Faculty Bibliography

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.

OBJECTIVE:The patient-physician relationship impacts patients' experiences and health outcomes. Physician attire is a form of nonverbal communication that influences this relationship. Prior studies examining attire preferences suffered from heterogeneous measurement and limited context. We thus performed a multicentre, cross-sectional study using a standardised survey instrument to compare patient preferences for physician dress in international settings. SETTING:20 hospitals and healthcare practices in Italy, Japan, Switzerland and the USA. PARTICIPANTS:Convenience sample of 9171 adult patients receiving care in academic hospitals, general medicine clinics, specialty clinics and ophthalmology practices. PRIMARY AND SECONDARY OUTCOME MEASURES:The survey was randomised and included photographs of a male or female physician dressed in assorted forms of attire. The primary outcome measure was attire preference, comprised of composite ratings across five domains: how knowledgeable, trustworthy, caring and approachable the physician appeared, and how comfortable the respondent felt. Secondary outcome measures included variation in preferences by country, physician type and respondent characteristics. RESULTS:The highest rated forms of attire differed by country, although each most preferred attire with white coat. Low ratings were conferred on attire extremes (casual and business suit). Preferences were more uniform for certain physician types. For example, among all respondents, scrubs garnered the highest rating for emergency department physicians (44.2%) and surgeons (42.4%). However, attire preferences diverged for primary care and hospital physicians. All types of formal attire were more strongly preferred in the USA than elsewhere. Respondent age influenced preferences in Japan and the USA only. CONCLUSIONS:Patients across a myriad of geographies, settings and demographics harbour specific preferences for physician attire. Some preferences are nearly universal, whereas others vary substantially. As a one-size-fits-all dress policy is unlikely to reflect patient desires and expectations, a tailored approach should be sought that attempts to match attire to clinical context.

PROBLEM/OBJECTIVE:Sexual and gender minority (SGM) people face multiple health disparities. Clinicians often lack adequate training to address the health needs of SGM people. In this setting, some health care organizations have sought to develop system-wide curricula to build clinician knowledge and capacity around SGM health. APPROACH/METHODS:NYC Health + Hospitals partnered with the National LGBTQIA+ [lesbian, gay, bisexual, transgender, queer, intersex, asexual] Health Education Center at The Fenway Institute to design and implement a novel SGM health care curriculum, offered from 2017-2020. The pilot program featured a 90-minute live introductory session, a pre-test, a post-test, and six 45-minute online modules focusing on a range of topics in SGM health care. OUTCOMES/RESULTS:Of approximately 35,000 employees from a range of settings and professional roles across NYC Health + Hospitals, 792 participated in the pilot program; most were clinicians at acute care hospitals, with the single largest group being attending clinicians. The proportion of eligible employees completing each component of the curriculum varied: 544 of 792 (68.7%) completed the online pre-test, while 373 of 792 (47.1%) completed the module on behavioral health. Of 373 participants who completed both the pre- and post-tests, mean scores rose significantly from 60.9 on the pre-test to 81.9 on the post-test (P < .001). NEXT STEPS/CONCLUSIONS:Future efforts should focus on increasing staff participation in the curriculum through scale-up efforts across the health care system, as well as measuring patient outcomes to assess the clinical impact of the initiative.

Introduction: Signet ring cell carcinoma accounts for about one percent of all colorectal cancers. It is an aggressive subtype of adenocarcinomas with the tendency for intramural spread and peritoneal carcinomatosis. Here, we reported a middle-aged male with circumferential colonic stenosis and inconclusive histology, found to have stage 4 colorectal signet ring cell carcinoma (SRCC). Case Description/Methods: A 41-year-old male without significant past medical history was referred to a gastroenterology clinic with bright red blood per rectum. Colonoscopy showed ulcerative rectosigmoiditis with rectal bleeding, and there was stricture in the rectum, in the recto-sigmoid colon, and from anus to descending colon (Figure A). Biopsy was obtained from the stricture. The pathology revealed granulation tissue and abundant fibrinopurulent exudate showing small clusters, and individual atypical cells stained positive for CDX-2 immunostain. Unfortunately, the patient subsequently lost follow-up. Three months later, the patient was hospitalized for small bowel obstruction. CT showed markedly enlarged heterogeneous and edematous rectum, an abnormal mass within the posterior pelvis/rectum, retroperitoneal and pelvic lymphadenopathy with thickening and nodularity of the peritoneum. Biopsy was obtained from an inguinal lymph node with histological examination showing metastatic adenocarcinoma composed of poorly cohesive signet-ring cells (Figure B). Immunostains revealed that the neoplastic cells were strongly and diffusely positive for CDX2 and CK20 while negative for CK7, confirming a colorectal primary. Accordingly, the diagnosis of colorectal signet ring cell carcinoma was made.
Discussion(s): The colonoscopic findings of colorectal SRCC could be nonspecific as diffuse circumferential thickening, stricture, or ulcerations. Typical pathological features may not appear on the initial biopsy sample. Immunohistochemical testing could help increase diagnostic yield and early identification of cancer cells. Our case hallmarked the importance of close follow-up for abnormal diffuse stricture and ulcerations in the colorectal area. These lesions may need to be rebiopsied, co-screened with abdominal imaging, and undergo an immunohistochemical investigation to characterize pathology further

OBJECTIVE:To evaluate the association of the built environment and neighborhood resources with exercise, diet, and body mass index (BMI). METHOD/METHODS:Person-level data were collected from 533 veterans with uncontrolled hypertension. Neighborhood measures were: (a) census-tract level walkability; and (b) healthy food proximity (HFP). Robust or logistic regression (adjusting for age, race, education, comorbidity, and clustered by provider) was used to evaluate associations between neighborhood and exercise duration (hours/week), exercise adherence (% adherent), saturated fat index (0-10), Healthy Eating Index (HEI; 0-100), HEI adherence (≥ 74 score), stage of change (SOC) for exercise and diet (% in action/maintenance), BMI (kg/m²), and obesity (BMI ≥ 30 kg/m²). RESULTS:= .034. CONCLUSIONS:Geographical location is associated with exercise and diet. Environment-tailored health recommendations could promote healthier lifestyles and decrease obesity-related cardiovascular disease. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An observational cohort study was conducted with data from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort to investigate weight gain among virologically suppressed people with HIV (PWH) switching to regimens containing tenofovir alafenamide/emtricitabine/ (TAF/FTC). Virologically suppressed, ART-experienced PWH switching to TAF/FTC with either darunavir/cobicistat (DRV/c), elvitegravir (EVG)/c, dolutegravir (DTG) or bictegravir (BIC) were selected. Cox proportional hazards models were used to assess the risk of excessive weight gain (i.e. ≥5% gain within 28 weeks or ≥10% within 54 weeks), by regimen. A linear mixed effects model with random intercept and restricted cubic splines on time was used to assess continuous changes in weight. Confounding was controlled for with both inverse probability of treatment weighting and traditional covariate adjustment. Among 5,536 PWH, 18% gained ≥5% of their weight within 28 weeks, and 9% gained ≥10% within 54 weeks. There were no differences in the risk of excessive weight gain by regimen, although there was a non-statistically significant 20% increase in the risk of gaining ≥10% within 54 weeks with all regimens compared to DRV/c. Throughout follow-up, the mean predicted weight remained fairly constant, with no notable differentiation between regimens. Expected weight gains ranged from +0.2 kg to +0.3 kg at 6 months and from +0.5 kg to +0.6 kg at 24 months. In conclusion, in this study of virologically suppressed, ART-experienced PWH switching to regimens containing TAF/FTC and either DRV/c, EVG/c, DTG or BIC, up to 18% experienced excessive levels of weight gain. However, no statistically significant difference was observed across regimens.

BACKGROUND:Pediatric MetS prevalence varies due to lack of consensus on evaluative criteria and associated thresholds, with most not recommending a diagnosis <10 years. However, MetS risk components are becoming evident earlier in life and affect races and ethnicities disproportionately. OBJECTIVES:To compare the prevalence of MetS based on existing definitions and elucidate racial- and ethnic-specific characteristics associated with MetS prevalence. METHODS:The baseline and follow-up samples included 900 and 557 children 7-10 years, respectively. Waist circumference, BMI percentile, blood pressure, fasting plasma glucose (FPG), insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured. Agreement between MetS definitions was quantified via kappa statistics. MetS and risk factor prevalence and the predictability of metabolic parameters on MetS eight months later was evaluated via logistic regression. McFadden pseudo-R2 was reported as a measure of predictive ability, and the Akaike information criterion evaluated fit of each model. RESULTS:The baseline sample was 55.0% male and 71.6% Hispanic, followed by non-Hispanic White (NHW) (17.3%) and non-Hispanic Black (NHB) (11.1%), with an average age of 9.2 years. MetS prevalence ranged from 7.6% to 21.4%, highest in Hispanic (9.0%-24.0%) and lowest in NHB children (4.0%-14.0%). Highest agreement was between Ford et al. and Cook et al. definitions (K = 0.88) and lowest agreements were consistently with the International Diabetes Federation criteria (K ≤ 0.57). Compared to NHW children, Hispanic children had higher odds for MetS (OR: 1.7; p = 0.03) and waist circumference, HDL-C, and FPG risk factors (p < 0.05), while NHB children had higher odds for the FPG risk factor (p ≤ 0.007) and lower odds for the plasma triglycerides risk factor (p = 0.002), across multiple MetS definitions. In longitudinal analyses, HDL-C was the strongest independent predictor of MetS in Hispanic and NHW children (p < 0.001 and p < 0.01, respectively), while plasma triglycerides was the strongest independent predictor of MetS in NHB children (p < 0.05). CONCLUSIONS:MetS prevalence was high in children ≤10 years, and proposed criteria are susceptible to racial and ethnic bias, diagnosing some populations more than other populations with high cardiovascular risk. Earlier preventative measures should be imposed in clinical settings, accounting for racial and ethnic differences, to mitigate disease onset.

Introduction: Biloma is an extrahepatic bile collection secondary to iatrogenic or traumatic biliary tree disruption. It is a rare complication of laparoscopy cholecystectomy with an incidence rate of approximately 2.5%. Without proper management, biloma can become infected and cause life-threatening complications such as peritonitis, biliary fistula, bilhemia and hemobilia. Here we described a case of complicated biloma after laparoscopic cholecystectomy. Case Description/Methods: The patient was a 24-year-old female with a past medical history of hypertension, obesity, and recent laparoscopic cholecystectomy complicated by hepatic subcapsular biloma. It was managed by biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous drainage during the previous hospitalization. However, 6 days later, she presented with fever, chills, nausea, and right upper quadrant pain. Vital signs were fever 102.3 F and tachycardia 110 to 120 per min. The CT abdomen revealed decreased size in perihepatic fluid collection with air bubbles (14 x 11 x 18 cm; Figure). It also showed a common bile duct stent in place and a percutaneous drainage catheter tip in the inferior aspect of the collection. Lab results showed leukocytosis to 10.3, normal AST/ALT, total/direct bilirubin 2.1/12 mg/dL, and GGT 152 U/L. Broad-spectrum antibiotics were given in ED. The surgery team performed a laparoscopic lavage and discovered that the drain was not connected with the biloma. Two new drains were placed during the operation. She was discharged with PO antibiotics, and an outpatient follow-up was scheduled for drain removal.
Discussion(s): The management of biloma depends on the severity of the disease. Endoscopic therapy, such as a transpapillary biliary stent placement, can decrease the transpapillary pressure gradient, thus allowing preferential transpapillary bile flow rather than accumulation at the leaking site. However, given that stent placement does not reabsorb formed collection, patients failing ERCP should undergo percutaneous drainage or bile duct repair.Iatrogenic biloma can be detected by post-operational physical exams and image studies. Laparoscopic lavage with drainage should be considered in unresolved or infected biloma due to the high risk of peritonitis

Introduction: As the inflammatory bowel disease (IBD) patient population ages, there will be an increasing number of individuals requiring advanced therapies. Although older age is thought to be associated with immunosenescence, there are data suggesting that older adults may be at higher risk for antibody development as the result of biologic use.
Method(s): Using a large commercial laboratory database (Prometheus Laboratories), we extracted infliximab (IFX) dosing as well as antibody to infliximab (ATI) levels for all individuals using this assay from 2015-2021. Our primary outcome was the presence of ATI (titer >3.1 U/mL). Frequencies were recorded as categorical variables with chi-square analysis used, and multivariable logistic regression was employed to assess the impact of IFX dose, age (< 60 years-old v. >=60 years-old), and IBD subtype on the development of ATI.
Result(s): Overall, there were 22,197 unique specimens, with 3,028 (13.6%) having ATI. When stratified by age, individuals >=60 years-old developed ATI 18.1% (473/2,612) of the time as compared to 15.0% (2,555/17,030) for individuals < 60 years of age (p< 0.01, Figure). Among all individuals with IFX dose < 10mg q8 weeks, older adults (>=60 years of age) were more likely to develop ATI as compared to younger adults (22.8% vs. 16.2%, respectively, p< 0.01); however, when IFX dose was >=10mg/kg q8 weeks, age >= 60 years-old was no longer significantly associated with the development of ATI (9.9% if < 60 years-old vs. 10.6% if >=60 years-old) on univariable analysis. Overall, older adults were less likely to receive IFX doses >=10mg/kg q8 weeks (38.4% in older adults vs. 49.7% in younger adults; p< 0.01). On multivariable analysis, age >=60 years-old (adjOR 1.35, 95%CI 1.20-1.51), IFX dose >= 10mg/kg q8 weeks (adjOR 0.53, 95%CI 0.49-0.57) and having ulcerative colitis as compared to Crohn's disease (adjOR 1.44, 95%CI 1.33-1.57) were independently associated with the development of ATI.
Conclusion(s): Older adults with IBD develop ATI more frequently than younger adults when adjusting for IFX dose and IBD subtype. However, when IFX dose >=10mg/kg q8 weeks, ATI was significantly less likely to develop among older adults, and occurred in a similar proportion of younger individuals. Further education is needed, highlighting that older adults with IBD are more likely to develop ATI as compared to younger adults, particularly when using lower doses of IFX, and that higher doses may decrease this likelihood. (Figure Presented)