Faculty Bibliography

The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.

Remdesivir has been the mainstay of coronavirus disease 2019 treatment since the start of the severe acute respiratory syndrome coronavirus 2 pandemic. Despite its growing use, safety data are limited. We present the case of an elderly man with obesity and coronavirus disease 2019 who developed acute liver failure after initiation of remdesivir. This report broadens our knowledge of the side effect profile of remdesivir and discusses potential risk factors and an approach to remdesivir-induced liver failure. Our case also highlights the importance of monitoring hepatic function after initiation of therapy with remdesivir.

BACKGROUND:Competency in endoscopy has traditionally been based on number of procedures performed. With movement towards milestone-based accreditation, new standards of establishing competency are required. The Thompson Endoscopic Skills Trainer (TEST) is a training device previously shown to differentiate between novice and expert endoscopists. This study aims to correlate TEST scores to other markers of performance in endoscopy. METHODS:Trainees of a gastroenterology fellowship program were guided through the TEST. Their scores and sub-scores were correlated to their endoscopic metrics of performance, including adenoma detection rate, cecal intubation rate, cecal intubation time, withdrawal time, fentanyl usage, midazolam usage, pain score, overall procedure time, and performance on the ASGE Assessment of Competency in Endoscopy Tool (ACE Tool). RESULTS:The Overall Score positively correlated with the ACE Tool Total Score (r = 0.707, p = 0.010) and sub-scores (Cognitive Skills Score: r = 0.624, p = 0.030; Motor Skills Score: r = 0.756, p = 0.004), and negatively correlated with cecal intubation time (r = - 0.591, p = 0.043). The Gross Motor Score positively correlated with cecal intubation rate (r = 0.593, p = 0.042), ACE Tool Total Score (r = 0.594, p = 0.042) and Motor Skills Score (r = 0.623, p = 0.031), and negatively correlated with cecal intubation time (r = - 0.695, p = 0.012). The Fine Motor Score positively correlated with the ACE Tool Polypectomy Score (r = 0.601, p = 0.039), and negatively correlated with procedure time (r = - 0.640, p = 0.025), cecal intubation time (r = - 0.645, p = 0.024), and withdrawal time (r = - 0.629, p = 0.028). CONCLUSION/CONCLUSIONS:This study demonstrates that performance on the TEST correlate to endoscopic measures. Given these results, the TEST may be used in conjunction with existing assessment tools for demonstrating competency in endoscopy.

INTRODUCTION: The regimen of glecaprevir and pibrentasvir is an effective treatment for hepatitis C (HCV), but FDA data suggests a risk of hepatobiliary toxicity. Here, we discuss the first description of hepatorenal syndrome secondary to hepatobiliary toxicity from glecaprevir/ pibrentasvir. CASE DESCRIPTION/METHODS: A 65-year-old man with chronic HCV (genotype 1a), alcohol use disorder, and hepatocellular carcinoma (HCC), presented with abdominal distention and jaundice for one month. He was diagnosed with HCC in 2014 and treated with resection and adjuvant sorafenib without evidence of recurrence, and thus began HCV treatment with glecaprevir/ pibrentasvir. At baseline he was Childs-Pugh class A with a total bilirubin of 0.9 mg/dL, INR of 0.95, and albumin of 3.2. Twenty-four days after initiation of glecaprevir/pibrentasvir he presented with fevers, fatigue, and dark urine. On exam he had jaundice, abdominal distension, and right upper quadrant tenderness. His labs showed a total bilirubin of 25.5 mg/dL, direct bilirubin of 16.1 mg/dL, INR of 1.64, and creatinine of 1.6 mg/dL (1.1 mg/dL two weeks prior). He was initially started on a three-day albumin challenge, but his renal function continued to decompensate, raising concern for a type 1 HRS, so he was transitioned to octreotide, midodrine, and albumin. Glecaprevir/pibrentasvir was also discontinued due to his acute liver decompensation after only 29 days of treatment. Eight days later, the patient's creatinine had decreased from 2.0 to 1.3 mg/dL and his total bilirubin decreased from 25.6 to 16.4 mg/dL. Four months after discharge he has continued to improve with creatinine as low as 1.2mg/dL and a total bilirubin of 3.7 mg/dL. Notably, despite just four weeks of glecaprevir/pibrentasvir, his hepatitis C viral load has remained undetectable. DISCUSSION: In 2019, the FDA distributed a safety communication outlining liver injury in 46 individuals on glecaprevir/pibrentasvir and suggested avoidance in Child-Pugh class B and C patients. While research of the safety profile for glecaprevir/pibrentasvir in Child-Pugh class A is needed, this case reports highlights the importance of early and regular monitoring of liver and renal function in patients on this regimen. Current glecaprevir/pibrentasvir regimens are 12 weeks, yet a shortened four-week regimen still provided virus eradication in this case, raising the possibility of personalized treatment based on viral load. This could reduce potential side effects as well as the cost of antiviral therapy

GOALS/BACKGROUND/OBJECTIVE:Patients who "no-show" for colonoscopy or present with poor bowel preparation waste endoscopic resources and do not receive adequate examinations for colorectal cancer (CRC) screening. Using the Health Belief Model, we modified an existing patient education pamphlet and evaluated its effect on nonattendance rates and bowel preparation quality. STUDY/METHODS:We implemented a color patient education pamphlet to target individual perceptions about CRC and changed bowel preparation instructions to include a low-residue diet instead of the previous clear liquid diet. We compared the nonattendance rate over a 2-month period before and after the introduction of the pamphlet, allowing for a washout period during which pamphlet use was inconsistent. We compared the Boston Bowel Preparation Scale (BBPS) in 100 consecutive patients who underwent colonoscopy during each of the 2 periods. RESULTS:Baseline characteristics between the 2 groups were similar, although patients who received the pamphlet were younger (P=0.03). The nonattendance rate was significantly lower in patients who received the pamphlet (13% vs. 21%, P=0.01). The percentage of patients with adequate bowel preparation increased from 82% to 86% after introduction of the pamphlet, although this was not statistically significant (P=0.44). The proportion of patients with a BBPS score of 9 was significantly higher in the pamphlet group (41% vs. 27%, P=0.03). There was no difference in adenoma and sessile serrated adenoma detection rates before and after pamphlet implementation. CONCLUSIONS:After implementing a theory-based patient education intervention with a low-residue diet, our absolute rate for colonoscopy nonattendance decreased by 8% and the proportion of patients with a BBPS score of 9 increased by 14%. The Health Belief Model appears to be a useful construct for CRC screening interventions.

Background/UNASSIGNED:This study was performed to compare patient-reported tolerability and its barriers in single- vs. split-dose 4-L polyethylene glycol (PEG) bowel preparation for colonoscopy in a large multiethnic, safety-net patient population. Methods/UNASSIGNED:A cross-sectional, dual-center study using a multi-language survey was used to collect patient-reported demographic, medical, socioeconomic, and tolerability data from patients undergoing outpatient colonoscopy. Univariate and multivariate analyses were used to identify demographic and clinical factors significantly associated with patient-reported bowel preparation tolerability. Results/UNASSIGNED:A total of 1023 complete surveys were included, of which 342 (33.4%) completed single-dose and 681 (66.6%) split-dose bowel preparation. Thirty-nine percent of the patients were Hispanic, 50% had Medicaid or no insurance, and 34% had limited English proficiency. Patients who underwent split-dose preparation were significantly more likely to report a tolerable preparation, with less severe symptoms, than were patients who underwent single-dose preparation. Multiple logistic regression revealed that male sex and instructions in the preferred language were associated with tolerability of the single-dose preparation, while male sex and concerns about medications were associated with tolerability of the split-dose preparation. Conclusions/UNASSIGNED:In a large multiethnic safety-net population, split-dose bowel preparation was significantly more tolerable and associated with less severe gastrointestinal symptoms than single-dose preparation. The tolerability of split-dose bowel preparation was associated with social barriers, including concerns about interfering with other medications.

Introduction: Effectiveness of colonoscopy is limited by inadequate bowel preparation. Failure of proper cleansing is multifactorial, but includes the inability of patients to tolerate the bowel preparation due to side effects. It is unknown whether or not the experience with split dose preparation increases adherence to recommendation for repeat colonoscopy. Few studies to date have evaluated potential barriers to bowel preparation in underserved populations. The purpose of this study was to identify whether adverse effects of bowel preparation affect the likelihood of repeating a colonoscopy in a split-dose versus a single dose cohort Methods: Demographic, socioeconomic, medical, education and tolerability data were collected prospectively using a multi-language questionnaire. Descriptive statistics and multivariate analyses were performed on all variables assessed by our questionnaire to evaluate for differences in patients who were likely or unlikely to repeat the preparation. Results: A total of 990 patients satisfied the study criteria (Figure 1). 54.6% of the patients were male, 39.7% Hispanic, 41.2% with less than a high school education, and 38.9% without medical insurance. 336 (34%) completed single dose and 654 (66%) completed split dose colon preparation. In the single dose cohort there were no statistically significant differences in the side effects experienced between patients who would and would not repeat the bowel preparation (Table 1). In contrast, in the split-dose cohorts, complaints of bad taste in mouth, nausea/vomiting and headache were statistically significant causes of a patient being unlikely to repeat the bowel preparation (p < .05) (Table 2). Despite the difference in the role of symptoms in willingness to repeat colon preparation between split dose versus single does preparation groups, there was no significant difference in overall willingness to repeat colon preparation between groups (69.0% versus 71.6%, p = 0.45). Conclusion: This study highlights differences in side effects experienced by patients taking a split dose compared to a single dose preparation. Despite these differences, patients in both groups were likely to repeat a colonoscopy. These results should give a provider confidence in prescribing a split dose preparation to a diverse patient population

Introduction: Efficacy of colonoscopy is limited by inadequate preparation. A high social deprivation index has been identified as a risk factor for failure to repeat a colonoscopy when indicated. It is unknown whether or not split dose preparation increases adherence to recommendation for repeat colonoscopy. Few studies to date have evaluated the potential barriers to likelihood of repeating a bowel preparation in an underserved population. The purpose of this study was to identify factors associated with an increased likelihood of repeating a bowel preparation in a population with a high social deprivation index in a split-dose versus a single dose cohort Methods: Demographic, socioeconomic, medical, education and tolerability data were collected prospectively using a multi-language questionnaire. Descriptive statistics and multivariate analyses were performed on all variables assessed by our questionnaire to evaluate for differences in patients who were likely and unlikely to repeat the preparation. Results: Demographics are presented in table 1 (N=990). 336 (34%) completed single dose and 654 (66%) completed split dose colon preparation. Split dose patients were equally willing-to-repeat colonoscopy preparation compared to single dose patients (69.0% vs. 71.6%; P=0.45) (Table 2). Patients who were not willing to repeat split preparation complained of significantly more adverse gastrointestinal symptoms and difficulty completing dosing instructions due to social barriers and tolerability issues compared to single-dose cohort. Multivariable analysis revealed that concerns with time off work (OR: 0.48; 95% CI: 0.29-0.80), availability of appropriate food/drinks (OR: 0.59; CI: 0.36-0.97), tolerability (OR: 0.72; CI: 0.57-0.92), and colonoscopy scheduling (OR: 0.77; CI: 0.63- 0.94) were all factors independently associated with decreased willingness to repeat in the split dose cohort. Nurse's instruction in preferred language (OR: 2.69; CI: 1.22-5.91) and tolerability (OR: 0.71; CI: 0.55-0.92) were independently associated with patient willingness-to-repeat in the single-dose cohort. Conclusion: This study highlights that tolerability significantly effects repeatability in both single and split dose cohorts. It should be noted that patients with a high social deprivation index identify different barriers to single and split dose preparations. This observation could impact choice of preparation as it affects adherence to physician recommendations. (Figure Presented)

BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then reproduced some of the putative relationships formed among these predictors by analyzing data from the pediatric RISK cohort. RESULTS: We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4 T cells. These SAA1-linked microbial and transcriptome interactions were further reproduced with data from the pediatric IBD RISK cohort. CONCLUSIONS: This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities, and their tissue environment in patients with IBD. A combination of T cell effector function data, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.