Nature Medicine最新文献

{"title":"Unlocking the broad health benefits and risks of GLP-1 receptor agonist drugs","authors":"","doi":"10.1038/s41591-024-03476-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03476-8","url":null,"abstract":"This study systematically analyzed 175 health outcomes in 2 million people using glucagon-like peptide-1 receptor agonists (GLP-1RAs) or other antihyperglycemics. GLP-1RAs reduce risks of neurocognitive, substance use, cardiovascular and respiratory disorders, but increase risks of gastrointestinal issues, hypotension and pancreatitis. The study provides important insights for clinical practice and future research.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"15 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020382","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":"The Access to Dialysis in Low- and Middle-Income Countries Commission: lessons for universal health coverage","authors":"Yot Teerawattananon, Kinanti Khansa Chavarina, Jeerath Phannajit, Jiratorn Sutawong, Natcha Yongphiphatwong, Sydney C. W. Tang, Talerngsak Kanjanabuch, Tanainan Chuanchaiyakul, Thunyarat Anothaisintawee, Valerie Luyckx, Wanrudee Isaranuwatchai, Kearkiat Praditpornsilpa, Kriang Tungsanga, Vivekanand Jha","doi":"10.1038/s41591-024-03448-y","DOIUrl":"10.1038/s41591-024-03448-y","url":null,"abstract":"Announced in this Comment and in collaboration with Nature Medicine is the convening of the Access to Dialysis in Low- and Middle-Income Countries Commission, which will explore Thailand’s experiences with changing its dialysis coverage policy, offering lessons for other countries with universal health coverage systems.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"19-21"},"PeriodicalIF":58.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992229","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":"The Future of Medicine","authors":"","doi":"10.1038/s41591-024-03464-y","DOIUrl":"10.1038/s41591-024-03464-y","url":null,"abstract":"As Nature Medicine celebrates its 30th anniversary, we reflect on the challenges ahead and what the future holds for medicine — and for our journal.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"1-1"},"PeriodicalIF":58.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03464-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial","authors":"Lin Shen, Yanqiao Zhang, Ziyu Li, Xiaotian Zhang, Xiangyu Gao, Bo Liu, Yusheng Wang, Yi Ba, Ning Li, Ruixing Zhang, Jingdong Zhang, Ye Chen, Jian Chen, Mingzhu Huang, Yang Fu, Mulin Liu, Zheng Liu, Jun Zhao, Wei Li, Jia Wei, Changzheng Li, Nong Xu, Zengqing Guo, Bangwei Cao, Lian Liu, Peng Nie, Lixin Wan, Lili Sheng, Zhenyang Liu, Yifu He, Kangsheng Gu, Guowu Wu, Weibo Wang, Futong Zhang, Wensheng Qiu, Jun Guo, Jieer Ying, Hongming Pan, Huiting Xu, Yuan Yuan, Yuansong Bai, Zhenghua Wang, Jiye Xu, Xuehong Zhao, Hao Liu, Xizhi Zhang, Wenxiang Dai, Hongyan Xu, Ming Liu, Lin Xie, Yong Tang, Jianying Jin, Xiujuan Qu, Xuefeng Fang, Mingwei Huang, Hao Chen, Zhendong Zheng, Ying Wang, Daqing Wang, Xiaoqin Li, Guohua Yu, Haiyan Liu, Yongjian Zhou, Diansheng Zhong, Shan Zeng, Mafei Kang, Meiqing Wang, Yong Gao, Wenxin Li, Zejun Wang, Minghui Zhang, Jinghua Zhang, Qingshan Li, Shujuan Sun, Aimin Zang, Lizhu Lin, Ming Xie, Zhixiang Zhuang, Tao Zhang, Zhifang Yao, Dongmei Lu, Wei Liu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Jiajia Zhang, Xiangji Ying, Drew M. Pardoll, Jiafu Ji","doi":"10.1038/s41591-024-03450-4","DOIUrl":"https://doi.org/10.1038/s41591-024-03450-4","url":null,"abstract":"<p>Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here. This was a randomized, double-blind, placebo-controlled phase 3 study. Eligible patients were adults with untreated, unresectable, locally advanced or metastatic G/GEJ adenocarcinoma. Patients were randomized 1:1 to receive cadonilimab (10 mg kg⁻¹ every 3 weeks) or placebo plus chemotherapy (every 3 weeks). The primary endpoint was overall survival (OS) in the intention-to-treat population (one-sided significance level, <i>P</i> = 0.025). Secondary endpoints included OS in patients with a PD-L1 combined positive score ≥5, progression-free survival, objective response rate, duration of response and safety. As of 18 August 2023, 610 patients from 75 study centers were randomized to cadonilimab (<i>n</i> = 305) or placebo (<i>n</i> = 305). With a median follow-up of 18.7 months, the cadonilimab group had a significantly longer median OS (14.1 versus 11.1 months; hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.54–0.81; <i>P</i> &lt; 0.001) than the placebo group. The primary endpoint was met. The median progression-free survival was 7.0 months versus 5.3 months (HR 0.53, 95% CI 0.44–0.65). The median OS in patients with a PD-L1 combined positive score ≥5 was 15.3 months versus 10.9 months (HR 0.58, 95% CI 0.41–0.82). The objective response rate was 65.2% versus 48.9% with a median duration of response of 8.8 months versus 4.4 months. Grade ≥3 treatment-related adverse events occurred in 65.9% of the cadonilimab group and 53.6% of the placebo group, and the most common were decreased platelet count, decreased neutrophil count and anemia. Most of the immune-related adverse events were grade 1 or 2. No new safety signals were observed. Cadonilimab plus chemotherapy significantly improved OS with a manageable safety profile in patients with advanced G/GEJ adenocarcinoma. ClinicalTrials.gov registration: NCT05008783.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"38 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992234","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":"The Quality Health Information for All Commission: reinventing health communication for the digital era","authors":"Scott C. Ratzan,&nbsp;Heidi J. Larson,&nbsp;Carolina Batista,&nbsp;Aleksandra Kuzmanovic,&nbsp;Paul E. Kalb,&nbsp;Kenneth H. Rabin,&nbsp;Lawrence O. Gostin","doi":"10.1038/s41591-024-03446-0","DOIUrl":"10.1038/s41591-024-03446-0","url":null,"abstract":"Announced in this Comment and in collaboration with Nature Medicine is the convening of the Quality Health Information for All Commission, to promote equitable access to quality health information from trusted sources and affirm the practice of health communication as a distinct public health discipline.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"22-23"},"PeriodicalIF":58.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03446-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2− breast cancer: a randomized phase 3 trial","authors":"Fatima Cardoso, Joyce O’Shaughnessy, Zhenzhen Liu, Heather McArthur, Peter Schmid, Javier Cortes, Nadia Harbeck, Melinda L. Telli, David W. Cescon, Peter A. Fasching, Zhimin Shao, Delphine Loirat, Yeon Hee Park, Manuel Gonzalez Fernandez, Gábor Rubovszky, Laura Spring, Seock-Ah Im, Rina Hui, Toshimi Takano, Fabrice André, Hiroyuki Yasojima, Yu Ding, Liyi Jia, Vassiliki Karantza, Konstantinos Tryfonidis, Aditya Bardia","doi":"10.1038/s41591-024-03415-7","DOIUrl":"https://doi.org/10.1038/s41591-024-03415-7","url":null,"abstract":"<p>Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER⁺/HER2⁻) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER⁺/HER2⁻ grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1–2 or T3–4, cN0–2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W. After surgery (with/without adjuvant radiation therapy), patients received adjuvant pembrolizumab or placebo for nine cycles plus adjuvant endocrine therapy. Dual primary endpoints were pathological complete response and event-free survival in the intention-to-treat population. In total, 635 patients were assigned to the pembrolizumab−chemotherapy arm and 643 to the placebo−chemotherapy arm. At the study’s prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0–27.8%) in the pembrolizumab−chemotherapy arm and 15.6% (95% CI, 12.8–18.6%) in the placebo−chemotherapy arm (estimated treatment difference, 8.5 percentage points; 95% CI, 4.2–12.8; <i>P</i> = 0.00005). Event-free survival was not mature in this analysis. During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab−chemotherapy and placebo−chemotherapy arms, respectively. In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients with high-risk, early-stage ER⁺/HER2⁻ breast cancer. Safety was consistent with the known profiles of each study treatment. Follow-up continues for event-free survival. ClinicalTrials.gov identifier: NCT03725059.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"138 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991066","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":"Author Correction: Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids","authors":"Mattia Francesco Maria Gerli, Giuseppe Calà, Max Arran Beesley, Beatrice Sina, Lucinda Tullie, Kylin Yunyan Sun, Francesco Panariello, Federica Michielin, Joseph R. Davidson, Francesca Maria Russo, Brendan C. Jones, Dani Do Hyang Lee, Savvas Savvidis, Theodoros Xenakis, Ian C. Simcock, Anna A. Straatman-Iwanowska, Robert A. Hirst, Anna L. David, Christopher O’Callaghan, Alessandro Olivo, Simon Eaton, Stavros P. Loukogeorgakis, Davide Cacchiarelli, Jan Deprest, Vivian S. W. Li, Giovanni Giuseppe Giobbe, Paolo De Coppi","doi":"10.1038/s41591-025-03504-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03504-1","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-024-02807-z, published online 4 March 2024.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"37 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991022","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":"Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial","authors":"Sherene Loi, Roberto Salgado, Giuseppe Curigliano, Roberto Iván Romero Díaz, Suzette Delaloge, Carlos Ignacio Rojas García, Marleen Kok, Cristina Saura, Nadia Harbeck, Elizabeth A. Mittendorf, Denise A. Yardley, Alberto Suárez Zaizar, Facundo Rufino Caminos, Andrei Ungureanu, Joaquin G. Reinoso-Toledo, Valentina Guarneri, Daniel Egle, Felipe Ades, Misena Pacius, Aparna Chhibber, Rajalakshmi Chandra, Raheel Nathani, Thomas Spires, Jenny Qun Wu, Lajos Pusztai, Heather McArthur","doi":"10.1038/s41591-024-03414-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03414-8","url":null,"abstract":"<p>Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2− BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10%) ER+/HER2− primary BC. In total, 510 patients were randomized to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo. The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; <i>P</i> = 0.0021), with greater benefit observed in patients with programmed death ligand 1-positive tumors (VENTANA SP142 ≥1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2− BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT04109066</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991065","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":"Our Future Health: a unique global resource for discovery and translational research","authors":"Michael B. Cook, Saskia C. Sanderson, John E. Deanfield, Fiona Reddington, Andrew Roddam, David J. Hunter, Raghib Ali","doi":"10.1038/s41591-024-03438-0","DOIUrl":"https://doi.org/10.1038/s41591-024-03438-0","url":null,"abstract":"Our Future Health has recruited more than 1 million participants in the UK, with biobanked bloods, making it the largest consented cohort of its type in the world.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"57 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991023","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":"Mapping the effectiveness and risks of GLP-1 receptor agonists","authors":"Yan Xie, Taeyoung Choi, Ziyad Al-Aly","doi":"10.1038/s41591-024-03412-w","DOIUrl":"https://doi.org/10.1038/s41591-024-03412-w","url":null,"abstract":"<p>Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (<i>n</i> = 215,970) and compared them to those who initiated sulfonylureas (<i>n</i> = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (<i>n</i> = 117,989) or sodium−glucose cotransporter-2 (SGLT2) inhibitors (<i>n</i> = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (<i>n</i> = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"46 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991070","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}