Digestive Diseases and Sciences最新文献

Purpose: Rapid advances in genomics have transformed our understanding of the biological mechanisms underlying inflammatory bowel disease (IBD). Although adult-onset IBD is predominantly polygenic, current applications of genetics lie in monogenic forms of IBD and pharmacogenetics. This review aims to serve as a primer for clinicians and outline the evolving role of genomics in IBD, identify clinical scenarios in which genetic testing is relevant, and highlight its implications for diagnosis and treatment.

Methods: A narrative review of the literature was performed, focusing on monogenic causes of IBD, diagnostic approaches to suspected monogenic cases, therapeutic implications and established pharmacogenetic associations relevant to clinical practice.

Results: Genome-wide association studies have identified more than 320 susceptibility loci associated with Crohn's disease and ulcerative colitis, implicating pathways involving innate immunity, autophagy, epithelial barrier integrity, and cytokine signalling. However, these common variants individually confer modest disease risk and explain only a limited proportion of heritability, restricting their direct clinical utility. In contrast, nextgeneration sequencing has enabled the identification of rare, high-penetrance monogenic defects, particularly in very-early-onset and treatment-refractory IBD. Recognition of these disorders has important therapeutic implications, including targeted biologic therapy and, in selected cases, curative hematopoietic stem cell transplantation. In parallel, pharmacogenetic testing, most notably for NUDT15 and TPMT variants, has become integral to optimising thiopurine safety.

Conclusions: Advances in genomics are steadily reshaping the clinical management of inflammatory bowel disease. Integration of genetic testing, particularly in patients with very early-onset or difficult-to-treat disease and in optimising drug safety, can support more informed, individualised treatment decisions. As genomic technologies become increasingly accessible, their incorporation into routine IBD care has the potential to improve outcomes and move clinical practice closer towards personalised medicine.

Background and aims: Peroral endoscopic myotomy (POEM) is a highly effective treatment option for achalasia cardia. However, lack of an anti-reflux mechanism predisposes patients to gastroesophageal reflux disease (GERD). This study was undertaken to assess the incidence of reflux esophagitis two years post POEM and to identify predictive factors associated with GERD development.

Methods: Consecutive patients who underwent POEM at our institution between July 2021 and December 2021 were prospectively studied to assess the incidence and predictors of GERD. Subjective GERD was evaluated using a validated questionnaire, while objective GERD was determined using PH impedance (AET > 6% or reflux) and esophagogastroduodenoscopy.

Results: Fifty four patients with achalasia cardia, underwent POEM during the study period. Evaluation of GERD was completed on 50 patients (92.5%).The majority of patients were treatment-naive (90%) and diagnosed with either type II achalasia (86%) or type I achalasia (14%). GERD was identified by pH impedance in 42%, by reflux esophagitis during endoscopy in 14%, and by symptomatic GERD in 18% of patients. Among these cases, 8 (16%) exhibited acidic reflux, while 13 (26%) demonstrated non-acidic reflux. An elevated acid exposure time (AET > 6%) was recorded in 11 patients (22%). The majority of cases were mild and non-erosive, with non-acidic reflux.

Conclusions: At two-year follow-up, objective GERD was more prevalent than symptomatic GERD following POEM, with rates comparable to laparoscopic Heller myotomy (LHM). Most cases were mild and non-acidic. No significant demographic or procedural predictors for symptomatic GERD were identified.

Purpose: Active cholangiocytes featured with massive proliferation activate hepatic stellate cells (HSCs) and could cause eventual liver fibrosis (LF), however, this crosstalk still remains unclear in biliary atresia (BA). We aimed to evaluate the involvement of cancer susceptibility candidate 15 (CASC15) in BA.

Methods: Cholangiocyte organoid culture and sequencing was used to identify differentially expressed long noncoding RNA associated with cholangiocyte proliferation. The expression level of CASC15 were detected in liver tissues. The CCK-8, EdU assay, co-culture experiments, and subcellular fractionation were employed to investigate its function and subcellular localization. Chromatin isolation by RNA purification coupled with mass spectrometry, RNA immunoprecipitation, and RNA sequencing were utilized to clarify the underlying mechanism of CASC15.

Results: CASC15 showed increased expression in cholangiocyte organoids and liver tissues of BA patients. Overexpressed CASC15 in cholangiocytes enhanced cell proliferation and promoted HSC activation in vitro. CASC15 predominantly located in the nucleus and was identified to interact with heterogeneous nuclear ribonucleoprotein U (HNRNPU) to maintain the expression of downstream target insulin-like growth factor binding protein 3 (IGFBP3), which could facilitate in the activation of HSCs.

Conclusion: This research revealed the crucial role of CASC15/HNRNPU-IGFBP3 regulatory network in the pathogenesis of LF in BA.

Background and aims: Dietary restrictions are critical for effective bowel preparation before colonoscopy. Milk has traditionally been considered to impair the quality of bowel preparation, and endoscopy centers commonly advise patients to avoid milk consumption prior to the procedure. However, no robust evidence currently supports this practice. We investigated whether milk intake affects bowel preparation quality and colonoscopy outcomes.

Methods: This prospective randomized controlled trial enrolled patients undergoing colonoscopy, randomizing them into either milk-inclusive low-residue diet group (Milk group) or standard low-residue diet group (LRD group). The primary outcome was the bowel preparation adequacy rate, evaluated using the Boston Bowel Preparation Scale. The secondary outcomes included colonoscopy quality metrics (polyp detection rate, adenoma detection rate, BBPS score, and cecal intubation rate), patient tolerability, participant preferences, and adverse event incidence.

Results: A total of 486 participants were randomly allocated to two groups. Non-inferiority of the Milk group to the LRD group was demonstrated, as the lower limits of the one-sided 97.5% confidence intervals for the difference in adequate bowel preparation rates (mITT: - 0.6%; PPS: - 1.7%) were both above the - 10% margin. Bowel preparation quality was slightly higher in the Milk group than in the LRD group ( mITT: P = 0.049; PPS: P = 0.030). The incidence rate of nausea (21.2 vs. 30.1%, P = 0.046) was lower in the Milk group than those in the LRD group, and the satisfaction scores (3.79 ± 0.86 vs. 3.61 ± 0.84, P = 0.005) were higher in the Milk group. No significant differences were observed in polyp and adenoma detection rates between the two groups.

Conclusion: During colonoscopy preparation, milk-inclusive low-residue diet is non-inferior to a standard LRD for bowel preparation and is associated with better patient-reported tolerability. Allowing milk consumption on the day before colonoscopy is a safe and patient-friendly strategy that can be adopted to enhance comfort without compromising the quality of the examination.

Registration number: ChiCTR2500103886, Registration date: 06 June 2025 (retrospectively registered).

Introduction: Inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). Janus kinase inhibitors (JAKi) are approved to treat IBD, but there are concerns over whether they increase the risk of MACE or venous thromboembolism (VTE) in patients with IBD. We aimed to compare the incidence risk of MACE and VTE in patients with IBD treated with JAKi agents versus anti-TNFs.

Methods: We conducted a retrospective cohort study using the TriNetX database to identify patients  ≥ 18 years with IBD and treated with JAKi or anti-TNF therapy. Patients in the JAKi cohort were matched with patients treated with anti-TNF by using 1:1 propensity score matching. Patients with a history of a prior cardiovascular event were excluded from the analysis. Co-primary outcomes were MACE and VTE within 1-year after medication initiation. Additional subgroup analyses were performed based on age, sex, and IBD type. Kaplan-Meier analysis with adjusted hazard ratios (HRs) and 95% CIs were used to compare time-to-event rates.

Results: In total, there were 8942 patients in the JAKi cohort matched with 8942 patients in the anti-TNF cohort. There was no difference between the two cohorts in the development of MACE (aHR: 1.08; 95% CI: 0.87-1.33; p = 0.49) or VTE (aHR: 1.06; 95% CI: 0.84-1.36; p = 0.61). In patients aged ≥ 65 years, there was no statistically significant difference between the two cohorts in MACE outcomes (aHR: 0.95; 95% CI: 0.69-1.31; p = 0.75). Consistent findings were observed when comparing ulcerative colitis to Crohn's disease, upadacitinib to tofacitinib, or JAKi to infliximab.

Conclusion: Our results suggest that patients with IBD, including patients ≥ 65 years, who are treated with JAKi, were not at increased risk of MACE or VTE over a 12-month period as compared to those treated with anti-TNF therapy. Further prospective studies are warranted to confirm these findings.