Nature Medicine最新文献

{"title":"Clinical translation of microbiome research","authors":"Jack A. Gilbert, Meghan B. Azad, Fredrik Bäckhed, Martin J. Blaser, Mariana Byndloss, Charles Y. Chiu, Hiutung Chu, Lara R. Dugas, Eran Elinav, Sean M. Gibbons, Katharine E. Gilbert, Matthew R. Henn, Suzanne L. Ishaq, Ruth E. Ley, Susan V. Lynch, Eran Segal, Tim D. Spector, Philip Strandwitz, Jotham Suez, Carolina Tropini, Katrine Whiteson, Rob Knight","doi":"10.1038/s41591-025-03615-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03615-9","url":null,"abstract":"<p>The landscape of clinical microbiome research has dramatically evolved over the past decade. By leveraging in vivo and in vitro experimentation, multiomic approaches and computational biology, we have uncovered mechanisms of action and microbial metrics of association and identified effective ways to modify the microbiome in many diseases and treatment modalities. This Review explores recent advances in the clinical application of microbiome research over the past 5 years, while acknowledging existing barriers and highlighting opportunities. We focus on the translation of microbiome research into clinical practice, spearheaded by Food and Drug Administration (FDA)-approved microbiome therapies for recurrent <i>Clostridioides difficile</i> infections and the emerging fields of microbiome-based diagnostics and therapeutics. We highlight key examples of studies demonstrating how microbiome mechanisms, metrics and modifiers can advance clinical practice. We also discuss forward-looking perspectives on key challenges and opportunities toward integrating microbiome data into routine clinical practice, precision medicine and personalized healthcare and nutrition.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"43 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818938","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: Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults","authors":"Magda Bosch de Basea, Isabelle Thierry-Chef, Richard Harbron, Michael Hauptmann, Graham Byrnes, Maria-Odile Bernier, Lucian Le Cornet, Jérémie Dabin, Gilles Ferro, Tore S. Istad, Andreas Jahnen, Choonsik Lee, Carlo Maccia, Françoise Malchair, Hilde Olerud, Steven L. Simon, Jordi Figuerola, Anna Peiro, Hilde Engels, Christoffer Johansen, Maria Blettner, Magnus Kaijser, Kristina Kjaerheim, Amy Berrington de Gonzalez, Neige Journy, Johanna M. Meulepas, Monika Moissonnier, Arvid Nordenskjold, Roman Pokora, Cecile Ronckers, Joachim Schüz, Ausrele Kesminiene, Elisabeth Cardis","doi":"10.1038/s41591-025-03689-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03689-5","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-023-02620-0, published online 9 November 2023.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"11 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819464","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":"Impact of the ONCOBIOME network in cancer microbiome research","authors":"Laurence Zitvogel, Lisa Derosa, Bertrand Routy, Sibylle Loibl, Lucie Heinzerling, I. Jolanda M. de Vries, Lars Engstrand, Nicola Segata, Guido Kroemer","doi":"10.1038/s41591-025-03608-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03608-8","url":null,"abstract":"<p>The European Union-sponsored ONCOBIOME network has spurred an international effort to identify and validate relevant gut microbiota-related biomarkers in oncology, generating a unique and publicly available microbiome resource. ONCOBIOME explores the effects of the microbiota on gut permeability and metabolism as well as on antimicrobial and antitumor immune responses. Methods for the diagnosis of gut dysbiosis have been developed based on oncomicrobiome signatures associated with the diagnosis, prognosis and treatment responses in patients with cancer. The mechanisms explaining how dysbiosis compromises natural or therapy-induced immunosurveillance have been explored. Through its integrative approach of leveraging multiple cohorts across populations, cancer types and stages, ONCOBIOME has laid the theoretical and practical foundations for the recognition of microbiota alterations as a hallmark of cancer. ONCOBIOME has launched microbiota-centered interventions and lobbies in favor of official guidelines for avoiding diet-induced or iatrogenic (for example, antibiotic- or proton pump inhibitor-induced) dysbiosis. Here, we review the key advances of the ONCOBIOME network and discuss the progress toward translating these into oncology clinical practice.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"108 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818937","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 cell atlas of human endometrium reveals key molecular and cellular alterations in PCOS","authors":"","doi":"10.1038/s41591-025-03672-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03672-0","url":null,"abstract":"A human cellular and molecular atlas of the proliferative endometrium in polycystic ovary syndrome (PCOS) was generated via single-nucleus RNA sequencing and spatial transcriptomics. This study reveals PCOS-specific alterations in cellular composition and gene expression, and identifies potential therapeutic targets. These findings could advance treatments for PCOS-related endometrial dysfunction and associated health challenges.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"106 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818941","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 WHO aims for financial stability despite US exit","authors":"","doi":"10.1038/s41591-025-03649-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03649-z","url":null,"abstract":"The World Health Organization’s inaugural Investment Round aims to instill stability in the face of global health headwinds and a US exit.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"12 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819398","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":"IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial","authors":"Sine Berntsen, Anne Zedeler, Bugge Nøhr, Morten Rønn Petersen, Marie Louise Grøndahl, Lars Franch Andersen, Kristine Løssl, Ellen Løkkegaard, Anne Lis Englund, Anette Vestergaard Gabrielsen, Lisbeth Prætorius, Ida Behrendt-Møller, Lea Langhoff Thuesen, Kilian Vomstein, Mette Petri Lauritsen, Aleksandra Ivanoska Trajcevski, Dea Frøding Skipper, David Westergaard, Anja Pinborg, Henriette Svarre Nielsen, Nina la Cour Freiesleben","doi":"10.1038/s41591-025-03621-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03621-x","url":null,"abstract":"<p>Intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (c-IVF) are widely used fertilization techniques in assisted reproduction, but their relative effectiveness in patients without severe male factor infertility remains debated. While ICSI’s role in couples with severe male factor infertility is well established, its routine use in cases with normal or nonseverely decreased sperm quality is not evidence-based. Here we conducted the INVICSI study, an open-label, multicenter randomized controlled trial, to compare cumulative live birth rates (CLBR) as the primary outcome between ICSI and c-IVF in patients without severe male factor infertility. Between November 2019 and December 2022, 824 women undergoing their first IVF cycle were randomized to ICSI (<i>n</i> = 414) or c-IVF (<i>n</i> = 410) across six public fertility clinics in Denmark. The CLBR was 43.2% (179/414) in the ICSI group and 47.3% (193/408) in the c-IVF group, yielding a risk ratio of 0.91 (95% confidence interval, 0.79–1.06). These findings demonstrate that ICSI does not improve CLBR compared to c-IVF and support c-IVF as the preferred first-line treatment for patients with normal or nonseverely decreased sperm quality. ICSI should be reserved for severe male factor infertility. ClinicalTrials.gov registration: NCT04128904.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"4 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818940","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":"Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial","authors":"Yongmei Yin, Ying Fan, Quchang Ouyang, Lihua Song, Xiaojia Wang, Wei Li, Man Li, Xi Yan, Shusen Wang, Tao Sun, Yuee Teng, Xianjun Tang, Zhongsheng Tong, Zhengkui Sun, Junyou Ge, Xiaoping Jin, Yina Diao, Gesha Liu, Binghe Xu","doi":"10.1038/s41591-025-03630-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03630-w","url":null,"abstract":"<p>Chemotherapy remains a standard treatment option for metastatic triple-negative breast cancer (TNBC) but is associated with limited survival. Although some targeted antibody–drug conjugates have demonstrated clinical benefits and are considered standard therapy, persistent unmet medical needs remain due to varying accessibility. The OptiTROP-Breast01 phase 3 trial assessed sacituzumab tirumotecan (sac-TMT) versus chemotherapy in patients with locally recurrent or metastatic TNBC who had received two or more prior therapies, including at least one for metastatic disease. Patients were randomized to sac-TMT (<i>n</i> = 130) or chemotherapy (<i>n</i> = 133). The primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) was met based on the protocol-specified interim analysis. At final analysis, the median PFS by BICR was 6.7 (95% confidence interval (CI), 5.5–8.0) months with sac-TMT and 2.5 (95% CI, 1.7–2.7) months with chemotherapy (hazard ratio (HR), 0.32; 95% CI, 0.24–0.44; <i>P</i> &lt; 0.00001). Concurrently, at the protocol-specified interim analysis for overall survival (OS), the median OS was not reached (95% CI, 11.2 months to not estimable (NE)) with sac-TMT and 9.4 (95% CI, 8.5–11.7) months with chemotherapy (HR, 0.53; 95% CI, 0.36–0.78; <i>P</i> = 0.0005). The percentage of patients with an objective response was 45.4% with sac-TMT and 12.0% with chemotherapy. The median duration of response was 7.1 (95% CI, 5.6–NE) months with sac-TMT and 3.0 (95% CI, 2.5–NE) months with chemotherapy. The most common treatment-related adverse event with sac-TMT was hematologic toxicity. Sac-TMT demonstrated statistically significant and clinically meaningful improvements in PFS compared to chemotherapy, with a manageable safety profile. The study findings support sac-TMT as an additional effective treatment option for pretreated metastatic TNBC. ClinicalTrials.gov identifier: NCT05347134.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"23 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818939","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":"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}