Faculty Bibliography

Background: Ozanimod, a sphingosine, 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in multiple countries for the treatment of relapsing multiple sclerosis and in the United States for the treatment of moderately to severely active Ulcerative Colitis (UC). A treat-to-target strategy for Inflammatory Bowel Disease (IBD) has been outlined in the Selecting Therapeutic Targets in IBD (STRIDE-II) consensus recommendations. Mucosal healing was identified as an important treatment target and may be associated with improved patient (pt) outcomes. Here we assess the relationship between early mucosal healing at week (wk), 10 and clinical outcomes at wk, 52 in ozanimod-treated pts with moderately to severely active UC in the phase, 3 True North trial (NCT02435992).
Method(s): A subset of pts in True North were randomised to and/or received oral ozanimod, 0.92 mg (equivalent to ozanimod HCl, 1 mg) during the, 10-wk induction period, achieved clinical response at wk, 10 and continued ozanimod during the maintenance period. For this post hoc analysis, we examined clinical remission, corticosteroid (CS)-free remission, and mucosal healing at wk, 52 in pts with versus without mucosal healing at wk, 10. Clinical remission was defined as rectal bleeding subscore = 0, stool frequency subscore <=1 (and >=1-point reduction from baseline), and mucosal endoscopy subscore (MES) <=1 without friability. CS-free remission was defined as remission with no CS use for >=12 wk. Mucosal healing was defined as MES <=1 without friability and a Geboes score <2.0.
Result(s): Demographics and disease characteristics were generally well balanced between ozanimod-treated pts with (n=44) and without (n=186) mucosal healing at wk, 10, albeit a higher proportion of pts without mucosal healing had prior biologic exposure. Higher proportions of ozanimod-treated pts who achieved mucosal healing at wk, 10 had clinical remission, CS-free remission, and mucosal healing at wk, 52 versus pts who did not achieve mucosal healing at wk, 10 (Figure). Among the ozanimod-treated pts who did not achieve mucosal healing at wk, 10, 24.2% went on to achieve mucosal healing at wk 52.
Conclusion(s): Using a novel, stringent definition for mucosal healing, which requires endoscopic improvement and histologic remission (Geboes <2.0), ozanimod-treated pts who achieved mucosal healing at wk, 10 had improved clinical, endoscopic, and histologic outcomes at wk, 52. A proportion of pts who did not reach mucosal healing at wk, 10 benefited from longer ozanimod treatment, achieving mucosal healing at wk 52. (Figure Presented)

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: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.

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.

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 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.

Introduction: Inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases characterized by dysregulation of the immune system. Evidence suggests that they share a common genetic and pathophysiologic pathway and that the presence of one increases the risk of developing others. While rates of PsO and PsA are increased in patients with IBD, data is lacking regarding whether phenotypic differences exist in patients with concurrent disease. In this study, we describe the disease characteristics of patients with IBD and PsO/PsA overlap.
Method(s): We performed a single-center case-control observational study. Eighty-five patients with IBD and PsO and/or PsA were identified and matched with a control group of patients with IBD alone in a 1:2 fashion based on age, sex and IBD type (n=190). Patient demographics, IBD phenotype and history, treatment patterns, and family history were collected.
Result(s): We identified 85 patients with IBD and PsO +/-PsA, matched with 190 controls. IBD 1 PsO/PsA patients were less frequently White (85% vs. 94%) and more frequently Asian (7% vs. 3%), compared with IBD only patients (P, 0.01, Table 1). There were no differences in extent of ulcerative colitis (UC) or distribution of Crohn's disease (CD), but patients with IBD alone were more likely to have penetrating Crohn's disease (48% vs. 7%; P, 0.01), prior hospitalizations (48% vs. 28%; P, 0.01), and prior surgeries (35% vs. 17%; P=0.02), compared to patients with overlap PsO +/-PsA. Rates of exposure to various biologic therapies were similar between the two groups, with the exception of decreased vedolizumab use in the IBD 1 PsO/PsA group (12% vs. 31% respectively; P, 0.01, Table 2). IBD only patients were more likely to have first-degree relatives (FDR) with IBD (35% vs. 23%; P=0.02) and numerically less likely to have a FDR with PsO or PsA (14% vs. 20%; P=0.21) than patients with PsO/PsA overlap (Table 1).
Conclusion(s): In this study, we report for the first time disease characteristics of patients with IBD and overlap PsO or PsA. Our results suggests that patients with IBD and PsO/PsA may have a less severe disease phenotype than patients with IBD alone, and that genetic risks may differ between these two groups. Further prospective studies are needed to confirm these findings

Introduction: Health disparities in health care utilization and clinical outcomes are strongly linked to race, ethnicity, socioeconomic, and insurance status in many diseases. We aimed to measure racial and socioeconomic disparities in inflammatory bowel disease (IBD) care including disease characteristics, treatment, health care utilization, and clinical outcomes.
Method(s): We performed a retrospective chart review of patients 18 years and older with established IBD care at a private or public hospital in New York City. Established care was defined as having at least 1 colonoscopy and 1 clinic visit within the same hospital. Patient demographics, disease characteristics, and outcomes were collected. Multivariate logistic regression was performed and reported as odds ratios (OR) with 95% confidence intervals (CI).
Result(s): A total of 322 patients, 50% from each hospital, were included in the analysis. Public hospital IBD patients were more likely to have Medicaid and visit the ED (17% vs 6%, OR 5.3, CI 2.1-14, and 41% vs. 11%, OR 4.0, 1.5-11,) compared to private hospital patients. Focusing on race, Black IBD patients were more likely to be hospitalized (36%, OR 7.6 CI 1.0-161) compared to other races. In terms of insurance, Medicare patients were more likely to be hospitalized and require surgery (28%, OR 4.9 CI 1.1-22 and 16%, OR 14, CI 1.7-120) compared to uninsured patients or those with Medicaid or private insurance. Unemployed IBD patients had higher rates of surgery (18% vs. 9%, OR 3.6, CI 1.2-10). CD patients who were unemployed had higher rates of prolonged steroid use, ED visits, and hospitalizations (OR 8.5, CI 1.2-79, OR 14, CI 1.7-173, OR 15, 1.9-191) compared to employed CD patients. UC patients with Medicaid were more likely to be hospitalized (OR 3.6, 1.0-14) compared to uninsured patients or those with Medicaid or private insurance. UC patients with private insurance were more likely to achieve mucosal healing (OR 5.3, 1.1-31) compared to uninsured patients or those with Medicaid or Medicare.
Conclusion(s): Race, employment, and insurance status were linked with disparities in IBD care. Public hospital use, Black race, unemployment, and non-private insurance were associated with various adverse IBD outcomes including increased ED visits, hospitalizations, requirement for surgery, prolonged steroid use, and decreased rates of mucosal healing. Future work should focus on identifying interventions to resolve disparities for these patient populations

Introduction: The etiology of acute diarrhea in solid organ transplant (SOT) recipients requires rapid diagnosis to avoid severe infection or graft loss, especially for those requiring hospitalization. We aimed to characterize factors associated with hospitalization for enteric infection as detected by multiplex gastrointestinal PCR panel (GI panel) stool testing in SOT recipients.
Method(s): We performed a cross-sectional study at two academic institutions of inpatient and outpatient SOT recipients who underwent stool testing over 3 years with a FilmArray GI panel during an acute episode of diarrhea. A multivariate analysis was performed to identify factors predictive of hospitalization.
Result(s): Of 300 SOT recipients with an acute episode of diarrhea, 68% (n=204) were hospitalized at the time of sample collection (Table 1). On univariate analysis, hospitalized patients were less likely to have a pathogen identified on the GI panel compared to non-hospitalized patients (33% vs 53%, p, 0.001) - specifically, fewer viral enteric infections (14% vs 27%, P=0.007). Hospitalized patients were more likely to have fever (29% vs 6.3%, p< 0.001) and had a higher 30-day mortality than those not hospitalized (16.9% vs 4.2%; P=0.002). The number of immunosuppressive agents was not associated with hospitalization (P=0.913). In the multivariate analysis adjusting for age, sex, race, Charlson's comorbidity index, antimicrobial prophylaxis, recent hospitalization, transplant type, degree of immunosuppression, and transplant age, fever (odds ratio [OR] 6.8; 95% confidence interval [CI] 2.9- 19), nausea/vomiting (OR 2.5; 95% CI 1.2-5.4) and negative GI panel (OR 2.0; 95% CI 1.1-3.7) were associated with hospitalization. Compared to other organs, renal transplant (OR 0.318, 95% CI 0.133- 0.723) was associated with lower likelihood of hospitalization.
Conclusion(s): In SOT recipients presenting with acute diarrhea, symptoms of severe illness, such as fever and emesis, and a negative GI Panel, were associated with hospitalization. Renal transplant was inversely associated with hospitalization. Diarrheal illness in SOT patients may be caused by pathogens not identified on the GI panel or from non-infectious causes such as immunosuppressive, antimicrobial, or bowel regimen medications. Further elucidation of these non-infectious diarrheal etiologies in SOT recipients hospitalized for acute diarrhea may potentially avoid major complications, such as graft loss, severe infection, and death.