Nature Medicine最新文献

{"title":"Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: phase 1/2 and phase 2 trials","authors":"Shen Zhao, Ying Cheng, Qiming Wang, Xingya Li, Jun Liao, Jordi Rodon, Xiangjiao Meng, Yongzhong Luo, Zhendong Chen, Wei Wang, Tienan Yi, Yongsheng Li, Yongmei Yin, Huiting Xu, Guohua Yu, Yanjun Mi, Yun Fan, Zev A. Wainberg, Xiang Wang, Cuiyun Su, Qitao Yu, Shuzhen Lai, Longhua Sun, Wu Zhuang, Xian Wang, Jiacheng Yang, Yaling Li, Junyou Ge, Jin Li, Li Zhang, Wenfeng Fang","doi":"10.1038/s41591-025-03638-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03638-2","url":null,"abstract":"<p>Trophoblast cell-surface antigen 2 (TROP2)-directed antibody–drug conjugate (ADC) is a promising anticancer agent that has shown remarkable efficacy in several malignancies. However, in lung cancer, two phase 3 trials on TROP2-ADCs in unselected patients with advanced non-small-cell lung cancer (NSCLC) have both failed. Sacituzumab tirumotecan (sac-TMT) is a novel TROP2-directed ADC. Here we report the efficacy and safety of sac-TMT in previously treated, advanced NSCLC with or without activating <i>EGFR</i> mutations from the phase 1/2 KL264-01 and phase 2 SKB264-II-08 studies. Primary endpoint was objective response rate (ORR). KL264-01 enrolled <i>EGFR</i>-wild-type and <i>EGFR</i>-mutant NSCLC (<i>n</i> = 43). Confirmed ORR was 40% (17 of 43; 95% confidence interval (CI), 25–56). Median progression-free survival (PFS) was 6.2 months (95% CI, 5.3–11.3). Post-hoc subgroup analyses found better outcomes in the <i>EGFR</i>-mutant subset (22 of 43, 51%) with a confirmed ORR of 55% (12 of 22) and median PFS of 11.1 months. These findings were independently supported by results from SKB264-II-08, where sac-TMT led to confirmed ORR of 34% (22 of 64; 95% CI, 23–47) and median PFS of 9.3 months (95% CI, 7.6–11.4) in 64 patients with <i>EGFR</i>-mutant NSCLC. For a total of 107 patients receiving sac-TMT, the most common treatment-related adverse events were hematologic toxicities. Diarrhea (4%) and interstitial lung disease (1%) were uncommon. Exploration of potential mechanisms revealed that the presence of <i>EGFR</i> mutation substantially increased the internalization and activity of sac-TMT in vitro. Overall, sac-TMT showed encouraging single-agent activity and manageable tolerability in previously treated, advanced NSCLC with EGFR mutations. Randomized phase 3 trials in treatment-naive and previously treated patients with EGFR-mutant NSCLC are ongoing. ClinicalTrials.gov Identifiers: NCT04152499, NCT05631262.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"8 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813470","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":"New approaches to opioid-free pain treatment","authors":"","doi":"10.1038/d41591-025-00024-w","DOIUrl":"https://doi.org/10.1038/d41591-025-00024-w","url":null,"abstract":"The success of new non-opioid drugs and other treatments for pain offer some relief for sufferers.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"241 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813402","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":"Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform","authors":"Sebastian Palmqvist, Noëlle Warmenhoven, Federica Anastasi, Andrea Pilotto, Shorena Janelidze, Pontus Tideman, Erik Stomrud, Niklas Mattsson-Carlgren, Ruben Smith, Rik Ossenkoppele, Kübra Tan, Anna Dittrich, Ingmar Skoog, Henrik Zetterberg, Virginia Quaresima, Chiara Tolassi, Kina Höglund, Duilio Brugnoni, Albert Puig-Pijoan, Aida Fernández-Lebrero, José Contador, Alessandro Padovani, Mark Monane, Philip B. Verghese, Joel B. Braunstein, Silke Kern, Kaj Blennow, Nicholas J. Ashton, Marc Suárez-Calvet, Oskar Hansson","doi":"10.1038/s41591-025-03622-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03622-w","url":null,"abstract":"<p>Global implementation of blood tests for Alzheimer’s disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts in Malmö (Sweden, <i>n</i> = 337), Gothenburg (Sweden, <i>n</i> = 165), Barcelona (Spain, <i>n</i> = 487) and Brescia (Italy, <i>n</i> = 230), and a primary care cohort in Sweden (<i>n</i> = 548). Plasma p-tau217 was primarily measured using the fully automated, commercially available, Lumipulse immunoassay. The primary outcome was AD pathology defined as abnormal cerebrospinal fluid Aβ42:p-tau181. Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93–0.96. In secondary care, the accuracies were 89–91%, the positive predictive values 89–95% and the negative predictive values 77–90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%), but was unaffected by chronic kidney disease, diabetes, sex, <i>APOE</i> genotype or cognitive stage. Using a two-cutoff approach, accuracies increased to 92–94% in secondary and primary care, excluding 12–17% with intermediate results. Using the plasma p-tau217:Aβ42 ratio did not improve accuracy but reduced intermediate test results (≤10%). Compared with a high-performing mass-spectrometry-based assay for percentage p-tau217, accuracies were comparable in secondary care. However, percentage p-tau217 had higher accuracy in primary care and was unaffected by age. In conclusion, this fully automated p-tau217 test demonstrates high accuracy for identifying AD pathology. A two-cutoff approach might be necessary to optimize performance across diverse settings and subpopulations.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805881","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: Pay-it-forward incentives for hepatitis virus testing in men who have sex with men: a cluster randomized trial","authors":"Ye Zhang, Jianjun Li, Yewei Xie, Dan Wu, Jason Ong, Gifty Marley, Adeeba Kamarulzaman, Haidong Lu, Fei Zou, Jennifer S. Smith, Joseph D. Tucker, Gengfeng Fu, Weiming Tang","doi":"10.1038/s41591-025-03690-y","DOIUrl":"https://doi.org/10.1038/s41591-025-03690-y","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-023-02519-w, published online 28 August 2023.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"21 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806256","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":"Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial","authors":"Martin Wermke, Dejka M. Araurjo, Manik Chatterjee, Apostolia M. Tsimberidou, Tobias A. W. Holderried, Amir A. Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B. Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M. Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J. Luke, Cedrik M. Britten","doi":"10.1038/s41591-025-03650-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03650-6","url":null,"abstract":"<p>In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02⁺ patients with PRAME⁺ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose for extension. Secondary objectives include the evaluation of IMA203 TCR-engineered T cell persistence in peripheral blood, tumor response as well as duration of response. A total of 27 patients were enrolled in the phase 1a dose escalation and 13 patients in the phase 1b dose extension. IMA203 T cells were safe, and the MTD was not reached. Of the 41 patients receiving treatment (that is, who started lymphodepletion), severe cytokine release syndrome was observed in 4.9% (2/41), and severe neurotoxicity did not occur. In the 40 patients treated with IMA203, an overall response rate consisting of patients with unconfirmed or confirmed response (u/cORR) of 52.5% (21/40) and a cORR of 28.9% (11/38) was observed with a median duration of response of 4.4 months (range, 2.4–23.0, 95% confidence interval: 2.6–not reached) across multiple indications. Rapid T cell engraftment and long-term persistence of IMA203 T cells were observed. IMA203 T cells trafficked to all organs, and confirmed responses were more frequent in patients with higher dose. T cell exhaustion was not observed in the periphery; deep responses were enriched at higher PRAME expression; and higher T cell infiltration resulted in longer progression-free survival. Overall, IMA203 showed promising anti-tumor activity in multiple solid tumors, including refractory melanoma. ClinicalTrials.gov identifier: NCT03686124.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"38 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805882","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: AI-guided precision parenteral nutrition for neonatal intensive care units","authors":"Thanaphong Phongpreecha, Marc Ghanem, Jonathan D. Reiss, Tomiko T. Oskotsky, Samson J. Mataraso, Davide De Francesco, S. Momsen Reincke, Camilo Espinosa, Philip Chung, Taryn Ng, Jean M. Costello, Jennifer A. Sequoia, Sheila Razdan, Feng Xie, Eloise Berson, Yeasul Kim, David Seong, May Y. Szeto, Faith Myers, Hannah Gu, John Feister, Courtney P. Verscaj, Laura A. Rose, Lucas W. Y. Sin, Boris Oskotsky, Jacquelyn Roger, Chi-hung Shu, Sayane Shome, Liu K. Yang, Yuqi Tan, Steven Levitte, Ronald J. Wong, Brice Gaudillière, Martin S. Angst, Thomas J. Montine, John A. Kerner, Roberta L. Keller, Gary M. Shaw, Karl G. Sylvester, Janene Fuerch, Valerie Chock, Shabnam Gaskari, David K. Stevenson, Marina Sirota, Lawrence S. Prince, Nima Aghaeepour","doi":"10.1038/s41591-025-03691-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03691-x","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-024-03601-1, published online 25 March 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"18 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806224","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":"Genomic census of invasive nontyphoidal Salmonella infections reveals global and local human-to-human transmission","authors":"Haiyang Zhou, Chenghao Jia, Ping Shen, Chenghu Huang, Lin Teng, Beibei Wu, Zining Wang, Haoqiu Wang, Yonghong Xiao, Stephen Baker, François-Xavier Weill, Yan Li, Min Yue","doi":"10.1038/s41591-025-03644-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03644-4","url":null,"abstract":"<p>Extraintestinal infections caused by Enterobacteriaceae represent a global concern, further exacerbated by the growing prevalence of antimicrobial resistance (AMR). Among these, invasive nontyphoidal <i>Salmonella</i> (iNTS) infections have become increasingly challenging to manage, and their global spread remains poorly understood. Here we compiled 1,115 patient records and generated a comprehensive genomic dataset on iNTS. Age and sex emerged as significant risk factors, with <i>Salmonella</i> Enteritidis identified as a major cause. We observed serovar-specific AMR patterns, with notable resistance to fluoroquinolones and third-generation cephalosporins. A global phylogenomic analysis of Enteritidis revealed three distinct clades, highlighting the accumulation of AMR determinants during its international spread. Importantly, our genomic and transmission analyses suggest that iNTS infections may involve human-to-human transmission, with diarrheal patients acting as potential intermediaries, deviating from typical zoonotic pathways. Collectively, our newly generated cohort and iNTS genomic dataset provide a framework for precise local iNTS burden and underscore emerging transmission trends.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"96 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805880","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":"A benchmarking crisis in biomedical machine learning","authors":"Faisal Mahmood","doi":"10.1038/s41591-025-03637-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03637-3","url":null,"abstract":"A lack of standardized benchmarks is hindering progress and patient benefits","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"35 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798022","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":"Inflammation and disrupted hematopoiesis drive clonal dominance in a mouse model of VEXAS syndrome","authors":"","doi":"10.1038/s41591-025-03670-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03670-2","url":null,"abstract":"We show that hematopoiesis in a mouse model of VEXAS syndrome is subverted by inflammation-resilient, senescent-like mutant HSPCs, which have dysfunctional differentiation and undermine hematopoiesis through their proinflammatory progeny. This disease mechanism explains clonal dominance and bone marrow failure (BMF) in patients with VEXAS syndrome and could have translational implications.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"89 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798037","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":"Whole diets, whole health","authors":"Eirini Trichia, Jakub G. Sobiecki, Keren Papier","doi":"10.1038/s41591-025-03646-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03646-2","url":null,"abstract":"Integrating insights from studies of individual nutrients, foods and diseases with studies of holistic dietary patterns and healthy aging can offer a comprehensive strategy for understanding and promoting public health.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"100 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798021","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}