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Abstract Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for refractory or complicated ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Pouchitis is the most common complication of this procedure and can occur in about 50% of patients. Treatment of pouchitis depends on the phenotype of disease. Pouchitis can be classified as acute, chronic/refractory, or secondary pouchitis, which includes pouchitis occurring due to Crohn's disease (CD). CD of the pouch is becoming an increasingly recognized problem, and management is challenging. This article reviews the literature and offers treatment recommendations regarding management of pouchitis and CD of the pouch.

Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD), and treatment depends on disease activity assessment requiring invasive procedures. We aimed to identify serum cytokines/chemokines that differ between CD and controls, and by clinical, endoscopic, and histologic disease activity. Serum samples were obtained from 103 CD to 40 non-IBD controls undergoing colonoscopy. Clinical information was obtained by questionnaire and chart review. Disease activity was determined: clinically (Crohn’s Disease Activity Index), endoscopically (Simple Endoscopic Score for Crohn’s Disease), and histologically from colonoscopic biopsies. Cytokines/chemokines were measured by Luminex assay and compared by disease activity assessments (control vs. inactive vs. active), with adjustment for multiple comparisons. Correlation between activity indices and versus analytes were performed. Multiple analytes were significantly altered between clinically, endoscopically, and histologically inactive and active CD vs. control. One analyte, CXCL9, was significantly increased in active vs. inactive CD in endoscopic and histologic activity assessments. CXCL9 was the only analyte with a significant correlation to both SES ( r  = 0.57, q < 0.001) and histologic severity ( r  = 0.42, q < 0.001). CXCL9 had the highest discriminatory capacity for active vs. inactive disease both endoscopically (AUC = 0.76, 95% CI 0.65–0.87) and histologically (AUC = 0.79, 95% CI 0.70–0.88). Cytokine/chemokine profiling differentiated CD vs. controls and by disease activity, with CXCL9 as a potential marker distinguishing activity in endoscopic and histologic assessments. Serum cytokine/chemokine profiling may be a non-invasive strategy to assess disease activity in CD.

Crohn’s disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as ‘LND’) with high expression of LCN2 , NOS2 , and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn’s ileitis and colitis. Crohn’s disease (CD) is a complex disease associated with immune dysregulation. Here the authors use multimodal data to identify and characterize an epithelial cell population, termed ‘LND’ cells, in both terminal ileum and ascending colon, with LND interacting locally with immune cells and potentially contributing to CD pathology.

BackgroundVedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population.AimsHere, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD.MethodsThis retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes.Results212 cases were identified—108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p < 0.001).ConclusionsIn a cohort of IBD patients over age 60, vedolizumab showed no statistically significant differences in infection, hospitalization, or surgical intervention-free survival as compared to anti-TNF. Vedolizumab was discontinued less frequently than anti-TNF. Patients on vedolizumab had higher rates of endoscopic remission and response.

BackgroundStudies suggest that there is a temporal relationship between depression and Crohn’s disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression–CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective–cognitive dimension of depression.MethodsWe studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective–cognitive index of depression. Crohn’s disease status and the affective–cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data.ResultsThe results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective–cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse.ConclusionsThe hypothesis that an affective–cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.