Inflammatory Bowel Diseases最新文献

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.

Inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), are defined by chronic, non-resolving inflammation of the intestinal mucosa. Neutrophils are the first responders in inflammation, executing various effector functions, including chemotaxis, phagocytosis, degranulation and the release of cytokines, reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Amongst all neutrophil functions, emerging evidence increasingly suggests that NET release may be particularly relevant in underpinning the pathogenesis of IBD. NETs are extracellular structures composed of chromatin, antimicrobial proteins, and oxidative enzymes released by neutrophils to trap and neutralize pathogens. In this review, we discuss the protective roles of NETs in intestinal health and how, under tight physiological regulation, they can prevent pathogenic invasion, exert anti-inflammatory effects, and play an important role in wound healing and intestinal tissue repair. Conversely, we consider how inflammation-driven changes in neutrophil activation, phenotype and immunometabolism can cause dysregulation in NET production and clearance and lead to harmful intestinal effects that can prolong intestinal and chronic inflammation in IBD. Specifically, we explore how uncontrolled NET production can damage intestinal epithelial integrity, increase bacterial translocation and increase thromboembolic risk, ultimately linking NETs to the pro-inflammatory pathogenesis of IBD.

Background: Pediatric Inflammatory Bowel Disease (IBD) is a chronic condition characterized by persistent intestinal inflammation in children. It often presents with distinct clinical phenotypes and is more frequently linked to rare monogenic variants affecting epithelial barrier function or mucosal immunity. Although over 100 genes are associated with monogenic IBD, their roles in the intestinal epithelium remain poorly defined. This study aimed to improve our understanding of epithelial dysfunction in early-onset IBD through molecular and cellular analyses to uncover patient-specific phenotypes and potential therapeutic targets.

Methods: We generated intestinal epithelial organoids (IEOs) from 94 pediatric IBD patients, including those with monogenic variants (BTK, TTC7A, IL10RA, LRBA, STXBP2, TRNT1, SKIV2L), along with 46 non-IBD controls. RNA sequencing was performed on 38 patient and 20 control lines, under both baseline conditions and after immunological stimulation, yielding a valuable dataset for studying epithelial responses in IBD.

Results: IEOs effectively initiated inflammation upon bacterial lysate stimulation, regardless of disease status, origin, or genotype. Inflammatory stimulation triggered upregulation of IBD-linked genes SERPINA1 and LIFR in IBD organoids, suggesting their role in epithelial innate immunity. However, network analysis showed no consistent transcriptional signatures across all IBD cases. Instead, specific genotypes (TTC7A, STXBP2, LRBA) revealed responses, with STXBP2 and LRBA showing shared upregulation of IL-1 and SLC30-mediated zinc trafficking pathways.

Conclusions: These findings underscore the potential of IEOs as a valuable model for studying IBD and offer key insights that could guide the development of targeted therapies for both monogenic and non-monogenic forms of IBD.

Background: Previous reviews for Crohn's disease (CD) treatment have rarely considered advanced and immunomodulator medical therapies together. Our aim was to compare all therapies for efficacy and safety in induction of remission.

Methods: We searched databases up to June 2025. Our outcomes were clinical remission and response, endoscopic remission, and safety outcomes. We performed network meta-analyses and estimated risk ratios (RR) and 95% CIs. We used GRADE to assess certainty of results, and surface under the cumulative ranking curve for ranking treatments.

Results: A total of 79 RCTs with 20 724 participants were included. Interventions ranged from 2 to 30 weeks. There was moderate GRADE certainty of effectiveness over placebo for clinical remission for combination of adalimumab with thiopurines (RR, 2.87; 95% CI, 1.99-4.14; RD (Risk difference)  = 35.3%; NNT (Number needed to treat) = 3, large magnitude), guselkumab (RR, 2.5; 95% CI, 1.95-3.21; RD = 28.4%; NNT = 4, moderate magnitude, adalimumab (RR, 2.46; 95% CI, 1.84-3.29; RD = 27.6% NNT = 4, moderate magnitude), combination of infliximab with thiopurines (RR, 2.43; 95% CI, 1.71-3.44; RD = 27%; NNT = 4, moderate magnitude), and ustekinumab (RR, 2.04; 95% CI, 1.69-2.46; RD = 19.6% NNT = 5, small magnitude). For endoscopic remission, there was moderate GRADE certainty of effectiveness for risankizumab (RR, 3.48; 95% CI, 2.18-5.58; RD = 17.4%, moderate magnitude). The certainty on safety varied, but treatments appear generally safe in the short term.

Conclusion: Combination of anti-tumor necrosis factors (anti-TNFs) and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for the induction of clinical remission. More novel therapies appear to have similar effect sizes but with increased imprecision of the estimates.