Digestive Diseases and Sciences最新文献

Objective: Intestinal ischemia/reperfusion (I/R) injury causes severe inflammation and disruption of the epithelial barrier, often leading to life-threatening complications. Although autophagy is known to provide tissue protection during I/R, the mechanisms linking autophagy to inflammasome regulation remain unclear. This study aimed to investigate the role of Beclin 1 (BECN1) in regulating NLRP3 inflammasome activation during intestinal I/R injury.

Methods: Intestinal I/R models were used to examine changes in BECN1 expression in intestinal epithelial cells. Conditional knockout mice lacking Becn1 in intestinal epithelial cells were generated to evaluate its functional role in vivo. Autophagic flux, NLRP3 ubiquitination, inflammasome activation, and inflammatory cytokine production were assessed using molecular and biochemical approaches. In addition, the therapeutic potential of a cell-penetratingTAT-BECN1 peptide was evaluated in the I/R model.

Results: BECN1 expression was significantly upregulated in intestinal epithelial cells following I/R injury. Mechanistically, BECN1 promoted ubiquitin-dependent degradation of NLRP3, thereby limiting inflammasome activation. Conditional deletion of Becn1 in intestinal epithelial cells exacerbated intestinal injury and increased inflammatory cytokine production. Conversely, administration of the TAT-BECN1 peptide restored autophagic flux, enhanced NLRP3 ubiquitination, and attenuated epithelial damage and inflammation after I/R.

Conclusion: BECN1 protects against intestinal I/R injury by promoting NLRP3 ubiquitination and suppressing inflammasome activation through the autophagy pathway. These findings reveal a previously unrecognized mechanism linking autophagy to inflammasome regulation and suggest that targeting the BECN1-autophagy axis may represent a promising therapeutic strategy for intestinal I/R injury.

The clinical presentation of Crohn's disease (CD) is heterogeneous, reflecting its involvement of any segment of the gastrointestinal tract. Acute right-lower-quadrant pain in CD can closely mimic appendicitis, creating diagnostic and therapeutic challenges. We report a 33-year-old man with established inflammatory ileocolonic CD in clinical remission on infliximab who presented with recurrent right-lower-quadrant pain and imaging findings consistent with acute appendicitis. Colonoscopy demonstrated only mild inflammatory changes without appendiceal orifice involvement. Though initial medical management with antibiotics led to transient improvement, symptoms recurred, prompting a limited appendectomy. Intraoperative evaluation revealed no active ileal or cecal inflammation. Pathology confirmed acute appendicitis without granulomas or definitive features of CD. The postoperative course was uneventful. This case highlights the importance of careful assessment of CD extent and severity using imaging and endoscopy to guide management decisions. Accurate differentiation between acute appendicitis and flare of CD is essential for optimizing medical therapy and surgical planning while minimizing complications.

Background: Recurrent flares are associated with disease progression and have a pronounced impact on the quality of life of people with Inflammatory Bowel Disease (IBD). Models using clinical characteristics only moderately predict flares and therefore difficult to implement in clinical practice. With the rise of remote monitoring platforms such as myIBDcoach, which capture besides clinical disease activity, modifiable lifestyle and psychosocial risk factors and patient-reported outcome measures (PROMs), harnessing real-world data may help improve flare prediction. The aim of this study was to develop and compare five predictive models for flares.

Method: The baseline demographic and clinical data and PROMs related to lifestyle and psychosocial factors were collected from the myIBDcoach telemedicine platform from November 2022 to June 2024. Associations between flares, baseline clinical variables alone, and PROMs variable categories from the myIBDcoach platform were estimated using stepwise group-LASSO logistic regression (G-LASSO) model, which was evaluated with performance matrices using accuracy, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Result: Four hundred and twenty-nine patients from a prospective observational cohort were selected to create the models. The performance of the G-LASSO regression model with baseline variables and myIBDcoach PROMs (psychosocial and lifestyle factors) was better (accuracy: 71%, ROC-AUC: 77%, sensitivity: 59%, specificity: 91%, PPV: 91%, NPV: 59%) than that of the model with baseline data alone (accuracy: 63%, ROC-AUC: 65%, sensitivity: 51%, specificity: 81%, PPV: 81%, NPV: 52%).

Conclusion: The inclusion of subjective health and modifiable lifestyle and psychosocial data improved flare prediction in contrast to clinical characteristics alone, which was evidenced in the model performance matrices (accuracy, AUC, sensitivity, specificity, PPV, NPV). In multifactorial disorders such as IBD, lifestyle, and psychological stressors may intensify inflammatory responses, all of which can be controlled by lifestyle choices including diet, exercise, and stress management, for which this model underscores the need.

Purpose: Buried Bumper Syndrome (BBS) is a significant complication of percutaneous endoscopic gastrostomy (PEG). Management strategies vary between endoscopic and surgical approaches. This systematic review compares the efficacy and outcomes of these modalities based on contemporary evidence.

Methods: A systematic literature search was conducted across multiple databases (MedLine, Scopus, Embase, Web of Knowledge) for studies reporting on BBS management. Case reports, case series, and cohort studies were included. Data on patient demographics, treatment type (conservative, endoscopic, surgical), and outcomes (success, morbidity) were extracted and analyzed.

Results: Analysis of 104 patients from case reports/series and 276 from modern cohorts was performed. In the detailed cohort, endoscopic management (n=63) had a success rate of 92.1% with 7.9% failure and 6.3% morbidity. Surgical management (n=25) had a 100% success rate and 8% morbidity. Modern management data (n=276) revealed an overwhelming preference for endoscopy (97.4%), with a very low rate of primary (2.6%) and salvage (1.9%) surgery CONCLUSIONS: Endoscopic management is the established first-line therapy for BBS, demonstrating high efficacy and safety in large, contemporary studies. Surgical intervention is highly effective but reserved for complex cases or after endoscopic failure, representing a crucial salvage option. This reflects a definitive paradigm shift towards minimally invasive endoscopic techniques as the standard of care.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and often underdiagnosed until advanced fibrosis, leading to increased morbidity and costs. While early identification can enable timely intervention, the cost-effectiveness of screening strategies for at-risk adults remains uncertain.

Aim: To evaluate the cost-effectiveness of an artificial intelligence (AI)-based risk stratification tool combined with transient elastography (AI + TE) compared with three alternative screening strategies and no screening for detecting advanced fibrosis in at-risk adults in the United States.

Methods: A decision-analytic Markov model simulated MASLD progression over 5-year and 10-year horizons from the US payer perspective, using a 3% discount rate. Four strategies were compared (AI + TE, FIB-4 + TE, TE-only, and no screening), followed by treatment with semaglutide or resmetirom for confirmed advanced fibrosis. Main outcomes were quality-adjusted life years (QALYs), total costs, and Incremental Cost-Effectiveness Ratios (ICERs).

Results: Over 10 years, AI + TE versus no screening provided an incremental gain of 0.107 QALYs at an ICER of $38,916/QALY (semaglutide) and $76,141/QALY (resmetirom). FIB-4 + TE and TE-only were less efficient, with ICERs above $72,500 for semaglutide. At the $100,000/QALY threshold, the probability that AI + TE was cost-effective exceeded 90% for semaglutide. Semaglutide consistently dominated or was more cost-effective than resmetirom across all strategies.

Conclusions: AI-based screening followed by transient elastography is a cost-effective strategy for identifying advanced fibrosis in at-risk adults in the US, particularly when paired with semaglutide therapy. These findings support payer and policy consideration of AI-enabled screening programs.