Faculty Bibliography

Introduction: Obesity is associated with an increased risk of colorectal neoplasia, but this relationship has not been studied in patients with inflammatory bowel disease (IBD). Both IBD and obesity induce a chronic inflammatory state, so the combination of the two could have an additive or synergistic effect on risk of colorectal neoplasia. Given the increased baseline incidence of dysplasia among IBD patients, identifying modifiable risk factors, such as obesity, could have a significant impact on long term cancer-related outcomes.
Method(s): We performed a retrospective case-control study of IBD colitis patients at an academic IBD Center between January 2006 and February 2022. Demographic and disease-related data, known risk factors for dysplasia, and median BMI during the follow-up period were obtained. Only patients with at least 5 years of colonoscopy reports were included. A case was defined as any patient with biopsy proven dysplasia-indefinite, low-grade, or high-grade-during the study period. A control was defined as any patient with absence of biopsy-proven dysplasia. Obesity was defined as BMI of 30 or greater. Univariate analysis was performed using T-test for continuous variables and chi-square for categorical variables. Multivariate analysis was performed using logistic regression to model dysplasia risk.
Result(s): 106 cases had biopsy-proven colorectal dysplasia (64 IND, 36 LGD, 10 HGD); 125 controls had no dysplasia. Number of colonoscopies (p < 0.001) IBD subtype ulcerative colitis (p = 0.016), maximum histologic severity (p = 0.127), pseudopolyps (p = 0.162), IBD duration (p = 0.098), sex (p = 0.18), age (p < 0.001), smoking history (p = 0.048), prior dysplasia (p < 0.001), and obesity (p < 0.001) were associated with dysplasia on univariate analysis. On multivariable regression, number of colonoscopies (OR 1.26, 95% CI 1.08 - 1.48, p = 0.004), prior dysplasia (OR 3.98, 95% CI 1.23 - 12.86, p = 0.021), and obesity (OR 2.90, 95% CI 1.21 - 6.95, p = 0.017) were each independently associated with increased dysplasia risk. (Figure)
Conclusion(s): Patients with IBD have an increased risk of colorectal neoplasia, but a variety of comorbid states may exacerbate this risk. Notably, we identified obesity as an independent risk factor for dysplasia. Further research is needed to determine whether this risk functions synergistically with IBD or just as an independent risk factor. Furthermore, targeted weight-loss interventions may reduce the incidence of dysplasia among patients with IBD. (Table Presented)

Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. Individuals with IBD are at increased risk for several malignancies originating in the intestine, such as colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. There are also several extraintestinal malignancies associated with IBD and IBD therapies, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, cervical cancer, and prostate cancer. The authors summarize the risk of cancer in patients with IBD, diagnosis and management of colorectal neoplasia in IBD, and management of patients with IBD and active or recent cancer.

BACKGROUND:Colorectal strictures have been considered independent risk factors for neoplasia in patients with inflammatory bowel disease (IBD). We examined the association between colorectal stricture and subsequent risk of colorectal neoplasia (CRN) in patients with IBD colitis undergoing colonoscopic surveillance. METHODS:We conducted a retrospective cohort analysis of patients with IBD colitis enrolled in colonoscopic surveillance for CRN at an academic medical center between 2005 and 2017. Inclusion criteria were IBD involving the colon for ≥8 years (or any duration with primary sclerosing cholangitis [PSC]) undergoing surveillance. Exclusion criteria were advanced CRN (ACRN; colorectal cancer [CRC] or high-grade dysplasia [HGD]) prior to or at enrollment, prior colectomy, or limited (<30%) disease extent or proctitis. Multivariable logistic and Cox regression analysis estimated the association between colorectal stricture on the index colonoscopy and ACRN, CRN (indefinite dysplasia, low-grade dysplasia, HGD, CRC), or colectomy. RESULTS:Among 789 patients with IBD undergoing CRC surveillance, 72 (9%; 70 with Crohn's colitis) had a colorectal stricture on index colonoscopy. There was no significant difference in the frequency of ACRN or requirement for colectomy between patients with vs without a colorectal stricture (P > .05). Colorectal stricture was not associated with subsequent ACRN (adjusted odds ratio [aOR], 1.41; 95% CI, 0.49-4.07), CRN (aOR, 1.15; 95% CI, 0.51-2.58), or colectomy (aOR, 1.10; 95% CI, 0.65-1.84). CONCLUSIONS:In this analysis of patients with IBD colitis undergoing CRN surveillance, the presence of a colorectal stricture was not independently associated with risk of ACRN or colectomy. Multicenter, prospective studies are needed to confirm these findings, particularly in patients with ulcerative colitis-associated colorectal stricture.

BACKGROUND & AIMS/OBJECTIVE:Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS:This was a multicenter cross-sectional study performed at 5 academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected, and the Inflammatory Bowel Disease Disability Index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI ≥35) were assessed in univariable and multivariable models. RESULTS:A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared with patients with medically managed UC (29.8 vs 17.9; P < .001). When stratified by disease activity, patients with active IPAA disease had significantly greater median IBD-DI scores compared with patients with active UC (44.2 vs 30.4; P = .01), and patients with inactive IPAA disease had significantly greater median IBD-DI scores compared with patients with inactive UC (23.1 vs 12.5; P < .001). Moderate-severe disability in patients with IPAA was associated with female sex, active disease, and public insurance. CONCLUSIONS:Patients with IPAA have higher disability scores than patients with UC, even after adjustment for disease activity. Female sex and public insurance are predictive of significant disability in patients with IPAA.

Gastrointestinal effects associated with Coronavirus Disease 2019 (COVID-19) are highly variable for reasons that are not understood. In this study, we used intestinal organoid-derived cultures differentiated from primary human specimens as a model to examine interindividual variability. Infection of intestinal organoids derived from different donors with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid-derived monolayers. Susceptibility to infection correlated with angiotensin I converting enzyme 2 (ACE2) expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue, indicating that this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike (S) protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.

The Th17 cell-lineage-defining cytokine IL-17A contributes to host defense and inflammatory disease by coordinating multicellular immune responses. The IL-17 receptor (IL-17RA) is expressed by diverse intestinal cell types, and therapies targeting IL-17A induce adverse intestinal events, suggesting additional tissue-specific functions. Here, we used multiple conditional deletion models to identify a role for IL-17A in secretory epithelial cell differentiation in the gut. Paneth, tuft, goblet, and enteroendocrine cell numbers were dependent on IL-17A-mediated induction of the transcription factor ATOH1 in Lgr5⁺ intestinal epithelial stem cells. Although dispensable at steady state, IL-17RA signaling in ATOH1⁺ cells was required to regenerate secretory cells following injury. Finally, IL-17A stimulation of human-derived intestinal organoids that were locked into a cystic immature state induced ATOH1 expression and rescued secretory cell differentiation. Our data suggest that the cross talk between immune cells and stem cells regulates secretory cell lineage commitment and the integrity of the mucosa.

BACKGROUND AND AIMS/OBJECTIVE:Thirty percent of inflammatory bowel disease (IBD) patients hospitalized with flare require salvage therapy or surgery. Additionally, 40% experience length of stay (LOS) > 7 days. No emergency department (ED)-based indices exist to predict these adverse outcomes at admission for IBD flare. We examined whether clinical, laboratory, and endoscopic markers at presentation predicted prolonged LOS, inpatient colectomy, or salvage therapy in IBD patients admitted with flare. METHODS:Patients with ulcerative colitis (UC) or colonic involvement of Crohn's disease (CD) hospitalized with flare and tested for Clostridioides difficile infection (CDI) between 2010 and 2020 at two urban academic centers were studied. The primary outcome was complex hospitalization, defined as: LOS > 7 days, inpatient colectomy, or inpatient infliximab or cyclosporine. A nested k-fold cross-validation identified predictive factors of complex hospitalization. RESULTS:Of 164 IBD admissions, 34% (56) were complex. Predictive factors included: tachycardia in ED triage (odds ratio [OR] 3.35; confidence interval [CI] 1.79-4.91), hypotension in ED triage (3.45; 1.79-5.11), hypoalbuminemia at presentation (2.54; 1.15-3.93), CDI (2.62; 1.02-4.22), and endoscopic colitis (4.75; 1.75-5.15). An ED presentation score utilizing tachycardia and hypoalbuminemia predicted complex hospitalization (area under curve 0.744; CI 0.671-0.816). Forty-four of 48 (91.7%) patients with a presentation score of 0 (heart rate < 99 and albumin ≥ 3.4 g/dL) had noncomplex hospitalization. CONCLUSIONS:Over 90% of IBD patients hospitalized with flare with an ED presentation score of 0 did not require salvage therapy, inpatient colectomy, or experience prolonged LOS. A simple ED-based score may provide prognosis at a juncture of uncertainty in patient care.

BACKGROUND:Obesity is associated with increased risk for death in most infections but has not been studied as a risk factor for mortality in Clostridioides difficile infection (CDI). This study tested obesity as a risk factor for death in patients hospitalized with CDI. This was a three-center retrospective study that included hospitalized adults with CDI at Columbia University Irving Medical Center, Brigham and Women's Hospital, and NYU Langone from 2010 to 2018. Multivariate logistic regression was used to assess the relationship between obesity, measured by body mass index, and death from any cause within 30 days after the index CDI test. RESULTS:Data for 3851 patients were analyzed, including 373 (9.7%) who died within 30 days following a diagnosis of CDI. After adjusting for other factors, BMI was not associated with increased risk for death in any BMI category [adjusted OR (aOR) 0.96, 95% CI 0.69 to 1.34 for BMI > 30 vs BMI 20-30; aOR 1.02, 95% CI 0.53 to 1.87 for BMI > 40 vs BMI 20-30]. After stratifying into three groups by age, there were trends towards increased mortality with obesity in the middle-aged (56-75 vs ≤ 55 years old) yet decreased mortality with obesity in the old (> 75 vs ≤ 55) (p = NS for all). Advanced age and low albumin were the factors most strongly associated with death. CONCLUSIONS:We found no association between obesity and death among patients with CDI, in contrast to most other infections. Obesity is not likely to be useful for risk-stratifying hospitalized patients with CDI.