Faculty Bibliography

Fatty acids derived from fish oil are long chain omega-3 (n-3) polyunsaturated fatty acids. The important polyunsaturated fatty acids of fish oil are eicosapentaenoic acid, and docosahexaenoic acid. For decades, there has been a debate about the use of omega-3 fatty acid supplements and their benefits on cardiovascular health. The more recent trials including the JELIS, REDUCE-IT, VITAL, STRENGTH, and the ASCEND trials addressed the paucity of data of omega-3 Fatty acids on primary as well as secondary prevention of cardiovascular events and risk-benefit balance of these supplements. Prior to these studies, many large randomized controlled trials have shown conflicting results on the effect of polyunsaturated fatty acids in patients with prior coronary artery disease, stroke or major vascular events. These inconsistent results warrant a better understanding of the effects of omega-3 fatty acids on the subtypes of cardiovascular diseases, and their use in primary and secondary prevention. More recently, the REDUCE-IT study showed a possible protective benefit of fish oil supplements (in purified form and higher than normal doses) in the reduction of Triglyceride levels. It is also noteworthy that omega-3 fatty acids have found their mention in the most recent American College of Cardiology guidelines for the management of hypertriglyceridemia as an adjunct to statins and fibrates. The aim of this review is to discuss these recent updates on use of fish oil in cardiometabolic diseases, and their surrounding controversies.

Background/Purpose : Several studies implicate gout and/or xanthine oxidase activity as risk factors for type 2 diabetes. However, no studies have directly evaluated the effect of the xanthine oxidase inhibition on type 2 diabetes development. We therefore assessed the impact of allopurinol use on diabetes incidence in a retrospective cohort study of Veterans' Affairs patients with gout. Methods : The New York Harbor VA Computerized Patient Record System was searched to identify patients with an ICD-9 code for gout also meeting at least 4 1977 American Rheumatology Association gout diagnostic criteria. Pharmacy records were reviewed, and subjects divided into subgroups based on >30 continuous days of allopurinol prescription, versus no allopurinol. Incident diagnoses of diabetes, defined as first hemoglobin A1c <= 6.5% or physician documentation, were identified during an observation period from January 1, 2000 through December 31, 2015. Categorical variables, including the primary endpoint, were analyzed utilizing Fisher's exact test. Continuous variables were analyzed using binomial regression and the Student's T test. Results : 1032 subjects were allopurinol users, and 485 subjects were allopurinol never-users. The average duration of allopurinol use was 48.4 months. There were significantly more Black subjects in the allopurinol group, whereas there were significantly more Asian subjects and subjects with chronic kidney disease in the non-allopurinol group. Over a mean 94.3 months of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (8.0/1000 person-years versus 11.3/1000 person-years, p=0.64). There was also no significant difference in diabetes incidence when subjects were analyzed by baseline serum urate level, colchicine use, allopurinol dose, extent of urate lowering with allopurinol or achieving target urate level. When stratified into quartiles by duration of allopurinol use, a significant difference was observed between diabetes incidence in the longest and shortest quartiles among subjects in the allopurinol cohort (7.3 per 1000 person-years versus 21.3 per 1000 person-years, p=0.007). Conclusion : In this study, allopurinol use was overall not associated with reduced diabetes incidence, but longer durations of allopurinol use may have been associated with decreased diabetes. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity and diabetes, and the potential impact of gout treatments on diabetes incidence. (Figure Presented )

INTRODUCTION: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI), but its precise mechanism remains unknown (1-2). Recent studies suggest that the restoration of gut bacteria, which carry necessary enzymes to convert primary bile acids (PBAs) to secondary bile acids (SBAs), may play a key role in rCDI risk (3, Figure 1). For example, in vitro studies have demonstrated that PBAs stimulate C. difficile spore germination and that deoxycholic acid, a SBA, inhibits toxin-producing C. difficile (4). As normal fecal bile acid pools consist predominantly of SBAs, we hypothesize that a contributor of rCDI risk is the decrease in SBAs from enteric bacteria loss following antibiotic use (5-8).We present the first case enrolled in our clinical trial using ursodeoxycholic acid (UDCA), a SBA, as an adjunct treatment to prevent future rCDI. CASE DESCRIPTION/METHODS: An otherwise healthy 46-year-old man presented with S. aureusbacteremia secondary to septic knee arthritis. While on an extended course of cefazolin, he developed profuse, watery diarrhea and stool C. difficile toxin PCR was positive. He was then treated with intravenous metronidazole for one week and oral vancomycin for two weeks, with resolution of symptoms. Six weeks later, CDI recurred and was successfully treated with oral vancomycin for two weeks, in conjunction with concurrent UDCA 300 mg twice daily for eight weeks. Stool samples were collected at two-week intervals and fecal bile acid compositions were assessed via liquid chromatography - mass spectrometry. Fecal bile acid analyses demonstrated a shift towards protective SBAs by the end of the 8-week course of ursodiol (Figure 2). This profile of increased SBAs remained consistent despite subsequent retreatment with cefazolin at 5 months for recurrent septic arthritis. The patient has been without rCDI now for almost 2 years. DISCUSSION: The findings in this case are consistent with our hypothesis that increasing SBAs through adjunct treatment with UDCA can be effective in breaking the rCDI cycle. While some CDI patients have adequate enteric bacteria to produce SBAs after antibiotic treatment, others may have a delayed normalization of their gut microbiome, and may therefore require ?bridge therapy? with supplementary SBAs (e.g., UDCA) until their endogenous microbial community is restored. Treatment and analysis of additional patients with rCDI in this clinical trial are in progress. (Figure Presented)

BACKGROUND & AIMS:Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps owing to H pylori-induced immunomodulation. However, findings vary. We performed a systematic review and meta-analysis of comparative studies to define the association between H pylori exposure and EoE more clearly. METHODS:We searched 4 large databases to identify comparative clinical studies that included sufficient detail to determine the odds or risk of EoE (primary outcome) or esophageal eosinophilia (secondary outcome) among individuals exposed to H pylori (exposed) vs individuals who were tested and found to be unexposed. Estimates were pooled using a random-effects model. Meta-regression and sensitivity analyses were planned a priori. Studies were evaluated for quality, risk of bias, publication bias, and heterogeneity. RESULTS:We analyzed 11 observational studies comprising data on 377,795 individuals worldwide. H pylori exposure vs nonexposure was associated with a 37% reduction in odds of EoE (odds ratio, 0.63; 95% CI, 0.51-0.78) and a 38% reduction in odds of esophageal eosinophilia (odds ratio, 0.62; 95% CI, 0.52-0.76). Fewer prospective studies found a significant association between H pylori exposure and EoE (P = .06) than retrospective studies. Effect estimates were not affected by study location, whether the studies were performed in pediatric or adult populations, time period (before vs after 2007), or prevalence of H pylori in the study population. CONCLUSIONS:In a comprehensive meta-analysis, we found evidence for a significant association between H pylori exposure and reduced odds of EoE. Studies are needed to determine the mechanisms of this association.

Little is known about the dietary patterns of Chinese Americans. Understanding their dietary patterns can provide insights for addressing cardiovascular disease (CVD) risk among Chinese American immigrants. The objective of this study was to identify dietary patterns among Chinese American immigrants living in New York City (NYC) and to describe associations with demographic and CVD risk factors. A validated Food Frequency Questionnaire assessed usual dietary intake in Chinese American immigrants living in NYC as part of the Chinese American Cardiovascular Health Assessment (CHA CHA) in 2010-2011 (n = 1973, age range 21-89 years). Principal components analysis with varimax rotation retaining three factors with eigenvalues > 1.5 identified dietary patterns. Multivariable linear regression models tested associations between CVD risk factors and dietary pattern scores. In multivariable analyses, each unit of increase in the Sweets factor was associated with 0.76 ± 0.33 (mean ± SD) mg/dL higher HDL cholesterol and a 6.2 ± 2.7% increase in HOMA-IR. In contrast, each unit increase in the Fried Noodles factor was associated with a 0.27 ± 0.11 inch greater waist circumference, - 0.89 ± 0.40 mg/dL lower HDL cholesterol, and also a 6.9 ± 2.6% increase in HOMA-IR. Each unit increase in the Vegetables factor was associated with a - 1.40 ± 0.43 mmHg and - 0.95 ± 0.27 mm Hg decrease in systolic and diastolic blood pressure, respectively. Dietary patterns are significantly associated with CVD risk factors among Chinese American immigrants in NYC. Future work will inform how dietary patterns relate to level of acculturation in order to guide the development of dietary interventions to reduce CVD risk.

Background. Pneumonia (PNU) is the second most common nosocomial infection in the United States and is associated with substantial morbidity and mortality. While definitions from CDC were developed to increase the reliability of surveillance data, reduce the burden of surveillance in healthcare facilities, and enhance the utility of surveillance data for improving patient safety - the algorithm is still laborious. We propose an implementation of a refined algorithm script which combines two CDC definitions with the use of natural language processing (NLP), a tool which relies on pattern matching to determine whether a condition of interest is reported as present or absent in a report, to automate PNU surveillance. Methods. Using SAS v9.4 to write a query, we used a combination of National Healthcare Safety Network's (NHSN) PNU and ventilator-associated event (VAE) definitions that use discrete fields found in electronic medical records (EMR) and trained an NLP tool to determine whether chest x-ray report was indicative of PNU (Fig1). To validate, we assessed sensitivity/specificity of NLP tool results compared with clinicians' interpretations. Results. The NLP tool was highly accurate in classifying the presence of PNU in chest x-rays. After training the NLP tool, there were only 4% discrepancies between NLP tool and clinicians interpretations of 223 x-ray reports - sensitivity 92.2% (81.1-97.8), specificity 97.1% (93.4-99.1), PPV 90.4% (79.0-96.8), NPV 97.7% (94.1- 99.4). Combining the automated use of discrete EMR fields with NLP tool significantly reduces the time spent manually reviewing EMRs. A manual review for PNU without automation requires approximately 10 minutes each day per admission. With a monthly average of 2,350 adult admissions at our hospital and 16,170 patient-days for admissions with at least 2 days, the algorithm saves approximately 2,695 review hours. Conclusion. The use of discrete EMR fields with an NLP tool proves to be a timelier, cost-effective yet accurate alternative to manual PNU surveillance review. By allowing an automated algorithm to review PNU, timely reports can be sent to units about individual cases. Compared with traditional CDC surveillance definitions, an automated tool allows real-time critical review for infection and prevention activities

Background/Purpose : DLE is a rare, disfiguring disorder in children. Small retrospective studies suggest 20-25% of patients progress to SLE. Progression risk factors are poorly understood, but DLE has been associated with delay in SLE diagnosis and reduced access to care. This multicenter retrospective cohort study aimed to describe baseline characteristics and clinical phenotypes of pediatric DLE patients at diagnosis. Methods : Medical records at eighteen sites were reviewed for pediatric dermatology and rheumatology patients with DLE. For inclusion, patients required clinical and/or histopathologic findings consistent with DLE. Baseline data were collected at the first documented visit including sociodemographic data, ACR/SLICC SLE criteria (i.e. DLE+SLE), date of DLE onset/diagnosis, DLE distribution, family history, comorbidities, and treatment. Outcome variables included ACR (primary outcome) /SLICC SLE criteria. Rates of progression from skin-limited DLE (DLE) to SLE (DLE+SLE) were evaluated. Analysis included descriptive statistics, chi-square and Wilcoxon tests. Results : Out of >1,000 patients reviewed, 441 met inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse (Table 1). A minority presented at baseline with SLE based on ACR and SLICC criteria, respectively (n=165, 37%; n=183, 42%). DLE+SLE patients were older (median 13.7y vs 10.2y) with shorter time from DLE onset to diagnosis (median 2 mo vs 7 mo), compared to DLE patients (p< 0.001). DLE patients presented with low incidence of renal involvement, serositis, seizures or psychosis (p< 0.001, Table 2). DLE+SLE patients had more positive serologies and higher-titer ANAs (p< 0.001, Table 3), although 5% were ANA negative. Among 231 DLE patients with31 follow up visit, median follow-up was 2.7 y (range 0-13.9y) with 747 total subject-years. Progression to SLE occurred in 20% and 25% of patients based on ACR and SLICC criteria, respectively. Conclusion : To date, this is the largest investigation of pediatric DLE. Patients with DLE+SLE were most likely to present in adolescence with abnormal serologies and end-organ disease. Progression of DLE to SLE occurred at rates consistent with previous literature. All patients with DLE require SLE surveillance at diagnosis and regular follow-up, particularly during adolescence. Limitations include the retrospective study design with potential for misclassification, and analysis restricted to the baseline visit. Further analysis of follow up visits will evaluate for baseline risk factors and biomarkers of evolving SLE, as well as timing of progression, identifying DLE patients at highest risk for systemic disease

INTRODUCTION: Maternal TDF treatment during the third trimester has been shown to reduce perinatal transmission of the hepatitis B virus (HBV) in highly viremic women in several RCTs. However, the data is limited on the effectiveness of TDF in the real-world setting. With this real-world study, we aimed to assess the efficacy and safety of TDF therapy for these mothers in a single center in the US.
METHOD(S): All Hepatitis B e-antigen positive mothers with HBV DNA .6log10 copies/mL who received TDF in the third trimester and delivered from July 2010 to September 2018 were retrospectively analyzed. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. Primary endpoints were the safety of TDF use and mother-to-child transmission rates. Secondary outcomes were maternal HBV DNA level suppression at delivery.
RESULT(S): Among the 75 patients enrolled, the mean (6SD) age of the patients was 30.47+/-4.49 years, mean (6SD) gestational age was 37.87+/-2.95 weeks, and the mean (6SD) treatment duration before delivery was 9.60+/-3.36 weeks. A significantly lower level of the mean (6SD) serum HBV DNA was achieved at delivery vs. baseline (4.2+/-1.2 vs. 7.6+/-0.80 log10 copies/mL, respectively; P- < 0.01). Additionally, 80% (60/75) of mothers achieved HBV DNA < 6log10 copies/mL at delivery. The median (Interquartile range) alanine aminotransferase (ALT) level before treatment was 26 (20) IU/L, and at delivery was 27 (20) IU/L respectively. Vertical transmission rate among infants was 0%, and all infants were hepatitis B surface antigen negative between 28 -52 weeks after birth. Fatigue was the most common complaint reported by 52% (39/75) of mothers. No infants had a birth defect. On treatment, ALT flares were observed in 4.5% (6/75) of mothers.
CONCLUSION(S): In this US cohort of real-world practice, TDF therapy for highly viremic mothers was well tolerated and reduced vertical transmission effectively. No severe adverse effects were reported in both mothers and infants. Our study supports the use of TDF treatment for highly viremic mothers in a real-world setting. (Figure Presented)