United European Gastroenterology Journal最新文献

{"title":"Update on Autoimmune Pancreatitis and IgG4-Related Disease.","authors":"Marco Lanzillotta, Miroslav Vujasinovic, Johannes-Matthias Löhr, Emanuel Della Torre","doi":"10.1002/ueg2.12738","DOIUrl":"https://doi.org/10.1002/ueg2.12738","url":null,"abstract":"<p><p>Autoimmune pancreatitis is an increasingly recognized inflammatory type of subacute pancreatitis; two subtypes of autoimmune pancreatitis have been identified so far: the \"lymphoplasmacytic\" type 1 variant and the \"neutrophilic\" type 2 variant. Type 1 autoimmune pancreatitis represents the most common manifestation of IgG4-related disease, a fibro-inflammatory disorder characterized by elevated IgG4 levels in the serum and affected tissues. Type 2 autoimmune pancreatitis is a pancreas-specific disorder that frequently occurs in the context of inflammatory bowel diseases. Due to the complexity of both diseases, a comprehensive work up with imaging, laboratory, and histological studies is required to achieve a diagnosis and rule out malignancies. Glucocorticoids represent the cornerstone of the treatment, often supported by other immunosuppressive drugs in case of steroid intolerance or aggressive disease. Maintenance treatment is often employed in type 1 autoimmune pancreatitis because of the higher relapse rate compared with type 2 autoimmune pancreatitis. In this review, we summarize the key concept of autoimmune pancreatitis, delve into the differential diagnosis between the two subtypes, and cover the recent relevant research findings and pressing unmet needs.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation remains a dynamic component of portal hypertension in regressive alcohol-related cirrhosis.","authors":"Benedikt Silvester Hofer, Benedikt Simbrunner, Philipp Königshofer, Ksenia Brusilovskaya, Oleksandr Petrenko, Vlad Taru, Thomas Sorz-Nechay, Kerstin Zinober, Katharina Regnat, Georg Semmler, Carolin Lackner, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger","doi":"10.1002/ueg2.12643","DOIUrl":"https://doi.org/10.1002/ueg2.12643","url":null,"abstract":"<p><strong>Background: </strong>Portal hypertension (PH) resulting from static and dynamic intrahepatic changes drives liver-related complications even after removing the underlying aetiological factor.</p><p><strong>Objective: </strong>We investigated the impact of inflammation on the dynamic component of PH during disease regression in animal models of toxin-induced cirrhosis and patients with alcohol-related cirrhosis.</p><p><strong>Methods: </strong>In mice, cirrhosis was induced via toxin application for 12 weeks followed by toxin-withdrawal allowing for one or 2 weeks of regression. Furthermore, 128 patients with alcohol-related cirrhosis and alcohol abstinence undergoing same-day hepatic venous pressure gradient (HVPG) and liver stiffness measurement (LSM) were included. The influence of inflammation on the dynamic PH component was assessed using linear models. Specifically, we explored proinflammatory changes in mice/patients in whom the measured portal pressure (PP)/HVPG was significantly higher than the PP/HVPG expected from the static PH component (histological collagen proportionate area [CPA; %] in mice, LSM in patients).</p><p><strong>Results: </strong>In mice, toxin discontinuation induced a significant decrease in PP, CPA, histological hepatic inflammation and hepatic expression of proinflammatory genes (Tnfa, Il6, Cxcl1, Mcp1; all p < 0.05 for one/2 week regression vs. peak disease). Similarly, prolonged abstinence in alcohol-related cirrhosis was linked to lower HVPG/LSM and longer abstinence was correlated to lower C-reactive protein (CRP), IL-6, immunoglobulin A (IgA) and IgG levels (all p < 0.05). Nevertheless, the persistence of a low-grade proinflammatory state during regression was linked to a higher PP/HVPG than expected from static PH components. In regressive mice, higher hepatic proinflammatory gene expression (Tnfa, Il6, Il1b; all p < 0.05) was linked to higher-than-expected PP. Similarly, higher CRP, IL-6, IgA and IgG and lower complement factor C3c (all p < 0.05) were associated with higher-than-expected HVPG in abstinent patients with alcohol-related cirrhosis.</p><p><strong>Conclusions: </strong>Although removing the underlying aetiological factor resulted in significant improvements, a persistent hepatic proinflammatory environment remained a key driver of the dynamic PH component in regressive liver disease.</p><p><strong>Clinical trial number: </strong>NCT03267615.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic and Idiopathic Pancreatitis-A Personalized Treatment Approach.","authors":"Julian Cardinal von Widdern, Jonas Rosendahl, Christoph Ammer-Herrmenau","doi":"10.1002/ueg2.12741","DOIUrl":"https://doi.org/10.1002/ueg2.12741","url":null,"abstract":"<p><p>Chronic pancreatitis is a fibroinflammatory disease of the pancreas with heterogeneous clinical features and a significant socioeconomic burden. Assessing its aetiology and early diagnosis of associated complications remain challenging. Personalized therapy necessitates precise knowledge of the genetic, biological, and clinical differences within a patient population. In this context, the identification of the underlying aetiology represents an essential cornerstone. This review elucidates current standards for identifying underlying aetiologies and the diagnostic work-up for idiopathic cases. It provides an overview of general therapeutic approaches and highlights individual treatment options. Additionally, the follow-up management of pancreatitis-associated complications, namely exocrine pancreatic insufficiency, post-pancreatitis diabetes mellitus, pain management, pancreatic fluid collections, and pancreatic cancer risk, is summarized.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Eligibility Criteria in Inflammatory Bowel Disease Clinical Trials: A Clinical Trial Databank Analysis.","authors":"An Outtier, Rosanne Janssens, Liese Barbier, João Sabino, Bram Verstockt, Séverine Vermeire, Isabelle Huys, Marc Ferrante","doi":"10.1002/ueg2.12731","DOIUrl":"https://doi.org/10.1002/ueg2.12731","url":null,"abstract":"<p><strong>Background: </strong>Eligibility criteria in clinical trials have been criticised for being overly restrictive without clinical justification.</p><p><strong>Objective: </strong>We aimed to investigate the types, evolution, and current status of eligibility criteria in clinical trials for inflammatory bowel diseases (IBD).</p><p><strong>Methods: </strong>We performed a clinical trial databank search on clinicaltrials.gov, and included all Phase 3 placebo-controlled randomised-controlled trials (RCTs) investigating biologics or small molecules as induction therapy for moderate-to-severe Crohn's disease (CD) and ulcerative colitis (UC). Eligibility criteria were analysed both quantitatively and qualitatively.</p><p><strong>Results: </strong>Fifty-nine RCTs were identified between the year 2000 and 2022 (30 for CD and 29 for UC). The median (interquartile range) number of eligibility criteria was 44 (38-49), and did not significantly change over the studied time period (p = 0.26). Qualitative analysis showed that common patient populations, such as older patients, therapy refractory patients, patients with comorbidities, prior malignancies, unclassified IBD type, ulcerative proctitis, stricturing and fistulizing CD, as well as patients with an ostomy, were often excluded. Heterogeneity in eligibility criteria across the different IBD clinical trials was found, such as for disease activity measurement, dosage of concomitant medication, wash-out period of advanced therapies, and laboratory tests.</p><p><strong>Conclusion: </strong>The median number of eligibility criteria for IBD RCTs did not significantly change over time. The eligibility criteria are however restrictive and complex, limiting the generalisability of efficacy and safety outcomes in daily practice when drugs are approved. Future research is needed to investigate the impact of broadening eligibility criteria to better encompass real-world practice.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical relevance of calprotectin in patients with perianal fistulas in Crohn's disease and cryptoglandular fistulas.","authors":"Marte A J Becker, Toer W Stevens, Floris A E de Voogd, Manon E Wildenberg, Geert R A M D'Haens, Krisztina B Gecse, Christianne J Buskens","doi":"10.1002/ueg2.12622","DOIUrl":"https://doi.org/10.1002/ueg2.12622","url":null,"abstract":"<p><strong>Background and aims: </strong>Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.</p><p><strong>Methods: </strong>In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included. Faecal and fistula tract scraping calprotectin levels were determined. The primary objective was to analyse whether FC levels could be used to differentiate between Crohn's disease and cryptoglandular perianal fistulas. Secondary outcome parameters were the levels of local calprotectin in fistula scrapings and their correlation with fistula characteristics.</p><p><strong>Results: </strong>Sixty-three patients were included in this study (perianal Crohn's disease; 45, cryptoglandular; 18). Faecal calprotectin levels were significantly higher in Crohn's disease patients compared with cryptoglandular fistula (354.3 [58.8-1076.3] vs. 47.3 [14.6-233.6] μg/g, p = 0.003). Faecal calprotectin could accurately discriminate Crohn's disease patients with active luminal disease from patients without luminal disease (median [interquartile range]) (1167.0 [557.0-2806.3] vs. 93.0 [47.5-571.6] μg/g, p = 0.001). Faecal calprotectin was not related to calprotectin levels in fistula scrapings. No fistula characteristic was found to be correlated to scraping calprotectin, but a correlation was found with the TOpCLASS classification system, which stratifies fistulas according to disease severity and outcome: class 2a (amenable for repair), class 2b (symptom control) and class 2c (gradually debilitating disease): 140[31.0-149.0]) μg/g versus 706[198.5-1936] μg/g versus 4000[1337-5894] μg/g, p < 0.001). Scraping calprotectin was also related to pronounced hyperintensity of the fistula tract on MRI in Crohn's disease patients: (69.0[30.0-821.0] vs. 1284.0[204.3-4185.5]; p = 0.01)) and cryptoglandular patients: (30.0[13.5-80.5] vs. 3012.0 [923.8-5021.0]; p = 0.002).</p><p><strong>Conclusion: </strong>Crohn's disease and cryptoglandular perianal fistulas differ in FC levels. Local fistula calprotectin production did not explain this difference, implying FC reflects the luminal condition. A correlation exists between scraping calprotectin levels and Crohn's disease fistula severity, which could be clinically relevant for prognostic cohorts and tailored treatment.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Biologics and Janus Kinase Inhibitors With Inflammatory Bowel Disease as Paradoxical Reactions: A Real-World Assessment.","authors":"Zhi-Qing Zhan, Jia-Xin Li, Ying-Xuan Chen, Jing-Yuan Fang","doi":"10.1002/ueg2.12719","DOIUrl":"https://doi.org/10.1002/ueg2.12719","url":null,"abstract":"<p><strong>Background and objective: </strong>With limited evidence connecting paradoxical inflammatory bowel disease (paradoxical IBD) to the newest biologics and Janus kinase inhibitors, our study aims to investigate the occurrence of paradoxical IBD induced by these agents in treating other immune-mediated inflammatory diseases (IMIDs). We aim to identify associated risk signals, the primary affected population, and the risk profile changes over time.</p><p><strong>Methods: </strong>We performed disproportionality analysis to evaluate paradoxical IBD risk signals using data from the FDA Adverse Event Reporting System. Stratification analyses according to IBD subtype, age, gender, and agents' indications were performed. Weibull shape parameter (WSP) test was conducted to assess paradoxical IBD risk changes over time. Linkage disequilibrium score regression and Mendelian Randomization were employed to evaluate genetic correlations and causality between these agents' indications (i.e., non-IBD IMIDs) and IBD.</p><p><strong>Results: </strong>This study included 3296 patients reporting 3407 occurrences of paradoxical IBD following using these agents as primary suspects. Among TNF blockers, consistent positive signals for paradoxical IBD were noted: Adalimumab (n = 1983, ROR [95%CI] = 1.55 [1.47-1.63]), Infliximab (n = 545, ROR [95%CI] = 2.12 [1.95-2.32]), Certolizumab Pegol (n = 342, ROR [95%CI] = 1.9 [1.71-2.12]), and Golimumab (n = 154, ROR [95%CI] = 1.64 [1.4-1.93]). Ustekinumab, an IL-12 and IL-23 antagonist, also showed a strong positive signal (n = 155, ROR [95%CI] = 2.03 [1.73-2.39]). Conversely, Upadacitinib, Tofacitinib (Janus kinase inhibitors), and Risankizumab (IL-23 antagonist) exhibited insignificant associations with paradoxical IBD. Crohn's disease (CD) is the mainly developing form. WSP analysis identified two temporal patterns of paradoxical IBD: early failure and random failure types. Significant genetic correlations between three IMIDs and IBD were uncovered, with psoriasis specifically found to causally elevate CD risk.</p><p><strong>Conclusions: </strong>This study identifies paradoxical IBD as a consistent positive signal across multiple IMID agents, predominantly manifesting as CD, potentially aiding in timely detection and therapeutic decision-making.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herniation of Pancreatic Intraductal Papillary Mucinous Neoplasm Into Hiatal Hernia.","authors":"Hideaki Kazumori","doi":"10.1002/ueg2.12727","DOIUrl":"https://doi.org/10.1002/ueg2.12727","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on the Pancreas: Disease Mechanisms and Therapeutic Strategies.","authors":"Iris J M Levink, Alberto Balduzzi, Lumir Kunovsky, Albrecht Neesse","doi":"10.1002/ueg2.12733","DOIUrl":"https://doi.org/10.1002/ueg2.12733","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Evaluation of Real-Time Artificial Intelligence for the Hill Classification of the Gastroesophageal Junction.","authors":"Ioannis Kafetzis, Philipp Sodmann, Bianca-Elena Herghelegiu, Markus Brand, Wolfram G Zoller, Florian Seyfried, Karl-Hermann Fuchs, Alexander Meining, Alexander Hann","doi":"10.1002/ueg2.12721","DOIUrl":"https://doi.org/10.1002/ueg2.12721","url":null,"abstract":"<p><strong>Background: </strong>Assessment of the gastroesophageal junction (GEJ) is an integral part of gastroscopy; however, the absence of standardized reporting hinders consistency of examination documentation. The Hill classification offers a standardized approach for evaluating the GEJ. This study aims to compare the accuracy of an artificial intelligence (AI) system with that of physicians in classifying the GEJ according to Hill in a prospective, blinded, superiority trial.</p><p><strong>Methods: </strong>Consecutive patients scheduled for gastroscopy with an intact GEJ were recruited during clinical routine from October 2023 to December 2023. Nine physicians (six experienced, three inexperienced) assessed the Hill grade, and the AI system operated in the background in real-time. The gold standard was determined by a majority vote of independent assessments by three expert endoscopists who did not participate in the study. The primary outcome was accuracy. Secondary outcomes were per-Hill grade analysis and result comparison for experienced and inexperienced endoscopists separately.</p><p><strong>Results: </strong>In 131 analysed examinations the AI's accuracy of 84.7% (95% CI: 78.6-90.8) was significantly higher than 62.5% (95% CI: 54.2-71) of physicians (p < 0.01). The AI outperformed physicians in all but one cases in the per-Hill-class analysis. AI was significantly more accurate than inexperienced physicians (85% vs. 56%, p < 0.01) and in trend better than experienced physicians (84% vs. 69.6%, p = 0.07).</p><p><strong>Conclusions: </strong>AI was significantly more accurate than examiners in assessing the Hill classification. This superior model performance can prove beneficial for endoscopists, especially those with limited experience.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT06040723.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascending the \"Hill\" of Artificial Intelligence in Upper Gastrointestinal Endoscopy.","authors":"Cem Simsek, Nasim Parsa, Lumir Kunovsky","doi":"10.1002/ueg2.12730","DOIUrl":"https://doi.org/10.1002/ueg2.12730","url":null,"abstract":"","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}