Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized during pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing (scRNA-seq). METHODS:We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n=15) and without an ileal pouch-anal anastomosis (n=11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches. RESULTS:In addition to tissue-specific signatures, we identified a population of IL1B/LYZ+ myeloid cells and FOXP3/BATF+ T cells that distinguish inflamed tissues which we further validated in other single cell RNA-seq datasets from IBD patients. Cell type specific transcriptional markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated myeloid cells expressing IL1B and S100A8/A9 calprotectin as interacting with stromal cells, and Bacteroidiales and Clostridiales bacterial taxa. We found that non-responsiveness to anti-integrin biologic therapies in ulcerative colitis patients was associated with the signature of IL1B+/LYZ+ myeloid cells in a subset of patients. CONCLUSIONS:Features of intestinal inflammation during pouchitis and ulcerative colitis are similar, which may have clinical implications for the management of pouchitis. scRNA-seq enables meta-analysis of multiple studies, which may facilitate the identification of biomarkers to personalize therapy for IBD patients.

BACKGROUND:Inflammatory bowel disease (IBD) patients who have Clostridioides difficile infection (CDI) have worse outcomes. AIMS/OBJECTIVE:We aimed to determine whether such outcomes are the result of CDI or whether CDI occurs in patients who have more severe IBD. METHODS:This was a retrospective study of patients hospitalized for ≥ 2 IBD flares from 2010 to 2019. The primary outcome was time to IBD flare between hospitalizations. First, time to flare was compared between patients who were hospitalized for a flare complicated by CDI and subsequently for a CDI-negative flare (cohort A, denoted +/-) versus patients who were hospitalized for two CDI-negative flares (cohort B, -/-). Second, time between flares was compared within the subset of cohort A patients who had three flares (cohort C, -/+/-) before and after CDI. RESULTS:Time between flares was a median of 4 months (IQR 1-9) among 51 cohort A patients versus 12 months (IQR 6-38) among 51 cohort B patients (log-rank P < 0.01). In contrast, the median time between flares was similar within cohort C before and after CDI (log-rank P = 0.54). At time of the second IBD flare, patients in cohort A (+/-) were more likely to have moderate or severe disease compared to patients in cohort B (-/-). CONCLUSIONS:Patients with prior CDI had shorter time to subsequent IBD flare relative to their CDI-negative counterparts. This is not likely due to CDI itself because there was no difference in time between flares before versus after acquiring CDI. Rather, patients who acquire CDI may have more severe IBD.

BACKGROUND:Sacroiliitis is an inflammatory arthritis of the sacroiliac joints and is associated with inflammatory bowel disease (IBD). Yet, sacroiliitis often goes undiagnosed in IBD, and the clinical association between IBD disease activity and sacroiliitis is not well established. Patients with Crohn's disease (CD) often receive magnetic resonance enterography (MRE) to assess disease activity, affording clinicians the opportunity to evaluate for the presence of sacroiliitis. We aimed to identify the prevalence and disease characteristics associated with sacroiliitis in CD patients undergoing MRE. METHODS:All CD patients undergoing MRE for any indication between 2014 and 2018 at an IBD referral center were identified. The MREs were reviewed for the presence of sacroiliitis based on bone marrow edema (BME) and structural lesions. We analyzed demographics, IBD characteristics, clinical and endoscopic disease activity, and management between CD patients with and without sacroiliitis. RESULTS:Two hundred fifty-eight patients with CD underwent MRE during the study period. Overall, 17% of patients had MR evidence of sacroiliitis, of whom 73% demonstrated bone marrow edema. Female gender, back pain, and later age of CD diagnosis were associated with sacroiliitis (P = 0.05, P < 0.001, P = 0.04, respectively). Disease location and CD therapy were not associated with sacroiliitis on MRE. Clinical, endoscopic, and radiographic disease activity were not associated with sacroiliitis on MRE. CONCLUSION/CONCLUSIONS:Sacroiliitis is a common comorbid condition in CD. With limited clinical clues and disease characteristics to suggest sacroiliitis, physicians may utilize MRE to identify sacroiliitis, especially in CD patients with back pain.

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