Faculty Bibliography

BACKGROUND:We aimed to characterize patients with inflammatory bowel disease (IBD) and novel coronavirus disease 2019 (COVID-19). METHODS:We performed a case series of patients with IBD and confirmed or highly suspected COVID-19 to assess rates of severe outcomes. RESULTS:We identified 83 patients with IBD with confirmed (54%) or highly suspected (46%) COVID-19. The overall hospitalization rate was 6%, generally comprising patients with active Crohn's disease or older men with comorbidities, and 1 patient expired. DISCUSSION/CONCLUSIONS:In this series of patients with IBD, severe outcomes of COVID-19 were rare and comparable to similarly aged individuals in the general population.

OBJECTIVE:Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN/METHODS:In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs). RESULTS:We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32). CONCLUSION/CONCLUSIONS:SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

Background: This study evaluated the prevalence of adjunctive pharmacotherapies use among ileal pouch-anal anastomosis (IPAA) patients. Methods: The IBD Partners database was queried to compare IPAA patients with and without pouch-related symptoms (PRS). Within the cohort of patients with PRS, patient reported outcomes were compared among opioid, nonsteroidal anti-inflammatory drug (NSAID), and probiotic users. Results: There were no differences in patient reported outcomes based on NSAID or probiotic usage. Opioid users reported increased bowel frequency, urgency, poor general well-being, abdominal pain, and depression (P < 0.05 for all variables). Conclusions: In IPAA patients with PRS, opioid use, but not NSAIDs or probiotics, was associated with a higher burden of PRS.

INTRODUCTION: Hospitalization for flare of inflammatory bowel disease (IBD) is associated with significant morbidity and healthcare costs. We aimed to examine the relationship between IBD severity at presentation and adverse outcomes in patients hospitalized with flare. Additionally, we aimed to create and validate a predictive model for length of stay (LOS) using markers of disease severity.
METHOD(S): We conducted a retrospective cohort study of IBD patients hospitalized with flare at two urban academic medical centers. We collected demographic and IBD-related data including the presence of Clostridioides difficile and markers of disease severity at presentation. The primary outcome was a composite of adverse inpatient IBD outcomes, including LOS >7 days, anti-TNF administration, and surgery. The data was split into training (70%) and validation (30%) samples. Employing variables of disease severity, models (including logistic regression, Classification and Regression Tree (CART), and Random Forest (RF) modeling techniques) were created to predict LOS >7 days using the training sample. These models were adjusted for surgery and anti-TNF administration, and their performance was subsequently validated.
RESULT(S): A total of 187 IBD patients hospitalized with flare were included (Table 1). The composite primary outcome was achieved in 71 patients (38%) with 51 (27%) hospitalized for >7 days. In univariate analyses, C-reactive protein and C. difficile positivity correlated with anti-TNF administration and surgery (Table 2). Adjusting for anti-TNF administration and surgery, tachycardia (OR 1.07; 95% CI 1.05-1.10), hypotension (1.07; 1.03-1.11), hypoalbuminemia (2.87; 1.81-4.74), leukocytosis (1.17; 1.09-1.27), anemia (1.10; 1.05-1.15) and C. difficile posi-tivity (2.63; 1.27-5.47) were predictive of prolonged LOS (Table 2). In multivariate analyses, tachycardia predicted the primary composite outcome of all adverse effects (OR 1.07; 95% CI 1.03-1.11). C. difficile positivity (OR 4.33; 95% CI 1.36-14.9), hypoalbuminemia (3.25; 1.29-9.01), and tachycardia (1.11; 1.06-1.16) predicted prolonged LOS (.7 days). The CART and RF models had acceptable accuracy, sensitivity, and specificity for predicting LOS >7 days (Table 3).
CONCLUSION(S): C. difficile positivity, hypoalbuminemia, and tachycardia at presentation predicted prolonged length of stay in a multicenter cohort of IBD patients hospitalized with flare. CART and Random Forest models perform well in predicting prolonged length of stay in these patients

INTRODUCTION: Current guidelines recommend preoperative risk stratification to guide postoperative prophylactic biologic therapy for the prevention of Crohn's disease (CD) recurrence1. Few data have corroborated the quantified risk of postoperative recurrence (POR) and validated the proposed risk stratification. We aimed to assess the impact of biologic therapy on POR based on guideline-recommended risk stratification.
METHOD(S): CD patients who underwent an ileocolic resection from 1992-2019 were identified at two tertiary referral centers. Patients were stratified into cohorts with high-risk features (smoking, age < 30 years, and >=2 prior surgeries) and low-risk features (nonsmokers, age >50 years, resection length < 10 cm, and disease duration < 10 years). POR, defined as endoscopic (Rutgeerts . i1) or radiographic evidence of disease at least >6 months after surgery, was compared between groups. Recurrence-free survival analysis using Cox proportional hazard modeling and Kaplan-Meier curves were used to estimate POR and the impact of biologic prophylaxis.
RESULT(S): A total of 950 patients with ileocolic resection for CD were included (mean age 37.9, 47%): 785 (82.6%) high-risk and 165 (17.4%) low-risk patients. In the high-risk group, the majority (58.2%) received biologic prophylaxis (43.4% anti-TNF, 7.1% vedolizumab, and 7.8% ustekinumab) while 41.8% had no therapy. In contrast, 60% of low-risk patients had no therapy while 40% received biologic prophylaxis (32.7% anti-TNF, 8% vedolizumab, and 2.4% ustekinumab). In the high-risk group, biologic prophylaxis was significantly associated with earlier POR compared to no therapy (P < 0.001). In the low-risk group, there was no significant difference between biologic and no therapy in time to POR (P = 0.10; Figure 1). When assessing specific risk factors on multivariable analysis, >=2 prior surgeries was the only independent risk factor for POR (P < 0.05) (Table 1).
CONCLUSION(S): The risk stratification proposed for POR in current guidelines may have limited utility in predicting disease recurrence. Low-risk individuals are unlikely to benefit from postoperative biologic prophylaxis. Multiple prior surgeries is the strongest risk factor for POR and these patients may benefit from postoperative biologic prophylaxis

INTRODUCTION: The outbreak of novel severe acute respiratory virus syndrome coronavirus 2 (SARS-CoV 2), the causative virus of coronavirus disease 2019 (COVID-19), has become a global pandemic. In the United States, cases exceed 2 million, with the New York City (NYC) metropolitan area at the epicenter. Patients with inflammatory bowel disease (IBD) are generally considered higher risk of infection due to immunosuppressive therapies, however, data are lacking regarding outcomes of COVID-19 in patients with IBD compared to the general population. We aim to investigate the impact of IBD on COVID-19 outcomes.
METHOD(S): We prospectively collected data on all patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] with confirmed or highly suspected COVID-19 (fever and/or close contact plus respiratory symptoms) and all non-IBD patients with confirmed COVID-19 from March 3 to May 10, 2020 at an academic medical center in NYC. Patient demographics, co-morbidities, and medication history were recorded. The endpoints were severe outcomes of COVID-19, including hospitalization, ventilator requirement, ICU admission and death. Adjusted analyses were performed for predictors of a composite endpoint of ventilator, ICU and death.
RESULT(S): We identified 83 patients with IBD [CD (n = 56, 67%) or UC (n = 27, 33%)] with confirmed or suspected COVID-19 and 8277 non-IBD patients with confirmed COVID-19 (Table 1). IBD patients had a lower median age (34 vs. 53 years; P < 0.001) and a higher proportion of Caucasians (69% vs. 41%; P < 0.001). IBD patients were less likely to have any co-morbidity (29% vs. 52%; P < 0.001), and had higher rates of immunomodulator (IMM) or biologic use. IBD patients with confirmed COVID-19 had lower rates of hospitalizations (14% vs. 51%; P < 0.001) and ICU admissions (2% vs. 13%; P = 0.04; Table 2). On multivariable analysis restricted to confirmed COVID-19, the presence of IBD was not associated with severe outcomes (OR 0.55, 95% CI 0.12-2.44, P = 0.43). Age, male gender, number of comorbidities, thiopurine and steroid use were significant predictors of severe COVID-19 outcomes, while TNF-antagonists had a protective effect (Table 3).
CONCLUSION(S): In this large cohort study, IBD was not a risk factor for severe outcomes of COVID-19. Age, co-morbidities, and exposure to thiopurines and steroids were associated with severe outcomes of COVID-19. TNF-antagonists may be protective from severe outcomes of COVID-19, but this requires further study

INTRODUCTION: Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on the effectiveness and safety in the real world are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from two US tertiary IBD centers.
METHOD(S): Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Medical Center (New York, NY) and University of Chicago Medical Center (Chicago, IL) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of 2, with a combined rectal bleeding and stool frequency subscore of #1.
RESULT(S): Sixty-six UC patients were included (Table 1). 61% of patients had extensive colitis and overall mean total Mayo score was 6.5 +/- 2.4. 92% of patients had prior exposure to biologics or tofacitinib. 43% and 45% of patients achieved clinical remission by 3 and 12 months, respectively (Figure 1). Anti-TNF non-response and endoscopic Mayo score of 3 were negative predictors of clinical remission at 3 months (Table 2). At 1 year, 50% of patients achieved endoscopic remission and 33% achieved mucosal and histo-endoscopic healing. The achievement of histo-endoscopic healing was significantly associated with lower partial Mayo score (0.5 +/- 0.6 vs. 3.5 +/- 1.7; P < 0.01) and lower stool frequency (0.3 +/- 0.5 vs. 1.4 +/- 0.7; P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis).
CONCLUSION(S): In this cohort of mostly biologic-refractory UC patients, treatment with usteki-numab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis (UC), indeterminate colitis (IC), or familial adenomatous polyposis syndrome (FAP). Tobacco smoking has been associated with protection from onset of UC. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. In this systematic review and meta-analysis, we examine the influence of smoking on the risk of pouchitis.
METHOD(S): We identified 16 studies evaluating smoking as a risk factor for developing pouchitis in patients with a history of IPAA in a systematic search performed from inception through May 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios.
RESULT(S): A total of 2,389 IPAA patients were included in the systematic review and meta-analysis. In the included studies, the percentage of patients with a diagnosis of pouchitis ranged from 22% to 72%. The percentage of patients with a history of smoking ranged from 7% to 63%. In total, 919 patients had pouchitis (330 current or former smokers; 589 non-smokers), and 1,470 patients did not have pouchitis (485 current or former smokers; 985 non-smokers). A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR = 0.96, 95% CI 0.78-1.17, I² 5 68.6%). There was also no significant risk of pouchitis when comparing current smokers versus non-smokers (RR = 1.09, 95% CI 0.93-1.28, I² 5 0%) and former smokers versus non-smokers (RR = 0.95, 95% CI 0.70-1.28, I² 5 79.8%).
CONCLUSION(S): Smoking, past or present, is not associated with an increased risk for the development of pouchitis. This is important to consider when counseling patients on the risks of smoking and pouchitis

INTRODUCTION: Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time to C. difficile PCR test order, collection, and result with adverse IBD outcomes.
METHOD(S): We performed a retrospective cohort study of IBD patients hospitalized with flare through the emergency department (ED) between 2013 and January 2020 at an urban academic medical center. The time from ED presentation to CDI test order (time-to-order), sample collection (time-to-collection), and test result (time-to-result) were collected. Time-to-result was stratified by within+/-hours, 6-24 hours, and 24 hours or longer. The primary outcome was length of stay (LOS). Secondary outcomes were inpatient anti-TNF administration and surgery. Separately, we used initial hemodynamic and laboratory values to create an IBD hospitalization severity score for evaluation against LOS and time-dependent variables.
RESULT(S): We identified 122 IBD patients hospitalized with flare. There were no significant differences in baseline characteristics among time-to-result groups. There was no difference in time-toorder between the+/-hours and 6-24 hours groups (Table 1). Despite a shorter time-to-result, the average LOS in the+/-hours group was 7.3 days, longer compared to the 6-24 hours group (4.3 days, P=0.018) and the 24 hours group (4.2 days, P=0.035Table 1). There were no differences in inpatient anti-TNF administration (P=0.10) or surgery (P=0.08) among time-to-result groups. Markers of disease severity correlated with longer LOS and earlier time-to-result (Table 2). A composite of these markers was used to stratify patients by disease severity. Those with more severe disease had earlier times-to-result (12.8 hours vs. 32.2 hours, P=0.014) and had a longer LOS (7.9 vs. 3.4 days, P=0.007) with no difference in time-to-order compared to patients with less severe disease (P=0.09Table 3).
CONCLUSION(S): Earlier time-to-result for CDI is associated with longer LOS in IBD patients hospitalized with flare. This inverse relationship is confounded by disease severity at presentation. Patients with more severe disease have a shorter time-to-result and a longer LOS without any difference in time-to-order. Delay in testing was not associated with higher rates of inpatient anti- TNF administration or surgery