Inflammatory Bowel Diseases最新文献

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa, extending proximally from the rectum. However, the segmental pattern of healing in UC remains unclear. Endoscopic improvement (EI), a key therapeutic endpoint, is typically assessed using the Mayo endoscopic score (MES), which scores the worst affected area and may miss partial/segmental healing. This study evaluates healing patterns in UC and compares conventional MES with a 3-segment MES approach for detecting treatment effects in clinical trials.

Methods: A post hoc analysis of HIBISCUS I/II and GARDENIA trials was conducted in UC patients with moderate-to-severe disease (MES >2 up to the descending colon). The primary outcome was the proportion of anti-tumor necrosis factor-treated participants achieving MES ≤1 in the descending colon, sigmoid colon, and rectum at week 10. Secondary outcomes included conventionally measured EI, segmental MES improvements, clinical response, and Patient-Reported Outcome 2 (PRO2) normalization. Outcomes were compared between adalimumab, infliximab, and placebo groups.

Results: Among 300 participants, 217 received infliximab or adalimumab, while 83 received placebo. Healing followed a proximal-to-distal pattern, with the highest EI in the descending colon and the lowest in the rectum. Infliximab-treated patients continued this trend at week 54. Anti-tumor necrosis factor therapy significantly improved EI vs placebo (42.9% vs 19.3%; P < .001). No segmental MES approach outperformed conventional MES for detecting treatment effects. Combined endpoints (MES ≤1 + PRO2 normalization) better captured therapeutic benefits than PRO2 alone (28.6% vs 13.3%; P = .006).

Conclusions: UC healing follows a proximal-to-distal pattern. Conventional MES remains superior for detecting treatment effects over segmental MES. Further studies should explore alternative endoscopic scoring methodologies.

Background: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), have complex pathologies requiring precise diagnostic tools. We evaluated the clinical utility of anti-integrin αvβ6 antibodies in diagnosing UC, focusing on differences between a U.S. cohort (self-reported White) and a Japanese cohort, and additionally assessed whether combining anti-αvβ6 with anti-EPCR improved diagnostic performance.

Methods: Serum anti-αvβ6 antibody levels were measured in 1138 participants (514 in the U.S. cohort, 624 in the Japanese cohort), including 1093 IBD cases and 45 healthy control subjects. Positivity rates and titers were compared between cohorts, and associations with clinical subphenotypes and anti-EPCR were examined.

Results: Anti-αvβ6 positivity was significantly higher in UC patients (85.4%) than in CD patients (16.4%) or control subjects (0%). Within UC, high positivity was observed across all disease extents, with only minor cohort differences. Longer disease duration was associated with lower positivity in both cohorts. In CD, the U.S. cohort showed higher positivity (23.4%) than the Japanese cohort (10.1%), particularly in colonic CD. Absence of ileal involvement, strictures, or perianal disease was associated with higher positivity. Anti-αvβ6 and anti-EPCR levels were strongly correlated, but their expression patterns differed in primary sclerosing cholangitis-associated IBD. Combining anti-αvβ6 and anti-EPCR improved UC diagnostic accuracy (area under the curve, 0.98; 95% confidence interval, 0.95-1.00) over either antibody alone (P = .00264).

Conclusions: Anti-αvβ6 is a valuable biomarker for UC diagnosis. However, this study demonstrated differences in its behavior between U.S. and Japanese cohorts, particularly in CD. Cohort-informed interpretation and combined antibody testing may improve diagnostic precision and disease stratification in IBD.

Background: Despite the transformative impact of biologics on the treatment of inflammatory bowel disease (IBD) in recent years, a substantial proportion of patients remain unresponsive to these advanced therapies. Overcoming resistance remains a significant clinical challenge, largely due to the incomplete understanding of its underlying mechanisms. This study explores the role of extracellular matrix (ECM) remodeling in the development of resistance to anti-TNFα therapy.

Methods: Using public single-cell and bulk transcriptomic datasets, combined with in vitro primary cell experiments and multiplex immunofluorescence validation, we investigated key factors contributing to therapy failure.

Results: Transcriptomic analysis revealed that ECM-related pathways were enriched in Crohn's disease patients and associated with resistance to anti-TNFα therapy. Single-cell analysis identified Fibroblast 2 (CD81+ fibroblasts) as the major ECM-related stromal subpopulation, exhibiting the highest capacity for ECM secretion and degradation. Matrix metalloproteinase-2 (MMP2) was identified as a key protease highly expressed in this subset, showing close interaction with macrophages. Co-culture of primary fibroblasts and macrophages led to increased release of inflammatory mediators such as TNFα and IL-6, which was partially reduced by MMP2 inhibition, suggesting a potential regulatory role of MMP2 in fibroblast-macrophage crosstalk. Spatial transcriptomics and multiplex immunofluorescence further supported the spatial colocalization and interaction of fibroblasts, macrophages, and MMP2 within the tissue microenvironment.

Conclusions: This study highlights the association of pathogenic fibroblasts and ECM remodeling in anti-TNFα therapy failure, identifies MMP2 as a potential target, and suggests that combination therapy may offer a potential strategy for patients with treatment resistance.

Background: Total abdominal colectomy (TAC) is a key surgical intervention for patients with ulcerative colitis (UC), particularly in the setting of acute severe disease or medically refractory colitis. While international studies have reported outcomes using registry data, these are often limited by diagnostic coding variability and inclusion of a heterogeneous surgical procedure mix.

Methods: A retrospective national audit of perioperative outcomes following TAC for UC in Ireland over a 10-year period (2013-2022) was performed. Data were collected at 13 hospitals, from review of clinical records, and validated by trained clinicians. Primary outcomes were 30-day postoperative morbidity and mortality. Secondary outcomes included reoperation, readmission, use of laparoscopy, and length of stay (LoS).

Results: A total of 469 patients with a preoperative diagnosis of UC underwent TAC. Median age was 40 years; 64.4% were male. Emergency surgery accounted for 67.3% of cases, with high rates of preoperative medical therapy (steroids 82.6%, biologics 69.3%). Laparoscopy was used in 71.8% of operations. Postoperative morbidity rate was 43.0%, severe morbidity was 11.7%, and 30-day mortality was 0%. Multivariable analysis identified open surgery, steroid use, and acute disease complications as predictors of morbidity and biologic use as protective.

Conclusions: This national audit demonstrates low mortality and acceptable morbidity following TAC for UC, with increasing use of laparoscopy over time. The robust, diagnosis-validated data support international standards of care and highlights key predictors of postoperative complications in this population. It identifies elderly, immunosuppressed patients requiring emergency open surgery as the highest risk patient subgroup.

Background: Patients with Crohn disease (CD) face an elevated risk of developing small bowel adenocarcinoma (SBA), a malignancy characterized by late-stage diagnosis and poor prognosis. In this study we aimed to characterize surgical management and oncologic outcomes for CD-associated SBA.

Methods: A retrospective review was conducted across 3 tertiary IBD centers, analyzing 99 patients with CD who underwent surgery for SBA between 1992 and 2025. Data included patient demographics, CD history, surgical details, and oncologic outcomes.

Results: The median time from CD diagnosis to SBA was 25 years. The SBA diagnosis was incidental in 74.8% of cases, discovered during surgery for other complications. Tumors were predominantly located in the ileum (80.8%) and showed aggressive features: 56.6% were poorly differentiated (grade 3), and 85.9% were pathologically advanced (T3/T4 on TNM staging). Nodal involvement was present in 45.5% of patients, and 18.2% had distant metastases at diagnosis. A complete (R0) resection was achieved in 90.9% of surgeries, with a 30-day morbidity rate of 26.3%. After a median follow-up of 36 months, the distant recurrence rate was 28.3%, and overall mortality was 27.3% (18.2% cancer related).

Conclusion: In patients with long-standing CD, SBA is typically an incidental diagnosis made at an advanced stage. While high rates of complete surgical resection are possible, the prognosis remains guarded due to aggressive tumor biology and high recurrence rates. These findings highlight a critical need for improved risk stratification to guide surveillance and for the development of evidence-based adjuvant treatment strategies.

Inflammatory bowel disease-related post-traumatic stress disproportionately affects Black and Latino/a patients and is driven by traumatic disease experiences, cumulative adversity, and unmeasured medication effects. Recognition of these factors and implementation of routine screening and trauma-informed care are essential to improve outcomes and reduce inequities in these patients.

Background: Mesenteric fat (MF) wrapping is a characteristic feature of Crohn's disease (CD). Current assessment methods are limited to binary classification (presence/absence), restricting their utility in assessing disease progression and treatment response. This study aimed to develop and validate a novel semi-quantitative metric for grading MF wrapping using intestinal ultrasound (IUS), and to evaluate its reliability and clinical relevance.

Methods: This cross-sectional study included 95 ultrasound scans from 63 patients with CD. The novel index described here categorized MF wrapping into 3 categories: none, incomplete, and complete. Images were independently assessed to evaluate inter- and intrarater reliability. Associations between MF wrapping and clinical characteristics, inflammatory markers, and IUS parameters were analyzed.

Results: Interrater reliability for the MF index was moderate (κ = 0.452), while intrarater reliability was substantial (κ = 0.653), similar to binary assessment (κ = 0.572 and κ = 0.674 for inter- and intrarater reliability, respectively). MF wrapping was significantly associated with increased bowel wall thickness (OR, 6.74; P < .001), loss of bowel wall stratification (OR, 22.05; P < .001), hyperemia (OR, 8.09; P = .002), and presence of strictures (OR, 4.30; P = .002). Smoking status and lower serum albumin were significantly associated with increased MF wrapping.

Conclusions: CMFI represents a proof-of-concept tool for semi-quantitative assessment of MF wrapping on IUS. While reproducible and associated with other disease markers, its incremental clinical utility remains to be established through prospective validation and longitudinal outcome studies.

Importance: Inflammatory bowel disease (IBD) encompasses chronic inflammatory conditions primarily affecting the small intestine and colon. Ulcerative colitis (UC) and Crohn's disease (CD) involve dysregulated immune responses to intestinal microbiota, influenced by genetic predisposition, environmental factors, and gut barrier dysfunction. This retrospective cohort study was carried out to understand the relationship between immune-modulating surgeries like tonsillectomy and the development of IBD.

Objective: To evaluate the association between tonsillectomy and the risk of developing IBD. Design, Setting, and Participants: This retrospective cohort study used the TriNetX research network, a large US-based collaborative platform, to identify 124,132,724 individuals from 2005 to 2023. After applying inclusion criteria, 1,420,302 matched participants (tonsillectomy vs nontonsillectomy) were selected using 1:1 propensity score matching.

Exposure: Tonsillectomy.

Main outcome and measure: The primary outcome was the incidence of IBD, including CD and UC, defined by validated diagnostic codes. Propensity score matching (PSM) (1:1) was used matching age, sex, race, body mass index, socioeconomic status, healthcare utilization, comorbidities, medications, and Creactive protein levels. Subgroup and sensitivity analyses were conducted to estimate the adjusted hazard ratio (HR) between surgical intervention and IBD risk.

Results: After matching, baseline characteristics were well balanced between surgical and nonsurgical groups. Tonsillectomy was associated with a significantly increased risk of developing IBD (HR, 1.30; 95% CI, 1.14-1.47). Elevated risks were observed for both CD (HR, 1.37) and UC (HR, 1.29). Increased IBD risk was consistent across demographic subgroups. Sensitivity analyses confirmed the robustness of these findings across varying follow-up periods.

Conclusions and relevance: This study highlights a significant association between tonsillectomy and increased risk of developing IBD. These observations underscore the potential role of tonsillectomy in influencing long-term gastrointestinal health, warranting further investigation into underlying mechanisms and preventative strategies.