Inflammatory Bowel Diseases最新文献

Background: Iron deficiency anemia (IDA) is the most common extra-intestinal complication in inflammatory bowel disease (IBD). The persistence of iron deficiency in patients living with quiescent IBD remains poorly understood. Given the extensive body of research linking IBD pathogenesis to microbiome disruptions, it is hypothesized that alterations in the microbiota or immune responses may drive the persistence of IDA in quiescent Crohn's disease. This study aimed to determine whether changes in the gut microbiota or immune phenotypes contribute to IDA, while uncovering potential mechanisms driving IDA in quiescent disease.

Methods: This cross-sectional, descriptive, and analytical study utilized 141 samples from pediatric Crohn's disease patients with and without iron deficiency as well as healthy controls for initial 16S microbiome analysis and a smaller subset for Shotgun Metagenomics and immunologic analyses. Fecal and peripheral blood samples were obtained from the Jill Roberts Institute Live Cell Bank.

Results: While no major differences were observed in the overall gut microbiome composition between pediatric patients with quiescent Crohn's disease, with or without IDA, notable shifts in specific microbial strains were identified. Specifically, levels of Anaerobutyricum soehngenii and Alistipes shahii were significantly altered. Metagenomic analysis revealed an enrichment of pathways related to short-chain fatty acid metabolism and ascorbate degradation, indicative of functional change in these microbes.

Conclusions: This is the first comprehensive microbiome analysis of quiescent pediatric Crohn's disease with concomitant IDA. The findings indicate modest but significant microbial strain-level differences and associated functional pathways, potentially implicating microbiota-mediated mechanisms in the persistence of IDA.

Background and aims: Progressive Crohn's disease (CD) often requires early initiation of biologic or immunomodulator therapy for disease management. However, some patients may have a milder disease course that may be managed with a less aggressive strategy. Our study aims to determine cross-sectional radiographic features that predict progression of CD.

Methods: This was a multi-institution, retrospective cohort of adult CD patients without prior immunomodulator or biologic use, prior surgery, or CD-related hospitalization, who underwent abdominal cross-sectional imaging prior to 2018. Index cross-sectional imaging was reviewed by 2 radiologists who extracted 37 features pertaining to the intestine, mesentery, or extra-luminal complications. The primary outcome was composite progression of disease defined as initiation of an immunomodulator or biologic agent, surgical intestinal resection, or CD-related hospitalization.

Results: Our study included 177 CD patients who underwent cross-sectional imaging (81% CT). 81 patients (45.8%) experienced composite progression of disease. On multivariable regression, small bowel wall thickening >5 mm (aOR 8.59; P < .001), distal colonic inflammation (aOR 3.95; P = .03), and segmental mural hyperenhancement (aOR 2.44; P = .04) were independently associated with progression of disease. Absence of radiologic features identified a subgroup with a low rate (13.7%) of disease progression.

Conclusions: Cross-sectional imaging can be used to identify patients with mild CD who are at higher risk for progression. Absence of these features may identify mild CD requiring less aggressive treatment strategies and define a population eligible for trials of management strategies for mild CD.

Background: Statins may have anti-inflammatory activity in inflammatory bowel disease (IBD). We aimed to investigate any impact of statins on disease progression in moderate-to-severe IBD.

Methods: We conducted a retrospective cohort study of patients with moderate-to-severe IBD and at least 2 outpatient visits between 2000 and 2023 at a large, urban hospital system. Using the Mount Sinai Data Warehouse, we collected data on biologic, small molecule, or immunomodulator use for IBD, cardiovascular (CV) medications, and International Classification of Diseases codes designating IBD hospitalizations and surgeries. Our primary outcome was IBD-related surgery in statin users and nonusers, adjusting for IBD and CV risk. Our secondary outcomes were IBD-related hospitalization, advanced therapy persistence, and time to IBD surgery. Multivariable regression analyses and propensity score matching were used to adjust for relevant clinical variables. Cox regression analysis assessed time to surgery in statin users versus nonusers.

Results: We identified 2421 patients with moderate-to-severe IBD who had longitudinal outpatient follow-up: 375 statin users and 2046 nonusers. Statin users had fewer IBD-related surgeries (5% vs 9%; P = .007). Statin users had a trend, but no significant difference, toward fewer hospitalizations per person (0.73 hospitalizations/person among statin users and 0.93 in nonusers; P = .09), although no difference in therapy persistence was noted. Statin users had lower hazards of surgery at 16 149 patient-years of follow-up (adjusted hazard ratio, 0.47; 95% confidence interval [CI], 0.26-0.85; P = .012). Propensity-adjusted odds ratios (ORs) showed a lower risk of IBD surgery (adjusted OR, 0.51; 95% CI, 0.27-0.95; P = .034) but not of IBD hospitalization (adjusted OR, 0.91; 95% CI, 0.73-1.14; P = .424) among statin users.

Conclusions: Patients with moderate-severe IBD using statins were less likely to experience IBD-related surgery in a real-world, electronic health record-based cohort.

Background: Antibiotic use in early childhood may alter the developing microbiome and has been proposed as a risk factor for inflammatory bowel disease (IBD). We conducted a systematic review to examine the association between childhood antibiotic use and subsequent risk of IBD.

Methods: In a systematic literature search, we identified cohort and case-control studies reporting the association between antibiotic use (exposure age <1 to 17 years) and development of IBD. MEDLINE and EMBASE databases were searched from inception through December 31, 2024. Studies reporting a hazard ratio, odds ratio, or risk ratio (RR) were included. To account for heterogeneity, pooled estimates were calculated using the DerSimonian-Laird random-effects model. Estimates were adjusted for potential confounding as reported in the original studies.

Results: We identified 10 studies, of which 8 (n = 2783 cases) reported associations between childhood antibiotics and IBD risk. Additionally, 2 studies on Crohn's disease (CD) and 1 on ulcerative colitis were included in disease-specific analyses. In pooled analyses, antibiotic exposure compared with no exposure was associated with increased risk of IBD (RR, 1.42; 95% confidence interval [CI], 1.23-1.66), CD (RR, 1.59; 95% CI, 1.39-1.81), and ulcerative colitis (RR, 1.23; 95% CI, 1.08-1.40). Heterogeneity was low to moderate (I2 = 0%-35%), and funnel plots did not indicate publication bias (Egger's test, P = .12-.43). Adjustment for infections did not attenuate the association between childhood antibiotic exposure and IBD development.

Conclusions: While causal interpretation should be cautious, childhood exposure to antibiotics was associated with an increased risk of later IBD, particularly for CD.

Background: Crohn's Disease patients are often subject to repeat computed tomography (CT) upon presentation to the emergency departments (ED). Due to early age of diagnosis and increase in ED visits, they can be exposed to substantial radiation posing long term increased risk of malignancy. In this retrospective study, we assess frequency of CT scans in the ED, urgent findings on CT, and patient characteristics correlating with multiple scans. We hope to identify predictive factors for urgent findings and for negative CT scans.

Methods: Six-hundred-and-sixty previously diagnosed Crohn's patients from four gastroenterology practices presented to three hospitals between April 15, 2015 and December 31, 2018 for 2473 total encounters. Patients were identified and cross-referenced with a radiology database search generating 1778 CT scans performed. Data was analyzed for presence of findings and demographics.

Results: CT scans were performed in 72% of encounters. There was a skewed distribution of CT scans (skew = 3.30), with 41% receiving only 1 scan, 43% receiving 2-4, and 16% receiving >5; the maximum was 24 scans for 1 patient. Positive findings including obstruction, perforation, or abscess were found in 28.5% of scans. Patients with barriers to healthcare had an increased rate of ED visits and imaging findings.

Conclusions: Radiation exposure in Crohn's patients is higher than that of the general population, owing to multiple CT scans often performed acutely in the ED. Factors we assessed could not reliably predict urgent findings on CT and a significant percentage of patients had urgent findings. However, we identified a group with multiple CTs associated with barriers to healthcare.

Introduction: Real-world data regarding subcutaneous infliximab (SC-IFX) in patients with pediatric inflammatory bowel disease IBD (PIBD) is scarce. We evaluated SC-IFX as maintenance therapy in PIBD patients who switched to SC-IFX from intravenous infliximab (IV-IFX) treatment.

Methods: In this retrospective multicenter study we identified PIBD patients who switched to SC-IFX. The primary outcome was treatment persistence at up to 12 months post-switch. Secondary outcomes included relapse rate (defined as Pediatric Ulcerative Colitis Activity Index [PUCAI]  ≥10/ weighted PCDAI  ≥ 12.5 with biochemical/endoscopic evidence of disease activity), IFX trough levels, immunogenicity, safety, and acceptance.

Results: Sixty-six patients switched to SC-IFX (48% males; median switch-age, 16.5 years; IQR, 14.9-17.3 years; median switch-weight, 60 kg; range, 13-102 kg), 41/66 (62%) with Crohn Disease. Pre-switch, the median IV-IFX maintenance dose was 10 mg/kg every 6 weeks; 58/66 patients (88%) were in clinical remission. The initial SC-IFX regimen was 120 mg every other week in 62/66 patients (94%). SC-IFX persistence was 78% (95% CI, 66-91) at 12 months post-switch, with 89% of patients persisting on IFX, either intravenous (IV) or subcutaneous (SC), at the end of follow-up. Relapses were observed in 11/66 patients (17%) over a median follow-up of 11.0 months (IQR, 5.1-12.0); 6 patients underwent SC-IFX dose intensification, with 3 successfully regaining clinical response. Regarding anti-drug antibodies (ADA), 3 out of 4 patients who were ADA positive on IV-IFX resolved post-switch. Overall, 19/66 patients (29%) reported 21 adverse events (AEs), including 3/21 severe AEs. The majority (53/66 patients; 80%) expressed a positive attitude toward SC-IFX.

Conclusions: The largest documented PIBD cohort switching to SC-IFX to date showed high treatment persistence at 1 year, confirming SC-IFX as an effective and safe maintenance alternative to IV-IFX.

Background: Some patients with ulcerative colitis (UC) develop advanced liver disease due to conditions such as primary sclerosing cholangitis (PSC) and may require liver transplantation (LT). However, data on the long-term course of UC and the use of advanced therapies in LT recipients are limited. We aimed to evaluate UC activity before and after LT, as well as the role of advanced therapies over extended follow-up in this population.

Methods: This was a retrospective, multicenter cohort study including 213 patients with UC who underwent LT between 2000 and 2022. Clinical disease activity (partial Mayo score), endoscopic disease activity (Mayo endoscopic subscore), and the use of advanced therapies were evaluated before and after transplantation.

Results: Among the 213 patients, the clinical remission rate was 84.7% before and 81.2% after LT, showing no significant change (P = .416). Despite stable clinical remission, 27.9% of patients exhibited moderate-to-severe endoscopic inflammation during long-term follow-up (mean: 110 months). The use of advanced therapies increased significantly after LT (from 3.7% to 12.7%, P = .005) and was not associated with an increase in infectious complications (P = .591).

Conclusions: In most patients, clinical disease activity remains stable after LT. However, persistent moderate-to-severe mucosal inflammation is observed in a substantial subset during long-term follow-up. Advanced therapies, particularly vedolizumab, are being used more frequently in this setting and may offer disease control without a corresponding increase in infection risk. These findings underscore the need for individualized, interdisciplinary management and further prospective evaluation of treatment strategies in this population.

Background: The inflammatory bowel disease (IBD) ulcerative colitis (UC) is characterized by colonic mucosal inflammation and barrier dysfunction. We hypothesized that UC causes persistent defects in mucosal homeostasis, evident even in the absence of active inflammation, contributing to disease chronicity.

Methods: To test our hypothesis, we grew patient biopsy-derived sigmoid colonoids into air-liquid interface (ALI) monolayers, characterizing them through microscopy, proteomics, bulk RNA Sequencing (RNAseq), and their susceptibility to UC patient-isolated Escherichia coli pathobiont p19A.

Results: Non-IBD ALI monolayers formed uniform crypt-like structures and a thick mucus layer containing all epithelial-derived proteins previously identified in human colonic mucus. In contrast, ALI monolayers from UC patients displayed a range of impairments, with classification ranging from a mild phenotype with distorted architecture and a thinner, more permeable mucus layer to a severe phenotype with defects in cellular differentiation and an inability to produce a mucus layer. With the use of transcriptome analysis, we identified activated pathways associated with extracellular matrix formation and cell signaling, including numerous cancer-associated genes in UC ALI monolayers, which also proved significantly more susceptible to E. coli p19A.

Conclusions: Taken together, the culturing of patient biopsies into ALI colonoid monolayers provides a powerful model to assess human colonic mucosal development, healing, homeostasis, and mucus barrier function, revealing that UC-derived colonoid monolayers display a range of developmental and functional defects that persist in the absence of inflammation.