Objectives: Perianal fistulizing Crohn's disease (pfCD) is a severe type of inflammatory bowel disease resulting in significant patient morbidity. Despite advancements in treatments, pfCD remains challenging to manage with low healing rates. Fecal diversion (FD) has previously demonstrated clinical improvement for patients with refractory disease. Our meta-analysis aimed to explore the clinical response to FD, rates of successful restoration of bowel continuity after FD, rates of re-diversion, and factors affecting the success of FD in pfCD.

Methods: A systematic review and meta-analysis was carried out of adult patients who had undergone FD for pfCD, with detailed patient outcome data. Studies were identified through a literature search of six bibliographic databases and one trial register, all run on February 28, 2025, including MEDLINE ALL, EMBASE, Emcare, APA PsycInfo, CINAHL, Cochrane Library, and Clinicaltrials.gov.

Results: Seventeen studies encompassing 714 adult pfCD patients were included. FD resulted in a 65% clinical improvement rate, yet considerable heterogeneity existed in study methodologies and outcome definitions. While 29% of patients achieved bowel restoration within a median follow-up of 58.2 months, challenges in sustaining the effects were evident, with 10% requiring repeat diversion and a 37% overall proctectomy/proctocolectomy rate. Factors associated with diversion success included the absence of rectal involvement and quiescent luminal disease, with biologic use showing no impact on outcomes.

Conclusions: FD offers symptom control in pfCD, although restoration rates remain low. These findings emphasize the need for individualized patient counseling. Future research should strive for uniform measures and refined approaches to enhance pfCD management.

Objectives: Endoscopic ultrasound-guided fine-needle aspiration and/or biopsy (EUS-FNA/B) is a diagnostic tool for gastrointestinal (GI) lesions. However, its effectiveness in the lower GI tract remains underreported. In this study, we aimed to evaluate the clinical utility of EUS-FNA/B for rectal and perirectal lesions.

Methods: Seventy-seven consecutive patients with rectal or perirectal lesions underwent EUS-FNA/B between 2009 and 2023. The histological diagnoses by EUS-FNA/B were compared with the final diagnoses to assess the former's diagnostic performance. Additionally, the therapeutic utility of EUS-FNA/B and its clinical applicability across various scenarios were investigated.

Results: Twenty-nine of the 77 patients had rectal lesions, with gastrointestinal stromal tumor (GIST) being the most common in 15 patients. Of the 48 patients with perirectal lesions, 27 and 21 had malignant and benign lesions, respectively. EUS-FNA/B was diagnostic in 61 (79.2%) patients, with the rates of 79.3% and 79.2% for rectal and perirectal lesions. EUS-FNA/B enabled timely treatment decisions by confirming malignancy (n = 32) and prevented unnecessary surgeries/procedures by establishing the benign nature of the lesions (n = 14). A definitive diagnosis of rectal GIST was made using EUS-FNA/B, thereby facilitating the initiation of neoadjuvant chemotherapy followed by anus-saving surgery (n = 10). EUS-FNA/B enabled the implementation of minimally invasive interventions such as EUS-guided drainage (n = 5). Adverse events occurred in five (6.5%) patients, with only one requiring hospitalization.

Conclusion: EUS-FNA/B is a valuable modality for patients with rectal or perirectal lesions, which facilitates accurate histological diagnosis, appropriate treatment, and favorable safety profiles.

Objectives: To develop a nomogram with easily available parameters to predict the risk of Crohn's disease (CD)-related bowel resection in patients with newly diagnosed CD.

Methods: We performed a retrospective cohort study by recruiting patients with newly diagnosed CD between 2005 and 2022. The patients were divided into the training and internal test sets in a 7:3 ratio. Adjusted multivariate Cox regression and least absolute shrinkage and selection operator analyses were used for feature selection. A nomogram was developed and evaluated using 10-fold cross-validation.

Results: Altogether 490 patients were included, among whom 67 (13.7%) received CD-related bowel resection during a median follow-up of 45.2 months. Stricturing or penetrating behavior, perianal involvement, and higher C-reactive protein (CRP) were independently associated with a higher risk of CD-related bowel resection, while higher white blood cell (WBC) and lymphocyte levels and hemoglobin levels were protective factors. The nomogram including disease behavior, hemoglobin, CRP, and lymphocyte and WBC counts yielded a C-statistic of 0.80 (95% confidence interval [CI] 0.74–0.86) in 10-fold cross-validation of the training set. Using the internal test set, the robust performance was verified with C-statistic, calibration slope, and calibration-in-the-large of 0.80 (95% CI 0.70–0.89), 1.10 (95% CI 0.61–1.56), and 0.28 (95% CI −0.17 to 0.67). Decision curve analyses indicated its potential clinical utility.

Conclusion: The nomogram integrating disease behavior and laboratory data might be a promising approach for early risk stratification of CD-related bowel resection, hence facilitating personalized treatment for newly diagnosed CD.

Objective: We aimed to investigate the prevalence of alexithymia in patients with functional defecation disorder (FDD) and its impact on treatment outcomes.

Methods: FDD patients who underwent high-resolution anorectal manometry and balloon expulsion test were enrolled. Symptoms, anorectal function, and treatment efficacy were assessed at baseline and after 4-week medication.

Results: Alexithymia was present in 29.5% of all 129 FDD patients. Compared to the non-alexithymia group, the alexithymia group had higher baseline scores for the Patient Assessment of Constipation-Symptoms (PAC-SYM) (19.0 vs. 15.0, p = 0.03), Patient Assessment of Constipation-Quality of Life (PAC-QOL) (67.0 vs. 26.0, p < 0.001), Zung's Self-Rating Anxiety Scale (SAS) (44.5 vs. 30.0, p < 0.001), and Self-Rating Depression Scale (SDS) (48.0 vs. 33.0, p < 0.001). Moreover, the improvements in post-treatment complete spontaneous bowel movements (CSBMs) (0.0 vs. 1.5, p = 0.041), PAC-SYM (0.0 vs. −11.5, p < 0.001), PAC-QOL (0.0 vs. −16.0, p < 0.001), SAS (0.0 vs. −1.0, p < 0.001), and SDS (0.0 vs. −3.0, p < 0.001) scores were less significant in the alexithymia group than in the non-alexithymia group. A high Toronto Alexithymia Scale-20 score was an independent risk factor for drug therapy failure in FDD patients (odds ratio 0.949, 95% confidence interval 0.919–0.980, p = 0.001).

Conclusion: Alexithymia is prevalent in FDD patients and significantly affects symptom severity, quality of life, mental state, and treatment outcomes.

Objectives: The association between reflux events and esophageal motility abnormality is unclear. We aimed to determine the relevance between reflux events and esophageal motility in proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD).

Methods: Patients with PPI-refractory or PPI-responsive GERD were enrolled. Ambulatory 24-h esophageal pH–impedance–pressure monitoring was performed. Reflux symptoms, reflux events, and esophageal motility during acid reflux episodes were recorded and compared between the two groups.

Results: Sixty patients with PPI-refractory GERD and 18 with PPI-responsive GERD were included, all of whom had pathological gastroesophageal reflux. There were no significant differences in the major acid reflux parameters (DeMeester score and proportion of patients with acid exposure time > 6%) between the two groups. However, the number of long acid reflux episodes and the time length of the longest reflux episodes were significantly higher in the PPI-refractory GERD group than in the PPI-responsive GERD group (both p < 0.05). Moreover, patients with PPI-refractory GERD had higher rates of ineffective primary (62.0% vs. 36.0%, p < 0.001) and secondary peristalsis (83.5% vs. 57.0%, p = 0.001) during long acid exposure (LAE) than those with PPI-responsive GERD. Patients with PPI-refractory GERD having LAE had a significantly lower frequency of primary and secondary peristalsis per minute and required a longer time to initiate secondary peristalsis than those without during their longest acid reflux period in the upright position (all p < 0.001).

Conclusion: Longer acid reflux episodes in patients with PPI-refractory GERD might result from frequent ineffective primary esophageal peristalsis and delayed initiation of effective secondary peristalsis.

Objectives: Difficult-to-treat Crohn's disease (DTT-CD) represents a critical unmet need in inflammatory bowel disease (IBD) management. However, its genetic architectures remain poorly understood. We aimed to evaluate the genetic characteristics and clinical manifestations of DTT-CD cases through integrated trio-based whole exome sequencing (WES) and longitudinal phenotyping.

Methods: In this cross-sectional cohort study, DTT-CD patients who met the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) criteria and their first-degree relatives underwent trio-WES analysis. Treatment persistence and remission rates were analyzed. Genetic variants were prioritized via cosegregation analysis, the American College of Medical Genetics and Genomics (ACMG) guidelines, and functional prediction algorithms.

Results: Among the 24 patients with DTT-CD, 87.5% failed at least two biologics, 33.3% required dual targeted therapy, and drug persistence declined across treatment lines (p = 0.0193). Remission rates were suboptimal (clinical: 41.7%; endoscopic: 50.0%). Trio-WES analysis identified 15 likely pathogenic candidate variants across 12 genes, including the established monogenic IBD gene XIAP (two novel variants: p.Asp247Glufs*19, p.Ser43X; two known variants: p.Arg381X, p.Arg238X), genome-wide association studies-implicated IBD risk genes (MAML2 and PLA2R1), and novel candidate variants (KIZ, LAMA5, SAMD9, etc.) that were potentially linked to epithelial-immune dysregulation.

Conclusions: This is the first trio-WES study of DTT-CD that reveals a high prevalence of monogenic XIAP deficiency (16.7%), advocating for genetic screening in refractory cases. Novel candidate genes implicate polygenic mechanisms of therapeutic resistance. Family-based sequencing may be used to elucidate the genetic background of DTT-CD cases to guide molecular diagnosis and personalized therapy.

Objective: To compare the efficacy and safety profile of arginine glutamate and L-ornithine-L-aspartate (LOLA) in treating mild hepatic encephalopathy (HE) and hyperammonemia in cirrhotic patients.

Methods: This single-center, open-label, non-inferiority, randomized controlled trial (RCT) enrolled patients aged 18–75 years with cirrhosis and mild HE. The patients were randomly allocated in the ratio of 1:1 using a randomization table to be treated with intravenous administration of arginine glutamate or LOLA for 7 days. The primary end-point was the clinical improvement of mild HE. Secondary end-points included post-treatment change in blood ammonia level and the time to complete the number connection test (NCT)-A. Adverse events and adverse drug reactions were documented.

Results: From July 2020 to June 2021, 108 cirrhotic patients with mild HE were included and randomized to receive either arginine glutamate or LOLA for 7 days. Clinical improvement was observed in 88.9% of the patients receiving arginine glutamate and 90.7% of those having LOLA (between-group difference −1.9%, 95% confidence interval −13.3% to 9.6%), indicating non-inferiority of arginine glutamate to LOLA. The two groups showed comparable reductions in blood ammonia levels and improvements in time to complete NCT-A. The rate of adverse events was similar between the two groups, with only four cases reported adverse drug reactions.

Conclusions: Both regimens effectively alleviated mild HE symptoms and reduced ammonia levels. Arginine glutamate showed non-inferiority to LOLA in terms of clinical improvement, ammonia reduction, and time to complete NCT-A, with no significant adverse events.

Objectives: Fenofibrate is widely used as add-on therapy for patients with primary biliary cholangitis (PBC) who have a suboptimal response to ursodeoxycholic acid (UDCA). We aimed to evaluate whether the UDCA biochemical response criteria, especially the GLOBE and UK-PBC risk scoring systems, could predict the long-term prognosis of PBC patients who received fenofibrate add-on therapy.

Methods: PBC patients receiving fenofibrate add-on therapy were included in this retrospective–prospective study. We compared the utility of nine biochemical response criteria and two scoring systems to predict clinical outcomes by Kaplan–Meier plots and the receiver operating characteristic (ROC) curve analysis.

Results: Sixty-three patients were included in this study, of whom 11 had a poor outcome (hepatic decompensation, liver-related death, or liver transplantation) and 52 had a good outcome. After a median follow-up of 45 months, fenofibrate add-on therapy steadily decreased the serum levels of alkaline phosphatase, γ-glutamyl transferase, and alanine aminotransferase in both groups. The patients with poor outcomes had a higher GLOBE score and UK-PBC risk score than those with good outcomes after 12 months of treatment. More importantly, both scores had better predictive performance for hepatic decompensation- and transplant-free survival than the other criteria. The areas under the ROC curve of the GLOBE and UK-PBC risk scores at 12 months were 0.878 (95% confidence interval [CI] 0.751–0.955) and 0.919 (95% CI 0.803–0.978), respectively.

Conclusion: The GLOBE and UK-PBC risk scores outperformed the other biochemical response criteria in predicting the clinical outcomes of PBC patients with suboptimal response to UDCA and receiving fenofibrate add-on therapy.