Digestive Diseases and Sciences最新文献

Background: The prevalence of type 2 diabetes mellitus (T2DM) and its associated hepatic steatosis has surged with the obesity epidemic. The influence of T2DM on the natural history of primary biliary cholangitis (PBC) remains poorly characterized.

Aims: This study aims to assess the prevalence of T2DM in a PBC cohort and evaluate its impact on hepatic steatosis, liver fibrosis, and clinical outcomes.

Methods: A retrospective analysis was performed. The presence of hepatic steatosis was defined by a controlled attenuation parameter (CAP) ≥ 285 dB/m, and clinically significant liver fibrosis was defined by a liver stiffness measurement (LSM) ≥ 8.5 kPa assessed using vibration-controlled transient elastography (VCTE). The cohort was further stratified into four subgroups: PBC with T2DM (PBC/T2DM), PBC without T2DM (PBC/non-T2DM), PBC with hepatic steatosis (PBC/steatosis), and PBC without hepatic steatosis (PBC/no steatosis). Group comparisons were performed using t-tests, chi-squared analyses, and Kaplan-Meier survival curves.

Results: 562 patients with PBC were identified. The prevalence of T2DM was 14.8%. 158 (28%) patients had VCTE measurements. The PBC/T2DM sub-cohort was more likely to have concomitant hepatic steatosis compared to PBC/non-T2DM (54% vs 28%, p-value 0.010). The prevalence of clinically significant fibrosis was similar between these two groups (69% vs 52%, p-value 0.097). All-cause mortality rates were similar between PBC/T2DM vs PBC/non-T2DM (p-value 0.960) and PBC/steatosis vs PBC/no steatosis (p-value 0.895).

Conclusion: T2DM is a risk factor for the development of hepatic steatosis in patients with PBC; however, it does not increase the likelihood of clinically significant liver fibrosis or all-cause mortality.

Background: Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC), but the pathogenesis remains poorly understood.

Aims: This study aimed to assess changes in fatigue prevalence during the first year after diagnosis and examine the association between disease course and substantial fatigue (SF) at the 1-year follow-up.

Methods: Adults with newly diagnosed CD or UC were recruited from the population-based IBSEN III cohort. Fatigue was assessed at diagnosis and the 1-year follow-up using the Fatigue Questionnaire. Associations between SF at the 1-year follow-up and disease-related factors were quantified using multivariate logistic regression adjusted for sex, age and comorbidities.

Results: In total, 596 patients were included (CD: 196, UC: 400). SF was present at both baseline and after one year of disease for 46.9% (n = 92/196) and 40.5% (n = 162/400) of patients with CD and UC, respectively. In CD, development of endoscopically non-passable stricture and/or surgically treated stricture within first year of disease (OR = 4.52, 95%CI [1.61;12.68]), self-reported flares since diagnosis (OR = 2.55, 95%CI [1.26;5.16]), female sex (OR = 3.12, 95%CI [1.53;6.37]) and comorbidities (OR = 4.05, 95%CI [1.89;8.69]) were independently associated with SF at the 1-year follow-up. In UC, SF was associated with current biological treatment (OR = 5.14, 95%CI [1.56;16.96]), increasing Mayo endoscopic score at the 1-year follow-up (OR = 1.54, 95%CI [1.01;2.35]), self-reported flares since diagnosis (OR = 2.66, 95%CI [1.24;5.72]) and female sex (OR = 2.20, 95%CI [1.06;4.57]).

Conclusions: Fatigue frequently persists through the first year after IBD diagnosis. Clinical factors reflecting a more severe disease course were associated with SF one year after diagnosis in both CD and UC.

Introduction: Patients with inflammatory bowel disease (IBD) are at higher risk of pneumonia due to the disease itself and the use of immune-modifying medications.

Methods: We conducted a retrospective analysis of TriNetX US Collaborative Network data on patients with IBD who received the 20-valent pneumococcal conjugate vaccine (PCV20). Propensity score matching was performed to adjust for differences in demographics and pneumonia-related risk factors.

Results: After propensity score matching, 12,796 patients were included in the analysis. The mean ages of the vaccinated and control groups were 55.2 ± 16.3 and 55.8 ± 17.1 years, respectively, with females comprising 53% of each group. The most commonly prescribed IBD therapies across both cohorts included prednisone, methylprednisolone, budesonide, and adalimumab. Compared to the control group, patients who received PCV20 experienced significantly lower risks of pneumonia, acute respiratory failure, hospital admissions, ICU admissions, and all-cause mortality.

Discussion: These findings align with current recommendations supporting pneumococcal vaccination in adult patients with IBD and highlight the importance of further studies to clarify the extent of vaccine-related benefit in this population.

Purpose: The gastrointestinal (GI) tract is a highly immunologically active organ where coordinated crosstalk between Toll-like receptor 4 (TLR4) and NLRP3 inflammasome maintains epithelial integrity, supports mucosal repair, and promotes immune tolerance. This review aims to summarize current understanding of TLR4-NLRP3 interactions in the gut, examine their in disease, examine their roles in disease, and evaluate emerging therapeutic strategies targeting this axis.

Methods: A comprehensive review of recent literature was conducted, focusing on regulatory mechanisms governing TLR4-NLRP3 signaling under homeostasis and dysregulation. Studies addressing epithelial barrier function, cytokine signaling, pyroptosis, metabolic endotoxemia, dysbiosis, and gut-brain axis communication were examined. Research using organoids, gut-on-chip system, microbiota modulation, and multi-omics approaches was also evaluated to understand therapeutic and translational advancements.

Results: Findings indicate that balanced TLR4-NLRP3 signaling preserves epithelial barrier integrity, regulates inflammatory responses, and supports immunological tolerance. Dysregulation disrupts these protective mechanisms and initiates feed-forward cycle of epithelial damage, metabolic endotoxemia, dysbiosis, and heightened cytokine-driven inflammation. Such aberrant activity contributes to major intestinal diseases-including inflammatory bowel disease, necrotizing enterocolitis, and colorectal cancer-as well as extraintestinal conditions such as obesity, type 2 diabetes, and neuroinflammation through gut-brain axis pathways. Novel therapeutic strategies, including selective small-molecule inhibitors and microbiota-based interventions, show potential for targeted modulation.

Conclusion: The TLR4-NLRP4 axis is a context-dependent regulator of gut and systemic immunity. Targeted modulation of this pathway represents a promising strategy to restore immune homeostasis while preserving host defense, supporting its relevance as a translational therapeutic target across multiple immune-mediated disorders.

Purpose: Various methods have been developed for mucosal defect closure after colorectal endoscopic submucosal dissection (ESD), but prolonged procedure time and technical complexity remain challenges. The SureClip Traction Band (SCTB; Micro-Tech, Nanjing, China), originally designed as a traction device, has recently been used for defect closure. This study evaluated its efficacy for defect closure following colorectal ESD.

Methods: We retrospectively analyzed colorectal ESD cases (≤ 50 mm) between January 2023 and August 2025 in which SCTB was used for defect closure. The primary outcome was the complete closure rate. Secondary outcomes included closure time, numbers of SCTBs and additional clips used, and the incidence of delayed bleeding (DB), delayed perforation (DP), and post-ESD coagulation syndrome (PECS). Historical control cases (non-SCTB group) were ESDs for lesions ≤ 50 mm performed between January 2022 and March 2023.

Results: In total, 55 lesions were closed using SCTB. The mean resected specimen size was 35.5 ± 9.0 mm, and the complete closure rate was 98.2%. The median closure time (IQR) was 8.6 (4.5) min, with an average of 1.1 ± 0.3 SCTBs and 6.6 ± 2.1 additional clips used per case. Complication rates in the SCTB versus non-SCTB groups were similar for DB (1.8% vs. 1.5%, p = 1.00) and DP (0% vs. 2.2%, p = 0.56). However, the incidence of PECS was significantly lower in the SCTB group (3.6% vs. 14.0%, p = 0.04).

Conclusion: Endoscopic closure using SCTB achieved a high complete closure rate with a short procedure time and reduced incidence of PECS after colorectal ESD.

Purpose: Outcome monitoring supports quality improvement (QI) by helping organisations track performance, identify gaps, and guide improvements. This is particularly important for the management of costly chronic diseases with high practice variation such as inflammatory bowel disease (IBD). Although the value of outcome data for QI is increasingly recognised, little is known about its use in practice. We explored how Dutch IBD centres implement outcome-based QI.

Methods: A survey was sent to 67 Dutch IBD centres covering outcome monitoring practices, data infrastructure, involvement of healthcare providers in QI discussions, and the perceived value of using outcomes for QI. Fourteen follow-up interviews explored experiences, barriers, and facilitators.

Results: Twenty-eight centres were included (54% non-academic teaching, 25% academic, and 21% general hospitals), of which 79% regularly discussed outcomes within their IBD teams to support QI efforts. Of those, 95% implemented ≥ 1 QI initiatives annually informed by these discussions and 47% assessed their effectiveness regularly. However, consistent use of outcome-based QI was uncommon-only 18% discussed outcomes > 2 times per year. Commonly monitored outcomes were medication use (68%) clinician-reported outcomes (55%), and patient-reported outcomes (55%). Interviews revealed QI efforts were often limited by informal discussions that lacked aggregate data use and clear goals. Data systems were fragmented, and staff responsibilities were unclear. Staff engagement and management support were key enablers.

Conclusion: While outcome monitoring is common, it is not consistently used to support QI. Clarifying roles, improving data integration, and support in selecting meaningful outcomes may strengthen sustainable outcome-based QI.