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2022 Western Medical Research Conference
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Adolescent medicine and general pediatrics I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#1 Quality improvement increases community hospital smoke exposure screening, education, and referral

E Daniel1*

MY Hamline2,3

1Sutter Health, Sacramento, CA

2UC Davis Children’s Hospital, Sacramento, CA

3Adventist Health Lodi Memorial, Lodi, CA

Purpose of Study

Tobacco use starts young and is the leading cause of preventable disease, disability, and death in the United States. Secondhand smoke increases ear and respiratory infections, asthma attacks, and risk of Sudden Unexpected Infant Death. Few smoking cessation studies in inpatient pediatrics are formal quality improvement projects and most are at academic institutions. We sought to increase smoke exposure screening, smoking cessation education, and referrals in our community hospital pediatric population. By improving screening and documentation, we anticipate increased provider awareness and smoking cessation interventions.

Methods Used

All pediatric ward, newborn nursery, and Level II nursery admissions were eligible. Interventions were education on smoke exposure screening and Helpline referrals, standardizing documentation for screening and discharge instructions, visual reminders, and Helpline wallet cards.

The primary outcome measure was monthly percentage of pediatric inpatients screened for smoke exposure. Secondary outcomes were percentage of pediatric inpatients screening positive for smoke exposure who received discharge instructions or who received a Helpline referral (self or family member). Length of stay (LOS) was monitored as a balancing measure.

Outcome measures were analyzed with statistical process control in SPC for Excel. Baseline and intervention periods for LOS were compared with t-tests.

Summary of Results

We increased baseline average smoke exposure screening rates from 14% to 73%, meeting criteria for special cause variation (figure 1). Education on smoke exposure avoidance increased from 5% to 57%. Helpline referrals increased from 0% to 21%. There was no significant change in length of stay.

Abstract #1 Figure 1

Vertical lines are timing of interventions. 1) Monthly Pediatrician education started 2) EMR documentation standardized, visual reminders posted 3) Helpline wallet cards available.UCL= Upper Control Limit, Avg= Average, LCL= Lower Control LimitBaseline: Dec 2019-Nov 2020. Intervention: Dec 2020-June 2021

Conclusions

Pediatrician-led smoking cessation interventions are feasible and effective in community hospital pediatric units with no significant impact on length of stay.

#2 Pilomatricoma in a child with turner syndrome: a rare entity

IS Horowitz

K Tappin*

Valley Children’s Healthcare, Madera, CA

Purpose of Study

Pilomatricoma is a rare, skin neoplasm that is often confused with dermoid or brachial cleft cysts. Julian et al., reported that pilomatricomas are commonly misdiagnosed pre-operatively in up to 75% of cases.

We report the case of a child with Turner’s syndrome with a pilomatricoma that was diagnosed on biopsy. We review the histopathologic features and emphasize its association with Turner’s syndrome.

Methods Used

Case Report.

Summary of Results

2 year old female with Turner Syndrome presented with a progressive mass above her right upper lip for 6 months.

On exam, she was well-appearing with phenotypical features of Turner’s syndrome. A 0.5 x 0.5 cm erythematous, verrucous, well circumscribed, nontender, mobile lesion was noted above her lip.

She underwent complete excision of the mass without complication. Excisional biopsy revealed the presence of viable basaloid cells and shadow cells confirming the diagnosis of pilomatricoma.

Conclusions

A pilomatricoma, otherwise known as pilomatrixomas, are benign subepidermic tumors of the hair follicle matrix. The lesions occur on the face and neck with a mean age of onset between 5.8- 7 years old.

Lesions are usually asymptomatic but, inflammation and ulceration can occur. The most common clinical presentation is a firm, subcutaneous lesion with an irregular surface. The overlying skin may be red, blue, or display the tent sign. Studies have reported the initial development of pilomatricomas in children with Turner’s syndrome. The exact cause of this is unknown although animal studies suggest a genetic component.

Histopathologically, a pilomatricoma appears as a mass composed of viable basaloid cells, shadow cells, calcification, and ossification. The mainstay of treatment of a pilomatricoma is complete surgical excision as the lesions do not regress spontaneously. Early excision within 12 months of diagnosis is associated with better cosmetic outcomes. Recurrence and malignant transformation is rare.

This case highlights the importance of considering pilomatricoma as a cause of solitary skin nodules, especially when on the head, neck or upper extremities. Additionally, physicians caring for children with Turner syndrome should be aware of the prevalence of pilomatricoma in this population.

#3 Mental health hopscotch: improving adolescent mental health one hop at a time

AS Rodriguez1*

M Flores1

T Fildes1

J Charbonnet1

K Colwell1

R Kinman2

1Fresno High School, Fresno, CA

2University of California San Francisco Fresno, Fresno, CA

Purpose of Study

Fresno High Women ‘s Alliance students continue to collaborate with UCSF Fresno pediatricians to create community action research projects on topics of adolescent concern using a ‘youth as partner’ approach. Given the social isolation and increasing depression students noticed amongst themselves and their peers due to COVID19, the Women’s Alliance teens chose to focus this last year on improving mental health amongst their peers. Mental Health Hopscotch was chosen for its simplicity and ease of use. The fact that it was created by an adolescent in response to the COVID19 pandemic provided further impetus for its use.

Methods Used

Students collaborated with the school’s Social Emotional Wellness and Support team, choosing to do their mental health intervention during National Mental Health Month. They created a Mental Health ‘Sunshine’ at their school entrance, chalking positive affirmations in a sun-shaped diagram for all to see, and chalked a Mental Health Hopscotch on the sidewalk in the front of the school. Silicone bracelets with motivational quotes and mental health awareness pencils, stickers, and mini buttons were handed out to those who completed the Hopscotch. A QR code linked to Google Forms was used to survey students who completed the Hopscotch.

Summary of Results

42 students were surveyed. 12% of students reported their average stress level was ‘just right’, 38% reported they could ‘handle’ their stress, 21% felt that they were ‘getting stressed’, 19% reported they were ‘starting to lose it’, and 10% described their stress as ‘getting out of control’. Students primarily dealt with stress by listening to music (31%), exercising (19%), and sleeping (14%). Half of students surveyed reported difficulty sleeping at night, while 90% of students felt that doing Mental Health Hopscotch helped boost their mood.

Conclusions

Although only a limited number of students were surveyed due to restricted numbers of students present on campus, the majority of students felt stressed with half the students reporting difficulty sleeping at night. Mental Health Hopscotch provided a simple, quick, yet no-cost approach to boost students’ mood, thus empowering teens concerned about the mental health of their peers to stage a mental health intervention on their own school grounds.

#4 Daylight savings and pediatric emergencies

V Wong1,2*

P Enarson1,2

J Lee1,2

1The University of British Columbia Faculty of Medicine, Vancouver, BC, Canada

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

Purpose of Study

Daylight Savings Time (DST) is a biannual time change where during ‘spring forward,’ clocks are set forward one hour, potentially resulting in sleep deprivation for much of society. During ‘fall back,’ the opposite occurs. Circadian rhythm disruption has been shown to have effects on cardiovascular, neuropsychiatric, metabolic, immune-related and accidental events in adults. A 2018 study showed increased emergency department (ED) visits for adults in the time after DST. These findings have not been verified in pediatric populations and if extant, may have implications on managing ED patient volume and expectations. We hypothesized that the large-scale sleep deprivation following spring time change would result in increased ED presentations, particularly among certain presentations (neurologic, psychiatric, accidental/traumatic) that may be especially susceptible to sleep deprivation, and that the fall time change would have an opposite effect.

Methods Used

We retrospectively collected and analyzed the primary medical complaint of all children (0–16 years) presenting to BC Children’s Hospital ED in the 2 weeks before and 3 weeks after the biannual DST time changes during 2011 to 2019. Incidence ratios (IR) of ED presentations were calculated over day 0 (day of time change) to day 7. IRs were calculated for all presentations and broken down by specialty.

Summary of Results

After excluding infectious presentations, the IR was increased during the first week following spring time change: Monday by 6%, Tuesday by 7% and Wednesday by 6%, though the results were statistical insignificant (p>0.05). There were significant decreases (p<0.05) after the fall time change: Monday by 12%, Tuesday by 13% and Wednesday by 8%.

Conclusions

Following the seasonal time change in the spring, there were increases in IR, though this did not reach statistical significance. There were significant decreases in IR during the three days following the fall shift. Together these findings suggest that the widespread sleep deprivation at spring time change results in adverse health effects among children, while extra sleep in the fall time change may be protective.

Circadian rhythm disruption from DST in the children shows potentially important effects on emergency visits and further study can lead to better patient care and ED preparation. This may be informative in developing policy regarding the need for DST.

#5 The relationship between self-perceived health status and chronic condition, access to care, and awareness of chronic condition among adults with history of adverse childhood experiences

L Trinh*

S Teklehaimanot

M Shaheen

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

Purpose of Study

Adults with a history of adverse childhood experiences (ACEs) are at increased risk for chronic disease and, thus, poor health outcomes. Yet, the effect of chronic disease awareness on health outcomes in adults with ACEs has not been examined. The objective of this study was to determine the relationship between general health status and chronic disease, access to care, and awareness of chronic condition among adults with history of ACEs.

Methods Used

Data from the 2019 Behavioral Risk Factor Surveillance System were analyzed. Descriptive statistics were used to determine the prevalence of ACEs, chronic disease, healthcare access, chronic disease awareness, general health status, and population characteristics. Bivariate analysis using Chi-squared test was performed on history of ACEs by all independent variables and general health status by all independent variables. Multivariable logistics regression was used to determine the relationship between general health status and ACEs, adjusting for chronic disease, healthcare access, chronic disease awareness, and demographics.

Summary of Results

Of the 78,112 respondents, 63% reported being exposed to at least one ACE. History of ACEs was associated with high prevalence of chronic diseases (p<0.002), lower healthcare coverage (p<0.0001), lower chronic disease awareness (p<0.006), and report of fair/poor general health status (p<0.0001). In adjusted analyses, adults with 2, 3, and ≥4 ACE events had 1.24, 1.22, and 1.45 times increased odds of reporting fair/poor health status compared to those reporting no ACEs.

Conclusions

Adults with history of ACEs face barriers to achieving good health. There is a need to expand ACEs screening in primary settings so that early intervention can improve general health outcomes.

#6 Childhood obesity, social determinants of health, social vulnerability and hospitalization

J Johnson*

M Baum

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

The prevalence of overweight adolescents has increased dramatically over the last decade. Although previous research has demonstrated the contribution of diet, exercise habits, and parenting on obesity rates, this early study addresses the relationship between hospitalization, social vulnerability index, social determinants of health, and childhood obesity.

Methods Used

We studied children between the ages of 5 and 17.9 years, seen in inpatient (n=39) and outpatient (n=35) settings at healthcare facilities affiliated with Loma Linda University Health between January 2020 through June 2021. We collected Body Mass Index scores (BMI) and demographic information. A standardized questionnaire gathered social determinants of health information available in the electronic health record. Using home addresses, we identified the Social Vulnerability Index score (SVI) (Flanagan, 2011) associated with their census tract (Center for Disease Control, 2018). The SVI ranks each tract on four main themes: socioeconomic status, household composition and disability, minority status and language, and housing and transportation.

Summary of Results

The most significant comparison were the differences in risk between the inpatient (n=39) and outpatient (n=35) populations. Inpatients were more likely to experience Social Connection risk (p=0.046), Financial risk (p=0.0006), and Food Insecurity (p=0.0077) than outpatients.

When comparing between patients living in the upper quartile (n=40) and the lower three quartiles (n=34) of SVI, there was little difference in BMI, Financial risk, Food Insecurity risk, Transportation risk, Physical Activity risk and Stress risk. There was similarly little difference when comparing age groups of younger versus older children.

Abstract #6 Table 1

BMI ≤ 85th percentile = normal weight or underweight, BMI > 85th percentile = overweight or obese (Kuczmarski, 2002). *Hisp = person of Cuban, Mexican, Puerto Rican, South/Central American, or other culture regardless of race (US Census Bureau, 2011).

Conclusions

There are significant disparities in risk between pediatric inpatient and outpatient populations. Steps could be taken to identify inpatients with reduced resources to improve food insecurity, social connection risk, and financial risk. Although SVI is important for understanding the context of each patient, every family has unique social determinants and risks that could be addressed by physicians.

#7 Subjective social status and food insecurity relationship with weight-specific quality of life among Latino adolescents and between sexes

A Penghat1*

KB Vander Wyst2

A Peña3

A Williams3

SL Ayers3

GQ Shaibi3,4

1Midwestern University Arizona College of Osteopathic Medicine, Glendale, AZ

2Midwestern University, Glendale, AZ

3Arizona State University, Phoenix, AZ

4Phoenix Children’s Hospital, Phoenix, AZ

Purpose of Study

Social status and food insecurity (FiS) may contribute to health disparities among youth. This study aimed to evaluate whether subjective social status (SSS) and FiS are associated with weight-specific quality of life (wQoL) among Latino youth with obesity. We further explored whether relationships differed by sex.

Methods Used

One-hundred and forty-one Latino youth (47% male; mean age: 15.3±0.9) with obesity completed surveys to assess SSS, perceived FiS, and wQoL (self, social, and environment). Separate linear regression models were performed to examine the relationship between SSS & FiS with wQoL, after controlling for sex and BMI percentile. Data were then stratified by sex to determine Pearson’s r for wQoL & SSS and wQoL & FiS.

Summary of Results

Mean total (64.1±24.9), self (57.3±29.3), social (69.5±25.6), and environmental (60.5±26.3) wQoL, with males reporting higher total, self, and environmental wQoL as compared to females (all p<0.05) after controlling for BMI. Over one-third of the cohort indicated very low food insecurity (36.2%) or marginal food insecurity (34%), which did not differ by sex. Despite no sex differences in SSS society (mean diff=-0.074, p=0.77) or SSS school (mean diff=-0.354, p=0.28), there was a positive relationship between SSS school and all scales of wQoL regardless of sex (all p<0.01). SSS school was a significant predictor of total wQoL (β=4.24, p<0.001) and the self (β=3.49, p=0.008), social (β=4.40, p<0.001), and environment (β=4.57, p<0.001) subscales. SSS school explained 9% of the variance in total, social, and environment wQoL, and 4% of the variance in self wQoL. There was an inverse relationship between FiS and all scales of wQoL, particularly for those experiencing marginal and high FiS (all p<0.03). This correlation was stronger for males for all wQoL scales at all levels of FiS except high FiS. Marginal FiS was a significant predictor of total (β=-12.94, p=0.006), self (β=-12.48, p=0.029), social (β=-12.06, p=0.013), and environment (β=-14.66, p=0.003) wQoL after controlling for sex and BMI percentile. High FiS was a significant predictor of total (β=-22.46, p<0.001), self (β=-18.56, p=0.016), social (β=-24.16, p<0.001), and environment (β=-22.76, p<0.001) wQoL after controlling for sex and BMI percentile. Marginal and high FiS explained 8% of the variance in total, social, environmental wQoL, and 3% of the variance in self wQoL.

Conclusions

Among Latino youth with obesity, social status is associated with wQoL while food insecurity is inversely associated with wQoL.

#8 Medical student knowledge and perceptions of pediatric obesity management

K Eckert

S Thomas

M Buls

M Cox*

E Chowdry

B Scott

University of Nevada Reno School of Medicine, Reno, NV

Purpose of Study

The prevalence of pediatric obesity continues to increase. In Nevada, approximately 40% of youth are overweight or obese and 70% of these children will remain overweight as adults. Traditional medical school curriculum does not adequately prepare students to counsel families on this subject. The purpose of this study was to evaluate the progression of third year medical student knowledge base involved in managing obesity in children and adolescents over the course of the pediatric clinical curriculum.

Methods Used

63 medical students in the third year clinical clerkship curriculum at the University of Nevada, Reno School of Medicine were given a survey to evaluate their knowledge on pediatric obesity and perceptions surrounding treatment before a six-week pediatric clerkship. During the clerkship, students received instruction on the diagnosis and treatment of obesity. At the conclusion of the clerkship, students took a post-survey to assess knowledge gained during the experience. Paired samples T-test and Chi-square tests were used to assess differences between pre- and post- surveys.

Summary of Results

After the clerkship, there was an increase in the mean score in knowledge and comfort level in recommending a treatment program for overweight/obese children between pre- (M=1.97, SD=0.91) and post-tests (M=3.55, SD=0.89) (t(62)=10.25, p<0.0001). There was also an increase in the mean score in their ability to effectively counsel overweight/obese children between pre- (M=2.40, SD=0.90) and post-tests (M=3.86, SD=0.77) (t(62)=10.33, p<0.0001). In addition, there was an increase in students believing in the overall efficacy of counseling in the treatment for overweight/obese children and adults between the pre- (M=2.91, SD=0.75) and post-tests (M=3.34, SD=0.76) (t(62)=3.23, p=0.0019).

Conclusions

The curriculum improved student knowledge and understanding of pediatric obesity. In particular, perceived comfort and ability to counsel patients and families about obesity prevention and treatment increased. As obesity continues to be a challenge, expansion of medical student education in this area is imperative to address this problem.

Cardiovascular I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#9 1-year outcomes of patients undergoing heart transplant during the covid pandemic

G Esmailian1*

N Patel2

T Singer-Englar2

S Kim2

M Hamilton2

J Kobashigawa2

1The George Washington University School of Medicine and Health Sciences, Washington, DC

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

The ongoing COVID-19 pandemic has brought considerable challenges to heart transplantation. Most notably, towards the start of the pandemic, changes in the outpatient care of post-transplant patients were brought forward at our center to further prevent the spread of the virus and protect highly immunosuppressed recipients. For example, blood draws for immunosuppression adjustments were conducted at home and early coronary angiograms were eliminated. Video visits were conducted for post-operative months 7, 9, and 11. Despite these changes in management, formal analyses on the impact of these changes on heart transplant recipient outcomes have yet to be conducted. Now over one year removed from the pandemic’s onset, we sought to examine if the modifications in outpatient care impacted 1-year outcomes of patients transplanted during the start of the COVID-19 pandemic.

Methods Used

Between March 6 and September 1, 2020, we assessed 50 heart transplant patients transplanted during the COVID-19 pandemic. These patients were compared to patients who were transplanted during the same months between 2011 and 2019 (n=482). Endpoints included subsequent 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV: stenosis ≥ 30%), 1-year freedom from any-treated rejection, 1-year freedom from acute cellular rejection, 1-year freedom from antibody-mediated rejection, hospital and ICU length of stay, and 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD/pacemaker, or stroke).

Summary of Results

Patients transplanted during the COVID-19 pandemic had similar outcomes compared to those of patients transplanted in years prior to the pandemic. There were no significant differences in hospital and ICU length of stay between the two groups. There were also no significant differences in 1-year survival, 1-year freedom from CAV, 1-year freedom from any treated rejection, and 1-year freedom from acute cellular or antibody mediated rejection between both groups. Patients transplanted during the pandemic had a significantly higher 1-year freedom from NF-MACE.

Abstract #9 Table 1

Conclusions

Despite necessary changes being made to post-transplant care to mitigate the spread of COVID-19 and protect an immunosuppressed population, heart transplantation during the COVID-19 pandemic appears safe with 1-year outcomes comparable to years prior.

#10 Covid pandemic and social mitigations improve outcomes for heart transplant patients

C Washington

S Kim*

N Patel

T Singer-Englar

M Hamilton

J Kobashigawa

Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

The COVID pandemic affected how our medical staff treated our heart transplant (HTx) patients during this period of time. Patients were seen virtually via telemedicine and patients self-isolated at home. What we do not know is the impact of this treatment during the COVID pandemic on HTx outcomes. As patients were self-isolating, it is possible that medication and medical compliance were increased and there may have been a decrease in non-COVID infection rates as exposure was minimized due to patients self-isolating. None of these factors have been assessed prior and, thus, we reviewed our large, single center patient population for this study.

Methods Used

Between March 2020 and September 2020, we assessed 55 HTx patients who were transplanted during this period of time and followed for 6 months. Patients were self-isolating and had every other clinic visit changed to a virtual visit to minimize exposure to COVID. Endpoints for this study included 6-month survival, re-hospitalization, number of non-COVID infections (defined as the need for intravenous antibiotics), any treated rejection (ATR), and maintenance of therapeutic immunosuppressive blood levels. The study patients were then compared to a control group of the previous three years, averaging each year at the same time points of March 13, 2017, March 13, 2018, and March 13, 2019, and followed for 6 months. Each group was averaged and then compared to the study group.

Summary of Results

The study group (during the COVID pandemic) demonstrated a significant decrease in re-hospitalization in the first 6 months following HTx compared to the control group. There was a numerical decrease in non-COVID infectious complications. There was no difference in survival and freedom from any-treated rejection episodes between the two groups. Reasons for rehospitalization included infections, various cardiac and renal issues, malaise, and fever.

Abstract #10 Table 1

Conclusions

The COVID pandemic demonstrated that self-isolation and virtual visits resulted in fewer hospitalizations possibly due to less infectious complications. This implies that perhaps stricter restrictions for community exposure might benefit HTx patients in the 6 months following transplantation.

#11 Sex disparities in heart transplant waitlist time following the donor heart allocation policy change

I Sindha1*

T Singer-Englar2

S Kim2

N Patel2

M Hamilton2

J Kobashigawa2

1University of California Los Angeles, Los Angeles, CA

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

There are many reports in organ transplantation that demonstrate that there are sex discrepancies in waitlist urgent status, time on the heart transplant waitlist, waitlist mortality. There are no differences in men versus women in terms of heart disease and in terms of mortality for these two sexes. It would be expected that both men and women would have similar percentages as urgent status, especially after the new donor heart allocation policy change took place in October 2018. We chose to assess our male and female patients to establish whether there exists a difference in patients listed as urgent status on the HTx waitlist.

Methods Used

Between November 2018 and December 2020 (after donor heart allocation change in October 2018), we assessed 276 patients on the HTx waitlist. Patients were followed for 6 months and censored after they were transplanted or removed from the waitlist. Percent of patients of each sex listed as urgent status (status 1, 2, 3) was recorded. Mortality on the waitlist, waitlist time, and removal from the waitlist due to being too sick were secondary endpoints.

Summary of Results

After the donor heart allocation policy change in October 2018, women were significantly less likely to be listed as urgent status compared to men. For those patients listed as urgent status, there was no significant difference in mortality for women versus men on the HTx waitlist. The waitlist time was shorter for men compared to women (see table 1).

Abstract #11 Table 1

Conclusions

There appears to be a sex disparity for women being less likely to be listed as urgent status on the HTx waitlist. Further studies are needed to determine whether this difference has a biologic mechanism or whether there is selection bias and/or treatment bias present in their care.

#12 Are oversized donor hearts associated with poor outcome after heart transplantation?

M Rubio1

N Patel2*

S Kim2

T Singer-Englar2

M Hamilton2

J Kobashigawa2

1University of California Los Angeles, Los Angeles, CA

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

In heart transplantation (HTx), donor-to-recipient size matching has been done by height and weight. More recently, predicted heart mass (PHM) has been found to be more clinically useful to reflect outcome. Using PHM, it has been demonstrated that under-sizing a donor heart for a larger recipient with high pulmonary artery pressures leads to increased mortality. It has recently been noted in the International Society for Heart and Lung Transplantation (ISHLT) registry that there may be increased risk in placing an oversized donor heart using weight into a smaller recipient. This clinical outcome has not been established using PHM. We sought to address this question in our large, single center experience using PHM.

Methods Used

Between January 2010 and June 2020, we assessed 588 donor-to-recipient donor heart matches. We used PHM to assess whether there were outcome differences when the donor hearts were oversized. We divided the donor-to-recipient PHM ratio into two categories: normal (90–110%, n=524), and markedly oversized (greater than 140%, n=64). Outcomes included 1-year survival, freedom from 1-year rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), freedom from cardiac dysfunction (defined as LVEF ≤40%), and freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke).

Summary of Results

Markedly oversized donor hearts using PHM compared to normal matching showed no difference in 1-year survival, freedom from 1-year ACR, freedom from CAV, freedom from NF-MACE, and freedom from cardiac dysfunction. There was a significantly lower 1-year freedom from AMR in the markedly oversized donor heart group which is due to more women recipients (sensitized due to previous pregnancies) in this group (71% oversized group vs. 20% normal group).

Abstract #12 Table 1

Conclusions

Markedly oversized donor-to-recipient matching using PHM does not result in poor outcomes after heart transplantation. This has potential to expand the donor pool, particularly for smaller patients.

#13 New approach to myocardial infarct sizing using long axis cardiac magnetic resonance imaging to improve in vivo validity

J Ref1*

S Daugherty2

IR Chinyere1

J Zeng1

J Lancaster2

L LD3

F Kenneth3

B Mark1

G Adrian1

J Koevary2

S Goldman2

R Avery4

1The University of Arizona College of Medicine Tucson, Tucson, AZ

2The University of Arizona Sarver Heart Center, Tucson, AZ

3Banner University Medical Center Tuscon, Tucson, AZ

4Northwestern University Feinberg School of Medicine, Chicago, IL

Purpose of Study

The AHA 17-segment model is the preferred clinical method to define LV MI size in CMR imaging, although can be subjective. We propose a novel measurement technique based on long-axis (LAX) CMR from a porcine model of MI to improve accuracy and reproducibility of infarct volume quantification. Data were collected from MRI exams and endpoint organ harvesting for histopathologic analysis.

Methods Used

Yucatan mini swine were subjected to 90-minute ischemia/reperfusion of the left anterior descending (LAD) coronary artery. Six-months after infarction, two observers evaluated four infarct sizing methods: myocardial contouring of post-mortem heart slices, contouring using cardiac MRI, AHA 17-segment model analysis and novel LAX MRI infarct sizing.

Novel LAX MRI infarct sizing was done in routine 2-, 3- and 4-Chamber LAX LGE MRIs. The precise length of MI could be measured in each plane. These measurements provide exact anatomic location of MI along each wall of the heart relative to the apex.

Total heart length (THL) from apex to base is measured in the 2-Chamber LAX MRI to standardize processing and provide a more accurate LV infarct percentage, since not every heart is the exact same size and infarct percentage is calculated relative to specific anatomy.

Infarct length measurements from each of the 3 LAX planes are summated and divided by THL to produce a Long-Axis Ratio (LAR) value. LAR values were plotted against MRI contoured infarct size to produce a table that approximates LV infarct percentage using the LAR value.

Summary of Results

LV infarct sizes ranges were 1.6% - 25.8% (n=10) of the left ventricle using reference standard histopathologic infarct sizing. Intraclass correlations (ICC) were calculated between two observers and averaged due to high similarity, ICC > .900. A t-test of .0006 and Bland-Altman plots show statistically significant differences in 17-segment model infarct size compared to histopathologic analysis while no significant difference was found when compared to our novel method with 0.8198. Linear correlation showed an R2 of 0.9111 between MRI contoured infarct size and our novel MRI infarct sizing model to predict infarct size as a percentage while the R2 of the 17-Seg model is 0.8197. A representative MRi from a patient is shown was produced to demonstrate the clinical relevance of this approach.

Conclusions

AHA 17-segment model provides inferior assessment of LV infarct size compared to proposed LAX infarct sizing suggesting it maybe a robust and easily implementable quantitative assessment of LV infarct size in advanced imaging.

#14 The importance of natural history data collection as demonstrated in danon disease echocardiogram analysis

G Storm1*

K Boynton1

A Barnard1

E Eshraghian2

K Hong2

L Mestroni1

E Alder2

M Taylor1

1CU SOM, Aurora, CO

2UCSD, La Jolla, CA

Purpose of Study

With over 7,000 rare diseases affecting 1 in 10 Americans, longitudinal data describing the clinical course of rare diseases is essential to understand disease natural history and prepare for studies of novel treatments. Traditionally, published data associated with these diseases is limited to cross-sectional times of diagnosis and major events making inferences on the progression and trajectory of various phenotypes difficult. A prime example is Danon Disease, a rare genetic cardiac disease with a malignant outcome of death or need for heart transplantation in most males.

Methods Used

To mitigate the lack of longitudinal natural history knowledge in Danon patients, a retrospective clinical database was developed using the REDCap database program. All current and past medical history for Danon patients enrolled internationally was collected and entered into the database by two research sites. To date, this registry has enrolled over 100 patients, with roughly equal representation of males and females. This includes the collection of data on over 550 echos.

Summary of Results

To demonstrate the power of this natural history study, echocardiogram data were collected over time and examined for trends in ejection fraction (EF) of the patients’ hearts over the age during that time of their illness. Data on the eight patients with the largest number of longitudinal EF data points, prior to transplant, were extracted and graphed. The data revealed that EF drops off much earlier, at almost half the age in males compared to females and that substantial variation in EF is present for subjects, rather than a smooth, gradual decline.

Conclusions

As this natural history data continues to be analyzed, further analysis will be done that aims to look at the progression of heart disease in Danon patients prior to transplant. These trends will be imperative in not only understanding the progression of the disease to drive best clinical practices, but also to utilize as controls in clinical trials for potential treatments of Danon Disease.

#15 Lifestyle counseling for veterans with symptomatic heart failure

C Taylor1*

A Edmeade1

CE Walters1

J Patel2

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

2VA Loma Linda Healthcare System, Loma Linda, CA

Purpose of Study

Lifestyle counseling has shown to be effective in modifying health behaviors and reducing cardiovascular risk in healthy patients. However, data supporting effectiveness of lifestyle counseling in patients with symptomatic heart failure is limited. This quality improvement study hypothesizes that lifestyle counseling focusing on sleep, activity, nutrition, medication adherence, and self-care will be associated with improvements in health behaviors in veterans with heart failure.

Methods Used

This study screened a selected cohort of patients with symptomatic heart failure from the Loma Linda VA Heart Failure program. The study included 5 counseling sessions over a 9 week interval. In week 1, pre-intervention surveys were completed using the following validated surveys: Pittsburgh Sleep Quality Index, Veterans Specific Activity Questionnaire, Mini Nutritional Assessment, Eight-Item Morisky Medication Adherence Scale, and Self-Care of Heart Failure Index. During weeks 2 through 8, three counseling sessions focusing on nutrition, sleep, exercise, and self-care were tailored to each patient following best practices from LLVA Heart Failure Program. In week 9, post-intervention surveys were completed.

Summary of Results

Out of 112 screened, 49 (44%) agreed to participate. Each patient was given a baseline score during the pre-intervention surveys during week 1. Baseline Pittsburgh Sleep Quality Index average score was 8.74 with post-intervention survey average of 7.68. Lower scores on the Pittsburgh Sleep Quality Index demonstrate higher quality sleep habits and sleep quality. For the Veterans Specific Activity Questionnaire baseline average score was 4.36 and post-intervention was 4.55. This questionnaire ranked activities according to metabolic equivalent of task from 1 to 13. At baseline in the Mini Nutritional Assessment patients reported an average score of 11.38. After lifestyle counseling, patients reported an average score of 12.40. The Mini Nutritional Assessment scoring system had a maximum of 14 with normal nutritional status ranging from 12 to 14, at risk of malnutrition from 8 to 11, and malnourished scores with score under 7. The Eight-Item Morisky Medication Adherence Scale had baseline and post-interventions average scores of 5.51 and 6.30, respectively.

Conclusions

All survey data indicated positive changes in lifestyle from pre to post surveys. Lifestyle counseling may improve health behaviors in patients with symptomatic heart failure.

#16 Atrial fibrillation, electroconvulsive therapy, and stroke risk

M Kapadia*

P Jagadish

M Hutchinson

H Lee

The University of Arizona College of Medicine Tucson, Tucson, AZ

Purpose of Study

To review the literature on stroke risk in patients with atrial fibrillation (AF) undergoing electroconvulsive therapy (ECT) as well as anticoagulation recommendations.

Methods Used

Two authors independently performed a literature review of PubMed, searching for ‘electroconvulsive therapy and atrial fibrillation.’ The resulting articles and their references were reviewed for relevance to AF and stroke risk.

Summary of Results

Rozig, et al. (2018) found that ECT is not associated with an increased risk of new or recurrent stroke. Among 23 studies, we found that post-ECT cardioversion of AF to normal sinus rhythm occurred in 2 cases. Neither was associated with stroke, though this finding may limited by low sample size. However, ECT has induced AF in at least 6 cases without stroke.

ECT requires fewer joules than does cardioversion for atrial fibrillation, and current is applied to the brain for ECT versus the heart for synchronized cardioversion. The mechanism of AF induction/cardioversion is a catecholamine surge and varied hemodynamic changes.

Because of the rarity of stroke in ECT patients, routine anticoagulation prior to ECT is controversial. Furthermore, direct electrical stimulation of the brain risks hemorrhagic stroke after ECT.

In patients with existing AF who are not anticoagulated, an alternative means of reducing cardioversion risk may involve modulation of post-ECT hemodynamic changes by beta-blockade. Beta blockade may exacerbate bradycardia in some while reducing reflex tachycardia in others and may even decrease in seizure length, thus, lowering the efficacy of ECT.

Conclusions

The risk of inducing stroke by cardioversion of AF in the setting ECT is very low despite a documented risk of cardioversion. Routine anticoagulation prior to ECT remains controversial. Imaging modalities such as echocardiography or mitigation of hemodynamic effects may further reduce the risk of stroke in these patients. Areas for further study are precise assessment of cardioversion and stroke risk in AF patients and the effect of routine beta-blockade on cardioversion risk.

#17 Critical role of specialized pro-resolving mediators in atherosclerosis

S Rangarajan*

P Rangchaikul

MM Radwan

Western University of Health Sciences, Pomona, CA

Purpose of Study

Coronary artery disease is the leading cause of death worldwide with over 17.9 million deaths per year according to WHO. There has been a vast amount of research done in understanding the causes, and therefore the treatments of this disease. Our body’s inflammatory processes have been identified as a nidus of the elaborate process that ultimately leads to life-threatening cardiovascular events. However, research around understanding how the body puts an end to such naturally occurring inflammation i.e., resolution of this inflammation, is gaining traction and has shed light into new avenues for future management of CV diseases. In this narrative review we discuss the pathophysiological and molecular mechanisms of atherosclerosis including inflammation, apoptosis and efferocytosis, the recent development in the understanding of a new class of molecules called Specialized Pro-resolving Mediators (SPMs), and the impact of such findings in the realm of cardiovascular treatment options.

Methods Used

We searched the MEDLINE database, PubMed restricting ourselves to original research articles as much as possible, and analyzed papers published in the last 20 years on the complex pathophysiology of atherosclerosis and the role of resolvins.

Summary of Results

Specialized Pro-resolving Mediators (SPMs) is a class of molecules that acts as strong local modulators of acute inflammation. It is further classified into resolvins (E and D series), maresins, protectins, and lipoxins. Resolvins mediate resolution of inflammation through a variety of actions. Some of them are reduced chemotaxis of neutrophils by blocking the action of LTB4, a strong neutrophil chemoattractant, reduced PMN chemotaxis by effecting changes in their actin polymerization, downregulation of leukocyte integrin activation thereby reducing their response to platelet activation factor (PAF), a potent pro-inflammatory cytokine. Maresins are involved in converting pro-inflammatory phenotype of macrophage M1 to pro-resolving M2, in reducing superoxide production by TNFα and nuclear translocation of p65, which together result in a reduction of pro-inflammatory NFκB pathway. Protectins act in a pro-resolving manner by downregulating certain markers for chemotaxis such as Vascular Cell Adhesion Molecule (VCAM-1) and Monocyte Chemoattractant Protein (MCP-1). Lipoxins are shown to facilitate resolution by stopping further recruitment of neutrophils, inducing nonphlogistic migration and induction of macrophages to clear apoptotic neutrophils.

Conclusions

We expect to see further research in translating these findings to bedside clinical trials in the treatment of conditions with a pathophysiological basis of inflammation such as coronary artery disease, asthma, periodontal disease, etc.

Endocrinology and metabolism I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#18 Coronary artery calcification scoring in transgender individuals

T Duro*

E Choi

P Kapsner

The University of New Mexico, Albuquerque, NM

Purpose of Study

To assess risk factors and the prevalence of coronary artery disease (CAD) using coronary artery calcium (CAC) scoring in transgender individuals receiving gender affirming hormone therapy (GAHT).

Transgender individuals are treated with cross sex hormone therapy. These hormones alter metabolic profiles and may be associated with risk factors for CAD. Little data is available on the atherosclerotic vascular risk due to GAHT in transgender individuals. CAC Scores have been validated as a noninvasive method to assess risk for cardiovascular events in the general population.

Methods Used

This is a pilot study assessing feasibility of obtaining baseline risk profiles and CAC scores in transgender patients over the age of 18, in order to establish a baseline risk assessment and the prevalence of CAD in this population. Patients with risk factors other than smoking and family history were excluded. Difference in CAC Scores were compared to those in The Coronary Artery Risk Development in Young Adults (CARDIA) study. Baseline characteristics were compared using t-tests.

Summary of Results

Out of 25 transwomen recruited, 24 completed CAC. 3/24 (12.5%) had CAC >0. One had CAC >100. Out of 22 transmen recruited, 16 completed CAC. 2/16 (12.5%) had CAC >0. None had CAC >100. CAC scores did not correlate with the presence of risk factors. Patient data in table 1.

Abstract #18 Table 1

Baseline characteristics

Conclusions

Overall, 12.5% of transgender people on GAHT had positive CAC scores. This is similar to the findings of the CARDIA study where the prevalence of positive CAC scores in the general population was 11.7%. There was a higher percentage of current smokers in transwomen who also had higher triglycerides, but a lower LDL. Transmen had a higher family history of CAD, percentage having ever smoked, and a higher hsCRP. This cross-sectional study shows that obtaining CAC scores in transgender patients is feasible and that the prevalence of positive CAC scores appears to be similar to that of the general population. A larger, longitudinal study will be performed to expand on these findings.

#19 Beyond binding: key questions regarding the role of shbg in male reproduction

K Schuppe*

K Roberts

Washington State University Elson S Floyd College of Medicine, Spokane, WA

Purpose of Study

Human Sex Hormone Binding Globulin (SHBG) is a homodimeric glycoprotein encoded by the SHBG gene on chromosome 17p13.1. The gene is predominantly expressed in the liver and SHBG is secreted into the blood whereas, in murine species where much of our understanding comes from, the ortholog of SHBG is expressed primarily in Sertoli cells. SHBG binds both steroidal and nonsteroidal ligands with high affinities and has been traditionally viewed as functioning as a reservoir and means of transport for steroids in serum. SHBG has also been implicated in androgen uptake by cells and as a signaling molecule with a cell surface receptor on target cells. More recently a germ cell-specific form has been identified in the human testis, raising questions about a role for SHBG in germ cell function and fertilization. The objective of this review was to determine aspects of SHBG function that require further investigation.

Methods Used

A systematic search of the literature, using NCBI and other databases compiling peer-reviewed publications, was conducted using keywords: Sex Hormone Binding Globulin; SHBG; SHBG Receptor; SHBG Isoform; SHBG Expression; Megalin; Androgen Binding Protein; ABP. Additional papers were found via citations, both forward and back. The focus of the review was on literature published in the last 25 years, prioritizing the most recent research. Studies were excluded where SHBG function, structure, genetic regulation was not a topic of investigation, such as studies focused on genome-wide analysis, SNP’s, and SHBG in the context of an upstream pathology.

Summary of Results

In total 95 publications were identified and kept for producing either new experimental evidence or analysis of prior data that provided new insights into the role of SHBG on reproduction. The literature search converged on studies investigating SHBG’s steroid-binding properties, protein-protein and protein-receptor interactions, novel germ cell forms of SHBG, and clinical findings from both normal and natural mutant phenotypes. The findings from these studies were summarized and gaps in our knowledge of SHBG’s role in reproductive function were identified

Conclusions

Four unanswered questions regarding SHBG/ABP function emerged from review of the literature. 1) Is SHBG essential in the development and regulation of the reproductive system? 2) What is the identity of the cell surface receptor for SHBG? A number of studies have demonstrated specific binding and subsequent signaling, yet no receptor has been identified. 3) Does the site of SHBG synthesis and secretion matter? 4) What is the function of the germ cell form of SHBG? Germ cells have the second-highest level of expression of SHBG, but we know very little about it. These questions seem key to future research on the role of SHBG in reproduction.

#20 Suprasellar and sellar meningioma in pregnancy presenting with worsening visual deficits and panhypopituitarism

SM Laies1*

J Fuh2

C Lovato1

1The University of New Mexico, Albuquerque, NM

2University of California Los Angeles Health System, Montecito, CA

Case Report

Meningiomas account for 13% of CNS tumors during pregnancy and are predominantly low grade WHO I tumors. Case series have reported rapid growth of these tumors during pregnancy, particularly during the second and third trimester, likely due to factors including intra-tumoral hypervascularity and tumor growth due to high sex hormone levels and the presence of progesterone receptors on tumor cells. As a result, patients can present with neurologic and visual field (VF) deficits and in rare cases, herniation and coma. We report a case of a pregnant patient with worsening of VF deficits and panhypopituitarism due to a meningioma in the suprasellar and sellar region. A 36-year-old woman G4P3 at 20 weeks, was transfered to our facility for neurosurgical intervention for acute worsening of VF deficits. She initially presented to her ophthalmologist with a 4-month history of headaches and right-sided vision loss and was found to have a sellar mass on imaging. She then began to have nausea and vomiting, weakness, and orthostasis which necessitated admission. The patient was given i.v. hydrocortisone (HC) due to a suspicion for adrenal insufficiency with improvement in symptoms. However, after receiving steroids, she developed polydipsia and polyuria. On arrival to our facility, the patient was noted to have urinary output (UO) of up to 6 liters per day with a low urine osmolality of 53 mosm/Kg (50–600 mosm/Kg) and serum Na as high as 147 mmol/L (134–144 mmol/L). She was given desmopressin (DDAVP) with improvement in serum Na and UO. Biochemical testing also revealed secondary hypothyroidism and L-thyroxine (L-T4) was initiated. An MRI of the brain on admission showed a 3.6 cm lobulated suprasellar and sellar mass with mass effect on the optic chiasm. Formal VF testing showed complete VF loss on the right and temporal loss on the left. After review of the patient’s case by a multidisciplinary team consisting of Neurosurgery, MFM, and Endocrinology it was decided to proceed with surgery. The patient underwent left pterional craniotomy and resection of the suprasellar component of the mass with decompression of the optic chiasm. Pathology showed a meningioma, WHO Grade I. Post-operatively, VF deficits improved and on discharge from the hospital, she was continued on DDAVP, L-T4 and HC. This is a rare case of a meningioma resulting in hormonal deficiencies in the anterior and posterior pituitary along with VF deficits which likely developed due to the location and rapid growth of the tumor in the setting of pregnancy. The decision for surgery during pregnancy should be based on clinical presentation and should involve a multidisciplinary team to determine the best management that limits complications to the mother and fetus.

#21 Unraveling the mystery of thyrotoxicosis in a patient with panhypopituitarism

AT Chuang*

BW Hager

M Bouchonville

University of New Mexico Health Sciences Center, Albuquerque, NM

Case Report

In the setting of panhypopituitarism, hypothyroidism develops as a result of TSH deficiency rather than a primary insult to the thyroid gland. We describe a case of a patient with acquired panhypopituitarism who developed severe thyrotoxicosis, which persisted despite discontinuation of replacement thyroid hormone.

A 24-year-old Hispanic female with panhypopituitarism following a craniopharyngioma resection in 2010 presented with severe thyrotoxicosis. She initially presented with anxiety and palpitations and was observed to have a mild free T4 (FT4) elevation, which prompted a reduction in her replacement dose of levothyroxine. With progression of her FT4 elevation, the levothyroxine was discontinued and she was ultimately referred to adult endocrinology when clinical presentation worsened. Upon further evaluation, she reported weight loss of more than thirty pounds, palpitations, insomnia, fatigue, muscle weakness, bilateral hand tremors, nausea, vomiting, and dizziness. She confirmed a period of several months without levothyroxine. Heart rate was 109 bpm, no proptosis was noted, thyroid examination revealed no thyromegaly, no tremors were appreciated, and there were no findings suggestive of heart failure. FT4 at that time was 7.6 ng/dL (reference 0.7–1.6 ng/dL). Thyroid peroxidase antibody and TSH receptor antibody levels were negative. Thyroid ultrasound demonstrated an atrophic left thyroid lobe; no nodules were identified. Thyroid uptake was low at 1.8% at 24 hours. This unexpected finding prompted a thyroglobulin (TG) level to distinguish between subacute thyroiditis or an ectopic source of thyroid tissue versus a low TG state such as factitious thyrotoxicosis. TG was low at 3.3 ng/ml, prompting a pharmacy query, which revealed that she was continuing to fill levothyroxine prescriptions at three pharmacies.

A more comprehensive review of her behavioral health history revealed persistent depressive disorder, PTSD, psychogenic nonepileptic seizures, and numerous recent psychosocial stressors. We approached her care in a non-confrontative manner by presenting a range of possible explanations for her clinical and laboratory findings and sharing our recommended treatment.

This case highlights an unexpected presentation of factitious thyrotoxicosis secondary to surreptitious use of levothyroxine in a patient with acquired panhypopituitarism, and the stepwise evaluation that led to this conclusion. We discuss the strategies implemented in managing this patient and review approaches to patients with factitious disorders.

#22 Feasibility of extending sleep in a pilot sample of teens with obesity and short sleep: the REM study

AE Bowen1*

S Simon2

M Cree-Green2

KJ Nadeau2

J Kaar2

1Children’s Hospital Colorado, Aurora, CO

2University of Colorado Anschutz Medical Campus, Aurora, CO

Purpose of Study

Insufficient sleep duration is common among adolescents and may contribute to insulin resistance, dysglycemia, and precursors to type 2 diabetes (T2D). Youth-onset T2D has devasting long-term effects, and thus prevention strategies for adolescents at risk for T2D are needed. Increasing total sleep time (TST) may be one such strategy. We tested the feasibility of a 4-week sleep extension intervention for adolescents treated within an outpatient weight management clinic.

Methods Used

High school students aged 14–19 years with insufficient sleep (<8 hours) on school nights were recruited during the academic year. Exclusion criteria included T2D, medications that affect sleep, and a schedule that precluded participants from adhering to sleep extension (e.g., night shift employment). Following sleep monitoring at home for 1 week, a revised sleep schedule was collaboratively created with a target of increasing time in bed (TIB) by 2 hours. Participants followed this schedule for 2 weeks (W2), returned to the clinic to discuss barriers to adherence to the prescribed schedule, and then followed the revised schedule for another two weeks (W4). Feasibility was assessed by adherence to wearing sleep watch and submitting sleep diaries, improvement in TIB and TST, and self-reported barriers to following prescribed sleep schedule. Data are reported as averages ± sd or medians (min, max).

Summary of Results

A total of 6 participants have been recruited for the study to-date; however, 2 were withdrawn due to COVID-19 school closures when shifted to online learning. Participants (n=4) were aged 17.0 ± 0 years, 100% Hispanic, with a BMI percentile of 98.4±0.9 kg/m2. All participants completed the intervention; 99.4% adhered to Actigraphy and 65.6% to the sleep diary. At baseline, the average TIB was 7.3±1.6 hours and TST was 5.8 ±1.5 hours. Compared to baseline, W2 hours of TIB [1.2 (-0.1,2.6)] and TST [1.2 (-0.4,2.1)] increased and W4 hours of TIB [0.1 (-1.8,5.3)] and TST [0.7 (-1.5,4.1)] increased. Increased TIB was primarily achieved by shifting bedtimes earlier, while waketimes remained relatively consistent. Barriers to adherence included homework, extracurricular activities, and parents’ and youths’ variable work schedules.

Conclusions

Initial findings indicate a 4-week sleep extension intervention in adolescents with short sleep seeking treatment for weight management is feasible. Participants increased TIB and TST by a median of 1.2 hours. However, additional strategies are needed to maintain such improvements. School and community efforts to delay high school start times may benefit youth at risk for T2D by enabling them to increase TST.

#23 Relationship between high carbohydrate and vitamin d intake on sleep quality among adult population of United States

C Brown*

M Shaheen

K Schrode

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

Purpose of Study

Quality of sleep depends on diet as carbohydrate or vitamin D. Sleep quality is challenging to study due to cost, resources, and availability of research subjects. There is a gap in the literature examining the impact of carbohydrates and vitamin D intakes on sleep quality. We aim to examine the association between carbohydrate and vitamin D intakes and sleep quality among adult US population.

Methods Used

We analyzed data from the National Health and Nutrition Examination Survey 2007–2014. Carbohydrate and vitamin D intakes were categorized into three groups based on the distribution. Sleep quality was assessed using hours of sleep, have sleep problem and doctor diagnosed sleep disorder. We used chi square and multiple logistic regression to analyze the data considering the design and sample weight.

Summary of Results

Of the 16,415 adults, 35% had high carbohydrate intake (>283 gm), 31% had low vitamin D intake, 36% slept <7 hours/day, 27% reported sleep problem, and 9% had sleep disorder. There was no relation between the high carbohydrate intake and low vitamin D intake and the hours of sleep (p>0.05). However, high vitamin D intake was associated with sleep disorders and troubled sleep (p<0.05) adjusting for the confounding variables. Minority, divorced/widowed, overweight/obese, smokers, with diabetes, kidney disease, depression were more likely to have low sleep hours relative to the other groups (p<0.05).

Conclusions

Our study indicated no association between carbohydrate and vitamin D intakes and sleep quality. Longitudinal prospective studies are needed to examine factors associated with quality of sleep and their mechanisms.

#24 Autoimmune hepatitis presenting as fulminant hepatic failure

NC Trang*

AS Gill

K Radicic

N Karapetians

S Mishra

Kern Medical Center, Bakersfield, CA

Purpose of Study

To present an interesting case with an atypical presentation of a rare disease.

Methods Used

A single patient case report was conducted after IRB approval.

Summary of Results

Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver that typically presents with the presence of AIH-related antibodies. There are two types of AIH: type 1 is associated with anti-smooth muscle antibody (anti-SMA) and type 2 associated with anti-liver/kidney microsome type 1 antibody or anti-liver cytosol type 1 antibody. About 25% of patients with AIH are asymptomatic. Rarely, patients with AIH present with features of fulminant hepatic failure with rapidly progressive liver impairment, coagulopathy, and hepatic encephalopathy or coma.

We present a case of a 63-year-old female who presents to the hospital with altered mental status (AMS) of one day duration. Her labs were significant for acute kidney injury (AKI), elevated liver function tests, and urinalysis consistent with urinary tract infection (UTI). Computerized tomography (CT) abdomen and pelvis showed bilateral pyelonephritis. Urine cultures grew pan-sensitive Escherichia coli, and she was treated with 10 days of Ceftriaxone. During this course, renal function worsened with uremic-range BUN and she became oliguric, thus hemodialysis was initiated with good response in both renal indices and mental status. Patient was also found to have coagulopathy with a worsening PT/INR of 32.2/3.24. Further workup of AKI revealed proteinuria and positive atypical p-ANCA and anti-SMA, raising concern for autoimmune disease in both kidneys and liver.

Conclusions

Our patient’s symptoms originally raised concerns for pyelonephritis secondary to a UTI. Despite a full course of antibiotics, her kidney function continued to decline until receiving dialysis. She was also determined to have fulminant hepatitis with coagulopathy followed by positive autoimmune antibodies. This course leads us to believe that the etiology of her encephalopathy was secondary to autoimmune liver and kidney disease.

The main interest of this case report lies in autoimmune hepatitis secondary to atypical P-ANCA and anti-SMA presenting as fulminant hepatic failure in the setting of AKI. Atypical P-ANCA seems to be more specific for autoimmune hepatitis than the typical P-ANCA [1]. Anti-SMA antibodies found in about 50% of type 1 AIH [1]. Both nephrology and gastroenterology recommended renal/liver biopsy for definitive diagnosis which will be done outpatient.

#25 Diabetic neuropathic cachexia – an uncommon mimic

JS Gilbert1*

K McCloskey2

P Gulani3

A Outon3

1University of Colorado, Denver, CO

2Beth Israel Deaconess Medical Center, Boston, MA

3Jacobi Medical Center, Bronx, NY

Case Report

A 52-year-old man with poorly controlled type 2 diabetes presented with four months of watery diarrhea. During this period, he also noticed an unintentional 80-pound weight loss, a ‘burning’ sensation on his anterior thighs, and new onset depression and anxiety. He had no recent history of fever, chills, or night sweats. He was not prescribed insulin, though glipizide was added to his diabetes regimen about six months prior. Physical examination revealed a cachectic man with a BMI of 18.4 kg/m2, normal vital signs, and an unremarkable rest of exam. Laboratory evaluation was notable for a white blood cell count of 21.8 x 10^3 cells/mm3, an anion gap of 26, and a glucose level of 280 mg/dL. He also had a CRP of 147.1 mg/dL and an HbA1C of 19.3%. Serology for HIV-1, HIV-2, HBsAg, and HCV were all negative, and a fecal fat test was normal. Chest x-ray was clear, a transthoracic echocardiogram showed no valvular vegetations, and CT scans of his chest, abdomen, and pelvis were completely normal.

This patient’s concerning cluster of symptoms provoked an extensive workup to rule out cancer, infection, and malabsorptive syndromes. However, this patient’s presentation matched an uncommon neuropathy syndrome found in diabetes. Diabetic neuropathic cachexia (DNC) is an extremely rare neuropathy – only 36 cases have been reported in the literature – but its unique cluster of symptoms often incites a search for a hidden malignancy or insidious infection. DNC most commonly presents in a type-2 diabetic after initiation of an oral anti-hyperglycemic medication with profound weight loss, mood symptoms, symmetric peripheral neuropathy, and painful limb paresthesias. Management of this neuropathy is directed at improving glycemic control, as most patients recover within one to two years with improvement in A1C, though some can suffer residual neurologic deficits.

#26 Upper extremity deep venous thrombosis secondary to thyrotoxic periodic paralysis with accompanying hyperphosphatemia and severe hypomagnesemia

J Rahesh*

L Al-Sukhni

B Quraishi

T Naguib

Texas Tech University Health Sciences Center, Lubbock, TX

Case Report

A 20 year old male with history of drug abuse and osteochondritis presented to the emergency department with bilateral leg weakness and feet numbness since the morning when he woke up unable to move his legs or his back and fell out of bed, after which he noticed that he had feeling in his legs but not his feet. He was found to be profoundly hypokalemic at 1.6 mmol/L and hypomagnesemic at 1.5 mg/dL. Phosphate levels were not taken but calcium was 9.0 mg/dL. These values were verified by a redraw and repeat chemistry. The patient denied nausea, vomiting, and diuretic use, but did report lose bowel movements for long months due to self-diagnosed IBS. He also reported alcohol use of 4–6 beers 1–2 times a week for years. The patient was admitted for potassium and magnesium intravenous replacement. Chest X Ray, MRI of the cervical spine, CT scan of the brain, and drug panel were all negative.

On day 1 of hospital stay the patient’s electrolyte levels improved, with a potassium of 3.6 mmol/L a magnesium of 1.8 mg/dL, a phosphate of 4.0 mg/dL, and a calcium of 8.9 mg/dL. On day 2, he reported improved strength after working with physical therapy but did not feel at baseline. His labs indicated a potassium of 3.6 mmol/L, a magnesium of 1.8 mg/dL a phosphate of 5.0 mg/dL and a calcium of 9.3 mg/dL. His SARS-CoV2 antigen, blood, and urine cultures were all negative. A negative TTG IgA test ruled out Celiac disease.

On day 3, potassium was 4.4 mmol/L, and magnesium was 1.7 mg/dL, and a newly elevated phosphate of 5.7 mg/dL was noted. Calcium was 9.0 mg/dL. Right arm edema and pain at the PICC line site prompted removal of the line but an ultrasound showed an occlusive DVT. A heparin drip was ordered, and a V/Q scan was negative. An asymptomatic run of ventricular tachycardia prompted an echocardiogram and troponin evaluation, but both were negative.

On day 4 his labs revealed a low TSH of <0.01 an hypomagnesemia of 1.8 mg/dL. Potassium was within normal limits. Phosphate was still elevated at 5.5 mg/dL and calcium was 10.0 mg/dL.

On day 5 a low TSH of<0.01 was confirmed once again, elevated T3 9.99 pg/ml and T4 2.86 ng/dL were also noted. Potassium at this time was 4 mmol/L, magnesium was within normal limits, phosphate was elevated at 7.0 mg/dL, and calcium was 9.5 mg/dL. A PTH was also measured at this time and was found to be normal at 36.7 pg/mL. Ventricular tachycardia was attributed to hyperthyroidism, and a diagnosis of thyrotoxic periodic paralysis was made. An ultrasound of the neck showed a hypervascular thyroid consistent with Graves’ disease or thyroiditis. Thyroid stimulating immunoglobulin was drawn, and the patient began a regimen of 10 mg methimazole 3 times daily.

On day 6 the patient had a potassium of 3.8 mmol/L, phosphate of 6.2 mg/dL, calcium of 9.6 mg/dL and a magnesium of 2.3 mg/dL. On day 7 the patient was discharged.

Healthcare delivery research I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#27 Diabetes prevention at work: 10-yearfollow-up of glycemic control and serum lipoproteins in healthy workers with and without health coaching and monetary incentives

LW Raymond1,2*

1Atrium Health, Charlotte, NC

2University of North Carolina System, Chapel Hill, NC

Purpose of Study

Knowing of the success of lifestyle changes in the Diabetes Prevention Program, we wondered if similar results could be achieved in a workplace setting with the collaboration of an employer in the Charlotte, NC region.

Methods Used

We compared diabetes incidence and serum lipoprotein concentrations in two groups. Cohort 1 comprised 504 workers (mean age 49, 88% males). Cohort 2 comprised 131 workers (age 52, 85% males). Cohort 1 received health coaching by a physician assistant or nurse practitioner who encouraged regular exercise, healthy weight, carbohydrate limitation, smoking abstinence, and blood pressure control. They compared baseline values of HbA1c with those associated with prediabetes and diabetes, >5.7 and >6.5, respectively. Cohort 1 workers also received up to $800 per year, based on the above lifestyle choices as well as HbA1c and lipoprotein levels. The latter were also measured in Cohort 2, but no incentives or health coaching were provided, other than individual letters containing their blood test results.

Summary of Results

Diabetes developed over 10 years in 59 Cohort 1 participants compared to 93 expected (chi-squared = 8.56, p = 0.003) on the basis of initial HbA1c values (Zhang X et al., Diabetes Care 2010;33:1665). Workers with prediabetes decreased from 192 to 141. In Cohort 2, five participants were diagnosed with diabetes, the same number as expected. However, workers with prediabetes increased from 28 to 36.

Serum lipoproteins improved in both cohorts (table 1).

Conclusions

Preventing diabetes benefits individual workers and their families. Employers who share in the health care costs of their workforce also stand to benefit substantially from diabetes prevention, as these costs are $9,601 per year higher in persons with this condition. Health coaching and monetary incentives were associated with improved glycemic control as well as lower lipoproteins. Only the latter improvement was found in the group of workers not provided either of the above interventions in this retrospective analysis. Further prospective observations may identify the respective roles of coaching and monetary incentives. Whether these improvements are associated with better outcomes in cardiovascular end points in these workers would also be of great importance.

Abstract #27 Table 1

Initial and follow-up biometrics in workers with (Cohort 1) and without (Cohort 2) health coaching

#28 Medical student perceptions of intimate partner violence screenings in in-person vs telemedicine settings

J Lai1*

A Cheng1

AL Nelson1,2

M Fraix1

M Hudson1

1Western University of Health Sciences, Pomona, CA

2University of California Los Angeles, Los Angeles, CA

Purpose of Study

Intimate Partner Violence (IPV) is a public health crisis that impacts 25% of women and 10% of men in the US, totaling 43 million women and 38 million men. IPV screenings traditionally occurred at doctor offices, which was to be a safe space, but with the transition to telemedicine, screening is done at home. This study sought to identify potential educational and practice gaps in care surrounding IPV screenings in different settings. We aimed to understand medical students’ general experiences (personal and professional), attitudes, and perceptions of IPV screening.

Methods Used

To assess student experiences with IPV screenings as both patients and clinicians-in-training, two separate IRB-approved surveys were created and beta-tested for Western U COMP/COMPNW medical students. One for those who had clinical rotations and the other for those who had not. Questions included personal experiences with in-person and telemedicine IPV screenings, how screenings were conducted, and their perceived importance. Fourth-year students were asked additional questions regarding their experiences observing patients being screened. We used descriptive analysis of the responses to determine the frequency of IPV screening and the modalities in which IPV screening was conducted in in-person and telemedicine environments.

Summary of Results

170 students participated in the study for a response rate of 13%: 140 students from the non-clinical cohort and 30 students from the clinical cohort. Overall, 36.9% of students, who had been seen for an in-person appointment, reported they had been screened for IPV, while only 12.5% of students seen in telemedicine appointments were screened. Among those with in-person appointments, screening was by written survey (31.7%), online survey (10%), and via verbal screen (58.3%). However, among those seen via telemedicine, screening was conducted by online survey (30%) and by verbal screening (70%). Healthcare staff who administered IPV screens shifted from medical assistants (MAs) (35.6%), doctors (35.6%) and nurses (26.7%) for in-person screenings to MAs (28.6%), doctors (28.6%) and receptionists (28.6%) in the telemedicine screenings. In the clinical cohort, 56% of students observed in-person IPV screenings during rotations, compared to 8.33% of students with telemedicine experience who observed IPV screenings via telemedicine.

Conclusions

Medical students reported IPV screening was decreased in the telemedicine setting, which could increase the risk of under detection. Virtual screening was more frequently done verbally and conducted by less trained personnel. This study is unique because it provides the perspective of medical students as both patients and healthcare providers in training and demonstrates both educational and practice gaps in this new environment.

#29 TDAP vaccine uptake and attitudes among English and Spanish speaking pregnant patients

E Jimenez1*

H Stohl2,3

AL Nelson1

1Western University of Health Sciences, Pomona, CA

2Harbor-UCLA Medical Center, Torrance, CA

3University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

Purpose of Study

Despite the recommendations of The American College of Obstetrics and Gynecology, and the health benefits that administering the T-dap vaccine can have on prenatal patients and their newborns, nearly 45% of prenatal patients do not receive the vaccine. We surveyed English and Spanish speaking prenatal patients, to measure uptake and assess patient knowledge and attitudes of the Tdap vaccine. We compared the responses of English and Spanish speaking patients to identify if inconsistencies existed.

Methods Used

Using an IRB approved protocol, we surveyed low-income patients at Harbor UCLA Medical Center Obstetrics clinic in Torrance, CA for 7 weeks in Summer 2021. Patients were at least 18 years of age and > 32 weeks gestational age. Upon obtaining verbal consent, we administered a 31-question beta-tested survey in their preferred language, English or Spanish.

Summary of Results

The response rate achieved by the survey was 97%. There was a total of 98 participants, 80 of which answered the survey in English and 18 in Spanish. 49% of subjects were Hispanic/Latino, 35% African American, 3% Caucasian and 13% were of other ethnicities. Most of our patients (67%) were between the ages of 20–30. 69% of English-speaking patients received the vaccine and 79% of Spanish speaking patients also received the vaccine. Among all our 98 participants there was an overall Tdap vaccine uptake of 70%. The most common reason for refusal of the Tdap vaccine among English speaking patients was due to safety concerns for their baby (47%), concerns for themselves (47%) or because they believed that they did not need the vaccination (47%). While, only 4% of English-speaking patients denied the vaccine because they were unaware they required it, this was the most common reason for refusal of the vaccine by Spanish speaking patients (66%).

Conclusions

Overall, 70% of patients received the Tdap, higher than national averages, but still short of the goal, leaving substantial numbers of women and their newborns unprotected. Both uptake and reasons for refusal of Tdap vaccine differed among English and Spanish speaking patients. This may suggest a need to look more closely at the how Tdap vaccine information is presented in both languages to ensure that the same information or information more relevant to different groups, is being relayed to all prenatal patients.

#30 Equity through the end-of-life: advancing palliative care for Northern California’s rural underserved

R George*

S Gill

UC Davis School of Medicine, Sacramento, CA

Purpose of Study

Interdisciplinary research has shown palliative care improves patient experience by addressing adverse symptoms and psychosocial needs during complex and life-limiting illness. The benefits of early inclusion of palliative care in medical management extends to caregivers, providers, and health systems. Additionally, the integrated interprofessional model of palliative care equips it for addressing health disparities for populations carrying a disproportionate burden of illness. Rural communities are among the systemically marginalized and underserved, and as such are poised to benefit from the advancement of palliative care. While prior research assessed challenges faced by rural palliative care providers, an analysis of the scope and equity of palliative care services for Northern California’s rural underserved has not been undertaken. Further, this study identifies areas of underservice, analyzes corresponding population demographics, and underlines opportunities for addressing specific health disparities.

Methods Used

This research included the collection and analysis of publicly available data pertaining to populations and palliative care organizations of Northern California. Population data sources included the Health Resources and Services Administration and the United States Census Bureau. Palliative care organization data sources included the Center to Advance Palliative Care and the National Hospice and Palliative Care Organization. Data were correlated to identify statistically significant factors pertaining to palliative care access, as well as benchmarks for determining underserved status within the region.

Summary of Results

Statistically significant correlations with key population, organizational, and access stratification data identified 13 factors found to be consistent with a county being underserved relative to palliative care access in the region. Several of these factors also represent risk for a county remaining underserved due to economic and organizational infrastructure deficits. Based on these factors, 19 of the 29 counties included in this study qualified as underserved and are at risk for remaining underserved. Additionally, strong evidence exists that protective factors enhancing palliative care access include increased population diversity across race, sex, and age groups. Significant opportunities were identified for expanding the scope, access, and equity of palliative care services based on these findings.

Conclusions

Our analysis provides a data-driven approach to improving the access and equity of palliative care services in rural Northern California. A collaborative, community-based, approach to the early inclusion of palliative care in medical management has the possibility of significantly improving health outcomes for medically underserved populations. Additionally, understanding how increased population diversity acts as a protective factor is worthy of further study.

#31 Beyond the blackout: the far reaching impact of traumatic brain injury on the hypothalamic-pituitary-gonadal-axis and reproductive function of naval special operations forces

K Schuppe1*

MG Johnston1

CC Lyons2

1Washington State University Elson S Floyd College of Medicine, Spokane, WA

2Naval Medical Center San Diego, San Diego, CA

Purpose of Study

Traumatic brain injury (TBI), is a common injury amongst veterans who have served in Iraq and Afghanistan. With the number of veterans from these conflicts now approaching 3 million, it is estimated that approximately 20% have suffered at least one TBI. Beyond the structural trauma, TBI may also lead to transient, or even permanent, pituitary insufficiency. Of particular interest are the consequences of TBI-induced hypogonadotropic-hypogonadism (HG) on short and long-term health. TBI clearly presents economic implications for the nation, related both to direct medical expenses and indirect costs. The purpose of this review is to summarize the knowledge about post-TBI hypopituitarism, its screening and treatment recommendations, costs, with a special focus on the potential impacts of post-traumatic hypogonadism on naval special operators.

Methods Used

We utilized DoD, CDC, and NIH datasets on TBI’s, alongside Endocrine Society and AUA Guidelines, and finally NCBI and Google Scholar searches of the following key terms: pituitary dysfunction, traumatic brain injury, hypogonadotropic hypogonadism, hypogonadism treatment, TBI screening, hormone therapy, fertility, special operations, special forces. The aforementioned sources were used to roughly predict prevalence of post-TBI Hypogonadism in special operators, it’s potential costs and consequences, and carry over its standards for screening and treatment.

Summary of Results

According to recent estimates, the range of TBI amongst all servicemen serving in Iraq or Afghanistan, taken together from 2000 to 2016, runs from 11–23%. Persistent hypogonadotropic hypogonadism following TBI meanwhile, amongst the general population, is predicted to fall within the wide range of 8–41%. It was found that hypogonadism was associated with incidence of PTSD among other physiologic consequences such as sexual dysfunction, osteoporosis, and neurodegeneration. Recent literature has proposed post-TBI pituitary dysfunction screening and therapy among the general public, but little for post-deployment special forces or veterans specifically.

Conclusions

While we can crudely postulate from comparisons to other groups, there is a distinct lack of recent data on TBI’s in naval special forces. But, what is clear is the connection between TBI’s and subsequent pituitary dysfunction, in which hypogonadotropic hypogonadism is likely the second most common subtype. Taken together, further retrospective and prospective studies are needed to further investigate hypogonadotropic pituitary dysfunction after TBI’s acquired in the line of duty by naval special forces servicemen with the purpose of establishing screening guidelines for these servicemen and ultimately provide appropriate treatment algorithms for the preservation of their quality of life, fertility, and protection against comorbid disease.

#32 Quantifying burden of care for cleft lip and palate patients from the patient, provider, and system perspectives

A Buchel1,2*

E Wells-Durand2,3

M Bucevska2,3

R Courtemanche2,3

J Staples2,3

R Thomson2,3

DJ Courtemanche2,3

S Palm2,3

T Gibson2,4

A Loo2,4

JS Arneja2,3

1The University of British Columbia Faculty of Arts, Vancouver, BC, Canada

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

3The University of British Columbia Faculty of Medicine, Vancouver, BC, Canada

4The University of British Columbia Faculty of Dentistry, Vancouver, BC, Canada

Purpose of Study

Management of cleft lip and palate (CLP) is complex and multidisciplinary, and can last until adulthood. This study aims to describe the healthcare utilization burden of care (BoC) for the management of patients with non-syndromic CLP by identifying a provider burden, characterizing an interaction burden, and calculating an economic burden associated with their health system interactions.

Methods Used

This study is designed as a retrospective chart review between January 1, 1999 and April 30, 2021 of patients with non-syndromic CLP cared for at British Columbia (BC) Children’s Hospital. Healthcare utilization data for inpatient, outpatient, and emergency encounters were extracted from paper and electronic health records. Community outpatient data were obtained from affiliated specialists. Bottom-up micro-costing was utilized for hospital costing, our tariff guide was utilized for provider reimbursement, and zip code was utilized to calculate patient costs.

Summary of Results

Our results indicate that 58 patients identified with cleft lip and palate had a mean of 156.4 healthcare interactions (consults/follow-ups/surgeries) between the ages of 0–18 years. The distribution of healthcare interactions was 92.4% outpatient, 7.3% inpatient, and 0.3% emergency. Patients had a mean of 11.4 surgical procedures, for which the primary services are plastic surgery (5.6), surgical ENT (2.6), oral surgery (1.2) and dentistry (1.2). The remainder consisted of emergency room visits (0.5) and interactions with outpatient speciality services including orthodontics (78.2), plastic surgery (14.7), and ENT (13.5) most frequently. Costing data will ultimately be provided at the physician, patient and system levels.

Conclusions

Patients born with non-syndromic CLP have a high frequency of healthcare encounters, suggesting a substantial BoC. These findings will inform parents, and motivate the development of more efficient healthcare systems to maximize patient access to care by right sizing resources (provider, support infrastructure, property/plant/equipment).

#33 The effectivness of a low-cost simulation-based module for tearching ultrasound-guided fine needle aspiration of thyroid nodules

H Huber1*

S Thevuthasan1

TJ Robinson2

M Sardesai1,3

T Tylee1,3

1University of Washington School of Medicine, Seattle, WA

2University of Wyoming, Laramie, WY

3Harborview Medical Center, Seattle, WA

Purpose of Study

High rates of thyroid nodules in the population often require fine needle aspiration (FNA) to rule out thyroid cancer. Competency guidelines for residents and fellows to properly perform FNAs are lacking, leading to these essential skills being taught on the job. Simulation based trainings offered by professional societies are effective but often require travel and are expensive. We created a brief hands-on module designed to be 1–2 hours in length to introduce trainees to basic thyroid ultra-sound (US) and US-guided FNA to improve trainees’ comfort with the procedures. This study evaluated whether participating in this module improves the comfort of resident and fellows with thyroid US and FNA prior to performing the procedure on patients while being cost- and time-effective.

Methods Used

A hands-on training module for US-guided FNAs was developed and offered yearly for 6 years to residents and fellows at Harborview Medical Center. The models used were purchased from Northwestern Medical Center for $25 each and one model was used for each session. 40 pre-surveys and 26 post-surveys were collected directly before and after the module. Participants were primarily otolaryngology residents (n= 15, 11) and endocrinology fellows (n=13, 8) with varying experience. The surveys assessed their comfort level performing US-guided FNAs on a scale of 1 to 5, with 5 being most comfortable and able to perform independent of supervision. The surveys also assessed their comfort with interpreting thyroid US, and long- and short-axis US-guided FNA. Effectiveness was assessed by calculating the change in comfort using population averages, regardless of specialty on the post-survey compared with the baseline level. Significance was determined using a permutation test.

Summary of Results

On average, participants’ comfort with US-guided FNA increased by 1.19 (p=0.0006) on the 1–5 scale, comfort level with long- and short-axis US-guided FNA increased by 1.54 and 1.51, and comfort with interpreting thyroid US improved by 0.97. For endocrinology fellows and otolatyngology residents specifically, their change in comfort level for performing US-guided FNA increased by 1.02 and 1.17.

Conclusions

Overall, residents and fellows showed an improvement in comfort level after completion of the module. This improvement was not only evident in performing US-guided FNA but also with FNA technique and US interpretation. Although comfort does not equivalate skill, at $25 per session our module is a promising alternative to costly and time-consuming simulations courses, which often cost upwards of $700 per individual. These training modules can be executed in most residency and fellowship training programs to provide accessible training of these important skills.

#34 Pre-operative iSTOP huddle for improved transition of care of pediatric and neonatal critical care patients

M Nolan1,2,3*

A Hadley2,3,4

M Baserga1

C Pries3

A Nicholson3

M Harrison3

N Dinh3,5

E Prentice3,4

K Miller3

J Huntington3,4

B Huizinga3

E Durkin2,3,6

1University of Utah Health, Salt Lake City, UT

2Michigan State University, Grand Rapids, MI

3Helen DeVos Children’s Hospital, Grand Rapids, MI

4Spectrum Health Medical Group, Grand Rapids, MI

5Neonatal Associates, PHC, Grand Rapids, MI

6Pediatric Surgeons of West Michigan, PC, Grand Rapids, MI

Purpose of Study

Patients admitted to the pediatric or neonatal intensive care units (PICU or NICU) at Helen DeVos Children’s Hospital in Grand Rapids, MI, prior to their surgery are taken directly from the PICU or NICU to the operating room (OR). Therefore, these patients do not undergo routine pre-operative (pre-op) checklists in the pre-op holding area. A critical care pediatric patient underwent a wrong-sided surgery, highlighting the need for a standardized approach to improve completion of the pre-op checklist and communication between the ICU and surgery teams in the perioperative period.

Methods Used

Using quality improvement methodology, the NICU, PICU, pediatric surgery, and pediatric hospital medicine teams completed an A3 form and performed a gap analysis. To address the concerns identified in the root cause analysis, we developed a bedside team huddle composed of ICU, surgery, and anesthesia teams to be performed in the ICU prior to the patient being taken to the OR. We created the acronym iSTOP to outline the components of the pre-op huddle: (i) introductions; (S) surgical procedure to be performed; (T) any tubes, lines, or drains; (O) ongoing plan/intra-operative plan; (P) post-operative care and pain management plan.

Summary of Results

Over the course of 90 days, 24 pre-op bedside iSTOP huddles were convened for ICU patients requiring surgery. All team members were present and all key elements of iSTOP were reviewed in over 90% of instances. Surgical site was appropriately marked 100% of the time, and pre-op checklist was completed at least 80% of the time. During this time period, there were zero serious safety events for ICU-to-OR patients.

Conclusions

The iSTOP huddle improved completion rate of the pre-op checklist and enhanced care team communication and patient safety surrounding care transitions between ICU and surgical departments. This huddle format can be extended to incorporate other bedside procedures within the ICUs and other areas of the hospital.

#35 Impact of a pre-operative checklist on surgical delays in complex spine surgery

LN DePledge1*

CE Drolet2

K Nold2

S Hermanson2

PK Louie2

R Sethi1,2

1University of Washington School of Medicine, Seattle, WA

2Virginia Mason Medical Center, Seattle, WA

Purpose of Study

Adult spinal deformity surgery is associated with high rates of perioperative adverse events (AE). To minimize the risk of AEs, patients must undergo a multitude of various labs, imaging, procedures, and evaluations before surgery. This process can be complicated for both patients and providers, which can lead to surgical delays. To address this problem, Virginia Mason Neuroscience Institute created a comprehensive preoperative checklist, detailing all necessary aspects of surgical optimization. The goal of this study was to evaluate the impact of a comprehensive preoperative checklist on surgical delays in patients undergoing adult spinal deformity surgery. We hypothesized that checklist-directed optimization would reduce the number of surgical delays and need for postoperative intensive care.

Methods Used

Appointed members of the complex spine surgery team were tasked with coordinating surgical optimization using a checklist from 9/1/20 to 8/1/21 (n = 51). Complex spine surgeries (to treat adult spinal deformity) between 1/1/18–8/31/20 (n = 142) were not medically optimized via checklist and thus served as a historical control. Indications for surgery including infection, tumor, and urgent/emergent cases were excluded. Surgeries that were delayed due to COVID, or those that deviated from the established care pathway were also excluded. Impact of the checklist on the frequency of pre-/peri-operative delays and need for postoperative intensive care were investigated. Chi-square analysis was used to interpret these data.

Summary of Results

Of 235 patients scheduled for complex spine surgery, 193 met our criteria. Checklist-directed surgical optimization did not significantly reduce surgical delays, with 19.0% of surgeries experiencing a delay in the historical control group compared to 15.7% in the study group (p = 0.38). However, patients in the study group were less likely to require postoperative intensive care (11.1%) compared to the control group (25.3%) (p = 0.031).

Conclusions

Checklist directed pre-surgical optimization was instituted at a single, high-volume spine surgery center. Although this intervention did not reduce the number of surgical delays, it does have the potential to increase patient safety, as use of the checklist was associated with reduced need for postoperative intensive care. Further research on ways to improve interdisciplinary coordination for preoperative optimization to reduce surgical delays is needed to maximize patient safety and minimize AEs.

Immunology and rheumatology I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#36 SARS-COV-2 immune complexes elicit tissue factor expression on human peripheral blood monocytes

J Plagenz1,2*

T Peters2

S Pincus1,2

N Meissner1,2

1University of Washington School of Medicine, Seattle, WA

2Montana State University Bozeman, Bozeman, MT

Purpose of Study

Innate and adaptive immune responses may play a role in severe complications of SARS-CoV-2 infection (COVID-19). The formation of virus-antibody immune complexes may result in aberrant activation of innate immune cells, including circulating monocytes. Thromboembolic complications are a hallmark of severe COVID-19, in which a hypercoagulable state is observed. Currently, the mechanism of this is poorly understood. Tissue factor, also known as Coagulation Factor III, is key to activating the clotting cascade; it is constitutively expressed extra-vascularly but can be upregulated on circulating monocytes during inflammation. Conditions that predispose patients to severe COVID-19, such as metabolic syndrome, are associated with elevated plasma levels of endotoxin. We postulate that aberrant inflammatory activation of monocytes via SARS-CoV-2/antibody immune complexes, in tandem with endotoxin, can upregulate tissue factor and induce hypercoagulability.

Methods Used

Immune complexes were formed by mixing inactivated SARS-CoV-2 with Bamlanivimab (Bam), a therapeutic monoclonal antibody specific for the spike receptor-binding domain of SARS-CoV-2. Antibodies to a different domain of the spike were used to capture immune complexes, which were then detected using biotin/avidin. Effects on monocyte cell-surface expression of tissue factor were investigated using flow cytometry. Human peripheral blood mononuclear cells were cultured with SARS-CoV-2, Bam, endotoxin, and combinations of the three. Monocytes were identified by forward/side scatter and CD14 expression.

Summary of Results

SARS-CoV-2 immune complexes were readily detectable by immunoassay. Immune complexes were also stable under different storage conditions. These complexes increased endotoxin-induced tissue factor expression on monocytes to a greater degree than did endotoxin alone. Incubation with neither Bam nor SARS-CoV-2 alone induced tissue factor expression.

Conclusions

Antibody-mediated mechanisms are key in clearing SARS-CoV-2 infection. Our results show that the formation of virus-antibody immune complexes may also result in aberrant activation of innate immune cells, including circulating monocytes, leading to tissue factor upregulation. These results may aid in understanding the hypercoagulable state seen in SARS-CoV-2 infection. The next step is to evaluate the effect of immune complexes on in-vitro coagulation by using tissue factor-induced Factor Xa activity assays.

#37 How the tfh response in neonates fed breast milk devoid of maternal antibodies impacts the composition and function of intestinal microbes

IT Vanteru1*

B Wang2

S Torres2

1University of Washington School of Medicine, Seattle, WA

2Fred Hutchinson Cancer Research Center, Seattle, WA

Purpose of Study

Breast milk is essential to the health and development of children. In addition to nutrients, breastmilk contains immune-modulating factors, including antibodies that protect infants from infections. However, breastfeeding is not available for all women and children. While infant formula is designed to meet growing infants’ basic nutrition needs, it does not contain factors like antibodies. We discovered that in the absence of breastmilk antibodies, mice develop increased levels of CD4 T follicular helper (Tfh) cells and germinal center (GC) B cells in gut draining lymphoid tissues. However, in germ-free mice that were also deficient in maternal antibodies (matAbs), the Tfh and GC B cell levels closely reflected antibody-sufficient neonates’ levels. These results suggest the significance of the microbiota in the role of Tfh and GC B cell responses. Tfh cells are essential for maintaining host-microbe homeostasis, and dysregulated increases in Tfh cells can alter the microbiota composition, potentially causing colitis. An indispensable role of the microbiota is to prevent the spread of pathogenic infections through colonization resistance. We hypothesize that the increase in Tfh and GC B cells in pups lacking maternal antibodies will alter the intestinal microbiota and its function.

Methods Used

To understand how the Tfh cells can alter the intestinal microbiota, we treated half of the mice that are sufficient and deficient in maternal antibodies with anti-ICOSL, which effectively dampens the Tfh cell expression. We then infected all the mice with Salmonella typhimurium, a bacterial pathogen. Fecal samples were collected daily for 5 days. On day 5 post-infection, fecal samples, cecum, and liver were harvested to determine infection burden.

Summary of Results

Our data indicates no significant difference in colony-forming units (CFU) between the matAb sufficient and deficient groups, signifying that the presence of maternal antibodies does not change the susceptibility to S. typhimurium infection. In addition, there was no difference seen between the groups treated with anti-ICOSL versus control, indicating that early life Tfh cells giving rise to GC B cells producing T-dependent antibodies do not play a role in conferring differential resistance to S. typhimurium. This trend was seen when examining both localized and systemic infection across all three organs.

Conclusions

Although neonates that do not receive matAbs in breastmilk have increased numbers of Tfh and GC B cells which have the potential to produce antibodies and change the microbiota composition of the gastrointestinal tract, there was no difference in S.typhimurium infectivity between mice transiently devoid of Tfh cells versus control. To continue exploring the role of colonization resistance, further research is needed to determine how Tfh cells influence host-microbe interactions and subsequently its change in infection susceptibility.

#38 Conservative management of knee osteoarthritis utilizing bone marrow aspirate concentrate

B Leiby1*

GB Foremny2

J Hawley2

J Galloway2

J Willford3

JC McGinley2,4

1University of Washington School of Medicine, Seattle, WA

2The McGinley Clinic, Casper, WY

3WWAMI Medical Education Program, Laramie, WY

4University of Washington School of Medicine, Seattle, WA

Purpose of Study

Bone marrow aspirate concentrate (BMAC), along with conservative patient management, offers a minimally invasive option in treating chronic pain from knee osteoarthritis. Knee osteoarthritis affects 35% of adults aged 65 years and older. BMAC has been shown to decrease inflammation and improve cartilage signal on MRI. We hypothesize BMAC injections, along with conservative care, will provide short- and long-term relief of pain associated with knee osteoarthritis.

Methods Used

A retrospective chart review was conducted to identify patients with knee osteoarthritis who received BMAC injections and conservative care in our clinic from November 2013 to November 2019. Under CT and ultrasound guidance, 60cc of bone marrow was aspirated from the posterior iliac crest. Each 60cc sample of aspirate was centrifuged, concentrated to 10cc, and injected into the knee joint under sonographic guidance. Patients were non-weight bearing utilizing crutches and a compartment specific off-loading brace for 3 weeks after the procedure and partial weight bearing with just the brace for an additional 3 weeks. All NSAIDs were held 10 days prior and 3 months following the procedure. A 0–10 patient self-reported pain scale was used as the primary outcome. Secondary outcomes included adverse events and additional treatments. Pain scores were collected on the day of treatment and fixed timepoints up to 3 years post-injection. A 2-tailed Wilcoxon signed rank test with a .05 alpha level was used to determine statistical significance between differences in reported pain level at each follow-up compared to baseline.

Summary of Results

Forty-seven patients (71 knees, 26 males, 21 females) with an average age 64±9 years, received BMAC injections and conservative management. These patients were followed for 3 years post treatment (mean follow-up 30.1±11.0 months). Reported pain level was significantly reduced 3 weeks post-injection compared to baseline (47 patients, 71 knees; mean Δ -2.0 points; p<.001; table 1). Pain continued to decrease up to 3 years post-injection compared to baseline (37 patients, 54 knees; mean Δ -3.9 points; p<.001). No adverse events were reported. Thirteen patients (17 knees) subsequently received additional treatments including injections (10 patients, 12 knees). Three patients (5 knees) underwent knee arthroplasty. Zero patients underwent repeat BMAC injections during the 3-year follow-up period.

Abstract #38 Table 1

Mean reported pain scores

Conclusions

BMAC injections, along with conservative management, represents a safe, effective, and minimally invasive treatment option for treating knee osteoarthritis pain for up to 3 years. Few patients in our study progressed to knee arthroplasty suggesting this approach to be a viable alternative to surgery.

#39 Prevalence of frailty and associated factors in a national observational cohort of rheumatic diseases

C Chang1*

N Singh1

J Andrews1

K Wipfler2

S Lieber3

SE Sattui4

JF Baker5,6

P Katz7

K Michaud2

K Wysham1,8

1UW, Seattle, WA

2FORWARD, Wichita, KS

3HSS, New York, NY

4UPitt, Pittsburgh, PA

5UPenn, Philadelphia, PA

6VHA, Philadelphia, PA

7UCSF, San Francisco, CA

8VHA, Seattle, WA

Purpose of Study

Frailty is associated with disability and early mortality and may be reversible. It is accelerated in patients with certain rheumatic musculoskeletal diseases (RMDs). The prevalence of and disease-specific factors associated with frailty across multiple RMDs is unknown.

Methods Used

Data were acquired from FORWARD, The National Databank for Rheumatic Diseases, an observational longitudinal US registry with biannual patient questionnaires. Frailty was measured by self-reported measure: the FRAIL scale, which queries 5 items: 1) fatigue, 2) resistance (climbing stairs), 3) ambulation, 4) illnesses, and 5) loss of weight and categorizes those with ≥3 items as frail. Those with missing RMDs or frailty variables were excluded (N=117). Prevalence of frailty across RMDs was described. Multivariable logistic regression was performed to identify variables independently associated with frailty in the entire cohort and stratified by RMDs.

Summary of Results

3,348 individuals were included and 1,084 were frail (32%). RMDs evaluated were rheumatoid arthritis (71%), osteoarthritis (OA) (16%), fibromyalgia (5%), systemic lupus erythematous (SLE) (4%), other connective tissue diseases (CTDs) (2%), spondylarthritis (1%), and vasculitis (1%). Frail participants were older (69.8±10.6) compared to non-frail (66.3±11.7) and had a higher prevalence of obesity (52% vs. 31%). The distribution of frailty was equal across RMDs (~33%) except vasculitis and CTDs, which had a lower prevalence of frailty (20% and 26%, respectively). Ambulation and fatigue were the most common frailty components across RMDs. In the primary multivariable model evaluating the entire cohort, increasing age (OR=1.05 [95%CI 1.04–1.06], female sex (OR=1.74 [95%CI 1.57–1.95]), overweight (OR=1.49 [95%CI 1.17–1.89]) and obesity (OR= 3.04 [95%Cl 2.42–3.82]), prior fracture (OR=1.87 [95%CI 1.56–2.26]), increased disease activity (OR=1.24 [95%CI 1.18–1.30]), and pain (OR=1.11 [95%CI 1.07–1.16]) had significant independent associations with frailty (table 1). Biologic use was associated with lower odds of frailty (OR=0.78 [95%CI 0.64–0.96]). Among the RMDs, SLE was associated with an increased odds of frailty with OA as the reference (OR=1.70 [95%CI 1.02–3.03]). Overall, disease-specific associations were similar to the primary multivariable model with obesity and disease activity maintaining statistical significance in most models.

Abstract #39 Table 1

Multivariable logistic regression evaluating factors associated with frailty in the entire cohort (N=2947)

Conclusions

Frailty is common among RMDs affecting nearly 1 in 3 participants. Obesity, prior fracture and a diagnosis of SLE had the highest associations with frailty. Future work is needed to identify factors that predict frailty onset and potential interventions to treat frailty within RMDs.

#40 Adjunct therapies for pemphigus disease: a systematic review

K Nguyen1*

S Worswick2

1Western University of Health Sciences, Pomona, CA

2University of Southern California, Los Angeles, CA

Purpose of Study

Pemphigus vulgaris (PV) and IgA Pemphigus are mucocutaneous autoimmune diseases that commonly present as painful blisters eroding the skin of the face, trunk, scalp, groin, and axillae in affected patients. The pathogenesis of pemphigus disease stems from autoantibodies against desmosomal proteins essential to maintaining keratinocyte adhesion. A histopathologic exam may reveal a reduction in desmosomal cadherin proteins and epidermal acantholysis. Currently, there is no cure for pemphigus, though corticosteroids and steroid-sparing agents are commonly used to control the proliferation of lesions and prevent disease progression. Frequently used non-steroidal agents include mycophenolate mofetil, azathioprine, IVIG and rituximab. Despite these treatment options, patients often succumb to long-term corticosteroid complications. Less oft-used therapies include dapsone and sulfasalazine for PV, and colchicine for IgA pemphigus which offer potential steroid-sparing alternatives with fewer adverse effects, however, their efficacies has not been clearly established. The objective of our systematic review is to investigate the use of dapsone, sulfasalazine, and colchicine in the treatment of PV and IgA pemphigus.

Methods Used

We searched the PubMed database using the search terms: ‘dapsone’ ‘sulfasalazine’ ‘pemphigus vulgaris’ ‘colchicine’ ‘IgA pemphigus disease.’ Our inclusion criteria included published articles written in English between 1970–2021 exploring the use of dapsone, colchicine or sulfasalazine for pemphigus, and included case series, retrospective studies, and randomized control trials. Our exclusion criteria eliminated reports with fewer than three patients, and review articles. 275 articles were identified, of which 27 relevant studies were eligible. 15 studies were excluded after screening, resulting in 12 remaining studies.

Summary of Results

46 (63%) out of 73 patients responded to dapsone, suggestive of its efficacy as either a monotherapy for or as a part of combination therapy for PV. In 65 patients receiving sulfasalazine adjunct therapy, 61 (94%) achieved clinical remission. Adequate data is lacking regarding colchicine therapy for pemphigus as the current literature only reports four IgA pemphigus patients treated with this agent.

Conclusions

More research is required to elucidate an effective and safe therapy for individuals burdened with pemphigus disease. Certainly, the rarity of this condition and the difficulty in finding adequate control groups present a major barrier for holding clinical trials on alternative therapies. Going forward, dermatologists may consider the use of dapsone or sulfasalazine adjuvant therapy in PV patients to slowly lower corticosteroid use as lesions begin to diminish and to prevent relapse of cutaneous flare ups for patients in remission.

#41 The adjunctive therapy for mycobacterium tuberculosis infection in type 2 diabetes mellitus

C Sisliyan1*

A Beever2

N Kachour2

J Owens1

K Sasaninia2

A Kalloli3

W Khamas4

S Subbian3

V Venketaraman1,2

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

2Western University of Health Sciences, Pomona, CA

3Rutgers New Jersey Medical School, Newark, NJ

4Western University of Health Sciences, Pomona, CA

Purpose of Study

Type 2 Diabetes Mellitus (T2DM) is an inflammatory disease that can alter the immune response resulting in several physiological manifestations. Glutathione (GSH), a thiol required to maintain intracellular redox state homeostasis, is classically deficient among individuals with T2DM. Glutathione also appears to be pertinent in the immune response against Mycobacterium tuberculosis (Mtb) infection. In our previous studies, we have identified L-GSH’s direct opposing effects against oxidative damage as well as its immune enhancing effects in HIV+ patients. We explored for similar effects in T2DM which also involves inflammatory and infectious states that could potentiate the replication of Mtb and further diminish the immune response. Specifically, our study aims to further elucidate GSH’s role in the granulomatous effector response. In this study, we attempted to uncover whether GSH deficiency in diabetic mice (db/db) impairs the formation of granulomas and the granulomatous effector response to further the understanding of the detailed mechanism of Mtb pathogenesis and the potential for novel therapies against the disease brought on by the infection.

Methods Used

Db/db mice were infected with Mtb and treated with one of 3 regimens, either: 1) an optimal dose of rifampicin (RIF), 2) a suboptimal dose of RIF, or 3) a suboptimal dose of RIF in addition to reduced form of GSH encapsulated in liposomes (L-GSH). 3 male and 3 female mice were sacrificed for each group over the span of 3h, 2, 4 wks, 6 wks, and 8 wks post-treatment to study the collective effects of L-GSH and RIF in Mtb infection. Granuloma samples from each group were formalin-fixed and analyzed accordingly. We are currently measuring the survival of Mtb along with the levels of cytokines, free radicals and GSH in untreated, RIF-treated and RIF+GSH-treated db/db mice.

Summary of Results

We expect to obtain the data from the aforementioned assays shortly.

Conclusions

If our data shows a marked elevation of immune defensive cytokines and granuloma formation with concurrent reduction in Mtb survival and free radical production in L-GSH treated mice, then we can support our hypothesis that GSH enhances the granulomatous effector response against Mtb infection in T2DM. In addition, if we observe greater immune responses in RIF+GSH treated db/db mice, we may further explore the use of GSH as an adjunct therapy in Mtb infection in T2DM.

#42 Actinic granuloma: a rare case of sun damage

K Nguyen1*

C Wong2

E Nguyen2

1Western University of Health Sciences, Pomona, CA

2Riverside Community Hospital, Riverside, CA

Case Report

A 53-year-old female with a past medical history of anxiety presented to the dermatology clinic with a pruritic eruption for six weeks. She had been gardening without gloves the day prior to the onset of the eruption. A review of systems was inconclusive. Her examination revealed diffuse red papules coalescing into plaques with mild scales involving the scalp, face, neck, torso, and upper and lower extremities including palms and soles, and sparing the ears, bilateral axillae, elbows, and knees. Her biopsy revealed solar elastosis and abundant multinucleated foreign body giant cells with ingested elastic fibers. The patient’s clinical presentation and histopathology was consistent with a diagnosis of actinic granuloma (AG). Her treatment included 20 mg of prednisone PO QAM for one month along with fluticasone 0.05% face cream BID and triamcinolone 0.1% cream BID applied to the affected skin on the body. After one month, all lesions flattened except for post-inflammatory erythema macules. Sun avoidance and daily sunscreen use was also recommended. At the most recent follow up, her lesions resolved demonstrating the efficacy of corticosteroid treatment.

AG is a rare skin eruption with an unknown pathogenesis, however, it is proposed that a sun-induced inflammatory response attracts giant cells to form granulomas and degrade elastic material. Lesions begin as multiple small pink papules and nodules that coalesce into demarcated, annular plaques and a hypopigmented center to form the classic ring shape. Actinic elastosis surrounds the outer annulus ring, with histiocytes and giant cells within the raised border, and the innermost central zone filled with minimal to absent elastic fibers. Lesions are commonly found on the forehead, neck, extremities, and hands. Our patient differed from the typical presentation in that she described intense pruritus associated with her eruption.

Abstract #42 Figure 1

Solar elastosis and abundant multinucleated foreign body giant cells with ingested elastic fibers

#43 Complete congenital heart block in a neonate

S Benke*

S Sukumaran

Valley Children’s Hospital, Madera, CA

Case Report

Congenital heart block (CHB) in neonates is associated with high morbidity and mortality. CHB generally occurs due to the presence of maternal autoantibodies of the Ro/La family or cardiac defects.

We describe a neonate born with CHB who was found to have neonatal lupus erythematosus (NLE).

Methods Used

Case Report

Summary of Results

A term female infant was born by cesarean delivery at 37 weeks to a 24-year-old healthy primigravida. At delivery, the baby’s heart rate was 55 beats per minute. The patient was admitted to the neonatal intensive care unit for further evaluation and management of fetal bradycardia.

Electrocardiogram demonstrated third-degree atrioventricular (AV) block and fetal echocardiogram showed a ventricular rate of 60–65 beats per minute and an atrial rate of 116–128 beats per minute. There was good ventricular function without evidence of hydrops.

Physical exam revealed a term, well-appearing infant female with bradycardia but normal S1 and S2 without murmurs. The remainder of her examination was within normal limits. Laboratory evaluation of the infant and the mother showed positive anti-SSA/Ro and anti-SSB/La antibodies.

The baby was diagnosed with NLE and CHB. The infant’s heart rate was monitored closely but she maintained a heart rate greater than 60 beats per minute and hence was discharged home. A pacemaker was scheduled for placement as an outpatient.

Conclusions

NLE is a rare acquired autoimmune disorder that occurs due to passive placental transfer of maternal autoantibodies to SSA/Ro and/or SSB/La. Anti-SSA/Ro autoantibodies are found in about 85–90% of mothers of neonates with CHB, and studies of pregnancies in anti-SSA/Ro positive mothers estimated the risk of CHB to be 1–5%.

Cardiac involvement in NLE is usually irreversible and characterized by second- or third-degree CHB. A ventricular rate of less than 55 beats per minute, hydrops fetalis, or atrioventricular valve regurgitation indicate poor fetal prognosis.

This case emphasizes the importance of considering NLE in infants with fetal bradycardia, congenital AV block or arrhythmias and evaluating the mother and infant for autoantibodies to SSA/Ro and/or SSB/La. We also highlight the need for early referral to cardiology and possible pacemaker implantation in infants who do not respond to medical therapies alone.

#44 Objective characterization of osteopathic lymphatic pump technique efficacy using serum covid-19 antibody levels following vaccination

A Comer*

E Lee

E Martinez

B Loveless

P Crone

S Fuchs

H Szurmant

J Sanchez

Western University of Health Sciences, Pomona, CA

Purpose of Study

Lymphatic Pump Technique (LPT) is an Osteopathic Manual Medicine technique involving external pressure to various lymphatic structures with the goal of improving lymph drainage. Because of the leukocyte content of lymph, LPT is often indicated for use as an adjuvant therapy in patients with acute or chronic infections. Previous studies have primarily characterized LPT efficacy in terms of clinical or symptomatic outcomes, typically with rather small cohorts of subjects, which has been a criticism of the technique. To address the limitations of past studies, we present a study in which the serum concentration of anti-spike protein COVID-19 antibodies are measured in 100 subjects following treatment with LPT (experimental group) and 100 subjects without LPT treatment (control group) in conjunction with COVID-19 vaccination. The ongoing study is designed to follow the subjects for one year after the first COVID-19 vaccine.

Methods Used

Subjects were split into treatment or control groups in a double-blinded randomized process. Participants returned for blood draws with the following schedule based on the day of their first vaccination: day 0 (1rst vaccine), day 7, day 21 (2nd vaccine), days 28, 35, 90, 182 and, 365. In the treatment branch, LPT was performed on the day of each vaccination and the following day for a total of 4 treatments. Blood draws were performed immediately prior to both vaccine administration and treatment with LPT. Blood samples were processed, and serum biobank is created. Serum anti-spike antibody levels are to be determined using quantitative ELISA. All recruited participants were over the age of 18 and were not vaccinated. The study was approved by the WesternU Institutional Review Board.

Summary of Results

Recruitment has been successful and is ongoing. Currently, 96 participants have been recruited. 12 participants have dropped out for various reasons, leaving 84 continuing participants. To address attrition, compensation has been changed from a total of $100 to $200, dispersed as $25 per blood draw. Attrition rate before the compensation change was 30% (6/20) but reduced to 7.9% (6/76) after the change. Total retention rate is 87.5% with 53.6% (45/84) of participants having completed the 5th blood draw. Additionally, the diversity of the participant population is promising with significant representation of LatinX individuals (55.9%) and females (58.3%).

Conclusions

The ongoing study is still recruiting participants, however significant progress has been made, with 84 participants currently on board. Additionally, retention and the diversity of the participant population are both promising. The first set of serum samples is soon to be subjected to ELISA antibody testing and results are forthcoming.

Infectious diseases I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#45 Anti-depressants and covid-19 severity: a retrospective study of hospitalized adult patients

SH Rauchman1*

S Mendelson2

C Rauchman1

A Pinkhasov3

LJ Kasselman3

AB Reiss3

1Fresno Institute of Neuroscience, Fresno, CA

2Providence Holy Cross Medical Center, Mission Hills, CA

3NYU Long Island School of Medicine, Mineola, NY

Purpose of Study

The SARS-CoV2 virus continues to have devastating consequences worldwide. Though vaccinations have helped to reduce the impact of the virus, new strains still pose a threat to the unvaccinated, and to a lesser extent vaccinated, individuals. Therefore, it is imperative to identify treatments to reduce the severity of Covid-19. Recently, acute use of selective serotonin reuptake inhibitor (SSRI) antidepressants in COVID+ patients has been shown to reduce the severity of symptoms compared to placebo. Since SSRIs are a widely used anti-depressant, the aim of this study was to determine whether COVID+ patients already on SSRI treatment upon admission to the hospital had reduced mortality compared to COVID+ patients not on chronic SSRI treatment.

Methods Used

A retrospective observational study design was used. Electronic medical records of 9,044 patients with a laboratory-confirmed diagnosis of Covid-19 from 03/2020 to 03/2021from six hospitals were queried for demographic information, admission date; discharge date and disposition; length of stay; admission diagnoses; medications on admission; co-morbidities; age; gender; ethnicity; admission to ICU; ventilator use; supplemental oxygen; oxygen saturation; discontinuation of antidepressant medications upon ICU admission.

Using R, a logistic regression model was run with mortality as the outcome and SSRI status as the exposure. An adjusted logistic regression model was run to account for R age category, gender, and race. All tests were considered significant at p of 0.05 or less.

Summary of Results

In this sample, no patients admitted on SSRIs had them discontinued. This is consistent with current recommendations.There was no significant difference in the odds of dying between COVID+ patients on chronic SSRIs vs COVID+ patients not taking SSRIs, after controlling for age category, gender, and race. The odds of COVID+ patients on chronic SSRIs dying was 0.90 (95%CI: 0.74, 1.09; n=832) compared to COVID+ patients not on SSRIs (p=0.29; n=8211).

Conclusions

In times of pandemics due to novel infectious agents it is difficult, but critical to evaluate safety and efficacy of drugs that might be repurposed for treatment. This large sample size of 9,044 patients suggests that there will be no significant benefit to use of SSRIs to decrease mortality rates for hospitalized patients with Covid-19 who are not currently on SSRI medications.This study shows the utility of large clinical databases in addressing the urgent issue of determining what commonly prescribed drugs might be useful in treating COVID-19.

#46 T-cell and antibody responses to mRNA vaccination in SARS-CoV-2-convalescent subjects

S Wanner1*

VL Campbell1

S Selke1

DM Koelle1,2

1University of Washington School of Medicine, Seattle, WA

2Fred Hutchinson Cancer Research Center, Seattle, WA

Purpose of Study

Natural and vaccine-induced immunity are important for SARS-CoV-2 control. We evaluated SARS-CoV-2-specific T cell-mediated immune responses in COVID-19 survivors followed through vaccination. We compared T cell tests from Oxford Immunotec (OI) with an in-house laboratory-developed test (LDT). Each used peptides covering Spike (S) and non-vaccine proteins within SARS-CoV-2. We hypothesized that T cell responses to S will increase after mRNA vaccination. We compared vaccine immune boost in persons previously hospitalized vs. non-hospitalized for COVID-19, and the relationship between T cell and neutralizing antibody (nAb) responses.

Methods Used

20 subjects (median age 62.7, 50% female, most White) with PCR-confirmed SARS-CoV-2 infection donated plasma and peripheral blood mononuclear cells (PBMCs). Samples were from a median of 49 days after recovery from COVID-19 (V0), just prior to the 1st vaccination (E01), and 2–4 weeks after each mRNA dose (E02 and E03). T cell responses were measured by interferon-gamma enzyme-linked immunospot assays (ELISPOT). We compared our LDT assay using the S and nucleocapsid (N) proteins with the OI assay including the S, N, and matrix (M) proteins. nAb levels were measured by fluorescence inhibition. Linear regression was used to assess correlation between tests. Wilcoxon matched-pairs signed rank tests were used to evaluate differences in immune responses over time. Mann-Whitney tests were used to examine differences between hospitalized and non-hospitalized groups.

Summary of Results

Strong correlation was noted between LDT and OI results for S protein at each time point (rho= 0.88, 0.85, 0.60, and 0.77, respectively). Between V0 and E02 (median of 327 days) and V0 and E03 (median of 345.5 days), there were significant increases in S-specific T cell responses (p= 0.0005 and 0.0006, respectively). No additional boost between E02 and E03 (p= 0.54) was observed. Low level (V0) responses to N and M were not boosted with vaccination. No significant difference in S-specific T cell responses between hospitalized and non-hospitalized groups were noted. For both hospitalized and non-hospitalized persons, nAb levels increased significantly after 1st dose of vaccine (p= <0.0001), with no additional nAb increase after the 2nd dose. No correlation between nAb and S-specific T cell responses at either V0 or E03 was noted.

Conclusions

The OI assay is suitable for assessing T cell responses to SARS-CoV-2 mRNA vaccines. T cell responses to N and M did not boost, as expected. In this cohort, primary infection severity did not impact vaccine responses 9 months later. nAb and T cell response increases were complete after one dose. This indicates that a second dose may not be needed, at least if given 3–4 weeks after the first in persons recovering from COVID-19 in the prior 9 months.

#47 Assessment of maternal and infant antibody response to COVID-19 and transplacental transfer ratios at labor & delivery

C Liu1*

M Cambou1

T Mok1

VM Fajardo1

D Battacharya1

T Kerin1

FJ Ibarronda1

T Fuller2

S Paiola1

G Aldrovandi1

R Rao1

O Yang1

K Nielsen-Saines1

1University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

2University of California Los Angeles, Los Angeles, CA

Purpose of Study

Newborn protection from infection is dependent on both neonatal innate immune responses & transplacental transfer of maternal antibodies (abs). Better understanding of maternal SARS-CoV-2 ab responses during labor & delivery (L&D) can help evaluate maternal risks for infection, dynamics of placental transfer, and neonatal vulnerability. Limited data describes how COVID-19 severity shapes maternal & infant ab responses. Stratification by severity can help characterize the protection to the newborn. The purpose of this study is to investigate maternal SARS-CoV-2 ab concentrations during L&D by disease severity, and compare infant ab responses at birth when exposed to varying severity in utero.

Methods Used

This project is part of the prospective observational cohort study COVID19 Outcomes in Mother-Infant Pairs, analyzing mother-infant dyads in the US & Brazil. Serology of 101 pregnant women in Los Angeles (delivery: April 15, 2020-May 28, 2021) were analyzed and confirmed SARS CoV-2 PCR+ during pregnancy. Maternal blood at L&D, cord blood, and infant blood at birth were analyzed by ELISA for IgA, IgG & IgM (anti-spike receptor binding domain).

Summary of Results

For 101 women, 72 had matched cord blood & 86 infant specimens. 76% of women produced all 3 anti-SARS-CoV-2 IgG, IgM, and IgA; 93% had at least one positive ab class; 5% had no detectable abs. Infant serum at birth contained only IgG and no IgM or IgA. With increased duration between onset of infection & delivery, maternal IgG levels waned, and conversely, transplacental transfer ratios increased (R2=0.27). Maternal IgG levels increased with disease severity. A significant increase in infant IgG levels was observed in children born to symptomatic mothers vs asymptomatic mothers (p<0.0001). A trend towards more robust ab responses was observed in infants with severe/critical COVID-19 exposure in utero (p=0.07).

Abstract #47 Table 1

Demographics and clinical characteristics of mother-infant dyads infected with SARS-CoV-2 during pregnancy

Conclusions

Our findings demonstrate how altered maternal responses across distinct COVID-19 disease severity categories influence neonatal protection against SARS CoV-2.

#48 Biomarkers predictive of mortality in covid-19 patients with diagnosed heart failure

T Nguyen1*

JY Hwang1

C Lee1

T Buck2

K Mun2

IT Vanteru2

A Lu2

D Tirschwell2

A Kim1

1Washington State University Elson S Floyd College of Medicine, Spokane, WA

2University of Washington School of Medicine, Seattle, WA

Purpose of Study

The purpose of this study is to identify common biomarkers and biosignals in COVID-19 patients with heart failure that are associated with increased risk of in-hospital mortality. COVID-19 is associated with worse outcomes in patients with pre-existing comorbidities, such as heart failure (HF). Biomarkers such as B-type natriuretic peptide, troponin, and interleukin-6 have been elevated in patients with HF and COVID-19 and may provide insight on the severity of disease but may not be collected in all patients. The exact association between patients with prior HF and the biomarkers commonly utilized is limited and should be evaluated further. Our study evaluates biosignals and biomarkers that may be predictive of mortality in COVID-19 patients with history of HF.

Methods Used

All patients included were 18 years of age or older, diagnosis of COVID-19 was confirmed by PCR test or hospital clinical criteria and were hospitalized in the University of Washington (UW) Medicine hospital systems between February 2020 to December 2020. The data was collected as part of a national effort for the American Heart Association COVID-19 CVD Registry. The biosignals that were analyzed include temperature, heart rate, respiratory rate, diastolic blood pressure, and systolic blood pressure. The biomarkers include admission white blood cell (WBC) count, platelets, serum creatinine, AST (u/L), ALT (u/L), and lymphocyte count. Patient data also tracked previous medical history and disposition at discharge. A LASSO multivariate regression model was used to identify the variables most predictive of mortality among patients with heart failure.

Summary of Results

The study included 54 of the 393 COVID-19 patients (13.7%) with previous diagnosis of heart failure (46% male, mean age 77). Our model estimates that for each standard deviation unit above average (z-score), patients with previously diagnosed heart failure were 13% more likely to die due to COVID-19 (p = 0.021). Among patients with prior heart failure, each z-score increase for WBC count and serum creatinine increased risk of mortality by 3.5% (p = .043) and 5.7% (p = .046), respectively.

Conclusions

Our data suggests that there may be significance in monitoring WBC count and serum creatinine levels among COVID-19 patients with prior heart failure. The WBC count and serum creatinine have a stronger relationship to mortality in patients with prior heart failure compared to those without heart failure. Immune response may be reduced in heart failure patients which can account for the decreased WBC count, but further studies are needed to elucidate the exact mechanism and relationship. The results of this study may provide a roadmap to triage heart failure patients based on admission lab values in the COVID-19 environment.

#50 Associations of congenital syphilis incidence and the female agricultural worker population in California

J Fang1*

R Silva1

K Pinkerton1

D Sankaran1,2

1University of California Davis, Davis, CA

2Adventist Health and Rideout, Marysville, CA

Purpose of Study

The national rate of congenital syphilis (CS) has dramatically increased recently. It remains unknown if the children of the agricultural worker population (AWP) are more susceptible to CS in California. Identifying subpopulations vulnerable to transmitting CS may inform the design of intervention efforts. Thus, this study set out to determine whether CS incidence rates are associated with the female AWP in California.

Methods Used

Data from all 58 California counties were retrospectively obtained from the California Department of Public Health and United States Department of Agriculture regarding CS incidence per 100,000 live births and female AWP from December 2014 and December 2018. Female AWP per county was estimated according to the national proportion of female to male agricultural workers provided by the Department of Agriculture. Data was analyzed using geographical information systems mapping and Pearson’s correlation coefficient (r) tests.

Summary of Results

The average statewide CS incidence was 68.2 cases per 100,000 live births in 2018. CS incidence and female AWP were concentrated heavily in California’s agricultural Central Valley, with a few coastal exceptions (figure 1 A-C). CS incidence and female AWP were moderately but significantly correlated (r = 0.343; 95% confidence interval = 0.093–0.552; p < 0.001) (figure 1D).

Abstract #50 Figure 1

Geographical distributions of CS incidence rates (A: in 2014, B: in 2018) per 100,000 live births, and agricultural worker populations (C: in 2017). Correlation between CS Incidence (2018) and female AWP (2017) (r= 0.343; 95% CI)= 0.093–0.552; p< 0.001) (D). CS – congenital syphilis

Conclusions

Our findings provide evidence that California counties with a higher incidence of CS tend to be home to a greater number of female agricultural workers than counties with low incidence of CS. Given these findings, this study suggests the urgent need to implement culturally appropriate and enduring prenatal healthcare interventions that prioritize treatment of maternal syphilis and prevention of CS in female AWP.

#51 Characterization of the highly diverse genomic regions of an important African vector of schistosomiasis

R Burd1*

J Cayton1

T Pennance2

JA Tennessen3

M Steinauer2

F Rawago4

M Odiere4

G Owino4

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

3Harvard University T H Chan School of Public Health, Boston, MA

4Kenya Medical Research Institute, Kisumu, Kenya

Purpose of Study

Schistosomiasis is a neglected tropical disease impacting the health of millions of humans primarily in regions of poverty. Freshwater snails are obligate vector hosts of the flatworm parasites (schistosomes) that cause this disease. Our research goal is to uncover the genetics underlying immunity of snails to schistosomes so that novel control strategies may be developed to prevent human infection. Pathogen recognition receptors (PRRs) are part of the first line of defense against pathogens. They are hypothesized to be under balancing selection due to selection pressure on pathogens to evolve novel epitopes to evade immune recognition and on host receptors to detect pathogens. Thus, PRRs and other immune loci are expected to be among the most diverse regions of the genome. Using whole genome data from an important

African snail vector, Biomphalaria sudanica, we hypothesize that diverse regions of the genome will be enriched with immune related loci, and that we can identify novel PRRs through annotation of these regions.

Methods Used

Five B. sudanica strains (collected: Lake Victoria, Kenya) were sequenced using the PacBio and Illuminapaired-endreads. Mean inter-line diversity was calculatedacross the genomes and segmented into smaller windows (10–100kb). Each window with a mean inter-line diversity value >1%, had up to 1Mb of surrounding nucleotides annotated and transmembrane domains (TMDs) identified using predictive software. To determine if TMD peptides were over-represented in high- diversity regions of the genome, we compared the proportion of TMD peptides against the proportion of those in 30 randomly assigned contig regions.

Summary of Results

67 of 6815 windows met our nucleotide diversity threshold of 1% divergence. 421 of 818 immune- suspected peptides were identified to have TMDs, over-represented in regions of high diversity when compared to randomized control regions, supporting our hypothesis. Immune-related genes associated with Schistosoma resistance in other species including PTC2 and GRC were also identified using this bioinformatic approach.

Conclusions

Our findings support the diversity-based approach to identifying PRRs which successfully identified known B. glabrata PRRs and novel PRRs in B. sudanica genomes. Our established list of candidate genes for pathogen recognition will provide a foundation guiding resistance studies, gene knockout and GWAS with Biomphalaria species.

#52 Is vitamin d deficiency associated with more severe COVID-19 infection?

C Ko1*

B Bajoua1

A Garg1

C Metz1

M Shean1

Talebi Dolouei I1

M To1

B Afghani1,2

1University of California Irvine, Irvine, CA

2Children’s Hospital of Orange County, Orange, CA

Purpose of Study

Vitamin D has been shown to be helpful in preventing certain respiratory tract infections, but the link between COVID-19 severity and vitamin D levels remains unclear. The purpose of this study was to clarify the relationship between COVID-19 severity and vitamin D levels through a literature review.

Methods Used

A systematic literature review using PubMed and Google Scholar was conducted. Our inclusion criteria included those studies that a) measured vitamin D levels, b) included both a control and subject group, c) measured the association between COVID-19 severity and vitamin D levels, and d) took into account other potential COVID-19 related comorbidities among controls versus subjects groups. Studies that measured only prevention of COVID-19 infection (positivity rate) or mortality were excluded.

Summary of Results

Eight studies satisfied our inclusion criteria (see table 1 below). A majority of studies showed significantly lower vitamin D levels in the more severe COVID-19 subjects compared to control patients with less severe COVID-19. Most studies that assessed COVID-19 outcomes based on vitamin D deficiency (VDD) found VDD to be associated with worse outcomes, including more severe disease and increased mortality. The limitations of this review include inter-study variability in the co-morbidities included in multivariate analysis, variability in the definition of VDD among different studies, and a lack of information on vitamin D supplements and other treatments before infection or during hospitalization in several studies. Finally, a causal relationship could not be assessed because all studies were observational, and information on the vitamin D levels before hospital admission, during healthy state, was not available in a majority of studies.

Abstract #52 Table 1

Studies evaluating the association between vitamin D level and COVID-19 disease severity

Conclusions

There may be an association between lower vitamin D levels and more severe COVID-19 disease. However, larger longitudinal studies that not only measure vitamin D levels pre-COVID-19 disease but also take into account all variables, such as comorbidities and treatments that could affect disease severity, are warranted.

#53 The use of vaginal probiotics suppositories in prevention of recurrent urinary tract infections in adult women: a literature review

D Devineni1*

I Bade1

C Diyakonov1

E Lee1

N Lulla1

K Parang1

S Soni1

B Afghani1,2

1University of California Irvine School of Medicine, Irvine, CA

2Children’s Hospital of Orange County, Orange, CA

Purpose of Study

Urinary tract infections (UTIs) are one of the most common bacterial infections in women. Concerns over the effectiveness of antibiotics in preventing recurrent UTIs, due to antibiotic resistance and the adverse effects of antibiotics on healthy microbiota, have raised the necessity to investigate reliable non-antibiotic treatments for preventing recurrent UTIs. It has been proposed that probiotics or lactobacillus may be effective in preventing infections by restoring the normal vaginal flora. The purpose of this study is to investigate the effectiveness of vaginal probiotic suppositories for prevention of recurrent UTIs in adult women.

Methods Used

A systematic literature review was conducted through databases such as PubMed and Google Scholar. Only studies that were published after 1990, and compared use of vaginal probiotics with a control group in adult women with recurrent UTI were included. Studies with follow-up period of <6 months were excluded.

Summary of Results

We found 5 studies that fit our inclusion criteria (See table 1). In majority of the studies, the frequency of recurrent UTIs was lower in patients who received probiotic vaginal suppositories when compared to controls. However, there was great variability among the studies with respect to the probiotic formulation as well as treatment dose and frequency. The applications were intermittent and varied from daily to weekly to monthly. The probiotic species used in different studies included L. Rhamnosus, L. Fermentum, and L. Crispatus. The sample sizes were small and did not divide the patients into different categories based on risk factors or co-morbidities. In addition, the bacterial cause of UTI was not mentioned in majority of the studies. Mild side effects were noted in both probiotic and control group, and included increased vaginal discharge, vaginal odor, mild irritation and dysuria.

Abstract #53 Table 1

Studies on the efficacy of intravaginal probiotics in preventing recurrent UTIs

Conclusions

Our review suggests a promising role for use of intermittent vaginal probiotic suppositories for prevention of recurrent UTIs in adult women. Larger prospective studies with longer follow-up period are needed to determine the optimal probiotic dosage and frequency in different groups of patients with recurrent UTI.

Neonatology general I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#54 Nucleated red blood cell emergence-time in newborn lambs following a dose of darbepoetin alfa

TM Bahr1,2*

K Albertine2

RD Christensen1,2

MJ Dahl2

A Rebentisch2

E Dawson2

E Major2

H Foreman2

D Headden2

Z Vordos2

A Nabi2

L Pettet2

P Badrov2

C Addison2

D Christensen2

1Intermountain Healthcare, Salt Lake City, UT

2University of Utah Health, Salt Lake City, UT

Purpose of Study

A high nucleated red blood cell (NRBC) count in a neonate at birth has been suggested as a biomarker for fetal hypoxia. However, it is not clear if it indicates when the hypoxia occurred. We aimed to measure the time between administering a high-dose of darbepoetin, simulating the marked rise in erythropoietin that follows a hypoxic event, and the first appearance of NRBC in the blood. Limited observations of this interval, the ‘NRBC emergence-time,’ in human neonates suggest it is greater than 24 hours.

Methods Used

We obtained serial blood counts on ten newborn lambs; five dosed with darbepoetin (10 µg/kg) and five placebo controls, to assess the NRBC emergence-time.

Summary of Results

The first appearance of NRBC was at 24 h (mean±SD, 2757±3210 NRBC/µL vs. 0/µL in controls). Peak was 48–72 h (16,758±8434/µL vs. 0/µL in controls), followed by fewer at 96 hours (7823±7114/µL vs. 0/µL in controls). Similarly, reticulocytes peaked at 48–72 h (113,094±3210/µL vs. 10,790±5449/µL in controls), with no changes in platelets or leukocytes.

Abstract #54 Figure 1

NRBC/µL (left) and NRBC/100 WBC (right), before (time 0) and at intervals following darbepoetin administration to five term lambs, as well as values in five similarly instrumented control lambs. Values from the darbepoetin recipients are shown by a solid black circle and those from the controls by a solid gray circle.

Conclusions

The NRBC emergence time in newborn lambs is similar to reports from newborn humans. By extrapolation, if a neonate has a high NRBC at birth, the erythropoietic stimulus likely occurred within the interval 24 to 96 hours prior to birth.

#55 Reference intervals for end-tidal carbon monoxide of preterm neonates

TR Christensen1*

S Pakdeeto2

TM Bahr1

E Gerday1

M Sheffield1

K Christensen3

S Supapannachart2

P Nuntnarumit2

S Sukwiset2

RK Ohls1

RD Christensen1

1University of Utah Health, Salt Lake City, UT

2Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand

3Brigham Young University, Provo, UT

Purpose of Study

Every molecule of heme metabolized to bilirubin releases one molecule of carbon monoxide (CO). On that basis, hemolysis can be detected and quantified by measuring CO in exhaled breath. We constructed reference intervals for end-tidal carbon monoxide (ETCOc) levels of neonates 28–34 weeks gestation to assess the hemolytic rate. New instrumentation allows providers to non-invasively measure ETCOc in preterm neonates with low tidal volumes and breathing rates up to 70bpm. Reference intrevals for term and late preterm neonates exist, but until now none have been created for preterm neonates.

Methods Used

Prospective four-NICU study in Bangkok, Thailand, and Utah, USA. Neonates born between 28–34 weeks and up to 28 days old were eligible. Once informed consent was received, a modified CoSense ETCOc analyzer was used to record results. Data from the CoSense devices were linked to patient charts to obtain demographic information.

Summary of Results

Values from days one through 28 were charted and upper (>95th percentile) reference interval limits were calculated. During the entire 28 days, the ETCOc upper reference intervals of babies in Bangkok were higher than those in Utah (p<0.01). No differences were found due to sex, or earliest vs. latest gestation at birth (both p>0.1). Preterm neonates in Bangkok and Utah had higher ETCOc values during the first 48 hours after birth than thereafter (p<0.01).

Abstract #55 Figure 1

The dashed line and the grey circles are preterm infants from Bangkok. The solid line and open circles are preterm infants from Utah, USA

Conclusions

Using the reference interval chart we created, the hemolytic rate of preterm infants ≥28 weeks can be assessed. This identification allows us to focus subsequent testing to find the cause of the hemolysis, administer more intensive phototherapy, and to assure consistent in-and out-patient follow-up to those with hemolytic jaundice.

#56 Anemic at birth

TM Bahr1,2*

LM Shelley2

ER Henry1

RK Ohls2

S Li1,3

S Illstrup1

RD Christensen1,2

1Intermountain Healthcare, Salt Lake City, UT

2University of Utah Health, Salt Lake City, UT

3University of Utah, Salt Lake City, UT

Purpose of Study

Using ten years of multihospital data, we identified neonates with ‘severe anemia at birth’, defined by a hemoglobin/hematocrit within the first six hours after birth below the 1st percentile. We determined whether caregivers recognized anemia within the first 24 hours after birth, the probable cause of the anemia, treatment given, and whether review suggested a different cause of anemia than listed in the medical record.

Methods Used

Data from neonates born 2011–2020 were obtained from the Intermountain Healthcare Data Warehouse. We reviewed records of all infants with severe anemia at birth. We then categorized the cause as either; hemorrhage, hemolysis, hypoproduction, a combination of etiologies, or unable to determine.

Summary of Results

Of 299,927 live births 344 had severe anemia. In 153 (44.5%) the anemia was unrecognized during the first 24 hours. The lowest hemoglobin/hematocrit values were among those with hemorrhage vs. hemolysis (P<0.013) or vs. hypoproduction (P<0.001). In infants with severe anemia secondary to hemorrhage, abruption/other perinatal event and fetomaternal hemorrhage (FMH) were the most likely etiologies. DIC was a common hemolytic cause of anemia, with 85% of DIC cases coincident with hemorrhagic anemia.

Abstract #56 Figure 1

Reference intervals for hemoglobin (A) and hematocrit (B) of neonates on the day of birth by gestational age. The bold line indicates the 1st percentile reference interval, below which we label neonates as having ‘severe anemia at birth’. Dashed lines show the 5th percentile, median, and 95th percentiles.

Conclusions

Severe anemia at birth often went unrecognized on the first day. Earlier recognition may be facilitated by an electronic medical record-associated hemoglobin/hematocrit nomogram, with values <1st percentile clearly identified.

#57 Fetomaternal hemorrhage: evidence from a multihospital healthcare system that up to 40% of severe cases are missed

NR Carr1*

ER Henry2

TM Bahr1,2

RK Ohls1

J Page1

SJ Ilstrup1

RD Christensen1

1University of Utah Health, Salt Lake City, UT

2Intermountain Healthcare, Salt Lake City, UT

Purpose of Study

We previously reported fetomaternal hemorrhage (FMH) in 1/9160 births, and only one neonatal death from FMH among 219,853 births. Recent reports indicate FMH is not uncommon among stillbirths. Consequently, we speculated we were missing cases among early neonatal deaths. We began a new FMH initiative to determine the current incidence.

Methods Used

We analyzed births from 2011 to 2020 where FMH was diagnosed. We also evaluated potential cases among neonates receiving an emergent transfusion just after birth, whose mothers were not tested for FMH.

Summary of Results

Mong 297,403 births, 1375 mothers were tested for FMH (1/216 births). Fourteen percent tested positive (1/1599 births). Of those, we found 25 with clinical and laboratory evidence of FMH adversely affecting the neonate. Twenty-one received one or more emergency transfusions on the day of birth; all but two lived. We found 17 others who received an emergency transfusion on the day of birth where FMH was not tested for, but was likely; eight of those died. The 42severe (proven + probable) cases equate to 1/7081 births. We judged that 10 of the 42 had an acute FMH, and in the others it likely had more than a day before birth.

Conclusions

We estimate that we fail to diagnose >40% of our severe FMH cases. Needed improvements include; 1) education to request maternal FMH testing when neonates are born anemic, 2) education on false negative FMH tests, 3) improved FMH communications between neonatology, obstetrics, and blood bank.

#58 Iron folic acid supplementation as a predictor of anemia in pregnant women in rural india

B Tomlin*

P Brahmbhatt

B Fassl

JW Thomas

A Judkins

University of Utah Health, Salt Lake City, UT

Purpose of Study

Perinatal anemia is a massive global public health burden with an estimated global prevelance of approximately 40%. Severe anemia increases the risk of maternal mortality and can adversely effect fetal development. Adequate correction of anemia is essential for a healthy pregnancy and infant, but universal screening and monitoring is not the care standard in most LMICs. In lieu of universal screening and treatment, providing access to Iron Folic Acid (IFA) tabs is considered an effective and cost-efficient intervention to prevent and treat anemia of pregnancy. However, despite widespread availability of IFA tabs, anemia prevalence continues to be high and the presence of IFA programs may falsely reassure clinicians that patients taking them have adequate hemoglobin.

Methods Used

The study took place at Mota Fofalia Community Health Center (MF-CHC) in Gujarat, India operated by a public-private partnership. The University of Utah operates an academic global health program in collaboration with MF-CHC and assists the health center in sustainable capacity building in maternal-child health. As part of a community-based antenatal care (ANC) program, we recruited a cohort of pregnant women from the surrounding community to complete a standardized nutrition and health survey and participate in scheduled prenatal visits according to WHO and Indian ANC guidelines which include measurement of vital signs and ANC guideline-based interventions . At each ANC visit, a blood hemoglobin level was drawn and each participant was asked if they are currently taking IFA or Albendozole, an antiparisitic.

Summary of Results

A total of 501 women were included in the study. 448 (89%) report taking IFA and 53 (11%) report not taking IFA. The average hemoglobin for those taking IFA was 10.11 g/dL (IQR 9.3–11.1) with an average gestational age at screening of 23.0 weeks while the average of those not taking was 10.41 g/dL (IQR 9.8–11.6) (p=.28) with an average gestational age of 10.9 weeks. In the group taking IFA tablets, 97% were also taking Albendozole while only 21% of mothers not taking IFA tablets were taking Albendozole.

Conclusions

In areas with a high prevalence of anemia, patient compliance with standard IFA antenatal therapy is not a an adequate indicator of intervention. While it appears many mothers begin taking IFA as they become pregnant, the presence of readily available IFA therapy to the community is not sufficient in addressing perinatal anemia.

#59 The validity of point-of-care hemoglobin measurements in neonates

AF Ahmed1*

JP Wang1

R Ramanathan2

AM Yeh2

1LAC+USC Medical Center, USC, Los Angeles, CA

2Keck School of Medicine, USC, Los Angeles, CA

Purpose of Study

Hemoglobin (Hb) analysis among patients in the Neonatal Intensive Care Unit (NICU) is essential in diagnosing anemia, a common problem among neonates of low birth weight or preterm infants. This same population is especially at risk for iatrogenic anemia, given the need for frequent laboratory analysis while having a small blood volume. Hb measured by way of point-of-care (POC) meters or blood gas analyzers, which each require 1–2 drops of blood per reading, could prevent significant phlebotomy in the NICU as compared to the Complete Blood Count (CBC), which requires 0.6 to 1 milliliter. This study aims to determine the validity of POC and blood gas Hb measurements as compared to Hb values from the CBC.

Methods Used

This is a retrospective study of patients admitted to the LAC+USC Medical Center NICU between January 2020 and April 2021 with paired Hb measurements from the laboratory-run CBC and either POC Hb from HemoCue B 201 or blood gas Hb from Gem Premier 5000. Qualifying data was divided into groups based on time between different blood draws, the first comprising of measurements collected within 12 hours of each other, the second of measurements collected between 12 and 24 hours of each other. POC or blood gas Hb and CBC Hb measurements collected over 24 hours from each other were excluded. T-tests were used for analysis of continuous, normally distributed variables. Regression analysis was performed to determine the relationship between paired Hb measurements. Statistical significance was set at p <0.05.

Summary of Results

We identified 250 subjects with qualifying paired Hb values from the CBC and POC Hb or blood gas Hb. There were 488 paired CBC and blood gas Hb samples in the <12 hour group, and 243 paired samples in the 12–24 hour group. There were 479 paired CBC and POC Hb samples in the <12 hour group, and 290 paired samples in the 12–24 hour group (table 1). Correlation coefficient (R) for the CBC-blood gas Hb groups were 0.89 in the <12 hour group and 0.83 in the 12–24 hour group. Correlation coefficient for the CBC-POC Hb groups were 0.87 in the <12 hour group and 0.75 in the 12–24 hour group (figure 1).

Abstract #59 Table 1

Correlation between CBC HB and paired POC/blood gas Hb

Conclusions

There was a strong correlation between paired POC Hb or blood gas Hb and CBC Hb values obtained within 12 hours of one another. Our results show that POC Hb or blood gas Hb should be considered as alternatives for CBC Hb. The patients in the NICU would benefit in prevention of iatrogenic anemia. Prospective studies with age- or weight-based grouping and planned pairing within pre-defined time periods would be beneficial in determining whether the correlation persists between POC and CBC Hb measurements in the NICU

#60 Alternative ways of acquiring bilirubin measurement in preterm and term infants admitted to neonatal intensive care unit

D Cho*

K Ramm

L Barton

R Ramanathan

M Biniwale

LAC+USC Medical Center, Los Angeles, CA

Purpose of Study

Measuring bilirubin levels in infants admitted to neonatal intensive care unit is done to avoid hyperbilirubinemia and bilirubin toxicity. Practitioners strive to minimize blood tests to reduce patient discomfort and iatrogenic anemia. To minimize blood draws in the monitoring of bilirubin levels, we assessed the accuracy of alternative methods of measurement via blood gas analyzers and transcutaneous bilirubin monitoring.

Methods Used

Using serum bilirubin as a gold standard, we analyzed the accuracy of simultaneous measurements from blood gas analyzer and transcutaneous monitoring. The accuracy of blood gas and transcutaneous bilirubin measurements was ascertained with correlation coefficient and by calculating mean differences between the serum bilirubin levels and the two alternative methods.

Summary of Results

Study consisted of 86 patients with gestational ages 24 to 41 weeks. The correlation coefficient for serum bilirubin vs transcutaneous measurements was r = 0.893 (p<0.00001). The correlation coefficient was r = 0.9283 (p<0.00001) for preterm infants, and r = 0.8392 (p<0.000013) for term infants. The mean difference between serum bilirubin vs transcutaneous measurements was 0.45 with a standard deviation of 1.55 mg/dL. The correlation coefficient for serum bilirubin vs blood gas bilirubin was r = 0.959 (p<0.00001). The correlation coefficient was r = 0.9291 (p<0.00001) for preterm infants, and r = 0.9742 (p<0.00001) for term infants. The mean difference between serum bilirubin vs blood gas bilirubin was 0.21 with a standard deviation of 0.87 mg/dL.

Conclusions

Both transcutaneous and blood gas analyzer bilirubin levels had a strong correlation with serum levels, with bilirubin using blood gas analyzer being slightly more accurate. We plan to continue collecting bilirubin data for a total of 6 months. If accuracy of transcutaneous or blood gas analyzer bilirubin measurements are acceptable, we plan to pursue these alternative methods of bilirubin measurements over the following 6 months and assess to what extent we were able to minimize blood draws.

#61 Predictors of home oxygen therapy in very low birth weight infants

Y Shao*

A Hisey

N Nanduri

K Ramm

C Marquez

L Barton

R Ramanathan

M Biniwale

Los Angeles County University of Southern California Medical Center, Los Angeles, CA

Purpose of Study

Very low birth weight (VLBW) infants with prolonged respiratory morbidities such as bronchopulmonary dysplasia (BPD) may need to be discharged home while receiving oxygen therapy. The risk factors causing prolonged respiratory support vary for these infants. The study was performed to characterize factors associated with VLBW infants who require oxygen therapy at discharge.

Methods Used

Data on all VLBW infants was gathered from the electronic medical record between the years of 2009 and 2021 retrospectively with IRB approval obtained prior. Oxygen therapy was statistically analyzed using SPSS Version 28 statistical software against early neonatal outcomes such as ventilation, intubation, chest compressions, or surfactant, or against common neonatal morbidities, including IVH, BPD, ROP, and patent ductus arteriosus (PDA).

Summary of Results

Of 560 VLBW infants, 144 (25.7%) were discharged home on oxygen. Significant maternal risk factors included histologic chorioamnionitis, intubation, and chest compressions at delivery. These infants had lower gestational age as well as lower birth weight. These infants were more likely to require surfactant, invasive ventilation at 24 hours, and receive additional ventilatory support including high-frequency oscillatory ventilation or jet ventilation (table 1). Infants who were discharged with home oxygen therapy were significantly more likely to have BPD and hemodynamically significant patent ductus arteriosus (PDA) requiring surgery. Associated comorbidities included retinopathy of prematurity (ROP) requiring treatment, severe intraventricular hemorrhage (IVH), and increased length of stay in NICU (table 1). Regression analysis revealed lower birth weight, longer duration of invasive ventilation, PDA requiring surgical intervention, and BPD to be the most significant predictors.

Abstract #61 Table 1

Home oxygen therapy requirement against common neonatal outcomes

Conclusions

The need for high-frequency ventilation such as jet and oscillatory ventilation, as well as chest compressions, is associated with home oxygen need at discharge. Additionally, VLBW infants who required home oxygen therapy were more likely to have needed invasive ventilation, delivery room intubation, and surfactant therapy. They were also more likely to have common neonatal morbidities such as BPD, severe IVH, severe ROP, and PDA.

#62 Consequences of maternal breast milk antibodies on the abundance of intestinal microbes in neonates

HL Wolf1,2*

B Wang1,2

J Schwensen2

M Koch2

1University of Washington School of Medicine, Seattle, WA

2Fred Hutchinson Cancer Research Center, Seattle, WA

Purpose of Study

Breast milk is an important contributor of the neonatal microbiome. Studies have associated breastfeeding with a decreased risk of acquiring inflammatory bowel disorders later in life. As breastfeeding is not possible for all mothers and children, gaining a mechanistic understanding of this process can lead to the development of early-life interventions that foster beneficial host-microbiota relationships.

We have previously shown that breast milk antibodies are important for maintaining mucosal homeostasis. Mice deficient in breast milk antibodies exhibit perturbations in mucosal immunity, including elevated T follicular helper (Tfh) cell and germinal center (GC) B cell responses in the gut-associated lymphoid tissues. We hypothesize that the Tfh and GC B cell response generated by the neonate in the absence of breast milk antibodies target resident mucosal bacteria and lead to long-term alterations in the abundance of gut-microbiota.

Methods Used

We extracted DNA from intestinal-wall associated microbes and quantified the abundance using quantitative-PCR of the bacterial 16s rRNA. We looked at both the small intestinal wall microbes and large intestinal wall microbes at ages 3, 5 and 11 weeks in maternal antibody sufficient or deficient pups. To explore the effects of Tfh cells and GC B cells, we treated half of each group with anti-Inducible T-cell Co-Stimulator Ligand (anti-ICOSL) antibody, which blocks Tfh and GC B cell formation. We used a paired T-test to determine the significance of our results.

Summary of Results

We found no significant difference in the abundance of wall-associated microbes across all four groups in the small or large intestine. These data suggest that the breast milk antibody dependent response as well as the Tfh-cell dependent response do not alter the abundance of wall-associated microbes.

Conclusions

Studies are ongoing to determine if breast milk antibodies affect intestinal microbe composition. Limitations to this study may include the drinking water our mice were exposed to throughout the duration of this experiment. Due to mouse husbandry standards operations within our institution our mice were given acidified water which we have recently discovered to significantly alter their microbial composition. Our goal is to repeat this experiment with non-acidified water as we suspect any potential differences in the microbial abundance may have been masked by the effects of acidified water.

Neonatology pulmonary I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#63 Effects of gestational long-term hypoxia on the collagen matrix of fetal sheep pulmonary arteries

RC Torres Chavez1*

C Gheorghe2

L Zhang1

M Yellon S2

S Wilson2

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

2Loma Linda University Department of Basic Sciences, Loma Linda, CA

Purpose of Study

Gestational long-term hypoxia (gLTH) is a significant stressor that leads to multiple diseases including pulmonary hypertension. Evidence indicates that gLTH causes oxidative stress and inflammation, which changes cell structure and function. These effects are driven by changes in cellular metabolism, protein expression, and transcriptional regulation. Our proteomic data show that gLTH leads to vascular remodeling and specifically to reduction of collagen 1A1, 1A2, and 3A1, though the data do not delineate where in the arterial wall these changes are occurring. We hypothesized that gLTH causes loss of collagen in all arterial layers which was tested by visualizing and quantifying the collagen content in different layers of fetal pulmonary arteries.

Methods Used

Fetal sheep pulmonary arteries from normoxic and gLTH environments were obtained and stained with picrosirius red dye (PSR) to visualize collagen in captured images of arterial biopsies by assessing the optical density (OD) of birefringence from polarized light. Fluorescence microscopy was used to capture images of the arterial samples. Data from Image J analysis of OD birefringence, inversely related to crosslinked collagen, of the various vascular layers and treatments were evaluated by analysis of variance.

Summary of Results

The image analysis showed a significant decrease in optical density, and therefore enhanced crosslinking, in the adventitia compared to the media for all samples belonging to either normoxic or gLTH groups. However, there was no significant difference in optical density of the adventitial versus medial layers between vessels from normoxic and gLTH fetuses.

Conclusions

The results indicate that optical density quantification can be used to detect substantial differences in collagen and crosslinked structure between the medial and adventitial layers. The findings also raise the possibility that neither collagen nor its crosslinked structure may be affected by gLTH. The data provides evidence that this technique needs refinement to properly visualize the locations where modest changes in expression may occur. Secondarily, the inability of PSR stain to distinguish among certain types of collagen subtypes leaves open the possibility that a shift in the type of collagen may affect biomechanical processes that are associated with pulmonary vascular development or gLTH. The PSR red staining method may not have been definitive, but this study is an important steppingstone towards developing an experimental strategy of visualizing modifications in vascular collagen isoform expression that complement contemporary analytical quantification techniques that provide unique insight into vascular structure and function.

#64 Mesenchymal stromal cell extracellular vesicles improve alveolar formation in mechanically ventilated preterm lambs

E Major1*

A Rebentisch1

E Dawson1

H Foreman1

D Headden1

Z Vordos1

MJ Dahl2

D Null3

A Mitsialis3

S Kourembanas4

K Albertine1

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

2University of California Davis, Davis, CA

3University of California Davis Health System, Sacramento, CA

4Harvard Medical School, Boston, MA

Purpose of Study

Bronchopulmonary dysplasia (BPD) is histopathologically characterized alveolar simplification in preterm infants who are chronically mechanically ventilated. Mesenchymal stromal cell extracellular vesicles (MEx) treatment improved alveolar formation in mouse neonatal hyperoxia models of BPD. We tested the hypothesis that MEx will improve alveolar formation in chronically mechanically ventilated preterm lambs.

Methods Used

Preterm lambs (128d; term ~150d; ~28w human gestation) were exposed to antenatal steroids, perinatal surfactant, and resuscitated and supported by mechanical ventilation for 6–7d (Drager VN500, SIMV). Physiological targets were PaO260–90 mmHg, PaCO245–60 mmHg, O2 saturation 88–92%, pH 7.25–7.35. One group was treated with MEx (60 x 106 cell equivalents; 10 mL; n=8; 4F 4M) at hours of life 6 and 78 (iv); the control group received vehicle (MEx diluent in saline; 10 mL; n=8; 4F 4M). We used morphometry and stereology to quantify structural indices of alveolar formation, and immunoblot to quantify apoptosis (cleaved caspase 3) and proliferation (PCNA).

Summary of Results

Radial alveolar count and secondary septal volume density were significantly greater (* p<0.05) in the MEx-treated group compared to the control group (figure 1A and B). Distal airspace wall thickness was significantly narrower in the MEx-treated group compared to the control group (figure 1C). Normalized cleaved caspase 3 protein abundance was not different between the MEx-treated and control groups (0.71±0.05 vs 0.69±0.04, respectively). Normalized PCNA protein abundance was significantly lower in the MEx-treated group versus the control group (0.43±0.05 vs 0.55±0.05, respectively). No differences were detected between females and males.

Abstract #64 Figure 1

Quantitative morphological results show that alveolar formation is signficantly better (* p

Conclusions

We conclude that MEx improved alveolar formation in chronically mechanically ventilated preterm lambs. We speculate that MEx may be an effective therapy to promote normal structural development of the lung in preterm infants who require mechanical ventilation and are at-risk of developing BPD.

#65 Regenerative response of alveolar type 2 cells to a genetically-induced mouse phenocopy of bronchopulmonary dysplasia

GA Kohbodi1,2*

F Gao1,2

C Li1,2

N Peinado1,2

R Ramanathan1

P Minoo1,2

1Los Angeles County University of Southern California Medical Center, Los Angeles, CA

2University of Southern California Keck School of Medicine, Los Angeles, CA

Purpose of Study

In adult lung, alveolar type II cells (AT2s) serve as facultative stem cells. They proliferate in response to injuries to regenerate and repair the alveoli. There is lack of information on whether AT2s in immature lungs undergoing alveologenesis, such as those of preterm neonates may act as resident stem cells and undergo proliferation in response to injuries that cause BPD. Genetic inactivation of both TGFβ receptors in secondary crest myofibroblasts (SCMF) arrested alveologenesis causing a BPD phenocopy. Alveolar arrest was accompanied by decreased number of SCMF and AT2s, thus suggesting cross-communication between the two cell types during alveologenesis. To determine the mechanism, we quantified AT2 cell numbers in control and mutant lungs at postnatal days 7 and 14 (PN7 and PN14) during alveologenesis.

Methods Used

A total of 12 mouse lungs, (control, n=6, and mutant, n=6) were examined at PN7 and PN14 (n=3 for each control and mutant.) Immuno-histochemistry and immuno-fluorescence were performed on multiple samples of lung tissues. AT2s were identified as SPC positive cells. Proliferating AT2s (pAT2s) were identified as SPC; KI67 double positive cell. To correct for hypoplasia in BPD samples, all results were normalized against total lung cells, identified as DAPI positive.

Summary of Results

In PN7 lungs, the ratio of AT2s/total cells (SPC+/DAPI+) was higher in mutant vs control (AT2s: 10.77% vs 8.58, respectively) likely due to reduction in DAPI+ cells that included reduced SCMF. The pAT2s remained unchanged (pAT2: mutant 0.47% vs control 0.54%). In contrast, in PN14 lungs, both total AT2s, and pAT2s decreased in the mutant lungs vs control (total AT2s: 8.62% vs 10.54%, respectively) and (pAT2: 0.50% vs 0.93%, respectively) indicating that proliferation of both SCMF and AT2s has decreased.

Conclusions

In mutant lungs, TGFβ receptors inactivation decreases SCMF numbers, while AT2s are unaffected in early phases of BPD-like pathogenesis. As the phenotype and loss of SCMF become more established and widespread, inhibition of AT2 proliferation becomes measurable. Two conclusions are derived from these observations: 1) targeted SCMF have a regulatory impact on AT2 proliferation, which is a regenerative response to injury. 2) Despite important differences between mouse phenocopy and human BPD, similar dynamics may occur in the lungs of preterm infants who develop BPD. Response of the endogenous stem cells (i.e. AT2s) in the lung to initial injuries may be governed by an orthologous mesenchymal cell type (SCMF-like) and their communications with AT2 stem cells.

Supported by NHLBI, NIH and the Hastings Foundation

#66 Mesenchymal stromal cell extracellular vesicles improve respiratory system physiological outcomes in mechanically ventilated preterm lambs

A Rebentisch1*

E Dawson1

E Major1

H Foreman1

D Headden1

Z Vordos1

MJ Dahl1

D Null2

A Mitsialis3

S Kourembanas3

K Albertine1

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

2University of California Davis, Davis, CA

3Harvard Medical School, Boston, MA

Purpose of Study

Mesenchymal stromal cell extracellular vesicle (MEx) treatment has therapeutic efficacy in murine neonatal hyperoxia models of bronchopulmonary dysplasia (BPD). Whether MEx will be beneficial in chronically ventilated preterm neonates is unknown. We tested the hypothesis that MEx will improve respiratory system physiological outcomes in chronically mechanically ventilated preterm lambs.

Methods Used

Preterm lambs (128d; term ~150d; ~28w human gestation) were exposed to antenatal steroids, perinatal surfactant, and resuscitated and supported by mechanical ventilation for 6–7d (Drager VN500, SIMV). Physiological targets were PaO260–90 mmHg, PaCO245–60 mmHg, O2 saturation 88–92%, pH 7.25–7.35. One group was treated with MEx (60 x 106 cell equivalents; 10 mL; n=8; 4F 4M) at hours of life 6 and 78 (iv); the control group received vehicle (MEx diluent in sterile saline; 10 mL; n=8; 4F 4M). We report daily physiological outcomes for respiratory severity score (RSS), oxygenation index (OI), Arterial-alveolar (A-a) gradient, and oxygen saturation/FiO2 (S/F) ratio. Liver and kidney function tests were assessed.

Summary of Results

MEx-treated preterm lambs were ~1d younger (* p<0.05) and weighed less (*) at delivery than control lambs (figure 1A and B). MEx-treated lambs tolerated enteral feeding and maintained weight (*) whereas control lambs were less tolerant of enteral feedings and lost weight over 7d (figure 1B). RSS, OI, and A-a gradient were lower for MEx-treated group (*) compared to the control group. S/F ratio was higher for the MEx-treated group (*) compared to the control group. Neither liver nor kidney toxicity was detected. Differences were detected between females and males.

Abstract #66 Figure 1

Respiratory system physiological outcomes for preterm lambs treated with MEx (black circles) or vehicle (white circles)

Conclusions

We conclude that MEx improved respiratory system physiological outcomes in chronically mechanically ventilated preterm lambs. We speculate that MEx may be an effective therapy for appropriate functional development of the lung in preterm infants who require mechanical ventilation.

#67 Oxidized phospholipid neutralizing antibody ameliorates hyperoxia induced lung injury

W Tang1*

X Sun1,2

JL Witztum1

C Glass1

E Sajti1

1University of California San Diego, La Jolla, CA

2The University of Texas Health Science Center at San Antonio, San Antonio, TX

Purpose of Study

Oxidized phospholipids (OxPL) are formed during inflammatory processes, and they are known to induce cellular stress and apoptosis. The role OxPL play in lung inflammation is not known. OxPL are recognized by the IgM natural antibody (Ab) E06, which can bind to and block many of the pro-inflammatory properties of OxPL.To investigate the role of OxPL in hyperoxia-induced acute lung injury (HALI) and whether neutralizing OxPL using E06 would ameliorate or prevent hyperoxia induced lung injury.

Methods Used

C57BL/6J (B6) sensitive and DBA/2J (DBA) resistant mice were exposed to hyperoxia for 48h to induce lung injury. We examined the content of OxPL by immunochemistry with E06 and examined inflammatory responses by measuring changes in immune cell composition in the lung by fluorescence-activated flow cytometry and by immunohistochemistry. We measured gene expression changes in whole lung by RNA-seq. Data were analyzed with FlowJo and HOMER. To examine the pathogenic role of OxPL, we also exposed E06-scFv transgenic mice to hyperoxia. These mice generate a high plasma level of functional E06-scFv (single-chain variable fragment of E06).

Summary of Results

Using immunohistochemistry, we observed an accumulation of OxPL in the lungs of sensitive B6 mice after hyperoxia. OxPL were more abundant in lungs of B6 mice compared to resistant DBA mice. To further explore the molecular determinants of interstrain susceptibility to oxygen, we performed transcriptomic analysis of the whole lung. Transcripts that most distinguished B6 from DBA mice were associated with apoptotic and cell death pathways. To test whether OxPL have a pathogenic role, we exposed E06-scFv mice-on B6 background-to same hyperoxic conditions. Unlike B6 mice, E06-scFv mice did not show activation of apoptosis and cell death related gene pathways.

Conclusions

We observed significant increases in OxPL accumulation following acute hyperoxia exposure in the lungs of injury sensitive compared to resistant mice. OxPL accumulation in the lungs of B6 mice was associated with upregulation of apoptosis and cell death related genes. Blocking of OxPL by the secreted E06-scFv Ab resulted in a significant reduction of apoptosis protecting the lung from HALI. These data suggest that OxPL are not only a useful biomarker for hyperoxia induced lung injury but that an OxPL neutralizing antibody could be used to ameliorate or prevent HALI. Furthermore, the magnitude of interstrain variability in lung gene expression could form the basis for understanding human interindividual variability in susceptibility to oxygen induced injury.

#68 Asynchronous chest compressions with high frequency ventilation improves gas exchange delivery in asphyxiated cardiac arrested preterm lambs

E Giusto1*

A Lesneski2

H Joudi2

M Hardie2

LI Zeinali2

D Sankaran2

S Lakshminrusimha2

P Vali2

1University of California Davis, Sacramento, CA

2University of California Davis, Davis, CA

Purpose of Study

Gas exchange is severely impaired during cardiopulmonary resuscitation (CPR) in the cardiac arrested lamb model despite ventilation with 100% O2. Optimizing gas exchange during neonatal CPR may improve cerebral oxygen delivery (cDO2), prevent rapid fluctuations in PaCO2, and stabilize cerebral blood flow. We hypothesize that asynchronous continuous chest compressions with high frequency percussive ventilation (HFPV) in preterm asphyxiated cardiac arrested lambs will result in improved gas exchange and cDO2compared to 3:1 compression-to-ventilation (C:V) resuscitation.

Methods Used

Time-dated preterm (~125d gestation; equivalent human ~25 weeks) fetal lambs were intubated, instrumented to measure cerebral blood flow and arterial blood pressure, and catheterized to collect venous and arterial blood. After instrumentation, lambs were asphyxiated by umbilical cord occlusion until asystole and delivered. Lambs were randomized to (1) 3:1 C:V resuscitation using a T-piece resuscitator following the neonatal resuscitation program (NRP) algorithm (control), or (2) asynchronous continuous chest compressions (120 compressions/min) with HFPV using a TXP-5 ventilator (intervention). First dose of epinephrine (0.03 mg/kg) was given at three minutes and repeated q3min until return of spontaneous circulation (ROSC). Lambs in the control group that achieved ROSC were managed on conventional ventilation and lambs in the intervention group were maintained on HFPV. Ventilation parameters and O2 were adjusted to maintain SpO2 at 90–95% and PaCO2 between 45–60 mmHg.

Summary of Results

Eight lambs were studied and all achieved ROSC. Baseline characteristics, time to ROSC, and epinephrine doses were similar between groups (figure 1). Mean (SD) PaCO2 was 158 (24) mmHg and the mean (SD) PaO2 was 47 (42) mmHg 15 minutes post-ROSC despite maximum ventilation support and 100% O2 in the control group compared to a mean (SD) PaCO2 of 50 (11) mmHg and a PaO2 of 60 (24) mmHg in the intervention group (table 1).

Abstract #68 Table 1

Comparison of blood gases at fixed timepoints

Abstract #68 Figure 1

Comparison of baseline characteristics between groups. There was no significant difference of characteristics between groups (p > 0.05)

Conclusions

Resuscitation using asynchronous continuous chest compressions during HFVP is feasible with similar success of ROSC and improved gas exchange in an asphyxiated cardiac arrested neonatal lamb model. Further studies are required to validate our results and to assess lung injury by immunohistochemistry and biomarkers.

#69 Early CPAP alters lung structure and mechanical function in neonatal rats

E Bye*

T Gonzalez

G Seedorf

B Smith

N Galambos

SH Abman

E Mandell

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Continuous positive airway pressure (CPAP) is an increasingly common method of non-invasive respiratory support for premature infants to avoid more invasive and potentially injurious ventilation strategies. However, the long-term effects of CPAP on the developing lung are poorly understood. Therefore, we seek to understand the effect of daily CPAP on the structure and mechanical function of the developing lung in neonatal rats.

Methods Used

Control dams were kept in room air and allowed to give birth spontaneously. At day 1, pups were divided into three groups: pups that were secured to CPAP device and receiving daily positive pressure of 6 cm H2O (CPAP-6); pups that were secured to CPAP device and receiving daily airflow but no pressure (CTL-0); and pups that were simply removed from their cage without being secured to the CPAP device for the duration of daily experiments (CTL). Daily CPAP lasted for 2 hours on days 1–2, and 3 hours on days 3–13. At day 14, we measured lung mechanics by flexiVent (total respiratory system resistance (Rrs) and compliance (Crs)). Lung structure was determined by mean linear intercepts (MLI), radial alveolar counts (RAC), and pulmonary vessel density (PVD).

Summary of Results

There were no differences in body weights between groups. CPAP-6 rats demonstrated decreased Rrs (p<0.05) compared to CTL and CTL-0, and increased Crs (p<0.01) when compared to CTL. Lungs from CPAP-6 rats showed impaired alveolarization compared to CTL as assessed by decreased RAC (p<0.05) and increased MLI (p<0.001). Pulmonary vessel density was reduced in CPAP-6 vs CTL rats (p<0.01). There were no significant differences in lung structure between CPAP-0 rats with CTL or CPAP-6 rats.

Conclusions

We found that daily CPAP decreased alveolar and vascular growth and altered lung mechanics in infant rats. We speculate that although less invasive than other ventilation strategies, non-invasive positive pressure respiratory support can potentially have negative effects on the normal developing lung, but its net benefits or harm in the setting of lung disease remains uncertain.

Surgery I

Concurrent session

12:45 PM

Thursday, January 20, 2022
#70 Hemoglobin A1c as a prognostic indicator of postoperative infection following immediate breast cancer reconstruction

CA Czaykowsky*

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Hemoglobin A1c (HgbA1c) is a marker of an individual’s glycemic exposure over a preceding 2–3 month period. Minimal evidence currently exists to support increased infection risk following mastectomy. We aimed to evaluate the association of HgbA1c with the incidence of surgical site infection (SSI) in patients undergoing mastectomy and immediate breast reconstruction.

Methods Used

An institutional database was queried for patients with CPT code for reconstruction AND diagnosis code for breast malignancy for patients from January 1, 2014 to June 20, 2021. We defined SSI incidence by diagnosis or procedure for SSI within 90 days following mastectomy. A one sample t-test was performed to determine if there is a significance difference in the average HgbA1c of the standard patient population and the sample SSI group. A chi-square test was used to analyze data for correlations between SSI rates in diabetics and non-diabetics. The patients were analyzed using a standard chi-square based on a 2x2 contingency table.

Summary of Results

A total of 1386 patients were included in the query; 268 of which having received a pre-op HgbA1c and with 136 having received a pre-op HgbA1c and a DM diagnosis. Only 22 patients fit our defined SSI sample group criteria. The average population HgbA1c was 6.74 (N=268), the average HgbA1c of diabetics was 7.33 (N=136), the average HgbA1c of non-diabetics was 6.13 (N=132). The average sample HgbA1c was 6.94 (N=22), the average HgbA1c of diabetics was 7.34 (N=17), the average HgbA1c of non-diabetics was 5.58 (N=5). The one sample t-test of the average HgbA1c value in patients with DM vs nondiabetics in the sample group was not significant, t(21) = -4.210, p = 3.94E-4. The chi-square test revealed diabetics more likely than non-diabetics to develop SSI following mastectomy, X2 (1, N = 1254) = 76.43, p < .001.

Abstract #70 Table 1

Characteristics of all patients and patients in the surgical site infection sample group

Conclusions

The association of HgbA1c with the incidence of surgical site infection (SSI) following undergoing mastectomy is evident. We found the presence of a DM diagnosis as a better prognostic tool for SSI than HgbA1c level alone. Chi-square analysis determined the relative risk of SSI following mastectomy in diabetic patients at 2.28x that of a nondiabetic. Considering the SSI sample group, a HgbA1c threshold of 7.34 is what we propose as presenting great additional post-surgical complication risk.

#71 The impact of the COVID-19 pandemic on spine surgery practice and outcomes in an urban healthcare system

J Parekh

B Attaripour

SY Xiang*

M Siow

B Mitchell

B Shahidi

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

Purpose of Study

To elucidate changes due to COVID-19 on patient demographics, surgical care, logistics, and patient outcomes in spine patients.

Methods Used

This is a retrospective study of patients who had spine surgery at UCSD from 3/1/19 to 5/31/19 (pre-COVID-19) and 3/1/20 to 5/31/20 (first COVID-19 surge). 331 subjects met the study criteria. Demographic and surgical data were collected from medical records. Pain levels at pre-operative, discharge, short- (3–6 month) and long-term(9–15 month) timepoints were extracted.

Summary of Results

There were no significant differences in patient demographics including age, BMI, gender, race, ethnicity, ASA rating, smoking status, or diabetes status between groups(p>0.14). The diagnostic indications for surgery (spondylolisthesis, tumor/infection, spondylosis, fracture) were not different between groups (p>0.13). There were no differences in operating room duration and skin-to-skin time (p>0.64), however length of stay was 4.7 days shorter during the COVID-19 pandemic (p=0.03) and more cases were classified as ‘urgent’ (p=0.04). Preoperative pain scores did not differ between groups (p=0.58), however pain levels at discharge were significantly higher in patients operated upon during COVID (p=0.04) and trended towards remaining higher in the short- (p=0.06) but not long-term (p=0.21) after surgery (table 1).

Abstract #71 Table 1

Conclusions

The pandemic resulted in a greater proportion of ‘urgent’ spine surgery cases and shorter hospital length of stay. Pain levels upon discharge and at short-term timepoints were higher following surgery, however these differences did not persist in the long term.

#72 Measuring the clinical value of secondary hand surgery in patients with complex hand injuries

BC Goodlin1*

CA Czaykowsky1

S Gupta2

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

2Loma Linda University, Loma Linda, CA

Purpose of Study

The objective of this study is to assess the value of performing secondary hand surgery in a population of complex hand procedures at a quaternary referral site academic medical center.

Methods Used

This was done by obtaining electronic medical records (EMR) of 166 patients over a five year period using specific keywords relating to the types of surgeries generally performed as secondary procedures such as tenolysis, contracture release, and capsulotomies. Of those patients, 50 were found to fit within the parameters of the study. For these 50 remaining patients, hand therapy data was obtained and the percentage of motion that each patient had before the secondary surgery and following the secondary surgery were calculated and this data was used to calculate the overall change in motion. A paired sample t-test was performed to determine if there is a significant difference in the average motion data in the measurements taken before and after secondary hand surgeries. One sample t-tests were performed to determine if there is a significance difference in the average change in the range of motion between common comorbidities (asthma, diabetes mellitus, hypertension, obesity, age over 45 years) or gender between the patient population and each subgroup.

Summary of Results

During a median follow-up period of 8.5 months and an average follow-up period of 18.87 months, a total of 75 complications in 50 patients were recorded. The average percentage of full motion before surgery was 49.43% and the average percentage of full motion after surgery was 66% to give an overall change in motion to be +16.58%. Hand motion measurements following secondary hand surgery (M = 0.491, SD = 0.188) compared to the hand motion measurements preceding secondary hand surgery (M = 0.660, SD = 0.259) demonstrated a significantly better change in motion percent change, t(50) = 24.50, p = 4.177E-5.

Conclusions

Although we speculate that we would have seen an even greater impact from secondary hand surgeries if there had been greater adherence to post-surgical hand therapy, our p value indicates results that are statistically significant. Therefore, we conclude that secondary hand surgery performed on patients with complex hand injuries has a significant measurable impact and we believe that a similar study in a larger population would yield similar results.

#73 Association of the geriatric nutrition risk index and postoperative complications in head and neck cancer

J Chen*

M Abouyared

University of California Davis, Sacramento, CA

Purpose of Study

Malnutrition is associated with increased morbidity and mortality in patients with head and neck cancer (HNC) undergoing surgery. Despite the profound impact malnutrition has on this patient population, objective screening tools are still lacking in a clinical setting. Without a clear approach to identify malnutrition, there is currently a barrier to capturing patients with inadequate nutrition, delaying interventions that could otherwise be implemented to optimize their nutritional status. Therefore, recognizing the need for a tool, the aim of this study is to assess the ability to use the geriatric nutrition risk index (GNRI) to screen for malnutrition among HNC patients and determine if there is an association between GNRI scores and postoperative complications.

Methods Used

A retrospective review of medical records was conducted for patients undergoing surgical resection at a tertiary academic hospital from June 2012 to June 2021. Patients were included if surgical excision was the primary treatment modality and if a serum albumin was obtained 6 months prior to their surgery. A total of 44 HNC patients were included in the study and analysis. Preoperative body weight and serum albumin were abstracted from medical records to calculate the GNRI.

Summary of Results

Of the 44 patients included in the study, there were 30 men (68%) and 14 women (32%), with a total mean age of 62 ±12 years. Malnutrition was defined by a GNRI score of <97.5 and was present in 27% of patients (n=12). Malnourished patients had significantly higher rates of postoperative complications and required discharge to a skilled nursing facility (SNF) more often compared to the control group.

Abstract #73 Table 1

Complications in patients with low and high GNRI scores

Conclusions

A low GNRI score appears to be a predictor of increased complications after head and neck surgery. The GNRI is a simple tool that utilizes serum albumin and body weight to objectively assess nutritional status. Results from this study suggest that, in the future, the GNRI may be a clinically useful approach to screen for malnutrition and identify patients who are at high risk for complications during the postoperative course.

#74 Demographics, fracture characteristics, and treatment strategies for periprosthetic distal femur fractures compared to native distal femur fractures

S Kong1*

B Bautista1

A Saiz2,3

MR Haffner2

J Kelley2

MA Lee2

1University of California Davis, Sacramento, CA

2University of California Davis Health System Department of Orthopaedic Surgery, Sacramento, CA

3The University of Texas Health Science Center at Houston, Houston, TX

Purpose of Study

The incidence of periprosthetic distal femur fractures is increasing due to the increasing number of knee arthroplasties being performed in the aging population. The purpose of this study was to analyze the demographics, fracture characteristics, and treatment strategies associated with periprosthetic distal femur fractures (PDFF) compared to native distal femur fractures (NDFF) in order to identify important clinical differences between these groups that might help guide management.

Methods Used

A retrospective study was conducted of 209 patients >18 years old who underwent surgical treatment for either a native distal femur fracture (NDFF) or a periprosthetic distal femur fracture (PDFF) about a total knee arthroplasty (TKA) from January, 2006 to December, 2020. Fracture classification of CT images by the Association for Osteosynthesis/Orthopedic Trauma Association (AO/OTA) was reported. Demographics, fracture characteristics, fixation constructs, and surgical outcomes were compared between subjects with PDFF vs. NDFF.

Summary of Results

Out of 70 patients with PDFF, 81.1% were female and 18.6% were male, with an average age of 80 years old (range= 49–102 yrs). PDFFs were most often isolated (80%) or comminuted (85%) injuries with AO classification 33A.3 (71.4%). Out of 139 patients with NDFF, 53.2% were female and 46.8% were male with an average age of 57 years old (range =18–96 yrs). NDFFs were commonly comminuted (92.1%) injuries with AO classification 33C.2 (28.1%) or 33A.3 (25.2%). NDFFs were extra-articular (54.0%) or intra-articular (46.0%). Nearly half of subjects with NDFF (48.2%) experienced concomitant fracture of the ipsilateral knee (14.4%) or tibial plateau (15.1%). Intramedullary nailing was the most common fixation construct for both fracture groups (42.6% PDFF;36.7% NDFF). The second most common fixation construct for PDFF was combined nail/plate (17.3%) and lateral locking plate (20.9%) for NDFF. Patients with PDFF experienced shorter length-of-stays (6.36 days vs. 11.4 days) but had higher complication rates compared to NDFF (5.7% vs 4.4%). Incidence of low bone density (osteopenia or osteoporosis) was higher in those with PDFF compared to NDFF (55.7% vs. 19.4%).

Conclusions

PDFFs frequently occur as isolated comminuted injuries with greater complication rates compared to NDFF. Though intramedullary nailing remains the most common fixation construct for both NDFF and PDFF, stabilization via combined plate/nail is increasingly being used for PDFFs. Elderly women with TKA and poor bone quality are a high risk group for PDFF. Further research should entail how physicians can improve their surgical and clinical approach for this type of fracture in the affected population.

#75 Effect of anticoagulant and antiplatelet use on dermatologic and cosmetic procedure intraoperative outcomes

M Gruber

E Foltz*

Washington State University Elson S Floyd College of Medicine, Pullman, WA

Purpose of Study

The use of antithrombotic medications in patients is widely utilized for numerous medical conditions. Research has demonstrated that antiplatelet and anticoagulant use can influence surgical outcomes as well as prolong intraoperative times. However, sparse literature exists examining the effects of antithrombotic use on dermatologic surgery outcomes, specifically in Mohs and cosmetic flap procedures. The purpose of this study is to elucidate the relationship of anticoagulant and antiplatelet therapy on intraoperative time and closure size in dermatologic and cosmetic surgery patients. We hypothesize that those who use daily antithrombotics will have resultantly longer intraoperative times and larger closure sizes in dermatologic flap procedures.

Methods Used

A retrospective medical record review was conducted of all patients who underwent Mohs or cosmetic flap surgery at Chesnut Institute of Cosmetic & Reconstructive Surgery in Spokane, Washington between March 5, 2019 and December 14, 2020. Procedures of 40 minutes duration or less were included. This yielded a total of 243 surgeries with complete information about intraoperative outcomes. Patients were stratified into 5 cohorts based on medication usage (table 1) with documentation of skin closure size and total procedure length.

Summary of Results

A statistically significant reduction in intraoperative times (p-value 0.03) was observed in patients who were not taking any form of antithrombotic medication (cohort 5), as compared to patients in cohort 4 who were actively taking anticoagulant medications. Other classes of antithrombotic medication (cohorts 1–3) were associated with higher average intraoperative times relative to cohort 5, however the difference was not statistically significant. There was no statistically significant difference in closure size across the cohorts.

Abstract #75 Table 1

Conclusions

The use of oral anticoagulants in patients undergoing Mohs and cosmetic flap surgeries results in significantly longer intraoperative times. Further investigation of this relationship and consideration of this finding may influence management of dermatologic and cosmetic procedures.

#76 Multimodal pain control utilizing buprenorphine for robotic assisted laparoscopic prostatectomy: a quality improvement comparison to conventional opioid management

M Hajiha1

D Lien1*

G Stier1

L Soloniuk1

H Ruckle1

A Amasyali1

K Shete1

M Douglas1

J Calvert1

M Chang1

R Tone1

J Johnson2

I Muchiutti2

S Wraich1

1Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

2Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

New persistent opioid use is recognized as a complication in both major and minor surgeries. Prolonged postoperative pain is often the impetus for patients seeking renewal of opioid prescriptions that can lead to persistent use and substance abuse. Clinicians have responsibilities to provide adequate pain relief and limit harmful unnecessary opioid use. By developing alternative analgesic pathways that are as effective as the opioid-inclusive analgesic protocol in managing post-operative pain levels, surgeons can decrease surgical patient’s need and access to opioids in an uncontrolled home environment. Buprenorphine, a mu receptor agonist, has been used for acute and chronic pain management since U.S FDA approval in 1981. However, few studies have tested its efficacy in perioperative administration.

Methods Used

Patients with localized prostate cancer scheduled for RALP were recruited to receive either of two pathways. Forty patients received the standard opioid pathway, and forty-one patients received the buprenorphine-inclusive pathway. In this novel pathway, intravenous buprenorphine was administered intraoperatively and as needed postoperatively. Post-operative analgesic management was as standard, while avoiding non-buprenorphine opiates. Patients were administered a questionnaire regarding their post-operative complications, pain level at discharge, and at-home analgesics used at five days post-op to monitor pain control. Our primary endpoint was adequate pain control, and our secondary endpoints were analgesic consumption at home, opioid-related side effects, and patient satisfaction.

Summary of Results

There was no difference between the buprenorphine group and the conventional group in length of stay (1.1 vs 1.3 days, p=0.18), pain control (0–10 scale) at the time of discharge (5.2 vs 5.7, p=0.4) and overall patient satisfaction (p=0.1). Our study demonstrates buprenorphine’s analgesic capabilities to maintain non-inferior levels of pain control, length of stay, and patient satisfaction comparable to patients on opioid-inclusive analgesia during RALP while decreasing post-surgical and home opioid use.

Conclusions

By markedly decreasing post-surgical opioids prescriptions, we can reduce the risk opioid addiction and the associated harm to the patient. This study is a proof of principle that buprenorphine use for perioperative analgesia during RALP is an alternative to traditional opioid-inclusive analgesic pathways. We believe such a strategy will decrease the incidence of opioid use disorder and have benefits including less associated healthcare spending, improved patient health and reduced social harm.

#77 Retrospective comparison of laminoplasty versus laminectomy with fusion for treating cervical spondylotic myelopathy

O Bakr1*

B Van1

B Bautista1

Z Booze1

RF Roberto2

1University of California Davis School of Medicine, Sacramento, CA

2University of California Davis Health System, Sacramento, CA

Purpose of Study

This study compares the outcomes, features, and costs of laminectomy and fusion (LEF) versus laminoplasty (LP) as surgical treatments for patients with cervical spondylotic myelopathy (CSM).

Methods Used

Elective LEF and LP procedures performed at a single institution between 2014 and 2020 were identified. Included patients had no prior cervical spine surgery. All patients received pre- and postoperative outpatient evaluations in the outpatient clinic. Only procedures involving three or more spinal levels were included. Clinical data was collected from electronic medical records. SPSS 27 was used for statistical analysis. Hospital costs were obtained from hospital billing for a subgroup of patients for whom this information was available.

Summary of Results

135 patients were included: 76 underwent LP and 59 underwent LEF. Mean follow-up time was 14 months. Compared to LEF, LP procedures involved fewer levels (4.2 vs 4.8 levels, p < .001) and trended shorter operative time per level (47 vs 62 minutes, p < .001). Intraoperative blood loss and fluid replacement were similar between groups (p = .79 and p = .08). Patients in the LP group were discharged an average of 1.1 days earlier (p = .001). LP was not associated with higher rates of C5 palsy (p = .28). Patients who underwent LEF were five times more likely to develop wound infection or dehiscence (risk ratio = 5.2, 95% CI:1.1 to 23.4). Postoperative ground-level falls requiring an emergency department (ED) visit occurred more frequently in the LEF group (11.9% vs 2.6%, p = .04). The frequency of ED visits for postoperative neck pain did not differ between groups (p = .42). Likewise, rates of new-onset neck pain were similar (p = .45). Both groups reported improved VAS neck pain over the course of follow-up (p = .001). Surgery type, involvement of the C7 level, and the number of levels involved were not predictive of differences in postoperative neck pain (p = .66, p = .31, and p = .87). Opioid analgesic needs in the year before and the year after surgery were similar between groups (p = .41 and p = .33). The LP cohort had greater preoperative cervical lordosis (C2-C7 cobb angle: 11.69 vs 6.59, p = .01) and lost more lordosis postoperatively (-7.9 vs -1.8, p = .004). LEF cases at this hospital incurred 18% and 34% greater fixed and variable costs (p = .03 and p < .001).

Conclusions

When used to treat patients with multilevel CSM, LP does not seem to be associated with new or worsening axial neck pain compared to LEF. Neck pain may be expected to improve similarly with either surgery. When cervical deformity is not prohibitive, LP could be offered as a less morbid and more cost-efficient alternative to LEF. Modern patient-reported outcomes and randomized controlled trials are still needed to optimize the utility of both procedures.

#78 Lower limb amputations in patients with diabetes hospitalized with foot burns – a national trauma databank analysis

D Perrault1

J Cobert2

V Gadiraju3*

G Gurtner1

T Pham4

C Sheckter1

1Stanford Medicine, Stanford, CA

2University of Rochester, Rochester, NY

3University of Washington School of Medicine, Seattle, WA

4University of Washington Medical Center, Seattle, WA

Purpose of Study

Diabetes Mellitus (DM) has a significant burden in the United States and results in worsening health outcomes. Patients are at risk of peripheral neuropathy, which increases the risk of lower extremity burns, delay in burn presentation, and more complications that translate to more amputations. However, there are limited reports regarding the incidence and outcomes of DM foot burns. We aim to better understand DM health outcomes, specifically lower limb amputations, in DM foot burns at national Level 1 and 2 trauma centers.

Methods Used

Implementing a retrospective cohort study design, we reviewed de-identified data on 116,796 adult admissions from 2007–2015 from the National Trauma Databank (NTDB) for patient age, DM, foot burn status, sex, race/ethnicity, region, burn size, and comorbidities. An exploratory logistic regression of factors associated with lower limb amputations was performed.

Summary of Results

Of the 7,963 (7%) foot burn patients, 1,338 (17%) had DM (median age 56 years [17]) and 378 (28%) were male. Common comorbidities included alcohol use, smoking, and chronic kidney disease (table 1). Using an exploratory logistic regression analysis, when all other variables were kept the same, factors (OR, CI) linked with total lower limb amputations are DM (3.70, [2.98, 4.59]), alcohol use (2.78, [2.13, 3.61]), smoking (0.78, [0.62, 1.00]), chronic kidney disease (2.90, [1.72, 4.88]), burn size>20% (4.12, [2.96, 5.73]), African-American/Black race (1.61, [1.29, 2.01], male sex (1.61, [1.28, 2.02]), and age>40 years. There was a higher rate of lower limb amputations in patients with DM foot burns.

Conclusions

There is a higher rate of total amputations in DM foot burn patients, which indicates the need for increased patient education and treatment protocols that address the incidence of complications in this group. Future steps include confirmatory research to assess the risk of lower limb amputations in DM foot burn patients.

Abstract #78 Table 1

NTDB DM foot burn cohort characteristics (2007–2015)

Abstract #78 Figure 1

Rate per 10,000 of total lower limb amputations increases in DM foot burn vs. non-DM foot burn populations from 2007–2015.

Cardiovascular II

Concurrent session

3:15 PM

Thursday, January 20, 2022
#79 Outcome of hospitalized heart transplant patients with covid infection at a large west coast center

A Mohanty1*

S Kim2

N Patel2

T Singer-Englar2

M Hamilton2

J Kobashigawa2

1Santa Clara University, Santa Clara, CA

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

The COVID-19 pandemic infected large portions of the US community and infected many heart transplant (HTx) patients, but in distinct geographical patterns. HTx programs have reported mortality in the range of 23–29% and in non-transplant patients in the range of 15–17%. The impact of hospitalized HTx patients with COVID infection in a large West Coast heart transplant program has not been reported. We now report our outcomes for hospitalized patients with COVID.

Methods Used

Between March 2020 and March 2021, we assessed 22 HTx patients who were admitted to the Cedars-Sinai Medical Center (CSMC) for COVID infections. COVID is known to affect many systems within the body, and we report the effects on lungs, heart, and kidney. Morbidity and mortality, including risk of death, were included within 90 days post-infection.

Summary of Results

Of the 22 HTx patients hospitalized at the CSMC, 7 patients died (31.8%). All patients had COVID pneumonia requiring supplemental oxygen and 5 patients required ventilatory support. The mean peak FiO2 of the patients was 79.7%. 16 of these patients also were noted to have an increase in serum creatinine, with 6 patients requiring kidney dialysis. Cardiac function was maintained in all patients with COVID-19 and no myocarditis or cardiac dysfunction was observed. 9 patients received remdesivir and 19 patients received corticosteroids. 4 patients received tocilizumab anti-inflammatory therapy.

Conclusions

COVID-19 resulted in significant morbidity and mortality in hospitalized HTx patients. The immunosuppressed state appears to be a risk factor for poor outcome and is higher compared to non-transplant hospitalized patients.

#80 Is sacubitril/valsartan a risk factor for vasoplegia/primary graft dysfunction after heart transplantation?

M Oda1*

T Singer-Englar2

N Patel2

S Kim2

M Hamilton2

J Kobashigawa2

1University of California Los Angeles, Los Angeles, CA

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

Primary graft dysfunction (PGD) is seen in approximately 7–29% of heart transplant (HTx) patients. Many of these patients with PGD also develop significant vasoplegia which requires high doses of intravenous vasoconstrictors. Outcomes of these patients with severe PGD is compromised within 30 days after HTx. Risk factors for the development of severe PGD have included angiotensin-converting enzyme inhibitors (ACEi). There may be a connection between ACEi and the kallikrein-kinin system whereby bradykinin is increased, thus resulting in more vasoplegia and PGD. It is not known whether the new drug sacubitril/valsartan (S/V) is also a risk factor for the development of vasoplegia/severe PGD as bradykinin is also increased with sacubitril. Therefore, we reviewed our large HTx program to see if there is a correlation of S/V as a risk factor for this complication.

Methods Used

Between 2015 and 2020, we assessed 65 HTx patients who were on S/V at the time of transplantation. Vasoplegia was defined as requiring more than 2 vasoconstricting drugs with BP systolic <90 mmHg, and PGD was defined as per the ISHLT classification scheme (within 24 hours post-transplant). These patients on S/V were compared to patients on ACEi/ARB (1:1 control group for age, sex, transplant year). Outcomes included death, cardiac dysfunction, and non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD/pacemaker, or stroke) in the first year after HTx.

Summary of Results

Compared to ACEi/ARB, S/V had similar risk for the development of vasoplegia or severe PGD. Furthermore, 1-year survival, and 1-year freedom from cardiac dysfunction and NF-MACE were not significantly different between groups.

Abstract #80 Table 1

Comparison of Entresto vs. ACEi/ARB

Conclusions

Patients undergoing HTx on S/V do not appear to be at risk for vasoplegia or severe PGD.

#81 The effect of hypomagnesemia post heart transplantation

K Ravellette1*

N Patel2

S Kim2

T Singer-Englar2

M Hamilton2

J Kobashigawa2

1University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

The calcineurin inhibitors (CNIs), including tacrolimus and cyclosporine, have revolutionized heart transplantation (HTx) in terms of maintaining low rejection rates. However, CNIs have significant side effects, such as nephropathy, hypertension, malignancy, and hypomagnesemia. It is this hypomagnesemia that has not been addressed as to whether this has an impact on outcome after HTx. Hypomagnesemia has been involved in muscle cramping and cardiac arrhythmias. Therefore, we reviewed our HTx patients and assessed magnesium (Mg) levels to assess outcome in the first 6 months after HTx.

Methods Used

Between 2010 and 2020, we assessed 956 HTx patients and recorded their Mg levels in the first 6 months after HTx. Patients with low Mg levels less than or equal to 1.8 mg/dL were assessed for complications including muscle cramping, cardiac arrhythmias, rehospitalization, rejection episodes, and death. Patients with low Mg levels were grouped into mildly low Mg levels (1.7–1.8 mg/dL) and moderately low Mg levels (1.4–1.7 mg/dL). Patients were compared to control patients who had normal Mg levels (>1.8 mg/dL) during this period of time.

Summary of Results

Patients with mildly or moderately low Mg levels compared to patients with normal Mg levels had no difference in muscle cramping, rejection episodes, cardiac arrhythmias, and use of antihypertensive medications. Kidney function was abnormal in those patients with normal magnesium levels.

Abstract #81 Table 1

Conclusions

Mild-moderate hypomagnesemia did not have significant adverse effects in heart transplant patients in terms of muscle cramping, cardiac arrhythmias, cardiac rejection, or cardiac function.

#82 Acute abdominal complications immediately following heart transplantation

K Duggin1*

S Kim2

T Singer-Englar2

N Patel2

M Hamilton2

J Kobashigawa2

1University of California Santa Barbara, Santa Barbara, CA

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

It is not uncommon to have an acute abdomen following heart transplantation. Patients who have atherosclerotic vascular disease (coronary artery disease) as the need for heart transplant may also have risk for ischemic bowel associated with their surgeries. In addition, patients who have had gallstones are at increased risk for having cholecystitis immediately following cardiac surgery. It has not been well established as to the frequency of these abdominal complications that warrant urgent abdominal surgery. Furthermore, the presence of increased inflammation in abdominal surgery may trigger an immune response and thereby cause a rejection episode. We sought to evaluate these complications in our large, single center experience.

Methods Used

Between 2010 and 2021, we assessed 1154 patients who underwent heart transplantation and reviewed the frequency of acute abdomen requiring surgical intervention (11 patients) in the first month following heart transplant surgery. These patients were assessed for 30-day and 1-year survival, episodes of cardiac rejection, and infectious complications requiring intravenous antibiotics and/or readmission in the ensuing 3 months. The acute abdomen patients were compared to a case-controlled group, matched by age, sex, and time of transplant.

Summary of Results

1.0% (11/1154 patients) of our patient population developed an acute abdomen and required surgical intervention within the 30 days following heart transplant surgery. Types of surgical interventions included hemicolectomy, cholecystectomy, and exploratory laparoscopy. Compared to the control group, the acute abdomen group had significantly worse 30-day survival and 1-year survival. In the study group, infectious complications occurred in an additional 36.4% of these patients who required rehospitalization with administration of intravenous antibiotics. Rejection episodes following these events was not different from the control population.

Abstract #82 Table 1

Conclusions

Acute abdomen immediately post-heart transplant resulting in urgent abdominal surgery requiring hemicolectomy and/or cholecystectomy has significant morbidity/mortality. For patients awaiting heart transplant with gallstones, prophylactic laparoscopic cholecystectomy might be considered.

#83 Clinical manifestation and prognosis of different cardiomyopathy types on the basis of genetic background

A Paldino1

K Medo2*

L Mestroni2

M Merlo1

M Taylor2

1Universita degli Studi di Trieste, Trieste, Italy

2University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Cardiomyopathies (CMP) are a heterogeneous group of heart disease characterized by structural and electrical abnormalities lacking secondary causative etiology and frequently related to mutations in CMP genes. Recent studies in this field have showed important phenotype overlaps between Dilated Cardiomyopathy (DCM) and Arrhythmogenic Cardiomyopathy (ACM), making the diagnosis a challenging task. The aim of this study is to assess whether a classification of CMP patients (not hypertrophic) based on genetic characterization outperforms in diagnostic and prognostic accuracy the classical, phenotype-driven, diagnostic approach.

Methods Used

We analyzed a population of patients affected by genetically determined DCM and ACM, including carriers of ‘pathogenic’ or ‘likely pathogenic’ (P/LP) variants, registered into the Heart Disease Centers of Trieste and Denver hospitals. We described the phenotype distribution in our population with a clinical and echocardiographic evaluation based on the different disease-related mutated genes. Then, we examined the prognostic impact of the single gene/genetic cluster in determining these outcomes: 1) all-cause mortality and heart transplant; 2) heart failure-related death, heart transplant or destination left ventricular assist device implantation (DHF/HTx/VAD); and 3) sudden cardiac death, sustained ventricular tachycardia/ventricular fibrillation or appropriate defibrillator shock (SCD/VT/VF/shock).

Summary of Results

281 patients carrying P/LP variants (82% DCM) were included in the study. Titin (TTN) and sarcomeric genes (SARC) variants were the most prevalent (TTN: 95 patients, 34% of total population; SARC: 63 patients, 22% of total population) and almost completely related to DCM phenotype (TTN: 100% DCM, SARC: 95% DCM); lamin (LMNA) patients (29 patients, 10% of total population, 96% DCM). A more heterogeneous phenotypic distribution between DCM and ACM were noted for desmoplakin (DSP), plakoglobin (PKP2) and filamin (FLNC) variants. Patients with uncategorized DCM phenotype and carriers of DSP, PKP2, FLNC and LMNA variants (arrhythmic genes) experienced more frequent SCD/VT/VF/shock events (p value=0.002 and p=0.023), compared to patients with DCM phenotype, during follow-up (median=132 months). The analysis shows only P/LP variants of arrhythmic genes, early age of onset and male gender, were associated with an increased risk of SCD/VT/VF/shock events during follow-up. Additionally, there were no differences in terms of HF events was significantly related to genotype.

Conclusions

In a large DCM and ACM population with a positive genetic test for P/LP variants, the classification based on specific genotypes is a useful tool in arrhythmic prognostication . These findings support the need of extensive genetic testing to support CMP diagnosis and prognosis.

#84 Sex differences in desensitization for patients awaiting heart transplantation: is there a difference?

N Yamamoto1*

N Patel2

T Singer-Englar2

S Kim2

M Hamilton2

J Kobashigawa2

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

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

For patients awaiting heart transplantation (HTx) who have high levels of circulating antibodies (greater than 70%), desensitization therapy may be indicated. This will allow expansion of the donor pool for a compatible donor. As women appear to be more highly sensitized (due to multiple pregnancies), it is not clear as to whether women can benefit from desensitization therapy. We sought to answer this question with review of our large, single center database.

Methods Used

Between 2008 and 2020, we assessed 49 patients awaiting HTx who underwent desensitization therapy. These patients were divided into groups by sex for their response to desensitization therapy. Our desensitization protocols consist of regimens including intravenous immune globulin, anti-CD20 monoclonal antibody, plasmapheresis, and/or proteosome inhibitors. A response to desensitization therapy was assessed by the decline of the dominant circulating antibody determined by mean fluorescence intensity (MFI). Post-HTx data was assessed for 1-year survival and freedom from rejections (acute cellular rejection [ACR], antibody-mediated rejection [AMR]). Rejection episodes were compared to a control group of non-sensitized patients transplanted during the same period (n=771).

Summary of Results

Desensitization therapy in women appeared to be comparable to men, considering similar desensitization protocols. There were no significant differences in waitlist mortality, time on the waitlist, 1-year post-transplant survival, or 1-year freedom from ACR or AMR between the two groups. Compared to non-sensitized patients, freedom from AMR was significantly lower in both sensitized men and women (72.7% men vs. 78.9% women vs. 96.5% control group, p≤0.001).

Abstract #84 Table 1

Conclusions

Sensitized women awaiting HTx compared to men appear to have similar response to various desensitization regimens. Post-HTx, there was more AMR in both groups, suggesting memory B-cells may be responsible.

#85 A case of post-COVID myocarditis in a 39 year old female with PCOS and incidental finding of CAD

S Ratnayake*

A Mesfin

L Moosavi

F Joolhar

A Ghandforoush

Kern Medical Center, Bakersfield, CA

Purpose of Study

Reports of cardiovascular manifestations in the setting of COVID-19 have included arrhythmia, pericarditis, heart failure, acute coronary syndrome, and myocarditis. Myocarditis is defined as inflammation of the heart muscle and is commonly associated with viral infection. Common symptoms of myocarditis can include chest pain, shortness of breath, as well as arrhythmia and fatigue. While endomyocardial biopsy remains the gold standard for diagnosis, clinically suspected myocarditis in low-risk patients can be established through presentation and non-invasive diagnostic findings. Here, we aim to highlight the association between coronavirus disease of 2019 infection (COVID-19) and cardiovascular complications such as myocarditis in this case report. In our case, heart catheterization demonstrated 60% stenosis of the proximal left anterior descending artery; however, this lesion was not suspected to be the culprit lesion causing myocardial injury. Etiology of injury was thought to be caused by global ischemia in the setting of post-COVID-19 infection.

Methods Used

Retrospective chart review after IRB approval.

Summary of Results

This is a 39-year-old Hispanic female with history of PCOS, hyperlipidemia, hypertension, Oral Contraceptive Pill, provoked Deep Vein Thrombosis and Pulmonary Embolism on Rivaroxaban, who presented to emergency department with 4 days of new onset intermittent severe substernal chest pain radiating down to her left arm. She had SARS-CoV-2 pneumonia the month prior to this presentation significant for cough, anosmia, and myalgias, which resolved without hospitalization. On arrival, she was hypertensive, tachycardic, and afebrile. Coagulation panel was normal, troponin-I was elevated at 6.25 with a peak of 9.27. Toxicology was negative for stimulants. She tested positive for SARS-CoV-2 but remained asymptomatic. Patient was started on dual anti-platelet therapy and anti-coagulation therapy. Repeat ECG showed no new changes. A second episode of chest pain revealed lateral ST-elevations and Q-waves in inferior leads. Troponin continued to downtrend. Left heart catheterization was performed with incidental finding of 60% stenosis of the proximal LAD with a smooth plaque. This patient clinically improved without further chest pain and was discharged with dual-antiplatelet therapy.

Conclusions

Evaluation and tracking of clinically suspected myocarditis in the setting of COVID-19 infection may give insight into the pathophysiology of infection in cardiomyocytes due to SARS-CoV-2. This case report aims to illustrate the possible association between COVID-19 and myocarditis in the hopes of decreasing morbidity and mortality.

#86 Apical hypertrophic cardiomyopathy mimicking as myocardial infarction

VK Narang1*

P Chan2

F Joolhar1

T Win1

1UCLA-Kern Medical, Bakersfield, CA

2Ross University School of Medicine, Miramar, FL

Case Report

Purpose

Hypertrophic cardiomyopathy (HCM) is known to have a wide spectrum of patterns. This case highlights an uncommon form of HCM called apical hypertrophic cardiomyopathy (ApHCM) which was seen to mimic myocardial infarction.

Methods

Retrospective Study.

Summary

A 46-year-old Punjabi male with hypertension presented to an outside hospital with chest pain and was to have elevated troponin levels of 0.31 ng/mL. Nuclear Lexiscan stress test at that time showed ‘reversible defect of the cardiac apex suggestive of ischemia’, cardiac catheterization was negative, and transthoracic echocardiogram (TTE) showed preserved left ventricular function and mild mitral regurgitation. Troponin trended down to 0.23 ng/mL and the patient was discharged.

Patient then comes to the medicine clinic to establish care and was complaining of palpitations that are intermittent and last about 2–3 minutes per episode. Patient reports that the episodes are initiated by physical activity such as walking about 100 feet and alleviated with rest. Patient denied any chest pain or shortness of breath. Positive history for heavy alcohol use, drinks 6–8 alcoholic beverages 2–3 times a week. Electrocardiogram (ECG) done in the clinic showed left ventricular hypertrophy and abnormal T waves in inferior leads. Repeat TTE showed left ventricular ejection fraction is estimated at >65% and apical to mild LV is unusually thickened which is consistent with ApHCM. Patient was then referred to the cardiology clinic for further management. The patient will be treated with appropriate beta-blocker and cardiac monitoring for further risk stratification.

Conclusion

There are many different spectrums to hypertrophic cardiomyopathy with the most common form being asymmetric septal hypertrophy (ASH). There is a more rare form called ApHCM which is more prevalent in the Asian population (25%) than in non-Asians (1% to 10%). Compared to the ASH, it is more sporadic and associated with more atrial fibrillation (AF) and different risk factors for sudden cardiac death (SCD). There are no current guideline recommendations for diagnosis, screening, or patient risk stratification available for ApHCM.

This case illustrates the importance of understanding and diagnosing patients with ApHCM since patient symptoms mimicked a myocardial infarction. The accurate and timely diagnosis may highly improve the clinical outcome and overall well-being of the patient.

Diversity, equity, inclusion I

Concurrent session

3:15 PM

Thursday, January 20, 2022
#87 Stakeholder engagement efforts to improve diversity in rare disease research: inspiring new science in guiding healthcare in turner syndrome (InsighTS) registry

S Davis1,2,3*

V Bamba1,4

W Brickman1,5

A Carl1,2,3

T Dowlut-McElroy1,6

M Good1,7

S Howell1,2,3

R Kanakatti Shankar1,8

J Law1,9

S Prakash1,10

K Ranallo1,7

1INSIGHTS Consortium, Overland Park, KS

2Children’s Hospital of Colorado, Aurora, CO

3University of Colorado – Anschutz Medical Campus, Aurora, CO

4The Children’s Hospital of Philadelphia Division of Endocrinology and Diabetes, Philadelphia, PA

5Ann Robert H Lurie Children’s Hospital of Chicago, Chicago, IL

6National Institute of Child Health and Human Development, Bethesda, MD

7Turner Syndrome Global Alliance, Overland Park, KS

8Children’s National Hospital, Washington, DC

9University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC

10The University of Texas Health Science Center at Houston, Houston, TX

Purpose of Study

Turner syndrome (TS) occurs in ~1 in 2,000 females who are born with partial or complete absence of the second sex chromosome. Like many rare disease conditions, most research in TS has been focused on specific features (particularly growth), limited to single centers, included minimal diversity, and lacked community engagement. The Inspiring New Science in Guiding Healthcare in Turner Syndrome (InsighTS) Registry was developed to address these limitations.

Methods Used

A Steering Committee with stakeholders comprised of researchers, multidisciplinary clinicians, and patient advocates was formed to develop the goals, infrastructure, data collection tools, protocols and engagement strategies for a national, collaborative clinic-based longitudinal registry for individuals with TS. Six institutions with multidisciplinary TS clinics across geographical regions were onboarded as recruitment sites with the goal of >80% of eligible patients enrolling with diversity in age, race, ethnicity, payor status, and timing of diagnosis. The team identified patient-centered multidisciplinary outcomes obtainable through medical records and optional additional study procedures.

Summary of Results

To date, 154 participants representing all regional centers have enrolled in InsighTS with an average enrollment rate of 15 per month. The average age at enrollment of 11.9 ± 11 years (range 0–67, 16.9% ≥18 at enrollment). 18.5% identify as Hispanic/Latinx ethnicity and racial distribution includes 6.2% Asian, 13.7% Black, 71.9% White, and 11.0% Other Race. TS was identified prenatally in 30.3% of participants. The majority of participants agreed to be contacted for future studies (89%), complete annual surveys (83%) and contribute to the biobank (61%).

Conclusions

Stakeholder engagement for the development of a national clinic-based registry for the rare genetic condition of TS has successfully led to a diverse cohort representative of the US population. Additional engagement strategies to increase enrollment while prioritizing diversity are underway.

#88 Parental perspectives towards COVID-19 vaccines and return to school: focusing on health disparities

K He1*

M Berra2,3

M Kung2,3

B Afghani2,3

1Children’s Hospital of Los Angeles, Los Angeles, CA

2UC Irvine School of Medicine, Orange, CA

3Children’s Hospital of Orange County, Orange, CA

Purpose of Study

The COVID-19 pandemic has disproportionately impacted children from low socioeconomic and minority groups. Parents encounter new decisions regarding vaccinating their child against COVID-19 and return to school in fall of 2021. Prior studies show COVID-19 vaccine hesitancy is associated with income, race, and marital status. However, few studies examine the demographics behind COVID-19 vaccine hesitancy in relation to return to school in vulnerable communities. Understanding both are crucial to addressing challenges for children with healthcare inequities.

Methods Used

A cross-sectional survey was conducted at inpatient and outpatient settings at an academic center and its affiliated site between September 2020 - September 2021. Parents were recruited to complete an anonymous mobile-phone based survey using REDCap regarding perspectives on COVID-19 vaccines and factors affecting children’s return to school during the pandemic. Statistical analyses were performed to examine the association between demographic factors (gender, marital status, education, ethnicity, and household income), COVID-19 vaccine hesitancy, and healthcare inequities affecting return to school.

Summary of Results

Of 189 respondents, 65.5% were married, 41.9% had less than college education, and 37.0% had households of > 2 people. 64.6% were minorities and 53.9% were from low income families. COVID-19 vaccine acceptance was positively associated with marital status and number of household members: 60.9% of married individuals reported they would vaccinate their child compared to 30.4% of unmarried individuals (p = 0.001). 62.1% of households of > 2 people would vaccinate compared to 43.1% with households 2 or less (p = 0.015, table 1). Those who accepted or rejected COVID-19 vaccines were more likely to prefer onsite school compared to those who were unsure (p = 0.020). Education, ethnicity, and income were not associated with COVID-19 vaccine acceptance (table 1) or parental decisions in having their child return to school. Those with less than college education, low income families, and minority groups favored returning to school because of school-provided lunches and availability of internet.

Abstract #88 Table 1

COVID-19 vaccine hesitancy and demographic factors

Conclusions

Our study shows that parents from all ethnicities and incomes may experience hesitancy towards COVID-19 vaccines. COVID-19 vaccine acceptance is positively associated with marital status and number of people in the household. Parents from vulnerable communities experience barriers influencing their decision of sending children back to school. Larger studies are needed to examine the underlying demographic factors behind COVID-19 vaccine hesitancy and return to school. Unique interventions are needed to target children experiencing healthcare inequities in order to increase COVID-19 vaccine confidence and promote safe return to school.

#89 Black individuals, healthcare utilization, and covid-19: preferences in accessing care

I Pasumarthi1*

T Hollar1

N Alety1

E Solano2

M Edman2

G Ochoa2

1Nova Southeastern University, Fort Lauderdale, FL

2YMCA of South Florida, Fort Lauderdale, FL

Purpose of Study

Black individuals in the United States have historically faced barriers to accessing healthcare, only exacerbated by the COVID-19 pandemic. The purpose of this study was to examine the self-reported likelihood of utilizing care within this population in the midst of the COVID-19 pandemic.

Methods Used

Housing authority residents in Broward County, Florida were asked about their likelihood of visiting their doctor during the COVID-19 pandemic as part of a COVID-19 testing and education initiative conducted by the YMCA of South Florida, in partnership with the Housing Authority of the City of Fort Lauderdale and the Broward County Housing Authority. Secondary data analysis of program data was conducted, including descriptive statistics for describing respondents, Chi-square and t-tests for detecting significant differences around likelihood of seeking care between groups, and logistic regression to determine the odds of particular groups’ likelihood of seeking care.

Summary of Results

Significant differences were found between respondents (n=147) reporting they were more likely to visit their doctors in terms of race/ethnicity (X2 [1,n=147] = 8.15, p < .01). Black respondents had three times the odds of claiming to be more likely to visit their doctor (aOR 2.76, 95% CI 1.36–5.60) than other groups. However, Black respondents reported being significantly more afraid of contracting the virus that causes COVID-19 on the way to the doctor’s office than non-Black respondents (X2 [1,n=147] = 4.23, p < .05). Black respondents also reported being more concerned of contracting the virus that causes COVID-19 at the doctor’s office than non-Black respondents (X2 [1,n=147] = 5.29 p < .05).

Conclusions

Black Housing Authority residents seemed to have a high likelihood of utilizing care if needed. However, this high utilization is coupled with a fear of contracting the virus that causes COVID-19 in the process of utilizing care. Areas for further research include determine the rationale behind this positive attitude toward healthcare utilization and figuring out specific areas of concern for contracting COVID-19 in the process of utilizing care (ex. fears of contracting the virus through the use of public transportation on the way to the clinic, etc.).

#90 The efficacy of educational workshops to improve human papillomavirus literacy in Hispanic populations

Y Hwang1*

C Aristizabal2,3

L Baezconde-Garbanati4,5

1Eastern Virginia Medical School, Norfolk, VA

2University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA

3NCI Center to Reduce Cancer Health Disparities, Bethesda, MD

4University of Southern California Keck School of Medicine, Los Angeles, CA

5NCI Center to Reduce Cancer Health Disparities, Bethesda, MD

Purpose of Study

Hispanic populations experience disparities with regards to human papillomavirus (HPV) vaccine uptake despite ranking highest among racial groups for rates of cervical cancer. It is well-established that HPV vaccination confers a high degree of protection against HPV-related cancers. Yet barriers to HPV vaccination contribute to low rates of vaccine initiation and series completion in Hispanic populations with only 35–46% of adolescents fully vaccinated against HPV. Notably, literature suggests low health literacy as a common deterrent to vaccine uptake. The purpose of this study is to assess the utility of educational workshops in the improvement of HPV literacy in Hispanic populations in the Los Angeles area.

Methods Used

Educational interventions, consisting of a one-hour slideshow presentation delivered via Zoom video platform, were conducted from August 2020 to April 2021 and addressed the clinical significance of HPV and the HPV vaccine. Study participants (n=92) were recruited through community partners and by word-of-mouth in a snowball fashion. A pre- and post-test design was used to investigate study participants’ knowledge of HPV and the HPV vaccine before and after educational intervention. Lecture presentations and pre-/post-questionnaires were offered in English and Spanish, depending on the participant’s language preference. A paired t-test was used to compare HPV and HPV vaccine literacy scores pre- and post-lecture. Analysis was completed using SPSS Statistics Version 28.0.

Summary of Results

Of the 92 study participants who attended the lectures, 58 (63.0%) completed both the pre- and post-questionnaires. Prior to educational intervention, HPV and HPV vaccine literacy scores for study participants were 70.4% and 70.7% accuracy, respectively. Post-lecture, HPV and HPV vaccine literacy scores increased to 83.1% and 77.8% accuracy, respectively, demonstrating a statistically significant improvement (p<0.001) in HPV literacy with educational intervention.

Conclusions

The implementation of educational lectures was effective in improving HPV and HPV vaccine literacy in a Hispanic population. These findings demonstrate the need for increased emphasis on HPV education to close the knowledge gap disproportionately affecting Hispanic populations. Future research should focus on vaccine acceptability post-educational intervention in Hispanic populations to identify possible strategies to improve HPV vaccination rates. A potential explanation behind the diminished response rate may be attributed to hesitancy among undocumented study participants to reveal personally identifiable information.

#91 Underrepresented in medicine minority physicians in emergency medicine residency leadership

J Smittick1

ET Reibling2

B Jones2

L Fierro2

M Kiemeney2*

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

2Loma Linda University, Loma Linda, CA

Purpose of Study

It’s evident in academic literature that representation of underrepresented in medicine (URiM) minorities in Emergency Medicine (EM) is sparse. This disparity is more drastic amongst EM leadership. Faculty and residents are directly involved in recruiting, interviewing, and ranking potential incoming residents. The lack of URiM participation in that process impacts the potential for future URiM physicians to be appointed to EM residency leadership positions. Our study sought to identify potential areas for increased representation in the future and factors that may increase URiM involvement.

Methods Used

We administered a survey to the U.S. Emergency Medicine Residency Program Directors (PDs) listed on FREIDA, the American Medical Association (AMA) residency and fellowship database. We drafted and piloted the online survey instrument before sending it to participants via Qualtrics. Survey items focused on ethnic identity in program leadership, career preparation such as mentors and previously held roles, and strategies used to encourage URiM recruitment. Participants received one announcement email and three reminder emails following the survey distribution. We used Microsoft Excel for primary data analysis.

Summary of Results

We received 57 completed surveys. 22% of the respondents identified as URiM, of which 9% identified as Black and 7% identified as Latinx. The median percentage of Residents identifying as URiM was 13% (IQR 1%-32%). Eight programs (14%) reported having at least one Chief Resident identifying as URiM. 72% of respondents reported that a mentor was instrumental in their ascension to PD. 11% reported that their mentor identified as URiM. We asked PDs to confirm which strategies they’ve implemented to encourage URiM participation (Boatright 2008). The most commonly implemented strategies were, ‘Know the institution’s local and community demographics, and address those needs’ (51%), followed by ‘Broaden selection criteria beyond USMLE scores to include intangibles such as leadership, community service, and other life experiences’ (49%), and ‘Develop curricula to address topics on diversity, cultural competence, and implicit bias’ (47%).

Conclusions

The disparity of URiM PDs in EM may be a result of a lack of URiM mentorship. 29% of respondents were URiM but only 11% reported having a URiM mentor. This lack of mentor-mentee concordance may be an area of further study and improvement. More intentional utilization of URiM recruitment strategies could also drastically improve representation. Increased URiM participation in EM leadership has great potential to improve diversity, equity, and inclusion in EM overall.

*Boatright N, et al. The Impact of the 2008 Council of Emergency Residency Directors (CORD) Panel on Emergency Medicine Resident Diversity. DOI: 10.1016/j.jemermed.2016.06.003.

#92 Novel health equity advocacy curriculum to incite engagement in medical trainees

C Conklin1*

N Rodman1

D Smith1

W Joshi1,2

1University of California San Diego School of Medicine, La Jolla, CA

2Rady Children’s Hospital San Diego, San Diego, CA

Purpose of Study

Medical education health equity curriculums rarely emphasize advocacy and community engagement, further exploiting the minority tax in pursuing health equity work. Health equity curriculums must include three components: history, outcomes and interventions. The Journal Club and Advocacy Lab (JC-AL) schema was added to the Health Equity Thread (HET) preclinical curriculum at UC San Diego (UCSD) School of Medicine to teach and support interventions to health disparities.

Methods Used

Preclinical students receive HET credit by attending JC-ALs. JC-AL workflow is depicted in figure 1; the JC and AL are held 1–2 weeks apart. Participants took a survey, approved by the UCSD Institutional Review Board, before the JC and after the AL. Survey responses from November 2020-June 2021 were gathered and summarized for each timepoint using R.

Summary of Results

Of participants surveyed, 141 (28.5%) identified as underrepresented in medicine. About a quarter of participants saw an increase in mood (25%), resilience (27%), sense of community (24%) and/or motivation (29%) regarding health equity work after the intervention. 158 participants (67.2%) reported being somewhat or very likely to stay involved in the advocacy project, and 93 participants (39.6%) reported being likely to lead a session in the future. Almost all of the JC-ALs have manifested long term projects including:

- Educational material for healthcare providers and preclinical students regarding removal of race from eGFR and adoption of cystatin C and addition of cystatin C in UCSD Health Laboratory Medicine Formula

- Learning modules for preclinical students on gender affirming and trauma informed care

- Elective on obtaining a health equity history in the emergency department

Abstract #92 Figure 1

Workflow for JC-AL

Conclusions

The JC-AL schema is a feasible approach to engage trainees in the community and institution to enact change. It is a well-received component of the HET ranging from 30–100 participants at each event.

#93 Using validated instruments to assess loneliness, social support, and burnout amongst racial and LGBTQ+ residents

DA Mesa*

University of Colorado, Denver, CO

Purpose of Study

There is very little data published exploring the impact that racial or sexual minority identity has on a resident’s training experience. Given that a high percentage of internal medicine training programs are predominantly white it’s important to understand the emotional and supportive barriers minority residents face. We began the important work looking into these barriers with a survey-based needs study.

Methods Used

174 residents enrolled in the University of Colorado Internal Medicine Residency Program were asked to participate in an online survey. This survey consisted of several validated instruments including: the PHQ-4, the MOS Social Support Survey, and the UCLA Loneliness scale. The survey included a demographics section and each respondent utilized a unique PID to maintain anonymity. 65 out of 174 residents responded to the survey. The answers to the survey were coded and scored per the original publications. Analysis of the data was done using two tailed T-Tests in the SAS software.

Summary of Results

The average MOS total support score was significantly lower in LGBTQ+ residents compared to Non-LGBTQ+ residents (Mean 65.80 vs. 79.16; P = 0.035). LGBTQ+ residents also trended towards having higher amounts of burnout, though this wasn’t statistically significant (Mean 0.38 vs 0.17; P = 0.19). Notably 3 out of 9 LGBTQ+ residents reported feeling burnt out compared to 9 out of 56 Non-LGBTQ+ residents (33% vs 16%). Notably most of the significant findings were amongst single vs non-single residents with significance in: UCLA loneliness scale (P = 0.03), MOS total support score (P <0.0001), MOS emotional support score (P = 0.008), MOS affectionate support score (P <0.0001), MOS tangible support score (P <0.0001), MOS positive interactions score (P = 0.001) and PHQ-Depression sub-domain (P = 0.025). Racial minority residents had lower average levels of burnout compared to non-minority residents (Mean 0.12 vs 0.23; P = 0.32). However, racial minority residents had lower average levels of overall social support compared to non-minority residents (Mean 73.16 vs 78.74; P = 0.270) with the tangible support subdomain score being the closest for significance (Mean 13.55 vs 15.93; P = 0.120).

Conclusions

The sample size for the survey-based study was smaller than anticipated. However, it was large enough to find significance for LGBTQ+ residents having less social support, and also revealed higher levels of burnout. It’s also important to note that while it didn’t reach significance minority residents experienced lower average levels of overall social support. Surprisingly minorities had fewer burnout numbers which may be an indicator of increased resilience or utilization of protective mechanisms. Further reasearch needs to be conducted to better understand the needs of LGBTQ+ and racial minority residents. Future directions include expansion nationwide to gather a larger sample size and assess for geographic differences.

#94 Idiopathic subglottic stenosis in non-caucasian women

A Suk1*

L Reder2

K O’Dell3

S Verma4

M Harmon5

P Weissbrod5

P Krishna6

B Crawley6

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

2Kaiser Permanente Baldwin Hills, Los Angeles, CA

3University of Southern California, Los Angeles, CA

4University of California Irvine, Irvine, CA

5University of California San Diego, La Jolla, CA

6Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

To analyze the presentation, disease course, and treatment of idiopathic subglottic stenosis of non-Caucasian women.

Methods Used

In this multi-institutional retrospective study, information extracted included date of birth, age at symptom onset, age and date of diagnosis, race, Cotton Meyer grade, stenosis length and distance from glottis, BMI, comorbidities, medication to manage iSGS, age at first surgery, additional treatment with serial intralesional steroid injections, the date of each surgery, occupation, autoimmune labs, and family history of autoimmune diseases.

Summary of Results

35 non-Caucasian women with idiopathic subglottic stenosis were identified. Of the 35 women, 31 were Hispanic while one was African-American, two were Asian, and one was non-Hispanic mixed race. Their average BMI was 31.8 ± 2.19 kg/m2 and 51.4% of the patients were obese (BMI>30). 31.4% had hypertension. Their average age of onset was 45.8 years old (95% CI, 42.2–49.3) with a range of 26–69 years old. The average age at diagnosis was 47.8 years (95% CI, 44.3–51.3) with a Charlson comorbidity index of 0.85 (95% CI, 0.42–1.28). At diagnosis, 13.4% were CM I, 43.3% were CM II and 43.3% were CM III (n=30). The average age at their first surgery was 46.8 (95% CI, 43.2–50.4) years and 17 received SILSI. While treatment type varied given this was a retrospective surgery, none of the 35 women received open reconstruction. 62.9% experienced disease recurrence after their first surgery with a median of 11 months between their first and second surgery and received an average of 2.5 surgeries.

Conclusions

Our results show that the non-Caucasian population does not differ from the majority Caucasian population published elsewhere in current literature on idiopathic subglottic stenosis, which calls into question the homogeneity of the disease and the need to adjust recruitment methods to include more people of color and provide a more accurate representation of the patient population.

#95 Scoping review of socioeconomic factors and hidradenitis suppurativa

OS Cherepakhin1*

K DeNiro2

1University of Washington School of Medicine, Seattle, WA

2University of Washington, Seattle, WA

Purpose of Study

Hidradenitis suppurativa (HS) is an autoinflammatory disease characterized by painful boils beneath the skin. While socioeconomic factors have been linked to HS individually, there has been no scoping review that synthesizes these correlations. Our objective was to assess the published data on the associations between HS and the factors of income, education, and work.

Methods Used

A search limited to English publications was conducted in PubMed, Embase, Web of Science and Cochrane from database origin to 07/26/21. The terms used were ‘hidradenitis’ combined with ‘socioeconomic,’ ‘insurance, ‘class, ‘disparities,’ ‘disparity,’ ‘education,’ ‘income,’ ‘work,’ ‘employment,’ ‘job,’ ‘insurer,’ ‘medicaid,’ or ‘professional activity.’ Eligible publications were peer-reviewed and examined the association between HS and income level, educational attainment, occupation class, employment status, work impairment, or insurance status. Records were evaluated by O.C. and K.D. In the event of a disagreement, another reviewer was available to resolve the discrepancy.

Summary of Results

After duplicate removal, 413 records were screened by title/abstract. 79 full-text records were then assessed for eligibility and 33 articles met inclusion criteria. By manually searching article references, an additional 3 papers were included. 29 research articles, 6 reviews, and 1 case report from 13 different countries were qualitatively synthesized according to the defined categories of associations.

3 articles found that HS patients had lower income levels but one of those studies, after adjusting for age/sex, found that this was not significant. 6 articles elucidated an association between HS and lower educational attainment. An association between HS and lower class of occupation was found by 1 study, and 7 publications (6 articles, 1 review) demonstrated a higher probability of being unemployed as an HS patient. 16 articles, 1 case report, and 5 reviews discussed the association between HS and work impairment. A higher likelihood for HS patients to have government-funded insurance was found by 3 studies. 4 articles utilized a combination of the factors as measures of SES. 3 of them found associations between low SES and HS, while one Israeli study found the opposite.

Conclusions

Our qualitative synthesis demonstrates that HS globally is linked with lower income levels, reduced educational attainment, unemployment, work impairment, and government-funded insurance coverage. Though one study found that higher SES is associated with HS, this can be explained by their usage of dermatologist-diagnosed HS patients and the fact that in Israel, dermatology encounters require co-payments unlike primary care visits. Though the directionality between HS and lower SES cannot be determined from the current research, our work shows the importance of considering SES when treating HS patients.

#96 American osteopathic association otolaryngology and ophthalmology program closures as a model to highlight challenges of maintaining graduate medical education in high need areas

K Vo1*

H Ahmed2

W Robbins3

1Western University of Health Sciences, Pomona, CA

2Loma Linda University, Loma Linda, CA

3OhioHealth, Columbus, OH

Purpose of Study

While 90% of former American Osteopathic Association (AOA) residency programs transitioned to Accreditation Council for Graduate Medical Education (ACGME) accreditation, surgical subspecialty programs such as otolaryngology (ENT) (62%) and ophthalmology (47%) struggled to gain accreditation. DOs have actively participated in serving underserved communities, and losing AOA surgical specialty programs may decrease access to surgical care in rural and non-metropolitan areas.

Methods Used

A directory of former AOA ENT and ophthalmology programs was obtained from the American Osteopathic Colleges of Ophthalmology and Otolaryngology-Head and Neck Surgery (AOCOO-HNS). A secured survey was sent out to16 eligible ENT and ophthalmology program directors. The survey contained both quantitative and qualitative aspects to help assess why these programs did not pursue or failed to receive ACGME accreditation.

Summary of Results

12 of 16 eligible programs responded: 6 ophthalmology and 6 ENT program directors. 83% of respondents did not pursue accreditation (6 ophthalmology and 4 ENT programs), and 17% (2) were unsuccessful in achieving accreditation despite pursuing accreditation. Across 12 respondents, 58% (7) cited lack of hospital/administrative support and 42% (5) cited excessive costs and lack of faculty support as reasons for not pursuing or obtaining ACGME accreditation.

Abstract #96 Table 1

Percentage of remaining osteopathic ENT and ophthalmology programs from 2014–2015 to 2020–2021 academic year under the SAS

Conclusions

The survey results reflect financial issues associated with rural hospitals. Lack of hospital/administrative support and excessive costs to transition to the ACGME were key drivers in the closures of AOA surgical specialty programs. Considering these results, we have 4 recommendations for various stakeholders, including program directors, designated institutional officials, hospital chief medical officers, and health policy experts. These recommendations include expanding Teaching Health Center Graduate Medical Education to surgical subspecialties, identifying and learning from surgical fields such as urology that fared well during the transition to ACGME, addressing the lack of institutional commitment and prohibitive costs of maintaining ACGME accredited subspecialty programs in under-resourced settings, and reconsidering Centers for Medicare & Medicaid Services (CMS) pool approach to physician reimbursement.

Hematology and oncology I

Concurrent session

3:15 PM

Thursday, January 20, 2022
#97 Novel perinephric neovascularity scoring system in renal cell carcinoma tumor staging

C Fateri*

A Peta

N Kar

T Bui

B Roth

J Glavis-Bloom

L Limfueco

J Landman

R Houshyar

University of California Irvine, Irvine, CA

Purpose of Study

Renal cell carcinoma (RCC) is the most common type of kidney cancer worldwide. Angiogenesis plays a major role in providing adequate blood flow and nutrients to promote tumor growth and RCC progression. While radiologists assess enhancement patterns of renal tumors to predict tumor pathology, to our knowledge, no formal scoring system has been created and validated to assess the level of neovascularity in RCC, despite its critical role in cancer metastases. In this study, we characterized and analyzed the level of angiogenesis in tumor-burdened kidneys and their benign counterparts. We then created and validated a scoring scale for neovascularity that can help predict tumor staging for RCC.

Methods Used

After Institutional Review Board approval, the charts of patients who had undergone surgery for RCC between January 13, 2014 and February 4, 2020 were retrospectively reviewed for inclusion in this study. Inclusion criteria were a diagnosis of RCC, simple/radical nephrectomy, pre-operative contrast enhanced computed tomography (CT) scans, and complete pathology reports. Neovascularity was scored on a scale of 0 to 4 where 0= no neovascularity detected, 1= a single vessel <3 mm wide, 2= a single vessel ≥3 mm wide, 3= multiple vessels <3 mm wide, and 4= multiple vessels ≥3 mm wide. Each patient was scored by a senior medical student and then validated by a board-certified abdominal radiologist. Statistical analysis was performed using RStudio® Version 3.5.1. Demographics and tumor characteristics were compared using a Kruskall-Wallis ANOVA or Chi-squared test; neovascular score was compared using a Wilcoxon Rank-Sum test. Statistical significance was considered as p < 0.05.

Summary of Results

A total of 217 patients were included in this study. There was no significant difference in patient demographics between tumor stages. Additionally, the majority of tumor pathology was clear cell carcinoma, regardless of tumor staging. The average neovascularity score was 1.07 for pT1x tumors, 2.83 for pT2x tumors, and 3.04 for pT3x tumors. The average neovascularity score for the benign counterparts was 0.124, 0.385, and 0.458, respectively. There was a significant difference in neovascularity score between pT1x and pT2x tumors (p = 0.0046), pT1x and pT3x tumors (p < 0.0001), and benign kidneys and kidneys with RCC (p = <0.0001).

Conclusions

Our novel vascular scoring system for renal cell carcinoma demonstrates a significant correlation with RCC pathological tumor staging. This scoring system may be utilized as part of a comprehensive radiological assessment of renal tumors, potentially improving tumor characterization and clinical decision making.

#98 Stress-induced differential miR-4633–5p expression in thyroid cancer health disparities

J Mancao1*

S Khan1

J Lee1

K Rood2

R Davis1

M Perez1

A Simental3

S Roy4

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

2Loma Linda University Department of Basic Sciences, Loma Linda, CA

3Loma Linda University Medical Center, Loma Linda, CA

4The University of Texas at El Paso, El Paso, TX

Purpose of Study

Filipino Americans (FA) are known to have higher rates of thyroid cancer incidence and disease recurrence compared to European Americans (EA). FA are also known to be two times more likely to die of thyroid cancer compared to EA. Epidemiological studies in California have shown that thyroid cancer is the second most common cancer among FA women. Currently, there are no studies that demonstrate the mechanism behind these discrepancies. Evidence shows a strong correlation between obesity and more aggressive forms of thyroid cancer; obesity has an increased frequency in FA populations. The exact connection between the mechanisms of obesity and cancer is poorly understood. This epigenetic phenomenon may be due to microRNAs (miRNAs), which post-transcriptionally regulate gene expression. Dysregulated miRNA profiles have been associated with various diseases including obesity and cancer. MiRNAs are linked to different types of cancer; tumor suppressor genes and oncogenes are subject to modulation by dysregulated miRNAs. No study elucidates the association of miRNAs to tumor staging or prognosis in thyroid cancer health disparities.

Methods Used

In this study, we determined miRNA expression profiles and found significant differences in the miRNA profiles between FA and EA thyroid cancer patients. Our pilot study showed several dysregulated miRNAs, from which we chose to assay dysregulated miR-4633–5p segments that are known to be associated with thyroid cancer signaling. We used QIAGEN’s miRNA extraction kit to obtain high-quality miRNA from paraffin-embedded thyroid tissues. We performed next-generation miRNA sequencing using equal number of FA and EA samples and identified the top ten significantly up- and down-regulated miRNAs from the pool of differentially expressed miRNAs by qPCR assays.

Summary of Results

Our investigation demonstrated a 1.5–2-fold higher expression of an upregulated miR-4633–5p in FA versus EA miRNA samples (n=70) after normalized to controls. In contrast, miR-323b-3p showed no difference between FA and EA after normalized to controls.

Conclusions

For our future work, we plan to analyze multiple up- and down-regulated miRNAs by qPCR, determine whether the miRNA signatures are consistent between samples from FA versus EA, and explore the use of these miRNA signature differentials for affordable and rapid thyroid cancer screening and prognosis.

#99 Melanoma of unknown primary: a single-institution evaluation of clinical outcomes

S Dwabe1,2*

G In1,2

1Los Angeles County University of Southern California Medical Center, Los Angeles, CA

2Keck Hospital of USC, Los Angeles, CA

Purpose of Study

Melanoma of unknown primary (MUP) is clinically uncommon and is understudied as a disease. There have been studies evaluating the utility of local resection with radiation therapy for treatment of MUP. However, it has been only within the last few years that MUP has been routinely treated with targeted or immunotherapy.

Methods Used

We conducted a retrospective review of patients with MUP treated at LAC-USC Medical Center and Norris Cancer Center from 2008 to December 1st, 2020. We recorded the presentation, treatment course, and outcomes of each patient within our database. Data points collected include demographic information, clinical staging, size of largest metastases, location and number of metastatic sites. Treatment modalities, including metastatectomy, and systemic therapy were reviewed. The primary outcomes studied were median overall survival and 1-year overall survival.

Summary of Results

Data was collected from 32 patients identified as having MUP. Sites of melanoma metastases included lymph node, soft tissue/muscle, lung, liver, brain/leptomeningeal disease, and bone. Thirteen patients (40.6%) were found to have one metastatic tumor, 6 (18.8%) were found to have 2–3 metastases, and 13 (40.6%) were found to have 4+ metastatic tumors on presentation. Two patients were lost to follow up shortly after their diagnosis. The 30 remaining patients had a 14.3-month median survival with 17 (56.7%) surviving past one year.

In total, 15 patients underwent surgical metastatectomy, and 18 patients were treated with immunotherapy. With all patients surviving after one year, the 13 patients who had a complete resection of their tumor burden were noted to have a median survival time of 37.0 months following their diagnosis compared to a 2.2-month median survival among the 17 patients who did not have surgery or who had incomplete resection of tumor. The 18 patients treated with immunotherapy (PD-1 ± CTLA-4 inhibition) were found to have a median survival time of 23.7 months with 16 (88.9%) surviving past one year. Eleven patients who were treated both with complete surgical resection and adjuvant immunotherapy, were found to have a median survival time of 35.0 months with 11 (100%) surviving past one year. When analyzing outcomes of patients with MUP based on the number of metastases, number of organs involved, and largest size of metastases, survival was correlated with less than 4 metastases and less than 2 organs involved. Size of largest metastases had no effect on survival outcomes.

Abstract #99 Table 1

Clinical outcomes

Conclusions

Outcomes among patients with MUP may vary, depending on treatment modality, and tumor burden. Based on our data, patients who have MUP with low burden of disease may benefit from multi-modality therapy, including both surgical metastatectomy, and immune checkpoint blockade. Further validation using larger cohorts is warranted to help confirm these findings.

#100 Second hits in NF1-tumors reveal prevalence of copy neutral loss-of-heterozygosity in individuals with neurofibromatosis type 1

S Tong1*

J Shieh2

P Devine2

1UCSF Benioff Children’s Hospital Oakland, Oakland, CA

2University of California San Francisco, San Francisco, CA

Purpose of Study

Multiple mechanisms may give rise to biallelic variants in NF1-related tumors. Deletion and copy-neutral loss of heterozygosity (LOH) are potential mechanisms of somatic NF1 loss, distinct from point mutations. Tumor multi-gene sequencing demonstrates co-mutations in genes in addition to NF1, which may be tumor dependent and which may help molecularly classify tumors seen in NF1. This study asks whether excised tumors from individuals with NF1 demonstrate additional gene variants and differentiates first and second hits in NF1 using paired germline and somatic sequencing.

Methods Used

The hypothesis is NF1 second hits and co-mutational patterns may be found by analyzing cancer driver genes. To test this hypothesis, data from 6381 tumors previously sequenced on a 529- cancer gene panel were analyzed to yield 391 NF1-mutated tumors. LOH analysis over NF1 was done for all cases.

Summary of Results

NF1 LOH was common, seen in 133/391 tumor samples. There were 40 tumors from individuals with constitution NF1. Tumors from individuals with constitutional NF1 had more prevalent copy neutral LOH (p-value <0.0001, two proportion z-test), suggesting somatic intrachromosomal recombination. Osteosarcoma was noted in association with NF1 with copy-neutral LOH, adding to accumulating reports of this rare tumor in NF1. NF1-associated MPNST versus non-NF1-associated MPNST, harbored co-mutations in TP53 as well as CDKN2A/2B deletion. Additionally, NF1 second-hit data from tumors were informative for annotating missense variants that were conflicting in ClinVar, potentially helping to improve NF1 annotation. The results provide an additional 162 deleterious NF1 variants to add to current gene annotation efforts.

Conclusions

Sequencing of paired tumor and normal samples in NF1-associated tumors uncovers a spectrum of second hits to the NF1 locus. Future work will be aimed at a mechanistic understanding of these distinct patterns of mutation and strategies aimed at mitigating tumor risk.

#101 Impact of sponsor on advanced non-small cell lung cancer clinical trial enrollment criteria

RA Cooper1*

Y Chai2

J Nieva1

1University of Southern California Keck School of Medicine, Los Angeles, CA

2Children’s Hospital of Los Angeles Saban Research Institute, Los Angeles, CA

Purpose of Study

Clinical trials use inclusion and exclusion criteria to control for confounding variables in patient populations. Largely inspired by the ASCO-Friends of Cancer Research recommendation documents (2017 and 2021), there has been a recent drive to loosen clinical trial enrollment criteria to improve generalizability in trial outcomes. We sought to determine if the sponsor of a clinical trial impacted the transparency and selection of inclusion and exclusion criteria.

Methods Used

Using clinicaltrials.gov, phase 2 and 3 non-small cell lung cancer (NSCLC) drug trials were sorted into one of three sponsor categories: Industry, government/cooperative group, and academic. Fisher Exact tests were used to assess variability in strictness of specific criteria and level of transparency in listing organ function requirements. Independent sample t tests were used to analyze differences in total number of criteria.

Summary of Results

Industry sponsored NSCLC drug trials more often omit from clinicaltrials.gov complete organ function requirements compared to government/cooperative group (p = 2.3 x 10–10, α = 0.01) and academic (p = 1.8 x 10–4, α = 0.01) sponsored trials. Industry sponsored trials are also more likely to have stricter performance status requirements compared to government/cooperative group sponsored studies (p = 5.7 x 10–6, α = 0.01).

Abstract #101 Figure 1

Percentage of studies with strict, loose, and no restrictions on performance status. Actual number of studies within each group are included as data labels

Conclusions

Industry funded NSCLC clinical trials are more rigorous in excluding patients with worse performance status and are less transparent in listing all study requirements on clinicaltrials.gov.

#102 Assessing adult patients’ understanding of terms in consent related to secondary malignancy risk in radiation therapy

N Vartanian*

M Wilson

R Ermoian

University of Washington School of Medicine, Seattle, WA

Purpose of Study

Informed consent entails that healthcare providers effectively describe adverse effects associated with medical treatments to patients. In radiation oncology, the terms ‘second tumors’, ‘secondary malignancies’, or ‘secondary tumors’ are used in patient consents to describe the appearance of new and different tumors caused by radiation treatment. Furthermore, these incidences are sometimes described in consents as ‘rare’, although the incidence varies greatly from nearly negligible in patients treated with palliative intent, to 20% in patients undergoing myeloablative total body irradiation for stem cell transplant. We evaluated whether non-cancer patients without prior knowledge of or exposure to radiation therapy interpret the terms ‘secondary malignancy’, ‘rare’, and ‘small chance’ in a way consistent with physician intent.

Methods Used

We screened 164 adult subjects who did not require medical interpreters at a university affiliated family medicine clinic, excluding cancer patients and those with any prior knowledge of or experience with radiation treatment. One hundred subjects were eligible for and completed our 12-question multiple choice questionnaire, which assessed their understanding of the term ‘secondary tumor’, and how they would interpret the terms ‘small chance’ or ‘rare’ in the context of a ‘bad side effect’ arising from medical treatment.

Summary of Results

Twenty-nine percent of subjects correctly identified that ‘secondary tumors’ referred to new and different tumors caused by treatment. Forty-nine percent thought the term referred to their original tumor coming back, and twenty-two percent thought the term referred to new and different tumors not caused by radiation therapy. In the context of a ‘bad side effect’ occurring ‘rarely’, 2% of subjects attributed ‘rare’ to a 1/10 chance; 16% to a 1/100 chance; 33% to a 1/1000 chance; and 49% to a 1/100,000 chance.

In the context of a ‘bad side effect’ having a ‘small chance’ of occurrence, 8% of subjects attributed ‘small chance’ to odds of 1/10; 33% to 1/100; 41% to 1/1000; and 18% to 1/100,000.

Conclusions

Patients without prior radiation therapy exposure have a demonstrably different understanding than radiation oncologists of the terms ‘secondary malignancy’, ‘second tumor’, or ‘secondary tumor’. Additionally, there is great variability in patient understanding of the terms ‘rare’ or ‘small chance’. Radiation oncologists must use different and more descriptive terms for secondary malignancies and their incidence, to ensure patients are truly informed when undergoing treatment. The results of this study may have implications for all medical fields in which patients are consented for procedures associated with a risk for consequential side effects.

#103 Regulation of chemoresistance by CHRM1 in non-small cell lung cancer

S Simpson*

T Bland

WWAMI, Seattle, WA

Purpose of Study

Chemotherapy is a mainstay treatment for late-stage non-small cell lung cancer (NSCLC), yet most tumors develop resistance to these agents. Studies in our lab have shown that chemoresistant NSCLC cells overexpress the muscarinic acetylcholine receptor 1 (CHRM1). We hypothesize that CHRM1 regulates chemoresistance in NSCLC cells, and that the combination of a repurposed CHRM1 antagonist dicyclomine, clinically used to treat IBS, and a chemotherapeutic agent has the potential to sensitize and kill chemoresistant NSCLC cells.

Methods Used

Chemosensitive (A549) and chemoresistant (A549R) NSCLC cells were utilized in this study. Cell survival and colony formation assays were utilized to measure DTX sensitivity by pretreating with designated drug (24 hr) before addition of DTX (48 hr). Western blot and phospho-kinase array were utilized to measure protein expression and intracellular pathway activation. The designed receptors exclusively activated by designer drugs (DREADD) system was utilized to isolate CHRM1 signaling. All data are expressed as the mean ± SEM. Multiple comparisons were analyzed using one-way ANOVA with post-hoc Tukey’s analysis and single comparisons were analyzed using a two-tailed, unpaired Student’s t test.

Summary of Results

CHRM1 expression is enhanced in A549R cells, suggesting that CHRM1 may play a role in chemoresistance. This was supported by the ability of a CHRM1 agonist, dicyclomine (Dic), to sensitize A549R cells to the chemotherapeutic agent docetaxel (DTX) measured by cell survival (IC50: DTX, not reached > 1M; DTX + Dic (10μM), 49.91μM; DTX + Dic (25μM), 12.11μM). Furthermore, these results were duplicated by colony formation assay. However, activation of a CHRM1 in A549 cells by the acetylcholine mimetic carbachol did not protect cells from DTX-induced cell death, suggesting that CHRM1 expression is necessary for chemoresistance in the A549R cells, but not sufficient. A phospho-kinase array was used to determine the intracellular signaling pathway activated by CHRM1, which showed increased phosphorylation of multiple kinases including CREB, EGFR, STAT3, and ERK1/2. Increased CREB phosphorylation was validated by western blot with carbachol stimulation in A549R and M1D samples suggesting these as possible targeting pathways downstream of CHRM1.

Conclusions

Chemoresistant NSCLC shows increased CHRM1 expression, which when antagonized, resensitizes these cells to DTX-induced cell death. While CHRM1 expression is not sufficient to instill resistance, it is necessary in the A549R cells, and may play a role in enhancing EGFR signaling. This provides a potential promising new therapy for lethal chemoresistant NSCLC which utilizes the repurposed IBS drug dicyclomine.

#104 Tissue is the issue: chemotherapy response score (CRS) is most predictive of response to neoadjuvant chemotherapy in advanced, high grade serous ovarian cancer

A Knickerbocker1*

K Kuchta2

C Donaldson2

E Diaz Moore2

M Lippitt2

G Rodriguez2

W Watkin2

T Jenkins Vogel2

1Washington State University, Spokane, WA

2NorthShore University HealthSystem, Evanston, IL

Purpose of Study

Favorable chemotherapy response score (CRS) has prognostic value and correlates with progression free and overall survival in advanced ovarian cancer. CRS has not been compared to other clinical measures used to gauge response to neoadjuvant chemotherapy (NACT). We sought to examine whether CRS is a better predictor of outcome compared to traditional clinical and radiographic response measures.

Methods Used

Clinical data from 2003–2020 was obtained through retrospective chart review. Radiographic review pre- and post-NACT was performed via RECIST 1.1 with responses characterized as complete/near-complete (CR/NCR), partial with >50% reduction in tumor (PR>50), partial with <50% reduction in tumor (PR<50), stable disease (SD) and progressive disease (PD). Histologic response in surgical specimens was characterized using CRS 1–3. Survival was assessed using the Kaplan-Meier method with log-rank tests, and Cox regression with hazard ratios (HR).

Summary of Results

128 patients who underwent NACT for high grade serous ovarian cancer (HGSOC) were included. Increasing CRS was associated with improved recurrence free (RFS) and overall survival (OS). OS at 5 years for CRS 1, 2 and 3 was 24.7%, 57% and 73.7% (p<0.0001). More favorable radiographic response was predictive of decreased recurrence risk with RFS at 3 years for PR<50 and CR/NCR (16.3% and 54.8%, p=0.0005) but not predictive of OS. Patients with CR/NCR more commonly had CRS 3 vs CRS 1 (47.1 vs 17.7%, p=0.022). Among radiographic response groups, increasing CRS was associated with decreased risk of recurrence and death. For example, in patients with CR/NCR risk of recurrence HR 5.38 (p=0.0243) and risk of death 8.24 (p=0.006) with CRS 1 vs 3. Number of NACT cycles prior to surgery did not differ among patients regardless of CRS. Rate of R0 resection was similar among all three CRS subgroups, and for the entire cohort was 85.2%. Recurrence rates were significantly higher with CRS 1 (89.1%) and 2 (73.9%) compared to CRS 3 (38.9%) (p<0.0001). Median CA 125 prior to surgery was lower with CRS 3 compared to CRS 1 (28 vs 81, p=0.0017). Of the 12 germline BRCA2+ patients in the study, 7 (58.3%) had a pathologic CRS 3.

Conclusions

Our data confirms that favorable CRS is associated with improved overall and recurrence free survival in HGSOC. While radiographic response appears predictive of recurrence, it was not associated with overall survival in our study. Among patients with similar radiographic response, CRS remained predictive of outcome and is associated with other clinical factors traditionally felt to confer favorable prognosis. Pathologic CRS is an important predictive factor in determining response to neoadjuvant chemotherapy in HGSOC and may provide the best means to characterize prognosis.

#105 The impact of an educational training program on COVID-19 and cancer: enhancing community understanding, for disease prevention, better treatment, and optimal outcomes

J Miller*

E McGhee

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

Purpose of Study

The CDC reported cancer patients as at-risk for severe illness from severe acute respiratory syndrome-related coronavirus 2 (COVID-19). Cancer patients were 2 times more likely than non-cancer patients to exhibit cellular sequelae due to COVID-19. Those with hematological malignancies exhibited a case-fatality rate 2 times more than those with solid tumors. This research aims to educate and enhance community understanding of factors that lead to increased mortality rates in COVID-19 cancer patients by using a community training program in SPA 6 of Los Angeles, California.

Methods Used

Data were obtained from post-training surveys of SPA 6 community members which included cancer diagnosis, demographics, and knowledge of COVID-19 with cancer. Impact assessments utilizing Likert-scale response options to analyze and measure the data. Fisher’s exact test was utilized to measure and evaluate participant understanding of the community training program in regards to increased mortality rates of COVID-19 cancer patients. Data analyses were performed using statistical tests SPSS. P-values of <0.05 were considered significant.

Summary of Results

There is a significant need for COVID-19 educational training programs for cancer patients in African American and Latino underserved communities. Impact assessments distributed to 100 participants demonstrated positive change in social behavior and willingness to be vaccinated. Post lecture reviews, quizzes, and feedback surveys were distributed to 100 participants. The information received showed a notable change in participants’ overall knowledge of COVID-19 regarding the increased risk in cancer patients.

Conclusions

The data exhibit educational training programs in underserved communities that were hardest hit by COVID-19 increase the understanding of COVID-19 cancer knowledge. The educational training program indicated an association with a greater increase in willingness to participate in COVID-19 prevention practices and willingness to be vaccinated. This research demonstrated the positive change from educational training programs to be utilized to make a significant impact on health outcomes and cancer mortality rates.

#106 Predictive value of the minute walk test in oncology and pre-rehabilitation: a literature review

RC Ellis1*

A Blough2

M Clark2

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

2University of Kansas Medical Center, Kansas City, KS

Purpose of Study

To review the predictive value of the minute walk physical function test in hematologic malignancy.

Methods Used

A literature review of PubMed using the terms and synonyms of ‘hematologic cancers’ and ‘functional evaluation’ on June 3, 2021 elicited 1,256 manuscripts. After reviewing each abstract for clinical outcomes in relation to minute walk physical function tests in hematologic malignancy, and with the exclusion criteria of confounding intervention or lack of original research, we included 3 published studies.

Summary of Results

Increased frailty before and during cancer treatments has been demonstrated to predict mortality, disability, and hospitalization for cancer patients. The minute walk test is an objective measurement of frailty that measures the distance walked in a set amount of time, with decreased distance walked indicative of increased frailty. While there are multiple published manuscripts documenting the association between the minute walk test and clinical outcomes in cancer patients, few studies validate this test in hematologic cancer patients. Our review found 3 studies using the minute walk test as a functional correlate for rates of mortality. Only 1 of the reviewed manuscripts reported significant increase in mortality with decreased physical function measured by the minute walk test, while the other 2 studies showed no significant change. The study that showed a significant change used a follow up period of 2 months, while the studies with nonsignificant results used a 1 to 2 year follow up.

Conclusions

The frequency of nonsignificant results and the shorter follow up period of the significant results suggest that the minute walk test may be an unreliable predictor of mortality in hematologic cancers. This affects oncology and physiatry alike. The minute walk is one of multiple frailty assessments that oncologists use to determine the intensity and type of treatment a patient should receive. This would also impact physiatry, as there is a growing practice of ‘pre-rehabilitation’, of improving physical function before and during cancer treatment to improve clinical outcomes. If the minute walk test is an inaccurate predictor of mortality, then pre-rehabilitation may focus less on walking mobility. It is possible that the minute walk test may be an accurate predictor of other outcomes in this patient population, such as patient satisfaction or unplanned hospitalizations. Further research, including a meta-analysis, is necessary to determine the predictive value of the minute walking test in hematologic malignancies. As more rehabilitation and oncology practices embrace pre-rehabilitation, the need for validated and standardized methods of objectively assessing physical mobility increases.

Neonatology general II

Concurrent session

3:15 PM

Thursday, January 20, 2022
#107 Preventing growth failure and characterizing microbiome in neonates with gastroschisis

K Strobel1*

K Kramer2

E Fernandez3

C Rottkamp4

C Uy5

L Moyer3

SL Leibel3

M Aslam5

F Poulain4

KL Calkins1

1University of California Los Angeles, Los Angeles, CA

2University of California San Francisco, San Francisco, CA

3University of California San Diego, La Jolla, CA

4University of California Davis, Davis, CA

5University of California Irvine, Irvine, CA

Purpose of Study

55% percent of infants with gastroschisis in the University of California Fetal Consortium (UCFC) have growth failure (GF). The etiology of GF is multifactorial and associated with caloric/nutrient deficiencies. Intestinal dysbiosis may play a role. In this prospective study of infants with gastroschisis, we aimed to investigate 1) if a nutritional pathway would decrease GF, and 2) the relationship between the microbiome and GF.

Methods Used

The UCFC implemented a pathway to decrease GF by standardizing parenteral nutrition dosing, human milk feedings, and GF detection and treatment. Adherence was monitored, and a contemporary cohort (n=45) was compared to a historical cohort (2015–2019, n=125). GF was defined as a decline in weight or length z-score ≥0.8. Shotgun next generation sequencing of the fecal microbiome was performed in a subset of gastroschisis (n=7) and late preterm infants (n=7).

Summary of Results

Good adherence to the pathway was noted. Demographics were similar for the cohorts except birth weight (table 1). Historical controls exhibited a decline in weight and length z-scores at 30 days (-0.10 z-score units/week and -0.11 z-score units/week, respectively, p<0.001 for all). In the prospective cohort, weight and length z-scores remained stable. When the cohorts were compared, the prospective cohort demonstrated a decrease in length GF at 14 days (p=0.002), 30 days (p=0.03), and discharge (p=0.002). However, weight GF was similar at all time points. When compared to preterm infants, gastroschisis infants had a higher abundance of Bacteroides thetaiotaomicon (q=0.003), Bacillus coagulans (q=0.061), Lactobacillus animalis (q=0.13), and Akkermansia municphilla(q=0.13), and less Bifidobacterium bifidum (q=0.19) and longum (q=0.19) even after adjustment for delivery mode and antibiotic days (figure 1).

Abstract #107 Table 1
Abstract #107 Figure 1

A) Heat map showing associations of bacteria with gastroschisis, delivery mode, and antibiotics; B) Dot plots showing relative abundances (log10 transformed) of species

Conclusions

This study suggests that a multi-institutional nutritional pathway is feasible and may decrease linear GF in infants with gastroschisis. Research is needed to determine how the microbiome contributes to GF in this population.

#108 Arachidonic and docosahexaenoic acid and retinopathy of prematurity

T Gillespie1*

E Kim2

H Kim2

I Tsui2

A Chu2

KL Calkins2

1University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

2University of California Los Angeles, Los Angeles, CA

Purpose of Study

Worldwide, 20,000 infants each year are legally blind from retinopathy of prematurity (ROP). We have demonstrated that preterm infants develop docosahexaenoic (DHA) and arachidonic acid (ARA) deficits after birth. These polyunsaturated fatty acids play an important role in regulating inflammation and angiogenesis. The aim of this research is to investigate DHA and ARA status in infants at risk for ROP.

Methods Used

Inclusion criteria for this single site retrospective study: ≤ 30 weeks gestational age (GA) or ≤ birthweight (BW) < 1.5 kg, and ROP screenings until ROP development, complete vascularization, or 42 weeks postmenstrual age. DHA and ARA in the red blood cell membrane were quantified with gas chromatography-mass spectrometry. DHA, ARA, and ARA:DHA were compared throughout the first month of life, stratified by either severity of (Type 1 ROP, low grade ROP, no ROP) or treatment for ROP.

Summary of Results table 1 depicts subject demographics. At week 1, ARA was lower in the Type 1 ROP group vs. the no ROP group (17.9±2.2% vs. 20.5±1.7%, p<0.01). At week 2, significant differences were noted in DHA and ARA (figure 1) but not ARA:DHA. No significant differences in DHA, ARA, and ARA:DHA were observed in weeks 3–4.

Abstract #108 Table 1

Conclusions

This study demonstrates that preterm infants with more severe ROP, either Type 1 or ROP requiring treatment, have lower ARA and DHA levels than infants without ROP. It remains unclear if DHA and ARA supplementation shortly after birth will improve ROP outcomes.

#109 Type of intravenous lipid emulsion and clinical outcomes in infants with gastrointestinal disease

LJ Lee*

E Kim

T Romero

KL Calkins

University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

Purpose of Study

Intravenous lipid emulsions (ILEs) are an important component of parenteral nutrition (PN) for neonates with gastrointestinal disorders (GD). Neonates with GD are at high risk for parenteral nutrition associated cholestasis (PNAC) and associated complications, including liver failure. 100% soybean oil (SO) contains a high concentration of hepatotoxic phytosterols and omega-6 fatty acids, which contribute to PNAC. A composite oil (CO) containing 15% fish oil has high amounts of a-tocopherol and omega-3 fatty acids, and less phytosterols. This study aims to compare PNAC and clinical outcomes in infants with GD who received SO or CO.

Methods Used

Inclusion criteria for this observational study included: 1) born between 2014 and 2019, 2) GD (gastroschisis, omphalocele, intestinal atresia, motility disorder, volvulus, necrotizing enterocolitis, or intestinal perforation), 3) exposure to SO or CO >7 days, and 4) survival to discharge. The primary outcome was cholestasis (conjugated bilirubin (CB) >1 mg/dL). Gas chromatography/mass spectrometry was used to measure fatty acids in the red blood cell membrane in a subset of infants.

Summary of Results

The mean (±SD) gestational age was 37±3 and 36±3 weeks for the SO (n=29) and CO (n=21) groups, respectively (p=0.47). The two groups were well matched for GD diagnosis (p=0.5) and number of GI surgeries (1.8±0.8 for both groups, p=0.90). Nutrition delivery was similar for the SO and CO groups, including days to full enteral feeds (33±32 vs. 30±25 days, p=0.85) and ILE days (25±21 vs. 30±27 days, p=0.77). Weight z-score declined from birth to discharge (-1.0±0.9 vs. -0.8±1.0, p<0.01 for both), but there was no difference between groups (p=0.52). There was no difference in PNAC incidence (48% vs 48%, p=0.99) and maximum CB (2.0±1.8 vs. 1.9±1.6 mg/dL, p=0.79) when the SO group was compared to the CO group (figure 1). Fatty acid profiles were similar between the two groups.

Conclusions

In this study of infants with GD, when compared to infants who received SO, infants who received CO had similar fatty acid trajectories, growth, and clinical outcomes, including PNAC. Further investigation is needed to determine the optimal ILE to decrease PNAC incidence in this population.

#110 Neonatal encephalopathy following selective serotonin reuptake inhibitor exposure in the third trimester of pregnancy: a population-based study

M Cornet1*

H Forquer2

A Scheffler1

A Yeaton-Massey1

T Newman1

M Kuzniewicz2

Y Wu1

1University of California San Francisco, San Francisco, CA

2Kaiser Permanente, Oakland, CA

Purpose of Study

About 4–8% of pregnant women are treated with selective serotonin reuptake inhibitors (SSRI). SSRI exposure in the third trimester may cause poor neonatal adaptation and abnormal movement in neonates, both potential signs of encephalopathy. We assessed whether exposure to SSRI during the third trimester of pregnancy, and dose of SSRI, are associated with neonatal encephalopathy (NE).

Methods Used

In a cohort study comprising all Kaiser Permanente Northern California births ≥ 35 weeks from 2011 to 2019, we defined NE as 5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes. We used logistic regression to adjust for potential confounders.

Summary of Results

Of 305,426 infants, 8,024 (2.6%) were exposed to SSRI in the third trimester, and 510 (0.17%) had NE. After adjusting for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (95% CI 1.9–3.8). The average risk difference between SSRI-exposed and unexposed mothers was 2.7/1000 (95%CI 1.8–4.1/1000). This relationship was dose-dependent. Each 25mg/d increase in the sertraline equivalent dose was associated with a 31% (95% CI: 23–39%) increase in the odds of developing NE.

Abstract #110 Table 1

Neurologic outcomes of neonates exposed and unexposed to SSRI

Conclusions

Exposure to SSRI in the third trimester is associated with increased risk of neonatal encephalopathy. Given that NE is rare, if this association is causal the number needed to cause is high (N~370) and should be balanced with the potential maternal and neonatal benefits of treatment. Future directions include EEG and MRI analyses to correlate SSRI exposure with severity of NE and brain abnormalities.

#111 Breastfeeding rate remains low during COVID-19 pandemic in infants with neonatal opioid withdrawal syndrome (NOWS)

A Fisher*

A McDougal

M McLaren

C Fung

University of Utah Health, Salt Lake City, UT

Purpose of Study

Breastfeeding is a well-established non-pharmacological way to improve severity of NOWS in infants with in-utero drug exposure. Given the barriers imposed on mothers during their inpatient stay in the COVID-19 pandemic, the purpose of this study was to assess breastfeeding rate among infants with NOWS during that time. This study also compared the rate of breastfeeding at discharge and the trends in substance use to our published cohort at the University of Utah prior to the COVID-19 pandemic.1

Methods Used

This was a retrospective chart review of a single academic center at University of Utah. Infants born at ≥34 weeks gestational age, between January 1-December 31, 2020, who received Neonatal Withdrawal Inventory (NWI) scoring were reviewed. Infants who received NWI for non-intrauterine drug exposure were excluded. We calculated the percentages of breastfeeding rates of eligibility, initiation, and continuation at discharge. Eligibility for breastfeeding was determined by the provider permitting such use. We additionally noted infant and maternal demographic data, modes of delivery, and drug exposures per cord toxicology screens.

Summary of Results

Of the 125 infants reviewed, 102 infants met eligibility. Table 1 summarizes the data. Mothers of 77% infants received medication-assisted therapy (MAT) compared to only 61% in our prior study. Similar to our prior study, 21% infants had isolated opioid exposure compared to 79% with polysubstance exposure which included opioid and non-opioid substances. Sixty-five (64%) of the infants were deemed eligible to breastfeed or to receive expressed maternal milk. Fifty-seven (56% of total, 88% of breastfeeding eligible) infants received maternal milk at least once during hospitalization. However, only 37 (36% of total, 57% of breastfeeding eligible) infants were receiving maternal milk at discharge compared to 48% in our prior study. 18 (18%) infants were discharged to adoptive family or state custody and three of them were eligible to receive maternal milk but did not due to social limitations.

Abstract #111 Table 1

Conclusions

Despite a higher rate of maternal MAT with no change in the substance exposure rates, infants with NOWS during COVID-19 suffered from the loss of benefits of breastfeeding/breastmilk feeding. The provision of maternal milk when medically safe in infants with NOWS is vital to optimizing short- and long-term outcomes. However, in this population of vulnerable mother-infant dyads, establishing and sustaining breastfeeding remains a complex challenge particularly during the COVID-19 pandemic when additional psychosocial factors and unanticipated barriers may dominate.

Reference

  1. Morris E, et al. Am J Perinatol 2020.

#112 Identifying barriers to mother’s milk feeding in early preterm black infants in an urban neonatal intensive care unit

MA Chang1*

S Curtis2

NL Davis2

1University of Southern California, Los Angeles, CA

2University of Maryland School of Medicine, Baltimore, MD

Purpose of Study

Greater use of mother’s milk (MM) is associated with improved outcomes for preterm infants admitted to neonatal intensive care units (NICUs). Healthcare disparities exist in MM provision to preterm infants and further research is needed to better identify barriers to providing MM in high-risk populations. Our urban Level IV NICU serves a patient population who are 60% non-Hispanic Black, allowing us to better study this important demographic. The study objective was to evaluate incidence and predictors of provision of MM to early preterm non-Hispanic Black infants in Baltimore, Maryland.

Methods Used

We performed a retrospective medical record review of non-Hispanic Black infants (as identified by their mother) born <34 weeks gestational age (GA), between 9/2014 – 12/2020 in an urban Level IV NICU. We performed bivariate analyses comparing: 1) maternal and neonatal characteristics of infants who received MM at any point during NICU admission vs. those who did not, and 2) neonatal outcomes based on exposure to any MM vs. none.

Summary of Results

We identified 422 early preterm, non-Hispanic Black infants during the study period, of whom 332 (79%) received some MM during their NICU admission. Maternal factors associated with receiving no MM during admission included higher maternal gravidity (p=0.0011), increased parity of term deliveries (p<.0001) and mothers with increased number of living children (p<.0001). Maternal age and medical comorbidities such as pre-eclampsia, chronic hypertension, and diabetes did not have a significant impact on provision of MM. Infants of mothers with bipolar disorder were less likely to receive MM (p=0.0068) while those of mothers with anxiety were more likely to receive MM (p=0.0245). There was no difference in MM provision for those whose mothers had pre-existing depression or who screened positive for postpartum depression. Mothers of infants who did receive MM were significantly more likely to have had documented lactation consultation during admission (74% vs. 20%, p<0.001). Infants who received no MM had higher birth weights (p<0.0001), were born less prematurely (p=0.0002), and were more likely to have been on a ventilator (p=0.0219) during their admission, though there was no difference in rates of intraventricular hemorrhages.

Conclusions

Identifying barriers to MM provision for non-Hispanic Black infants will allow clinicians to focus supportive and educational interventions. Interestingly, although medical comorbidities such as diabetes, hypertension, and depression did not lower likelihood of providing MM, having more living children did decrease incidence of MM provision. Inpatient lactation consultation had one of the strongest associations, so enhancing access to lactation consultation may significantly increase MM provision in early preterm neonates.

#113 Improving enteral feeding practices and human milk consumption in multiple NICUs: a quality improvement project

J Parker1*

L Ulm2

S Kaprolet2

C Wieweck2

M Shea2

S Akey2

J Wickland2

W Ruben2

O Kudin2

J Weber2

M Ellsworth2

K Ellsworth2

P Griffiths2

K Allred2

K Marshall2

N Whittington2

M Elkhwad2

G Martin2

NS Bhopal2

1The University of Arizona College of Medicine Phoenix, Phoenix, AZ

2Division of Neonatology, Phoenix Children’s Hospital, Phoenix, AZ

Purpose of Study

Optimal nutrition is essential to overcome common disease processes in preterm and high-risk term newborns; however, introduction of enteral feedings creates a possible risk of developing necrotizing enterocolitis (NEC). NEC is a potentially devastating inflammatory disease of the gastrointestinal tract, which can result in intestinal perforation and possibly death. Simple interventions such as prioritizing human milk over formula feeds and following a standardized feeding protocol for initiating and advancing feeds are well established practices for improving outcomes and reducing NEC. Phoenix Children’s Hospital Division of Neonatology was established in 2020, providing medical services to a level 4 NICU and to two level 2 NICUs. We introduced a standardized feeding protocol and used quality improvement methodology to measure compliance with our non-surgical infants < 37 weeks, with a goal to increase compliance by > 10% and measured human milk use during hospitalization and at discharge in infants of all gestational ages with a goal to increase human milk consumption by >10%.

Methods Used

We collected data on our feeding practices at all 3 NICUs to measure compliance with the feeding protocol from December 2020 to July 2021. Outcomes were compared in 2 distinct epochs: Epoch 1 from December 2020 to March 2021 and Epoch 2 from April to July 2021. To increase compliance with our feeding protocol, we educated providers, and nurses about the protocol upon its roll-out. Awareness was increased by posting copies at medical provider work stations (February 2021), reviewing interim compliance data with the medical team (April 2021) and placing copies in bedside charts (May 2021).

Summary of Results

Feeding data was tracked on 265 infants. The mean gestational age and birth weight were 36 weeks (± 3 weeks) and 2700g (± 100g). In both epochs, breast milk was used for the initial feed in 58% of all babies admitted to the NICU. The mean time to full feeds was 4 days ± 2 days in preterm infants < 34 weeks. Compliance with protocol improved with time from 72% in epoch 1 to 77% in epoch 2 in babies <37 weeks, and from 66% to 75% in babies < 34 weeks. Babies discharging home exclusively on breast milk increased from 16.9% in epoch 1 to 43.5% in epoch 2. There was 1 case of medical NEC in both epochs and no cases of surgical NEC.

Conclusions

In this quality improvement project, we improved compliance with a feeding protocol and increased exclusive human milk usage through hospital discharge. While there was 1 case of medical NEC in both epochs, there were no cases of surgical NEC in our data set.

#114 Clinical and economic impact of using exclusive human milk in very low birth weight infants

M Tetarbe*

M Chang

L Barton

E Toushin

R Ramanathan

R Cayabyab

University of Southern California, Los Angeles, CA

Purpose of Study

The AAP recommends use of expressed breast milk (EBM) or donor human milk (DHM) in preterm infants fortified with proteins, minerals, and vitamins to ensure optimum nutrient intake. Unfortunately, the implementation of EBM/DHM fortified with human milk-based fortifiers (EHM) can place an economic burden on individual institutions raising concerns on the economic feasibility of such products. The objective of this study is to assess the clinical impact of using EHM in very low birth weight infants (VLBW) infants, and to perform a cost-benefit analysis of its use.

Methods Used

Retrospective study of all VLBW infants admitted to neonatal intensive unit before and after the implementation on the use of EHM. Neonatal demographics and clinical outcomes such as necrotizing enterocolitis (NEC), severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), late-onset sepsis (LOS), and average length-of-stay (ALOS) were collected from January – December 2016 (before implementation) and January – December 2020 (after implementation). The net cost to the institution was estimated using published data for each outcome measure.

Summary of Results

After excluding deceased infants in both time periods, 45 infants were included in the pre-EHM analysis period, (mean birth weight (BW): 1034 g, mean gestational age (GA): 27.9 weeks), and 27 infants were included in the post-EHM analysis period (mean BW: 1070 g, mean GA: 28.8 weeks). Our institution’s product acquisition cost in 2020 was estimated to be $313,784. The implementation of the EHM protocol saw a reduction in the ALOS by 12.9 days and average total parenteral nutrition (TPN) use by 7 days per infant in the post-EHM group equating to a net savings of $1,176,670. While there was a small difference in the number of morbidities between the two time periods, when combining the cost avoidance to include medical NEC, and BPD, the estimated financial impact excluding insurance reimbursement rose to $1,331,130 (table 1).

Abstract #114 Table 1

Conclusions

Our preliminary findings suggest that implementation of exclusive human-milk feeding in VLBW infants is a cost-effective option for NICUs that can result in decrease in NEC, BPD, TPN use and length of stay for these infants at nominal cost.

Neonatology pulmonary II

Concurrent session

3:15 PM

Thursday, January 20, 2022
#115 Perinatal electronic cigarette-exposure induces asthma in rat offspring

A Harb*

C Yu

J Liu

R Sakurai

Y Wang

V Rehan

The Lundquist Institute, Torrance, CA

Purpose of Study

An exponential increase in the use of electronic cigarettes (e-cig), including by pregnant women, exposes an increasing number of fetuses to potentially harmful e-cig chemicals with little knowledge of its repercussions. Perinatal nicotine exposure-induced asthma is associated with downregulated PPARγ signaling and upregulated Wnt signaling in the developing lung. However, the impact of maternal nicotine vaping on the developing lung is unknown. Here, we use an established rat model to determine the effect of perinatal maternal e-cig vaping on offspring pulmonary function and markers of airway contractility.

Methods Used

Pair-fed pregnant rat dams received saline, vehicle (e-cig without nicotine), or e-cig with nicotine daily from embryonic day 6 until postnatal day (PND) 21. Using an established e-cig delivery system and mimicking real-life puffing topography, dams were exposed to four-sec puffs, one puff (puff volume 35 ml) every 30s, 3h/day, and 7 days/week. Average maternal plasma nicotine level (7±4 ng/ml) using this vaping regimen is well within the range observed in moderate cig smokers. Pups delivered spontaneously at term and breastfed ad-lib, but not directly exposed to e-cig aerosols at any time. At PND21, lung resistance and compliance were determined following the methacholine challenge. At sacrifice, the lungs were collected to determine the expression of airway contractility markers, i.e., α-SMA, Calponin, Fibronectin, Collagen I/III, and key Wnt/PPARγ signaling intermediates by qRT-PCR, immunoblotting, and immunostaining.

Summary of Results

Compared to controls, perinatal e-cig exposure resulted in a significant increase in airway resistance and decreased airway compliance following the methacholine challenge. mRNA levels of Collagen III and LEF-1 increased, and those of PPARγ and ADRP decreased in the e-cig group. Immunoblotting showed that in the e-cig group, airway contractility markers (α-SMA, Calponin, Fibronectin, Collagen I and III), Wnt signaling intermediates (β-catenin and LEF-1), and nicotinic acetylcholine receptors α3 and α7 levels increased. In contrast, compared to controls, PPARγ, which interacts directly with Wnt signaling intermediates, levels decreased. Immunostaining of whole lung sections confirmed immunoblotting data.

Conclusions

For the first time, we unequivocally demonstrate offspring asthma following perinatal maternal e-cig vaping and explain likely molecular mechanisms involved. Our data add to the accumulating evidence contradicting the idea that e-cigs are’safe.’

Grant Support

NIH (HL151769, HD127237, HD071731, and HL152915)) and TRDRP (23RT-0018, 27IP-0050, and T29IR0737).

#116 Combined pre- and postnatal growth restriction increase expression of a novel dominant negative PPARγ splice variant in the rat lung

A Cohen*

R Gage

T Benally

H Wang

J Zhao

L Joss-Moore

University of Utah Health, Salt Lake City, UT

Purpose of Study

Preterm infants frequently suffer growth restriction, increasing the risk and severity of neonatal lung disease, characterized by impaired alveolar development and worse outcomes in male infants. We showed that growth restriction in the prenatal (IUGR) or postnatal (PGR) period reduces rat lung PPARγ gene expression, which results in impaired alveolar development. PPARγ variants, including the novel delta 5 splice variant (PPARγΔ5), can impact the downstream effects of PPARγ activation. As PPARγΔ5 is a dominant negative variant, the effect of increasing PPARγΔ5 is a reduction in PPARγ signaling. Whether PPARγΔ5 is expressed in the rat lung, and the effect by growth restriction on expression is unknown. We hypothesize that PPARγΔ5 will be expressed in rat lung, and that the combination of IUGR and PGR will increase expression of PPARγΔ5.

Methods Used

IUGR and PGR were generated in Sprague Dawley rat pups by bilateral uterine artery ligation and variation in litter size respectively. Lungs were collected at postnatal day 12 from Control, IUGR only, PGR only, and PGR+IUGR rat pups. Male and female rats were treated as sperate groups. PCR, gel electrophoresis, and sequencing were used to confirm the presence of PPARγΔ5 in the rat lung. Full length and PPARγΔ5 mRNA and protein were assessed using real-time RT PCR and western blotting. Differences were assessed by one-way ANOVA and fishers post hoc test.

Summary of Results

Results are IUGR as% of control±SD, *P<.05. Sequence confirmed PPARγΔ5 mRNA is expressed in rat lung at postnatal day 12. PGR model resulted in significantly lower weights on D12 (66.9±3% for PGR only, 64.8±3.2% in IUGR+PGR). In male rat lung, PPARγΔ5 mRNA was increased (325±79%*) by IUGR+PGR. Similarly, in the male rat lung, PPARγΔ5 protein was increased by IUGR+PGR (163±14%*). In female rat lung, neither PPARγ transcript was affected. However, lung protein levels of PPARγΔ5 were increased in female IUGR+PGR (146±24%*).

Conclusions

We conclude that the PPARγΔ5 is expressed in rat lung, and that IUGR+PGR increase expression. We speculate that increased PPARγΔ5 expression in male IUGR+PGR rat lungs may further impair PPARγΔ5 signaling, leading to impaired alveolar development.

#117 Evidence for the intergenerational pulmonary expression of genes differentially methylated in sperm cells of perinatally nicotine exposed rats

L Afrose*

Y Wang

J Liu

C Yu

T Rho

T Dao

D Hatai

V Rehan

The Lundquist Institute, Torrance, CA

Purpose of Study

Nicotine exposure to the developing fetus results in asthma that can be transmitted across generations. However, the underlying mechanism remains unknown. We recently demonstrated differential DNA methylation in the proximity of nicotine-response genes in sperms of the perinatally nicotine exposed F1 animals. Gene ontology and pathway enrichment analysis suggested a possible link between the spermatozoal differential DNA methylation and the offspring asthma phenotype. We hypothesize that nicotine-induced spermatozoal epigenetic changes drive the intergenerational transmission of nicotine-induced asthma. The expression of genes in F2 lungs differentially methylated in the spermatozoa of nicotine exposed F1 males was determined to test this hypothesis.

Methods Used

Sprague Dawley rat dams (F0) received nicotine (1 mg/kg, sc) or saline from embryonic day 6 (E6) until postnatal day 21 (PND21). Pups (F1) were weaned at PND21 and used as breeders to generate F2 without any subsequent exposure to nicotine in the F1 progeny. F2 pups were weaned at PND21. At PND60, F2 males (n=20; 10 control, 10 nicotine) were sacrificed, and their lungs were collected and flash frozen for performing qRT-PCR for the top 11 differentially methylated genes (AABR07051515.1, Dio1, Gabra4, Htr6, Map4k2, Men1, Mnu, Orai2, Rars, Sec1415, and Slc7a11) in sperm cells of the nicotine exposed F1 males.

Summary of Results

In line with data from F1 lungs, the expression of the top 2 differentially hypermethylated genes AABR07051515.1, a lincRNA, known to modulate lung function, and Dio1 (iodothyronine deiodinase 1) in the nicotine exposed F1 sperm cells was upregulated or downregulated, respectively (p ≤ 0.05), in F2 lungs. In addition, similar to the F1 progeny, Mnu and Sec1415 genes’ expression was downregulated (p ≤ 0.05) in F2 lungs of the nicotine-exposed group. In contrast, the expression of the other 7 differentially methylated genes in F1 spermatozoa did not change significantly.

Conclusions

Our data further support the concept that perinatal nicotine exposure-induced spermatozoal epigenetic reprogramming, specifically DNA methylation alterations in nicotine response- and lung development-related genes, likely drive the intergenerational transmission of perinatal nicotine-induced asthma.

Grant Support

NIH (HL151769, HD127237, HD071731, and HL152915) and TRDRP (23RT-0018; 27IP-0050; and T29IR0737).

#118 The effect of serotonin depletion on hypoxia induced neonatal murine bronchopulmonary dysplasia and pulmonary hypertension

D Roberts*

JN Posey

J Archambault

E Nozik

C Delaney

University of Colorado – Anschutz Medical Campus, Aurora, CO

Purpose of Study

Pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) leads to worse outcomes in former preterm neonates. Serotonin (5-hydroxytryptamine, 5-HT) is a potent pulmonary vasoconstrictor, smooth muscle mitogen, and is increased in the lungs of infants who died with severe BDP. Tryptophan hydroxylase 1 (TPH1), the rate limiting enzyme in 5-HT synthesis, is increased in adult patients and animals with experimental PH. Serotonin signaling blockade decreases pulmonary vascular resistance and prevents pulmonary vascular remodeling in preclinical models. We hypothesized that TPH1 knock-out (KO) neonatal mice would be protected from hypoxia induced BPD associated with PH.

Methods Used

Neonatal wild-type (WT) and TPH1 KO offspring were placed in hypoxia or remained in normoxia at Denver altitude for 2 weeks. To assess alveolar development, inflation fixed lungs were analyzed for surface area (SA) and mean linear intercept (MLI). To identify total number of small vessels (<30 μm), lung sections were immunostained with Factor VIII. PH was assessed by Fulton’s index and right ventricular systolic pressures (RVSP). Platelet poor plasma (PPP), platelet, and lung homogenate 5-HT levels were measured by ELISA. Data were analyzed by Prism with unpaired t-test or 2-way ANOVA with Bonferroni post-hoc analysis. Significance level p<0.05.

Summary of Results

At baseline, WT mice have more platelet poor plasma, platelet, and lung 5-HT than KO mice (53±6 — 9±1, p<0.0001; 275±11 — 56±12, p<0.0001; 18±2 — 10±1, p<0.004; respectively, ng/mL). TPH1 KO mice were not protected from hypoxia-induced alveolar simplification, shown by no difference compared to WT mice MLI and SA, nor were they protected against hypoxia-induced pulmonary vascular simplification, shown by no difference compared to WT mice vessel density. TPH1 KO mice were attenuated to hypoxia-induced pulmonary vasoconstriction, shown by reduction in RVSP (32±0.66 — 29±0.55, p<0.006, mmHg). There was less PPP and platelet 5-HT in hypoxia-exposed WT mice compared to WT mice at baseline (20±2 — 53±6, p<0.0001 and 117±27 — 275±11, p<0.0001, respectively, ng/mL). There was less lung 5-HT in hypoxia-exposed KO mice than in KO mice at baseline (2±1 — 10±1, p<0.001, ng/mL).

Conclusions

Neonatal TPH1 KO mice are not protected against hypoxia-induced lung injury. Surprisingly, this study contradicts the current understanding of the role of 5-HT in adults with PH and in adult models of hypoxia-induced PH. We found decreased plasma and platelet 5-HT following hypoxia exposure. We speculate that decreased 5-HT observed in hypoxia may contribute to neonatal hypoxia-induced alveolar simplification and impaired vascular development. Further studies are needed to elucidate the role of 5-HT in the developing lung.

#119 The effect of platelet alpha granule deficiency on hypoxia induced neonatal pulmonary hypertension

D Roberts*

JN Posey

E Nozik

C Delaney

University of Colorado – Anschutz Medical Campus, Aurora, CO

Purpose of Study

Pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) leads to worse outcomes in former preterm neonates. Elevated platelets at birth are an independent predictor of BPD, increased platelet derived protein after birth is associated with higher rates of neonatal pulmonary vascular disease, and perinatal platelet transfusions are associated with higher rates of mortality and BPD. Circulating platelets from neonatal mice with experimental PH are increased and express a higher percentage of active αIIbβ3, a marker of platelet activation. NBEAL 2 knock-out (KO) mice lack platelet alpha granules, have low platelet counts, and have decreased platelet function in vitro and in vivo. We hypothesized that NBEAL 2 KO neonatal mice would be protected from hypoxia-induced PH.

Methods Used

Neonatal wild-type (WT) and NBEAL 2 KO offspring were placed in hypobaric hypoxia (18,000 feet) or remained in normoxia at Denver altitude for 2 weeks. PH was assessed by Fulton’s index as a marker of right ventricular hypertrophy (RVH) and right ventricular systolic pressures (RVSP). Data were analyzed by Prism with unpaired t-test or 2-way ANOVA with Bonferroni post-hoc analysis. Significance level p<0.05.

Summary of Results

Right ventricular systolic pressure is higher in NBEAL2 KO mice than in WT mice at baseline (24.2±0.5 — 21.5±0.3, p<0.0001, mmHg). There is no difference between baseline right ventricular hypertrophy between NBEAL2 KO mice and WT mice (0.27±0.01 —0.31± 0.01, ns). NBEAL2 KO mice display comparable hypoxia-induced increase in RVSP compared to WT mice (29±1 — 30±1, ns, mmHg). NBEAL2 KO mice display comparable hypoxia-induced increase in RVH compared to WT mice (0.3± 0.03 — 0.4±0.03, ns).

Conclusions

Platelet alpha granule deficiency is a risk factor for neonatal pulmonary vasoconstriction at baseline. Further studies are needed to elucidate the role of platelets in neonatal PH associated with BPD.

#120 Metabolites important in the differentiation of human pluripotent stem cells to lung progenitor cells

SL Leibel1*

I Tseu2

A Zhou3

A Hodges4

J Yin4

C Bilodeau2

O Goltsis2

M Post2

1University of California San Diego, La Jolla, CA

2SickKids Research Institute, Toronto, ON, Canada

3Johns Hopkins University, Baltimore, MD

4Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA

Purpose of Study

Metabolism is vital to cellular function and tissue homeostasis during human lung development. In utero, embryonic stem cells undergo endodermal differentiation towards a lung progenitor cell (LPC) fate that can be modeled in vitro using pluripotent stem cells (hPSCs). We previously showed differences in lung cell composition and gene expression between wild type and surfactant protein B (SP-B) deficient lung organoids. These differences may be impacted by changes in metabolites during early lung development. We hypothesize that SP-B deficient cells will express a different metabolomic profile compared to wt cells during the differentiation to lung progenitor cells.

Methods Used

To examine metabolites that differ during endodermal differentiation, we used an untargeted metabolomics approach to evaluate the changes in metabolites at the stem cell (hPSC), definitive endoderm (DE), anterior foregut endoderm (AFE) and lung progenitor (LPC) stage between wt and SP-B deficient cell lines. At each differentiation step, the cells were sorted for surface markers specific to their differentiation stage in quadruplicate. The homogeneous cell lysates were analyzed using a Biocrates p180 metabolite kit including hexoses, amino acids, phosphatidylcholines, lysophosphatidylcholines, sphingolipids, acylcarnitines, and biogenic amines. The metabolomic multivariate data analysis was performed using XLSTAT.2016 software (Addinsoft) and MetaboAnalyst.

Summary of Results

We found that the largest metabolic changes during endodermal differentiation occurred from hPSC to DE with a change from glycolytic respiration to oxidative phosphorylation. The metabolites most enriched during the differentiation from hPSC to LPC, independent of cell line, were sphingomyelin and lecithin. In the wt cell lines, metabolites for oxidation of fatty acids and tryptophan metabolism were up-regulated, while metabolites for ammonia recycling and aspartate metabolism were down-regulated. In the SP-B deficient cells, metabolites in fatty acid oxidation and carnitine synthesis were up-regulated and metabolites for amino acid metabolism, the urea cycle, and multiple energy-based pathways were down-regulated.

Conclusions

Differentiation to lung progenitor cells from pluripotent stem cells resulted in increased fatty acid metabolism and decreased urea cycle and aspartate metabolism in both wt and SP-B deficient cell lines. Therefore, metabolite composition in early lung development is not influenced by the loss of SP-B expression.

#121 Effects of vitamin A and vitamin D treatment on lung growth and function in offspring from maternal vitamin D deficient rats

N Galambos1*

E Bye1

T Gonzalez1

G Seedorf1

B Smith1

JC Fleet2

SH Abman1

E Mandell1

1University of Colorado – Anschutz Medical Campus, Aurora, CO

2The University of Texas at Austin College of Natural Sciences, Austin, TX

Purpose of Study

Maternal vitamin D deficiency (M-VDD) is associated with perinatal pulmonary morbidities. We have demonstrated that offspring of rodent maternal VDD dams have sustained abnormalities of distal lung structure, increased airway hyperreactivity and abnormal lung mechanics. In pulmonary endothelial cells, vitamin A (VA) and vitamin D (VD) co-dimerize on retinoid x receptor. VA therapy has been shown to improve lung development in pre-clinical and clinical studies, but whether combined postnatal (PN) treatment with VA and VD further enhances lung development in offspring of M-VDD dams is unknown. Therefore, we seek to determine if PN VA and VD supplementation improves lung development and function in offspring of M-VDD dams.

Methods Used

Newborn rats from control (CTL) and M-VDD dams received daily treatment of retinoic acid (VA) alone, VA and 1,25-OHD (VD) (VA-VD) or saline (SAL) for 14 days. On DOL 14 lung structure was assessed by mean linear intercept (MLI), radial alveolar count (RAC) and pulmonary vessel density (PVD). Lung mechanics were measured using flexiVent.

Summary of Results

Lungs from VDD-SAL rats had increased MLI (p<0.001) and decreased pulmonary vessel density (p<0.05) as compared to CTL-SAL. VDD rats that received VA had increased RAC compared to VDD-SAL (p<0.05). VDD-SAL rats had increased resistance (p<0.01) and decreased compliance (p<0.01) as compared to CTL-SAL. VDD-VA rats had decreased elastance as compared to VDD-SAL pups (p<0.05).

Conclusions

M-VDD decreases distal lung and vascular development and impairs lung function in infant rats. PN VA therapy improved RAC and decreased elastance in VDD pups. These findings suggest that abnormal lung development after PN VA therapy may improve alveolarization and lung mechanics of M-VDD pups. We speculate that M-VDD leads to persistent abnormalities in infant lung growth that may be responsive to PN VA.

#122 Maternal vitamin D deficiency alters pulmonary endothelial cell growth and mRNA expression in newborn rats

T Gonzalez1*

E Bye1

N Galambos1

G Seedorf1

JC Fleet2

SH Abman1

E Mandell1

1University of Colorado – Anschutz Medical Campus, Aurora, CO

2The University of Texas at Austin College of Natural Sciences, Austin, TX

Purpose of Study

Vitamin D deficiency (VDD) during pregnancy is associated with chronic lung disease in preterm infants, and the underlying mechanisms are not understood. We have shown that vitamin D (VD) preserves lung structure and prevents pulmonary hypertension (PH) in an experimental model of bronchopulmonary dysplasia, and that VD treatment increases pulmonary artery endothelial cell growth and function. However, the direct effects of maternal VDD on pulmonary endothelial cell (PEC) growth and function are unknown. Thus, we seek to determine whether PEC from newborn rats exhibit altered growth and mRNA expression at birth after exposure to maternal VDD and whether these changes persist during infancy.

Methods Used

Female rats were fed VDD chow and shielded from UV-B light to achieve 25-OHD levels less than 10 ng/ml before mating. PEC were isolated from offspring of maternal VDD (VDD) or control (CTL) dams at postnatal days 0 and 14. PECs were used for proliferation assays and response to exogenous VEGF and 1,25-OHD. PEC lysates were also collected for RT-qPCR analysis.

Summary of Results

PEC isolated from VDD pups at both D0 and D14 demonstrate decreased growth compared to CTL D0 and D14 (p<0.01). VEGF or 1,25-OHD treatment increased CTL PEC growth from both D0 and D14 when compared to untreated CTL D0 and D14 PEC (p<0.01). In contrast, neither VEGF nor 1,25-OH treatment increased D0 VDD PEC growth. D14 VDD PEC showed an increased growth with VEGF treatment compared to untreated D14 VDD PEC (p<0.01). RNA isolated from D0 VDD PEC demonstrate decreased expression of KDR and eNOS and increased VEGF expression compared to D0 CTL PEC (p<0.01), no expression changes seen at D14.

Conclusions

We found that D0 PEC from newborn offspring of maternal VDD dams demonstrate decreased baseline PEC growth and no responsiveness to angiogenic stimuli. At D14 VDD PEC grew poorly at baseline, and were responsive to VEGF but not 1,25-OHD treatment. We speculate that maternal VDD disrupts normal PEC function, which persists into postnatal life and may contribute to high risk for late cardiopulmonary disease.

#123 The effect of perinatal nicotine exposure on the lung circadian molecular clock

D Hatai*

Y Wang

R Sakurai

J Liu

L Afrose

T Dao

T Rho

C Yu

V Rehan

The Lundquist Institute, Torrance, CA

Purpose of Study

Dysregulated peripheral circadian rhythm is associated with enhanced inflammatory response and cellular senescence. Recent studies have demonstrated an association of exposure to cigarette smoke and dysregulated peripheral molecular clock in Chronic Obstructive Pulmonary Disease (COPD) and asthma patients. This has also been confirmed in rodent models. Although developmental smoke/nicotine exposure predisposes to asthma and COPD, its impact on circadian clock genes is unknown. Here, we test the hypothesis that developmental nicotine exposure alters the molecular clock, which lasts well into adult life.

Methods Used

Pair-fed pregnant Sprague-Dawley rat dams received once-daily 1mg/kg nicotine or saline diluent from embryonic day 6 (E6) to postnatal day 21 (PND21). Lungs from pups were collected on E21, PND21, or PND60 and flash-frozen for later mRNA and protein analysis. The expression of core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, Per2, Rev-erba, Rev-erbb, Rora, and Sirt1) was determined by qRT-PCR on mRNA isolated from lungs. Protein levels of key clock genes Bmal1, Clock, and Rev-erba were determined using western analysis on proteins extracted from PND 21 lungs.

Summary of Results

Overall, the mRNA expression of Bmal1, Clock, Cry1, Cry2, Per1, Per2 , Rev-erba, Rev-erbb, Rora, and Sirt1 was significantly decreased (p<0.05) in the nicotine treated group vs. the control group at E21 and PND21. Perinatal nicotine exposure-induced downregulation of key clock genes Bmal1 and Rev-erba was also confirmed by their down-regulated protein levels by western analysis at PND 21. Interestingly, the expression of several down-regulated clock genes at E21 and PND21 in the nicotine-treated group was either not different or upregulated versus the control group at PND60, suggesting a dynamic response of perinatal nicotine exposure on the peripheral molecular clock.

Conclusions

Perinatal nicotine exposure leads to peripheral clock dysregulation in the lung that lasts at least through adolescence. These results suggest a new mechanism that underlies the effects of perinatal nicotine-induced lung injury. Further studies are needed to determine the impact of perinatal nicotine exposure-induced dysregulated peripheral clock on lung health, gender specificity, and how long these effects last.

Grant Support

NIH (HL151769, HD127237, HD071731, and HL152915) and TRDRP (23RT-0018; 27IP-0050; and T29IR0737).

#124 Association of systemic serotonin with persistent pulmonary hypertension of the newborn

J Archambault1*

C Palmer1

E Nozik1

CC Galambos2

C Delaney1

1University of Colorado, Aurora, CO

2University of Colorado Denver – Anschutz Medical, Aurora, CO

Purpose of Study

Pulmonary hypertension (PH) is a life-threatening condition that affects infants, children, and adults. However, treatment strategies are limited, and morbidity and mortality remain significant. We have previously demonstrated in robust animal models that serotonin (5-HT) contributes to the pathogenesis of experimental neonatal PH and know that infants who died due to severe lung disease have a 34-fold increase in lung 5-HT. We designed an exploratory pilot study to test the hypothesis that systemic 5-HT is increased in infants with persistent pulmonary hypertension of the newborn (PPHN).

Methods Used

Near term and term infants (≥36 weeks) were recruited from the NICUs at Children’s Hospital Colorado and University of Colorado Hospital beginning in March 2021. Infants with culture proven sepsis, metabolic/genetic abnormality, major cardiac defect, renal failure, or antenatal exposure to SSRIs were excluded. PH was defined on echocardiogram by an estimated systolic pulmonary artery pressure ≥40 mm Hg, end-systolic eccentricity index ≥1.16, or presence of a right-to-left shunt. 5-HT is an unstable neurotransmitter that degrades quickly; thus, we measured its more stable metabolite 5-hydroxyindolacetic acid (5-HIAA). Urine samples were collected on DOL 1 and DOL 3, and 5-HIAA was analyzed via mass spectrometry. Monthly follow up samples were collected if PH persisted. Demographics, clinical characteristics, and interventions were obtained through chart review and summarized for the patient cohort. 5-HIAA levels were summarized using medians and ranges.

Summary of Results

To date, 6 infants with PPHN and 7 age-matched controls have been enrolled. 54% were male and 46% female. The mean gestational age was 38.2 weeks. All infants with PPHN were classified as having severe PH on initial echo. 83% were born with congenital diaphragmatic hernia (CDH) and 100% had a patent ductus arteriosus (PDA). 83% required vasopressors, with 60% initiated in the delivery room. 100% required steroids for blood pressure and/or respiratory support. 83% required pulmonary vasodilators with inhaled nitric oxide and sildenafil being the most common. 50% of infants with PPHN were followed for refractory PH for a mean of 2.67 months. At DOL 1, the median 5-HIAA level was 14.89 (min, max: 14.17, 19.1) in the PPHN group and 14.17 (11.56, 16.63) in the control group. At DOL 3, the median was 18 (8.89, 40.5) in the PPHN group and 15 (10.95, 17.14) in the control group.

Conclusions

This study investigated the association of PPHN with systemic alterations in 5-HIAA. Our current results offer a preliminary description; however, enrollment is ongoing. With additional data we will test our hypothesis that 5-HIAA is significantly associated with PH severity. Ultimately, we aim to establish it as a noninvasive biomarker to follow treatment response and predict the later development of PH in high-risk infants.

Neuroscience I

Concurrent session

3:15 PM

Thursday, January 20, 2022
#125 Combined superotemporal retinal amyloid and retinal venular tortuosity index predicts verbal memory performance in cognitively impaired subjects

T Torbati1,2*

J Sheyn2

DS Sherman2

MM Khansari3

KL Black2

PD Lyden2,3

Y Koronyo2

M Koronyo-Hamaoui2

OM Dumitrascu4

1Western University of Health Sciences, Pomona, CA

2Cedars-Sinai Medical Center, Los Angeles, CA

3University of Southern California Keck School of Medicine, Los Angeles, CA

4Mayo Clinic Arizona, Scottsdale, AZ

Purpose of Study

Alzheimer’s disease (AD) is commonly characterized by pathognomonic amyloid-beta (Aβ) burden in the brain, and recent reports demonstrate the vital role of cerebral vascular pathology in AD development. Given that the retina is a CNS organ amenable to noninvasive imaging, our team previously pioneered retinal curcumin-fluorescence imaging (RFI) and identified a significant correlation between retinal amyloid burden in the proximal mid-periphery (PMP) of the superotemporal retina with cognitive performance and hippocampal volume. The rising hypothesis of vascular neuropathology in AD, coupled with RFI clinical feasibility targeting both vasculature and Aβ, warrants the implementation of both neurovascular and retinal Aβ for early AD detection. Considering the crucial yet unmet need for such multimodal detection models, we used RFI to examine retinal vascular parameters in relation to retinal Aβ in patients with varying neurocognitive status.

Methods Used

29 subjects underwent neuropsychometric cognitive evaluations and quantitative RFI to measure retinal amyloid burden. We also quantified vessel tortuosity index (VTI), inflection index and branching angle from segmented retinal blood vessels. Using linear regression models, we conducted correlation analyses between retinal vascular and amyloid measures in relation to various cognitive domain Z-scores.

Summary of Results

Total and PMP retinal amyloid count were markedly increased in patients with cognitive impairment (CI) as compared to those with normal cognition (NC, p = 0.0012). Venous VTI was significantly different across levels of Clinical Dementia Rating (CDR) cognitive scores (p = 0.026). Patients with CI displayed considerably higher combined PMP amyloid-venous VTI index in comparison to NC subjects (p = 0.0068). Increased combined PMP amyloid-venous VTI index significantly correlated with decreased WMS-IV Z-scores (r = -0.537, p = 0.001) as well as with reduced SF-MCS-36 Z-scores (r = -0.338, p = 0.039).

Conclusions

This study reveals that combined PMP amyloid count-venous VTI index may predict verbal memory loss and cognitive-related quality of life performance. Future larger investigations are needed to further refine the practical utility of RFI in a clinical setting.

#126 Thyroid hormone treatment reveals gene expression plasticity in cone photoreceptors of adult zebrafish

P Thomas1,2*

A Farre1

D Stenkamp1

1University of Idaho, Moscow, ID

2University of Washington School of Medicine, Seattle, WA

Purpose of Study

In humans, as well as other vertebrates, color vision requires the differential expression of specific cone opsins in photoreceptor cone cells. One model for the regulation of the human long and medium wavelength sensitive (LWS/MWS) opsin tandem array suggests an upstream regulatory region interacts with replicated opsin genes at random, resulting in mutually exclusive expression of a specific opsin. A similar orthologous long wavelength sensitive (lws1/lws2) array in zebrafish provides a good model for study of this regulation. However, our prior investigations into this array suggest that thyroid hormone (TH) and retinoic acid serve as trans regulators in larvae/juveniles (Mitchell et al., 2015, PLOS Genetics; Mackin et al., 2019, PNAS). This study investigates whether cone opsin expression remains plastic to TH treatment in adult zebrafish, where cone distribution is considered stable.

Methods Used

Adult zebrafish (6–18 months old) were treated with NaOH (0.01%, control) or TH (386 nM) for 1 or 5 days. qRT-PCR was performed on homogenized eyes. Whole retinas were treated by hybridization chain reaction in-situ and then analyzed by confocal imaging for mRNA expression.

Summary of Results

In adult zebrafish, exogenous TH drastically increased lws1 expression in both 1 and 5 day-treated groups (p<1e-7, 0.01, respectively) while decreasing lws2 expression (p<0.001, 0.001). Other phototransduction-related transcripts (gngt2b, rh2–1) also demonstrated expression changes following TH treatment. Exogenous TH induced a drastic shift from lws2 to lws1 in adult zebrafish, consistent with previous studies of larvae and juveniles.

Conclusions

This shift from lws2 expression to lws1 expression occurs as rapidly as 1 day when exposed to TH, which shows that cones remain highly plastic even into adulthood. Plasticity in spectral sensitivity (to be sensitive to higher wavelengths) in response to TH suggest a role in visual system function well into adulthood. These results oppose earlier models suggesting that regulation between tandemly replicated opsin genes is stochastic and fixed.

#127 Effects of methamphetamine on fenfluramine-induced head-twitch response and c-fos expression in mice prefrontal cortex

Y Sun

S Chebolu

S Skegrud

S Kamali*

N Darmani

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

Purpose of Study

The head-twitch response (HTR) is evoked following stimulation of postsynaptic serotonin 2A (5-HT2A) receptors in the prefrontal cortex (PFC). D-Fenfluramine (FF) is a selective 5-HT releaser, it produces the HTR via release of serotonin from nerve terminals through the 5-HT uptake carrier working in reverse. Methamphetamine (MA) is a non-selective releaser of monoamines 5-HT, norepinephrine (NE) and dopamine (DA). We investigate whether pretreatment with either MA (1–5 mg/kg, i.p.) or the 5-HT2A receptor selective antagonist EMD 281014 (0.001, 0.005, 0.01, 0.05 mg/kg, i.p.) can alter: 1) the mean frequency of FF-induced HTR at different ages (20-, 30- and 60-day old), and 2) the expression of c-fos evoked by FF in different regions of the PFC. We also explored whether blockade of serotonergic 5-HT1A- or adrenergic α2-receptors can alter the effect of MA on FF-induced HTR across the above ages.

Methods Used

The HTR was observed for 30 min following the injection of FF in each mouse. We use immunohistochemistry study to evaluate the changes of c-fos expression in the PFC.

Summary of Results

Pretreatment with MA (1–5 mg/kg, i.p.) dose-dependently suppressed the FF-induced HTR across different ages. MA at 1 mg/kg in 20- and 30-day old mice, and at 5 mg/kg in 60-day old mice significantly suppressed the FF-induced HTR. Pretreatment with EMD 281014 (0.001, 0.005, 0.01, 0.05 mg/kg, i.p.) also blocked the FF-induced HTR in an age- and dose-dependent manner. The selective 5-HT1A receptor antagonist WAY 100635 (0.25 mg/kg, i.p.) and the adrenergic α2-receptor antagonist RS 79948 (0.1 mg/kg,i.p.) significantly reversed the inhibitory effect of MA on the mean frequency of HTR in 20-day old mice, but not in 30- and 60- day old mice. Moreover, FF significantly increased c-fos expressions in several PFC regions in 30-day old mice. Despite the inhibitory effect of MA or EMD 281014 on FF-induced HTR, pretreatment with either MA (1 mg/kg, i.p.) or EMD 281014 (0.05 mg/kg, i.p.) significantly increased c-fos expression in different regions of the PFC in 30-day old mice.

Conclusions

The inhibitory effect of MA on the FF-evoked HTR appears to be mainly due to functional interactions between the stimulatory 5-HT2A - and the inhibitory 5-HT1A- and/or adrenergic α2-receptors. The MA-induced increase in c-fos expression in different PFC regions is probably due MA-evoked increases in synaptic concentrations of 5-HT, NE and/or DA. EMD 281014 failed to prevent the increase in c-fos expression induced by FF, which may be due to the increased 5-HT synaptic concentration that activates other serotonergic receptors, such as, 5-HT1A.

#128 Progression of geographic atrophy in age-related macular degeneration patients treated with levodopa

G Muigai1*

RW Snyder2

C Christensen2,3

S Purewal4

1Vanderbilt University, Nashville, TN

2University of Arizona, Tucson, AZ

3Des Moines University College of Osteopathic Medicine, Des Moines, IA

4Banner University Medical Center Tucson, Tucson, AZ

Purpose of Study

Geographic atrophy (GA) is a severe and poorly understood progression of dry age-related macular degeneration (AMD). Patients with GA are also more likely to develop choroidal neovascularization. Carbidopa-levodopa treatment has demonstrated successful reduction in neovascular AMD. In this study, we investigate the effects of carbidopa-levodopa treatment on progression of GA.

Methods Used

A retrospective analysis of patients with already existing GA who participated in our proof-of-concept study was performed. Fundus autofluorescence (FAF) and optical coherence tomography (OCT) were utilized to confirm the presence of geographic atrophy. This study followed the 2018 retina consensus meeting requirements to measure geographic atrophy markers in patients. The primary outcomes measures were complete retinal pigment epithelium and outer retinal atrophy (cRORA), hypertransmission through Bruch’s membrane, and mm/year change from initiation of study drug.

Summary of Results

We included 5 patients with already existing geographic atrophy in 6 eyes. This cohort consented to carbidopa-levodopa treatment and was predominantly male (3 patients) with a median (IQR) age of 82 (5). The mean GA change in cRORA 1 year before and after treatment initiation was -0.000433 mm/year and 0.0061 mm/year. The mean GA change in hypertransmission 1 year before and after treatment initiation was 0.0085 mm/year and 0.135 mm/year.

Conclusions

Geographic atrophy progressed in all eyes except one. According to a 2021 Ophthalmic Research meta analysis, the average GA growth rate seen across 23 studies was 0.33 mm/year. Thus, our results indicate that the carbidopa-levodopa treatment provides benefit in slowing progression rates of GA. Further studies are indicated into the pathogenesis of GA and the role that carbidopa-levodopa might play in its treatment.

#129 How do medical and physical therapy students learn about concussions?

W Cheung1,2*

EA Tangog1,2

L McKay1,2

T Alsky3

D Baron1

1Western University of Health Sciences, Pomona, CA

2Western University of Health Sciences College of Osteopathic Medicine of the Pacific, Pomona, CA

3The University of Arizona College of Medicine Tucson, Tucson, AZ

Purpose of Study

This study assesses medical and physical therapy students’ knowledge level in concussion symptoms, diagnosis, and treatment. Parameters we evaluated included how education level, sports background, and concussion history influenced students’ concussion knowledge. The study assessed how these students learn about concussions and whether gaps in knowledge exist. The ultimate goal is to use the survey results to help educators better prepare medical and physical therapy students for patient care.

Methods Used

The first phase of our study involved sending a 14-question electronic survey to osteopathic medical schools across the United States, which assessed demographics, concussion knowledge level, source of concussion education, and interest in curriculum-based learning. The second phase consists of sending a similar electronic survey that expanded to allopathic and physical therapy schools. This survey consisted of 16 questions, with 2 additional demographic questions inquiring about gender and type of pursued degree.

Summary of Results

Preliminary collection of over 800 responses and analysis of the data show that 60.2% of MD, DO, and physical therapy students played sports in either high school, college, or professionally. In addition, 42.7% of participants reported sustaining at least one concussion throughout their lives. 26.9% of our participants reported learning about concussions through non-academic means, while 70% reported learning via academic means such as through lectures, literature reviews, or clinical rotations. Our results showed that 80% of our participants agreed they would like more formal education on concussions.

Conclusions

While data collection is still ongoing, the preliminary results of our study indicate that having a sports background or personal experience with concussion may influence their knowledge in concussion diagnosis and treatment. A large percentage of our participants learned about concussions through non-academic methods. While data is forthcoming, this may indicate that an alternative means to learning about concussions is through a sports background and/or concussion history. Participants agree that in order to solidify or supplement concussion knowledge, more education is needed to best prepare rising health care professionals in clinical settings.

#130 New thrombus formation immediately after andexanet alfa infusion: a case report and literature review

T Torbati1,2

OA Elshaigi3*

M Kayyali2

OM Dumitrascu3

1Western University of Health Sciences, Pomona, CA

2Cedars-Sinai Medical Center, Los Angeles, CA

3Mayo Clinic Arizona, Scottsdale, AZ

Case Report

Andexanet alfa was FDA approved in May 2018 to reverse anticoagulant effects of Factor Xa inhibitors like Apixaban and Rivaroxaban, thereby generating pro-thrombotic mechanisms. Thromboembolic complications within 30 days of Andexanet alfa administration have been reported. Here, we present for the first time a thrombotic cerebral event that appeared immediately after Andexanet alfa infusion in a patient with acute intraventricular hemorrhage (IVH).

A 73-year-old man presented to our emergency department with sudden onset of a severe headache. Head CT demonstrated 2.4 mL of IVH. CT angiogram showed 60% stenosis of the left supraclinoid internal carotid artery (ICA). The patient had been taking 5 mg Apixaban twice daily for atrial fibrillation, with his last dose 5.5 hours prior to presentation. IVH indicated the patient may benefit from anticoagulation reversal via Andexanet alfa.

A 400 mg bolus of Andexanet alfa was administered followed 30 minutes later by a 2-hour infusion of an additional 480 mg, immediately upon which the patient exhibited global aphasia, temporarily alleviated by head-of-the-bed flattening. A left ICA territory mismatch (342 mL) and 76 mL core infarct were observed on CT perfusion. Shortly afterwards, the patient developed a persistent and severe left middle cerebral artery (MCA) stroke syndrome with NIH stroke scale (NIHSS) score of 23. Emergent cerebral angiogram was then performed, revealing a new sizeable thrombus in the left cervical ICA. Successful thrombectomy yielded a resulting TICI score of 2B. However, neurologic status remained poor due to development of a large left MCA territory infarct, and the patient’s family chose to withdraw supportive care.

Our observation of a thrombotic event induced immediately after Andexanet alfa challenges current administration guidelines. The ANNEXA-4 phase 3 trial reported thrombotic events within 7 days of Andexanet alfa administration in 4% of subjects and within 30 days in 10%. The earliest event in literature was noted 1 day following treatment. Also, Andexanet alfa appears to have a higher thrombotic risk than other reversal agents like four-factor prothrombin complex concentrate by as much as 7%. Further elucidation of its effects on the coagulation cascade are warranted to improve safe clinical practices. Interestingly, no thrombotic events were reported in ANNEXA-4 patients who restarted anticoagulation protocols. Thus, it may be advisable to monitor patients closely and broadly for thrombotic events until future studies update protocols for resuming anticoagulation therapy after reversal treatment.

Pulmonary and critical care

Concurrent session

3:15 PM

Thursday, January 20, 2022
#132 Plasma neutrophil extracellular trap levels correlate with acute respiratory distress syndrome severity

J Aoki*

F Denorme

J Rustad

D Perry

M Cody

E Harris

EA Middleton

CC Yost

University of Utah Health, Salt Lake City, UT

Purpose of Study

Acute Respiratory Distress Syndrome (ARDS) is characterized by hypoxic respiratory failure, multi-organ dysfunction, and mortality. ARDS results from inflammatory alveolar injury precipitated by direct and indirect lung injury. Neutrophils play a central role in the pathology of ARDS and release neutrophil extracellular traps (NETs) to trap and kill pathogens. Dysregulated NET formation, however, can cause inflammatory tissue damage and exacerbate acute lung injury as in COVID-19 associated ARDS. Whether NETs participate pathogenically in non-COVID-19 associated ARDs remains unknown. We hypothesized that plasma NET levels correlate directly with disease severity and mortality in non-COVID-19 ARDS patients.

Methods Used

We obtained previously collected plasma samples from patients (n=200) with moderate to severe ARDS enrolled in the Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) trial at three different time points (admission, 24 hours, and 48 hours after admission) complete with clinical outcome data through 28 days after admission. We also examined age- and gender-matched healthy donor plasma (n=20). We assayed cell-free DNA levels via fluorescence as a surrogate for NETs in each plasma sample. Clinical outcomes from ROSE trial participants were correlated with the quantification of NETs. We also assessed NET formation by neutrophils isolated from healthy adults following incubation with ARDS patient and healthy donor plasma samples using live cell imaging and confocal microscopy.

Summary of Results

We demonstrated elevated cell-free DNA in ARDS plasma compared to healthy donor plasma. Deceased study participants demonstrated higher plasma cell-free DNA levels on admission and at 48 hours as compared to ARDS survivors (admission: p = 0.0045 and 48 hours: p = 0.0050). Increased cell-free DNA on admission, at 24 hours, and 48 hours also correlated with illness severity. Furthermore, ARDS plasma samples induced NET formation in vitro in neutrophils isolated from healthy donors while control plasma did not.

Conclusions

NET formation is increased in plasma from patients with ARDS compared to healthy donor plasma, consistent with the inflammatory alveolar injury seen in ARDS. Additionally, plasma from ARDS patients induces NET formation in vitro in PMNs isolated from healthy adult donors. We speculate that exaggerated NET formation may serve as a novel biomarker for inflammatory lung injury in ARDS resulting from multiple etiologies and strategies targeting NET formation may improve outcomes in ARDS.

Pulmonary and critical care

Concurrent session

3:15 PM

Thursday, January 20, 2022
#133 Platelet alpha granule deficient mice are protected against the development of hypoxia-induced right ventricular hypertrophy

JN Posey1*

E Nozik2

C Delaney1

1University of Colorado Denver School of Medicine, Aurora, CO

2University of Colorado Denver Department of Medicine, Aurora, CO

Purpose of Study

Pulmonary Hypertension (PH) is a life-threatening disorder characterized by increased pulmonary vascular resistance, right ventricular systolic pressures (RVSPs) and right ventricular hypertrophy (RVH), driven in part by inflammation. Our previous studies have demonstrated that platelets are activated in mice with hypoxia exposure, leading to the release of the proinflammatory chemokines Platelet Factor 4 (PF4) and CCL5, contributing to hypoxia induced lung inflammation. Nbeal2 KO mice are platelet alpha-granule deficient. Alpha granules contain numerous chemokines, including PF4 and CCL5. We hypothesized that Nbeal2 KO mice would be protected from hypoxia-induced PH.

Methods Used

Male and female C57BL/6 and Nbeal2 KO mice were exposed at 8–9 weeks of age to 10% hypobaric hypoxia or remained in normoxia for 21 days. Whole blood was collected via RV cardiac puncture using heparin coated syringes and analyzed immediately. RVSPs were obtained by closed-chest RV puncture. Hearts were dissected to obtain the weights of the RV and septum + left ventricle (LV). Fulton’s index, (RV/LV+S) was used to determine RV hypertrophy as an indicator of the development of PH.

Summary of Results

Nbeal2 KO mice have lower platelet numbers (434 ± 43.5 - 780± 39.6 [x103/uL], p<0.001) and larger platelets, demonstrated by increased mean platelet volume (MPV) (4.7 ± 0.05 - 5.3 ± 0.04 [fL], p<0.0001) compared to WT controls. RVSP under control conditions was similar in Nbeal2 KO and WT mice (28.14±0.91 – 31.04±1.01 [mmHg]). There was a significantly greater hypoxia-induced increase in RVSP in Nbeal2 KOs compared to WT mice (34.5 ± 1.05 - 37.8 ± 0.66 [mmHg], p<0.05). Though, we saw statistically higher Nbeal2 KO RVSP compared to WT, they both showed a 22% increase in RVSP with hypoxia exposure (WT CO vs. HPX 28.1 ± 0.91 - 34.5 ± 1.1 [mmHg], p<0.001; KO CO vs. HPX 31.0 ± 1.01 - 37.8 ± 0.66 [mmHg], p<0.0001). Fulton’s index under control conditions was similar between Nbeal2 KO and WT mice. (0.29±0.014 – 0.29±0.001). As expected, WT mice show the development of RVH when exposed to prolonged hypoxia (0.29 ± 0.01 - 0.39 ± 0.02, p<0.001). Nbeal2 KO mice did not develop hypoxia-induced RVH (0.29±0.001 – 0.32±0.02).

Conclusions

Mice deficient in alpha granules (Nbeal2 KO) have similar hypoxia-induced pulmonary vasoconstriction, but are protected against the development of RVH. Our future studies will address whether Nbeal2 KO mice demonstrate impaired platelet activation and/or decreased recruitment to the pulmonary circulation conferring protection from inflammatory mediated pulmonary vascular remodeling and PH.

#134 Evaluation of the accuracy of minimally-invasive cardiac output monitors before and after cardiopulmonary bypass

K Cheung*

N Fleming

University of California Davis, Sacramento, CA

Purpose of Study

Cardiac output (CO) monitoring is an important tool for hemodynamic optimization. Bolus thermodilution (iCO) with a pulmonary artery catheter (PAC) remains the gold standard for CO measurement, but is invasive and has been associated with complications. This study evaluates the level of agreement of CO values measured from multiple minimally-invasive CO monitor systems before and after cardiopulmonary bypass (CPB). CCO uses a modified thermodilution technology. Cheetah is based on thoracic bioreactance. ClearSight reconstructs the brachial arterial pressure waveform from the finger arterial pressure. CNAP CO is based on continuous non-invasive arterial pressure from the finger. LiDCO is based on the radial arterial blood pressure waveform. FloTrac calculates CO from the radial arterial pulse contour.

Methods Used

The IRB reviewed and approved this quality improvement study. Sixty patients were enrolled. 8 patients were excluded due to missing iCO measurements. CO measurements from 52 patients were evaluated using Bland-Altman analysis. CO values were measured simultaneously by bolus thermodilution with a PAC and the CO monitors listed above.

Summary of Results

All values were not available at all time points. The Bland-Altman plots are presented in figure 1 and the corresponding values are summarized in table 1.

Abstract #134 Table 1

Bland-altman analysis of minimally-invasive CO monitors

Abstract #134 Figure 1

Bland-altman analysis of minimally-invasive CO monitors pre-bypass and post-bypass

Conclusions

Based upon percentage errors, the relative accuracy of the minimally-invasive CO monitors when compared to iCO were: CCO>Cheetah>ClearSight>FloTrac>CNAP>LiDCO. Measurements after CPB have slightly smaller percentage of errors. Percentage error <30% is considered acceptable (Critchely et al., 1999). On this basis, the minimally-invasive CO monitors cannot replace the PAC for accurate CO measurement in cardiopulmonary bypass surgery.

#135 A case of dabbing-induced lipoid pneumonia

LW Boucher*

GA Loh

Dwight David Eisenhower Army Medical Center, Fort Gordon, GA

Case Report

Introduction

Dabbing is an emerging form of cannabis consumption. Similar to vape-associated lung injury, it can result in acute respiratory distress syndrome (ARDS), and diagnosis is often obscured by a broad infectious differential.

Case Description

The patient is a 36 year old male with recurrent admissions for various infections in the setting of a splenectomy who was admitted for an undifferentiated inflammatory syndrome. He presented with fever, leukocytosis with bandemia, several episodes of emesis, and fatigue. He denied any cough, dyspnea, sputum production, or chest pain. Aside from fever, his vital signs were otherwise normal and he was admitted to the general medical ward. Given his immunocompromised state and lack of clear infectious source he was started on vancomycin, azithromycin, and meropenem. Despite this regimen his fever persisted, leukocytosis worsened, and hypoxia developed; the latter rapidly progressed requiring intubation for hypoxemic respiratory failure. CT scan of the chest revealed bilateral consolidation and ground glass opacities. He met Berlin criteria for ARDS and he was started on glucocorticoids. Cytology from bronchoscopy revealed abundant alveolar macrophages with oil red O staining and mixed inflammatory cells. Comprehensive infectious workup including Covid-19 PCR x2, 3 sets of blood cultures, urine culture, and bronchioaveolar lavage for bacteria, acid fast organisms, and fungus was negative. This negative infectious workup coupled with cytology findings indicates lipoid pneumonia as the etiology of his illness. His clinical condition improved after several days and he was successfully extubated and eventually discharged on room air. It was discovered that the patient had been vaping with THC products including dabs. Dabs, a wax-like THC product, are likely the mechanism by which lipids were introduced into his lungs resulting in pneumonia.

Discussion

This case represents a presentation of lipoid pneumonia secondary to ‘dabbing,’ a relatively novel form of ingesting cannabis. There have been few reported cases of respiratory failure secondary to ‘dabbing,’ and this case identifies lipoid pneumonia as the cause of lung injury. This case highlights the need for physicians to be aware of specific forms of recreational drugs and routes of delivery.

#136 Lung epithelial cell environment modulates temporal kinase signaling dynamics

N DeCuzzi*

D Murphy

A Ram

M Pargett

K Chmiel

AA Zeki

J Albeck

University of California Davis, Davis, CA

Purpose of Study

Signaling in lung epithelial cells plays a role in respiratory disease pathogenesis. ERK, NFκB, and AMPK are key kinases regulating cell growth and proliferation that are implicated in airway inflammation and disease. Importantly, ERK and AMPK display heterogenous and temporally dynamic signaling activity that can be linked to cell behavior but has yet to be investigated in the context of airway disease. We hypothesize that unique signatures of short-term oscillatory signaling activity (minutes) differentially regulate long-term (>24 hour) inflammatory responses in part via regulation of the transcription factor STAT3 at the cellular level.

Methods Used

Using fluorescent biosensors and live-cell imaging, we track single-cell kinase signaling activity in our Human Bronchial Epithelial (HBE1) cell line, and primary human bronchial epithelial cells (pHBE), continuously at 6-minute intervals, both in submerged and Air-Liquid Interface (ALI) culture conditions. Computational image analysis extracts kinase signaling activity profiles in response to growth factors, and inflammatory cytokines. After 24 hours of ligand exposure, cells are fixed and immunofluorescent stain for nuclear pSTAT3 is performed to measure cellular inflammatory response.

Summary of Results

Comparison of HBE1’s ERK signaling activity from control and ligand stimulated cells, reveals heterogeneous and dynamic single-cell responses to inflammatory ligands relevant to both subtypes of asthma and COPD (IL-6, IL-1β, & TNFα), that are both ligand- and concentration- dependent. Intriguingly, pHBE cells in submerged culture display dynamic and heterogeneous ERK signaling activity, that is similarly dependent on ligand and concentration, but are unique from those seen in HBE1 cells. Notably, both HBE1 and pHBE cells displayed unique ERK responses to inflammatory ligands than those of EGF treated cells. We note a similar heterogeneity in STAT3 activation dependent on inflammatory ligand, that is attenuated in the presence of metabolic perturbation and AMPK activation.

Conclusions

These results support our central hypothesis and demonstrate the importance of this novel and unique approach using both airway epithelial cell lines and primary bronchial epithelial cells in ALI. Ongoing work: 1) Finishing data collection for ERK and NFκB in pHBE cells cultured in ALI, and AMPK activity in HBE1 cells, 2) Using statistical modeling to determine ERK, AMPK, and NFκB’s contribution to modulating the STAT3 response to inflammatory ligands, and 3) Assessing how pharmacological agents alter activity profiles to modulate long-term inflammatory responses in these model systems. Our technique will reveal deeper knowledge about airway epithelial kinase signaling mechanisms relevant to asthma and COPD, and potentially, other lung diseases.

#137 The effects of acute and chronic kidney injury on mortality in older patients critically ill with COVID-19

MD Rockstrom*

S Windham

KM Erlandson

J Hippensteel

University of Colorado, Denver, CO

Purpose of Study

Older age is a well-recognized risk factor for increased mortality due to COVID-19. Similarly, older age is associated with high rates of critical illness and admission to intensive care units. Limited data suggests that frailty, as measured by the presence of comorbidities prior to admission, may predispose to severe illness. There is currently an inadequate description of what factors can be attributed to the increase in mortality in aged, critically ill patients with COVID-19.

Methods Used

In this retrospective, cohort study, we examined 200 patients admitted to a quaternary referral center intensive care unit (ICU) with COVID-19 from March to June of 2020. Data collected included demographics, number of comorbidities, residence in assisted living or skilled nursing facilities prior to admission, vital signs, and laboratory findings at time of admission to the hospital and the ICU.

Bivariate analysis was performed with age, comorbidities, and place of residence prior to admission as independent variables and mortality, length of stay, rates, and severity of acute respiratory distress syndrome (ARDS), rates of acute kidney injury (AKI) and hemodialysis, and rates and severity of shock as dependent variables. Multivariate analysis evaluated the relationship of age, comorbidities, end organ dysfunction, and disease severity.

Summary of Results

ICU mortality was positively correlated with age (p < 0.001) and number of comorbidities (p < 0.001). Furthermore, age and number of comorbidities were directly correlated with development of AKI (p = 0.012); age was inversely correlated with severity of lung disease as measured by P:F ratio (p = 0.0092). Pre-existing chronic kidney disease (CKD) was highly predictive of development of AKI (OR 6.93, p = 0.003) Multivariable analysis demonstrated that the odds of mortality were higher with increasing age (OR = 1.06 [95% CI 1.02, 1.11] per year, p = 0.005), decreased with increasing P:F ratio (OR 0.336 [95% CI 0.16, 0.61] for every increase in P:F of 50, p < 0.001), and increased with AKI requiring hemodialysis (OR = 4.61 [95% CI 1.185, 19.7], p = 0.031).

Conclusions

Recognition of CKD in older adults critically ill with COVID-19 is critical in identifying those who are high risk of severe kidney dysfunction and death. CKD has been shown previously to be associated with mortality in COVID-19 and this study offers a mechanistic understanding of this relationship. This is especially important given that older patients do not seem to have the same propensity for severe lung disease seen in younger patients. The role of kidney disease in the mortality of older patients critically ill with COVID-19 needs to be better defined prospectively.

#138 Effect of positive end expiratory pressure in prevention of postoperative pulmonary complications in obese patients under general endotracheal anesthesia: systematic review and meta-analysis of randomized trials

JY Choi*

MA Al-Saedy

BJ Carlson

Washington State University, Spokane, WA

Purpose of Study

In non-obese patients, low positive end-expiratory pressure (PEEP) of < 5cmH2O is a widely accepted practice. Although the safety of low tidal volume plus low PEEP has been established in non-obese patients, this strategy may induce atelectasis and post-operative pulmonary complications in obese patients. In obese patients, use of PEEP > 10cmH2O has shown to prevent intraoperative atelectasis but there is no conclusive data for the postoperative complications from high PEEP. Therefore, this meta-analysis aims to compare the rate of postoperative complications (PPCs) associated with high PEEP and low PEEP in obese patients who received surgery under endotracheal general anesthesia.

Methods Used

The protocol for this meta-analysis was published on PROSPERO (CRD42021224041). We searched MEDLINE, EMBASE, CENTRAL, and CINAHL databases using pre-specified search strategies. We included only RCTs that compared the effect of low PEEP and high PEEP in obese patients (BMI>30 kg/m2) who received open or laparoscopic surgeries under endotracheal general anesthesia. All patients received the tidal volume of 6–8 ml per kg of predicted body weight. Risk of bias was assessed using the Covidence review manager. Statistical analysis was conducted using Cochrane RevMan software (Mantel-Haenszel, Fixed Effects, Risk Ratio). Primary outcome was the number of PPCs. Secondary outcomes included extrapulmonary complications, intraoperative complications, and mortality during hospital stay.

Summary of Results

There was no significant difference in the rate of postoperative complications between low PEEP and high PEEP groups (RR=0.93; 95%CI 0.79 to 1.10; P=0.41). We identified 4 randomized controlled trials involving 2,116 participants. Two trials had a low risk of bias, and the other two trials had an immediate and substantial risk of bias. We observed significant heterogeneity within included trials (I2=53%). Secondary outcomes were not reported by all trials. Incidence of intraoperative hypotension was reported in 3 trials and was significantly lower in the low PEEP group (RR=1.84; P<0.01).

Conclusions

Overall, the evidence is not robust enough to determine the protective effect of high PEEP and low PEEP in obese patients. Out of 2,116 total participants, 1,976 participants were from 1 trial that included both laparoscopic and open abdominal surgery. This may explain the heterogeneity observed since the other three trials only included patients who received laparoscopic abdominal surgeries. Although exclusion of the large study significantly lowered the incidence of PPCs in the low PEEP group with relative risk of (RR=8.0m P=0.05), the other trials were smaller studies and had higher risk of publication bias. More multi-center RCTs are warranted to compare the rate of PPCs between low PEEP and high PEEP in obese patients under endotracheal general anesthesia.

#139 Alveolar hemorrhage due to secondary pulmonary vasculitis in a patient with new features of autoimmune disease

A Garcia1*

T Issa2

R Garcia-Pacheco2

J Oberndorf1

1Ross University School of Medicine, Miramar, FL

2Kern Medical Center, Bakersfield, CA

Case Report

Pulmonary Vasculitis is a manifestation of a specific set of disorders pathologically defined by inflammatory destruction of blood vessels within the lungs. Secondary immune mediated vasculitis, as in autoimmune processes like rheumatoid arthritis (RA), is one subset of these disorders. We present a rare case of alveolar hemorrhage caused by pulmonary vasculitis in a patient positive for anti-CCP antibody but no laboratory or imaging to meet diagnostic criteria for RA.

CASE

A 50-year-old female with history of pulmonary embolism (PE) presented to the ED with three episodes of hemoptysis. She also complained of chest pain, arthralgias and fatigue. She was not on anticoagulation therapy. Family history was positive for lupus and RA in two sisters. Vital signs were stable. Labs showed ESR 36, CRP 1.53, and D-dimer 749. CT chest angiogram revealed scattered ground glass and patchy alveolar densities throughout lung fields; no evidence of PE. Flexible bronchoscopy with bronchoalveolar lavage (BAL) was diagnostic for alveolar hemorrhage. Cytology from BAL yielded numerous red blood cells and macrophages with hemosiderin granules. Autoimmune panel was significant for elevated ANA 1:80 and CCP Ab IgG >250. Patient was started on Prednisone 60 mg/day for diagnosis of alveolar hemorrhage secondary to immune mediated capillaritis and discharged home. As an outpatient, X-rays of wrists and hands revealed no inflammatory or crystalline arthropathy. Labs showed normal rheumatoid factor (RF), but persisting elevation in CRP and ESR. Methotrexate was started to prevent recurrent alveolar hemorrhage and Prednisone was continued pending rheumatology referral.

Discussion

Although there have been some rare cases of diffuse alveolar hemorrhage (DAH) preceding the diagnosis of RA, DAH commonly arrives as a manifestation of long standing RA. Anti-CCP antibody is known to not only be as sensitive as RF but significantly more specific when diagnosing RA. Studies have shown a subgroup of patients testing positive for anti-CCP antibodies with no evidence of RA, who subsequently developed RA within short followup.

Conclusion

The unique disease course of DAH in patients with underlying features of autoimmune disease is not well documented. Implications of positive anti-CCP antibody but no definitive diagnosis of RA in patients with lung disease still requires further investigation. Anti-CCP antibody has been shown to be highly predictive of future development of RA. Patients that present with pulmonary symptoms like hemoptysis due to autoimmune vasculitis and capillaritis should be closely monitored. Whether to initiate early treatment for RA should also be strongly considered. As such, clinicians need to remain vigilant when suspecting immune-mediated DAH in patients with unclear autoimmune disease.

#140 Use of strict spinal precautions for spinal cord injuries by ski patrols: do they work?

C O’ Driscoll

D Deng*

E Guenther

Western University of Health Sciences College of Osteopathic Medicine of the Pacific-Northwest, Lebanon, OR

Purpose of Study

For decades, hard backboards have been the standard of care for emergency medical personnel and ski patrollers treating known or suspected spinal cord injuries in the field. Recent studies have shown that prolonged immobilization on hard backboards can cause injuries to patients and are no longer recommended unless specific criteria are met. In 2018, the National Ski Patrol implemented guidelines consistent with the Position Statement of the National Association of EMS Physicians and the American College of Surgeons Committee on Trauma. The effectiveness of those guidelines for ski patrollers in the field are quantified in this survey study.

Methods Used

This study was approved by the Western University of Health Sciences Institutional Review Board. An anonymous online survey was distributed electronically to 168 ski patrols across the United States using contact information obtained from the National Ski Patrol website. The survey was optional, and participants voluntarily completed the survey between April 2 and April 27, 2021. A total of 19 ski patrols responded to the survey and 19 are represented in the data. They were asked questions regarding how many backboards they used per season before and after the new guidelines were implemented, frequency of backboard-specific training, whether the mountain also has a paid patrol division, as well as confidence of their patrol utilizing the new spinal protection guidelines.

Summary of Results

The majority of respondents (14 out of 19) reported a decrease of at least 5 backboards used in the season following implementation of the new guidelines. Patrols that conducted more than two backboard-specific trainings per year reported a larger decrease in backboards (6–10 per season) in the season following the new guidelines than patrols that conducted 1–2 yearly trainings (up to 5 per season). The average reduction in backboards in both patrols that have a paid division and those that do not was approximately 5 backboards per year. 10 out of 19 patrols reported that they were ‘very confident’ their patrols could implement the new guidelines and 9 out of 19 reported they were ‘somewhat confident’. No respondents reported that they were ‘not very confident’.

Conclusions

The new guidelines and training from the National Ski Patrol resulted in a decrease in hard backboard use by the majority of surveyed patrols while still allowing ski patrols to utilize potentially life-saving devices when necessary.

Surgery II

Concurrent session

3:15 PM

Thursday, January 20, 2022
#141 Displaced femoral neck fractures in elderly patients should not be fixed with closed reduction and percutaneous pinning

D Skerrett1*

M Coale2

W Lack2

1University of Washington School of Medicine, Seattle, WA

2University of Washington Department of Medicine, Seattle, WA

Purpose of Study

The Garden classification has been used to grade femoral neck fractures since 1961. Nondisplaced fractures on AP radiographs are described as Garden I or II, while displaced fractures are designated Garden III or IV. These distinctions are useful when selecting an operative treatment. In elderly patients, nondisplaced fractures are often treated with internal fixation (i.e. screws) while displaced fractures are often treated with arthroplasty. Poor bone quality in the elderly limits screw purchase and impairs healing, particularly in the setting of Garden III/IV fractures. Nonetheless, many displaced fractures in elderly patients are treated with internal fixation operations, such as closed reduction and percutaneous pinning (CRPP). This observational study compared rates of failure between displaced and nondisplaced femoral neck fractures treated with closed reduction and percutaneous pinning in Seattle.

Methods Used

We identified 374 patients who suffered femoral neck fractures and were treated with internal fixation between 2010 and 2020 at 3 hospitals in Seattle. Patients older than 50 and fixed with CRPP met the inclusion criteria. Pathologic fractures and fractures fixed with dynamic hip screw, dynamic helical hip screw, arthroplasty, or open approach/visualized reduction were excluded. Treatment failure was defined as avascular necrosis, nonunion, or conversion to arthroplasty. 267 records met these criteria. For each patient, data was collected on displacement, age, sex, dementia status, ASA, baseline ambulation, independence, and injury mechanism. Chi-squared tests were used to assess correlation between these variables and treatment failure.

Summary of Results

Displaced fractures treated with CRPP were significantly more likely to fail than nondisplaced fractures treated with CRPP (p < 0.00001). Absence of dementia was also associated with CRPP failure (p = 0.0197). Age, sex, ASA, baseline ambulation, independence, and injury mechanism were not found to be associated with treatment failure.

Conclusions

In elderly patients, displaced femoral neck fractures are significantly more likely than nondisplaced fractures to fail treatment with CRPP. Initial treatment with hemiarthroplasty or total arthroplasty should therefore be considered in this demographic to reduce the risk of pain and reoperation. Absence of dementia was also correlated with treatment failure; however, dementia patients’ differing goals of care and impaired communication with caretakers confound this result. Future studies could compare outcomes between displaced fractures treated with CRPP versus arthroplasty. In addition, future work may further examine the association between absence of dementia and CRPP failure.

#142 Alterations in shoulder tendon structural proteins in atherosclerosis

WH Fang*

S Sekhon

FG Thankam

DK Agrawal

Western University of Health Sciences, Pomona, CA

Purpose of Study

Hyperlipidemia is a hallmark of the atherosclerotic process and can impact every system of the body, including the musculoskeletal system as evident from the increased comorbidity of tendinopathies in atherosclerotic patients. Indeed, lipid deposits within the extracellular matrix (ECM) have been found in tendon tissues with changes in the biomechanical properties of the tendon. However, there is limited information on the development and progression of tendon pathology in atherosclerotic patients. Here, we examined the expression status and molecular crosstalk of the ECM proteins in atherosclerosis using hyperlipidemic microswine model.

Methods Used

Shoulder tendons tissues (N=12) from hyperlipidemic Yucatan microswine were harvested, fixed, embedded in paraffin and longitudinal thin sections were used for tissue morphology with hematoxylin and eosin (H&E), Masson trichrome, and Pentachrome staining.

Immunofluorescence staining (IF) was performed for collagen types I, III, IV, V, VI, and XVII, MMP2, and MMP9 following standard protocols. The fluorescence intensity (MFI) of each protein was quantified using ImageJ software. The variation with respect to control (tendon tissue harvested from normal swine) was calculated from the average MFI/nuclei and the results are presented as log2 fold-change (FC).

Summary of Results

H&E staining showed disorganized ECM in atherosclerotic tissue with greater deposition of adipocytes. Trichrome staining revealed disorganization in collagen fibers with poorly defined vasculature and increased infiltration of adipocytes in atherosclerotic tendons compared to the control. The pentachrome staining highlights decreased collagen expression and increased mucin deposition in the atherosclerotic tissues. Also, the atherosclerotic shoulder tendons demonstrated decreased expression of COL III (FC=-0.38 ± 1.49), COL IV (FC= -0.61 ± 1.75), and a pronounced decrease in COL XVII (FC=-1.6 ± 1.85) and COL I (FC=-2.24 ± 0.41). However, there was an increased expression of COL V (FC=1.02 ± 2.13), MMP-9 (FC=0.9 ± 0.60), and a marked increase in MMP-2 (FC=2.05 ± 1.53).

Conclusions

The findings demonstrated that there was considerable structural alteration in ECM composition and components in hyperlipidemic tendon when compared with normal shoulder tendons. There was a decrease in collagen proteins and an upregulation of the MMP class of proteolytic enzymes. The decreased collagen and increased MMP expression are correlated with increased tendon injury and rupture. Such pathological alterations support the existence of increased co-morbidity of tendinopathies in hyperlipidemic patients.

#143 An investigation in the evidence base for adaptogens in wound healing and skin rejuvenation

D Sokolov*

S Gupta

Loma Linda University, Loma Linda, CA

Purpose of Study

Despite having a long history of use in traditional and herbal medicine, adaptogens have recently reentered the spotlight due to their potential to augment the body’s response to stress. Originally mentioned in 1974 in a Soviet literature review as ‘New substances of plant origin that Increase non-specific resistance’, the term ‘adaptogen’ has grown to include most any compound that increases the body’s resilience against a variety of mechanisms of cellular stress. Considering that the skin is highly affected by many of these pathways, this implies a potential application for adaptogens in the context of specialties concerned with aesthetic outcomes. This study identified adaptogens with an evidence-based clinical application in the areas of skin health and wound healing.

Methods Used

A literature search was conducted using the term ‘adaptogen’ in the article databases of Google Scholar, JSTOR, NCBI and PubMed. Upon finding mention of specific compounds, separate searches were then performed for each compound. Inclusion criteria consisted of articles pertaining to skin improvement and anti-inflammatory properties. Additionally, special attention was given to studies that used human keratinocyte cell lines. Exclusion criteria included general information articles, and articles with described benefits outside the realm of skin and regenerative capacity.

Summary of Results

The number of relevant articles found spoke to a large need for further research. While there are numerous articles and studies done on the systemic benefits of various adaptogens, research specific to skin and wound healing is very limited. However, the research completed consistently shows agreement in the nature of the benefits of various adaptogens. A common theme of inflammation reduction quickly emerged through the course of the search, with the most prevalent pathway affected being NFkB. While Ashwagandha, Schisandra and Triphala held the most promise in terms of an evidence base, the number of applicable articles often corresponded with the total amount of available literature on a certain compound.

Abstract #143 Table 1

Conclusions

This serves to highlight how much potential there is in this area for further research. If the benefits proposed in the current literature stood the test of clinical studies, adaptogens could become part of standard perioperative and post traumatic care.

#144 How does dimethyl sulfoxide affect in-vitro fat graft viability?

NM Sarli*

S Gupta

Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

Purpose of Study

Since the popularization of fat grafting in the 1980s, surgeons have sought to improve the viability of the grafts. Research demonstrates that the majority of harvested cells die within hours to days of transplantation. One of the most promising interventions which may improve survival during this time are pharmacologic agents added to the graft or recipient site. Several additives have been trialed. One such compound is dimethyl sulfoxide (DMSO). In one study, rats treated with DMSO showed improved fat graft survival. Due to the challenge of studying new treatments in humans we sought to observe the impact of DMSO on viability of adipocytes in vitro.

Methods Used

DMSO was added to samples of human lipoaspirate to produce three concentrations: 500:1, 2000:1, and 8000:1 and a control sans DMSO. The samples were centrifuged to isolate the fat from the aqueous fraction. Each sample was then divided into several 900µL portions and incubated with 100µL of AlamarBlue at 37C for 4 hours. Each portion was then diluted with 3mL of saline and centrifuged to suspend the dye. Absorbance was measured at 570nm and 600nm. The experiment was repeated thrice. The patients were females aged 41, 61, and 48. Normalized absorbances were calculated by subtracting the 600nm absorbance from the 570nm absorbance.

Summary of Results

Trial #1, (figure 1), showed a decrease in absorbance across all doses of DMSO tested [ Control (0.386), 1:8000 (0.251 p = 0.004), 1:2000 (0.317), and 1:500 (0.381)]. Trial #2 (figure 2), demonstrated a dose-dependent decrease in absorbance across the three concentrations [Control (0.201) 1:8000 (0.186, p = .03), 1:2000 (0.183, p = 0.2), 1:500 (0.145, p = 0.02)]. Finally, trial #3, (figure 3) yielded an increase in absorbance at a low (1:8000) concentration of DMSO (0.182, p = 0.02) vs Control (0.140). 1:2000 and 1:500 were found to have a negative effect on absorbance (0.106 p = 0.1 and 0.102 p = 0.07, respectively).

Conclusions

Our results are, thus far, inconclusive. However, we believe that there are confounds which can be eliminated. The researcher noted an inconsistent mixing of assay with fat and also noted that small variations in pipetting technique introduced bubbles in the cuvette that could affect readings. If minor technique changes rectify these errors, more consistent results are possible.

If future in vitro trials find DMSO to offer a viability benefit to graft cells, further research could be done on topical applications in humans as DMSO has been safely used topically for years.

#145 Comparison of complications in patients with normal and compromised renal function undergoing adjuvant radiation therapy following robotic-assisted laparoscopic radical prostatectomy

R Chen1*

S Song2

A Amasyali2

C Ritchie2

C Baas1

D Baldwin2

1Loma Linda University, Loma Linda, CA

2Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

Purpose of Study

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with high morbidity and mortality. Kidney transplantation may be a life-saving therapy for these patients. However, ESRD patients with untreated prostate cancer may be excluded from transplantation due to risk for cancer progression, while patients treated with robotic-assisted laparoscopic radical prostatectomy (RALP) who have undetectable PSA’s may be cleared for immediate transplantation. Patients with detectable PSA’s may require adjuvant radiation, which may result in radiation cystitis, a clinical diagnosis ranging from mild dysuria to severe hematuria. In patients with prior RALP, adjuvant radiation therapy (XRT) may result in a higher mean radiation dose to the bladder due to its low volume and new post-surgical location, which may increase the risk for hemorrhagic cystitis. The purpose of this study was to compare the complications between patients with normal and compromised renal function undergoing adjuvant radiation therapy following RALP.

Methods Used

A retrospective review was conducted of all patients in a single academic institution undergoing RALP followed by XRT between December 2006 and July 2020. Demographic variables, surgical parameters, cancer stage, outcomes and complications were compared between patients with CKD 0–2 and CKD 3–5. The primary outcome was radiation related bladder complications including hematuria, catheter insertion, blood transfusions, continuous bladder irrigation, surgical clot evacuation, and bladder fulguration. Statistical analysis was performed by Mann Whitney U and Independent T test with p<0.05 considered significant.

Summary of Results

When comparing the 101 patients with CKD 0–2 who underwent RALP followed by XRT, to the 9 patients with CKD 3–5, there was no difference in age (67.7 vs. 63.7 yrs.), length of follow-up (39.6 vs. 38.2 mos) or cancer stage (p>0.05 for all). However, patients in the CKD 3–5 group were significantly more likely to require Foley placement for clot evacuation (33.3% vs 1.1%; p<0.01), hospitalization for continuous bladder irrigation (33.3% vs 1.1%; p<0.01), blood transfusion (33.3% vs 1.1%; p<0.01), hyperbaric oxygen treatment (33.3% vs 0%; p<0.01) and surgical fulguration (22.2% vs 1.1%; p<0.01).

Conclusions

Individuals with CKD 3–5 are at significantly greater risk for severe radiation-induced hemorrhagic cystitis. Lower volume bladder combined with increased risk of coagulopathy may partly explain this finding. Adjuvant radiation should be used with caution in patients with significant renal dysfunction.

#146 Factors associated with spontaneous lateral skull base cerebrospinal fluid

JS De Armas*

E Miles

A Miller

Y Liu

N Wycliffe

Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Most lateral skull base CSF leaks have an identifiable cause, however, spontaneous cerebrospinal fluid (CSF) leaks do not. We aimed to determine risk factors for spontaneous lateral skull base CSF leaks.

Methods Used

Retrospective chart review of all patients seen at a tertiary referral center over the last 10 years for spontaneous lateral skull base CSF leak who underwent temporal bone CT scan. Patients with spontaneous CSF otorrhea were included. Patients with lateral skull base CSF leaks secondary to known causes such as trauma, cholesteatoma, or iatrogenic were excluded. Sex and age-matched controls were randomly selected from all patients seen at the same center with temporal bone CT scan and without major otologic pathology. Demographics collected and main outcomes analyzed included age, sex, ethnicity, body mass index (BMI), smoking status, diagnosis of obstructive sleep apnea, and other comorbid medical conditions. Statistical analysis included analysis of variance, student t-test, and chi-squared between CSF leak patients and controls.

Summary of Results

Fourteen patients were identified with spontaneous lateral skull base CSF leak. 32 sex and age-matched controls with CT temporal bone imaging were randomly selected. 93% of patients in the CSF leak group were female with an average age of 66.9 years. Patients in the CSF leak group had higher BMI (33.4 vs 27.4, p<0.01) with higher rates of cardiovascular disease (93% vs. 63%, p=0.04) and sleep apnea or snoring (43% vs. 3%, p <0.01).

Conclusions

Risk factors associated with spontaneous lateral skull base CSF leaks include female gender, elevated BMI, OSA, and cardiovascular disease. Further research is warranted to identify potential associations between lateral skull base thickness and spontaneous lateral skull base CSF leaks.

#147 Utility of pediatric vesicostomy in protecting the urinary tract

J Byer1*

C Ritchie2

J Chamberlin2

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

2Loma Linda University, Loma Linda, CA

Purpose of Study

In pediatric patients, a vesicostomy is a surgical option for temporary or permanent urinary diversion as a protective measure for the integrity of the patient’s urinary tract and renal system. The objective of this study is to quantify the indications for the pediatric patient population undergoing vesicostomies at an academic children’s hospital.

Methods Used

We performed a retrospective chart review of all pediatric patients (0–18 years) who underwent cutaneous vesicostomy from a single tertiary children’s hospital from 2002 to 2021. Demographic information, pathological indications for vesicostomy, medical management, urinary tract infections, urodynamics, renal function, complications, and reversal of vesicostomy were evaluated. The primary outcome was improvement in hydronephrosis and vesicoureteral reflux, comparing before and after vesicostomy. Two-tailed, Student-t tests were calculated, with p values less than 0.05 considered significant.

Summary of Results

At our institution, 33 pediatric patients (20 males and 13 females) underwent vesicostomy. The age at time of surgery ranged from 0 to 179 months (mean 39.2 months) with median follow-up 70.5 months (range 2–210). The indication for vesicostomy included neurogenic bladder (14), chromosomal anomalies (8), anatomical malformation (7), prune belly syndrome (4), secondary vesicoureteral reflux (3), posterior urethral valves (3), and solitary kidney (3). Two patients underwent vesicostomy prior to kidney transplant clearance and one had a vesicostomy concurrently with kidney transplant. Prior to surgery, 21 (63.6%) were started on clean intermittent catheterization and 20 (60.6%) were on an anticholinergic. Fifteen (45.5%) had ≥2 confirmed UTIs before surgery (range 0 to 11). Either unilateral or bilateral SFU Grade ≥2 Hydronephrosis was present in 25 patients (75.8%) prior to surgery and present in 12 (36.4%) after surgery (p<0.01). Vesicoureteral reflux Grade ≥2 was present in 15 patients (40.5%) prior to surgery and persistent in 5 (15.2%) after surgery (p=0.036). The median percentage of expected bladder capacity was 83.3%. Complications after vesicostomy included vesicostomy site fungal rash (23), sepsis due to a UTI (10), and renal or bladder calculi (4). Additionally, 4 developed stricture, 4 developed stomal stenosis, 8 had to catheterize the stoma to maintain patency, and 5 had bladder prolapse through the vesicostomy site with 2 requiring revisional surgery. Six underwent excision and closure of their vesicostomy. One had their cutaneous vesicostomy modified to an ileovesicostomy. Two underwent repeat vesicostomy.

Conclusions

Cutaneous vesicostomy are useful and effective forms of urinary diversion in pediatric patients with unsafe urinary tracts that have otherwise been refractory to medical treatment.

#148 Does a needle holder reduce fluoroscopic radiation exposure to the surgeon’s hand compared to lead gloves and conventional gloves?

E Joo1*

C Baas1

R Chen1

JC Hartman1

JD Belle2

A Amasyali2

D Baldwin2

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

2Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

Purpose of Study

Fluoroscopy is commonly employed while gaining needle renal access prior to removal of kidney stones during percutaneous nephrolithotomy (PCNL). Excess radiation exposure has been linked to possible deleterious outcomes for both patients and surgeons. Some of the radiation the surgeon receives is due to scatter radiation, but the surgeon’s hand may be exposed to the highest radiation dose when placed directly in the fluoroscopy beam. To reduce this exposure, some surgeons wear lead gloves, and more recently, a specialized needle holder has been developed. The purpose of this study is to compare direct radiation dose to the surgeon’s hand while holding the needle with a conventional surgical glove, a lead glove, or a novel needle holder.

Methods Used

A PCNL procedure was simulated using a cadaver to represent a patient and a separate cadaver arm to mimic a surgeon’s hand. Three different techniques for holding the needle were tested: holding the needle directly in the fluoroscopy beam while wearing a conventional surgical glove, holding the needle while wearing a lead glove, and using a novel needle holder designed to distance the surgeon’s hand from the direct beam. Thermoluminescent dosimeters were attached to the thumb, middle finger, hypothenar eminence, wrist of the cadaver hand, and skin of the cadaver patient, dorsal to the kidney. Five trials were performed for each treatment arm. In each trial, five minutes of fluoroscopy was delivered using automatic exposure control. Radiation doses between treatment arms were compared using ANOVA with p<0.05 considered significant.

Summary of Results

Using a lead glove resulted in a significant reduction of radiation to the surgeon’s hand compared to when the surgeon directly held the needle wearing a conventional glove (mean dose 248.4 vs. 391.9 mRad; p<0.001). However, the greatest radiation reduction was seen when using the novel needle holder (137.3 mRad) compared to a lead glove (248.4 mRad) and a conventional glove (391.9 mRad; p<0.001). An unexpected finding was a significant reduction in the cadaver patient’s radiation dose when the novel needle holder was used, compared to the use of a lead glove and a conventional glove (703 vs 842.90 and 816.65 mRad, respectively; p= 0.024).

Conclusions

This study showed that using a needle holder during PCNL reduced radiation exposure to the surgeon’s hand compared to the use of a lead glove and a conventional glove. In addition, by removing dense objects from the radiation field, the dose to the patient was significantly less when a needle holder was used. These findings demonstrate that keeping the surgeon’s hand out of the beam will reduce radiation exposure, not only to the surgeon, but also to the patient, and may thereby decrease the risks of radiation exposure, including cancer.

#149 Risk factors for urinary tract infections in children with prenatal hydronephrosis

A Fisher1*

C McKinney1

C Ritchie2

J Chamberlin2

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

2Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Prenatal hydronephrosis is common in pregnancy and is detected in up to 5% of pregnancies. Children with PNH are at risk of developing a UTI in childhood. The aim of this study was to determine the incidence and risk factors for urinary tract infections (UTIs) in children diagnosed with prenatal hydronephrosis.

Methods Used

We performed a retrospective review of children who presented to a tertiary children’s hospital with confirmed prenatal hydronephrosis between 2012–2021. Longitudinal data was collected in demographics, imaging studies, sex, grade of hydronephrosis, presence or absence of vesicoureteral reflux, and presence or absence of dilated ureter. The primary outcome was the development of a clinically diagnosed UTI treated with antibiotics. Statistical analysis was completed using a Chi-square test, where a p < 0.05 is significant.

Summary of Results

259 children with prenatal hydronephrosis were included in the study. Of these, 51 developed UTIs. 175 of the patients underwent a voiding cystourethrogram (VCUG) to determine if vesicoureteral reflux was present. Of these, 38 patients had vesicoureteral reflux. 39.5% these patients with reflux developed UTIs. 17.3% of patients who did not have reflux 17.3% of patients developed UTIs. (p=0.004). Ureteral dilation was also examined. 79 patients had ureteral dilation diagnosed on ultrasound. 29.9% of these patients developed UTIs, vs 15.7% of patients without ureteral dilation developed UTIs (p=0.011).

Conclusions

In children with prenatal hydronephrosis, a dilated ureter and vesicoureteral reflux increase the risk of UTI.

#150 Comparison of smartphone to wearable sensors for assessment of gait in an orthopaedic clinic

D Ahmadian1*

G Coyle2

M Dohm1

1The University of Arizona College of Medicine Tucson, Tucson, AZ

2The University of Arizona, Tucson, AZ

Purpose of Study

Recently, a host of smartphone-based applications have been developed that advertise the ability to effectively measure gait kinematics compared to traditional methods. These applications, if proven to have clinical utility, would provide a more accessible and affordable alternative for measuring gait on a long-term, continual basis. Thus, the aim of this study is to compare the utility of a smartphone-based gait analysis platform to that of an inertial motion capture (IMC) wearable sensor in a clinical setting.

Methods Used

Gait data was collected from 7 patients presenting to the Orthopaedic clinic over a 1-month period. During each appointment, the patient performed a Self-Paced Walking Test (SPWT) with 5 LEGSys wearable sensors attached to their thighs, shanks, and waist. After this test, the most recent values for the patient’s Step Length and Walking Speed were obtained from the Health application found in their iPhone and recorded in RedCap, a secure web application for managing online databases. A paired t-test was performed to compare the means of the values of Stride Length (m) and Walking Speed (m/s) recorded from the patient’s iPhone compared to that of the LEGSys sensors. This quality study was granted an IRB exemption, and patient data was de-identified before analysis.

Summary of Results

Overall, the means for the iPhone and LEGSys Stride Length were 1.13 (m) and 1.17 (m), respectively, with a p-value of 0.6. The means for the iPhone and LEGSys Walking Speed were 0.906 (m/s) and 0.963 (m/s), respectively, with a p-value of 0.3. (Table 1).

Abstract #150 Table 1

Conclusions

In this study of 7 participants, it was shown that there is not a notable difference between the mean measurements of Stride Length (m) and Walking Speed (m/s) as measured by iPhone and LEGSys wearable sensors, thus providing evidence that smartphone sensors may be useful in measuring these gait parameters. Smartphone-based gait sensors have the potential to serve as a useful clinical alternative to traditional wearable sensors in measuring gait. They are cost-effective and easily accessible in a clinical setting, saving time for the clinician during a patient encounter. Future research should focus on collecting data on more patients comparing these two technologies to increase the sample size and power of the study.

Poster session

Adolescent medicine and general pediatrics

6:00 PM

Thursday, January 20, 2022
#152 Implementing telehealth into pediatric trauma consultations

S Garrison*1

JP Marcin1

J Galante1

JL Rosenthal2

T Rinderknechkt1

K Grether-Jones2

MY Hamline2

M Zwienenberg1

B Haus3

K Matthews1

K Rominger1

A Sanders1

R Dizon1

N Kuppermann1

1UC Davis Health, Sacramento, CA

2UC Davis Children’s Hospital, Sacramento, CA

3University of California Davis Health System Department of Orthopaedic Surgery, Sacramento, CA

Purpose of Study

We are evaluating the implementation of telehealth and image sharing services to connect pediatric trauma specialists to rural and community hospital emergency departments to create a Virtual Pediatric Trauma Center (VPTC). The goal of the study is to compare the current standard of care to the VPTC model of care with regards to the parent/family experience of care, distress, healthcare utilization, and out-of-pocket cost burden.

Methods Used

We are comparing the current standard of care to the VPTC model of care with regards to: 1) the parent/family experience of care and distress at 3, 30, 60 and 90 days following a childhood injury; 2) the 30-day healthcare utilization following the injury event; and 3) the out-of-pocket costs and financial burdens experienced by parents/families 3-days and 30-days following the injury. We’ve implemented a stepped wedge trial among a stratified selection of 10 hospital EDs in Northern California, with a goal of enrolling 380 patients by November 2022. We’ve deployed pole mounted videoconferencing units with high-definition monitors, omnidirectional microphones, and remote-controlled pan-tilt-zoom cameras. Pediatric trauma providers were provided access to workstations as well as video capable mobile devices.

Summary of Results

To date, 122 pediatric trauma patients have been enrolled. Protocol adherence for videoconferencing has occurred in 18 of 43 eligible patients; adherence for image sharing has occurred in 16 of 38 eligible patients. Collection rates of surveys of parent/family experience of care, distress, and financial burden surveys has been 65%. The ability of the specialty providers to connect using telemedicine has been limited by other clinical responsibilities, and protocol relies heavily on the NPs to administer telehealth communications and recommendations. Changes in implementation strategies and the workflow were made to increase the reliability and fidelity of the intervention, which will be shared in the presentation.

Conclusions

Implementing telehealth into acute pediatric trauma care is challenging. Challenges include incorporating videoconferencing by busy providers and implementing project-specific platforms at partner sites. However, with this commitment, acutely injured children can receive regionalized pediatric trauma expertise at the bedside in a receiving hospital ED. Current findings illustrate the need for qualitative data to improve the family experience.

Poster Session

Behavior and Development

6:00 PM

Thursday, January 20, 2022
#153 A survey of student attitudes about online learning via the zoom platform

C Bauer*

A Craft

Western University of Health Sciences, Pomona, CA

Purpose of Study

Despite decreasing attendance at live in-person lectures, this teaching method has remained a mainstay in medical education. Prior surveys of medical students have found that M1 students attend live lectures more than M2 students, while both years utilize the lecture recordings to supplement their education. With the COVID-19 pandemic, more lecture content has moved online, with some delivered synchronously and some recorded for asynchronous review.

A study of dental students’ perception found that 44% of students felt learning ‘somewhat worsened’ and 26% thought learning ‘significantly worsened’ with the move to online platforms during COVID-1. The same study found that students preferred synchronous learning experiences despite often choosing not to attend live lectures prior to the pandemic. This study seeks to evaluate similar issues in osteopathic medical students to determine a preferred mode of online learning, perception of their learning, and signs of burnout.

Methods Used

An anonymous survey was created and distributed via email to the students in the Classes of 2022, 2023, and 2024 at the College of Osteopathic Medicine of the Pacific. The survey consisted of 8 questions, three were yes or no responses, two were categorical responses, and three questions were based on a 10-point Likert scale. A goal of a 20% return of surveys was pre-established.

Summary of Results

Of the 995 students who received the survey, 292 (29.3%) completed the anonymous online survey. 54.1% of respondents were in the Class of 2024, 34.2% were in the Class of 2023, and 11.6% were in the Class of 2022.

On a 10-point scale, with 1 being highly dissatisfied, 55 (18.8%) students selected a score between 1 and 4 when evaluating satisfaction with a synchronous lecture via Zoom video conference technology compared to a live-in person lecture. 231 (79.1%) students found the video conference lecture as or more helpful than an in-person lecture. 165 (56.5%) respondents noted they were MORE likely to ask a question via the video conference lecture platform, compared to an in-person lecture.

When asked how likely they were to attend live in person lectures in the future, the responses demonstrated that students were evenly distributed, with 41 students (14.1%) responding absolutely not and 45 students (15.4%) responding definitely. Overall, 171 (58.6%) students stated that synchronous video conference-based lectures could fully replace live in person lectures.

Conclusions

Overall, students at this single medical school appear to have no significant preference for synchronous video conference-based lectures compared to live in-person lecture. Some students even suggested a greater willingness to participate and ask questions, whether verbally or via the chat function, during video, conference-based lectures. This preliminary data may allow for further investigation into how technology may impact the pedagogy for future generations of medical students.

#154 How do medical students rate resiliency in a pandemic?

S Dulani*

E Salimi

AL Nelson

M Hudson

Western University of Health Sciences College of Osteopathic Medicine of the Pacific-Northwest, Lebanon, OR

Purpose of Study

To assess the perceptions of medical students about the importance of resiliency in general and their own resiliency in a time of pandemic and to assess what external factors contribute to resilience, especially in the midst of a pandemic.

Methods Used

This IRB approved a survey for osteopathic medical students. The student survey questions were beta tested 3 times by students at other universities as well as examined by a professional in the field. All enrolled students at COMP/COMP-NW were sent an invitation to participate (~ 1,300 students) ages 18 and up. The invitation letter asked them to self-exclude if they were pregnant or believed that participation in the study could cause them to feel uncomfortable. We based our questions on the academic resilience scale to see if there are any associations between self-perception of stress, relationship style, negative affect and resilience levels in students. The survey consisted of 9 Likert scale questions, 4 multiple choice questions, and 1 open ended question. Multiple questions are derived from previous resilience scales.

Summary of Results

We obtained 130 responses (10% response rate). 46% were first year, 24% second year, 14% third year and 16% fourth year students. 51% were female. 40% said they had above average self-esteem, while 30% were neutral and 30% had below average self- esteem. 96% admitted to having anxiety in personal or professional relationships. 52% were likely to reflect on a stressful day, while 54% were likely to reflect on a successful day. This may show that students can be optimistic amid ongoing stress. 85% of students felt confident in their ability to persevere through challenging times. 65% of students were willing to ask for help in times of need while 16% were not willing to, and 19% were unsure. Students are most likely to turn to their spouse, friends, and themselves for support. 75% of respondents who had an opinion said that medical school had been the hardest time of their life. Only 40% of students were satisfied with their academic performance, and only 42% were satisfied with their general wellbeing. Financial hardship contributes to stress levels in 40% of students. The financial hardship does not seem to correlate with those that are unhappy in their academic performance and general well-being.

Conclusions

The students surveyed are optimistic; more of them were likely to reflect on a successful day compared to a stressful one. The high rate of anxiety in personal as well as professional relationships may impede students’ ability to seek personal or professional support when they need it. Students who do not have access to friends or family during times of hardship may have a harder time coping with stress.

#155 Impact of COVID-19 on rocky vista university medical students’ mental health: a cross-sectional survey

D Paz*

V Kuo

M Bains

V Bandi

M Zueger

M Payton

R Ryznar

Rocky Vista University, Parker, CO

Purpose of Study

The high prevalence of anxiety and depression among medical students has been previously linked to the rigor of medical school curriculums. Since late 2019, the COVID-19 pandemic has forced schools to make unprecedented yet unavoidable changes to their educational curriculums. This study is a quantitative analysis of the educational and psychological impacts of COVID-19 on first and second-year osteopathic medical students at Rocky Vista University.

Methods Used

A cross-sectional survey was administered to students at Rocky Vista University during the COVID-19 pandemic. Anxiety and depression levels were measured using validated questionnaires GAD-7 and PHQ-9. The remainder of the survey was a self-designed questionnaire that investigated potential associated factors, including sociodemographic characteristics, educational changes, and COVID-19 related concerns. The questionnaire also gauged the impact of COVID-19 on behavioral changes and strategies used to cope with the pandemic.

Summary of Results

One hundred fifty-two Rocky Vista University OMS-I and OMS-II students across both campuses participated. Overall, depression and anxiety levels due to the COVID-19 pandemic were increased from previously reported prevalence rates. Results showed that while the transition to an online based-curriculum was met with mixed feelings, most students found ways to effectively adapt their study habits amidst the pandemic. Notably, students reported feeling concerned that the transition in the curriculum will negatively impact their preparedness for clinical rotations. Overall, COVID-19 was found to have a negative impact on students’ mental health according to nearly all measures. However, the majority of students also reported finding new ways to cope with their stress and anxiety levels and nearly all students reported a willingness to assist with the pandemic.

Conclusions

This study demonstrates the significant detrimental effects of the pandemic on medical student mental health, which could impact the quality of care these future physicians provide. Thus, it is imperative to establish effective interventions to mitigate the negative repercussions of the pandemic.

* This work was presented in part at Rocky Vista University Appreciation Day (virtual) on October 15, 2021.

#156 Surveys of the perceptions of faculty about stress and resilience

E Salimi*

S Dulani

AL Nelson

M Hudson

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

Purpose of Study

To find out what the faculty’s perceptions are about resilience and its relationship to academic success in osteopathic medical school. Can resilience be acquired or is it an innate trait? If it can be acquired, then can it be formally taught? Who is responsible for this formal training and when could it be provided? Should resilience be a part of the DO curriculum?

Methods Used

This is an IRB-approved survey for all COMP faculty who interact within students in the pre-clinical years. The questionnaire was beta tested by 10 outside physicians and researchers. It consisted of 13 multiple choice questions and 2 open ended questions. 4 of the 13 questions used Likert scales. Letters of invitation that outlined the study purpose and its voluntary and anonymous nature were sent with the link to the survey, conducted via Qualtrics. Faculty were asked not to participate if they were pregnant or if they anticipated that the topic might cause them discomfort. We also sent out a reminder ~3 weeks after the initial letter that thanked those who had already responded and ask them not to do so again. At the same time, select faculty were approached to see if they would be willing to encourage their colleagues to participate in the study. We calculated the response rate and percentage distribution of the answers.

Summary of Results

The response rate is 21%. 55% of the respondents were clinical faculty, 30% basic science faculty, 5% both. 60% thought that resilience is more learned than intrinsic. 34% believed that resilience can be learned through life experiences and another 34% believed that it can be learned through informal teaching in context of individual challenge. 35% believed that there should be a more formal screening for resilience in applicants during the admissions process while 30% disagreed. 100% believed that resilience is either very important or extremely important to a medical student’s success. 75% believed that financial burdens are either very important or extremely important to students’ stress levels to their growth as a physician. 90% believed that resilience improves student’s academic performance by a lot or a great deal. All respondents reported that they work with students in some way to increase their resilience. 65% believe that formal resilience training should be a part of the DO curriculum for students and 85% believe that faculty would benefit from formal training about how to teach resilience.

Conclusions

Although osteopathic medicine places importance on holistic approaches to health, there are no requirements in the COCA curriculum to explicitly provide resilience training. The majority of the faculty thought that resilience is more learned than intrinsic. Therefore, it could be worthwhile to explore the possibilities of providing resilience training for both students and faculty.

Poster session

Cardiology

6:00 PM

Thursday, January 20, 2022
#157 Novel cholesterol lowering agents in setting of statin intolerance

S Noh1*

K Mai1

M Shaver1

S Yong1

M Mostaghimi1

G Oh2

MM Radwan1

1Western University of Health Sciences, Pomona, CA

2University of the Pacific Thomas J Long School of Pharmacy, Stockton, CA

Purpose of Study

Statins are the gold standard lipid-lowering therapy for atherosclerotic diseases. However, there is increasing evidence in support of combination therapies providing greater benefits to certain patient populations, particularly those intolerant to statins. Here, we discuss the efficacy, safety, and practical use of novel alternative and adjuvant agents that target low-density lipoprotein cholesterol (LDL-C) or lipoprotein(a) (Lp(a)).

Methods Used

A literature review was conducted on PubMed and Google Scholar based on research and clinical trials of cholesterol modulators primarily within the past decade.

Summary of Results

PCSK9 antibodies have been effective as adjuvant therapies in further reducing LDL-C levels and coronary atherosclerosis progression when added to statins. Importantly, the FOURIER and ODYSSEY OUTCOMES trials demonstrated that the addition of evolocumab and alirocumab remarkably reduced the risk of major cardiovascular events, respectively. Yet, expensive cost and administrative burden are impediments to practical use. PCSK9 siRNA inclisiran is an appealing alternative because of the marked reduction of LDL-C without significant adverse events as well as its lower cost and administrative burden. Bempedoic Acid (BemA) is another promising LDL-C lowering agent highlighted for its efficacy as both monotherapy and add-on to statins. BemA exhibits a favorable tolerability profile due to its exclusive activation in the liver, suggesting its potential as an alternative to statin-related myopathies. Future studies on its impact on cardiovascular outcomes may provide a greater appreciation of where BemA stands among LDL-C therapies. Antisense oligonucleotide therapies IONIS-APO(a)rx, IONIS-APO(a)Lrx, and AKCEA-APO(a)-Lrx have emerged as encouraging alternatives due to their efficacy and safety as Lpa(a)-lowering agents. Continued investigation as phase 3 trials may establish the potential of Lp(a) therapies as treatments for atherosclerotic disease.

Conclusions

Further investigation for all these novel approaches is needed to better appreciate the long-term efficacy, safety, and effects on cardiovascular outcomes. Overall, these cholesterol targeting therapies provide a promising outlook as alternatives for atherosclerotic patients for whom statins have been ineffective or intolerable.

Poster session

Diversity, equity, inclusion research

6:00 PM

Thursday, January 20, 2022
#158 Impact of implementation of smart goals for radiology trainee research and mentorship

T Bui1*

C Fateri1

D Kwan1

J Glavis-Bloom1

A Ushinsky2

M Helmy1

D Floriolli1

R Houshyar1

1University of California Irvine, Orange, CA

2Washington University in St Louis School of Medicine Mallinckrodt Institute of Radiology, Saint Louis, MO

Purpose of Study

Active research programs are particularly crucial to the field of radiology because the development of imaging technologies and subsequent translation of them into clinical practice drives the field forward. The SMART (Specific, Measurable, Attainable, Realistic, Time-bound) Goals framework is a validated goal-setting tool that has been successfully applied to medical education. In this prospective cohort study, we evaluated the implementation of the SMART Goals framework in radiology research. We hypothesized that engaging research trainees in formalized goal-setting would result in higher engagement in research and greater productivity.

Methods Used

After Institutional Review Board approval, medical students and radiology residents from a radiology research lab at a major academic center between the academic year of August 1, 2020 to July 31, 2021 were invited to participate. Inclusion criteria were those who filled out a SMART Goals form and participated in a formal review meeting. The comparison group was comprised of lab members from previous academic years (August 1, 2016 to July 31, 2020). Productivity was assessed by the number of publications, abstracts, and grants. For purposes of streamlining the data, the acceptance year was defined as the same as the submission year to best match the timeframe during which most of the work was completed. Additionally, participants’ beliefs about their knowledge and abilities were assessed using five-point Likert scale pre- and post-surveys. Descriptive statistics and two-tailed t-tests were calculated. Statistical significance was considered to be p <0.05.

Summary of Results

There were 19 individuals in the post-SMART group and 28 individuals in the pre-SMART group. The mean number of publications was 0.79 and 1.54 per individual in the pre-SMART and post-SMART groups, respectively (p = 0.02). The mean number of abstracts was 1.04 and 2.37 per individual in the pre-SMART and post-SMART groups, respectively (p = 0.02). The mean number of successful grants was 0.05 and 0.347 per individual in the pre-SMART and post-SMART groups, respectively (p = 0.01). Based on survey results, participants’ knowledge and comfort with research goals increased 1.54 points (p <0.01); with manuscript writing increased 1.21 (p <0.01); and with abstract submission increased 0.60 points (p = 0.01).

Conclusions

Dedicated learning goal creation through the SMART Goals framework has the potential to significantly increase the number of radiology trainees producing high-quality research, improve medical student and resident knowledge in research, and increase trainees’ confidence in their research skills.

#159 COVID-19 in ravalli county, montana: capturing the voices of healthcare leaders

N Johnson*

University of Washington School of Medicine, Seattle, WA

Purpose of Study

COVID-19 has strained rural Montana healthcare resources. Ravalli County, MT, is a rural county, and has dealt with the consequences of COVID-19 in its small towns. The National Humanities Center (NHC) in partnership with the University of Washington School of Medicine gave medical students the opportunity to perform qualitative research by gathering oral histories at rural sites. The interviewer for this project worked to record and preserve the stories of healthcare leaders in Ravalli County. The interviewer’s goal was to remain unbiased, listen openly to all stories, limit interruptions, and learn about the effect COVID-19 had on the county.

Methods Used

Interviewees for the project were recruited through email, phone call, and text message. Connections were made with the help of Ravalli Family Medicine. Four total interviews were done with folks in healthcare positions including: two Directors, an Administrator, and a Technical Supervisor. All were conducted in person at private locations, each being audio recorded and lasting about an hour. The same set of questions was used with all interviewees. Interview skills training was led by Jacqueline Kellish, Ph.D., Director of the COVID-19 Oral History Initiative at the NHC. Training emphasized skills in active listening and communication, focusing on building trust with interviewees.

Summary of Results

Information gathered on the community response to COVID-19, how folks worked to survive during the pandemic, and how vaccination roll-out happened in the county created a story of the pandemic in rural Montana. These oral histories and their take-aways will be used to educate others about rural experiences during the pandemic and contribute to the larger NHC collective database. In the county, these interviews sparked discussion about vaccines and education.

Conclusions

Ravalli County was hit hard by COVID-19 and serves as a window into the rural experience of the pandemic. Leaders emphasized the importance of advocacy, education, and preparedness and have brought these lessons to their communities. Strategies for vaccine education and confidence would benefit rural communities and reduce a strain on resources. This individual project is limited by its small sample set of four interviews. Sharing these stories and their lessons will contribute to a meaningful positive discourse on living through a pandemic.

#160 Journal club implementation as an educational tool for medical trainee research and mentorship in radiology, a pilot study

D Kwan*

T Bui

C Fateri

J Glavis-Bloom

R Houshyar

University of California Irvine, Orange, CA

Purpose of Study

Interpreting medical literature is an essential skill set for physicians to acquire as physicians must be able to determine the validity of research that may influence their practice. A baseline competency in the basic components of research (i.e., identifying bias, data interpretation, etc.) is imperative for effective clinical practice and clinical research. The purpose of this study is to assess the impact of a journal club on trainee’s confidence and knowledge base in fundamental components of research literature.

Methods Used

After Institutional Review Board approval, members of the Computational Abdominal Radiology research lab, predominantly medical students and radiology residents, at a major academic center were invited to participate in this study. Journal club sessions were conducted from April to September 2021. Articles from leading peer-reviewed radiology journals were selected to highlight a specific component of research. Pre and post journal club session surveys were distributed among lab members via Microsoft Forms using Likert scales to assess trainee confidence and multiple-choice questions to assess knowledge base. Survey results were compared using a paired two-tail t-test with statistical significance set as p < 0.05.

Summary of Results

On average, participants displayed an increase in confidence in topic knowledge (pre-test mean = 4.29 ± 0.31 versus post-test mean = 5.91 ± 0.33, p = 0.004). However, the difference in percent correct answers between the pre-test (mean = 0.77 ± 0.25) and post-test (mean = 0.85 ± 0.13) indicated that there was not a significant increase in correct answers after the journal club sessions (p = 0.42).

Conclusions

The results of this pilot study indicate that a journal club can be effective in increasing participants’ confidence in the basic fundamentals of research, although its limited application has not yet been shown to increase aptitude. Additional journal club sessions, repeated exposure to key topics, and longer follow up beyond this pilot study are needed to better assess the efficacy of the impact of journal clubs in the setting of research and clinical mentorship in radiology.

#161 Indoor walking track as opportunity for older adults to exercise during winter in Valdez, Alaska

M Weyhrauch*

University of Washington School of Medicine, Seattle, WA

Purpose of Study

The two most recent community health need assessments performed in Valdez, Alaska identified ‘lack of physical activity/overweight’ as a top health need. 66% of Valdez adult residents are reportedly overweight or obese and about 10% report they do not engage in any form of physical activity. Rural residents are generally less physically active than their urban counterparts and disproportionately affected by chronic diseases associated with insufficient activity. Getting the amount of recommended exercise in rural areas is a challenge where lack of infrastructure, weather dependency, and safety are common barriers.

Methods Used

Information was gathered in the context of a clinical immersion in Valdez, Alaska. Patient and provider interviews were conducted at the Valdez Medical Clinic to discover community health concerns and local organizations that are working to counter concerns. An interview at the Department of Parks, Recreation, and Cultural Services (DPRCS) for the City of Valdez detailed available programs, resources, and future proposals. A literature review was then conducted to examine interventions that could build on Valdez’s existing assets.

Summary of Results

A literature review identifies that increasing steps per day is an easy way to start and maintain a healthy lifestyle, however this is a challenge during the extended winter months. Step count drops precipitously as snow level increases, daylight decreases, and temperatures drop. Fear of falling is a major environmental barrier for older adults in rural areas. DPRCS has an ongoing feasibility study for a new recreation facility that could include an indoor track if community members show interest. This research highlighting the potential benefits of an indoor walking track has been sent to a manager at the DPRCS. This could potentially be used to advance the current feasibility study.

Conclusions

An indoor track, as part of a new recreation facility, could provide a safe, affordable, and accessible place for older adults to exercise year-round. Annual property taxes paid to Valdez by the Trans-Alaska Pipeline could provide an avenue to pay for the infrastructure. This indoor track could combat the tough environmental conditions that make exercise particularly challenging during the Valdez winter.

Poster session

Genetics

6:00 PM

Thursday, January 20, 2022
#162 Variable expressivity in NTRK1-congenital insensitivity to pain with anhidrosis (CIPA)

AD Niehaus*

CG Tise

M Manning

D Stevenson

Stanford University, Stanford, CA

Purpose of Study

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare disorder caused by biallelic loss-of-function (LOF) pathogenic variants in NTRK1. NTRK1 encodes TrkA, a receptor tyrosine kinase for nerve growth factor essential for survival of autonomic sympathetic postganglionic neurons. The disorder is characterized by decreased pain perception and inability to perspire effectively, as well as varying degrees of intellectual disability for which the underlying mechanism is not well understood. Insensitivity to pain often leads to repeated injuries, oral self-mutilation, skin infections, and fractures; anhidrosis predisposes individuals to hyperthermia and seizures. Here we describe two individuals with CIPA secondary to different homozygous LOF pathogenetic variants in NTRK1 and provide further evidence of the extreme phenotypic variability of the disorder.

Methods Used

Chart review, physical examination, and literature review.

Summary of Results

The first individual was a male evaluated at 20-months of age with severe global developmental delay, diffuse hypotonia, and extreme self-mutilation habits including tongue-biting requiring tooth extraction and finger-biting requiring restraints/bandages. He was found to be homozygous for a novel intragenic deletion including exons 4 and 5. The second individual was a typically-developing girl evaluated at 5 years of age with a history of irritability as an infant secondary to anhidrosis, successfully recognized and since treated by her parents with cold, wet towels. She had no history of autonomic or temperature crises, severe self-mutilation, fractures, nor prior hospitalizations, but was found to be homozygous for the founder variant NTRK1 (c.851–33T>A) after parents were identified as carriers by preconception carrier testing prior to their second child.

Conclusions

While the individuals described here were found to have different variants in NTRK1, the profound differences in their outcomes highlights the phenotypic variability of this disorder. These cases support a previously published hypothesis that individuals homozygous for the founder variant (c.851–33C>T) may present with a milder phenotype, despite this variant having a deleterious effect on protein structure (Wang et al., 2018). Lack of a clear genotype-phenotype correlation in the literature indicates genetic or environmental modifiers may be at play. Lastly, the value of early diagnosis should be further explored, especially if there is evidence suggesting earlier intervention improves outcomes.

#163 Novel heterozygous P3H2 variants in a child with early-onset non-syndromic degenerative high myopia

VD Tang1*

A Egense1

M Estrada1

SP Shankar1,2

1University of California Davis, Sacramento, CA

2University of California Davis, Davis, CA

Purpose of Study

To report on P3H2 variants causing non-syndromic high degenerative myopia guiding precision medical care.

Methods Used

Chart review, Next-generation sequencing (NGS) panel, and exome trio genetic testing.

Summary of Results

A 3-year-old male with bilateral degenerative high myopia (-12.75 diopter spherical (DS)) and refractive amblyopia diagnosed at 2 years of age, was referred to genomic medicine. He was born full-term with an unremarkable prenatal and birth history. His developmental milestones were normal other than mild articulation difficulty. Family history was significant for myopia of -3.00 DS. Physical exam was normal other than midfacial hypoplasia and depressed nasal bridge. Testing in the connective tissue panel, including Stickler syndrome genes and FBN1 for Marfan’s syndrome, was negative. Several rare non-syndromic myopia genes have been reported; however, given the lack of NGS panel, an exome trio was ordered. This identified two pathogenic variants in the P3H2 gene, c.1372 C>T, p.Q458* and c.1328del, p.G443Vfs* in trans, confirmed by parental testing. P3H2, also called LEPREL1, encodes the Prolyl 3-hydroxylase-2 enzyme, which performs the 3-hydroxylation of proline residues in collagens. Tissues from the eye, including the sclera, cornea (type 1), and lens capsule (type 4), are composed of collagen. The abnormal collagen molecule processing may cause weakened collagen in eye tissues. Mutations in the P3H2 gene have been associated with non-syndromic early-onset severe myopia with cataracts, lens instability, vitreoretinal degeneration, and risk of retinal detachment mostly in consanguineous families as homozygous variants. There are no reported skeletal issues or syndromic features. The variants in our proband have not been published in the past, but they have been reported once in ClinVar with different variants considered pathogenic.

Conclusions

The degenerative high myopia in our proband is due to pathogenic heterozygous variants in the P3H2 gene, consistent with non-syndromic severe myopia and refractive amblyopia. This molecular diagnosis guides management of potential ocular risks and prevents unnecessary systemic evaluation, such as echocardiograms. It will influence the patient’s future lifestyle choices, such as avoiding contact sports and choosing suitable careers. It also eased parental anxiety and offered more accurate inheritance and recurrence risk counseling for parents and extended family.

#164 Improved access to clinical genetics services via genetic counselor led hearing loss clinic

M Dutra-Clarke*

S Glover

B Russell

University of California Los Angeles, Los Angeles, CA

Purpose of Study

There are over 200 genes associated with non-syndromic and syndromic hearing loss (HL). Knowing the underlying genetic etiology helps to determine prognosis including whether it is expected to be stable vs progressive, isolated, or associated with other organ systems requiring surveillance (e.g. eyes, heart, kidneys), and when planning for cochlear implant. It guides medical management such as early access to developmental services, inform recurrence risks for the family, eligibility for future gene therapy, and avoidance of invasive imaging (e.g. CT scan) and aminoglycosides. Early genetic diagnosis is critical. Due to long wait times to see a clinical geneticist, we developed a genetic counseling (GC) clinic where patients with non-syndromic HL receive genetic counseling and testing by a certified genetic counselor. The purpose of the study was to compare wait times for a consult with a GC vs clinical geneticist and determine the diagnostic yield on genetic testing for apparently non-syndromic HL. The intent was to track productivity, measure the effort allocated for this clinic, and plan adjustments and future needs.

Methods Used

We conducted a retrospective chart review of patients with apparently non-syndromic HL seen in the Genetics Division at UCLA between Jan 2020–Sept 2021 (ages 2 mos-58 yrs). We separated patients into two groups: (1) seen by a clinical geneticist with a genetic counselor (MD+GC) or (2) seen only by a genetic counselor (GC-only). We compared time from referral to initial visit to return of results. Panel-based genetic testing of 150–224 genes was done in a clinical setting.

Summary of Results

There were 25 patients seen by MD+GC and 17 patients seen by GC-only. The average time from referral to initial visit was 80 days for MD+GC (n=22) and 16 days for GC-only (n=17). The average time for testing was 48 days in the MD+GC group (n=25) and 79 days in the GC-only group (n=6), which varied between labs. The average time from referral to return of results was 207 days for MD+GC (n=21) and 126 days for GC-only (n=6). The diagnostic yield on genetic testing was 53%, and up to 69% when filtered for prelingual bilateral sensorineural hearing loss. In total, 17 were positive, 5 had variants of uncertain significance, and 10 were negative (n=32). Four patients with postlingual onset HL had pathogenic variants in GJB2, MYO7A, SLC26A4, CEACAM16. Two patients with unilateral prelingual onset HL had pathogenic variants in MITF and MT-TK.

Conclusions

A genetic counseling (GC) clinic for non-syndromic HL was effective as measured by improved turnaround time for results, patient satisfaction, feedback from referring providers, and reimbursement by insurance. GC clinics allow genetic counselors to practice at the top of their scope and improves patient care.

#165 Uncommon neuroimaging findings in inborn errors of metabolism

JA Morales1*

FP Velez-Bartolomei2

M Ruzhnikov1

GM Enns1

1Stanford University, Stanford, CA

2San Jorge Children and Women’s Hospital, San Juan

Purpose of Study

Inborn errors of metabolism (IEM) are often associated with neurodevelopmental/neurological features such as intellectual disability, autism, epilepsy, hearing loss, hypotonia and movement disorders.

Underlying structural brain abnormalities, like disorders of neuronal migration and/or primarily symmetric signal abnormalities of basal ganglia or white matter, are also common features for certain IEMs.

In this study, we describe two individuals with distinct IEMs: Glutaric acidemia type 1 (GA1) and Congenital disorder of glycosylation type IIs, (CDGIIs), who presented with intracranial abnormalities not previously or rarely described.

Methods Used

Literature & retrospective chart review, clinical evaluations.

Summary of Results

1. An 18-year-old male previously diagnosed with GA1, presented with a first-time generalized tonic-clonic seizure. Comorbidities include spastic quadriparetic cerebral palsy and lack of verbal speech, likely secondary to past metabolic crises.

Brain MRI showed diffuse cerebral white matter, basal ganglia and brainstem abnormal diffusion. Multiple subependymal nodules along the ventricular margins were also detected.

A comprehensive brain malformations gene panel was not clinically relevant.

2. A 21-year-old male with an underlying diagnosis of CDGIIs, presented with an episode of left face and arm numbness, and left facial droop at age 15 years. His comorbidities include complex partial epilepsy, hypogammaglobulinemia, beta-thalassemia intermedia, tethered cord, kyphosis, cirrhosis, and portal hypertension. Brain MRI demonstrated severe narrowing of the supraclinoid internal carotid arteries concerning for Moyamoya disease. This was confirmed through cerebral angiogram, and corrected by bilateral cerebral artery bypass grafts.

Conclusions

These specific brain imaging findings have rarely been reported in IEMs. Subependymal nodules have been found in four other patients affected by GA1, three of whom were adults. Moyamoya disease is thought to arise from either tunica intima proliferation or abnormal angiogenesis and can be associated with genetic disorders such as Down syndrome or RNF213. While the number of known patients with CDGIIs is small, none have been identified with Moyamoya disease and we are unaware of other CDG subtypes associated with this.

Given the low incidence of these rare conditions, it is not possible to determine a pathophysiologic link or direct correlation. However, in the absence of a secondary condition that could explain these findings, it is worth considering them as part of the broad phenotypic spectrum for these particular IEMs. Neuroimaging should be part of the diagnostic work-up upon presence of suggestive neurologic symptoms.

#166 Pediatrics residents and fundamentals of genetic testing: self-perceived knowledge and confidence

R Gates*

L Hudgins

LC Huffman

Stanford University, Stanford, CA

Purpose of Study

Genetic testing is becoming ubiquitous in the field of medicine and is often ordered or requested by primary care providers, non-genetics subspecialists, and patients themselves. Previous studies have demonstrated that primary care providers are often not comfortable ordering genetic testing and counseling families about genetic testing results. There have been initiatives to teach these concepts to practicing physicians via continuing medical education, however, there is no standardized training to teach resident physicians about genetic testing.

Methods Used

This was an IRB-exempt study. In September-October 2020, we recruited all active Stanford pediatrics residents via email (n=102). Participant residents completed an investigator-developed Qualtrics electronic survey that addressed self-perceived current level of knowledge about fundamentals of genetic testing, as well as confidence discussing these fundamental issues with families. The survey included 19 items, with Likert scale and open-text response formats. Likert scale responses (Not at All/Slightly and Moderately/Very/Extremely) were combined into two response categories (Insufficiently and Adequately). Chi-Square test of independence was performed using IBM SPSS Statistics software.

Summary of Results

Response rate was 46/102 (45%); all training levels were represented (PGY1 33%, PGY2 24%, PGY3+ 42%). Proportions of respondents who were ‘Adequately’ knowledgeable about fundamentals of genetic testing ranged from 20% to 72%. Smaller proportions of respondents were ‘Adequately’ confident discussing these concepts with families, ranging from 7% to 65%. Self-reported knowledge and confidence were highest across items for the PGY1 group, with statistically significant differences in proportions of PGY1, PGY2, and PGY3+ describing themselves as ‘Adequately’ knowledgeable of basic concepts (93%, 73%, and 53%, respectively; p=0.034) and in proportions describing themselves as ‘Adequately’ confident during discussions of genetic testing limitations (64%, 9%, and 27%, respectively; p=0.045). The majority (89%) of pediatrics residents agreed that a curriculum teaching basics of genetic testing would be helpful to them. Desired curricular topics included: indications/limitations of genetic testing, procedure for testing, and counseling families.

Conclusions

Despite its increasing importance in medicine, medical genetics education is lacking in pediatrics residency programs. This single-institution educational needs assessment suggests that more advanced pediatrics residents have a greater awareness of deficits in genetics-related knowledge and confidence. Residents agree that they would benefit from a curriculum that teaches fundamentals of genetic testing during training. Future studies should evaluate these themes across multiple institutions and implement a curriculum that assesses pre- and post- intervention knowledge and confidence.

#167 Neonatal COVID-19 encephalitis with an incidental PTEN pathogenic variant

A Sosa1*

J Woods1,2

1Valley Children’s Healthcare, Madera, CA

2Stanford Medicine, Stanford, CA

Purpose of Study

Neonatal COVID-19 encephalitis is a disease that has been rarely reported during the COVID-19 pandemic. Given the rarity of the disease the signs associated with neonatal COVID-19 encephalitis may easily be confused with other encephalopathies. Here we describe a case of neonatal COVID-19 encephalitis that prompted genome sequencing due to findings on a brain MRI. Genome sequencing discovered a pathogenic variant in PTEN, which is likely unrelated to the COVID-19 encephalitis but has serious lifelong health implications.

Methods Used

Chart review.

Summary of Results

The patient was a 3 week-old female who was admitted to the PICU for seizures and upper respiratory tract infection signs in the setting of COVID-19 positive contacts at home. An MRI of the head demonstrated patchy white matter degeneration interpreted by radiology as consistent with viral encephalitis or a metabolic disorder. The genetics service was then consulted and determined that the patient likely had COVID-19 encephalitis. However, out of an abundance of caution rapid trio genome sequencing was sent. The genome demonstrated a de novo pathogenic missense variant in PTEN (chr10–89720679 C>T). This variant is well known to be pathogenic of PTEN hamartoma tumor syndrome (PHTS). This variant was determined to be unlikely relevant to her inpatient care and the baby discharged home on Keppra five days later.

Conclusions

Rapid genetic testing is a powerful tool for clinical decision support, though incidental findings may complicate genetic counseling and clinical care. There is no evidence supporting pathogenic variants in PTEN increasing the susceptibility to COVID-19 encephalitis. Neonatal onset PHTS would also be unusual and macrocephaly would be expected and the patient was actually microcephalic. The parents opted not to learn about incidental findings, which further complicated the disclosure of results as the PTEN variant was reported by the lab despite the fact that it was an incidental finding unrelated to the patient’s current illness. However, the parents were thankful to learn about the PTEN variant given the risks for neurodevelopmental delay and neoplasms associated with PHTS. PHTS is associated with a variety of neoplasms, most of which are adult onset. However, follicular or papillary thyroid cancer can occur as young as seven years of age in PHTS. Thus the patient will follow up with genetics for evaluation of neurodevelopment and thyroid cancer screening.

Poster session

Healthcare delivery research

6:00 PM

Thursday, January 20, 2022
#168 Trust in Oregon health authority policies during COVID-19

H Graham*

M Gentry

M Jette

E Kim

J Spaan

Western University of Health Sciences College of Osteopathic Medicine of the Pacific-Northwest, Lebanon, OR

Purpose of Study

The purpose of this project was to discern trust in the healthcare system during the COVID-19 pandemic in Oregon communities. Our hypothesis was that if a person trusted the health care system, then they would agree with the statements and follow the COVID-19 policies put forth by the Oregon Health Authority (OHA).

Methods Used

We measured trust by analyzing when behavior matched opinion in accordance with the research by Lazarus et al, 2019 that said higher trust in a healthcare system can be demonstrated by higher compliance with policies. To assess this, we conducted a survey that asked people about their behavior during the timeframe of April 2020 through November 2020 with a yes or no question. We then asked them to answer if a specific OHA policy would help prevent the spread of COVID-19 on a Likert scale. Our survey was distributed via email and over social media from the timeframe of April 4th, 2021, through April 7th, 2021. We closed our survey on April 7th, 2021, after we realized we had aberrant data most likely due to a computer-generated survey hack that began to occur on April 8th, 2021. After closing the survey, we were left with a total sample size of 124 responses from 12 different Oregon counties aged 18 years and older.

Summary of Results

In order to analyze the data, we gave a numerical value to each question response so that the higher values would be awarded to the responses that aligned with the OHA policies. In the policy agreement section, the scores were: strongly disagree = 1, disagree = 2, agree = 3, strongly agree =4. If they answered with a ‘neutral’ regarding their feeling of OHA policies protecting against COVID, they were assigned a score of 0. The lowest scores correlated with people that never followed OHA recommended behavior and who strongly disagreed that the OHA policies would prevent infections. The higest possible score was 38 which represented the most trust in OHA. When analyzing the results, we found our respondents demonstrated a spectrum of trust in OHA with the total lowest score being 13 and our highest score being 38 with an average score of 31.4. This average score correlates with people having COVID conscious behaviors and agreeing or strongly agreeing with most of the OHA statements.

Conclusions

In conclusion, these data points align with our hypothesis because they illustrate an agreement with OHA policies and a behavior that acts in accordance with that policy. Further research should include a larger sample size to better represent the population of Oregon, as well as measures to prevent survey hacking. Results could also be collected at multiple time points as the status of the pandemic is constantly in flux. When applied on a larger scale, this data could help public health officials gauge the trust of the populations they serve and lead to better health outcomes.

#169 Does insurance status influence maternal mortality: a scoping review

J Hannan1*

A Bertotti Metoyer1,2

1University of Washington, Seattle, WA

2Gonzaga University, Spokane, WA

Purpose of Study

Maternal mortality in the US is the highest of all developed countries. Change in health insurance policy, such as extension of postpartum Medicaid, is frequently proposed as a possible solution to reduce maternal deaths. The goal of this review is to identify and summarize literature describing association of health insurance status on maternal mortality.

Methods Used

We performed a scoping search of the databases PubMed, Web of Science Core Collection, Embase, and CINAHL using keywords related to maternal mortality and health insurance. Inclusion criteria required studies to be within the US and use empirical data from 1990 to present. Studies were excluded if they did not compare more than one insurance type or did not examine mortality separately from morbidity. Any numerical data related to mortality was extracted. Search results and articles were screened by two researchers.

Summary of Results

Our database search yielded 894 results, of which 38 proceeded to full text screening and 17 were included in this review. Our study found that literature directly examining the association of insurance on maternal mortality is not very prevalent. Among the literature that is available, study design is varied. Units of analysis are either state aggregate data or individual mortality data. Additionally, some studies focus only on in-hospital mortality, while others include postpartum deaths within six weeks to one year of delivery. Three included studies examine state level policy, and within aggregated data, generally show increased insurance coverage rates are correlated with lower maternal mortality rates. The remaining 14 included studies use individual mortality data. Only two specifically examine insurance type as a causal factor. The other 12 examine insurance as one of many factors related to mortality and within a subsection of larger analyses, such as investigations of specific causes of maternal deaths or regional mortality case reviews. Two case control studies show a non-statistically significant effect of insurance, and one showed a higher proportion of private insurance among women who died. The remaining nine individual data studies show varying degrees of mostly beneficial correlation between being insured and reduced maternal mortality, with private insurance being more protective than Medicaid when examined. Effect size varies significantly by racial group both in state and individual data.

Conclusions

Despite significant commentary on the topic, literature examining the effect of health insurance status on maternal mortality is scant. However, state-level research suggests that health insurance access may reduce probability of maternal mortality. This trend requires further examination at the individual level to determine mechanism and degree of effect. Understanding this effect would aid development of future health insurance policy accordingly.

#170 Interventions to address health disparities in colorectal cancer screening among the minority populations in the United States

S Hosseinian1*

S Afzal1

E Bolt1

J Gu1

D Lee1

P Pragash1

S Sacchetto1

B Afghani1,2

1UC Irvine school of medicine, Orange, CA

2Children’s Hospital of Orange County, Orange, CA

Purpose of Study

Colorectal cancer in underserved or minority populations is associated with increased morbidity and mortality. Factors related to this disparity are complex and multifactorial but one of the reasons is due to lower participation rates in colorectal cancer (CRC) screening. The purpose of this study is to review the interventional studies and compile the best practices to increase CRC in minority populations.

Methods Used

A literature review was conducted through PubMed, Google Scholar, and Sci-Hub databases using keywords: ‘colorectal cancer’ ‘screening’ ‘minority’ African-American’ ‘Hispanic’ and ‘intervention.’ Inclusion criteria included interventional studies: that included a control group, consisted of a population of at least 50% minority, participants over the age of 50, and published after 2005.

Summary of Results

A total of 8 studies satisfied our inclusion criteria (see table 1). The majority of the studies showed an improvement in CRC screening rates but the outcomes measured varied, and included fecal occult blood test, sigmoidoscopy, or colonoscopy. Interventions also varied, and included patient navigation in most of the studies and/or physician-level education in a few studies. Therefore, it was difficult to compare the interventions in different studies because of different study designs and outcomes. After intervention, the CRC screening rate ranged from 27% to 94% in different studies. It appears that interventions that were more personalized and required repetitive reminders or contact seemed to be more effective.

Abstract #170 Table 1

Interventional studies to improve colorectal cancer (CRC) screening among the minority population

Conclusions

Our literature review suggests interventional strategies are useful in increasing colorectal cancer screening in the minority population. However, even after intervention, CRC screening remained suboptimal. Larger studies are needed to identify barriers at the individual, health provider and community level and measure the impact of targeted intervention to overcome those barriers.

#171 A comprehensive review of women’s questions following miscarriage on different social media platforms

EG Ong1*

L Davis1

A Sanchez1

R Curiel1

H Stohl2

A Nelson1

N Robinson2

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

2Harbor-UCLA Medical Center, Torrance, CA

Purpose of Study

The purpose of this study was to investigate common questions and the accuracy of advice related to miscarriage that women post on social media to identify any gaps in miscarriage care, counseling and give learners insight into the experience of miscarriage.

Methods Used

Public social media posts from January 1st 2019 to June 30th 2021 were searched using the keywords of ‘miscarriage’, ‘preterm birth’, ‘pregnancy loss’, ‘early pregnancy loss’, ‘early fetal loss’, ‘spontaneous abortion’, ‘spontaneous pregnancy loss’ and ‘#IHadAMiscarriage’. Only public posts in English and originating from the United States were included. No private identifiable information was collected. The inclusion criteria for posts varied by site: all posts in public Facebook Miscarriage groups, YouTube videos with ≥1000 views, Reddit r/Miscarriage with ≥175 upvotes, Instagram photos with ≥50 likes and Tweets with ≥1 interaction were analyzed for mentions of questions, advice, and conflicts of interest. Each theme in a post was counted. Advice was classified into categories of ‘accurate’ if it was supported by current professional association guidelines, including the American College of Obstetricians and Gynecologists (ACOG). ‘Insufficient evidence’ was advice only supported by published reports, and ‘inaccurate’ if any part was against clinical guidelines or was unsupported.

Summary of Results

For women and families experiencing miscarriage, social media has become a popular outlet and resource for support. 103 posts were identified for common themes. The most common themes identified included: questions on grief (20.4%), blame (19.4%), quality of post-partum counseling (14.6%), and lack of medical support/follow-up (13.6%). 82.9% of advice mentioned the emotional consequences of loss. 17.1% of posts offered medical advice eligible for evaluation, with the most accurate platforms being YouTube (66.6%), Instagram (100%) and Reddit (100%). The least accurate platform was Facebook (33.3%). Twitter yielded the fewest results that met the inclusion criteria.

Conclusions

Many women who post on social media struggle with grief, blame and look for better support from the medical community. The majority of the online community of women who have had miscarriages offer advice related to grief and coping with loss rather than questions regarding medical information. Thus, clinicians may advise women to use social media as a resource to connect with others in their loss and grief. Social media may also be used as an invaluable resource for learners to empathize with women and their families after miscarriage. The ability to better understand the experience and impact of miscarriage will hopefully improve the quality of miscarriage care.

#172 Medical learners views on learner feedback to build program camaraderie

R Buller1

AG Raja2*

P Poysophon1

T Allison-Aipa1

1Riverside University Health System, Riverside, CA

2Western University of Health Sciences, Pomona, CA

Purpose of Study

There is little focus on how residents and fellows can give feedback to program faculty in residencies and fellowships in the United States. This study aims to determine if learners feel comfortable giving feedback, the preferred method of feedback, and whether this feedback correlates with a culture of camaraderie between residents and faculty. It has been shown that building camaraderie improves health outcomes for patients and improves physician wellness by creating an overall positive atmosphere.

Methods Used

A questionnaire using both multiple choice and open response questions was sent to all 125 residents and fellows at the Riverside University Health System medical program. The survey was composed of questions regarding honesty in giving feedback, preferred feedback method, and if learners thought increased feedback helped build camaraderie. Cronbach’s alpha was calculated to determine internal validity. Descriptive statistics and a correlation coefficient were calculated from survey responses.

Summary of Results

From the 26 responses, results showed that 54% of learners felt comfortable giving feedback to their program and 50% of learners preferred individual, anonymous, written feedback as their method of choice. There were strong correlations between the use of feedback and feelings of camaraderie. Learners who were able to provide feedback had a strong correlation with learners who felt camaraderie with their faculty (p<.001). 75% of learners who preferred one-to-one verbal feedback in general also preferred this method to improve camaraderie, compared to 14% of learners who chose group written feedback. When they differed, students chose group verbal feedback to improve camaraderie.

Conclusions

Our study shows that allowing residents to give feedback to their mentors can increase camaraderie, which is known to improve outcomes: patient health outcomes and physician wellness. Furthermore, this study provides a look into learners perspective and leads the way for future studies to provide more causal links between learner feedback to physician wellness and patient health.

#173 Options to expand home healthcare in Cordova, AK

JT Bramante1,2*

1University of Washington, Seattle, WA

2University of Alaska Anchorage, Anchorage, AK

Purpose of Study

Patients in Cordova, Alaska lack access to standard home healthcare services such as home health agencies (HHAs) or assisted living facilities (ALFs). Patients with complicated medical issues who are homebound and often do not have robust social support in the community must rely on physician home visits or be admitted to the hospital’s long term care facility. In order for either of the primary care clinics to bill medicare for home visits, a physician must be present, which significantly limits availability of home visits.

Methods Used

Patient and provider interviews were conducted at the Cordova Community Medical Center and Ilanka Community Health Center (Ilanka). An asset-based research approach was used to identify other community entities that could potentially impact health for homebound individuals. An interview was conducted with the Cordova Police Department, which provides wellness checks for individuals in the community. A literature review was conducted to evaluate the efficacy of home health intervention programs in addressing needs present in the community such as hospice and wound care. State and national regulatory institutions were then contacted to ascertain the options for expanding Centers for Medicare & Medicaid Service (CMS) coverage of the local primary care centers to include visiting nurse services.

Summary of Results

It was determined that Ilanka, which is registered as a Federally Qualified Healthcare Center with CMS, would be eligible to be compensated for visiting nurse services given that there is a shortage of HHAs in the area. However, since they are not located in an area that has been officially designated as having a shortage by the state, and there is no official path to achieve this in Alaska, they must petition their CMS Regional Office.

Conclusions

This asset-based research approach identified a strong community need in Cordova for expanded home healthcare. A CMS regulation was identified that would allow Ilanka to be compensated for visiting nurse services. However, information on the approval process was very difficult to find. This need is likely shared by other rural communities in the state that are large enough to have a primary care center but not necessarily support an independent HHA or ALF, but there are no governmental processes to support approval. Recent efforts in the state of Washington might provide a template for centralized support and streamlining of the approval process.

#174 The impacts of covid-19 on the social perceptions of breastfeeding

A Mehta1*

EA Wright1

AL Nelson1

H Stohl2

M Economidis2

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

2University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

Purpose of Study

There is a growing concern amongst physicians that the increased stress of COVID-19 has significantly impacted the number of women choosing to breastfeed. However, not many qualitative studies address whether COVID-19 has impacted breastfeeding perceptions. This study aims to identify hidden challenges women face while breastfeeding and to determine if those changed with the onset of the pandemic.

Methods Used

This research was conducted manually across two social media sites, Reddit and TikTok, using the search terms ‘breastfeeding,’ ‘breastisbest,’ and ‘fedisbest.’ Posts with the most comments from pre-pandemic times [Jan 1, 2018 to March 15, 2020] were compared to the posts with the most comments from [March 15, 2020 to June 15, 2020]. Each post and comment was categorized into a theme, and thematic saturation was achieved after three comments mentioned the same theme. In order to establish a theme, there must be at least five posts speaking about that topic.

Summary of Results

248 posts were analyzed with a total of 433 mentions of the selected themes. Fifteen themes were noted across both Reddit and TikTok, and the top 2 themes across both platforms were ‘providing medical advice’ and ‘supporting women’s breastfeeding decisions.’ On Reddit, ‘supporting women’s breastfeeding decisions’ was the most mentioned theme before the onset of the pandemic (37.2%), but ‘providing medical advice’ became the most mentioned theme after COVID-19 (42.4%). 60.0% of the posts on TikTok: After COVID19 included ‘providing medical advice’ while only 42.4% of the posts on Reddit: After COVID19 provided medical advice. Despite data showing reduction in breastfeeding support on the maternity ward and a shortage of breastfeeding support equipment, 10.6% of posts on Reddit noted COVID-19 positively affected breastfeeding. Some comments included the fact that not allowing visitors in hospitals and in their homes initially allowed them to successfully connect with their babies and initiate breastfeeding. Two women mentioned that they could choose to stay away from their in-laws who discouraged breastfeeding, using the excuse of the pandemic. Other comments mentioned a more flexible online work schedule allowed them to plan their meetings around scheduled breastfeeding sessions.

Conclusions

Social media platforms provide a niche community for breastfeeding women to communicate with and support each other. Despite the stress of COVID-19, posts on Reddit illustrated that the pandemic positively impacted women’s abilities to breastfeed. We hope that this study encourages physicians to engage in deeper conversations with their breastfeeding patients to help them better critically analyze information online but still receive the positive community support they need.

#175 Function of social media on premenstrual dysphoric disorder

N Poladian*

A Maron

T Ghazarian

AL Nelson

Y Fernandez-Sweeny

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

Purpose of Study

Premenstrual Dysphoric Disorder (PMDD) is a common and debilitating disorder that affects reproductive age women. With society’s growing reliance on social media and the emergence of various social platforms, many patients turn to social media outlets for information. This practice also holds true for women seeking information surrounding PMDD, and those investigating their symptoms. This study was designed to provide clinicians with a better understanding of the content, support, as well as wealth and accuracy of information surrounding PMDD found in a popular social media site, Reddit, often used to investigate medical topics.

Methods Used

In this IRB-approved study, we analyzed the content of posts on the subreddit titled ‘PMDD,’ in public domain Reddit, from January 2020 through May 2021. Posts needed to include greater than five upvotes and at least three comments. Posts with only photos were excluded. These posts and their respective comments were manually analyzed for qualitative data, and were categorized by prevalent themes that all authors confirmed.

Summary of Results

We analyzed a total of 232 posts that fulfilled the inclusion criteria. The most prevalent theme in posts regarding PMDD was expression of feelings (n=116), centered around the topics of depression, anxiety, identity crisis, rejection, and frustration about the lack of support and understanding from both their community and healthcare providers. The second most common theme was sharing of experience-based insight (n=56), which contained advice suggesting varying therapeutics and coping strategies to decrease PMDD symptom severity. While therapeutic suggestions of SSRI’s, NSAID’s, and lifestyle modifications have clinical relevance, user misconceptions were noted regarding contraceptive use and hysterectomy for PMDD symptom relief. The third most common theme was relationship complications due to PMDD (n=31). Health-related questions (n=28), such as whether a new or recurring symptom was associated with PMDD, were the least frequent. Analysis of commentary on user posts led to further identification of four themes: offering support, sharing stories/advice, validating one another’s feelings, and showing appreciation for one another’s insights.

Conclusions

This study provides clinicians with insight on the interactions between patients, not observed in clinic. Reddit primarily serves for PMDD as a positive space for promoting belonging, and in doing so, may be beneficial to patients. Furthermore, identification of user frustration and discussion pertaining to failed therapies may set realistic expectations of treatment efficacy. Clinicians may inform patients about specific therapeutic misinformation seen online, promoting further open discussion between patient and physician.

#176 Internal medicine education for medical trainees in Naivasha, Kenya

LV Savochka1*

D Li1

L Onofrey1,2

D Bosibori3

J Beste1,2

C Farquhar1

1University of Washington School of Medicine, Seattle, WA

2Harborview Medical Center, Seattle, WA

3Naivasha County Referral Hospital, Naivasha, Kenya

Purpose of Study

In Kenya, there has been a decrease in government funding for medical education which has led to outdated educational guidelines to treat common diseases. In this project, the Clinical Education Partnership Initiative (CEPI) between the Naivasha County Referral Hospital (NCRH) and University of Washington (UoW) was used to strengthen the medical education curriculum for internal medicine trainees and pharmacy students from the University of Nairobi (UoN) who are obtaining their medical training at NCRH.

Methods Used

The NCRH internal medicine trainees and pharmacy students were surveyed via Zoom on what internal medicine curriculum topics they would like updated over the course of this 8-week long project. The most popular topics were updated using current medical guidelines and recommendations from World Health Organization, UptoDate and Kenya Ministry of Health. The community CEPI partners at the NCRH helped tailor the guidelines to their resource availability. The updated curriculum was then presented at weekly seminars to the medical trainees and was also shared with the medical community to be used as a reference in the future.

Summary of Results

A total of six internal medical education curriculums were updated and six seminars were delivered on topics such as asthma, chronic obstructive pulmonary disease, COVID-19, meningitis, liver failure, acute coronary syndrome and acute kidney injury. The attendance of each seminar ranged from 5–10 students and included internal medicine residents, as well as pharmacy students. Throughout the project, positive feedback regarding the sessions was given by the site coordinator, as well as the attendees. In the end-of-project survey, 83% of the attendees strongly agreed that they felt more up-to-date with the topics presented and have been using the information presented in clinical settings. Additionally, 63% of the attendees strongly agreed that they felt more confident in diagnosing and 83% felt more confident treating based on those topics. Participant feedback also revealed that case-based questions and Zoom polling were an effective way to engage attendees.

Conclusions

This project successfully updated six outdated internal medicine curriculum didactic sessions for internal medicine trainees and pharmacy students at NCRH. Participants reported to have an improved confidence in diagnosis and treatment on the presented topics. The plan is for future lectures to continue incorporating case-based questions and polling to emphasize teaching points using Zoom. The presentations were also sent to the site coordinator for future use and reference by NCRH trainees.

#177 Development of a whatsapp-based pilot program to improve stroke education and risk factor reduction in patients with arterial hypertension in Huaral, Peru

K Turk1*

J Zunt1

C Abanto2

A Sanchez3

1University of Washington School of Medicine, Seattle, WA

2Instituto Nacional De Ciencias Neurologicas, Lima, Peru

3Universidad Peruana Cayetano Heredia, Lima, Peru

Purpose of Study

Cerebrovascular disease and stroke are the second-leading cause of death in Peru. Despite the high burden of stroke, Peru lacks a national stroke program, and there is a shortage of neurologists, stroke units, and thrombolytic therapy, particularly in rural areas. It is imperative to reduce patients’ risk factors for stroke, especially hypertension since it is the most significant modifiable risk factor in preventing stroke. WhatsApp, one of the most popular communication platforms in Peru, provides an exciting opportunity to disseminate health information to patients. The aim of this project was to develop materials for a WhatsApp-based pilot program to improve stroke education and risk factor reduction in patients with hypertension living in rural areas of Huaral, a province in the Lima Region of Peru.

Methods Used

A stakeholder analysis was conducted to identify key partners whose input was essential in creating this project. Guidelines from the National Institute of Neurologic Sciences (INCN) in Peru and the American Heart Association/American Stroke Association were used to create infographics addressing stroke awareness and risk reduction. An informative outline of the pilot program was created for Huaral Hospital partners. A cohort of patients with hypertension was identified by the Huaral Hospital Teaching and Training Unit Director. Surveys addressing patients’ stroke knowledge and comfort using WhatsApp were generated. To ensure content was medically accurate and culturally appropriate, all materials were first edited by a medical student in Peru and subsequently by Peru’s Chief of the Center of Research in Cerebrovascular Disease at the INCN.

Summary of Results

Materials created for the pilot program include a detailed program outline, an informed consent adapted to WhatsApp, pre- and post-program surveys, and five educational infographics. These materials are ready to be sent to patients with hypertension in Huaral via WhatsApp. There is enthusiasm and optimism from hospital staff about the potential impact of the pilot program.

Conclusions

This project will increase access to accurate stroke education for patients with hypertension living in Huaral. Now that the materials have been created, the next step is to pilot their use in the selected cohort of patients. The program’s success will be determined by comparing participants’ pre- and post-program survey responses. By using WhatsApp, this program could provide a sustainable means to improve stroke education while limiting travel and financial burdens for patients living in rural areas. If successful, this program could be replicated in other rural areas in Peru.

Poster session

Infectious diseases

6:00 PM

Thursday, January 20, 2022
#178 A case of pseudomonas aeruginosa associated diarrhea in a long-term hospitalized patient

C Besmanos*

N Raza

H Lai

S Mishra

S Ragland

A Heidari

Kern Medical Center, Bakersfield, CA

Purpose of Study

Pseudomonas aeruginosa associated diarrheal disease is not common in adults and if seen, is mostly reported in pediatric population. It has been classified into Shanghai fever, enterocolitis and antibiotics associated diarrhea in pediatric literature. In adults, immunocompromising conditions such as malignancies, neutropenia, and admission to long-term care and intensive care unit (ICU) are known risk factors. Here we describe a case of Pseudomonas aeruginosa associated diarrhea in a long-term hospitalized patient who had rectal tube.

Methods Used

Retrospective case review

Summary of Results

A 53-year-old Caucasian man with a history of alcohol use disorder, hypertension, and hypothyroidism presented with myxedema coma with TSH 148 requiring intubation. He had a complicated hospital course with ventilator-associated pneumonia with MRSA, sepsis with candida, and abdominal compartment syndrome requiring decompressive laparotomy. The patient slowly recovered despite 43 days of hospitalization. Before leaving his 31 days of admission to ICU, a flexi-seal rectal tube was placed due to fecal incontinence. Five days later when he was already transferred out of the ICU, he started having loose watery stools with leukocytosis and left shift. Clostridioides difficile (C.diff.) colitis was suspected and he was placed on oral vancomycin empirically. His stool test for C.diff. came back negative, and his rectal tube was subsequently removed. Imaging did not show any abscess, perforated viscus, or fistula formations. His stool culture grew heavy colony numbers of Pseudomonas aeruginosa. Vancomycin was stopped and he was started on oral ciprofloxacin 750 mg twice a day with complete resolution of his diarrhea and leukocytosis.

Conclusions

Pseudomonas aeruginosa associated diarrheal disease is not common in adults. Complicated prolonged hospitalization, administration of broad-spectrum antibiotics, and immunocompromising conditions perhaps play role in colonization and eventually infection in the right setting. The role of rectal tube is unknown.

#179 HHV-8 associated multicentric castleman disease: a diagnostic challenge in a patient with acquired immunodeficiency syndrome and fever

R Dunn*

F Venter

R Jariwal

S Mishra

J Bhandohal

E Cobos

A Heidari

Kern Medical Center, Bakersfield, CA

Purpose of Study

HHV-8 associated Multicentric Castleman Disease (MCD) is an angiofollicular lymphoproliferative disorder that affects multiple regions of lymph nodes simultaneously. Incidence of Castleman Disease is about 6500 to 7700 in the United States, 75% of them being associated with HHV-8. All cases of MCD in HIV patientd are HHV-8 associated. Common symptoms include fever, lymphadenopathy, Hepatosplenomegaly, pulmonary involvement, edema, and ascites. Here we describe a case of HIV with fever of unknown orgin in that after extensive work up diagnosed with MCD.

Methods Used

This is a single case review after IRB approval.

Summary of Results

A 28 year old male with history of HIV, non-aherence with antiretroviral therapy (ART) presents with constant abdominal pain, vomiting, and fevers over 5 days. CBC showed pancytopenia with a CD4 count of 27 cells/mcL and an HIV viral load of 95,200 copies/mL. Work up for Syphilis, Gonorrhea, Chlamydia, Hepatitis A/B/C, Cocci, Cryptococcus, TB, Toxoplasma, Histoplasmosis, Bartonella, Giardia, Brucella, CMV PCR, Parvo B19 PCR, Coxiella brunetii, Cryptosporidium and all of his cultures were negative. Bone marrow biopsy and culture were negative. Imaging showed diffuse lymphadenopathy in the mediastinum, hilar, axillary, retroperitoneum, iliac and inguinal lymph nodes. IR Lymph node excision and HHV-8 staining confirmed HHV-8 associated MCD with serum HHV-8 levels of 2,288,277 copies/ml. Patient was given Rituximab infusions and started on ART.

Conclusions

Diagnosis of HHV-8 Multicentric Castleman Disease in HIV host could be challenging and usually is delayed. Starting antiretroviral and Rituximab is the most agreed upon therapeutic modality. This approach almost doubles the survival rate at 2 years from 42% to 90%.

#180 Elevated adenosine deaminase levels in a case of coccidiomycosis

C Salib*

L Moosavi

K Radicic

Kern Medical Center, Bakersfield, CA

Purpose of Study

Elevated adenosine deaminase (ADA) levels have been a useful diagnostic tool associated with tuberculosis (TB). Diagnostic testing for Coccidioidomycosis (Cocci) involves serologic testing of IgM and IgG antibodies. Though there are a variety of diagnostic testing options for TB, in a case of high clinical suspicion, pleural fluid analysis for ADA is often completed as an additional confirmatory test, due to its high sensitivity and specificity. This case demonstrates a patient who presented with elevated ADA levels despite having negative sputum cultures for TB and with elevated serological titers for Cocci.

Methods Used

A single patient case report was conducted after IRB approval.

Case Presentation

A 26-year-old male with history of uncontrolled Type 1 diabetes presented to the ED with shortness of breath and productive cough of two day duration. The patient denied history of travel and reported a nonspecific amount of weight loss over the past few months. He presented febrile, tachycardic, and hypoxic. CT scan found a lung abscess and empyema. He was seen by Interventional Radiology for placement of a pigtail catheter for drainage of pleural fluid. He was initially treated with Fluconazole but then transitioned to Ambisome.

During his admission, patient remained consistently tachycardic and tachypneic with worsening hypoxia. Requiring ICU admission, he was intubated three times and was subsequently extubated within a few days. The patient underwent bronchoscopy and was found to have pleural ADA level of 468. Despite having negative QuantiFERON results, the patient was started on RIPE therapy due to suspected TB infection.

Results from Mycobacterial sputum culture returned negative weeks after patient was discharged from the hospital, confirming that the patient did not have an active TB infection. However, serologic test was confirmatory for Cocci.

Conclusions

ADA levels have been known to have both a high sensitivity and specificity for diagnosing TB, which makes it an ideal diagnostic tool. In this instance, there was the unusual presentation of increased levels of ADA along with a negative AFP culture. The role and expected actions of the ADA enzyme can be indicative of T-lymphocyte activity. When thought of more generally, this diagnostic tool can be used to diagnose disease conditions other than TB, such as Cocci.

#181 Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers from India: a meta-analysis

RB Stricker*

MC Fesler

Union Square Medical Associates, San Francisco, CA

Purpose of Study

While vaccines have taken center stage in the battle against COVID-19, alternate approaches for prevention of SARS-CoV-2 infection have been ignored. Hydroxychloroquine pre-exposure prophylaxis (HCQ PrEP) has been used to prevent COVID-19 in high-risk healthcare workers (HCWs) in a number of studies from India. We have performed a meta-analysis to evaluate the safety and efficacy of a standard HCQ PrEP regimen in HCWs enrolled in these studies.

Methods Used

We performed a search of the medical literature based on the PRISMA checklist (http://www.prisma-statement.org/) using PubMed, Google Scholar, medRxiv and ResearchGate to obtain all relevant publications and preprints. Using this method we obtained eleven nonrandomized controlled trials of weekly HCQ PrEP involving 7,616 HCWs in India (3,489 treated, 4,127 controls). The HCQ PrEP regimen consisted of an 800mg loading dose in the first week, then 400mg weekly thereafter according to the guidelines of the Indian Council of Medical Research. SARS-CoV-2 infection was documented by seroconversion or positive polymerase chain reaction (PCR) testing. We used random-effects meta-analysis to summarize the risk ratio (RR) of infection across the studies.

Summary of Results

Sex distribution was available for nine studies and age distribution was available for eight studies. The sex distribution was 58% male and 42% female, and the mean age was 33.1 ± 7.7 years. In eight studies that reported HCW roles, 63% were involved in direct patient care (doctors and nurses) while 37% provided support services (laboratory technicians, housekeeping staff and other hospital workers). In the 11 studies that included HCWs who used any HCQ PrEP, the infection rate was significantly decreased (RR 0.56, 95% CI 0.37–0.83, p = 0.0040). In the five studies that included HCWs who took at least six doses of weekly HCQ PrEP, the infection rate was reduced even further (RR 0.25, 95% CI 0.13–0.50, p < 0.0001). No deaths were recorded in either the HCQ PrEP or control group. Three studies involving 667 HCWs reported adverse events (AEs). The most common AEs were headache (8%) followed by nausea (7%) and dyspepsia (6%). No arrhythmias were reported by the HCWs. AEs were generally mild and well tolerated, as shown in one study where the HCQ discontinuation rate due to AEs was 4%.

Conclusions

Weekly HCQ PrEP appeared to be safe and effective for prevention of COVID-19 in high-risk HCWs from India. Further studies of HCQ PrEP are warranted to supplement vaccines in the prevention of COVID-19.

#182 A unique case of COVID-19 presented as focal seizures with impaired awareness

R Sharma*

S Ratnayake

H Lai

S Mishra

A Heidari

Kern Medical Center, Bakersfield, CA

Purpose of Study

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has rapidly become a global pandemic with millions of confirmed cases worldwide. Encephalitis and seizure associated with COVID-19 has been seen and reported. Here described is a unique case of SARS-CoV2 infection presented with focal seizure with impaired awareness.

Methods Used

A retrospective review following IRB approval.

Summary of Results

A 54-year-old man unvaccinated for COVID-19 with no known past medical history presented to the emergency department with altered mental status. Three days prior to presentation he complained of frontal headaches and blurry vision and one day prior his son noticed he was unable to speak. Minutes upon arrival he suffered a focal seizure for which levetiracetam was administered. He was found to be oriented to self and age with difficulty finding words answering only with ‘yes’. EEG was performed and he was diagnosed with focal seizure with impaired awareness. His chest x-ray showed multifocal bilateral hazy infiltrations. SARS-Cov2 PCR test came back positive. His brain MRI revealed 2 acute subcortical superior right frontal lobe lacunar infarcts. His lumbar puncture was negative. He suffered nine seizures of left occipital origin despite being treated with levetiracetam and valproic acid. Phenytoin was added which eventually controlled his seizure and he became fully oriented. Overcoming a tumultuous hospital course, he was also found to have newly diagnosed poorly controlled diabetes and pulmonary cavitary coccidioidomycosis. He was discharged stably on hospital day 16.

Conclusions

Focal seizure with impaired awareness associated with SARS-CoV2 has not been reported. Further studies are warranted to understand the pathophysiology and definitive treatment.

#183 Methicillin-resistant staphylococcus epidermidis endocarditis, from tunnel to spine

VK Narang1*

H Sidhu2

C D’Assumpcao1

L Moosavi1

TT Win1

A Heidari1

1Kern Medical-UCLA, Bakersfield, CA

2Ross University School of Medicine, Miramar, FL

Case Report

Staphylococcus epidermidis is a common clinically encountered species of coagulase-negative staphylococci. Its ability to produce biofilm particularly in the presence of central lines can lead into serious infections including endocarditis. Here we demonstrate a case of a 68-year-old female on hemodialysis with exposed tunnel part of her dialysis catheter resulting in infective endocarditis and spinal osteomyelitis.

Methods

Approval was obtained from IRB. A single patient case report was conducted.

Case Presentation

Patient is a 68-year-old female with End Stage Renal Disease on hemodialysis who presented with 4 weeks of worsening lumbar spine pain. Upon presentation she was afebrile. Her examination was significant for lumbar spine point tenderness and left jugular tunneled catheter entry site dehiscence exposing the catheter. Patient stated the skin over the tunnel opened five months prior. Her laboratory studies showed ESR of 100 and CRP of 25. Her blood culture grew Methicillin-resistant S. epidermidis (MRSE). Her tunneled catheter was removed, and a new catheter was place in same area due to lack of access and stenosis of central venous on the other side. MRI lumbar spine showed near complete loss of the intervertebral disc at L4-L5 with severe erosive endplate changes.

An Interventional radiology (IR) guided bone biopsy of lumbar spine also grew MRSE. The patient persistently remained bacteremic with MRSE despite IV antibiotics. Transesophageal echocardiogram revealed sub-aortic 0.6x0.9 cm with no signs of abscess or valvular dysfunction. Despite lack of alternative access for dialysis due to stenosis there was no choice but to remove the tunneled catheter again and temporary catheter was placed at an alternate site. IR performed balloon angioplasty for central venous stenosis and insertion of left, IJ tunneled dialysis catheter after blood cultures remained negative.

Conclusion

Persistent bacteremia with Staphylococcus epidermidis in the presence of central line can lead into serious and metastatic infections. This requires successful source control in addition to antibiotic therapy.

#184 Pulmonary giant cavitary coccidioides with fungal ball and hemoptysis

VK Narang1*

K Dao2

S Jaratanian2

C D’Assumpcao1

R Kuran1

A Munoz1

A Heidari1

1Kern Medical-UCLA, Bakersfield, CA

2Ross University School of Medicine, Miramar, FL

Case Report

Coccidioidomycosis is a fungal pneumonia with risk of cavitation in select populations, such as diabetics. Cavitary lesions can hemorrhage and have superimposed infections. We discuss a case of giant cavitary coccidioidomycosis in an uncontrolled diabetic presenting with hemoptysis and mycetoma.

Methods

A single patient case report was conducted after approval from IRB.

Case Presentation

A 48-year-old Hispanic male with diabetes, untreated pulmonary coccidioidomycosis, and history of COVID-19 infection one year prior presented with sudden hemoptysis, night sweats, and a 45-lb weight loss. He was diagnosed with coccidioidomycosis seven years prior but did not start treatment. Three years prior he was admitted elsewhere with shortness of breath. Serum coccidioidal complement fixation titer was 1:32. Imaging found a right lower lobe cavity measuring 4 x 3 cm with right sided pneumothorax and bronchopulmonary fistula. He underwent video-assisted thoracotomy with pleurodesis and treated with fluconazole for 4 months, improving his titers to 1:4. He was then lost to follow.

Upon presentation to our facility with worsening hemoptysis, he had a larger cavity measuring 10 x 8 x 7 cm in the right lower lobe with central filling mass . He hemoptysized daily while admitted. Bronchoscopy confirmed coccidioidal mycetoma by direct stain and fungal cultures. Interventional radiology performed arterial embolization of right tracheobronchial and intercostal bronchial arteries to control hemoptysis. He was restarted on fluconazole and discharged home. One week later he returned in respiratory distress with fever, shortness of breath, and hypoxemia. Imaging revealed new left lower lobe and lingular consolidations. He was thought to have aspiration of right sided cavitary material to the left lung. His oxygen requirements increased significantly, concerning for severe pulmonary coccidioidomycosis and he was placed on steroids and liposomal amphotericin B. His symptoms improved and steroid was stopped. His antifungal was switched to Posaconazole and was able to go home on room air.

Discussion

Management of giant pulmonary cavitary coccidioidomycosis with mycetoma and bleeding is challenging. Poorly controlled diabetics are already at increased risk for cavitation. In a patient presenting with hemoptysis and a cavitary lesion, a multidisciplinary team consisting of pulmonology, infectious diseases, thoracic surgery and interventional radiology is essential.

#185 A case of pseudoterranova, having ceviche with special flavor

S Prasad1,2*

C D’Assumpcao2

R McPheeters2

W Stull2

A Heidari2

1Adtalem Global Education Inc, Downers Grove, IL

2Kern Medical Center, Bakersfield, CA

Case Report

Anisakiasis is a parasitic disease of the gastrointestinal tract caused by Anisakis species or Pseudoterranova species. Humans acquire this disease by ingestion of raw or undercooked fish that are infected with larvae of these parasites. We describe a 17-year-old male who had consumed ceviche one week prior and presented after he coughed up a worm. The worm was identified as Pseudoterranova species. Epidemiology of food sources in Southwestern United States is discussed.

Methods Used

Retrospective case study.

Summary of Results

A 17-year-old male with no significant medical history presented to our hospital after he coughed up a worm earlier that morning. He also complained of ongoing rhinorrhea and sore throat for the past four days. He denied nausea, vomiting, rash, diarrhea, fever, chills, night sweats, hematochezia, hematemesis, abdominal pain, abdominal bloating, headache, weight loss, or change in appetite. Patient stated that he was from Mexico but had been living in the United States for the past two years. A dietary history revealed that one week ago he had eaten his favorite ceviche made from fresh fish brought by a family member visiting from Ensenada, Mexico. Patient’s physical examination, lab values, and imaging were all unremarkable. He had brought the worm, which he had coughed up, to the hospital. The worm was sent to the pathology lab and identified as Pseudoterranova species. Patient was discharged with instructions to return if symptomatic. He was referred for follow-up in the outpatient setting.

Conclusion

Anisakiasis is rare with current United States food handling regulations. The clinical suspicion is raised when raw fish from alternative sources of fresh seafood is consumed. Removal of the worm via endoscopy or even surgery might be necessary and is considered therapeutic. Diagnosis is made by direct visualization of the nematode.

#186 Mandibular osteomyelitis due to aggregatibacter actinomycetecomitans

S Ratnayake1*

H Sidhu1,2

C D’Assumpcao1

G Petersen1

A Heidari1

1Kern Medical Center, Bakersfield, CA

2Ross University School of Medicine, Miramar, FL

Case Report

Aggregatibacter actinomycetemcomitans is frequently associated with localized aggressive periodontitis. A. actinomycetemcomitans is a Gram-negative facultative anaerobe that is a member of the HACEK group of fastidious Gram-negative bacteria that can rarely cause endocarditis. We report a 21 year-old Hispanic male with osteonecrosis of the mandible from a tooth infected with A. actinomycetecomitans requiring antibiotics and surgical intervention.

Case Description

A 21-year-old Hispanic male with no known past medical history presented to the emergency department with a purulent right jaw and neck abscess. Two weeks prior he began having right lower tooth pain. Over the next 10 days his pain and swelling progressed, limiting his ability to open his mouth and to eat and drink. He then noticed an enlarging mass over the right jaw and neck with purulent discharge. Intolerable pain brought him to the ED. Admission CT of the soft tissue of the neck found right mandibular angle and ramus osteomyelitis, adjacent masticator and sternocleidomastoid infectious myositis, reactive right parotiditis, and severe right cervical cellulitis. There were also small periapical abscess of the right mandibular first molar, and small pockets of localized edema in the right suprahyoid neck without organization and right upper cervical adenopathy. He was started on vancomycin and pipericillin-tazobactam. Ear nose and throat surgeon aspirated the abscess. Aspirated abscess culture grew A. actinomycetecomitans. Antibiotics were narrowed to ceftriaxone and metronidazole. ENT then performed incision and drainage of the right jaw and neck abscess and extracted two infected teeth. He was successfully discharged on post-operative day one on moxifloxacin with goal of 6 weeks of therapy with close ENT follow up.

Conclusion

Early recognition and treatment of periodontal infections is important to prevent complications such as abscess formation and osteonecrosis from osteomyelitis. We report a prototypical example of an acute progression of a simple tooth ache developing into severe osteonecrosis by a rare HACEK organism not commonly encountered requiring aggressive antibiotics and surgical management.

#187 Mallet finger complicated by distal phalanx osteomyelitis

D Deng1*

N Hatchard2

R Patel3

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

2Philadelphia College of Osteopathic Medicine, Philadelphia, PA

3Inspira Health Network, Vineland, NJ

Case Report

A 24-year-old male presented with a right index finger injury which occurred during a soccer game. The mechanism of injury was the ball hitting the top of the second digit and lacerating the most distal portion of the digit. A diagnosis of mallet finger was made, and later on osteomyelitis of the distal phalanx.

The patient was initially evaluated in the emergency room where he was diagnosed with mallet finger and placed in a distal interphalangeal (DIP) extension QuickCast splint. A follow-up visit revealed five degree DIP flexion posture and ten degree proximal interphalangeal extension posture. DIP active range of motion flexion was noted at 30 degrees and only 45 degrees and painful for PIP active and passive range of motion. As X-ray of the right index finger revealed no evidence of fracture, dislocation, or degenerative changes, surgical intervention was not indicated at the time. However, patient was showing persistent edema, erythema, and pain 8 weeks after the initial accident. Follow-up MRI imaging identified fluid collection in the DIP joint. With suspicion for infectious process, surgical debridement of the finger was performed which revealed necrotizing tissue at the mid dorsal metaphysis of the distal phalanx spreading through a crevice to the germinal matrix. This impacted the patient’s recovery and rehabilitation of the joint along with the structural and functional outcome. The patient was ultimately diagnosed through MRI and bone biopsy and found to have Enterobacter kobei osteomyelitis of the distal interphalangeal joint. The patient was treated with oral ciprofloxacin post-surgical debridement and was able to fully recover from the osteomyelitis infection. However, continued and permanent droop of the DIP with inability to regain full ROM, strength, and utility in the right index phalanx was seen during the patient’s follow-up appointment.

Our aim with this case study is to demonstrate the possible complications of open mallet finger injury and its rehabilitation considerations. In this case, the patient’s lacerated mallet finger led to osteomyelitis of the digit. While mallet finger itself is a very common injury, its recovery is rarely complicated by infection in previously healthy individuals.

This case highlights the importance of considering bone infection in non-healing joint injuries such as mallet finger and subsequently appropriately adjusting therapies to include prophylactic antibiotics and splinting to facilitate the structural and functional rehabilitation.

Poster session

Morphogenesis and malformations

6:00 PM

Thursday, January 20, 2022
#188 Preaxial polydactyly: characterizing sonic hedgehog regulation

M Malone1*

K Ball2

C Pira3

K Oberg3

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

2Loma Linda University Department of Basic Sciences, Loma Linda, CA

3Loma Linda University, Loma Linda, CA

Purpose of Study

Preaxial polydactyly is associated with ectopic Sonic hedgehog (Shh) expression in the presumptive thumb. Shh is secreted from the zone of polarizing activity (ZPA), the signaling center that directs limb development along the radial-ulnar (anterior-posterior) axis. Shh is necessary for development of the ulna and posterior four digits, while the thumb develops in the absence of Shh. A limb-specific enhancer, the ZPA regulatory sequence (ZRS), is necessary for Shh expression, although little is known about how the ZRS restricts Shh expression to the ZPA. Single nucleotide variations (SNVs) within the ZRS cause ectopic Shh expression resulting in preaxial polydactyly. These SNVs are spread across three highly conserved regions: peaks 1, 2, and 3. We hypothesize that one or more of these peaks is necessary for ZRS activity.

Methods Used

Plasmids containing full-length ZRS, or each peak respectively were electroporated into Hamburger-Hamilton stage 14 chicken embryo presumptive limb buds. The embryos were incubated for 48 hours then observed by fluorescence microscopy. Fluorescent activity of each peak was then compared to that of full-length ZRS.

Summary of Results

Constructs containing peak 1 and peak 2 have no detectable activity in the limb. Peak 3, however, maintains some activity, but markedly less than full-length ZRS.

Conclusions

Peak 3 is necessary and sufficient for activity while peaks 1 and 2 are not, suggesting peak 3 contains core sequences necessary for ZRS activity. It is surprising that peaks 1 and 2 lack activity as many clinically relevant SNVs occur in these two regions and the reported Hand2 binding site is in peak 2. Since peak 3 activity is less than that of full-length ZRS, peaks 1 and 2 likely enhance the activity of peak 3. Further studies will assess the quantitative difference in ZRS peak activity and determine how the ZRS localizes Shh expression to the ZPA. Mapping the ZRS will clarify the role of critical sequences in Shh regulation that contribute to limb development and malformation.

#189 Variations in the peroneus tertius muscle: evolutionary and clinical perspectives

K Kay*

J Scott

M Wedel

Western University of Health Sciences, Pomona, CA

Purpose of Study

Peroneus tertius (PT) is a muscle in the anterior compartment of the leg that functions in dorsiflexion and eversion of the foot at the ankle. PT was long thought to be unique to humans, but it is now known to be variably present in many other primates, including bonobos, chimpanzees, gorillas, and several species of monkeys. However, there is still disagreement between anthropologists and comparative anatomists regarding the evolutionary origin of the muscle. PT is highly variable in origin, insertion, size, and number of musculotendinous slips. Previously published studies have also reported PT to be extremely variable in terms of prevalence, ranging between 38% and 100% in different populations. Our goals are to summarize the evolutionary origin, anatomical variations, and clinical implications of the muscle.

Methods Used

We synthesized information from the literature on the evolution, prevalence, variability, and clinical correlations of the PT using Google Scholar, NCBI, and ResearchGate. For statistical analysis, we measured prevalence using the number of limbs with PT present per number of legs total. In particular, we compared studies that observed the muscle in human cadavers (n=11) versus studies that used palpation on living subjects (n=11).

Summary of Results

Numerous variants of PT have been identified, including an origin from the extensor hallucis longus. The muscle is occasionally doubled, in both humans and gorillas. Peroneus tertius is associated with multiple causes of ankle pain, and can be used in surgery for repair of other tendons. We found that the prevalence of PT varies depending on the method of data collection. Studies that use cadaveric dissection consistently report a significantly (p < 0.0001) higher prevalence of PT (86–100%) than studies that rely on palpation of the muscle in living subjects (38–84%).

Conclusions

Although the higher prevalence of PT in humans than in other primates has been linked to the evolution of bipedality, PT is not crucial for an erect bipedal gait. Recent studies have found no significant difference in ROM or in the strength of dorsiflexion or eversion among patients with and without PT. PT has been used in tendoplasty, tendon transfer, resection surgeries, transposition to correct ankle laxity, and transplantation surgeries for foot drop. The significant difference between dissection and palpation studies in the reported prevalence of PT suggests that palpation consistently underestimates the true prevalence of the muscle. We suggest that the variability in the size and course of PT, as well as with the potential for a small PT to be difficult to palpate through the extensor retinaculum, combine to make the muscle difficult to diagnose via palpation. Although palpation studies are potentially faster and less expensive than dissection-based studies, we urge caution in interpreting their results.

Poster session

Neonatology general

6:00 PM

Thursday, January 20, 2022
#190 Genetic associations with preeclampsia, intrauterine growth restriction, and spontaneous preterm birth

AL Baranoff1*

A Paquette1,2

1Seattle Children’s Research Institute, Seattle, WA

2University of Washington School of Medicine, Seattle, WA

Purpose of Study

Pregnancy-related conditions are attributable to a combination of factors and may increase one’s risk for later disease. Three of the most common conditions are preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth/delivery (SPTB/SPTD). The genetic basis of these conditions is illustrated through the findings that women who experience SPTB/D are at increased risk of subsequent SPTB/D of the same gestational age, and women who experienced PE or IUGR are also more likely to experience these same complications in subsequent pregnancies. We investigated the genetic profiles of each outcome and analyzed which maternal and fetal genomic variants are most associated with multiple pregnancy complications. This knowledge will increase our ability to better treat and/or prevent adverse pregnancy outcomes by identifying persons who may be at higher risk of complications prior to their manifestation in disease.

Methods Used

We conducted a literature review of studies that assessed the association between fetally and/or maternally-based single nucleotide polymorphisms (SNPs) and PE, IUGR, and SPTB/D. We selected genetic variants that were significantly associated with these pregnancy outcomes in an initial candidate gene study, genome-wide association study (GWAS), or summarized in a meta-analysis (MA). The significance of association between SNP and pregnancy outcome was reported at either a study-wide significance level (for GWAS and MA studies) or p < 0.05 for candidate gene studies.

Summary of Results

Our search yielded 103 articles, of which 59 investigated genetic associations in PE, 27 in IUGR, and 18 in SPTB. We identified five variants found in both PE and IUGR: rs1918975, rs10774624, rs3184504, rs4769612, rs1884082 which were in regulatory regions of four genes: FLT1, SERPINA3, MECOM, and SH2B3. We identified no variants found in both IUGR and SPTB. We identified five genes that contained SNPs in both IUGR and SPTB (ADCY5, WNT4, IGF1R, EBF1, IGF1), although none of the SNPs overlapped. No genetic variations or gene profiles were found to be shared amongst all adverse pregnancy outcomes.

Conclusions

We identified five genetic variants associated with both PE and IUGR which correlated to four genes as well as five genes associated with both IUGR and SPTB. Several of these gene variants are also risk factors for the development of diseases that impact health throughout life, such as cardiovascular and kidney disease as well as neurological delay, revealing that adverse pregnancy outcomes and adult disease have shared and complex genetic risk factors. The contribution of the identified shared genetic variants in the pathogenesis of PE, IUGR, and SPTB/D should be the focus of future studies.

#191 Factors associated with hypothermia and hypoglycemia on admission in very low birth weight infants

C Marquez*

K Ramm

Y Shao

NS Nanduri

A Hisey

L Barton

R Ramanathan

M Biniwale

LAC + USC Medical Center, Los Angeles, CA

Purpose of Study

Maintaining temperature and glucose in preterm infants are vital as these abnormalities can predispose them to many undesirable complications in early neonatal period. The present study was conducted to identify the factors associated with hypothermia and hypoglycemia in very low birth weight (VLBW) preterm infants.

Methods Used

The data consisting of VLBW infants born at our hospital was collected retrospectively from 2009 through 2021. Maternal factors, delivery room events and early neonatal morbidities were analyzed against infant’s first temperature and glucose done on admission to NICU. Hypothermia was defined as temperature <36.5 C. Hypoglycemia was defined as blood glucose <45 mg/dl on admission checked by point of care testing. IRB approval was obtained to review the data from electronic medical records. SPSS version 28 statistical software was used to analyze the data.

Summary of Results

From all VLBW infants born during this period 152/642 (23.7%) had temperature below 36.5 C on admission to NICU while 104/652 (15.9%) were diagnosed to have hypoglycemia. Birth weight or gestational age had no impact on either hypothermia or hypoglycemia on NICU admission. Infants needing resuscitation including chest compressions and epinephrine administration were at highest risk for hypothermia. These infants were also noted to have metabolic acidosis and low 5 min apgar scores. Infants presented with hypoglycemia were small for gestational age (37% vs 24% p=0.009). Maternal medical conditions including diabetes did not put these infants at additional risk for hypoglycemia. Hypoglycemia on admission was also associated with additional risk of requiring higher ventilation as well as oxygen requirement in the first 24 hours of NICU stay.

Abstract #191 Table 1

Conclusions

VLBW Infants needing resuscitation in the delivery room are at risk for hypothermia. These infants may present with metabolic acidosis on admission to NICU. Hypoglycemia on admission may predispose VLBW infants for more respiratory support.

#192 The effect of SARS-CoV-2 on the rates of breastfeeding in the newborn nursery

J Wang1*

AF Ahmed2

R Ramanathan2

A Yeh2

1LAC+USC Medical Center/USC, Los Angeles, CA

2LAC+USC Medical Center, Keck School of Medicine of USC, LA, CA

Purpose of Study

Exclusive breastfeeding for the first six months of life is recommended by the American Academy of Pediatrics and the Centers for Disease Control for its benefits to infant immunity, maternal-child bonding, and long-term health. While these benefits are well studied, the SARS-CoV-2 pandemic raises questions about the safety of breastfeeding among SARS-CoV-2-positive mothers. In addition, the pandemic’s effects on hospital staffing, patient-provider facetime, and healthcare access may impact breastfeeding rates. This study aims to explore the effect of the SARS-CoV-2 pandemic on breastfeeding in the newborn nursery.

Methods Used

This is a retrospective cohort study comparing breastfeeding rates between neonates at LAC+USC Medical Center Newborn Nursery from January 2019 to April 2021. We defined the pre-SARS-CoV-2 group as all neonates born prior to April 2020, and the during-SARS-CoV-2 group as those born from April 2020 to April 2021. Maternal data gathered included gravidity and parity, ethnicity, age, mode of delivery, and pregnancy complications. Infant data gathered included gestational age, birth weight, sex, and hyperbilirubinemia requiring intensive phototherapy. Newborns with maternal contraindications to breastfeeding, such as positive toxicology screen, positive HIV status, incarceration, and placement in foster care were excluded. Rates of exclusive breastfeeding and any breastfeeding were calculated for each month within this time period and compared using T-test. P-value less than 0.05 was considered significant.

Summary of Results

Of the 964 newborns screened in the pre-SARS-CoV-2 cohort, 913 were included. Of the 800 screened during-SARS-CoV-2 cohort, 763 newborns were included. There were no significant differences in the demographics between the two cohorts (table 1). We found a 11% decrease in the rate of exclusive breastfeeding (p <0.05) and a 4% decrease in any breastfeeding (p <0.05) during the SARS-CoV-2 period (Image 1).

Abstract #192 Table 1

Maternal and neonatal demographics and characteristics

Abstract #192 Figure 1

Breastfeeding rate at LAC+USC medical center before and during SARS-CoV-2

Conclusions

The SARS-CoV-2 pandemic had a negative impact on the rates of both exclusive breastfeeding and any breastfeeding among newborns in the normal nursery from a single center in Los Angeles. These results prompted the creation of a specific task force to counter the detrimental effect of the pandemic on breastfeeding. Prospective studies would be useful in assessing the long-term effects of the SARS-CoV-2 pandemic on breastfeeding rates and associated effects on infant immunity, maternal-child bonding, and long-term health.

#193 Expected growth trends in a large cohort of almost 7000 preterm infants from birth to eighteen years

J Barnard1,2*

A Defante2

J Ryu1,2

1University of California San Diego, La Jolla, CA

2Rady Children’s Hospital San Diego, San Diego, CA

Purpose of Study

Despite numerous studies about the growth of preterm infants (PI) postnatally, there is still no consensus on expected growth rates for PI through childhood. The standard of care is to correct for gestational age (GA) until age two years during which time PI are expected to ‘catch up.’ In addition to correcting for GA, there may be a need to account for growth restriction. There are conflicting studies on whether infants born small for gestational age (SGA) ‘catch up’ by age two years. However, to the best of our knowledge, there are no studies with this cohort size following the growth of SGA PI over 18 years.

Methods Used

This retrospective cohort study of 6916 followed infants born between 23–32 weeks over 18 years. Data was pulled from Rady Children’s Hospital electronic medical record system which includes specialists as well as over 30 general pediatrician offices. Being the main institution for follow up of premature infants in a very large catchment area allowed for longitudinal follow up of a large cohort. Infants were categorized as SGA if their birthweight was ≤ tenth percentile birthweight for their GA, AGA if tenth to ninetieth percentile and LGA if ≥ 90th percentile based on the WHO Fetal Growth Charts. Their weights and BMIs at ages two through 18 years were categorized as below the tenth percentile, between the tenth and ninetieth percentiles and above the ninetieth percentile by CDC standards.

Summary of Results

Using a Chi Squared test, preliminary results show statistically significant differences (p-values all < 0.001) in the counts of PI who are below the tenth percentile, between the tenth and ninetieth percentiles and above the ninetieth percentile by CDC standards at ages two through 18 years based on whether they were born SGA, AGA, or LGA. Those born SGA had more infants remain ‘small’ than those born AGA or LGA. But for all groups, we observed significantly more PI stay ‘small,’ less than the tenth percentile for weight, at ages two through 18 years than expected. This held true for BMI as well for ages two through 18 years for PI born SGA, AGA, or LGA with p-values all <0.001.

Conclusions

As more extremely premature and very low birth weight infants are surviving, there is a need for further assessment of this subpopulation’s expected postnatal growth. The observed distribution of PI over two through 18 years differed significantly by their size at birth. Infants born SGA may continue below the tenth percentile for weight for several years and this may not be ‘abnormal’ growth for them. These infants may be seen by various specialists for failure to thrive but might just need different standards. This study validates the need for different expectations of growth for infants born growth-restricted and very premature.

#194 General movement assessments in the surgical gastrointestinal neonatal population

S Bell

S Espinosa*

K Kesavan

KL Calkins

University of California Los Angeles, Los Angeles, CA

Purpose of Study

Infants with gastrointestinal disorders (GD) have increased survivorship with advances in neonatal medicine and surgery. GD infants are at risk for neurodevelopmental impairment; they require surgery and are at high risk for sepsis, growth failure, and prolonged hospital stays. There is evidence that the General Movement Assessment (GMA) is an early biomarker of motor delays, including cerebral palsy. Most studies have focused on extremely low birth weight infants (ELBWs) and have neglected GD infants.

Methods Used

In this retrospective single-site study, GD infants (i.e, gastroschisis, omphalocele, atresias) who underwent surgery within the first 90 days of life were compared to ELBWs (2/20/18 – 5/01/2021). The primary outcome was GMA results during the writhing stage at 36–49 weeks corrected gestational age (normal or abnormal (poor repertoire (PR), cramped synchronous (CS), or chaotic)) and fidgety stage at 3–4 months corrected gestational age (normal or abnormal). Abnormal fidgety was defined as fidgety movements that were not observed or movements that have exaggerated amplitude, speed, or jerkiness.

Summary of Results

There were 55 GD infants; 31 (56%) had at least one GMA. There were 33 ELBWs; 28 (85%) with one GMA. Gestational age and birth weight were significantly different when the cohorts were compared. However, the number of surgeries were similar (1.5 (0.8) vs. 1.7 (0.9), p=0.3) for the GD an ELBW cohort, respectively (table 1). Of the GD infants, 60% had an abnormal writhing stage GMA (0% CS, 60% PR) and 20% had an abnormal fidgety stage GMA. Of the ELBW infants, 35% had abnormal writhing stage GMA (15% CS, 20% PR) and 22% had an abnormal fidgety stage GMA. Rates for abnormal GMAs were similar when the groups were compared (p= 0.1, 0.9).

Abstract #194 Table 1

Characteristics of GD and ELBW infants

Conclusions

In this study, GD and ELBW infants were at high risk for abnormal GMAs. GMAs maybe a helpful tool to ensure that GD infants receive long-term follow-up and resources required to reach their developmental potential. Further longitudinal research is required to determine the accuracy of GMAs in the GD population.

#195 Abnormal blood gas and oxygen requirements in first 24 hours of life as indicators of morbidity in very low birth weight infants

NS Nanduri1,2*

A Hisey1,3

Y Shao1

K Ramm1

L Barton1

R Ramanathan1

M Biniwale1

1Los Angeles County University of Southern California Medical Center, Los Angeles, CA

2Drexel University College of Medicine, Philadelphia, PA

3Loyola University Chicago Stritch School of Medicine, Maywood, IL

Purpose of Study

Oxygen requirement as well as abnormal blood gas values have often been used as indicators of morbidity in the premature neonate, however, there is mixed evidence regarding its utility to predict short and long term morbidity. This study aims to assess the impact of abnormal pCO2, pH, and FiO2 values in the first 24 hours of life of very low birth weight (VLBW) infants on short and long term outcomes.

Methods Used

Data on all VLBW infants was retrospectively gathered from the electronic medical record between the years of 2009 and 2021. IRB approval was obtained prior. For blood gas levels, significance was calculated based on pH of 7.15 and CO2 of 50 mm Hg. FiO2 was considered significant if the infant required 50% in the first 24 hours of life. Each category was statistically analyzed against common neonatal outcomes including intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).

Summary of Results

Of 564 VLBW infants studied 46.6% had an abnormal pCO2 and 53.4% had a normal pCO2. 78.7% of these infants had an abnormal pH and 19.5% had a normal pH. 87.2% had a normal FiO2 and 12.8% had an abnormal FiO2. Infants with elevated pCO2, decreased pH, and high FiO2 were significantly more likely to need intubation in the delivery room, emergently, remained intubated at 24 hours and had significantly higher days of invasive mechanical ventilation (table 1). These infants were more likely to need surfactant and had higher mortality (table 1). Lastly, these infants were at increased risk of IVH and ROP (table 1). BPD was correlated with higher FiO2 as well as low pH. Neonates with abnormal FiO2 also showed an increased risk for having abnormal MRI before discharge (51.6% vs 69.0% p = 0.034).

Abstract #195 Table 1

Conclusions

Abnormal blood gas and higher FiO2 in the first 24 hours of life is associated with increased need for intubation as well as invasive mechanical ventilation in the delivery room and NICU. VLBW infants showed increased likelihood of developing long term complications including BPD, severe IVH, and severe ROP.

#196 Intubation in the first 24 hours as an indicator of neonatal morbidity

N Nanduri1*

A Hisey1,2

Y Shao1

K Ramm1

C Marquez1

L Barton1

R Ramanathan1

M Biniwale1

1Los Angeles County University of Southern California Medical Center, Los Angeles, CA

2Loyola University Chicago Stritch School of Medicine, Maywood, IL

Purpose of Study

Delivery room intubation in the premature neonate has been previously correlated with an increased risk for neonatal morbidities such as bronchopulmonary dysplasia (BPD). Invasive ventilation for longer duration also puts these infants at similar risk . This study further assessed relationships between infants needing invasive ventilation at 24 hours of life and short term neonatal outcomes.

Methods Used

Retrospective data of preterm VLBW infants born between 2009 and 2021 at LAC + USC Medical Center was evaluated for invasive ventilation at 24 hours of life and common neonatal morbidities. Institutional IRB approval was obtained. Maternal factors, delivery room interventions and standard neonatal outcomes were analyzed.

Summary of Results

Out of the 313 infants meeting inclusion criteria, 136 (43.5%) required invasive ventilation beyond 24 hours of life. Infants born to mothers with histologic chorioamnionitis were more likely to need invasive respiratory support at 24 hours. These infants had lower birth weight as well as lower gestational age. Resuscitation in the delivery room including intubation and chest compressions were also strongly correlated. These infants had a higher incidence of patent ductus arteriosus (PDA) as well as severe intraventricular hemorrhage (IVH). Bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and MRI abnormalities by term gestation were also more often seen.

Abstract #196 Table 1

Factors associated with intubation at 24 hours

Conclusions

VLBW infants who had invasive ventilation in the first 24 hours of life were more likely to have BPD, PDA, abnormal brain MRIs, and severe ROP during their NICU stay.

#197 Characterizing risk factors and investigating testing at birth for congenital hepatitis C virus infection

H Ko1*

M Dodd2

T Borunda2

K Page1

I Cervantes3

J Maxwell1

RO Castillo1

1University of New Mexico Health Sciences Center, Albuquerque, NM

2Rhodes Group, Albuquerque, NM

3University of New Mexico School of Medicine, Albuquerque, NM

Purpose of Study

Hepatitis C virus (HCV) is the leading cause of blood-borne infection globally with an associated increase from the ongoing opioid epidemic. Current recommendations call for antibody screening of HCV-exposed infants after 18 months of age or RNA testing after 2 months of age, however, studies have shown low compliance. We hypothesize that many women with HCV do not receive appropriate screening during pregnancy resulting in gaps in infant care. We seek to identify factors associated with suboptimal pediatric HCV screening that could improve screening and subsequent treatment in perinatally exposed and chronically infected children.

Methods Used

A retrospective chart review was completed using data obtained by Tricore Laboratories. The data assessed the yearly proportion of HCV in pregnant women who were tested from 2014–2019 at our institution, characterize their demographic and health information, and identify their infants and HCV testing status. Demographics of mothers and infants with HCV testing were compared to those without testing to determine if certain demographics portend a greater probability of follow up care for infants with possible congenital HCV infection.

Summary of Results

From 2014–2019, a total of 14,709 women delivered at our institution with 63% (n=9,310) receiving HCV testing. Of these women, 139 (1.5%) were antibody positive; 107 mother-infant pairs were included in our analysis. Only 29 infants (27%) had antibody testing and 4 infants (3.7%) received viral load testing. One child was found to be antibody and viral load positive. The majority of these infants (n=81) were discharged to their birth parent from the nursery or neonatal ICU regardless of testing status. Mean infant gestational age, mothers’ gravida/parity, liver enzyme levels, time between initial positivity of the mother and birth of infant, and maternal viral load at prenatal care onset did not differ significantly between the infant groups. However, urine positivity for opioid replacement therapy (ORT; methadone or buprenorphine) appeared to approach significance (p=0.08) for mothers whose infants were tested. Maternal and infant ALT levels showed a 0.34 correlation.

Conclusions

Mothers receiving ORT were more likely to have infant testing completed. This could be partly due to involvement of these mothers in programs which subsequently screen their infants. Additionally, a correlation between maternal and infant ALT levels seemed to exist however it is known that LFTs can fluctuate in those with HCV and in newborns. Thus, we are unable to conclude that this finding was clinically significant especially given the small number of infants who had LFT testing.

#198 Paid family leave and very low birthweight infant health outcomes

J Feister1*

H Lee1

L Greenberg2

M Parker3

M Rossin-Slater4

E Edwards2

1Lucile Salter Packard Children’s Hospital at Stanford, Palo Alto, CA

2Vermont Oxford Network, Burlington, VT

3Boston University School of Medicine, Boston, MA

4Stanford University, Stanford, CA

Purpose of Study

Paid family leave (PFL) is associated with improved infant health, potentially through increased breastfeeding. Little is known regarding the effects of PFL on very low birthweight (VLBW) infants, a population in which human breast milk (HBM) is critical. California (CA) was the first state to implement PFL in 2004. The primary aim of this study was to determine the impact of California’s PFL program on use of HBM at discharge, necrotizing enterocolitis (NEC), and in-hospital mortality in VLBW infants.

Methods Used

We conducted a quasi-experimental study by employing a difference-in-differences design using data from Vermont Oxford Network. PFL was defined as the intervention with CA as the exposed group and the rest of the Western U.S. (WUS) as the unexposed group . Singleton infants with birthweight <1500g cared for at VON participant hospitals in CA & rest of the WUS from 2001–2010 were included. Infants with early mortality or congenital anomalies were excluded. Relative risk (RR) and adjusted RR (aRR) of each outcome for infants born pre 2004 and post 2004 (the year of PFL implementation) were calculated using multivariate regression models, controlling for maternal race/ethnicity, birthweight, mode of delivery, and antenatal steroids. Trends pre/post PFL in CA vs. the WUS were compared to identify the effect of PFL on the outcomes of interest.

Summary of Results

Of 41,633 infants who met inclusion criteria, both CA and WUS infants were more likely to receive HBM at discharge post vs pre PFL enactment in CA (CA RR 1.19 [95% CI 1.15–1.23], aRR 1.17 [1.11–1.24]); WUS RR 1.03 [0.99–1.07], aRR 1.04 [0.98–1.10]). Both groups had higher incidence of NEC post vs pre PFL (CA RR 1.32 [1.18–1.47], aRR 1.29 [1.15–1.45]); WUS RR 1.43 [1.25–1.64], aRR 1.43 [1.24–1.64]). Incidence of NEC was lower in CA compared to WUS throughout the study period. There were no significant differences in mortality in either group pre vs post PFL. There was a trend of increasing use of HBM at discharge in CA but not WUS both pre and post PFL. Trends in NEC and mortality did not differ between CA and WUS. Overall, no statistically significant effect of PFL on the outcomes of interest was found when comparing difference in differences.

Conclusions

Implementation of PFL legislation in CA did not have a clear, significant impact on use of HBM at discharge, NEC, and mortality in VLBW infants. Inadequate duration or utilization of PFL may account for the lack of observed impact. PFL may also not be sufficient for families who spend long periods for NICU hospitalizations. Further research investigating individual level effects of PFL on VLBW infants and patterns of PFL utilization by families with infants in the NICU is warranted.

#199 Telemedicine exposure and training in neonatal-perinatal medicine fellowship programs: a national survey of fellowship directors

J Rajkumar1*

K Lund2

T Hyunh1

A Hoffman1

W Lapcharoensap1

1Oregon Health and Science University, Portland, OR

2University of Utah Health, Salt Lake City, UT

Purpose of Study

To describe the prevalence of Neonatal-Perinatal Medicine (NPM) fellow exposure to telemedicine, and the amount and type of telemedicine training fellows receive.

Methods Used

This study is a cross-sectional national survey of NPM fellowship training program directors. The survey was distributed electronically via the Organization of Neonatal-Perinatal Medicine Training Program Directors (ONTPD) listserv and answers were collected using Qualtrics.

Summary of Results

21 individuals responded to the survey with 18 total completed surveys. 8 (47.37%) programs had a neonatal telemedicine program. Of these, the types of consultation offered (number of programs in parentheses) included general neonatal consults (7), resuscitation guidance (3), counseling for fetal conditions or anomalies (4), perinatal viability counseling (3), remote rounding (1), and NICU follow-up (2). One program noted during the COVID pandemic, intrahospital consultations, rounds and parental visitation were being conducted via telemedicine. NPM fellows conducted the telemedicine consultations in 3 programs (37.5%). One program started fellow consultations during the first year, and two started in the second year. One program provided real-time fellow oversight by an attending during the first year of training and the other 2 indicated none was required. No programs had specific training or curriculum for fellows conducting telemedicine consultations. The overall perception of telemedicine and fellowship telemedicine training is described in table 1. Programs were generally in agreement that telemedicine is important in modern NICU practice, that fellows would likely encounter it in their careers, and that telemedicine training should be provided during fellowship.

Abstract #199 Table 1

Perception of telemedicine and fellow telemedicine training

Conclusions

Telemedicine has a rapidly expanding presence in neonatology. There appears to be minimal involvement of fellows throughout NPM fellowship programs. Further studies describing fellowship telemedicine training (including platform capabilities, demonstration of proficiency, communication techniques, documentation, medicolegal aspects, and simulated encounters) as well as the impact of such training on telemedicine program effectiveness are needed. Furthermore, development of expectations and curricula for telemedicine education in NPM fellowship should be standardized and widely adopted.

#200 Infant and maternal factors associated with developing necrotizing enterocolitis in very low birth weight infants

MA Sacks1*

YS Mendez1

FA Khan1

G Gollin2

A Radulescu1

1Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

2Rady Children’s Hospital San Diego, San Diego, CA

Purpose of Study

The purpose of this study was to understand the relationship between maternal and infant risk factors associated with developing necrotizing enterocolitis in premature infants.

Methods Used

Following Institutional Review Board (IRB) approval (#5190190), this prospective study was performed at two large academic Neonatal Intensive Care Units (NICU) in southern California. Our recruitment targeted mothers of very low birth weight infants(<1500 grams). After informed consent, they completed a questionnaire including demographics, health, substance usage and socioeconomic status. The infant data was collected from birth until NICU discharge and monitored if the development of NEC.

Descriptive statistics and quatitative analysis were performed as appropiate. P values <0.05 were considered statistically significant.

Summary of Results

Seventy infants were enrolled: 37(57.9%) male and 33(47.1%) female. Only 12(17.1%) developed NEC ≥ Bell stage 2. NEC infants had a lower gestational age than infants without NEC 25.9 vs. 29.0 weeks (*p<0.05), and lower birth weight at 752.8 vs. 1082.3 grams (*p<0.05). There were no significant differences in mechanical ventilation, vasopressors, intracranial hemorrhage, infection, or feed initiation.

Mothers of NEC infants reported, on average, more overall stressors 1.5 vs 0.5 and specifically more emotional stressors 10/12 (83.3%) vs. 20/58 (35.7%) during pregnancy (*p<0.05) (table 1). Other maternal factors were not significantly associated with NEC: age at conception, pregnancy complications, smoking history, alcohol and drug usage, household income, education level, first born child and family history of prematurity.

Abstract #200 Table 1

Conclusions

Very low birth weight infants (<1500 grams) with necrotizing enterocolitis (NEC) were smaller and born earlier. Our findings suggest that specifically emotional stressors and overall number of maternal stressors during pregnancy may be risk factors for developing necrotizing enterocolitis.

#201 Evaluating the effects of breastfeeding versus bottle feeding on the preterm infants’ microbiome and metabolome

K Schulkers Escalante1,2*

SS Bai-Tong1,2

M Thoemmes1

K Weldon1

S Hansen1

D Motazavi1,2

J Kitsen1,2

S Jin Song1

J Gilbert1

P Dorrestein1

R Knight1

S Leibel1,2

SL Leibel1,2

1University of California San Diego, La Jolla, CA

2Rady Children’s Hospital San Diego, San Diego, CA

Purpose of Study

Breast milk provides numerous benefits to preterm infants including decreasing the risk of necrotizing enterocolitis and sepsis. Providing breast milk via direct breastfeeding versus a bottle has been shown to improve long term outcomes in term infants. As preterm infants transition from tube to oral feeds, the impact of the route of oral feeds on the infants’ microbiome and metabolome is unknown. The purpose of this study is to determine if direct breastfeeding changes the preterm infants’ oral and gut microbiome and metabolome versus exclusive bottle feeding.

Methods Used

This study proposes using stool, saliva and milk samples collected from a cohort of preterm infants from the study: ‘The Association Between Milk Feedings, the Microbiome and Risk of Atopic Disease in the Preterm Population (MAP) Study’ (NCT04835935). This study recruited 46 babies <34 weeks gestational age. Their clinical data was collected as well as weekly samples of their milk feeds, saliva and stool until discharge. Stool samples were analyzed for microbiome and metabolomic profiles in a subcohort of 18 infants. For each subject, 3 longitudinal stool samples were analyzed (at birth, 2 weeks of age, and 4–6 weeks of age). Fifty-four stool samples, including 18 meconium samples, were analyzed. Metabolites were analyzed by untargeted gas chromatography-mass spectrometry and Kruskal-Wallis H test was used for statistical analysis. Bacterial compositions were analyzed by shotgun metogenomic. Differences in bacterial community composition were compared using a permutational multivariate analysis of variance (PERMANOVA).

Summary of Results

Forty-two (91%) infants experienced at least one episode of breastfeeding during their NICU stay. Only 17 infants (40%) were discharged home primarily receiving maternal breast milk. Analysis of the 54 stool samples showed there was a strong differentiation in bacterial community composition after the initiation of bottle (p = 0.014) and breast feeding (p = 0.014). This indicated changes to the stool microbiome at the onset of oral feeding following full enteral feeds via a nasogastric tube based on shotgun analysis. Metabolomic analysis showed a trend toward differentiation in the stool after initiation of bottle feeds (p = 0.07) but did not show significant difference after the initiation of breastfeeding (p = 0.31).

Conclusions

While analysis of stool samples has demonstrated microbiome and metabolomic changes after the initiation of breast versus bottle feeds in a subcohort of preterm infants, the future direction is to analyze all of the stool, saliva and breast milk samples for distinct microbiome and metabolome signatures of preterm infants who were exclusively bottle fed versus breastfed.

#202 Variations in parent participation in nursing care sessions in the NICU by medicaid status

S Takamatsu*

AM Cunningham

J Dempsey

J Kelleher

AG Dempsey

University of Colorado – Anschutz Medical Campus, Aurora, CO

Purpose of Study

Parents are faced with the challenge of navigating other external responsibilities (e.g., parenting of other children, work) while their infant is hospitalized in the NICU. Families may have financial barriers impacting stability of housing, childcare, and transportation. As a result, increasing and stabilizing engagement is a common research interest, as it is influential in skill development and caregiver efficacy. Cares sessions with nursing occur in the NICU throughout the day, offering a structured time to observe and partake in the care of the infant. Participation in cares lends itself to demonstration of skills, explanation of care, and can be helpful for parents to feel competent interacting and caring for their baby. The present study collected data on the frequency of parents’ attendance of cares sessions in the NICU. To begin to understand differences in potential social barriers to engagement, differences were compared based on mother’s Medicaid status.

Methods Used

Our sample included 122 premature infants in the NICU who were part of a larger quality improvement study to enhance family engagement. Attendance of four or more cares sessions with nursing per seven days was set as the target goal. Bedside nurses entered data into the infant’s medical record. A X2 test was performed to detect a difference in goal attainment by Medicaid status.

Summary of Results

A X2 test of independence showed the relation between these variables (e.g., goal attainment and Medicaid status) was significant, X2 (1, N = 122) = 21.5, p = .000. Infants with mothers with commercial insurance were more likely than infants with mothers with Medicaid to attend 4 or more cares sessions per week.

Abstract #202 Figure 1

Difference in goal attainment by mediciad status

Conclusions

The data show a difference in participation in cares sessions at least 4 times per week or more when compared by insurance status of the mother, a proxy of socioeconomic status. Further exploration is needed to fully understand barriers to parental engagement. Assessment of potentially related factors to Medicaid status (e.g., other family demands, distance from hospital, transportation difficulties) is recommended. The findings highlight the need for NICU providers to be cognizant of social determinants to bedside engagement and consider virtual options for parents to engage in care.

#203 Prevalence of neonatal intesnive care unit admisison among patients with genetic testing

SB Zoucha*

J Jensen

JL Bonkowsky

University of Utah Health, Salt Lake City, UT

Purpose of Study

Genetic disease is estimated to affect many critically ill neonates, but an unbiased determination of genetic disease prevalence in Neonatal Intensive Care Units (NICU) has been unclear. Since rapid and extensive genetic testing is increasingly available and practical and can impact outcomes, there is a need for identifying best clinical practices for genetic testing use. We hypothesized that a history of NICU admission is more common in patients with known or presumed genetic disease; and that neonatal NICU characteristics can guide best use of genetic testing.

Methods Used

We performed a retrospective population-based cohort analysis of children on whom genetic testing was performed at a tertiary children’s hospital. The hospital and specialists are the only providers of pediatric sub-specialty care in a 500-mile radius. We analyzed the cohort for a history of NICU admission, and clinical characteristics of the admission. We identified 3894 patients with a history of genetic testing with birthdates between 1/1/09 and 6/1/21 to identify a final cohort of 1611 patients.

Summary of Results

Of this cohort, 132 patients with a history of NICU admissions were identified (8.2% of the cohort). Of patients with a history of NICU admission; 36% had a positive (diagnostic) genetic test result, 30% had a negative test, and 34% had an uncertain (VUS) result. Compared to children without a history of NICU admission; 38% had a positive test result, 26% negative, and 36% uncertain; differences between these groups was not significant (p 0.34). The age at testing was lower in those with a history of NICU admission (3.4 years vs 4.6 years; p < 0.001).

Conclusions

Our study suggests that a genetic condition is present in a minority of children with a history of NICU admission. Further work into clinical characteristics of NICU children in whom genetic diagnoses are considered will help prioritize use of genetic testing.

#204 What is the evidence for an association between first trimester vaginal microbiota abnormalities and preterm birth?

N Holden1*

N Field2

1Western University of Health Sciences, Pomona, CA

2University College London, London, UK

Purpose of Study

Contemporary research has increasingly explored the possibility that preterm births (PTBs), the livebirth of babies prior to 37 weeks of completed pregnancy, are associated with first trimester vaginal microbiota abnormalities; yet the association between the two remains unclear.

Methods Used

A systematic literature review was conducted to assess current evidence for the role of first trimester vaginal microbiota abnormalities driving PTBs. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines, scientific databases, including Medline, Embase, and the Maternity & Infant Care Database (MIDIRS), were searched from January 2009 to March 2019. The search terms used were (vagina* microb* OR vagina* bacteria OR vagina* flora OR vagina* microflora* OR vaginal dysbiosis OR bacterial vaginosis) AND (preterm OR pre term OR premature OR early term OR early birth). Details on population/sample, study design, method of microbiota determination, measures of microbiota associations with PTBs, and Lactobacillus prevalence were extracted.

Summary of Results

Thirteen studies (nine cohort, four randomized control trial) were included in the review. The results provided strong evidence for an association between abnormal first trimester vaginal microbiota and PTBs. Specifically, low-Lactobacillus, high-diversity microbial econiches were found to be associated with an increased likelihood of PTB outcomes. Notably, two studies reported contradictory findings showing a negative association between first trimester AVF and PTBs, and three studies reported no significant association. Possible explanations for the negative association reported in Farr et al., 2015 include regional bias and inclusion of women with chronic conditions. Selection bias was also of concern in Koumans et al., 2010, which also reported a negative association, as participant recruitment was not randomized, possibly shifting the baseline health demographic of recruited women. No definite taxa-specific trends associated with PTB were identified; however, different studies reported Mycoplasma and Ureaplasma parvum increase the odds of PTB manifestation.

Conclusions

Associations were largely consistent and strong, suggesting vaginal flora measurements might hold the potential to enable early prediction of PTBs. It is important to note that causality and a biological mechanism for AVF-associated PTBs is not yet proven, with more research being recommended.

#205 Implementing screening for neonatal delirium in the NICU at rady children’s hospital

M Karmarkar1,2*

M Speziale2

W Jenkins2

D Heath2

J Kang2

J Suvak2

P Grimm2

L Moyer2

1University of California San Diego, La Jolla, CA

2Rady Children’s Hospital San Diego, San Diego, CA

Purpose of Study

Delirium is defined as fluctuating changes in awareness and cognition occurring in the setting of a medical illness, and is associated with adverse neurodevelopmental outcomes. Although delirium is recognized in pediatric ICUs, it is not commonly diagnosed in the neonatal population. The NICU at Rady Children’s Hospital is comprised of medically complex patients that are often on multiple medications for pain and sedation. Early recognition and treatment of delirium in the NICU may be helpful in improving clinical outcomes. We conducted a QI project to implement screening for neonatal delirium in high-risk patients. Our objective is to increase delirium screening (RASS/CAPD scores) from 0% to 85% in eligible NICU patients by 10/2021. Inclusion criteria are defined as NICU patients > or = 38 weeks corrected gestational age who are mechanically ventilated > 7 days and who are receiving any sedatives or opiates.

Methods Used

Multiple interdisciplinary meetings were initiated with key stakeholders to develop an algorithm for the evaluation of neonatal delirium. Completion of the RASS (Richmond Agitation and Sedation Scale) and age-adjusted CAPD (Cornell Assessment of Pediatric Delirium) scores were used as the objective tool for delirium screening. Weekly nursing compliance with RASS/CAPD score documentation (figure 1) is the primary process measure. Outcome measures include child psychiatry consultations and a diagnosis of delirium.

Summary of Results

Implementation of screening and data collection began in October 2020. After implementation, data from 10/2020 through 2/2021 showed an average weekly screening compliance of 76%. Our data shows a sustained shift with an average compliance of 88%, placing us above our goal of 85% compliance. Targeted future interventions to sustain our goal include: creation of an order set in the medical record and required documentation.

Conclusions

Through this QI project, we have increased awareness of neonatal delirium as a diagnosis in our NICU. Our expectation is that early recognition of delirium in our chronic patients will lead to more timely management of symptoms and decreased use of narcotic and sedative medications. This early recognition will be important to these patients’ overall recovery.

#206 Improving electrolyte and mineral homestasis in extremely premature infants

S Markee

J Fuller

A Yaroslaski*

E Shenk

J Maxwell

University of New Mexico Hospital, Albuquerque, NM

Purpose of Study

Infants ≤ 28 weeks gestational age (GA) are at increased risk for developing electrolyte and mineral abnormalities due to reduced baseline bone mineral content. ~80% of fetal calcium stores are obtained in the third trimester and ~54% of extremely preterm infants have metabolic bone disease. These infants rely heavily on early parenteral nutrition (PN) to provide appropriate electrolytes, but there is limited evidence on how to optimize calcium and phosphorus. Our primary outcome is to improve calcium and phosphorus by day of life (DOL) 7 in infants ≤ 28 weeks GA.

Methods Used

This Quality Improvement project is currently in the fourth Plan-Do-Study-Act (PDSA) cycle. We reviewed electrolyte and PN data in infants ≤ 28 weeks GA in 2019 (cohort 0; n=16). In March 2020, we obtained daily serum calcium and phosphorus levels in infants ≤ 28 weeks GA during the first postnatal week (n=13). Upon review, a custom PN form was designed for the next cohort (n=9), introducing calcium and phosphorus in PN earlier. In our third PDSA cycle we implemented new stock fluids, which included calcium gluconate 0.5 mEq/dL, dextrose, and amino acids for immediate use following birth for those born ≤ 28 weeks GA (n=10). A comparison was made between all three prospective cohorts. Additionally, serum creatinine and ionized calcium (ical) levels were compared. A Grubb’s analysis was used followed by a student’s t-test.

Summary of Results

Mean serum calcium on DOL1 between cohort 1 and 2 were similar (6.57 ± 0.25 mg/dL and 6.74 ± 0.12 mg/dL, respectively (p=0.6)). In cohort 3, the calcium level was noted to be lower on DOL3 compared to cohort 0, (9.6 ± 0.24 mg/dL and 9.03 ± 0.09 mg/dL, respectively (p=0.08)). Interestingly, mean serum creatinine on DOL1 nearly significantly decreased in cohort 2 (0.76 mg/dL ± 0.05 mg/dL), compared to cohort 1 (0.90 mg/dL ± 0.05 mg/dL), p=0.07. Mean serum creatinine remained < 1 mg/dL throughout the first week of life for infants in cohorts 2 and 3, while it trended higher in cohorts 0 and 1 over the first week of life.

Conclusions

The new PN allowed a more consistent and gradual increase in serum calcium levels, while remaining in normal limits, during the first postnatal week. Additionally, creatinine levels were lower and ical levels remained in goal range, requiring less therapeutic intervention. Addition of calcium gluconate to stock fluids for infants ≤ 28 weeks GA on DOL0, as seen in cohort 3, augmented the improvement and stabilization of serum calcium and creatinine levels. Surprisingly, we have found that although we have been unable to show an improvement in our serum phosphorus for this patient population, we have seen improvement in calcium and creatinine levels in the first postnatal week.

#207 Implementation of a neonatal massive transfusion protocol

H Ko1*

JR Griggs1

J Raval1

T Zamora2

1University of New Mexico Health Sciences Center, Albuquerque, NM

2Regents of the University of Minnesota, Minneapolis, MN

Purpose of Study

A Massive Transfusion Protocol (MTP) is an institutional plan created to facilitate communication, ensure timely lab monitoring and reduce delays/errors when ordering multiple blood products. Though adult and pediatric (MTPs) exist, they are ill-suited for use in the neonatal population. Given the unique nature of neonates, this population could benefit from a neonatal-specific MTP.

Methods Used

A pre-implementation survey was sent out to physicians, nurse practitioners, physician assistants, and nurses in the NICU. A multi-disciplinary team was then put together, involving clinical staff from the NICU, transfusion medicine, and the transfusion committee in order to develop a neonatal-specific MTP.

Summary of Results

Fifty responses were recorded to 5 questions. 64% were aware of MTPs in general. Almost all participants (96%) correctly identified that MTPs were generally used for any patients requiring large blood volume replacements and/or multiple blood products. Forty-six percent responded that they had previously experienced a clinical situation in which there was difficulty obtaining blood products. Of the 46% who experienced difficulty getting blood products, 67% identified that the delay was mostly attributed to waiting for blood products to arrive.

Conclusions

Our multi-disciplinary group collectively developed a neonatal-specific MTP to allow for a safer, timelier, and standardized approach to administering multiple blood products. Massive transfusions are rare but high-risk events in the NICU setting thus this study will hopefully improve patient outcomes related to transfusions. Our pre-implementation survey shows educational and practical barriers exist when attempting to order multiple blood products and further work will need to be done to address these barriers.

#208 Hospital variation in extremely preterm birth

GP Goldstein*

P Kan

C Phibbs

E Main

GM Shaw

H Lee

Stanford University, Stanford, CA

Purpose of Study

To assess between-hospital variation in extremely preterm birth (EPTB) frequency when stratifying by hospital level of care, and determine the proportion of variance explained by differences in maternal and hospital factors.

Methods Used

We assessed 7,072,562 births in California from 1997 to 2011, using hospital discharge, birth and death certificate data. We estimated the association between maternal and hospital factors and EPTB using multivariable regression, calculated hospital-specific EPTB frequencies and estimated between-hospital variances, intra-class coefficients, and median odds ratios stratified by hospital level of care.

Summary of Results

Hospital frequencies of EPTB ranged from 0.01% to 3.0%. Between-hospital EPTB frequencies varied substantially, despite stratifying by hospital level of care and accounting for confounding factors. This variation appeared to be related to differences in a collection of hospital, maternal sociodemographic and medical factors, and other factors not accounted for in our study, such as barriers to maternal transfer prior to delivery.

Abstract #208 Figure 1

Hospital frequencies of extremely preterm birth (EPTB) among hospitals with level 1, 2 and 3A NICUs and by hospital rank

Conclusions

Our results demonstrate differences in EPTB frequency among hospitals when stratifying by hospital level of care. Proportion of EPTBs at level 1 and 2 NICUs should be further investigated and considered as a hospital quality measure.

#209 Perceived motivations and barriers of neonatal nurse practitioners in fellow evaluation: a pilot case study

N Dyess*

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Fellowship programs must provide objective performance evaluations of trainees that are formative and come from multiple evaluators including nonphysicians. The utility of multisource feedback has been well demonstrated in the literature; however, it is difficult to ensure nonphysician staff fill out evaluations. The purpose of this study is to elucidate the neonatal nurse practitioner’s (NNP’s) perceived motivations and barriers to completing fellow evaluations. As a pilot study, an additional purpose was to assess feasibility and refine methods.

The research questions guiding this study are: how do NNPs view their role in the trainee evaluation process, what motivates NNPs to fill out evaluations, what are the self-perceived barriers to evaluations, and how can we increase NNP evaluation of trainees.

Methods Used

I performed a pilot study of a phenomenological, qualitative case study of NNPs at the University of Colorado. A convenience sample of 3 NNPs, selected via purposive sampling, participated in semi-structured, one-on-one interviews to explore the perceived motivations and barriers to evaluating fellows. A constructivist epistemological framework guided the study. The data was viewed through a theoretical framework inspired by Maslow’s motivation theory. Interview transcripts were coded inductively via the constant comparative method and then clustered into emergent themes using phenomenological reduction, horizontalization, imaginative variation, and thematic analysis.

Summary of Results

A conceptual framework emerged from the data, consisting of five themes of driving and restraining forces to completing evaluations which interact in a process akin to a neuronal cell’s action potential. The framework describes the implicit weighing of these forces to determine if a threshold for activation is reached to complete an evaluation. Themes are supported by Maslow’s motivation theory, with each of Maslow’s levels of need equating to a NNP’s level of need for completion of fellow evaluations.

The Fellow Characteristics theme describes how extremes of behavior, repetitive behavior, and a fellow’s value of feedback affect evaluation completion. The NNP-Fellow Relationship theme describes how increased exposure and knowledge of fellow repercussion affect evaluation completion. The Evaluation Characteristics theme illustrates how anonymity, specificity, feasibility, and timeliness affect evaluation completion. The NNP-Evaluation Relationship theme describes how knowledge of evaluator role/value and the evaluation process is critical to evaluation completion. The NNP Characteristics theme describes how alignment with preferred feedback strategies and seniority affect evaluation completion.

Abstract #209 Table 1

Themes of driving and restraining forces and representative quotes

Conclusions

The conceptual framework provides insights into the motivations and barriers to completion of fellow evaluations by NNPs that can inform measures to increase completion rates of trainee evaluations by nonphysicians.

#210 Evaluating a neonatal opioid withdrawal syndrome currriculum to improve care in rural hospitals

J Patel1*

S Sanders2

H Brakey2

T Ozechowski2

A Sussman2

A Kong2

H Pratt-Chavez2

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

2University of New Mexico Health Sciences Center, Albuquerque, NM

Purpose of Study

The incidence of neonatal opiate withdrawal syndrome (NOWS) in the US has grown dramatically over the past two decades. Many rural hospitals are not equipped with resources and materials to manage best practices of these patients resulting in transfers to hospitals in bigger cities. The purpose of this study is to evaluate a curriculum we created to support rural hospitals to keep healthy infants with NOWS for observation instead of transferring them.

Methods Used

The curriculum was used for quality improvement at a rural hospital and shared with providers in another state that expressed interest. To evaluate the curriculum, we conducted pre- and post-surveys of NOWS knowledge, attitudes, and care practices, plus post-curriculum interviews and focus groups.

Summary of Results

Fourteen participants completed both pre- and post-curriculum surveys. They indicated an increase in knowledge and care practices, and a decrease in belief that infants with NOWS should be cared for in a critical care environment. Most respondents agreed with positively worded attitude items pre-test and post-test. Although few respondents expressed negative attitudes about mothers of infants with NOWS at pre-test, the training curriculum appeared to have no impact on such attitudes at post-test. Sixteen participants participated in focus groups or interviews. Qualitative data reinforced quantitative results, plus the need to reduce stigma and improve provider/staff interactions with patients.

Conclusions

This curriculum has strong positive impacts on NOWS knowledge and care practices. Incorporating focus on core concepts of trauma-informed care and self-regulation in future iterations of the curriculum may strengthen the opportunity to change attitudes and address the needs expressed by participants and improve care and well-being of families and babies with NOWS.

#211 Effects of postnatal glucocorticoids on brain structure in preterm infants, a scoping review

I Robles*

MA Eidsness

HM Feldman

SE Dubner

Stanford University School of Medicine, Stanford, CA

Purpose of Study

Postnatal GCs (GC) are given for many indications in infants, including for the reduction in incidence and severity of bronchopulmonary dysplasia, a major risk factor for morbidity, mortality, and neurodevelopmental disability in children born preterm. Variation exists in medication, dosing, timing, and reported outcomes. Clinical neurodevelopmental outcomes after GC administration may be due, in part, to GC induced alterations in neonatal brain development. The objective of this scoping review is to identify what is known about the effects of GC treatment on brain structural development in preterm human infants in order to identify potential mechanisms by which GCs may affect later clinical neurodevelopmental outcomes and to identify gaps in the literature.

Methods Used

A search query was developed to search online databases for original research on human infants, GCs, and brain structure. Potential article titles and abstracts were screened by two reviewers to identify papers for full text review.

Summary of Results

6565 titles were identified based on the search query for title and abstract review. Inclusion and Exclusion criteria are shown in the table. 70 were included for full text review. Multiple imaging modalities and outcomes were reported.

Abstract #211 Table 1

Inclusion and exclusion criteria for title and abstract review

Conclusions

GC effects on brain are of interest to a wide audience of researchers across the lifespan and across many clinical conditions. Relatively few human studies have directly assessed the effect of this intervention on early brain structural development. This study highlights the need for additional research on neonatal GCs and their potential effects on brain development.

#212 Does maternal age impact feeding outcomes in preterm infants?

A Patel1*

C Bradley2

1University of California Irvine School of Medicine, Irvine, CA

2University of California Irvine Department of Pediatrics, Irvine, CA

Purpose of Study

For preterm infants in the Neonatal Intensive Care Unit (NICU), successful and safe oral feeding is a requirement for discharge from the hospital. There are a variety of factors that contribute to feeding outcomes as neonates learn to coordinate breathing during oral feeding. While studies have detailed the effects of advanced maternal age on various neonatal morbidities, there is a dearth of literature exploring the association between maternal age and feeding outcomes in neonates. This analysis sought to examine whether a correlation exists between maternal age at delivery and feeding outcomes in preterm infants.

Methods Used

A retrospective chart review was conducted for 12 healthy infants born at less than 37 weeks gestational age who were admitted to the NICU and were transitioning from gavage to bottle feeding. Data was collected on maternal age at delivery, rate of milk transfer (in milliliters per minute), oral feeding performance (in percentage of milliliters taken during the feeding per milliliters prescribed), and feeding proficiency (in percentage of milliliters taken during the first five minutes of the feeding per milliliters prescribed). A correlation matrix was then developed via a linear regression model using these, and other, maternal and infant health factors to assess for possible correlations.

Summary of Results

Maternal age showed a moderately positive correlation with two of the three feeding outcomes studied. The Pearson correlation coefficient (R) for the association between maternal age and feeding performance was +0.66. The R for the association between maternal age and feeding proficiency was +0.48. Maternal age was not associated with rate of milk transfer, with an R of +0.04.

Conclusions

This preliminary analysis shows that increased maternal age may serve as a protective factor for the complex oral feeding process that is challenging for preterm infants due to immature neurodevelopment. Maternal age at delivery may be valuable to consider in studying progression to full oral feeding, and ultimately discharge from the NICU, in this population. While the power of this exploratory study is limited due to small sample size and potential for confounding, this warrants further research that examines the association of maternal age at delivery on various feeding outcome measures.

#213 Wee nuzzle: a quality initiative to promote non-nutritive breast feeding in order to increase breastmilk at discharge for preterm infants in the neonatal intensive care unit

K Schulkers Escalante1,2*

J Barnard1,2

E Clemens1

R Hammer1

C Ritter1

K Ko1

J Wood1

S Freeman1

J Cook1

K Weiss1,2

SL Leibel1,2

1University of California San Diego, La Jolla, CA

2Rady Children’s Hospital San Diego, San Diego, CA

Purpose of Study

Reduced opportunities for preterm infants to practice oral feeding can contribute to issues such as delayed hospital discharge and oral aversion. Furthermore, a lack of opportunity for direct latching may discourage mothers and reduce breastmilk feeding at discharge. The NICU at Jacobs Medical Center, University of California, San Diego has a low rate of non-nutritive breast feeding (NNBF) in preterm infants due to: 1) varying practices and comfort levels, especially for preterm infants on non-invasive respiratory support (NRS), 2) lack of formal guidelines, and 3) NNBF not frequently integrated into medical team’s daily discussions or documented by bedside staff. The goals of this QI project are to support early introduction to the breast to promote latching and ultimately milk transfer, promote maternal-infant bonding, and facilitate early positive oral experiences. Our SMART AIM is to increase eligible preterm infants attempting at least one session of NNBF at least once weekly from a baseline of 0% to ≥ 50% by July 2022.

Methods Used

To support the development of oral feeding skills, called Wee Feeds, in premature infants, a multidisciplinary team was developed that included providers, occupational and respiratory therapists, lactation consultants, nurses, and parents. A new pathway called ‘Wee Nuzzle’ was created as a pre-feeding developmental pathway primarily focusing on promoting breast feeding by encouraging Skin-to-Skin, Milk Drops, and NNBF. Premature infants’ ≥ 30 weeks are included if they are receiving enteral breast milk, are on NRS or room air, and the parent desires to do NNBF. Infants are excluded if they were intubated or within a week of extubation, have an umbilical arterial catheter, and/or have significant congenital or neurological abnormalities making it unsafe to attempt NNBF. Education for NICU staff has occurred at department meetings, nurse staff meetings and huddles, nursing fair skills day, and via multiple emails over the past 6 months. The primary process measure is percentage of eligible infants attempting at least one NNBF session per week. Outcome measures include the number of preterm infants discharged home on breastmilk and time to discharge from start of Wee Nuzzle. Balancing measures include an increase in respiratory support within 24 hours of NNBF without another explanation.

Summary of Results

Implementation of our project is currently ongoing. We plan to measure data monthly and implement PDSA cycles as needed.

Conclusions

The oral feeding pathway, Wee Feeds, has been widely accepted and supported by all levels of staff in our NICU and we hope to gain the same support for Wee Nuzzle. We will continue education, data collection and analysis with the hope to achieve our measures and aims.

Adolescent medicine and general pediatrics II

Concurrent session

8:00 AM

Friday, January 21, 2022
#214 Impact of age, sex, and race on velopharyngeal anatomy within the first two years of life

S Levene1*

I Neuberger2

K Barhaghi2

A Piccorelli3

K Kotlarek3

1University of Washington School of Medicine, Seattle, WA

2Children’s Hospital Colorado, Aurora, CO

3University of Wyoming, Laramie, WY

Purpose of Study

Children born with cleft palate typically undergo primary palatoplasty within the first 2 years of life with the goal of anatomic restoration of the palate to allow for the development of normal speech and swallowing patterns. To the best of our knowledge, no large-scale quantitative data exists regarding typical velopharyngeal (VP) structures for children within this age range. This retrospective study aimed to (1) quantify the impact of age, sex, and race on the size and orientation of VP structures during the first 2 years of life and (2) provide normative data for future comparison to infants with cleft palate. Based on existing literature, it was hypothesized that VP dimensions would not display sexual dimorphism but would display a significant racial effect.

Methods Used

An a priori power analysis was completed. A retrospective chart review was completed for all patients under 24 months of age that underwent an MRI of the head for medical necessity using a 3D FLAIR sequence at a large pediatric hospital within the past 18 months. After excluding patients based on scan quality and medical diagnoses or structural conditions affecting the region of interest (e.g. cleft palate), VP measurements were obtained for 184 patients using ThermoFisherTM AmiraTM software. Participants were divided into 5 groups based on corrected age. A multivariate analysis of covariance was used to assess differences in VP variables by age group while controlling for sex and race. Inter- and intra-rater reliability was completed for all variables based on 20% of participants using a Pearson product-moment correlation.

Summary of Results

Inter- and intra-rater reliability were excellent (r=.90+). There was a statistically significant (p<.0001) difference between age groups based on overall combination of dependent variables after controlling for sex and race. Regarding corrected age, follow-up analyses revealed significant differences in adenoid depth (p=.0001), effective velar length (p=.0079), levator length (p<.0001), origin to origin distance (p<.0001), pharyngeal depth (p=.0021), sagittal angle (p=.0016), velar insertion distance (p<.0001), velar length (p<.0001), and velar thickness (p<.0001). Regarding sex, follow-up analyses revealed significant differences for effective velar length (p=.0225), levator length (p<.0001), origin to origin distance (p=.0019), velar insertion distance (p<.0283), and velar length (p=.0166). No significant differences were observed between race groups.

Conclusions

Variations in VP dimensions based on both age and sex were observed among children under 2 years of age. Data from the present study provide a normative database for future comparison to children born with atypical VP anatomy (e.g. cleft palate).

#215 Limping through a differential: an uncommon presentation to a common pediatric diagnosis

J Smith*

J Gardner

K Dreher

S Sanders

University of Arkansas for Medical Sciences, Little Rock, AR

Case Report

A 4-year-old previously healthy boy presented to the pediatric emergency department (ED) with a one-month history of a progressively worsening limp with concerns for osteomyelitis. He was recently evaluated by an orthopedic surgeon with x-rays of the ankle showing medial metaphyseal lucency and joint effusion concerning for infection as well as distal fibular sclerosis concerning for a healing fracture. His limp progressed to the inability to bear weight due to worsening left lower extremity pain. There was no history of trauma to the area. He complained of no other bone pain.

Physical Exam

Exam was notable for left ankle swelling with tenderness to palpation and pain with passive movement. The left lower extremity had normal sensation and perfusion. The liver edge was palpated several centimeters below the costal margin. No lymphadenopathy was appreciated. No rashes or bruising noted.

Diagnostic Evaluation

Laboratory evaluation was significant for elevated inflammatory markers. A complete blood count revealed a borderline microcytic anemia, but was otherwise normal. Magnetic resonance image (MRI) of the ankle showed diffuse abnormal bone marrow enhancement consistent with an infiltrative process. Further questioning revealed a history of night sweats, increasing fatigue, and intermittent fevers over the past month. Lactate dehydrogenase and uric acid were elevated and a peripheral smear showed atypical lymphocytes.The patient underwent bone biopsy. No drainable fluid collection was found. Cultures did not grow bacteria. Bone marrow aspirate with flow cytometry showed 60% B-lymphoblasts consistent with B-cell acute lymphoblastic leukemia (ALL).

Discussion

Acute onset limping and acute lymphoblastic leukemia are commonly encountered problems in the ED. Extremity pain with limping carries a wide differential diagnosis in a child. Studies have shown that the initial diagnosis in a patient with limp is only correct 42% of the time. ALL often presents with diffuse bone pain; however, presentation with limp as the primary problem is rare. This case highlights the importance of a thorough history and physical exam. It was not until they were asked specifically about night sweats, weight loss, and fevers that the patient’s guardians responded in the affirmative. In the workup of the limping child, it is imperative to have malignancy on the differential even for localized bone pain.

References

  1. Herman MJ, Martinek M. The limping child. Pediatr Rev 2015;36(5):184–197. doi:10.1542/pir.36–5-184

  2. Lefèvre Y, Ceroni D, Läedermann A, et al. Pediatric leukemia revealed by a limping episode: A report of four cases. Orthop Traumatol Surg Res 2009;95(1):77–81. doi:10.1016/j.otsr.2008.09.004

#216 Protein concentration of human milk varies within a feed and over a 24-hour period

KA Bull1*

AC Gogel2

JE Williams2

Y Bonney2

MA McGuire2

MK McGuire2

1University of Washington School of Medicine, Moscow, ID

2University of Idaho College of Agricultural and Life Sciences, Moscow, ID

Purpose of Study

Fundamental to understanding human milk composition is determining what is a representative milk sample. Many factors can influence the concentration of some milk components, and controlling for these variables is essential to documenting ‘typical’ milk composition. While variation in lipid content has been widely studied, there is less research on macronutrients. The purpose of this project was to determine if total protein concentration varies with time of day and during a feed. We hypothesized that we would detect no differences in protein based on these factors.

Methods Used

This was an epidemiologic, repeated-measures trial involving 17 healthy women from Moscow, ID and surrounding areas who were ≥18 y of age, not taking antibiotics, and nursing healthy infants. Participants were 31.4 ± 3.6 y old and 223 ± 175 d postpartum. Milk collection kits were delivered to each mother’s home with detailed sampling instructions, and study personnel were available (via phone) during most of the sample collection times. During d 1, participants collected milk representing the foremilk, mid-milk, and hindmilk of a feed during a single breast expression. On d 2, milk was collected 4 times (T1-T4), 6 ± 1.5 h apart, the first being between 0500–0900 hr. Protein concentrations in milk were measured using a colorimetric method (Pierce BCA Protein Assay Kit) with human serum albumin (Sigma-Aldrich) as the standard. Data were analyzed using linear mixed models with participant as a random variable while assuming an autoregressive correlation structure for the repeated measures within participant as implemented in SAS (v 9.4).

Summary of Results

Contrary to our hypotheses, protein concentration varied within a feed (p = 0.0058) and over a 24-hr period (p = 0.0046). Protein concentrations of foremilk and mid-milk were lower than that of hindmilk (17.66 ± 0.46, 17.80 ± 0.46, and 18.56 ± 0.57 g/L, respectively; p =0.0210 and p=0.0015, respectively). Protein concentrations increased in a stepwise fashion over the 24-hr period (17.31 ± 0.51, 17.83 ± 0.44, 18.37 ± 0.45, and 19.15 ± 0.44 g/L at T1, T2, T3, and T4, respectively).

Conclusions

Our results demonstrate that human milk protein concentration increases from the beginning to the end of a feed and over a 24-hr period. These findings contradict the majority of published studies and bring into question current published values of ‘typical’ human milk protein concentration. Our data suggest that time within a feed and time of day must be considered when collecting a representative milk sample for protein analysis.

#217 A case report of the association of klinefelter syndrome and autoimmune scleritis

S Michalsky

C Klinhom

M Malwane*

K Eckert

University of Nevada Reno, Reno, NV

Case Report

Autoimmune (AI) diseases have been shown to be more common in patients with Klinefelter Syndrome (KS) than the general population. To our knowledge, there are no known records of autoimmune scleritis in Klinefelter Syndrome. We report a unique case of a 13-year old male with KS and AI scleritis.

Methods

The medical records of a patient with KS and autoimmune scleritis were reviewed over a 3-year period.

Results

A 13-year old male with KS presented 1–2 week of right eye edema, erythema, decrease in vision, and mild ophthalmalgia and ophthalmodynia, worsened with eye movement. Patient reported concurrent pain in knees and shoulders. Patient was noted to have ‘red eyes’ as a child and diagnosed with keratitis. Family history was positive for arthritis, unexplained deep vein thrombosis in his mother, and antiphospholipid syndrome in grandfather. Physical exam was notable for the right eye with red, injected sclera and conjunctiva.

Further studies included MR of the right orbit showing mild right proptosis, as well as right periorbital, intraorbital and extraconal intraorbital edema and enhancement. Right uveal thickening and enhancement was seen and the extraocular muscles were normal in caliber and symmetry. The globes were otherwise unremarkable and the optic nerve/sheath complexes were normal in configuration. Final MRI impression was significant for right orbital and periorbital cellulitis with retinitis and mild proptosis. Patient had a mildly elevated white blood cell count at 12.7 K/uL and was started on IV Vancomycin and Unasyn. There was no clinical response after 2 days of treatment. Ophthalmology determined that presentation was most consistent with a likely autoimmune etiology, after which prednisone treatment was started at 80 mg daily. The patient showed immediate improvement in symptoms. Primary immune screen included: Antinuclear antibodies (ANA) was positive, but titers <1:40 (titers in the range of 1:40 to 1:60 are considered low), anti-neutrophilic cytoplasmic autoantibody (ANCA), rheumatoid factor (RF), Immunoglobulin (Ig) G subclasses, IgM, and IgA were all normal, SSA/SSB and HLA-B27 were negative. Initial erythrocyte sedimentation rate (ESR) was 31 and normalized to 2 (normal ESR in males : ≤15 mm/hr) after being on prednisone treatment. There are no specific tests available to confirm autoimmune scleritis; however, patient was unresponsive to appropriate antibiotic therapy and highly responsive to prednisone treatment, implying an autoimmune etiology.

At the age of 14, gonadal failure and delayed puberty were diagnosed.

Conclusions

Appropriate autoimmune screening should be part of the medical management of patients with KS. As presented in this case report, it is also important to be aware of eye symptoms, particularly scleritis, as the first symptom of autoimmunity in KS patients.

#218 Perception and contraception: attitudes towards hormonal birth control on tiktok

H Egnew

V Yu*

AL Nelson

E Guenther

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

Purpose of Study

Social media sites, such as Twitter, have been used to sample informal attitudes and messages shared about birth control between users. TikTok is a newer platform that appeals to younger users, that has not been used to study this topic. On TikTok, content creators openly share their experiences with birth control through dialogue and humorous interpretations. TikTok’s largest age group is 18–24, while Twitter’s is 30–49. Identification of sentiment about hormonal birth control in the previously untapped TikTok population could provide insight into younger patients’ attitudes towards birth control.

Methods Used

In this qualitative IRB-approved study, 100 videos per hormonal birth control method (oral contraceptive pills [OCP], injections, intrauterine devices [IUD] and implant) were identified through hashtags. Given interest in user experience, we excluded videos posted by self-identified medical providers or commercial agents. Videos were then analyzed for sentiment, factual accuracy, and theme saturation.

Summary of Results

60% of the content we surveyed on TikTok was negative, while 8% was positive. A previous study on Twitter had found a majority of birth control content was neutral or positive.

TikTok content most commonly highlighted side effects (59.5%), experiences with providers (19.5%), and humor (18.5%). OCP videos discussed side effects the least (37%) and were more likely to include humor (37%). Implant (70%), IUD (67%) and injection (64%) videos focused on side effects much more than OCP videos. IUD (18%) and OCP (13%) videos were most likely to contain misinformation. IUD contained the most videos mentioning complications (17%).

We found that videos discussing short-acting methods were over twice likely to be positive (12%) compared to long-acting methods (5%). A previous study found that Tweets mentioning long-acting methods were more likely to be positive than short-acting methods.

Humor was utilized most in OCP (37%) and IUD (16%). Many of the humorous videos joked about the onset and severity of side effects, or used humor to make fun of children’s misbehavior as their motivation for using birth control. One content creator stated, ‘I take the pill so my boyfriend doesn’t have to be a teen dad’. Much of the humorous content on TikTok relied on trending audio tracks, self-deprecating jokes, and facial expressions.

Conclusions

Attitudes and themes towards hormonal birth control options presented on TikTok differ from previous studies on public platforms, and introduce humor and use video formats that both resonate with the application’s younger users. Recognition of different perceptions of birth control by younger TikTok users in comparison to the older Twitter users can be used to strategically target misinformation and potentially identify generational differences in perception of birth control.

#219 Kidz MedEd: empowering youth to create animated medical education videos to foster stem identity in underrepresented youth

M Jayakumar1*

A Balasubramaniam2

R Alyssa3

N Garza4

K Piri5

R Kinman6

1Oakland University, Rochester, MI

2University of Leicester, Leicester, UK

3University of California San Francisco, San Francisco, CA

4University of California Merced, Merced, CA

5California State University Fresno, Fresno, CA

6University of California San Francisco Fresno, Fresno, CA

Purpose of Study

Inequalities in educational opportunities and lack of STEM identity have contributed to underrepresentation of various minority backgrounds in medical professions. We developed Kidz MedEd, an innovative pipeline program to increase STEM identity in impoverished minority youth interested in health careers through the creation of animated medical education videos and medical infographics.

Methods Used

High school students were recruited from the UCSF Fresno Doctors Academy Summer Program while pre-medical college students volunteered to provide mentorship to the high school students. Learners were divided into 3 groups containing medical, college, and high school student(s). Each group was headed by a pediatric subspecialist and met weekly via Zoom for mentorship and medical education. Animated medical education videos were created with Powtoon, with Canva used to create visually appealing medical infographics.

Summary of Results

Students learned digital literacy skills and improved their fund of medical knowledge while collaborating with both peers and near-peers to make informative infographics and videos on a variety of topics. An emphasis was placed on copyright literacy, gender and racial neutrality, and provision of medically accurate information to those with low literacy levels. Students were able to make informative infographics and videos on a variety of topics including asthma, constipation, diabetes, hepatic steatosis, hormones, obesity, and thyroid disease.

Conclusions

The Kidz MedEd project has provided underrepresented minority high school and college students from California’s impoverished Central Valley with an opportunity to gain insight into the medical field, learn valuable digital literacy skills, while simultaneously receiving mentorship from healthcare professionals. It demonstrates that educational technology can be used to create innovative medical learning experiences for high school and college students interested in health careers. Collaborations such as this can benefit both disadvantaged students who wish to gain greater exposure to the medical field and physicians who lack the time to create educational tools such as animated medical videos, infographics, and other social media content.

Cardiovascular III

Concurrent session

8:00 AM

Friday, January 21, 2022
#220 SMIDT heart institute takotsubo registry: adjudication methods

J Maughan1*

O Obrutu1

B Tjoe1

R Herscovici2

P Moy1

N Rojas1

P Marano1

J Wei1

C Shufelt1

C Bairey Merz1

1Cedars-Sinai Medical Center, Los Angeles, CA

2Sheba Medical Center, Tel Hashomer, Israel

Purpose of Study

Takotsubo syndrome (TTS) is an acute transient left ventricular dysfunction often triggered by emotional or physical stressors and seen predominantly in post-menopausal women. The Smidt Heart Institute Takotsubo Registry at Cedars-Sinai Medical Center aims to understand the prevalence, recurrence and prospective status of TTS. Rigorous medical record review is needed to adjudicate the diagnosis of TTS according to the International Takotsubo (InterTAK) Diagnostic Criteria.

Methods Used

Once enrolled into the Takotsubo Registry, research staff obtain medical records of all prior TTS events from the enrollees directly (upload via HIPAA secure BOX), through medical record request using a signed medical Release of Information Authorization form, or via the electronic health record EPIC and Care Everywhere system. Once medical records are obtained, study staff detail the completion of the records and note the TTS clinical picture, hospitalization labs, TTS triggers, electrocardiograms (ECG), echocardiograms (ECHO) during admission and recover, coronary angiography and ventriculogram findings, past medical history, and past and present medications. The minimum records needed for adjudication are troponin levels with ECGs during event, ECHOs, angiography and hospitalization summary. Once medical records are complete, they are sent to be adjudicated by two board-certified cardiologists in consensus using the following InterTAK Diagnostic Criteria: 1) transient left ventricular dysfunction with or without right ventricular dysfunction presenting as apical ballooning or midventricular, basal, or focal wall motion abnormalities, typically extending beyond a single epicardial vascular distribution, 2) absence of culprit atherosclerotic coronary artery disease 3) new and reversible ECG abnormalities, 4) positive elevation in cardiac troponin, 5) absence of infectious myocarditis. Events are adjudicated on REDCap as definite TTS, probable TTS, probable not TTS and definite not TTS based on the medical record review. Enrollees receive written adjudication results.

Summary of Results

From January 2019 to July 2021, 104 of the 131 participants enrolled in the registry have been adjudicated. Of the baseline events, 101 events were adjudicated as 61 definite TTS, 22 probable TTS, 10 probable not TTS and 8 definite not TTS. Furthermore, 32 enrollees reported a total of 55 recurrent events (between 2–5 events per enrollee) which include 14 definite TTS, 11 probable TTS, 7 probable not TTS and 23 definite not TTS events.

Conclusions

The Smidt Heart Institute Takotsubo Registry aims to investigate TTS pathophysiology and gain an accurate estimation of TTS reoccurrence. Limitations of the adjudication process include time intensive collection of medical records from institutions which is a focus for improvement.

#221 Risk factors for seizures following heart transplantation

L Mishalani1*

N Patel2

T Singer-Englar2

S Kim2

M Hamilton2

J Kobashigawa2

1Columbia University, New York, NY

2Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

Purpose of Study

Seizures following heart transplantation is not uncommon. Patients who have had previous strokes have a higher propensity to develop seizures after open heart surgery. Patients who undergo heart transplant may also have underlying atherosclerotic vascular disease and have a history of stroke or cerebral microvascular disease. Both of these entities may be a risk for developing seizures after heart transplant. It has not been well established what the frequency of seizures is and whether or not we can identify risk factors as to who will develop these seizures.

Methods Used

Between 2015 and 2020, we assessed 560 patients undergoing heart transplantation and found that 40 patients developed seizures within the first month postoperatively. We identified risk factors for these patients such as previous stroke, atherosclerotic vascular disease, previous history of seizures, history of diabetes, history of smoking, and male gender. The main endpoint was to establish the frequency of seizures following heart transplant surgery and to assess risk factors to develop seizures. These patients with seizures were compared to patients without seizures.

Summary of Results

The incidence of seizure was 7.1% following heart transplant surgery. Univariate analysis found that hypertension, history of atherosclerosis, and history of seizures were significant risk factors to developing seizures immediately postoperative. Multivariate analysis found that only hypertension and history of previous seizures were significant for the development of seizures post-heart transplant. Patients who were on tacrolimus appear to have a lower threshold to experience seizures and these patients were subsequently switched to cyclosporine.

Abstract #221 Table 1

Univariate analysis

Abstract #221 Table 2

Conclusions

Patients undergoing heart transplant with hypertension and history of seizures are at risk to develop seizures postoperatively. These patients may be considered for prophylactic anti-seizure therapy for the first 30 days following heart transplant surgery.

#222 Myocarditis as an early manfiestation of systemic lupus erythromatosus in a young female

P Chan1*

VK Narang2

F Joolhar2

T Win2

1Ross University School of Medicine, Miramar, FL

2UCLA-Kern Medical, Bakersfield, CA

Case Report

Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system can attack its own tissue and causes damage to many organs, even the heart. This case report shows a rare presentation of SLE myocarditis in an 18 year old female.

Methods

Approval was obtained from IRB. A single patient case report was conducted.

Case Presentation

A 18-year-old Filipino female with no past medical history presented to the emergency department with bilateral extremities and periorbital swelling for 10 days with recent development of oral mucosal ulcers. Patient was found to have hyponatremia and nephrotic range proteinuria; in addition to a positive family history of autoimmune disorder, an autoimmune workup was ordered. The work up showed high antinuclear antibodies titer of 1:1280 and high double-stranded DNA antibody of 6 IU/mL which was highly suspicious of SLE related cause of patient’s symptoms. Further workup with ultrasound-guided renal biopsy resulted in lupus podocytopathy. Chest x-ray showed cardiomegaly so transthoracic echocardiogram (TTE) was ordered to rule out pericarditis and pericardial effusion. The TTE showed left ventricular ejection fraction (LVEF) 60%. Eight days later, the patient was found to be tachycardic to 130–140s with oxygen saturation of 88% so computerized tomography angiogram of the chest was obtained. It showed no evidence of pulmonary emboli but there was right lower lobe pneumonia, right sided small pleural effusion, and borderline cardiomegaly. Electrocardiogram showed no abnormalities but BNP was elevated to 3608 pg/mL and repeat TTE showed concentric left ventricular hypertrophy with LVEF 20% and small circumferential pericardial effusion. Guideline-directed medical therapy (GDMT) with lisinopril and carvedilol initiated. The patient was discharged with outpatient follow up.

Conclusion

SLE can affect virtually all organs by the immune system attacking its own tissue and causing widespread inflammation and tissue damage. The heart is a common affected organ usually presenting with pericarditis or premature coronary artery disease in patients with long standing disease while myocarditis is less common.

This case shows a rare presentation of SLE myocarditis in an acute setting seen with a huge decline in cardiac function over 8 days. One can argue that this could be a case of stress myocarditis due to the acute presentation. A better understanding of patients with SLE and the risk for specific cardiac manifestations of SLE should be researched for improvement of clinical outcome for future patients.

#223 Smidt heart institute takotsubo registry – study design

O Obrutu1*

J Maughan1

B Tjoe1

R Herscovici2

P Moy1

N Rojas1

P Marano1

J Wei1

C Shufelt1

T Rutledge3,4

C Bairey Merz1

1Cedars-Sinai Smidt Heart Institute, Los Angeles, CA

2Chaim Sheba Medical Center, Tel-Hashomer, Israel

3VA San Diego Healthcare System, San Diego, CA

4University of California, San Diego, CA

Purpose of Study

Takotsubo syndrome (TTS) is an acute form of transient systolic heart failure that occurs predominantly in women, often triggered by emotional or physical stressors. The Smidt Heart Institute Takotsubo Registry at Cedars-Sinai Medical Center aims to establish a database for deep phenotyping of this syndrome.

Methods Used

Registry participants are recruited from multiple sources: Deep 6-based medical records review, physician referrals, peer and self referrals (Abstract #223 figure 1). Deep 6 is an artificial intelligence software that analyzes clinical data to identify patients that match complex clinical trial criteria. Peer and self referrals are sourced through social media advertisements on a Facebook support group for TTS survivors. Recruited participants remotely sign consents and provide detailed information via questionnaires on REDCap. Medical records of TTS events are adjudicated by cardiologists using the International Takotsubo Diagnostic Criteria. MITRA kits are used to remotely collect blood samples for further analysis.

Summary of Results

From January 2019 to July 2021, 131 participants (99% female, mean age: 61.2±9.8 years) enrolled in the registry across 25 US states and 3 other countries. About 41% of enrollees are self or peer referrals. Overall, 89% completed all baseline questionnaires and 78% returned filled MITRA kits. Completed questionnaires provide information about participants’ general health status, physical function, psychosocial history, and TTS events.

Abstract #223 Figure 1

Recruitment and enrollment flowchart

Conclusions

The Takotsubo Registry will reach a large and diverse participant base by using a multifaceted approach to recruitment as well as tools to facilitate remote enrollment and study participation. Study questionnaires, blood samples and medical record review will allow for deep phenotyping of participants in order to deepen our understanding of TTS pathophysiology.

#224 Cardiac transcriptome analysis of the electronic cigarette-induced cardiac dysfunction mouse model treated with acipimox

JL Arambulo1*

J Espinoza-Derout1

K Hasan1

MC Jordan2

CJ Lao1

J Wilson1

K Luna2

A Sinha-Hikim1

K Roos2

T Friedman1

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

2University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

Purpose of Study

Electronic cigarettes (e-cigarettes) have increased in popularity and pose a public health crisis, demanding further research on their cardiovascular health effects to better inform future interventions. We have shown that mice treated with e-cigarettes containing nicotine develop increased serum free fatty acid levels (FFAs) and systolic dysfunction associated with inflammation. As such, we aim to study the differentially expressed genes between the hearts of e-cigarette and saline-treated mice and to define the genes controlling the physiological normalization produced by acipimox (a lipolysis inhibitor). We hypothesize that acipimox will reverse the transcriptomic changes associated with e-cigarette-induced cardiomyopathy.

Methods Used

C57BL/6J wild type mice were exposed to saline, e-cigarettes, and e-cigarettes plus acipimox for 12 weeks. Left ventricular RNA was sequenced for differential gene expression and analyzed using Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA).

Summary of Results

Our preliminary echocardiographic data showed that acipimox abrogates the e-cigarette-induced increases in serum FFAs and cardiomyopathy. RNA-sequencing analysis showed that 79 genes were dysregulated by e-cigarette treatment, and IPA showed that these changes are associated with inflammation. 30 of these genes were normalized by acipimox treatment and are implicated in inflammation, atherogenesis, and cardiac function. GSEA revealed that acute myocardial infarction, circadian rhythm, and G2/M DNA damage checkpoint genes are enriched in e-cigarette-treated mice compared to e-cigarette plus acipimox and saline-treated mice.

Conclusions

Our RNA-sequencing analysis offers a mechanistic insight into how acipimox prevents cardiomyopathy in e-cigarette-treated mice. These findings provide gene expression evidence suggesting that lipolysis is necessary for e-cigarette-induced cardiac dysfunction. This study and future studies will not only illuminate the harms involved with e-cigarettes, but will also aid in the identification of targets for intervention to address complications associated with e-cigarette usage.

#225 Long-term cardiac outcomes of multi-system inflammatory syndrome in children (MIS-C)

K Ghasemian1*

J Chuang1

S Datta1

A Koka1

F Shaik1

D Sun1

M Sunkara1

B Afghani1,2

1University of California Irvine School of Medicine, Irvine, CA

2Children’s Hospital of Orange County, Orange, CA

Purpose of Study

Due to the novelty and severity of the COVID-19 pandemic, the long-term cardiac outcomes of children diagnosed with multi-system inflammatory syndrome (MIS-C) have not been extensively studied. The purpose of this study was to evaluate cardiac outcomes, comparing echocardiogram and lab results at admission and follow-up periods.

Methods Used

A literature review using Google Scholar and Pubmed was conducted, utilizing keywords such as ‘long-term cardiac outcomes’, ‘multi-system inflammatory syndrome in children’, and ‘Coronarivus Disease 2019’. We included studies of MIS-C patients that reported echocardiographic data and outcomes, troponin levels, and a minimum follow-up period of two weeks. Studies only evaluating electrocardiogram results were excluded.

Summary of Results

Left ventricular (LV) dysfunction or decreased LV ejection fraction (LVEF) were the most common initial finding and seen in up to 60% of patients with MIS-C. Upon follow-up, these abnormalities had resolved in the vast majority of patients, with residual dysfunction seen in a few patients. Coronary artery dilations and aneurysms were seen in up to 33% of patients initially, and resolved in almost all patients, especially when follow-up period was longer. Elevated troponin levels had normalized at follow-up. Other common MIS-C-associated cardiac abnormalities included myocarditis, mitral valve regurgitation, and pericardial effusion, which were often resolved by the follow-up period.

Abstract #225 Table 1

Cardiac characteristics and long-term outcomes in patients with multisystem inflammatory syndrome in children (MIS-C)

Conclusions

Our review suggests that patients with MIS-C have favorable long-term cardiac outcomes. In general, the initial cardiac complications and findings substantially improve or resolve by follow-up. Persistent cardiac abnormalities are rare, and often mild in severity. Further research with larger sample sizes and longer follow-up periods must be evaluated to better understand the long-term cardiac outcomes of MIS-C.

#226 Wet beriberi in a patient with ischemic cardiomyopathy and gastric bypass: a case report

T Azenkot*

OM Campa

University of California Davis Health System, Sacramento, CA

Case Report

A 49-year-old woman with hypertension and Roux-en-Y gastric bypass 9 years prior presented for subacute exertional dyspnea and chest pain. Her home medications were multivitamins. On admission, blood pressure was 163/123 mmHg and heart rate 96 bpm. Hemoglobin was 12.9 g/dL. Troponin was 22 and unchanged on repeat. B-type natriuretic protein was 276 pg/mL. An electrocardiogram was without changes concerning for acute coronary syndrome. An echocardiogram showed global hypokinesis with an estimated left ventricular ejection fraction (LVEF) of 25%. Coronary angiography demonstrated complete total occlusion of the right coronary artery, though her global akinesis was out of proportion to this finding. She was discharged on guideline directed medical therapy for heart failure (HF).

Four months later, the patient returned to the emergency department for dizziness. Her blood pressure was 53/43, with improvement to 91/53 after fluids. Creatinine was 2.29 and granular casts seen on urinalysis. Her alkaline phosphatase and aspartate and alanine transaminases were 1,213 U/L, 615 U/L, and 338 U/L, respectively, a pattern consistent ischemic hepatopathy. An echocardiogram showed improved LVEF to 32% with no focal wall motion abnormalities. Thiamine level was 51 (normal 70–180) nmol/L, concerning for component of thiamine deficiency-induced cardiomyopathy, or wet beriberi. Supplementation was initiated. HF medications were held. Her dizziness and lab abnormalities resolved with fluids.

The prevalence of thiamine deficiency in patients admitted for HF is estimated to be 30% (Hanninen et al., 2006). This may be in part due to the association of diuretics, including furosemide, with increased renal excretion and decreased intestinal absorption of thiamine. Post gastric bypass patients also have a prevalence of thiamine deficiency up to 30% due to disruption of thiamine absorption in the duodenum and jejunum (Wilson, 2020). This renders patients with HF and gastric bypass, such as the present case, dually vulnerable to thiamine deficiency. Several small studies have demonstrated improved HF outcomes (i.e., improved LVEF and decreased hospital admission rates) with thiamine supplementation, though further studies are needed (Jain et al., 2015).

#227 Malignant effusions: a rare case of subacute, severe regional cardiac tamponade

N Shamapant*

C Duarte

University of Colorado, Denver, CO

Case Report

Identify clinical manifestations of regional cardiac tamponade

Case Presentation

The patient is a 31 year old female with stage IV ER+, PR+, Her2- breast cancer complicated by recurrent malignant pleural effusions who presented with worsening dyspnea. Vitals on admission included BP 121/91, HR 124, RR 32 and oxygen saturation of 99%. Shortly after admission, blood pressure dropped to 92/68 and oxygen saturation was 97% on 2L nasal cannula. On exam, patient had increased work of breathing with elevated neck veins. EKG showed low voltage QRS complexes with electrical alternans. CTA chest revealed a large pericardial effusion with no evidence of pulmonary embolus (PE). Given the pericardial effusion, a manual pulsus was checked and was negative. TTE showed a large pericardial effusion with moderate right ventricular (RV) collapse, dilated inferior vena cava and normal left ventricular systolic function. Based on the echocardiographic evidence of pericardial effusion with RV collapse in the context of worsening hypotension and tachycardia, the diagnosis of regional cardiac tamponade was made. Pericardiocentesis was performed with an opening pericardial pressure of 23mmHg and 680mL of fluid was drained with cytology confirming malignant pericardial effusion. Following the pericardiocentesis, the patient’s dyspnea and tachycardia resolved. Significant post-procedure pericardial drainage prompted placement of a pericardial window and the patient was discharged to hospice.

Discussion

This patient’s presentation of dyspnea, tachycardia, progressive hypotension and distended neck veins fits multiple illness scripts including PE and cardiac tamponade. When the CTA was negative for PE, the team pursued tamponade as a possible diagnosis. Normally the lack of a pulsus paradoxus would argue against clinical tamponade physiology. However, this case is particularly unique for the echocardiographic finding of isolated RV collapse, leading to clinically significant regional tamponade. Collapse of a cardiac chamber occurs when pericardial pressure is greater than chamber pressure. Regional tamponade is often seen after procedures (pericardiotomy, cardiac surgery) or myocardial infarction where a loculated effusion or pericardial hematoma forms in a particular region1. Regional cardiac tamponade fails to produce pulsus physiology because the increased pericardial pressure is localized to the RV2. The RV’s inability to expand prevents interventricular septum from bowing into the left ventricle (LV) on inspiration. As a result, there is no compression of the LV, a phenomenon which is required for the clinical manifestation of pulsus paradoxus. This patient’s presentation of dyspnea, hypotension, and tachycardia with negative pulsus paradoxus but echocardiographic findings of pericardial effusion merited a high level of suspicion for regional cardiac tamponade.

Case reports I

Concurrent session

8:00 AM

Friday, January 21, 2022
#228 Extensive left ventricular and mitral valve thrombus in a gastric cancer patient on direct oral anticoagulants

P Chan1*

VK Narang2

F Joolhar2

T Win2

1Ross University School of Medicine, Miramar, FL

2UCLA-Kern Medical, Bakersfield, CA

Case Report

Thrombotic events are a common complication of cancer but it is rare to have arterial thrombosis. This is an unusual case of left ventricular thrombus and multiple thrombi on the mitral valve while taking direct oral anticoagulants (DOAC) in a patient with stage IV gastroesophageal signet ring adenocarcinoma.

Methods

Approval was obtained from the IRB at Kern Medical. A single patient chart review was conducted.

Summary

A 45-year-old female with no past medical history presented to the emergency department (ED) with decreased appetite, fatigue, dysphagia, abdominal pain, and unintentional weight loss for 4 months. Initial workup with esophagogastroduodenoscopy (EGD) showed an epigastric mass that was biopsied. The pathology came back showing stage IV gastroesophageal signet ring adenocarcinoma. During this hospitalization, the patient also had a computerized tomography (CT) of the chest done which showed pulmonary emboli (PE), and was started on apixaban for PE therapy.

Four weeks later, a CT of the chest, abdomen, and pelvis was ordered for evaluation of port-a-cath placement evaluation which demonstrated a filling defect within the left ventricular apex measuring 19 x 17 mm. The patient was referred for a transthoracic echocardiogram (TTE) which revealed a large left ventricular thrombus and multiple thrombi on the mitral valve. The patient was then admitted to the hospital for initiation of anticoagulation with therapeutic Lovenox. The patient was then discharged home with therapeutic Lovenox and instructions to follow up with cardiology outpatient.

Conclusion

It is well known that there is a link between thromboembolism and cancer but the underlying mechanism is poorly understood. It is believed that there are many ways the cancer cells activate the coagulation system such as having the ability to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common complications in patients with cancer but arterial thrombosis secondary to malignancy is rare. The case highlights a rare presentation of a large left ventricular thrombus and multiple thrombi in the mitral valve in a patient with stage IV gastroesophageal signet ring adenocarcinoma that was already on a DOAC for a known PE.

#229 Cardiovascular manifestations in adolescent males after the Pfizer COVID-19 vaccine

M Arhin1*

H Hamad2

C Iheagwara3

J Hales4

1University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC

2Geisinger Commonwealth School of Medicine, Scranton, PA

3North Carolina State University, Raleigh, NC

4HCA Holdings Inc, Nashville, TN

Case Report

The Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for the Pfizer BioNTech mRNA (BNT162b2) and Moderna COVID-19 vaccines in December 2020 to address rising COVID-19 infections across the nation. Clinical trials showed the vaccines to be effective and safe. Once these vaccines became publicly available, some minor adverse events were reported to the Vaccine Adverse Event Reporting System (VAERS); they included fever, fatigue, and joint pain. Additionally, there have been cases of post-immunization myocarditis and/or pericarditis reported to VAERS.

This case series describes the clinical course of the first three adolescent patients in our hospital that presented with myocarditis or pericarditis within two to four days after administration of their first or second dose of the Pfizer mRNA covid-19 vaccine. The COVID-19 status of the patients was assessed by reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs. Laboratory tests for all patients included a routine complete blood count, basic metabolic panel, troponin, and inflammatory markers. Two patients had testing for SARS-CoV-2/Covid-19 and other viral causes of myocarditis and pericarditis, including the Epstein-Barr virus, cytomegalovirus, parvovirus B19, respiratory syncytial virus, influenza A virus, influenza B virus, Roseola, and human herpesvirus 6. These tests were all negative.

The three cases at our hospital consisted of previously healthy male adolescents between the ages of 14 and 17 that presented with chest pain within 4 days of receiving their first or second mRNA covid-19 vaccine. On admission, they all had an abnormal electrocardiogram (ECG), elevated C-reactive protein (CRP), and elevated troponin I levels (table 1). Brain natriuretic peptide (BNP) levels were tested in two patients and found to be within normal limits. All patients had a normal echocardiogram, except for a residual patent foramen ovale in one patient. All patients showed down-trending troponin levels and inflammatory markers as well as complete resolution of symptoms before discharge on hospital day 4. All patients had normal troponin and CRP levels at post-discharge follow-up with an outpatient pediatric cardiologist visit. No causal relationship has been proven between the vaccine and myocarditis or pericarditis. Currently, the Centers for Disease Control and Prevention (CDC) continues to recommend the COVID-19 vaccination for anyone older than twelve years old as the known risks of illness and possible severe complications far outweigh having a possible rare adverse reaction. Suspected cases of myocarditis and pericarditis after COVID-19 vaccination should continue to be reported to VAERS

Abstract #229 Table 1

Clinical and diagnostic summary of each case

#230 Metastatic and persistent bacteremia with methicillin-resistant staphylococcus aureus, associated with COVID-19 pneumonia, a management nightmare

C Besmanos1,2*

C D’Assumpcao2

I Fong2

R Kuran2

A Heidari2

1American University of the Caribbean School of Medicine BV, Cupecoy, Sint Maarten (Dutch part)

2Kern Medical Center, Bakersfield, CA

Case Report

Telavancin is a vancomycin-derivative semisynthetic lipoglycopeptide that has antimicrobial activity against resistant gram-positive organisms, namely methicillin-resistant Staphylococcus aureus (MRSA). The purpose of this study is to describe a case in which telavancin clinically failed in treating persistent MRSA bacteremia in a patient.

Methods Used

Retrospective case review.

Summary of Results

A 61-year-old man with nasal MRSA colonization and history of previous abscesses was initially admitted for severe COVID-19 pneumonia requiring high flow nasal cannula oxygen support and dexamethasone protocol as per current guidelines. He developed MRSA pneumonia and persistent polyclonal resistant MRSA bacteremia with hematogenous seeding causing lumbar vertebral osteomyelitis despite treatment with vancomycin for 5 days follow with telavancin for 11 days. MRSA susceptibility to the glycopeptide antibiotics as well as ceftaroline and daptomycin were evaluated using E-test to interpret minimum inhibitory concentration (MIC) according to the manufacturer’s instructions. Telavancin MIC was initially 0.064 but then on retest was 0.125. Since MRSA continued to grow in repeated blood cultures after 11 days, telavancin was considered to have clinically failed. He was switched to combination of ceftaroline and daptomycin and subsequently developed daptomycin associated eosinophilic pneumonitis. He was started on prolonged course of prednisone. He was switched to ceftaroline and rifampin to complete 6 weeks total of antibiotics after blood sterilization. Outpatient MRSA decolonization protocol was also started just prior to discharge.

Conclusion

Secondary bacterial infection associated with COVID-19 is on the rise particularly after adoption of dexamethasone as standard of care in severe cases. Persistent bacteremia with MRSA complicated with metastatic seeding in this setting is not described and perhaps is due to host-pathogen mediated mechanisms. Clinical failure of telavancin in deep seeded MRSA infections has not yet been reported.

#231 A severe case of recurrent herpes simplex virus-1 encephalitis with autoimmune component

VF Civelli1*

C D’Assumpcao2

M Kaur3

R Kuran2

K Sabetian2

A Heidari2

1Clinica Sierra Vista, Bakersfield, CA

2Kern Medical Center, Bakersfield, CA

3Ross University School of Medicine, Miramar, FL

Case Report

The incident of Human Herpes Simplex Virus-1 (HSV-1) encephalitis is 4 in one million cases worldwide. From that 5–27% can become recurrent a rare phenomenon with serious sequela. Differentials include induced autoimmune-mediated sequelae or paraneoplastic encephalitis. Knowing that 69–89% of first HSV-1 encephalitis will result in permanent neurological deficits, the degree of damage in recurrent cases is estimated to be higher. The pathophysiology of recurrent HSV-1 encephalitis and its aftermath are poorly understood. We report a case of recurrent HSV encephalitis with evidence of autoimmune dysfunction.

Methods Used

Retrospective Study

Summary of Results

A 58-year-old Hispanic female presented elsewhere for acute onset of confusion. She was diagnosed with HSV-1 encephalitis by PCR testing of the CSF and received 28 days on intravenous (IV) Acyclovir and recovered. She presented to our facility with new onset of seizures, expressive aphasia, short-term memory loss, bowel/bladder incontinence, and unsteady gait. Her mental status declined, and diagnosis of autoimmune encephalitis was made due to negative HSV-1 PCR and brain MRI findings. A 5-day course of IV Immuglobulin and high dose methylprednisolone resulted in transient reliefe of her symptoms. She was discharged home with prednisone for 5 weeks. Autoimmune CSF panel showed elevated acetylcholine receptor ganglionic (alpha 3) Ab at 172, and elevated VGCC Type P/Q Ab at >30, and VGCC Type N Ab at 69. She had two episodes of recurrent neurological symptoms resulted in courses of IV high dose steroid with transient relief each time CSF only was positive for mild pleocytosis with negative HSV-1 PCR. Her brain MRI continued to show progressive disease now spreading to both sides. On the third recurrence episode of rapid decline in mentation CSF came back positive for HSV-1 PCR. She was started on a 3-week course of IV Acyclovir. Follow up CSF was negative for HSV-1 PCR and she is placed on prolong course of oral valacyclovir with unknown duration perhaps lifelong.

Conclusion

Differential diagnosis of recurrent encephalitis after the first episode of HSV-1 infection includes immune-mediated HSV-1 viral encephalitis vs recurrence of HSV-1 itself. Residual irreversible neurocognitive deficits are expected and may result in protracted disease. The diagnosis is challenging and prognosis is poor.

#232 Human herpesvirus-6 meningoencephalitis in an immunocompetent male

VK Narang1*

C D’Assumpcao2

M Valdez1

K Radicic1

L Moosavi1

R Kuran2

A Heidari2

1UCLA-Kern Medical, Bakersfield, CA

2Kern Medical-UCLA, Bakersfield, CA

Case Report

Meningoencephalitis with Human herpesvirus 6 (HHV-6) in adults is rare. It is known to occur as a result of reactivation of infected dormant brain cells during childhood, when host becomes immunocompromised in conditions such as organ or bone marrow transplantations. New primary infection in adults has also been described. Diagnosis is difficult and challenging particularly in immunocompetent adults due to low level of suspicious and undefined clinical, central spinal fluid (CSF) and neuroimaging findings. The duration and choice of antiviral also have not been well reported. We present a case of HHV-6 meningoencephalitis in an immunocompetent elderly male who presented with fever and altered mental status.

Methods

A single patient case report was conducted after IRB approval.

Case Presentation

Patient is a 79-year-old male with a history of dementia and diabetes mellitus who presented after being found down by a bystander. Patient arrived lethargic, tachypneic, and febrile to 39.4 °C. Physical exam was remarkable for rigid extremities with laboratory studies demonstrating a leukocyte count of 14.6x10^3 cells/mm3 without left shift and hyperglycemia to 550 mg/dL. He was empirically placed on antibiotics to cover bacterial etiologies plus acyclovir. CT of the head demonstrated moderate to severe global volume loss and periventricular leukomalacia. CSF showed WBC count of 17 with 76% monocytes and 22% lymphocytes. Extensive initial work up and all cultures came back negative. MRI brain with gadolinium found atrophic and chronic microangiopathic changes without enhancement. CSF Meningoencephalitis Panel (BioFire, BioMerieux, Salt Lake City, Utah) found HHV-6 positivity. HHV-6 serology testing found negative IgM and positive IgG. Serum HHV-6 PCR confirmed the diagnosis with > 2 million copies/mL. Patient was started on ganciclovir which resulted in significant improvement in symptoms. He was discharged to rehabilitation facility to complete a 30 day course of ganciclovir.

Conclusion

HVV-6 meningoencephalitis is a serious but rare condition particularly in otherwise immunocompetent adults. Clinicians should be aware of this infection when initial work up is not diagnostic.

#233 A case of concurrent disseminated coccidioidomycosis and embryonal carcinoma when lice and fleas coexist

M Ke

A Heidari

M Valdez*

A Tsiyer

R Kuran

R Johnson

Kern Medical Center, Bakersfield, CA

Case Report

Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United Stated with a wide range of clinical presentations depending on the infected organ systems. CM causes a primary pulmonary infection. 1 percent of cases disseminate, via hematogenous or lymphatic spread. It is in these cases, that more severe symptoms may present and potentially overlap with those characteristics of other systemic illnesses. We report a case of CM disseminated to lymph nodes in a 24-year-old man with concomitant metastatic embryonal carcinoma. It is difficult to identify the primary etiology for many components of his presentation and the relationship between these concurrent disease processes is not entirely clear. Factors that may contribute include locus minoris resistentiae or a shared immune response between infectious organisms and malignant cells.

Case Description

24-year-old man from the central valley of California presented with a new rash. Examination showed periorbital edema and diffuse raised, erythematous, hyperpigmented skin lesions. Differential included psoriasis and CM. CM serology showed nonreactive IgM, very weakly reactive IgG, and complement fixation (CF) titer <1:2. The patient was lost to follow-up but returned 6 weeks later with 17-pound weight loss, progression of the rash, and proximal muscle weakness. He had a heliotrope rash and elevated CK. He was prescribed prednisone 60 mg daily for dermatomyositis. 2 weeks later, he developed fevers and CM CF titer was 1:16. He was started on fluconazole 800 mg daily. 5 weeks later, he developed diffuse lymphadenopathy and imaging showed multiple pulmonary nodules, destructive lesion in the iliac bone, and retroperitoneal and pelvic lymphadenopathy. CM CF titers were now 1:64 and he was started on liposomal amphotericin B. New retroperitoneal and right testicular masses were then identified. Histopathology from orchiectomy and retroperitoneal mass biopsy revealed embryonal carcinoma while inguinal lymph node excision showed granulomatous inflammation with endosporulating spherules diagnostic for CM. He completed 9 weeks of amphotericin and bone scan showed no foci of increased uptake. He is on track to complete 4–6 cycles of chemotherapy. On subsequent clinic visits, weight was up-trending and improvement in both rash and lymphadenopathy were noted.

Conclusion

As CM and several types of malignancies may have similar or overlapping presentations, a thorough examination and tissue sampling are generally necessary to distinguish. In rare cases, coexistence may occur. ‘Läuse und Flöhe haben.’ A German phrase, which translates to ‘Having lice and fleas,’ refers to having two reasons for a problem. Understanding the etiology or identifying the relationship between the concomitant conditions is essential to formulate the most appropriate treatment plan.

#234 A rare case of neisseria meningitidis pneumonia in the absence of meningitis

J Johal

M Valdez*

HK Sandhu

S Mishra

A Heidari

Kern Medical Center, Bakersfield, CA

Case Report

Neisseria meningitidis (NM) is a gram-negative diplococcus that typically colonizes the nasopharynx after inhalation of aerosolized particles containing meningococci. NM may also be transmitted via direct contact with respiratory secretions. Once local tissues are colonized, NM can invade the bloodstream, causing numerous forms of meningococcal diseases. The most common manifestations are meningitis and septicemia. Meningococcal pneumonia (MP) is a rare manifestation of meningococcal disease. The incidence of MP is estimated at 5%–15% in patients with invasive meningococcal disease. Only 344 MP cases have been documented worldwide between 1906 and 2015. At least 13 serogroups of meningococci have been identified. Serogroups A, B, C, X, Y, and W-135 are associated with meningococcal disease in humas. Y and W-135 are most associated with pneumonia. The clinical presentation of MP is indistinguishable from pneumonia caused by other infectious organisms. We report a case of an 88-year-old female with concurrent SARS-CoV-2 and NM pneumonia.

Case Presentation

88-year-old woman with diabetes and hypertension presented with 3-day history of dyspnea, productive cough, and subjective fevers. On presentation, she met SIRS criteria and was hypoxic. Initial labs were significant for lactic acid 2.5, procalcitonin 3.62, and testing for SARS-CoV-2 RNA positive. CXR revealed a 7cm RUL opacity. CTA chest showed a large RUL consolidation with scattered ground-glass opacities. She was initially started on Ceftriaxone 1g Q24H and Azithromycin 500 mg Q24H for community acquired pneumonia as well as a 10-day course of dexamethasone for hypoxia associated with SARS-CoV-2. Preliminary blood cultures grew gram-negative diplococci in 1 of 2 bottles and final culture revealed NM. Ceftriaxone was then increased to 2g Q24H. Patient remained alert and oriented. She denied headaches and neck stiffness. Neck was supple with no nuchal rigidity or signs of meningismus. Bronchoscopy was considered but was eventually deferred in the setting of concurrent covid pneumonia and given that symptoms improved with appropriate antibiotic therapy. Repeat blood cultures showed no growth and patient was discharged with supplemental oxygen for covid associated hypoxia and oral Amoxicillin/Clavulanic acid to complete a 14 day total course of antibiotics for MP.

Conclusion

Neisseria Meningitidis as the underlying etiology for pneumonia should always be considered when blood or sputum cultures identify gram-negative diplococci. Early recognition is critical in order to reduce the risk of transmission to close contacts and health care personnel. Finally, given the high mortality rates associated with untreated meningococcal disease, early initiation of appropriate antibiotic therapy is essential in attempting to improve the outcomes of meningococcal disease.

#235 Gastric mucormycosis in an adolescent with new onset diabetes mellitus

J Timberman*

C Kupelian

Valley Children’s Healthcare, Madera, CA

Case Report

Mucormycosis is a rare angioinvasive fungal infection associated with a high mortality rate, especially in children and neonates. Recent data suggests the incidence is rising in the United States. Risk factors include diabetes, glucocorticoids, hematological malignancies and iron overload. The most frequent types of mucormycosis include rhinoorbitocerebral, pulmonary, and cutaneous disease.

Here we present a child with newly diagnosed type II diabetes mellitus who developed hematemesis and was found to have gastrointestinal mucormycosis.

Methods Used

Case Report

Summary of Results

A 17-year old obese male presented to the emergency department with a 1-day history of abdominal pain, vomiting and respiratory distress. Weight loss, polyuria and polydipsia were reported. He had no other significant medical or surgical history. On examination his temperature was 37.8 C, pulse 137, BP 116/77, RR 44, and Pox 96% in room air. He was altered, mucus membranes were dry, and abdomen was distended and diffusely tender. He was subsequently admitted to our pediatric intensive care unit.

The patient was found to be in diabetic ketoacidosis with acute pancreatitis, for which he was treated accordingly. During his hospital course, he acutely developed severe hematemesis and anemia. Esophagogastroduodenoscopy demonstrated the presence of active bleeding and multiple ulcerations in the stomach. Biopsy showed fungal elements with ribbon like hyphae, identified as Rhizopus microsporus.

The patient was diagnosed with hemorrhagic gastritis secondary to mucormycosis. He was started on liposomal amphotericin and posaconazole with resolution of his hematemesis. He received 6 weeks of liposomal amphotericin and was discharged home on a prolonged course of posaconazole.

Conclusions

Our case emphasizes the importance of considering gastrointestinal mucormycosis in children with diabetic ketoacidosis and hematemesis.

Gastrointestinal mucormycosis is thought to occur due to ingestion of spores amongst immunocompromised hosts. The angioinvasive nature of the gastrointestinal lesions places children at risk for perforation, bowel infarction, and hemorrhagic shock. Although the prognosis is poor, early initiation of antifungal therapy has been shown to improve outcomes and reduce mortality rates. In this case, biopsy allowed for timely diagnosis and initiation of appropriate therapy, resulting in a favorable outcome.

Endocrinology and metabolism II

Concurrent session

8:00 AM

Friday, January 21, 2022
#236 Neural correlates of obesity and inflammation in youth with classical congenital adrenal hyperplasia

MS Kim1,2*

TA Pickering3

DL Cotter3

NR Fraga1

S Luo4

C Won1

M Geffner1,2

M Herting2

1Children’s Hospital of Los Angeles, Los Angeles, CA

2Children’s Hospital of Los Angeles Saban Research Institute, Los Angeles, CA

3University of Southern California Keck School of Medicine, Los Angeles, CA

4University of Southern California, Los Angeles, CA

Purpose of Study

Patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit an increased prevalence of obesity over their lifetime. We have previously shown that CAH youth exhibit smaller gray matter brain region volumes, including the prefrontal cortex (PFC), amygdala, and hippocampus, as well as white matter microstructure abnormalities. Here, we aim to study the relationship between these patterns of altered brain structure with obesity and inflammation in youth with and without CAH.

Methods Used

We studied 27 youth with CAH (12.6 ± 3.4 yr, 16 females) and 35 controls (13.0 ± 2.8 yr, 20 females) via 3-T MRI, and examined the PFC and its subregions, amygdala, and hippocampus regions of interest (ROIs), as well as white matter tracts including the fornix and stria terminalis (ST). Relaimpo (relative importance for linear regression: R2lmg) analyses identified body composition and inflammatory markers, as well as gray and white matter ROIs most associated with CAH status. Regression analyses examined associations between brain structure, CAH, and other variables.

Summary of Results

Waist-to-height ratio (WHtR; R2lmg = 0.12) and monocyte chemoattractant protein-1 (MCP-1 R2lmg = 0.21) exhibited the strongest associations with CAH status amongst body composition variables and inflammatory markers respectively. Analysis of gray matter ROIs showed the PFC was most strongly associated with CAH status (R2lmg = 0.13). Superior frontal (SF) was the only PFC subregion associated with all key variables: CAH status (β = -0.58, P = 0.001), WHtR (β = -0.23, P = 0.009), and MCP-1 (β = -0.35, P < 0.001). CAH youth exhibited significantly larger WHtR and MCP-1, and smaller SF volume than controls (P ≤ 0.001 for all). White matter microstructure showed fornix and ST associations with CAH (fornix β = 0.15, P = 0.02; ST β = 0.22, P < 0.001) and WHtR (fornix β = 0.36, P = 0.01; ST β = 0.35, P = 0.02), but only ST associations with MCP-1 (β = 0.30, P = 0.02).

Conclusions

Youth with CAH demonstrate an important relationship between altered gray and white matter brain structure, WHtR, and MCP-1 that could have implications for neuroinflammation and obesity in CAH.

#237 Population-based assessment of cardiometabolic-related diagnoses in youth with klinefelter syndrome: a PEDSnet study

S Davis*

N Nokoff

A Furniss

A Valentine

L Pyle

A Dempsey

University of Colorado, Denver, CO

Purpose of Study

Diabetes and cardiovascular diseases are common among men with Klinefelter syndrome (KS) and contribute to higher morbidity and mortality. Cardiometabolic health outcomes have not been evaluated in a large population of youth with KS.

Methods Used

Data from electronic health records from six pediatric institutions were used to compared the prevalence of five cardiometabolic-related outcomes among 1,080 youth with KS to 4,497 youth without KS matched for sex, age (mean 13 years at last encounter), year of birth, race, ethnicity, insurance, site, and duration of care (mean 7 years). Odds ratios (OR) and 95% confidence intervals (CI) both unadjusted and adjusted for potential covariates including obesity, testosterone, and antipsychotic use were computed using generalized estimating equations.

Summary of Results

The odds of overweight/obesity (OR 1.6 (95%CI 1.4–1.8)), dyslipidemia (3.0 (2.2–3.9)), and liver dysfunction (2.0 (1.6–2.5)) were all higher in KS compared to controls. While the adjusted model attenuated the effect of KS on these outcomes, boys with KS still had 45% greater odds of overweight/obesity (CI 1.2–1.7) and 70% greater odds of liver dysfunction (1.3–2.2) compared to controls, and both dyslipidemia (1.6 (1.1–2.4)) and dysglycemia (1.8 (1.1–3.2)) were higher in KS but of borderline statistical significance when accounting for multiple comparisons. The odds of hypertension were not different between groups in unadjusted or adjusted models.

Conclusions

This large, population-based cohort of youth with KS found a higher odds of many cardiometabolic-related diagnoses compared to matched controls. Investigation into the mechanisms that underlie risk for cardiometabolic dysfunction in youth with KS independent of obesity and testosterone is needed.

#238 Reactive hypoglycemia following a sugar challenge is accompanied by higher insulin in adolescent girls with obesity

MA Ware1,2*

A Carreau3

Y Garcia-Reyes1

H Rahat1,2

C Diniz Behn4

M Cree-Green1

1University of Colorado – Anschutz Medical Campus, Aurora, CO

2Rocky Vista University, Parker, CO

3Universite Laval Faculte de medecine, Quebec, QC, Canada

4Colorado School of Mines, Golden, CO

Purpose of Study

Adolescent girls can present with postprandial, episodic symptoms of dizziness and excess sweating, which are often clinically disregarded. These symptoms can be associated with idiopathic reactive hypoglycemia (RH), reproduced with a glucose challenge, and may relate to increased risk of insulin resistance and type 2 diabetes (T2D). We sought to determine the prevalence of and glycemic measures associated with RH among adolescent girls with obesity following an oral sugar tolerance test (OSTT).

Methods Used

Secondary analysis of 112 adolescent girls with obesity (age 12–21 yrs; body mass index (BMI)≥90th percentile). Participants completed a 4-hr OSTT (75 g glucose, 25 g fructose) and were stratified by glucose nadir between 120–240 mins: ≦60 mg/dL as RH, ≥80 mg/dL as normoglycemic (NG), and 61–79 mg/dL as indeterminate. Area under the curve (AUC) of glucose, insulin, glucagon, and C-peptide and measures of insulin sensitivity and β-cell function including oral minimal model, insulinogenic index, and oral disposition index were calculated. Demographic, physical, and metabolic characteristics between RH and NG were compared with Student’s t-tests or Mann-Whitney U tests. OSTT curves were compared with repeated measures ANOVA.

Summary of Results

12% of girls had RH (n=13) and 36% had NG (n=40). Groups were similar in age, race, ethnicity, and BMI. Glucose concentrations were lower in RH than NG when fasting (p=0.033), at 210 mins (p=0.001), and 240 mins (p<0.001). In RH, glucose nadir occurred at a median time of 210 min postprandial. RH had higher glucagon AUC for 90–240 min of the OSTT (p=0.035) and a lower insulin at 240 mins (p=0.007) confirming a counterregulatory response. Insulin AUC (p=0.074) and C-peptide AUC (p=0.054) for 0–120 min trended to be higher. Groups had similar hemoglobin a1c, family history of T2D, insulin sensitivity, and β-cell function.

Conclusions

RH was relatively common in this cohort of adolescent girls with obesity and occurred at 3–4 hrs. Early higher insulin secretion preceded the counterregulatory RH responses but was not related to insulin sensitivity. Future studies should aim to further understand the long-term effects of RH during adolescence and its significance in predicting future hyperglycemia.

#239 Dietary quality and one-year progression of glucose intolerance in subjects with obesity

A Thatte*

SJ Melhorn

J Rosenbaum

M De Leon

M Webb

E Schur

University of Washington, Seattle, WA

Purpose of Study

Previous longitudinal cohort studies have shown that improved dietary quality is correlated with a reduction in the risk of cardiovascular disease and potentially diabetes. There has been limited research into whether a similar relationship holds for the progression of glucose intolerance. The hypothesis for this study is that better dietary quality is correlated with reduced progression in glucose intolerance over the course of one year in people with obesity.

Methods Used

This was a prospective cohort study. Participants (N=38) at baseline completed three 24-hour dietary recalls. The majority (N=37) were obese and subjects with diabetes were excluded. Each participant’s Healthy Eating Index–2015 (HEI) score was calculated from the dietary recalls. The HEI is a measure of dietary quality that assigns weights to meeting adequacy targets (i.e., getting sufficient vegetables) and not exceeding moderation targets (i.e., limiting saturated fat) for a total score between 0 and 100. All participants underwent a 2-hour 75-gram glucose tolerance test at baseline and at 12 months. Glucose tolerance was calculated as the percentage change in the incremental area under the curve (iAUC) between these two time points. Linear regression analysis in STATA was used to determine the relationship between HEI score at baseline (and other dietary measures), and progression of glucose intolerance over one year. One statistically influential outlier with percentage change in glucose iAUC of >150% was excluded.

Summary of Results

A trend was observed showing that higher dietary quality by HEI score was correlated with less progression of glucose intolerance (ß = -1.27, R2 = 0.102, p = 0.054). When age was added as a covariate, the values were (ß = – 1.21 R2 = 0.103, p = 0.098). Higher saturated fat intake was correlated with greater progression of glucose intolerance (ß = 5.07, R2 = 0.168, p = 0.012). There were no statistically significant relationships between vegetable, added sugar, or dietary fiber intake and progression of glucose intolerance.

Conclusions

In this small study of people with obesity, higher baseline dietary quality as measured by HEI correlated with less progression of glucose tolerance with borderline statistical significance (p = 0.054). Higher saturated fat intake correlated with greater progression of glucose intolerance (p = 0.012). The clinical relevance of this work would be to help optimize dietary recommendations to prevent progression of glucose intolerance which can be seen before manifestation of overt disease. Limitations of this study include the small number of subjects, lack of normal weight subjects, limited follow-up period, and self-reported dietary data. Future directions of research could include increasing sample size, studying normal weight subjects over a longer timeframe, and exploring methods for collecting dietary data that do not rely on self-report.

#240 Oral contraceptive use in adolescents with polycystic ovary syndrome and obesity is associated with altered fat metabolism

E Finn1,2*

C Severn1

Y Garcia-Reyes2

MA Ware2

H Rahat2

M Cree-Green1,2

1University of Colorado, Aurora, CO

2Children’s Hospital Colorado, Aurora, CO

Purpose of Study

Polycystic ovary syndrome (PCOS) is a common endocrine condition characterized by reproductive and metabolic hormone dysregulation and increased risk for metabolic disease. Combined oral contraceptive pills (OCPs) are first-line treatment for management of hyperandrogenic symptoms and menstrual regulation, yet data on the cardiometabolic effects in youth are limited.

Methods Used

Participants were enrolled in a cross-sectional trial of girls aged 12–21 years, BMI% >90th ile with PCOS per NIH 1990 criteria (NCT02157974). Measurements included anthropomorphics, fasting metabolic and hormonal assessments, 6-hour oral sugar tolerance test (OSTT), hepatic fat per MRI, DXA for body composition, and vascular function by EndoPAT and dynapulse. Area under the curve (AUC) for responses to the OSTT were calculated, as were several indices of insulin sensitivity. Participants treated with OCP’s for at least 6 months were matched 1:2 with replacement with untreated participants on BMI, race, and ethnicity. The effect of treatment was estimated with paired t-tests.

Summary of Results

Data from 10 participants taking OCPs (age 15.7±1.3 years, BMI 34.2±5.6 kg/m2) were compared to that from 20 untreated girls (age 15.6±1.9, BMI 33.6±5.0). The OCP group had decreased free testosterone (p≤0.001), increased sex hormone binding globulin (p=0.001), and decreased free androgen index (p≤0.001). The OCP group had higher total cholesterol (p=0.045), body fat percentage (p=0.028), and serum leptin (p=0.038). The OCP group also had higher free fatty acids AUC (p=0.007) and glycerol AUC (p=0.011) during the OSTT. No differences between the groups were noted in glucose metabolism including fasting glucose and insulin, HOMA-IR, c-peptide, glucose AUC, or insulin AUC. Vascular function and hepatic fat fraction were similar between groups.

Conclusions

Treatment with OCPs was not associated with worsening dysglycemia or markers of vascular dysfunction. However, there was evidence of altered fat metabolism, including a shift towards greater fat mass and adipose insulin resistance with persistent lipolysis. Additionally, hepatic fat was not improved. The overall therapeutic benefit of OCP’s in girls with PCOS and obesity who are at high cardiometabolic risk needs to be carefully evaluated.

#241 Acipimox prevents cardiac dysfunction induced by electronic cigarettes in mice

CJ Lao1*

J Espinoza-Derout1

K Hasan1

MC Jordan2

J Wilson1

J Molina1

K Luna2

JL Arambulo1

A Sinha-Hikim1

K Roos2

T Friedman1

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

2University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA

Purpose of Study

Tobacco use is a leading cause of preventable death in the United States. In recent years, electronic cigarettes (e-cigarettes) use by youth has augmented at a disturbing rate. Cardiac dysfunction can lead to heart failure, which is responsible for 287,000 deaths each year in the United States. In a mouse model, we will analyze whether acipimox treatment can rescue the cardiac dysfunction phenotype caused by e-cigarettes with 2.4% nicotine through the inhibition of lipolysis.

Methods Used

For 12 weeks, mice were exposed to saline, e-cigarettes (2.4%), and e-cigarettes plus acipimox in 12-hour cycles through specialized chambers. Acipimox (0.05%) was delivered in the drinking water. Mouse weights and food consumption data were collected weekly. Echocardiograms were used to analyze heart function.

Summary of Results

Weight data indicates that acipimox decreases the rate of weight change over time when compared to both saline control and e-cigarette groups. Acipimox treatment rescued e-cigarette induced phenotypes in fractional shortening, ejection fractions and velocity of circumferential fiber shortening. Triglyceride levels were increased in e-cigarette groups but were not fully rescued after acipimox treatment. Acipimox treatment reduced circulating levels of free fatty acids (FFA), Macrophage Colony-Stimulating Factor (M-CSF), and Interleukin-6 (IL-6) when compared to e-cigarette treatment alone. Gene set enrichment analysis (GSEA) indicates that genes involved in the G2/M checkpoint were upregulated by e-cigarette treatment and rescued by acipimox treatment. Heme oxygenase 1 (HO1) and Poly(ADP-Ribose) Polymerase 1 (PARP1) protein levels were rescued after acipimox treatment.

Conclusions

E-cigarette use led to an increase in free fatty acids which resulted in increased inflammation and reactive oxygen species within cardiac tissue. This resulted in DNA damage in the heart and halting of the cell cycle at the G2/M checkpoint. The DNA repair pathway was activated with increased levels of PARP1, a protein known for cellular recovery. This led to the cardiac dysfunction phenotype after e-cigarette use. Acipimox rescued this phenotype by inhibiting lipolysis and preventing downstream effects of dysfunctional adipose tissue and increased FFAs on cardiac tissue. In conclusion, the data obtained so far shows that lipolysis is necessary for the e-cigarette induced cardiac dysfunction. Lipolysis may become a new therapeutic target to curve the harmful cardiovascular effects produced by e-cigarettes.

#242 Access to care for metabolic syndrome and cardiovascular disease among immigrant populations in the united states

J Beltran*

M Shaheen

D Pan

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

Purpose of Study

It is estimated that one-quarter to one-third of adults meet the Metabolic Syndrome (MetS) criteria in the United States. MetS could be responsible for approximately 7% of total mortality and up to 17% of cardiovascular disease (CVD). This research aims to determine the relationship between metabolic syndrome, cardiovascular disease, and access to care by immigration status.

Methods Used

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 using bivariate chi-square and multiple logistic regression, considering the design and sample weight. We presented the data as an adjusted odds ratio and 95% confidence interval, and a p-value of <0.05 will be considered statistically significant.

Summary of Results

Of the 5,265 adults, 19.3% were immigrants, 8.7% had CVD, and 34.3% had MetS. Immigrants had lower prevalence of CVD (5.4%) compared to non-immigrants (9.5%) (p<0.05). A higher percentage of immigrants were uninsured (24%) compared to non-immigrants (11%) (p<0.05). In the multiple logistic models, there was no significant difference in the odds of CVD, MetS, and access to care among immigrants relative to non-immigrants after adjusting for the confounding variables. Though, in four of the five risk factors for MetS, immigrants had higher odds of CVD than non-immigrants (p<0.05).

Conclusions

Though the prevalence of CVD is not statistically different from non-immigrant, immigrants are more susceptible to the risk factors of MetS which increases the likelihood of developing CVD. Resources need to be distributed to the vulnerable immigrant population to decrease the risk factors of MetS, CVD and increase access to healthcare.

#243 Can medical care providers prevent heart attacks and strokes?

J Giannini*

J Padilla

RP Eaton

K Gonzales

DS Schade

University of New Mexico School of Medicine, Albuquerque, NM

Purpose of Study

Cardiovascular disease prevention is an important goal of medical care providers. In the clinical setting, we addressed whether myocardial infarctions and strokes can be prevented in asymptomatic patients with proven subclinical cardiovascular disease.

Methods Used

Two hundred six asymptomatic self-selected individuals requested a coronary artery calcium scan (CAC). Of these individuals, 125 had positive scans (Agatston score >1) and were recommended for medical treatment to prevent heart attacks and atherosclerotic strokes. Eighty-one individuals had zero scores and were not treated. Of the 125 individuals with positive scans, 110 followed medical treatment (rosuvastatin 10 mg/d, ezetimibe 10 mg/d, and a low cholesterol diet) and achieved a low density lipoprotein cholesterol (LDL-C) of ≤60mg/dl. The other 15 individuals did not follow recommended treatment and maintained an elevated LDL-C.

Summary of Results

All patients were followed for an average of 3.5 years (minimum 1 year – maximum 5 years). No atherosclerotic clinical events were observed in the group that achieved an LDL-C ≤60 mg/dl. The expected number of atherosclerotic cardiovascular events based on their calcium scores and published observational data was 12.6. Two patients died of non-atherosclerotic causes (an auto accident and Alzheimer’s disease.) In the non-compliant group, two heart attacks were observed (one patient died, one had a stent). No events were observed in the zero CAC group. No adverse effects of the treatment regimen occurred.

Abstract #243 Table 1

Change in clinical parameters in the LDL-C ≤60 mg/dl group with Rx

Conclusions

Medical care providers can prevent atherosclerotic heart attacks and strokes by treating asymptomatic patients who have positive calcium scores to an LDL-C goal of ≤60 mg/dl. A simple regimen of rosuvastatin, ezetimibe, and a low cholesterol diet has no major adverse effects, is inexpensive, and is acceptable by almost all patients.

Gastroenterology

Concurrent session

8:00 AM

Friday, January 21, 2022
#244 Diabetic hyperglycemia exacerbates inflammatory bowel disease in mice with diet-induced obesity

K Francis1,2*

MC Pacheco1

K Alonge2

BA Phan2

S Hu2

M Schwartz2

J Scarlett1,2

1Seattle Children’s Hospital, Seattle, WA

2University of Washington School of Medicine, Seattle, WA

Purpose of Study

Inflammatory bowel disease (IBD), obesity, and type 2 diabetes (T2D) are chronic inflammatory conditions that are increasing in prevalence. Obesogenic high-fat diets (HFD) that promote diet-induced obesity (DIO) and T2D have been shown to worsen IBD. Furthermore, comorbid T2D in patients with IBD is a predictor of poor disease-related outcomes. To determine the mechanisms whereby T2D worsens IBD pathology, we examined the impact of hyperglycemia on disease activity in a DIO mouse model of IBD, focusing on measures of intestinal barrier integrity.

Methods Used

Wild-type C57BL/6J mice were fed HFD for 8 weeks to induce DIO and then given intraperitoneal injections of vehicle or low-dose streptozotocin (STZ) to induce hyperglycemia. At week 12, 2% dextran sodium sulfate (DSS) or vehicle control was administered in drinking water for 7 days to induce colitis. Outcomes included serial measures of body weights, blood glucose, and disease activity index (DAI) scores, which incorporate weight loss, rectal bleeding, and stool consistency. Animals were euthanized at the end of DSS course and colon tissue was collected and processed for immunohistochemical staining.

Summary of Results

As predicted, STZ administration raised mean blood glucose levels significantly compared to vehicle-treated controls (267mg/dL vs. 159mg/dL, p=0.006). Hyperglycemic mice treated with DSS (DSS/STZ) manifested clinical signs of colitis 2 days earlier than their normoglycemic counterparts (DSS/Veh), and their DAI scores were significantly higher from Days 2–7 of DSS (p<0.0001). Colon length and histologic damage scores also demonstrated higher disease burden in DSS/STZ mice (colon length 5.93cm vs. 6.88cm, p=0.0003; histologic score 8.0 vs 6.5, p=0.03). Colonic tissues demonstrated significantly decreased quantity of the tight-junction protein E-cadherin (E-cad) in DSS/STZ mice compared to DSS/Veh (percent area 24.1 vs. 34.9, p=0.004), and a similar decrease in colonic mucin barrier was detected by Alcian Blue (AB) staining (percent area 55.3 vs. 71.0, p<0.0001). Notably, measures of both colonic E-cad and AB were inversely correlated with both DAI scores and blood glucose levels.

Conclusions

In DIO mice, clinical and pathological IBD outcomes are exacerbated by moderate hyperglycemia in a DSS model of colitis. We identify two potential mechanisms by which hyperglycemia contributes to intestinal pathology: 1) reduced tight-junction protein quantity in the colonic epithelium and 2) a decrease in the protective colonic mucin barrier. These results support the hypothesis that hyperglycemia induces intestinal barrier dysfunction, which, in combination with an obesogenic diet, increases the risk for IBD progression.

#245 Accuracy of intraoperative cholangiogram for the evaluation of choledocholithiasis

SK Choi1*

M Syed2

J Kim2

JJ Kim2

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

2Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Intraoperative cholangiography (IOC) is frequently performed during cholecystectomy and considered definitive testing for evaluation of common bile duct (CBD) stones. Previous studies evaluating the accuracy of IOC for the evaluation of choledocholithiasis are inconsistent, and false-positive testing may lead to increased utilization of diagnostic ERCP. The aim of this study is to evaluate the diagnostic property of IOC and to assess the clinical outcomes of patients who underwent ERCP with or without retained choledocholithiasis.

Methods Used

Consecutive hospitalized patients who received cholecystectomy with IOC at Loma Linda University Medical Center (1/2014–6/2021) were identified. Positive IOC was defined by the presence of filling defect, meniscus sign, and/or failure to drain contrast into the duodenum necessitating additional diagnostic evaluations. Definitive diagnosis of choledocholithiasis was defined by the presence of choledocholithiasis and/or sludge on any of the definitive testing for choledocholithiasis (MRCP, EUS, and/or ERCP) performed after IOC. Patients who had prior sphincterotomy or negative IOC without documented >2-year follow-up were excluded.

Summary of Results

The mean age of 259 patients who underwent same-day cholecystectomy and IOC was 46.0±19.8 years, 189 (73%) were female, and 144 (56%) were of Latino ethnicity/race. On presentation, 22 (9%) patients had bilirubin >4.0g/dL, 111 (43%) had a dilated CBD >6 mm, and 7 (3%) had choledocholithiasis detected on abdominal ultrasound. During cholecystectomy, 103 (40%) patients had abnormal IOC including the presence of filling defect in 94 (36%), meniscus sign in 2 (1%), and failure of passage of contrast to the duodenum in 7 (3%). Subsequently 122 (46%) patients had definitive testing including ERCP in 102 (39%), MRCP in 45 (17%), and EUS in 14 (5%). Diagnostic property of IOC for choledocholithiasis are shown in the table 1. ERCP was performed at a median of 2 days (range, 0–141 days) from IOC. Of 102 patients, 8 (3%) had adverse events including pancreatitis in 6 (moderate in 3, mild in 3) and perforation in 2; five patients with adverse events received diagnostic ERCP for evaluation of false-positive IOC.

Abstract #245 Table 1

Diagnostic property of intraoperative cholangiography for choledocholithiasis

Conclusions

Although IOC demonstrated high sensitivity and negative predictive value of >90% for ruling out retained CBD stones, nearly a third of the patients received diagnostic ERCP. Given adverse events associated with ERCP, other less invasive definitive tests such as MRCP and EUS should be considered for evaluations of patients with positive IOC prior to ERCP.

#246 Role of ethnicity in predicting the severity of liver fibrosis by the implementation of four clinical liver cirrhosis prediction models among hispanic and caucasian women: a pilot study

Xu LC1*

JR Fine2

A Molfino3

V Medici1

1University of California Davis Health System, Sacramento, CA

2University of California Davis, Davis, CA

3Sapienza University of Rome, Rome, Italy

Purpose of Study

To determine whether ethnicity and other risk factors can predict the severity of fibrosis or cirrhosis in women with NAFLD applying the four predictor models FIB-4, NFS, BARD, and APRI.

Methods Used

We performed a retrospective study among Hispanic (n=567) and Caucasian (n=136) women with history of NAFLD (mean age 55.7 ± 11.4 SD years) at The University of California Davis Medical Center. Univariate analyses for their FIB-4, NFS, BARD, and APRI scores were conducted by using Chi-Square or Fisher’s Exact Test for categorical variables, two-sample t-test for continuous variables, and Wilcoxon-Mann-Whitney test for continuous non-parametric variables. Associations between ethnicity (Hispanic vs. Caucasian) and liver fibrosis severity calculated using the four cirrhosis predictor models were explored using backward selection multinomial logistic regression.

Summary of Results

We observed that Hispanic women compared to Caucasian showed lower BMI (p<0.001), higher HDL (p<0.05), higher HbA1c (p<0.001), higher prevalence of stage 4 and 5 CKD (p = 0.005) , lower prevalence of bariatric surgery (p=0.002), lower likelihood to smoke (p=0.002), and had lower APRI score (p=0.03). The percentage of advanced fibrosis in each models and ethnicity was as follows: Hispanic NFS: 35.1%, BARD: 82.6%, FIB-4: 3.5%, and APRI: 1.3%; in Caucasian NFS: 36.3%, BARD 83.2%, FIB-4: 7.7%, APRI: 6.3%. The odds of having a severe fibrosis or cirrhosis was not significantly higher in those who are Hispanic compared to Caucasian in FIB-4, NFS, BARD, and APRI (p=0.16, 0.78, 0.97, and 0.18 respectively).

Conclusions

Based on our preliminary results, we cannot conclude that ethnicity alone can be used to predict the severity of fibrosis or cirrhosis in women with NAFLD in the multiple predictor models.

#247 Examining clinical presentation and workup of veterans with irritable bowel syndrome in a single medical center

PL Claassen1*

M Riddle2

1Washington State University Elson S Floyd College of Medicine, Spokane, WA

2VA Sierra Nevada Health Care System, Reno, NV

Purpose of Study

Irritable Bowel Syndrome (IBS) is a disorder of gut-brain interaction (DGBI) that afflicts about 5% of the population with significant quality of life and economic impacts. Recent ACG guidelines have been established to improve diagnosis and management of IBS. Within the Veteran population, there is poor understanding of the epidemiology of DGBI despite significant occupation exposures, comorbid mental health problems and risk of deployment-associated diarrhea. Less is known about the management of DGBI in Veterans compared to other populations.

Methods Used

As part of a quality improvement initiative, a case series analysis of Veterans seen at a new IBS Clinic was performed to better understand the patient population and their preceding diagnostic workup. Data from the VA Electronic Health Record and a standardized IBS Clinic intake form was retrieved. All charts were comprehensively reviewed to determine the dates of gastrointestinal (GI) symptom onset, first functional GI disorder diagnosis, first IBS diagnosis, as well as basic demographics, current comorbidities and medications. Descriptive analytic methods were applied.

Summary of Results

A total of 11 Veterans referred to the IBS Clinic were included with a median age of 43 years, all male, majority Caucasian (81.8%) and predominantly from the Persian Gulf war (72.7%), post-Vietnam (18.2%) and Vietnam eras (9.1%). A median of 4 (IQR 2.5–14.5) years delay between time of symptom onset to first functional GI disorder diagnosis was noted. Of those diagnosed with IBS, the phenotypes were diarrhea (57.1%), mixed (28.6%) and unclassified (14.3%). Patients had a median of 10 (IQR 6–15) comorbidities and took a median of 9 (IQR 5–10) medications (i.e. selective serotonin reuptake inhibitors) which could contribute to diarrhea. Mental health problems were very common, with 55% having post-traumatic stress disorder. Additionally, 60% of patients presented with at least one red flag symptom that warranted colonoscopy. With respect to ACG guidelines, less than 50% received testing for celiac disease and inflammatory bowel disease. Only 20% received unnecessary stool ova or parasite testing and 10% an unneeded colonoscopy.

Conclusions

IBS is understudied in Veterans. Many of these patients have psychological comorbidities and take medications which may contribute to their symptoms. While some aspects of their workup aligned well with guidelines, others did not. Future efforts are needed to improve diagnosis and management of Veterans with DGBI.

#248 Risk factors associated with increased fibrosis and steatosis in non-alcoholic fatty liver disease utilizing transient elastography (fibroscan) in a community multispecialty practice

B Stratford1*

C Gonzales2

1Weber State University College of Science, Ogden, UT

2Ogden Clinic, South Ogden, UT

Purpose of Study

Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of fibrosis in patients with obesity, diabetes, and metabolic syndrome. Noninvasive liver assessment using FibroScan is an important part of the evaluation of these patients. The aim of this study is to assess the efficacy of the FibroScan in helping to risk stratify patients with NAFLD in order to improve patient outcomes.

Methods Used

Over a 16 month period (3/2020 to 6/2021), 331 patients with suspected NAFLD underwent liver FibroScan assessment. A retrospective chart review was conducted for risk factors of metabolic syndrome (obesity, HTN, diabetes, sleep apnea, hyperlipidemia), FibroScan measurements of liver stiffness (MLS), steatosis, and liver biopsy outcomes.

Summary of Results

A total of 331 patients were reviewed with a mean age of 49 years and mean BMI of 35 (range 18–58). Fifty-three percent of patient were obese (BMI > 30) and 20% were morbidly obese (BMI > 40). Metabolic risk factors were common; HTN (45%), hyperlipidemia (37%), sleep apnea (31%) and diabetes (23%). Greater fibosis risk was seen with increased BMI (normal vs. morbidly obese BMI, mean MLS 5.5 kPa vs. 9.9 kPa, p< 0.001), metabolic risk factors (0 vs. 5 risk factors, mean MLS 5.7 kPa vs. 13.5 kPa, p< 0.0003) and presence of diabetes (no diabetes vs. diabetes, mean MLS 7.3 kPa vs. 10.3 kPa, p< 0.003). Increased steatosis scores were seen in increased BMI (normal vs. morbidly obese BMI, mean CAP 236 dB/m vs. 334 dB/m, P < 0.0001), metabolic risk factors (0 vs. 5 risk factors, mean CAP 265 dB/m vs. 340 dB/m, p < 0.0001) and presence of diabetes (no diabetes vs. diabetes, mean CAP 307 dB/m vs. 333 dB/m, p< 0.0005). Twenty-five patients underwent liver biopsy evaluation and all patients were diagnosed with non-alcoholic steatohepatitis (NASH). Stage II-III fibrosis was diagnosed in 12 patients (48%) and stage 4 bridging fibrosis/cirrhosis in 3 patients (12%).

Conclusions

This cohort of patients undergoing Fibroscan testing in a community practice were mostly obese and had >1 metabolic syndrome risk factors. Elevated liver stiffness and steatosis were significantly correlated with increasing BMI, presence of diabetes and increased risk factors for metabolic syndrome. These results will help guide clinician utilization of Fibroscan testing in clinical practice.

#249 Antiphospholipid antibody syndrome in a young male with biliary adenocarcinoma

H Ipalawatte1,2*

S Sathian1,2

K Radicic1

S Mishra1

1Kern Medical Center, Bakersfield, CA

2Ross University School of Medicine – Barbados Campus, Bridgetown, Barbados

Case Report

Cholangiocarcinoma(CC) is a rare cancer of the biliary system, common in elderly patients. Risk factors vary including alcoholic liver disease, hepatitis, HIV infection, or parasitic infection. Common associations include ulcerative colitis(UC) and primary sclerosing cholangitis (PSC), in which case CC can arise decades sooner (Lowe 2021; Anderson 2021). Here, we present an atypical presentation of a 27yo male with PSC in the absence of UC symptoms diagnosed with CC and antiphospholipid syndrome(APS), a condition that is more prevalent in women.

Case Presentation

A 27yo male with history of alcohol abuse, hypertension and polysubstance abuse presented to the Emergency Department (ED) with jaundice, scleral icterus, and pruritus. He was found to have abnormal liver function tests(LFTs) during a routine evaluation with a month history of exacerbating symptoms.

In the ED, labs showed an albumin level of 3.3, alkaline phosphatase of 972, ALT 219, AST 131, direct bilirubin 5.9, total bilirubin 7, and total protein 8.6. Urine analysis showed urobilinogen of 2 and moderate bilirubin levels. At this time, there was a concern for any autoimmune processes, and further studies, found positive anticardiolipin IgG and IgM in the serum, anti-smooth muscle antibodies. There was high suspicion for APS. Ultrasound of the abdomen showed stigmata of cirrhosis with suboptimal visualization of the right liver lobe with dilated intrahepatic bile ducts. CT scan showed a mass-like bulge in the inferior aspect of the right hepatic lobes with heterogeneous enhancement involving the right hepatic lobe. MRCP showed a ‘beaded’ appearance of the bile ducts and obstruction at the confluence of the main hepatic ducts.CA 19–9 was elevated. Findings were highly suggestive of malignancy such as CC. He underwent ERCP with sphincterotomy with biopsy confirming biliary adenocarcinoma. He was referred for hepatobiliary surgery and further evaluation with hematology/oncology.

Conclusion

CC is a rare condition with a low 5-year survival rate (Nakeed, 1996). The faster a diagnosis is made, the more options that a patient has in terms of therapy. Our patient had PSC leading ho more work up and finding CC, a condition often seen much later in life, and has APS, which is often seen in females rather than males. He did not exhibit any ulcerative colitis symptoms, which are commonly associated with CC. He deviates from many common associations.

In the real world, we may encounter atypical presentations that do not fit into previously learned models. With this case, we wanted to emphasize the importance of being vigilant, have broad differentials and early intervention based on clinical suspicion.

#250 Ileal endocrine tumor without metastasis

VR Mendiola

J Rahesh*

B Quraishi

S Pathapati

Texas Tech University Health Sciences Center School of Medicine, Amarillo, TX

Case Report

A 65-year-old Caucasian male with a past medical history of hypertension and alcohol abuse presented to the ED with 2 months of watery diarrhea consisting of 3–4 episodes a day. He was transferred from an outside facility for acute renal failure, severe metabolic acidosis, diarrhea, dehydration, and hypokalemia.

Initial episodes of watery diarrhea presented with fever, chills, and nausea. Watery diarrhea increased to about 10 episodes a day during this initial course. He also reported generalized weakness and recurrent falls due to syncope. He self-medicated Ivermectin in high doses meant to be used for horses that he was able to buy from his hometown veterinarian with no prescription meant to treat his diarrhea as well as prevent Covid-19 infections. He used this drug for 10 days and reported a 20 pounds weight loss over 2 months as well as worsening oliguria.

Follow this initial course, his diarrhea continued at a lesser rate of only 3–4 episodes a day. However, three days prior to presenting to the ED he noticed fresh blood in his stool, prompting him to seek medical attention. On admission he denied abdominal pain, flushing, dyspnea, or chest pain. On examination, he had mild diffuse abdominal tenderness. The patient denied any history of hepatitis, pancreatitis, peptic ulcer disease or GERD. He had never had a colonoscopy or endoscopy at this point.

On admission his labs showed acute renal failure with an SCr of 18, a BUN of 161, and bicarb of 6. After he was started on fluid resuscitation his kidney function improved and urinary output increased, and his acute kidney injury eventually resolved.

His CT abdomen was remarkable for ‘misty mesentery’ suggestive of panniculitis. There was also an enhancing nodularity of the distal small bowel mesentery in the right mid abdomen with mild to moderate circumferential bowel wall thickening of the underlying small bowel loops. In addition to this there were scattered diverticula of the sigmoid colon with no diverticulitis. The carcinoid tumor was also able to be identified on CT.

Colonoscopy showed a large 3 cm submucosal polypoid nodular mass at 10 cm distance from ileocecal junction. Biopsy reported a well differentiated neuroendocrine tumor (carcinoid), spanning at least 2 mm involving the lamina propria and submucosa. Liver ultrasound showed only hepatic steatosis with no lesions. 24hr urine HIAA was 12.5, chromogranin A 1048ng/ml and serum serotonin level of 883ng/ml. TTE showed no valvular abnormalities.

Right hemicolectomy with small bowel mass was resected, surgical pathology reported well differentiated neuroendocrine tumor, forming multiple (13) mucosal masses extending up to 2.3 cm with focal angiolymphatic invasion and 3/18 regional lymph nodes involvement. After this, diarrhea improved, and patient followed up with a medical oncologist.

#251 A challenging case of colitis: inflammatory or infectious or both

S Ratnayake1*

K Grewal1

G Singh1

S Kaur1

N Singh2

A Heidari1

G Petersen1

1Kern Medical Center, Bakersfield, CA

2Ross University School of Medicine, Miramar, FL

Purpose of Study

Indeterminate colitis (IC) is a form of Inflammatory Bowel Disease (IBD), when the diagnosis of Ulcerative colitis (UC) or Crohn’s disease cannot be made due to mixture of findings. The incidence of Clostridioides difficile (C. diff) infection is 6–9% in patients with IBD, which can lead to increased risk for colectomy or death. Here we discuss a case of newly diagnosed IC with superimposed C. diff infection.

Methods Used

Retrospective chart review after IRB approval.

Summary of Results

A 26-year-old male with no known medical history presented to our facility with progressive one month history of abdominal cramping pain and bloating. This was associated with watery hematochezia up to 15 episodes per day. Upon admission, he was found to have fever as high as 39.4C, WBC 7.5, CRP 23.8 mg/dL, ESR 68 mm/hr, Hgb 12.7 g/dL. His work up also showed stool Calprotectin 3520 mcg/g, positive stool Lactoferrin, and atypical P-ANCA titer of 1:160, commonly elevated in UC. Stool studies were also positive for C.diff toxin B PCR and GDH antigen, and oral vancomycin was started. Colonoscopy with biopsies showed mixture of findings, from 2 pathology readings, for UC and CD with focal active colitis with focal ulcerations (consistent with UC), involvement of the crypts, lamina propria, and submucosa (consistent with CD). The diagnosis of IC was made and he was started on Methylprednisolone 60 mg TID and Mesalamine 1600 mg BID. Patient eventually improved with less frequency of hematochezia. Upon follow up in outpatient clinic his was down to only 5 episodes of diarrhea without hematochezia. Follow up colonoscopy when C.diff infection is resolved is planned for making a definitive diagnosis between UC and CD.

Conclusions

Diagnosis of Ulcerative Colitis vs Crohn’s Disease can be challenging in the setting of superimposed infection with Clostridioides difficile. Management of this coexistence is difficult, and duration of treatment is also not well studied. Further work up and repeat biopsy might be needed for definitive diagnosis.

Session: genetics I

Concurrent session

8:00 AM

Friday, January 21, 2022
#252 DPH5 : a novel gene causing diphthamide biosynthesis disorders

SP Shankar1*

K Grimsrud2

L Lanoue1

A Egense1

B Willis1

P Shankar1

J Horberg3

L Albadi4

K Mayer5

K Ütkür7

K Monaghan6

J Krier8

J Stoler8

R Schaffrath7

F Alkuraya4

U Brinkmann5

L Eriksson3

K Lloyd1

KA Rauen1

1University of California Davis, Sacramento, CA

2University of California Davis, Davis, CA

3Goteborgs universitet, Goteborg, Sweden

4King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

5F Hoffmann-La Roche AG Research and Development Division, Penzberg, Germany

6GeneDx, Gaithersburg, MA

7Universitat Kassel Institut fur Biologie, Kassel, Germany

8Boston Children’s Hospital, Boston, MA

Purpose of Study

Neurodevelopmental disorders (NDDs) are genetically heterogeneous lifelong conditions with a known etiology in approximately 50% of individuals. Here, we report DPH5 (Diphthamide biosynthesis protein 5) as a novel cause of embryonic lethality, multisystem dysfunction and profound NDDs in three unrelated families. DPH5 is critical to the biosynthesis of diphthamide, a post translationally modified histidine on eEF2 (eukaryotic elongation factor 2), essential for ribosomal translocation and protein synthesis in cells.

Methods Used

Exome or genome sequencing, transgenic Dph5 pH260R knockin (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) mouse model development, patient recrutiment through GeneMatcher program, ADP–ribosylation assays in DPH5ko cells transfected with pN110S, pN174fs, pR207*, and p260R, site-directed mutagenesis in yeast cells for the missense variants and functional assays, computational modeling to evaluate effect of variants on DPH5 protein structure and assess its interaction with eEF2.

Summary of Results

DPH5 variants, homozygous pH260R, compound heterozygous pN110S and pR207* and homozygous pN174fs were found in three unrelated families (F1, 2 & 3). Similar craniofacial features such as broad forehead, sparse eyebrows, epicanthal folds, short upturned nose, downturned corners of the mouth, profound NDDs, CNS anomalies such as enlarged cisterna magna, cardiac features such as ventricular septal defect, pulmonary stenosis and pericardial effusion, and digital anomalies were noted. Dph5_pH260R targeted knockin mouse model generated only one homozygous (HOM) female exhibiting extremely low birthweight, craniofacial dysmorphism, polydactyly and abnormal behaviors with early death at 24-days of age. Embryonic studies of HOMs revealed abnormal head shape, exencephaly, eye anomalies, edema shortened frontonasal prominence, facial cleft and polydactyly. ADP ribosylation assays showed absent to decreased function in KO and yeast cells. Insilico modeling showed disruption of interaction of DPH5 with eEF2.

Conclusions

We provide clinical and functional evidence that DPH5 variants in three unrelated families are likely pathogenic establishing DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement expanding the Diphthamide biosynthesis disorders.

#253 Macroangiopathy, not so common in melas?

JP Ramos*

JA Morales

M Manning

Stanford Medicine, Stanford, CA

Purpose of Study

MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episode) is a multisystem disorder caused by a known mitochondrial DNA mutation most commonly affecting the MT-TL1 gene. The majority of individuals develop symptoms between the ages of 2 to 40 years old.

When MELAS affected patients present with stroke-like symptoms, the expected etiology is the underlying mitochondrial disorder causing a stroke-like episode. Common clinical findings include stroke-like episodes, encephalopathy with seizures or altered mental status, muscle weakness, hearing impairment, peripheral neuropathy amongst others. MELAS is a condition with phenotypic variability due to multiple causes (heteroplasmy, tissue distribution and threshold effect).

There are approximately 13 reported cases of macroangiopathy in patients with MELAS. We report a previously undiagnosed cause of MELAS in an adult patient who presented with right middle cerebral artery (MCA) ischemic stroke and found to have severe intracranial atherosclerosis, a finding not typically reported in MELAS patients.

Methods Used

Chart review, physical examination, and literature review

Summary of Results

A 44 year-old female was evaluated for a possible mitochondrial condition given a past medical history of sensorineural hearing loss following physiologically demanding circumstances (pregnancy), type 1 diabetes and acute neurologic symptoms concerning for a stroke after removal of a cochlear implant. Molecular testing revealed a mtDNA pathogenic variant: 3243A>G (tRNA Leu gene) with 24.7% heteroplasmy, a finding highly indicative of MELAS. Head CT angiography found severe intracranial atherosclerosis involving large vessels requiring thrombectomy. Imaging noted a tapering occlusion in a large segment of the right MCA, multifocal irregularity and moderate stenosis of the left internal carotid artery and proximal left middle cerebral artery, with diffusely narrowing caliber of the internal carotid arteries.

Conclusions

Of the MELAS reported cases, intracranial large vessel involvement (macroangiopathy) is a rare finding in MELAS, described in very few individuals. Macroangiopathy can include stenosis, vasoconstriction, atherosclerosis, and aneurysms, and theoretically could be a lesser-known finding in patients with chronic MELAS. Given the severity of clinical complications in our patient, we call attention to macroangiopathy as a possible complication in patients with MELAS to inform their clinical team when preparing for invasive procedures, especially those involving intracranial vascular system.

#254 MT-ATP6-associated mitochondrial disease can present with low citrulline by newborn screening and more: defining the biochemical phenotype

CG Tise1*

C Lee1

B Mendelsohn2

J Woods1,3

K Cusmano-Ozog1

1Stanford University, Stanford, CA

2Kaiser Permanente, Oakland, CA

3Valley Children’s Healthcare, Madera, CA

Purpose of Study

MT-ATP6 encodes a subunit of mitochondrial complex V (ATP synthase). Pathogenic variants are associated with a form of Leigh syndrome exhibiting considerable phenotypic heterogeneity and maternal inheritance. We have identified seven children from five families with MT-ATP6-associated disease who presented with low citrulline by California newborn screening (NBS). Further evaluation revealed abnormalities on plasma amino acids (PAA), urine organic acids (UOA), and acylcarnitine profile (ACP), and in several cases, maternal relatives with a similar phenotype. We report these findings and characterize the biochemical phenotype associated with MT-ATP6-associated disease.

Methods Used

Medical literature and chart review, physical examination, and laboratory testing.

Summary of Results

Seven probands were found to have a maternally-inherited homoplasmic pathogenic variant in MT-ATP6 (m.8993 T>G, p.L156R) after presenting with abnormal NBS for low citrulline. Biochemical evaluation revealed PAA with low citrulline and high alanine, UOA with elevations of lactate and 3-hydroxyisovaleric acid without orotic aciduria, and ACP with elevations of propionylcarnitine (C3) and 3-hydroxyisovalerylcarnitine (C5-OH). Overall findings were suggestive of a mitochondrial disorder, as opposed to the intended primary screening target of a proximal urea cycle disorder, warranting mitochondrial DNA studies. Some maternal relatives were found to have the same biochemical phenotype as the probands (n=3), as well as clinical features of this disorder including ataxia, neuropathy, myopathy, and/or retinitis pigmentosa; others are reportedly asymptomatic.

Conclusions

MT-ATP6-associated disease can present with low citrulline by NBS and a unique biochemical phenotype consisting of the triad of low citrulline, elevated C3, and elevated C5-OH, in addition to evidence of mitochondrial dysfunction by PAA and UOA. For this reason, we recommend including ACP in the evaluation of individuals who screen positive by NBS for low citrulline; maternal history and laboratory studies should also be considered. Future studies include metabolomic profiling of NBS dried blood spots from individuals with MT-APT6-associated disease and relevant negative and positive controls to further delineate the biochemical phenotype and aptly identify individuals with this mitochondrial disorder.

#255 Zellweger spectrum disorder in california’s central valley: evidence of a founder mutation in mixteco patients affected with a novel PEX6 variant

KR Wong1*

J Woods1,2

J Carmichael1

CI Galarreta Aima1

1Valley Children’s Hospital, Madera, CA

2Stanford Medicine, Stanford, CA

Purpose of Study

Zellweger spectrum disorders (ZSD) are a group of autosomal recessive disorders caused by mutations in the PEX genes essential for peroxisomal biogenesis. Affected patients have defective lipid metabolism and cell detoxification, resulting in hypotonia, neurologic deficits, congenital malformations, adrenocortical dysfunction, and liver disease. Prevalence varies among different regions of the world and founder mutations in distinct populations have previously been reported. California’s Central Valley has a large Mixteco population compared to other parts of the United States as many of these families have emigrated from the southern Mexico states of Oaxaca, Guerrero, and Puebla. We have observed an increased frequency of ZSD at our center over the past few years in patients of Mixteco ethnicity. This study reports the spectrum of clinical and genotypic features of ZSD patients at our institution.

Methods Used

We performed a retrospective chart review by searching for ZSD patients seen at our center between 2010 and 2020 using ICD-10 codes E71.50, E71.51, E71.511, E71.518, E71.53 and E71.54, and ICD-9 code 277.86. Patients with an alternative diagnosis were excluded.

Summary of Results

Seven patients with ZSD were identified, all diagnosed over the past four years, presenting at birth with generalized hypotonia and facial dysmorphisms such as large anterior fontanelles. Two had poor visual response to light, three had lagophthalmos, and four had failed hearing tests. Four patients are now deceased and three died prior to one year of age. Although two were lost to follow-up, they both presented with severe symptoms including worsening hypotonia and poor feeding by three months of age. One patient is currently alive at 12 months of age. Biochemical testing demonstrated characteristic elevations of very long chain fatty acids. Six patients were found to be homozygous for the PEX6 novel variant c.1409G>C (p.Gly470Ala) and were of Mixteco ethnicity. One was homozygous for PEX6 c.2095–21_2095del and was the only patient with parental consanguinity. This patient’s ethnicity is unknown.

Conclusions

ZSD has a prevalence of 1:50,000 to 1:75,000 in the United States. In the Central Valley, we found an increased frequency of ZSD per zip code population in which these patients lived, ranging from 1:4,477 to 1:72,280, with a mean of 1:44,891. This over-representation of the novel PEX6 variant affecting ZSD patients of Mixteco ethnicity suggests a founder mutation within this patient population.

#256 Clinical findings in CRB2-related syndrome

M Adutwum1,2*

A Hurst3

G Mirzaa4

A Slavotinek5

1Children’s Hospital Oakland Research Institute, Oakland, CA

2UCSF Benioff Children’s Hospital Oakland, Oakland, CA

3University of Alabama at Birmingham, Birmingham, AL

4Center for Integrative Brain Research, Seattle, WA

5University of California, San Francisco, San Francisco, CA

Purpose of Study

CRB2-related syndrome was first described as a triad of cerebral ventriculomegaly, renal findings including nephrotic syndrome (NS), and greatly elevated alpha-fetoprotein levels. Additional clinical manifestations in CRB2-related syndrome have included congenital heart defects and retinitis pigmentosa (RP). The condition is rare and caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2-related syndrome have highlighted NS which can be associated with severe presentations. The objective of this project was to compile a list of the clinical and variant data for CRB2-related syndrome.

Methods Used

We conducted a literature review of reported patients with biallelic pathogenic variants in CRB2 and identified additional unreported cases. We compared clinical features, survival, and variant location in CRB2 in patients with manifestations in different body systems. For those with NS, treatments and their effectiveness were recorded.

Summary of Results

We ascertained 31 patients with biallelic, pathogenic variants in CRB2; detailed information was available for the majority. 18/29 (62%) were diagnosed during pregnancy and 9/29 (31%) from 0 to 10 years of age. Two patients were diagnosed at 46 and 51 years and had RP as the sole clinical finding. Of the 30 patients with recorded outcomes, 20 (66.7%) were alive, whereas 10 (33.3%) were deceased, 7 from termination of pregnancy. An analysis of clinical findings showed that renal involvement was the most frequent (22/31; 71%), with 11 (35%) patients having only renal manifestations with NS. 17/31 (55%) patients had manifestations in multiple body systems, and cardiac findings and abnormal retinae were each found in 3/31 (10%). Pathogenic variants were mostly located in exons 7, 8, 10, 12, and 13, with greatest representation of exon 10 in all patients, whereas exon 7 had the greatest representation in patients with only renal disease. Details of treatments and their effectiveness were inconsistently reported and prevented comparison, but one patient transiently responded to steroids and only one surviving patient required a renal transplant.

Conclusions

Most patients with CRB2-related syndrome included in this review survived. The commonest clinical finding in recently reported patients with pathogenic CRB2 variants was NS. Further information is needed to determine optimal treatment and patient care.

#257 Asymptomatic thalassemia: a reason to reform current screening algorithms in regions of Asia

K Mai

K Chen*

Western University of Health Sciences, Pomona, CA

Purpose of Study

Many regions in Asia including Taiwan hold a high thalassemia carrier rate. The diagnosis of thalassemia in these regions mainly consists of a screening algorithm relying on mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values. However, individuals who are silent carriers and who do not phenotypically fit the screening algorithms tend to go undiagnosed, leading to future complications. While genetic screening panels may be useful in this context, a standardized regime is limited in this region. Thus, this study evaluates the clinical significance of implementing a standardized genetic screening panel for α-thalassemia. Overall, the study assesses the efficacy of this screening in identifying phenotypically asymptomatic patients who were otherwise undiagnosed, and the risk posed in passing down more severe carrier traits.

Methods Used

This is a cross-sectional study utilizing next-generation sequencing (NGS) carrier screening panels to identify α-thalassemia silent carriers in a population within Taiwan. Long range PCR is followed to confirm patient’s genetic status.

Summary of Results

A total of 22 patients were identified as thalassemia silent carriers. 21 out of 22 individuals (95.5%) were α-thalassemia silent carriers, with 2 of them being couples. Therefore, in this population set there is a 9.5% chance of passing down more severe alpha thalassemia carrier traits. Furthermore, only 1 out of 22 patients (4.5%) were found to be β-thalassemia carriers. These individuals were asymptomatic, and all held a MCV of >80. Of these individuals, only 4 were identified with a low hemoglobin level.

Conclusions

Our data suggests the implementation of a standardized genetic screening for α-thalassemia will be beneficial in many regions within Asia, including Taiwan. Previous screening algorithms focused on measuring MCV and MCH levels. However, in this study we demonstrate that MCV and MCH levels alone may be insufficient in identifying carriers. Maintenance of this screening algorithm would thus result in false negatives within this patient population. Overall, the use of NGS-based carrier screening panels allowed for the diagnosis of individuals who were previously undiagnosed due to them not phenotypically conforming to the current regional screening algorithms. This study also allowed for the identification of individuals at an increased risk of passing down traits such alpha thalassemia carriers and hemoglobin H (HbH). The utilization of genetic screening for α-thalassemia would be cost-efficient and beneficial especially in these patients by allowing for earlier genetic counseling, education, and potential treatment to prevent costly complications later in life.

#258 Linkage disequilibrium score regression analyses to determine the genetic architecture of the differences between depression and bipolar disorder

S Assaf*

University of California Los Angeles, Los Angeles, CA

Purpose of Study

Psychiatric illness is a pressing health concern and there is a greater need to understand genetic differences between influencing traits. This project analyzed genome-wide differences among three genome-wide association studies (GWAS), aiming to understand genetic differences between patients with depression and bipolar disorder. Being influenced by several genes and confounding factors complicates the genetic study of these polygenic illnesses. One tool available to help understand genome wide differences from GWAS is linkage disequilibrium score regression (LDSC) which allows for the analysis of differences among psychiatric patient cases who present with bipolar disorder (BP) or major depressive disorder (MDD) with different onsets.

Methods Used

Three GWAS files were analyzed through LDSC: daner13 (case-only BP vs. MDD file), danerD (BP-onset-MDD vs. MDD file), and danerM (BP-onset-mania vs. MDD file). Unix and Python shell scripting were used to run a series of awk commands and the ldsc command-line tool was used to munge summary statistics. Once the files were munged, LDHub computed genetic correlation for psychiatric and educational traits along with the heritability of traits amongst two cohorts. The three GWAS were then compared using observed heritability values and genetic correlation of the traits.

Summary of Results

The genetic correlation of 16 traits for each of the GWAS were plotted with their respective standard errors (figure 1). The heritability values for the daner13, danerD, and danerM files were 0.2184 (SE 0.0209), 0.2079 (SE 0.0478), and 0.1556 (SE 0.057), respectively. Psychiatric traits showed higher genetic correlation than educational traits with BP, PGC cross-disorder analysis and schizophrenia having the strongest correlation (>0.5) across all GWAS. Major depressive disorder and depressive symptoms had weak negative correlations across all GWAS.

Conclusions

These heritability results demonstrate that genetic differences exist between MDD and BP. The greater heritability of traits in the danerD file than the danerM file could be attributed to the higher number of BP patients who are first diagnosed with MDD before switching to BP. In addition to genome-wide analyses, individual-level genotype data may also help to predict risk scores for patients who switch from MDD to BP. In the future, these genetic differences may be used to predict the course of illness in depression patients.

#259 Different exons, different disorders: athelia and branchial sinus anomalies are features of a distinctive KMT2D-associated disorder

R Frankel1*

CG Tise1

M Sanyoura2

J Bernstein1

LH Philipson3

1Stanford University, Stanford, CA

2The University of Chicago, Chicago, IL

3University of Chicago Department of Medicine, Chicago, IL

Purpose of Study

Here we describe two individuals with KMT2D-associated disorder to highlight distinct features, helping to define the phenotype associated with variants in this gene. In 2020, Cuvertino et al. described a cohort of nine individuals with heterozygous variants in exons 38 and 39 of KMT2D presenting with a multisystem disorder distinct from Kabuki syndrome. Overlapping clinical features of the nine individuals included typical intelligence, choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal ducts anomalies, hearing loss, external ear malformations, and thyroid abnormalities.

Methods Used

Clinical evaluation, molecular sequencing, chart review, and literature review.

Summary of Results

Two unrelated individuals were found to have the same de novo pathogenic variant in exon 39 of KMT2D (c.10784A>G, p.Tyr3595Cys) by exome sequencing after presenting with multiple congenital malformations. The first individual is a 27 year-old female with a coloboma, choanal atresia, congenital deafness, absent ribs, small teeth, bilateral 2nd branchial cleft sinus tracts, aplasia of the posterior semicircular canals, loose anagen hair, amastia/athelia, non-autoimmune diabetes mellitus, and typical cognitive development. The second individual is an 11 year-old female with bilateral microtia, bilateral sensorineural hearing loss, right facial nerve palsy, left sided branchial cleft cyst or pit, bilateral breast hypoplasia, and typical development.

Conclusions

Typical intelligence, branchial sinus anomalies, and amastia/athelia in females appear to be distinct features of KMT2D-associated disorder. This syndrome presents with features overlapping with other multiple malformation syndromes including Kabuki, CHARGE, and brachiootorenal syndrome. These individuals exemplify the distinct phenotype of KMT2D-associated disorder and highlight the need for a natural history study of this condition to allow for better characterization and ultimately improved diagnosis and outcomes.

Neonatology general III

Concurrent session

8:00 AM

Friday, January 21, 2022
#260 Predictive value of patent foramen ovale measured at birth for development of atrial septal defect in extremely low birthweight infants

S Gaffar*

B Siassi

R Cayabyab

M Ebrahimi

M Uzunyan

R Ramanathan

Los Angeles County University of Southern California Medical Center, Los Angeles, CA

Purpose of Study

The foramen ovale (FO) is a fetal channel that allows right-to-left (R-L) shunting throughout fetal development. After birth, some term infants have minor incompetence of the flap valve, allowing a small left to right (L-R) shunt which usually resolves by 18 days of postnatal life. The aim of this study is to evaluate the echocardiographic change in FO size with postnatal growth to determine if progression to atrial septal defect (ASD) can be predicted in extremely low birth weight infants (ELBW).

Methods Used

Descriptive study of all inborn ELBW infants admitted to a neonatal intensive care unit between 2015 and 2021 who had echocardiograms (ECHO) performed within the first week of postnatal life and before discharge. Size of valve-incompetent FO was determined by measuring the width of L-R color doppler flow in coronal posterior and sagittal subcostal viewing windows. The largest measurement was taken as the diameter of the septal defect.

Summary of Results

Fifty-two infants with median gestational age (GA) of 25 weeks (IQR; 24–26) and median birth weight (BW) of 733 grams (IQR; 633–835) were included in the study. First ECHO was obtained at a median postnatal day of life 2. Forty-eight infants had initial median FO diameter of 1.9 mm at birth that grew to 2.2 mm by median postmenstrual age (PMA) of 36 weeks. Majority of infants at birth (37/46, 80%) and at discharge (39/44, 89%) had L-R shunt. Only 1 infant (1.9%) at birth and 4 infants (7.7%) at discharge had a closed FO. In contrast, 4 ELBW infants born at median GA of 25 weeks (IQR; 24–26) and median BW of 700 grams (IQR; 615–748) had initial FO diameter of 3.3 mm that grew into a 6.2 mm septal defect by 38 weeks PMA. All 4 infants had L-R shunt at FO on discharge. Table 1 shows other echocardiographic parameters measured that were within normal limits.

Abstract #260 Table 1

Conclusions

This study demonstrated that in ELBW infants, FO greater than 3 mm in diameter at birth enlarges with postnatal growth to possibly become a large atrial septal defect that needs echocardiographic follow up as outpatient. If these large defects remain as atrial septal defects o