Frontiers in gastroenterology (Lausanne, Switzerland)最新文献

Background and aims: Post-ERCP pancreatitis (PEP) is the most common complication following ERCP, leading to significant clinical and economic consequences. Predictive models for PEP can help identify high-risk patients and guide preventive strategies. However, the performance of these models varies, and a comprehensive evaluation is lacking. This study aims to assess the accuracy, reliability, and risk of bias in existing predictive models for PEP.

Methods: A comprehensive search was conducted across five databases (PubMed, Embase, Web of Science, Cochrane Library, and CNKI) for studies published until January 2025. Studies that developed or validated predictive models for PEP were included. Models with external validation sets were included in a meta-analysis. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and calibration. A random-effects meta-analysis was performed, with heterogeneity assessed using I² statistics. Data extraction and risk of bias were conducted using a standardized template combining the CHARMS and PROBAST tools.

Results: Twenty-three studies (21 model development studies and 2 external validation studies) were included, presenting 21 predictive models for PEP. Nine models incorporated external validation, with one study recalibrating an existing model and another externally validating two prior models. The mean events per variable (EPV) across studies was 10.2 (2.2 to 22.4). The pooled AUC for externally validated models was 0.79 (95% CI: 0.75-0.83). Machine learning models demonstrated higher AUC (0.84) than traditional logistic regression models (0.76). Common predictive factors included difficult cannulation, female sex, pancreatic duct dilation, and a history of pancreatitis.

Conclusions: Predictive models for PEP show potential for improving patient risk stratification. However, variability in model performance, lack of external validation, and significant bias in many studies limit their clinical applicability. Further external validation, model refinement, and improved bias control are essential for broader clinical implementation.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024626168, identifier CRD42024626168.

Objective: Angiodysplasia of the gastrointestinal (GI) tract is a leading cause of occult GI bleeding, and its management remains challenging. Various pharmacologic and endoscopic therapies are used with limited success. This systematic review evaluates the clinical efficacy of thalidomide in angiodysplasia-related GI bleeding.

Methods: A comprehensive literature search was conducted across PubMed, Embase, Scopus, and CINAHL using MeSH terms "Vascular malformations" OR "Angiodysplasia" AND "Thalidomide," covering the period from 1994 to February 16, 2024. We included clinical trials and case series with at least five adult patients treated with thalidomide for angiodysplasia-related GI bleeding. Six studies met the inclusion criteria: two randomized controlled trials (RCTs), one retrospective observational study, and three case series.

Results: A total of 265 patients were included, with a median age of 63.5 years; 37% were male. Angiodysplasia was diagnosed using endoscopy, colonoscopy, or push enteroscopy. Clinical outcomes varied across studies. Garrido et al. reported an 84% response rate based on hemoglobin improvement. In an RCT, Chen et al. demonstrated reduced bleeding episodes in 68.6% of patients receiving thalidomide 100 mg compared with 51% in the 50 mg group. Ge et al. reported a response rate of 71.4% (20/28) in the thalidomide group versus 3.7% (1/27) in the iron group (risk difference 67.7%, 95% CI 51.1-84.2). Common adverse effects included constipation, dizziness, fatigue, limb numbness, and peripheral neuropathy.

Conclusion: Thalidomide appears effective in reducing bleeding episodes in angiodysplasia-related GI bleeding. However, heterogeneity in dosing, outcome definitions, and safety reporting highlights the need for larger, standardized trials to clarify optimal treatment strategies and long-term safety.

The number of pediatric liver transplant recipients with long-term follow-up exceeding 20 years is steadily increasing. These patients are characterized not only by their extensive medical histories but also by their long future life expectancy. In this context, careful management of post-transplant complications, including biliary issues, is essential. We identified 40 patients from our 193 pediatric transplants performed since the program's inception in 1995, with more than 20 years of follow-up at our center. Thirteen of these patients developed either early or late biliary complications. Five developed complications within the first post-transplant year, while eight developed late complications, which are the main focus of this study. We detail the management of biliary complications in these patients, providing an in-depth analysis of four case models and an overview of the remaining patients. In addition to the standard interventional options, such as percutaneous bilioplasties and surgical revisions of anastomoses, we identified a subgroup that may benefit from a more conservative approach, provided they are closely monitored through a rigorous follow-up protocol.

Ulcerative colitis is a chronic inflammatory bowel disease with rising global prevalence. Despite therapeutic advances including biologic agents targeting tumor necrosis factor-alpha, integrins, and interleukin pathways, alongside Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators, substantial unmet needs persist in moderate to severe disease. Current advanced therapies achieve clinical response rates of only 30-60% in trials, with approximately 20% of patients requiring hospitalization and 7% undergoing colectomy within five years of diagnosis. The therapeutic pipeline for moderate to severe ulcerative colitis currently encompasses over 100 investigational agents in Phase II and III clinical development. Emerging mechanisms include next-generation Janus kinase and tyrosine kinase 2 inhibitors with enhanced selectivity, novel cell trafficking modulators, advanced tumor necrosis factor-alpha inhibition strategies, and selective interleukin-23 pathway antagonists. Tumor necrosis factor-like ligand 1A pathway inhibitors demonstrate particularly robust efficacy in early trials, with clinical remission rates exceeding 25% compared to less than 2% for placebo. Additional promising approaches target immune checkpoint pathways, receptor-interacting protein kinase 1, and intracellular signaling cascades. innovative combination therapy approaches demonstrated to achieve superior response rates compared to monotherapy. The convergence of novel therapeutic targets, gut-selective compounds minimizing systemic immunosuppression, and biomarker-guided therapy selection represents a paradigm shift toward precision medicine. These advances hold genuine promise for transforming moderate to severe ulcerative colitis management.

Metabolic dysfunction-associated steatohepatitis (MASH), along with other chronic liver diseases, leads to progressive fibrosis and, ultimately, cirrhosis. Liver fibrosis is a major cause of global morbidity and mortality. Although past efforts to develop antifibrotic drugs have largely failed, recent advances in MASH metabolic therapies offer new hope. These include both indirect-acting agents such as glucagon-like peptide 1 (GLP-1) analogues, which reduce liver fat by promoting weight loss, and therapies with direct-acting mechanisms on the liver, such as thyroid hormone receptor beta (THRβ) activators and fibroblast growth factor 21 (FGF21) analogues. This perspective summarises emerging antifibrotics, from the fast-evolving class of metabolic therapies through to the more sluggish development of non-metabolic antifibrotics. We consider future therapeutic combinations and patient stratifiers that may impact patient outcomes, and close by asking if fibrosis reversal should be the only goal.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by late-stage manifestation and relative resistance to standard therapies. Challenges with early detection and a paucity of effective therapies lead to one of the lowest 5-year survival rates among all cancers. Individuals around 50 years and over presenting with new onset diabetes (NOD) have a higher risk for PDAC diagnosis within 3 years of diabetes onset compared to the rest of the population. In this review, we contextualize NOD within other types of diabetes presentations such as type 1 diabetes (T1D), type 2 diabetes (T2D), and type 3 diabetes (T3cD), unravel the bidirectional relationship between diabetes and PDAC, and highlight potential biomarkers that may distinguish PDAC-associated diabetes from other predominant types of diabetes. Although practical applications of NOD currently fall short from being clinically actionable, clinical trials are underway to stratify NOD patients with PDAC-associated diabetes. Ultimately, these efforts could offer the rationale to implement early detection screening strategies to this subgroup of PDAC patients.

Ischemic proctitis is a rare but severe condition characterized by ischemic injury to the rectum due to insufficient blood supply from the vessels feeding the rectum. Due to the rectum's rich collateral circulation, ischemic proctitis is uncommon. We present a case of a 61-year-old man with ischemic proctitis presenting primarily with rectal bleeding. Angiography confirmed the presence of a superior rectal arteriovenous fistula. The diagnostic process was quite challenging. The patient underwent endoscopic hemostasis and interventional embolization, and eventually underwent proctectomy due to rectal stenosis. A literature review on ischemic proctitis is also included.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a leading global cause of chronic liver disease, affecting 25-30% of the population. While MASLD is traditionally associated with obesity, lean MASLD-a subset characterized by hepatic steatosis and metabolic dysfunction in individuals with a normal body mass index (BMI)-is increasingly recognized as a distinct clinical entity. Lean MASLD accounts for approximately 5.1% of the global population and is more prevalent in Asia, where genetic predispositions such as PNPLA3 and TM6SF2 polymorphisms, visceral obesity, and high-carbohydrate dietary patterns are key risk factors. Lean MASLD is also associated with significant liver and non-liver complications, as well as increased all-cause mortality risk. Therefore, lean MASLD may pose a significant challenge for practitioners.

Introduction: There is accumulating evidence that certain perinatal and prenatal factors may contribute to the onset of IBD, however evidence on some risk factors is inconsistent. The present study seeks to extend current knowledge on these risk factors and provide a comprehensive overview of which factors are associated with IBD onset and their direction of effect.

Methods: A Systematic review and meta-analysis of case-control, cohort studies and randomised controlled trials (RCTs) investigating the association between parental and perinatal factors and onset of IBD was conducted. Studies were included if they reported details on patients with a diagnosis of IBD (including Crohn's Disease [CD] and/or Ulcerative Colitis [UC]), defined and measured according to endoscopic, radiological, and histopathological findings, confirmed by a gastroenterologist or physician. Computerised bibliographic searches of Ovid MEDLINE, Web of Science, and the Cochrane Library were conducted from 01/01/2002 to the 01/01/2022. Where possible, summaries of the effects of perinatal and prenatal variables for each study were provided by calculating risk estimates using the DerSimonian and Laird random effects model. Levels of heterogeneity were evaluated using the I² statistic. Data were analysed using Stata version 17. Study protocol details are published on the International prospective register of systematic reviews (PROSPERO), registration number: CRD42022290798.

Results: Fifteen eligible studies were identified, encompassing 9 case-control and 6 cohort studies, with no RCTs identified. A total of 6,507 patients with IBD were described in these studies (1,819 UC; 3,908 CD; 754 IBD; 4 IBD-unclassified patients). Three predictors of IBD risk were identified. Any poor maternal health or disease in mother during pregnancy (Pooled RR 1.78, 95% CI 1.24-2.31), maternal IBD (Pooled RR 4.59, 95% CI 1.68-7.50), and familial history (Pooled RR 2.87, 95% CI 1.80-3.93), were associated with an increased risk of overall IBD.

Discussion: This systematic review and meta-analysis suggests parental and perinatal factors may have a role in the onset of IBD. These findings highlight the importance of early-life exposures for later IBD development and indicate a requirement for further research in this area.

Systematic review registration: PROSPERO, identifier (CRD42022290798).