Faculty Bibliography

Introduction: Clostridium difficile infection (CDI) occurs frequently in patients with inflammatory bowel disease (IBD) and is associated with increased disease activity. Due to concern for complications, immunosuppressive medication (ISM) is often withheld after CDI, although few data exist to inform this decision. This study aims to assess the influence of ISM on outcomes following CDI in IBD patients. Methods: This multicenter, retrospective cohort study was performed at 4 academic medical centers in New York City. Patient demographic and clinical data was abstracted from databases at each site for adult patients with an established diagnosis of IBD also diagnosed with CDI. Escalation of therapy was defined as initiation or dose escalation of corticosteroids or new biologic use following antibiotic therapy for CDI. Outcomes were assessed at 30 and 90 days after last positive C. difficile test. Continuous variables were compared using two-sided T-tests and proportions were compared using Chi-squared tests. Exact methods were used for expected cell size. Results: 207 patients met inclusion criteria (49 outpatient, 158 inpatient). Demographic information is listed in Table 1. Escalation of IBD regimen (Table 2) was more frequent in outpatients at 90 days (43% vs. 22%, P<0.01), with 49% (39/61) of ISM escalation occurring within 14 days of CDI.) Patients not escalated had higher rates of sepsis than escalated patients (11% vs. 2%, P=0.04). Severe outcomes (death, sepsis, or colectomy) at 90 days were markedly increased in the non-escalation group (15% vs 2%, P<0.01). There was no difference in CDI recurrence or rehospitalization between groups. Conclusion: In this multicenter study assessing outcomes of ISM use in patients with IBD and CDI, initiation of steroid or biologic therapy following CDI treatment was not associated with adverse clinical outcomes. While no difference was observed between CDI recurrence or rehospitalization among groups, sepsis and severe outcomes were significantly more common in patients not undergoing escalation. These data suggest that escalation of IBD therapy following CDI is not associated with worse clinical outcomes and a subset of patients may benefit from timely treatment of underlying inflammatory disease. Prospective studies are needed to validate these data and to inform clinical guidelines regarding the timing of ISM use following CDI

Introduction: Colonoscopy is the most commonly used test for colorectal cancer screening in the US, but patients often find the oral bowel preparation difficult, inconvenient, or intolerable. Suboptimal bowel prep occurs in 20-24% of colonoscopies, leading to inadequate examinations that necessitate additional procedures. Colonic irrigation is an FDA-approved method of colon cleansing using a warm water lavage, but few studies have evaluated it as preparation for colonoscopy. The purpose of this study is to evaluate colonic irrigation as an alternative to oral bowel prep in patients undergoing screening/ surveillance colonoscopy. Methods: We conducted a single-center, single-arm feasibility study using the Hydro-San Plus system. Patients followed a low-residue diet and took 2 doses of polyethylene glycol the day before the procedure. Colonoscopy was performed immediately following colonic irrigation. Boston Bowel Prep Scale (BBPS) and adverse events were recorded. A telephone questionnaire was administered within 7 days of the procedure. Results: Of the 21 patients enrolled, 48% had at a medical risk factor for poor prep (Table 1). Eighteen patients completed irrigation, of whom 12 (67%) had an adequate bowel prep, defined as BBPS>1 in all segments (Table 2). Two irrigations were not completed due to minor adverse events (discomfort from speculum insertion and rectal abrasion) and 1 was aborted for mechanical repair. There were no major adverse events. Patients with no risk factors for poor prep were 4 times more likely to have an adequate prep, although this was not statistically significant (P=0.14). Half of the patients felt that irrigation was easy (47%) and comfortable (53%), while most felt it was tolerable (71%) and convenient (82%). Among participants who had previous a colonoscopy with oral prep, the majority felt that irrigation was easier (85%), more tolerable (77%), and more convenient (85%) than oral prep. 82% of respondents said they would ask for irrigation again and only 12% said they would refuse if it were offered. Conclusion: Colonic irrigation is a safe and moderately efficacious alternative to oral bowel prep for screening/surveillance colonoscopy. A more potent oral pre-prep, especially for patients with risk factors for poor prep, may improve efficacy. Importantly, patient satisfaction with colonic irrigation appears to be higher than with oral bowel prep. (Table Presented)

Introduction: Inflammatory bowel disease (IBD) therapy is continuously evolving with novel drugs targeting various inflammatory pathways. Ustekinumab (USK), a monoclonal antibody inhibiting the IL-12/23 pathway, was approved in September 2016 to treat moderate-to-severe Crohn's disease (CD). While safety data in IBD is limited, USK has been used to treat other autoimmune diseases with favorable safety profiles. We aimed to establish rates of adverse events (AE) and demonstrate non-inferiority of AE of USK compared to placebo and other biologics. Methods: MEDLINE, PubMed and Embase databases were searched in May 2017 using terms "ustekinumab" and "clinical trials." Two authors independently performed quality assessment and dual extraction. Randomized control trials comparing USK to placebo or other biologics regardless of disease were included. The primary outcome was the odds ratio (OR) of AE of USK vs placebo, expressed as pooled OR and 95% confidence interval (CI). Secondary outcomes included OR of mild/moderate and serious AE (SAE) in USK vs placebo, USK vs biologics, and low vs high-dose USK, respectively (Table 2). A sub-analysis of outcomes in CD trials was performed. Random effects meta-analysis was performed for all outcomes. Results: 16 papers with 6756 subjects (44% female) were included (Fig 1). Infections were the most common AE (Table 1). The OR of serious AE in USK vs placebo was 0.76 (95% CI 0.56-1.03, Fig 2). The OR of mild-to-moderate AE in the USK vs placebo was 1.12 (95% CI 1.01-1.24), suggesting increased risk of mild/moderate AE with USK (Fig 3). However, this was no longer significant after sub-analysis of the three CD trials. Analysis of 5 trials comparing low vs high-dose USK revealed an OR of 0.96 (95% CI 0.46-2.04) for SAE and 1.17 (95% CI 0.98-1.39) for mild-to-moderate AE. Use of USK was not associated with increased AE compared to other biologics, with OR of 0.91 (95% CI 0.61-1.35) for SAE and 0.98 (95% CI 0.85-1.13) for mild/moderate AE. Heterogeneity was low for all calculations. Conclusion: USK has a comparable safety profile to placebo and other biologics in the treatment of various diseases, although we did find a mildly elevated risk of mild/moderate AE with USK; however, this (Figure Presented) was not seen in CD trials. The favorable safety profile of USK is of clinical importance with the advent of USK in CD and ongoing clinical trials for ulcerative colitis. More data on long-term safety data in the IBD population is needed

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.

Receptive anal intercourse and its association with sexually transmitted infections and human papillomavirus-related anal dysplasia has been well studied in various at-risk groups including men who have sex with men. However, the relationship between receptive anal intercourse and its potential complications in patients with inflammatory bowel disease is not fully understood. This narrative review discusses sexually transmitted infections and anal dysplasia in patients with inflammatory bowel disease who engage in receptive anal intercourse and the lack of evidence-based data to guide clinical practice. It addresses the psychosocial effects of stigmatization in these patients and its consequences in the clinical encounter. We review the need for sufficient data on infection, cancer prevention, and precoital and postcoital hygienic practices with hopes that future studies establish standardized guidelines and recommendations.