University Gastroenterology

While commonly prescribed in patients with inadequate bowel preparation, split-dose, 2-day bowel preparation (2DBP) with 8L of polyethylene glycol-electrolyte lavage solution (PEG-ELS) has unknown effectiveness and safety. To assess the effectiveness of a split-dose, 8L-2DBP in patients with a prior failed bowel preparation. We retrospectively identified all outpatients with inadequate bowel preparation on index colonoscopy with a 1-day split-dose prep who had repeat colonoscopy with a split-dose 2DBP (2015 to 2021) at a single Veterans Affairs medical center. We then assessed adequate bowel preparation (outcome), defined as excellent/good or Boston Bowel Prep Score (BBPS) 6 or greater, with a score of 2 in all colon segments. We also collected data on patient factors associated with inadequate preparation. Logistic regression was used to identify associations between these factors and inadequate preparation after split-dose 2DBP. All patient records were manually reviewed to identify potential adverse effects resulting in emergency room presentation. Among 400 patients given 2DBP, 83.5% (95% CI: 79.5%-87.0%) achieved an adequate preparation. In multivariable analysis, a higher CCI (OR: 1.14, 95% CI: 1.04-1.25), opioid use (OR: 1.97, 95% CI: 1.03-3.77), and rural home address (OR: 1.87, 95% CI: 1.01-3.46) were associated with inadequate bowel preparation. No attributable adverse events were recorded. In this difficult-to-prep population, split-dose 2DBP is effective in more than 80% of patients without evidence of severe adverse events. This intensive prep was less effective in patients with greater comorbidity burden, opioid use, or a rural home address.

To evaluate the clinical and endoscopic characteristics of esophageal mucosal white plaques (EMWPs) and to investigate potential underlying etiologies. A total of 162 patients presenting with EMWPs were included as the case group. An equal number of patients without EMWPs served as the control group. Clinical symptoms, endoscopic findings, and fungal examination results were compared between the groups to identify potential contributing factors. EMWPs were most frequently observed in the middle and lower segments of the esophagus (87.1%). Compared with the control group, patients in the case group exhibited significantly higher frequencies of psychological stress (P=0.036), heartburn (P<0.001), acid regurgitation (P<0.001), retrosternal pain (P<0.001), pharyngitis (P=0.017), and globus sensation (P=0.042). Endoscopic examination revealed significantly higher detection rates of reflux esophagitis (P<0.001), hiatal hernia (P<0.001), duodenogastroesophageal reflux (P<0.001), antral hyperemia (P=0.019), and fundic hyperemia (P<0.001) in the case group. Helicobacter pylori (H. pylori) infection was significantly less prevalent among patients with EMWPs compared with controls (P=0.001). Among 142 patients who underwent fungal examination, no significant differences were identified between those with positive and negative results regarding reflux esophagitis, H. pylori infection, or ulcerative disease. EMWPs primarily involve the middle and lower esophageal segments and are associated with symptoms, such as heartburn, acid regurgitation, retrosternal pain, pharyngitis, and globus sensation. The lower prevalence of H. pylori infection, along with elevated rates of psychological stress and reflux-related findings, indicates a possible association with gastroesophageal reflux disease and stress-related factors.

IntroductionCystic lesions of the pancreas have continued to present a clinical challenge for the past decades now. The increasing rate of detection, the lack of high-quality data on the natural biology of pancreatic cysts and the resulting difficulty to predict malignant transformation in different types of pancreatic cysts make patients with these diseases hard to manage. The German Pancreas Club Cyst Registry (GerPaCyst) (DRKS00025927) aims to establish a platform to discover and survey the natural and specific biology of pancreatic cysts such as IPMNs (main and branch ducts), SCNs, SPPT and MCNs, in a multicenter manner.Materials and methodsThis manuscript is written according to the SPIRIT guidelines (See S2 and S3 Tables). Ethical approval was obtained from the University of Luebeck (2020-20-225) and all participating centers. In GerPaCyst patients aged ≥18 years with a pancreatic cyst under surveillance or scheduled for surgery should be enrolled. Participating centers will complete an electronic Case Report Form (eCRF) via REDCap which is designed as a longitudinal study minimizing the input of repeated measures. Changes in patient baseline data, cyst characteristics, both endoscopic and imaging data will be entered typically every 6–12 months during patient follow-up. Biobanking will be performed, when available. Duration of observation per patient is up to a maximum of 20 years or until end of follow-up or death.ResultsThe primary goal is to assess and calculate individual risk models for malignancy/high-grade dysplasia based on the collected clinical, molecular and imaging data (multi-omics prediction models) for each included cyst entity, therefore the primary outcome of this trial is the development of high-grade dysplasia/invasive cancer during follow-up or the absence of it. The secondary outcomes are death, quality of life measured by EQ-5D-5L questionnaire, end-of-follow up and perioperative characteristics, if applicable such as complications, length of hospital stay and clavien-dindo classification. Another goal will be to build a multicenter, interdisciplinary database to generate high-quality cyst biology data, which can then be used for further research questions. Additionally, this database will be utilized for registry- based interventional trials in the future.DiscussionGerPaCyst will provide a valuable platform for clinical outcomes research. Fundamental factors affecting the development of pancreatic cysts over time will be identified. New research questions might be answered during the study period and will be made available through continuous publications.Trial registrationThe study was prospectively registered at the German Clinical Trial Register (DRKS) under DRKS00025927 on September 14th, 2021, before inclusion of the first patient. The Universal Trial Number (UTN) is U1111-1302–9822.

Advanced histologic fibrosis is a major predictor of mortality in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to identify advanced fibrosis clinical determinants across diverse MASLD populations and to assess the prognostic value of noninvasive markers (NITs) of fibrosis for adverse outcomes. The Global MASLD (G-MASLD) enrolled biopsy-confirmed MASLD patients with clinical, histologic, and noninvasive test (NIT) data. Factors associated with the presence of advanced histologic fibrosis (F3-F4) in MASLD and clinical outcomes were assessed. There were 17,792 patients with MASLD. Advanced fibrosis (≥F3) was present in 35%. The prevalence of type 2 diabetes (T2D) increased stepwise with fibrosis stage, from 28% in F0 to 70% in F4 (trend p <0.0001). Independent predictors of advanced fibrosis included older age, T2D, and obesity, although the association with obesity varied by region. Among patients with follow-up (mean 6.6y), 6.5% died and 10.1% experienced a clinical event. Older age, male sex, T2D, and obesity were independent predictors of both mortality and clinical events ( p <0.05). Fibrosis severity, whether defined histologically or by NITs, was strongly associated with higher risks of death and liver-related outcomes (all adjusted HR>1.0, p <0.001). Five-year mortality was 2.1% overall, rising to 8.3% in patients with cirrhosis, and exceeded 10% among those with high-risk NIT score values. In this large global biopsy-based MASLD cohort, advanced fibrosis was highly prevalent and strongly linked to T2D. Both histologic fibrosis and NITs were independent predictors of mortality and clinical outcomes, underscoring the prognostic value of fibrosis assessment with NITs.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with adverse clinical outcomes, impaired health-related quality of life, and significant economic burden. The growing burden of MASLD and MASH has led to the publication of a large number of MASLD/MASH guidelines by national and international societies. However, important differences among the recommendations have created confusion, contributing to a low implementation rate and suboptimal management of MASLD and MASH. Creating a consensus recommendation has become more important since the approval of a selective agonist of thyroid hormone β receptor (resmetirom) for MASH treatment in the United States. We built a consensus among the most recently published recommendations for MASLD/MASH. A comprehensive search for MASLD and MASH guidelines, guidance documents, or similar publications from January 2018 to January 2025 using PubMed, Embase, Web of Science, and society websites was conducted. Each selected document was assessed across 8 specific domains with 145 variables. Variables with <50% concordance were used for the Delphi statement development. A supermajority threshold of 67% was set for statement acceptance. There were 61 documents published from 2018 through January 2025. Four rounds of Delphi were conducted: 46 statements were generated for Round 1, 32 statements for Round 2, 16 statements for Round 3, and 8 statements for Round 4, whereby 100% of statements achieved a greater than 90% agreement. All final consensus recommendations were summarized in tables and algorithms. Our study provides an extensive set of recommendations generated based on a comprehensive review of the most recent MASLD/MASH guidelines and a consensus-building process.

Methylmalonic acidemia (MMA) is a severe metabolic disorder affecting multiple organs because of a distal block in branched-chain amino acid (BCAA) catabolism. Standard of care is limited to protein restriction and supportive care during metabolic decompensation. Severe cases require liver/kidney transplantation, and there is a clear need for better therapy. Here, we investigated the effects of a small molecule branched-chain amino acid transaminase (BCAT) inhibitor in human MMA hepatocytes and an MMA mouse model. Mitochondrial BCAT is the first step in BCAA catabolism, and reduction of flux through an early enzymatic step is successfully used in other amino acid metabolic disorders. Metabolic flux analyses confirmed robust BCAT inhibition, with reduction of labeling of proximal and distal BCAA-derived metabolites in MMA hepatocytes. In vivo experiments verified the BCAT inhibition, but total levels of distal BCAA catabolite disease markers and clinical symptoms were not normalized, indicating contributions of substrates other than BCAA to these distal metabolite pools. Our study demonstrates the importance of understanding the underlying pathology of metabolic disorders for identification of therapeutic targets and the use of multiple, complementary models to evaluate them.