Nature Medicine最新文献

{"title":"Author Correction: Propagative α-synuclein seeds as serum biomarkers for synucleinopathies","authors":"Ayami Okuzumi, Taku Hatano, Gen Matsumoto, Shuko Nojiri, Shin-ichi Ueno, Yoko Imamichi-Tatano, Haruka Kimura, Soichiro Kakuta, Akihide Kondo, Takeshi Fukuhara, Yuanzhe Li, Manabu Funayama, Shinji Saiki, Daisuke Taniguchi, Taiji Tsunemi, Deborah McIntyre, Jean-Jacques Gérardy, Michel Mittelbronn, Rejko Kruger, Yasuo Uchiyama, Nobuyuki Nukina, Nobutaka Hattori","doi":"10.1038/s41591-025-03521-0","DOIUrl":"10.1038/s41591-025-03521-0","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 2","pages":"698-698"},"PeriodicalIF":58.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-025-03521-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026993","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":"Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial","authors":"Christian Kurzeder, Bich Doan Nguyen-Sträuli, Ilona Krol, Alexander Ring, Francesc Castro-Giner, Manuel Nüesch, Simran Asawa, Yu Wei Zhang, Selina Budinjas, Ana Gvozdenovic, Maren Vogel, Angela Kohler, Cvetka Grašič Kuhar, Fabienne D. Schwab, Viola Heinzelmann-Schwarz, Walter Paul Weber, Christoph Rochlitz, Denise Vorburger, Heike Frauchiger-Heuer, Isabell Witzel, Andreas Wicki, Gabriela M. Kuster, Marcus Vetter, Nicola Aceto","doi":"10.1038/s41591-024-03486-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03486-6","url":null,"abstract":"<p>The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na⁺/K⁺ ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na⁺/K⁺ ATPase inhibitor digoxin could reduce mean CTC cluster size. An analysis of nine patients treated daily with a maintenance digoxin dose (0.7–1.4 ng ml⁻¹ serum level) revealed a mean cluster size reduction of −2.2 cells per cluster upon treatment (<i>P</i> = 0.003), meeting the primary endpoint of the study. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell–cell adhesion and cell-cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. No treatment-related adverse events occurred. Thus, our data provide a first-in-human proof of principle that digoxin treatment leads to a partial CTC cluster dissolution, encouraging larger follow-up studies with refined Na⁺/K⁺ ATPase inhibitors and that include clinical outcome endpoints. ClinicalTrials.gov identifier: NCT03928210.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"2 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026968","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":"Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria","authors":"Caitlin Bond, Olivia J. Bednarski, Dibyadyuti Datta, Ruth Namazzi, Robert O. Opoka, Giselle Lima-Cooper, Anthony Batte, Keerthi Udumula, Deepali Balasubramani, Marilyn Vasquez, Ana Rodriguez, Claire Liepmann, Paul Bangirana, Marco Abreu, Tae-Hwi Schwantes-An, Yi Zhao, Tarek M. El-Achkar, Nathan W. Schmidt, Chandy C. John, Andrea L. Conroy","doi":"10.1038/s41591-024-03430-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03430-8","url":null,"abstract":"<p>We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl⁻¹) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM &lt; 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (<i>Escherichia</i> and <i>Shigella</i>) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026989","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":"Imatinib and the dawn of precision cancer therapy","authors":"","doi":"10.1038/s41591-024-03436-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03436-2","url":null,"abstract":"Brian J. Druker describes how his research on imatinib validated protein kinases as therapeutic targets for cancer and led to a life-saving treatment for leukemia.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"57 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020381","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":"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,&nbsp;Kinanti Khansa Chavarina,&nbsp;Jeerath Phannajit,&nbsp;Jiratorn Sutawong,&nbsp;Natcha Yongphiphatwong,&nbsp;Sydney C. W. Tang,&nbsp;Talerngsak Kanjanabuch,&nbsp;Tanainan Chuanchaiyakul,&nbsp;Thunyarat Anothaisintawee,&nbsp;Valerie Luyckx,&nbsp;Wanrudee Isaranuwatchai,&nbsp;Kearkiat Praditpornsilpa,&nbsp;Kriang Tungsanga,&nbsp;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,&nbsp;Joyce O’Shaughnessy,&nbsp;Zhenzhen Liu,&nbsp;Heather McArthur,&nbsp;Peter Schmid,&nbsp;Javier Cortes,&nbsp;Nadia Harbeck,&nbsp;Melinda L. Telli,&nbsp;David W. Cescon,&nbsp;Peter A. Fasching,&nbsp;Zhimin Shao,&nbsp;Delphine Loirat,&nbsp;Yeon Hee Park,&nbsp;Manuel Gonzalez Fernandez,&nbsp;Gábor Rubovszky,&nbsp;Laura Spring,&nbsp;Seock-Ah Im,&nbsp;Rina Hui,&nbsp;Toshimi Takano,&nbsp;Fabrice André,&nbsp;Hiroyuki Yasojima,&nbsp;Yu Ding,&nbsp;Liyi Jia,&nbsp;Vassiliki Karantza,&nbsp;Konstantinos Tryfonidis,&nbsp;Aditya Bardia","doi":"10.1038/s41591-024-03415-7","DOIUrl":"10.1038/s41591-024-03415-7","url":null,"abstract":"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; P = 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 . In this prespecified interim analysis of the KEYNOTE-756 phase 3 trial, pembrolizumab and chemotherapy treatment of patients with high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor-negative breast cancer improved the pathological complete response rate compared with chemotherapy alone.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 2","pages":"442-448"},"PeriodicalIF":58.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03415-7.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}