The Lancet最新文献

{"title":"Early-onset type 2 diabetes: no time for defeatism","authors":"","doi":"10.1016/s0140-6736(25)01295-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01295-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker risk stratification with capsule sponge in the surveillance of Barrett's oesophagus: prospective evaluation of UK real-world implementation","authors":"W Keith Tan, Caryn S Ross-Innes, Timothy Somerset, Greta Markert, Florian Markowetz, Maria O'Donovan, Massimiliano di Pietro, Peter Sasieni, Rebecca C Fitzgerald","doi":"10.1016/s0140-6736(25)01021-9","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01021-9","url":null,"abstract":"<h3>Background</h3>Endoscopic surveillance is the clinical standard for Barrett's oesophagus, but its effectiveness is inconsistent. We have developed a test comprising a pan-oesophageal cell collection device coupled with biomarkers to stratify patients into three risk groups. We aimed to prospectively evaluate the prespecified risk stratification tool to establish whether it can identify those at highest risk of dysplasia or cancer to prioritise the timing of endoscopy; and safely be used to follow up the low-risk group, thus sparing patients from unnecessary endoscopies.<h3>Methods</h3>Participants were recruited as part of two multicentre, prospective, pragmatic implementation studies from 13 hospitals in the UK. Patients with non-dysplastic Barrett's oesophagus had a capsule-sponge test which was assessed in an ISO-accredited laboratory. Patients were included if they were aged at least 18 years with a non-dysplastic Barrett's oesophagus diagnosis at their last endoscopy who were undergoing surveillance according to the published UK guidelines. Patients were assigned as low (clinical and capsule-sponge biomarkers negative), moderate (negative for capsule-sponge biomarkers, positive clinical biomarkers—age, sex, and segment length), or high risk (p53 abnormality or glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group assignment.<h3>Findings</h3>910 patients recruited between August, 2020, and December, 2024 participated, of whom 138 (15%) were classified as high risk, 283 (31%) moderate risk and 489 (54%) low risk. The positive predictive value for any dysplasia or worse in the high-risk group was 37·7% (95% CI 29·7–46·4). Patients with both atypia and aberrant p53 had the highest risk of high-grade dysplasia or cancer (relative risk 135·8 [95% CI 32·7–564·0] relative to the low-risk group). The prevalence of high-grade dysplasia or cancer in the low-risk group was 0·4% (95% CI 0·1–1·6); the negative predictive value for any dysplasia or cancer was 97·8% (95% CI 95·9–98·8). Applying a machine learning algorithm as part of a digital-pathology workflow reduces the proportion needing p53 pathology review to 32% without missing any positive cases.<h3>Interpretation</h3>The risk-panel substantially enriches for dysplasia and capsule-sponge-based surveillance could be used in low-risk Barrett's oesophagus in lieu of endoscopy.<h3>Funding</h3>Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"636 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future of once-weekly insulins in type 2 diabetes: efficacy and safety","authors":"Edith Wing-Kar Chow, Elaine Chow","doi":"10.1016/s0140-6736(25)01098-0","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01098-0","url":null,"abstract":"","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial","authors":"Thomas Blevins MD, Dominik Dahl MD, Federico C Pérez Manghi MD, Sreenivasa Murthy MD, Ramon Ortiz Carrasquillo MD, Xiaoqi Li PhD, Annette M Chang MD, Molly C Carr MD, Michelle Katz MD","doi":"10.1016/s0140-6736(25)01069-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01069-4","url":null,"abstract":"Insulin efsitora alfa (efsitora), a once-weekly basal insulin, has the potential to reduce the treatment burden of people with type 2 diabetes who require insulin. We aimed to assess the efficacy and safety of once-weekly efsitora compared with insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial","authors":"Prof Athena Philis-Tsimikas MD, Richard M Bergenstal MD, Timothy S Bailey MD, Hideaki Jinnouchi MD, James R Thrasher MD, Liza Ilag MD, Jit Mitra MS, Kristen Syring PhD, Rebecca J Threlkeld MS","doi":"10.1016/s0140-6736(25)01044-x","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01044-x","url":null,"abstract":"Once-weekly insulin efsitora alfa (efsitora) is in development for the treatment of people with diabetes. The aim of the current study was to assess the efficacy and safety of once-weekly efsitora compared with daily insulin degludec (degludec) in adults with type 2 diabetes using basal insulin.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"179 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial","authors":"Agnes Gasiorek, Arne Heydorn, Sanaz Gabery, Julie B Hjerpsted, Katrine Kirkeby, Thomas Kruse, Signe B Petersen, Søren Toubro, Andreas Vegge, Cassandra Key","doi":"10.1016/s0140-6736(25)01176-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01176-6","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;GLP-1 receptor agonists and amylin receptor agonists have shown clinically relevant weight loss and glucose-lowering effects in people with overweight, obesity, and type 2 diabetes. Amycretin is a novel, single-molecule GLP-1 receptor and amylin receptor agonist. We aimed to investigate the safety, tolerability, pharmacokinetic properties, and pharmacodynamic effects of single ascending doses (part A) and multiple ascending doses (parts B and C/D) of amycretin in adult participants with overweight or obesity.&lt;h3&gt;Methods&lt;/h3&gt;In this phase 1, first-in-human, randomised, double-blind, placebo-controlled multipart study, participants were recruited at a single clinical research unit in San Antonio (TX, USA). Eligible individuals were men or women (including women of childbearing potential) aged 18–55 years at the time of signing informed consent with a BMI of 25·0–34·9 kg/m&lt;sup&gt;2&lt;/sup&gt; for parts A and B and a BMI of 27·0–39·9 kg/m&lt;sup&gt;2&lt;/sup&gt; for part C/D. For part A, participants were randomly assigned across six treatment groups (single ascending doses of oral amycretin [1 mg, 3 mg, 6 mg, 12 mg, 18 mg (12 + 6 mg per adaptive study design), or 25 mg]) or placebo (6:2 to amycretin groups &lt;em&gt;vs&lt;/em&gt; placebo). Part A consisted of a 28-day screening period, a 1-day (single dose) intervention period, and a 21-day follow-up period. In part B, participants were randomly assigned across three treatment groups (multiple ascending doses of oral amycretin [3 mg, 6 mg, or 12 mg once daily]) or placebo (9:3 to amycretin groups &lt;em&gt;vs&lt;/em&gt; placebo). Part B consisted of a 28-day screening period, a 10-day intervention period, and a 21-day follow-up period. In part C/D, 60 participants were randomly assigned to one of three dose-escalation treatment groups (multiple ascending doses of oral amycretin in a fixed titration regimen for all participants [part C1: from 3 mg to 50 mg once daily; part C2: from 6 mg to 2 × 50 mg (two tablets in a single daily dose); and part D: from 3 mg to 2 × 25 mg (two tablets in a single daily dose)]), or placebo (16:4 to amycretin groups &lt;em&gt;vs&lt;/em&gt; placebo). Part C/D consisted of a 4-week screening period, a 12-week intervention period, and a 3-week follow-up period. The primary endpoint was the number of treatment-emergent adverse events reported from before dosing on day 1 (baseline) until the end-of-study visit on day 22 (part A), day 31 (part B), or day 105 (part C/D). Supportive secondary pharmacokinetic endpoints for parts A–D were area under the amycretin plasma concentration–time curve and maximum plasma concentration. Exploratory pharmacodynamic endpoints in part C/D were change in bodyweight (%) and fasting plasma glucose (mmol/L) from before dosing on day 1 until day 85. The safety analysis set, comprising all participants who were exposed to treatment, was used to analyse the endpoints and assessments related to safety. The full analysis set, comprising all randomly assigned participants, was used to an","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral palsy","authors":"Iona Novak, Michelle Jackman, Megan Finch-Edmondson, Michael Fahey","doi":"10.1016/s0140-6736(25)00686-5","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00686-5","url":null,"abstract":"Cerebral palsy is a lifelong physical disability affecting movement and posture. The motor impairments of cerebral palsy result from non-degenerative brain injuries, brain malformations, and genetic variations, arising from multiple risk factors and causal pathways during preconception, pregnancy, birth, or within the first 2 years of life. Over the past decade, substantial progress in diagnosing, preventing, and managing the condition has transformed treatment approaches. A key discovery is that up to 30% of individuals with CP have a genetic contribution. In high-income countries, the prevalence has decreased by as much as 40%, from 2·1 per 1000 livebirths to 1·6 per 1000 livebirths. However, the prevalence is higher in low-income and middle-income countries. Advances in early diagnosis make identification of cerebral palsy at as early as age 3 months possible, enabling timely, intensive early intervention that improves child and parent outcomes. Additionally, new medical, regenerative, and rehabilitation therapies have emerged, enhancing function and participation. Growing awareness of the health challenges and physical decline faced by adults underscores the need for a lifelong approach. This Seminar highlights the best available evidence and recent progress to help clinicians address key questions identified by individuals with lived experience.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 and amylin receptor multiagonism with amycretin for obesity management","authors":"Bernard Khoo, Tricia M-M Tan","doi":"10.1016/s0140-6736(25)01250-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01250-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptospirosis deaths in children in the Amazon: syndemic inequities","authors":"Esteban Ortiz-Prado, Juan S Izquierdo-Condoy, Camila Salazar-Santoliva, Jorge Vasconez-Gonzalez","doi":"10.1016/s0140-6736(25)01204-8","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01204-8","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clade IIb mpox outbreak in Sierra Leone","authors":"Oriol Mitjà, Deborah Watson-Jones, Edward M Choi, Mohamed Boi Jalloh, Foday Sahr","doi":"10.1016/s0140-6736(25)01203-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)01203-6","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}