mean length of stay (difference -11.1 hours, 95% CI -12.8 to -9.5 hours) and mean cost per episode of care (difference -$768, a 7.8% decrease, 95% CI -$1,262 to -$273), without an immediate change in readmission rate (difference 0.2%, 95% CI -0.3 to 0.7%). These findings have been sustained for 7 years after implementation and represent more than $5 million in hospital cost savings.

Conclusions

The home oxygen therapy CPM has demonstrated sustained decreases in hospital length of stay and cost without an increase in readmissions.

308 Improving transition home from the neonatal intensive care unit using a discrete choice experiment: the clinician perspective

C Gong1,2,*

P Friedlich1,2

L Yieh1,2

A Lakshmanan1,2

1Children’s Hospital of Los Angeles, Los Angeles, CA

2University of Southern California, Los Angeles, CA

Purpose of study

Discharge from a neonatal intensive care unit (NICU) requires significant medical and social support. Discrete choice experiments (DCE) are based in economic theory and are used to estimate an individual’s preferences when faced with a choice scenario. We used a DCE to identify key features of a NICU transition-of-care (TOC) program among NICU clinicians nationally.

Methods used

We designed a DCE survey containing 6 attributes of various levels based on qualitative focus groups with families of NICU infants: follow-up duration (3-24 months), financial support ($500-4000/month), medical communication (appointment reminders, printed care plan, or directory of specialists), resource information (nutrition, housing, transportation, and financial aid), social support (peer, nursing, social work, or mental health), and medical information (durable medical equipment, diagnoses, medications, or early intervention services). Clinicians chose a preferred TOC program from 2 alternatives composed of varying levels of each attribute. Responses were analyzed via mixed logit models, and odds-ratios and willingness-to-pay for each attribute was estimated.

Summary of results

234 clinicians completed the survey. Each month of follow-up was worth $113. Appointment reminders were preferred vs. care plans or directory of specialists (OR=1.03, p=0.08 and 2.33, p<0.0001 respectively). Compared to housing, transportation, and financial aid information, nutrition information was more preferred (OR=1.35, 1.39, and 1.92 respectively, p<0.05). Nursing and social work support were preferred over peer support (OR=1.24 and 1.43, p<0.05) and worth $2,368 and $3,911, but mental health support was not (OR=0.93, p=0.06). Compared to durable medical equipment information, medication and early intervention services information were preferred (OR=1.19 and 2.08 respectively, p<0.05) and worth $1855 and $7992 while diagnosis information was not (OR=0.68, p=0.01).

Conclusions

Clinicians value longer duration of follow-up, nursing and social work support, and information about medications and early intervention services. Future work will compare results with those of patients’ families.

309 Readmission risk factors after hospitalization for pneumonia in diabetic adults

M Yu1,*

A Firek2

1Loma Linda University, Loma Linda, CA

2Riverside University Health System, Moreno Valley, CA

Purpose of study

Readmissions to the hospital are considered an indicator of quality of care. Pneumonia is a common cause of hospitalization, and diabetes (DM) is a known risk factor for both admission and readmission in patients with pneumonia. However, there is a lack of studies specifically evaluating readmission risk factors and fatal readmission risk factors in patients with DM originally admitted for pneumonia. Determining these risk factors may direct efforts in decreasing readmission for these common diagnoses. In this project we determined the risk factors for readmission in patients with pneumonia and DM.

Methods used

The 2013 National Readmission Database (NRD) was used to identify DM adults discharged alive after hospitalization for pneumonia (weighted N=229849), whether these adults were readmitted within 30 days of discharge, and mortality during the readmission. We identified readmission risk factors including comorbidities, procedures, and demographics. We also determined risk factors specifically for readmissions resulting in mortality.

Summary of results

Overall, 18.1% of DM patients were readmitted. Top three readmission reasons were pneumonia (14.7%), heart failure (9.4%), and septicemia (8.7%). This differed from non-DM patients in which the top three readmission reasons were pneumonia (17.2%), septicemia (9.2%), and COPD (6.5%). In DM patients, independent risk factors for readmission included metastatic cancer (adjusted OR 1.68), solid tumor (aOR 1.61), drug abuse (aOR 1.56), and hemodialysis (aOR 1.38). Independent protective factors included private insurance (aOR 0.78). Independent risk factors for mortality during readmission included metastatic cancer (aOR 3.62), solid tumor (aOR 2.36), age >65 (aOR 2.03), blood transfusion (aOR 1.96), lymphoma (aOR 1.72), and weight loss (aOR 1.65).

Conclusions

Our study demonstrates that pneumonia is the leading reason for readmission in both DM and non-DM patients. In addition, patients with DM are at higher risk for readmission due to heart failure compared to non-DM. The risk factors could be used to identify patients who are at higher risk such as focused specific post discharge support. Since drug abuse is a modifiable risk factor, interventions to decrease drug abuse in DM patients may decrease readmission rates.

310 Timing of addiction consultation in hospitalized patients starting buprenorphine

H Sandhu1,*

J Takagi-Stewart2

JI Tsui1,2

E Bhatraju1,2

JO Merrill1,2

M Iles-Shih1,2

JW Klein1,2

1University of Washington, Seattle, WA

2Harborview Medical Center, Seattle, WA

Purpose of study

A growing body of evidence supports initiation of medications for OUD, including buprenorphine, during hospitalization. It is unclear what factors during hospitalization are associated with likelihood of linkage with ongoing addiction treatment after discharge. This study explores the associations between early addiction consultation and medication initiation during hospitalization and successful linkage with outpatient treatment.

Methods used

A retrospective chart review was completed at an urban, academic hospital for hospitalized patients with opioid use disorder. All hospitalized patients with opioid use disorder who were evaluated by the addiction medicine consult service from January 2018 to June 2019 and agreed to start buprenorphine were included. Timing of consultation was determined based on the proportion of hospitalization completed (days from admission to consult ÷ length of stay). Binary logistic regression was used to compare timing of consultation with inpatient buprenorphine initiation. An additional logistic regression was used to compare the odds of successful linkage (defined as any outpatient follow up within 30 days of discharge) between patients initiated on buprenorphine during hospitalization with those receiving a prescription at discharge. All analyses were completed with Stata, version 16.

Summary of results

During the study period, 145 patients met eligibility criteria. Individuals with earlier addiction consultation were more likely to start buprenorphine during hospitalization compared to those evaluated closer to discharge (p=0.000, OR=0.04). There was no significant difference in successful linkage between the 115 patients with inpatient buprenorphine induction versus 30 patients that started at discharge (p=0.15, OR=1.89).

Conclusions

Hospitalized patients with OUD who have earlier addiction consultation are more likely to have inpatient buprenorphine induction. Additional engagement with clinicians and opportunities to discuss treatment goals may allow patients to start buprenorphine early. Inpatient initiation of buprenorphine is not associated with increased odds of linkage within 30 days of discharge compared to providing a prescription of buprenorphine at discharge.

311 Deep learning classification of prostate MRI sequences

P Bhatter1,*

M Bardis1

C Chahine1

A Ushinsky2

D Fujimoto1

WA Grant1

P Chang1

R Houshyar1

1University of California Irvine Medical Center, Orange, CA

2Washington University, St. Louis, MO

Purpose of study

An early imaging preprocessing step involves uniformly labeling data sources. For MRIs, this represents a challenge due to the (1) heterogeneity in vendors, sequences, and protocols, and (2) potential mislabeling that has been reported to be as high as 10%. Furthermore, for multiparameteric assessment for prostate MRIs, this can be a hurdle for research and clinical studies that rely on comparisons. Therefore, we develop a neural network that can automatically label sequences.

Methods used

This retrospective study included patients who had a prostate MRI and an ultrasound MRI fusion transrectal biopsy between September 2014 and August 2018. For this study, the DICOM header information was used to classify 57,063 images as either T2W, DWI, or DCE. The number of T2W, DWI, and DCE images used were 17,195, 23,576, and 5,918 respectively. The convolutional neural network (CNN) used 46,689 images for training and 11,412 images for validation. The two-layered convolutional neural network was then trained for 8,000 iterations (figure 1). A fully connected layer with one hidden layer was used before the output layer. The softmax cross entropy loss function was used to adjust the weights during training.

Summary of results

In validation, the CNN accurately classified 11,410 out of 11,412 images for an accuracy of 99.2%.

Conclusions

A CNN can be accurately used to identify the sequences of T2W, DWI, or DCE. By using a CNN to complete the series identification, the process of automatically examining a prostate mpMRI and determining the PI-RADS score for a lesion will be expedited. The time needed to classify the series will be reduced and the DICOM header descriptions that are entered by the technologists can be ignored.

312 Cranial computed tomography utilization and pecarn compliance among pediatric head trauma patients

C Chan*

C Vercio

Loma Linda University, Loma Linda, CA

Purpose of study

Cranial computed tomography uncovers a variety of injuries in pediatric blunt head trauma patients. However, cranial CT poses many risks for these children and compliance with the Pediatric Emergency Care Applied Research Network (PECARN) recommendations seeks to reduce the number of CT scans ordered without missing significant traumatic brain injuries. The aim of this project is to assess the degree of compliance with the PECARN criteria following blunt head trauma among children in a single emergency department and identify the common findings that prompted cranial CT utilization over observation.

Methods used

This is an observational cross-sectional study looking at patients under the age of 18 who received cranial CT scans over 6 months in a single county emergency department. Via retrospective chart review, we determined whether or not PECARN criteria were met and identified symptoms common among patients in the category in which either CT or observation would be acceptable.

Summary of results

253 head CTs were obtained in the pediatric emergency department from January to June of 2019—68 without head trauma, 24 with unknown head trauma, and 137 with recorded head trauma. Among the 137 patients with head trauma, 69.3% of the patients were categorized as ‘CT vs. observation’ under PECARN criteria, 21.2% as PECARN negative, and 10.2% as PECARN positive. 7 out of 95 CT vs. observation patients were discovered to have traumatic brain injuries such as subdural hemorrhages and fractures on CT, although none required neurosurgical intervention. Among these 95 patients, we identified the most common presenting symptoms of headaches, loss of consciousness, vomiting, nausea, and lethargy. Headaches were reported in 55% of the CT vs. observation cases, loss of consciousness in 40%, and vomiting in 26%.

Conclusions

In accordance with PECARN criteria, cranial CT may be over-utilized in pediatric head trauma patients presenting to this hospital site, as there were a number of patients who did not meet PECARN criteria but had a cranial CT performed. We will use quality improvement methodology to decrease the utilization of cranial CT in those who do not meet PECARN criteria. We will additionally look to discover what drives decision-making processes for providers when a patient is in the CT vs. observation category.

313 Comparison of computer and face to face delivery of the sport concussion assessment tool symptoms

L Cone1,2,*

P Holmberg2

S Olmon2

C Owens2

K Davis2

L Kelly2

1Western University of Health Science, College of Osteopathic Medicine of the Pacific, Pomona, CA

2California Lutheran University, Thousand Oaks, CA

Purpose of study

With an increase in sport-related concussions and heightened accessibility of technology, computer-based assessments via direct entry have become widely used among sports medicine professionals. The advantages of direct participant entry via computer over person to person interview protocols include instantaneous results and a greater capacity to gain larger study populations via ease of response entry and removal of the need for a qualified interviewers. In addition, privacy among participants via the direct computer entry may limit some bias as a consequence of threat of disclosure and social desirability related to in person interviews. Currently no studies exist which compare the validity of results of SCAT using computer-based vs in person interview, thus the aim of this study was to compare the differences between collection methods.

Methods used

Three hundred and eighty-five (N=385) National Collegiate Athletic Association Division III student-athletes from CLU completed the SCAT symptoms via face to face interviews and a direct entry platform. Correlations and KAPPA statistics were used to compare the results of the assessment protocols.

Summary of results

Spearman’s rank correlation coefficient ranged from r=0.189 - 0.775 (P<0.001) for the total group; r=0.142 - 0.788 (P<0.001) among males; and, r=0.093-0.743 (P<0.001) among females. KAPPA statistics for the total group ranged from 0.089-0.586 (P<0.001), demonstrating poor-to-good strength, for males ranged from 0.130 – 0.620 (P<0.001), demonstrating poor-to-good strength, and for females ranged from 0.091 – 0.529 (P<0.001), demonstrating poor-to-moderate strength.

Conclusions

Overall, these results demonstrate a significant relationship between direct computer entry and face to face delivery of the SCAT for both group and gender. In addition, these findings suggest that the direct computer entry platform is as accurate as the in-person interviews, and either method of SCAT administration would be reliable for use by medical practitioners in determining athlete concussion symptoms and status.

314 The role of do not attempt resuscitation directives in treatment of patients with out-of-hospital cardiac arrest

R Winchell1,*

J Blackwood2

CR Counts1

C Drucker2

A Jennerich1

K Pompeo3

J Waldron1

S Feder4

T Rea1,5

M Eisenberg1,5

M Sayre1

P Kudenchuk1

1University of Washignton, Seattle, WA

2Seattle and King County, Division of Emergency Medical Services, Seattle, WA

3Shoreline Fire Department, Shoreline, WA

4King County Medic One, Seattle, WA

5King County EMS, Seattle, WA

Purpose of study

A Do Not Attempt Resuscitation (DNAR) directive is a physician order that conveys patient wishes to not be resuscitated from a cardiac arrest. Emergency medical services (EMS) providers encounter DNAR orders when managing out-of-hospital cardiac arrest (OHCA). Little is known about their prevalence or how they might affect care provided.

Methods used

We retrospectively analyzed all treated adult OHCA patients in 2018 that had DNAR orders per EMS in a large urban community. Data were abstracted from EMS PCRs, 911 dispatch audio recordings, and defibrillator ECG and audio recordings. We compared patients who received full resuscitative efforts to those with some limitation of their resuscitation.

Summary of results

Of the 98 included patients, the average age was 80 years (SD ±10.6), 54 (55%) were male, 54 (55%) had their OHCA at home, and 53 (54%) received bystander CPR. Twenty-three patients (23.5%) received full efforts, while 75 (76.5%) received limited efforts. The full efforts group were more likely to have an initially shockable rhythm (17% vs. 7%), and twice as likely to have a witnessed arrest (70% vs. 33%, p<0.05). Twenty patients (87%) who received a full resuscitation had limited or no interventions on their DNAR. DNAR orders were onsite in 78% of cases and obtained by EMS on average 6.5 minutes (SD ±4.6) and 7.1 minutes (SD ±6.1) after their on-scene arrival in the full efforts and limited efforts groups, respectively. Family confusion/contradiction of DNAR orders occurred in the full efforts group in 9 patients (39%) compared to 10 patients (13%) in the limited efforts group. Nineteen patients (83%) receiving full efforts and six patients (8%) in the limited efforts group achieved ROSC.

Conclusions

Delays in the presentation of DNAR orders during OHCA are common. This delay combined with family member confusion/contradiction of the DNAR orders results in undesired resuscitation. How DNAR directives are best operationalized and implemented requires further evaluation.

315 Coexisting chronic disease increases the risk of misclassification of type 1 diabetes

E Choi1,*

F Qeadan2

MR Burge1

1University of New Mexico HSC, Albuquerque, NM

2University of Utah, Salt Lake City, UT

Purpose of study

An accurate of diagnosis of diabetes type in the Electronic Medical Record (EMR) is essential for effective treatment, prevention of medical errors, and the validity of research that depends upon these large databases. We hypothesize that Type 1 Diabetes (T1D) patients with chronic comorbidities will be more likely to be misclassified as having Type 2 Diabetes (T2D) compared to those without such comorbidities.

Methods used

Data were collected from HealthFacts® from 2006 to 2017 from patients diagnosed with T1D or T2D using ICD-9/10 codes. Of those, 9,676 patients were coded for T1D alone and were compared to 271,428 patients who were coded for both T1D and T2D. Patients coded for T2D alone were excluded from analysis. Multiple logistic regression was used to estimate the odds of misclassification for patients with coexisting comorbidities, including hypertension, cardiovascular disease (CVD), asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), alcohol use disorder (AUD), and depression as compared to those without such comorbidities. The model is adjusted for age, sex, race, urban place of residence, marital status, and health insurance.

Summary of results

Of 3.3 million diabetes patients, 8.3% were misclassified at least once. Of 281,104 T1D patients, 47.9% had coexistent hypertension, 54.4% had CVD, 1.1% had asthma, 13.4% had CKD, 6.7% had COPD, 9.0% had depression and 1.8% had AUD. In general, patients with chronic disease were at higher risk for misclassification of diabetes (see table 1). For example, patients with a history of CVD or depression had significant 2.24-fold and 2.20-fold increases, respectively, in the odds of diabetes misclassification compared to those without such a history.

Conclusions

A history of comorbid hypertension, CVD, COPD, CKD, AUD, and/or depression significantly increases the risk of misclassification of T1D.

Hematology and oncology II

Concurrent session

10:15 AM
Friday, January 24, 2020
316 Fusion-negative oncogenes rescue fusion-positive rhabdomyosarcoma from GATOR2 dependence

DA Fajardo1,*

AJ Sabnis2

1University of Nevada, Reno School of Medicine, Reno, NV

2University of California, San Francisco, San Francisco, CA

Purpose of study

Rhabdomyosarcoma (RMS), the most common pediatric soft-tissue sarcoma, is comprised of two genetic subtypes. Fusion-positive (FP) RMS is characterized by PAX3-FOXO1 or related translocations, while fusion-negative (FN) RMS harbors mutations in the RAS/PI3K pathway. Patients with high-risk RMS have poor outcomes. Characterizing the molecular connections between genomic drivers and cellular fitness may enable future therapeutic advancements in RMS.

Using a CRISPRi screen, we identified two components of the GATOR2 signaling complex, an activator of mTOR, as necessary in FP RMS but not FN RMS. We hypothesize that FN oncogenes are sufficient to overcome dependence on GATOR2 for mTOR-regulated proliferation.

Methods used

To characterize the effects of FN oncogenes on GATOR2 loss, we conducted competition growth assays using FP RMS cells, and FP cells transduced with the FN oncogenes NRASQ61H and FGFR4V550E. We used CRISPRi to knockdown GATOR2 components in these cells and compared the growth of parental and oncogene-modified cell lines. We measured mTOR activation in these conditions by immunoblotting for p70S6K phosphorylation and 4EBP1 binding to m7-GTP sepharose beads.

Summary of results

We confirmed that knockdown of GATOR2 components in FP RMS cells decreased their growth compared to control cells. However, introduction of FN oncogenes partially rescued cells from GATOR2 loss. This was also seen with inactivation of the negative mTOR regulator TSC1. Immunoblots showed that FN oncogenes did not rescue p70S6K phosphorylation after GATOR2 loss. By contrast, they did induce dissociation of 4EBP1 from m7-GTP, suggesting a restoration of cap-dependent translation.

Conclusions

Our data demonstrate that loss of GATOR2 in FP RMS limits mTOR activation by environmental amino acid signaling. However, we find that FN oncogenes are sufficient to rescue cells from GATOR2 loss. Additionally, our data indicate that reduced cap-binding by 4EBP1, but not phosphorylation of p70S6K, is tied to the survival and proliferation of FP RMS. Based on our findings, we plan future investigation of the specific roles of 4EBP1 in RMS. Our work provides molecular insights into the pathways upstream (eg, GATOR2) and downstream (eg, 4EBP1) of mTOR which are critical for RMS survival.

317 Exploring T2-flair mismatch among idh-mutant astrocytomas: patterns of evolution and further characterization

J Graber1,2

P Throckmorton3,*

1University of Washington, Seattle, WA

2Alvord Brain Tumor Center, Seattle, WA

3University of Washington School of Medicine, Seattle, WA

Purpose of study

The T2-FLAIR mismatch sign (T2FM) is a newly defined biomarker on MRI which demonstrates high predictive value for isocitrate dehydrogenase (IDH) mutant astrocytomas among lower grade gliomas, helping facilitate early diagnosis and treatment planning. The purpose of this study is to further explore T2FM by characterizing tumors which display the sign, evaluating the predictive value of its various definitive criteria (T2 homogeneity and hyperintense FLAIR rim), and describing patterns in its temporal development.

Methods used

Medical records from 64 patients with astrocytomas treated at the Alvord Brain Tumor Center were assessed for age at diagnosis, gender, WHO grade, molecular status, seizure history, tumor characteristics on pre-treatment CT, MRI, and pathology, documentation of T2FM, treatment course, and temporal changes in tumor appearance. Cases were divided into those meeting ‘classic’ T2FM definitive criteria (homogenous T2, FLAIR rim positive), those considered ‘ambiguous’ and not fulfilling all criteria (heterogeneous T2, FLAIR rim positive), and those which were T2FM negative (FLAIR rim negative). Groups were compared using Chi square and qualitative analyses.

Summary of results

Including ‘ambiguous’ tumors increased T2FM sensitivity for IDH mutant astrocytomas 30% without decreased specificity. Tumors with T2FM characteristics were more cystic, less enhancing, and affected younger patients. T2FM was 100% persistent in subtotally resected residual tumors and disappeared with radiotherapy, persisted in 5/8 recurrent tumors which were originally T2FM positive, and was identified in tumors with high grade characteristics. Trends were identified among patient age, tumor location, mismatch status, and IDH status.

Conclusions

A hyperintense FLAIR rim, regardless of T2 appearance, demonstrates high predictive power for IDH mutation among astrocytomas and may be used to determine T2FM status. Additionally, T2FM evolves in predictable patterns and may be seen in higher grade gliomas, findings which have not been previously described. Lastly, trends among patient age, tumor location, and T2FM may allow inference of IDH status when sequencing information is not available, further expanding its clinical utility.

318 EphrinB2 and EphB4 modulates invasion and proliferation pathways in glioblastoma multiforme

S Bhatia

S Bukkapatnam*

S Karam

University of Colorado School of Medicine, Aurora, CO

Purpose of study

The aggressive nature of Glioblastoma Multiforme may be attributed to the complex invasive and proliferative pathways that these tumors commandeer to promote tumorigenesis. EphrinB2, a receptor tyrosine kinase, has recently emerged as a therapeutical target responsible for modulating those pathways, but is embedded in controversy. The literature is contradictory with tumor-promoting and suppressive roles of ephrinB2, depending on the model used. This study was initiated with a goal to decipher the true role of ephrinB2 in GBM.

Methods used

GBM cell lines were modified to overexpress or knockdown ephrinB2. Upon implanting these tumor cells orthotopically in mouse brains or flanks, tumor volumes and survival were monitored. Whole brains were harvested to examine via immunohistochemistry.

Summary of results

Transcript levels of ephrinB2 in gliomas showed that ephrinB2 was overexpressed in GBM, correlating with poor survival outcomes. Hypothesizing an oncogenic role for ephrinB2, we initiated in vivo studies with analysis using imaging systems like CT scans. In contrast to our initial hypothesis, our data showed that ephrinB2 was decreasing tumor volumes (p=0.0003) and enhancing survival (p=0.027). Therefore, we examined ephrinB2’s receptor, EphB4. We dissected this bidirectional axis of signaling and identified downstream effects on invasion and proliferation. Consistent with the literature, we found a dichotomous relationship. Our data show that activating or inhibiting forward EphB4 receptor versus reverse ephrinB2 ligand signaling have opposing effects on GBM tumor invasion and proliferation.

Conclusions

We illustrate that the activation of EphB4 by ephrinB2 produces an anti-proliferative and pro-invasive effect, based on activating either forward or reverse signaling, in GBM. These data highlight the importance of considering the signaling of both the receptor and ligand, rather than either in isolation, to truly understand the downstream effects of ephrinB2 on GBM behavior, explaining the controversial results. This is of particular gravity when designing therapeutic interventions targeting the EphB4-ephrinB2 signaling complex in GBM, as the downstream effects of inhibiting or activating ephrinB2 must be considered, as it also affects the signaling function of EphB4 in the adjacent cell.

319 Cytokine and growth factor profiling for the differentiation of multiple myeloma patients from those with monoclonal gammopathy of unknown significance

TB Martins1,*

D Atanackovic2

T Luetkens2

D Banerjee1

HR Hill3

1ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT

2Huntsman Cancer Institute, Salt Lake City, UT

3University of Utah School of Medicine, Salt Lake City, UT

Purpose of study

To determine if we could differentiate individuals with multiple myeloma (MM) from those with monoclonal gammopathy of unknown significance (MGUS) based on bone marrow (BM) and peripheral blood (PB) plasma cytokine and growth factor profiles. MM is a disease of dysplastic plasma cells that localize to bone marrow, producing high levels of immunoglobulin heavy and light chains, which can lead to hypercalcemia, renal disease, anemia, and bone lesions. MM is often preceded by increased immunoglobulin production but no clinical symptoms referred to as MGUS. IL-16 is an important growth factor in the development of myeloma with B cell activating factor (BAFF), and IL-17 related to the increase in IL-16.

Methods used

A multiplexed assay was developed for IL-2r, IL-6, IL-8, IL-16, IL-17, VISTA (V-domain Ig suppressor of T cell activation) and BAFF. Bone marrow and plasma samples obtained from 154 diagnosed multiple myeloma and 16 MGUS patients were tested.

Summary of results

BAFF expression was significantly elevated in MM compared to MGUS patients in both BM (3,529 vs 1430 pg/mL, p<0.05) and PB (2,167 vs 948 pg/mL, p<0.05). IL-16 and IL-2r were also more strongly expressed in MM vs MGUS, but statistical differences were only observed in the BM samples. IL-16 BM (378 vs 124 pg/mL, p<0.05) and IL-2r BM (1001 vs 124 pg/mL, p<0.05). Matched BM and PB samples from the MM patients demonstrated no strong correlation for BAFF (Slope 0.349, r2 0.362), IL-16 (Slope 0.014, r2 0.029) or IL-2r (Slope 0.313, r2 0.244).

Conclusions

IL-16 and BAFF, known tumor promoting factors, and IL-2r, an immune inflammatory marker, were significantly increased in multiple myeloma when compared to MGUS patients. All markers investigated were expressed in greater concentrations in the BM then the peripheral blood, but no direct correlation was observed. Monitoring IL-16, BAFF and IL-2r marker profiles of MGUS patients may allow us to predict the onset of Multiple Myeloma and may potentially lead to anti-cytokine therapy for this malignancy.

320 The effect of previous chemotherapy treatment on ovarian follicle count in ovarian tissue cryopreserved for fertility preservation

AS Robles1,2,*

K Lakhoo2

S Lane2

1University of Nevada Reno School of Medicine, Reno, NV

2University of Oxford, Oxford, UK

Purpose of study

In the last several years, ovarian tissue cryopreservation (OTC) has become a more widely accepted method of fertility preservation for children and young adults who are at high risk of infertility as a result of cancer treatment but who are not unable to store mature eggs. In some fertility preservation programs, prior exposure to chemotherapy is an absolute exclusion criterion. In the Oxford Programme, patients are eligible for tissue storage if they have undergone chemotherapy prior to collection. This abstract presents the result of comparative analysis of follicle counts across this cohort of patients.

Methods used

The pathology data from 306 female patients enrolled in the Oxford Reproductive Tissue Cryopreservation Programme (ORTC) between September 2013 to June 2019 was analyzed. This cohort included patients between the ages of 2 months to 38 years old who fulfilled the ORTC eligibility criteria. Follicle counts were analyzed by age, prior exposure to chemotherapy and diagnosis.

Summary of results

All patients regardless of age, diagnosis or previous exposure to chemotherapy had follicles within the tissue analyzed in the pathology laboratory. Age, across all data sets, had the most significant effect on follicle numbers. For patients who had previously been exposed to chemotherapy, while the follicle count across the age range was lower than age matched patients who had not had pre-chemotherapy treatment, the effect of previous chemotherapy was most significant in the older patient cohort. Diagnosis as an independent variable did affect follicle numbers per se.

Conclusions

These results demonstrate that ovarian tissue collected from patients both pre- and post-chemotherapy contains significant numbers of primordial follicles. Age had a more significant effect on follicle numbers than previous exposure to chemotherapy. This data supports the inclusion of patients who have had non sterilizing treatment in ovarian tissue cryopreservation programs for children and young adults.

322 Use of aromatherapy as a complementary therapy in alleviating chemotherapy related adverse effects in cancer patietnts

Jl Williams1,2,*

I Bade2

S Arora2

M Ell2

G Shen2

S Udata2

B Afghani2,3

1University of Southern California, Los Angeles, CA

2University of California Irvine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Use of aromatherapy in relieving anxiety and pain in different settings has been reported but its use in alleviating the side effects related to chemotherapy or radiation therapy in cancer patients is less clear. The purpose of this study was to investigate the effectiveness of aromatherapy in alleviating the adverse effects related to chemotherapy or procedures in cancer patients.

Methods used

A literature review using online resources including Pubmed and Google Scholar with the keywords ‘cancer aromatherapy’ was performed. Only studies of adult cancer patients with a control group published after 2005 were included in our analysis.

Summary of results

Of the 20 articles, only 7 met our inclusion criteria (table 1 below). The primary reason for exclusion was the lack of a control group. The types of essential oils and length of aromatherapy treatment was variable among the studies. In 5/7 studies, aromatherapy showed improvement in symptoms, such as nausea, vomiting or pain but the beneficial effect on vital signs was less clear. In addition to the included studies, we searched for reports of side effects associated with aromatherapy. Allergic reactions were seen in minority of patients, and one study found an association between nosocomial outbreak of drug resistant Pseudomonas infections and use of inhalation aromatherapy.

Conclusions

Our review suggests aromatherapy may have a role in alleviating some of the symptoms associated with chemo/radiation therapy in adult cancer patients. However, due to potential serious side effects, caution should be taken in the use of aromatherapy in cancer patients. Larger studies that control for the type of aromatherapy and other confounding variables are needed.

323 Online hepatocellular carcinoma patient resources – meaningful impact or poor ‘de-livery’?

J Li1,*

J McLeod2

P Ingledew1,3

1UBC Faculty of Medicine, Vancouver, BC, Canada

2University of Alberta, Edmonton, AB, Canada

3BC Cancer, Vancouver, BC, Canada

Purpose of study

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer-associated death, claiming 800,000 lives each year globally. At the same time, an increasing number of patients are using the Internet as a source of health information. However, limited research has been done on assessing the quality of HCC websites. Therefore, we aim to systematically evaluate the quality of online HCC information.

Methods used

The term ‘hepatocellular carcinoma’ was searched using the search engine Google and the meta-search engines Dogpile and Yippy. The overall highest-ranked 100 websites were extracted based on pre-specified inclusion and exclusion criteria. A previously validated tool was used to evaluate quality based on several parameters including affiliation, accountability, interactivity, structure & organization, readability, and content quality.

Summary of results

The search yielded over 1,100 websites. Of the top 100, 53% were commercial. Although 95% disclosed ownership and sponsorship, other measures of accountability were poor – only 30% identified their author(s), 42% cited sources, and 33% were updated within the past two years. Average readability was judged to be at a grade 11.8 level using the Flesch-Kincaid grading system, which is significantly higher than the recommended grade-six level (p<0.0001). Definition and symptoms were the most commonly covered topics, while prognosis and prevention were the least covered. Content accuracy was high among covered topics, except for incidence, for which 23% had mostly inaccurate information. Overall, non-commercial websites were higher in quality compared to commercial ones (p<0.002).

Conclusions

Although website contents are generally accurate, authorship, attribution, currency, and coverage are currently deficient among many HCC websites. Additionally, difficult readability may pose a barrier for patient comprehension. Despite high public demand for information regarding prevention and prognosis, very few websites cover those topics. Healthcare professionals should be aware of the limitations of online HCC information, so they can be proactive in guiding patients to reliable resources to address their specific needs.

324 A rare case of abdominal pain:related to idiopathic left ovarian vein thrombosis

G Petersen1,2

M Kalluri1

N Trang1,*

1Kern Medical, Bakersfield, CA

2UCLA, Los Angeles, CA

Purpose of study

Ovarian vein thrombosis(OVT) first described in 1956 is a rare thrombotic condition with an incidence of 60-fold lower compared with leg DVT, yet could be potentially life threatening. Upon literature review, OVT cases are most often seen on the right ovarian vein. We describe an unusual case of idiopathic OVT, probably the first reported case of idiopathic left OVT

Methods used

Retrospective case report

Summary of results

We report the case of a 47 year old G7P7 Caucasian female with no past medical history who presented to a local hospital for acute onset of back pain radiating to her ribs and colicky left lower quadrant pain for 1 day. She denied any associated symptoms. CT scan of the abdomen and pelvis with IV contrast revealed left gonadal vein thrombosis. She was then transferred to our facility for further management and treatment. On admission, patient was afebrile and hemodynamically stable. Pelvic ultrasound showed normal endometrium, no mass or cyst in the uterus or ovary with left ovary measuring 2.4cmx1.5cm with normal blood flow. Work up for inherited and acquired thrombophilia was obtained and later proved unremarkable. Therefore, the diagnosis of OVT was made and anticoagulation treatment was initiated with low molecular weight heparin (Levonox 1mg/kg q12h).Patient‘s symptoms completely resolved in the next 24 hours and she was discharged home on direct oral anticoagulant (Rivaroxaban) for 3 months. At her two month follow-up appointment, CT of abdomen and pelvis with IV contrast showed complete resolution of the left ovarian vein thrombosis

Conclusions

OVT is an uncommon yet potentially life threatening thrombotic condition with a 25% risk of developing into PE and 4% mortality rate. Based on our research, 70-90% OVT cases occur on the right ovarian vein, whereas 11-14% are bilateral. OVT affects mostly pospartum women but might also be associated with pelvic inflammatory disease, malignancies, and pelvic surgical procedures. This is probably the first case reported for idiopathic left OVT in a healthy woman. Standard guidelines for managing OVT are lacking. Historically, heparin followed by bridging to warfarin until a therapeutic INR is achieved was the main stay of treatment. Recently, direct oral anticoagulants offers a potentially useful alternative even the efficacy of these drugs has not been studied yet.

Infectious diseases II

Concurrent session

10:15 AM
Friday, January 24, 2020
325 Measles vaccine response varies in 12-month-old kenyan children which may increase measles transmission

DS Mason*

R Rochford

University of Colorado School of Medicine, Aurora, CO

Purpose of study

Measles is a preventable infectious disease, but still presents a large burden of disease throughout the world. In 2017, measles caused roughly 110,000 deaths worldwide. The measles vaccine has greatly reduced measles-related morbidity and mortality. Despite this, Africa still suffers from this disease. Reduced measles vaccine efficacy has been reported in Sub-Saharan Africa. The aim of this study was to determine the response to measles vaccine following routine 9-month vaccination in infants living in a malaria endemic region of sub-Saharan Africa.

Methods used

Plasma samples were collected from children from Kisumu, Kenya, at 12 months of age, three months after routine vaccination for measles. These plasma samples were tested by indirect ELISA to measure anti-measles antibodies. Each sample was analyzed in triplicate. Samples that had one well with an optical density >0.5 different from the other two wells were trialed again to account for pipetting error. If after reanalysis the wells of the sample no longer had a well with a difference >0.5, the sample was included in analysis with its original wells excluding the well that differed >0.5. However, if the sample again had a well that differed in optical density from the other two wells by >0.5, the sample was considered an outlier and excluded from analysis. Eleven samples were excluded, leaving 143 samples included in the final analysis.

Summary of results

The mean optical density was 1.83 (SD ± 0.72; 95% CI 1.71-1.94), with a minimum optical density of 0.42 and maximum optical density of 3.92. Twenty-two participants had an OD of 1.0 or less, raising concern of not being immunoprotective against measles.

Conclusions

These twenty-two participants represent 15% of the total participant sample. For the measles vaccine to be protective, roughly 95% of the community must be vaccinated to prevent transmission. This then represents a possibility for transmission of measles to occur in these communities, particularly in young children who are more at risk of infection. The variability in levels of anti-measles antibodies following routine measles vaccination in this sample are not entirely understood and will be the subject of ongoing analysis.

326 Incorporating zinc oxide nanoparticles in contact lens material to improve biocompatability

G Davis1,*

A Gapeeva1,2

T Cho1

F Spors3

S Fuchs1

1Western University of Health Sciences, Pomona, CA

2Christian Albrechts Universitat, Kiel, Germany

3Western University of Health Sciences, Pomona, CA

Purpose of study

Zinc oxide nanoparticles (ZON) have been found to filter UV radiation, prevent bacterial growth and encourage wound healing. Our purpose is to harness these useful properties by incorporating ZON into gels which are otherwise chemically identical to modern contact lenses. We will then test our enhanced contact lenses to see how their hydrophilicity, UV filtration and antimicrobial properties have changed. If successful, the implications may someday afford contact lens wearers a safer and more comfortable contact lens experience.

Methods used

Gels chemically identical to modern contact lenses were produced with varying ratios of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA), crosslinked with ethylene glycol dimethylacrylate (EGDMA), and heat polymerized in presence of 4,4’-Azobiz(4-cyanovaleric acid).

The wettability of these gels was measured by photographing a fully submerged, .2 cc, sessile air bubble as it contacted the gel surface in both deionized water and saline solutions. The angle between air bubble and gel quantified how varying ratios of HEMA:MAA impacted the hydrophilicity of the gels.

Summary of results

To date, we have successfully produced polymerized material that resembles modern contact lenses in strength, flexibility, hydrophilicity and transparency. By experimenting with different ratios of HEMA:MAA and polymerization methods, we have established that a 70:30 HEMA:MAA ratio coupled with thermoinitiator consistently produces the strongest, clearest and most flexible lenses.

Conclusions

Now that we have successfully established a method for polymerizing gels. We will be able to move to the next steps which include:

  • Incorporating ZON into gels with the established 70:30 HEMA:MAA ratio.

  • Comparing how ZON impacts lens wettability using the sessile drop technique.

  • Growing bacteria on lenses to test antimicrobial properties of nanoparticles in lens polymer.

327 Assessment of mutant staphylococcus aureus and MRSA strains for drug lead optimization

AC Lazarski1,*

N Molasky2

JR Gillespie2

F Buckner2

1The University of Texas at El Paso, El Paso, TX

2The University of Washington, Seattle, WA

Purpose of study

Antibiotic resistance is an issue for the treatment of bacterial infections. S. aureus, especially methicillin resistant S. aureus (MRSA), has developed resistance to many current treatments. The increase in resistance demands a response to develop alternative therapies. The methionine t-RNA synthetase (MetRS) enzyme of bacteria is a novel drug target for many gram-positive species, including S. aureus. A series of small molecule inhibitors is being developed that bind this target. To understand and mitigate the risk of resistance developing to this new target, experiments were performed to characterize mutations that confer resistance.

Methods used

Using tryptic soy agar plates containing four times the MIC of three different MetRS inhibitors, resistant S. aureus mutants were generated. Eight to 12 resistant colonies were selected and DNA sequenced to locate mutations in the MetRS gene. Mutations in the enzyme were modelled using I-TASSER and SWISS Model for visualization of the mechanism of resistance, and MICs of resistant strains were measured following CLSI guidelines.

Summary of results

Mutant S. aureus colonies contained mutations I57N, V108M, H101P, and V105F in the MetRS gene. The magnitude of shifts in the MIC of inhibitors was dependent on the mutation present, with I57N causing the highest increase in MIC of the newly sequenced mutations. Molecular models of previously identified MRSA mutants elucidated potential mechanisms of resistance. Mutations affected one of two binding regions in the MetRS enzyme, the methionine binding pocket or auxiliary pocket (AP). Changes in the AP pocket caused greater shifts in MIC, but occurred less often. Assessment of the inhibitors MIC revealed that molecules with no halogen substituents in the AP binding region, or flexible regions, maintained better activity on mutant MRSA strains.

Conclusions

To optimize MetRS inhibitors for S. aureus and other gram-positive bacteria, mechanisms of resistance and cross resistance were investigated. Through experiments on resistant strains, new MetRS inhibitors have been generated limiting the effects of resistance mutations. This work adds to our progress of developing a novel antibiotic class that is not susceptible to inducing antibiotic resistance.

328 Palmitic acid potentiates mycobacterial growth in macrophages

S Schwarz*

A Reynolds

AD Gaustein

GJ Peterson

JD Simmons

TR Hawn

University of Washington School of Medicine, Seattle, WA

Purpose of study

Mechanisms that mediate natural resistance to Mycobacterium tuberculosis (Mtb) infection in highly exposed individuals are unknown. Using transcriptomic profiling of primary monocytes, we identified palmitic acid (PA)-induced genes that were enriched in donors with latent Mtb infection (LTBI) when compared to donors who resist infection despite high exposure. PA has known pleiotropic effects on macrophage responses including the activation of the NLRP3 inflammasome to increase IL-1β secretion. We hypothesized PA treatment of infected macrophages would impact the early mycobacterial response.

Methods used

Intracellular BCG-cherry and Mtb-mlux replication within WT U937 macrophages was measured by fluorimetry and luminometry, respectively. Mtb-mlux growth was also measured in U937 cells with inactivating mutations in inflammasome genes (NLRP3 and NLRC4). IL-1β secretion from WT U937 cells was measured by ELISA.

Summary of results

PA potentiated BCG and Mtb growth in WT U937 cells in a dose-dependent pattern. In contrast, oleic acid (OA) treatment did not modulate mycobacterial growth. Furthermore, Mtb whole cell lysate (TBWCL)-induced IL-1β secretion was increased in PA-conditioned WT U937 cells. However, Mtb growth potentiation by PA was similar in WT, NLRP3-deficient and NLRC4-deficient U937 cells.

Conclusions

PA induced mycobacterial growth and IL-1β secretion in Mtb/BCG-infected and TBWCL-stimulated macrophages, respectively. Although the induction of IL-1β is consistent with known effects of PA on the inflammasome, alternative host pathways are presumed to be responsible for the PA-induced potentiation of mycobacterial growth since the NLRP3- and NLRC4-deficient cells had a similar phenotype as WT. Targeting these PA-dependent pathways with host-directed therapies could provide adjunctive treatments for tuberculosis.

329 Varicella zoster virus open reading frame 9 dominates skin tissue-resident memory CD8 T cell response after zoster

MS Elder Waters*

VL Campbell

K Basu

S Mortazavi

R Tu

K Laing

C Johnston

DM Koelle

University of Washington, Seattle, WA

Purpose of study

Varicella Zoster Virus (VZV) causes chickenpox during primary infection and establishes latency in dorsal root ganglia. Herpes zoster (HZ) occurs when VZV reactivates to cause a painful dermatomal rash. T cells specific for VZV are generated during VZV infection and are thought to be important for limiting HZ. Recently, a subset of T cells, tissue resident memory (TRM), have been described that do not recirculate after assuming residence in barrier tissues and are hypothesized to provide early surveillance against (re)infection. Placement of TRM is an aspirational goal for vaccines but little is known about their basic biology. In this study we measured if TRM persist in skin up to 1-year post-HZ and investigated which specific VZV proteins are most commonly recognized.

Methods used

Subjects with HZ were recruited and skin biopsies taken 45 (n=18), 90 (n=12), and 360 days (n=5) after rash onset from healed HZ and control skin. Skin T cells were non-specifically expanded for functional assays. A panel of subject-specific artificial antigen presenting cells (aAPC) was created by transfecting Cos-7 cells with HLA cDNA corresponding to each subject’s HLA type, and co-transfected with each VZV open reading frame (ORF). After skin TRM were added, CD8 T cell activation was measured by IFN-g ELISA. Synthetic peptides internal to VZV confirmed reactivity to VZV ORFs.

Summary of results

We readily detected skin VZV-specific CD8 TRM skin up to 1 year after zoster. The most commonly recognized VZV protein was ORF9, with reactivity detected in 75%, 42%, and 20% of samples on days 45, 90, and 360 respectively. Overall, skin TRM decreased over the first year, paralleling a decline in blood.

Conclusions

VZV-specific skin CD8 TRM are detectable up to 1 year after HZ. For unknown reasons, the abundant tegument ORF9 protein is commonly targeted by TRM. Ongoing studies will determine if the same CD8 T cell clonotypes persist in skin over time and measure how T cell clonotypes are compartmentalized in skin versus blood. Ultimately, we hope that combined single cell mRNA and T cell receptor sequencing of skin-derived T cells will permit determination of the transcriptional signature of pathogen-specific skin TRM.

330 Characterizing clinical manifestations of congenital zika syndrome in non-microcephalic infants

JS Cranston1,*

SF Tiene1

K Nielsen-Saines1

M Moreira2

Z Vasconcelos2

A Da Costa2

1David Geffen School of Medicine, Los Angeles, CA

2Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

Purpose of study

The full spectrum of abnormalities due to antenatal exposure to Zika Virus (ZIKV) have not been delineated. We analyzed the various clinical manifestations in children with Congenital Zika Syndrome (CZS) from Rio de Janeiro, Brazil.

Methods used

Newborns of women with nonspecific viral symptoms during pregnancy or referral to Instituto Fernandes Figueira (IFF) for suspected ZIKV were included. Vertical exposure to ZIKV was determined by PCR or IgM serology. For neurodevelopmental evaluation, Bayley-III Scales of Infant and Toddler Development was used.

Summary of results

The study enrolled 296 newborns born during the ZIKV outbreak in Brazil. In utero exposure to ZIKV was confirmed in 219 cases.

Among the non-microcephalic infants (N=161), 76.8% had failure to thrive (FTT) and 68.1% had a neurologic abnormality. Among non-microcephalic infants with Bayley III exam scores (N=112), head circumference was a significant indicator of abnormal cognitive (p=0.004) and developmentally delayed language score (p=0.011).

Conclusions

ZIKV exposed infants without microcephaly suffer from congenital symptoms similar to those with microcephaly. Infant head circumference z-score at birth of non-microcephalic infants is significantly associated with neurocognitive development. Recognition of the various CZS phenotypes and spectrum of severity can help ensure early intervention.

331 Early predictors of neurodevelopment in infants antenatally exposed to ZIKA

SF Tiene1,*

JS Cranston1

K Nielsen-Saines1

M Moreira2,3

Z Vasconcelos2,3

A Da Costa2,3

1David Geffen School of Medicine, Los Angeles, CA

2Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

3Instituto Fernandes Figueira, Rio de Janeiro, Brazil

Purpose of study

Identify early predictors of poor neurocognitive outcomes in non-microcephalic infants antenatally exposed to ZIKV, and evaluate their prognostic validity.

Methods used

This study enrolled pregnant women with fever and rash during the ZIKV epidemic in Rio de Janeiro, Brazil from September 2015 through June 2016. Infants were also enrolled due to an abnormal prenatal ultrasound, confirmed antenatal ZIKV exposure, or clinical suspicion of CZS. We compared clinical findings identified prior to 3 months of age to neurocognitive outcomes, as measured by the Bayley III assessment after 6 months of age.

Summary of results

Antenatal exposure to ZIKV was confirmed in 219 cases by positive maternal or infant PCR or IgM serology. 161 of these infants were non-microcephalic, 53 were microcephalic. Of the non-microcephalic infants, 112 received Bayley III exams after 6 months of age. Neuromotor abnormalities are correlated with abnormal motor scores (p=0.038, PPV=27.1%), and lower composite cognitive scores (p=0.048). Neurodevelopmental abnormalities are correlated with abnormal cognitive scores (p=0.044, PPV=31.3%). Auditory Abnormalities are correlated with abnormal language scores (p=0.004, PPV=100%) and lower composite language scores (p=0.009).

Conclusions

This study found that early neuromotor, neurodevelopmental, and auditory abnormalities are correlated to poor neurocognitive outcomes; however, the prognostic validity of these findings is poor and all infants that are antenatally exposed to ZIKV are at increased risk of developmental delay and should be monitored closely.

332 The use of ceftaroline in the treatment of pediatric infections with a focus on methicillin resistant staphylococcus areus (MRSA): a literature review

R Chow1,2,*

Z Bustami2

S Afzal2

R Durvasula2

S Madireddy2

T Gupta2

B Afghani2,3

1University of California, Riverside School of Medicine, Riverside, CA

2UC Irvine School of Medicine, Irvine, CA

3CHOC Hospital of Orange County, Orange, CA

Purpose of study

Ceftaroline, a novel cephalosporin was recently approved for treatment of community acquired bacterial pneumonia (CABP) and soft tissue infections (STI). However, literature on the effectiveness of ceftaroline in treatment of serious infections due to MRSA is limited. The purpose of this study is to investigate the clinical effectiveness of ceftaroline in pediatric patients with serious infections, with a focus on MRSA infection.

Methods used

An extensive literature search was conducted on PubMed and Google Scholar using keywords ‘ceftaroline, ‘community-acquired pneumonia,’ ‘skin infection’ and ‘MRSA.’ Only studies or case reports of patients <18 years of age, diagnosed with serious infections which included evaluation of patients with MRSA infection were included.

Summary of results

Of the 19 studies, 4 met our inclusion criteria (table 1 below). Ceftaroline was as effective as other antibiotics for treatment of CABP and STI. It was not possible to make a firm conclusion regarding its effectiveness for MRSA infections because of the low number of MRSA cases. However, addition of ceftaroline to daptomycin was successful in treatment of a pediatric patient with fasciitis and persistent bacteremia who had failed vancomycin and/or daptomycin therapy. In addition, two patients with severe MRSA infections were successfully treated with ceftaroline after failure with prior antibiotic therapy. The incidence of side effects due to ceftaroline was low and included rash, coombs seroconversion and gastrointestinal discomfort.

Conclusions

Our review suggests that ceftaroline is effective and well tolerated in pediatric patients and may be considered as an adjunctive therapy in patients with MRSA infection. Larger controlled trials are needed to study the effectiveness of ceftaroline in MRSA infections.

333 Cinematic portrayal of infectious diseases

W Vu1,*

B Holbrook2

W Dehority1

1University of New Mexico, Albuquerque, NM

2Scientific Technologies Corporation, Albuquerque, NM

Purpose of study

Uptake of harmful activities (e.g. use of cigarettes and alcohol by children) is associated with viewing movies with these themes. To our knowledge, no studies have characterized the cinematic portrayal of infectious diseases. We hypothesized that over the last 4 decades, these films would feature an increasingly negative portrayal of the scientific/medical community.

Methods used

1567 films were identified using 149 infection-related search terms on the Independent Movie Database (IMDB), a validated tool for cinematic research. Synopses were reviewed on IMDB, Wikipedia, or American Film Institute (AFI) websites. Movies without synopses, without infectious diseases as a major theme, or without a domestic theatrical release were excluded. Year of release, box office data, media references, Academy Awards, genre, pathogen, themes, and portrayal of the scientific/medical community were assessed.

Summary of results

440 films (21.8% foreign-productions) released domestically from 1910 to 2018 were eligible. Drama (43.5%) and horror (37.4%) were the most common genres. Major themes included apocalyptic (27.3%), pandemics (20.1%), government conspiracies (19.8%), and bioterrorism (14.0%). The most common pathogens were viruses (55.4% of films), with human immunodeficiency virus most frequent (61 films) and fungi the least (7 films). Fictional viruses were increasingly depicted in modern movies in a linear regression model (p=0.0078), while bacteria (real/fictional) were more commonly featured in older movies (p=0.0012/p=0.0001). Films averaged 31.9 media references (median 4, range 0-655). Box office mean was $27,400,000 (median $2,856,712; range $0-$409,000,000). There were no significant relationships between media references and box office totals with ‘negative’ or ‘positive’ themes. 13 films won academy awards. Of films portraying the scientific/medical community, 69.0% depicted negative/mixed portrayals (e.g. unethical medical research, 15.5%). Negative themes were not more common over time when analyzed by decade in a logistic regression model (p=0.074).

Conclusions

The scientific/medical community has been negatively portrayed in films depicting infectious diseases. Research on the ability of cinema to create mistrust towards the medical/scientific community is warranted.

Morphogenesis and malformations

Concurrent session

10:15 AM
Friday, January 24, 2020
334 Variants in QRICH1- a new neurodevelopmental syndrome with variable hypermobility, leg pain, congenital heart disease and mild dysmorphic features- report of a new patient

CJ Curry1,*

L Higa2

1UCSF Fresno, Fresno, CA

2Community Regional Medical Center, Fresno, CA

Case Report

Loss of function variants in QRICH1 have recently been reported in 5 patients (Ververi et al 2018 and Lui et al 2019). QRICH1 encodes the glutamine-rich protein 1, likely to be involved in apoptosis and inflammation. These 5 patients had mild developmental issues, 2 had leg pain with elevated CK’s, 2 had short stature with a mild chondrodysplasia and 1 had congenital heart disease. A relatively consistent craniofacial appearance was reported with thin upper lip and prominent nasal tip.

Our patient presented at 15 months with a large secundum ASD, mild developmental delays, gastroesophageal reflux and subtle dysmorphic features. A oligoarray was normal She returned at age 11 with a history of hypermobility, migraine and a diagnosis of a childhood amplified pain syndrome. She had obstructive sleep apnea, suboptimal school performance and normal growth parameters. Dysmorphic features included a long face, high palate, prominent nasal tip, a mildly thin upper lip and mild micrognathia. Her Beighton score was 8/9. Her CK was normal. Her mother had a diagnosis of fibromyalgia.

Trio exome sequencing revealed a de novo heterozygous splice site variant in intron 8 of QRICH1 (NM_017730.3 c.1896-2A>G;IVS8-2A>G) predicting loss of function. Her symptoms and dysmorphic findings correspond well to those described in the 3 original patients (limited description in other two). We are aware of 3 other unpublished children, at least one of whom has hyperflexibility and headache. Two of the published patients have leg pain. QRICH1’s role in inflammation may explain at least part of the reported clinical symptomatology. This new syndrome may be underacertained due to the relative non-specificity of the clinical findings and the prominent symptom of hypermobility in at least some, leading to a suspicion of benign hypermoblie Ehlers Danlos syndrome and a decision not to perform genetic testing.

335PDGFRB-related overgrowth syndrome with aneurysm: a second example

J Chenbhanich*

S Hetts

D Cooke

C Dowd

P Devine

I Yeh

I Frieden

J Shieh

UCSF, San Francisco, CA

Purpose of study

Activating germline variants in PDGFRB have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and premature aging (Penttinen syndrome). Whether these conditions are distinct or overlapping entities is not clear. We report a patient with PDGFRB-related condition identified by next-generation sequencing (NGS)-based somatic genetic testing.

Methods used

A 26-year-old female with extensive unrevealing investigations for congenital differences in skin, soft tissues, and blood vessels presented with progressive left eye blindness. On exam, she looked older for age, with sparse hair and coarse facial features. The left leg and right arm were larger and longer than their counterparts. Nodular lesions of the tongue and widespread asymmetric vascular cutaneous patches were noted. MRA showed a fusiform aneurysm of the internal carotid artery compressing the left optic nerve. A mosaic somatic overgrowth syndrome was suspected and NGS-based somatic tumor testing of 479 genes was performed on biopsied lesions. Previous case reports were reviewed.

Summary of results

The missense variant in PDGFRB p.Y562C was detected in all somatic samples with variant frequencies (9%, 14%, 17%) but absent in blood. This variant was reported in only one case with the same phenotype. Interrogation of an inhouse database of 2,399 specimens revealed four other tumors with somatic variants in PDGFRB, including in myofibromas. We found that features of the mosaic condition can overlap with germline PDGFRB variants, sharing multiple features of Kosaki syndrome and Penttinen syndrome; also, aneurysms have been reported in a child with infantile myofibromatosis.

Conclusions

Primarily used to identify cancer treatment, NGS-based somatic tumor testing may implicate this novel overgrowth condition by detecting low-level somatic mosaicism that would have been missed by traditional methods. The PDGFRB-related conditions represent a spectrum of manifestations. PDGFRB variants are also the first known genetic cause of these fusiform aneurysms, suggesting roles of aneurysm surveillance and therapies targeted to the pathway such as kinase inhibitors.

336 Identification of novel candidate risk genes for myelomeningocele within the glucose homeostasis and folate and one carbon metabolism networks

C Baker1,2

P Hillman2

L Hebert2

J Hixson3

A Ashley-Koch4

H Northrup2,*

K Au2

1Stanford University, Stanford, CA

2McGovern SOM at UTHealth Houston, Houston, TX

3School of Public Health at UTHealth, Houston, TX

4Duke University Medical Center, Durham, NC

Purpose of study

Neural tube defects (NTDs) occur secondary to incomplete closure of the neural tube. Studies have shown an etiology with both genetic and environmental factors, but the underpinning of NTDs are yet to be elucidated. Two associated metabolic pathways are folate one carbon metabolism (FOCM) and glucose homeostasis/oxidative stress (GHOS). The purpose of this study is to apply WES data from a cohort of patients born with myelomeningocele (MM) to the hypothesis that analysis of damaging mutational burden will give insight into genes related to increased NTD risk.

Methods used

Case data was generated with ~500 exomes of MM patients, split evenly between the ethnic groups with the highest birth prevalence in the United States: Mexican Americans and Caucasian Americans. Control data was obtained through the public Genome Aggregation Database (gnomAD). Using an in-house bioinformatic pipeline, variants were filtered for quality and functional annotation. Variants included had an allele frequency <1% and are predicted to be damaging (stop gain, stop loss, canonical splice site, or combined annotation dependent depletion (CADD) phred score 20). Gene lists related to FOCM and GHOS were generated using gene ontology.

Summary of results

We identified ~4000 qualifying variants in 1056/1469 genes, with 63 genes meeting nominal significance (p<0.05) for mutational burden (44 in the FOCM network, 22 related to GHOS, and 3 overlap). No genes reached mutation burden significance after applying Bonferroni correction. Overall, 64% of our population had at least one variant in a nominally significant gene and 28% had more than one.

Conclusions

We present the largest WES cohort of NTD patients to date and propose using a large public database as a control. Interestingly, there was no overlap of implicated genes between ethnicities in either pathway. Only 6 genes have previously been implicated in neural tube defects, but 17 of them are expressed during human neural tube closure. Thus, we present 58 new genes as consideration for potential NTD risk.

337 Wnt16 regulates vertebral size and patterning during zebrafish development

AR Cronrath1,*

Y Hsu2

RY Kwon1

CJ Watson1

1University of Washington, Seattle, WA

2Harvard Medical School, Boston, MA

Purpose of study

WNT16 has a critical role in chronic diseases of the spine, as evidenced by its link to genetic osteoporosis susceptibility. However, the function of WNT16 in axial skeletal development remains elusive. To better understand the spinal roles of wnt16, we tested the hypothesis that Wn