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2021 Western Medical Research Conference
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Genetics I

Concurrent session

8:10 AM

Friday, January 29, 2021
1 Prospective study of epilepsy in NGLY1 deficiency

RJ Levy*

CH Frater

WB Galentine

MR Ruzhnikov

Stanford University School of Medicine, Stanford, CA

Purpose of Study

To refine the electroclinical phenotype of epilepsy in NGLY1 deficiency via prospective clinical and electroencephalogram (EEG) findings in an international cohort.

Methods Used

We performed prospective phenotyping of 28 subjects with NGLY1 deficiency via standardized clinician interviews every 4 months of medical, developmental and seizure history. Seizure and medication history was confirmed with prior records. 14 subjects also underwent in-person evaluations including EEG, obtained via 20 lead standard array. Descriptive statistics are provided for the first year of an ongoing natural history study.

Summary of Results

All subjects had typical symptoms including: global developmental delay and/or intellectual disability, hypo- or alacrima, hyperkinetic movement disorder and transient elevation in transaminases. 17/28 (60.7%) had a history of epilepsy, with mean seizure onset at 37 months (interquartile range 5–60 months, range 2 months to 19 years). Seizure types included myoclonic (8/17, 47%), astatic (7/17, 41%), and absence (6/17, 35%); focal with secondary generalization, tonic, generalized tonic clonic, and infantile spasms were also reported. 10/14 (71%) subjects had generalized interictal epileptiform activity on EEG. EEG background was otherwise normal without slowing in the majority of subjects. Commonly used antiseizure medications were valproate, levetiracetam, lamotrigine, and clobazam. 7/17 subjects achieved complete seizure control on a variety of medications.

Conclusions

We highlight a significant risk of epilepsy in NGLY1 deficiency and detail the clinical and electrographic features identified in our international cohort. Seizure semiology is varied, with predominant myoclonic, astatic and absence seizure types with onset most commonly in infancy or early childhood. EEG abnormalities are non-specific and indicate a genetic risk of epilepsy, but most patients do not have EEG slowing which is a correlate of encephalopathy. Seizures often require treatment with multiple medications. Commonly used medications in various combinations include valproate and clobazam, indicating hepatic tolerance of these medications. Providers should educate caregivers about varied seizure types to ensure prompt detection and treatment of epilepsy.

2 Clinical whole genome sequencing in young children with autism spectrum disorder: a pilot study

K Wigby1*

T Carr2

M Feddock2

A Jindal1

D Dimmock2

S Kingsmore2

J Friedman1

C Hobbs2

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

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

Purpose of Study

Genomic sequencing has identified a growing number of genes associated with developmental brain disorders and revealed the overlapping genetic architecture of autism spectrum disorder (ASD) and intellectual disability (ID). Children with ASD are often identified first by psychologists or neurologists and the extent of genetic testing or genetics referral is variable. Applying clinical whole genome sequencing (cWGS) early in the diagnostic process has the potential for timely molecular diagnosis and to circumvent the diagnostic odyssey. Here we report a pilot study of cWGS in a clinical cohort of young children with ASD.

Methods Used

Children with ASD and cognitive delays/ID were referred by neurologists or psychologists at a regional healthcare organization. Medical records were used to classify probands as 1) ASD/ID or 2) complex ASD (defined as 1 or more major malformations, abnormal head circumference, or dysmorphic features). cWGS was performed using either parent-child trio (n=16) or parent-child-affected sibling (multiplex families; n=3). Variants were classified according to ACMG guidelines. Pathogenic/likely pathogenic variants associated with ASD/ID were considered molecular diagnoses while variants of uncertain significance were considered candidate variants.

Summary of Results

19 children (9 females) received cWGS at a median age of 4 yrs (range 2.0–7.5 yrs). Six children were classified as complex ASD. cWGS identified a molecular diagnosis in 6 females of which 5 were complex ASD. All molecular diagnoses were due to rare de novo variants (CSNK2B, DDX3X, LZTR1, MED12, PUM1, SMARCA2). No molecular diagnoses were reported for males; 4 males had candidate variants. Three females had medical management changes including condition-specific surveillance and eligibility for targeted therapy.

Conclusions

These preliminary results highlight the contribution of rare de novo variants in children with ASD with cognitive delays, consistent with prior research literature. Additional diagnostic testing beyond MECP2 sequencing and chromosomal microarray should be considered for females with ASD, particularly with complex phenotypes.

3 Phenotypic characterization of WAC related intellectual disability due to a novel splicing variant

JA Morales1*

MI Valenzuela2

B Isidor3

I Cusco-Marti2

DR Matalon1

N Gomez-Ospina1

1Stanford University, Stanford, CA

2Hospital Universitari Vall d’Hebron, Barcelona, Spain

3CHU de Nantes – Hôtel Dieu, Nantes, France

Purpose of Study

Describe the phenotype/natural history of 3 non-related individuals with a novel splicing variant in the WAC gene (c.381+4_381+7delAGTA). Provide proof of pathogenicity to support variant reclassification as pathogenic.

Methods Used

Literature & retrospective chart review, clinical evaluation, in-silico & in-vitro RNA splicing studies.

Summary of Results

We identified 3 non-related boys from Mexican (P1), Spaniard (P2) and French (P3) ancestry carrying the same de novo splicing variant (c.381+4_381+7delAGTA) in the WAC gene. All patients manifested with global developmental delay and intellectual disability (borderline - moderate). Except for non-specific mild dysmorphism, patients are healthy without major medical comorbidities.

All patients were ascertained through whole-exome sequencing. For P1, variant was initially classified as of uncertain significance (ClinVar). In-silico analysis showed location in the 5’ splice site of intron 4 and predicted loss of a splice site in exon 4. RNA experiments derived from P2 confirmed aberrant splicing and showed a truncated protein: p.Gly92Alafs*2.

Review of literature & patient databases supported that WAC related intellectual disability is a condition characterized by neurodevelopmental features of variable severity. Additional findings might include dysmorphism & seizures. Compared to patients with other variants, only 1 of our cohort shared the described facial gestalt. Another overlapping condition, 10p11.2-p12.1 deletion, encompassing WAC and other genes, manifests with neurodevelopmental disorders and facial dysmorphism, suggesting that dysmorphism might be related to other gene/factor interactions.

Conclusions

In our small cohort with WAC intron 4 splicing variant, the common feature was developmental delay and intellectual disability of variable severity. These data suggest weak genotype-phenotype correlations and support the contribution of other factors to the cognitive and dysmorphic phenotype. Based on the guidelines for interpretation of sequence variants, by performing functional studies and identifying non-related individuals we provide sufficient evidence to classify this variant as pathogenic.

4 Identification of CEP68 as a candidate gene for insulin clearance and type 2 diabetes

JH Nguyen*

M Peterfy

Western University of Health Sciences, Pomona, CA

Purpose of Study

Insulin clearance (IC), the removal of insulin from the circulation, is a major determinant of plasma insulin levels and has been implicated in the development of type 2 diabetes (T2D). However, the molecular mechanisms regulating insulin clearance remain poorly understood. Through a genome wide association study (GWAS) in mice, we previously identified chromosomal loci regulating insulin clearance, 9 of which overlapped with established T2D human loci suggesting a causative relationship between the two. The aim of this study was to identify candidate genes for insulin clearance based on these loci for future experimental studies.

Methods Used

We used publicly available databases and bioinformatic approaches to analyze genes and genetic variants at each of the chromosomal loci. Candidate genes were identified by expression quantitative trait locus (eQTL) analysis as implemented at the GTEx Portal. The functionality of coding variants was predicted by PolyPhen and SIFT, whereas non-coding variants were analyzed through HaploReg and RegulomeDB.

Summary of Results

Our initial analysis identified candidate genes at 3 chromosomal loci. ZNF771 harbored a missense variant associated with T2D, whereas CEP68 and JAZF1 showed significant cis-eQTLs in the liver. JAZF1 and ZNF771 were not pursued further, as JAZF1 has previously been characterized in insulin secretion and the ZNF771 coding variant was predicted to be benign. Further analysis of T2D-associated noncoding variants within the CEP68 gene identified a single nucleotide polymorphism (rs2252867) predicted to affect chromatin binding of the PRDM10 transcription factor.

Conclusions

Through bioinformatic analyses, we identified CEP68 as a novel genetic determinant of insulin clearance and T2D. Our results suggest a model, where genetic variation at rs2252867 affects CEP68 expression through altered chromatin-binding and transcription factor activity of PRDM10. Endosomal trafficking, a process mediated by microtubules, which are organized in centrosomes, is integral to insulin clearance. Based on our results, we hypothesize that, as a centrosomal protein, CEP68 may have a role in the endosomal process of insulin clearance and T2D susceptibility. The role of CEP68 and PRDM10 in IC and T2D will be tested in future functional studies.

5 Urine luck: a rare case of a congenital disorder of glycosylation diagnosed by urine oligosaccharides

R Gates*

K Cusmano-Ozog

N Gomez-Ospina

Stanford University, Stanford, CA

Purpose of Study

Congenital Disorders of Glycosylation (CDG) are a group of disorders caused by defective synthesis and processing of glycoconjugates. Diagnosing CDGs can be difficult due to their varied clinical presentations and multi-system organ involvement. Mannosyl-oligosaccharide glucosidase CDG (MOGS-CDG aka type IIb) is a very rare CDG with fewer than ten reported cases in the literature. In addition to being poorly characterized, carbohydrate-deficient transferrin is typically normal, hindering the diagnosis. Here, we report a case of MOGS-CDG, summarize the medical literature, and describe a useful biomarker in urine.

Methods Used

Medical literature and chart review, physical examination, laboratory testing.

Summary of Results

A 13-month old boy with global developmental delay, microcephaly, laryngomalacia, hepatomegaly, and poor vision was admitted to the intensive care unit for hypercapnia and hypoxemia. Physical examination was notable for hypotonia, high-arched palate, pectus excavatum, clenched hands, and limited purposeful movements. A CDG was suspected; however, carbohydrate-deficient transferrin analysis was normal. Whole Exome Sequencing revealed biallelic missense variants of uncertain significance in MOGS NM_006302.2:c.[2126T>C];[1619G>A]. Urine qualitative oligosaccharide analysis by liquid chromatography-tandem mass spectrometry identified an abnormal elevation of a tetrasaccharide distinct from glucose tetrasaccharide (Glc4) and maltotetraose (M4), likely consistent with the known metabolite in this condition, Glc3Man1.

Currently, there are eight cases of MOGS-CDG reported in the literature from six families. Marked hypotonia, hypogammaglobinemia, and hepatomegaly are among the common features reported. The fatality rate before age one is 56% (5/9, including our study).

Conclusions

CDGs should be considered in any child with severe developmental delay, failure to thrive, multi-system organ disease, and characteristic facial features. Normal carbohydrate-deficient transferrin analysis can be seen in CDGs, especially type II CDGs like MOGS-CDG. Urine oligosaccharide analysis may be useful for obtaining the correct diagnosis. Additional cases are needed to better delineate the phenotype and solidify diagnostic techniques for this ultra-rare disorder.

6 Short bones, renal stones, and diagnostic moans: hypercalcemia in a girl found to have coffin-lowry syndrome

CG Tise*

M Grover

DR Matalon

H Byers

Stanford University, Stanford, CA

Purpose of Study

Coffin-Lowry syndrome (CLS) is an X-linked semidominant disorder caused by pathogenic variants in RPS6KA3. In hemizygous males, CLS is characterized by intellectual disability, distinctive facial features, digit anomalies, and progressive kyphoscoliosis. Heterozygous females may also have features of CLS; however there is considerable phenotypic variation thought to be secondary to ratios of X-inactivation in various tissue types. While skeletal anomalies and short stature are hallmarks of CLS, hypercalcemia has not been reported.

Methods Used

Clinical evaluation, molecular sequencing, chart review, and literature review.

Summary of Results

Here we describe a 21 month-old girl with gross motor delays, progressive short stature, and dysmorphic features requiring multiple admissions for idiopathic hypercalcemia necessitating bisphosphonate infusions at 12 and 15 months of age. Family history is notable for mother with decreased height compared to 1st-degree relatives and bilateral genu valgum; no hypercalcemia or developmental delays reported. Exam revealed frontal bossing, depressed nasal bridge with anteverted nares and bulbous nasal tip, everted lower vermillion border, and tapered fingers. Prior evaluation included a normal skeletal survey, chromosomal microarray, and calcium homeostasis panel. Exome sequencing revealed a maternally-inherited likely-pathogenic variant in RPS6KA3, consistent with the diagnosis of CLS in our patient, as well as her mother. No other variants were reported.

Conclusions

Hypercalcemia is not a reported feature in CLS; however, there is evidence of interrupted osteoblast differentiation, providing a potential mechanism for hypercalcemia. The hypercalcemia in this case may represent a severe presentation of an unrecognized phenotype that resolves with age. Exome sequencing provided this family a diagnosis with valuable reproductive implications for parents and maternal relatives. This case highlights the intrafamilial phenotypic variation of CLS among females. Future aims include X-inactivation studies and evaluation of maternal relatives.

7 Novel phenotype of bone marrow failure in HUWE1-associated intellectual disability and skewing of X-chromosome inactivation in maternal blood support role of HUWE1 in hematopoesis

C Carlston1*

SL Sell2

JA Sullivan3

S Brown4

A Bentley5

D Mettman6

I Thiffault6

P Bayrak-Toydemir4,5

L Botto5

1UCSF, San Francisco, CA

2Hershey Medical Center, Hershey, PA

3Duke University Medical Center, Durham, NC

4ARUP Labs, Salt Lake City, UT

5University of Utah, Salt Lake City, UT

6Children’s Mercy Hospital, Kansas City, MO

Purpose of Study

Missense variants in the HUWE1 gene are associated with X-linked intellectual disability (ID) and non-familial features including deep-set eyes, epicanthic folds, blepharophimosis, broad nasal tip and thin upper lip. Mild, intermittent neutropenia has also been reported and induced ablation of Huwe1 in mice results in depletion of hematopoietic stem cell populations. Although girls can be affected, some affected boys inherit HUWE1 variants from unaffected mothers. Skewed X-chromosome inactivation (XCI) is speculated to attenuate the effect of HUWE1 mutation in these individuals. Our study investigates the extent of skewed XCI in this condition and discusses the importance of HUWE1 in hematopoietic homeostasis.

Methods Used

We performed literature review and chart review of patients who underwent exome sequencing at ARUP laboratories or identified through GeneMatcher. XCI studies were performed on maternal blood to assess skewed X-inactivation patterns.

Summary of Results

Here we report a male who presented prenatally with hydrops fetalis and intrauterine growth restriction and at birth was found to have severe pancytopenia. Exome sequencing identified a HUWE1 missense variant (p.Arg3805Lys) inherited from his unaffected mother. Two additional boys with clinical findings consistent with HUWEI-associated ID harbored different missense variants inherited from healthy mothers. XCI analysis of all three mothers demonstrates extremely skewed X inactivation (>90:10).

Conclusions

The finding of bone marrow failure in a patient with HUWE1-associated ID recapitulates the Huwe1 hematological phenotype observed in mice and may represent the most severe presentation of this condition. Mechanistically the dependence of hematopoietic stem cell renewal on HUWE1 could account for the XCI skewing observed in heterozygote mothers. We provide further evidence for the utility of XCI studies in ascribing pathogenicity to inherited missense HUWE1 variants.

8 A rare co-occurrence of aicardi goutieres syndrome with bi-allelic POLG1 variants in a child of consanguineous parents

AE Lee1,2*

A Feigenbaum2,3

D Dimmock2,3

D Malicki2,4

1University of California San Diego, San Diego, CA

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

3University of San Diego, San Diego, CA

4University of California San Diego, La Jolla, CA

Purpose of Study

To describe the first reported patient in literature to be simultaneously affected by both Aicardi Goutieres and a mitochondrial depletion syndrome. To discuss the utility of the Adrenoleukodystrophy screen in picking up Aicardi Goutieres, and the use of muscle and liver biopsies to evaluate the pathogenicity of novel POLG1 variants.

Methods Used

Infant was born to parents who were first cousins, presenting with a history of severe IUGR. The child was admitted to NICU and his newborn screen returned positive for Adrenoleukodystrophy (ALD). Whole genome sequencing (WGS) was performed. WGS was negative for changes in the ABCD1 gene (ALD) but was positive for biallelic likely pathogenic variants of TREX (Aicardi Goutieres) as well as biallelic variants of unknown significance of POLG1. Liver and muscle biopsies were sent to evaluate for mitochondrial disease.

Summary of Results

Patient was homozygous for identical variants of both conditions, suggesting both parents were carriers due to consanguinity. Aicardi Goutieres is a disorder which often mimics congenital infection with a period of regression and neonatal encephalopathy resulting in neurological devastation. POLG1 produces a subunit of a DNA polymerase (Pol γ) which is active in mitochondria and is involved in the replication of mtDNA. Pathological variations produce a wide range of mitochondrial disorders. Patient phenotype included neonatal encephalopathy seen in Aicardi Goutieres, but regression characteristic of mitochondrial dysfunction.

Conclusions

Patient was positive for ALD on newborn screen, and literature shows previous Aicardi Goutieres patients similary identified. Patient‘s muscle and liver biopsy were abnormal, suggesting pathogenicity of his POLG1 variants.

Healthcare research I – therapies

Concurrent session

8:10 AM

Friday, January 29, 2021
9 The accuracy of clinical and obstetrical point of care ultrasound (POCUS) in estimating fetal weight versus actual birth weight: a pilot prospective study of rio bravo family medicine residency program

V Marquez*

Rio Bravo Family Medicine Residency Program, Bakersfield, CA

Purpose of Study

The purpose of this study is to compare the accuracy of clinical and obstetric POCUS methods of predicting fetal weights at term via a pilot prospective study of 35 antepartum patients.

Methods Used

A total of 40 full term pregnant women were included in the study. Five were excluded for insuffienct data. Clinical fetal weight were estimated using Dare’s formula (abdominal circumference x fundal height) and ultrasound (Hadlock) measurements.

Summary of Results

Analysis of the data showed that clinical estimation of the fetal weight using Dare formula (DFW) over-estimated the actual birth weight(ABW). Ultrasound(UFW) estimation of fetal weight showed no significance when compared to ABW. The ABW had a mean of 3247.46 ± 434.27 grams (g) while UFW had a mean of 3182.2 ± 410.44 g. The p-value of UFW and ABW was 0.2991 indicating no statistical significance.

The mean of DFW was 3948.1 ± 534.12 g. When comparing DFW versus ABW, the average difference was 700.64 g. A p-value of 0.00 indicated statistical significance with DFW being greater than ABW.

BMI of the mothers was considered with the mean was 30.71 ± 4.72. Minimum BMI was 24 and a maximum BMI of 42. When taking into account hte absolute errors, no correlation was found between BMI and clinical weight estimation.

Conclusions

In the study, DFW overestimated fetal weight. UFW and ABW showed no significance in estimation. Similar results were seen in a 1994 study by Shamley et al. Clinical overestimation of fetal weight can lead to earlier intervention in macrosomia infants which can lead to decreasing the risk of labor complications especially in a population where the utilization of ultrasounds is not possible. When properly trained in clinical techniques, clinicians can determine the course of management.

10 Effects of mindfulness meditation on patient satisfaction during urodynamic study

H Wagner

M Baranda*

F Jellison

A Staack

Loma Linda University, Zephyrhills, FL

Purpose of Study

Urodynamics (UDS) are used frequently to assess lower urinary tract symptoms (LUTS) and bladder function. UDS requires intravesical, vaginal or rectal transducer placements, and placement of perineal electrodes. Prior studies show that although well tolerated in most, some patients may have heightened anxiety and feelings of discomfort. Some studies suggest that a mindfulness-based stress reduction (MBSR) protocol may help improve a patient’s emotional health and perception of UDS.

Methods Used

A retrospective review was conducted of patients who underwent UDS between June and August 2020. All patients underwent a standardized educational protocol about UDS prior to the study. Patients were divided into meditation group and non-meditation group. The meditation group listened to a pre-recorded meditation prompt with audio headsets prior to starting UDS. All patients completed validated questionnaires to assess their anxiety and pain levels, LUTS before and after intervention including STAI-6, VAS, and a UDS-validated perception questionnaire. Statistical analysis was conducted using paired T-Test, independent T-test, and Chi squared. A p-value of <0.05 was considered statistically significant.

Summary of Results

Out of 30 patients identified, meditation was used in 16 patients and non-meditation in 14 patients. The patients of both groups were comparable in age, gender, living situation, education level, and ethnicity. Patient’s in the meditation group had higher pelvic pain rates (1.7 compared to 1.1 p=0.002). There were no statistically significant differences in pre- and post- UDS rates of overall anxiety. There was increased pain in the non-meditation group post-UDS (4.1 compared to 2.8, p=0.02). Patients in the meditation group reported more often that UDS was better than expected than in the non-meditation group (64.7%, n=11 versus 20%, n=3, p=0.01).

Conclusions

Utilizing a mindfulness-based stress reduction (MBSR) protocol may improve a patient’s perception of pain and satisfaction after UDS. Future randomized prospective studies are needed for further evaluation.

11 The effects of cough suppression therapy on voice severity

D LaTour1*

R Hahn1

B Crawley2

P Krishna2

T Murry2

1Loma Linda University, Loma Linda, CA

2Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Chronic cough (CC) is a global problem, affecting nearly 10% of the world population.1,2Patients report negative psychological effects of CC on their quality of life and voice.3 However, the relationship between CC and voice disorders remains unclear. The purpose of this study was to determine if treatment of CC using Cough Suppression Therapy (CST) contributed to improvement in the self-reported severity of both cough and voice disorders. We also examined if length of CST treatment was related to patients’ self-assessment of changes in their chronic cough and voice disorder.

Methods Used

Subjects were selected from patients presenting with CC to the Loma Linda University Voice and Swallowing Center. Forty-four adult patients met the inclusion criteria of CC > 8 weeks, CST therapy, and pre and post-treatment Voice Handicap Index-10 (VHI-10) and Cough Severity Index (CSI) measures. All subjects underwent pre and post-treatment exam by videostroboscopy and completed pre and post-treatment validated VHI-10 and CSI assessments. Subjects received CST from a licensed Speech Language Pathologist. All subjects had an additional diagnosis of a voice disorder. Patients were divided into two groups based on their VHI scores. Twenty-seven patients were assigned to the cough (C) group and seventeen to the cough-voice (CV) group. Descriptive statistics were used to determine the differences between pre and post-treatment VHI-10 and CSI scores. A nonparametric Rho correlation coefficient was used to determine the relationship between the number of treatment sessions and changes in the VHI-10 and CSI.

Summary of Results

Post-test analysis showed significant improvement in cough for both groups and significant improvement in voice for the 17 subjects in the CV group. The VHI-10 scores for the C group did not change significantly. The correlation between voice disorder severity and number of treatment sessions was not significant at the tested level.

Conclusions

This study demonstrated that patients with CC and voice disorders have favorable responses to CST. Exercising or massaging a group of muscles in the larynx with the intent of decreasing cough demonstrated a crossover effect to the treatment of the voice. This plasticity effect has also been observed in other therapeutic conditions.

12 Development of a questionnaire on access to sickle cell disease care in the indigenous tharu population of Nepal

SY Starkey*

K Gray

C Lanz

J Taylor

SA Lim

K Patterson

V Kapoor

University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Sickle cell disease (SCD) disproportionately affects the Tharu population of Nepal, a marginalized indigenous group concentrated in the Dang district. SCD is a structural hemoglobinopathy resulting in abnormal red blood cells with a tendency to occlude microvasculature. Since 2015, University of British Columbia medical students and a local community partner, Creating Possibilities, have improved access to SCD screening and diagnosis for the Tharu population. However, interviews conducted in 2016–2017 found that SCD-afflicted community members encounter a number of challenges to obtain treatment once diagnosed. The purpose of this study was to develop a questionnaire on barriers to accessing SCD care in this community.

Methods Used

The Barriers to Accessing SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners. Reviewing literature on barriers to accessing healthcare in the Western region of Nepal informed region-specific questionnaire items, while literature on accessing SCD treatment in resource-limited settings informed SCD-specific questionnaire items. We also reviewed the literature on barriers to treatment for various stigmatized chronic health conditions in low-resource settings.

Summary of Results

Qualitative interviews with SCD-afflicted Tharu individuals in 2016–2017 identified inadequate local medical resources, transportation, financial strain, and limited awareness as barriers to care. Based on the literature review, we organized all survey items under the themes transportation, medical infrastructure, finances, community attitudes, and personal attitudes. The questionnaire includes closed-ended questions using a Likert scale, as well as open-ended interview prompts. It was made in collaboration with local community members to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire received ethics board approval, and interviews will begin once local health authorities lift COVID-19 restrictions.

Conclusions

Results from the Barriers to Accessing SCD Care questionnaire will guide future community-based interventions.

13 Telemedicine training to improve healthcare access for senior living community residents in Lewistown, Montana

W French*

University of Washington School of Medicine, Seattle, WA

Purpose of Study

In response to the coronavirus pandemic, the Central Montana Medical Center (CMMC) in Lewistown, Montana bolstered its telemedicine program while restricting in-person visits. Patients inexperienced with technology—especially the elderly—forwent care. The purpose of this study was to determine how telemedicine access can be improved for residents of Lewistown senior living communities (SLCs), defined as independent, assisted living and nursing home facilities for older adults.

Methods Used

CMMC administration cite patient inexperience with technology and clinician buy-in as the largest barriers to telemedicine utilization (personal communication, July 28, 2020). To elucidate, Lewistown SLC administrators were surveyed. The vast majority did not assist residents with telemedicine visits, but almost all expressed interest in offering it if training were provided. CMMC clinicians were also surveyed. Most had no telemedicine training and few felt comfortable using it. Therefore, SLC staff and clinician training were identified as avenues to improve telemedicine delivery. Two studies were evaluated to ascertain the benefit of such interventions.

Summary of Results

The first study found access to telemedicine and telemedicine-trained staff reduced emergency department (ED) use among SLC residents by 18% annually. Residents without access to such services experienced a 1% growth in ED visits (Shah et al., 2015). The second study assessed variability in medical care between virtual visit companies. Significant variations were observed across all measures, underscoring the necessity of provider telemedicine training (Schoenfeld et al., 2017). Both studies and SLC/clinician survey results were presented to CMMC administration.

Conclusions

Training SLC staff to assist residents with telemedicine visits may increase telemedicine usage and healthcare access. Similarly, training CMMC clinicians on virtual physical exams and history collection may improve their confidence in telemedicine technology and quality of virtual care. The survey results and literature suggest both interventions would have a significant impact on telemedicine delivery in Lewistown. Future steps include determining level of training for SLC staff and exploring telemedicine training programs for providers.

14 Knowledge and risk perception about hepatitis c: preliminary evidence from a cross-sectional study of adults living in Louisiana

B Novak*

K Panbechi

J Matacotta

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

Purpose of Study

In 2013, HCV killed more Americans than all other infectious diseases according to the CDC. In Louisiana, HCV affects underserved populations at a disproportionate rate. Even though direct-acting antivirals (DAAs) treatment is available, many barriers prevent adequate screening and treatment of at-risk populations.

The purpose of this study is to evaluate HCV risk perception and knowledge about testing and treatment. The larger goal is to understand how a telemedicine-enhanced healthcare model can be utilized to improve access and quality of care.

Methods Used

This preregistered cross-sectional online study was approved by the IRB of Western University of Health Sciences (X20/IRB/031). Preliminary data was analyzed from a quantitative survey, collected between April 29-September 15, 2020, of volunteer participants, aged 18–99 years old, who were recruited online via social media platforms and in-person at various Access Health Louisiana Clinics. N=39 for preliminary data, with a goal of N=100. The survey includes questions regarding demographics, risk perception, access to care, and knowledge of HCV. Data was analyzed using ANOVA.

Summary of Results

3 out of 39 participants reported taking a DAA and were not included in the study. Most respondents (80.6%) perceived their overall health as excellent, very good, or good and correlated with risk perception. 14% reported HCV testing while 67% never tested. The two most cited reasons for not testing were believing they were not at risk and lack of provider recommendation for testing. Those who never tested included 24% from the Baby Boomer generation. Additionally, 66.7% had not heard of DAAs or knew that HCV was a curable disease. 52.7% of respondents believed that people with HCV would be treated differently if they disclosed their status and 69.5% believed that shame kept people from seeking treatment.

Conclusions

These findings offer preliminary but critical evidence that increasing public knowledge and addressing stigma about HCV are key to increasing HCV screening and treatment. The various barriers impeding diagnoses and treatment of HCV patients include lack of awareness, access barriers, and affordable medication.

15 Adequacy of anesthesia information received by pediatric patients’ parents and their preferred method of education

L Nguyen*

University of California San Diego, La Jolla, CA

Purpose of Study

Anesthesiologists perform critical roles prior to, during, and following operations. Nonetheless, one of the most common misconceptions patients have is that the anesthesiologist’s responsibilities consist solely of keeping them asleep and awakening them. Education during the preoperative visit is important, but the optimal methods of disseminating information to patients remains elusive. Previous studies have assessed patient perceptions about anesthesia. However, there is minimal published literature looking at how education level affects patient understanding of the role of anesthesiologists and the methods by which these patients prefer to receive the necessary information. The goal of this project is to better understand patients’ existing knowledge about anesthesia and their preference for the method by which this information is delivered.

Methods Used

We asked parents of patients to complete a survey that would allows us to better understand their knowledge of the anesthesia administered to their child and opinions on how this information is shared. There is one version of the paper survey form, which includes 8 simple questions regarding how they obtained information regarding anesthesia, if the information was complete, and their preferences for how additional information should be delivered. We asked the parents to fill out the brief survey either during their child’s preoperative or postoperative visit.

Summary of Results

62% of parents stated that anesthesia was a factor in their consenting to the procedure. 45% of these parents felt that more information regarding the anesthesia would have been helpful. 53% stated that receiving information directly from their doctor during the office visit is the preferred method of education.

Conclusions

Anesthesia plays a significant role in parents’ consenting to their child’s procedure. Many questions remain surrounding the nature of the information that patients require and the methods by which such information is delivered. Directly exploring the views of patients and their family members will improve understanding of how to best educate them, which will hopefully decrease the degree of anxiety that patients face and lead to better anesthetic care.

16 Addressing alcohol use disorder in plains, mt through online mutual support groups

M Napier*

University of Washington School of Medicine, Spokane, WA

Purpose of Study

Plains, MT is a rural town of 1,149 people located in Sanders County. Within the county, 21.07% of people are considered heavy drinkers, compared to the national average of 14.71%. The need to address alcohol use disorder is outlined in the Clark Fork Valley Hospital (CFVH) 2017 Health Assessment and Implementation Plan, as a top priority. This need was further highlighted in community conversations that revealed a strong drinking culture within the town.

Methods Used

Engagement with the community was informed by an asset-based approach. Community assets were identified through both clinical observation and interviewing CFVH’s mental and behavioral health specialist and licensed clinical psychologist. Interventions were assessed using CFVH 2017 Health Assessment and Implementation Plan, integrated review, community conversations, and clinical observations.

Summary of Results

Close teamwork between physicians and the Mental and Behavioral Health Department (MBHD) is one of CFVH’s strongest assets in addressing alcohol use disorder. This close communication allows for screening by providers and direct referral to the MBHD. The strong longitudinal relationship between patients and their providers results in better follow up, as they are referred by a trusted clinician. One potential interventional approach includes online mutual support groups focused on addressing the strong drinking culture. One advantage of this approach is continuous accessibility to ‘someone like me.’ This can be difficult to find in small towns with limited in-person participation. Further, online support groups offer a greater degree of anonymity, which can be of significant value to small communities. Lastly, online peer support groups offer a more flexible recovery plan compared to 12-step programs.

Conclusions

This project identified a community asset as well as a potential intervention in addressing alcohol use disorder. One key element to increase intervention success is to take advantage of local and available community assets. Next steps include capitalizing on the patient referrals to the MBHD and providing online mutual support group resources. Potential challenges include limited access to computers/internet which can be addressed by simultaneously directing patients to computer access at the public library.

Neonatology – perinatal biology I

Concurrent session

8:10 AM

Friday, January 29, 2021
17 Antenatal selenium deficiency decreases neonatal hepatic and plasma glutathione peroxidase

D Balasubramaniyan*

L Zheng

R de Dios

T Sizemore

E Nozik

CJ Wright

L Sherlock

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels and worse neonatal outcomes. Se deficiency in infancy increases the risk of morbidities related to oxidative stress. The mechanisms explaining this are unknown, and preclinical models of antenatal Se deficiency have not tested the impact of low Se during pregnancy on the neonate. Adult models demonstrate circulating and hepatic glutathione peroxidases (GPx) are selenoenzymes highly sensitive to Se intake. Thus, we developed a model of antenatal Se deficiency and assessed the effect on pregnancy, as well as plasma and hepatic selenoenzymes in the pups.

Methods Used

C57Bl/6 mice received SeS (0.4 ppm Se) or SeD (<0.01 ppm Se) diets 2–4 weeks before breeding. Pups were sacrificed at P0. Liver was assessed for Gpx1 mRNA, and GPx1, Trxrd1, SOD1, SOD2, SOD3, catalase and HO-1 protein content by Western blot. GPx activity was measured in liver and plasma by enzyme assay. F and M pups were analyzed as separate groups.

Summary of Results

SeD pups had similar weights per littler but smaller litters than SeS (p<0.05, n=8–9 litters). Plasma GPx activity was decreased in SeD pups (p<0.01, n-2). Hepatic Gpx1 mRNA, GPx1 protein and GPx activity were decreased in SeD pups (p<0.001, n=4–5). Hepatic Trxrd1 protein was not decreased if dams received short exposure to SeD diet (<10 weeks) but decreased if dams received prolonged SeD diet (>10 weeks) (p<0.05, n=3–5). To test if other antioxidant enzymes (AOE) increased in the setting of SeD, hepatic SOD1, SOD2, SOD3, catalase and HO-1 protein contents were measured and were not different between SeS and SeD pups, either with short or prolonged duration (n = 4). Sex differences were not observed in the mRNA, protein content or activity level of selenoenzymes or other AOE of SeS or SeD pups.

Conclusions

Antenatal SeD decreases neonatal plasma and hepatic GPx, without sex differences in SeS or SeD pups. With prolonged SeD in dam, hepatic Trxrd1 is also decreased. Neonatal SeD pups do not demonstrate an increase in compensatory AOE. We speculate that both male and female SeD neonates may be vulnerable to oxidative stress secondary to low hepatic and circulating antioxidant enzymatic defense.

18 Hypoxemia does not potentiate hypoglycemia induced glucose production in fetal sheep

P Mukherjee1*

AK Jones1

P Rozance1

LD Brown1

S Limes2

S Wesolowski1

1University of Colorado, Aurora, CO

2University of Arizona, Tucson, AZ

Purpose of Study

Fetuses with placental insufficiency induced IUGR are hypoxemic, hypoglycemic and have early activation of hepatic glucose production (HGP). In previous work, hypoglycemia (5d to 8wk) activates both HGP and gluconeogenic gene expression while hypoxemia for 10d only potentiates gluconeogenic gene expression. Here, we test if hypoxemia and hypoglycemia (HOX+HG) would activate HGP more than hypoglycemia (HG) alone.

Methods Used

Late gestation sheep were made HG via maternal insulin infusion to reduce fetal glucose (n=11). A second group was made HOX+HG via maternal N2 gas insufflation plus insulin to reduce fetal oxygen and glucose (n=12). Fetal metabolic studies were performed before (d0) and after 5 days of treatment (d5). Data were analyzed with mixed model ANOVA to test for main effect of treatment (d0 vs d5), with post-tests comparing HG vs. HG+HOX on d5.

Summary of Results

Glucose concentrations were 51% lower in both groups on d5 vs. d0 (P<0.001). In HG+HOX fetuses, pO2 decreased by 25% compared to HG fetuses on d5 and compared to both groups on d0 (P<0.001). HG+HOX fetuses had increased lactate, cortisol, and norepinephrine (NE) concentrations compared to HG fetuses (P<0.005) on d5. Insulin concentrations were decreased in both groups on d5 vs. d0 (P<0.001) and were decreased further in HG+HOX compared to HG (P=0.05). Glucose utilization rates were decreased while glucose production rates were increased similarly in both groups on d5 compared to d0 (P<0.05).

Conclusions

HGP was activated in both HG and HG+HOX fetuses. Thus, while glucose uptake from the placenta and fetal glucose utilization were lower on d5, utilization remained higher than uptake, demonstrating increased endogenous fetal HGP. Interestingly, despite decreased insulin and elevated cortisol and NE levels in the HG+HOX fetuses, these hypoxemia associated effects did not potentiate HGP. These data support a dominant role for hypoglycemia, not hypoxemia, in activating HGP in fetuses with placental insufficiency.

19 Reduced VEGFA is associated with differences in the microvascular structure in IUGR skeletal muscle

T Dear1*

E Chang1

A Heintz1

S Wesolowski1

S Jonker2

P Rozance1

L Brown1

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

2Oregon Health and Science University, Portland, OR

Purpose of Study

Skeletal muscle growth is reduced in the intrauterine growth restricted (IUGR) fetus. We previously reported that external iliac blood flow was similar between late gestation control (CON) and IUGR fetal sheep when normalized to hindlimb weight, indicating that hindlimb muscle growth slowed to match blood supply. Oxygen delivery due to lower blood oxygen content and oxygen consumption rates were reduced in the IUGR hindlimb. Acute hypoxemia is known to stimulate angiogenesis, but whether chronic hypoxemia induces angiogenesis is controversial. We hypothesized that muscle microvasculature would be reduced in the IUGR fetus as an adaptation to slow growth.

Methods Used

Biceps femoris (BF) and tibialis anterior (TA) muscles were harvested from CON (n=8) and IUGR (n=13) late gestation fetal sheep. Genes that regulate angiogenesis were measured in BF using real-time qPCR. VEGFA protein was measured in TA by Western blot. Cross-sections of BF were incubated with anti-dystrophin to identify myofibers and Griffonia simplicifolia lectin to quantify vessel area and density. Total vascular, capillary-specific, and arteriole/venule-specific area to muscle area ratios and capillary number per myofiber were determined using Visiopharm Image Analysis software. Student’s t-test was used, and P<0.05 was designated as significant.

Summary of Results

Angiogenic regulatory gene expression was either similar (NOS3, THBS1, KDR, DLL4, NOTCH1/4, SPP1) or lower (ANGPT1, NCL, PGC-1α, and CCL2) in IUGR BF compared to CON (P<0.05). Protein expression of VEGFA was 45% lower in IUGR TA (P<0.0005). Vascular/muscle area, capillary/muscle area, and capillary number/myofiber ratios were similar between groups. However, arteriole and venule/muscle area tended to be lower in IUGR (P=0.06), and the capillary area/total vascular area was higher in IUGR (P<0.05).

Conclusions

Contrary to our hypothesis, microvasculature was maintained in IUGR muscle. However, an increase in the ratio of capillary area to total vascular area may indicate differences in branching morphogenesis in an attempt to compensate for chronic hypoxemia. We further speculate that reduced VEGFA may contribute to reduced skeletal muscle growth in IUGR.

20 Cerebral regional oxygen saturation during resuscitation in perinatal asphyxial cardiac arrest

LI Zeinali1*

M Hardie2

A Lesneski2

D Sankaran1

S Lakshminrusimha1

P Vali1

1University of California Davis, Sacramento, CA

2University of California Davis, Davis, CA

Purpose of Study

Cerebral regional oxygen saturation (CrSO2) measured by near-infrared spectroscopy (NIRS) can be used as an adjunct to oxygen saturation (SpO2) monitoring in the delivery room. No studies have assessed the accuracy of NIRS in perinatal cardiac arrest.

Methods Used

Nine fetal lambs were instrumented to measure blood pressure, carotid blood flow, preductal SpO2, SaO2 and CrSO2. Cardiac arrest was induced by umbilical cord occlusion and lambs were resuscitated following NRP guidelines.

Summary of Results

Average lamb weight was 4.0 ±0.7 kg. Median time (IQR) to asystole was 17 (14–18) min. Median time (IQR) to return of spontaneous circulation (ROSC) was 4.4 (3.5–4.8) min. Figure 1 shows the relationship between CrSO2, SpO2 and SaO2. CrSO2 values quickly rise following ROSC along with increased O2 delivery to the brain (figure 2). Pearson correlation comparing brain O2 delivery to CrSO2, SaO2 and SpO2 were 0.76, 0.76, and 0.61, respectively. Correlation comparing SaO2 to CrSO2 and SpO2 were 0.77 and 0.59, respectively.

Abstract 20 Figure 1

Shows the relationship between CrSO2, SpO2 and SaO2

Abstract 20 Figure 2

CrSO2 values quickly rise following ROSC along with increased O2 delivery to the brain

Conclusions

In a perinatal asphyxiated lamb model, CrSO2 correlates better than SpO2 with brain oxygen delivery and SaO2 and may help guide titration of FiO2 following ROSC. Further studies are needed before implementation into clinical practice.

21 Distinct populations of developing macrophages in embryonic mouse livers and lungs

S Hietalati*

L Butcher

L Prince

University of California San Diego, La Jolla, CA

Purpose of Study

Macrophages play important roles in the innate immune system and inflammatory response. These phagocytic cells engulf and digest pathogens, infected or dying cells and debris, as well as recruit and regulate other immune cells and the inflammatory response and assist in tissue repair. Prior studies have shown that separate populations of macrophages exist in the developing fetus: fetal liver monocyte derived macrophages (CD11bHI/F4/80LOW) and yolk sac derived macrophages (F4/80HI/CD11bLOW). It has also been suggested that these populations serve different functions and have distinct inflammatory properties. Our study aims to further characterize the differences of these populations and identify their locations during early immune system development.

Methods Used

Whole lungs and livers from E15 C57BL/6 mice were fixed with 4% PFA and passed through sucrose gradients prior to embedding in OCT compound for sectioning. Incubation of primary antibodies for macrophage markers CD14, CD68, F4/80, ID3 and immune response markers Ccl4, C1qA, IL-1ß and NLRP3 followed blocking for non-specific binding. Secondary antibodies were added after washing, followed by DRAQ5 nuclear staining. Imaging was done using a Leica TCS-SPE confocal microscope.

Summary of Results

We were able to clearly identify the known macrophage marker CD68 in both lungs and livers. In addition, Kuppfer cell marker ID3 showed robust expression in the liver samples. Interestingly, hematopoietic islands of yolk sac derived F4/80 macrophages were seen throughout the tissues rather than isolated in only one location. C1qA expressed was colocalized with some F4/80 expression and appeared to be in adjacent cells in the same area of the tissues.

Conclusions

We were able to identify macrophage populations in the lungs and liver of E15 mice. Our identification of F4/80 hematopoietic islands demonstrate that the yolk sac derived cells do not remain in one location but disperse throughout the liver. The nearby location of C1qA could indicate that the F4/80 macrophage populations are involved with the complement system during development and, potentially, could indicate a functional difference of these cells. Learning the roles of these populations can lead to better understanding of neonatal immune system development, eventually enabling better therapeutic opportunities.

22 In vitro inhibitory potency of D-penicillamine on heme oxygenase isozyme activity

K Fuwa*

CM Konecny

DK Stevenson

RJ Wong

Stanford University School of Medicine, Stanford, CA

Purpose of Study

Heme oxygenase (HO) is the rate-limiting enzyme in the bilirubin production pathway and exists as 2 well-described isozymes: HO-1 and HO-2. Identifying compounds that can selectively inhibit the inducible HO-1 without affecting the constitutive HO-2 isozyme is desirable for use in treating neonatal hyperbilirubinemia. D-Penicillamine, a compound primarily used for treating heavy metal (e.g. copper, lead) poisoning, has been shown previously to be effective in lowering total bilirubin levels in newborns, but its proposed mechanism of action via HO inhibition and, more importantly, its selectivity for the HO-1 isozyme, has not been explored. In this study, we evaluated the in vitro potency and selectivity of D-Penicillamine for the inducible HO-1 isozyme.

Methods Used

Adult female FVB mice (28–30 g) were sacrificed to harvest spleen and brain, tissues containing primarily HO-1 and HO-2, respectively. D-Penicillamine (final concentration of 8.3 mg/mL) was added to reaction mixtures containing tissue sonicates, heme, and NADPH. After incubation in a 37°C water bath for 15 min, HO activity, as indexed by carbon monoxide (CO) production, was determined using gas chromatography and expressed as pmoles of CO produced/hr/mg fresh weight. Percent inhibition of HO activity was calculated. A selectivity index (SI) for HO-1, defined as the percent inhibition of HO-1 (spleen) over HO-2 (brain) activities, was calculated, with a SI of > 1.0 indicative of a selectivity for the HO-1 isozyme.

Summary of Results

D-Penicillamine at a concentration 8.3 mg/mL effectively decreased in vitro HO activity 37 ± 3% (n = 3), and 43 ± 11% (n = 3), for the HO-1 (spleen) and HO-1 (brain) isozymes, respectively. In addition, the calculated SI for HO-1 was 0.87, indicating an almost equal selectivity for each HO isozyme.

Conclusions

D-Penicillamine can decrease in vitro HO activity and appears to have equal selectivity to inhibit both HO-1 and HO-2 isozymes. Further work is warranted to investigate whether D-Penicillamine has potential for use in the treatment of neonatal hyperbilirubinemia.

23 A novel rat model of inflammation driven diffuse white matter injury

J Waddell*

K Carter

N Ojeda

Y Pang

University of Mississippi Medical Center, Jackson, MS

Purpose of Study

Brain white matter injury (WMI) is a leading cause of neurological disabilities in preterm infants that can affect sensory, motor, and cognitive brain function. WMI ranges from severe, necrotic periventricular leukomalacia (PVL) to mild diffuse WMI that involves changes to Oligodendrocyte (OL) lineage cells and neurons. Diffuse WMI has emerged as the most prevalent form in modern neonatology. This has led to calls for relevant animal models that can more accurately mimic diffuse WMI. Previously, we have established a PVL-like model by intracerebral injection of a high dose of lipopolysaccharide (LPS) to neonatal rats. The aim of this study was to test the hypothesis that low-grade neuroinflammation caused by intracerebral injection of a lower dose of LPS may produce clinically relevant diffuse WMI.

Methods Used

Sprague Dawley rats on postnatal day 5 (P5) were injected intracerebrally with LPS (100 µg/kg, in saline) or saline. On P7, we investigated injury and dysmaturity of OL lineage cells and neurons, activation of astrocytes and microglia, as well as damage to axons and dendrites, by immunohistochemistry and Western blot. Cells were quantified by stereological cell counting methods.

Summary of Results

Our data show that a lower dose of LPS (1/10 of previous model) led to an activation of Iba1+ microglia and GFAP+ astrocytes across brain regions including the periventricular white matter and hippocampus. LPS treatment led to acute axonal damage shown by beaded ß-amyloid precursor protein (ß-app) positive fibers in the cortex, corpus callosum, and hippocampus; This was rarely observed in the control rats. In addition, reduction of Microtubule Associated Protein 2 (MAP2) staining and Doublecortin (DCX) protein levels in the hippocampus suggests neuronal dysmaturation. LPS resulted in a reduction in Rip+ later stage OLs but not PDGF receptor+ OL progenitor cells. There were no apparent necrotic brain damages noted in LPS-treated rats.

Conclusions

The results suggest that a lower dose of LPS produces cellular and molecular features of diffuse WMI, characterized by injury and dysmaturation in both OLs and neurons that are increasingly seen as critical cellular substrates underlying cognitive and behavioral deficits in very premature infants.

24 Standardized chitosan nanoparticles

AC Jaeger1,2

N Iwakoshi3

W Kirsch1,2*

1Loma Linda University, Loma Linda, CA

2Karamedica, Raleigh, NC

3Walla Walla University, College Place, WA

Purpose of Study

Bypassing the blood-brain barrier via nasal insufflation, Diethylethylamine-Chitosan (DEAE-CH) nanoparticles (NP) show promise as a gene delivery system to the brain. Manual NP creation means sample inconsistency. The positive charge from DEAE-CH amines and the negative phosphates of a plasmid form an NP, but how they interact informs the size and shape of the particle. Past protocols produced particles too large and varied. Since microfluidics impacts NP formation, inconsistencies are likely due to the variability inherent in turbulent mixing. We hypothesize standardizing the mixing procedure for the creation of DEAE-CH NPs will provide smaller NPs between sample preparations.

Methods Used

To investigate this, we assembled a device with software to create qualifying NPs with batch consistency. A prepared solution of DEAE-CH is combined with a substituted phosphate via motorized syringes connected to a ‘Y’ joint creating a laminar flow ideal for reliably consistent NPs. NPs were measured by dynamic light scattering.

Summary of Results

Preliminary results suggest that our standardized system using this encapsulator produces nanoparticles in a much smaller range of 10 to 30 nanometers for an average of 18.4 nm, much smaller than previous manual attempts.

Abstract 24 Figure 1

Two mounted motors extrude the content of syringes at fixed rates

Conclusions

Further study will determine what mixing rate provides the best laminar flow to create a predictable DEAE-CH NP for an effective gene delivery system.

Neuroscience I

Concurrent session

8:10 AM

Friday, January 29, 2021
25 Preclinical prenatal alcohol exposure and placental insufficiency result in altered cerebellar peduncle microstructure

D Marquez*

N Pavlik

S Davies

D Savage

J Maxwell

University of New Mexico, Rio Rancho, NM

Purpose of Study

Prenatal Alcohol Exposure (PAE), a continued common occurrence worldwide, is associated with neurodevelopmental abnormalities including impairments of behavioral and cognitive functioning. Additionally, placental insufficiency (PI), occurs concomitantly with PAE. The effect of PAE+PI on the cerebellum, a brain structure that functions in coordinating voluntary movements, is not fully understood. In this study we use magnetic resonance imaging (MRI) to assess whether PAE+PI results in microstructural abnormalities within the white matter fiber tracts that connect the cerebellum to the brainstem.

Methods Used

Pregnant Long-Evans rats voluntarily drank 5% ethanol or saccharin water until embryonic day 18 (E18) to mimic moderate PAE. On E19, an open laparotomy was completed, and the uterine arteries were occluded for one hour. Pups delivered normally on E22 and matured with their dams. At postnatal day 100 (P100), tissue was collected, and the brains were scanned on a Bruker 7.0T MRI. Regions of Interest were analyzed with Bruker’s Paravision 5.1 and diffusion eigenvectors measured. One-way ANOVA was used, with p<0.05 significant (n=15–30/group).

Summary of Results

Diffusion tensor imaging (DTI) analyses of the cerebellar peduncles showed decreases in fractional anisotropy (FA) in PAE+PI rats compared to controls. FA was decreased by nearly 16% (p<0.01) in the superior cerebellar peduncle. In the inferior and middle cerebellar peduncle, the FA was decreased in PAE+PI compared to controls (decreased by ~5%) but did not reach significance. Additionally, increases in axial, radial and mean diffusivity were noted in PAE+PI compared to controls within the cerebellar peduncles, but significance was not reached.

Conclusions

The cerebellar peduncles are sensitive to injury following PAE+PI in this preclinical study. Specifically, the superior cerebellar peduncle, which consists primarily of efferent pathways, is more vulnerable to injury following these prenatal insults compared to other areas of the cerebellum. Additional studies are needed to further characterize this injury and the impact this may have on function related to these critical brain regions.

26 Somatic mosacism of a single platelet derived growth factor receptor beta variant: the role of allele frequency on phenotype

F El-Ghazali*

M Ferreira

University of Washington, Sammamish, WA

Purpose of Study

Aneurysmal dilatations weaken arterial walls and put them at risk for catastrophic rupture. Germline variants and environmental contributions account for a minority of aneurysms and little is known about the role of somatic events in pathogenesis. Recently, our group described an index patient with a somatic mosaicism pattern of a unique vascular and cutaneous phenotype. Whole exome sequencing of affected vascular tissue revealed an activating somatic variant in platelet derived growth factor beta (PDGFRB) with allele fractions between 2–40%. This variant was absent from matched blood DNA and unaffected tissues from throughout the body. Ten years later, the patient suffered a deadly subarachnoid hemorrhage and the family elected scientific donation. We aimed to study the PDGFRB allele fraction to histopathologic phenotype relationship throughout the patient’s body.

Methods Used

The institutional review board at the University of Washington approved all research conducted. Postmortem tissue specimens along with cell lines were harvested and mirrored tissue specimens were processed for both DNA extraction and histology. A unique digital droplet polymerase chain reaction (ddPCR) assay specific for the PDGFRB variant (p.Tyr562Cys [g.149505130T>C (GRCh37/hg19) was developed to study allele fractions at a 20,000x depth coverage. Obtained allele frequencies were compared to the pathogenic phenotype.

Summary of Results

The patient developed intracranial, radial and coronary artery aneurysms ipsilateral to the cutaneous phenotype. There was no aortic involvement and contralateral vasculature was normal. ddPCR revealed the presence of variant gradient in all affected tissue. Interestingly, the aorta and unaffected arteries did not harbor the variant. We will discuss the allele frequency relationship to phenotype throughout the patient’s vascular tree and tissues.

Conclusions

The PDGFRB variants are associated with both cerebral and coronary aneurysms. The aorta was spared without evidence of aneurysmal changes. This is in contrast to inheritable connective-tissue diseases such as Ehlers-Danlos (vascular type) syndrome and Loeys-Dietz syndrome, where an aortic phenotype is uniform. This is the first described case of a PDGFRB variant - gradient map showcasing somatic mosaicism with a vascular phenotype.

27 Effect of preoperative opioid use on post operative opioid demand and length of stay following spinal fusion for trauma

L Castellini1*

R Saigal1,2,3

1University of Washington School of Medicine, Seattle, WA

2University of Washington Department of Medicine, Seattle, WA

3Harborview Medical Center, Seattle, WA

Purpose of Study

Preoperative opioid use (POU) has been well-studied in elective spinal surgery and correlated with numerous postoperative complications. Prior to this study, there was a paucity of data available on surgery for spine trauma, possibly because there are minimal options for opioid reduction prior to emergent spinal surgery. Patients with spine trauma are at a high risk for adverse postoperative outcomes. This retrospective cohort study investigated the effects of POU on postoperative opioid demand (POD) and length of stay (LOS) in traumatic spinal surgery.

Methods Used

130 patients were grouped into two groups for primary comparison: Group 1 (Preoperative Opioid Use, N=16) and Group 2 (No Opioid Use, N=114). Two subgroups of Group 2 were used for secondary comparison: Group 3 (No Substance Abuse, N=95) and Group 4 (Other Substance Abuse, N=19). POD was defined as average morphine equivalents per day (mg/day) and LOS was defined as number of days between surgery and discharge. Multivariate analysis was used to determine if there were significant differences in the POD and LOS between groups.

Summary of Results

Primary analysis demonstrated that preoperative opioid users required an estimated 97.5 mg/day more opioid medications compared to non-opioid users (p<0.001). Secondary analysis showed a similar increase in POD when comparing preoperative opioid users to patients with no history of substance abuse (p<0.001) and to patients with history of other substance abuse (p<0.001). Neither primary nor secondary analysis showed a difference in LOS between any of the groups.

Conclusions

Preoperative opioid users had increased POD compared to non-opioid users, but there was no difference in LOS between the groups. Preliminary investigation reveals very similar results when comparing preoperative opioid users to non-substance abusers and other substance abusers. We theorize the lack of difference in LOS between groups may be due to the enhanced perioperative recovery protocol used for these patients, which has been demonstrated to reduce LOS. Further investigation into long-term outcomes is the next step for this research.

28 Bioinformatic comparisons of zebrafish and rats after spinal cord injury

AG Navarro1*

K Mruk2,3

1WWAMI Medical Education, University of Washington School of Medicine, Spokane, WA, USA, Spokane, WA

2School of Pharmacy, University of Wyoming, Laramie, WY, USA, Laramie, WY

3WWAMI Medical Education, University of Wyoming, Laramie, WY, USA, Laramie, WY

Purpose of Study

Humans respond to spinal cord injury (SCI) similarly to rats by forming a glial scar with limited functional recovery. In contrast, zebrafish regenerate their spinal cords after injury with functional recovery. This study was designed to explore the similarities and differences between the molecular mechanisms of SCI in zebrafish and rats.

Methods Used

We analyzed transcriptional datasets from zebrafish and rats deposited in the Genome Expression Omnibus. To analyze differentially expressed genes, we used the online tool, GEO2R. We adjusted p-values using the Benjamini & Hochberg procedure for control the false discovery rate and identified differentially expressed genes. For each dataset, we compared sham-controls to injured spinal cord samples using the author-defined identification provided. We next obtained Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results of the differentially expressed genes. Lastly, we compared these results between injuries and species.

Summary of Results

There were a total of 43,289 differentially expressed genes with an adjusted p-value cutoff of 0.01 identified between sham and injured samples. Analysis across species with the same mechanism of injury identified 609 differentially expressed genes that overlapped. Differentially expressed genes were enriched in pathways related to cell cycle, development, RNA/DNA processes, and neuron function/anatomy. In addition, we found overlap between zebrafish and rats.

Conclusions

The differences in regenerative capacity between zebrafish and rats were highlighted by the significant difference in how these common pathways are upregulated or downregulated across species and mechanism of injury. For example, zebrafish regulate genes for intracellular processes whereas rats regulate more extracellular processes. These differences may contribute to the contrasting functional recovery seen between these species after spinal cord injury. Identifying these differences may lead to identification of new therapeutic targets and strategies to promote regeneration in humans.

29 Altered expression of HSPA1B and DNAJB1 in brain of calpain-1 knockout mice

S Shiehzadegan

M Baudry*

Western University of Health Sciences, Chino Hills, CA

Purpose of Study

A major isoform of calpains in the brain, calpain-1, participates in both synaptic plasticity and neuroprotection. While calpain-1 activation is required for long-term potentiation induction and is neuroprotective, calpain-2 activation limits the magnitude of LTP and is neurodegenerative.

Methods Used

Using RNASeq analysis, we identified several differentially expressed genes, including HSPA1B and DNAJB1, in the brain of calpain-1 KO mice as compared to wild-type mice. HSPA1B codes for a heat shock protein, which stabilizes proteins against aggregation and helps folding of newly synthesized proteins. DNAJB1 is another member of the heat shock protein family and participates in protein folding and protein complex assembly. In the present study, we examined the expression of the two proteins encoded by these two genes using quantitative immunohistochemistry in frozen brain sections from adult wild-type and calpain-1 KO mice.

Summary of Results

We found that knockout mice have lower expression of DNAJB1 and HSPA1B proteins.

Conclusions

These results suggest a novel role for calpain-1 in the regulation of heat shock proteins in the brain.

30 Superotemporal retinal amyloid imaging signals pathologic neurodegeneration and memory deficits in subjects with cognitive decline

T Torbati1,2*

OM Dumitrascu2

J Sheyn2

PD Lyden2

A Sherzai3

D Sherzai3

DS Sherman2

S Verdooner4

KL Black2

Y Koronyo2

M Koronyo-Hamaoui2

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

2Cedars-Sinai Medical Center, Los Angeles, CA

3Loma Linda University, Loma Linda, CA

4NeuroVision Imaging Inc., Sacramento, CA

Purpose of Study

Considerable evidence reveals that amyloid-beta (Aβ) abnormality consistent with Alzheimer’s disease (AD) pathology manifests early before clinical symptomatology, including cognitive decline. However, current amyloid-PET brain imaging visualizes cerebral Aβ plaque with limited accessibility. Given that retina is the only CNS organ not enclosed by bone, newly developed direct and noninvasive retinal amyloid imaging (RAI) bypasses the shielded brain and aims to improve clinical relevance. Despite advances in imaging retinal amyloidosis, quantitative and topographical investigation of retinal Aβ burden in patients with cognitive impairment was never reported. Here, we used specific amyloid-binding fluorophore curcumin and laser ophthalmoscopy to examine RAI in patients with cognitive decline.

Methods Used

All 34 subjects underwent neurological examination and neuropsychological tests including Montreal Cognitive Assessment (MOCA) and Clinical Dementia Rating (CDR) scale. We quantified retinal amyloid count (RAC) and area in the superotemporal quadrant and its sectoral segmentations and conducted correlation analyses with cognitive and brain volumetric parameters.

Summary of Results

Total RAC was significantly different between CDR groups. On subregion analysis, the proximal mid-periphery (PMP) showed significantly more amyloid in subjects with worse dementia. Patients with lower MOCA scores had increased RAC and area in the PMP, along with decreased total intracranial volume and hippocampal volume (HV). Notably, total RAC and PMP RAC significantly correlated with HV and CDR.

Conclusions

RAI is feasible and detects increased retinal Aβ burden, especially in the PMP, in patients with mild cognitive impairment. PMP retinal Aβ may predict HV, supporting retinal Aβ as a useful biomarker to trace AD progression.

31 Prenatal alcohol exposure and placental insufficiency alter neuronal complexity in rat prefrontal cortex

N Pavlik*

J Newville

S Davies

C Jose

D Savage

J Maxwell

University of New Mexico, Rio Rancho, NM

Purpose of Study

Prenatal alcohol exposure (PAE) produces long-term neurological deficits and is associated with placental insufficiency (PI). Alas, the combined neurological impact of PAE and PI remains unknown. Here, we utilized a three-dimensional (3D) Sholl analysis to compare PAE, PI, and PAE+PI neuronal morphology in the frontal cortex, a critical region for cognition. We hypothesized that PAE+PI would induce a distinct pattern of altered dendritic complexity relative to either insult alone.

Methods Used

Pregnant rats voluntarily drank 5% alcohol or saccharin water until embryonic day 18 (E18) to mimic moderate PAE. On E19, a laparotomy was performed to induce PI via transient uterine artery occlusion. On postnatal day 100, brains from PAE+PI (n=16), PAE (n=12), PI (n=11) and control (n=15) groups, processed with Golgi-Cox, were sectioned coronally. Imaris 3D Sholl analysis was conducted on the apical and basal processes of confocal-imaged neurons in the medial prefrontal cortex (mPFC) and Area 25 of the Cingulate (A25). For statistical comparisons, 2-way ANOVAs and t-tests were used.

Summary of Results

Within the mPFC, PAE and PI groups showed increased basal complexity (PAE: 10–80µm, PI: 10–80µm), whereas PAE+PI showed decreased basal complexity at 100µm, relative to controls. Conversely, the mPFC apical processes of PI show increased complexity (70, 80µm), while PAE and PAE+PI exhibited decreased complexity (PAE: 60–100µm, PAE+PI: 70, 90µm). Within A25, we found that only the apical dendritic complexity of PAE neurons differed from controls, showing increased complexity at 40 and 120µm.

Conclusions

Here, we demonstrate that the pattern of brain injury exhibited by preclinical PAE+PI, characterized by decreased basal and apical dendritic complexity in the mPFC, is distinct from that of PAE or PI alone. Intriguingly, the A25 region of the prefrontal cortex demonstrated reduced vulnerability to PAE, PI, and PAE+PI insult, compared to the mPFC as a whole. These data suggest heightened susceptibility of the apical dendritic arbor to PAE+PI insult.

COVID – infectious diseases I

Concurrent session

9:05 AM

Friday, January 29, 2021
32 Association of coronavirus disease 2019 (COVID-19) and strokes in young and middle-aged adults

S Marquina1*

N Le1

S Narayanan1

K Parang1

L Um1

D Villegas1

B Afghani1,2

1UC Irvine School of Medicine, Irvine, CA

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

Purpose of Study

COVID-19 has been associated with endothelial damage and coagulopathy. Data on characteristics of cerebrovascular disease due to COVID-19 in non-elderly adults is scant. The objective of this study is to investigate the characteristics of young and middle-age adults who presented with strokes as the main manifestation of COVID-19.

Methods Used

A literature review was performed on PubMed and Google Scholar databases using the key terms ‘stroke’, ‘COVID-19’, ‘young adult’, and ‘SARS-CoV-2’. We included studies that described patients under the age of 60 who were admitted for neurological signs or strokes. For studies that included adults of all ages, we describe the characteristics of patients who were younger than 60 years old.

Summary of Results

Of the 23 articles found, 8 satisfied our inclusion criteria. A total of 31 patients younger than 60 years old with stroke as the primary manifestation of COVID-19 were identified. All patients had a positive test for COVID-19, and all had neurological symptoms on admission. The vast majority had a confirmed stroke diagnosis upon admission, and only a few were diagnosed within the first few days of admission. Of 31 patients, 24 (77%) showed mild to moderate respiratory symptoms, and 4 patients presented with neurological symptoms but no other COVID-19 related symptoms. Stroke was defined as cryptogenic or involved the large vessels leading to cerebral infarcts in majority of cases.

Abstract 32 Table 1

Studies of Young and Middle-Aged Adults with COVID-19 and Strokes.

Conclusions

Our literature review suggests that there is an association between strokes as the main manifestation of COVID-19 in young and middle-aged adult patients. Healthcare provider awareness of this association can facilitate early recognition, diagnosis, and prompt treatment.

33 Case control study: d-dimer as a prognostic factor for disease severity in covid-19 infections

Y Eslami*

E Kuhn

T Saylor

College Medical Center Long Beach, Long Beach, CA

Purpose of Study

The Novel coronavirus was named COVID-19 by World Health Organization as it became an epidemic that swept across the world with over thirty million people infected. As biological research advances our understanding of this virus, clinical research has been critical in advancing our clinical management of the disease. It has been shown that covid-19 is associated with a hypercoagulable state and therefore an elevated d-dimer in this setting would be an appropriate response. However, the question remains whether an elevated d-dimer can be used as a marker of disease severity and as a prognostic factor for the patient.

The goal of this study is to assess the relationship between d-dimer and the severity of covid-19 infection. We aim to show that an elevated d-dimer at the time of covid-19 diagnosis is associated with increased severity and poor prognosis.

Methods Used

We retrospectively analyzed the labs of 161 consecutive covid-19 positive patients at College Medical Center in Long Beach, CA from March 1st through September 21st of 2020. All patients who tested positive for COVID-19 were assessed through multiple logistic regression to examine the relationship between an elevated d-dimer level at time of diagnosis and the severity and inpatient mortality.

A list of all patients admitted to our community hospital in Long Beach, CA was created. Each patient was chart reviewed and all patients who tested negative or indeterminate for covid-19 were excluded. Furthermore, all who didn’t have a d-dimer result during that admission were also excluded.

Other exclusion criteria included any patient who was on anti-coagulation therapy prior to admission, pregnant patients, those with active deep vein thrombosis, active pulmonary embolism, active malignancy, or history of genetic hypercoagulable state.

Summary of Results

This is an ongoing study,

Conclusions

This is an ongoing study

34 Epidemiologic characteristics of multisystem inflammatory syndrome in children (MIS-C) with a focus on outcomes

K Ghasemian1*

A Axelson1

A Mommileti1

D Ramesh1

R Syed1

S Wang1

B Afghani1,2

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

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

Purpose of Study

Treatment outcomes of children diagnosed with MIS-C are unclear and warrant investigation. The purpose of this study is to investigate the characteristics of pediatric patients diagnosed with MIS-C and their treatment outcomes with an emphasis on fatalities associated with MIS-C.

Methods Used

A literature review using Google Scholar and Pubmed using keywords such as ‘Multisystem Inflammatory Syndrome in Children’, ‘Pediatric Inflammatory Multisystem Syndrome’, and ‘Coronavirus Disease 2019’ was conducted. We included studies of hospitalized MIS-C patients with a sample size of more than 15.

Summary of Results

Of ten studies published before August 2020, five reported hospitalized MIS-C cases in the United States and five in Europe. A total of 514 hospitalized patients were reported with a sample size of 15 to 186 in various studies. Of 514 patients, 431 (84%) tested positive for SARS-CoV-2 via RT-PCR or serology. In different studies, 50% to 100% of MIS-C patients required PICU admission, 10% to 54% were intubated, and up to 80% required vasopressors. In studies that reported echocardiogram results, coronary artery dilations or aneurysm were noted in up to 93%, and depressed cardiac function was reported in 51–100% of MIS-C patients. Treatment of MIS-C patients included intravenous immunoglobulins (IVIG) 388/514 (75%) plus steroids 288/514 (56%), along with anticoagulants and Anakinra 26/514 (5%). In total, 23 patients were put on ECMO, and of those, 16 (70%) survived. The larger studies reported fatality rate of 2% to 3% in hospitalized MIS-C patients. A total of 10 deaths were reported. Of the fatality causes that were described, 3 were associated with cerebral infarction after ECMO, 2 had not received IVIG, systemic glucocorticoids, or immunomodulators, and another 2 had co-morbidities.

Conclusions

Our review suggests that children with MIS-C who are hospitalized typically have a severe disease course. The outcome in vast majority of patients is favorable but death can occur, most likely as a result of cardiac dysfunction or cerebral infarction. Larger studies are needed to identify clinical features as well as laboratory and diagnostic parameters that predict disease severity and outcome.

35 Impact of covid-19 infection on patients post-discharge

KR Stanek*

S Garimella

M Huey

D Davis

JB Leary

R Becerra

R Lam

University of Colorado, Colorado Springs, CO

Purpose of Study

There is growing literature on the global psychological, social, and economic impact of COVID-19. Psychological outcomes including isolation, anxiety, and depression, are associated with adverse outcomes in patients with other diseases. There is little research examining the impact of infection on hospitalized COVID-19 patients post-discharge. The objectives of this study were to follow patients hospitalized with COVID-19 to evaluate symptom resolution, personal impact, and lasting worries.

Methods Used

Patients were identified following discharge for COVID-19 infection from March-June 2020. Medical students called patients, obtained verbal consent, and administered a questionnaire about the impact of COVID-19 infection. Responses were recorded with direct quotes. Clinical information on treatment and medical history was collected. Thematic analysis was conducted for responses to personal impact and worries. Two investigators coded responses on separate occasions and achieved code consensus.

Summary of Results

Altogether 164 patients were identified. Of those, 66 individuals consented to the interview. Coded data resulted in table 1. The most common theme was isolation, closely followed by reinfection/transmission.

Abstract 35 Table 1

Emergent themes and frequencies

Conclusions

In our population recovering from infection, there was a trend to isolate due to desire to not infect others or be reinfected. We hypothesize that future recovering patients will face similar psychological distress reentering into society. Anticipatory support with education on isolation and safety around reinfection may help reduce the impact of disease on discharged patients continuing recovery.

36 Potential for recurrence of coronavirus 2019 (covid-19) in recovered patients

S Arumalla1*

M Attar1

A Lim1

W Lin1

B Mukkamala1

K Shirish1

B Afghani1,2

1UC Irvine School of Medicine, Irvine, CA

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

Purpose of Study

The objective of this study is to describe the characteristics of patients reported as having reinfection, recurrence or reactivation of COVID-19.

Methods Used

A literature-based review of articles was conducted through databases Google Scholar and PubMed using key words: ‘COVID-19’, ‘SARS-CoV-2’, ‘re-positive’, ‘reinfection’ and ‘recurrence’. Only studies which identified patients with a positive viral RT-PCR during the 1st and 2nd episodes were included in our review.

Summary of Results

We found 9 studies that satisfied our inclusion criteria. A total of 132 patients were identified as having a ‘reinfection’, ‘reactivation’ or ‘re-positive test’. At least one negative RT-PCR test was documented between the 1st and 2nd episode for all patients, except in the study by Batisse et al. All symptomatic patients at the time of 2nd positive test had mild to severe symptoms. 11/13 (84.6%) of the patients with severe symptoms during the 2nd episode were elderly or had comorbidities. The timing of the 2nd positive test by PCR from the 1st ‘clinical cure’ was 4–38 days. In studies that measured antibody response, variance was observed in antibodies detected during the 2nd episode: some had IgG and IgM, some IgG only, and some had undetectable antibodies (Batisse, Loconsole, & Mei studies).

Abstract 36 Table 1

Recurrence of COVID-19 Case Studies

Conclusions

Our review suggests that COVID-19 recurrence can rarely occur. The 2nd episode was more severe in high risk patients, and more likely due to reactivation or lack of recovery from the 1st infection rather than a reinfection. To prevent recurrence, close follow-up needs to be ensured upon discharge. Whether the severity of the 2nd episode is due to immune response, host factors or viral clearance needs to be evaluated in larger studies.

37 An observational study of COVID-19 in a public academic medical center

R Sharma*

A Heidari

L Moosavi

M Miyakee

J Joliff

R Kuran

J Bhandohal

R Johnson

Kern Medical Center, Bakersfield, CA

Purpose of Study

Symptomatic patients presenting to Kern Medical were evaluated for clinical characteristics and severity. The study includes symptomatic patients seen at Kern Medical.

Methods Used

The Institutional Review Board approved as minimal-risk research. Consecutive patients (age ≥ 18 years) with confirmed SARS-CoV-2 infection between March 13 and July 15, 2020 were included. Inmates, pregnant females and persons < 18 years were excluded. Data extracted includes demographics, baseline comorbidities, smoking status, clinical presentation, routine laboratory tests, inflammatory markers, radiographic features, treatment and outcomes.

Summary of Results

420 confirmed cases with SARS-CoV-2, including 312 (74%) ambulatory care and 108 (26%) hospitalized patients were included. Average age (n = 420) was 47 years. 53% were females. Average BMI was 33.5. Ethnicity/race comprised of 83% Hispanics, 14% Caucasian and 5% African American. There were no observed differences between the rate of hospitalization and death based on ethnicities and smoking status. Compared to outpatients, inpatients were older (average age: 54 vs 41 years). Inpatients had more underlying chronic conditions (median = two) compared to outpatients (median=one) (diabetes, cardiovascular disease and chronic respiratory disease). Symptoms and outcomes are displayed in tables 1 and 2.

Abstract 37 Table 1

SYMPTOMS

Abstract 37 Table 2

Inpatient outcomes (n=108)

Conclusions

This study confirmed previous observations that underlying comorbidities are associated with an increased risk of admission and death. Limitations include retrospective design and incomplete data. It appears that compared to the population we serve, Caucasians (37%) and AA (10%) are underrepresented and Hispanics (61%) are substantially overrepresented. The reasons for this are not evident.

38 Mobile health clinics to combat the spread of covid-19 in migrant farmworkers of Skagit County, Washington

PS Fallah*

University of Washington School of Medicine, Seattle, WA

Purpose of Study

In Skagit County, the Hispanic community has been disproportionately affected by the COVID-19 pandemic. One particularly vulnerable group is the essential farmworkers who not only face the disease itself, but many socioeconomic challenges with it. Thus, there is great need for improved outreach to this population.

Methods Used

A strength-based, asset-focused community assessment was performed using personal interviews with staff at Sea Mar, a community health clinic (CHC) serving low-income Latinx patients. Local organizations that offer additional assistance to the community were identified during these interviews. One group that provides COVID-19 related assistance to the Latinx community was interviewed and two meetings attended. Follow-up conversations and a literature search was then conducted.

Summary of Results

In June 2020, it was found that 60% of Skagit County COVID-19 cases were from the Hispanic community, despite their making up just 18.6% of the population. In response, the Latinx COVID Prevention Team (LCPT), a coalition of 20–40 organizations, was formed. The LCPT meets weekly to discuss new challenges faced by the community. They also organize free events for the community and periodically communicate with Sea Mar regarding migrant farm worker (MFW) testing. Sea Mar utilizes their MHC to provide COVID-19 testing and education at farms for Latinx workers using Mixtec and Spanish interpreters. In a literature review of MHCs for MFWs, it was found that MHCs create safe spaces for MFWs that promote trust in the healthcare system.

Conclusions

A strength-based framework centers both the community’s assets and needs, identifying what resources the community has and where to put them. During this pandemic, Skagit County Sea Mar has outfitted their MHC to provide COVID-19 testing and education to MFWs. Two improvements could be made to the current framework: (1) LCPT staff on site could directly offer legal and food assistance to MFWs and (2) MHC staff could share information about LCPT’s free community events with MFWs. This community partnership would further reduce barriers to care, address social determinants of health, and provide awareness of COVID-19 related programs for Skagit County Latinx farmworkers.

39 Effectiveness of convalescent plasma therapy in coronavirus disease 2019 (covid-19) cases

I Okwuosa1*

B Barsoum1

E Flores1

A Kasargod1

D Nassir1

A Pammidimukkala1

B Afghani1,2

1UC Irvine School of Medicine, Irvine, CA

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

Purpose of Study

The purpose of this literature review is to assess the effectiveness of convalescent plasma therapy in patients with critical or severe illness due to COVID-19.

Methods Used

A literature review was conducted through PubMed, Google Scholar, and Sci-Hub databases using keywords: ‘convalescent’, ‘plasma’, ‘COVID-19’, ‘coronavirus’, ‘therapy’, and ‘treatment’. Only studies that evaluated more than 20 patients with a convalescent plasma therapy (CPT) group and a separate control group (no plasma therapy) were included in our literature review.

Summary of Results

A total of 6 studies published before August 7, 2020 matched our inclusion criteria (table 1). Majority of the studies did not show a significant difference in mortality rate between the CPT and control group but a few studies showed some clinical improvement in the CPT group. The studies that evaluated viral load, showed decreased viral load in the CPT group soon after start of therapy. There were variations in the disease duration and dosage of plasma used among the participants. The time of administration of CP from symptom onset varied from 4 to 54 days, with the most significant improvements observed with earlier rather than later administration. The other medication used for the participants were variable, which could possibly confound the certainty of the actual effectiveness of the convalescent plasma therapy on patient outcomes.

Abstract 39 Table 1

Use of convalescent plasma in COVID-19 patients

Conclusions

Our literature review indicates the potential of convalescent plasma as a COVID-19 treatment, especially in severe cases. But further studies are needed to determine the optimal dose, including antibody compositions as well as the timing of its administration in relation to the disease course.

Healthcare research II – learning

Concurrent session

9:05 AM

Friday, January 29, 2021
40 Teaching caregivers to identify respiratory distress using different modes of education

K Houmpheng1*

R Hassler1

P Sosa2

L Fullerton3

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

2Children’s Hospital at Montefiore, Bronx, NY

3University of New Mexico Health Sciences Center, Albuquerque, NM

Purpose of Study

To compare two modes of education in teaching caregivers to identify respiratory distress in children 3 years old and younger.

Methods Used

We enrolled 116 caregivers who brought a patient between the ages of 0–3 years to the University of New Mexico Pediatric emergency department. Exclusion criteria were: caregivers of children who presented with a chief complaint of cough or had a history of a respiratory or congenital heart condition. Prior to the intervention, caregivers were shown 8 video clips of children and asked to state if each child was breathing normally. This was followed by a randomized educational intervention. Caregivers were either shown 1) a video of a physician explaining breathing patterns found in respiratory distress (verbal group) or, 2) a video that showed the same explanations with supplemental visual examples (visual group). We assessed learning through a post-test featuring 8 new clips of children breathing normally or abnormally.

Summary of Results

Pre-intervention, the verbal group scored higher (87.5% correct) than the visual group (78.2% correct) in identifying whether children were breathing normally (p=0.0002). Both the verbal (0.00013) and visual group (0.046) were better at identifying abnormally breathing children than those breathing normally. The total proportions of correct answers for the post-test videos were lower in both groups. The verbal group declined significantly in the post-test video clips (from 87.5% to 79% correct, p=0.0006), but the visual group declined less (78.2% to 75.5% correct, p=0.4), and their performance was comparable to that of the verbal only group (p=0.22). Consistent with the pre-test videos, abnormally breathing children were more easily identified in the post-test videos (verbal group, p=0.037; visual group, p=0.00001).

Conclusions

Our results suggest that mode of education impacts a caregiver’s ability to identify respiratory distress in children. We found that pairing verbal education with video images of abnormally breathing children was associated with improved recognition of abnormally breathing children but not of normally breathing children.

41 Student perspective of team dynamics before and after a disaster response course

E Cha1*

E Madsen1

ET Reibling1

E Richards2

P Savino1

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

2Loma Linda University, Loma Linda, CA

Purpose of Study

We need to understand the COVID-19 pandemic impact on healthcare students. Loma Linda University requires an annual Critical Incident Response Course for graduating students about the importance of interprofessional teamwork in a disaster response. We surveyed students about the pandemic impact on their lives.

Methods Used

This is a mixed methods multidisciplinary cohort study of healthcare students (n=442). The 2020 course consisted of asynchronous content (eight hours) and a synchronous virtual meeting (two hours) focusing on triage, disaster simulation, and interprofessional teamwork. Students completed a pre/post survey on the COVID-19 pandemic response. We report both descriptive statistics and qualitative results from two independent coders.

Summary of Results

Respondents included Medicine (n=149), Nursing Undergraduate (n=169), Nursing Graduate (n=16), Pharmacy (n=45), Dentistry (n=58), Other (n=5). Inter-rater reliability for coded answers exceeded, κ=0.827 (Cohen’s kappa analysis). Students reported observing examples of efficient teamwork (77%) compared to 42% reporting inefficiencies. The most common efficiency was Mutual Support/Collaboration (50%) and the least reported was Team Structure (6%). Most common inefficiency was communication (41%) and the least was adaptability (4%). Students believed their profession will be different after COVID-19 (76%). The most reported anticipated change was Disaster Preparedness/Infection control (59%). Post-coursework survey showed 55% reported a stronger understanding of their profession’s impact on disaster management. Individuals reported changing behavior during the pandemic (84%). The biggest change was in sleep: 15% reported a decrease and 41% reported an increase, followed by connecting with people (21% decrease, 39% increase). The biggest unmet need was Money (27%). The most helpful resources were Friends/Family (89%) and Social Media (43%). 34% volunteered or worked at an essential workplace.

Conclusions

Healthcare students reported that communication, mutual support, and understanding one’s interprofessional contribution are the core of fighting a pandemic. Healthcare students have unique challenges and resource requirements during a pandemic.

42 A quality improvement project impacts resident satisfaction with the depart process

K Upplegger*

M Heubeck

L Lopez

A Subbaswamy

G McCauley

T Ozechowski

A Belmonte

R Craig

A Duran

K Fath

S Lunderman

E Jimenez

University of New Mexico Health Sciences Center, Albuquerque, NM

Purpose of Study

The current depart process resulted in slow work-flow and patient safety and equity concerns. The QI project aimed to improve resident satisfaction with the hospital discharge process.

Methods Used

The QI project was designed using the Model for Improvement. Starting April 2020, Plan-Do-Study-Act cycles included: hiring clinical team coordinators; creating standard depart instructions for diabetic ketoacidosis, pyelonephritis, seizures, croup and dehydration; uploading instructions to Powerchart; and clinician reminders to use instructions with families. Measures examined monthly, included resident satisfaction and patient readmissions.

Summary of Results

Resident satisfaction improved from 4.8 (February 2020) to 7.8 (August 2020) for the overall discharge process; from 5.3 to 7.9 for family education on all key points; from 6.0 to 7.7 for smooth transition of care; from 3.0 to 7.4 for no language barriers; and from 3.0 to 6.7 for no unnecessary delays, on a scale of 0/strongly disagree/terrible to 10/strongly agree/excellent. Readmissions also trended downward.

Abstract 42 Figure 1

Run chart for readmissions of pediatric patients diagnosed with diabetes

Conclusions

During this QI project to address the depart process, resident satisfaction improved and readmissions declined. These results are encouraging, but should be interpreted in the context of decreased patient census due to COVID-19 and non-respiratory season, which may have decreased workload and increased education time and interpreter access. Next steps include PDSAs related to health literacy and Spanish translation.

43 A university collaboration in creating a powered air purifying respirator: an emergency innovative response

SC Wasden*

S Simister

B McRae

S Jayaraman

B Fassl

University of Utah Hospital, Salt Lake City, UT

Purpose of Study

In March of 2020, the World Health Organization declared the coronavirus (COVID-19) a global pandemic. As the number of cases increased worldwide, existing hospital infrastructure struggled to keep up with the demand for equipment and supplies.This exposed healthcare workers to contracting the disease. The purpose of this study is to demonstrate an emergency innovation response in overcoming shortages of personal protective equipment within a university hospital setting, with a special focus on powered air purifying respirators (PAPRs).

Methods Used

The Center for Medical Innovation (CMI)—a center designed to promote research and development of high-impact healthcare products at the University of Utah (UofU)—enlisted university engineers to develop an open source PAPR system made from readily available commercial materials. Parts were selected to meet filtration, airflow, and protection specifications as outlined by industry standards. Commercially available parts consistent with these specifications were assembled into a novel PAPR system which utilized 3D printed pieces on demand to achieve compatibility. Once assembled, each PAPR went through protection testing to demonstrate health worker safety. A fit factor of 200 is the minimum requirement needed as defined by NIOSH. Testing procedures were carried out with industry standard equipment.

Summary of Results

A human centered design approach was utilized in iterating versions of the product based on repeated fit testing. Failures were addressed in subsequent models. All PAPRs passed fit testing with a score of > 1000. Following the lean processing standard of just in time inventory, materials to fabricate 1000 PAPRs were procured and assembled on demand. PAPRs are now being used by the UofU Hospital as well as other affiliate entities globally and are filling the gap needed for PPE. Approximately 200 units have been donated to Navajo Nations hospitals in the state of Utah and others have been donated to university sister entities in India, Nepal, and Kenya.

Conclusions

The Center for Medical Innovation at the University of Utah has facilitated a rapid emergency innovative response in filling the PPE needs locally and abroad by creating this open source accessible PAPR system.

44 Leaders in women’s health: 2020 progress report on advancing women’s health and leadership

JE Maughan1*

CN Bairey Merz1

M Jenkins2

JG Regensteiner3

W Klein4

M Carnes5

M Gulati6

1Cedars Sinai Heart Institute, Los Angeles, CA

2Texas Tech University Health Sciences Center, Lubbock, TX

3University of Colorado School of Medicine, Aurora, CO

4Virginia Commonwealth University, Richmond, VA

5University of Wisconsin-Madison, Madison, WI

6University of Arizona College of Medicine, Phoenix, AZ

Purpose of Study

The Leaders Empowering the Advancement of Diversity in Education, Research and Science (LEADERS) in Women’s Health sought to determine if a focused approach in expanding endowed professorships and chairs in women’s health subspecialties can reduce sex-based inequalities by promoting women’s health and research. Currently, numerous disparities in women’s health exist, notably in treatment of cardiovascular disease, chronic obstructive pulmonary disease and joint replacements.

Methods Used

A survey was distributed to LEADERS members to assess the impact that endowed chairs or professorships have on advancing women’s health through establishment of clinical women’s health programs, research programs, impacted salary, academic achievements, national presentations and grant funding.

Summary of Results

The LEADERS survey was completed by 26 members: 50% endowed chairs, 15% professorships, and 35% women’s health national leadership roles. Administrative leadership, protected research time and national recognition were impacted in part or strongly by holding an endowed chair or professorship (67%, 52%, 80%, respectively). However, an endowed chair or professorship had little to no impact on salary, first authorship, National Institute of Health (NIH) grant funding or being a lead investigator (71%, 76%, 100%, 67%, respectively). Chairs and professorships had little to no impact on establishing a new clinical entity in 62% of respondents but leading a new curriculum in women’s health and research was impacted through endowments in 50%.

Conclusions

Endowed chairs and professorships help advance women’s health through curriculum development. They also advance national recognition and amplify administrative and protected research time. However, salary, NIH funding, first authorship, and establishment of women’s health clinical programs have yet to be impacted. Further work needs to be done to understand how to strengthen the influence of an endowed chair or professorship to further advance women’s health.

45 A global survey of patient and caregiver experiences throughout care for developmental dysplasia of the hip

M Gibbard1*

I Zivkovic1

B Jivraj1

E Schaeffer2,3

JM Robillard3

Knowledge Transition Advisory Board I1

K Mulpuri2,3

1BC Children’s Hospital Research Institute, Vancouver, BC, Canada

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

3University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Diagnosis and treatment for developmental dysplasia of the hip (DDH) varies depending on severity, age at diagnosis, and professional opinion. Little is known about patient experiences globally. We aimed to characterize global patient and caregiver experiences during DDH care and to highlight family priorities.

Methods Used

We collaborated with seven DDH outreach organizations to develop an online cross-sectional survey for DDH patients or their caregivers (>18 years old) globally. Participants were recruited through web media of collaborating organizations over 3 months. Descriptive statistics were used to analyze quantitative results. Qualitative content analysis was used to categorize open-ended responses.

Summary of Results

A total of 739 participants completed the survey, representing 638 (86.3%) caregivers of DDH patients, and 101 (13.7%) patients. 386 (52.2%) patients received diagnosis by 3 months of age; mean age of diagnosis was 15.96 months (90% CI = 12.04,19.91). Out of 211 patients with DDH family history, 68 (32.3%) did not receive DDH screening. Out of 187 patients born breech, 82 (43.9%) did not receive DDH screening. In total, 36/94 (38.3%) patients with both family history and breech birth did not receive DDH screening. Most (696/730, 95.3%) participants reported treatment with brace, surgery, and/or closed reduction. In total, 144 participants reported more than one surgery; 82 reported three or more surgeries. Participants reported a range of 1–400 visits to health care professionals for DDH care across 1–66 years. Lack of information on treatment practicalities and timelines, along with emotional burden of diagnosis, were greatest challenges reported.

Conclusions

Results show that DDH care can pose significant burden on patients and caregivers. Reliable public information is needed to support those affected. Global educational efforts are needed to raise awareness of DDH risk factors, signs and symptoms among care providers to improve identification, screening, and monitoring of at-risk children.

46 Impact of laboratory test cost and blood volume education on resident test ordering habits

N Banyi*

J Simons

University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Campaigns such as Choosing Wisely® Canada have recently brought into consideration that a significant proportion of inpatient laboratory testing is unwarranted, lowering the quality of care and increasing healthcare expenditures. Prior studies have shown reductions in non-specific test ordering through interventions that are labour intensive, costly, and conducted with notable reviews and audits. This study investigates how educational interventions on test costs and blood volumes (BV) impact internal medicine (IM) resident ordering habits independently of other management activities.

Methods Used

Two independent four-week IM resident blocks were studied. After two weeks, cost and BV information for the 32 most commonly ordered tests were distributed through physical and digital pamphlets to residents during a 10-minute intervention. Resident surveys measuring importance, influence, and knowledge of the intervention information were conducted prior to the interventions and following the resident block. All tests ordered by the residents within the block were analyzed. The number of tests and blood collections ordered each day, normalized to patient volumes, were analyzed using an interrupted time series analysis.

Summary of Results

There was no significant change in either the level (p=0.23) or the trend (p=0.17) of daily physician ordering rates between the pre- and post-intervention periods. An insignificant change was also observed for the level (p=0.83) and trend (p=0.81) of blood collection rates. Further, there was no observable difference in physician ordering rates between tests for which information was provided and tests for which information was not provided. Despite this, 74% (N=34) and 63% (N=29) of pre-intervention responses predicted that cost and BV information respectively would impact their ordering, while all post-intervention responses (N=46) stated that it had. Residents were unaware of the intervention information beforehand.

Conclusions

A disparity between IM resident test ordering habits and their perceived impact of the intervention was observed. Education on cost and BV alone was not effective in changing resident test ordering habits. Effective methods for influencing resident ordering seem to require a reiterative emphasis on the importance of conscientious test ordering and additional systems to audit residents.

47 Audit of medication reconciliation forms

G Peck*

K Afshar

D Courtemanche

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

Purpose of Study

Medication Reconciliation (MedRec) is an important safeguard against medication errors and should be completed within 24 hours of admission to avoid delays in patient care. It involves reviewing outpatient medication history upon inpatient admission to ensure medication information is accurate and up to date. Verifiers (physicians, pharmacists, and nurses) conduct a Best Possible Medication History (BPMH) cross-referenced with a MedRec form generated by PharmaNet (province-wide database of all prescriptions dispensed from pharmacies in BC, Canada). If the Verifier is a pharmacist or a nurse, the MedRec form requires additional review by a Prescriber (physician). This study assesses barriers preventing MedRec form adherence by quantifying the data entered by Verifiers and Prescribers and evaluating the timeliness of the form’s completion.

Methods Used

Patient charts for those admitted to one ward at BC Children’s Hospital (BCCH) between 6 January - 9 March 2020 were reviewed. Fourteen fields were evaluated: Weight, Allergies, Verification (of medicines), Prescriber’s Orders (home medicines, and new orders), five Verifier Identification items (Printed Name, Date, Time, Signature, Designation) and five Prescriber Identification items (Printed Name, Date, Time, Signature, and College ID#). Time of completion was calculated from admission to Prescriber Time.

Summary of Results

124 patient charts were reviewed and 84 MedRec forms were included in the analysis; 40 were excluded as 19 did not have a MedRec form and 21 were repeat reviews of the same admission. There were low rates of completion in the following categories: Weight (42%), Allergies (31%), Verifier Date (38%), Verifier Time (25%), and Prescriber Time (45%). In terms of timeliness, 29 forms were at least partially completed in 24 hours; however, only three forms were fully complete and reviewed by a Prescriber within 24 hours. There were no complete forms reviewed by both a Verifier and Prescriber.

Conclusions

Verifiers and Prescribers have a low rate of completion in terms of information logging, as well as completing the form within 24 hours. More investigation is required on several fronts: why some variables are unrecorded; identifying obstacles deterring the timely completion of the form; and the possible relationship between the low rate of MedRec form completion and patient care/outcomes.

Morphogenesis and malformations

Concurrent session

9:05 AM

Friday, January 29, 2021
48 Schizencephaly in collagen type iv vasculopathies: the vascular hypothesis and implications for management

M Penon Portmann*

J Chang

J Shieh

UCSF, San Francisco, CA

Purpose of Study

Schizencephaly involves a cleft in the brain extending from the ependyma to the pial surface. Although schizencephaly can arise from malformation syndromes (SHH, ATP1A3), increasing evidence suggests it may also arise from disruptive vascular events. Maternal Vit K deficiency and twinning are possible etiologies for vascular disruption, but heritable bleeding conditions may be the most important to identify.

Methods Used

To examine the phenotypic spectrum of COL4A1/2 and its role in schizencephaly, we analyzed all pre/postnatal cases reported to date and addressed several gaps in knowledge: 1) Are there subtle COL4A1/2 phenotypes suggesting patients are being missed, 2) What are possible environmental triggers for intracranial hemorrhage, 3) Which medications may be associated with bleeding episodes? Here present 220 cases involving COL4A1/2 from the literature.

Summary of Results

We found that 90% of cases involve COL4A1 and 10% COL4A2. 78% of the COL4A1/2 cases involved the CNS (e.g. schizencephaly, hemorrhage), 47% the eye (anterior chamber anomaly, keratoconus), and 15% the kidneys. Only 21% of cases were identified prenatally and the majority as children or adults. Here we identified 113 unique pathogenic variants; while only 20% of the variants were cataloged in ClinVar. Importantly, missense mutations affecting glycine residues of the Gly-X-Y triple helix occurred 82% of the time. Some individuals may present symptoms in only one organ system (e.g. ophthalmologic, renal), but complete organ system evaluation should be considered. We aggregated all data on reported triggers for brain hemorrhage and concurrent medications in verified COL4A1/2 cases. We found 16 cases with reported medication use. Aspirin and warfarin were reported in those with and without hemorrhage. 14 cases described possible triggers ranging from vigorous exercise to sports.

Conclusions

COL4A1/2 conditions are diverse and potentially under-recognized. Since patients may be at risk for complications, early recognition and management is recommended. Further studies regarding natural history are needed for optimal medical recommendations.

49 Investigation of ITGAM on fracture development and vertebral morphology in zebrafish

T Loose1*

CJ Watson2

RY Kwon2

Y Hsu3

1University of Washington School of Medicine, Laramie, WY

2University of Washington School of Medicine, Seattle, WA

3Harvard Medical School, Boston, MA

Purpose of Study

Recently the gene ITGAM was identified in a human GWAS as a frequently mutated gene in human patients with increased fracture rates. Our study aimed to investigate the role of itgam in a zebrafish model to better understand the morphologic changes this gene may contribute to as it relates to fractures and vertebral bone morphology.

Methods Used

The itgam mutants were created via CRISPR/Cas9, had a 7 base pair deletion in exon 7 of the zebrafish itgam gene, and were bred to homozygosity. 13 homozygous (itgam-/-) and 9 wildtype control (itgam+/+) zebrafish clutchmates were compared. Genotyping of each fish was preformed using tissue from caudal fin clips and each adult subject was scanned with microCT imaging at 136 days of age. Images were analyzed for qualitative effects such as observable fractures with Fiji ImageJ. Quantitative analysis of bone morphology was preformed using FishCuT software and a custom R script to assess for patterns of difference in vertebral morphology (bone mineral density, volume, and thickness) at three different locations on each vertebra (centrum, haemal arch/ribs, and neural arch). Both analyses were preformed blinded to genotype.

Summary of Results

A nearly 2-fold increase in fracture prevalence was found in itgam-/- fish (0.846 fx/subject) as compared to controls (0.444 fx/subject). Quantitative FishCuT analysis demonstrated that centrum total mineral density was significantly changed in the itgam-/- group as compared to controls (p=0.022). In a secondary analysis, itgam+/+ fish were allometrically scaled to itgam-/- fish to control for variation in bone development between groups. Following allometric scaling, there was no statistically significant change in any bone morphology measure between groups, although a trend of decreased mineral density was seen in all vertebral locations in itgam-/- fish.

Conclusions

Our preliminary research of ITGAM, a novel gene associated with fractures in humans, reveals an increased prevalence of fractures in a zebrafish model without demonstrating specific morphologic changes within the vertebral column.

50 Characterization of patterned limb development: regulation of the FGF-SHH reciprocal loop

J Amoah*

Loma Linda University, Loma Linda, CA

Purpose of Study

Fibroblast growth factors (FGFs) secreted from the apical ectodermal ridge (AER) coordinate proximal-distal patterning, while sonic hedgehog (SHH) from the zone of polarizing activity (ZPA) directs anterior-posterior growth of the limb. These signaling centers maintain each other’s expression in a reciprocal feedback loop; however, the molecular intermediates involved are only partially characterized. LIM homeobox 2 (LHX2) has been identified as an intermediate regulator downstream of FGF in the reciprocal loop. We have identified a cis-regulatory module (CRM) located upstream of the LHX2 promoter that is active in the sub-AER LHX2 expression domain. In silico analysis of this LHX2-associated sub-AER regulatory module 1 (LASARM1) revealed several putative E26 transformation-specific (ETS) binding sites. We identified three ETS binding sites within LASARM1 and hypothesized that mutation of one or more of these sites would disrupt FGF-mediated enhancer activity.

Methods Used

To determine whether the ETS transcription factor binding sites contribute to LASARM1 activity, we performed site-directed mutagenesis on the ETS sites within a LASARM1-reporter construct. We then used targeted regional electroporation (TREP) to transfect chicken limb buds and evaluate modified LASARM1 constructs. After 24 hours of incubation, LASARM1 activity was determined by fluorescence microscopy.

Summary of Results

Mutation of all three sites ablated LASRAM1 activity in the distal mesoderm of Hamburger-Hamilton stage 24 chicken limb buds.

Conclusions

Our findings suggest that FGF signaling utilizes ETS transcription factors to regulate LHX2 expression through the LASARM1 enhancer.

51 Recessive arthrogryposis and progressive leukodystrophy: linking neonatal and adult phenotypes of GBE1

J Chenbhanich*

J Shieh

University of San Francisco, San Francisco, CA

Case Report

Arthrogryposis conditions are diverse and sometimes distinctive. Central nervous system involvement is seen in up to 25 percent of patients. Biallelic variants in GBE1 gene, affecting the glycogen branching enzyme, cause a severe neonatal arthrogryposis, glycogen storage disease (GSD-IV) with infantile-onset progressive liver cirrhosis, or adult polyglucosan body disease (APBD), an adult-onset neurodegenerative disorder with leukodystrophy. Herein, we report a novel combination of GBE1-pediatric and adult phenotypes.

We evaluated a 26-year-old man with Klippel-Feil anomaly and arthrogryposis affecting his upper extremities since birth. Contractures of bilateral shoulders, elbows, and fingers were noted on exam. He completed school without difficulty. Two years prior to presentation, he was hospitalized for acute psychosis. His behavior continued to be complicated by episodes of disorganized thought, hallucinations, social withdrawal, and food aversion. Dilated eye exam and laboratory tests including liver function tests were unrevealing. Electrodiagnostic studies demonstrated a sacral radiculopathy. Brain MRI showed diffuse supratentorial and infratentorial leukodystrophy, sparing U-fibers. Exome sequencing identified compound heterozygous variants in GBE1: a likely-pathogenic c.1597G>A (p.E533K) variant and a pathogenic c.691+2T>C canonical splice site variant. We also reviewed the literature on GBE1 but we were only able to identify one other pediatric case with arthrogryposis involving the upper limbs, similar to our patient.

We highlight here the phenotypic continuum of GBE1-related disorders. The musculoskeletal subtype of GSD-IV has been reported in neonates with fetal akinesia and arthrogryposis multiple congenita with perinatal lethality. Abnormal muscle biopsies showing polyglucosan bodies in musculoskeletal GSD-IV, as well as the presence of leukodystrophy in APBD, suggests myogenic and/or neurogenic etiologies underlying the development of arthrogryposis. Further enzyme activity in fibroblasts and testing in family members is recommended, and the risk for white matter disease/leukodystrophy is important to consider in individuals who are tested. We propose that GBE1-related conditions should be considered in patients presenting with arthrogryposis.

52 A novel pancreatic phenotype in a child with WDR19-related ciliopathy

MN Keyser1*

LM Bird2

J Beauchamp2

M Huang2

1University of California San Diego, San Diego, CA

2University of California San Diego, La Jolla, CA

Case Report

Ciliopathies are a group of genetic disorders caused by ciliary dysfunction. WDR19 is one member of the nephronophthisis (NPHP)-related ciliopathy gene family. WDR19 mutations manifest various phenotypes that involve the kidneys, liver, retina, and ectodermal structures. We describe a 5-year-old female with a complex phenotype that does not fit into the previously described WDR19-related ciliopathies.

A 5-year-old female was born at 39 weeks gestation following an uncomplicated pregnancy. She presented at 10 days old with respiratory distress, weight loss, metabolic acidosis, elevated transaminases and creatinine. She progressed to end stage renal disease (ESRD) requiring peritoneal dialysis (PD) by age 1. She had hypotonia, developmental delay, feeding intolerance, wheezing, short-limbed short stature and small thorax. Skeletal survey demonstrated a short rib thoracic dysplasia. Despite bilateral chest wall reconstruction, she was ventilator-dependent by age 3 due to mixed restrictive and obstructive lung disease. She had recurrent pancreatitis complicated by pseudocysts requiring surgical drainage and drain placement. Liver and pancreas biopsies showed intrahepatic bile duct dilation with portal fibrosis, small pancreatic mesenteric cysts with focal cystic duct dilatation and strictures. Whole exome sequencing (GeneDx) showed 2 likely pathogenic WDR19 variants in trans (maternally-inherited: c.742G>A, p.G248S; paternally-inherited: c.617T>C, p.L206P). She is awaiting kidney, liver and pancreas transplantation.

This patient with WDR19 mutations displays many features consistent with NPHP-related ciliopathies including renal disease, hepatic fibrosis and skeletal dysplasia. However, her phenotype does not fit neatly into the WDR19-related syndromes. Particularly her severe pancreatic involvement has not been previously described. Although her pancreatitis was initially thought related to PD, the ongoing and severe pancreatic disease with pseudocysts suggests her underlying disorder is causative. This patient illustrates one of the many phenotypes resulting from WDR19-related ciliopathy, and adds pancreatitis to the spectrum of problems that can be seen.

53 5th digit nail hypoplasia in trisomy 9p

A Renck*

D Stevenson

M Manning

Stanford University School of Medicine, Stanford, CA

Purpose of Study

Fifth digit nail hypoplasia is a feature that is thought to be pathognomonic for Coffin-Siris syndrome. Multiple single gene mutations associated with Coffin-Siris syndrome affect subunits of the ATP-dependent chromatin remodeling complex BAF, which is crucial for the regulation of gene expression. We present a case of 5th digit nail hypoplasia in trisomy 9p and hypothesize that genes on 9p influence digit development, and that trisomy 9p should be included in the differential diagnosis for patients with 5th digit nail hypoplasia.

Methods Used

Chart review, physical exam, and literature review.

Summary of Results

We describe a 4 day old girl with hypotonia, dysphagia, pulmonary hypertension, ASD, bicuspid aortic valve, transverse arch hypoplasia, and microgyri. Exam demonstrated hypertelorism with telecanthus and prominent nasal root. Extremity exam was notable for bilateral 5th distal phalanx hypoplasia with significant 5th fingernail hypoplasia. She also had nail hypoplasia of index fingers and of all toes, most prominently noted on the 5th toes. Postnatal karyotype showed an abnormal female karyotype with a derivative of chromosome 18 resulting from an unbalanced translocation of chromosome 9p13 distal segment onto 18p11.2. This resulted in a terminal deletion at 18p11.2 (18p deletion) and terminal gain at 9p13 (trisomy 9p). A microarray was obtained to delineated breakpoints and demonstrated copy number gain from 9p24.3 to 9p11.2, and copy number loss from 18p11.32 to 18p11.21.

Conclusions

Although 5th fingernail hypoplasia is thought as pathognomonic for Coffin-Siris syndrome, we have demonstrated that this feature can also be found in other conditions. Others report nail hypoplasia and digit anomalies in trisomy 9p, and we predict that the nail hypoplasia in our patient is due to trisomy 9p. There are currently no reported genes associated with Coffin-Siris syndrome located on chromosome 9p. However, given that there is some clinical overlap between trisomy 9p and Coffin-Siris syndrome, it is possible that there are genes on 9p that impact the BAF complex. Trisomy 9p should be included in the differential diagnosis of individuals with 5th fingernail hypoplasia.

54 A case of non-finnish mulibrey nanism

ED Novatcheva1*

MN Lau1

K Tygart1

M Wright2

N Shareef2

LM Bird1,3

1University of California San Diego, La Jolla, CA

2Rady Children’s Institute for Genomic Medicine, San Diego, CA

3Rady Children’s Hospital, San Diego, CA

Purpose of Study

Mulibrey nanism (MN) is a rare autosomal recessive syndrome affecting the muscle, liver, brain, and eye. Of 150 worldwide reports, 110 describe Finnish MN. Non-Finnish MN (nFMN), which has been noted to consistently present with cardiac involvement, is exceedingly rare. Herein, we report a case of a 3-year-old Afghan boy fulfilling clinical criteria for Russell-Silver syndrome who presented with anasarca. He was found to have refractory hypoalbuminemia, hepatomegaly, constrictive pericarditis, hypogammaglobulinemia, and T-cell lymphopenia. Extensive workup did not yield a satisfactory explanation for his problems, and parental fourth-degree consanguinity raised concern for a hereditary disorder. The patient’s 4 siblings were healthy, and there was no family history of growth delay.

Methods Used

Rapid whole genome sequencing (rWGS) was performed, and variants were identified with the Illumina DRAGEN Bio-IT Platform. Gene burden was overlapped with the patient’s phenotype. Structural variants were filtered for coding regions of known disease-associated genes and with allele frequencies <2% in an internal database. Comprehensive review of published literature on MN was completed.

Summary of Results

A ~45kb homozygous deletion located at 17q22 and encompassing exons 3–16 of the TRIM37 gene was identified. Deletions involving TRIM37, which encodes peroxisomal Ubiquitin E3 ligase, are an established cause of MN. To our knowledge, this variant has not been previously reported or functionally characterized in literature.

Conclusions

A novel variant in TRIM37 was identified by rWGS in a nFMN patient formerly carrying a diagnosis of Russell-Silver syndrome. While many of the patient’s symptoms, such as failure to thrive, ascites, hepatomegaly, constrictive pericarditis, and hypogammaglobulinemia, have been previously associated with MN, hypoalbuminemia and T-cell lymphopenia have not. This case expands the phenotype of nFMN and highlights the importance of rWGS in securing a diagnosis in the setting of an atypical presentation of a rare disorder.

55 The role of the SOX11 transcription factor in regulating growth differentiation factor-5 during joint formation

NA Sandoval*

R Damoah

A Cooper

C Pira

K Oberg

Loma Linda University, Loma Linda, CA

Purpose of Study

Growth differentiation factor 5 (GDF5) has been associated with the formation and maintenance of joints. Disruption of GDF5 expression has also been linked to accelerated osteoarthritis. We have identified a GDF5 Associated Regulatory Region (GARR) that contains several Sox binding sites. The SOX11 transcription factor has been shown to upregulate GDF5 and we hypothesized that SOX11 is necessary for GARR mediated expression of GDF5 during in joint development and maintenance.

Methods Used

To test this hypothesis, we compared the expression of SOX11 and GDF5 in chicken limbs during development using in situ hybridization. We also generated a GARR reporter construct and mutated the Sox binding sites. The native and mutated GARR reporter was transfected into developing chick wings. We also co-transfected a SOX11 expression vector with GARR in ectopic, but joint-related sites.

Summary of Results

Our results showed that in chicken, SOX11 expression overlaps GDF5 expression in joint spaces (elbow and fingers) at Hamburger-Hamilton stages (HH) 25–27. The SOX11 expression primarily surrounded that of GDF5. At HH 29–35, the expression of SOX11 and GDF5 colocalized in joint spaces. However, the expression of SOX11 was not confined to joints but also colocalized with MyoD, a muscles (MyoD expression) marker, and tendons (as well as TNMD expression). Disruption of the Sox binding sites greatly reduced GARR activity within joint spaces. Co-transfection of GARR and a SOX11 expression vector demonstrated increased GARR activity.

Conclusions

We conclude that GARR is active within joint spaces, and the colocalization of SOX11 and GDF5 in joints supports the hypothesis that SOX11 may play a role in the regulation of GDF5 through GARR. Additionally, it may be a competency factor for the formation and organization of joint-related tissues like muscles or tendons. Our data further suggests that SOX11 is required for GARR activity and ectopic expression can enhance its activity. Further experiments are needed to clarify the role of SOX11 in regulating joints and joint associated tissues.

Neonatology general I

Concurrent session

9:05 AM

Friday, January 29, 2021
56 Do bilirubin/albumin (B/A) ratios correlate with unbound bilirubin levels in preterm infants?

S Abe1*

K Fujioka1

RJ Wong2

K Iijima1

1Kobe University Graduate School of Medicine, Kobe, Japan

2Stanford University School of Medicine, Stanford, CA

Purpose of Study

A strong correlation between the bilirubin/albumin (B/A) ratio and unbound bilirubin (UB) levels in newborns ≥ 35 wks’ of gestation has been reported previously. However, in preterm infants, the usefulness of B/A ratios is unclear.

Methods Used

We obtained serum samples from 381 newborns < 35 wks’ of gestation, who were admitted to Kobe University Hospital from 2014 to 2018. UB levels were measured using the glucose oxidase-peroxidase method. Total serum/plasma bilirubin (TB) and albumin (Alb) concentrations were measured spectrophotometrically. We stratified the samples into two groups based upon phototherapy use. B/A ratios were calculated and correlated with UB levels. The samples from infants not treated with phototherapy were then stratified by gestational age (GA) epochs: 22–27, 28–29, 30–31, and 32–34 wks of gestation, and B/A ratios correlated with UB levels.

Summary of Results

B/A ratios significantly correlated with UB levels in samples from infants who never received phototherapy (n = 1,250; y = 1.83x - 0.15, r2= 0.93), when compared with samples from those who received phototherapy (n = 2,039; y = 1.05x + 0.09, r2= 0.69). When stratified by GA, the correlation remained.

Abstract 56 Figure 1

Correlation of the B/A ratio and serum UB levels in (a) non-irradiated, and (b) irradiated samples

Conclusions

Even in preterm infants < 35 wks of gestation, B/A ratios strongly correlated with UB levels. Therefore, we conclude that B/A ratios can be used as an index of UB levels with high sensitivity and specificity in infants who never received phototherapy.

57 Increasing incidence of asthma in children with prenatal opioid exposure

I Cervantes1*

S Shrestha2

S Ruyak1

J Maxwell1

1University of New Mexico, Rio Rancho, NM

2Tufts University, Boston, MA

Purpose of Study

Opioid use disorder (OUD) in pregnancy is an acknowledged public health crisis. An estimated 1 in 3 women of reproductive age filled an opioid prescription every year from 2008 to 2012 in the United States. Furthermore, the number of women admitted for labor and delivery with OUD quadrupled from 1999 to 2014. The impact on long-term outcomes for those exposed continues to be investigated. Given the proinflammatory state that results from Prenatal Opioid Exposure (POE), we hypothesized that infants with POE or Neonatal Opioid Withdrawal Syndrome (NOWS) diagnoses during the newborn hospitalization would have an altered immune reactivity that persisted into childhood, defined by asthma diagnosis by 8 years of age.

Methods Used

A retrospective cohort design utilizing a comprehensive CERNER HealthFacts® U.S. national database was completed. ICD-9-CM and ICD-10-CM diagnosis codes identified infants born at term with known POE or NOWS and were compared to control infants with only normal newborn codes. This cohort was followed out to 8 years of age with ICD-9-CM and ICD-10-CM diagnosis codes for asthma queried to determine the incidence of asthma. Descriptive statistics of frequencies and percentages were calculated for all variables and a Chi-Square test was conducted to examine the relation between asthma diagnosis and POE/NOWS.

Summary of Results

A total of 3,021 records were included in the analysis. Briefly, 47% of the infants were female and 50% of the infants were male; the remaining 3% was not specified. Roughly 42% of infants were on Medicaid and the vast majority of the participants (92.5%) were located in an urban community, with only 7.5% of the participants being located in a rural community. The odds of an infant developing asthma were two times higher for the group exposed to opioids prenatally (OR 2.0, 95% CI: 1.45–2.77) and this was statistically significant (p < 0.0001).

Conclusions

These emerging results suggest infants with POE may have altered immune reactivity that not only impacts the newborn period but persists into childhood. Additional investigations are needed to further characterize the impact POE has on the developing immune system so that potential follow up strategies and interventions can be established.

58 Persistent bacterial vaginosis and risk for spontaneous preterm birth

YJ Blumenfeld*

I Maric

DK Stevenson

GM Shaw

Stanford University School of Medicine, Stanford, CA

Purpose of Study

An association between first trimester bacterial vaginosis (BV) and spontaneous preterm birth (sPTB) has been previously described. While up to 25% of BV cases are persistent, there is a paucity of data on the association between persistent BV and risk of sPTB. Our aim was to analyze the association between persistent BV and sPTB.

Methods Used

A large commercial claims database, IBM MarketScan, was analyzed. A cohort of women with a singleton gestation was identified using International Classification of Diseases (ICD-9/10) codes and linked with outpatient medications data. Diagnosis of BV was based on the presence of BV ICD-9/10 codes and a prescription for Metronidazole or Clindamycin. Persistent BV was defined as BV requiring a prescription in both the first and second trimester, or BV requiring more than one prescription. sPTB was defined as PTB occurring after preterm premature rupture of membranes or preterm labor using ICD codes. Odds ratios (ORs) were used to estimate associations between BV and sPTB.

Summary of Results

Among 2,538,606 pregnant women, 63,817 had an episode of BV. sPTB in women without BV was 5.7%, and 7.5% in those with BV (OR 1.33 (95% CI 1.29, 1.37)). Women with BV in both the first and second trimester had a slightly higher risk for sPTB (OR 1.66 (95% CI 1.52, 1.81)) than those treated in either the first (OR 1.42 (95% CI 1.36, 1.48)) or second trimester (OR 1.47 (95% CI 1.41, 1.53)) alone. Women with two prescriptions had (OR 1.35 (95% CI 1.26, 1.44)) similar risks for sPTB as those with only one prescription (OR 1.30 (95% CI 1.26, 1.35)). The risk was highest among those treated with 3 or more prescriptions during the course of the pregnancy (OR 1.48 (95% CI 1.35, 1.63)).

Conclusions

BV in pregnancy is associated with an increased risk for sPTB. Women with persistent BV in both the first and second trimester, or those requiring 3 or more prescriptions had at least a 50% higher risk for sPTB than those without BV in pregnancy.

59 Evaluating variations in neonatal intensive care: longitudinal, population-based trends in clinical management and care of newborns in California

EM Pang1*

J Liu1,2

T Lu1,2

H Lee1,2

1Stanford University School of Medicine, Palo Alto, CA

2California Perinatal Quality Care Collaborative, Palo Alto, CA

Purpose of Study

Identifying hospital and patient populations that are susceptible to variations in newborn management can inform potential overuse in neonatal intensive care unit (NICU) services and guide health equity measures. Recent investigations have suggested that there may be growing numbers and variation of NICU admissions nationwide, with an increasing number of neonates of higher gestational age, greater birth weight, and lower illness acuity receiving resource-intensive care. Given concerns of inefficient resource utilization, we aimed to elucidate whether these longitudinal trends in neonatal management were reflected in California.

Methods Used

We evaluated NICU utilization in California from 2008–2018, comparing statewide data on live births and NICU admissions across gestational age and birth weight categories. We analyzed birth certificate data from the California Children’s Services (CCS) and hospital- and admission-level data from the California Perinatal Quality Care Collaborative (CPQCC), which capture >95% of all births and NICU admissions in California. Trends in live births and inborn admissions were analyzed with linear regression models over the study period.

Summary of Results

Between the two linked datasets, we identified 474,750 inborn admissions and 3,972,494 live births, representing a 12% NICU admission rate across 146 hospitals. Among these admissions, 112,207 infants were born with high acuity medical needs, at very low birth weight, and/or at very premature gestational age. Yearly trends in live births and inborn admissions were not statistically significant (p=0.145 and p=0.359). However, admission of neonates with birth weight ≥ 2500g varied when stratified by perinatal region (n=11), with different regions experiencing significantly increasing or decreasing rates of inborn NICU admissions over time (p<0.001).

Conclusions

Nationwide trends of increasing NICU admissions are not reflected overall in California, with NICU admissions remaining constant over the past decade. A closer examination suggests that variations in care may be masked by broad-level analysis; further research is needed to reveal how these trends may differ across hospital- and infant-level characteristics.

60 Accuracy of transcutaneous CO2 monitoring in newborns undergoing therapeutic hypothermia

P Garlapati1*

R Phan2

S Lakshminrusimha1

P Vali1

1University of California Davis, Rancho Cordova, CA

2University of California Davis, Davis, CA

Purpose of Study

Therapeutic hypothermia (TH) at 33.5oC is standard of care in infants with hypoxic ischemic encephalopathy (HIE). Carbon dioxide (CO2) has a strong effect on cerebral blood flow and temperature corrected PaCO2 < 35 mm Hg has been shown to lead to adverse neurological outcomes. Transcutaneous Carbon dioxide (TCO2) monitor is a reliable non-invasive tool to measure continous CO2. We aim to study the accuracy of TCO2 in newborns undergoing TH.

Methods Used

Retrospective chart review of 10 neonates undergoing TH for HIE on respiratory support. Partial tension of arterial CO2 (PaCO2) was compared to simultaneously measured TCO2.

Summary of Results

Ninety-one PaCO2 and TCO2 pairs were available for analysis. Temperature corrected (Tc) and non-corrected (Tnc) PaCO2 concentrations were compared to TCO2. Tc PaCO2 had a strong positive correlation with TCO2 (r= 0.8, p<0.05;), but with a poor mean difference (95% agreement) of 8.8 (figure 1). Tnc PaCO2 compared to TCO2 showed a better mean difference (95% agreement) of 3.5(figure 2) with a similar r of 0.8, p<0.05.

Abstract 60 Figure 1

Tc PaCO2 had a strong positive correlation with TCO2 (r = 0.8, p<0.05;), but with a poor mean difference (95% agreement) of 8.8

Abstract 60 Figure 2

Tnc PaCO2 compared to TCO2 showed a better mean difference (95% agreement) of 3.5 with a similar r of 0.8, p<0.05

Conclusions

Targeting corrected PaCO2 during TH results in cerebral hyperemia and homogenous brain cooling. Transcutaneous CO2 monitoring correlates better with uncorrected PaCO2 possibly due to sensor skin warming. Incorporating a mathematical correction model to adjust TCO2 to corrected PaCO2 will increase cerebral blood flow and potentially improve outcomes.

61 Severe small-for-gestational-age infants are exposed to increased oxidative stress condition

M Ashina*

K Fujioka

K Iijima

Kobe University Graduate School of Medicine, Kobe, Japan

Purpose of Study

The purpose of this study was to clarify the oxidative stress levels at birth in severe SGA (birthweight less than –2 standard deviations (SD) for gestational age) and AGA infants.

Methods Used

This study was conducted under the approval of the ethical committee of the Kobe University Graduate School of Medicine (approval number, 180083). The serum samples of 16 severe SGA and 17 AGA infants, who was born in our hospital during March 2017 to December 2018, were used in this study with parental consent. Oxidative stress (d-ROM; derivative of reactive oxidative metabolites) and anti-oxidant potential (BAP; biological anti-oxidant potential) were measured by using FREE Carrio Duo (WISMERLL), and then compared between the groups. Next, we defined ‘increased oxidative stress condition’ when the d-ROM exceeded the average value + 2SD for full-term AGA infants (= 109.2 U.CARR), and compared the frequency. Data are expressedas the median (range) or mean ± SD. The Student’s t-test and Chi-square test were used to compare the data of severe SGA and AGA. Differences were deemed statistically significant for p < 0.05.

Summary of Results

There was no significant difference in gestational age, rate of preterm infants, birth weight, Apgar score and umbilical artery blood pH between severe SGA and AGA infants, except significant lower birth weight SD (p <0.0001) and higher lactate level (p =0.02) in SGA children. To elucidate the effect of preterm birth, we have compared preterm and term AGA infants (n=9 and 8, respectively), and found that no significant difference in d-ROM (preterm; 50.9 ± 54.9, vs. term; 78.5 ± 11.7 U.CARR) and BAP (2323.1± 267.0, vs. 2479.0 ± 152.1 uM) between the groups. Despite no significant difference found in BAP (SGA; 2602±479, vs. AGA; 2397±229 uM), severe SGA infants showed significantly higher d-ROM levels (110.7±75.2, vs. 63.9±42.0 U.CARR, p=0.03). The incidence of increased oxidative stress condition was significantly higher in severe SGA infants than in AGA infants (8/16 (50%) vs. 1/17 (6%), p=0.004).

Conclusions

While the effect of gestational age on oxidative stress is not significant, SGA infants were exposed to increased oxidative stress condition at birth.

62 Incidence of hypospadias in severe small-for-gestational-age Asian infants: a multicanter populayion study

M Ashina1

K Fujioka1

S Yoshimoto2

T Ioroi3

K Iijima1

1Kobe University Graduate School of Medicine, Kobe, Japan

2Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

3Japanese Red Cross Society Himeji Hospital, Himeji, Japan

Purpose of Study

To characterize the incidence of hypospadias in severe SGA [birthweight (BW) < –2 standard deviations (SD) of appropriate-for-gestational-age (AGA)] infants.

Methods Used

This retrospective study was conducted under the approval of the ethics committee of the Kobe University Graduate School of Medicine (#170127). Records were reviewed for 592 SGA male infants who were admitted to one of 3 tertiary perinatal centers in Japan from 2008 to 2017. Infants with chromosomal anomalies (n=61) were excluded. Clinical data, such as GAs, BWs, BW Z-scores, Apgars at 1 and 5 min, and diagnoses of neonatal asphyxia (Apgar score ≤6 at 1 min) and hypospadias were collected from electronic medical records. Data are expressed as the median (range) or mean±SD. Mann–Whitney nonparametric rank and Chi-square tests were used to determine statistical significance (p<0.05).

Summary of Results

Clinical characteristics of the hypospadias and non-hypospadias groups are shown in the table 1. BW Z-scores were significantly lower in infants with hypospadias than those without (p=0.002). The incidence of hypospadias in severe SGA infants was 6.4% (34/531) overall and 4.9%, 7.7%, and 5.5% for each center, which were not significantly different.

Abstract 62 Table 1

Clinical characteristics

Conclusions

Our data demonstrate a possible relationship between a higher risk of hypospadias with the severity of SGA. Therefore, further study is warranted to evaluate the relationships between SGA, testosterone levels, and hypospadias risk.

63 Neonatal resuscitation in the emergency room: testing knowledge and confidence of residents

S Liu*

LE Yaeger

E Sander

FB Wertheimer

R Ramanathan

M Biniwale

LAC USC Medical Center, Los Angeles, CA

Purpose of Study

Emergency Medicine (EM) residency training is a diverse discipline, encompassing many facets of adult and pediatric medicine. Currently, neonatal resuscitation program (NRP) training is not a required ACGME milestone. As neonatal cardiopulmonary compromise in the emergency department is rare, it is difficult for EM residents to learn and master the necessary skills to stabilize critically ill newborn infants.

Methods Used

Our prospective interventional study assessed EM residents’ knowledge and confidence in neonatal resuscitation skills. We randomized EM residents to receive a single baseline session (control) or two sessions 6 months apart (intervention) of high fidelity simulation training led by NRP instructors. All participants completed pre and post surveys and quizzes assessing their confidence and knowledge in implementing NRP guidelines. The study period was 10 months. A 5-point Likert scale was used.

Summary of Results

A total of 48 (65%) residents representing all four postgraduate years enrolled in the study with 19 (39%) completing all components of the study. Importance of NRP skills scored highly, with majority of participants expecting to resuscitate newborn infants in their future career (95%) and eager for structured training (98%) within their existing resident curriculum. Within the last academic year, 65% had attended at least 1 term infant delivery, whereas only 15% participated in resuscitation of a preterm infant. Residents reported lowest confidence with neonatal intubation (65%) and emergent umbilical venous catheter insertion (70%), and greatest confidence in their ability to provide adequate chest compressions (90%). There was minimal improvement in post test scores comparing the knowledge in control and intervention groups (48% ± 4.3 vs. 50% ± 3.7, p=0.36).

Conclusions

EM residents desire structured training in neonatal resuscitation. They report discomfort in leading a resuscitation but moderate confidence with skills required to resuscitate a newborn; however, when tested on content they scored poorly. Two high fidelity simulation training sessions 6 month apart may not be sufficient to improve EM residents’ knowledge. A structured simulation curriculum specifically geared towards EM residents to learn NRP skills needs to be implemented.

Adolescent medicine and behavior development I

Concurrent session

10:10 AM

Friday, January 29, 2021
64 Maternal mental health and postpartum depression in the COVID-19 pandemic

M Waschmann*

K Rosen

L Gievers

S Khaki

A Laird

A Hildebrand

Oregon Health and Science University, Portland, OR

Purpose of Study

Previous studies examining the impact of natural disasters noted that in the setting of consistent rates of major depressive disorder, postpartum depression (PPD) increased in vulnerable postnatal subgroups. COVID-19 may affect maternal health in similar ways. Given the significant impact of PPD on both mother and child, this study aimed to characterize the effect of COVID-19 on the incidence of PPD and identify subgroups at elevated risk for PPD.

Methods Used

This retrospective chart review of maternal–newborn dyads, born at ≥ 37 weeks’ gestation, admitted to the Mother Baby Unit, was conducted at a quaternary academic medical center over two time periods: pre–COVID-19 (Jan 1 – Jun 1, 2019) and during COVID-19 (Jan 1 – Jun 1, 2020). PPD was defined as an Edinburgh Postnatal Depression Scale score of ≥ 10 at any postnatal appointment. History of and/or current mental health diagnoses [major depressive disorder (MDD), generalized anxiety disorder (GAD)] were recorded. Data were analyzed using chi-square and t-tests.

Summary of Results

The study included 1073 dyads (567 in the 2019 epoch, 506 in the 2020 epoch). The cohorts had similar clinical and sociodemographic characteristics. Rates of PPD between the cohorts were similar (18.5% to 18.2%, p=0.95). In subgroup analyses, PPD rates were similar amongst primiparous births (18.7% to 21.9%, p=0.44) and publicly-insured mothers (26.7% to 25.7%, p=0.94). The 2020 cohort exhibited higher incidence of current mental health diagnoses: MDD (10.1% to 14.2%, p<0.05) and GAD (10.6% to 18.6%, p<0.01). However, incidence of PPD among women with current mental health diagnoses decreased from 47.1% in 2019 to 30.4% in 2020 (p=0.02).

Conclusions

Few prior studies have investigated the effect of the COVID-19 pandemic on PPD. Notably, a stable PPD rate despite an increase in current mental health diagnoses, highlights the complexity of the biopsychosocial milieu contributing to PPD. Decreased PPD in women with mental health diagnoses may reflect improved treatment success in those with current diagnoses or decreased identification from limited screening or healthcare access. Further study of psychiatric care access and treatment is an important next step in understanding the relationship between mental health diagnoses and PPD during the COVID-19 pandemic.

65 Parental involvement in children’s eating behaviors for healthy BMI

D Jhang*

BM Rodriguez

R Guest

M Baum

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

The estimated childhood obesity rate in the U.S. is one in three and predicted to increase. Obesity’s negative impacts on health have been consistently demonstrated. Parents are significant influences for their children in the development of healthy eating behaviors by modeling eating behavior and providing food. This study aims to determine if a significant relationship exists between healthy BMI (<85%ile) and unhealthy BMI (>85%ile) children regarding two aspects: involvement of parents in their children’s eating behaviors and the children’s own eating behaviors.

Methods Used

Children aged 9–15 yrs, were referred from a local FQHC by pediatric and family medicine clinics to a 1-week healthy interventional day camp in Loma Linda, CA, called Operation Fit. Kids learned healthy eating behaviors and participated in various physical activities. Kids were of either healthy (5th-85th percentile) or unhealthy BMI (>85th percentile) and completed pre-camp surveys regarding eating behaviors and parental involvement. Data from 2011–2019 was analyzed.

Summary of Results

A chi-square statistical test and odds ratio showed that parents of healthy BMI children were more likely to discuss food choices [X2 (1, N = 803) = 13.07, p = 0.0003; OR = 1.83]; healthy BMI kids were less likely to think about making healthier food choices [X2 (1, N = 800) = 5.05, p = 0.025; OR = 0.49]; healthy BMI kids were slightly more likely to eat less than 3 times per day [X2 (1, N = 798) = 6.91, p = 0.0086; OR = 1.07].

Conclusions

Parental involvement in discussing food choices with kids most significantly correlated with healthy BMI. Healthy BMI kids were less likely to think about making healthier food choices, which might correlate with already formed healthy eating behavior. The least significant difference was seen with the number of times a child ate per day. The quality of the food may most likely matter more than the quantity consumed.

66 Behavior change in youth based on type of familial loss

JL Carlson*

M Castella-Chin

D Jhang

C Irani

M Baum

Loma Linda University, Loma Linda, CA

Purpose of Study

Grief following the death of a loved one creates emotional trauma on family members, especially the youth. The purpose of this study is to examine the differences in behavior depending on if the familial loss was a sibling or another family member.

Methods Used

Children and youth that experienced death of a family member were invited to attend Camp Good Grief (CGG), while children that experienced a violent death of a family member were invited to attend Special Victims Camp (SVP). These camps focused on helping the campers manage their grief. Parents of the children filled out questionnaires documenting behavioral, emotional, relationship, etc. responses regarding their child prior to the death, pre-camp, and post-camp. Problematic behavior traits were split into 15 categories with rankings within those categories of 1–6, with 1 meaning the behavior never happened and 6 meaning the behavior always happened. A rating of 1–3 was indicative of the child not displaying the behavior, while a rating of 4–6 indicated the behavior. The number of behaviors each child displayed was tallied.

Summary of Results

The results of the survey showed that there was statistically significant difference between the behavior change of CGG campers based on whether the death was that of a sibling or another family member (p<.00001), indicating children experiencing the death of a sibling are at 50% lower odds for behavior change than children experiencing the death of another family member. However, no statistical significance was shown between SVP camper behaviors based on sibling or other familial loss (p=.45491). There was also no statistically significant difference between the behavior changes exhibited by SVP campers and CGG campers (p=.849701).

Conclusions

It appears that there is a correlation between increased behavior change in children that experience the death of a non-sibling family member. This outcome is reasonable due to the influential effects of older relatives as role models for young people. Further exploration is needed to determine the true directionality of behavior change whether that means acting out more or withdrawing.

67 What are parents reading about the sunscreen controversy?

J Shiosaki*

L Yamamoto

University of Hawai’i at Manoa, Honolulu, HI

Purpose of Study

Despite the benefits of sunscreen use, downside risks include vitamin D deficiency, oxybenzone-related hormone disruption, nanoparticle skin penetration, and harm to coral reefs. Benefits of sunscreen are likely greater in children, but the long-term risk of prolonged chemical exposure harm starting in childhood is difficult to confirm to be benign. With this confusing backdrop of sunscreen debates, parents may be looking to the internet as their source of sun safety information. The purpose of this study is to survey and summarize the sunscreen recommendations presented to parents on the internet to provide healthcare professionals with a general awareness of this.

Methods Used

We read and evaluated the first 50 websites after searching ‘sunscreen safety in children’ on Google. To standardize our evaluation of the websites, we created criteria to apply to each website based on nationally recognized main points on sunscreen benefits, previously debated issues surrounding sunscreen use, the stance of the website’s recommendation of sunscreen, and the intention of the website to inform the reader or sell a product.

Summary of Results

A summary of our results is detailed in table 1.

Abstract 67 Table 1

Summary of website results

Conclusions

Most of the websites aimed to inform parents (rather than sell a product) and recommended the use of sunscreen. However, many of these websites were blogs or personal opinion pieces; these websites incompletely detailed the benefits of sunscreen use and overlooked the anti-sunscreen debates parents may have previously been aware of. This variability of the online information lacks clarity to determine the overall benefit of sunscreen in reducing their child’s skin cancer risk, and may be useful for physicians to be aware of when counseling parents.

68 Outcomes of initial conservative treatment in adolescent patients with stable osteochondritis dissecans of the elbow

B Sandridge*

D Howell

JC Albright

Children’s Hospital Colorado, Aurora, CO

Purpose of Study

Osteochondritis dissecans (OCD) is a disorder characterized by separation of subchondral bone and articular cartilage from underlying bone due to lack of blood supply. Effective treatment of elbow OCD is still debated. The purpose of this study is to compare the characteristics and clinical outcomes of adolescent patients diagnosed with stable OCD of the elbow who either progressed to surgery or did not after initial conservative treatment.

Methods Used

We performed a retrospective chart review of patients 5–18 years of age who were diagnosed with stable OCD of the elbow and initially underwent conservative treatment at Children’s Hospital Colorado. Demographic and radiographic variables such as age, sex, skeletal maturity, and lesion size were collected. Clinical outcomes collected included time to return to sport and need for second surgery. Statistical analysis was performed using T-tests, Mann Whitney U tests, and Fisher’s exact tests with Stata version 15.

Summary of Results

We identified 18 patients to meet inclusion criteria; 11 progressed to surgery and 7 did not. There were no significant differences between groups regarding sex, age, skeletal maturity or insurance type. Loss of range of motion in the elbow was seen in 64% of patients who progressed to surgery and in 29% of those who did not (p = 0.34). While there were no significant differences in radiographic measurements between groups, those who progressed to surgery had greater average lesion sizes than those who did not (p=0.22). We did not observe any significant differences in time from diagnosis to return to sport.

Conclusions

Overall, there were no significant differences between patients who progressed to surgery versus those who did not regarding patient characteristics or clinical outcomes. However, it may be clinically useful to consider loss of range of motion and size of lesion when treating these patients. The high percentage of patients progressing to surgery emphasizes that stable OCD lesions in the elbow behave differently than those in the knee, where the rate of progression to surgery can be as low as 15%. Factors associated with healing of stable OCD lesions and the benefits of conservative treatment should be further investigated.

69 Disruptive behaviors among children and teens who experienced either a traumatic/unexpected or natural loss

D Jhang*

M Castella-Chin

JL Carlson

M Baum

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Understanding the grief process in children and the effects of experiencing a death/loss is critical for caregivers to provide appropriate support. Losing a loved one can impact several aspects of a child’s life, such as functioning at home, school, peer relationships, spiritual beliefs, and concept of self. Moreover, the grief process and its manifestations can differ depending on whether or not the loss was traumatic/unexpected. This study aims to determine if disruptive behaviors are more likely to be reported at a higher frequency among children who experience traumatic/unexpected losses.

Methods Used

Children/teens 10–16 years old who have lost a sibling or parent attended a 3-day grief therapy camp in Loma Linda, CA called Camp Good Grief. It provided a safe space to share thoughts and feelings with others who have experienced a loss in order to understand and normalize the grief process. Parents filled out pre-camp surveys categorized as either traumatic/unexpected loss (SVP group) or natural loss (CGG group). 194 CCG and 110 SVP surveys were analyzed for questions regarding disruptive behaviors, reported as low or high frequency. Behaviors included temper tantrums, lies, manipulates situations, steals, something terrible, discipline problem home, discipline problem school, fighting, and family problems.

Summary of Results

A chi-square statistical test showed a statistically significant difference between the two groups for only one behavior – discipline problem school; X2 (1, N = 294) = 5.68, p = 0.017. Parents of children who experienced a traumatic/unexpected loss were 91% more likely to report temper tantrums as a high frequency behavior at a 95% confidence interval (OR = 1.91).

Conclusions

Parents of children, part of the SVP group were more likely to report ‘discipline problem school’ as a high frequency behavior. This behavior was the only one to primarily occur outside of the home environment. Due to the traumatic nature of the loss, SVP kids may be more likely to exhibit behavioral issues outside of the home. The significance may also be explained by the fact that parents were unable to directly observe the behavior and not available to respond. At school, no adults may be available to spend quality time with the child about the behavior.

70 Team nemo consult service: extending the implementation of early diagnosis and intervention for cerebral palsy prior to discharge from the NICU

S Iyer1

K Jiang2*

S Espinosa2

K Kesavan2

1University of California Los Angeles, Agoura Hills, CA

2University of California Los Angeles, Los Angeles, CA

Purpose of Study

Early diagnosis of cerebral palsy (CP) is the key to early intervention. The HRIF clinics at UCLA implemented guidelines for early diagnosis and early intervention for CP and decreased the average age of CP to under 12 months. Team NEMO (Neurodevelopment and Early Movements Observation) consult service was formed to sustain gains made during the first year of implementation and extend screening to the NICU.

Methods Used

Setting: UCLA NICU and HRIF clinic

Patients and methods: Our process included 4 stages:

1. Exploration – SIPOC analysis, SWOT analysis, IRB approval

2. Installation – process flow design, pre and post surveys to assess effectiveness of consult, preparation of materials

3. Initial implementation – data collection, refining process flow design, weekly team meetings, monthly site calls

4. Full implementation – monitoring fidelity, sustaining gains

GMA of all babies in the NICU were assessed. Those who met criteria for HRIF and those with Cramped Synchronized (CS) GMA were identified for a NEMO in-patient consult. Families received counseling about the GMA and about follow up at the HRIF clinic. At the 3–4 mo HRIF visit, parents completed a survey. This data was compared to parents who were surveyed prior to implementation of the NEMO consult.

Summary of Results

To date, 27 Team NEMO in-patient consults have been completed. Of these, 6 had CS GMA and 2 had absent fidgety movements at 3 months corrected age. Parent knowledge about the HRIF clinic increased in multiple categories (purpose of HRIF appointment increased from 78% to 100%, need for neurodevelopmental follow up increased from 46% to 92%, appointment duration increased from 41% to 73%). 92% families reported being aware of the GMA post-NEMO consult. During year 2, there were 6 new diagnosis of CP with the average age being 10.7 months.

Conclusions

Team NEMO consult service improved parent knowledge about HRIF and GMA and helped maintain successful implementation of evidence-based guidelines. Future directions include expanding the program to include other sites, improve the quality of our existing process flow and to provide support for families that receive a diagnosis of cerebral palsy.

71 Addressing the loneliness epidemic: the impact of learning communities on medical students’ sense of connection and belonging

HJ Chi*

UE Oyoyo

A Hayton

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

In an increasingly digital age, social isolation underlies many mental and physical health concerns. Medical students are especially at risk, given the stressful workload and high performance demands. However, emerging medical education research highlights the potential of learning communities (LCs) to ‘positively influence the overall learning environment’ (Smith et al., 2016), so we seek to discover if LC group sizes make a difference in students’ connection and belonging with their class.

Methods Used

A LC consists of a group of students assigned to a physician faculty mentor throughout medical school. Two cohorts of first year students, Class of 2022 (C2022) & Class of 2023 (C2023), were compared. C2022 LCs consisted of 12–15 students per group, while C2023 LCs had 8–10 students per group. Both cohorts met with their LC about 20 times in the year for curriculum and mentorship. Students were asked to assess statements on Likert scales as part of their end-of-year surveys about their perceptions of the impact of LCs, such as sense of belonging within LCs, mentor’s role and students’ abilities to foster connection, and students’ sense of appreciation for their class contributions.

Summary of Results

C2022 had 161 responses, while C2023 had 137 responses. C2023 scored significantly higher (p<0.001) when assessing the statements ‘[learning] communities contributed to connections I made’ and ‘facilitator fosters connection in the group’. Regarding students’ sense of belonging in the class, C2023 demonstrated narrower yet more positive response distributions, but evidence is inconclusive (p =0.116). Regarding student appreciation for their class contributions, C2023 had a more positive and homogeneous distribution than C2022, but with marginally inconclusive evidence (p= 0.051).

Conclusions

Compared to C2022, C2023 reported more positive perceptions about LCs. This may be due to the decrease in student-mentor ratio, thus allowing for more interpersonal interactions. C2022 was also the first class to implement LCs, demonstrating how new programs can take time to become integrated. These results shed light on optimal LC sizes and are promising for future research regarding their value to medical students.

Immunology and rheumatology

Concurrent session

10:10 AM

Friday, January 29, 2021
72 Clinical characteristics of late-onset spondyloarthritides

KY Anishchenko1,2*

E Cheng2

L Caplan1,2

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

2Rocky Mountain Regional VA Medical Center, Aurora, CO

Purpose of Study

Spondyloarthritides are a group of inflammatory rheumatic diseases with a global prevalence of 1%. Late onset spondyloarthritis (SpA) is considered rare but cases are expected to increase as the U.S. life expectancy increases. Early and late-onset SpA are considered pathologically similar, but several small observational studies suggest that they present with different clinical characteristics. Further, few research studies have quantified the effectiveness of tumor necrosis factor inhibitor (TNFi) therapy in late-onset SpA. This study examined the clinical differences and reasons for TNFi discontinuation in early-onset and late-onset spondyloarthritis in the U.S. Veteran Affairs health care system.

Methods Used

US veterans enrolled in the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) from 2007 – 2019 who were diagnosed with ankylosing spondylitis, psoriatic arthritis, reactive arthritis, undifferentiated spondyloarthritis, and IBD-associated arthritis were included in the study. Late-onset SpA was defined as symptom onset beginning after age 50.

Summary of Results

115 individuals with late-onset SpA treated by 136 TNFi courses were compared to 424 individuals with early-onset SpA treated by 498 TNFi courses. The mean age of enrollment was 65.73 for the late-onset group, compared with 51.86 for the early-onset group. Significantly more patients with early-onset SpA were human-leukocyte antigen (HLA) B27 positive (P<0.01). For both late-onset and early-onset SpA patients, the most common reason for TNFi discontinuation was secondary failure (42% early-onset, 36% late-onset), defined as loss of efficacy after >6 months of treatment, followed by adverse events (23% early-onset, 27% late-onset).

Conclusions

This study suggests that late-onset SpA patients have a lower frequency of HLA B27 and the reasons for TNFi discontinuation are similar for early-onset and late-onset SpA. In contrast to the approach of prior studies, use of the data of symptom onset, rather than the date of diagnosis, likely resulted in a more accurate classification of cases in the study. Further studies should evaluate clinical outcomes in older onset spondyloarthritis patients to better quantify the effectiveness of treatments for this population.

73 Novel corona virus pandemic- 2019 and patient experience comparing telemedicine with conventional clinic visit in patients with juvenile idioapthic arthritis and childhood systemic lupus erythematosus

T Gross1*

S Sukumaran2

1Valley Children’s Hospital, Madera, CA

2Valley Children’s Healthcare, Madera, CA

Purpose of Study

The COVID-19 pandemic changed the physician- patient interaction. Telemedicine has emerged as the universal method of communication with patients. We compared conventional clinic visit (CCV) with telemedicine (TM) in clinic administered through video conferencing. Physician patient communication is key in determining treatment outcome and patient satisfaction in complex auto immune disease process including Systemic Lupus Erythematosus (cSLE) and Juvenile Idiopathic Arthritis (JIA).

Methods Used

We performed a quality improvement project using a telephone questionnaire survey in rheumatology clinic at Valley Children’s Healthcare. We surveyed 25 patients total. The respondents in the survey experienced both CCV before and during pandemic and TM during pandemic.

Summary of Results

Among the 25 patients surveyed 15 had JIA and 10 had cSLE. Among JIA patients 95% felt doctor was paying attention, able to make shared decision regarding the medications and treatment options. All the JIA and cSLE patients in the group felt that doctor listened and asked appropriate questions. Patients in both groups felt they were able to discuss all their problems and had a strong positive impact on the quality of care during the TM visit as compared with CCV. In cSLE group 70% felt shared decision making and ability to discuss their medical problem via TM was not as good as CCV.

Conclusions

This survey divulged patient perspective regarding clinic visit during pandemic. Telemedicine is preferred by 95% and 75% of the respondents over the conventional clinic visit during the pandemic among JIA and CSLE groups. The main concerns were breakdown of the physician-patient relationship and issues regarding the technologies with connectivity along with organizational challenges. Patients in both groups strongly agreed that TM met the need for their care compared to conventional clinic visit. Patients in the JIA group were satisfied with TM visit in handling complex medical problems and shared decision making. Patients in cSLE group preferred CCV especially in addressing complex medical issues and shared decision making.

74 Patient experience with telehealth in a pediatric rheumatology clinic during the novel coronavirus pandemic 2019

Y Moufarrej*

D Singh

R Patel

S Sukumaran

Valley Children’s Hospital, Madera, CA

Purpose of Study

Physician interactions with their patients have changed drastically during the COVID-19 pandemic. However, physician-patient communication remains key in determining treatment outcomes in complex autoimmune disease processes. Telehealth has emerged as one of the major methods of communication during this time. Appropriate communication with patients and caregivers is critical in not only patient satisfaction but also adherence with the treatment plan.

Methods Used

We performed a quality improvement project using a telephone questionnaire to survey patients seen via telehealth by the rheumatology clinic at Valley Children’s Healthcare. The survey was performed 3–6 weeks after the telehealth visit.

Summary of Results

We surveyed 53 patients, of which 93% had previous experience with telehealth. Of the total respondents, 98% found telehealth convenient; 90.5% preferred telehealth due to not having to take time off from work, 95% as they did not have to travel to the appointment, and 93% due to fear of the pandemic. Among the participants, 95.5% felt the doctor was listening and asking appropriate questions, 95% stated that the doctor explained the medications and workup appropriately, and 98% felt that the doctor answered all of their questions. Conversely, 2% of participants felt that the doctor was in a hurry, and 7.54% felt that the physical exam performed over telehealth was inadequate for their condition.

Conclusions

Our study demonstrates that telehealth is not only acceptable but also beneficial overall for rheumatology patients, particularly due to expediency. Respondents agreed that telehealth met the needs for their care. Technology, difficulties with connectivity, and the ability to perform a physical exam, however, remain limiting factors in telehealth that must be addressed. Despite this, participants had a positive outlook as to the use of telehealth in rheumatology and believed it posed no burden on the patient-physician relationship and instead felt heard and cared for by their physician. In the future, it has the ability to improve access to care and facilitate timely diagnosis as well as appropriate intervention.

75 An interesting case of statin induced autoimmune myopathy

M Nemati*

M Srai

San Joaquin General Hospital, French Camp, CA

Case Report

Statins are one of the most widely prescribed drugs in the world. One of the common side effects of statin use is myopathy. We report a rare case of statin induced autoimmune myopathy, which is a rare variant of statin-induced myopathy. A 56-year-old female with a history of hypertension, hyperlipidemia, cerebral aneurysm status post clipping, and seizure disorder presented with progressive muscle weakness. Her initial laboratory results demonstrated elevated liver function tests and an elevated creatine phosphokinase (CPK) of 17144 IU/L. Patient’s atorvastatin was discontinued and she was placed on high rate intravenous fluids, but despite this, her CPK remained elevated. Patient underwent further blood testing for specific autoimmune etiologies. As there was high concern for autoimmune myositis, she was started on high dose steroids. Anti-HMG CoA reductase antibody returned strongly positive. While the patient was on steroids, her muscle weakness, CPK level, and liver functions gradually improved. She was discharged on oral steroids. She also had imaging and lumbar puncture to rule out other causes of her motor weakness on initial presentation. Statin induced autoimmune myopathy should be considered with high suspicion when there is significant elevated CK level and discontinuation of statin therapy does not lead to muscle recovery or improvement in the CPK level. Diagnosis is confirmed by positive anti-HMG-CoA reductase autoantibody and biopsy.

76 Platelet/lymphocyte ratio as a potential biomarker for disease activity in ankylosing spondylitis

EJ Kim1*

R Sen1,2

E Manning1,2

E Anderson1

K Maier1

E Cheng2

L Caplan1,2

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

2Rocky Mountain Regional VA Medical Center, Aurora, CO

Purpose of Study

Ankylosing spondylitis (AS) is a chronic inflammatory disease involving the sacroiliac joint (SIJ) and the spine. These joints can be involved with erosions or fusion, which can be debilitating and affect quality of life. Though several medications are available for use in AS, clinicians face challenges in classifying patient’s disease activity. The most commonly used biomarker of disease activity—the c-Reactive Protein (CRP)—has been shown to have low specificity and sensitivity. Prior studies have shown that the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) are associated with disease activity and severity for inflammatory diseases such as malignancies and ulcerative colitis. This study evaluates the utility of the NLR/PLR as biomarkers for AS disease activity and severity by examining their association with CRP and SIJ damage scores.

Methods Used

Data were drawn from the Program to Understand Long-Term Outcomes of Spondyloarthritis registry; only patients treated at the Rocky Mountain Regional VA Hospital were included. SIJ radiographs were scored for sacroiliitis based on the modified New York (mNY) radiographic criteria. Patients not meeting criteria were excluded. Absolute neutrophil count, lymphocyte count, platelet count, and CRP were collected within 6 months of the radiograph. Demographic data including HLAB27 status were collected. The relationship between NLR, PLR, CRP and mNY scores was determined using regression techniques in the STATA (v13) statistical package.

Summary of Results

42 patients met radiologic mNY radiologic criteria for sacroiliitis. No statistically significant correlation was found between mNY radiograph scores and the NLR nor the PLR. However, CRP concentration was associated with the PLR (R2= 0.3205, p < 0.001).

Conclusions

A more accurate biomarker for AS disease activity would be very helpful. Though our study did not show a correlation between NLR and PLR, we did identify a relationship of PLR and CRP. Further studies are needed to validate these results in other populations, explore the relationship of PLR with patient reported outcomes, and determine if PLR is associated with findings from other imaging modalities.

77 Use of anakinra for coronavirus disease 2019 associated multisystem inflammatory syndrome in children

KS Jin*

S Sukumaran

Valley Children’s Healthcare, Madera, CA

Purpose of Study

To discuss the diagnosis and management of a child treated with Anakinra for the COVID-19 associated pediatric disorder, Multisystem Inflammatory Syndrome in Children (MIS-C).

Methods Used

Retrospective Chart Review

Summary of Results

A 7-year-old male presented to our institution with 5 days of fever, sore throat, vomiting, diarrhea and abdominal pain. Physical examination was remarkable for a febrile, ill-appearing child with tachycardia and respiratory distress. He was hypoxemic to 89%. He had with oral ulcers, hepatomegaly and poor perfusion. He was started on oxygen and inotropic agents and admitted to the PICU.

Laboratory evaluation revealed a positive SARS-CoV-2 PCR and SARS-CoV-2 IgG. Additional pertinent labs included leukopenia, lymphopenia, thrombocytopenia, hyperferritinemia, and elevated CRP. ECHO showed depressed left ventricular systolic function with ejection fraction of 43%. Child’s troponin was 2.7 ng/ml and BNP 2439 ng/L.

He was started on remdesivir but continued to clinically deteriorate with persistent fever and increase in ferritin. His soluble IL-2 receptor and IL-6 level were highly elevated. Repeat ECHO demonstrated dilatation of the coronary arteries.

Based on clinical and laboratory evaluation, child met the American College of Rheumatology criteria for MISC-C. He received IVIG and steroids, without improvement in fever or markers of inflammation and therefore was started on anakinra for 5 days. Within 24 hours of initiation of anakinra, child demonstrated clinical and laboratory improvement and was discharged home on low dose aspirin on hospital day 12.

Conclusions

Anakinra is among several biologic drugs that inhibit specific inflammatory cytokines which have an essential role in the cytokine storm that occurs in children with MIS-C. Anakinra targets and inhibits the IL-1β receptor protein which prevents activation of the cytokine storm and subsequent organ dysfunction.

Our patient was refractory to conventional treatment with IVIG and steroids but responded well to anakinra and completely recovered. As the cases of COVID-19 in children continue to rise, clinicians should be aware of the clinical presentation of MIS-C and its treatment to prevent adverse outcomes.

78 Proliferation and differentiation potentials of clonal human articular cartilage progenitor cells

LC Snyder*

P Lam

K Weekes

A Elhance

B Parkway

B Johnstone

Oregon Health and Science University School of Medicine, Portland, OR

Purpose of Study

The aim of this study was to compare human articular cartilage progenitor clones from different zones in terms of their expansion and differentiation.

Methods Used

Cells were isolated from superficial and deep zones of normal human articular cartilage. Clones were stimulated to undergo chondrogenesis in vitro in 3D pellet culture for 14 days at 20, 40, and 60 population doublings.

Summary of Results

Superficial clones have a significantly higher percentage survival at 20, 40, and 60 population doublings compared with deep clones. Superficial clone-derived pellets had significantly increased (p<0.05) total glycosaminoglycan (GAG, a measure of proteoglycan production) and hydroxyproline content compared with their deep zone counterparts at 20 population doublings. Collagen X production was significantly increased (p<0.05) in deep compared with superficial ACP clones. All zonal differences were no longer evident once cells had undergone 40 or greater population doublings. No differences in the level of gene expression (p>0.05) were detected for COL1A1, COL2A1, SOX9, or PRG4 either prior to chondrogenesis (day 0) or 14 days after induction for clones at 20, 40 or 60 population doublings. A significant increase in COLXA1 gene expression (p<0.05) in deep clones was observed at 40 population doublings after chondrogenic induction for 14 days but not prior to induction (day 0) or at either day for clones of 20 or 60 population doublings. ACAN gene expression was also significantly increased (p<0.05) in day 14 deep zone pellets at 40 population doublings compared with superficial zone pellets.

Conclusions

These data reveal the differences between populations of chondrogenic progenitors residing in different zones of human articular cartilage. Superficial zone clones have increased survival and propensity to form stable articular cartilage in vitro compared to deep zones clones. Differences seen in the matrix production at 20 population doublings are lost at 40 doublings and higher; this may be due to the survival of only higher matrix-producing clones from the deep zone with increased doublings.

79 Validating a scoring system for immunoglobulin unresponsiveness in high risk kawasaki disease

S Nayak1

A Florea2

S Sin2*

M Soneji3

1Loma Linda University Children’s Hospital and Loma Linda University Medical Center, Loma Linda, CA

2Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

3Loma Linda University, Loma Linda, CA

Purpose of Study

The purpose of this study is to report outcomes of children with high-risk Kawasaki disease (KD). We aim to validate the prediction model for unresponsiveness to intravenous immunoglobulin (IVIG), and to determine if there is a change in responsiveness to IVIG if steroids are given additionally in high-risk KD patients.

Methods Used

This is a single center retrospective study examining outcomes in children from 0 and 18 years old with KD before and after the introduction of a protocol for the treatment for high-risk KD. Criteria to qualify for the high risk protocol included: age ≤ 12 months or ≥ 8 years, Z score of LAD or RCA ≥ 3.5, or CRP ≥ 15 mg/dL with one additional finding of the following WBC >20,000, Platelet count <150,000, Sodium <133, Albumin <2.8, Hemoglobin <8, and/or ALT>100. We compared the rate of unresponsiveness to IVIG among the children who would have met these criteria before the protocol was implemented and after. A patient will be considered unresponsive to IVIG therapy if they received additional therapy (IVIG, steroids, infliximab or another biologic) or the Z-score for the RCA ≥ 3.5 or LAD ≥ 3.5.

Summary of Results

There was a total of 129 patients and 74 were female (57%). The number of patients who met high risk KD criteria was 49, 25 were female (51%), and 31 (63%) met criteria by age alone. Prior to the implementation of the protocol 42 (37%) patients met criteria and 7 (50%) after. There were 39 patients (30%) who failed to respond to IVIG during the entire time, 36 (31%) prior and 3 (21%) post implementation.

Conclusions

After the implementation of the high-risk KD protocol, there was a significant improvement in the responsiveness to IVIG. We believe that early steroid administration in these high-risk patients can prevent the need for additional therapy.

Infectious diseases I

Concurrent session

10:10 AM

Friday, January 29, 2021
80 Increased susceptibility to infectious diseases due to measles-induced immunosuppression: a systematic review

P Natcher1*

J Mosser2,3

1University of Washington School of Medicine, Anchorage, AK

2Institute for Health Metrics and Evaluation, Seattle, WA

3Seattle Children’s Hospital, Seattle, WA

Purpose of Study

Measles continues to be one of the leading causes of vaccine-preventable illness and death worldwide. Current studies have suggested that measles can induce immunosuppression for approximately 2–3 years following a primary measles infection, increasing a host’s susceptibility to infectious diseases. In low- and middle-income countries (LMICs) with lower rates of measles vaccine coverage and higher rates of infectious diseases, post-measles immunosuppression (PMI) may contribute to disparities in health outcomes. This systematic review aims to investigate the degree of increased susceptibility of a host to infectious diseases due to measles-induced immunosuppression.

Methods Used

We searched PubMed, Embase, Cochrane, and Web of Science for articles on PMI published between January 1, 2000 to July 8, 2020. We included observational studies, modeling studies, review articles, and RCTs involving populations of any age in any geographic location with quantitative estimates of the change (or lack thereof) in the risk of infection or mortality from non-measles infectious diseases following measles infection. We excluded studies with no relevant data, that used non-human models, and that were written in languages other than English.

Summary of Results

Of 1,048 articles screened, 6 studies met inclusion criteria for this review. In children with previous measles infection, two studies found a 3 fold increased risk of infection-related rehospitalizations between 1 month and 1 year following measles, two studies found a 2–3 fold increased risk for infectious disease symptoms for 2 to 3 years following measles, and two studies found a 1.5 fold and 10–85 fold increased susceptibility to VZV and whooping cough, respectively, following measles.

Conclusions

Current studies that do not account for PMI likely underestimate the global burden of measles. More studies are needed to better characterize PMI, particularly in LMICs. These results will help policy-makers better understand the true global health burden of measles and accurately assess the full benefits of the measles vaccine.

81 Assessing online content on tdap vaccination in pregnancy using instagram & facebook

S Feng*

T Le

K Lee

J Matacotta

AL Nelson

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

Purpose of Study

Tdap vaccine is recommended for pregnant women and newborn contacts are to be up-to-date to provide infant protection from pertussis (cocooning). Many women turn to social media platforms. We surveyed two social media platforms to assess the questions women asked about the Tdap vaccination and the quality of responses received.

Methods Used

Instagram and Facebook were chosen for this project because users can write posts without any word limits. Keywords related to Tdap vaccination during pregnancy were used to search related posts from 2012 to Feb. 2020. For Facebook, only Tdap-related posts with either more than 10 comments or 10 shares were included. Instagram posts needed to have either more than 10 comments or 10 likes. CDC guidelines were used to judge the accuracy of the posts.

Summary of Results

We performed a detailed scoping of 100 Facebook posts, 95 Instagram posts and comments related to Tdap during pregnancy. Inaccuracies were found in 79% of advising posts from Facebook nonprofessional users and 32% of such advising posts on Instagram. Common themes found within Facebook advising posts were questions about Tdap side effects, Tdap safety, and issues related to cocooning. Disturbingly, the most popular subtheme was that Tdap vaccination leads to spontaneous abortion. Common themes found within Instagram posts were advice to take Tdap, and cocooning support, but also reasons for not getting Tdap. The most popular subtheme was advice for Tdap during the 3rd trimester.

Looking at the comments, the top three themes from 537 Instagram comments were side effects of Tdap vaccination (32%), safety of Tdap vaccine (26%) and cocooning (17%). On the other hand, the top three themes from the 2877 Facebook comments related to those posting were concerns that the FDA labeling said Tdap had not been tested in pregnancy (39.8%), Tdap safety (35.2%), and Tdap ingredients (10.6%). Lastly, professional postings were analyzed separately; 23% of Facebook posts and 25% of Instagram posts from health care professionals and organizations contained inaccuracies.

Conclusions

Women have residual questions about the safety and need for Tdap vaccines for themselves and those who will be around the newborn. Clinicians should clear up this misinformation when offering the vaccine.

82 Epidemiology of pediatric osteoarticular infections in the United States

K Disch1*

W Dehority2

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

2University of New Mexico, Albuquerque, NM

Purpose of Study

Osteoarticular infections in pediatric patients are a cause of significant morbidity. Previous studies have estimated that long-term complications arise in up to one-third of children recovering from acute osteomyelitis or septic arthritis, with limb length discrepancies occurring in about 10% of children recovering from chronic osteomyelitis. Information on the epidemiology and clinical outcomes of osteoarticular infections in children is scarce, however. Using data from the national HealthFacts database, we herein report what to our knowledge is one of the largest descriptions of pediatric osteoarticular infections.

Methods Used

Children ≤18 years of age at the time of diagnosis were included. Osteoarticular infections were classified using 360 different International Classification of Diseases (ICD) version 10 diagnosis codes for acute osteomyelitis (AOM), chronic osteomyelitis (COM) or acute septic arthritis (ASA). The diagnosis codes were then entered into the HealthFacts national medical database. Utilizing this database, we analyzed cases of pediatric osteoarticular infections over a 3 year period (2015–2017) and assessed long-term outcomes (up to 2 years) following discharge. P-values were assessed with a Welch’s t-test.

Summary of Results

Overall, 1,908 subjects were identified. ASA was the most common presentation (54.5%), with COM the least common (18.0%). In all three conditions, boys were more commonly affected (58.0% overall). Children with COM were slightly older on average than those with AOM or ASA (10.6 years vs 8.8 years and 8.1 years, respectively). The most common season for diagnosis was winter for all conditions (33.0% of all cases). A pathogen was isolated only 40.0% of the time, with S. aureus the most common. In COM, 34.1% of patients developed a limb-length discrepancy, vs 12.8% of those with AOM (p<0.0001) and 4.4% of those with ASA (p<0.0001). Long-term orthopedic follow-up (≥ 1 year) was more often required in children with COM (14.0% of subjects) than in those with AOM (4.8%, p<0.0001) or ASA (2.5%, p<0.0001).

Conclusions

Chronic osteomyelitis is associated with the worst morbidity of all pediatric osteoarticular infections. Further study into this condition is warranted.

83 Re-emergence of arbovirus diseases in the state of Rio de Janeiro, Brazil 2014–2019

O Man1*

T Fuller2

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

Cyclic re-emergence of arboviruses has been attributed to the dynamic interplay among the human population, environment, and mosquito vector. We sought to determine how seasonal arbovirus outbreaks change population conditions to impact circulation of Chikungunya, Dengue, and Zika.

Methods Used

We assessed the spatial and temporal distributions of Chikungunya, Dengue, and Zika cases from the Brazil’s national notifiable disease information system (SINAN) and precipitation and temperature data from WorldClim. We adapted a vector-host compartmental model to evaluate the effects of human population dynamics and the environmental on arbovirus risk to understand current patterns.

Summary of Results

424,829 clinical cases of Chikungunya, Dengue, and Zika, with 0.15% mortality, were reported in Rio de Janeiro, Brazil from 2014–2019. Each year, we estimate that these arboviruses were associated with an average of 10,211 lost Disability-Adjusted Life Years. Of the clinical cases, 42,636 (30%) Chikungunya, 84,836 (41%) Dengue, and 5,962 (7.8%) Zika were laboratory confirmed. Overall, cases were high in 2015–2016, plummeted in 2017–2018, and resurged in 2019. Outbreaks commonly occurred after large rainfall events. Our models showed that the observed transmission patterns were better explained by human population dynamics than climate variations.

Conclusions

Dynamic arbovirus patterns in Rio de Janeiro may be related to vector control interventions, human demographic processes, or temporary cross immunity. Mechanistic modeling may help predict future predominance of certain arbovirus species.

84 Rise in serum magnesium levels in hospitalized patients infected with COVID-19

R Sharma*

A Heidari

R Johnson

G Petersen

UCLA-Kern Medical, Bakersfield, CA

Purpose of Study

Hypermagnesemia is an uncommon electrolyte disorder. It occurs in approximately 10% to 15% of hospitalized patients with renal failure. In the care of 108 COVID-19 infections admitted to Kern Medical an increase in serum magnesium was noted.108 records were reviewed. 43 did not have hypermagnesemia (≥ 2.5 mg/dL) and 65 did. Renal dysfunction (AKI) was noted in 12 (18%) patients with average GFR - 100.75 mL/min. The records of the remaining 53 patients were evaluated. Correlation was made between serum magnesium and severity of disease.

Methods Used

IRB approved this study. Patients included were diagnosed with SARS-CoV-2 and admitted from March 13 to July 15, 2020. Extracted data included demographics, medical history, and laboratory data including magnesium. 53 inpatients with increased magnesium were reviewed for oxygen requirement, intensive care, ventilator support and death.

Summary of Results

53 admitted patients with COVID-19 and hypermagnesemia and 43 without hypermagnesemia did not reveal AKI. Of the 53 patients, the average age was 50 years. 21 (40%) were females. All 53 patients had findings of bilateral opacities on radiographic imaging. Symptoms, comorbidities, treatment and outcomes are displayed in tables 1,2,3 and 4.

Abstract 84 Table 1

SYMPTOMS (n=53)

Abstract 84 Table 2

Comorbidities (n=53)

Abstract 84 Table 3

Treatment

Abstract 84 Table 4

Outcomes

Conclusions

We studied the correlation between elevated serum magnesium and outcome in admitted patients with COVID-19. We believe serum magnesium is another hallmark of disease severity.

85 Carotid artery thromboembolism in the setting of sars-cov-2 positive hypercoagulability

C Spates*

A Tran

T Schainker

F Espinoza

H Huth

West Suburban Medical Center, Oak Park, IL

Case Report

SARS-COV-2 hypercoagulability is now a commonly observed complication in severely ill patients. This state of hypercoagulability leads to venous and arterial, large and small vessel thrombotic disease through a number of pathways. These pathways are discussed as well as the potential role of point-of-care thromboelastic assays to monitor dynamic changes in coagulopathy.

A 38 yo male with history of seizures was admitted after being found unresponsive at home. NIH stroke scale was 14 for altered mental status, right-sided weakness and dysarthria.CT head was negative for acute stroke or bleed and the patient was given tPA. Carotid ultrasound revealed a large thrombus at the carotid bifurcation. Heparin infusion was started and patient was taken for emergent thrombectomy by the vascular surgeon. The patient was found to be positive for SARS-COV-2 IgM, IgG and PCR. Repeat CT head without contrast at 48-hour interval revealed a large MCA infarct. Aspirin, clopidogrel and atorvastatin were started. Workup for other causes of hypercoagulable state was unremarkable. On hospital day 8 patient had worsening mental status and decreased responsiveness with fixed, dilated pupils. The patient quickly deteriorated and expired. It is postulated that the patient underwent hemorrhagic conversion of his ischemic stroke leading to his death.

Given projected growing number of COVID-19 infected patients with arterial and venous thromboembolic disease, thromboelastic point-of-care monitoring could provide a rapid monitoring to reduce COVID-19-related vascular and anti-thrombotic complications.

86 Protecting newborns from pertussis: what online professional websites say about Tdap

K Lee*

S Feng

T Le*

J Matacotta

AL Nelson

Western University of Health Sciences, Pomona, CA

Purpose of Study

Tdap is a combination vaccine for three different bacterial diseases – tetanus, diphtheria, and pertussis. Pertussis, especially, can be a life-threatening disease for newborns because they rely on passive transfer of maternal antibodies and immunization of others they will contact until they are old enough to be vaccinated. Often, pregnant women search medical advice and information online before and/or after visiting a medical professional. The objective of this study was to estimate the accuracy and completeness of the information provided on professional or organizational websites about Tdap.

Methods Used

To investigate this objective, we graded websites that posted advice by a medical advisor or representing hospitals or other experts on their accuracy and completeness using the CDC guidelines as the gold standard. The CDC specifies which vaccine to use and when to administer and emphasizes the importance of making certain that all those who will come in contact with the newborns are up-to-date with their pertussis vaccination - a condition that CDC calls ‘cocooning’. A desktop search using Google search engine was performed starting in May, 2020 and ending August, 2020, using the following keywords: ‘Tdap during pregnancy’ and ‘Pertussis vaccination in pregnancy’. The automatically generated results were used to identify experts’ websites from the first 15 pages. The websites that required subscriptions, based its information on standards outside of the U.S., presented research paper format, or contained its information on a video were not included in the study. Our target was 100 sites.

Summary of Results

Out of the 100 scored expert websites, 33 websites offered correct and complete information and 4 websites offered information that was both incomplete and incorrect. Out of 67% websites that were missing some information coverage, 52% were missing information regarding cocooning strategy. We also noted that more visited websites that appear on the front pages of Google search engines or more recently updated websites did not necessarily have the most accurate and complete information.

Conclusions

This study shows that doctors need to counsel their patients carefully about which websites to consult for its accuracy and completeness and provide them concrete advice about cocooning.

87 A novel compound with antimicrobial activity against staphylococcus aureus

N Amin1*

D Vosburg2

H Szurmant1

1Western University of Health Sciences, La Jolla, CA

2Harvey Mudd College, Claremont, CA

Purpose of Study

Antibiotic resistance in bacteria is becoming a growing concern in the health care industry, causing greater than 32,000 deaths and over 2 million bacterial infections yearly in the USA alone. One way to combat this ardent threat to public health is by studying the antimicrobial properties of a variety of novel compounds. Triazolodiazepines are an underexplored bicyclic skeleton with numerous pharmacologic activities. We hypothesized that among this class of compounds, antimicrobial hit compounds can be identified. Our confidence underlying the hypothesis stems from the fact that the triazole nucleus is a common and integral feature of a variety of natural products and medicinal agents, including some with antifungal and antimicrobial activity.

Methods Used

A one-pot organic synthesis scheme was employed to generate a number of novel triazoldiazepine derivatives and related compounds. Antimicrobial activities of 20 novel compounds against Staphylococcus aureus were assessed by Kirby-Bauer disk diffusion assays following Clinical & Laboratory Standards Institute guidelines. The minimal inhibitory concentrations (MIC) of the most promising compound was tested utilizing micro-broth dilution assays against methicillin-resistant S. aureus.

Summary of Results

Antimicrobial screening of the 20 compounds identified a single one with antibacterial activity against methicillin-resistant S. aureus. This compound was subjected to micro-broth dilutions assays, revealing killing activity in the microgram range. Similar activities were forthcoming against several other Gram-positive pathogens.

Conclusions

A novel compound with promising antimicrobial activity against methicillin-resistant S. aureus and other Gram-positive pathogens was identified. Medicinal chemistry efforts are under way in order to improve this initial hit compound. In addition, cytotoxicity studies and cellular target identification studies will be initiated

Neonatology general II

Concurrent session

10:10 AM

Friday, January 29, 2021
88 Optimizing chest compressions targeting gas exchange in neonatal cardiac arrest

V Agrawal1,2*

S Gugino1

C Koenigsknecht1

J Helman1

M Rawat1

J Nair1

B Mathew1

S Berkelhamer1

D Sankaran3

P Rivera-Hernandez1

S Mani1

S Lakshminrusimha3

P Chandraskharan1

1University at Buffalo, Buffalo, NY

2Loma Linda University Adventist Health Sciences Center, Loma Linda, CA

3University of California Davis, Davis, CA

Purpose of Study

We hypothesized that feedback from a respiratory monitor (RM) that displays respiratory rate (RR) and exhaled carbon dioxide (ETCO2) could help target the chest compressions (CC) rate and depth as recommended by neonatal resuscitation program (NRP).

Methods Used

In an ovine cardiac arrest model, 1/3rd depth was predetermined. During CC a depth of 1/3rd and ETCO2 levels of >7 mmHg was targeted with the use of RM. Resuscitation per NRP with epinephrine was continued till return of spontaneous circulation (ROSC) or until 20 min. ROSC was defined as a heart rate of >60 bpm with diastolic pressures >20 mmHg. We analyzed the peak carotid, pulmonary and coronary flows during CC based on ETCO2 (≤5, 6–10, ≥11 mm Hg) and the CC depth achieved (<25%, 25–32%, 33%, 34–50%,>50%).

Summary of Results

From 16 lambs, 11,375 CC events were analyzed with similar baseline characteristics. Carotid and pulmonary flows were higher with ETCO2 ≥11 mmHg while coronary flow was higher with ETCO26–10 mmHg (Figure 1a). 33–50% depth of CC led to better carotid, pulmonary and coronary flows (Figure 1b). The use of a RM helped achieve 90 CC: 30 breaths per min during resuscitation along with the majority of CC between 33–50% depth. ETCO2 ≤5 mmHg was associated with no ROSC.

Conclusions

Adequate gas exchange reflected by RM reflects perfusion to the lungs. Our findings support current NRP recommendations to target 1/3rd depth during CC although it is practically difficult. With the help of a feedback device like RM, targeting ETCO2 of ≥6 mmHg could help achieve adequate perfusion in complete cardiac arrest.

89 Comparison of procalcitonin and high sensitivity C-reactive protein as screening test for late onset sepsis

A Vachhani*

A Chambliss

M Durand

R Ramanathan

R Cayabyab

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

Purpose of Study

To compare procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) as screening tests for late onset sepsis (LOS).

Methods Used

Retrospective study of infants admitted to the neonatal intensive care unit at LAC+USC Medical Center from 2018–2020. Infants with one paired PCT and hsCRP values and blood, urine or CSF culture obtained after 72 hours of life were included. Demographics and laboratory results were collected. Infants were classified as healthy, infected (positive blood, urine or CSF culture) and presumed to be infected (negative culture with clinical signs and elevated biomarkers). Data were analyzed with Chi square, Kruskal Wallis and Spearman correlation coefficient. Sensitivity and specificity were calculated.

Summary of Results

A total of 72 infants met inclusion criteria. Nineteen infants were admitted from labor and delivery and 53 from the emergency department. There were 14/72 (19.4%) infants documented to be infected. There was no difference in demographics between the three groups. PCT and hsCRP were highest in the infected group (table 1). PCT and hsCRP levels were moderately correlated (r= 0.64, p <0.0001). The sensitivity, specificity, positive predictive value and negative predictive value of PCT was slightly higher than hsCRP (table 2).

Abstract 89 Table 1

Demographics and comparison of biomarkers between groups

Abstract 89 Table 2

Comparison of Biomarkers

Conclusions

Our preliminary findings indicate that PCT and hsCRP can be used to screen infants for LOS. However, PCT may be a better diagnostic test to help identify infants at risk of serious bacterial infection. Additional studies are needed in very preterm infants.

90 Effects of postnatal steroids on total brain volume in preterm infants

JJ Keel1*

LK Lee2

W Surento1

M Shiroishi1

N Jahanshad1

R Ramanathan1

R Cayabyab1

1LAC+USC, Los Angeles, CA

2Kaiser Foundation Hospital, Fontana, CA

Purpose of Study

To determine if the use of postnatal steroids (PS) in premature infants is a risk factor for smaller total brain volume

Methods Used

Retrospective review on all preterm infants <1250 grams at birth who had magnetic resonance imaging (MRI) of the brain performed prior to hospital discharge from 2009–2014. MR images were manually masked by neuroanatomical experts to remove non-brain tissue and obtain an estimate of overall brain volume (BV). Data on maternal and neonatal demographics, clinical characteristics and MRI results were collected. Infants were divided into 4 groups: those who received no steroids, only hydrocortisone, only dexamethasone, or combined. Data was analyzed using Kruskal-Wallis and Chi Square or Fischer Exact test and Linear regression.

Summary of Results

One hundred and twenty-seven preterm infants met inclusion criteria. The more immature, smaller and medically complex infants with bronchopulmonary dysplasia, severe retinopathy of prematurity, and intracranial hemorrhage received PS. There was no significant difference in BV of infants between the 4 groups however infants receiving PS had MRIs obtained at a later postmenstrual age (table 1). After adjusting for confounders, the presence of intraventricular and cerebellar hemorrhage (intracranial hemorrhage) was the only morbidity negatively associated with total brain volume (Coef. -38, 95% CI -57 to -20, p≤0.001) and not the use of PS (Coef. 4.9; 95% CI 0 -3.9,13.74 p=0.27).

Abstract 90 Table 1

Demographics and outcomes between the 4 groups

Conclusions

The presence of any intracranial hemorrhage adversely affected the BV but not the use of PS in this extremely high risk preterm population. Referral for early intervention and close follow up is necessary after hospital discharge.

91 Virtual family centered rounds in the neonatal intensive care unit: a pilot study

J Ranu*

K Hoffman

H Sauers-Ford

J Williams

JL Rosenthal

University of California Davis, Davis, CA

Purpose of Study

Family Centered Rounds (FCR) are multidisciplinary bedside rounds with active family engagement and are standard of care in pediatrics. Often, due to geographical distance, financial burdens, work obligations and family responsibilities, parents are unable to attend FCR in the Neonatal Intensive Care Unit (NICU). Our objective was to measure the feasibility of conducting a virtual FCR (vFCR) pilot trial.

Methods Used

We conducted a 7-month two-arm randomized controlled pilot trial of hospitalized infants in the NICU. Infants were randomized to participate in vFCR (intervention) or standard bedside rounds (control) in a 2:1 ratio, respectively. We specified four a priori feasibility objectives for this pilot trial: (1) among intervention arm patients, use of the intervention at least once will be ≥ 75%; (2) among attempted vFCR connections, ≥ 90% will have no technical issues; (3) the duration (minutes) of FCR encounters for the intervention arm will be no longer than the control arm; (4) parent-reported exploratory outcomes survey response rate will be ≥ 75%. Proportions and means were calculated for the feasibility objectives.

Summary of Results

Among the 110 included infants, 74 were randomized to the intervention arm and 36 to the control arm. Of the 74 intervention arm infants, attendance at vFCR at least once occurred for 35 of these patients (47%). In total, the intervention was used by parents for 216 virtual rounding encounters. Among the 216 vFCR connection attempts, 94% occurred without technical issues. The median rounding time for intervention arm patients was 5.6 minutes (SD = 4.0) and the median rounding time for control patients was 6.0 minutes (SD = 4.2). Surveys were completed by 82% of intervention patients and 75% of control patients at discharge.

Conclusions

We successfully delivered the intervention of vFCR. Our feasibility data show that we met our objectives for minimal technical issues, no burden in rounding duration, and good survey response rate. We did not achieve our intervention uptake goal; however, the 216 vFCR encounters among the 35 intervention users supports good uptake among the users.

Adolescent medicine and behavior development II

Concurrent session

11:05 AM

Friday, January 29, 2021
92 Evaluating middle school students’ understanding of topics pertinent to, and emotional outlook on the COVID-19 pandemic

BI Stepanyuk1*

EC Cornish1

M Overbeck1

M Abdel-Maksoud1,2

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

2University of Colorado Denver, Denver, CO

Purpose of Study

The COVID-19 pandemic interrupted the education of nearly 80,000 students throughout Denver Public Schools (DPS). This change lead to academic impairments and mental health challenges. The COVID Virtual Summer Camp was created to engage middle school students from DPS in discussions about topics pertinent to COVID-19 in an effort to increase understanding and decrease anxiety induced by the pandemic.

Methods Used

Students were recruited to the virtual camp via email. Two camps were conducted with 55 participants. The camps took place July 13th- 24th, lasting 4 days each, with 4 hours of programming each day. Topics included microbiology, immunity, health disparities, and mental health. Emphasis was placed on the veracity of sources, and how to verify information found on social media. The mental health curriculum was introduced to help students recognize, label, and regulate emotions regarding the COVID-19 pandemic. Topics were presented using short lectures, small group discussions, and Q&A sessions with medical and public health professionals. Participants completed pre- and a post-camp surveys, assessing their level of understanding of topics pertinent to COVID-19 as well as their emotions associated with the pandemic. Participants chose words from a word bank to describe their emotions associated with the COVID-19 pandemic. Each word corresponded to a particular position on a pleasantness and energy intensity axes (RULER Mood Meter).

Summary of Results

Completed pre- and post-camp surveys showed a 54.5% increase (p<.00001) in confidence discussing infectious diseases and a 40% increase (p<.00001) in self-reported knowledge about the spread of infectious diseases. Pre-camp surveys showed 62% of words chosen to describe emotions regarding the COVID-19 pandemic to be in the unpleasant, high-energy quadrant. The post-camp surveys found 67.5% of words selected to be in the same quadrant.

Conclusions

The COVID Virtual Summer Camp increased self-reported knowledge and confidence in discussing infectious diseases. We demonstrated that the majority of emotions towards the pandemic were associated with higher energy and unpleasantness, regardless of level of understanding.

93 Redesigning the door reduces the potential for finger injuries in children

I Yang1*

L Yamamoto1,2

1University of Hawaii at Manoa, Honolulu, HI

2Kapiolani Medical Center For Women and Children, Honolulu, HI

Purpose of Study

The standard door is a safety hazard for young children often resulting in crush injuries, nail avulsions, fractures, lacerations, and amputations. The purpose of this study is to redesign the door to reduce the risk of finger injuries in children.

Methods Used

A safety door was designed and a model of it was constructed for study. Its two major features utilize silicone rubber fins at the pinch points and a ‘piano’ hinge running the entire door length (instead of the conventional two or three separate hinges) to eliminate the space between the hinges. Ten door slams using five finger models (beef stick, green beans, string cheese, crayons, red licorice twists) were performed to observe and assess the resulting injuries from the safety door compared to a standard door. The severity of the resulting injuries were scored using a 0 – 8 numerical score.

Summary of Results

The safety door resulted in 1 amputation (0.7%) compared to 120 amputations in the standard door (60%, p<0.0001) and had significantly lower numerical injury scores (0.2 vs 4.8, p=0.0001).

Abstract 93 Table 1

Mean injury scores (SD) and 95%CIM in each of the doors using various models. *Not applicable because the safety door’s piano hinge eliminates this possible injury

Abstract 93 Table 2

Amputations in each of the doors using various models (10 trials per model item).

Conclusions

The safety door is less injurious than the conventional door and re-designing of the door will likely lower the risk of finger injuries in young children.

94 What’s the beef? Empowering youth to address bullying through art

P Xiong1*

L Rodriguez1

A Avila1

E Gastelum2

R Kinman2

1University of California Davis, Fresno, CA

2UCSF-Fresno, Fresno, CA

Purpose of Study

Although bullying is one of the most significant public health concerns for adolescents worldwide, school bullying prevention programs have been generally unsuccessful. Since adolescents generally listen more to their peers than to adults, we partnered with high-risk minority adolescents in a ‘youth-as-partner’ approach to increase awareness of bullying through innovative peer-led means.

Methods Used

UC Davis medical students and UCSF-Fresno Department of Pediatrics collaborated with the Men’s Alliance Programs at a local middle and high school to create a feeder program between the schools. Anonymous surveys and focus groups were used to ascertain student knowledge and awareness of bullying on campus, its psychosocial effects, and how to prevent or respond to bullying. Through peer-led focus groups, students defined the concepts of ‘bullying’ vs ‘beef’, with the term ‘beef’ new to the medical students and their supervising physicians. Middle school students shared their personal experiences with peers through the creation and performance of rap lyrics, while high school students wrote letters to mentor their middle school peers.

Summary of Results

Of 71 students who completed the survey, 35% reported having been bullied, while 2.7% reported having bullied someone else. They were bullied about their size (21%), friends (10%), and how they talked (8%), with bullying occurring in the classroom (17%), hallway (10%), and other unspecified places (28%). 35% of students felt that more than 50% of students on campus were bullied, while 8% believed that bullying happened to more than 75% of students. 17% of students were ‘strongly familiar’ with school anti-bullying services and 40% were ‘not familiar’. The student-written rap lyrics and letters were made into an electronic book for faculty, students, and physicians to view.

Conclusions

Adolescents were empowered to raise awareness of bullying through music and letter writing, defining bullying as about dominance, whereas beef was defined as a ‘glorified’ and ‘respected’ altercation between two equal persons. Although high-risk minority adolescents can successfully identify and address these two concepts within their own lives, physicians may need to differentiate between the two when discussing these concepts with their adolescent patients.

95 Walkability of San Bernardino County’s elementary schools in relation to school district sizes

R Guest1*

M Baum2

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

2Loma Linda University, Loma Linda University, Loma Linda, CA, US, Loma Linda, CA

Purpose of Study

Studies estimate that children get half of the recommended hour of physical activity throughout the school day. This study evaluates the relationship between the walkability loops around elementary schools in San Bernardino County’s (SBC) school districts and the districts’ sizes. This relationship is then used to determine if district size is a good diagnostic tool to decide which districts need increased resources allotted to families for exercise.

Methods Used

Using Google Maps, two walking loops were scored, using a modified version of the Center for Disease Control’s Walkability Audit Tool. The school’s highest value was used. Districts with 16 or more schools were compared to districts with less than 16 schools. Process was repeated with ten schools and five schools as thresholds. A Chi-Square calculator was used to analyze the data.

Summary of Results

District size was not shown to have an impact on the corresponding average loop score.

Conclusions

Low loop scores indicate that walking around the school for exercise is not feasible. Therefore, more resources should be provided to make their schools more fitness-friendly. The results above demonstrated that district size should not determine which schools need more physical activity resources because any district is susceptible to having low loop scores. Future research may reveal correlations between schools’ academic success and students’ physical activity.

96 Just-in-time training for video laryngoscopy in pediatric intubations

E Lum1*

S Sommer-Candelario2

S De Los Santos2

K Aeby1

S Choi1

J Lee-Jayaram1,2

1University of Hawai’i at Manoa, Honolulu, HI

2Kapiolani Medical Center for Women and Children, Honolulu, HI

Purpose of Study

Video laryngoscopy (VL) may augment pediatric intubations outside the operating room (OR). Training methods for skill development vary. We aimed to describe use of and intubation complications with VL before and after the implementation of a VL just-in-time-training (JITT).

Methods Used

We performed a retrospective chart review of non-OR intubations at a single hospital from January 2015 to March 2020. Intubation procedure notes were reviewed and data were collected on patient age, intubation method, operator characteristics, adverse events, number of attempts, and hospital department. The data were separated into pre-JITT (January 1, 2015-April 31, 2018) and post-JITT (May 1, 2018-March 1, 2020) periods. Our institutional review board deemed this study exempt. The change in VL use pre- and post-JITT was tested using Fisher’s exact test. Descriptive statistics were used comparing pre- and post-JITT complications of intubations with multiple attempts (IMAs) and intubations with 1 or more adverse event (AE).

Summary of Results

A total of 268 patients were intubated during the study period; 231 were pediatric patients. Among pediatric patients, 154 pre-JITT intubations and 77 post-JITT intubations were documented. Pre- and post-JITT VL use was 17(11%) and 17(22%), respectively (p=0.03). Pre-JITT, pediatric intubations in the emergency department (ED) and pediatric intensive care unit (PICU) numbered 72(49%) and 74(50%) with 12(16%) and 5(7%) intubations using VL. Post-JITT, pediatric intubations in the ED and PICU numbered 32(42%) and 44(58%), with 14(44%) and 3(9%) intubations using VL. In pre-JITT VL, there were 2(12%) IMAs and 0(0%) intubations with 1 or more AE. In post-JITT VL, there were 3(18%) IMAs and 1(6%) intubation with 1 or more AE.

Conclusions

VL use for pediatric intubations increased in the ED and PICU from pre- to post-JITT. The infrequency of pediatric intubations makes drawing significant conclusions regarding the impact on IMAs and AEs challenging. JITT shows the potential to increase VL use for pediatric intubations outside the OR but a decrease in complications was not observed.

97 The effect of parental income on children’s bmi

BM Rodriguez*

D Jhang

R Guest

C Irani

M Baum

Loma Linda University, Loma Linda, CA

Purpose of Study

Childhood obesity is a known epidemic that poses a concerning health and wellness consequence to children now and for their future health as adults. Childhood unhealthy weight is defined as a BMI > 85%ile. Normal BMI range fall between 5–85%ile for children less than 17.9 years. Combating this epidemic is difficult often due to complex socioeconomic contributors (Maziak, et al. 2008). Families with lower financial resources report having increased difficulty providing healthy meals for their family. These factors can increase the chance of the children becoming overweight or obese. This study aims to find a correlation between families with low incomes (less than $10,000–19,000) having children with a high BMI (>85%ile) compared to children with a healthy BMI (<85%ile).

Methods Used

Children identified as overweight or obese (BMI>85%ile) from a federally qualified community pediatric clinic were referred to attend a daily week long ‘Operation Fit Camp’ in Loma Linda, CA. At this camp, the parents answered questions regarding annual income. The BMI of the child camper was recorded.

Summary of Results

The sample size was N=639. Odds ratio and Chi-square statistics were calculated and showed that children with healthy BMI were 44% more likely to have low income parents than children with a high BMI [X2 (1, N = 639), p = 0.041].

Conclusions

Even though these results did not line up with previous literature, 71% of the children in the sample size had an elevated BMI. These were the results from a sample size in San Bernardino County, further studies should continue to explore the aspects affecting childhood obesity.

98 Drug use and the desire to quit among youths experiencing unstable housing

JL Carlson*

M Castella-Chin

BM Rodriguez

C Irani

M Baum

Loma Linda University, Loma Linda, CA

Purpose of Study

Drug use has been noted as a significant problem among homeless youth populations. Within those populations, youth can be further classified by age and gender. The goal of this study is to determine the most at risk demographic characteristics for ‘drug use’ in homeless youth and the demographic characteristics for youth that are ‘most wanting help quitting drugs’.

Methods Used

Surveys were distributed to homeless youth at first arrival for a day program at YouthHope Foundation in Redlands, CA. These surveys included demographic, social, and educational information questions. Data from these surveys was used to examine ‘drug use’ and the ‘desire to quit’ among the youth.

Summary of Results

The results of the surveys showed that statistically significant difference existed in drug use between youth differentiated by age: Female minor vs female adult (p<.00001) and male minor vs male adult (p<.00001) as well as their desire to quit(p<.00271 female age groups, p<.01093 male age groups). This indicated that female minors are at 45% lower odds for drug use, but also at 25% lower odds for wanting to quit than female adults. Male minors are at 42% lower odds for drug use, but also at 38% lower odds for wanting to quit than male adults.

However there was no significant difference in drug use based on gender: Male adult vs female adult (p=.363539), male minor vs female minor (p=.513002), and male vs female (p=.129936), or in their corresponding desires to quit (p=.596082, p=.647921, p=.356779 respective groups).

Conclusions

It appears that there is a correlation between drug use and aging, as well as aging and a desire to quit. This is not unexpected as drug exposure increases the longer youths are on the streets. It is insightful to note that older adults as a whole exhibit a stronger desire to quit. Further research is needed to determine if there are further correlations between increased desire to quit and certain drugs.

Endocrinology and metabolism I

Concurrent session

11:05 AM

Friday, January 29, 2021
99 Diabulimia: the hidden eating disorder

A Khine*

R Kinman

UCSF-Fresno, Fresno, CA

Background

Diabulimia is a condition where a person with diabetes restricts insulin use to lose weight. Diagnosis and treatment of diabulimia or other eating disorders in diabetic patients can be challenging as patients often have poor insight about their condition and are unwilling to pursue treatment.

Clinical Case

A 22-year-old woman presented with nausea, vomiting, and abdominal pain. She was found to be in diabetic ketoacidosis (DKA) with a HbA1c >15%. Her past medical history was notable for chronic idiopathic pancreatitis requiring total pancreatectomy and islet cell transplantation. She subsequently developed post-pancreatectomy diabetes, likely due to glucose toxicity of the transplanted islet cells. She was started on an insulin drip and transitioned to subcutaneous insulin when the DKA resolved. Her insulin doses decreased as her glucose toxicity improved, but her abdominal pain persisted and she was noted to have binging/purging episodes. She was evaluated by psychiatry who was concerned for anorexia with purging, and they initially determined that she did not have capacity to leave against medical advice due to poor insight. After multiple conversations with the primary team, endocrinology, psychiatry, and social work, she eventually admitted to an eating disorder and acknowledged withholding of insulin therapy. Due to showing some acceptance of her condition with a modest improvement in accepting therapy while in the hospital, she was then determined to have capacity to decide if she wanted further inpatient treatment. She declined an inpatient eating disorders program and was discharged on subcutaneous insulin.

Conclusion

This case illustrates the complex challenges associated with diagnosing and treating diabetic patients which can include medication noncompliance, diabulimia, and concomitant eating disorders. Although this patient eventually admitted to having an eating disorder, she still declined treatment and is at significant risk for continuing poor glycemic control, which can result in future complications. Recognition of eating disorders in diabetic patients is critical to institution of appropriate therapy. Management requires a multidisciplinary approach between the diabetic team and mental health services.

100 Retrospective analysis of total pancreatectomy with islet auto transplantation outcomes in pediatric patients with chronic pancreatitis

NJ Khatter1

JA Mark2

G Forlenza3

TM Triolo3*

1Oakland University William Beaumont School of Medicine, Auburn Hills, MI

2University of Colorado, Denver, CO

3University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Total pancreatectomy with islet auto transplantation (TPIAT) is a potentially curative treatment for patients with chronic pancreatitis (CP) refractory to medical and endoscopic therapies. Outcomes of patients who have undergone TPIAT are limited to single center follow-up. We characterized the traits and outcomes of pediatric patients in Colorado who underwent TPIAT.

Methods Used

We analyzed data of 9 pediatric patients who underwent TPIAT at the University of Minnesota over 13 years. We collected baseline and follow-up data of insulin total daily dose (TDD), HbA1c, c-peptide, BMI and weight, pancreas related hospitalizations, narcotic use, mental health, and nausea. Data are shown as mean±SD.

Summary of Results

Patients presented with CP at age 7.6±4.9 years. All patients presented with a genetic cause of CP: 6/9 PRSS1, 2/9 CFTR and one with PRSS1 and CFTR. Patients had 2.7±1.5 ERCPs prior to TPIAT and underwent TPIAT at 11±3.1 years. Islet mass transplanted was 5260±2663 IEQ/kg. Subjects had a follow-up of 4.63±3.6 years. Intestinal complications and surgical revision was required by 3/9.

No patients used insulin prior to TPIAT. At least 6 months post-TPIAT, 7/9 patients required insulin therapy with 5/9 still requiring treatment with subcutaneous insulin. At most recent follow up, TTD was 0.3±0.3 units/kg.

For those whom data was available (7/9) prior to TPIAT, average HbA1c was 5.3±0.3. Average HbA1c at 1 year post TPIAT was 5.9±0.8. Average HbA1c at most recent follow up was 6.7±1.7%. Of note, 4/9 paitents have HbA1c’s >6.5%.

Data on active narcotic prescriptions was available for 8/9 patients. Prior to TPIAT 8/8 patients required narcotics for pain control, post TPIAT, 4/8 keep an active narcotic prescription.

Conclusions

In the 9 known pediatric TPIAT patients in Colorado, all had genetic mutations for CP. More than half require insulin after TPIAT, but at a relatively low TDD. This may suggest endogenous graft insulin production and 4/9 patients have HbA1c’s in the non-diabetic range. Patients have reduced narcotic usage post-TPIAT as half of patients have a current active narcotic prescription.

101 Hypercalcemia heralds poor outcomes in multiple myeloma

K Gonzales1

MR Burge1

LC Sanchez2*

E Choi2

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

2University of New Mexico Health Sciences Center, Albuquerque, NM

Purpose of Study

Multiple Myeloma (MM) is often complicated by hypercalcemia of malignancy (HCM). Severe hypercalcemia is known to cause a variety of complications, as well as decreased survival. The degree of hypercalcemia among patients with MM can occur across a wide spectrum and may have variable effects on patient-related outcomes. Thus, we aimed to investigate the role of HCM on relevant endpoints and comorbidities among patients with MM.

Methods Used

De-identified patient data were obtained from the UNM Electronic Medical Record (EMR) Data Repository. A total of 717 individuals with an ICD-9/10 diagnosis of MM were identified from 2010 to 2019, and after exclusion criteria, 627 individuals remained. These were separated into two groups according to the presence (MM+HCM, n=54) or absence (MM-HCM, n=573) of HCM within 1 year of MM diagnosis. Clinical laboratory and outcome data were collected for 1 year after the diagnosis of MM, and the occurrence of specific comorbidities were collected using the entirety of the EMR data following diagnosis of MM. Binary logistic regression was used to assess the odds for clinical outcomes and common comorbidities between groups.

Summary of Results

Patients in the MM+HCM category had significantly higher serum calcium concentrations (10.0 vs. 9.3 (mg/dL), p <0.001) lower phosphate concentrations (3.2 vs. 3.5 (mg/dL), p = 0.03), and higher BUN levels (22 vs. 17 (mg/dL), p = 0.02) compared to those in the MM-HCM group. Hospital length of stay was significantly longer in the MM+HCM group (4.8 vs. 1.6 (days), p < 0.0001). The odds of readmission within 30 and 90 days of MM diagnosis was 2–3 fold higher in the HCM+MM group, and they had a mortality OR of 4.2 when compared to MM-HCM patients (p < 0.0001). Additionally, the odds of being diagnosed with heart failure, chronic kidney disease, acute renal insufficiency, or sepsis were significantly higher in the MM+HCM group compared to the MM-HCM group.

Conclusions

Patients with MM and HCM demonstrate significantly worse clinical outcomes and a higher burden of comorbidities compared to MM patients without hypercalcemia. HCM may aide in prognostication and risk stratification for patients with MM.

102 Impaired dietary decision-making in youth with congenital adrenal hyperplasia

LN Overholtzer1,2

S Luo2

S Lim3

E Kim1*

N Fraga1

M Herting1,2

VK Tanawattanacharoen1

M Geffner1,2

MS Kim1,2

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

2University of Southern California, Los Angeles, CA

3University of Missouri Kansas City, Kansas City, MO

Purpose of Study

Youth with congenital adrenal hyperplasia (CAH) have an increased prevalence of obesity, early adiposity rebound, and increased fat mass compared to controls. The inability to control food desire could contribute to obesity, and understanding food-seeking behavior could guide prevention. Key brain regions implicated in reward and dietary decision-making, including limbic brain regions and prefrontal cortex, have been shown to be smaller in CAH patients. However, little is known about dietary behavioral manifestations of these brain differences in CAH. We therefore aim to study food choices in youth with and without CAH.

Methods Used

37 CAH youth (12.2 ± 3.1 years, 60% male, BMI-Z 1.6 ± 0.8) and 100 controls matched for age and sex (11.7 ± 2.4 years, 57% male, BMI-Z 0.9 ± 1.2) completed a computer-based behavioral food choice task.They rated 30 high- and 30 low-calorie food cues for tastiness, healthiness, and preference for each food item. Youth then chose between food pairs discordant for tastiness and healthiness based on the individual’s own ratings. A successful food-choice trial (i.e., successful self-control) was evident when the healthier food was chosen. Cursor-trajectory analyses measured the area under the curve (AUC) and maximum deviation time (MDT) per choice trial.

Summary of Results

CAH and control youth did not display overall differences in their ratings of food cues (all P > 0.30) or in the percentage of total successful food choice trials (P = 0.16). However, CAH youth had larger average AUCs compared to controls [T(135) = -2.15; P = 0.03] for all choice trials, indicating greater cognitive conflict or increased cognitive effort during decision-making. In successful food choice trials, CAH youth had longer average MDTs [T(102) = -2.59; P = 0.01] indicating a later time window at which the final decision was made.

Conclusions

CAH youth have similar evaluations of food but different decision-making performance in our behavioral task compared to control youth. Greater cognitive conflict during food choice could reflect factors inherent to CAH such as abnormal hormones or neural pathways regulating dietary self-control and reward.

103 Analysis of enigma gene-signaling pathways in thyroid cancer

R Niihara*

N Churdsuwanrak

K Rood

C Yamauchi

K Wright

S Adil

S Mirshahidi

M Perez

A Simental

A Firek

S Khan

Loma Linda University, Loma Linda, CA

Purpose of Study

Fine-needle aspiration (FNA) is one of the most accurate modes of obtaining thyroid nodule biopsies, however, up to 25% of biopsies still yield indeterminate results. There is an increasing number of thyroidectomies due to indeterminate nodules by FNA alone. Therefore, more accurate and time efficient diagnostic approaches for analyzing indeterminate thyroid nodules is required. Recent studies showed that Enigma is associated with different cancer types, including thyroid cancer progression and calcification through its interaction with bone morphogenic protein-1 (BMP-1) and tyrosine kinases linked to mitogen-activated protein kinase (MAPK) signaling pathway.

Methods Used

Our published data on Enigma protein analysis with immunohistochemistry showed promising findings to discriminate malignant versus benign nodules. We also showed a thyroid cancer stage-dependent enhancement of Enigma protein expression. In this study, we are investigating Enigma at a gene expression level by quantitative reverse transcription polymerase chain reaction (RT-qPCR), which is more time-efficient, quantitative, and requires less tissue than immunohistochemistry. We extracted mRNA/DNA/proteins from fresh malignant and benign thyroid nodules using a Qiagen AllPrep DNA/RNA/Protein Mini Kit. After verification of the quantity and purity by NanoDrop, isolated mRNA was then run through Enigma-RT-qPCR. MAPK assay was done by western blotting using MAPK-antibody.

Summary of Results

Our initial results found that Enigma-mRNA expression level was 3-fold higher in malignant compared to benign thyroid tissues. This finding supports our previous protein expression data with a relative quantitative difference in Enigma-mRNA expression level between malignant and benign thyroid nodules. MAPK expression was upregulated in thyroid cancer compared to benign nodules.

Conclusions

We conclude that Enigma-RT-qPCR can be used effectively in FNA samples derived from thyroid nodules, which could potentially enhance the diagnostic accuracy of indeterminate nodules and decrease unnecessary thyroidectomies. Furthermore, both Enigma and MAPK were highly expressed in advanced tumor in the same tissues. Future study is needed to establish the functional interaction of Enigma-MAPK activity in thyroid cancer cells.

104 One month of supplemental testosterone does not significantly change the metabolome in transgender males

J Lo*

K Alexander

A D’Alessandro

T Heap

S Staggs

N Nokoff

M Cree-Green

University of Colorado Anschutz, Aurora, CO

Purpose of Study

Testosterone may be associated with cardiovascular disease (CVD) and recent studies suggest transgender males (TGM) on long-term exogenous testosterone have a higher risk of CVD than cisgender women but not men. We sought to determine whether there were significant changes in the metabolic/metabolomic profile in TGM adolescents receiving testosterone therapy.

Methods Used

Ten TGM adolescents [Age 15.2 (14.6–16.3) years, BMI 21.5 (18.4–27.6) kg/m2] were evaluated prior to and after 1 month of exogenous testosterone treatment in a longitudinal observational study. Demographics, physical exam, fasting laboratory measurements were collected. HOMA-IR was calculated as an estimate of insulin sensitivity. Untargeted and targeted serum metabolomics were performed with mass spectrometry. Metabolomic profiles before and after treatment and correlated with clinical variables. T-tests or Mann Whitney U were used to compare variables pre-post treatment and change with treatment was calculated for correlations. Metabolomic data analysis was performed with MetaboAnalyst.

Summary of Results

Per study design, participants had a significant change in total testosterone (250±107 ng/dL, p<0.001) and SHBG (-11.7±7.8 mg/dL, p=0.004) after treatment, although the cardiometabolic profile in terms of fasting total cholesterol (-1.50 mg/dL, p=0.82), triglyceride (3.3±17.3 mg/dL, p=0.84), HDL (-0.5±3.9 mg/dL, p=0.84),glucose (-1.2±7.1 mg/dL, p=0.81) and HOMA-IR (p=0.92) were unchanged. Principal component analysis indicated no significant difference in metabolomic profile with treatment. In the untargeted metabolomics analysis, the only significantly different metabolite was 2,3-Phospho-D-Glycerate. Exploratory analyses showed that increases in serum testosterone were associated with increases in several bile acids. Improvements in HOMA-IR were associated with increases in bile acids and several polyunsaturated fatty acids.

Conclusions

Exogenous short-term testosterone (1 month) does not significantly affect the cardiometabolic profile or the metabolome in TGM adolescents. Future studies will investigate the effect of 12 months of exogenous testosterone on the metabolomic profile in TGM adolescents.

105 Interventions to address health disparities in management of diabetic retinopathy among African Americans in the United States (US)

S Marquina1*

S Afzal1

R Chava1

A Cheong1

I Dastgheib1

J Hockman1

N Lingineni1

B Afghani1,2

1UC Irvine School of Medicine, Irvine, CA

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

Purpose of Study

Diabetic Retinopathy (DR) is a serious downstream effect of uncontrolled diabetes. Our objective is to assess the effectiveness of intervention strategies to improve the care of African Americans with diabetic retinopathy.

Methods Used

A literature review was performed on PubMed, and Google Scholar databases using the key terms: race, diabetic retinopathy, intervention, management, and African American. Only prospective controlled studies of adults (>18 years of age) that primarily involved diabetic African Americans in the US were included in this review.

Summary of Results

Of the 21 articles found, only 7 met our inclusion criteria (table 1). At baseline, the rate of dilated eye exams for patients with DR ranged from 19.2% to 65.1% in different studies. Although the majority of studies showed an increase in dilated eye exams after the intervention, the study with a multidimensional education and behavioral intervention showed the highest improvement (34.1% to 87.1%, p<0.001). Possible explanations for lack of significant improvement in 2 of the studies include small sample size as well as exposure of both control and intervention groups to other health initiatives which could have improved outcome in both groups.

Abstract 105 Table 1

Studies of diabetic retinopathy management in African-Americans

Conclusions

Our literature review suggests that intensive multidimensional and tailored intervention strategies are effective in improving the rate of eye exams in the African-American population with diabetic retinopathy. Follow-up studies to evaluate the long-term effectiveness of different interventions are needed to explain why a gap exists even after intervention.

106 11-oxygenated androgen metabolite concentrations are affected by pubertal progression and obesity

E Breslow*

A Taylor

C Severn

CL Chan

L Pyle

M Kelsey

M Cree-Green

U of Colorado Anschutz, Aurora, CO

Purpose of Study

The 11-oxygenated androgen metabolites are emerging as significant, bioactive compounds. These androgen compounds rise in early adrenarche and have unique expression patterns throughout the lifespan. The pattern of 11-oxyandrogen expression during normal puberty and the effects of obesity have not yet been reported.

Methods Used

This is a secondary analysis of healthy youth of both sexes, any BMI, enrolled in 5 prior endocrine studies (N=203). A subset of participants had longitudinal puberty data (51 participants with 129 visits). Pubertal development was assessed by a pediatric endocrinologist using Tanner stage criteria and fasting serum samples collected. Three 11-oxygenated androgens, 11-hydroxyandrostenedione (11OHA4), 11-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT), were analyzed via liquid chromatography tandem mass spectroscopy (Lapcorp/Esoterix). Linear mixed effect models were used to assess for difference by sex and pubertal stage, controlling for the effect of body mass index (BMI).

Summary of Results

In both cohorts, 11OHA4 and 11OHT increased in normal weight youth of both sexes between early (Tanner 2/3) and late (Tanner 5) puberty (p < 0.05). 11KT was non-significantly elevated as puberty progressed in normal weight youth in the cross-sectional cohort (p = 0.06). 11KT increased significantly in normal weight females between Tanner 2/3 and 4 in the longitudinal cohort (p < 0.05). 11KT differed between sexes (p < 0.006) with levels higher in normal weight males compared to normal weight females most notably at Tanner 2/3 (p = 0.02) and Tanner 5 (p = 0.02). 11KT differed between normal weight and obese youth (p = 0.01) with obese males having lower levels than normal weight males at Tanner 2/3 (p < 0.005) and Tanner 4 (p = 0.02). Trajectories of 11OHA4 expression throughout puberty differed between normal weight and obese youth of both sexes (p = 0.05).

Conclusions

11-oxyandrogens rise during pubertal development and may play a role in the phenotypic effects of puberty. 11KT expression differs between sexes, suggesting possible gonadal origin of this androgen that becomes evident during puberty. Obesity appears to influence the expression of 11-oxyandrogens.

Healthcare research III – machine

Concurrent session

11:05 AM

Friday, January 29, 2021
107 Development and evaluation of a volumetric assessment tool using an IOS-based app for three-dimensional clinical measurements

B Andreasen*

S Gupta

Loma Linda University School of Medicine, Redlands, CA

Purpose of Study

Objective clinical measurement of volume enhances clinical and surgical decision making by enabling physicians to rely on quantitative data rather than visual judgment. While complex systems have been developed for this purpose, a simple and cost-effective method to obtain such data has not been validated. This study investigates the feasibility of using an inexpensive, portable 3D scanner to clinically assess volume.

Methods Used

Balloons were filled to known volumes of fluid in 30cc increments between 300cc and 900cc, 100cc increments between 1000cc and 1500cc, and 250cc increments from 1500cc to 3000cc. The balloons were suspended and scanned with a Structure Sensor ST01 connected to an Apple iPad Mini. Two scans were taken at each volume. Resulting 3D scans were imported into Blender, a 3D creation suite, which calculated the volume of the balloons using the 3D scanner data. Calculated volumes were then compared to known volumes to evaluate the accuracy of the scanner.

Summary of Results

The 3D scanner yielded an overall average absolute percent error of 2.94% with a standard deviation of 1.54% (table 1). Analysis of the data revealed that the scanner was less accurate at the extremes (300–450cc and 1400–3000cc) and tended to be least precise at the larger volumes (1400–3000cc). Absolute percent error was less than 5% in 84.85% of all individual scans.

Abstract 107 Table 1

3D scanner yielded an overall average absolute percent error of 2.94% with a standard deviation of 1.54

Conclusions

The Structure Sensor ST01 used with an iPad Mini and a 3D creation suite yields sufficient accuracy for clinical assessment of volume. Although accuracy was not constant at all volumes, the pattern of absolute percent error present in the data followed the same pattern as the ability of individuals to perceive changes in volume – that is, the just-noticeable change in volume is relative to the initial volume. Larger errors were observed in the scans from 300–450cc and 1400–3000cc. Observable patterns in the data from the 3D scanner suggest that this method of measuring volume yields measurements that are sufficiently accurate to be valuable for clinical use.

108 Diagnosing musculoskeletal diseases using artificial intelligence and ensemble machine learning

JH Miao1,2*

KH Miao2,3

1Stony Brook University Renaissance School of Medicine, Stony Brook, NY

2Cornell University, Ithaca, NY

3New York University School of Medicine, New York, NY

Purpose of Study

From bone fractures to chronic joint diseases, one out of three people in the world are affected by a musculoskeletal (MSK) condition, impacting over 2 billion people globally. To diagnose and treat patients, physicians order X-rays and other medical imaging to evaluate patients’ MSK conditions. Especially during emergencies and in underserved areas, there is a high volume of imaging that needs to be analyzed with speed and accuracy, but there is often limited physician availability. Detecting abnormalities in MSK radiology with high accuracy and precision is thus essential. In this research, artificial intelligence is applied to create a machine learning model to evaluate musculoskeletal abnormalities in radiology, aid physicians in analysis, and ultimately improve patient outcomes through accurate MSK disease detection.

Methods Used

In this research, an ensemble machine learning model was designed and developed to help detect abnormalities in musculoskeletal radiographs. The ensemble machine learning model was applied to MURA, a musculoskeletal radiographic clinical patient dataset containing over 40,500 images from Stanford University. Data from 60% of the patients were used to train the machine learning model, and the remaining 40% of the patient data was used for testing performance.

Summary of Results

In diagnosing the MSK diseases in patients, the machine learning model achieved 78% sensitivity and 80.2% specificity.

Conclusions

Thus, based on the results, computer-aided diagnoses using artificial intelligence and ensemble machine learning can help detect abnormalities in MSK radiographs to aid patient outcomes. Furthermore, in areas where there are fewer radiologists present and limited access to healthcare, the machine learning model may be utilized as a cost-effective option to aid in the early detection and accurate diagnosis of MSK diseases in underserved populations.

109 Pain detection and diagnosis using machine learning

KH Miao1,2

JH Miao2,3

1New York University School of Medicine, New York, NY

2Cornell University, Ithaca, NY

3Stony Brook University Renaissance School of Medicine, Stony Brook, NY

Purpose of Study

According to the Centers for Disease Control and Prevention, more than 100 million Americans are affected by pain. Pain is multimodal and often complex to evaluate and diagnose. With early detection and diagnosis, patients can be counseled, treated, and managed with more optimal outcomes and a higher pain control rate. Therefore, detecting, predicting, and diagnosing pain early and accurately is critical for patient outcome optimization as well as improving quality of life for patients.

Methods Used

Expressive behaviors in facial emotion recognition and bodily movement detection from individual body parts have been found to aid in the detection of pain. In this research project, a machine learning model is developed using artificial intelligence with the above listed methodologies and clinical patient data to aid the detection and diagnosis of pain to increase its diagnostic accuracy.

The machine learning model was built using deep network algorithms to predict and diagnose pain in patients. Clinical data from patients with chronic pain and healthy participants was used to develop, train, and test the machine learning model. To train the model, 60% of the patient data was randomly selected, while the remaining 40% of the data was utilized for testing pain diagnosis capabilities of the model.

Summary of Results

In evaluating pain levels in patients, the machine learning model was able to achieve an overall accuracy of 58% compared to previously published methods ranging from 31% - 53% in accuracy.

Conclusions

Thus, machine learning algorithms can be used to help medical professionals globally for enhancing early detection and diagnostic accuracy of pain for optimizing quality of life in patient care.

110 Telemedicine solutions to improve HIV pre-exposure prophylaxis access in Fremont County, Wy

HJ True*

University of Washington School of Medicine, Laramie, WY

Purpose of Study

Fremont County, WY has a rural population of 39,803 with above average poverty rates. The county holds 9% of HIV cases (n=31) in Wyoming while holding 6% of the population. Sexually transmitted infection (STI) trends are above the Wyoming average and rising. The rural nature of the county makes access to HIV care and pre-exposure prophylaxis remarkably difficult. Limited access, high stigma, and low awareness creates a concerning public health environment for the future of HIV cases in the county. This paper examines the use of a public telemedicine service as a community-asset based approach to improve access to HIV pre-exposure prophylaxis.

Methods Used

The investigation into HIV pre-exposure prophylaxis (PrEP) in Fremont County was guided by two factors: 1) interviews with local providers, patients, and community organizations and 2) literature review. A patient interview provided context to the local community and sought to investigate both community assets and deficits. An interview with a public health nurse and two local providers further focused on public health concerns and highlighted local assets. Review of Wyoming public health reports, community needs assessments, and relevant literature were conducted to understand the importance of PrEP, HIV trends, and efficacy of telemedicine.

Summary of Results

A local provider cited a concern with the complete absence of PrEP care in the county and limited public education about STIs. Both interviews with public health and local patients revealed substantial access to technology required for telemedicine. Technology access, established relationships between public health and the nearest PrEP providers, and an existing communicable disease treatment program creates an excellent opportunity to capitalize on community assets to address deficits in PrEP access. Wyoming public health reports further reinforced the need for access to PrEP as a method of combating HIV in the state. Literature review provided promising insights into implementation of a ‘TelePrEP’ program for Fremont County.

Conclusions

Thoughtful implementation of a Fremont County TelePrEP program could significantly reduce the challenges to PrEP access while utilizing community assets already in place. If successful, there is great potential for expansion to a statewide program.

111 Efficacy of a high school ecosystem program on underrepresented minority student attainment of health professional careers

E Williams

N Hinds*

University of Washington School of Medicine, Los Angeles, CA

Purpose of Study

The purpose of this study is to explore the stories and career trajectory of high school students who participated in the U-DOC summer program at the University of Washington School of Medicine and regional sites from 1994–2012.

Literature concerning the effectiveness of pipeline programs’ role in increasing diversity in medicine is becoming more scarce due to the closure of several medicine-related ecosystem programs in recent years. This may further exacerbate the already severe lack of diversity within health professions and it is important to explore the impact these programs have in addressing physician workforce diversity.

Methods Used

During the tenure of the U-DOC program, there were 901 participants. We were able to track 244 and 91 went into health professions. 14 interviews were conducted with alumni after participants were identified via the snowball method. Of the 14 interviewed, 7 went into medicine or dentistry. A standardized set of questions was developed which elicited vivid accounts of the program as well as the interviewee’s career paths after that summer. Dedoose was used to analyze emerging themes identified.

Summary of Results

Interviewees noted the program’s significance in their later career choices. Themes that emerged were support and being surrounded by a diverse and driven group of peers. Interviewees reported the support and encouragement of the program’s faculty and their peers as helpful in pursuing advanced degrees. Some limitations in the program mentioned by the interviewees included difficult S.T.E.M. coursework in college and the need for longitudinal support after the program.

Conclusions

Students from low-income, first-generation households, and those who identify as underrepresented in medicine need support in pursuing medicine and other healthcare fields. The social support from peers as well as program faculty can be fundamental in their pursuit of S.T.E.M. studies in college as well as their perseverance when faced with obstacles. Summer-long residential ecosystem programs, like U-DOC, are conducted at an impressionable time in adolescence. The guidance, encouragement, and structure offered to students who are not typically encouraged to pursue S.T.E.M. fields can be life-changing, even if it leads to other professional careers outside of medicine.

112 Evaluating ethical concerns with machine learning to guide advance care planning

D Cagliero1

N Deuitch2

N Shah3

D Char4*

1University of Toronto Faculty of Medicine, Toronto, ON, Canada

2National Human Genome Research Institute, Bethesda, MD

3Stanford University School of Medicine, Stanford, CA

4Stanford University, Stanford, CA

Purpose of Study

To generate ethical guidance for machine learning-guided advance care planning (ML-ACP), using a prediction of 3–12 month mortality as a proxy to identify patients who could benefit from ACP, we sought to (1) understand the attitudes of clinicians, patients, and designers impacted by the ML-ACP and (2) identify where ethical problems were emerging or likely to emerge with deployment of the ML-ACP. The ML-ACP screened patients at admission to an adult, inpatient general medicine ward.

Methods Used

Our analytic framework relied on 5 premises: (1) multiple stakeholders are impacted by the ML-ACP and can be identified; (2) stakeholders have different explicit or implicit values/goals for the ML-ACP, that can be ascertained; (3) ML-ACP design involves making a series of decisions; (4) how a stakeholder makes these decisions, or would want these decisions made, reflects their underlying values/goals; (5) where stakeholder groups disagree about decisions are where ethical problems are most likely to emerge.

We used snowball sampling to identify stakeholders involved with or impacted by the ML-ACP and conducted 17 semi-structured interviews (computer scientists, primary care physicians, palliative care clinicians, oncologists and patients). Interviews were analyzed using modified grounded theory. All interviews were co-coded by two researchers and any areas of discordant coding were discussed to consensus through an iterative process.

Summary of Results

Stakeholders’ values/goals were in conflict on whether patients should be informed of their mortality predictions, who should receive the prediction (primary physician, palliative care, patient), and whether and how the working of the ML-ACP should be made transparent.

Conclusions

ML-ACP has the potential to improve ACP delivery by expanding patients’ access to needed palliative care services. However, our analysis suggests several areas where ethical concerns are likely to emerge and should be pre-emptively addressed prior to full ML-ACP deployment. Our analysis also suggests that pilot ethical analysis can be done and may be valuable to design teams considering ML solutions to other clinical problems.

113 Human-centered design in response to a pandemic: a health system and innovation center collaboration

S Simister*

SC Wasden

B McRae

S Jayaraman

B Fassl

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

Purpose of Study

In the spring of 2020, the coronavirus pandemic brought new challenges to healthcare systems as the rising demand for protective equipment led to product and resource inequalities around the globe. The inability to safeguard workers led to increased infection rates and deaths of healthcare professionals worldwide. The purpose of this study is to evaluate the response of an in-house innovation committee to meet the unforeseen needs faced by healthcare systems during an acute medical crisis.

Methods Used

Housed directly within the University of Utah’s health system (U Health), The Center for Medical Innovation (CMI) teamed up with the hospital’s administration, BME, COVID task force, and occupational health to create an innovative think-tank to tackle the challenges brought in by the coronavirus pandemic, with the purpose of stratifying clinical needs based upon acuity, frequency, and urgency. While prioritizing equipment needs, CMI used human-centered design to analyze common industry practices, engineer comparable solutions from commercially available materials, test reimagined products against known gold-standards, and create open-source assembly guides that allowed others facing similar shortages to do the same.

Summary of Results

The close-working relationship between CMI and U Health allowed for the rapid identification, innovation, and engineering of products that met the needs of healthcare workers during the months following the COVID pandemic. Many of these were directly adopted in clinical settings, including aerosol containment tents, powered air-purifying respirators, and self-testing stations. Additionally, CMI identified and engineered 20 additional readily producible, rapid-response products in anticipation of future needs, such as a bubble CPAP, containment boxes, and re-usable PPE. From these, dozens of open source, ‘Improvised Personal Protective Equipment’ manuals were shared with global partners to address the inequality of medical equipment in low-resource settings.

Conclusions

The rapid development of easily-producible, low-cost solutions for acute clinical needs—especially those faced by the equipment shortages seen during a pandemic—is improved via the partnership between health systems and a center for medical innovation.

114 Content analysis of frequency of information about developmental dysplasia of the hip on twitter

N Kodali1*

BV Sidhu1

E Schaeffer1,2

J So1

E Habib1

K Mulpuri1,2

1BC Children’s Hospital, Vancouver, BC, Canada

2University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Developmental dysplasia of the hip (DDH) is a spectrum of pediatric hip conditions. Early detection and screening of DDH is critical in reducing complications; thus, advocacy and awareness are paramount. Social media, particularly Twitter, connects users based on their content engagement, allowing a global audience to interact with one another. Twitter’s limitations on word count facilitate precise, condensed communication. Social media platforms were chosen in the study because of their strength to quickly disseminate information to a wide range of individuals; it is crucial that the published information is not misinforming the public. The objective of this study was to assess the frequency and content of information being published on Twitter pertaining to DDH.

Methods Used

An a priori coding guide using search terms was created to establish a framework to extract information regarding DDH on Twitter. Data was extracted over one-week periods in June and July of 2019 and 2020. An Excel-based coding guide was developed to organize and analyze the extracted data.

Summary of Results

A total of 146 tweets were extracted for analysis; 46 in 2019 and 101 in 2020. The most frequently-used search terms were hip dysplasia, developmental dysplasia of the hip, and dislocated hip. The most frequent authors were healthcare professionals and healthcare organizations in 2019 and patients in 2020. Prevention, treatment, and general discussions were top categories in 2019, compared to education, awareness and general discussions in 2020.

Conclusions

Our data indicates that over the span of a year, user engagement with DDH content on Twitter increased by 58.4%. We found similar patterns regarding the types of authors and content type in 2019 and 2020. Our analysis identified gaps in the use of Twitter that could be implemented by users to optimize messages, such as connecting directly and conversing with users through replies. Findings also indicate the importance of multi-author engagement to increase the breadth of distribution of information. Through analysis on how users utilize Twitter to inform the public about DDH, we aim to create tools that would promote advocacy and increase early detection and screening.

Neonatology pulmonary

Concurrent session

11:05 AM

Friday, January 29, 2021
115 Acetaminophen-induced neonatal lung injury and developmentally regulated CYP2E1 expression

E Dobrinskikh*

T Sizemore

L Sherlock

D Balasubramaniyan

R de Dios

L Zheng

CJ Wright

University of Colorado, Aurora, CO

Purpose of Study

Acetaminophen (APAP) during the perinatal period are rapidly increasing. Exposures occur with maternal ingestion during gestation, and postnatally for analgesia and treatment of the PDA. Study of the APAP-induced liver injury demonstrated that toxic exposures cause cellular injury due the CYP2E1 mediated production of the toxic metabolite NAPQI. In the mature lung, pulmonary CYP2E1 expression results in APAP-induced lung injury with toxic ingestions. However, whether the developing lung expresses CYP2E1, or is susceptible to the toxic effect of APAP exposure is unknown.

Methods Used

Pulmonary tissue was collected from the canalicular (e15), saccular (e18, P0, P3) and alveolar (p7 and p21) and pulmonary Cyp2e1 expression was determined using RNAscope and qPCR. Neonatal (P7; n=4–6 per time point) male mice were exposed to APAP (5 and 24 hrs; 280 mg/kg, IP). APAP-induced pro-inflammatory cytokine expression was assessed using qPCR, while liver and lung injury was assessed using previously validated morphometric measures.

Summary of Results

Pulmonary Cyp2e1 expression peaked in the saccular stage of development (e18) and was present in the early alveolar stage lung. RNAscope revealed very little Cyp2e1 expression in the canalicular stage lung, with expression becoming more diffuse in the developing pulmonary mesenchyme by e18. APAP induced significantly increased pulmonary expression of Cxcl1, Cxcl2, Cxcl10, Il1a and Il1b at both 5 and 24 hours of exposure (P<.05). No hepatic injury was noted histologically. In contrast, at 24 hours of exposure, the lung demonstrated significant increase in objective measures of respiratory and terminal bronchiolar injury, peripheral lung macrophage load and peripheral lung emphysema.

Conclusions

Cyp2e1, the enzyme responsible for converting APAP into the toxic metabolite NAPQI is expressed in the developing lung. Consistent with this observation, following toxic APAP exposures, the developing lung demonstrates injury in both the proximal and distal lung. These findings have implications for the use of APAP in the pediatric population. Further work is necessary to determine whether lung injury occurs with lower dose exposures or with repetitive exposures, and the implications of early life APAP exposure on pulmonary function later in life.

116 Impaired infant lung growth and function in mice with genetic deletion of endothelial cell-specific vitamin D receptor expression

E Bye1*

T Gonzalez1

G Seedorf1

E McGinn1

B Smith1

J Fleet2

SH Abman1

E Mandell1

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

2University of Texas, Austin, TX

Purpose of Study

To determine whether endothelial cell-specific genetic deletion of the VDR gene in mice (VDR-ECKO) disrupts normal lung growth during infancy, and whether these VDR knockout mice demonstrate impaired lung function during infancy.

Methods Used

We generated a mouse model with endothelial cell-specific VDR deletion using Cre-Lox recombination. Tie2Cre transgene mice expressing endothelial cell-specific Cre recombinase (Tie2Cre) were bred with mice expressing LoxP sites bordering exon 3 in the VDR gene. At two weeks of age, we measured distal lung structure by morphometric analysis (radial alveolar counts (RAC); lung mechanics by Flexivent (total respiratory system resistance and compliance; and right ventricular hypertrophy (RVH) by standard methods.

Summary of Results

At 2 weeks of age, body weight was not different in VDR-ECKO mice when compared with controls. Histologically, lungs from VDR-ECKO mice had impaired alveolar structure in comparison with controls as assessed by decreased RAC (P<0.05). In comparison with controls, lung mechanics were abnormal in VDR-ECKO mice, which included increased total respiratory resistance (p<0.01) and decreased respiratory lung compliance (p<0.01). RVH was not different between study groups.

Conclusions

We found that endothelial cell-specific genetic disruption of VDR impaired lung structure and mechanics in infant mice. We speculate that endothelial VDR plays an important role in endothelial cell function, which contributes to normal lung growth and development.

117 The effect of serotonin depletion on hypoxia induced bronchopulmonary dysplasia and pulmonary hypertension in mice

D Roberts1*

L Sherlock1

J Posey1

J Maltzahn2

E Nozik-Grayck2

C Delaney1

1University of Colorado Anschutz Medical Campus, Aurora, CO

2University of Colorado Anschutz, Aurora, CO

Purpose of Study

Pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) leads to worse clinical 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 patients and animals with experimental PH. Serotonin signaling blockade decreases pulmonary vascular resistance and prevents pulmonary vascular remodeling in preclinical neonatal PH models. We hypothesized neonatal TPH1 knock-out (KO) mice would be protected from hypoxia induced BPD and 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. Weights were recorded at 2 weeks. Plasma 5-HT levels were measured by ELISA. 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 VWF. PH was assessed by Fulton’s index and right ventricular systolic pressures (RVSPs). Data were analyzed by Prism via unpaired t-test or 2-way ANOVA via Bonferroni post-hoc analysis. Significance level p<0.05.

Summary of Results

TPH1 KO mice weighed less than WT mice in normoxia and hypoxia. Serotonin levels were significantly decreased in TPH1 KO mice. However, measurable levels of 5-HT remained in TPH1 KO mice. Alveolar development, vascular development, and RVSPs were similar in TPH1 KO and control mice. TPH1 KO mice were not protected from hypoxia induced alveolar simplification or hypoxia induced pulmonary vascular simplification. TPH1 KO mice displayed attenuated hypoxia induced pulmonary vasoconstriction, shown by reduction in RVSPs (32±0.66 — 29±0.55, p<0.006).

Conclusions

We speculate the lack of protection against hypoxia induced lung injury observed in TPH1 KO mice may be the result of decreased growth in KO animals and/or be a consequence of 5-HT levels.

118 Angiopoietin like protein-3 expression in neonatal lung and its role in experimental BPD

M Sahni1,2*

K Sandhu3

P Das4

V Prahaladan4

D Shah4

V Bhandari4

1University of Nevada Las Vegas, Boulder City, NV

2Pediatrix Medical Group, Sunrise Children’s Hospital, Las Vegas, NV

3Drexel University, Philadelphia, PA

4Cooper University Health Care Allied Health Programs, Camden, NJ

Purpose of Study

To demonstrate the presence of ANGPTL3 in human & mouse lung tissue & to evaluate its potential role in a mouse model of experimental BPD

Methods Used

ANGPTL3 expression was demonstrated in mice lung tissue, human lung tissue and human fetal endothelial cells using western blot. Newborn C57BL/6 mice were exposed to 60% O2 for the first 4 postnatal(P) days of life and recovered in room air (RA) for the next 10 days. ANGPTL3 silencing(si) RNA was administered in RA and BPD groups to evaluate its effect on pulmonary phenotype.

Summary of Results

Expression of ANGPTL3 was increased at P4 & BPD time points in mouse model of BPD when compared to RA controls. ANGPTL3 levels also increased in human lung tissue & human fetal lung endothelial cells, when compared to their controls. Administration of ANGPTL3 siRNA to the mouse model of BPD was associated with decreased BAL fluid cell counts, improved lung phenotype- decreased chord length, septal thickness & improved radial alveolar counts (all p<0.0001). It was also associated with a decrease in inflammatory markers, increase in Ang1 & decrease in cell death (figure 1)

Abstract 118 Figure 1

Administration of ANGPTL3 (si)RNA decreased IL’s, increased ANG1 & decreased cell death

Conclusions

ANGPTL3 is expressed in lungs and is increased in human and experimental BPD. Decreased ANGPTL3 was associated with decreased inflammation & cell death, & improved pulmonary phenotype in the experimental model of BPD, suggesting a potential role in the pathogenesis of human BPD.

119 Prostacyclin analog treprostinil enhances neonatal rat lung endothelial cell growth and angiogenesis in vitro

KG Thayapran*

G Seedorf

SH Abman

University of Colorado School of Medicine, Aurora, CO

Purpose of Study

Bronchopulmonary dysplasia (BPD) is the chronic lung disease that often follows preterm birth. Characterized by abnormal lung structure due to impaired alveolar and vascular growth, BPD is strongly associated with mechanisms such as postnatal hyperoxia and the risk for pulmonary hypertension (PH). Previously, we found that treprostinil (TRE), a synthetic prostacyclin analog, preserved lung structure and function, improved vascular growth, and prevented right ventricular hypertrophy in a hyperoxia-induced neonatal rat model of BPD. To determine whether the effect of TRE on neonatal lung development is partly due to the stimulation of angiogenesis, we studied the effect of TRE on rat lung endothelial cell (LEC) growth and tube formation in vitro.

Methods Used

LECs were isolated from 2-week old rats and grown in 10% FBS. To assess cell proliferation, LECs were plated in 2.5% FBS (5000 cells/well), grown in normoxia with daily media changes, and counted after 3 days. To assess angiogenesis, LECs were plated in 1% FBS (10,000 cells/well) on collagen and fixed in 4% PFA after 18–24 hrs in normoxia. Cells were imaged at 10x and tube formation was assessed by counting branch points per high powered field. For both assays, the following treatments were studied: untreated FBS (control), TRE (1uM), Axitinib (AX, selective VEGF receptor inhibitor; 10nM), and TRE+AX.

Summary of Results

TRE increased LEC growth and tube formation by 109% and 51%, respectively (p<0.01 and p<0.05). AX alone did not decrease LEC growth, and when TRE was administered with AX, the effect of TRE was not attenuated. However, AX alone decreased tube formation by 38% (p<0.01) but TRE administration with AX restored tube formation to control values.

Conclusions

TRE enhances LEC growth and angiogenesis in vitro, supporting our previous findings that TRE improves lung alveolar and vascular growth in vivo. Further, we found that VEGF receptor blockade reduces tube formation but not cell growth, but this effect can be reversed by TRE. We speculate that these findings suggest interactions between the VEGF and prostacyclin pathways that can be targeted to develop novel therapies to prevent BPD and BPD-associated PH.

120 IUGR reduces phospholipid containing DHA in the developing rat lung

A Cohen*

H Wang

J Cox

A Maschek

L Joss-Moore

University of Utah Health, Salt Lake City, UT

Purpose of Study

Intrauterine growth restriction (IUGR) reduces neonatal circulating docosahexaenoic acid (DHA). Human preterm neonates with reduced circulating DHA have an increased incidence bronchopulmonary dysplasia (BPD). BPD is characterized by impaired development of the lung periphery, a process driven by cell-to-cell communications and the epithelial-mesenchymal transition. The precise role of DHA in the developing lung, and thus its contribution to BPD, is not well understood. An unexplored and potential role of DHA in promoting lung development is via its contribution to cell-to-cell communication and membrane fluidity, something known to be enhanced by DHA incorporation into phospholipids (PL). To date however, the location of DHA within lipid fractions of the developing lung is unknown, as is the effect of IUGR on this DHA partitioning.

We hypothesize that DHA is highly represented within the PL fraction of the lung, and that IUGR reduces PL DHA. We further hypothesize that maternal DHA supplementation restores PL DHA in IUGR rats.

Methods Used

IUGR was induced by bilateral uterine artery ligation, control damns received anesthesia only. Maternal rats were randomized regular diet or diets supplemented with 0.1% DHA. At postnatal day 12 (d12) (toward the end of alveolar transition in the rat), rat pups were euthanized and lung tissue collected. Lung DHA content in all lipid fractions was measured using GC/MS, analysis was performed using MetaboAnalyst.

Summary of Results

IUGR rat pups weighed significantly less than control at birth, and continued to weigh less that control at d12. Maternal DHA did not affect rat pup weight. The majority of lung DHA was confined to the PL fraction and the triglyceride fraction. IUGR decreased DHA content in the lung PL fraction by 50%*, without significantly altering DHA content in TG fractions. Maternal DHA normalized the PL DHA content in IUGR rats, while reducing DHA content in the TG fraction by 20%*. *P<0.05.

Conclusions

We conclude that DHA is highly represented in the PL fraction of the developing lung, and that maternal DHA supplementation can restore IUGR-induced reductions in PL DHA. The implications of reduced PL DHA are less membrane fluidity and impaired cell-to-cell signaling, thus compromising lung development.

121 Blood transfusion in preterm infants and the subsequent development of bronchopulmonary dysplasia

T Lum1,2*

J Sugar1,2

R Yim2

S Fertel2

A Morales2

A Katheria2

1Western University of Health Sciences, Pomona, CA

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

Purpose of Study

Preterm infants are frequently transfused with red blood cells (RBC) in the NICU. Previous studies in neonates have found a need to escalate mean airway pressure or FiO2 in the hours immediately following RBC transfusion suggesting that there may be negative effects on lung function leading to bronchopulmonary dysplasia (BPD). The purpose of this study was to investigate the relationship between RBC transfusions and the subsequent development of BPD among preterm infants born at <32 weeks gestational age.

Methods Used

This study utilizes a retrospective cohort design to evaluate preterm infants born <32 weeks between May 2007 to August 2020. BPD was defined as supplemental oxygen dependency at 36 weeks postmenstrual age. Bivariable and multivariable regression were used to evaluate the association between RBC transfusion and the subsequent development of BPD.

Summary of Results

622 infants were evaluated. Three hundred ten (50%) infants received a total of 1397 RBC transfusion exposures. 50% received their first and/or only RBC transfusion after 72 hours of life. Bivariable regression revealed a significant association between RBC transfusion and the successive development of BPD (OR, 13.2 [95%CI, 7.7–22.7], P<0.0001). After adjusting for maternal age, placental transfusion, gestational age, birth weight, gender, surfactant administration, 5-minute APGAR score, and sepsis, receipt of RBC transfusion was associated with a 4.5-fold increased likelihood to later develop BPD (adjusted-OR, 4.5 [95%CI, 2.3–8.8], P<0.0001). This relationship was also retained in sub-cohort analysis of extremely preterm infants born <28 weeks (adjusted-OR, 2.6 [95%CI, 1.0–6.5], P=0.046).

Conclusions

Red blood cell transfusion was an independent predictor of the subsequent development of bronchopulmonary dysplasia in preterm infants after adjusting for prematurity and severity of illness at birth. Prospective studies employing therapies to reduce the need for blood transfusion, such as erythropoietin administration or ensuring placental transfusion at birth, are needed to confirm this association.

122 Active vitamin D is safe for postnatal supplementation in newborn rats

E McGinn1*

E Bye1

T Gonzalez1

G Seedorf1

B Smith1

J Fleet2

SH Abman1

E Mandell1

1University of Colorado, Denver, CO

2University of Texas System, Austin, TX

Purpose of Study

Maternal vitamin D deficiency (VDD) is associated with perinatal pulmonary morbidities. We have demonstrated that offspring of rodent VDD dams have sustained abnormalities of distal lung structure, increased airway hyperreactivity and abnormal lung mechanics. Active vitamin D, 1,25-OHD, treatment preserves lung structure and prevents pulmonary hypertension (PH) in an experimental model of bronchopulmonary dysplasia (BPD). However, due to potential systemic side effects of 1,25-OHD the therapeutic use has been limited. Our goal was to determine the safety of postnatal 1,25-OHD supplementation on lung development in infant rats.

Methods Used

Newborn control (CTL) rats received daily intra-peritoneal (IP) injections of either 1,25-OHD (1 ng/g) or saline. At two weeks, serum calcium, phosphate (phos) and 25-OHD levels were measured. Rat lung structure was assessed by radial alveolar counts (RAC), mean linear intercept (MLI), and pulmonary vessel density (PVD), and right ventricular hypertrophy (RVH) was determined by Fulton’s Index. Lung function was measured (total respiratory system compliance and resistance) under baseline conditions and after administration of methacholine (a bronchoconstrictor; 0–25 mg/ml) and albuterol (a bronchodilator; 0.83 mg/ml) to determine airway reactivity.

Summary of Results

In comparison with CTL rats, daily 1,25-OHD treatment did not affect body weight, serum 25-OHD, calcium or phos. Additionally, infant rats that were treated with postnatal 1,25-OHD did not have any differences in lung structure regarding MLI, RAC, and PVD, or the presence of RVH as compared to CTL. As compared to CTL, rats who received 1,25-OHD had no differences in total respiratory resistance or compliance, nor differences in reactivity to methacholine and albuterol treatment.

Conclusions

Daily 1,25-OHD treatment does not alter body weight, Ca-phos homeostasis, or 25-OHD levels. In addition, 1,25-OHD treatment neither alters distal lung structure or function, nor causes RVH. We speculate that postnatal treatment with biologically-active VD is potentially safe as a short term strategy but requires further study to determine efficacy for BPD prevention.

WAFMR and WSPR plenary award session and presentations

1:10 PM

Friday, January 29, 2021

123 Smooth muscle cell piezo1 in small bowel contractility and growth

G Bautista1*

Y Du1

N Martin2

M Martin1

1University of California Los Angeles, Los Angeles, CA

3California State University Northridge, Northridge, CA

Purpose of Study

Piezo1 is a recently described mechanosensitive Ca2+channel expressed in smooth muscle cells (SMCs) within the small bowel muscularis (SBM) yet its role in stretch-induced changes remains unknown. In vitro and in vivo methods were used to determine whether Piezo1 expressed in SMCs of the SBM is necessary for mediating acute and chronic stretch-induced intestinal contractility and growth of small bowel.

Methods Used

Using the Piezo1/Myh11-ERT2/CreLoxP system, we generated a mouse model with a tamoxifen (Tam) inducible-Piezo1 knockout (Piezo1ΔSMC) in SMCs. In vitro, SBM was isolated and developed on thermoresponsive hydrogel to acutely induce stretch when cooled to 33C. Confocal microscopy was used to record contractility/Ca2+ flux using gCaMP-6f indicator. In vivo, mice were given Tam and underwent distal SBO surgery to model chronic stretch.

Summary of Results

In vitro results show that acute stretch of Piezo1ΔSMC cells displays decreased frequency and a disorganized pattern of contractility/Ca2+ flux compared to an increase in frequency in control (Piezo1WT) cells. When treated with Piezo1 shRNA lentivirus, Piezo1WT cells had a cessation of contractility/Ca2+ flux with and without stretch. Similar results were obtained using human SBM. In vivo results show that Piezo1ΔSMC mice had longer villi and crypts, and increased Olfm4+ stem cells compared to Piezo1WT mice. The chronic stretch of Piezo1ΔSMC leads to an altered response to obstruction with significant attenuation in crypt and villi elongation and fewer Olfm4+ cells. Both in vitro and in vivo models of Piezo1ΔSMC led to downstream transcriptional changes expressed in SBM.

Conclusions

Our data suggest that Piezo1 in the SMCs of the SBM of humans and mice is essential for the maintenance of regular, rhythmic SMC contractility. In vivo, Piezo1 in SMCs partly mediate epithelial, crypt and stem cell expansion at homeostasis and chronic stretch. This data improves our understanding of how mechanosensitive channels mediate these changes and may have implications for future therapies for patients with gastrointestinal pathologies.

124 Lipid emulsion with fish oil and extremely premature infants: clinical outcomes

LJ Lee1*

E Kim1

T Romero1

KL Calkins1,2

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

2Mattel Children’s Hospital UCLA, Los Angeles, CA

Purpose of Study

100% soybean oil (SO100) emulsions are associated with low docosahexaenoic acid (DHA) concentrations in preterm infants. DHA is important for growth and neurodevelopment and may protect against parenteral nutrition associated cholestasis (PNAC). This study aims to compare DHA and clinical outcomes in premature infants who received SO100 or a lipid emulsion with DHA (15% fish oil, FO15).

Methods Used

Inclusion criteria for this observational study: 1) born between 2014–2019, 2) birth weight <1 kg, 3) received SO100 or FO15 >7 days, and 4) survival to hospital discharge. Gas chromatography/mass spectrometry was used to measure fatty acids in the red blood cell membrane (RBC).

Summary of Results

The mean (±SD) gestational age was 26±2 and 27±3 weeks for FO15 (n=43) and SO100 (n=43), respectively (p=0.2). Despite a greater RBC DHA% in FO15 (n=12) vs. SO100 (n=19) at study weeks 1–4 (p>0.05 for all), DHA decreased over time in both groups (-0.25%/week and -0.18%/week in FO15 and SO100, respectively, p<0.03 for both) with no difference in the rate of change between the two groups (p=0.7). When compared to SO100, FO15 reached full enteral feeds sooner (28±17 vs. 36±17 days, p=0.02). When compared to SO100, maximum conjugated bilirubin was lower in FO15 (1.3±3.0 vs. 1.9±3.3 mg/dL, p=0.001), and FO15 was less likely to develop PNAC (14% vs. 37%, p=0.03). The mean z-score change for weight was smaller in FO15 vs. SO100 (-0.3±1 vs. -0.8±1, p=0.02). After controlling for days to reach full enteral feeds, SO100 was associated with a non-significant increased risk for PNAC (OR 3.1, 95% CI 0.96–10.1, p=0.06), and growth trajectories were similiar regardless of lipid type (p=0.9). The incidence of chronic lung disease, retinopathy of prematurity, late onset sepsis, and necrotizing enterocolitis was similar when the two groups were compared (p>0.6 for all).

Conclusions

In this study, when compared to SO100, extremely premature infants who received FO15 had greater concentrations of DHA, but DHA still declined over time. Despite improved DHA status, infants who received FO15 had similar clinical outcomes when compared to infants who received SO100. Research is warranted to determine the optimal lipid emulsion for premature infants.

125 Investigating fetal body composition using magnetic resonance imaging

K Strobel*

S Kafali

S Shih

HH Wu

KL Calkins

University of California-Los Angeles, Los Angeles, CA

Purpose of Study

Skinfold thickness and nuchal subcutaneous fat (nSAT) in adolescents has been associated with metabolic syndrome. In a retrospective study, we hypothesized fetal nSAT would correlate with birth weight z-score and pre-pregnancy body mass index (BMI). Information from the study was used to develop a pilot study that aims to create free-breathing MRI (FB MRI) sequences for fetal body composition analysis.

Methods Used

We retrospectively analyzed fetal MRI in the second and third trimesters. Fetal nSAT (cm3) was measured from the tentorium attachment to vertebra T2. Inclusion criteria for the prospective study included healthy pregnant women. Total SAT, nSAT, and hepatic fat were measured by volume and proton density fat fraction (PDFF) maps.

Summary of Results

We analyzed nSAT in 17 MRI scans. Gestational age and pre-pregnancy BMI did not correlate with nSAT, but nSAT had a strong predictive value for birth weight and length z-scores (slope=0.5 and slope=0.8, respectively, p<0.01 for both). Infants with intrauterine growth restriction (IUGR) and born small for gestational age (SGA) had a significantly lower nSAT than non-IUGR and non-SGA fetuses (p=0.001 and p=0.02, respectively). In our prospective study, we completed 2 MRIs (figure 1).

Abstract 125 Figure 1

32 week fetus FB MRI. A. Anatomical MR images. Green line marks the scan plane for B. B. PDFF maps. Green marks subcutaneous fat ring. Blue indicates the liver. Black indicates 0% and white indicates 100% PDFF

Conclusions

This study demonstrates fetal nSAT can be measured using clinical MRI sequences and is a predictor of birth weight and length. Our on-going prospective study using FB MRI for fat analysis may provide insight into fetal origins of metabolic syndrome.

Adolescent medicine and behavior development III

Concurrent session

2:20 PM

Friday, January 29, 2021
126 Using myheartsmap to measure the association between psychosocial factors and persistent post-concussive symptoms in children

S Sparanese1*

KO Yeates2

MH Beauchamp3

R Zemek4

W Craig5

Q Doan6

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

2University of Calgary, Calgary, AB, Canada

3University of Montreal, Montreal, QC, Canada

4University of Ottawa, Ottawa, ON, Canada

5University of Alberta, Edmonton, AB, Canada

6University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Following mTBI, roughly 30% of children will experience persistent post-concussive symptoms (PPCS). This study will describe the association between psychosocial concerns and PPCS, using the Health and Behavior Inventory (HBI) and Post-Concussion Symptom Interview (PCS-I) scores.

Methods Used

Children aged 8 to 17 years seeking care for mTBI or for orthopedic injuries (OI) as controls, were recruited in the emergency department as part of a larger prospective cohort study. We have created three linear regression models to examine the association between severity of psychosocial issues by MyHEARTSMAP domain (Psychiatry, Social, and Function) and PPCS.

Summary of Results

We approached 153 participants and enrolled 122 (79.7%) to this study; 72 with mTBI and 50 with OI. Table 1 summarizes the adjusted coefficients among predictor variables on each measure of PPCS. Once adjusted for covariables, significant positive associations were found between scores on the Psychiatry domain and HBI Cognitive subscale, and Function domain with both HBI Somatic and PCS-I.

Abstract 126 Table 1

Regression coefficients between time-correlated MyHEARTSMAP scores and PPCS measures

Conclusions

Across all measures of PPCS, elevated scores in 2 of the 3 MyHEARTSMAP domains had a significant influence on count and severity of post-concussive symptoms. This suggests that multiple facets of psychosocial well-being have clinical utility in their association with functional outcome following concussion.

127 Quality assessment of youtube as an information source for public education related to national standards for concussion assessment in athletic youths

B Stothers

A Macnab*

The University of British Columbia, Vancouver, BC, Canada

Purpose of Study

National standards on the recommendations for the diagnosis of concussion have resulted in the standardization of clinical assessments and outcomes following injury. Purpose: to assess quality of public information on YouTube against national standards for concussion management in youth.

Methods Used

We used the YouTube search feature to select videos for relevance by using the terms concussion, head trauma, and sports head injury. Data were collected using a standardized questionnaire by 4 reviewers assessing nformation from YouTube against the protocols for assessment from the Canadian National Concussion Management Guideline (2017). Top viewed videos were rated for: voice, creation by health care, patient or third party. The DISCERN criteria for video assessment of consumer health information were used for evaluation (1 low quality through 5 high quality). T tests compared accuracy of information based on videos created by health professionals versus non health professionals. Agreement between assessors was determined by Pearson correlation coefficient (r).

Summary of Results

275 videos were identified published since 2017 of which 80 were related to concussion assessment. Of these 80, 25 were created by health professionals and the remainder were published by non-medically trained persons. Mean length was 10.25 minutes (range 1.5 to 15 min). The mean DISCERN score was 2.5 (range 1 to 4.5). 54% contained mis information, varying from guideline recommendations regarding how assessment for concussion is carried out and when to seek further medical attention. There was good correlation between reviewers answers which was (r >0.8).

Conclusions

Although YouTube is a population choice for the public when seeking information about medical conditions, the information regarding concussion assessment was deemed of poor quality and varied from recommendations by national guidelines. Importantly, the majority of videos were not created by medical health professionals and those that were had statically fewer views than those created by the lay public. Patients who use YouTube for health information regarding concussion may be misled as to the current rec9mmendations regarding assessment and treatment.

128 Developing tools to improve parent health literacy in nephrotic syndrome

EK Chan*

J Usprech

The University of British Columbia, Vancouver, BC, Canada

Purpose of Study

With prior research demonstrating that parent health literacy impacts pediatric patient nephrotic syndrome health outcomes, the project aimed to develop online lesson-plans that support parent health literacy by teaching immunology topics and condition-specific topics.

Methods Used

Lesson-plans were developed through research into effective online facilitation techniques and important aspects of nephrotic syndrome from a family and patient care perspective. The selected activities were then developed into lesson-plans, integrating parent and child engagement in each activity. All lessons were run over Zoom, allowing for continued engagement in a socially and geographically distanced format.

Summary of Results

Three lesson-plans were developed as hands-on activities that utilized accessible materials families could find in their kitchen (figure 1). These lessons were facilitated through three sessions to 8 families who were surveyed on their knowledge confidence pre- and post-lesson.

Abstract 128 Figure 1

Lesson Plan Highlights1) Innate Immune System Layered-Liquid Tower2) Active Immune System Annotation Game3) Coffee Filter Nephrotic Syndrome Demonstration

Conclusions

Parent feedback, while preliminary, suggested an increase in parental confidence in the discussed immunology and nephrotic syndrome topics. The creation of the lessons was successful, with three accessible online-facilitation based lesson-plans created to address three aspects of the condition. Research into the impact of lesson-plans on specific health literacy metrics is ongoing.

129 Racial disparities in pain management of children in the emergency department (ED)

HV Dayag1*

C Diyakonov1

I Kane Gomez1

A Martinez1

H Samiullah1

N Smyth1

B Afghani1,2

1UC Irvine School of Medicine, Irvine, CA

2CHOC Hospital of Orange County, Orange, CA

Purpose of Study

Inequities in management of a variety of illnesses has been described, but data on disparities in pain management in children is lacking. The objective of this study is to assess racial and ethnic disparities in pain management among pediatric patients seen in emergency departments (ED).

Methods Used

A literature review was conducted through Google Scholar and PubMed. Keywords included: racial disparities, bias, pain management, pediatric population, and health inequity. Only pediatric studies that were published in the U.S. within the last 10 years and focused on racial disparities in pain management in ED settings were included.

Summary of Results

Of 21 studies, 7 satisfied our inclusion criteria (table 1). The sample size ranged from 818 to 0.94 million pediatric ED patients. Minority children were more likely to recieve analgesics (any pain medication) for acute pain management, but compared to whites, minority children were less likely to receive opioids for moderate to severe pain. The retrospective nature of the studies poses some limitations, such as the of patient refusal to take analgesics, lack of documentation of pretreatment prior to ED visit or the misclassification of patient‘s race/ethnicity.

Abstract 129 Table 1

Management of pain based on ethnicity

Conclusions

Our review demonstrates possible racial and ethnic disparities in pain management in the ED setting. Although confounding variables and outcomes were not taken into account in some of the studies, all studies consistently showed that minority children were less likely to receive opioids for management of moderate to severe pain. Further investigation is necessary to better understand differential treatment in the emergency departments, and to create a standardized plans to eliminate any disparities.

130 Patient- and provider-level predictors of inappropriate imaging in pediatric urology referrals

A Nguyen1,2*

MB Iyer1,2

K Kieran1,2

1University of Washington School of Medicine, Seattle, WA

2Seattle Children’s Hospital, Seattle, WA

Purpose of Study

Bedwetting (MNE), undescended testes (UDT), and retractile testes (RT) are common reasons for referral to pediatric urology. Practice guidelines in multiple specialties strongly discourage imaging for these conditions, yet imaging is still prevalent. We sought to identify patient and provider characteristics associated with an increased risk of unnecessary imaging studies.

Methods Used

We identified all patients seen at our institution for MNE, UDT, or RT. Demographic information was collected, as were characteristics of the referring provider and practice setting. Personal, provider, and practice characteristics of patients with and without imaging were compared.

Summary of Results

We identified 287 patients referred for testicular issues and 137 patients referred for MNE. Imaging was ordered by the referring provider for 45.7% (16/35) of RT patients, 24.1% (47/195) of unilateral UDT patients, 26.3% (15/57) of bilateral UDT patients, and 8.8% (12/137) of MNE patients. Patients with and without testicular imaging were similar in age (median age 3.13 vs 3.71 years, p=0.50), and patients with imaging for MNE were older than those without (median 15.1 vs 11.6 years, p=0.0007). Female and male patients with MNE were equally likely to have imaging performed prior to referral (OR=2.29; 95% CI: 0.69–7.56). Of 317 providers, 64 (15.1%) were advanced practice providers (48 nurse practitioners [NPs], 16 physician assistants [PAs]) and 253 (84.9%) were physicians. Compared with patients referred by physicians, NPs were more likely to order imaging for testicular location and MNE (OR=3.32 [95% CI: 1.4–7.9] and OR=8 [95% CI: 2.73–23.41], respectively), while PAs were equally likely to order imaging for both diagnoses (OR=0.44 [95% CI: 0.05–3.6] and OR=0.73 [95% CI: 0.04–13.8], respectively). Providers working in academic and non-academic practices were equally likely to order inappropriate imaging (OR=0.48; 95% CI: 0.16–1.44).

Conclusions

Older children with MNE were more likely to undergo imaging, and NPs were more likely to order imaging for evaluating testicular location and MNE compared to physicians and PAs. These findings underscore the need for ongoing provider-level education on appropriate imaging for these conditions.

131 Urinary tract infections and associated risk factors in children with prenatal hydronephrosis

C McKinney*

C Ware

M Reimer

M Keheila

A Amasyali

D Chamberlin

C Chen

M Chau

J Chamberlin

Loma Linda University, Loma Linda, CA

Purpose of Study

The aim of this study was to describe the incidence of urinary tract infections (UTI) among children with prenatal hydronephrosis (PNH) and to identify associated risk factors.

Methods Used

The researchers retrospectively reviewed children who presented with confirmed PNH at a single tertiary children’s institution between 2012–2020. The primary outcome was the development of a UTI, defined as positive pyuria and single organism urine culture. Clinical data collected included sex, degree and laterality of hydronephrosis, and presence and degree of vesicoureteral reflux. Comparative analysis was completed using Fisher’s exact test with P value <0.05 considered significant.

Summary of Results

A total of 116 children with PNH were included in the study. Of these children, 7% developed a UTI during an eight-year follow-up period. On univariate analysis, there was statistically significant association between UTI rates and bilateral high-grade hydronephrosis (p=0.01). There was no significant association between UTI and sex, degree of hydronephrosis, unilateral hydronephrosis, or the presence of vesicoureteral reflux on univariate analysis. The cohort was 69% male and 31% female. At the first postnatal ultrasound, 40% had high-grade hydronephrosis (SFU grade 3–4), 44% had low-grade hydronephrosis (SFU grade 1–2), and 16% had resolved hydronephrosis. Of the hydronephrosis cases, 57% were unilateral and 43% bilateral. In this cohort, 92% underwent a voiding cystourethrography, with 12% found to have vesicoureteral reflux. Some required surgery including pyeloplasty in 28%, ureteral reimplantation in 3%, and Deflux injection in 2%. Of the cohort, 28% of patients had dilated ureter and 8% had a duplicated ureter.

Conclusions

In this cohort of children with PNH, the incidence of UTI was 7%. Bilateral high-grade hydronephrosis was associated with increased risk of UTI.

132 Variable drug and alcohol use among youths experiencing unstable housing and variable parental situations

JL Carlson*

BM Rodriguez

M Castella-Chin*

C Irani

M Baum

Loma Linda University, Loma Linda, CA

Purpose of Study

Drug and alcohol use has been noted as a significant problem among homeless youth populations. Within those populations, young people come from a variety of different parental marriage situations. Due to these different parental influences, the propensity of drug and alcohol use is also varied. This study looked at the influence of living with both parents or a single parent on youth drug and alcohol use.

Methods Used

Surveys were distributed to homeless youth at first arrival for a day program at YouthHope Foundation in Redlands, CA. These surveys included demographic, social, and educational information questions. Data from these surveys was used to examine drug and alcohol use among the youth and their parents.

Summary of Results

The results of the surveys showed that significant differences exist between youth coming from dual parent and single parent situations in regards to youth drinking (p<.012712), familial drinking problems (p<.000037), youth drug use (p<.000798), and familial drug uses problems (p<.000021). These values indicated that dual parent households are at 47% lower odds for familial drinking problems and 74% lower odds for youth drinking than single parent households. In addition, dual parent households are at 42% lower odds for familial drug use problems and 68% lower odds for youth drug use than single parent households.

Conclusions

In this study, there is a correlation between the parental situation of a household and family’s drug and alcohol use. Based on this data, it can be suggested that having both parents in the home has a positive impact on reduced alcohol and substance use of the youth and family. Further exploration is needed to determine if there is any relationship between drug and alcohol use having a causality in the separation of families and pressuring of youths to use drugs and alcohol.

133 Are housing instable LGBTQ youth at greater risk for abuse in San Bernardino?

M Castella-Chin

JL Carlson

BM Rodriguez

C Irani

M Baum

Loma Linda University, Loma Linda, CA

Purpose of Study

LGBTQ youths face many stigmas from society as well as their own family. A common reason for youth to run away from home is the abuse that they are subject to there. The purpose of this study was to determine if a subset of housing instable LGBTQ youth in the San Bernardino area has an increased risk for a history of abuse.

Methods Used

Surveys were collected from youth at a drop-in youth program in Redlands, California totaling 1398 surveys over the course of 10 years. The youth surveyed upon entrance into the program were all housing instable and had a mean age of 17.99 years old. They ascertained the history of abuse as well as each individual’s sexual preference. The surveys also collected information on ethnicity, mental illness history, education, relationship status, children, criminal history, parental marriage status, the location they sleep, history of street living, relationship with family, if they had run away or been kicked out before, history of alcohol and drug use, family history of alcohol and drug use, if they receive free lunches, and areas they need assistance in. Based on the information provided the surveys were divided into two groups based on answers to sexual orientation: LGBTQ or straight. Survey questions regarding the history of abuse and the type of abuse they experienced. The data was then analyzed using chi data squares and odds ratios.

Summary of Results

There were 618 surveys completed. Statistics reveal that total youth (N=618) that housing instable LGBTQ youth (N=88) are at a greater risk for abuse than housing instable straight youth(N=530) (p-value <0.05). Straight individuals have 41% lower odds of being abused than an LGBTQ+ individual. Straight males had 27% lower odds of being abused than LGBTQ males. Straight females had a 38% lower odds of being abused than LGBTQ females.

Conclusions

This study revealed that housing instable LGBTQ youth are at a greater risk for abuse in San Bernardino. Housing instable straight youth in San Bernardino are at a lower risk to have a history of abuse. Addressing stigma and biases experienced by those who are LGBTQ may be helpful in reducing the levels of abuse that they experience.

Hematology and oncology

Concurrent session

2:20 PM

Friday, January 29, 2021
134 EGFR, ERBB2 and ERBB4 fusions are recurrent alterations in multiple cancer types

L Schubert*

RC Doebele

University of Colorado School of Medicine, Aurora, CO

Purpose of Study

Gene fusions involving the HER family of genes, EGFR, ERBB2 and ERBB4 are rare, but potentially amenable to treatment with targeted therapies. The incidence of these fusions across cancers has not yet been comprehensively described. We sought to assess the frequency and characteristics of fusions involving the HER family of genes.

Methods Used

We utilized publicly available next generation sequencing data to assess the frequency of gene rearrangements involving EGFR, ERBB2 and ERBB4. We queried the TCGA PanCancer Analyses, MSK Impact and AACR GENIE data bases through cBioPortal (accession dates 6/18/20, 8/8/20, 8/8/20 respectively).

Summary of Results

The overall frequency of each type of fusion by data set is displayed in table 1. We found that EGFR fusions were most frequent in glioblastoma multiforme, oligoastrocytoma and astrocytoma. ERBB2 fusions were found most often in breast cancer, stomach adenocarcinoma and cervical adenocarcinoma. ERBB4 fusions were the least common overall, but most frequently found in breast cancer and non-small cell lung cancer. We assessed fusion partners in each category and the most common EGFR and ERBB2 fusions were EGFR-SEPT14 and ERBB2-PPP1R1B, respectively. There were no recurrent ERBB4 fusions identified in this study. We evaluated these fusions for co-occurrence of mutations in tumor suppressor genes within the TCGA datasets. Interestingly, we found that TP53 mutations cooccurred with ERBB2 fusions more often than in samples without ERBB2 fusions (74% in ERBB2 fusions vs. 36% of non-ERBB2 fusion samples).

Abstract 134 Table 1

Frequency of EGFR, ERBB2 and ERBB4 fusions

Conclusions

EGFR, HER2 and HER4 fusions are individually rare events but collectively represent up to 1% of all cancers, a significant number of patients with potentially actionable genomic alterations. These data highlight the importance of assaying for these mutations during clinical sequencing and suggest that further investigation into HER fusion biology and potential treatment options would be impactful.

135 CDK8-mediator complex plays positive transcriptional role in myc-amplified medulloblastoma

C Ritz1*

K Madhavan1,2

S Venkataraman1,2

R Vibhakar1,2

1University of Colorado, Aurora, CO

2Children’s Hospital Colorado, Aurora, CO

Purpose of Study

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and a heterogenous cancer with four distinct molecular subtypes. Group 3 MB, characterized by MYC amplification, carries a poor prognosis with a 50–60% 5-year survival expectancy. Current molecular therapies fail to outperform the standard therapy of surgical resection, CSI, and adjuvant chemotherapy. This treatment outcome is unsatisfactory due to significant long-term therapy induced morbidity. Therefore, there is a critical need to identify effective novel therapeutic targets. In this study, we investigate the role of cyclin dependent kinase 8 (CDK8), a mediator complex-associated transcriptional regulator as it was identified in a CRISPR druggable target screen in MYC-amplified MB.

Methods Used

Group 3 MB cells grown in DMEM supplemented with FBS, sodium pyruvate, penicillin-streptomycin, and non-essential amino acids or L-glutamine. Protein expression analysis completed with western blotting on 4–20% SDS-PAGE. Spheroid live cell imaging used to observe growth inhibition with titrated CDK8 chemical inhibitors Senexin B (10–2000 nM) and BI-1347 (0.25–50 nM).

Summary of Results

Here we demonstrated the role of CDK8 in survival and proliferation of MB. We found amongst multiple MB subtypes, cells express CDK8 at levels 20 to 30-fold higher than normal cerebellum. Spheroid live cell imaging revealed marked reduction in cell growth with chemical inhibition of CDK8 with IC50 in the nanomolar range (Senexin B IC50 = 218.6 nM; BI-1347 IC50 = 2.591 nM). We are investigating the biology of CDK8 in giving growth advantage to MYC expressing tumor cells and the impact of CDK8 depletion on mediator-complex stability.

Conclusions

Our results suggest that CDK8 plays a positive transcriptional role in MYC-amplified MB. We hypothesize this is occurring through loss of kinase phosphorylation at the CTD of RNA polymerase II, an interaction well characterized in yeast. While CDK8 has previously been implicated in colorectal cancer and BCR-ABL leukemia, its role in MB has not been established. The mechanistic elucidation of CDK8 in MYC-amplified MB could provide further information into its potential role as a clinical therapeutic candidate.

136 Use of natural products and over the counter supplements in breast cancer

M Hauer*

A Rossi

J Funk

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

Purpose of Study

The aim of this study was to identify the current use of dietary supplements, including natural products (e.g. fish oils), vitamins and minerals, by those diagnosed with breast cancer (BrC), including concurrent use with BrC treatments, and to examine the primary source of information used when choosing to take these supplements.

Methods Used

We developed an anonymous, online survey for subjects to self-report dietary supplement use as well as information regarding their diagnosis and treatment, recruiting patients through social media.

Summary of Results

Of 749 participants, most were non-Hispanic (94%), Caucasian (88%), and female (100%), with ER+ (Estrogen Receptor +) and/or PR+ (Progesterone Receptor +) (58%) the most common reported BrC subtype and 57 years the average age at diagnosis. Half reported current hormone therapy use, with aromatase inhibitors being the most common (83.6%). Vitamin and/or mineral use was reported by 81.9%, with prevalence of use highest for: vitamin D (69%), calcium (46%), multivitamin (38%), and vitamin C (27%). A health care provider was the most common primary source of information when choosing to take vitamins/minerals (e.g. 89% of calcium use was heath care provider recommended). Botanical supplement use was reported by 59%, the most common being: probiotic (21%), fish oil and/or omega-3 (22%), turmeric (18%), melatonin (17%), and cannabis (15%). The primary source of information for botanical supplement use was more diverse. For example, for turmeric, only 28% of use was health care provider recommended, with a similar prevalence (26%) attributable to information obtained via the internet. Some studies suggest antioxidant use with chemotherapy is associated with higher rates of breast cancer recurrence and mortality; thus it is concerning that 22% of patients undergoing chemotherapy were taking vitamin C simultaneously.

Conclusions

A majority of women diagnosed with breast cancer reported use of vitamin/mineral supplements and natural product-based supplements, as well as concurrent breast cancer treatment, with use of the former primarily based on health care provider recommendations, whereas the decision to take natural products supplements is based on information from a variety of sources and may have associated risks.

137 Associations between coffee or tea consumption and risk of upper aerodigestive tract cancers

CJ Yang*

M Kawasumi

University of Washington, Seattle, WA

Purpose of Study

Upper aerodigestive tract cancers (UADTC), which comprise oral, pharyngeal, esophageal, and laryngeal cancers, are a major global burden with approximately 1,407,000 new cases and 940,000 deaths annually. Given growing evidence for the anti-cancer effects of coffee and tea, we performed a meta-analysis to investigate whether there is a dose-dependent association between UADTC risk reduction and consumption of these beverages and to identify which regions in the world may experience the strongest benefit from these effects.

Methods Used

We used PubMed, Embase, and Scopus to search for observational studies that assessed the relative risk of UADTC with coffee or tea intake up to June 2020. Relevant and high-quality studies were selected by using the Newcastle-Ottawa Quality Assessment Scale for further data extraction and analysis. Summary relative risk (SRR) was determined by the DerSimonian and Laird random effects model, and dose response was estimated using linear regression.

Summary of Results

A database search yielded 32 high-quality studies with 27,866 cases of UADTC. High coffee consumption (≥3 cups/day) exhibited a reduced risk of UADTC with an overall SRR of 0.79 (95% confidence interval: 0.69–0.89). A significant dose-response effect of coffee was observed in oral and pharyngeal cancers with 9.4% risk reduction per cup, but not in esophageal or laryngeal cancers. Importantly, decaffeinated coffee had no effect on preventing UADTC. Compared to coffee, high tea consumption (≥1.6 cups/day) had a smaller effect on reducing the risk of UADTC with an SRR of 0.87 (0.78–0.97). The dose-response effect of tea was also observed in oral and pharyngeal cancers with 6.3% risk reduction per cup. The effects of coffee on preventing oral and pharyngeal cancers were most prominent in Europe and North America, and the effects of tea were strongest in East Asia.

Conclusions

Coffee or tea intake significantly reduces an individual’s risk for oral and pharyngeal cancer in a dose-dependent manner. This meta-analysis is limited by imprecise measurements of beverage consumption, particularly in retrospective studies. Future studies should explore other factors that may modify the effects of coffee or tea on UADTC, such as temperature, concentration, and regional preparations of the beverage.

138 Caffeinated or decaffeinated coffee consumption and risk of cancer incidence: a meta-analysis of prospective cohort studies

TN Nguyen*

D Eng

M Kawasumi

University of Washington School of Medicine, Seattle, WA

Purpose of Study

Cancer is the second leading cause of death globally. Coffee consumption has been reported to reduce the incidence of various cancers. However, previous studies showed variable results, and few studies have addressed the effect of caffeinated versus decaffeinated coffee on cancer incidence. We performed a meta-analysis to investigate what types of cancer are prevented by caffeinated or decaffeinated coffee.

Methods Used

We utilized PubMed, Scopus, and Embase databases to comprehensively identify peer-reviewed cohort studies that associate coffee consumption with cancer risk. The Newcastle-Ottawa Scale was used to assess the quality of nonrandomized studies in meta-analyses. Summary relative risk was calculated by using the DerSimonian and Laird random effects model. Dose response was analyzed by using linear regression.

Summary of Results

A total of 65 studies for 10 major cancer types were used for our meta-analysis. For all 10 cancer types combined, we found a 7% decreased risk of developing cancer in individuals who consumed large amounts of coffee (relative risk (RR) 0.93, 95% confidence interval (CI) 0.89–0.97). Caffeinated coffee consumption significantly reduced the risk of hepatocellular, endometrial, and skin cancers by 46% (RR 0.54, 95% CI 0.39–0.74), 39% (RR 0.61, 95% CI 0.44–0.84), and 17% (RR 0.83, 95% CI 0.74–0.92), respectively, whereas decaffeinated coffee had less or no effect in these three cancer types. Significant dose-response effects of caffeinated coffee were observed in hepatocellular, endometrial, and skin cancers with 9.9%, 7.4%, and 7.8% risk reductions per cup, respectively. In contrast, consuming caffeinated coffee may increase the risk of ovarian cancer (13% increase (RR 1.13, 95% CI 0.78–1.63)). Interestingly, decaffeinated coffee may reduce the risk of colorectal cancer (12% reduction (RR 0.88, 95% CI 0.73–1.07)). Coffee consumption had no association with risks of breast and prostate cancers.

Conclusions

Our meta-analysis demonstrates that caffeinated coffee consumption decreases the risk of liver, endometrial, and skin cancers and may increase the risk of ovarian cancer. These findings suggest that caffeine may prevent some types of cancer.

139 Histone demethylase kdm4b: a novel epigenetic target in atypical teratoid/rhabdoid tumor (ATRT)

EJ Wang*

I Alimova

S Venkataraman

R Vibhakar

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive childhood brain tumor. Current treatment options are limited with intensive chemotherapy and radiation which often create therapy-related toxicity that is especially critical in this young patient population. Previous studies reported the loss of SMARCB1, a member of ATP-dependent SWI/SNF chromatin remodeling complex, as the hallmark molecular feature of ATRT, creating an overall epigenetic dysregulation of ATRT genome. We utilized an unbiased epigenome-wide RNAi screen and identified KDM4B, a histone lysine demethylase 4B, as one of the novel epigenetic regulators that is critical for ATRT growth. Therefore, the objective of this study is to provide a mechanistic rationale for targeting KDM4B in SMARCB1 deleted ATRTs.

Methods Used

ATRT cell lines and patient tumor samples were used to validate the screen through both genetic perturbation and pharmacologic small-molecule inhibition. Chromatin immunoprecipitation (chIP) sequencing was performed to understand the epigenetic remodeling driven by KDM4B using these knockdown cells.

Summary of Results

Genetic inhibition of KDM4B in ATRT has decreased cell viability by 79.3% and impaired the ability of tumor cells to form colonies. KDM4B has been shown to regulate oncogenetic pathways by demethylating the repressive mark, H3K9Me3, which promotes compaction in promotors. Here we found that suppression of KDM4B leads to a global increase in protein expression of H3K9Me3. This suggests an hinderance of transcriptional activation which is currently being explored using integrated chIP and RNA-sequencing. Importantly, KDM4B is highly expressed in ATRT tumor cells and patient tumors compared to normal cells, thus making it is an excellent candidate to specifically target ATRT tumors while protecting the normal cells. In line with this, the small molecule inhibitors of KDM4B shows preferential suppression of ATRT cells in comparison to normal astrocytes.

Conclusions

We anticipate this finding to implicate a promising translatable potential of KDM4B as a new target with a favorable therapeutic window. It additionally furthers our understanding of ATRT epigenetic biology and is a starting point to develop better targeted therapies that can be translated to the clinic.

140 University of British Columbia nepal sickle cell project status report 2015–2020

S Lim*

J Taylor

K Patterson

SY Starkey

K Gray

C Lanz

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

Purpose of Study

In 2015 the University of British Columbia partnered with Creating Possibilities (CP), a charitable organization located in Dang, Nepal. Each year, a team of medical students is sent to assist CP in the long term management of sickle cell disease (SCD) in rural Western Nepal. Due to COVID-19 limitations, we were unable to travel to Nepal this year for the field component of our project. Instead, we took this opportunity to reflect on the project as a whole and create a project status report, outlining the past five years of work. The purpose of this report included: summarizing overall project progress, identifying future project directions, and improving communication amongst project stakeholders.

Methods Used

To create the project status report, our team reviewed all project documents since 2015. We also conducted virtual interviews with previous team leads to clarify questions and fill in gaps. Project progress was assessed by comparing activities completed to date to the project’s initial three main objectives.

Summary of Results

The first objective of characterizing the prevalence of SCD among the Tharu population is currently ongoing. Since 2015, we have conducted large-scale screening of the Tharu population, with 4483 individuals having been screened by our team. Thus far, a hemoglobin S prevalence of 9.3% has been estimated. Our second objective of identifying barriers to SCD management is also ongoing. Since 2016, yearly focus groups and needs assessments have been conducted with community members and health workers. Common themes of barriers included accessibility, financial limitations, and education. Finally, our third objective of implementing sustainable solutions for long term detection and management of SCD still needs to be addressed.

Conclusions

Screening and needs assessments will continue as we progress toward addressing our first two objectives. Following consultation with experts and a literature review, we have identified a pilot newborn screening program for SCD as the first step in addressing our third objective.

141 Quality of life and comorbid mental health conditions in patients with cutaneous t-cell lymphoma

T Olmstead1*

M Shinohara2

D Hippe2

1University of Washington School of Medicine, Seattle, WA

2University of Washington, Seattle, WA

Purpose of Study

Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that present in the skin. Previous research on CTCL indicates that quality of life (QoL) is decreased. Given that co-occurrence of mental health (MH) conditions in patients with cancer is as high as 58%, we seek to explore quality of life (QoL) for patients with CTCL and comorbid mental health conditions. In addition, we will place our results in context by comparing QoL in patients with CTCL to those with other dermatologic conditions such as non-melanoma skin cancer (NMSC), psoriasis, and vitiligo.

Methods Used

A cross-sectional, anonymous electronic survey was administered via a link posted on the Cutaneous Lymphoma Foundation (CLF) Facebook page and via email listserv to members of the CLF from February-April 2019. The survey included two validated instruments: Skindex-16 and the Functional Assessment of Cancer Therapy: General (FACT-G). Numeric results were additionally compared to existing data for other skin conditions.

Summary of Results

372 total survey responses were received, with 73 incomplete responses. 45% of respondents reported at least one MH condition. The emotional subscale of Skindex-16 was objectively higher than both symptoms and functioning subscales, indicating worse QoL for those with comorbid MH conditions. Fact-G also assesses QoL, with lower scores corresponding to worse QoL. The emotional well-being subscale score was comparable to other subscale scores including physical well-being, social/family well-being, and functional well-being.

Conclusions

Roughly half of respondents with CTCL in our study had comorbid MH conditions. QoL for patients with CTCL is negatively affected by MH conditions. When compared to other research on CTCL using the same study instruments, our overall QoL is similar or slightly lower. QoL for our cohort was generally worse than that of patients with NMSC and vitiligo, and similar to psoriasis.

Neonatology general III

Concurrent session

2:20 PM

Friday, January 29, 2021
142 Predictors of venous thromboembolism in neonates: a pediatric health information system study

MC Easterlin1*

Y Li2

L Yieh2

C Gong2

P Friedlich2

A Lakshmanan2

1LAC+USC Medical Center, Los Angeles, CA

2Fetal and Neonatal Institute, Children’s Hospital Los Angeles, Los Angeles, CA

Purpose of Study

The prevalence of venous thromboembolism (VTE) is increasing in newborns. However, this trend is not well understood. We sought to: 1) examine the prevalence of VTE in neonatal patients 2) assess patient-level and hospital-level risk factors for VTE and 3) examine secondary outcomes related to VTE including length of stay and mortality.

Methods Used

We included infants <6 months discharged from Pediatric Health Information System (PHIS) NICUs between Jan. 1, 2016-Dec. 31, 2019. Multivariable logistic regression examined associations between VTE and demographic factors (birthweight, sex, race, ethnicity), socioeconomic status (insurance), and hospital region. We also examined clinical factors (hyperalimentation, mechanical ventilation, infection, extracorporeal membrane oxygenation (ECMO), operations).

Summary of Results

201,033 infants were included; 2,319(1.15%) had a VTE. Infants who had a VTE were of lower birthweight and gestational age. There was variability among hospitals in incidence of VTE (0.1–4.7%). In multivariate analysis, birthweight <1000 grams (OR 3.03, 95% CI [2.65–3.46]), 1000–1500 grams (OR 1.77, 95% CI [1.51–2.06]) vs. 2500-<4000 grams, and public insurance (OR 1.20, 95% CI (1.09–1.32]) vs. private insurance were associated with significantly increased risk of VTE; while Black race (OR 0.87, 95% CI [0.77–0.99]) and other race (OR 0.71, 95% CI [0.58–0.86]), vs. White, were associated with significantly lower risk of VTE. In multivariable regression assessing clinical factors, TPN, mechanical ventilation, infection, ECMO, and surgery were associated with significantly increased risk of VTE (table 1). Mortality (13.4% vs. 3.5%, p<0.001) and length of stay (mean 65±28 vs. 21±65 days, p<0.001) were significantly increased among infants with VTE.

Abstract 142 Table 1

Regression of clinical factors on VTE adjusting for demographics, insurance, and hospital location

Conclusions

Neonatal VTE was significantly associated with low birthweight, White race, public insurance, TPN, mechanical ventilation, infection, ECMO, and surgery. Infants with these characteristics may require closer monitoring for VTE.

143 Sociodemographic factors associated with attendance at high risk infant follow-up clinic among neonates with hypoxic ischemic encephalopathy

A Cera*

JG Anderson

P Joe

UCSF Benioff Children’s Hospital Oakland, Oakland, CA

Purpose of Study

Hypoxic ischemic encephalopathy (HIE) is a leading cause of neurologic injury amongst term neonates. HIE patients should be followed longitudinally by a multidisciplinary team through a high risk infant follow-up (HRIF) clinic. While studies have evaluated lack of follow-up among premature infants, few have examined HIE patients, a group at high risk for neurodevelopmental deficits.

Methods Used

Retrospective analysis of infants with HIE born between 2010–2016 and discharged from the UCSF Benioff Children’s Hospital Oakland NICU. Data was collected from the California Perinatal Quality Care Collaborative database. Sociodemographic characteristics associated with at least one follow-up visit at HRIF were examined.

Summary of Results

Of the cohort of 192 babies, 146 (76%) had at least one HRIF visit. On univariate analysis Hispanic ethnicity (p=.03), public insurance (p=.024) and greater household distance from BCHO (p=.017) were associated with follow-up. On multivariate analysis, primary caregiver education beyond high school was most strongly associated with follow-up [OR 5.1, p=.04, 95% CI (1.04–24.7)].

Abstract 143 Table 1

Characteristics of infants with follow-up vs infants with no follow-up.

Abstract 143 Table 2

Summary of multivariate analysis for characteristics predicting follow-up

Conclusions

Awareness of caregiver educational level may offer an opportunity for targeted interventions to improve follow-up rates at HRIF clinic.

144 The impact of low hematocrit at birth on very low birth weight infants

A Hisey1,2*

S Sakhamuru2

T Tagliaferro2

L Barton2

R Ramanathan1,2

M Biniwale1,2

1Keck School of Medicine, Los Angeles, CA

2LAC + USC Medical Center, Los Angeles, CA

Purpose of Study

Low hematocrit (HCT) at birth has been associated with intraventricular hemorrhage (IVH) in extremely premature infants. However, there is limited evidence of other neonatal outcomes in those with a low HCT. This study aims to evaluate the effects of low HCT at birth on neonatal outcomes in very low birth weight infants (VLBW).

Methods Used

Retrospective data of all VLBW infants born at LAC + USC from 2009–2019 was gathered. Low HCT at birth was defined as a value of 40% or less. Short term neonatal and long term developmental outcomes were analyzed against low HCT.

Summary of Results

Of 311 patients included in the study, 97 (31.2%) had low HCT at birth compared to 214 (68.8%) with normal HCT. Presence of a low HCT at birth was significantly associated with presence of acidemia in cord blood gas at delivery (24.2% vs 9.9% p = 0.001). Infants with low HCT were more likely to have a lower birth weight (1025 g vs 811 g, p < 0.001) and gestational age (GA) (28.2 w vs 25.8 w, p < 0.001). These infants also had lower 5 minute APGAR scores (p < 0.001) and were significantly more likely to need intubation at birth (56% vs 43.4% p = 0.046), chest compressions in delivery room (23.1% vs 13.6% p = 0.045), and use of epinephrine in delivery room (7.9% vs 2.6% p = 0.038). Infants with low HCT levels were also significantly more likely to have IVH (60.5% vs. 28.1% p < 0.001), severe IVH (11.2% vs 2.1% p = 0.001), bronchopulmonary dysplasia (BPD) (53.8% vs 24.6% p < 0.001), retinopathy of prematurity (ROP) (81.7% vs 43.1% p < 0.001), and severe ROP (22% vs 8.9% p = 0.004). Long term developmental outcomes were not significantly affected for infants born with low HCT.

Abstract 144 Table 1

Regression analysis of infants with low HCT adjusting for gestational age.

Conclusions

VLBW infants with low HCT at birth may require more extensive resuscitation at the time of delivery and are at higher risk to develop IVH, BPD and ROP. Long term neurodevelopmental outcomes may not be significantly affected in infants born with low HCT.

145 Neurodevelopmental outcome at 18 months of corrected age for late preterm infants born at 34 and 35 gestational weeks

R Nakasone*

K Fujioka

K Iijima

Kobe University Graduate School of Medicine, Kobe, Japan

Purpose of Study

This study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age of late preterm infants (LPI) born at 34 (LPI-34) and 35 (LPI-35) gestational weeks (GW) and to elucidate factors predicting neurodevelopmental impairment (NDI).

Methods Used

Records of all LPI born at 34 (n=93) and 35 (n=121) GW from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and patients without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the KSPD at 18 months of corrected age. NDI was defined as DQ < 80 or the condition that neurodevelopmental assessment was impossible because of severe neurological disability. The clinical characteristics and DQ value of the subjects were compared between LPI-34 (n=62) and LPI-35 (n=73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared the clinical factors between NDI (n=17) and control (n=118) groups. Differences were deemed statistically significant for p<0.01.

Summary of Results

No significant difference was found in DQ values at 18 months of corrected age between the groups in each and all areas. Among clinical factors, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had high prevalence rates in the NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI (0.284, p<0.001).

Abstract 145 Table 1

Psychomotor development data of the late preterm infants born at 34 and 35 gestational weeks

Conclusions

No significant difference in neurodevelopmental outcome at 18 months of corrected age was found between LPI-34 and LPI-35. Thus, routine neurodevelopmental evaluation for both LPI-34 and LPI-35 might be beneficial to detect NDI.

Surgery I

Concurrent session

2:20 PM

Friday, January 29, 2021
146 Simulation of post-procedural compression on autologous fat grafts: a pilot study

H Peterson*

A Park*

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Autologous fat grafting, or autologous fat transfer (AFT), is a procedure during which fat is grafted from one part of the body to another. AFT is widely used, but the impact of post-procedural care options remains largely unstudied. This study examined the impact of post-procedural compression on adipocyte viability in an in vitro simulation of autologous fat graft under a compression garment.

Methods Used

Adipose tissue was harvested with low-pressure liposuction from an abdominoplasty and buttock lift procedure and from a bilateral mammoplasty reduction. The tissue was placed into 3 oz plastic cups to a depth of 3 mm, and cups containing lead weights were stacked on top. The weights were used to simulate pressures ranging from 15–30 mmHg. The adipose tissue was incubated at 37°C, 5% CO2 for 4 hours.

Adipocyte viability was measured with the alamarBlue assay. AlamarBlue reagent was mixed with the adipocytes in a 1:9 ratio. The mixture was incubated at 37°C, 5% CO2 for 2 hours, then diluted 3x with Ringer’s Lactate. Absorbance was measured at 570 nm.

Summary of Results

Results are summarized in Abstract 146 figure 1.

Abstract 146 Figure 1

The effects of compression on adipocyte viability. A) The absorbance of alamarBlue viability assays on adipocytes compressed at various pressures. This graph represents compiled data from 3 separate trials of the experiment, with each trial being conducted in triplicate. The x axis represents the different pressure conditions that were intended to simulate various pressures created by post-surgical compression garments. The y axis represents normalized absorbance by subtracting absorbance at 600 nm from absorbance at 570 nm, as indicated by the alamarBlue protocol. Normalized absorbance was directly proportional to adipocyte viability. Compression at any or the pressures was not found to significantly affect adipocyte viability compared to the control condition of 0 mmHg. B) Relative viability of adipocytes compressed under various pressures compared to the control of 0 mmHg, using compiled data from 3 separated experimental trials. The x axis represents the different pressure conditions, while the y axis represents% viability of the experimental group compared to the control group with an assigned viability of 100%. C) The absorbance of alamarBlue viability assays on adipocytes compressed at various pressures, from the second trial of the experiment. Samples were set up in triplicate for each pressure condition. The axes possess the same meanings as those in graph A. This graph demonstrates a trend observed over two of the experimental trials, each using adipocytes from a different patient: while no statistically significant differences in absorbance were observed in the compiled data, on select occasions 25 mmHg of Pressure was found to increase adipocyte absorbance (and thus viability) while 30 mmHg was found to decrease adipocyte absorbance and viability. For this trial. significant differences were observed between 25 mmHg and the other pressurized conditions of 15 mmHg, 20 mmHg, and 30 mmHg. D) Relative viability of adipocytes from the second experimental trial compressed under various pressures compared to the control condition of 0mmHg. The axes possess the same meaning as those in graph B.*p<0.05**average of 8 replicates

Conclusions

Compression was not found to significantly affect adipocyte absorbance and extrapolated viability. However, on select occasions moderate pressure (25 mmHg) seemed to increase adipocyte absorbance and viability while the higher pressure of 30 mmHg had the opposite effect. Further studies investigating this potential trend are warranted.

147 Fat graft harvest ergonomics: characterization of force based on anatomical location and cannula size

A Park

H Peterson

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

ForceData, a force measuring smart phone application, was used to characterize the applied force generated during liposuction of different anatomical locations, patients and cannula sizes.

Methods Used

The force of liposuction was measured from two surgeons using a 4-mm diameter (416 g) cannula and a 6-mm diameter (322 g) cannula on the abdomen and buttock of patient 1, and the abdomen of patient 2. An iPhone wrapped in a sterile drape was strapped to the mid-dorsal surface of a surgeon’s forearm with IV tubing. Force measurements were collected every 0.04s for 1 minute. Peak force values were normalized to a biological zero obtained by stimulating liposuction in air.

Summary of Results

The buttock, a high resistance area, produced consistent results with the 6-mm cannula: the 6-mm cannula produced more force than the 4-mm cannula and the buttock required more force than the abdomen (figure 1). The abdomen, an expected lower resistance area, and the use of the 4-mm cannula, produced less consistent results. Patient 1, with a history of multiple abdominal surgeries, required more force exerted than the patient 2 (figure 2).

Abstract 147 Figure 1

Force exerted from Surgeon 1 and Surgeon 2 in Patient l’s abdomen and buttock with a 4-mm diameter cannula and 6-mm diameter cannula.Black brackets - comparing locations with same cannulaGray brackets- comparing cannulas in the same location*Indicates a significant difference p<0.05

Abstract 147 Figure 2

Comparison of force exerted the in abdomen of Patient 1 and Patient 2 by Surgeon 1 and Surgeon 2 with a 4-mm diameter cannula and a 6-mm diameter cannula.* Indicates a significant difference p<0.05.

Conclusions

Results were consistent with the qualitative description of forces exerted by the surgeons. The use of the ForceData app during fat harvesting procedures is a promising method of characterizing the forces exerted during liposuction.

148 A pilot study to evaluate a simple short-term storage method for preservation of harvested lipoaspirate

A Park

H Peterson

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Cryopreservation studies have been described in literature for long-term adipocyte storage, but no simple, validated method exists for storing adipocytes for short periods of time. The purpose of this study was to investigate the efficacy of a mixture of Ringer’s Lactate (RL) and Dextrose 5% in Water (D5W) as a method of preserving adipocytes for up to a week after harvest.

Methods Used

Adipocytes were harvested from a patient using liposuction with a 4-mm diameter cannula. Isolated adipocytes after centrifugation were gently mixed in a 1:1 ratio with the preservation mixture consisting of 3-parts RL and 1-part D5W. The preserved adipocytes were stored at 4°C. An AlamarBlue assay was used to assess the viability of the adipocytes on postoperative days 1, 2, 5, 7 in experiment 1 and postoperative days 0, 1, 2, 5, and 7 in experiment 2. Absorbance values at 570 nm were compared using a t-test with an alpha value of 0.05. Relative percent viability was determined.

Summary of Results

The results are presented in figure 1.

Abstract 148 Figure 1

The effects of a preservation mixture on adipocyte viability over time. A mixture of one-part Ringer’s Lactate (RL) and three-parts Dextrose 5% in Water (D5W) was added to a specimen vial in a 1:1 ratio with isolated fat cells. The mixture was stored at 4°C A) An AlamarBlue assay was used to measure absorbance at 570nm. Absorbance from post-operative days 2, 5, 7 were compared to post-operative day 1 using a t-test. B) An AlamarBlue assay was used to measure absorbance at 570nm. Absorbance from post-operative days 1, 2, 5, 7 were compared to post-operative day O using a t-test. C) Relative percent viability was calculated with post-operative day 1 assigned as 100% viable. D) Relative percent viability was calculated with post-operative day o assigned as 100% viable.*indicates p<0.05

Conclusions

This preliminary study suggests that a 1:1 fat to preservation solution (3-parts RL and 1-part D5W) mixture is a promising method of short-term preservation defined as a 48-hour post-harvest period. Further replication and additional studies are needed. Future studies should assess efficacy of the preservation mixture over longer periods of time.

149 A cluster of comp, SFRP4, LEF1 AND PDGFRB genes predicts worse survival for colon cancerpatients especially in the young

E Wusterbarth1*

P Omesiete2

A Cruz2

J Jandova1

V Nfonsam2

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

2The University of Arizona Department of Surgery, Tucson, AZ

Purpose of Study

Colon cancer (CC) incidence has decreased overall in the last three decades but continues to increase in young patients. Early onset CC (EOCC) presents at advanced stage with more aggressive features. Expression of Cartilage Oligomeric Matrix Protein (COMP), Secreted Frizzled-Related Protein 4 (SFRP4), Lymphoid Enhancer Factor 1 (LEF1) and Platelet Derived Growth Factor Receptor Beta (PDGFRB) confer aggressiveness in EOCC. This study explores association between the co-expression of these genes and overall survival.

Methods Used

CC and matching noninvolved tissues from 6 EOCC and 6 late-onset CC patients were obtained from pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated, and profiled for expression of 770 cancer-related genes. cBioPortal for cancer genomics was used for survival analysis of 379 patients from TCGA COADREAD database. Gene-level transcription estimates are shown as log2(x+1) transformed RSEM normalized count.

Summary of Results

There is significant overexpression of COMP, SFRP4, LEF1 and PDGFRB in EOCC compared to late-onset. All four genes showed significantly poorer survival when they were queried individually with p-values as follows: COMP=0.0413, SFRP4=0.0277, LEF1=0.00306 and PDGFRB=0.0212. As a group, the decrease in overall survival was more profound with p-value 0.000235.

Conclusions

COMP, SFRP4, LEF1 and PDGFRB are individually significantly overexpressed in EOCC and associated with poorer survival. When co-expressed, survival is significantly worse. Gene clusters are potential prognostic biomarkers for EOCC and aggressive CC in general.

150 Applying process improvement to autologous fat transfer: ranking quality of evidence

H Peterson*

A Park*

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Autologous fat transfer (AFT) is a procedure where fat is grafted from one part of the body to another. Despite its various clinical uses, a standardized procedure for AFT does not exist, and there is large variability in reported outcomes. Clinical process improvement is the practice of identifying and improving existing processes to optimize performance and improve the outcome of a procedure. This study applied the process improvement method to evaluate the current quality of evidence for each step of AFT in order to highlight areas requiring further research.

Methods Used

A literature search on PubMed was conducted for each step of AFT. The key words were ‘Autologous Fat Transfer/Grafting AND [step terms] AND [survival/outcome of interest]’. 130 articles were examined. An ‘A’ rank indicated that high-quality evidence such as large randomized clinical trials and prospective observational studies exist for that step. A ‘B’ indicated a mix of small clinical trials and anecdotal pieces. A ‘C’ indicated that only anecdotal, animal, and/or basic science literature exist, or that no supporting literature currently exists. Rankings of ‘A/B’ or ‘B/C’ were used when different aspects of the step had differing levels of evidence.

Summary of Results

Results are summarized in table 1.

Abstract 150 Table 1

Ranked quality of evidence for each step of AFT.

Conclusions

A process improvement approach successfully revealed that the majority of the steps in AFT lack high-quality supporting evidence. Larger clinical trials are needed to standardize and optimize the AFT method.

151 Applying process improvement methodology to autologous fat transfer: a guide to future research

H Peterson

A Park

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Autologous fat grafting, or autologous fat transfer (AFT), is a procedure during which fat is grafted from one part of the body to another. Despite its wide range of clinical uses, a standardized process for AFT does not exist, and there is large variability in reported outcomes. Clinical process improvement is the practice of identifying and improving existing processes to optimize performance and improve the outcome of a procedure. A previous study by our group conducted a literature review to evaluate the current quality of evidence existing for each step of AFT. This study continued the process improvement of AFT by identifying the remaining research questions in order to organize progress towards optimization of AFT.

Methods Used

Current quality of evidence for the AFT process was examined by evaluating this group’s previous literature review and ranking of evidence. All of the ‘C’ ranking steps were selected. A ‘C’ ranking meant that the literature that existed for that step, if any, was anecdotal, animal, and/or basic science evidence. The studies supporting these steps were then revisited to determine which questions did not have definitive answers in the literature. These questions were then compiled into a table.

Summary of Results

Results are summarized in table 1.

Abstract 151 Table 1

Research questions for AFT without definitive answers in the current literature. Questions due to a lack of high-quality evidence are not bolded, while questions due to minimal evidence overall are in bold

Conclusions

There are many research questions regarding the AFT process with no high-quality evidence or minimal evidence of any quality to answer them. Further studies to answer these questions are warranted in order to improve AFT outcomes.

152 Ideal cannula characteristics for increased adipose cell viability in autologous fat grafting measured with alamar blue assay

A Park

H Peterson

S Gupta

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Process improvement autologous fat grafting techniques have been described in literature but few address cannula hole characteristics and none have conducted studies in which hole characteristics are compared when all other parameters, such as cannula diameter and hole number, are constant. Two groups of cannula pairs were used to collect fat through liposuction from female patients in order to compare adipocyte cell viability based on cannula hole arrangement and size.

Methods Used

Group 1 compared 2-mm 3-holed cannulas arranged in a circumferential and one-sided fashion. Group 2 compared 4-mm 3-holed cannulas with 7 mm x 2 mm and 10 mm x 2 mm hole sizes. Besides the characteristic in question, all other parameters where equal. The lipoaspirate collected from each cannula were centrifuged. The isolated adipocytes were mixed in a 1:1 ratio with a preservation solution (3-parts RL and 1-part D5W). Cell viability was analyzed through an AlamarBlue assay. Absorbance values at 570 nm were compared using a t-test with an alpha value of 0.05. The experiment was replicated twice. Experiment 1 was analyzed a day post-operation while Experiment 2 was analyzed the day of.

Summary of Results

The results are presented in figure 1.

Abstract 152 Figure 1

Comparison of absorbance between cannula hole arrangement and cannula hole size in Experiment 1 and Experiment 2.* Indicates a significant difference p<0.05

Conclusions

This preliminary study suggests that cannula hole arrangement and an increase in cannula hole area does not hold a significant effect on adipocyte viability in liposuction procedures. Further replication and additional studies are needed. Future studies should compare cannula holes of various different arrangements and sizes along with a comparison between different numbers of holes.

153 Examining the disease burden of the diffuse sclerosing variant of papillary thyroid carcinoma, a retrospective review

C Brady1*

E Rudzinski2

J Dahl2,1

S Manning2

D Hawkins2

1University of Washington, Seattle, WA

2Seattle Children’s Hospital, Seattle, WA

Purpose of Study

Little data exists on the clinical course of the diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC); however limited reports suggest it is a more aggressive variant of differentiated thyroid carcinoma. We aim to characterize the disease burden at initial presentation, treatment outcomes, and clinical course for patients with DSV compared to a cohort of PTC patients.

Methods Used

Single institutional retrospective review of patients undergoing treatment for PTC and its variants at Seattle Children’s Hospital from 1/1/05 to 4/1/20. Patients were included in the study if they had their initial thyroid surgery at Seattle Children’s and were under the age of 23 years old at the time of presentation. Statistical analysis was performed using descriptive statistics and the Fisher Exact Test.

Summary of Results

A total of 72 patients were included in the study; 63 (87.5%) with PTC and 9 (12.5%) with DSV. Mean follow-up times for DSV and PTC were 29.88 ± 8.91 months and 37.84 ± 6.32 months. DSV patients required surgery at a younger age than PTC (14.63 ± 2.23 years and 15.61 ± 0.72 years). DSV were significantly more likely to have with regional cervical (n=9 vs n=38, p < 0.03) and distant metastasis (n=6 vs n=14, p < 0.02) at time of presentation. Of those with 5-year follow-up data available, DSV were significantly less likely to be disease free (n=0 vs n=20, p < 0.05) and were significantly more likely to experience persistence and/or progression of disease, compared to PTC (n=8 vs n=28, p < 0.02). DSV were significantly more likely to have RET-CCDC6 mutation (n=3 vs n=1, p < 0.02).

Conclusions

Our findings contribute to the understanding of DSV’s prognostic significance as patients had a worse disease burden related to age at surgery, metastasis, persistence and progression of disease compared to PTC. This will help clinicians prepare patients and families for the potential of more aggressive primary surgery as well as for the possibility of persistence and/or progression of disease. Finally, we showed an association between DSV and the RET-CCDC6 mutation. Larger studies are needed to confirm the association between the RET-CCDC6 mutation and DSV as novel therapies targeting the RET protein may change disease management.

Genetics II

Concurrent session

3:15 PM

Friday, January 29, 2021
154 MECP2 mutations in two male patients and natural history of the disease

MK Haanpää

Turun yliopisto Laaketieteellinen tiedekunta, Turku, Finland

Purpose of Study

MECP2 pathogenic variants cause Rett syndrome (OMIM 312750). It is an X-linked neurodevelopmental condition characterized by loss of spoken language and hand use with the development of distinctive hand stereotypies. Initially normal progress is followed by a period of regression. Other characteristic features are feeding problems, seizures and severe intellectual disability. It is predominantly in females with a high rate of early loss in hemizygous male pregnancies.

The function of MECP2 protein is not completely understood. It binds to methylated CpGs and can both activate and repress transcription. It is required for maturation of neurons and is developmentally regulated. The majority of RTT-causing mutations are de novo events.

Methods Used

Recent studies have shown male patients with MECP2 mutations with higher phenotypic variation. The clinical spectrum of Rett syndrome in males is considered to be wider that previously expected. Both clinical symptoms and specific genetic mutations might modulate disease severity. Males with MECP2 mutations display quite significant neurodevelopmental issues.

Summary of Results

We report here on two male patients with MECP2 pathogenic variants of non-consanguineous European parents. One of them is the oldest male patients described. Thus, this will lighten the natural history of the male disease phenotype. Other patient is a young toddler and other one is in his 40’s. They have different pathogenic variant in MECP2 gene found in exome sequencing. Detailed clinical and molecular description will be presented.

We demonstrate that some consistent clinical features occur in male with MECP2 mutations, including features similar to females with RTT. However, these features are variable and remain less distinctive than in females. Clinical involvement in males with MECP2 mutations is remarkably broad, ranging from cognitive impairment to neonatal encephalopathy associated with early death.

Conclusions

In conclusion these findings provide broader insights into the MECP2 in males and extend the mutation spectrum and describe natural history of the disease. MECP2 is a severe and progressive condition with a grave prognosis. Securing a diagnosis provides crucial information to the family.

155 Atypical presentaton of imprinting defect angelman syndrome with expressive language

R Punatar*

A Egense

SP Shankar

UC Davis, Sacramento, CA

Purpose of Study

Describe an atypical presentation of Angelman syndrome (AS) with expressive language.

Methods Used

Chart review, literature review, and clinical evaluation. Genetic testing included cytogenomic SNP microarray, fragile X (FMRI) studies, AS/PWS methylation studies.

Summary of Results

A 16-year-old boy initially presented due to obesity, hyperphagia, and intellectual disability. He was reported to have hypotonia as an infant. At 3 years of age he developed hyperphagia, and he was obese by 7 years. His speech and language milestones were severely delayed with first word approximately at 7 years. Currently, he speaks in 3–5 word phrases. He has a no history of seizures. Initial testing included normal cytogenomic SNP microarray and normal fragile X (FMR1) studies. AS/PWS methylation studies came back positive for AS with no evidence of mosaicism.

Conclusion

AS is an imprinting disorder caused by disruption of the maternally inherited UBE3A gene in the 15q11.2-q13 region. AS is usually characterized by severe developmental delay, seizures, absent speech, gait ataxia, and happy demeanor. Individuals with atypical AS with history of hyperphagia, obesity, and verbal language ability have been described. A recent study of 22 individuals with mosaic AS found similarities which included developmental delay and preserved expressive language skills. Mosaicism in AS is believed to occur due to a postzygotic loss of imprinting in some of the cell lines, resulting in a somatic mosaicism.

While it is tempting to speculate that this individual is also a mosaic AS given his clinical presentation, there was no evidence for mosaicism in the blood sample. To our knowledge this is the first description of an individual with AS with preserved expressive language skills where mosaicism was not identified, although mosaicism in other tissues has not been tested. This case illustrates the atypical phenotypic spectrum of AS and need for additional evaluation when confronted with atypical clinical features of a well described genetic syndrome.

156 A case of familial COL4A1 mutations, an important differential diagnosis on neonatal porencephaly

LT Forero1*

M del Campo1

J Friedman2

R Troxell2

1University of California San Diego, San Diego, CA

2University of California San Diego, La Jolla, CA

Case Report

We describe two siblings with COL4A1 mutations and porencephaly presenting in early infancy. Our goal is to contribute to the literature supporting the assessment for this condition in neonatal stroke and porencephaly.

Patient 1: Presented at 6 months with global developmental delay and hemiplegic cerebral palsy (CP). Pregnancy was remarkable only for preterm labor at 30 weeks, requiring steroids. Patient was born via vaginal delivery at 38 1/7 weeks. Initial eye exam showed esotropia, amblyopia, hypermetropia and astigmatism. Family history was positive for hemiplegic CP and seizures in a 4-year-old sister (patient 2). MRI brain showed severe white matter volume loss, cystic encephalomalacia, ex-vacuo dilatation of lateral ventricles, small left thalamus and thin corpus callosum. Whole genome sequencing (WGS) revealed a paternally inherited, heterozygous, likely pathogenic variant in COL4A1, affecting the canonical splice site.

Patient 2: Presented at 6 months with GDD and asymmetrical tone, and later developed global developmental delay and seizures. Eye exam showed bilateral esotropia and hypermetropia. MRI brain showed large bilateral porencephalic cysts and later periventricular leukomalacia as well. WGS revealed the same mutation as sibling.

We present a case of familial porencephaly, one of the 5 COL4A1 related disorder phenotypes. It is characterized by fluid-filled cavities in the brain, caused by prenatal or perinatal parenchymal hemorrhage. Symptoms include infantile hemiparesis, seizures, intellectual disability, dystonia, stroke and migraine. The AHA 2019 neonatal stroke statement recommends considering mutations in COL4A1 in neonates with porencephaly. Our case supports these recommendations. As father of the proband also harbors the variant, brain MRI, eye exam, UA and CK, hypertension management, smoke cessation, and avoiding anticoagulants were recommended.

COL4A1 mutations are now recognized as a cause for hereditary porencephaly. There are actionable recommendations for surveillance and circumstances to avoid for both the proband and family. COLA41mutation should be part of the differential in porencephaly and perinatal stroke, even without a family history.

157 A connection between breast cancer and hirschsprung disease? the answer may just be RET under our noses

C Verscaj1*

B Nightingale2

DR Matalon1

1Stanford University, Stanford, CA

2Lucile Packard Children’s Hospital, Stanford, CA

Purpose of Study

Hirschsprung disease (HSCR) is a congenital absence of the myenteric and submucosal neural plexus of the GI tract with severity dependent on affected segmental length. Loss of function variants in the RET proto-oncogene have been associated with HSCR. Gain of function variants in RET typically lead to increased risk for tumorigenesis, including breast cancer. Here we present an individual with total colonic and ileal HSCR due to a RET variant found also in the mother diagnosed with ductal carcinoma in situ (DCIS) breast cancer. To our knowledge there is no similar inheritance or mechanism for breast cancer reported in the literature, which has implications for counseling and management.

Methods Used

Chart review, physical examination, literature review, and targeted sequencing.

Summary of Results

Here we describe a 5 yo boy with total colonic and ileal biopsy-proven HSCR diagnosed at birth after failure to pass meconium. He had an early expressive speech delay that has since resolved and no other medical concerns. Physical exam was unremarkable. His mother was diagnosed with DCIS at 34 yo and found to have a heterozygous pathogenic loss of function variant in exon 6 of RET, likely present in a mosaic state. Targeted testing of the familial variant was performed, and was detected in our patient.

Conclusions

Our case is illustrative of a severe isolated HSCR phenotype due to a loss of function RET variant inherited from a mother with breast cancer. The role of RET in breast cancer is still being investigated but has been implicated in ER+ breast cancer with over-expression being a negative prognostic factor. Interestingly, there has been one report of two RET variants typically associated with Multiple Endocrine Neoplasia type 2 that are associated with a relatively high percentage of long segment and total colonic HSCR (Coyle et al., 2014). If, as we hypothesize, this variant is associated with both severe HSCR and breast cancer, it would be the first described with this inheritance pattern and another example of increased pathogenicity of this particular variant in association with a disorder of oncologic significance, and further supports the role of RET variants in the pathogenesis of breast cancer.

Neonatology general IV

Concurrent session

3:15 PM

Friday, January 29, 2021
158 Effect of brain temperature and injury severity on apparent diffusion coefficient changes in newborns undergoing therapeutic hypothermia

C Zenobi1*

J Wisnowski2

B Tamrazi2

S Bluml2

T Wu2

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

2Children’s Hospital Los Angeles, Los Angeles, CA

Purpose of Study

Apparent diffusion coefficient (ADC) changes are useful in detecting ischemic brain injury by the principle that cytotoxic edema restricts Brownian motion of water molecules. Other than pathology, brain temperature may affect the kinetic movement of water. We hypothesize that lower temperature conditions such as therapeutic hypothermia (TH) is associated with lower ADC values.

Methods Used

Brain temperature (T) was measured by MR thermometry during and after TH. The injury severity was scored by pediatric neuroradiologist and dichotomized to normal-mild (NM) and moderate-severe (MS). We compared ADC values and T in thalamus, basal ganglia, parietal gray matter (pGM) and white matter (WM), and magnitude of ADC change between NM vs MS.

Summary of Results

34 infants with HIE (22 NM; 12 MS) were enrolled. Mean duration between scans was 3.7±1.1 days. Mean ADC and T significantly increased during and after TH (table 1, all p<0.0001). In NM group, whereby ADC changes due to injury evolution is minimal, ADC increased after rewarming (838±86 vs. 910±84×10–6 mm2/s, p<0.0001). ADC value increased 25×10–6 mm2/s per degree Celsius (ΔADC/ΔBrain Temp). The magnitude of ADC change was significantly higher in MS (867±171 vs. 1057±240, p<0.0001). When comparing regions, pGM and WM had the greatest increase in ADC for all injury groups.

Abstract 158 Table 1

Brain Temprature and ADC values during and after therapeutic hypothermia

Conclusions

Aside from brain injury, tissue temperature may contribute to diffusion restriction on MRI in infants with HIE during TH.

159 Association between umbilical cord management and 5 minute peripheral oxygenation in preterm infants

S Wong1,2*

R Yim2

D Poeltler2

W Rich2

S Sanjay2

A Katheria1,2

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

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

Purpose of Study

Delay Cord Clamping (DCC) is recommended for all preterm newborns. However, effects of delaying resuscitation and oxygen administration in resuscitated preterm newborns are largely unknown. A recent post hoc exploratory analysis of the major TO2RPIDO trial done by Kei Lui et. al. found that infants with 80% or less 5-minute mean peripheral arterial oxygenation (SpO2) were more likely to die or have neurodevelopmental impairment. This study aims to determine if resuscitated preterm infants that received DCC had lower 5-minute SpO2 compared to those with umbilical cord milking (UCM) or early cord clamping (ECC).

Methods Used

This was a retrospective review of resuscitated premature infants born between 2014-present at 23 to 31 weeks of gestation receiving either ECC (N=20), DCC (N=178), or UCM (N=130) before resuscitation. Data gathered was SpO2 (measured by pulse oximetry), and various physiologic data including administered inspired fraction of oxygen (FiO2). Mean 5-minute SpO2 and FiO2 levels of each treatment group were compared with 2-sample t tests for continuous variables using a critical alpha level of 0.05.

Summary of Results

There were no statistically significant differences between the three groups using ANOVA for continuous measures and Chi square for categorical variables in maternal or neonatal demographics. Mean SpO2 and FiO2 at 5 minutes were compared. FiO2 at 5 min was higher in ECC compared to UCM (p=0.031) and DCC (p=0.025), with no difference found between UCM and DCC. The 5-minute SpO2 was higher in UCM compared to DCC (79.4% vs 74.8%, p= 0.028). There was no difference between mean 5-minute SpO2 of ECC and UCM (P= 0.72) or DCC (p=0.16)

Conclusions

ECC and UCM allow for resuscitation to occur quickly and may lead to improvements in oxygenation within 5 minutes of life. However, both have increased risk of mortality or intraventricular hemorrhage. Despite receiving similar amounts of supplemental oxygen, infants receiving DCC had a lower 5-min SpO2 compared to UCM. Providing higher supplemental oxygen during DCC or immediately following clamping and cutting of the umbilical cord may improve 5-minute SpO2 and neonatal outcomes.

160 Higher rates of readmission for phototherapy in term infants exposed to delayed cord clamping

M Chu1*

S Sakhamuru2

JJ Keel2

L Barton2

R Ramanathan2

R Cayabyab2

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

2LAC + USC, Los Angeles, CA

Purpose of Study

To compare the need for phototherapy during birth admission and readmission for hyperbilirubinemia requiring phototherapy in term infants with immediate cord clamping (ICC) vs. delayed cord clamping (DCC).

Methods Used

Retrospective study of term infants born at LAC+USC Medical Center between 2016–2019. Demographics, clinical data, and duration of DCC were collected from electronic medical records and paper records. Infants with ABO incompatibility were excluded. Data was analyzed with Wilcoxon Rank Sum and Chi Square test. Associations of hemoglobin level, rate of readmission and delayed cord clamping were determined with linear and logistic regression respectively.

Summary of Results

There were 149 infants included in the study. Demographics were not different between the two groups except for Hispanic race. Hemoglobin level was higher in infants with DCC. The rate of infants exposed to phototherapy was not different, but the rate of readmission was higher in infants with DCC. (Table 1) This association persisted after adjustment of confounders in a regression model. Hemoglobin level [Coef. 1.46 (95% CI; 0.65–2.2 p=0.001); Rate of readmission [OR=4.6 (95% CI; 1.13–19.92) p=0.03]

Abstract 160 Table 1

Demographics and outcomes between groups

Conclusions

Delayed cord clamping in term infants did not result in an increased rate of phototherapy during birth admission, however, the rate of readmission for phototherapy was higher. The importance of outpatient bilirubin follow-up should be emphasized to parents.

161 Quality improvement initiative to increase the consistency and effectiveness of iron supplementation for nicu patients

TM Bahr1*

NR Carr1

TR Christensen1

J Wilkes2

OA Elizabeth1,2

K German3

RK Ohls1

D Ward1

RD Christensen1

1University of Utah, Salt Lake City, UT

2Intermountain Health Care Inc, Salt Lake City, UT

3University of Washington, Seattle, WA

Purpose of Study

We devised and conducted a program aimed at reducing iron deficiency among infants of diabetic mothers, small for gestational age neonates, and very low birth-weight premature neonates in the NICUs of Intermountain Healthcare.

Methods Used

This was a quality improvement project establishing iron dosing guidelines among multihospital NICUs and assessing; 1) compliance with the guidelines, and 2) iron deficiency at one month.

Summary of Results

During the ten years before establishing guidelines, only 18% of >4000 NICU patients in the three at risk groups had iron dosing begun by hospital discharge; only 3% had it begun before 2 weeks of age. During the 30 months since guideline initiation, 98% (534/543) had iron started before discharge and 74% (399/543) had it started by 2 weeks. Dosing as early as seven days resulted in no more intolerance (episodes of emesis/day) than when dosing was started at 2, 3, or 4 weeks. However, even when dosed according to guidelines, 16.0% were iron deficient at one-month (as judged by RET-He <25 pg). None who received a transfusion were iron deficient. Iron deficiency was found in 26.1% of 153 who received darbepoetin vs. 3.3% of 122 who did not receive darbepoetin (p<0.001).

Conclusions

Iron dosing increased considerably after instituting guidelines. Earlier enteral iron was tolerated just as well as late enteral iron. Certain patients, including some darbepoetin recipients, apparently needed more iron than we provided. Further advances are needed to assure iron sufficiency of all NICU patients.

162 Neonatal hypotension and relationship with cerebral saturation

KJ McKim1

S Lucafo2

S Bhombal1

L Bain1*

VY Chock1

1Stanford University School of Medicine, Palo Alto, CA

2Milipore, Burlington, MA

Purpose of Study

Neonatal hypotension can be defined by various threshold mean arterial blood pressures (MAP) such as 30 mmHg, postmenstrual age (PMA), or gestational age (GA) ± 5 mmHg. Cerebral saturation (cNIRS) is non-invasively measured by a near-infrared spectroscopy sensor on the forehead and assesses perfusion to a critical end-organ, the brain. We hypothesize that currently used MAP ranges do not correlate with cNIRS changes in neonates on dopamine for hypotension.

Methods Used

Clinical data were reviewed for neonates admitted to the NICU and treated with dopamine between August 2018 and August 2019. Vital signs and lab values during treatment were collected from the electronic medical record. Definitions of hypotension included MAP less than PMA, 30 mmHg, PMA at time of therapy ± 5 mmHg, and GA ± 5 mmHg. Values were compared to time with cNIRS <55%, a lower limit for adequate cerebral oxygenation. Patients were stratified by PMA during therapy.

Summary of Results

70 patients were treated with dopamine with average GA of 34.3 ± 5.3 weeks, average birthweight of 2.29 ± 1.17 kg, and mean age at treatment of 36.2 ± 4.7 weeks. Infants experienced hypotension between 6–33% of their time on dopamine per examined definitions. Hypotension was more common in patients <36 weeks PMA than in term infants. Hypotension did not correlate with abnormal cNIRS overall or in PMA PMA strata. Patients <29 weeks PMA had the greatest correlation between hypotension and abnormal cNIRS measures ranging from 5% using PMA threshold to 9% using 30 mm Hg threshold (table 1).

Abstract 162 Table 1

Conclusions

cNIRS as an indicator of brain oxygenation during periods of hypotension may be more clinically significant than MAP. cNIRS were mostly in a normal range, despite the frequency of MAP alterations in the neonatal population. More work is needed to determine what parameters are most appropriate to define and treat neonatal hypotension.

163 Trends in gastrostomy tube placement and reource utilization in down syndrome neonates in the united states, 2006–2017

H Doshi1*

S Shukla2

S Patel2

N Bhatt3

F Dapaah-Siakwan4

K Donda5

1Golisano Children’s Hospital of Southwest Florida, Fort Myers, FL

2University of Florida college of medicine, Jacksonville, FL

3University of Washington School of Medicine, Seattle, WA

4Valley Children’s Hospital, Madera, CA

5University of South Florida, Tampa, FL

Purpose of Study

Feeding difficulty is one of the major co-morbidities in neonates with DS. Consequently, some neonates with DS may require gastrostomy tube (GT) placement. However, there is paucity of data on rate and associated factors of GT placement in this population. We aimed to determine the trends in GT placement and resource utilization in DS neonates born at ≥ 35 weeks gestational age (GA) in the U.S from 2006 to 2017.

Methods Used

Retrospective data analysis was performed using the National Inpatient Sample, the largest health care database in the US. We included all neonatal hospitalizations with GA > 35 weeks who had International Classification of Diseases (ICD) 9th or 10th revision codes for DS and GT placement. Data was analyzed using trend analysis and multivariate logistic regression.

Summary of Results

Over the study period, 1914 (3.7%) out of 51,463 neonates with DS had GT placement. Among neonates with GT, 46% were male, 24.8% were 35–36 weeks GA at birth, 48% White, 62% with Medicaid or self-pay, 95.1% in teaching hospital, and 69.9% in a large bed-size hospital. Rate of GT placement (per 100 neonates with DS) increased significantly from 2006 to 2017 (see table 1). On multivariate analysis, GA 35–36 weeks at birth was associated with increased odds of GT placement. Medicaid/Medicare insurance was associated with increased length of stay and hospitalization cost. Median length of stay and inflation adjusted hospital cost did not show any significant trend.

Conclusions

Frequency of GT placement among neonates with DS increased significantly over the study period without any associated change in resource utilization. Future studies should probe the reasons and factors behind these trends.

Abstract 163 Table 1

Percent of DS neonates receiving Gtube

164 Improving placental transfusion rates at ucsd

M Karmarkar*

E Fernandez

University of California San Diego, La Jolla, CA

Purpose of Study

Placental transfusion by delayed cord clamping (DCC) has significant benefits over immediate cord clamping in infants. However, less information is known about risks and benefits of cord milking. A recent study found an increased risk of intraventricular hemorrhage (IVH) in preterm infants who received cord milking. Due to the multidisciplinary involvement around placental transfusion, targeted actions to improve this metric can be complex.

Methods Used

A multidisciplinary team was developed at UCSD Jacobs to decrease the rate of cord milking in preterm infants <28 weeks GA and to increase the rate of DCC in all infants. Multiple meetings were held to design a hospital policy on DCC. Education was given across all staff to ensure consistency in resuscitation care. Documentation of DCC will be used as the primary process measure. Balancing measures planned are frequency of phototherapy and IVH.

Summary of Results

Baseline data in 2019 showed 81% of all infants born at UCSD received DCC; 51% in preterm and 84% in term infants. Results from the first PDSA cycle showed that DCC rates for preterm infants increased to 61%; rates for term infants were 83%. For infants <28 weeks GA, the% DCC increased from 29% to 65% (figure A) and cord milking decreased from 38% in to 2.2% (figure B).

Conclusions

The rate of placental transfusion in preterm infants improved while reducing cord milking by implementing the first step of creating a multidisciplinary committee. The next step is to further streamline the resuscitation process for providers to further increase the rates of DCC.

165 The effects of parental leave policies on pediatric fellows

N Dyess*

B Weikel

J Barker

T Garrington

TA Parker

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

To identify the specific elements of parental leave policies among pediatric fellowship programs and to understand the impact of those elements on fellows.

Methods Used

A national web-survey was sent to fellows at ACGME-accredited pediatric fellowship programs, either directly or through their program.

Summary of Results

Of the 1474 fellows who opened the survey, 853 (58%) completed it. 76% of respondents were female. 43% reported having children among which approximately half reported having at least one child during fellowship. 48% of respondents did not know whether their program had a written policy governing parental leave.

Of fellows with knowledge of their program’s parental leave policy, 61% and 24% stated the policy does not apply equally to fathers/partners and to adoption/fostering, respectively. Allowance of paid leave varied by program. 96% and 56% of fellows stated vacation/holiday time and sick time, respectively, is used to construct or extend leave. 34% of fellows reported they do not get sick leave. 73% indicated unpaid leave is used to construct or extend parental leave. 76% stated make up time is expected and 58% stated fellows often take on a greater than usual load of clinical responsibilities to ‘pay for’ their parental leave.

The mean satisfaction with parental leave policy score of the cohort was 3.0 (SD = 0.7) on a 5-point scale, with a score of 5 indicating highest satisfaction. Satisfaction scores did not differ by program size, a fellow’s educational debt, or whether or not a fellow had children. Of 7 candidate changes to leave policy intended to minimize the stress of having or adopting a child during training, fellows chose establishing/extending paid leave and the cultivation of a more supportive culture among faculty and peers as the most impactful.

Conclusions

Parental leave policies vary widely among pediatric fellowship programs, are often not known by fellows, and create substantial burden on fellows. Our results indicate fellows are not currently satisfied with parental leave policies in fellowship and that there are a number of areas that would improve the experience of parental leave for fellows.

Pulmonary and critical care

Concurrent session

3:15 PM

Friday, January 29, 2021
166 Hyperglycemia and hypoglycemia contributions to acute respiratory distress syndrome

JJ Repine*

PV Wilson

ND Elkins

JE Repine

University of Colorado, Denver, CO

Purpose of Study

Non-diabetic COVID-19 patients with elevated admission fasting blood glucose levels (‘hyperglycemia’) inexplicably have an increased 28 day mortality and higher in-hospital complications including the Acute Respiratory Distress Syndrome (ARDS) but potentially contributing blood glucose changes during ARDS development were not reported (Wang S et al: Diabetologia 2020). Our goal was to determine blood glucose alterations before and during acute lung injury development in a rat model used to study ARDS.

Methods Used

We sequentially evaluated blood glucose levels for 24 hours and lung lavage protein levels (lung permeability) and lung lavage neutrophil numbers (lung inflammation) at 24 hours to assess acute lung injury (‘ARDS’) in young (~3 month) and old (~12 month) control and a novel strain of hyperoxia surviving ‘resistant’ rats before and after administering high and low insulin doses and before and after interleukin-1/lipopolysaccharide (IL-1/LPS) insufflation.

Summary of Results

Glucose levels increase rapidly and sequentially in young control, but not young resistant, rats peaking ~2 hours after insufflation. Glucose levels also increase in old control and old resistant rats after insufflation compared to young control and young resistant rats after insufflation. The pattern of glucose levels at 2 hours after insufflation resembles lung lavage proteins and neutrophils at 24 h after insufflation (table 1). Administering high insulin (High In) doses decreases glucose levels (‘hypoglycemia’) and worsens ARDS while administering low insulin (Low In) doses correct glucose levels and improve ARDS.

Abstract 166 Table 1

Glucose and ‘ARDS’ After IL-1/LPS Insufflation

Conclusions

Hyperglycemia develops in both young and old rats developing ARDS and high or low glucose levels parallel worse acute lung inflammation and acute lung injury (‘ARDS’). Controlling glucose judiciously with insulin may be beneficial in combatting ARDS caused by SARS-CoV-2 infection and other insults.

167 Association of small adult ventilation bags with return of spontaneous circulation in out of hospital cardiac arrest

BD Snyder1*

NE Bulger1

RG Walker2

AJ Latimer1

BY Yang1

C Maynard3

NJ Johnson1

T Rea1

CR Counts1

M Sayre1

1University of Washington School of Medicine, Anchorage, AK

2Stryker Emergency Care, Redmond, WA

3University of Washington School of Public Health, Seattle, WA

Purpose of Study

Excess minute ventilation adversely affects hemodynamics during cardiac arrest. In July 2017, Seattle Fire Department began using smaller ventilation bags, delivering approximately 450 mL per breath, in adults with out-of-hospital cardiac arrest (OHCA). We hypothesized that the rate of return of spontaneous circulation (ROSC) at hospital arrival would increase after this change.

Methods Used

This retrospective analysis of prospectively acquired data evaluated adults treated for OHCA between January 1, 2015 and December 31, 2019 who received advanced airway management. Using waveform capnography, we calculated ventilation rate and mean end-tidal carbon dioxide (ETCO2) values for each eligible minute during cardiac arrest. We examined whether ventilation rate, ETCO2, and ROSC differed before and after the smaller ventilation bag implementation using linear and logistic regression.

Summary of Results

Of the 1278 patients evaluated, 668 (52%) were treated with a small adult bag. Utstein characteristics did not differ between the two cohorts. Mean±SD ventilation rates were higher in the large bag cohort compared with small, 12.5±5.1 vs. 11.7±4.7, p < 0.01. Mean±SD ETCO2 values were lower in the large bag cohort compared with small, 31.5±17.0 mmHg vs. 34.5±18.2 mmHg, p < 0.01. A ventilation rate > 18 was recorded in 10% of the 18,709 minutes evaluated. Mean ETCO2 was less than 15 mmHg in 14% of all minutes. The incidence of ROSC on hospital arrival (39% vs. 34%) was not significantly different between the large and small bag cohorts (p=0.07). After adjusting for initial rhythm, age, witnessed arrest, and bystander CPR, ROSC on hospital arrival among the small bag cohort was not different (OR 0.82, CI 0.65–1.04).

Conclusions

Use of a small adult bag during OHCA was not associated with a difference in incidence of ROSC. The clinical significance of the slight differences in ventilation rate and ETCO2 are unclear. Hyperventilation was uncommon. Future studies should examine impact on downstream lung injury and acid-base status.

168 Diagnostic utility of point-of-care ultrasound in the evaluation of necrotizing soft tissue infections

A Wesley

A Ratesic

R Kelley

S Adhikari

O Rizvi*

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

Purpose of Study

Necrotizing soft-tissue infections (NSTIs) are potentially life-threatening medical emergencies that require rapid identification and aggressive treatment. Emergency physicians are utilizing point-of-care ultrasound (POCUS) for a wide variety of applications. The objective of this study was to determine the diagnostic utility of POCUS in the evaluation of patients with suspected SSTI in an Emergency Department (ED).

Methods Used

This was a retrospective review of ED patients presenting to an academic center with symptoms suspicious for NSTI and received a POCUS. POCUS findings were collected from ED POCUS archiving database. Medical records were reviewed for history, physical examination findings, laboratory results, additional diagnostic testing, operative intervention, disposition, and final diagnosis. POCUS findings were compared with LRINEC scores and operative findings.

Summary of Results

A total of 65 patients (15 females, 50 males; mean age, 55 years ± 13.6) were included in this study. Patients presented with pain (46/65), swelling (33/65), redness (28/65) and open wound (21/65). Most common symptomatic sites were feet (27%) and upper arm (21%). Nineteen patients reported injection drug use. In triage, 53% patients were tachycardiac and 5 patients were hypotensive. Pain out of proportion was documented in 3 patients. Based on operative findings, 38% (25/65) patients were found to have NSTI. All patients with final diagnosis of NSTI had sonographic findings (hypoechoic fluid tracking along deep fascial layers, fluid accumulation > 4 mm in depth along the deep fascial layers, air in the soft tissues) indicating NSTI on POCUS. In addition POCUS demonstrated abscess (28%), cellulitis (62%), pyomyositis (2.9%) and superficial Fasciitis (27%). Subcutaneous Gas was noted in 11 patients. Early surgical consultation was obtained in these patients prior to laboratory results and additional imaging studies. Six patients with LRINEC Score < 6 were found to have NSTI and all 6 patients had sonographic findings suggestive of NSTI on POCUS. Only 1 of these patients had abnormal vital signs in triage.

Conclusions

Our study suggests that POCUS can be a useful adjunct in the evaluation of patients with NSTI. Integration of POCUS findings into LRINEC Score could improve risk stratification.

169 Emergent cricothyrotomy training for non-surgeons

C Zagona-Prizio*

J Maloney

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

Cricothyrotomies are lifesaving procedures performed in critical care (CC) settings when an oral endotracheal (ET) intubation is not possible. Simulations are the main method of training and are most often performed in simulation labs on synthetic materials or pig tracheas. Cadaveric training is superior to simulation training due to landmark and tissue fidelity, but it is uncommon due to cost and access.

Methods Used

We implemented a program to train CC fellows and attendings on cadaveric donors. The program was enhanced by an educational training video produced by our team and narrated by an ENT, as well as endoscopic visualization of the trachea that allowed participants to review their technique. All participants performed both scalpel-bougie-6.0 ET tube and Seldinger kit methods.

Participants responded to a pre-survey that assessed their level of experience and anxiety with performing a cric. We then assessed for changes in their confidence after watching the video and after the cadaveric training. We reviewed the endoscopic recordings to assess any excursions of scalpels or needles beyond the midplane of the trachea. We also assessed procedure duration, puncture-to-tube time (PTTT), from initial entry to ET tube placement.

Summary of Results

Response rate for the first session of 10 participants was 100% and showed that the session was helpful to all participants. 20 endoscopic recordings were analyzed, 10 from the bougie method and 10 from the kit method. They revealed that 1 trocar needle hit the posterior tracheal wall, and 2 scalpels passed the midpoint of the trachea lumen. PTTT ranged from 15–83 seconds (s), with 83s being a clear outlier and explained by a long coaching time. The mean PTTT with the outlier excluded was 29.2±12.7s. Additionally, during the training 1 bougie was placed parallel to the trachea but not within it. This was made immediately clear through the endoscopic visualization and feedback was given to the participant who was thereafter successful in intubating.

Conclusions

Endoscopic enhancement of the emergent cadaveric cricothyrotomy training was valued by trainees. It helped detect 3 complications in 20 attempts which was important in refining trainee technique to avoid real-life complications and improve confidence. Adoption of ET endoscopy may enhance regional and national cadaveric emergent cricothyrotomy training programs.

170 Barriers and facilitators to longitudinal lung cancer screening: a qualitative study

AK Holman1*

EK Kross1

K Crothers1

AM Cole1

M Triplette1,2

1UW, Seattle, WA

2FHCRC, Seattle, WA

Purpose of Study

One of the implementation challenges faced by lung cancer screening (LCS) programs is replicating the high rate of adherence reported by the National Lung Screening Trial (NLST). The goal of this qualitative study was to identify factors influencing adherence and understand patients’ attitudes towards a novel screening navigation program.

Methods Used

We enrolled 40 participants, all of whom had a negative (LungRADS 1 or 2) baseline LCS CT. Participants were interviewed about their screening experiences as well as barriers and facilitators to follow-up. Interviews were transcribed, coded, and analyzed using thematic analysis.

Summary of Results

Of 40 participants (22 men, 18 women, median age 66), 17 were adherent to screening follow-up while 23 were nonadherent. There were seven major themes that emerged from interviews of both groups: (1) most patients report favorable screening experiences and attitudes; (2) provider recommendation is a near-universal facilitator of baseline and follow-up screening; (3) while most patients understand lung cancer risk factors, some do not understand the importance of asymptomatic LCS; (4) concerns over insurance coverage, screening accessibility, and other medical conditions are often cited as barriers to ongoing LCS; (5) some patients have residual questions about their results, LCS guidelines and the importance of follow-up; (6) reminders are an important facilitator of annual LCS; (7) most patients believe a navigator would be beneficial and emphasize the importance of a variety of services. Some differences were observed between the adherent and nonadherent cohorts. Adherent participants reported more interaction with their providers, while nonadherent participants reported less contact with providers and more frequent consideration of symptoms in their decision of whether or not to screen.

Conclusions

Though patients’ experiences with LCS are generally favorable, adherence may be improved by providing facilitators (such as reminders and transportation) and addressing barriers (such as lacking LCS knowledge) through an LCS navigation program. By targeting these deterrents of screening, LCS programs could improve adherence and better reproduce the benefits of LCS demonstrated by the NLST.

171 Point of care ultrasound evaluation of airspace disease before and after prolonged surgery

S James*

E Gow-Lee

J Hinson

M Martinez

B Austin

D Ramsingh

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Point-of-care ultrasound (POCUS) has rapidly emerged as a modality to improve bedside assessment of pulmonary air-space disease. Indeed, POCUS has demonstrated to be superior for the assessment of air-space disease in comparison to both Chest x-ray and stethoscope auscultation. Given that patients undergoing a long surgical procedure requiring general anesthesia are at risk for pulmonary complications the ability to assess air-space disease perioperatively is of interest. The authors designed a pilot study to evaluate the utility of point of care ultrasound to evaluate the development of air-space disease in this patient population.

Methods Used

Adult patients were screened for those undergoing a surgical procedure scheduled for more than 3 hours of surgical time. Patients were then scanned using a validated POCUS examination to detect both the presence and severity of air-space disease across 5 lung fields for each side (total of 10 views). POCUS exams were performed immediately before and after their surgical procedure. Air-space disease was defined by the presence of B-lines, as previously validated. Presence of air-space disease was compared to a threshold using binomial test. Level of significance was set to 0.05.

Summary of Results

For our analysis we set a threshold value of 40% of the lung fields demonstrating B lines as the level of significance. Patients only surpassed this threshold after their surgery (p = 0.03917) and not before (p = 0.2115). All zones of lung parenchyma were able to be scanned on all patients.

Conclusions

POCUS examination of the lungs fields can be successfully performed in the perioperative setting. Our preliminary data supports this tool be useful in the assessment of the change in the aeration of lung tissue from pre to post surgery. Specifically, for patients undergoing long surgical procedures, this modality may be useful to detect the development of new areas of air-space disease.

172 Embolization of superior mesenteric arteriovenous fistula identified during consultation for a transjugular intrahepatic portosystemic shunt procedure

A Shinagawa1*

Z Billah2

K Kansagra2

K Lam2

G Vatakencherry2

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

2Kaiser Permanente, Los Angeles Medical Center, Los Angeles, CA

Case Report

The present case report describes a 75-year-old female patient with a history of two small bowel resections who presented with variceal bleeding resulting in hematemesis and bright red blood per rectum. She was initially referred to vascular and interventional radiology (VIR) for a transjugular intrahepatic portosystemic shunt procedure (TIPS). However, her past medical history and imaging indicated that the patient likely did not have cirrhotic liver disease, prompting further review of the imaging. Closer inspection of an abdominal computed tomography angiography scan identified a superior mesenteric arteriovenous fistula (SMAVF) as the probable etiology of the varices, the presence of which was confirmed on angiography. The fistula was embolized with a vascular plug and post-embolization angiogram demonstrated an absence of portal venous filling. Upper endoscopy at 1-month postprocedurally demonstrated complete resolution of varices.

The primary etiologies of SMAVF are traumatic, iatrogenic, and congenital. This rare vascular anomaly may be discovered incidentally, but more often presents with sequelae of portal hypertension, heart failure, or mesenteric ischemia. The presentation of SMAVF is widely variable, though common signs and symptoms include abdominal pain, diarrhea, upper or lower gastrointestinal bleeding, ascites, and anemia. The most consistent specific physical exam finding is an abdominal bruit. One of the most concerning complications is variceal bleeding as a result of portal hypertension, suspected to be the leading cause of mortality associated with SMAVF. If a SMAVF is initially not identified, such patients presenting with acute gastrointestinal bleeding might be referred for a TIPS procedure, as occured in this case. However, careful review of the imaging can preclude the potentially catastrophic consequences of creating a portosystemic shunt in the presence of an existing SMAVF, including potentially life-threatening right-sided heart failure. This report highlights the necessity of the interventional physician performing a comprehensive consultation prior to invasive procedures.

173 Time-to-prescription of trikafta for remote and local people with cystic fibrosis

R Loudenback1*

K Daratha2

KB Daratha1,2

AA Lambert1,2

1University of Washington School of Medicine, Spokane, WA

2Providence Medical Research Center, Spokane, WA

Purpose of Study

We aimed to describe time-to-prescription of Trikafta, a newly FDA approved cystic fibrosis (CF) therapy.

Methods Used

We conducted a retrospective observational study to determine time-to-prescription of Trikafta in remote versus local people with CF. Among patients actively receiving care at the Providence Medical Group CF Center in Spokane, Washington, we included participants in the CF Foundation Patient Registry who were eligible for Trikafta. Participants were dichotomized into remote (≥120 minutes of driving time from home to CF center ZIP code) and local (<120 minutes) groups. The primary outcomes were prescription for and time-to-prescription of Trikafta. Analyses were completed using Kaplan-Meier and Cox proportional hazard models (controlling for insurance as a proxy for healthcare access) using an a priori α=0.05.

Summary of Results

Of the 84 participants, 36 (43%) were remote; median travel time to CF center was 45 minutes (interquartile range, IQR 20–160). The majority were male (n=46, 55%) and adults (n=64, 76%), with a median age of 27 years (IQR 22–33) among adults and 15 years (IQR 14–17) among children. Private insurance was used in 2019 by 51 (61%), and median time to prescription was 92 days (IQR, 43–132) for those who received a prescription. Eight months after FDA approval, 61% of remote participants were prescribed Trikafta, compared to 81% of local participants (p=0.04). Kaplan-Meier survival analysis, comparing prescription for and time-to-prescription of Trikafta, yielded no significant group differences (p=0.28). A Cox proportional hazard model, controlling for insurance type, reported no differences between local and remote groups (p=0.11).

Conclusions

A smaller proportion of remote participants were prescribed Trikafta at the time of this analysis; however, the time to prescription did not differ by distance to CF center, even after adjusting for insurance type. At our center, caring for patients living at a median travel time of 45 minutes, timely delivery of novel therapies is achieved regardless of location.

Surgery II

Concurrent session

3:15 PM

Friday, January 29, 2021
174 Quality assessment of surveys administered to pediatric orthopaedic surgeons

C Matthews1*

A Vasireddi1

E Schaeffer1,2

K Mulpuri1,2

1BC Children’s Hospital, Vancouver, BC, Canada

2University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Successful physician-administered surveys can advance care and practice quality. There is a lack of research on physician-administered survey quality in pediatric orthopaedics. This study aims to identify essential survey features, evaluate published surveys over two time periods to highlight core strengths and weaknesses, and suggest methods to improve clinical impact.

Methods Used

A literature review of MEDLINE and EMBASE databases was conducted for studies published in JPO, JPO B, JBJS, BJJ, JCO, Spine Deformity, or Spine in the years 2007–2009 and 2017–2019. Studies eligible for inclusion contained a survey assessing patients <18 years administered to pediatric orthopaedic surgeons and had the full text published. Surveys in the literature were studied to compile a list of elements essential to surveys. Two independent reviewers screened titles and abstracts for inclusion, then assessed included studies for quality using a 17-item checklist. Surveys were grouped into scored categories according to how many items were fulfilled (<25%, 25–50%, 50–75%, >75%).

Summary of Results

54 articles were included for analysis. Studies in 2017–2019 fulfilled a greater percentage of checklist items compared to 2007–2009. Mean respondent rate marginally decreased over time (71.2% in 2007–2009 vs 64.1% in 2017–2019). 13 studies had response rates >90%.

Abstract 174 Figure 1

Bar graph showing score category according to how many items were fulfilled or reported from the 17-item checklist with a score of 1 being the lowest and score 4 the highest. Score 1: <25% items, Score 2: 25-50% items, Score 3: 50-75% items, Score 4: >75% items

Conclusions

The use of surgeon-administered surveys in pediatric orthopaedics has substantially increased; however, survey quality has not improved correspondingly. We suggest that surveys aim to report >75% of items (Score 4) from the 17-item checklist to create higher quality, comprehensive surveys. A limitation of our study is the smaller sample of studies included in 2007–2009 vs. the 2017–2019 sample. Future surveys could be improved by following a standardized checklist prior to distribution.

175 Factors influencing female medical students’ decisions to pursue surgical specialties: a systematic review

E O’Rorke1

L Trinh2

M Mulcahey2

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

2Tulane University School of Medicine, New Orleans, LA

Purpose of Study

Gender inequality within the medical field continues to be a prominent issue, particularly for surgical specialties. This systematic review evaluates and summarizes the factors that influence female medical students’ decision to pursue a career in surgery, including general surgery and surgical subspecialties.

Methods Used

A literature search was conducted by two independent researchers searching PubMed, Medline, Embase, Web of Science, and Science Direct databases, in accordance with PRIMSA guidelines. Keywords included ‘female,’ ‘medical students,’ ‘surgery,’ ‘gender,’ ‘career,’ ‘surgical subspecialty,’ ‘plastic surgery,’ ‘ophthalmology,’ ‘otolaryngology,’ ‘neurosurgery,’ ‘orthopedics,’ and ‘urology.’ Studies were identified that evaluated factors influencing female medical students’ decision to pursuing surgical specialties.

Summary of Results

2,200 articles were identified in the initial search. 527 duplicates were removed, and 1,993 studies were removed in accordance with pre-identified inclusion and exclusion criteria. 61 articles underwent full-text review. 26 additional studies were identified from references. A total of 14 articles were included in the review. Female medical students were positively influenced by mentorship, specialty exposure, intellectual challenge, and the rewarding nature of surgery. Surgical lifestyle, gender discrimination, and societal and cultural barriers were deterrents for female medical students. Female medical students valued the importance of prestige and expected financial rewards less than their male counterparts.

Conclusions

This systematic review identifies mentorship, specialty exposure, gender discrimination, nature of the surgical field, and personal factors to be major determinants in female medical students’ decisions to pursue surgery. These areas can be improved to attract more women to surgical residencies. Specific recommendations to increase female students’ interest in a surgical career include matching medical students with role models early on, implementing structured outreach programs for women, improving residency parental leave policies, and reducing pregnancy-related stigma.

176 Association of neuraxial anesthesia with postoperative opioid use in pediatric burn patients

J Chen1

P Nguyen1

J Liu2

1University of California Davis, Sacramento, CA

2Shriners Hospitals for Children, Sacramento, CA

Purpose of Study

Pain management is an essential part of recovery among pediatric patients with burn injuries. Studies show that it remains inadequately treated, leading to long-term sequelae of anxiety, depression, and PTSD. However, the use of opioids poses significant risks as well, including opioid dependence later in life. While general anesthesia is the mainstay, studies suggest that regional anesthesia, including neuraxial anesthesia, is one strategy to decrease postoperative pain and reduce opioid use. The purpose of this study is to assess whether neuraxial anesthesia is associated with decreased opioid use among pediatric patients receiving excision and graft repair for burn injuries.

Methods Used

A retrospective review of hospital charts from 01/2017 to 06/2018 was conducted. Patients who were hospitalized for split thickness skin grafting and received intraoperative neuraxial anesthesia were included. A study published, which included pediatric burn patients given general anesthesia, served as the control for this study (Bussolin et al). Patients who were >10 years old were excluded from the data analysis in order to match the historical control. The amount of opioids administered postoperatively were converted to oral morphine milligram equivalents (MME) and adjusted for body weight (kg).

Summary of Results

In the neuraxial anesthesia group (n=42), the average (range) amount of opioids given was 0.6 (0–1.9) MME/kg/24h. In the general anesthesia group (n=30), the average amount of opioids given was 36.9 (10.5–126) MME/kg/24h (Bussolin et al).

Abstract 176 Table 1

Comparison between groups

Conclusions

Neuraxial anesthesia was associated with lower opioid use compared to general anesthesia from a historical control. However, interpretation of the data is limited as the studies were conducted at different institutions. Further research is warranted to determine the benefit of neuraxial anesthesia and pain management with pediatric burns.

177 Pain assessment for office based urologic procedures

L Hunt

R Hahn

D LaTour

S Tamares

B Crawley

D Baldwin

Loma Linda University, Loma Linda, CA

Purpose of Study

The purpose of this review was to characterize how pain and patient discomfort is reported in the literature for office-based urologic procedures. Available data was gathered regarding pain assessment and control and then subsequently evaluated for methodology and management techniques during in-office procedures.

Methods Used

Searching PubMed, Embase, Web of Science, CINAHL from inception to 2020, terms and second-layer article collection yielded 948 unduplicated articles. After subsequent screening with exclusion criteria, 134 articles were included investigating urology office-based procedure pain management. Each article was subject to review with the ROBINS-I tool for bias assessment. Data was extracted and included in final analysis.

Summary of Results

134 articles with reference to pain management during five major office based procedures were included. The majority of the articles assessed pain management during prostate biopsy, cystoscopy, urodynamics and other minor procedures. Anesthesia included local, topical, oral, as well as methods of distraction such as music or virtual reality. The most common assessment of pain was the visual analog score (VAS 0–10) pain intensity scoring scale (68%) followed by VAS (0–100) (9%), numerical rating scale (8%), categorical pain rating (3%), other pain scoring methods (McGill, Spanish Pain, Visual Numeric, 5-point verbal descriptor scales; 4%) or some combination thereof (7%). The majority of studies assessed pain only after the procedure (67%), while the remainder assessed pain at some combination of before, during and after the procedure.

Conclusions

This review sought to characterize studies investigating pain management for office-based urologic procedures. Compiling a database of articles yielded a conglomeration of differences with investigating procedural pain. While several themes emerged, such as the type of pain scale and when discomfort was assessed, standardization of pain assessment and management will likely be beneficial for both patients and their urologic care providers.

178 A call to bridge the divide in breast reconstruction research: a systematic review

R Xu1

S Yuan1

N Almuqaimi1

M Elemi2

K Isaac1

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

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

Purpose of Study

Breast reconstruction requires multidisciplinary clinical-decision making; however, cross-discipline collaborative research is often limited. This study aims to evaluate multidisciplinary involvement in breast reconstruction research.

Methods Used

A systematic review of breast reconstruction literature published from 2000–2019 using Ovid MEDLINE, Ovid EMBASE, and PubMed was conducted. Authors’ affiliations defined multidisciplinary involvement. Quality of research was evaluated using level of evidence and journal impact factor (IF).

Summary of Results

Of the 1679 articles screened, 784 met the inclusion criteria. Only half (50.6%) involved an author outside plastic surgery. Compared to non-multidisciplinary studies, multidisciplinary studies were more likely to be of higher level of evidence (I or II) (p<0.001), and published in journals of higher IF(p<0.0001), after adjusting for year of publication, journal type, clinical question, and number of authors.

Abstract 178 Table 1

Multidisciplinary and non-multidisciplinary breast reconstruction studies by journal type (n=784)

Abstract 178 Figure 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart of the search and screening process with exclusion criteria

Conclusions

Breast reconstruction outcomes research often fails to offer multi-disciplinary involvement; collaboration is strongly recommended to improve the quality and impact of clinical studies.

179 The impact of patient, surgical, and staffing factors upon percutaneous nephrolithotomy cost

J Lee*

M Keheila

A Amasyali

N Chen

N Srikureja

J Belle

D Baldwin

Loma Linda University, Loma Linda, CA

Purpose of Study

In the US, the estimated cost for the management of nephrolithiasis was $2.07 billion in 2000 and is expected to reach $4.1 billion by 2030. Percutaneous nephrolithotomy (PCNL) is indicated for the management of kidney stones larger than 2 cm. Awareness of the factors contributing to PCNL case costs could reduce health care spending. The purpose of this study was to determine the factors associated with increasing PCNL cost.

Methods Used

A retrospective review of PCNL cases performed at a single institution was conducted between January 2017 and May 2020. For each case, procedural cost and cost of hospital stay were determined. Procedural variables studied included patient age, sex, BMI, ASA, STONE score, surgeon’s training (general urologist vs. endourologist), presence of a urology-specific circulating nurse or scrub technician, presence of fellows or residents, operating room time, and whether access was performed by a urologist, radiologist, or both. Multivariate analysis was performed to determine which variables predicted increased cost, with p<0.05 considered significant.

Summary of Results

Of the 213 cases, 201 had complete cost data available. In these cases, average procedural cost was $11,600 and average total cost of hospital stay was $21,058. Multivariate analysis found OR time increased procedural cost at an average of $34.50 per minute (p<0.0001, SD=2.055). The presence of a urology-dedicated scrub technician decreased average cost per procedure by $1585.18 (p=0.0002, SD=414.459). Collaboration between urologist and radiologist in placing access increased cost by an average of $961.64, compared to access placed unaided by a urologist (p=0.04, SD=326.175).

Conclusions

OR time, presence of a urology-dedicated scrub technician, and urologist-obtained access are the primary determinants of PCNL case cost. Institutions should work to improve efficiency by creating urology specific operative teams to reduce the cost of PCNL.

180 Risk factors for hypospadias repair

B Stanyer

G Harianja

M Keheila

D Chamberlin

M Chau

C Chen

J Chamberlin

Loma Linda University, Loma Linda, CA

Purpose of Study

We aim to review risk factors for postoperative complications in hypospadias repair.

Methods Used

We performed a retrospective analysis of 516 boys undergoing hypospadias repair at a single institution between 2004 and 2020. Degree of severity was stratified by native meatus location: distal, mid shaft, or proximal, with proximal hypospadias being considered most severe. Glans width was measured with calipers at the start of surgery. We collected data regarding surgeon, type of hypospadias repair, degree of ventral chordee, and anesthesia block type (caudal block or penile nerve block). Postoperative complications were defined as meatal stenosis, urethral stricture, urethrocutaneous fistula, and glans dehiscence. Descriptive statistics and multivariate analysis were performed using SPSS with p<0.05 being considered statistically significant.

Summary of Results

A total of 516 hypospadias surgeries were performed by four surgeons using either tubularized incised plate (376) or meatal advancement and glanuloplasty (140). Median age at surgery was 10.1 months [7.37 – 18.45]. Mean follow-up time was 7.8 months. The severity of hypospadias was distal in 83.7% of cases, midshaft in 7.9%, and proximal in 8.3%. The overall complication rate was 8.3%. The complication rate for distal hypospadias was 4.9%, versus 12.2% for midshaft and 39.5% for proximal. Hypospadias location and glans width were significant predicting factors for postoperative complication (p<0.001, CI 95% [1.50, 3.67]), (p=0.002, CI 95% [0.61, 0.90]) respectively. Surgeon, type of hypospadias repair, degree of ventral chordee, and anesthesia block type were not found to be statistically significant on multivariate analysis.

Conclusions

Severity of hypospadias and smaller glans size are predictive for post-operative complications. Predictive risk factors can help guide discussion during preoperative counseling.

181 A retrospective study of risk factors and outcomes in the surgical management of slipped capital femoral epiphysis

W Jin1

S Farrell2

E Habib1

A Sandhu3

J Bone3

E Schaeffer1,3

K Mulpuri1,3

1BC Children’s Hospital, Vancouver, BC, Canada

2Children’s Hospital Queensland, South Brisbane, Australia

3University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Slipped Capital Femoral Epiphysis (SCFE) is conventionally treated with in-situ pinning (ISP) and more recently, the Modified Dunn Procedure (MDP). This study retrospectively examines the pre-operative risk factors and post-operative complications of patients treated with either ISP or MDP in a 12 year period.

Methods Used

A single-centre, retrospective review was performed on patients diagnosed with and surgically treated for SCFE from 2004 to 2016. Patients must have had pre-operative imaging and a minimum of six months of clinical follow-up. Pre-operative demographic data (age, gender, intensity of symptoms, stability, trauma, and severity of slip), operative details, and treatment outcomes were collected. Descriptive statistics were used to identify pertinent pre-operative risk factors and post-operative complications in each treatment group.

Summary of Results

A total of 129 hips in 98 patients were treated (118 with ISP, 11 with MDP). Complications developed in 12 hips (12 patients); six hips developed AVN, two developed AVN and chondrolysis, two developed AVN and slip progression, and two developed slip progression only. In hips treated with MDP, 4/11 (36.4%) developed complications; while 8/118 (6.8%) hips treated with ISP developed complications.

Conclusions

Complications developed in 9.3% of hips treated with ISP or MDP, with a higher rate of complications observed in the MDP group compared to the ISP group. The study is limited by the small sample size of the cohort and the disproportionate number of cases in each treatment group. A multi-centre study with larger sample sizes will be required to confirm these findings.

Gastroenterology

Concurrent session

4:20 PM

Friday, January 29, 2021
182 Clinical associations with myeloid-derived suppressor cell (MDSC) levels in hepatocellular carcinoma (HCC) patients

K Franke

L Yu

M Apodaca

R Yeung

W Harris

C Morishima

University of Washington, Seattle, WA

Purpose of Study

MDSC are immature myeloid cells with immunosuppressive capabilities. Elevated MDSC levels have been described in HCC and are associated with greater tumor burden and poorer response to treatment and survival. In this analysis, we sought to refine clinical associations with elevated MDSC levels to identify potential clinical utility for this biomarker.

Methods Used

Between June 2016 and September 2018, 46 HCC patients were tested for MDSC levels using a clinically validated whole blood flow cytometric assay (Apodaca et al, JITC (2019) 7:230). Total MDSC (T-MDSC) were defined as CD45+CD3-CD19-CD20-CD56-CD16-HLA-DR-CD33+CD11b+ cells/μL. All clinical data, with the exception of death, transplant and treatment variables, were obtained within 30 days of the MDSC test date.

Summary of Results

T-MDSC levels ranged from 14–617 cells/uL. Patients were divided into high (N=20) or normal (N=26) T-MDSC groups based on a single whole blood measurement.

The high T-MDSC group had higher total bilirubin (1.33±0.88 vs 0.9±0.44 mg/dL, p=0.04), lower serum albumin (3.46±0.48 vs 3.83±0.46 g/dL, p=0.01), higher WBC count (7.02±1.76 vs 5.35±1.42 x103/uL, p=0.001), and more ascites (p=0.04) compared to the normal group. High T-MDSC patients were more likely to be categorized as Child-Turcotte-Pugh (CTP) class B or C (vs A) (p = 0.0004) and Barcelona Clinic Liver Cancer (BCLC) stage C or D (vs A or B) (p=0.03) than the normal patients. Elevated T-MDSC levels were not associated with tumor size or number, vascular invasion, or AFP level. Although the high T-MDSC group experienced more deaths (12/20) than the normal group (10/26), the difference was not significant (p=0.15). Using Cox Proportional Hazard analysis, T-MDSC levels were not associated with patient survival before (hazard ratio 1.90, 95% CI 0.80–4.47) or after adjusting for age, CTP class, ECOG performance status and BCLC stage (hazard ratio 0.47, 95% CI 0.10–2.21).

Conclusions

Elevated MDSC levels were associated with more advanced disease and liver cancer stage but not with tumor characteristics or death. Additional studies are needed to investigate the relationship between MDSC levels and advanced cirrhosis.

183 The role of gut microbiota and diet in health outcome of covid-19 patients with comorbidities

E Eshaghian

B Singh

M Covasa

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

Purpose of Study

COVID-19, caused by the SARS-CoV-2 virus, is a novel infectious disease that has led to a global pandemic. SARS-CoV-2 gains cellular entry via ACE2 receptors which are localized to the lungs and gut, contributing to the respiratory and gastrointestinal symptoms in patients with COVID-19. Comorbidities such as obesity, diabetes, as well as advanced age represent high risk factors that have led to more severe symptoms and fatalities in COVID-19 patients. Obese, diabetic, and elderly patients have been characterized by a compromised immune system, overall systemic inflammation, disruptions in the gut microbiota composition profile (i.e. gut dysbiosis), poor nutritional status and nutrient deficiencies. The purpose of this paper is to discuss how these factors may contribute to the clinical manifestation of COVID-19 patients and how diet through specific nutrients and bioactive compounds can be used to restore and maintain proper immune cell function, increase protection against chronic inflammation, restore gut dysbiosis and improve health outcomes.

Methods Used

We searched manuscripts from the emergence of the pandemic from Dec. 2019 to Aug. 2020 as they relate to COVID-19’s impact on the gut, immune system, diet, and comorbidities. We related these observations with past articles conducted on these subjects.

Summary of Results

The gut microbiome has been shown to contribute to the host’s immune system development in addition to helping balance inflammatory responses. Dysbiosis of the microbiome has been associated with severe symptoms of COVID-19 through the gut lung axis by increasing systemic inflammation. Improper diet can also contribute to increased inflammatory signaling, which is the hallmark condition in COVID-19. There is a direct relationship between COVID-19 severity and inflammatory cytokines through the production of the cytokine storm. Diabetic, obese, and elderly patients have impaired gut microbiomes and nutritional deficiencies that may contribute to their vulnerability to COVID-19.

Conclusions

Proper diet and nutritional supplementation have shown to both improve gut microbiota composition profile and reduce systemic inflammatory effects. This could have a beneficiary role in these immuno-compromised at risk populations during the COVID-19 pandemic.

184 Systematic review of resident discrepancies in emergency abdominal radiology

M Rupasinghe

T Bui

R Mehta

J Glavis-Bloom

K Tran-Harding

R Houshyar

University of California Irvine, Orange, CA

Purpose of Study

Radiology call is a challenging endeavor for radiology residents. Although general diagnostic error rates are overall low,1 having a resident on call and an emergent setting like the emergency department can increase the frequency of mistakes. These diagnostic imaging errors are typically multifactorial and can be classified by body location and etiology of the mistake.2 3 Errors in interpretation of diagnostic imaging can lead to delays in patient care, patient morbidity or mortality, and increased cost of care. This study analyzed primary discrepant cases in abdominal imaging to elucidate patterns of error location and type in order to inform pre-call resident education.

Methods Used

Resident discrepancies for abdominal imaging in the emergency setting at a level 1 trauma academic medical center between 2015–2020 were reviewed. Discrepant cases were classified by error type, body part involved, and diagnosis. Descriptive analysis was performed.

Summary of Results

A total of 197 studies had resident discrepancies, and several of these studies had more than one discrepant finding. When classified by error types, 61.4% stemmed from satisfaction of search, 34.0% from inadequate search pattern, and 8.6% from inadequate assessment of peripheral locations. When classified by body parts missed, 47.7% involved solid organs, 22.8% involved hollow visci, and 16.8% involved musculoskeletal structures.

Conclusions

Most resident call interpretation errors in abdominal imaging were attributable to satisfaction of search or inadequate search patterns. Nearly half of all errors involved solid organ structures, and the most commonly misdiagnosed entities involved the lymph nodes, pancreas, appendix, and kidneys. By shedding light on error patterns, we hope to improve resident education prior to call to reduce diagnostic errors.

185 Characterizing the morphologic spectrum of diverticulosis and associating risk of developing diverticulitis

M Levy

LL Strate

RL Kosowicz

University of Washington School of Medicine, Seattle, WA

Purpose of Study

Diverticula are the most common finding on colonoscopy; about 4% of these patients will develop diverticulitis. Diverticular morphology in the colon varies greatly in both size and distribution; this variability has not yet been systematically quantified or studied in relationship to diverticulitis. The primary goal of this study was to characterize and categorize the morphologic spectrum of diverticulosis diagnosed on colonoscopy and study the association between morphology and risk of diverticulitis.

Methods Used

We performed a retrospective, case-control study of 85 patients with a history of diverticulitis and 85 controls with diverticulosis without diverticulitis matched on gender, age (within 5 years) and year of colonoscopy, identified using a search of the electronic medical record. The variables for morphologic characteristics were obtained from review of electronically available endoscopy reports and included extent, number and size of diverticula. We also assessed characteristics of diverticulitis in cases including the presence of complications. Baseline characteristics were compared in cases and controls using the McNemar Chi-Square test and odds ratios and 95% confidence intervals were calculated for diverticulosis severity, location, and size.

Summary of Results

Baseline characteristics in diverticulitis cases and controls were similar except that cases were more likely to have a diagnosis of IBS (P=0.043) than controls. Among the cases with a history of diverticulitis, 69% of diverticulitis was located in the sigmoid colon and 27% had complicated diverticulitis. Cases were more likely to have severe diverticulosis on endoscopy compared to controls (OR=4.09, 95% CI=1.85–9.07), less likely to have mild diverticulosis (OR=0.22, 95% CI=0.11–0.42), less likely to have diverticulosis present only in their right colon (OR=0.11, 95% CI=0.02–0.51), and less likely to have small diverticula present (OR=0.35, 95% CI=0.16–0.76).

Conclusions

In our study, cases with a history of diverticulitis were more likely to have severe diverticulosis on colonoscopy and less likely to have small diverticula and diverticula located only in the right colon when compared to controls. Diverticular morphology is a novel risk factor for diverticulitis.

186 Congenital narrowing of CBD and pancreatic duct causing pancreatitis in otherwise healthy 18 y/o female

U Brar

Adtalem Global Education Inc, Fresno, CA

Purpose of Study

To share this interesting case with the medical community

Methods Used

Retrospective study

Summary of Results

An 18-year-old Hispanic female with no significant past medical history presented with sharp epigastric abdominal pain for four days with radiation to right upper quadrant. The pain was associated with nausea and five episodes of yellow bilious vomiting over the past 24 hours. The patient denied consuming alcohol or illegal drug abuse. She also denied using any new medication or herbal treatment and history of trauma. Patient had cholecystectomy at the age of 9. When asked about the detail’s patient stated she had to wait for few days for her pancreas level to come down before cholecystectomy. On physical examination, she was afebrile, had blood pressure of 124/77 mm Hg, and heart rate of 68 beats/min with respiratory rate of 18.

Her laboratory tests on admission revealed a WBC of 20.1 × 103/μL with neutrophil of 87.7%. She had unremarkable basic metabolic panel. The urine HCG was negative, but urine toxicology was positive for cannabinoids. Her serum lipase was 13,121. The CT scan showed pancreas with peripancreatic fat stranding and trace amount of peripancreatic fluid consistent with pancreatitis. Patient was admitted to the floor and kept NPO. She was treated with intravenous fluids, analgesics and antibiotics. The following day patient had MRCP done showing narrowing of the pancreatic duct worse in common bile duct. Patients abdominal pain resolved, tolerated clear liquids and subsequently advanced to full liquids then GI soft diet. Patient was discharged with outpatient follow up with gastroenterology and IM clinic. The autoimmune labs were positive for ANA with titer of 1:40, CA 19–9 of 37 units/mL, smooth muscle ab titer of 1:20 and negative for IgG4 of 37.9.

Conclusions

Patient presented with the typical case of acute pancreatitis and was subsequently managed with conservative treatment. But due to the patient being 18 years of age an underlying etiology was suspected. The MRCP showing narrowing of the pancreatic duct. The patient got better over the course of two days so there was no indication for ERCP. Also, autoimmune etiology was suspected as narrowing of the pancreatic duct is associated with underlying autoimmune pancreatitis.

187 Digital clubbing and eosinophilic esophagitis

J Liu

PC Do

M Haight

UCSF Fresno Center for Medical Education and Research Edward and Ann Hildebrand Medical Library, Fresno, CA

Background

Digital clubbing is regarded as one of the most ancient clinical signs in medicine, characterized by an increase in nail plate convexity, resulting in excessive sponginess of the nail base. Digital clubbing is associated with a variety of diseases, including infections, inflammatory disease, cardiopulmonary and gastrointestinal disorders. Previously there have been no reported cases of digital clubbing in association with eosinophilic esophagitis (EoE).

Case

A 17-year-old male initially presented with a 3-year history of joint pain, myalgia, digital clubbing, chronic chest tightness, difficulty sleeping, chronic vague abdominal pain, loose stools and difficulty swallowing medications. In addition he had stiffness of his hands, knees and shoulders and intermittent swelling of his knees. His initial evaluation showed normal vital signs. His physical exam was unremarkable except for moderate digital clubbing.

An evaluation for endocrine, rheumatologic, pulmonary and cardiac processes showed normal laboratory values. His chest computer tomography scan, sweat chloride test and echocardiogram were also normal. An esophagogastroduodenoscopy (EGD) showed increased intraepithelial eosinophils at 25 eosinophils per high-powered field (HPF) on midesophageal biopsy consistent with EoE. His bronchoscopy showed laryngeal and airway inflammation and tracheobronchomalacia. Evaluation for primary ciliary dyskinesia revealed normal ultrastructure and two variants of unknown significance on genetic testing. He was started on omeprazole and eventually oral budesonide with improved gastrointestinal, sleep, and respiratory symptoms and his digital clubbing reduced in severity.

Discussion

This is a rare presentation of digital clubbing with EoE. Treatment of his EoE led to improved symptoms as well as digital clubbing on examination. The correlation between digital clubbing and EoE in this case remains unclear. Previous research shows some similarities between the two diseases in angiogenesis based on biomarkers. Given the lack of reports of patients with EoE and clubbing this raises the potential that his EoE may be causing respiratory disease such as aspiration or sleep apnea, though it also raises the question whether this relationship is being under-reported in general.

188 Blindness in a healthy child

R Gonzalez

J Snider

C Schmidt

Valley Children’s Healthcare, Madera, CA

Case Report

Our patient is an 8 year-old previously healthy male with many months of red eyes, irritation, photophobia, and red bumps on eyelids with discharge who presented to the emergency department with acutely worsening symptoms. He was initially diagnosed with styes and discharged home with instructions for warm compresses. He followed up with primary pediatrician who recommended antibiotic ophthalmic drops. This was ineffective and he was eventually referred to two ophthalmologists who both prescribed steroid eye drops. He was not given a formal diagnosis, according to mother. He returned to our emergency department with worsening eye symptoms, new onset night blindness, and was found to have bilateral eye cloudiness and right corneal abrasion on exam. A comprehensive history revealed poor diet consisting primarily of fast food. He was admitted for evaluation of vitamin A deficiency versus infectious cause. Eye exam under anesthesia revealed bilateral conjunctival xerosis with right-sided Bitot’s spots, stromal loss, and bilateral deep interstitial keratitis. Vitamin A level returned critically low at <2.5 µg/dL. Infectious workup was negative. 50K units of vitamin A supplementation daily was started. On subsequent follow up visits patient reported improved photophobia, eye edema, and pain, but visual acuity was slower to recover.

In the developing world vitamin A deficiency is usually caused by food deprivation and is a major cause of preventable blindness worldwide. In high-income countries, where vitamin enriched foods are more readily available, vitamin A deficiency is rare and primarily related to underlying medical conditions (i.e. malabsorption) or restrictive eating habits. However, it is also possible that this condition is underdiagnosed because of nonspecific early symptoms, which could have been the case for our patient. Furthermore, there was also question if our patient had an undiagnosed behavioral condition such as autism that would cause picky eating. It is well documented that children with autism and very rigid behaviors can suffer from significant malnutrition, which can result in severe vitamin deficiencies. This case further highlights the importance of thorough history taking, including diet, eating habits and behavioral habits, when patients present with nonspecific complaints.

Surgery III

Concurrent session

4:20 PM

Friday, January 29, 2021
189 An evaluation of the impact of 0.05% chlorhexidine on the prevalence of surgical site infections in aesthetic breast surgery

Y Han1

V Lee1

NK Srikureja1

S Gupta2

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

2Loma Linda University, Loma Linda, CA

Purpose of Study

Surgical site infections (SSI) burden U.S. hospitals with around $1.5 billion annually. To reduce SSI, irrigating the incision with an antimicrobial solution before closure is recommended. Hence, we evaluate the impact of Irrisept, a form of diluted chlorohexidine 0.05%, on reducing the prevalence of SSI in a high-risk breast cosmetic surgery population.

Methods Used

We conducted a retrospective cohort study using data in the electronic medical record for breast implant exchange patients in one practice and analyzed infection rates between 42 patients from July 2018-June 2019 that did not receive Irrisept irrigation (control group) with 16 patients from July 2019-July2020 that received Irrisept irrigation (experimental group; significantly less due to Covid-19). We executed descriptive analyses, independent T test, ANOVA (for 3 types of incision location), and Chi-squared to assess comorbidities and intraoperative factors.

Summary of Results

Among the control group (n=42), 4 patients had a postoperative infection; in the experimental group (n=16), 0 had an infection (9.52% vs. 0%; p=0.04) suggesting the use of Irrisept significantly decreases SSI. The p values from the T test and ANOVA (p<0.05=significant) showed no significant differences in breast cancer (0.84), previous radiation (0.32), history of chemotherapy (0.57), obesity (0.40), renal failure (0.32), smoker/previous smoker (0.41), type of implant (0.32), incision location (0.68), acellular dermal matrix use (0.32), or drain use (0.58) between two groups. The only significant comorbidity was diabetes (p=0.04) with 9.52% (control) vs. 0% (experimental). However, greater percentage of experimental group were obese (25% vs.14.29%) and had a history of smoking (25% vs. 9.52%).

Conclusions

A concern regarding the implementation of Irrisept irrigation is associated costs. However, the results show the use of Irrisept decreases the infection rates, ultimately relieving the financial burden of postoperative infections. Therefore, we recommend irrigating the incisions of breast surgery patients with Irrisept as both a preventative and economic measure.

190 Intraoperative maneuvers to optimize the healing of surgical incisions: an evidence-based review

Y Han1

V Lee1

S Gupta1

K McMath2

KB Hanson2

S Gupta1

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

2Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Incisions vary in intricacy as procedures advance to meet the increasingly complex physiology of the patient pathology. Optimizing the healing of incisions is paramount in the care of surgical patients. Many different interventions are used with the aim to reduce the risk of surgical site infections (SSI) and enhance wound care after surgery. This review presents a compilation of evidence-based, safe, and effective intraoperative interventions for most populations undergoing surgery.

Methods Used

A broad literature review was performed to identify publications on optimizing the healing of surgical incisions with an emphasis on intraoperative maneuvers. Key words and phrases that were used to search the literature include: SSI control AND prevention, intraoperative maneuvers AND SSI, surgical incision healing, SSI bundles AND effective interventions, adoption of incision healing methods, epidemiology of SSI, and intraoperative measures. Out of all the searches, 34 articles were selected to develop an evidence-based compilation of the safest and most effective interventions.

Summary of Results

A summary of the interventions is presented in table 1.

Abstract 190 Table 1

Intraoperative Maneuvers to Optimize Surgical Incision Healing

Conclusions

Evidence suggests that the effective interventions presented optimize surgical incision healing; however, compliance and implementation of these maneuvers remain a challenge. Knowledge of the risks to incision healing and the benefit of various post-operative incisional dressings guide providers’ decision making.

191 Does the novel thulium laser generate more heat than the conventional holmium laser?

NK Srikureja

JD Belle

N Chen

M Keheila

AS Amasyali

D Baldwin

Loma Linda University, Loma Linda, CA

Purpose of Study

The novel thulium fiber laser (TFL) has been shown to break stones more rapidly than the traditional Ho:YAG laser. However, evidence suggests that the TFL may result in more thermal injury. The purpose of this study is to compare ureteral temperatures during flexible ureteroscopic laser lithotripsy.

Methods Used

A 1-cm Bego Stone was manually impacted 3 cm from the ureteropelvic junction in a 3D printed Dragon Skin kidney-ureter stone-patient replica submerged in 35°C saline. Lithotripsy was performed using a 7.6 French flexible ureteroscope and a 200 m laser fiber without a ureteral access sheath, comparing 3 lasers (Dornier 30W, Olympus Empower 100W, and Olympus Thulium 60W). The laser tip was positioned on the stone, 2 mm from the needle thermocouple. Irrigation was maintained at 35cc/min and 23.8 ± 1.5°C. Ureteral temperature was continuously recorded for 60 seconds of laser activation. 5 trials were performed for each of 5 different power settings: 3.6, 6.4, 10, 20, and 30 Watts. ANOVA and Mann-Whitney U tests were performed, with p<0.05 considered significant.

Summary of Results

Table 1 shows the average temperature for each laser at each setting. The TFL produced significantly higher temperatures at 3.6W and 30W settings.

Abstract 191 Table 1

Average Ureteral Temperatures for Dornier, Empower, and Thulium lasers

Conclusions

The TFL generates more heat at both 3.6W and 30W settings. Supraphysiologic ureteral temperature generated by this laser could cause ureteral injury with extended use at high energy settings and low irrigation rates. Understanding the heat generation properties of the TFL is important to maintain safety during ureteroscopic laser lithotripsy.

192 Comparison of thulium fiber laser core diameters in treating in situ lower pole nephrolithasis

N Chen

A Amasyali

N Srikureja

J Lee

JD Belle

M Keheila

D Baldwin

Loma Linda University, Redlands, CA

Purpose of Study

Recent studies have found the thulium fiber laser (TFL) to be a positive alternative to the conventional holmium: YAG (Ho:YAG) laser for intracorporeal lithotripsy. One advantage of the TFL is its ability to support higher frequency settings with smaller diameter fibers that allow for better deflection, irrigation and visibility; however, this must be weighed against its efficacy in stone treatment. The purpose of this study was to test this by comparing the TFL against a conventional Ho:YAG laser in the treatment of in situ lower pole kidney stones.

Methods Used

A benchtop study was conducted using a 3D printed kidney model. 1.0 cm BegoStone phantom stones of calcium oxalate monohydrate consistency were placed in the lower pole calyx. A 60W Olympus Soltive TFL was trialed with both a 150 mm and 200 mm fiber at 1J x 20Hz (20W), 0.4J x 50Hz (20W) and 0.2J x 100Hz (20W). A 30W Dornier Medilas Ho:YAG was trialed using a 200 mm fiber at 0.6J x 15Hz (9W). Stones were treated by the same urologist using a flexible ureteroscope with the stone free endpoint of <2 mm and several parameters were recorded. Mann – Whitney U test was done for analysis with p<0.05 considered significant.

Summary of Results

Procedure time was significantly lower in the TFL trials with a 150 mm fiber at all settings when compared to the TFL trails with a 200 mm fiber and the Ho:YAG trials (table 1).

Abstract 192 Table 1

TFL vs. Ho:YAG Results

Conclusions

Stones treated by TFL with a small fiber diameter required less procedure time with better scope deflection and visibility. Additional in vivo trials are needed but these findings suggest that there are significant advantages in treating lower pole stones with TFL.

193 Retrospective cohort assessment of prokinetic properties of azithromycin on postoperative ileus

R Ong

I Dorotta

M Eby

R Raval

Loma Linda University School of Medicine, Loma Linda, CA

Purpose of Study

Postoperative ileus has been reported in 10 to 20% of cesarean patients. Macrolides are traditionally used as antibiotics, but they also have promotility properties. Previous studies failed to show beneficial effect of erythromycin on ileus but azithromycin has not been thoroughly investigated. This study evaluates the utility of azithromycin to reduce postoperative ileus.

Methods Used

A retrospective cohort analysis of 3993 patients undergoing cesarean section were divided into two groups based on pre-operative azithromycin (n=2632) or no azithromycin administration (n=1361). Patients were selected from medical record database search who were cesarean patients from June 2015 to September 2019. Primary outcome was patients with post-operative bowel movement (BM) within 24 hrs of azithromycin administration. We also analyzed flatus, and postoperative nausea and vomiting (PONV) within 24 hours of azithromycin, post-operative length of stay (LOS), time to diet, and discharge disposition.

Summary of Results

Age, race, gravidity, parity, and ASA classification were all clinically comparable between both groups. (Table 1) BM within 24 hours was seen in 37% of the patients with azithromycin compared to 14% of patients without azithromycin (P<0.00001). Flatus within 24 hours was seen in 3.9% of patients with azithromycin compared to 2.0% with no azithromycin (P=0.00135). Post-operative LOS was shorter with the patients with azithromycin at 76±18 h compared to no azithromycin group at 79±14 h (P=0.00005). (Table 2).

Abstract 193 Table 1

Cesarean patient selection characteristics

Abstract 193 Table 2

Cesarean patient significant outcomes

Conclusions

The shorter time to BM, flatus and post-operative LOS is likely attributed to decreased ileus in patients administered azithromycin. This study shows that azithromycin deserves future prospective investigation as an agent to reduce post-operative ileus.

194 Impact of montgomery T-tubes on treatment of laryngotracheal stenosis and voice outcomes

R Hahn

D LaTour

P Krishna

B Crawley

Loma Linda University School of Medicine, Studio City, CA

Purpose of Study

Placement of a Montgomery T-tube is indicated for patients as a stent to maintain airway patency in those presenting with laryngotracheal stenosis with intention to also treat secondary aphonic or dysphonic symptoms. The objective of this paper is to identify the indications, complications, and airway and voice outcomes of patients that were managed with Montgomery T-tube stenting.

Methods Used

A retrospective chart review was done on patients treated with Montgomery T-tubes for laryngotracheal stenosis due to either iatrogenic causes or other etiologies. Patient demographics including age, gender, and BMI were analyzed along with their indication for t-tube placement, duration of t-tube placement, and numbers of surgeries related to their t-tube placement. Treatment outcomes were also recorded, including Voice Handicap Index, VHI-10 scores before and after t-tube placement, complications, and time since the definitive procedure.

Summary of Results

13 patients were included (4M9F), of which nearly half of were aphonic prior to tube placement. The most common indication for t-tube placement was management of secondary subglottic and tracheal stenosis. Other indications included treatment of fractured cricoid ring, post arytenoidectomy defects, preferral of t-tube over trach tube, and post-laryngotracheal resection with reanastomosis. The data presented statistically significant improvements in VHI-10 scores after t-tube placement (p<0.05). Eight patients were successfully decannulated, four patients are still being treated, and one was lost to follow-up. The most common complication related to t-tube placement was the accumulation of granulation tissue, with all patients having to undergo granulation excisions. There were no deaths related to t-tube placement.

Conclusions

Treatment with Montgomery T-tubes can show improvement in voice quality in patients with severe dysphonia secondary to laryngotracheal stenosis and traditional tracheostomies. However, the complication rate and contraindications should be taken into consideration. More research regarding the methods of placement, treatment course and care are necessary to understand the role of t-tubes in treating laryngotracheal stenosis.

195 Surgical debridement frequency during use of negative pressure wound therapy with instillation versus control: a systematic review and meta-analysis

E O’Rorke1

RM Gold1

A Gabriel2

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

2Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Meta-analyses have become increasingly important in health care decision making. Currently, there are no published meta-analyses comparing outcomes with the use of negative pressure wound therapy (NPWT) with instillation and dwelling of a topical solution (NPWTi-d) versus alternative wound care strategies. To address this gap, a systematic review and meta-analysis were performed to report the integrated results of studies describing use of NPWTi-d versus any other wound care strategy (ie, control) in any wound type.

Methods Used

720 patients across thirteen studies were included in the analysis. Weighted standardized mean difference or odds ratios as well as 95% confidence intervals were calculated in order to pool study and control group results in each publication for analysis.

Summary of Results

Results showed wounds in the NPWTi-d group received significantly fewer surgical debridements and were prepared faster for surgical closure versus the control group (2.23 v. 3.07, p=0.01 and 3.02 days v. 4.16 days, p = 0.03, respectively). The odds of reducing bacterial count from baseline in the NPWTi-d group was 4.4 times greater than control group wounds (p=0.003), and percent reduction of bacterial count in NPWTi-d wounds was evident in all studies that included that endpoint. Wounds in NPWTi-d group had successful closure 2.39 times more than control group wounds (p=0.01). There was a significantly shorter length of therapy with NPWTi-d versus control wound care strategies (p=0.03). Length of hospital stay was not significantly reduced for NPWTi-d patients compared to control patients (p=0.06).

Conclusions

These meta-analysis results show a positive overall effect of NPWTi-d on various wound types in comparison with other wound care strategies.

196 Initial experience with closed incision negative pressure therapy specialty dressing over sternal reconstruction incisions

C Lee1

E O’Rorke1

A Gabriel2

1Elson S Floyd College of Medicine, Vancouver, WA

2Loma Linda University Medical Center, Loma Linda, CA

Purpose of Study

Following median sternotomy, surgical site complications (SSCs) such as sternal dehiscence have an incidence of 0.06% to 12.50%, with associated perioperative mortality as high as 47%. Closed incision negative pressure therapy (ciNPT) administers continuous subatmospheric pressure, removes fluid and infectious materials, holds incision edges together, provides a barrier to contaminants and reduces the incidence of edema. Recently, a ciNPT specialty dressing with an expanded coverage area was developed to protect incisions. We describe our experience using this ciNPT specialty dressing to help manage sternal reconstruction incisions in 4 patients.

Methods Used

The ciNPT specialty dressing was applied to incisions stemming from revised sternal dehiscences of patients (n = 4) who had developed SSCs following index cardiothoracic procedures. Perioperative antibiotics were administered. A single surgeon performed debridement and chest wall reconstruction with bilateral pectoral flaps to revise the dehiscence. Incisions were stapled or sutured. Surgical drains were placed as necessary. Immediately postoperatively, the ciNPT specialty dressing was placed over the closed incision and ciNPT (-125 mmHg) was initiated. Dressing changes occurred every 7 days.

Summary of Results

2 female and 2 male patients had a mean age of 52.8 ± 13.1 years. Comorbidities among the patients included: hypertension, coronary artery disease, hyperlipidemia, ischemic cardiomyopathy, myocardial infarction, and sternal osteomyelitis/surgical site infections. Incisions measured 20 cm on average. Incisions remained closed at dressing change/removal in all 4 patients. Drains were removed between POD 7 and POD 34. Hospital length of stay ranged from 2–13 days. One patient developed a hematoma. Patients reported reduced pain and swelling postoperatively. In all patients, incisions remained closed at 30-day follow-up appointments. There were no reports of flap failure post defect reconstruction.

Conclusions

In these patients, the ciNPT specialty dressing facilitated positive healing outcomes following the revision of a sternal dehiscence. These outcomes support the use of ciNPT specialty dressings in the management of sternal dehiscence incisions.

Cardiovascular I

Concurrent session

9:00 AM

Saturday, January 30, 2021
197 Cardiac sodium/calcium exchanger is necessary for normal atrioventricular node function

AT Hazan1*

R Zhang1

S Lotteau1

T Ribeiro Mesquita1

Y Lin1

D Gonzalez1

N Cuk1

KD Philipson2

M Ottolia2

JI Goldhaber1

1Cedar’s-Sinai Medical Center, Los Angeles, CA

2UCLA, Los Angeles, CA

Purpose of Study

The sodium-calcium exchanger 1 (NCX1) is an essential component of the ‘calcium clock,’ one of two coupled oscillators that generates pacemaker activity in the sino-atrial node (SAN). However, it is uncertain to what degree NCX and the ‘calcium clock’ are responsible for pacemaker activity (i.e. escape rhythm) or conduction in the atrioventricular node (AVN).The purpose of this study was to determine whether NCX1 is required for normal automaticity and conduction through the AVN.

Methods Used

We used our previously described atrial-specific NCX1 knock-out (KO) mice, which live to adulthood. We used surface electrocardiograms (ECG) in anesthetized mice during right atrial overdrive pacing to assess AV conduction. The generation of spontaneous calcium (Ca) transients in resected AVN tissue was recorded using 2D confocal microscopy. Membrane currents and voltage of isolated AVN cells were determined using single cell patch clamp.

Summary of Results

In patch clamped enzymatically isolated AVN cells from NCX1 KO mice, NCX1 current was eliminated completely in about half of cells tested, while the remainder retained about 20% of WT activity (average 2.29 ± 0.23 pA/pF in WT vs 0.29 ± 0.08 pA/pF in KO). Using overdrive pacing, we observed that NCX1 KO mice developed Mobitz I second degree AV block at slower pacing rates than WT mice. AV block developed in KO mice when the pacing rate was increased by 19% whereas WT mice did not develop AV block until the rate was increased by 43% (p < 0.0001). In NCX1 KO mice, resected AVN tissue loaded with the Ca indicator CalBryte520 exhibited spontaneous Ca waves but little to no coordinated Ca transients. In isolated AVN cells, ICa was reduced from 3.73 ± 0.39 pA/pF in WT to 1.59 ± 0.18 pA/pF in KO. If was also reduced in NCX1 KO mice (-39.07 ± 10.52 in WT vs -14.71 ± 3.80 in KO). Finally, spontaneous action potentials were eliminated in almost all NCX KO AVN cells (10 out of 13).

Conclusions

NCX1 and the ‘calcium clock’ are essential for normal AVN automaticity and conduction on the single cell, tissue, and intact mouse levels, though adaptations in other membrane currents (ICa, If) may also alter function.

198 The vagrancies of donor selection: is quality that important?

K Tor1*

T Singer-Englar2

N Patel2

M Hamilton2

J Kobashigawa2

1Creighton University, Omaha, NE

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

Purpose of Study

Donor selection in heart transplant is not standardized. Many donor hearts (DH) are declined due to quality issues such as older age, low left ventricular ejection fraction, left ventricular hypertrophy, diastolic dysfunction, underlying coronary artery disease. Yet, DHs declined at one center are subsequently accepted at another center. It is not well known whether DHs declined due to quality and accepted by another program have acceptable post-transplant outcomes.

Methods Used

Between 2017 and 2019, we assessed 532 DHs that were allocated to a single center (Cedars-Sinai). We declined 218 offers due to quality. We had follow-up with organ procurement organizations and found that 45 of these DHs that we turned down were accepted by another program and transplanted. 1-year post-transplant survival of these patients were compared to those patients whose donor was accepted and transplanted at Cedars-Sinai (n=314).

Summary of Results

45 declined DHs were subsequently accepted by another program and transplanted into their patients. These 45 declined DHs had the following issues: abnormal cardiac studies (n=12), donor cardiac history (n=6), other medical history including cirrhosis or infectious processes (n=6), nature of the cause of death (n=3), older age (n=14), estimated prolonged ischemic time (n=1), and other reasons (n=3). Compared to those patients transplanted at Cedars-Sinai, the declined donor recipients had similar age and gender but had a longer cold ischemic time. There were significantly fewer patients in the declined DH group compared to the Cedars-Sinai group who were listed as high urgency status at transplant (46.7% vs 78.7%, p<0.001). There was no difference in 1-year patient or graft survival between the two study groups (see table 1).

Abstract 198 Table 1

Conclusions

DHs declined for quality may be accepted at another program with good post-transplant survival. Contrary to belief, these DHs were mostly not transplanted into high urgency waitlist patients. Donor declines due to quality should be reviewed as they could lead to more lives saved.

199 4D-Flow MRI intracardiac flow hemodynamic patterns can phenotype pulmonary hypertension subtypes

LK Ross1*

AJ Barker2

BS Frank2

K Hunter2

GJ Morgan2

MB Mitchell2

BE Fenster2

M Schäfer1

D Ivy2

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

2Children’s Hospital Colorado, Aurora, CO

Purpose of Study

Idiopathic Pulmonary Arterial Hypertension (PH-Type I) and PH due to pulmonary disease (PH-Type III) arise from different pathophysiologic processes, yet both culminate in increased right ventricular (RV) afterload and eventual failure. Previous investigations have demonstrated that 4D-Flow MRI-derived intracardiac vorticity (ω) correlates with markers of ventricular interdependency and diastolic dysfunction in PH, however none have attempted to use these metrics to phenotype PH subgroups. This investigation explores whether 4D-Flow MRI can detect diastolic dysfunction differences that make it possible to phenotype Type I and Type III PH.

Methods Used

Type I PH patients (n=12, mean age 61 yrs), Type III PH patients (n=15, mean age 63 yrs), and healthy controls (n=10, mean age 58 yrs) underwent standard cardiac MRI and 4D-Flow MRI to determine RV intracardiac flow markers including early (ω-E) and late (ω-A) diastolic vorticity. Standard MRI-based RV and LV size and function markers were also collected.

Summary of Results

ω-E was decreased in the Type I PH group compared to the Type III PH group (P=0.035) and to controls (P<0.001). There was no difference in ω-E between the Type III group and controls (P=0.216). RVEF was decreased in both the Type I (P<0.001) and Type III (P=0.012) group compared to controls. There was no difference in RVEF between the Type I and Type III groups (P=0.917). RVEDV was increased in both the Type I (P=0.008) and Type III (P=0.006) groups compared to controls. No significant differences were detected in ω-A and other RV or LV volume and functional indices.

Conclusions

4D-Flow MRI can distinguish among different PH subtypes using intracardiac diastolic vorticity. Comparative studies with standard echocardiography and catheterization are necessary to assess the sensitivity of 4D-Flow MRI to detect diastolic dysfunction.

200 Phospholamban and A-kinase anchoring protein 6 modulation of calcium cycling in the heart

F Hakem Zadeh1,2,3*

AC Teng1,2

U Kuzmanov2

PJ Chambers4

AR Tupling4

AO Gramolini1,2

1University of Toronto Faculty of Medicine, Toronto, ON, Canada

2Translational Biology and Engineering Program, Toronto, ON, Canada

3Western University of Health Sciences College of Osteopathic Medicine of the Pacific, Pomona, CA

4University of Waterloo, Waterloo, ON, Canada

Purpose of Study

Phospholamban (PLN) is an important modulator of Ca2+ cyclin at the sarcoplasmic reticulum (SR) of striated muscles. It inhibits sarcoplasmic reticulum Ca2+ ATPase (SERCA) function. Upon phosphorylation of PLN at serine 16 by protein kinase A (PKA)-dependent mechanism this inhibition is reversed. The underlying mechanism of this inhibition is not fully understood. In this study, using informatics approach, we identified A-Kinase Anchoring Protein 6 (AKAP6) as a candidate that play some roles in PLN phosphorylation.

Methods Used

To demonstrate colocalizations, we performed immunofluorescence and 3D reconstruction on AKAP6 and PLN in cotransfected HEK293T cells, cultured mouse neonatal cardiomyocytes (CMNCs) and adult rat cardiomyocytes. To confirm biochemical interactions we conducted coimmunoprecipitation between wild type PLN, as well as PLN mutants (PLN-R9C, PLN-RΔ14, PLN-L39Stop) that lead to dilated cardiomyopathy, and AKAP6. Functionally, Ca2+ uptake activity of AKAP6, PLN and SERCA proteins was investigated using Ca2+ ATPase assays.

Summary of Results

Our immunofluorescence studies demonstrated colocalization between AKAP6 and PLN in cotransfected HEK293T cells and CMNCs. Coimmunoprecipitation assays further confirmed the interactions in HEK293T and isolated adult rat cardiomyocytes in response to isoproterenol stimulation. PLN mutations exhibited altered interaction with cotransfected AKAP6, compared to wild type PLN. Functionally, AKAP6 promoted Ca2+ uptake activity of SERCA1 in cotransfected HEK293T cells despite the presence of PLN. These results were further confirmed in adult rat cardiomyocytes. Immunofluorescence showed colocalization of both proteins around the perinuclear region. Protein–protein interaction was identified by immunoprecipitation specifically in the nucleus enriched fraction of rat hearts.

Conclusions

Our results are suggestive of regional regulation of PLN by AKAP6 at perinuclear region. Our findings suggest AKAP6 as a novel interacting partner to PLN in HEK293T and murine cardiomyocytes.

201 Myocardial injury but not dysfunction identifies hospitalized patients with covid-19 at high mortality risk

ET Vazquez*

KB Atsina

A Shulkin

EC Toledo

JE Lopez

UC Davis Health, Sacramento, CA

Purpose of Study

Myocardial injury is clinically defined by an elevated cardiac troponin (cTn) value above the 99th percentile upper reference limit and is frequently reported in hospitalized adults dying from Coronavirus disease 2019 (COVID-19). However, the relationship between myocardial injury and dysfunction i.e. left ventricular ejection fraction (LVEF) < 50% by echocardiogram is not yet reported. Our objective was to evaluate this relationship in a single center using a pragmatic approach.

Methods Used

The electronic medical records (EMR) of hospitalized patients with COVID-19 from 3/1 to 9/19/2020 were reviewed using SlicerDicer, an EMR self-service search tool. Survival, demographics, clinical, laboratory and echocardiographic data were analyzed as a function of myocardial injury.

Summary of Results

Of the 328 patients evaluated, 240 (73%) had a high-sensitivity cTn T (hs-cTnT) test, as a serum biomarker for myocardial injury. Among those tested, 102 (42.5%) had at evidence of myocardial injury. Patients with injury had a significantly higher rate of in-hospital mortality compared to those with a negative test or no test (29.4% vs. 3.5%, p < 0.001, unadjusted OR 11.4, 95% CI 5.0 – 25.9). Among patients with myocardial injury with echocardiograms, there was no significant difference in LVEF between the patients who died (n=14) and those who survived (n=27), (52.4% vs 60.8%, p = 0.072). Age over 50 years (OR 6.1, 95% CI 3.1 – 11.7, p < 0.001), hypertension (OR 4.6, 95% CI 2.8 – 7.5, p < 0.001), coronary artery disease (CAD) (OR 4.3, 95% CI 1.9 – 9.8, p < 0.001) and male sex (OR 1.8, 95% CI 1.1 – 2.9, p = 0.019) were associated with injury. BMI > 30 kg/m2 was associated with a negative hs-cTnT test or no test (OR 0.6, 95% CI 0.4 – 1.0, p = 0.031). Diabetes and chronic obstructive pulmonary disease had no association with myocardial injury.

Conclusions

Among adult hospitalized COVID-19 patients, myocardial injury, but not LV dysfunction, was associated with a higher rate of in-hospital death. Further prospective studies are needed to understand how COVID-19 contributes to myocardial injury and death, without inducing dysfunction in older hypertensive patients with CAD if death is to be prevented.

202 Donor heart coronary calcification: is it bad?

P Hage*

N Patel

T Singer-Englar

M Hamilton

J Kobashigawa

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

Purpose of Study

The donor shortage in heart transplantation (HTx) has led to programs accepting older donors. Coronary calcification is common in older people and is known to correlate with underlying coronary artery disease. It is not known whether these donors with coronary calcification impart an increased risk for the recipient to develop cardiac allograft vasculopathy.

Methods Used

Between 2010 and 2017, we assessed 31 heart transplant patients who were found to have coronary calcification within the first 3 months after heart transplantation, either by coronary angiography or chest CT scans. These patients were compared to a contemporary cohort of 192 patients (transplanted with donors >30 years old) without coronary calcification for the following outcomes: 3-year survival, 3-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), 3-year non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR).

Summary of Results

Those patients with donor coronary calcification compared to those without had a significantly lower 3-year freedom from CAV (64.5% vs 85.9%, P=0.001). There was no significant difference in 3-year survival, freedom from NF-MACE, and 1-year rejection episodes. The severity of CAV observed in the donor coronary calcification group included: CAV1 = 13, CAV2 = 1, CAV3 = 0.

Abstract 202 Table 1

Conclusions

Donor coronary artery calcification appears to be a marker for greater risk for developing CAV after heart transplantation. Caution must be taken to accept these organs and if accepted, early modification of immunosuppression with a proliferation signal inhibitor may be indicated.

203 Prophylaxis for chagas disease reactivation: is it necessary?

M Oda*

T Singer-Englar

N Patel

M Hamilton

J Kobashigawa

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

Purpose of Study

Chagas disease (CD) is a well-known parasite known to be reactivated in organ transplant patients who are on immunosuppression. The incidence of CD has been increasing in southern California mainly due to the parasite increasing its endemic area from South America to Central America to the southwest United States. Several patients have contracted this disease which has led to the development of Chagas cardiomyopathy to the point that they required heart transplantation. These patients are at risk for reactivation of CD after heart transplant due to immunosuppression. There are now prophylaxis medications available, however it has not been clearly established whether prophylaxis is effective in preventing reactivation of infection.

Methods Used

Between 1999 and 2019, we assessed 13 heart transplant patients who had a history of CD prior to transplant. These patients were monitored closely post-transplant with CD serologies at 1-, 3-, 6-, 12-months post-transplant. 7 of these patients were given prophylaxis with nifurtimox (n=2) or benznidazole (n=5) as they were found to have IgG antibodies to CD. The other 6 patients did not develop antibodies and were not given prophylaxis. Outcome of these 2 groups of patients were compared for symptomatic disease and 1- and 5-year survival.

Summary of Results

Of the 13 patients with history of CD, 1 patient (prophylaxis group) developed symptomatic disease and recovered. Following prophylaxis therapy, none of the 7 patients had reactivation of CD. Reactivation occurred in 3 of the 6 no treatment patients. The prophylaxis patients compared to the no treatment group had better 1- and 5-year survival (see table 1). However, the causes of death for the no treatment group was non-liver related except for 1 patient who may have died from CD-related disease.

Conclusions

Heart transplant patients with a history of CD appear to have acceptable outcome when closely monitored and administered prophylaxis when indicated. Administration of prophylaxis to all CD, even without IgG antibodies, should be considered.

Abstract 203 Table 1
204 Bromocriptine improves central aortic health in adolescents with type 1 diabetes

M Schäfer*

K Hunter

JE Reusch

AJ Barker

KJ Nadeau

University of Colorado Denver School of Medicine, Aurora, CO

Purpose of Study

The presence of global vascular dysfunction and central aortic stiffness is a well-recognized feature in youth with type 1 diabetes (T1D). This predisposes young patients to the life-long exposure to elevated ventricular afterload and increased incidence of cardiovascular events. Therapeutic strategies to mitigate vascular dysfunction are urgently needed. We hypothesized that bromocriptine quick release (BCQR) therapy would improve vascular health in youth with T1D.

Methods Used

This was a placebo-controlled, random-order, double-blinded, cross-over study investigating BCQR as adjunct therapy on central aortic stiffness as measured by phase-contrast MRI. Participants also underwent flow mediated dilation test and brachial distensibility evaluation using tonometry. Adolescents with T1D were randomized 1:1 to phase-1 of 4-week BCQR (minimum dose 1.6 mg daily) or placebo therapy after which all vascular measurements were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment.

Summary of Results

Forty-two adolescents (mean age 15.9 yrs, HbA1c 8.6%, BMI%ile 71.4, TD duration 5.8 yrs) with T1D were enrolled. BCQR therapy decreased systolic (Δ= -5 mmHg, p < 0.001) and diastolic blood pressure (Δ = -2 mmHg, p = 0.039). BCQR therapy reduced ascending aortic pulse wave velocity (PWV) (Δ = -0.4 m/s, p = 0.005), and increased relative area change (RAC) (Δ = -2.6%, p = 0.022), and distensibility (Δ = 0.08%/mmHg, p = 0.010). In the thoraco-abdominal aorta, BCQR decreased PWV (Δ = -0.2 m/s, p = 0.013) and increased distensibility (Δ = 0.05%/mmHg, P = 0.032). In contrast, BCQR decreased reactive hyperemia index (RHI) (Δ = -0.34, p = 0.006).

Conclusions

BCQR therapy improved central aortic stiffness and pressure hemodynamics in adolescents with T1D over 4 weeks. However, BCQR decreased peripheral RHI. BCQR therapy might serve as a potential clinical intervention to attenuate accelerated aortic stiffness in youth with T1D supporting future longer-term studies.

Neonatology – perinatal biology II

Concurrent session

9:00 AM

Saturday, January 30, 2021
205 IGF-1 infusion in late gestation fetal sheep does not increase beta-cell replication and inhibits insulin secretion

A White1*

J Stremming1

B Boehmer1

S Louey2

E Chang1

S Jonker2

S Wesolowski1

LD Brown1

P Rozance1

1University of Colorado, Aurora, CO

2Oregon Health and Science University, Portland, OR

Purpose of Study

Insulin and insulin-like growth factor-1 (IGF-1) are fetal growth hormones with overlapping mechanisms of action. Complications of pregnancy such as gestational diabetes can lead to higher fetal insulin and IGF-1 concentrations and fetal overgrowth. Insulin secretion is determined by β-cell function and number, and IGF-1 increases β-cell replication in vitro. We previously demonstrated that a 7 d infusion of IGF-1 LR3 into late gestation fetal sheep increased fetal weight but lowered plasma insulin concentrations despite higher pancreatic insulin content. Therefore, we hypothesized that IGF-1 LR3 would attenuate fetal glucose-stimulated insulin secretion (GSIS) and increase β-cell replication.

Methods Used

Late gestation fetal sheep were infused with IGF-1 LR3 (IGF-1, n=8) or saline (CON, n=9) for 7 d. Fetal arterial plasma insulin and glucose were measured. On the final day of infusion (133±2 days gestation; term 147 d), GSIS was measured with a hyperglycemic clamp. β-cell replication was measured in pancreases from a second cohort of fetuses (IGF-1, n=8; CON, n=7) with triple immunofluorescence for insulin, DAPI, and Ki-67. Data were analyzed by Student’s T-test or ANOVA.

Summary of Results

Plasma insulin and glucose concentrations in IGF-1 fetuses were 57% and 15% lower, respectively, at the end of infusion compared to CON (P<0.05). During the GSIS study, hyperglycemic clamp glucose concentrations were similar, but insulin concentrations were lower in IGF-1 fetuses versus CON (P<0.05). The percentage of Ki-67+ β-cells was not different between groups.

Conclusions

IGF-1 LR3 lowers plasma insulin and attenuates GSIS in late gestation fetal sheep but does not induce β-cell replication. Higher pancreatic insulin content with lower insulin secretion indicates the defect in GSIS is not due to an inability to synthesize insulin. Fetal hypoinsulinemia and hypoglycemia may have prevented the expected increase in β-cell replication. We speculate that alterations in the insulin/IGF-1 axis inhibit β-cell development and contribute to the long-term reduction in β-cell function following pregnancies complicated by diabetes or fetal overgrowth.

206 Metabolic patterns of infants born to mothers with preeclampsia and diabetes show underlying metabolic vulnerability

J Reiss1*

A Chang1

J Mayo1

DK Stevenson1,2

GM Shaw1,2

N Aghaeepour1

K Sylvester1

1Stanford University School of Medicine, Stanford, CA

2March of Dimes Prematurity Research Center Ohio Collaborative, Stanford, CA

Purpose of Study

Pregnancy conditions such as preeclampsia and diabetes can profoundly affect fetal and newborn growth and consequent newborn health. Disturbances in intrauterine metabolism and associated molecular mediators of fetal growth alterations remains poorly defined. The objective of this study is to determine whether there is a metabolic pattern at birth associated with infants born to mothers with preeclampsia or diabetes.

Methods Used

Case-control study of 41,412 infants born in California between 2005 - 2010 with newborn screen results matched with California Perinatal Quality Care Collaborative and California Office of Statewide Health Planning and Development birth and hospitalization records. Elastic net logistic regression modeling with repeated 10-fold cross validation, where controls were defined as samples where the clinical record did not indicate the presence of any of the maternal outcomes of interest.

Summary of Results

A select grouping of analytes consistently demonstrated area under the receiver operating characteristics > 0.80 for maternal conditions including type 1 diabetes, severe preeclampsia and severe preeclampsia with preexisting hypertension. Short chain acylcarnitines and free carnitine were significantly associated with maternal diabetes. Acetylcarnitine, free carnitine and ornithine were significantly associated with severe preeclampsia and preeclampsia with preexisting hypertension.

Conclusions

This population study observed unique newborn metabolite patterns associated with the common maternal conditions of preeclampsia and diabetes. Several metabolites were common to the maternal morbidity, either hypertensive disorder or diabetes. The unique metabolic patterns associated with the maternal conditions suggest that new metabolic markers may be used to determine degree of neonatal morbidity secondary to intrauterine conditions.

208 A prospective study of placental imaging and pregnancy outcomes in the setting of ischemic placental disease and gestational diabetes

B Lee*

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

Purpose of Study

Ischemic placental disease (IPD) and gestational diabetes (GDM) are conditions that adversely affect placental growth, perfusion, and maternal and fetal outcomes. Ultrasound doppler studies can indirectly measure placental function, but the positive predictive value and sensitivity are poor in the prediction of pregnancy outcomes. More recently, MRI studies of placental blood flow have shown potential in the prediction of adverse pregnancy outcomes.

The purpose of this study is to record maternal development of IPD and GDM, and assess their correlation to pregnancy and neonatal outcomes. We will determine any associations between placental MRI findings, and pregnancy outcomes and placental pathology.

Methods Used

We recorded the maternal medical history and pregnancy course through 4 study visits (11–14 weeks, 19–22 weeks, 36 weeks, and at delivery). Postnatal outcomes up to 4 months were documented. Placental pathology was performed through our pathology department. Placental MRIs were performed using volumetric free-breathing technique for placental imaging and measurement of regional placental perfusion. Chart reviews were conducted on the subjects and their newborns to gather maternal and infant clinical data. Data was analyzed using REDCap.

Summary of Results

IPD: A total of 199 subjects were included for the analysis. 43 (23.9%) of women developed IPD; 46 (25.6%) developed inflammatory disease, and 91 (50.6%) did not develop either. Of the women with IPD, 20 (41.7%) had gestational hypertension, 18 (37.5%) had preeclampsia, and 9 (18.8%) had FGR. No women had placental abruption.

GDM: 22 women developed GDM; 14 by the second study visit, and 8 by the third study visit. 3 women had diabetes prior to pregnancy. Of these women, 39% were insulin-controlled; 3% were controlled by an oral hypoglycemic agent, and 50% were diet-controlled.

MRI: 199 women completed two pCASL MRI scans, at 14–18 weeks and at 19–24 weeks.

Conclusions

Our data analysis is currently ongoing. We will evaluate pregnancy outcomes, such as any placental pathology and neonatal morbidities and mortalities, and correlate them with the development of IPD and GDM. We will also correlate our MRI findings with pregnancy outcomes, neonatal outcomes, and placental pathology.

209 Effects of an oral probiotic preparation on the vaginal microbiome during early pregnancy

C Wang*

P DeHoff

L Laurent

University of California, San Diego, Irvine, CA

Purpose of Study

The vaginal microbiome can influence pregnancy outcomes, with a decrease in Lactobacillus species being associated with adverse outcomes such as preterm birth. There may be certain protective bacteria, such as Lactobacillus, that can be used to prevent these adverse pregnancy outcomes. Previous studies have had conflicting findings regarding the effectiveness of using oral probiotics to increase levels of protective bacteria within the vaginal microbiome. This study investigated whether the administration of an oral probiotic preparation containing Lactobacillus species during early pregnancy could increase the levels of protective bacteria present in the vaginal flora.

Methods Used

DNA was extracted from patient samples taken from the vagina, anus, and urine prior to and after intervention. qPCR was performed on the extracted vaginal DNA to analyze the relative abundance of different bacterial strains between the experimental and control groups.

Summary of Results

The qPCR results indicated no significant difference between the relative enrichment and expression of Lactobacillus species both pre- and post-treatment between the experimental and control groups. The pre- and post- enrichment data also revealed that there was no uniform trend for any change in enrichment for either the experimental or control groups.

Conclusions

The vaginal microbiome did not significantly change after administration of the oral probiotic preparation used in this study, with the overall vaginal microbiome remaining relatively stable across the first half of pregnancy.

210 Maternal antenatal marijuana use lowers the biologic potential of umbilical cord mesenchymal stem cells

A Ismail*

Y Nicolau

C Uy

F Bany-Mohammed

M Aslam

UC Irvine Medical Center, Irvine, CA

Purpose of Study

Human umbilical cord derived mesenchymal stem cells (MSCs) have been extensively studied with therapeutic efficacy in several injury models. Our work has shown therapeutic efficacy of MSCs and their secreted factors in experimental neonatal chronic lung disease and pulmonary hypertension models. Maternal antenatal drugs and disease states can affect the efficacy of MSCs. At present, very limited data are available on maternal marijuana use during pregnancy affecting the MSC biologic potential.

We hypothesized that human umbilical cord Wharton’s jelly MSCs harvested from marijuana exposed cords will lack biologic potential compared with non-exposed cords. Our aims were:

  1. To generate human umbilical cord MSCs from marijuana exposed and non–exposed cords.

  2. To determine in vitro properties and secreted factors between the two groups.

Methods Used

Human umbilical cord Wharton’s jelly MSCs from marijuana exposed and non-exposed umbilical cords were isolated and cultured according to our modified protocols. Marijuana exposure was considered positive if mothers have smoked marijuana within the prior two weeks before delivery with a positive urine drug test. In vitro growth, differentiation, and secreted factors were analyzed utilizing duplication time, Western immunoblot, and proteomics analysis.

Summary of Results

MSCs were harvested from 3 pooled marijuana exposed cords with 3 non-exposed cords as control. Marijuana exposed MSCs had much shorter duplication and differentiation time compared to non-exposed MSCs. Interestingly, although the marijuana exposed MSCs grew faster, they had lower concentration of cardiopulmonary protective secreted factors compared to non-exposed MSCs.

Conclusions

Marijuana exposure during pregnancy leads to a reduction in biologic potential of human umbilical cord MSCs. Further in vitro and in vivo studies are underway to determine the extent of this relationship.

211 Role of alternative splicing in left vs right ventricle in neonatal mouse heart maturation

Z Mehta*

UCLA, University of California Los Angeles, Los Angeles, CA, US, academic, Los Angeles, CA

Purpose of Study

Alternative splicing (AS) of messenger RNA (mRNA) is known to play an important role in development of the mammalian heart. Distinct transcriptomic profiles between the left ventricle (LV) and right ventricle (RV) have been documented under both normal and pathologic conditions. We hypothesized that alternative mRNA splicing events are important regulators of chamber specificity during neonatal heart maturation.

Methods Used

To profile the transcriptome of the LV and RV, deep RNA-seq was performed on male neonatal mouse (C57BL/6) LV and RV at three time points of perinatal circulatory transition: P0, P3 and P7. AS events were identified and quantified using rMATs (robust Multivariate Analysis of Transcript splicing). For functional assessment, gene ontology (GO) analysis was performed.

Summary of Results

1162 AS events were identified during perinatal heart maturation, with exon skipping events accounted for 44%. Interestingly, the majority of identified exon skipping events were specific to either LV or RV. Although some events overlapped between the two ventricles, these events exhibited different pattern of regulation between LV and RV throughout neonatal heart maturation windows. Further characterization of the differentially spliced exon skipping events, using GO analysis, revealed significant functional enrichment with mRNA processing, lipid metabolism and transcriptional regulation.

Conclusions

These results suggest that alternative splicing events contribute to regulation of chamber specificity during postnatal heart maturation. Additional bioinformatics and mechanistic studies of potential splicing regulators may reveal targets for chamber-specific therapies.

Neuroscience II

Concurrent session

9:00 AM

Saturday, January 30, 2021
212 Prehospital hemodynamic status and neurologic outcomes following acute traumatic spinal cord injury

KT Patterson1*

MM Cook1

J Barber1

VN O’Reilly-Shah1

AH Dagal1

C Fong2

H Weaver1

R Saigal1

1University of Washington School of Medicine, Seattle, WA

2University of Washington Medical Center, Seattle, WA

Purpose of Study

Current treatment of traumatic spinal cord injury (SCI) targets secondary neurological injuries, such as hypoperfusion and ischemia, that underlie much of the pathophysiology following a traumatic SCI. This study investigates the correlation between prehospital mean arterial pressure (MAP) and the degree of neurological recovery.

Methods Used

In this retrospective cohort study, conducted at a large level 1 trauma center, acute traumatic SCI patients from 2017–2019 were assessed for neurologic recovery at discharge from hospital and inpatient rehabilitation. Neurologic outcome was measured as the change in the American Spinal Injury Association (ASIA) motor score at the outcome time points. Major exclusionary criteria included: greater than two days from time of injury to spinal decompression surgery, age <16 years old, insufficient prehospital data, and missing/incomplete motor exams. Prehospital MAP exposure was characterized for each subject using an area-under-the-curve approach. The total bounded area below 85 mmHg was calculated over the entire monitoring period, then divided by the duration of monitoring to achieve a normalized ‘average depth’ MAP value. 85 mmHg was used as the threshold value for this analysis as it represents the current MAP target in SCI treatment. Linear regression was used to examine the relationship of prehospital MAP values with the change in motor score.

Summary of Results

The chart review identified n=109 patients at hospital discharge and n=79 at rehab discharge who met the study’s inclusion criteria. Linear regression analysis demonstrated a non-significant (p>0.05) relationship between average depth MAP values and change in the motor score at both hospital discharge and rehab discharge.

Conclusions

Prehospital MAP values below the current clinical recommendations of 85 mmHg did not show a significant association with motor score change in traumatic SCI patients. Further work is necessary to adjust for confounders as well as validate these findings in additional settings.

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

JC Huang1,2*

A Farre2

A Duncan2

D Stenkamp2

1University of Washington School of Medicine, Bellevue, WA

2University of Idaho, Moscow, ID

Purpose of Study

Vertebrate color vision requires opsin-containing cone photoreceptor cells in the retina. A popular model 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, then associates with only one opsin gene such that mature cones do not express more than one opsin. However, our prior studies investigating the orthologous long wavelength sensitive (lws1/lws2) array in zebrafish suggest that thyroid hormone (TH) and retinoic acid serve as trans regulators of this gene array in larvae/juveniles. This study investigates whether cone opsin expression remains plastic to TH treatment in adult zebrafish, where cone distribution is considered stable.

Methods Used

Adult WT zebrafish were treated with NaOH (control) or TH for 1 day or 5 days (n=12, 6 fish each). Left eyes were harvested for quantitative polymerase chain reaction (qPCR) analysis and right eyes for cryosections and in situ hybridization. A set of lws reporter transgenics were also treated for 5 days with TH (n=6). The eyes underwent cryosectioning and confocal imaging.

Summary of Results

In adult zebrafish, exogenous TH drastically increased lws1 expression in both 1 day and 5 day-treated groups (p= 4.51*10-12, 2.02*10-9 respectively). Other opsin genes that were shown to decrease in embryos and juveniles in response to TH also showed a significant decrease in both groups: lws2 (p=4.07*10-07, 4.72*10-10 respectively); gngt2b (p=5.49*10-07, 6.29*10-4 respectively). TH treated transgenic lws reporter line revealed a clear switch from lws2 to lws1 dorsally, consistent with the qPCR data. This confirms that there is not only a shift in lws1/2 expression but also changes in topographic distribution of lws1/2-expressing cones of adult zebrafish in response to TH.

Conclusions

Exogenous TH induced a drastic shift from lws2 to lws1 in adult zebrafish, consistent with previous studies of larvae and juveniles. This shift occurs as rapidly as 1 day when exposed to TH, which shows that cones remain significantly plastic even into adulthood. Plasticity in overall spectral sensitivity (to be sensitive to higher wavelengths) in response to TH suggests a role in visual system function well into adulthood.

214 Bioinformatic comparison of grey matter: control tissue v multiple sclerosis

KR Dowell1*

K Mruk1,2

1WWAMI Medical Education, University of Washington School of Medicine, Laramie, WY, Laramie, WY

2University of Wyoming School of Pharmacy, Laramie, WY

Purpose of Study

Multiple Sclerosis is an immune-modulated demyelinating disease of the CNS. Recently, grey matter lesions and atrophy have been found to contribute to the disease state. This study was designed to examine the differences of gene expression between post-mortem samples of grey matter from controls, MS normal-appearing grey matter (NAGM), and MS lesion grey matter (LGM). We sought to identify genes that may play a role in early stages of MS by comparing normal-appearing grey matter (NAGM) and grey matter with lesions (LGM) to healthy controls.

Methods Used

Samples from a study previously submitted to NCBI’s Gene Expression Omnibus, GSE131282 by Enz et al, 2020, were analyzed in multiple comparisons using GEO2R analysis tool, processed in Excel, and identified using Database for Annotation, Visualization and Integrated Discovery (DAVID 6.8) to obtain Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results of differentially expressed genes. In Excel, GO terms with a P-Value < 0.01 were sorted into categories for ease of visualization and their up- or downregulation average was determined using Logarithmic Fold Change (Log FC). KEGG pathway results with P-Value < 0.01 were used to search literature for a known connection to MS.

Summary of Results

A greater number of significant genes, GO terms, and KEGG pathways were found in Comparison D: NAGM v LGM than in B: Control v LGM or C: Control v NAGM. Gene expression on average was downregulated in all GO categories for all comparisons except one, Comparison J: Frontal NAGM v Parietal NAGM. No significant genes were expressed within each tissue type when frontal and parietal tissue samples were compared except NAGM, in which one GO term, ‘nuclear body’, was upregulated. In all other comparisons the genes within this group were downregulated. A total of 30 KEGG pathways were found in this review, 13 have known connections to MS, and 17 do not.

Conclusions

The greater number of significant genes, GO terms, and KEGG pathways in Comparison D above Comparisons B and C indicates greater difference between NAGM and LGM than between either tissue and control. The results of Comparison J elicit further research. We identified 17 KEGG pathways that are not known to have connection to MS.

215 Workers with higher stress levels have altered dynamic neuroimaging

K Kuehl*

K Mackiewicz-Seagate

D Elliot

J Ballin

C DeFrancesco

W McGinnis

K Gallemore

Oregon Health and Science University School of Medicine, Portland, OR

Purpose of Study

The adverse mental, physical and performance effects of stress are well documented. The central nervous system correlates of chronic stress are not well established. Those working in prisons (correction professionals [CPs]) have high stress levels. We used functional MRI to assess whether cognitive processes differed among higher and lower stress CPs.

Methods Used

Participants were recruited from a cross-sectional study of CPs. An established self-report stress index stratified the sample (total = 328), and the lowest and highest quartile were invited to undergo fMRI imaging. 25 lower stress (mean ± SD stress score 6.32 ± 0.95) and 25 higher stress individuals (stress score 13.10 ± 1.76) were imaged. While scanned participants performed a manual-response version of the standardized Stroop task.Functional images were acquired with a GE Signa 3T MRI scanner with a T2*-weighted gradient-echo planar imaging.

Summary of Results

Stress scores were repeated the day of imaging, and the two scores were highly correlated (r2 = 0.7 p < 0.001), suggesting consistent groupings. Groups were not different in demographic and basic biometrics (blood pressure, BMI, C-reactive protein, hemoglobin A1c, lipids, cortisol). Higher stress participants had greater activation of a frontal-parietal executive network implicated in cognitive control (p < 0.01, uncorrected). In particular, higher stress group demonstrated robust activation of the posterior dorsolateral prefrontal cortex and middle frontal gyrus. Both regions are involved in maintaining attention when conflicting information is relevant. In contrast, the lower stress group demonstrated greater activation of regions that may be involved in basic visual processing.

Conclusions

Results provide evidence that stress impacts functional activation of neural systems involved in cognitive control. More stressed CPs appeared to need greater top-down control when information was conflicting.

216 Learning types during interpretation bias training to treat irritability

T Trujillo1*

J Stoddard1

S Haller2

M Brotman2

M Jones3

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

2National Institutes of Health, Bethesda, MD

3University of Colorado Boulder, Boulder, CO

Purpose of Study

A potential treatment target for chronic irritability is hostile interpretation bias (HIB), a tendency to interpret ambiguous stimuli as threatening. HIB may be targeted and changed via a computer-based interpretation bias training (IBT). IBT is amenable to the application of category learning theory to measure behavioral and neural changes. The goal of this study was to apply a principled, model-based analysis of categorical learning to identify learning types during IBT.

Methods Used

A session of IBT learning was assessed in 63 transdiagnostic youth with varying severity of irritability and anxiety. Participants judge a continuum of facial expressions and train in IBT towards less angry and more happy judgments of ambiguous faces on the continuum. A computational model of categorical learning, ALCOVE, was applied to each person’s training data. Two major model parameters were of interest: 1) learning rate with higher values representing a greater speed at which individuals change their associations to faces, and 2) generalization with higher values reflecting a lower precision of applying feedback to a specific face on the morph continuum. We assessed associations with psychopathology, (anxiety and irritability), dimensionally via multivariate linear models. We then empirically assessed for types of learners using generalized mixture models.

Summary of Results

The computational model demonstrates different types of IBT learners with unique associations to age and psychopathology. In multivariate linear modeling, individuals with higher generalization tended towards anxiety (b=1.7 (0.9), p=.05) and were younger (b=-0.5 (0.2), p=0.02). Learning rate was reduced with both anxiety and irritability (b=-0.11 (0.04), p=0.01). Generalized mixture modeling identified two learning types, those with very high generalization and those with lower generalization. Younger individuals were more likely to be in the high generalization group (Cohen’s d=0.66, p=0.01).

Conclusions

The model-based analysis empirically detected distinctive pathology and age associated learning styles. Understanding learning will improve the ability to identify learning types, improving precise prescription of IBT.

217 Impact of obesity on brain response to food cues following non-nutritive and nutritive sweetener ingestion

AG Yunker*

S Luo

S Jones

B Angelo

AW DeFendis

K Page

University of Southern California, Los Angeles, CA

Purpose of Study

Non-nutritive sweeteners (NNS) are marketed for weight loss by providing sweet taste without calories, but the health consequences of NNS are debated. Uncoupling sweet taste from calories may stimulate feeding through neural mechanisms, yet the impact of obesity on neural responses to NNS vs caloric sugars is unknown. We examined brain responses to high-calorie (HC) food cues after acute consumption of sucralose (NNS) vs. sucrose (caloric sugar) in obese, overweight, and lean individuals.

Methods Used

On 2 separate visits, 72 adults (26 lean, 24 overweight, 22 obese) consumed a drink containing sucrose (75 g) or sucralose (sweetness matched) and underwent a functional magnetic resonance imaging food cue task that measured the blood-oxygen-level-dependent (BOLD) response to HC food and non-food cues. A priori brain regions-of-interest (ROI) are areas implicated in feeding regulation: the nucleus accumbens, amygdala, dorsal striatum, medial frontal cortex (MFC), hippocampus, insula, orbital frontal cortex (OFC), and hypothalamus. Linear mixed models were used to examine neural reactivity to HC food cues in response to sucralose vs sucrose. We tested for interactions between BMI group and drink, and stratified results by BMI group. Analyses were adjusted for age and sex. False discovery rate (FDR) was applied to p-values to correct for multiple ROI comparisons.

Summary of Results

We found BMI group by drink interactions in the MFC (p=0.04); individuals with obesity had greater MFC reactivity (β=0.39, p=0.02) after consuming sucralose vs sucrose than overweight (β=0.05, p=0.93) and lean (β=-0.002, p=0.98) persons. While there was no BMI group by drink interaction in the OFC (p=0.28), individuals with obesity, but not overweight or lean, had greater OFC responses to HC food cues after sucralose vs sucrose (β=0.20, p=0.02). Similar patterns were seen in other ROIs but did not survive multiple comparisons.

Conclusions

Obesity was related to heightened cortical responses to HC food cues after acute consumption of sucralose vs. sucrose. These findings highlight the need to consider obesity-related effects on the neurobehavioral consequences of NNS consumption.

218 Ascorbic acid attenuates hydrogen peroxide induced oxidative stress and osteoblasts demonstrate antioxidant recycling potential

RT Tran*

J Morgenstern

S Droho

J Olson

University of Colorado – Anschutz Medical Campus, Englewood, CO

Purpose of Study

Oxidative stress is strongly implicated in disease progression of age-related macular degeneration. Oral supplements, including ascorbic acid (AA), target this oxidative etiology, yet efficacy is limited due to insufficient ocular distribution. One possible avenue is restoring the antioxidant potential of the vitreous by improving recycling of the inactive oxidized form of AA, dehydroascorbic acid (DHA), back to its active reduced form. Here, we demonstrate the antioxidant potential of AA to improve common retinal pigment epithelium (ARPE-19) cell viability in the setting of H2O2 induced oxidative stress and evaluate osteoblasts as a potential source of antioxidant recycling.

Methods Used

In vitro evaluation was performed by incubating ARPE-19 in culture media containing 0.2 mM H2O2 with and without 100 uM AA. MTT assay was performed to assess for cell viability. Osteoblast antioxidant recycling potential was tested by exposing MG-63 osteosarcoma cells to culture media containing 100 uM DHA. At each time point from 0 to 80 minutes, media was collected and concentrations of DHA and AA were assessed using HPLC. Statistical comparisons were performed using a student’s t-test.

Summary of Results

AA successfully attenuated the toxic effects of H2O2, with 88% of ARPE-19 cells remaining viable after exposure to both H2O2 and AA, compared to 61% viable after incubation with H2O2 alone (P < 0.001). Osteoblast antioxidant recycling of DHA was observed with an increase of AA concentration and a concomitant decrease in DHA levels over time. At 80 minutes, the concentration of AA had a 2-fold increase with a paired 2-fold decrease in DHA levels.

Conclusions

These experiments demonstrate the antioxidant potential of AA to attenuate the effects of oxidative stress and its physiologic importance in managing cellular exposure to reactive oxygen species. Osteoblasts exhibited the potential for antioxidant regeneration of AA outside their biological niche. While preliminary, these results demonstrate the promise of an implantable device that continuously recycles antioxidant, eliminating the need for constant injections.

219 Novel methodology for probing microglial metabolism in situ

N Cleland1*

MC Neal2

M Tang2

E Dobrinskikh3

K Bruce2

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

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

3University of Colorado School of Medicine, Aurora, CO

Purpose of Study

Microglia play a role in the pathogenesis of multiple sclerosis (MS) and other neurodegenerative diseases (ND) by taking on both adaptive and injurious phenotypes in response to their environment. Understanding adaptive phenotypes may guide the development of novel therapeutics. Recent single-cell RNA sequencing (scRNAseq) analyses of microglia ex vivo found that genes associated with lipid and lipoprotein metabolism are tightly regulated during ND. We hypothesize that microglial activation is paired with a metabolic switch that is key in the development of ND. However, our current understanding of microglial metabolism draws on what is known about peripheral macrophages and invasive techniques like scRNAseq that could alter microglial phenotype and metabolism. Therefore, there is a need for methodologies that allow assessment of microglial metabolism in situ, as a first step to develop metabolism-focused interventions.

Methods Used

We take advantage of endogenous fluorophore NADH to probe the metabolic profile of microglia in situ via fluorescence lifetime imaging microscopy (FLIM). This technique excites NAD in the sample, and tracks the fluorescence lifetime (FLT) to determine whether it is free or enzyme-bound. More free NADH suggests more glycolysis taking place and presents as a longer NAD FLT, whereas bound NAD indicates more oxidative phosphorylation. We use an experimental autoimmune encephalitis (EAE) mouse as a model of MS and neuroinflammation. Mice were scored based on the severity of their MS-like symptoms. Brains were frozen before sectioning and analysis.

Write out

Summary of Results

Preliminary data in high and low scoring EAE mice suggest that a higher score is associated with a shorter NAD FLT. This suggests a higher reliance on glycolysis to meet energy demands in an MS model. This also suggests that microglia have adopted an injurious phenotype.

Conclusions

The data support our hypothesis that microglial activation in the setting of MS is paired with a metabolic switch towards more glycolysis. This study also supports FLIM being used to probe microglial metabolism in situ to better understand other NDs.

Adolescent medicine and behavior development IV

Concurrent session

10:05 AM

Saturday, January 30, 2021
220 Screening for and diagnosing malnutrition in hospitalized pediatric patients

SL Thompson1*

E Lamers-Johnson2

K Kelley2

L Woodcock1

J Long2

C Bliss2

J Abram2

A Steiber2

EY Jimenez1,2

1University of New Mexico, Albuquerque, NM

2Academy of Nutrition and Dietetics Foundation, Chicago, IL

Purpose of Study

Malnutrition is often underdiagnosed, and consequently undertreated, in hospitalized patients. A nationwide study is being conducted to validate indicators (the Malnutrition Clinical Characteristics [MCC]) to diagnose malnutrition in hospitalized patients.

Methods Used

For the full study, sixty pediatric hospitals will collect patient medical history, patient STRONGKids malnutrition screening score, and nutrition intervention data. Six hundred pediatric patients will be randomly selected from the cohort to be assessed for the MCC and the Nutrition Focused Physical Exam (NFPE). Medical outcomes will be collected for all patients for a three-month period thereafter. Baseline data from a subset of sites that have started data collection were descriptively analyzed using Stata 15.

Summary of Results

As of August 2020, 113 pediatric patients are enrolled in the study, with 50 children ages 1–24 months and 63 children and adolescents ages 2–17. Based on the STRONGkids screener, 73% (n = 82) of participants were ‘at risk’ for malnutrition. A higher proportion of participants in the older age group screened at risk (n=54; 86%) compared to the younger group (n=28; 56%). Fifty-seven of the 113 participants were included in the MCC subgroup, of whom 35 (61%) screened at-risk for malnutrition. Based on the MCC criteria, 49% (n = 28) were diagnosed with malnutrition. Inadequate nutrient intake was the MCC indicator most often used to support a malnutrition diagnosis in younger participants, while weight loss was the most commonly used indicator for older participants. Across both age groups, muscle wasting and subcutaneous fat loss were the most commonly reported NFPE indicators that further supported a malnutrition diagnosis.

Conclusions

Screening-based risk for malnutrition and malnutrition indicators differ for infants and young children compared to older children and teens. Differences in risk factors for malnutrition by age group and the validity of the MCC will be further assessed as more data are collected.

221 Identifying gaps in sexual health care and barriers to providing recommended care to adolescents at an academic primary care clinic

S Kaye*

R Byrd

L Kester

S Crossen

UC Davis Children’s Hospital, Sacramento, CA

Purpose of Study

We assessed the level of adherence to recommended sexual health care practices for adolescents at our institution’s general pediatrics clinic and explored provider perspectives on barriers to the delivery of recommended sexual health care to adolescents.

Methods Used

We reviewed EHR data for patients ages 15–20 years who presented for preventative care at our clinic between 7/1/19 and 9/30/19. The following elements were assessed: documentation of sexual activity status, discussion of pregnancy prevention, and STI screening among those who were sexually active. We then surveyed physicians in our practice to explore potential barriers to the delivery of recommended sexual health care to adolescents.

Summary of Results

The majority of patients (95%) had sexual activity status documented somewhere in the EHR; however, less than one quarter (23%) of patients had sexual activity status documented in the sexual activity tab in EHR. Most patients had sexual activity status documented in the provider note (82%) and/or in the scanned ‘staying healthy’ form (74%) found through the media tab. Additionally, most teens had some documentation of pregnancy prevention counseling (95%), but for the majority this documentation consisted of standardized language in the provider note (52%) and/or after-visit summary (56%). Only 15% had patient-specific language in the provider note, and only 5% had patient-specific language in the AVS. Less than half of sexually active teens had HIV (42%) or chlamydia (9%) tests ordered.

Provider surveys were sent to 20 resident and 19 attending physicians. Overall response rate was 82%. Confidentiality concerns were the primary reason providers cited for not documenting patient-specific sexual health information in after-visit summaries (81%) and for not ordering STI screening, including concerns about parents seeing the test on insurance bills (66%) or after-visit summaries (56%).

Conclusions

At our academic primary care clinic, documentation of patient-specific sexual health counseling and ordering of recommended STI screening are occurring at suboptimal rates due primarily to concerns about patient confidentiality. These data will inform our QI efforts to improve teen care.

222 Sex differences in prenatal exposure to maternal obesity and breastfeeding on cardiometabolic markers in children

AW DeFendis1*

J Alves1

AG Yunker1

AH Xiang1,2

K Page1

of Southern California, Los Angeles, CA

2Kaiser Permanente Southern California, Pasadena, CA

Purpose of Study

Prenatal exposure to maternal obesity has been linked to increased risk of cardiometabolic disease, whereas breastfeeding may have beneficial effects. Emerging data suggest that prenatal exposures may have sex-specific effects. We investigated overall and sex-specific associations between maternal pre-pregnancy BMI and breastfeeding exposures on cardiometabolic risk markers in childhood.

Methods Used

Data includes 160 children (64 boys) ages 7–10 born to mothers with a range of pre-pregnancy BMI. Breastfeeding duration and measures of systolic and diastolic blood pressure (SBP; DBP), height, weight,%body fat, waist and hip circumference were obtained at in-person visits. Multiple regression analysis was used to assess associations between maternal pre-pregnancy BMI and breastfeeding exposures on cardiometabolic outcomes in childhood. Models were unadjusted or adjusted for child age, sex (in full cohort), BMI-z, maternal diabetes, and SES.

Summary of Results

In the full cohort, maternal pre-pregnancy BMI was associated with elevated cardiometabolic markers in unadjusted models (BMI-z: β= 0.03, p=0.01;%body fat: β=0.018, p=0.05; waist to height ratio (WHR): β=0.002, p=0.002; SBP: β=0.11, p=0.26; DBP: β=0.10, p=0.19). Breastfeeding was marginally associated with decreased BP (SPB: β= -0.13, p=0.12; DBP: β=-0.11, p=0.07), but not other outcomes. Adjusting for co-variates attenuated the associations. In the sex-stratified analyses, among girls, maternal pre-pregnancy BMI was associated with elevated cardiometabolic markers in unadjusted (data not shown) and adjusted models (SBP: β=0.25, p=0.05; DBP: β=0.21, p=0.02; BMIZ: β=0.05, p=0.01;%body fat:β=0.03, p=0.04; WHR:β=0.004, p=0.001); breastfeeding > 6 months was associated with lower SBP (β=-0.20, p=0.04) and lower DBP (β=-0.12, p=0.07) but was attenuated in the adjusted model (SPB: β=-0.13, p=0.10; DBP: β=-0.10, p=0.09). Neither exposure was associated with cardiometabolic markers in boys.

Conclusions

Sex-specific observations point to a greater sensitivity to early-life exposures on cardiometabolic outcomes in girls.

223 Targeting gun violence, improving screening for access to firearms in emergency department pediatric psychiatric patients

C Stegall*

J Ayala

K Barton

K Allen

A Kumar-Veeraswamy

Medical University of South Carolina, Charleston, SC

Purpose of Study

Increase the frequency and documentation of provider screening for access to firearms amongst pediatric psychiatric patients presenting to the emergency department. Goal to increase screening rates by 50% in 3 months, as well as increase interventions made for positive screens to educate families on safe firearm storage.

Methods Used

This is a resident driven quality improvement project in a pediatric emergency department setting. We collected baseline data of firearm screening rates with a retrospective chart review of patients (N=340) who presented to the Shawn Jenkins Pediatric ED with the chief complaint of ‘psychiatric evaluation’. Intervention made on 7/1 included education to residents about the project, as well as BeSmart training, BeSmart materials in the ED, the creation of a smart phrase to use in notes with reminders on desktop computers, and gun locks to distribute. Chart reviews were conducted monthly to determine frequency of firearm screening and what interventions were made for positive screens (total N=477).

Summary of Results

The baseline mean rate of monthly firearm screening prior to our first intervention was 14.38%. After our first intervention with implementation of a dot phrase with resident education and distribution of BeSmart materials, firearm screening rates for the months of August and September increased to 25.8% and 32.4% respectively. Amongst providers, we found a clinically, but not significantly, difference between screening rates conducted by pediatric residents compared to others (ie EM, FM, and NP).

Conclusions

We have significant room for improvement in our rates of firearm screening. We will continue to work towards improving this rate as it is our responsibility as healthcare providers to screen and counsel on safe firearm storage.

224 The epidemic of stress and anxiety among today’s high school students: do students need a ‘life’ class?

C Santos1*

O Washington1

E Bustinza1

N Garcia1

A Perez1

R Kinman2

1UCSF-Fresno, Fresno, CA

2Edison High School, Fresno, CA

Purpose of Study

Stress and anxiety are an ever-growing epidemic among today’s youth, especially for those located in impoverished communities where adverse childhood experiences are abundant. Although school districts have responded by placing therapists into schools to respond to mental health crises, there have not yet been consistent efforts put into place to help students build resilience to stress. A group of high school students participating in the first ever Fresno County Youth Health Corps thus surveyed students in their own school about stress before proposing a student-led solution to this problem.

Methods Used

4 students at an impoverished high school in Fresno conducted an online survey distributed to all students at their school, and conducted interviews with a high school counselor and the Fresno County Department of Public Health Assistant Director about the causes of stress in high school students and what schools could do to mitigate these effects.

Summary of Results

Of 1,017 students responding, 74% felt that school was their leading cause of stress, with 62% enrolled in at least 3 AP classes per semester and 25% enrolled in 6–7 AP classes per semester. 88% of students felt pressure to succeed in school, 65% felt overwhelmed by the amount of homework assigned, and 71% often felt drained or tired. The majority of the remaining students felt that their stress originated primarily from their personal lives, but only 20% of students felt comfortable about sharing personal issues with a counselor, teacher, or coach, with these findings confirmed by the school counselor. Student takeaway messages from the Fresno County Department of Public Health interview included the following: 1) ‘Identify the problem before it becomes too late’, 2) ‘Lessen the stigma of talking about stress’, and 3) ‘Make it easier for students to be helped’.

Conclusions

Results from the above survey indicate that students are overwhelmed by stress and anxiety. As high school students, we would propose that all high schools implement a mandatory hour-long monthly Mental Health Advocacy (or LIFE) class to help students build resilience to stress and anxiety while serving as a safe place for students to talk about their problems or providing students with time to simply de-stress.

225 Patient/parent administered epinephrine in acute anaphylaxis

MA Murata*

Hawaii Pacific Health, Kaneohe, HI

Purpose of Study

The purpose of this study was to investigate the rate of and factors associated with immediate patient/parent epinephrine administration in cases of anaphylaxis.

Methods Used

The electronic medical records of patients from 217 encounters (143 of these being pediatric encounters)—either with an ED diagnosis of peanut anaphylaxis or diagnosis of anaphylaxis with a known epinephrine prescription from 2010 through May 2020—were reviewed for physician notes and demographic factors.

Summary of Results

Epinephrine was administered on-scene by 22.6% of all anaphylaxis patients and in 25.2% of pediatric cases. Of the 6 health care professionals identified, 100% administered epinephrine on-scene. Females (32.0%) were administered epinephrine on-scene more frequently than males (19.8%; p = 0.043). Using multivariate analysis, the relationship between sex and rate of administration was only significant when controlled for insurance as well as age. Rate of epinephrine administration increased from 2010 through 2019 (p = 0.004).

Conclusions

Administration rates of 22.6% and 25.2% observed among non-physicians suggests that the majority of patients prescribed epinephrine have not used their EAIs, even when presented an opportunity for application. A rate of 100% observed among physicians indicates that comfort with EAIs facilitates willingness to administer on-scene. EAIs can range up to $900 in expense, thus physicians should employ EAI training devices and other educational modes in order to increase patient comfort with EAIs.

226 ‘How do you see yourself?’: Applying youth-defined mental health domains to support the balance of mental health and academics

CM Suarez1*

A Panh1

E Gastelum2

R Kinman2

1University of California Davis, Sacramento, CA

2UCSF Fresno, Fresno, CA

Purpose of Study

Current definitions of mental health in youth recognize the interrelated nature of various domains, including social, psychological, and cognitive factors. Further investigation into how youth themselves define mental health can help identify the most effective domains to target through efforts that emphasize youth engagement. UC Davis medical students and the UCSF Fresno Department of Pediatrics partnered with sophomore students at Design Science Middle College High School in Fresno, CA, with the aim to understand what youth perceive as important mental health domains in order to guide interventions for mental health promotion.

Methods Used

A needs assessment was performed utilizing Photovoice to identify youth mental health concerns. Students were asked to share photos that represented ‘How do you see yourself?’ and ‘How do others see you?’ Reflections were gathered on what students would change about these representations. An anonymous survey gathered additional perspectives on themes from the needs assessment.

Summary of Results

Initial survey results revealed that students reported low confidence in their time management and study skills, followed by their abilities to understand different coping skills to deal with stress and access different mental health resources. Common themes influencing mental health were identified, with a primary focus on the domain of academics. Themes included how to achieve higher education, develop study strategies, manage stress, recognize healthy relationships, respect the diversity of others, and create positive community change. As a result of the above, a longitudinal workshop series was developed with high school student input to address youth-identified needs, with co-educators including the youth themselves, pediatric residents, and community partners.

Conclusions

Students emphasized academic concerns as a primary influence on mental health, as well as intrapersonal and interpersonal factors. With a youth as partner approach, longitudinal community engagement interventions can be developed that address student-identified needs and amplify student-led efforts in order to encourage a healthy balance of mental health and academics.

227 An innovative hybrid learning model in pediatric critical care medicine during the severe acute respiratory syndrome coronavirus 2 pandemic

CM Suarez1

T Bunnalai2

1University of California Davis, Sacramento, CA

2UCSF Fresno, Fresno, CA

Purpose of Study

The disruption in undergraduate medical education due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic led to various modifications of traditional clerkship rotations. Models that provided an optimized, immediate learning environment were needed to establish alternative experiences. UCSF Fresno pediatric critical care faculty created a hybrid (virtual plus limited in-person) learning model in critical care medicine for medical students in order to overcome educational barriers posed by SARS-CoV-2 and continue providing a high quality learning environment.

Methods Used

Critical care faculty identified essential sub-internship topics, including vascular access, electrolyte disturbances, sepsis management, cardiopulmonary medicine, neurocritical care, pharmacology, procedures, and medical literature appraisal. Students accessed the evidence-based curriculum, assignments, calendar, notifications, and real-time group discussions with peers, pediatric residents, and faculty using a free application (Canvas Student® by Instructure) on a mobile device or computer.

Summary of Results

A 4-week hybrid pediatric critical care curriculum was successfully implemented during the pandemic using a free learning management system. This model combined virtual and limited daily in-person clinical activities in compliance with SARS-CoV-2 prevention guidelines. Learning topics were explored daily with faculty and residents and through self-directed student learning, while reducing unnecessary clinical area exposure. Students participated in virtual patient sign-out and limited multidisciplinary family-centered rounds, observed procedures, attended lectures, led presentations, and received a virtual evaluation.

Conclusions

When the in-person learning experience is severely limited, a hybrid virtual learning environment can be an effective alternative to optimize undergraduate medical education without limiting student engagement. This model has the potential to supplement traditional rotations while providing a framework for future medical education disruptions. A hybrid learning format can be beneficial in other areas of medicine in addition to critical care. Future directions for this model should include real-time simulation-based education.

Cardiovascular II

Concurrent session

10:05 AM

Saturday, January 30, 2021
228 Metformin improves left ventricular size and function in adolescents with type 1 diabetes

A Nguyen1*

U Truong1

M Schäfer1

A Baumgartner1

AJ Barker1

K Hunter1

D Burkett1

JE Reusch1,2

KJ Nadeau1

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

2VA Eastern Colorado Health Care System, Aurora, CO

Purpose of Study

People with type 1 diabetes (T1D) have higher rates of cardiovascular disease (CVD) despite modern advances in glucose control. While insulin resistance (IR) in type 2 diabetes (T2D) is known to relate to cardiovascular disease (CVD), less is understood about IR in T1D-related CVD. We previously showed vascular dysfunction and cardiac dysfunction, including left ventricular (LV) dyssynchrony, in adolescents with T1D, and in the Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes (EMERALD) study showed that metformin improves BMI, body composition, insulin dose, arterial stiffness, and carotid intimal media thickness in these T1D adolescents. We hypothesized that metformin, with insulin-sparing effects, improves CV function measured by echocardiogram, a commonly used clinical measure.

Methods Used

49 T1D youth ages 12–21 years (mean age 16.8 ± 2.5 years, HbA1c 8.6 ± 1.5%, BMI 25.1 ± 4.3 kg/m2, diabetes duration 7.7 ± 4.2 years) in the EMERALD study were randomized to 3 months of either 2000 mg of metformin daily or placebo. Echocardiograms with speckle tracking to evaluate traditional echocardiographic measures and cardiac strain were performed in 43 participants at baseline and 3 months. One-way ANOVA and paired t-tests were utilized to analyze whether metformin usage had significant impacts.

Summary of Results

LV diameter (4.45 ± 0.47 vs. 4.26 ± 0.50 cm, p = 0.019) at end-diastole and at end-systole (2.89 ± 0.39 vs. 2.69 ± 0.36 cm, p = 0.022) and LV dssynchrony (98.0 ± 36.9 vs. 81.7 ± 27.5 milliseconds, p = 0.014) showed significant improvement within the metformin group. Aortic root diameter (2.51 ± 0.39 vs. 2.73 ± 0.28 cm, p = 0.042) was also significantly lower in the metformin vs. placebo group post-treatment.

Conclusions

Metformin may be beneficial in improving or reversing early cardiovascular changes in T1D. A better understanding of T1D-related CVD and the benefits of improving insulin action in T1D longer-term should be investigated further as a target for new treatment modalities.

229 Outcome of the development of restrictive physiology after heart transplantation

A Deshpande1*

N Patel2

T Singer-Englar2

M Hamilton2

J Kobashigawa2

1Smidt Heart Institute, Cedars-Sinai, Los Angeles, CA

2Western University of Health Sciences, Pomona, CA

Purpose of Study

Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival. A severe form of CAV is small vessel disease which results in restrictive cardiac physiology (RCP). This RCP causes a very stiff heart which leads to significant reduction in cardiac index and elevation of cardiac pressures. The pathophysiology behind this RCP is most likely due to small vessel CAV with scarring and fibrosis. The outcome of patients with this RCP has not been well established.

Methods Used

Between 2010 and 2017, we assessed 23 heart transplant patients who developed RCP defined by right atrial pressure ≥ 15 mmHg, pulmonary artery diastolic pressure ≥ 15 mmHg, pulmonary capillary wedge ≥ 15 mmHg, and cardiac index ≤ 2.2 mm. Subsequent outcomes after diagnosis of RCP were 3-year survival, freedom from CAV (angiographic stenosis>30%), non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), development of donor-specific antibodies (DSA), and re-hospitalizations. 1-year freedom from acute cellular rejection (ACR) was also assessed as risk factor for the development of RCP. The study group was compared with a case-controlled group 2:1 matched by age, gender, and era.

Summary of Results

The average time from transplant to the diagnosis of RCP was 1.5 ± 1.4 years. The RCP group compared to control had significantly lower 3-year survival and 3-year freedom from CAV, NF-MACE, and hospitalizations. There were also lower 1-year freedom from cellular rejection episodes and DSA in the RCP group compared to control.

Abstract 229 Table 1

Conclusions

Heart transplant patients who develop RCP appear to have significantly reduced survival. ACR and DSA are associated with the development of RCP. As these patients do not appear to have a reversible cause, these patients may be assessed for re-transplantation if appropriate.

230 Long-term effects of monotherapy with low dose tacrolimus

M Froch*

N Patel

T Singer-Englar

M Hamilton

J Kobashigawa

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

Purpose of Study

Monotherapy with tacrolimus alone (TAC-A) was found to be safe and effective in the TICTAC Trial. However, in that trial, tacrolimus levels were maintained at 10–12 ng/mL over the first year which resulted in a higher serum creatinine level compared to those left in combination. We have been using TAC-A in patients who have developed leukopenia or thrombocytopenia due to immunosuppression or a natural state. The presence of cytomegalovirus infections and other viruses excluded those patients from being administered monotherapy. It has not been established whether TAC-A is safe and effective.

Methods Used

Between 2010 and 2017, we assessed 151 heart transplant patients who are maintained on monotherapy with TAC-A. Patients were maintained on a low level of TAC-A between 4–7 ng/ml. These patients were assessed for subsequent 1-year rejection, subsequent 3-year survival, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), cardiac allograft vasculopathy (CAV, epicardial disease with angiographic stenosis>30%), and cardiac dysfunction (LVEF ≤ 40%). Furthermore, periodic testing was done with the T-cell immune function test to assess whether these patients were adequately immunosuppressed.

Summary of Results

Patients who were maintained on TAC-A had comparable outcomes compared to patients left in combination immunosuppression (see table 1). The T-cell immune function test showed that these patients had adequate immunosuppression (average was 276 ng/mL with the therapeutic range being 200–550 ng/ml).

Abstract 230 Table 1

Conclusions

Low dose TAC-A appears safe and effective in select patients after heart transplantation. Further studies with larger number of patients will be needed to confirm these findings.

231 Approach to the highly sensitized patient awaiting heart transplantation

C Villa1*

T Singer-Englar2

N Patel2

M Hamilton2

J Kobashigawa2

1University of Washington, Seattle, WA

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

Purpose of Study

Approximately 30% of patients awaiting heart transplantation develop pre-formed anti-HLA antibodies due to previous surgeries, blood transfusions, pregnancies, and previous organ transplants. Patients who are considered highly sensitized have calculated Panel Reactive Antibody (cPRA) levels ≥ 80%. We reviewed our highly sensitized patients who are awaiting heart transplantation to assess effect of desensitization therapy.

Methods Used

Between 2010 and 2019, we assessed 85 patients who are awaiting heart transplant who had a cPRA ≥ 80%. These patients were given desensitization therapy and were divided into those that received intravenous immunoglobulin (IVIG) alone, rituximab-based therapy, plasmapheresis (PE) alone, bortezomib-based therapy, and finally combination therapy with rituximab/bortezomib-based therapies. cPRAs and immunodominant antibody strength (mean fluorescent intensity, MFI) were obtained before and after treatment.

Summary of Results

Desensitization with rituximab- and bortezomib-based therapies appeared most effective in reducing cPRA. Treatment response also appeared to be dependent on class of antibodies, whereas Class I were generally responsive to all therapies and Class II were less so but only to rituximab/bortezomib therapies. All of these patients underwent successful heart transplantation although DSA were crossed at the time of surgery.

Abstract 231 Table 1

Conclusions

Highly sensitized patients respond to desensitization therapies, with specific treatments proving more beneficial depending on the class of antibodies detected. Desensitization therapies enable these highly sensitized patients to undergo successful heart transplantation.

232 Genetic determinants of variable expressivity of obstructive left heart disease

C Rosputni*

M Kelly Galindo

S Klewer

The University of Arizona College of Medicine, Tucson, AZ

Purpose of Study

Bicuspid aortic valve (BAV) is the most common congenital heart defect yet the exact cause is unclear. Multiple genes have been implicated and evidence suggests an autosomal dominant (AD) inheritance with reduced penetrance. Some experts believe obstructive left heart disease may be a spectrum where BAV is mild and hypoplastic left heart syndrome (HLHS) is severe. This study explores the genetic determinants responsible for phenotypic variance in obstructive left heart disease by examining exomes of a family with BAV and HLHS. The father and brother have BAV, one sister has HLHS, one sister is unaffected and the mother is presumed unaffected.

Methods Used

Whole exome sequencing data was obtained on the affected and unaffected family members. Raw data was processed using the Galaxy web platform. The remaining analyses were performed using National Center for Biotechnology Information tools including Genome Data Viewer to assess variants by mutation type, dbGaP to review allele frequency (>15% were excluded) and ClinVar to determine clinical significance of identified variants.

Summary of Results

The father, brother and sister have an AD disruptive 3bp in-frame insertion in FOXC1 (rs76840944). The father and brother have three AD variants: GATA4 missense (rs3729856, likely pathogenic), GATA4 intron (rs10503425, conflicting interpretation of pathology), EGFR 3’UTR (rs17337528). The sister has de-novo heterozygous NEXN frameshift and MYH6 missense variants. Only the GATA4 variants were in ClinVar.

Conclusions

The observed phenotypes are likely due to separate variants rather than the hypothesized spectrum of disease. Of those described, the GATA4 variants are likely responsible for BAV while MYH6 contributed to HLHS. The GATA4 missense mutation was previously reported as likely pathogenic and literature shows noncoding variants near GATA4 may lead to increased penetrance. MYH6 variants cause decreased contractility and dystrophic sarcomere structure that may contribute to HLHS. This in-depth analysis highlights the complexity of BAV genetics and the spectrum of familial obstructive left heart lesions. Study limitations include lack of comparative data from the unaffected sister and unknown history of the mother. We will follow-up with data for the unaffected sister to aid in familial variant analysis.

233 Effect of sleep apnea on atrial arrhythmia recurrence rates after ablation

RR Maheshwary1*

E Ovruchesky1

P Malhotra2

X Zhang2

R Makhija2

U Srivatsa2

1University of California Davis, Sacramento, CA

2University of California Davis, Davis, CA

Purpose of Study

Obstructive sleep apnea (OSA) is a risk factor for both atrial fibrillation (AF) and atrial flutter (AFL). Non-pulmonary triggers have been described in patients with OSA. The objective of this study is to compare the rate of recurrence of AF and AFL after different ablation techniques in patients with and without OSA.

Methods Used

We retrospectively analyzed 219 patients who had ablations at our center. We compared the effect of ablation on recurrence of AF and AFL at one year in patients with and without documented sleep apnea. We also analyzed the posterior wall area (PWA) and effect of posterior wall isolation (PWI) vs conventional ablation (CA) at pulmonary veins, on clinical outcomes.

Summary of Results

Our study included 219 patients (table 1); patients with OSA were more likely to have persistent atrial fibrillation (70% vs 50%) (p = 0.007). There was a trend towards higher recurrence of both AF (29% vs 25%) and AFL (17% vs 10%) at one year after CA in OSA patients (figure 1). In the subset of patients undergoing PWI, there was no significant difference in PWA measured between roof and floor lines by CT scan among the patients with and without OSA (18.2 cm2 vs 18.3 cm2, ns). In patients with OSA, AF recurrence in patients who had PWI was 25.6% vs 33.3% (ns) in CA. In patients without OSA, AF recurrence was 17% in those that received PWI vs 30% (p=0.09) in CA (figure 2).

Abstract 233 Table 1

Baseline characteristics for entirc cohort. N = 219

Abstract 233 Figure 1

AF and AFL Recurrence in OSA+ vs OSA- Following Conventional AblationAFL and AF Recurrence values were compared in OSA+ (n = 64) vs OSA (n =155) patients following 1 year after conventional ablation. AF recurrence was 29% (OSA+) vs 25% (OSA-) (p = ns). AFL recurrence was 17% (OSA+) vs 10% (OSA-) (p = ns)

Abstract 233 Figure 2

AF Rccurrence in OSA+ and OSA-. Patients Following Posterior Wall Isolation and Conventional AblationAF recurrence was compared 1 year following posterior wall isolation (PWI) VS Conventional Ablation in OSA+ patients and OSA- patients. AF recurrence in the OSA- group (n = 55) was 17% with PWI vs 30% w/ Conventional Ablation (p = 0.09). AF recurrence in the OSA+ group (n = 5) was 25.60% with PWI vs 33.30% w/ Conventional Ablation (p = ns)

Conclusions

In our study, we found a trend towards higher recurrence rates of AF and AFL after conventional ablation in patients with OSA. PWI appears to be more effective in those without OSA than those with OSA. Further investigation for non-pulmonary triggers in this subgroup are needed.

234 Refined methods for transcriptome analysis in ischemic cardiomyopathy

A Cullen1

L Mestroni1

S Graw1

D Grine1

G Storm1

S Gao1

S Chen1,2

M Taylor1*

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

2The University of Texas Health Science Center at Houston, Houston, TX

Purpose of Study

Sweet et al. (2018) reports that severity of heart failure (HF) symptoms and left ventricular dysfunction determine current HF treatment. An approach based on underlying biology may ultimately facilitate a precision medicine approach to HF[1],[2]. Using the same data from this 2018 study, we developed a novel modification for bioinformatic analysis of differentially expressed genes (DEG’s) between ischemic cardiomyopathy (ICM) and non-failing (NF) heart tissue. Our process also permitted easy adjustment of statistical parameters in DEG analysis of this and other datasets.

Methods Used

RNA-seq from 13 ICM and 14 NF control human left ventricular samples with expression data for 57974 genes. Matlab analysis began with purging data of missing and nonsensical entries. We replicated the analysis of Sweet et al. and also adjusted threshold stringency for a) fold-change and b) mean absolute change between ICM and NF gene expression levels to identify smaller, more focused DEG sets. We will also present results of bioinformatic validation testing on a newly generated human heart tissue transcriptome dataset.

Summary of Results

Using the DEG cutoff conditions of the 2018 study, we closely replicated its gene list. With various cutoff conditions for mean and fold-change, we produced narrower DEG lists for joint pathway analysis with corresponding metabolomic data. Applying the same algorithm to a new, larger dataset will test repeatability.

Conclusions

Our bioinformatic pipeline provides for flexible adjustment of DEG identification parameters, allowing for tailored generation of DEG lists. Joint pathway analysis incorporating metabolomic data adds another dimension for discovering the underlying biology of HF due to ICM.

235 Bystander CPR and ventricular fibrillation waveform measures in out-of-hospital cardiac arrest

B Bessen1*

J Coult1

J Blackwood2

T Rea1

P Kudenchuk1

H Kwok1

1University of Washington, Seattle, WA

2Public Health Seattle and King County, Seattle, WA

Purpose of Study

Bystander CPR (BCPR) is associated with improved survival after out-of-hospital cardiac arrest (OHCA). The mechanism of this benefit is not clear. We used Amplitude Spectrum Area (AMSA), a quantitative measure of the ventricular fibrillation (VF) ECG, as a surrogate for myocardial physiology to investigate the mechanism by which BCPR improves survival.

Methods Used

We conducted a retrospective cohort study of witnessed OHCA cases presenting with an initial rhythm of VF in a metropolitan EMS system between 2005–2018. Defibrillator recordings were annotated for rhythm and CPR. The AMSA waveform measure was calculated from the first available 3-s ECG segment without CPR prior to initial shock. Utstein elements including witnessed status, BCPR provision, and survival to discharge were ascertained from the OHCA registry. Median AMSA according to BCPR status was compared with the Wilcoxon rank-sum test. We performed logistic regression and model-based causal mediation analyses to evaluate the associations between BCPR, AMSA, and survival.

Summary of Results

Of 1072 eligible patients, AMSA, survival and neurologic outcome were significantly greater in 814 patients who received BCPR compared to 258 patients who did not (p<0.01, table 1). In the multivariable logistic model adjusted for Utstein variables, BCPR was associated with an increased odds of survival (OR=1.6 [95% CI: 1.2, 2.1]). The odds ratio between BCPR and survival was attenuated by addition of AMSA to the model, and no longer statistically significant (OR=1.3 [95% CI: 0.92, 1.7]). Model-based mediation analysis indicated that AMSA mediated 53% (p<0.01) of the association between BCPR and survival.

Abstract 235 Table 1

VF Waveform and Outcome Characteristics by Bystander CPR Status

Conclusions

BCPR is associated with greater AMSA and survival. Furthermore, AMSA appears to mediate over half of the survival benefit associated with BCPR. These findings support a myocardial mechanism by which BCPR improves survival after OHCA.

Healthcare research IV – psychology

Concurrent session

10:05 AM

Saturday, January 30, 2021
236 Are males and females alike? The role of central sensitization in patients with chronic rotator cuff tears

C Bauer1*

A Hegarty2

F Pozzi3

M Tsay2

B Liebeskind2

L Michener2

1Western University of Health Sciences, Pasadena, CA

2University of Southern California, Los Angeles, CA

3University of Florida, Gainesville, FL

Purpose of Study

Women have a higher prevalence of chronic pain conditions, partially explained by presence of central sensitization (CS). In CS, pain sensitivity increases across the body. Evidence suggests CS may play a role in persistent musculoskeletal pain; and up to 30% of individuals with shoulder pain demonstrate CS. This study determined if outcomes of a physical therapy exercise program were influenced by CS or sex in patients with shoulder pain.

Methods Used

In a longitudinal study, 11 patients with full-thickness rotator cuff (RC) tears (5 male, 66±7 years of age) were examined pre and post 12 sessions of strength and aerobic exercise over 8 weeks. We measured pressure pain threshold (PPT) over the tibialis anterior - distal from the injury and a marker of CS. A group of sex-matched healthy control (HC, 64±6 years of age) was recruited. CS was assessed as the difference between RC and HC groups via the mean difference (MD) with 95% confidence interval (CI95). Recovery in the RC group was assessed via the Penn shoulder score (function subscore), reporting change over the intervention as MD and CI95. These analyses were stratified by sex.

Abstract 236 Table 1
Abstract 236 Table 2

Summary of Results

Males demonstrated lower PPT versus control at baseline, whereas females did not (table 1). Post-intervention, females demonstrated larger clinically meaningful improvements in shoulder function compared to males (table 2).

Conclusions

At baseline males with RC tears had lower PPT indicating CS. After intervention, males exhibited less treatment benefit compared to females. These results are in line with prior data demonstrating lower PPT with poorer outcomes, although our study uniquely identified males as centrally sensitized in contrast to classic understanding of pain. Despite small sample size, these data suggest classic assumptions of CS in female patients may not hold for patients with chronic RC related shoulder pain.

237 Substance use and mental health comorbidities among patients in a low-barrier HIV clinic

EE Altwies1*

L Chwastiak1

JI Tsui1

E Bhatraju1

MR Golden1,2

M Ramchandani1,2

JC Dombrowski1,2

1University of Washington, Seattle, WA

2Public Health — Seattle and King County, Seattle, WA

Purpose of Study

Untreated psychiatric and substance use disorders can pose barriers to HIV treatment success. We evaluated the prevalence of and treatment receipt for psychiatric and substance use diagnoses in the Max Clinic, a novel low-barrier HIV clinic for people with complex needs, in order to inform service improvement.

Methods Used

We reviewed the electronic medical records of persons enrolled December 2014 - June 2020, excluding those enrolled for <1 month. We used text notes and diagnosis codes to identify, at enrollment, substance use and injection drug use in the past year, housing status, and prior psychiatric diagnoses. Among patients with substance use or psychiatric diagnoses, we reviewed treatment at enrollment, medications prescribed in the Max Clinic, referrals to specialty care, and completed specialty visits. We conducted a descriptive analysis and examined service receipt stratified by substance type and psychiatric diagnosis, focusing on mental health treatment and medications for opioid use disorder (MOUD).

Summary of Results

Of 227 total enrolled patients, 69% had a psychiatric diagnosis, including depressive (51%), anxiety (26%), psychotic (19%), and bipolar (16%) disorders. Most patients (85%) had chart-documented active substance use, including methamphetamine (60%) or heroin (30%); 42% injected drugs. Of 219 patients with a psychiatric diagnosis or substance use, 71% were living homeless or unstably housed. Of 128 patients with a psychiatric diagnosis not receiving treatment at enrollment, 46% were prescribed medications in clinic and 86% were referred to specialty care, of whom 38% completed ≥1 visit. Of 45 patients with chart-documented heroin use at enrollment not on MOUD, 25% were prescribed MOUD in clinic and 60% were referred for MOUD, of whom 40% completed ≥1 visit.

Conclusions

This study identified a large unmet need for behavioral health treatment among patients enrolled in a low-barrier HIV clinic. External referral to behavioral health specialists resulted in low rates of engagement, as less than half of Max Clinic patients referred to mental health care and MOUD complete even one specialty care visit. Integrating mental health treatment and MOUD on-site is likely needed to improve patient care.

238 Adverse childhood experiences and developmental delay in young us children

C Nivens*

A Hoyt-Austin

E Bimla Schwarz

University of California Davis, Sacramento, CA

Purpose of Study

Adverse childhood experiences (ACEs) have been associated with developmental delay and poor health outcomes in late childhood and adolescence. Health promoting practices such as breastfeeding and daily reading have been associated with lower rates of developmental delay. This study aims to investigate the association between early ACE exposure, protective health behaviors, and the diagnosis of developmental delay in early childhood.

Methods Used

In this cross-sectional analysis of population-representative date from the 2017–2018 National Survey of Children’s Health, we examined the relationship between ACEs, prior breastfeeding, daily reading, and diagnosis of developmental delay among 7837 children aged 3–5 years, using multivariate logistic regression to adjust for family, personal (i.e. premature birth, or low birth weight), and sociodemographic characteristics.

Summary of Results

We found a dose-dependent relationship between ACEs and developmental delay; compared to those with no ACE, developmental delay was more common among those with either 1 ACE (aOR=1.57, 95% CI 1.03–2.40) or 2 or more ACEs (aOR=3.22, 95% CI 2.0–5.19). Developmental delay in this age group was also associated with very low birth weight (aOR 3.98, 95% CI 1.62–9.77) and premature birth (aOR 2.21, 95% CI 1.34–3.65). Neither breastfeeding (breastfed for 6 months versus none aOR=0.70, 95% CI 0.36–1.36) nor daily reading (no reading versus daily reading aOR=1.10, 95% CI 0.47–2.60) were associated with reduced incidence of developmental delay in study participants.

Conclusions

Children with early ACEs are at risk of developmental delay, regardless of whether they are breastfed or read to on a daily basis.

239 Naloxone availability throughout California

S Vyas*

A Garfinkel

E Dini

R Ozawa

V Gerriets

Z Nicolas

California Northstate University College of Medicine, Elk Grove, CA

Purpose of Study

Naloxone is an opioid receptor antagonist that is administered to reverse the effects of opioid overdose. We will investigate several variables to understand how/why we see differences in naloxone availability to gain greater insight into how availability and barriers impact the opioid epidemic. As we expand our research to urban and rural areas, we expect to see a greater amount of pharmacies stock naloxone in San Francisco county compared to Sonoma County due to higher population density and implemented legislation.

Methods Used

A list of pharmacies was obtained from the California State Board of Pharmacy. A phone survey was administered to pharmacists and pharmacy technicians to geographically assess and analyze naloxone availability in Sacramento county. This phone survey will be expanded to other counties.

Summary of Results

Of all pharmacies contacted thus far, only 44% of pharmacies had naloxone availability in 2018. Of those pharmacies 75% carried Narcan© intranasal spray, 17.9% carried intramuscular injections, 3.6% carried Evzio© auto injector, and 3.6% carried intranasal via atomizer. Only 1 pharmacy was found to carry all 4 formulations, and 49% of pharmacies surveyed furnished naloxone without a prescription. In 2019, we saw an increase in stocking naloxone as 98% of surveyed pharmacies carrying it with 86% of those pharmacies only carrying Narcan© intranasal spray. Naloxone furnishing without a prescription in 2019 jumped to 76%.

Conclusions

Our findings suggest that pharmacies have improved their strategies for naloxone use. In the surveyed areas, more than 50% of pharmacies provide an indirect barrier by not carrying naloxone in 2018. About 50% of pharmacies surveyed adhere to voluntary guidelines aimed to increase naloxone availability and limit barriers to access. When surveyed in 2019, 98% were found to carry Naloxone and pharmacies that furnished Naloxone without a prescription increased to 76%. We found that more pharmacies that stock naloxone were willing to furnish without prescription boosting protocol adherence and lowering barriers to availability. Additional data collected emphasizes pharmacies’ unfamiliarity with naloxone use, protocols and guidelines. A similar growth was seen in protocol adherence and naloxone training when resurveyed with a 40% increase in training.

240 Association between mental illness and cardiovascular outcomes among emergency department patients presenting with chest pain

S Kumar*

H Duber

A Sabbatini

University of Washington School of Medicine, Seattle, WA

Purpose of Study

Patients with mental illness often experience disparities in treatment that can impact health outcomes. Few studies have examined the difference in cardiovascular (CV) outcomes for emergency department (ED) patients with mental illness compared to those without. The goal of this project was to examine mental health-related disparities in acute care outcomes among Medicaid beneficiaries with an ED visit for nonspecific chest pain.

Methods Used

We conducted a retrospective review of 82,807 nonspecific chest pain ED visits of Washington state adult Medicaid beneficiaries from 2010–2017. Patient exposure was determined by ICD codes that identified any mental illness and serious mental illness. Our primary outcome was the incidence of a CV hospitalization within 30 days of the index visit date. Secondary outcomes included acute myocardial infarction (AMI) within 30 days and 6 months, and CV hospitalization within 6 months. We performed multivariate logistic regressions to assess the associations between mental illness/serious mental illness and the outcomes of interest, controlling for race, gender, age, Elixhauser comorbidities, and baseline ED visits and inpatient hospitalization rates from the past year.

Summary of Results

Patients with mental illness had similar odds of CV hospitalization within 30 days compared to those without mental illness (OR, 1.53; 95% CI, 0.97 to 2.44; P = 0.070). Patients with mental illness had increased odds for CV hospitalization within 6 months (OR, 1.60; 95% CI, 1.13 to 2.27; P = 0.008), and had similar odds of AMI at 30 days and 6 months compared to those without mental illness. Serious mental illness was associated with higher odds of AMI within 6 months (OR, 1.47; 95% CI, 1.00 to 2.15; P = 0.048).

Conclusions

Neither mental illness nor serious mental illness were associated with increased odds of CV hospitalization within 30 days. However, mental illness was associated with increased odds of CV hospitalization within 6 months. Further investigation is warranted to examine the strength of this finding and the relationship between mental health, ED treatment, and short and long-term health outcomes.

241 Transition of care from the emergency department for patients with opioid use disorder

L Nguyen1*

K Jablonowski2

K Hallgren3

D Taniguchi4

L Whiteside2

1University of Washington School of Medicine, Seattle, WA

2Department of Emergency Medicine, University of Washington, Seattle, WA

3Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA

4Department of General Internal Medicine, University of Washington, Seattle, WA

Purpose of Study

The Emergency Department (ED) is increasingly becoming an important site for buprenorphine initiation for patients with opioid use disorder (OUD), but barriers to continued treatment post ED-discharge remain. Transitional care clinics bridge patients to outpatient care, but little is known about the barriers and facilitators to attendance for patients with OUD. Our study assessed the predictors of attendance at the Harborview Medical Center (HMC) After Care Clinic (ACC) for patients with OUD who visited the ED to understand how to connect these vulnerable patients to ongoing treatment.

Methods Used

A retrospective study of patients prescribed or dispensed buprenorphine in the HMC ED from June 1, 2019 – June 1, 2020 and referred to the ACC. Patient and visit-level characteristics were abstracted from the medical records of these patients. Multiple logistic regression was used to identify factors associated with attendance at After Care.

Summary of Results

A total of 146 patients were included in the sample, of which 44 (30.1%) attended their ACC visit. Of all 146 patients, 105 (71.9%) were un-housed, 129 (88.4%) were not employed, and 86 (58.9%) were concurrently using methamphetamine. Being un-housed (odds ratio [OR], 0.32, confidence interval [CI], 0.12 – 0.86), uninsured (OR, 0.17, CI, 0.03–1.09), and having a history of incarceration (OR, 0.28, CI, 0.10–0.77) were all negatively associated with ACC attendance. Having a cell phone (OR, 1.53, CI, 0.55–4.27), a history of a psychiatric disorder (OR, 1.89, CI, 0.75–4.76) and being treatment-seeking (OR, 1.81, CI, 0.70–4.71) were all positively associated with attendance.

Conclusions

This study found that social determinants of health such as experiencing homelessness, being uninsured, and previous incarceration all present barriers to post-ED follow-up, suggesting that these patients warrant increased resources and attention to support their continued healthcare engagement.

242 Factors associated with pain-related high-cost care settings in hidradenitis suppurativa

JM Fernandez1

AM Thompson1*

JL Hsiao2

VY Shi3

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

2University of California Los Angeles, Los Angeles, CA

3University of Arkansas for Medical Sciences, Little Rock, AR

Purpose of Study

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis with tender nodules, abscess, and sinus tracts in intertriginous areas. HS has been associated with recent increases in inpatient hospitalization rates. We aimed to evaluate factors affecting pain-related utilization of high-cost care (HCC) in HS.

Methods Used

An anonymous online survey was sent to Facebook HS groups asking ‘In the past 12 months, have you gone to urgent care, the emergency department, or been hospitalized because of pain from HS?’ Participants selected which of 20 pain intervention therapies they have tried for HS. A rating scale (0–10) was used for baseline pain. A multivariate logistic regression model was adjusted for Hurley stage (significance p<0.05). Odds ratios (OR) contain 95% confidence intervals.

Summary of Results

Of the 438 participants, 93.8% were female. HCC was reported in 32.2% which included 41.7% (15/36) of those with Hurley stage I (mild), 30.8% (72/234) of stage II (moderate), and 32.1% (54/168) of stage III (severe). Those with HCC had significantly higher mean baseline pain than those who did not (4.2 vs 3.4; OR=1.11 [1.03–1.19]; p=0.01). Males were more likely than females to have HCCs (55.6% vs 30.7%; OR=2.86 [1.29–6.47]; p=0.01). Current tobacco smokers were more likely to have HCCs than those who never smoked (40.0% vs 25.8%; OR=1.97 [1.23–3.19]; p=0.01).Rates of HCCs were higher in users verses nonusers for the following pain management modalities: opioids (51.4% vs 25.8%; OR 3.38 [2.21–5.43]; p<0.01), gabapentin (48.8% vs 30.4%; OR=2.26 [1.17–4.39]; p=0.02), marijuana smoking (44.5% vs 27.1%; OR=2.22 [1.44–3.42]; p<0.01), tramadol (44.6% vs 30.0%; OR=1.99 [1.14–3.45]; p=0.01), massage therapy (45.5% vs 30.7%; OR=1.96 [1.03–3.70]; p=0.04), bleach baths (39.5% vs 29.6%; OR=1.66 [1.04–2.66]; p=0.03), and topical numbing creams (37.6% vs 28.7%; OR=1.55 [1.02–2.34]; p=0.04).

Conclusions

Some HS patients require additional education on appropriate use of HCC. Pain control may reduce HCC utilization in HS patients.

243 An asset-based approach to reducing opioid-related mortality among the lummi community

T Huynh*

University of Washington School of Medicine, Seattle, WA

Purpose of Study

Lummi Nation is a Native American tribe of the Coast Salish peoples in Western Washington. Opioid use and opioid-related mortality disproportionately affect American Indians and Alaska Natives (AI/AN) in the Northwest, including the Lummi people. In 2016, the drug overdose death rate among AI/AN was 2.4 times that of the NW regional average, with 67% involving an opioid. The purpose of this study is to apply an asset-based approach of community development to identify potential interventions for reducing opioid-related mortality among the Lummi community.

Methods Used

Individuals, institutions, and local organizations helping to reduce opioid-related mortality in the Lummi community were identified by interviewing providers and patients at a local health clinic, and through community conversations with individuals in a harm reduction program. A literature review was conducted to explore risk factors associated with opioid use among AI/AN and other possible interventions for reducing opioid-related mortality. A public health report was drafted to assess feasibility of the translation of these interventions to the Lummi community.

Summary of Results

Community members and clinicians identified opioid use, overdose, and opioid use disorder as public health concerns of the Lummi community. Community assets addressing these issues included office-based opioid treatment, a crisis outreach program for those experiencing recent opioid overdose, and a peer-run community-based harm reduction program. Other assets were a buprenorphine treatment program with counseling and mental health services.

Conclusions

Incorporating a strengths-based framework for community development allowed individuals to contribute their skills and social networks to the development of their community. Institutions also contributed via the development of programs serving the community. The next steps are to build upon community assets by examining the programs and support systems already in place that can help to address opioid-related mortality in the Lummi community. For instance, counseling services already established as a part of buprenorphine treatment may also be used to instate a methadone maintenance treatment program. In this way, such a program becomes a potentially feasible and beneficial intervention for the Lummi community.

Neonatology general V

Concurrent session

10:05 AM

Saturday, January 30, 2021
244 Effects of Sars-Cov-2 on pregnant women at delivery and neonatal outcomes at a single institution in Los Angeles

MC Easterlin1,2*

R Ramanathan1,2

A Yeh1

S Yamaguchi2

M Biniwale1,2

1LAC+USC Medical Center, Los Angeles, CA

2PIH Health Good Samaritan Hospital, Los Angeles, CA

Purpose of Study

To evaluate the effects of SARS-CoV-2 infection on pregnant women and neonates. 2) To stratify neonatal outcomes by whether the mother was symptomatic.

Methods Used

Retrospective review of data on pregnant women admitted for delivery and infants from a center serving a population of predominantly lower socioeconomic status in Los Angeles. We report descriptive statistics and bivariate analyses examining whether neonatal outcomes differed by maternal symptomatology.

Summary of Results

We included 51 mother/newborn-dyads with SARS-CoV-2 positive mothers at delivery by nasopharyngeal PCR. Most mothers were Caucasian (96%) and Hispanic (96%). The majority of mothers were asymptomatic (46/51, 90%); 4(7%) were symptomatic; 1(2%) required hospitalization for COVID-19. Mothers had symptoms from 0–7 days before delivery. One mother was severely ill and required mechanical ventilation and convalescent plasma. Her infant was delivered due to worsening maternal condition. Following delivery, the mother was transferred for ECMO.

All 51 infants were inborn, liveborn, and singletons. 73% were born by vaginal delivery and 27% by C-section. Mean gestational age was 38.9±1.8 weeks; 5 infants(10%) were preterm. Mean birthweight was 3161±444 grams. One infant needed resuscitation with CPAP. For all but one infant, the 5-minute Apgar score was 9. 16/51(31%) presented with respiratory distress; 6 needed supplemental oxygen; 2 needed CPAP. All neonates had SARS-CoV-2 testing by PCR of nasopharyngeal swab – 51/51 were negative at 24 hours and 43/43 were negative at 48 hours. There were no significant differences in neonatal outcomes by maternal COVID-19 symptomatology.

Conclusions

The majority of SARS-CoV-2 positive mothers were asymptomatic, supporting universal testing of mothers admitted for delivery. One mother became critically ill emphasizing close monitoring of pregnant women. Even though all infants tested negative for SARS-CoV-2 reflecting the low rate of perinatal transmission almost 1/3 had transient respiratory symptoms. There was no difference in neonatal outcomes by maternal symptomatology.

245 Assessment of ultrasound-guided peripheral arterial line placement in infants after implementation of a bedside ultrasound program

R Dasani*

V Pai

S Vallandingham

C Noh

A Davis

S Bhombal

Stanford University School of Medicine, Palo Alto, CA

Purpose of Study

Peripheral arterial line placement is a technically challenging procedure in infants due to small caliber vessels. Repeated unsuccessful attempts can lead to complications, increase procedure time and decrease overall success rate. In pediatric and adult populations, ultrasound-guided placement of peripheral arterial lines has been shown to improve procedural accuracy and lead to fewer attempts and complications compared to a landmark-based approach. A bedside ultrasound program was implemented in our neonatal intensive care unit (NICU) in December 2018. The purpose of this study was to assess whether use of ultrasound (US) decreased the number of peripheral arterial line attempts and increased first attempt success in infants after this program was established.

Methods Used

We conducted a retrospective chart review of infants admitted to the neonatal intensive care unit (NICU) who had a successfully placed peripheral arterial line from January 2019 to July 2020 by a NICU provider. We collected demographic information, number of attempts and whether US was used. Student’s t-test and chi-square test were used to compare variables between groups.

Summary of Results

A total of 59 arterial lines (23 ultrasound-guided, 36 non-US guided approach) were placed on 49 patients. Ultrasound was used more frequently on larger and older infants. Lines placed by US had fewer attempts for successful placement (p=0.01) and resulted in higher first attempt success rates, though did not reach statistical significance.

Abstract 245 Table 1

Conclusions

Following implementation of a bedside US program, use of US had fewer mean attempts for successful arterial line placement although US was used more often in older and larger infants. Further research is needed to evaluate the utility of US for arterial access in infants.

246 Reconciling markedly discordant values of serum ferritin versus reticulocyte hemoglobin content

TM Bahr1*

V Baer2

RK Ohls1

TR Christensen1

D Ward1

S Bennett2

RD Christensen1

1University of Utah, Salt Lake City, UT

2Intermountain Health Care Inc, Salt Lake City, UT

Purpose of Study

The serum ferritin level is commonly used to screen neonates for iron deficiency. A more recent method used to assess iron stores is the reticulocyte hemoglobin content (RET-He), which measures the hemoglobin within reticulocytes. The RET-He serves as a metric of the iron available for hemoglobin production during the previous several days. We do not routinely measure both the serum ferritin and the RET-He. However, on rare occasions both tests are obtained simultaneously; and occasionally we observe discordant results. The purpose of this study was to determine why serum ferritin and reticulocyte hemoglobin (RET-He), drawn to assess neonatal iron sufficiency, sometimes have markedly discordant results.

Methods Used

We assembled a data set from laboratory tests obtained in five NICUs over 28 months, identifying all patients with a ferritin and RET-He drawn simultaneously (within 48 hours of each other). We compared the group with concordant ferritin and RET-He values, with the group where results of the two tests were discordant. We considered significant discordance if one value was >95th% reference interval, while the was other <5th%, and we sought explanations for these.

Summary of Results

Of 190 paired ferritin and RET-He measurements, 16 (8%) were significantly discordant. Fifteen of the 16 involved a high ferritin and a low RET-He. These 15 had a higher immature to total neutrophil ratios (P=0.008) and a higher CRP than did those with concordant values (P<0.001). Eight of the 15 also had clinical evidence of an inflammatory process and five others had suspicion of infection. In these 15, a low MCV and a high%Micro-R, and a low MCH and a high%HYPO-He suggested iron deficiency.

Conclusions

When ferritin and RET-He were discordant, inflammation likely cause an elevation in ferritin. Erythrocyte microcytosis and hypochromasia suggested that the low RET-He gave the more accurate interpretation; that iron deficiency was present.

247 Outcomes of very low birth weight preterm infants with maternal chorioamnionitis and funisitis

S Sakhamuru1*

A Hisey2

T Tagliaferro1,3

L Barton1,3

R Ramanathan1,3

M Biniwale1,3

1Los Angeles County, University of Southern California, Granada Hills, CA

2University of Southern California, Los Angeles, CA

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

Purpose of Study

There is conflicting evidence regarding the effect of funisitis on morbidities and mortalities in preterm infants while chorioamnionitis has been implicated in adverse outcomes. This study aims to evaluate funitis(FU), histologic chorioamnionitis (HC), and clinical chorioamnionitis(CC) as risk factors for short and long term outcomes of very low birth weight (VLBW) infants.

Methods Used

This is a retrospective observational study with data obtained for VLBW (birth weight < 1500 grams) infants, born at our institution between 2009–2018. Electronic medical records and neonatal data bases were used for maternal information, delivery details and the most common neonatal morbidities and mortality. Neurodevelopmental outcomes were based on Bayleys III Scale completed by a psychologist over three years in a subgroup of patients.

Summary of Results

Of the 308 infants studied, those with HC had a higher risk of Intraventricular hemorrhage(IVH) (47.3% vs 32.5%, P=0.021) and a higher risk of mortality of (17.6% vs. 7.7%, P=0.024). Those with CC had a significant risk of having severe IVH (14.1% vs 2.5%, P=0.001). For those with FU, there was no increased risk for IVH (34.1% vs. 45.8%, P=0.119) or mortality (12.5% vs. 9.5%, P=0.394 ). Those with HC or CC, there was a decrease in cognitive scores and percentiles (90.36 vs. 96.26, P=0.021), (P=0.039) at 16–24 months. Language percentiles were also impacted( P=0.018). Similarly, in the 26–36 month group, the cognitive percentile(P= 0.049) and language percentile(P=0.031) were impacted significantly. Those infants with FU did not have a difference in cognitive or language percentiles when evaluated in either time frame.

Conclusions

FU was not a risk factor in VLBW infants with short term outcomes, mortality, or a significant change in long-term neurodevelopmental outcomes. HC is a risk factor for higher mortality. Having either HC or CC increases the risk for IVH and a delay in cognitive and language development. Early evaluation and intervention for vulnerable preterm infants may be necessary to decrease the unfavorable neurodevelopmental outcomes.

248 Delivery room resuscitation practice trends in a population-based cohort of infants born at periviable gestational age

X Chen1*

T Lu1

J Gould1

SR Hintz1

DJ Lyell2

X Xu3

H Lee1

1Stanford University School of Medicine, Stanford, CA

2Stanford University School of Medicine, Stanford, CA

3Yale University School of Medicine, New Haven, CT

Purpose of Study

To determine the rate and trend of active resuscitation in a population-based cohort of infants born at periviable gestational age and to examine maternal and clinical factors associated with active resuscitation.

Methods Used

Infants born in 2011–2018 at a gestational age of 22 to 25 weeks at California Perinatal Quality Care Collaborative (CPQCC) affiliated hospitals were analyzed. Active resuscitation in the delivery room was defined as either: 1) intubation, cardiopulmonary resuscitation, and/or epinephrine; or 2) CPAP and/or NIPPV if the infant survived beyond 12 hours after birth. The difference in rate of active resuscitation by gestational age and time period (2011–2014 versus 2015–2018) were compared using a 2-sample proportion test. Multivariable logistic regression was used to identify significant maternal and infant factors that impacted the primary outcome of delivery room active resuscitation.

Summary of Results

There were 8252 live born infants included and 6630 infants (80%) were provided active resuscitation. Rates of active resuscitation were low at 22 weeks (19%) and increased with each advancing week (e.g., 95% at 25 weeks). The rate of active resuscitation was significantly higher for those born between 23 weeks 4–6 days (78%) compared to those born at 23 weeks 0–3 days (66%, p<0.001). Furthermore, the rate of active resuscitation among those born at 23 weeks significantly increased from 2011–2014 (66%, 95% CI [62%, 70%]) to 2015–2018 (76%, 95% CI [73%, 79%]) (p<0.001). In multivariable analysis, factors associated with greater odds of active resuscitation included maternal black race, increasing gestational age, PPROM, antenatal steroids exposure, cesarean section, singleton birth, and appropriate for gestational age birth weight.

Conclusions

Rates of active resuscitation in the delivery room remained low at 22 weeks within CPQCC hospitals. However, at 23 weeks, rates increased significantly over the later part of the week and in 2015–2018 than in 2011–2014. Several maternal and infant level factors influenced the likelihood of active resuscitation.

249 Factors affecting outcomes of infants delivered in an emergency setting

MP Martes Gomez1*

S Liu2

B Gordon2

R Ramanathan2

M Biniwale2

1LAC+USC, Glendale, CA

2LAC+USC, Los Angeles, CA

Purpose of Study

Most neonates transition to extra uterine life without any complications during the delivery process. There are multiple unpredictable and unpreventable obstetric emergencies that may lead to undesirable consequences in newborns. The objective was to review maternal and infant characteristics of emergency deliveries occurring in the labor and delivery unit (LDU) at LAC+USC Medical Center.

Methods Used

This is a retrospective chart review of pregnant women admitted to LDU delivering emergently between May 2019 and August 2020. Emergency deliveries outside of the LDU and those with intrauterine fetal demise were excluded. Maternal and neonatal electronic medical records were reviewed and analyzed.

Summary of Results

50 live births met inclusion criteria. The median maternal age was 26 years (IQR24-33 yrs), median gravida 3. The majority (82%) of women presented in labor. 86% of deliveries were via Cesarean section (CS). 54% of women were obese. 56% of women had prenatal complications. 58% had prenatal care starting the 1st trimester; 6% had no prenatal care. Non reassuring fetal heart tracings was the most common reason for emergency CS (72%), followed by uterine rupture (14%), cord prolapse (9%) and placental abruption (5%). Median infant gestational age was 39 weeks (IQR37-40wks) with mean birth weight of 2933 g (SD833 g). Large for gestational age infants constituted 10% of the population. 6% of infants had shoulder dystocia. Advanced resuscitation in the delivery room (DR) was required in 40% of infants, including positive pressure ventilation (38%), intubation (4%), chest compressions (2%), vascular access (2%). Half of the infants required NICU admission. 76% required respiratory support. Most of the infants admitted to NICU required non-invasive positive pressure ventilation (79%), 21% required invasive mechanical ventilation. All infants intubated in the DR underwent therapeutic hypothermia (8% of total infants). Overall mortality rate was 2%.

Conclusions

A high numbers of infants require DR resuscitation and NICU admission after delivery in emergency setting. Majority of NICU admissions were secondary to respiratory compromise. A significant number of infants were at risk for hypoxic ischemic encephalopathy. Better methods to predict emergency deliveries need to be elucidated.

250 Quality improvement initiative to reduce time to full feeds in infants with gastroschisis

A Vachhani1*

A Zepeda-Tiscareno1

J Rosoff2

E David3

A Walther4

W Moses4

S Nair3

J Shepherd3

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

2Children’s Hospital Los Angeles, Los Angeles, CA

3Children’s Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA

4Children’s Hospital Los Angeles, Los Angeles, CA

Purpose of Study

To evaluate the effectiveness of a new feeding guideline for infants with gastroschisis in reducing time to full feeds (140 cc/kg/day) from initiation by 15%. Baseline data of patients prior to implementation of the guideline is presented.

Methods Used

A feeding guideline for infants with gastroschisis was developed by a multidisciplinary team and implemented in February 2020. Baseline data was collected retrospectively for infants who underwent gastroschisis repair at Children’s Hospital Los Angeles from 2016–2019. Exclusions were intestinal atresia, gestational age (GA) less than 32 weeks and birth weight (BW) less than 1250 grams.

Summary of Results

A total of 32 infants met the criteria with a mean GA of 37 weeks (35.7–38.3) and median BW of 2576 grams (2246–2880). Twenty infants underwent silo placement with the median time to closure of 8 days. The median time from initiation to full feeds was 13 days and median day of life to achieve full feeds was 32 days. Thirteen infants (41%) required suspension in feeding advancement.

Abstract 250 Table 1

Baseline characteristics N=32

Conclusions

Baseline data for our gastroschisis population is presented. A guideline was implemented to standardize feeding advancement. The first PDSA cycle is currently underway to help reach our aim of reducing time to full feeds by 15% from 13 to 11 days.

Adolescent medicine and behavior development V

Concurrent session

11:00 AM

Saturday, January 30, 2021
251 Perception and prevalence of withdrawal as a contraceptive method amongst medical students

SY Li*

P Desai*

J Lin

H Choi

AL Nelson

Western University of Health Sciences, Pomona, CA

Purpose of Study

Withdrawal was reportedly used by 5.3% of U.S. women in the latest national study; however, it is not routinely recommended as a birth control method by professional organizations. A dichotomy thus exists between the perception of withdrawal and the extensiveness of its use. The purpose of this study is to determine the prevalence of withdrawal use amongst medical students and identify possible factors associated with greater use of this contraceptive method.

Methods Used

In an electronic survey, 150 medical students, who have engaged in heterosexual intercourse when not trying to conceive, were asked about their use of withdrawal as a contraceptive method and factors affecting their choice of contraceptive use.

Summary of Results

Of the 57% who reported having used withdrawal to prevent pregnancy, 48% reported having relied on it by itself for birth control. When asked the selection criteria for their most frequently used method recently, ease of use (77%) was the most commonly selected criteria, followed by effectiveness (59%), availability (39%), and cost (33%). When asked the reasons for potentially using withdrawal as their only form of contraception, availability (52%) was the most commonly selected reason, followed by ease of use (47%), difficulty obtaining other methods (29%), and cost (25%). Majority (57%) of respondents said they would be unlikely to use withdrawal in the future; 91% credited low efficacy/unreliability as the reason why.

Conclusions

Despite this perception of withdrawal as a poor contraceptive method, this study confirms that withdrawal has been used by a majority of medical students due to its availability, ease of use, and cost. These findings provide more insight into withdrawal use to help health professionals understand the features young adults value in a free method.

252 Impact of sexual health education on withdrawal use and perception amongst graduate students

P Desai

SY Li

H Choi

J Lin

AL Nelson

Western University of Health Sciences, Pomona, CA

Purpose of Study

Withdrawal, formally known as ‘coitus interruptus’, is a widely used but often discounted method of contraception in the United States. Despite the widespread use and low failure rate of withdrawal when used correctly, use of withdrawal is infrequently discussed in sexual education courses or in medical settings. The purpose of this study is to address associations between sexual health education and perception and use of withdrawal amongst graduate students, and to identify gaps in knowledge regarding withdrawal as a method of contraception.

Methods Used

In an IRB-approved project on an exempt basis, 84 male and 100 female medical graduate students were asked about their knowledge and perception of withdrawal, amount of contraceptive counseling received, and their personal practices in an anonymous electronic survey.

Summary of Results

Of the 160 students who had taken sexual education courses, 45% reported that withdrawal, or the ‘pull-out’ method, was discussed. Furthermore, less than 2% of those respondents reported ever being counseled about withdrawal in a medical setting. A majority of surveyed students (91%) also reported low efficacy as a reason to not use withdrawal as their only method of contraception, despite 56% of respondents having used withdrawal in the past. Of note, 58% of surveyed students who admitted to ever having used withdrawal for birth control were female, versus 42% of whom were male.

Conclusions

The results of this study reveal that there is not a significant association between use and perception of withdrawal and contraceptive education about withdrawal in either medical counseling or sexual education courses. However, the study sheds light on the limited awareness of withdrawal and its efficacy in spite of receiving sexual health education in various settings. Existing research on coitus interruptus suggests that individuals who are unfamiliar with other contraceptive methods and individuals who have been unsatisfied with all other contraceptive choices are most inclined to use withdrawal. These findings highlight the need for health care professionals and sexual health educators to expand their efforts to include more comprehensive information on a commonly used method of contraception.

253 Effect of interventions to improve childhood vaccination with a focus on underserved populations

C Fang1*

N Sussman1,2

B Afghani1,3

1UC Irvine School of Medicine, Irvine, CA

2U of Arizona, Phoenix, AZ

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

Purpose of Study

Vaccination compliance continues to be a challenge. Although there are several studies on interventions to improve influenza and adolescent vaccination rates, studies of interventions to improve vaccinations in low income or minority young children are sparse. The objective of this study is to determine the efficacy of interventions to improve vaccination status in very young children.

Methods Used

A comprehensive literature search was utilized through multiple search engines, such as PubMed, Google Scholar using key words, ‘reminder’, ‘vaccine’, ‘health disparity’, ‘low income’, ‘intervention’ and ‘children’. Only studies performed in the United States that focused on use of interventions to improve timely administration of childhood (≤24 months) vaccines in low income or minority populations were included.

Summary of Results

We found 5 studies that matched our inclusion criteria. The populations studied were predominantly African American, on public insurance, or from low-income families. The 24-month vaccination rates before the intervention ranged from 49% to 55% in underserved population. After the interventions, the rate increased by 13–43%. Studies that involved more intensive interventions, such as in-person education, voucher incentives, and combination of phone call, mail, and text message reminder systems were very effective in increasing vaccination rates in children ≤24 months of age.

Abstract 253 Table 1

Intervention studies to improve childhood vaccinations

Conclusions

Our review suggests that various intervention methods are effective in increasing vaccination rates in underserved populations. However, even after the intervention, vaccination rates remained suboptimal in some studies. Additional prospective controlled trials comparing different targeted intervention methods with a focus on health inequities are needed.

254 Improving access to etonogestrel implant at children’s hospital los angeles (chla)

C Kim1*

A Hidirsah2

AL Nelson1,2

C Borzutzky2

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

2Children’s Hospital Los Angeles, Los Angeles, CA

Purpose of Study

Although etonogestrel implants are considered first-line contraception for adolescents, they may not be accessible to providers at CHLA-affiliated AltaMed clinic, nor is learning to place them a requirement for pediatric trainees per American College of Graduate Medical Education (ACGME) guidelines. This study identifies number of providers trained, provider comfort level counseling benefits and side effects of implants, potential barriers that prevent providers from getting trained, and provider-perceived likelihood of placing implants if trained.

Methods Used

An 11-question survey was distributed three times via RedCap to ~270 AltaMed pediatricians and CHLA pediatric residents. Responses were compared by provider status (Attending vs. Resident) and adolescent patient volume (4+/month vs. 1–2/month). Chi-square analysis was done to compare responses between groups.

Summary of Results

There was a 21% survey response rate (n=56). 89% of respondents were not trained, including 97% of residents and 87% of those who saw 4+ teenagers per month. 64% and 38% of respondents respectively felt comfortable counseling about benefits and side effects of implants. Top reported barriers to training were: training not offered (24%), lack of access to training (20%), insufficient time for training (19%), and low patient volume to justify training (14%). More residents reported lack of access to training, while more attendings reported time constraints preventing training. Greater than two-thirds of providers estimated placing 1–5 implants/month if trained.

Conclusions

The greatest barrier reported was lack of access to training, with residents more likely to seek training and report fewer time constraints. Although fewer providers were comfortable counseling about side effects, it was not a perceived barrier. To improve future access to contraceptive implants, training of pediatric residents should be required by ACGME. However, lack of trained attendings and need for coordination of the entire medical team may limit current use in clinics. Impacts of formal training on short- and long-term provider behaviors and patient access to implants should be studied in future projects.

255 A rare presentation of henoch-schonlein purpura as hemorrhagic bullous lesion in an adolescent

M Kaur

M Khamlong*

A Abad

T Nandhagopal

Kern Medical Center, Bakersfield, CA

Purpose of Study

Henoch-Schonlein purpura (HSP) also known as Immunoglobulin A vasculitis is the most common childhood systemic vasculitis affecting the skin, gastrointestinal tract, joints, and kidney. Skin lesions of HSP typically present with non-thrombocytopenic palpable purpura of the buttocks and lower extremities. <2% of children with HSP cases develop hemorrhagic bullous lesions (Trapani et al, 2010). We present an unusual case of hemorrhagic bullous HSP in an adolescent female who responded well to dapsone.

Methods Used

Single patient case report.

Summary of Results

A 16-year-old female with a history of DM type 1 presented with palpable, purpuric lesions on her foot and arthritis of the ankle joints. The rash progressed to involve her lower extremities and buttocks. She reported a self-limiting URI two weeks prior. She denied any fever, abdominal pain, or dysuria. Two days later, the rash progressed to the trunk and extensor surfaces of upper extremities, with blistering and painful hemorrhagic bullous lesions. CBC with diff was unremarkable, CRP 5.01 mg/dL, and ESR 27 mm/hr. Autoimmune, vasculitis, and infectious panels were negative. Renal function remained normal. Initial skin biopsy was inconclusive due to sample size. Oral prednisone was initiated and IVIG was added due to minimal skin improvement. A repeat skin biopsy revealed leukocytoclastic vasculitis, consistent with HSP. The patient was discharged home with steroid dose taper. Patient relapsed with new skin lesions. She responded well to dapsone and penicillin was started as prophylaxis for extensive skin lesions.

Conclusions

Hemorrhagic bullous HSP is rare in children and may require more aggressive care than the typical presentation of HSP especially in adolescents. Treatment includes corticosteriods for anti-inflammatory effects and IVIG for lesions refractory to corticosteroid (Mauro et al, 2018). Dapsone has been shown effective due to its anti-IgA, antioxidant and anti-neutrophilic effect (Iqbal & Evans, 2005). Additionally, bullous lesion in pediatric population warrants an early skin biopsy to rule out bullous pyoderma gangrenosum, a neutrophilic dermatosis and to initiate treatment accordingly. Further studies are needed to determine the pathophysiology and management of hemorrhagic bullous HSP.

256 Posterior reversible encephalopathy syndrome following steroid treatment for drug rash in a pediatric patient

T Mills*

D Balyozian

M Huang

University of California San Diego, San Diego, CA

Case Report

DRESS (drug rash with eosinophilia and systemic symptoms) is a syndrome of severe drug reaction that typically presents with fever, morbilliform rash, lymphadenopathy, eosinophilia and transaminitis. Symptoms develop, on average, 23.8 days after drug exposure. Treatment involves prompt removal of the causative agent and systemic steroids in severe cases. PRES (posterior reversible encephalopathy syndrome) is characterized by headache, seizures, and encephalopathy, often associated with hypertension.

We present the case of a 9 year old boy with a history of well-controlled epilepsy on levetiracetam who presented with 13 days of fever and rash. Four weeks prior to admission, levetiracetam was switched to zonisamide for concerns of weight gain. On arrival, he was febrile, with erythematous lesions on buccal mucosa, bilateral conjunctival injection, and generalized papules and macules with significant anasarca. Laboratory findings were remarkable for leukocytosis, transaminitis, elevated inflammatory markers, and elevated HHV-6 serology. He was treated with steroids (dosing based on admission weight) for a presumed diagnosis of DRESS secondary to zonisamide, then developed hypertension and subsequent acute encephalopathy. MRI findings showed multifocal, bilateral gyriform foci in a posterior distribution consistent with PRES. His altered mental status improved as steroids were weaned and blood pressure stabilized.

In our literature review, we found one patient with PRES following treatment for DRESS. Our patient presents a clinically complex pediatric case of DRESS, treated with steroids, who developed hypertension and eventually PRES, a rare phenomena in the pediatric population. Thus, we urge clinicians to: (1) stay vigilant in monitoring elevated blood pressures in the pediatric population, where it can be easy to dismiss or miss; (2) monitor steroid use and resulting HTN and; (3) be mindful of acute weight changes when dosing, as differences can lead to substantial consequences.

Abstract 256 Table 1

Clinical course timeline

257 Variations in clinical and laboratory presentation of uti in medically complex patients

MB Iyer*

A Nguyen

J Beck

K Kieran

University of Washington School of Medicine, Seattle, WA

Purpose of Study

In medically complex children (MCC), evaluating for urinary tract infections (UTI) can be complicated due to vague and nonspecific presentation. The current American Academy of Pediatrics criteria for UTI diagnosis is based on findings in otherwise healthy children, thus this poses an issue for MCC. We sought to describe urinalyses and clinical presentations in symptomatic children with varying levels of medical complexity.

Methods Used

A retrospective cross-sectional analysis was performed of all patients admitted to a single freestanding children’s hospital with an ICD-9 or ICD-10 diagnosis of UTI (cystitis or pyelonephritis) from January 1, 2018-December 31, 2019. Demographic data were collected, as were urinalysis characteristics and culture results. Continuous data were assessed with measures of central tendency, and comparisons among groups of MCC (complex chronic [CC], non-complex chronic [NCC] and non-chronic [NC]) were performed using t-tests and analyses of variance, while proportional outcomes were assessed using chi-square and Fisher’s exact tests.

Summary of Results

A total of 119 patients had 133 admissions. Males comprised 47.1%, 17.6%, and 23.5% of CC, NCC, and NC patients, respectively (p=0.10). CC patients were significantly older (median age 11.1 years) than NCC or NC patients (median age 4.2 and 7.0 years, respectively; p=0.0035). While patients in all three groups were equally likely to be febrile, CC patients (35.4%) were less likely than NCC (82.4%) or NC (70.6%) patients to have vomiting/nausea (p<0.0001). Elevated CRP was more often seen in NC patients (75%) than in CC (18.2%) or NCC (33.3%) patients (p=0.007), while pyuria was seen in fewer NCC (47.5%) than CC (70.7%) or NC (73.5%) patients (p=0.02). Three patients had negative urine cultures. All patients received a 10–14 day antibiotic course (82% orally).

Conclusions

CC patients presented with symptoms less likely to align with ‘typical’ UTI symptoms; however, the finding that three patients had negative urine cultures underscores the need for comprehensive evaluation of all children with suspected UTI. Clinicians must be aware of variations in UTI presentation and balance prompt initiation of therapy with the potential harms of antibiotic administration.

258 Improving completion rates of maternal depression screening in an academic pediatric practice

K Habib1*

K Mullens2

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

2Phoenix Children’s Hospital, Phoenix, AZ

Purpose of Study

The American Academy of Pediatrics recommends that Pediatricians screen all postpartum women for maternal depression. Maternal depression not only affects mothers, but also can have negative consequences on the child’s health and development. The purpose of this study is to determine whether there is a provider bias among Pediatricians in screening for maternal depression at well-child check-ups. The results will shed light on provider biases and will help increase screening rates.

Methods Used

This was a retrospective study within the Division of Primary, Complex Care at Phoenix Children’s Hospital from 7/1/19 to 3/31/20. Maternal depression screening was conducted utilizing a validated 2-question screening tool, the Patient Health Questionnaire (PHQ2). This tool was administered to mothers at their well-child check-ups (months 1, 2, 4, and 6). Analysis was based on completion of the screening, race/ethnicity of the mother, maternal language, infant age, and socioeconomic status.

Summary of Results

A total of 401 patient encounters were collected and patient demographic characteristics were reported. Individual comparisons between the 4 time points were assessed using the McNemar’s test followed by multiple comparisons adjustment. Results showed statistically significant increases in depression screening between 1 month (N=156, 38.9%) and 2 months (N=187, 46.6%) for all patients (p<0.008) and patients with public insurance from 1 month (N=117, 39.4%) to 2 months (N=142, 47.8%) (p<0.008) following the Bonferroni Correction. A logistic regression analysis showed that Hispanic mothers were two times more likely to be screened at 1 month (odds ratio 2.08, CI 1.01, 4.32). For longitudinal analysis, the generalized estimating equation showed that at 2 months, the odds of all mothers being screened was 8% higher than at 1 month (OR 1.08, p<0.002). Mothers with boys had a 3% increase in being screened at each well-child visit (OR 1.03 p<0.039 and patients with private insurance had a 5% increase in screening at each visit (OR 1.05 p<0.032).

Conclusions

This study suggests that there are screening biases among Pediatricians for postpartum depression that are influenced by infant gender, race/ethnicity of the mother, maternal language, and socioeconomic status.

COVID – Infectious diseases II

Concurrent session

11:00 AM

Saturday, January 30, 2021
259 Effects of covid-19 on morbidity amongst patients with pre-existing asthma in the central valley during the early pandemic

A Singh1*

R Plasencia2

V Plasencia2

AZ Ahmad2

1University of California San Francisco, Fresno, CA

2UCSF Fresno, Fresno, CA

Purpose of Study

Current data is unclear as to whether asthma increases morbidity due to SARS-CoV-2 infection1. In Central Valley counties, rates of asthma range from 18 to 26.8% compared to 15.2% statewide2. This study investigated asthma as risk factor in confirmed COVID-19+ patients in this region during the initial phase of the pandemic.

Methods Used

De-identified data was obtained from a registry of COVID-19+ cases in a tertiary hospital system in the Central Valley Apr-May 2020, &amp classified based on health outcomes. Outcomes obtained: # of hospitalizations w/in the past 90 days, length of hospital stay (LOS), ICU admission, risk scores based on chronic conditions, age, gender, length of ICU stay, & deaths of patients with & w/o asthma. ICU patients were delineated by COVID as primary or secondary with other co-morbidities.

Summary of Results

The study had 360 patients, where 18.6% had asthma, 80.3% w/o asthma, & 1.1% were unknown. Due to COVID, 35.8% of the asthmatic patients were hospitalized, & 11.9% in the ICU. In comparison, 22.5% of the non-asthmatic patients (controls) were hospitalized & 9.3% in the ICU. The avg. age was 46.7 yrs., & male to female ratio was 1.2:1. Patients with asthma had significantly higher risk of hospitalization compared to controls (1.21 vs. 1.08, p = 0.04). The LOS did not differ between the two groups. Yet, asthmatic patients when admitted with COVID, had avg. longer ICU stay (17.4 to 12.7 days p = 0.166). When risk stratification was applied, asthmatic patients had avg. greater general risk score of 3.6 to 3.1 compared to control (p = 0.159). They also had a significantly greater avg. # of chronic meds (8.6 vs. 5.3 p = 0.000) and co-morbidity score (1.2 vs 0.78, p = 0.006). Of the 4 deaths from COVID related disease, 3 had asthma & required ICU care.

Conclusions

Patients with asthma had a greater: admission rate, ICU stay, general risk, # of chronic meds, & comorbidities. Whether their COVID disease severity was primary or secondary to comorbidity factors needs further study. Pre-assessment of asthma risk & comorbidity is useful to predict outcomes during this pandemic. This particularly applies to patients in the Central Valley, where asthma prevalence is greater across all age & demographic groups.

260 A unique host in HIV and morbid obesity for covid-19

NM Winicki1*

J Parker1,2

1University of California Riverside, Riverside, CA

2University of California Los Angeles, Los Angeles, CA

Case Report

Introduction: Severe acute respiratory syndrome (SARS-CoV-2) is part of the beta-coronaviridae family. This virus has been shown to cause pneumonias which can rapidly progress to acute respiratory distress syndrome. We present a case of an HIV+, morbidly obese (BMI – 56) patient that survived infection with SARS-CoV-2.

Case description

On March 17, a 45-year-old male with a significant medical history of a BMI 56, previous pulmonary embolism, HIV and diabetes mellitus was admitted to the hospital with shortness of breath (SOB) after several days of cough and flu-like symptoms. He had a qSOFA score of 0 and his blood cultures were negative. WBC was within range at 9.1K/uL. Computed tomography angiography was performed and showed no pulmonary embolism. On March 25th, he tested positive for COVID-19 via PCR. The patient was discharged on March 30th to self-isolate. He presented with SOB on a telemedicine follow-up visit on April 2nd and retested positive for COVID-19 via PCR. CT values were monitored from the first positive CT PCR test on March 25th to April 30th when the virus was no longer detected.

Discussion

Both diabetes and a BMI greater than 40 have shown to be high risk factors for severe illness in SARS-CoV-2 infection in addition to high IL-6 levels. Furthermore, obesity is considered a state of low-grade inflammation, with IL-6 being one of adipose tissue’s major interleukins released. While IL-6 was not elevated in this patient’s case, he was HIV positive which can increase IL-6, and lead to worse outcomes with COVID-19. Importantly, greater visceral adipose tissue has shown to increase the need for intensive care in COVID-19 cases. As such, SOB and lack of oxygen are what categorize COVID-19 patients as ‘symptomatic,’ however, they are also common presentations in morbidly obese patients. This poses a challenge for clinicians when deciding how to classify their patient per CDC/WHO guidelines.

Both HIV and obesity are thought to have played a role in this patient’s viral persistence and extended shedding period. While more research is needed for this subset of patients, this case provides a look into how HIV and obesity serve as a unique host for the novel SARS-CoV-2 virus, as well as provide a picture of how difficult such cases can be to manage.

261 Sex differences in anxiety disorders and low socioeconomic status during the covid-19 pandemic

C Roose*

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

Purpose of Study

The coronavirus disease 2019 (COVID-19) pandemic imposes an unprecedented stressor on all aspects of society, including mental health and economic instability. The objective for this study was to analyze information regarding the psychological responses and economic consequences males and females are experiencing. Based on prior literature (Jainapurkar, 2018), females are more likely to develop anxiety compared with men due to social roles and income (de Mola, 2020). In light of this, it is anticipated the economic and psychological effects of the pandemic will disproportionately affect females compared to males during the COVID-19 outbreak.

Methods Used

A nationally representative survey was administered to 1,006 healthy individuals over the age of 18 in the month of April, 2020, near the outset of the nationwide attempts to control the spread of COVID-19. A total of 439 males and 567 females participated in this study. Participants completed the Zung Self-Rated Anxiety scale, General Anxiety Disorder 7-item scale (GAD 7), and annual income report. Finally, participants reported if they experienced the loss of their primary job.

Summary of Results

A GAD 7 cut score of ≥8 (Plummer, 2016) was used to assess clinically significant anxiety. Significantly more females (n = 107; 25.2%) exceeded this cutoff than males (n = 210; 38.1%; p < 0.001). Additionally, a Zung Self-Rated Anxiety cut score of ≥45 (Dunstan, 2020), was used to assess clinically significant levels of anxiety. Again, a greater proportion of females (n = 121; 21.4%) exceeded this cutoff compared to males (n = 72; 16.5%; p = 0.049). There was no statistically significant difference in the annual income of males versus females. However, there were significantly different levels of anxiety associated with income quantiles between sexes. There is a higher proportion of anxiety among people in the lower income group. In addition, females exhibit higher rates of anxiety than males regardless of income. Finally, females showed a trend toward higher rates of primary job loss (n = 110; 19.4%) than males (n = 65; 14.8%) (p=.057).

Conclusions

Females reported higher levels of anxiety than males, regarless of income, in addition to higher rates of primary job loss. Finally, higher rates of anxiety are present among people in the lower income group.

262 Impact of altitude on coronavirus-disease-2019 per capita infection, death, and mortality rates in the United States: a modeling and observational study

KE Stephens*

DR Bruns

P Chernyavskiy

University of Washington School of Medicine, Anchorage, AK

Purpose of Study

We sought to determine if COVID-19 infection, death, and case mortality rates differed in high altitude (HA) versus low altitude (LA) U.S. counties.

Methods Used

Using publicly available geographic and COVID-19 data, we calculated per capita infection, death, and case mortality rates in HA and LA U.S. counties matched by population density. We also performed population-scale regression analyses to investigate the association between county elevation and COVID-19 infection rates.

Summary of Results

Comparison of LA (< 914 meters above sea level, n=58) counties of similar population density as HA (>2133 meters above sea level, n=58) counties yielded significantly lower COVID-19 per capita cases at HA versus LA (615 cases versus 905 cases per 100,000 population, p=0.034). HA county per capita deaths due to COVID-19 were significantly lower than LA county per capita deaths (9.4 deaths versus 19.5 deaths per 100,000 population, p = 0.017). However, COVID-19 case mortality did not differ between HA and LA counties (1.78% versus 1.46%, p = 0.267). Regression analysis, adjusted for relevant covariates, demonstrated decreased COVID-19 infection rates by 12.26%, 11.68%, and 11.40% per 495 m of county elevation, for cases recorded over the preceding 30, 90, and 120 days, respectively.

Conclusions

This population-adjusted, controlled analysis suggests that residence at HA attenuates the risk of COVID-19 per capita infection and death, but does not attenuate mortality. Further research is required to identify the specific environmental, biological, and social factors of residence at HA that contribute to infection, transmission, and pathogenesis of COVID-19.

263 Decreased mortality rate among COVID-19 patients using statins: data from us electronic health records

T Oskotsky1

I Maric2*

I Kosti1

BL Le1

RJ Wong2

GM Shaw2

M Sirota1

DK Stevenson2

1University of California San Francisco, San Francisco, CA

2Stanford University School of Medicine, Stanford, CA

Purpose of Study

The use of statins has been associated with a reduced rate of mortality and other severe outcomes among patients with coronavirus disease 2019 (COVID-19). Our goal was to leverage data from Electronic Health Records (EHR) to investigate this hypothesis in a diverse population in the United States.

Methods Used

Data were obtained and analyzed from Cerner’s large COVID-19 EHR database containing nearly 120,000 records of COVID-19 patients across 62 healthcare centers. All patients had an emergency room visit or were hospitalized. Only patients with a COVID-19 diagnosis confirmed by a lab test were considered. COVID-19 patients with exposure to statin medications, defined as at least one medication order for a statin within a period of 10 days before and 7 days after a positive COVID-19 lab test, were compared to COVID-19 patients who did not have a medication order for statins. Propensity-score (PS) matching with a 1–2 ratio was used to match patients by demographics (age, sex, ethnicity, race), and by comorbidities (hypertension, diabetes, COPD) and medication indication (high cholesterol, hyperlipidemia) as identified by ICD codes.

Summary of Results

2,855 patients were taking statins, and 18,875 patients had not. After matching, the average age among statins patients (66.9 years) equated to an average age in non-statin patients (66.8 years). Among statins patients, the mortality rate was 16.0%. We carried out 10 iterations of PS matching by demographics and comorbidities, and observed significantly higher mortality among control patients (17.4% to 19.7%) in 8/10 times (Chi-square test, p < 0.05). When carrying out 10 iterations of PS matching by medication indication as well as demographics and comorbidities, we again found significantly higher mortality in controls (17.7% to 20.0%) in 9/10 times (Chi-square test, p < 0.05).

Conclusions

Among COVID-19 patients using statins we observed a statistically significant decrease in mortality when compared to matched controls. These results support previous evidence that statins may reduce severity of COVID-19-related mortality.

264 Hispanic paradox in the setting of the COVID-19 pandemic

H Tazhibi1*

P Wahba2

1Western University of Health Sciences, Granada Hills, CA

2Progressive MD Clinic, Mission Hills, CA

Purpose of Study

The Hispanic Paradox is an epidemiological finding in which Hispanic Americans tend to have better, mortality rates than Non-Hispanic White Americans and a decreased prevalence stroke, cancer, and hip fracture. Our purpose was to observe the Hispanic Paradox during the COVID-19 pandemic in regards to mortality.

Methods Used

The published data of Hispanics and NH-Whites were obtained from the Department of Public Health of California and spans from April to September. It was compiled in excel to show the Hispanic Paradox in percent cases and percent deaths related to COVID-19.

Summary of Results

According to the California Department of Health, as of April 2020, Hispanics made up 36% of cases of COVID-19, which is the highest percentage amongst all populations that occupy California. This number was comparable to the 32% of cases accounted for by NH-Whites. Hispanics made up the second highest percentage of deaths at 28% which is second to the 41% of NH-White deaths. This data gives an overall picture of the early stages of the pandemic. As the pandemic continued Hispanics have higher cases and deaths than NH-White. The cases and deaths are the greatest for Hispanics aged between 18 and 79, however, they are steadily decreasing for Hispanics while increasing for Caucasians. This trend continues until the age of 80 where there is a complete reversal of the trend and percent cases and percent deaths for Caucasians is greater than that of Hispanics.

Conclusions

We show that over the age of 80, Hispanics in California have less percent death related to COVID-19 compared to NW-Whties. With differing hypotheses for this anomaly and no agreed upon explanation, the recent pandemic has shed more light on the Hispanic Paradox that coincides with other disease states, and it is noteworthy to see its effects in a novel viral pandemic.

265 Evaluating the risk of COVID-19 illness among EMS providers following cardiopulmonary resuscitation and aerosol generating procedures

AD Brown1*

L Schwarcz2

CR Counts1

L Barnard2

BY Yang1

J Emert2

AJ Latimer1

C Drucker2

J Blackwood2

P Kudenchuk1

M Sayre1

T Rea1

1Univ. of Wash. School of Medicine, Seattle, WA

2Public Health Seattle and King County, Seattle, WA

Purpose of Study

Emergency Medical Services (EMS) providers may treat patients with COVID-19 illness without knowing the patient’s COVID-19 status. Aerosol generating procedures (AGPs) are believed to increase occupational risk. The magnitude of risk from AGPs while wearing personal protective equipment is unclear. We evaluated the risk of EMS providers acquiring COVID-19 when AGPs were vs. were not used during the care of COVID-19 patients.

Methods Used

This retrospective cohort study identified patients from a statewide COVID-19 registry with a positive COVID-19 nasopharyngeal swab (RT-PCR+) within 10 days of an EMS encounter, between Feb. 16 and July 31, 2020 in King Co., WA. AGPs were defined as endotracheal intubation, supraglottic airway insertion, bag-valve mask ventilation, continuous positive airway pressure, non-rebreather (NRB) oxygen, and nebulizer or metered dose inhaler medication therapy. COVID-19 transmission was attributed to the encounter if the EMS provider’s RT-PCR+ test occurred ≤14 days after the encounter.

Summary of Results

3231 EMS provider-encounters involved 1722 unique EMS providers who cared for 1155 COVID-19 patients. Of the 1382 COVID-19 patient encounters,1162 involved no AGP and 220 had at least one AGP. The most common AGPs were NRB oxygen (77%), positive pressure ventilation (27%), and advanced airway (18%); 25 (11%) required chest compressions. During the study period, 3 of the 1722 EMS providers became RT-PCR+ within 14 days of the COVID-19 patient encounter. One provider had both AGP and no AGP encounters, while one performed no AGPs and the third only had AGP encounters. Overall incidence of EMS COVID-19 infection after occupational exposure was low (0.93/1000 provider encounters).

Conclusions

EMS COVID-19 occupational risk attributable to patient encounters was quite low. The analysis was limited by the very small number of RT-PCR+ providers precluding a meaningful comparison by AGP encounters. Continued analysis and surveillance are ongoing to refine these results and enable a robust comparison of AGP-specific risk.

266 Incorrect face mask use and potential covid-19 exposures in public locations

D Button1*

P Brown1

R Somogyi1

A Chang1

H Nguyen1

S Buerk1

B Chen1

T Zimmerman1

T Funari1

C Colbert1

B Kea1

C Atzema2,3,4

1Oregon Health and Science University, Portland, OR

2University of Toronto, Toronto, ON, Canada

3Sunnybrook Health Sciences Centre, Toronto, ON, Canada

4ICES, Toronto, ON, Canada

Purpose of Study

To evaluate proper mask use and social distancing behaviors that prevent COVID-19 transmission among the general public.

Methods Used

This was a prospective, observational study in a large, urban city. In accordance with CDC guidelines, we developed study definitions for breaches (two persons with mouth or nares exposed while coming within six feet of each other), and incorrect mask-wearing (mouth or nares exposed). Ten medical students were trained on data collection using a standardized data collection instrument and sample videos. Over a two-week period, data collectors observed the public in numerous public settings. Information was collected on estimated age group and gender, socially grouped vs alone, mask use, style of incorrect mask use, and the number of breaches.

Summary of Results

From August 23rd - September 5th, 2020, 16084 individuals were observed over 139 hours, of which 2960 (18.4%) were not wearing a mask. Of those wearing a mask, 1495 (11.4%) were wearing the mask incorrectly. In total, there were 2903 breaches. The percentage of people not wearing masks varied by location type: airport (4.4%), grocery store (13.1%), hardware store (1.7%), street intersection (36.2%), city park (29%), city square (31.6%), public transit (29.3%), and waterfront (44.3%). Incorrect mask use varied by location type: airport (7.0%), grocery store (9.4%), hardware store (3.8%), street intersection (17.5%), city park (18.5%), city square (37.7%), public transit (20.1%), and waterfront (15.4%).

Conclusions

In a city where mask use is required on public transit and indoor public spaces, our results suggest that most people are compliant with mask-wearing mandates. Outdoors, however, people commonly do not wear masks, or wear them incorrectly and do not appropriately maintain physical distancing.

Health care research V

Concurrent session

11:00 AM

Saturday, January 30, 2021
267 Evaluation of data transfer of perinatal hepatitis c virus exposure risk data in a multisite health system

M Geist1*

A Schumacher2

LD Nolen3,4

1University of Washington, Wasilla, AK

2Southcentral Foundation, Anchorage, AK

3Arctic Investigations Program, Anchorage, AK

4Centers for Disease Control and Prevention, Anchorage, AK

Purpose of Study

Ensuring adequate testing for children born to mothers infected with hepatitis C virus (HCV) is imperative to identify and treat HCV-positive children. Previous studies have indicated <30% of exposed children are appropriately tested for HCV infection. One key part is accurate transfer of HCV test results from the maternal to infant chart. We evaluated data transfer in our regional clinics.

Methods Used

To evaluate the data sources and documentation related to HCV infection, we performed qualitative interviews with clinical staff at six large clinics that provide prenatal and newborn care within Southcentral Foundation. This center provides a wide range of health services through multiple regional clinics; all of which share a single electronic medical record system. Variation in provider type was incorporated within the selection of interviewees.

Summary of Results

Most interviewees (12/13) noted a lack of consistency regarding the placement of HCV information within both maternal and infant records and how this increases time spent reviewing charts. Five participants reported maternal HCV data could be provided in six different locations within the chart note, with variability between departments. Inconsistent placement of information was also noted regarding the location of infant HCV information and the placement of infant HCV exposure information.

Many interviewees (9/13) identified a benefit of direct communication, either verbal or through a patient message, between the obstetrics and pediatric teams to bring attention to infant HCV exposure. Participants suggested including follow up instructions in the discharge summary for infants at risk of perinatal HCV infection. Six interviewees identified the ideal solution for ensuring proper transfer of HCV data as an add-on within the medical record program that would automatically transfer all maternal laboratory data into the infant chart.

Conclusions

We conducted interviews with different clinicians and identified a lack of consistent data reporting and placement as well as key issues regarding data transmission of HCV information from the maternal chart to infant chart.

268 Unplanned hospital readmissions at british columbia children’s hospital

A Wachtel1,2*

MA Irvine1

R Courtemanche2,3

M Bucevska2,3

D Courtemanche2,3

1BC Children’s Hospital Research Institute, Vancouver, BC, Canada

2The University of British Columbia, Vancouver, BC, Canada

3BC Children’s Hospital, Vancouver, BC, Canada

Purpose of Study

An unplanned hospital readmission (UHR) occurs when a patient is discharged from the hospital and is then unexpectedly readmitted within 30 days. UHRs are linked to adverse health outcomes and cost Canada $1.8 billion annually. Anticipating UHRs may improve patient care and decrease cost. This study identified factors associated with UHRs at BC Children’s Hospital (BCCH) and analyzed how they have changed across 10 years.

Methods Used

The BCCH discharge abstract database (DAD) was used to retrospectively analyze all admissions from April-March of 2007–09 and 2017–19. Admissions were categorized as index admissions (preceding a UHR) or control admissions (all other). Covariables were extracted from the DAD and stratified by admission type.

Summary of Results

From 2017–19 there were 11,850 admissions, of which 777 were index admissions (6.6%). Compared to the control group, index admissions were associated with: a longer length of stay (6.7 vs 6.1 days), more admissions via the ER (64.2% vs 47.5%), older age (8.0 vs 7.6 years), longer ICU stay (4.68 vs 3.18 days), more ER visits in the 6 months prior (31.5 vs 8.1), more pre-admission comorbidities (1.2 vs 0.7), and fewer post-admission comorbidities (0.3 vs 0.6). The 3 most common diagnoses associated with index admissions were chemotherapy for a neoplasm (6.4%), vomiting alone (3.0%), and unspecified acute lower respiratory infection (2.2%). The 3 most common diagnoses associated with the control group were chemotherapy for a neoplasm (6.2%), predominantly allergic asthma without status asthmaticus (2.6), and obstructive sleep apnea (1.7%).

In comparison, from 2007–09 there were 11,223 admissions, of which 1,149 were index admissions (10.2%). Similar trends were shown, however, differences in index admissions included a longer length of stay (7.6 days), fewer admissions via the ER (51%), longer ICU stay (5.3 days), and more surgical day care visits in the 6 months prior (10.3 vs 4.8).

Conclusions

Covariables associated with index admissions have been identified and hold potential predictive value. We will use these to develop UHR risk prediction models which may allow for future quality improvement projects to decrease UHRs.

269 Understanding gaps in care: exploring neighborhood level resources for cervical cancer screening in Chicago, Il

KP Oelerich1*

D Oshomuvwe2

K Munoz3

N Lee3

S Dewdney1

1Rush Medical College of Rush University, Chicago, IL

2University of Chicago, Chicago, IL

3UChicago Medicine, Chicago, IL

Purpose of Study

Cervical cancer is the third leading cause of gynecologic cancer in women in the United States. While studies have demonstrated that certain characteristics of a woman’s neighborhood, including socioeconomic status and clinical resources, put her at a greater risk for developing different types of cancers, this link is yet to be studied in cervical cancer incidence and mortality in Chicago.

This community needs assessment was designed to assess health care facilities in Chicago that perform pap smears and colposcopies to better understand geographical gaps in accessibility. Then, to compare these possible gaps to incidence and mortality of cervical cancer in neighborhoods with barriers such as: socioeconomic status, race and geographic location.

Methods Used

An analysis of 76 healthcare facilities was performed in Chicago, IL. Brief interviews were conducted with each health care facility, including Federally Qualified Health Centers, physician’s offices and hospitals. Information obtained included: ability to perform pap smears and colposcopies, insurance accepted and where referrals were sent. The data collected from these interviews was mapped alongside population data from the Chicago Health Atlas evaluating socioeconomic status, race, cervical cancer mortality and incidence.

Summary of Results

The analysis of the facilities show that 89% conduct pap smears, while only 56% perform colposcopies. In the review of the Chicago Health Atlas from 2012 to 2016, the highest rates of cervical cancer occur in Hispanic and African American women compared to Non-Hispanic white patients at an incidence of 12.1, 11.7 and 7.3 per 100,000 respectively. Initial geographic overlay of incidence rates showed higher cervical cancer incidence rates in regions without screening resources for colposcopy.

Conclusions

While pap smears are available throughout Chicago, the availability of colposcopies is limited. This is likely another barrier to screening and treatment for cervical cancer. Our review suggests that the neighborhood of residence and accessibility to screening resources play a role in the disparities in cervical cancer diagnosis and treatment in Chicago.

270 Trends of pediatric hospital admissions for acute asthma between 2005–2019

A Chambers*

B Fassl

F Nkoy

University of Utah Health, Salt Lake City, UT

Purpose of Study

Asthma is the most common chronic illness in the US, affecting 8% of children. Asthma exacerbations often result in hospitalization and significant healthcare costs. The purpose of this study is to describe the long-term trend in asthma admission rates over fifteen years at a tertiary care hospital following implementation of an asthma quality improvement project in the hospital, surrounding community, and state of Utah.

Methods Used

The study took place at Primary Children’s Hospital (PCH) in Salt Lake City, which is a tertiary care facility admitting 80–90% of asthma patients in the state of Utah. Starting in 2007, a multidisciplinary team consisting of clinicians, researchers, administrative stakeholders and representatives from the HMO (Intermountain Healthcare) implemented a series of asthma quality improvement interventions. This included a standardized inpatient care process model based on Joint Commission on Accreditation of Healthcare Organizations criteria, first implemented at PCH (2008–2010), then statewide across the Intermountain Healthcare system (2011–2013). Additional interventions consisted of a standardized inpatient-to-outpatient care transition program, Continuing Medical Education and Maintenance of Certification activities at PCH and affiliated Intermountain facilities, and several research projects in clinics throughout the state to assist with managing chronic asthma control in the outpatient setting. We abstracted asthma admission rates and quality metrics from the hospital database that maintains a dedicated asthma registry and describe trends in annual admissions.

Summary of Results

Between 2005 and 2019, 5344 patients were admitted to PCH for acute asthma with an annual average of 356 patients. Between 2005–2009 the annual admission average was 303 patients (range 247–450) per year, which subsequently increased to 472 (range 348–578) between 2010–2014 and then decreased to 294 (range 271–325) between 2015–2019. Compliance with evidence based asthma care measures remained >80% following implementation of the quality improvement program.

Conclusions

Changes in pediatric asthma admissions over time may be associated with implementation of a comprehensive asthma quality improvement program across a health system.

271 Hip surveillance for children with what? The conundrum of diagnosis

S Miller

J Coates*

K Mulpuri

BC Children’s Hospital, Vancouver, BC, Canada

Purpose of Study

Lack of a diagnosis of cerebral palsy (CP) has been identified as a barrier to enrollment in the Child Health BC Hip Surveillance Program for Children with CP. To overcome this barrier, children do not require a diagnosis of CP to be enrolled. This study aimed to investigate the diagnoses provided at the time of enrollment.

Methods Used

All children enrolled in the program were included. Enrollment data related to a child’s diagnosis and age were obtained. Chart notes from the province’s only children’s hospital, including those available from specialty clinics, inpatient records, and the hip surveillance program, were reviewed for all children enrolled without a diagnosis of CP to determine if a diagnosis of CP had been confirmed since enrollment. For those without a CP diagnosis, etiological diagnoses were compared to a list of conditions used in established CP registries.

Summary of Results

Data from 959 children were reviewed. Based on population and prevalence rates, it is estimated this represents 42% of the expected number of children with CP in the province. Mean age at enrollment was 6.7 years (SD=4.2). The enrolling diagnosis was CP for 64.0% (614), possible CP for 12.5% (120), other for 22.7% (218), and no diagnosis for <1% (7). Chart review was completed for the 345 enrolled without a CP diagnosis. No charts were available for 19 children. A CP diagnosis was confirmed for 106 children, and 48 patients were identified as having a progressive condition not in keeping with the definition of CP. The diagnosis provided at enrollment was found in the list of CP conditions for 71 of 176 (40%) children that remained, while the remaining 105 had a variety of diagnosis, such as chromosomal abnormalities, developmental delay, seizure disorders, and syndromes, that could not be confirmed as CP.

Conclusions

At enrollment, only 64.0% of children in surveillance were diagnosed with CP. While a large number of children were enrolled without a diagnosis of CP, enrollment remains well under the number of children expected. Lack of diagnosis may be a barrier to early enrollment and consequently a delay in detection of hip displacement.

272 Healthcare resource utilization in children with cerebral palsy

M Juricic1,2

S Miller1,2

N Fajardo1,2

C Chapman1

J Coates1

E Habib1

E Schaeffer1,2

K Mulpuri1,2

1BC Children’s Hospital, Vancouver, BC, Canada

2University of British Columbia, Vancouver, BC, Canada

Purpose of Study

Cerebral palsy (CP) is the most common cause of motor impairment in children. Management involves care by medical/paramedical professionals and use of assistive devices. The purpose of this study was to learn about use and funding for health professionals and equipment accessed by children with CP.

Methods Used

Caregivers of children with CP attending a pediatric orthopaedic clinic were invited to participate in an anonymous survey. Demographics, frequency of healthcare visits by provider, types of devices accessed, and how these services were funded were collected.

Summary of Results

Surveys were completed by 234 caregivers of children across all Gross Motor Function Classification System (GMFCS) levels. Children at GMFCS IV/V and III/V were more frequently reported to have hospital admissions and emergency room visits, respectively. Children saw an average of 4.9(SD=1.5) medical professions and 3.4(SD=1.5) paramedical specialists. Total healthcare visits and professionals visited showed a trend towards increasing by GMFCS level. Total average annual visits with healthcare professionals was 78.8(SD=66), with children at GMFCS V reporting 107.4(SD=83.1). Children at GMFCS III [82.3(SD=52.7)] and V [91.9 (70.8)] reported the highest number of paramedical visits. Funding was primarily government for physiotherapy (PT) at 79%(131/166) and for occupational therapy (OT) at 80%(133/166). Alternate funding for PT/OT included private insurance (18/7%), self-pay (23/7%), charity (5/5%), and others (8/12%). Caregivers most often reported including self-pay for orthoses and wheelchairs.

Conclusions

Caregivers of children with CP reported a high number of annual visits with healthcare providers with a trend suggesting an increasing number of visits and providers with increasing GMFCS level. Funding for resources was often supplemented by families, suggesting a need for additional funding and services for children with CP.

273 Correlation of rail systems with lower traffic fatality rates

K Abe*

L Yamamoto

University of Hawaii John A. Burns School of Medicine, Honolulu, HI

Purpose of Study

Traffic fatality is a significant public health concern globally, and several factors may affect traffic fatality. We aimed to evaluate the relationship between rail systems and traffic fatalities and investigate whether this relationship contributes to the decrease in traffic fatality rates.

Methods Used

Traffic fatality data, motor vehicle registrations, and rail lines of 34 U.S and 8 non-U.S cities from 2018 were obtained. Pearson correlation (linear regression) analyses were performed between all variables (figure 1).

Summary of Results

The correlation coefficient (r) for rail systems (n=42) and total traffic fatality rates, child traffic fatality rates, and the number of motor vehicle registrations per capita were -0.49 (p<0.01), -0.31 (p<0.05), and -0.46 (p<0.01), respectively, while the correlation coefficients for the number of motor vehicle registrations per capita and all traffic fatality and child traffic fatality rates were 0.54 (p<0.01) and 0.18 (p=0.24), respectively (table 1).

Abstract 273 Table 1
Abstract 273 Figure 1

Scatter plots and regression lines for each comparison

Conclusions

A higher number of rail lines correlated with reduced traffic fatalities and lower numbers of motor vehicle registrations per capita.

274 Improving oncology education for family medicine residents: how does bc compare?

A Janz*

P Ingledew

L Wang

S Bortnik

J Garcha

UBC, The University of British Columbia, Vancouver, BC, CA, academic, Vancouver, BC, Canada

Purpose of Study

Despite a rising incidence and prevalence of cancer in Canada, there are gaps in postgraduate medical curriculum related to oncology. Family medicine (FM) physicians provide a key role at all stages of the cancer journey and as such FM training programs should include relevant education. The purpose of our study was to assess the current state of oncology education in the University of British Columbia (UBC) FM residency program. Results were compared to the same recently completed national Canadian FM residency program survey (CFMRSPS) that did not include UBC.

Methods Used

A web-based survey, utilizing the previously conducted CFMRSPS, was distributed to 348 UBC FM residents (FMR) and 20 site directors (SD). The survey assessed presence of an oncology curriculum, current teaching methods and perceived gaps. Results were compared to CFMRSPS data (non-UBC) and interpreted with descriptive statistics.

Summary of Results

54/348 UBC FMR and 10/20 SD completed the survey. 3% of UBC and 7% of non-UBC FMR felt their program adequately prepared them to care for oncology patients. Between UBC FMR/SD and non-UBC FMR/SD there was uniformity in perceived importance of a list of oncology topics to be covered in training. There was discordance in the perceived frequency of topics taught between all FMR residents and SD. This discordance was more prominent in the BC data, than nationwide.

Conclusions

This study can inform further development of oncology specific curriculum in FM residency programs. Further study is required to understand areas of discordance between FMR and SD and across the country.

Neonatology general VI

Concurrent session

11:00 AM

Saturday, January 30, 2021
275 Vancomycin usage optimization in neonatal intensive care unit

M Chang1*

K Mongkolrattanothai2

S Chin2

Y Li2

R Orbach2

L Stach2

S Nair2

V Milisavljevic2

1LAC USC, Los Angeles, CA

2CHLA, Los Angeles, CA

Purpose of Study

Vancomycin is frequently used for empiric treatment in suspected late onset sepsis (LOS) in neonatal intensive care units (NICU), however, inappropriate or unnecessary use can lead to additional morbidities and emergence of drug resistance. Standardization and appropriate vancomycin utilization are imperative for safer patient care.

Methods Used

This study was a part of qualitative improvement (QI) initiative to optimize vancomycin use in a level 4 NICU by introducing standardized LOS guideline with defined indications and criteria for empiric antibiotics. Implementation was started in 09/19 after completion of providers education. Periods evaluated were 12/18–03/19 (pre-guideline) and 12/19–03/20 (post-guideline). Data was retrospectively compared, including demographics, indications, days of therapy/1000 days (antibiotic utilization rate - AUR), cultures, isolated pathogens and resistance profiles. Clinical outcomes and adherence to the guideline were evaluated. Wilcoxon rank sum test was applied for continuous variables and Pearson chi-square test was applied for categorical variables. p<0.05 was considered significant.

Summary of Results

There were 63 LOS antibiotic courses given to 40 patients pre-guideline, and 121 courses in 63 patients in post-guideline period. We found a significant decrease in vancomycin AUR in the post-guideline period (76.56 in the pre-guideline vs 61.42 in the post-guideline; p=0.036). Clinical outcomes and mortality within 30 days of antibiotic usage were not significantly different between two periods (table 1). Adherence to the LOS antibiotics guideline was 66.31%.

Abstract 275 Table 1

Conclusions

Development of a standardized guideline for LOS evaluation and empiric antibiotic utilization resulted in reducing vancomycin AUR, while not negatively affecting clinical outcomes or morbidities. Further analysis is needed in order to identify factors contributing to unnecessary vancomycin use, as well as educational needs to ensure appropriate antibiotic use overall.

276 Differences in blood glucose levels in preterm infants less than 1250 grams at birth fed exclusive human milk or bovine milk based fortified human milk

M Chang

L Barton

R Ramanathan

R Cayabyab

LAC USC Medical Center, Pasadena, CA

Purpose of Study

Comparison of blood glucose (BG) levels in preterm infants less than 1250 grams at birth fed with exclusive human milk (EHM) versus bovine milk based fortifier (HMF) after reaching full enteral feeding and off parenteral nutrition or intravenous fluids.

Methods Used

Retrospective study on preterm infants less than 1250 g at birth admitted to NICU from January 2016 to November 2019 who were fed EHM-26cal/oz (carbohydrate: 0.0774 g/ml) or HMF-24cal/oz (carbohydrate: 0.085 g/ml). Demographics, BG levels, diagnosis of hypoglycemia (BG £60 mg/dL) and need for intervention were collected. Full enteral feeding was defined as 120 cc/kg/d of tolerated enteral feedings for at least 72 hours. Chi square test, Wilcoxon rank sum and linear regression were used for data analysis.

Summary of Results

Eighty-nine preterm infants were included in the study. Infants fed EHM had lower gestational age. The median (25th,75th percentile) minimum BG values in mg/dL within 72 hours of full feeding was significantly lower in EHM group (61 (50,66) vs HMF 71 (59,77); p=0.002). The diagnosis of hypoglycemia was not significantly different between the two groups (EHM 28/59 (47.7%) vs. HMF 9/30 (30%), p=0.20). (Table 1) Ten infants who developed hypoglycemia required intervention (EHM group 8/10 vs. HMF 2/10). Regression analysis showed that lower BG levels were significantly associated with EHM (p=0.017) after adjustment of confounders.

Abstract 276 Table 1

Demographics and outcomes of study population

Conclusions

BG levels in preterm infants less than 1250 grams were significantly lower when fed exclusive human milk potentially because of its slightly lower carbohydrate content. However, the rate of hypoglycemia was not significantly different between the two groups. BG levels should be continuously monitored in preterm infants fed EHM once off parenteral nutrition or intravenous fluids. Our findings need to be verified with larger sample size.

277 Effects of postnatal steroids on neurodevelopmental outcomes in preterm infants

JJ Keel1*

LK Lee2

W Surento3

M Shiroishi3

N Jahanshad3

R Ramanathan1

R Cayabyab1

1LAC+USC, Los Angeles, CA

2Kaiser Foundation, Fontana, CA

3Imaging Genetics Center, Los Angeles, CA

Purpose of Study

To determine if the use of postnatal steroids in premature infants is a risk factor for poor neurodevelopmental outcomes.

Methods Used

Retrospective review of all premature infants <1250 grams at birth seen at high risk infant follow up clinic at LAC+USC Medical Center. Infants with magnetic resonance imaging (MRI) of the brain and measurement of brain volume (BV) included. Infants followed at 18 months corrected age (CA) and at 3 years with Bayley Scales of Infant and Toddler Development Third Edition to assess for cognitive, motor, and language skills as well as social-emotional scoring based on parental report. Infants divided into two groups: those who received steroids (hydrocortisone and/or dexamethasone) and those who did not. Data analyzed using Kruskal-Wallis and Chi Square and linear regression.

Summary of Results

Forty-eight infants followed up at 18 months while 28 followed up at 3-years old. Infants who received postnatal steroids (PS) were smaller, immature and with neonatal morbidities (table 1). The composite scores in cognitive, language, and motor skills at 18-months CA were significantly lower in infants receiving PS. However, lower composite scores persisted only in motor skills at 3 years of age (table 2). After adjustment of confounders, the use of PS negatively affected the motor composite score (Coef. -13.76; 95% CI -24.95,-2.57, p=0.02).

Abstract 277 Table 1

Demographics and outcomes

Abstract 277 Table 2

Neurodevelopmental outcomes between groups

Conclusions

The use of postnatal steroids did not significantly affect brain volume; however, its use negatively impacted the composite motor score in preterm infants. Judicious use of PS is important when caring for these infants. Early intervention should be started as soon as infants are stable.

278 Quality improvement initiative to improve patient care for neonatal abstinence syndrome

A Iacob*

Y Nicolau

R Koeppel

P Aron-Johnson

C Uy

University of California – Irvine, Long Beach, CA

Purpose of Study

Almost 100 babies are born in U.S. every single day suffering from in-utero substance exposure. Some will experience neonatal abstinence syndrome (NAS) through fussiness, irritability, excoriating skin, difficulty sleeping, eating, and even growing. Pharmacological interventions are often required to manage symptoms. We initiated a quality improvement (QI) project to improve patient care for babies with NAS through a multiprong approach.

Methods Used

Using the Plan-Do-Study-Act (PDSA) approach, we analyzed our inpatient data by doing retrospective chart review of newborns with history of in-utero drug exposure. After understanding our population, a new management algorithm was implemented to standardize screening criteria, non-pharmaceutical interventions, and pharmaceutical interventions using morphine– both escalation and de-escalation with a commitment to complete inpatient wean when possible.

Summary of Results

In 2019, a total of 48 neonates had in-utero substance exposure [28 males, 20 females, birth gestational age 28–41 weeks], of which 20/48 (42%) had opiate exposure. Of the total 48 infants, 15 (31%) required pharmacological treatment using either methadone or morphine, at the discretion of the provider. Sixty-seven percent (10/15) of treated infants were discharged on opioids to complete a wean outpatient; only 5 infants completed treatment inpatient. The average inpatient length of treatment (LOT) for these 5 infants was 14 days. The remaining 10 infants who completed an outpatient wean, experienced an average outpatient LOT of 66 days. The average LOT for the treated infants weaned inpatient and outpatient was 53 days with an average LOS of 24 days.

After implementing the new management algorithm, three patients met criteria for treatment. The average inpatient LOT decreased from 14 days to 11 days, with all patients completing pharmacologic treatment during their inpatient stay. The average LOS decreased by 25%, from 24 days to 18 days.

Conclusions

In our institution, using an algorithm for management of NAS shows promise in decreasing length of pharmacological treatment while simultaneously decreasing length of hospital stay for infants who show signs and symptoms of drug withdrawal.

279 Benefits of delayed cord clamping in preterm infants at 23–28 weeks of gestation at birth

S Sakhamuru1,2*

M Chu2

JJ Keel1,2,3

L Barton1,2,3

R Ramanathan1,2,3

R Cayabyab1,2,3

1Los Angeles County, University of Southern California, Granada Hills, CA

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

3Los Angeles County University of Southern California Medical Center, Los Angeles, CA

Purpose of Study

To compare short-term outcomes in preterm infants 23–28 weeks of gestation exposed to delayed cord clamping (DCC) vs. immediate cord clamping (ICC).

Methods Used

This is a retrospective study of all preterm infants born at 23–28 weeks of gestation at LAC+USC Medical Center between 2016–2020. Demographics, DCC and clinical data were extracted from electronic medical records and the neonatal database. Data was analyzed with Chi-Square or Fischer Exact test and Wilcoxon Rank Sum test.

Summary of Results

Fifty-three infants met inclusion criteria. Majority of infants 39/53 (74%) were in the ICC group. The median gestational age, birth weight and hemoglobin at 24 hours of life in infants with DCC were significantly higher. These infants received fewer packed red blood cell transfusions with the first occurring at a later day of postnatal life. The rate of intraventricular hemorrhage and necrotizing enterocolitis was not different between the groups, but the rate of hypotension requiring vasopressors was lower in infants with DCC. (Table 1) No infant suffered from hypothermia in the DCC group.

Abstract 279 Table 1

Demographics and outcomes

Conclusions

Our preliminary findings show that DCC is beneficial in this preterm population. It is imperative to perform DCC whenever possible, especially in the smallest and most immature infants. Larger sample size is needed to confirm our findings.

280 Nicu clinicians’ perspective on telephone communication with parents: a qualitative study

JA Williams1*

R Patterson2

B Macauley2

L Gievers1

K Zuckerman2

1Oregon Health and Science University, Portland, OR

2Oregon University System, Portland, OR

Purpose of Study

During a NICU hospitalization, it is impossible for parents to always be at the infant’s bedside; resulting in medical updates occuring via telephone. As telephone communication is inevitable within this setting, it is important to understand the experience of clinicians and families in this modality of conversation.

Methods Used

We had a purposeful sample of 3 nurses, 4 residents, and 2 nurse practitioners and explored barriers and facilitators to telephone communication in the NICU. Interviews followed a semi-structured guide covering topics such as content and reason of calls, connectedness with parents, and comfort discussing difficult issues. All interviews were conducted in-person by a NICU fellow, were recorded, and transcribed. Two investigators independently coded all transcripts with Dedoose qualitative software, using a phenomenological approach. Codes were reviewed by a third researcher who helped resolve disputes, review the coding scheme, and collapse codes into major themes.

Summary of Results

Six themes and 24 sub-themes emerged from the transcripts. The themes were: pre-work before a call, barriers to calls, downsides of telephone calls, phone call logistics, other ways to update families, and ways to improve calls. Some of the subthemes for these categories include: one-sided communication, workload, difficulty comforting on the phone, and no standardization of calls. Please see table 1 for the sub-themes and representative quotes for each theme.

Abstract 280 Table 1

Conclusions

Communicating with an infant’s family is challenging to do over the telephone. Given the heterogeneity and lack of training, next steps include standardized call guidelines and a document to set family call expectations. Video calls and text messages could add more visual forms of communication and providing protected time could help the workload barrier.

281 Active care at 22–23 weeks and hospital outcomes of more mature infants in California, 2014–18

S Bane1*

MA Rysavy2

SL Carmichael1

X Chen1

H Lee1

1Stanford University School of Medicine, Stanford, CA

2University of Iowa Healthcare, Iowa City, IA

Purpose of Study

To determine if hospitals with higher rates of active care for infants born at 22–23 weeks have better outcomes for extremely preterm infants at older gestational ages.

Methods Used

A population-based cohort of infants born during 2014–2018 at 22–27 weeks (n=8635) in 96 California Perinatal Quality Care Collaborative (CPQCC) hospitals was included (inborn only). Active care was defined as receiving surfactant, ventilation, epinephrine, or cardiac compressions. Correlation was assessed between rates of active care in 22–23 week infants and outcomes in infants born at 24–25 and 26–27 weeks (mortality and survival without comorbidities).

Summary of Results

Hospital rates of active care in 22–23 week infants (median: 61%, IQR: 29%) were not correlated with mortality or survival without morbidity among infants born at 24–25 or 26–27 weeks (range of correlation coefficients: -0.02 to -0.13, p >0.1; figure 1). The most common comorbidity was chronic lung disease in 24–27 week infants (39%).

Abstract 281 Figure 1

Comparison of rates of active care in infants born at 22–23 weeks and mortality in older infants

Conclusions

Hospitals that more frequently pursue intensive care for infants born at 22–23 weeks do not necessarily experience improved outcomes for extremely preterm infants at older gestational ages.

282 Impacts of deliberate practice simulation on neonatal outcomes

M Nguyen*

I Purdy

M Leng

J Enciso

University of California Los Angeles, Los Angeles, CA

Purpose of Study

There is no current data to show that simulation based deliberate practice in Neonatal Resuscitation Program (NRP) training improves patient outcomes. We hypothesize that NRP simulation, using deliberate practice, can improve patient outcomes and NRP performance.

Methods Used

The project design consisted of a prospective pre- and post-intervention study at a 22-bed, level IV neonatal intensive care unit (NICU). Nine neonatal-perinatal medicine fellows completed a boot camp followed by 2–6 in situ mock codes. The boot camp served as a baseline level of performance, and the subsequent in situ mock codes provided repetitive opportunities for practice and evaluation of NRP performance. Resuscitations of 734 infants and resuscitations of 697 infants, who were born at the hospital and admitted into the NICU, were reviewed and gathered in baseline and prospective databases, respectively.

Summary of Results

There were no differences in NRP performance (adherence scores, mean=4.98, p=0.18) between the 2 groups. The post-intervention group had more infants with major congenital anomalies (20.44% vs 75.04%, p=0.04). There were no differences in patient outcomes: death within 12 hours (0.41% vs 1.29%, p=0.07), length of stay (p=0.63), disposition (death, discharge home, or transported) from the hospital (p=0.23), and hypoxic ischemic encephalopathy (1.89% vs 2.81%, p=0.40). The post-intervention group had more complex resuscitations (41.01% vs 54.23%, p≤0.0001) requiring positive pressure ventilation (PPV) (25.48% vs 32.28%, p=0.01) and intubation (6.4% vs 9.61%, p=0.03).

Conclusions

There was no performance decay over time which showed that deliberate practice maintained NRP skills. The need for more complex resuscitation could be due to the increased number of infants with major congenital anomalies in the post-intervention group. The increased use of PPV and intubation in the post-intervention group could imply effective resuscitation skills emphasizing effective ventilation. Patient outcomes were not worse in the post-intervention group, despite the fact that it had more infants with major congenital anomalies. Our data suggest that deliberate practice has value in maintaining optimal NRP performance and patient outcomes.

Cardiovascular, nephrology and hypertension concurrent session

1:00 PM

Saturday, January 30, 2021

283 Age-specific association between standing height and pulse pressure in adults

A Visaria1

P Maniar2*

B Dave2

S Kumarapuram1

D Lo1

1Rutgers New Jersey Medical School, Newark, NJ

2New Jersey Institute of Technology, Newark, NJ

Purpose of Study

While standing height is positively associated with blood pressure in the pediatric population, studies have suggested an inverse association in adults. We sought to determine whether age modified the association between standing height and hypertension (HTN) and pulse pressure (PP).

Methods Used

The study included 11,807 adults ≥20 years not taking antihypertensives and without history of cardiovascular disease. Standing height was categorized into sex-specific quartiles (male: <168.9, 168.9–174.1, 174.1–179.3, ≥179.3 cm; female: <155.6, 155.6–160.7, 160.7–165.5, ≥165.5 cm). HTN was defined as BP ≥130/80, and elevated PP was defined as PP ≥55 mmHg. We estimated odds ratios (OR) using logistic regression, adjusting for covariates, accounting for the complex survey design, and stratifying by 10-year age groups.

Summary of Results

Among the 11,807 adults, 24% had elevated PP and 26% had HTN. Those in the highest quartile (Q4) of height were younger, had greater waist circumference, and had lower proportions of microalbuminuria and diabetes compared to those in the lowest quartile (Q1). Those in Q4 had 15% lower unadjusted odds of HTN compared to Q1, losing significance after adjustment (OR [95% CI]: unadjusted OR = 0.85 [0.74, 0.98], adjusted OR = 1.12 [0.95, 1.32]). Stratifying by race/ethnicity revealed 60% higher adjusted odds of HTN in Hispanics (Q4 vs. Q1; adjusted OR = 1.60 [1.14, 2.23]) but not non-Hispanic Whites or Blacks. Those in Q4 had 21% lower adjusted odds of elevated PP compared to Q1, (unadjusted OR: 0.61 [0.51, 0.73], adjusted OR: 0.79 [0.65, 0.95]). These lower odds of elevated PP were evident only in non-Hispanic Whites. When stratifying by 10-year age groups, odds of elevated PP significantly decreased with increasing age up to 70 years (Q4 vs. Q1; ‘20–29 yrs’: 1.19 [0.9 1.57], ‘30–39’: 1.12 [0.80, 1.55], ‘40–49’: 0.92 [0.57, 1.46], ‘50–59’: 0.62 [0.39, 0.99], ‘60–69’: 0.31 [0.19, 0.52], ‘70+’: 0.57 [0.32, 1.00]; P-trend <0.001).

Conclusions

Standing height was found to be negatively associated with HTN and elevated PP, especially in older adults ≥50 years; however, there exist differences among race/ethnicities. The association with PP and significance in older adults may suggest that age-related arterial stiffness plays an important role.

284 Understanding access to healthy options in food banks as part of community-based chronic disease prevention and management efforts

LJ Archuleta*

C Vargas

A Knoblock-Hahn

E Jimenez

University of New Mexico School of Medicine, Albuquerque, NM

Purpose of Study

Food insecurity is a major public health issue in the United States associated with increased chronic disease burden and negative health outcomes. Studies show adults with very low food security are 42% more likely to have hypertension compared to adults in food-secure households. Traditionally, food banks have offered shelf-stable, calorie dense, high sugar and salt foods. Recently, food pantries have aimed to provide more nutritious food options to their clients. The purpose of this study is to describe current attitudes and practices of food bank staff regarding access to and promotion of healthy foods and nutrition education.

Methods Used

This study consisted of a cross-sectional, anonymous online survey and semi-structured interviews with staff from a network of food banks that operate mobile food pantries in the United States.

Summary of Results

Staff from 16 of 32 eligible food banks (50%) responded to an electronic survey. Five survey respondents went on to complete an interview. A large proportion of responding pantries (81%) reported always or almost always offering a wide variety of fresh produce during distributions. Fewer pantries always or almost always encourage whole-grain over refined-grain products (44%) and offer three or more kinds of canned food without added sugar (31%) or added salt (25%). Half of responding sites have a formal policy on the types of food they will accept (50%), with one-fourth only accepting food considered healthy (25%). Challenges related to food donations that were identified during the interviews included difficulty with determining what could be done with ‘unhealthy’ food donations, and the fact that national partnerships can make it difficult to turn away food. Half of responding pantries always or almost always offer recipes and cooking tips, but few (6–13%) routinely employ more active education techniques, such as tastings, cooking demos or ‘walk-the-line’ nutrition education. 75% want to do more nutrition education.

Conclusions

There is some evidence that mobile food pantries are stocking and promoting healthy foods, but more support is needed around managing the donation process, offering whole grains and canned foods without added sugar and salt, and developing interactive nutrition education activities.

285 Does liver surface nodularity contraindicate heart transplant?

I Singh*

T Singer-Englar

N Patel

M Hamilton

J Kobashigawa

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

Purpose of Study

The criteria for combined heart-liver transplant (HL) has not been well established. Liver cirrhosis in a heart failure patient would require consideration for HL. Investigators have used (NIT) such as ultrasound and CT scans to assess for liver surface nodularity which suggests cirrhosis. Biopsies are then performed to assess for liver disease. However, pathology findings can be heterogeneous and therefore the biopsy may not be reliable to exclude cirrhosis due to sampling error. It is not known whether abnormal NIT suggesting cirrhosis alone renders poor outcome if heart transplant (HTx) proceeds.

Methods Used

Between 2012 and 2017, we identified 24 patients with an abnormal NIT demonstrating liver surface nodularity suggestive of cirrhosis. Patients had liver biopsies without cirrhosis by pathology. Of these 24 patients, the worst pathology finding was seen in only 3 patients who had 3–4+ fibrosis. Study endpoints included 3-year survival, freedom from non-fatal major adverse cardiac events (NF-MACE: MI, CHF, PCI, ICD implant, stroke), and freedom from cardiac allograft vasculopathy (CAV, defined by stenosis ≥30%). Freedom from 1-year rejection [acute cellular rejection (ACR), antibody-mediated rejection (AMR)] was also recorded. We compared these 24 patients to patients who underwent HTx without liver disease (n=523) during this same time period.

Summary of Results

Patients who had liver nodularity with HTx had similar 3-year survival, freedom from NF-MACE, and freedom from CAV compared to control patients who had HTx without liver disease. Furthermore, 1-year freedom from rejection was similar between study groups (see table 1). The 3 patients with 3–4+ fibrosis on liver biopsy were survivors.

Abstract 285 Table 1

Conclusions

In our single center experience, surface nodularity suggesting cirrhosis by NIT without confirming liver biopsy of cirrhosis does not appear to be a contraindication to proceed with HTx alone.

286 The correlation between executive function and coping mechanisms in individuals with congenital heart defects

VF Eller*

S Mathena

J Andrews

S Klewer

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

Purpose of Study

Adults with congenital heart defects (CHD) are more likely to exhibit executive dysfunction and have psychiatric disorders when compared to the general population, yet they are less likely to be diagnosed. Literature suggests the etiology of the psychiatric diagnosis in CHD patients is inconclusive. The lack of understanding of this population’s psychiatric deficits is a probable factor affecting why psychiatric comorbidities are underdiagnosed in individuals with CHD. This is a growing concern due to an increasing number of adults who are currently living with CHD.

Methods Used

Individuals were eligible for this mixed methods pilot study if: (1) diagnosed with CHD; (2)18–24; (3) experienced extended hospital stays, open heart surgery, or other genetic conditions. We assessed risk for various factors contributing to psychiatric disorders including autism, executive functioning, sense of coherence, sleep and fatigue issues, depression, anxiety, parental style, and coping mechanisms. We compared scales, interviews, and medical record data checking for concordance across all modalities.

Summary of Results

We received surveys from 7 individuals. The sample was 28% male and 57% Hispanic. All participants reported self-control and initiative executive function deficits >2 s.d. above normal. An average of 55% (range 42% - 62%) of their coping strategies were considered negative, 42% showed risk for anxiety, 28% for depression, and 57% for fatigue; only 2 participants had been diagnosed with mental health concerns. Interviews (N=4) revealed that participants demonstrated poor executive functioning and an overinflated sense of coherence making them likely to engage in negative coping mechanisms when a life stressor occurred.

Conclusions

This study provides a model to explain the etiology of mental health issues in CHD patients. This study suggests a need for a large-scale investigation of the psychological health in individuals with CHD, a rapidly growing population whose quality of life may be detrimentally affected by psychiatric comorbidity. Recruitment is ongoing to ensure results are representative.

287 High incidence of obstructive sleep apnea among patients referred for atrial fibrillation ablation diagnosed by active screening

E Ovruchesky*

RR Maheshwary

R Makhija

X Zhang

U Srivatsa

University of California Davis, Sacramento, CA

Purpose of Study

We sought to determine undiagnosed OSA and risk factors in patients referred to tertiary care center for AF ablation.

Methods Used

Through a retrospective, single center analysis we assessed patients screened for OSA then compared the groups with and without known OSA for comorbidities and risk factors that included age, sex, HTN, T2DM, CVD, stroke/TIA, CHF, CHADS2VASC score and BMI.

Summary of Results

Patients presenting for ablation of AF (n=109, age 67 + 8.5 yrs, 40% female, 72% HTN, 17% T2DM, 22% CVD, 17% stroke/TIA, 29% CHF) were evaluated for OSA by symptom screening including, daytime somnolence, fatigue, snoring, witnessed apnea and known HTN. During the referral, OSA history was present in 42 patients (38.5%). Epworth score was documented in 43 patients- mean 4.76 + 5.01. Formal STOP BANG documentation was only noted in nine patients (mean 4.4 + 2.3). Fifty-five patients with and without OSA underwent a sleep study. AHI during the sleep study was 38 + 35 vs 10.7 + 13.8 ( p=0.001), respectively. Of 66 patients without a past history of OSA, (n=18) 26.7% screened positive, with final diagnosis of OSA in 52%. Patients who screened positive had a higher BMI than those who had not 30 + 4 vs 27.3 + 3.2 (p=0.01). There was no difference in other demographics or comorbidities.

Abstract 287 Table 1

Baseline characteristics of patients referred for AF ablation (n=109)

Abstract 287 Table 2

Comparison of those with and without presenting diagnosis of OSA

Conclusions

Undiagnosed OSA might be risk factor for AF even among those with BMI < 30. Active clinical screening is recommended.

288 Does timing of renal dysfunction after heart transplant result in worse outcomes?

N Patel*

T Singer-Englar*

M Hamilton

J Kobashigawa

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

Purpose of Study

Chronic kidney disease after heart transplantation is not uncommon due to the nephrotoxicity of calcineurin inhibitors (CNIs). It is well established that kidney dysfunction does impact post-transplant survival. What is not known is whether early or later development of kidney dysfunction has greater impact on outcomes.

Methods Used

Between 2010 and 2017, we assessed 149 heart transplant patients and followed their course over the first 5 years. Patients were categorized as having kidney dysfunction detected with creatinine > 1.5 mg/dL at 1-year, 3-years, and 5-years after heart transplant. These patients were subsequently followed for 5 years to assess for subsequent 5-year survival, subsequent 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), subsequent 5-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30%), and 5-year freedom from left ventricular dysfunction (LVEF ≤ 40%).

Summary of Results

Patients who developed kidney dysfunction at 1 year post-heart transplant appear to have similar subsequent survival compared to those at 3 and 5 years after heart transplant. However, significantly more patients at 1-year required kidney dialysis. Subsequent 5-year freedom from NF-MACE and CAV were similar amongst all 3 study groups.

Abstract 288 Table 1

Conclusions

Early development of kidney dysfunction appears to lead to more patients needing kidney dialysis compared to those patients that develop kidney dysfunction later post-heart transplant. Renal sparing protocols or CNI minimization should be aggressively approached in these early patients to prevent worsening of kidney dysfunction.

289 Effects of donor age on heart-kidney transplantation in older recipients

T Singer-Englar

N Patel

M Hamilton

J Kobashigawa

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

Purpose of Study

Heart-kidney transplantation is limited by donor availability, and further limited by donor age. The ISHLT registry has suggested increased risk of mortality with the use of older donors. Research has similarly suggested that older recipients have less favorable outcomes. However, it is not well established if older donors into older recipients have acceptable post-transplant outcomes. Therefore, we sought to answer this question in our large single center program.

Methods Used

Between 2010 and 2018, we assessed 50 heart-kidney transplant patients 60 years of age and older. We divided those into patients having donors greater than 50 years of age, 40 to 49 years of age, and less than 40 years of age. 5-year survival, freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30%), 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) were assessed. Freedom from 1-year rejection [acute cellular rejection (ACR), antibody-mediated rejection (AMR)] was also evaluated.

Summary of Results

Older heart-kidney transplant patients who received older donor organs appeared to have greater freedom from CAV at 5 years, although the number of patients is small. 5-year survival and freedom from NF-MACE were similar with all donor age groups. 1-year freedom from rejection was also similar among all the three donor age groups (see table 1).

Abstract 289 Table 1

Conclusions

Older donors appear to be acceptable in older heart-kidney transplant recipients. The use of older donors may enable more patients to undergo these life-saving surgeries.

290 Clostridium difficile in post-heart transplant recipients: is there an immune modulatory effect?

S Rashidi*

N Patel

T Singer-Englar

M Hamilton

J Kobashigawa

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

Purpose of Study

Heart transplant patients develop many opportunistic infections due to chronic immunosuppression. One of the more common complications is that of Clostridium difficile (CDif) causing gastroenteritis, usually represented as diffuse diarrhea. It appears that opportunistic infections such as CDif may have an impact on the immune system via the microbiome. It has not been demonstrated whether patients who develop CDif are at higher risk for the development of rejection or chronic rejection known as cardiac allograft vasculopathy (CAV) years after the event.

Methods Used

Between 2010 and 2018, we assessed 69 heart transplant patients who developed CDif within the first year of post-transplantation. These patients were assessed for the development of subsequent 1-year survival, 1-year freedom from CAV (stenosis ≥30% by angiography), 1-year freedom from non-fatal major adverse cardiac event (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), and 1-year freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR). These patients were compared to a control group who did not develop CDif.

Summary of Results

The average time to infection following transplant was 2.2 ± 3.0 months. The heart transplant patients who developed CDif had significantly lower subsequent 1-year survival and lower 1-year freedom from AMR compared to the control group. There was no significant difference in the development of NF-MACE or CAV (see table 1). Assessment of specific immunosu