Inflammatory Bowel Diseases最新文献

Autophagy is a crucial cellular process involved in the degradation of cytoplasmic components through lysosomal machinery. It is essential for maintaining cellular homeostasis and responding to various stressors. Autophagy has emerged as a key regulator of immune responses, particularly in the context of chronic inflammatory diseases, such as inflammatory bowel diseases and cancer. Increasing evidence highlights its dual role in both exacerbating and controlling inflammation, depending on the disease context. This review critically examines the molecular mechanisms of autophagy, its regulation within immune cells, and its complex involvement in chronic inflammation. We explore how dysregulated autophagic processes contribute to disease pathogenesis, with particular focus on inflammatory bowel disease and how these conditions increase cancer risk. Furthermore, we discuss the potential of autophagy modulation as a therapeutic strategy for these diseases. Current therapeutic approaches targeting autophagy are reviewed, alongside emerging strategies and their clinical implications. This comprehensive analysis underscores the importance of understanding the multifaceted roles of autophagy in immune regulation, with the aim of advancing therapeutic interventions for inflammatory and cancer-related conditions.

Background: The Mayo endoscopic score (MES) provides a criterion-based, but still subjective, human assessment of endoscopy and related endpoints in therapeutic clinical trials in ulcerative colitis (UC). A novel solution to address issues of reproducibility is the use of machine learning (ML) models to standardize MES evaluations. Broader applicability of this solution requires an understanding of the models and related performance characteristics. The objective of this study is to provide a systematic review on training and testing of ML MES prediction models on full-length endoscopic videos from patients with UC.

Methods: PubMed/MEDLINE, EMBASE, and Web of Science were systematically searched on December 31, 2024, and supplemented by reference checks and Google search to identify studies on training or testing of ML models to produce an automated MES grade on endoscopic procedure videos in UC.

Results: A total of 7 studies met the inclusion criteria, and of those, 5 were eligible for reporting on model performance. Accuracy in predicting ordinal MES grades (0, 1, 2, 3) ranged from 56.8% to 83.3%. Accuracy in predicting MES 0, 1 vs 2, 3 and MES 0 vs 1, 2, 3 (each aligned with a definition of endoscopic improvement and remission in trials) ranged from 84% to 90.2% and from 90% to 95.5%, respectively.

Conclusions: Our review demonstrates strong performance characteristics of ML models to assess the MES on endoscopic videos in UC, potentially offering a standardized and reproducible solution to measure endoscopic severity. Further research will investigate the impact of this technology on clinical trial outcomes.

Background: Poor sleep is common in Crohn's disease (CD), prospectively predicts worse disease course, and is often attributable to insomnia. Cognitive behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia disorder. CBT-I improves sleep and may improve pain intensity, pain interference, and inflammation. We sought to investigate whether CBT-I impacts these factors in patients with active CD.

Method: We recruited patients with insomnia and mild-to-moderate CD symptoms from an inflammatory bowel disease center. Exclusion criteria were other sleep disorders, significant psychiatric concerns, and presence of other common influences on sleep. Participants completed baseline assessments of sleep, pain, and inflammation then were randomized to receive CBT-I immediately, or wait 12 weeks and then repeat the baseline assessment and complete CBT-I. Similar assessments occurred immediately post-CBT-I and 1 month later. CBT-I included sleep restriction, stimulus control, sleep hygiene, arousal reduction, and cognitive therapy.

Results: A total of 26 participants completed the study. In group × time analyses, CBT-I led to greater reductions in insomnia severity (P < .001) and wake after sleep onset (P = .02) than waitlist. In pre- to post-treatment analyses, participants reported significant improvements in subjective measures of sleep continuity, CD symptom severity, pain intensity, and pain interference. C-reactive protein trended toward improvement.

Discussion: This study provides preliminary evidence of efficacy of CBT-I in people with CD. CBT-I improved self-reported sleep and may improve pain and CD symptoms. The results highlight the importance of addressing sleep concerns in inflammatory bowel disease, particularly in people with persistent pain or fatigue. Future trials powered to detect changes in pain and inflammation are warranted.

Background: The diagnosis of microscopic colitis (MC) is based on endoscopic biopsy with histological assessment. Histological outcomes (remission, response or improvement) are important treatment targets in clinical trials. Although a substantial body of research on MC has been published in recent years, no standardized criteria currently exist for its histological outcomes. We sought to review and summarize the histological evaluation of MC in published systematic reviews (SRs) assessing the efficacy of interventions and to examine the heterogeneity in histological evaluation among the randomized controlled trials (RCTs) included in those SRs.

Methods: We conducted an umbrella review (ie, an overview of systematic reviews) of published SRs. A literature search of the Cochrane Database of Systematic Reviews, MEDLINE, and Embase was performed up to May 2025. Definitions of histological evaluation and monitoring following interventions were extracted and summarized from the published SRs and the RCTs included within them.

Results: Fourteen SRs with meta-analyses that focused on interventions were included. Nineteen RCTs were included in these SRs. Of them, 12 fully published RCTs reported histological outcome data and met our inclusion criteria. The definitions for histological outcomes varied between RCTs but were generally based on reduction in lamina propria cellularity, intraepithelial lymphocytes, or collagen band thickness.

Conclusions: This umbrella review highlights the heterogeneity in the definitions of histological outcomes in MC RCTs. The summarized evidence will support ongoing efforts to develop consensus definitions for histological outcomes in order to facilitate clinical trials of medical therapies for MC.

Background: There is lack of data regarding the associations between perianal fistulizing disease and other disease characteristics at diagnosis in children with Crohn's disease (CD). We sought to investigate the associations between perianal fistulizing disease and other disease characteristics at diagnosis in children with CD.

Methods: This was a multicenter, registry-based, inception cohort study conducted in Korea. Children newly diagnosed with CD were included. Baseline clinicodemographics; results from laboratory, endoscopic, histologic exams; and Paris classification factors were collected, and associations between factors were investigated.

Results: A total 699 patients were included. The median age at diagnosis was 14.3 years (IQR, 12.3-15.9 years), and the male-to-female ratio was 2.66:1. Perianal disease modifiers comprised 50.6% (n = 354 of 699) of the patients. The proportion of perianal disease modifiers was higher in males (81.1% vs 64.1%; P < .001), in those with upper gastrointestinal tract involvement (85.3% vs 75.7%; P = .002), and in those with B1 behavior (89.5% vs 79.7%; P < .001). Albumin was higher (P = .006) and CRP was lower (P < .001) in patients with perianal disease modifiers. Females had a higher proportion of B2/B3 behavior (21.4% vs 14.4%; P = .029), higher Pediatric Crohn's Disease Activity Index scores (median 40 vs 32.5; P < .001), higher CRP (P = .017), higher Simple Endoscopic Score for Crohn's Disease scores (P = .01), and more frequent detection of noncaseating granulomas in the lower gastrointestinal tract (P = .008).

Conclusions: Perianal fistulizing disease was more common in boys who exhibited milder disease activity, indicating the importance of recognizing perianal fistulizing disease as a clinical clue to the early diagnosis of underlying luminal CD.

Introduction: Up to 50% of patients with Crohn's disease (CD) will require surgery, and 70% to 90% experience endoscopic recurrence (ER) within the first year postoperatively. Despite various treatments, there are scant data on their comparative efficacy to prevent recurrence. This study aimed to compare the efficacy of medical treatments in preventing postoperative recurrence of CD.

Methods: A comprehensive literature review was conducted through January 2025. We included randomized controlled trials and prospective cohort studies, excluding pediatric studies, single-arm trials, and dose comparison studies. The primary endpoint was assessing ER (Rutgeerts score ≥i2) at 6 months, and secondary outcomes were clinical recurrence (Crohn's Disease Activity Index ≥150, Hanauer score ≥2, or Harvey-Bradshaw Index ≥8) at 6, 12, and ≥18 months postoperatively. Frequentist random-effects network meta-analysis was conducted, reporting odds ratios (ORs) with 95% confidence intervals (CIs).

Results: A total of 42 studies were included, of which 38 were randomized controlled trials, with a total of 2260 patients. At 6 months, adalimumab (ADA) ranked highest in reducing ER (surface under the cumulative ranking curve [SUCRA] = 84.5%), followed by vedolizumab (VDZ) (SUCRA = 74.5%). ADA significantly reduced ER compared with thiopurines (THPs) (OR, 0.33; 95% CI, 0.12-0.91), probiotics (OR, 0.17; 95% CI, 0.03-0.99), and vitamin D (OR, 0.07; 95% CI, 0.01-0.37). VDZ did not significantly differ from THPs, ADA, or metronidazole. At 12 months, infliximab (IFX) (SUCRA= 93%) and ADA (SUCRA = 90%) had the lowest ER, with IFX showing significant reductions compared with THPs, metronidazole, and 5-aminosalicylic acid. Similar findings were observed at 18 months, with IFX and ADA maintaining the lowest ER rates. For clinical recurrence, no significant differences were observed among therapies at 6 months; however, at 12 months, ADA and IFX were superior to most therapies, including THPs and budesonide.

Conclusion: Anti-tumor necrosis factor agents, namely ADA and IFX, are the most effective treatments in reducing postoperative recurrence of CD, followed by VDZ. THPs and antibiotics ranked lower than biologics. Nonpharmacological interventions such as curcumin, vitamin D, and probiotics did not demonstrate efficacy in reducing postoperative recurrence.

Background: Pouch failure after ulcerative colitis (UC) necessitates either pouch excision or establishment of a permanent diverting stoma. The aim of this study was to explore if rectal inflammation prior to pouch creation affected the risk of developing pouch failure.

Methods: Patients 18 years and older with ulcerative colitis undergoing J-pouch surgery at Odense University Hospital between 1983 and 2020 were included. Pouch failure was defined as either the presence of ileostomy more than 1 year after ileo pouch-anal anastomosis (IPAA) or pouch removal. Rectal inflammation was defined by 3 measures: using the Nancy index on pathology examination of the resected rectum, endoscopically using latest Mayo score from the year preceding the IPAA, and as active anti-inflammatory treatment four weeks prior to IPAA.

Results: A total of 434 patients met the inclusion criteria, with 66 patients (15%) experiencing pouch failure with mean time of 5.63 years. Acute inflammation (Nancy grade 2-4) was observed in 70% of the patients. Active anti-inflammatory treatment was observed in 37% of patients, and 67% had undergone endoscopy within 1 year prior to IPAA. No significant association was found between the Nancy Index Grade and pouch failure, time to pouch failure, postoperative complications, or long-term pouch complications. Furthermore, neither the Mayo score grade nor active medical UC therapy predicted the risk of pouch failure.

Conclusion: Rectal inflammation prior to IPAA does not increase risk of pouch failure, postoperative complications, or long term pouch dysfunction.