Lancet Gastroenterology & Hepatology最新文献

{"title":"Treatment strategies and biomarkers in Crohn's disease: the PROFILE trial.","authors":"Jack Satsangi, Jan Nowak, Rahul Kalla, Jean-Frederic Colombel","doi":"10.1016/S2468-1253(24)00082-7","DOIUrl":"10.1016/S2468-1253(24)00082-7","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment strategies and biomarkers in Crohn's disease: the PROFILE trial.","authors":"Vinay Borkar, Yatin Lunagariya, Shivani Chopra, Deepak Sasikumar, Meghraj Ingle","doi":"10.1016/S2468-1253(24)00112-2","DOIUrl":"10.1016/S2468-1253(24)00112-2","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resmetirom for MASH-related cirrhosis.","authors":"Gong Feng, Virginia Hernandez-Gea, Ming-Hua Zheng","doi":"10.1016/S2468-1253(24)00124-9","DOIUrl":"10.1016/S2468-1253(24)00124-9","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the EGFR signalling pathway in metastatic colorectal cancer.","authors":"Stefania Napolitano, Giulia Martini, Davide Ciardiello, Sara Del Tufo, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello","doi":"10.1016/S2468-1253(23)00479-X","DOIUrl":"10.1016/S2468-1253(23)00479-X","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) and its activated downstream signalling pathways play a crucial role in colorectal cancer development and progression. After four decades of preclinical, translational, and clinical research, it has been shown that blocking the EGFR signalling pathway at different molecular levels represents a fundamental therapeutic strategy for patients with metastatic colorectal cancer. Nevertheless, the efficacy of molecularly targeted therapies is inescapably limited by the insurgence of mechanisms of acquired cancer cell resistance. Thus, in the era of precision medicine, a deeper understanding of the complex molecular landscape of metastatic colorectal cancer is required to deliver the best treatment choices to all patients. Major efforts are currently ongoing to improve patient selection, improve the efficacy of available treatments targeting the EGFR pathway, and develop novel combination strategies to overcome therapy resistance within the continuum of care of metastatic colorectal cancer.</p>","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":35.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking colorectal cancer prognosis: beyond microsatellite status.","authors":"Elisabetta Fenocchio","doi":"10.1016/S2468-1253(24)00129-8","DOIUrl":"10.1016/S2468-1253(24)00129-8","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":35.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Alexander G Miethke, Adib Moukarzel, Gilda Porta, Joshue Covarrubias Esquer, Piotr Czubkowski, Felipe Ordonez, Antonella Mosca, Amal A Aqul, Robert H Squires, Etienne Sokal, Daniel D'Agostino, Ulrich Baumann, Lorenzo D'Antiga, Nagraj Kasi, Nolwenn Laborde, Cigdem Arikan, Chuan-Hao Lin, Susan Gilmour, Naveen Mittal, Fang Kuan Chiou, Simon P Horslen, Wolf-Dietrich Huber, Thomas Jaecklin, Tiago Nunes, Anamaria Lascau, Lara Longpre, Douglas B Mogul, Will Garner, Pamela Vig, Vera F Hupertz, Regino P Gonzalez-Peralta, Udeme Ekong, Jane Hartley, Noemie Laverdure, Nadia Ovchinsky, Richard J Thompson","doi":"10.1016/S2468-1253(24)00080-3","DOIUrl":"10.1016/S2468-1253(24)00080-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders, the most prevalent being BSEP deficiency, resulting in disrupted bile formation, cholestasis, and pruritus. Building on a previous phase 2 study, we aimed to evaluate the efficacy and safety of maralixibat-an ileal bile acid transporter inhibitor-in participants with all types of PFIC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;MARCH-PFIC was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study conducted in 29 community and hospital centres across 16 countries in Europe, the Americas, and Asia. We recruited participants aged 1-17 years with PFIC with persistent pruritus (&gt;6 months; average of ≥1·5 on morning Itch-Reported Outcome [Observer; ItchRO(Obs)] during the last 4 weeks of screening) and biochemical abnormalities or pathological evidence of progressive liver disease, or both. We defined three analysis cohorts. The BSEP (or primary) cohort included only those with biallelic, non-truncated BSEP deficiency without low or fluctuating serum bile acids or previous biliary surgery. The all-PFIC cohort combined the BSEP cohort with participants with biallelic FIC1, MDR3, TJP2, or MYO5B deficiencies without previous surgery but regardless of bile acids. The full cohort had no exclusions. Participants were randomly assigned (1:1) to receive oral maralixibat (starting dose 142·5 μg/kg, then escalated to 570 μg/kg) or placebo twice daily for 26 weeks. The primary endpoint was the mean change in average morning ItchRO(Obs) severity score between baseline and weeks 15-26 in the BSEP cohort. The key secondary efficacy endpoint was the mean change in total serum bile acids between baseline and the average of weeks 18, 22, and 26 in the BSEP cohort. Efficacy analyses were done in the intention-to-treat population (all those randomly assigned) and safety analyses were done in all participants who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT03905330, and EudraCT, 2019-001211-22.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between July 9, 2019, and March 4, 2022, 125 patients were screened, of whom 93 were randomly assigned to maralixibat (n=47; 14 in the BSEP cohort and 33 in the all-PFIC cohort) or placebo (n=46; 17 in the BSEP cohort and 31 in the all-PFIC cohort), received at least one dose of study drug, and were included in the intention-to-treat and safety populations. The median age was 3·0 years (IQR 2·0-7·0) and 51 (55%) of 93 participants were female and 42 (45%) were male. In the BSEP cohort, least-squares mean change from baseline in morning ItchRO(Obs) was -1·7 (95% CI -2·3 to -1·2) with maralixibat versus -0·6 (-1·1 to -0·1) with placebo, with a significant between-group difference of -1·1 (95% CI -1·8 to -0·3; p=0·0063). Least-squares mean change from baseline in total serum bile acids was -176 μmol/L (95% CI -257 to -94) for maralixibat versus 11 μmol/L (","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration of risk reduction in colorectal cancer incidence and mortality after a complete colonoscopy in Ontario, Canada: a population-based cohort study.","authors":"Arlinda Ruco, Rahim Moineddin, Rinku Sutradhar, Jill Tinmouth, Qing Li, Linda Rabeneck, M Elisabetta Del Giudice, Catherine Dubé, Nancy N Baxter","doi":"10.1016/S2468-1253(24)00084-0","DOIUrl":"10.1016/S2468-1253(24)00084-0","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy.</p><p><strong>Methods: </strong>We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality.</p><p><strong>Findings: </strong>5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]).</p><p><strong>Interpretation: </strong>Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed.</p><p><strong>Funding: </strong>Canadian Institutes of Hea","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":35.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment strategies and biomarkers in Crohn's disease: the PROFILE trial.","authors":"Arno R Bourgonje, Marijn C Visschedijk, Eleonora A M Festen, Rinse K Weersma, Gerard Dijkstra","doi":"10.1016/S2468-1253(24)00120-1","DOIUrl":"10.1016/S2468-1253(24)00120-1","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scottish Parliament votes to increase minimum unit price for alcohol.","authors":"Udani Samarasekera","doi":"10.1016/S2468-1253(24)00125-0","DOIUrl":"10.1016/S2468-1253(24)00125-0","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":30.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecogastroenterology: cultivating sustainable clinical excellence in an environmentally conscious landscape.","authors":"Kassem Sharif, Enrique Rodriguez de Santiago, Paula David, Arnon Afek, Ian M Gralnek, Shomron Ben-Horin, Adi Lahat","doi":"10.1016/S2468-1253(23)00414-4","DOIUrl":"10.1016/S2468-1253(23)00414-4","url":null,"abstract":"<p><p>Gastrointestinal practices, especially endoscopy, have a substantial environmental impact, marked by notable greenhouse gas emissions and waste generation. As the world struggles with climate change, there emerges a pressing need to re-evaluate and reform the environmental footprint within gastrointestinal medicine. The challenge lies in finding a harmonious balance between ensuring clinical effectiveness and upholding environmental responsibility. This task involves recognising that the most significant reduction in the carbon footprint of endoscopy is achieved by avoiding unnecessary procedures; addressing the use of single-use endoscopes and accessories; and extending beyond the procedural suites to include clinics, virtual care, and conferences, among other aspects of gastrointestinal practice. The emerging digital realm in health care is crucial, given the potential environmental advantages of virtual gastroenterological care. Through an in-depth analysis, this review presents a path towards sustainable gastrointestinal practices, emphasising integrated strategies that prioritise both patient care and environmental stewardship.</p>","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":null,"pages":null},"PeriodicalIF":35.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}