Pub Date : 2026-02-04DOI: 10.1038/d41591-026-00007-5
{"title":"Whose ethics govern global health research?","authors":"","doi":"10.1038/d41591-026-00007-5","DOIUrl":"https://doi.org/10.1038/d41591-026-00007-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"287 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116012","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}
Pub Date : 2026-02-04DOI: 10.1038/s41591-025-04180-x
Indira Dewi Kantiana, Aprajita Kaushik, Divya Lakhotia, Nima Asgari-Jirhandeh, Margaret Chan, Harvy Joy Liwanag, Angkana Lekagul, Soumya Swaminathan, Kun Tang, Viroj Tangcharoensathien, Yik Ying Teo, Jasper Tromp, Suwit Wibulpolprasert, Kiesha Prem, Afifah Rahman-Shepherd
{"title":"Asia Pacific perspectives on global health architecture reform","authors":"Indira Dewi Kantiana, Aprajita Kaushik, Divya Lakhotia, Nima Asgari-Jirhandeh, Margaret Chan, Harvy Joy Liwanag, Angkana Lekagul, Soumya Swaminathan, Kun Tang, Viroj Tangcharoensathien, Yik Ying Teo, Jasper Tromp, Suwit Wibulpolprasert, Kiesha Prem, Afifah Rahman-Shepherd","doi":"10.1038/s41591-025-04180-x","DOIUrl":"https://doi.org/10.1038/s41591-025-04180-x","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"234 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116013","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}
Pub Date : 2026-02-04DOI: 10.1038/s41591-026-04245-5
Léna Rivard, Paul Khairy, Mario Talajic, Jean-Claude Tardif, Jeffrey S. Healey, Sandra E. Black, Jason G. Andrade, Thalia S. Field, Isabelle Nault, Louis Bherer, Fadi Massoud, Stanley Nattel, Sylvain Lanthier, Normand Racine, Jean-François Roux, Isabelle Greiss, Laurent Macle, Peter G. Guerra, Rafik Tadros, Hélène Mayrand, Gilbert Gosselin, David Conen, Christian Bocti, Céline Chayer, Yan Deschaintre, Roopinder K. Sandhu, Jaimie Manlucu, Yaariv Khaykin, Atul Verma, Blandine Mondésert, Katia Dyrda, Julia Cadrin-Tourigny, Bernard Thibault, Alexandre Raymond-Paquin, Martin Aguilar, Judith Brouillette, André Roussin, Alain Robillard, Maxime Tremblay-Gravel, Louis-Philippe David, Mariève Cossette, Ratika Parkash, Marie-Claude Guertin, Denis Roy, , A. Shekhar Pandey, Francis Pichette, Miguel Barrero, Teresa Kus, Ariane Lemieux, Valérie Gaudreault, Peiman Marzban, Jorge Wong, Peter Leong Sit, David Laflamme, Ronald Fowlis, Kenneth Quadros, Anmol Kapoor, Umjeet S. Jolly, Stephen Wilton, Fabian Alejandro Azzari, Paul Dorian, François Deslongchamps, Yves Pesant, Saul Vizel, TunZan Maung, Michael Heffernan, Pablo Nery, Greg Curnew, Stéphanie Bourgeois, Vidal Essebag, Simon Kouz, Luc Cormier, John Vyselaar, Raja Chehayeb, Clarence Khoo, Anil Gupta, Ricardo Bessoudo, Rakesh Bhargava, Franco Sandrin, Gernot Schram, François St-Maurice, Winston Tsui, William Liang
{"title":"Publisher Correction: Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial","authors":"Léna Rivard, Paul Khairy, Mario Talajic, Jean-Claude Tardif, Jeffrey S. Healey, Sandra E. Black, Jason G. Andrade, Thalia S. Field, Isabelle Nault, Louis Bherer, Fadi Massoud, Stanley Nattel, Sylvain Lanthier, Normand Racine, Jean-François Roux, Isabelle Greiss, Laurent Macle, Peter G. Guerra, Rafik Tadros, Hélène Mayrand, Gilbert Gosselin, David Conen, Christian Bocti, Céline Chayer, Yan Deschaintre, Roopinder K. Sandhu, Jaimie Manlucu, Yaariv Khaykin, Atul Verma, Blandine Mondésert, Katia Dyrda, Julia Cadrin-Tourigny, Bernard Thibault, Alexandre Raymond-Paquin, Martin Aguilar, Judith Brouillette, André Roussin, Alain Robillard, Maxime Tremblay-Gravel, Louis-Philippe David, Mariève Cossette, Ratika Parkash, Marie-Claude Guertin, Denis Roy, , A. Shekhar Pandey, Francis Pichette, Miguel Barrero, Teresa Kus, Ariane Lemieux, Valérie Gaudreault, Peiman Marzban, Jorge Wong, Peter Leong Sit, David Laflamme, Ronald Fowlis, Kenneth Quadros, Anmol Kapoor, Umjeet S. Jolly, Stephen Wilton, Fabian Alejandro Azzari, Paul Dorian, François Deslongchamps, Yves Pesant, Saul Vizel, TunZan Maung, Michael Heffernan, Pablo Nery, Greg Curnew, Stéphanie Bourgeois, Vidal Essebag, Simon Kouz, Luc Cormier, John Vyselaar, Raja Chehayeb, Clarence Khoo, Anil Gupta, Ricardo Bessoudo, Rakesh Bhargava, Franco Sandrin, Gernot Schram, François St-Maurice, Winston Tsui, William Liang","doi":"10.1038/s41591-026-04245-5","DOIUrl":"https://doi.org/10.1038/s41591-026-04245-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116011","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}
Pub Date : 2026-02-04DOI: 10.1038/s41591-025-04079-7
Benjamin Besse, Jessica J. Lin, Lyudmila Bazhenova, Koichi Goto, Adrianus Johannes de Langen, Dong-Wan Kim, Jürgen Wolf, Christoph Springfeld, Sanjay Popat, Darren W. T. Lim, Misako Nagasaka, Jung Yong Hong, Christina S. Baik, Alice Hervieu, Victor Moreno, Nong Yang, Kanthi Kollengode, Haisu Yang, Yuanfang Xu, Christophe Y. Calvet, Yong Yuan, Amy B. Hammell, Alexander Drilon, Benjamin J. Solomon
Early-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating NTRK fusion–positive ( NTRK+ ) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including NTRK+ disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort ( n = 51; 95% confidence interval (CI)), the response rate was 59% (44–72); the median DOR was not estimable (NE); and the median PFS was 30.3 months (9.0–NE). In the TKI-pretreated cohort ( n = 69; 95% CI), the response rate was 48% (36–60); the median DOR was 9.8 months (7.4–13.0); and the median PFS was 7.4 months (3.9–9.7). Of 30 TKI-pretreated patients with NTRK solvent front mutations, 16 had a response (53%; 95% CI: 34–72). Intracranial responses were observed in two of three TKI-naive patients and in four of six TKI-pretreated patients with measurable intracranial disease at baseline. Among all treated patients ( n = 565), the most common any-grade treatment-related adverse event (TRAE) was dizziness (57%); most TRAEs were low grade; and 4% discontinued repotrectinib due to a TRAE. Here repotrectinib demonstrated durable systemic and intracranial responses with generally low-grade adverse events in patients with NTRK+ solid tumors, including those with previous TRK TKI treatment and solvent front mutations. These results support the use of repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .
{"title":"Repotrectinib in NTRK fusion–positive advanced solid tumors: a phase 1/2 trial","authors":"Benjamin Besse, Jessica J. Lin, Lyudmila Bazhenova, Koichi Goto, Adrianus Johannes de Langen, Dong-Wan Kim, Jürgen Wolf, Christoph Springfeld, Sanjay Popat, Darren W. T. Lim, Misako Nagasaka, Jung Yong Hong, Christina S. Baik, Alice Hervieu, Victor Moreno, Nong Yang, Kanthi Kollengode, Haisu Yang, Yuanfang Xu, Christophe Y. Calvet, Yong Yuan, Amy B. Hammell, Alexander Drilon, Benjamin J. Solomon","doi":"10.1038/s41591-025-04079-7","DOIUrl":"https://doi.org/10.1038/s41591-025-04079-7","url":null,"abstract":"Early-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating <jats:italic>NTRK</jats:italic> fusion–positive ( <jats:italic>NTRK</jats:italic> <jats:sup>+</jats:sup> ) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including <jats:italic>NTRK</jats:italic> <jats:sup>+</jats:sup> disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort ( <jats:italic>n</jats:italic> = 51; 95% confidence interval (CI)), the response rate was 59% (44–72); the median DOR was not estimable (NE); and the median PFS was 30.3 months (9.0–NE). In the TKI-pretreated cohort ( <jats:italic>n</jats:italic> = 69; 95% CI), the response rate was 48% (36–60); the median DOR was 9.8 months (7.4–13.0); and the median PFS was 7.4 months (3.9–9.7). Of 30 TKI-pretreated patients with <jats:italic>NTRK</jats:italic> solvent front mutations, 16 had a response (53%; 95% CI: 34–72). Intracranial responses were observed in two of three TKI-naive patients and in four of six TKI-pretreated patients with measurable intracranial disease at baseline. Among all treated patients ( <jats:italic>n</jats:italic> = 565), the most common any-grade treatment-related adverse event (TRAE) was dizziness (57%); most TRAEs were low grade; and 4% discontinued repotrectinib due to a TRAE. Here repotrectinib demonstrated durable systemic and intracranial responses with generally low-grade adverse events in patients with <jats:italic>NTRK</jats:italic> <jats:sup>+</jats:sup> solid tumors, including those with previous TRK TKI treatment and solvent front mutations. These results support the use of repotrectinib to treat patients with <jats:italic>NTRK</jats:italic> <jats:sup>+</jats:sup> solid tumors. ClinicalTrials.gov identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://www.clinicaltrials.gov/study/NCT03093116\" ext-link-type=\"uri\">NCT03093116</jats:ext-link> .","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"301 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116016","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}
Pub Date : 2026-02-04DOI: 10.1038/s41591-026-04242-8
Manav Korpal, Brian J. Ell, Francesca M. Buffa, Toni Ibrahim, Mario A. Blanco, Toni Celià-Terrassa, Laura Mercatali, Zia Khan, Hani Goodarzi, Yuling Hua, Yong Wei, Guohong Hu, Benjamin A. Garcia, Jiannis Ragoussis, Dino Amadori, Adrian L. Harris, Yibin Kang
{"title":"Editorial Expression of Concern: Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization","authors":"Manav Korpal, Brian J. Ell, Francesca M. Buffa, Toni Ibrahim, Mario A. Blanco, Toni Celià-Terrassa, Laura Mercatali, Zia Khan, Hani Goodarzi, Yuling Hua, Yong Wei, Guohong Hu, Benjamin A. Garcia, Jiannis Ragoussis, Dino Amadori, Adrian L. Harris, Yibin Kang","doi":"10.1038/s41591-026-04242-8","DOIUrl":"https://doi.org/10.1038/s41591-026-04242-8","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"46 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116015","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}
Pub Date : 2026-02-04DOI: 10.1038/s41591-026-04215-x
Ivan Nenadic, Marat Fudim, Zak Loring, Abhinav Sharma, Jan Fedacko, Venkatesh Murthy, Jonathan Piccini
{"title":"Physicians as context engineers in the era of generative AI","authors":"Ivan Nenadic, Marat Fudim, Zak Loring, Abhinav Sharma, Jan Fedacko, Venkatesh Murthy, Jonathan Piccini","doi":"10.1038/s41591-026-04215-x","DOIUrl":"https://doi.org/10.1038/s41591-026-04215-x","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116014","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}
Pub Date : 2026-02-03DOI: 10.1038/s41591-026-04219-7
Hanna Fink, Oliver Langselius, Jérôme Vignat, Harriet Rumgay, Jürgen Rehm, Ricardo X. Martinez, Marilina Santero, Lucero Lopez-Perez, Manami Inoue, Hongmei Zeng, Kevin Shield, Eileen Morgan, André Ilbawi, Isabelle Soerjomataram
Cancer remains a leading cause of morbidity globally, largely attributable to modifiable risks. We estimated the 2022 global and national cancer burden attributable to 30 such factors, including tobacco smoking, alcohol consumption, high body mass index, insufficient physical activity, smokeless tobacco and areca nut, suboptimal breastfeeding, air pollution, ultraviolet radiation, 9 infectious agents and 13 occupational exposures, to inform prevention efforts. Using GLOBOCAN data for 36 cancer sites in 185 countries, we applied prevalence data from around 2012 to reflect exposure−cancer latency and estimated Levin-based or Miettinen-based population-attributable fractions (PAFs) or direct estimates where applicable. Combined PAFs accounting for overlapping exposures were derived by cancer, sex, country and region. In 2022, an estimated 7.1 million of 18.7 million new cancer cases (37.8%) were attributable to 30 modifiable risk factors—2.7 million (29.7%) in women and 4.3 million (45.4%) in men. The proportion of preventable cancers ranged from 24.6% to 38.2% in women and from 28.1% to 57.2% in men across regions. Smoking (15.1%), infections (10.2%) and alcohol consumption (3.2%) were the leading contributors to cancer burden. Lung, stomach and cervical cancers represented nearly half of preventable cancers. Strengthening efforts to reduce modifiable exposures remains central to global cancer prevention.
{"title":"Global and regional cancer burden attributable to modifiable risk factors to inform prevention","authors":"Hanna Fink, Oliver Langselius, Jérôme Vignat, Harriet Rumgay, Jürgen Rehm, Ricardo X. Martinez, Marilina Santero, Lucero Lopez-Perez, Manami Inoue, Hongmei Zeng, Kevin Shield, Eileen Morgan, André Ilbawi, Isabelle Soerjomataram","doi":"10.1038/s41591-026-04219-7","DOIUrl":"https://doi.org/10.1038/s41591-026-04219-7","url":null,"abstract":"Cancer remains a leading cause of morbidity globally, largely attributable to modifiable risks. We estimated the 2022 global and national cancer burden attributable to 30 such factors, including tobacco smoking, alcohol consumption, high body mass index, insufficient physical activity, smokeless tobacco and areca nut, suboptimal breastfeeding, air pollution, ultraviolet radiation, 9 infectious agents and 13 occupational exposures, to inform prevention efforts. Using GLOBOCAN data for 36 cancer sites in 185 countries, we applied prevalence data from around 2012 to reflect exposure−cancer latency and estimated Levin-based or Miettinen-based population-attributable fractions (PAFs) or direct estimates where applicable. Combined PAFs accounting for overlapping exposures were derived by cancer, sex, country and region. In 2022, an estimated 7.1 million of 18.7 million new cancer cases (37.8%) were attributable to 30 modifiable risk factors—2.7 million (29.7%) in women and 4.3 million (45.4%) in men. The proportion of preventable cancers ranged from 24.6% to 38.2% in women and from 28.1% to 57.2% in men across regions. Smoking (15.1%), infections (10.2%) and alcohol consumption (3.2%) were the leading contributors to cancer burden. Lung, stomach and cervical cancers represented nearly half of preventable cancers. Strengthening efforts to reduce modifiable exposures remains central to global cancer prevention.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"176 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102155","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}
Pub Date : 2026-02-03DOI: 10.1038/s41591-025-04193-6
Richard S. Finkel, Thomas O. Crawford, Eugenio Mercuri, Charlotte J. Sumner, Maria del Mar Garcia Romero, John W. Day, Jacqueline Montes, Peng Sun, Ben Tichler, Angela D. Paradis, Emily Boesch, Jennifer Inra, Ross Littauer, Jihee Sohn, Michael Monine, Giulia Gambino, Richard Foster, Raechel Farewell, Stephanie Fradette
Despite the remarkable benefits of nusinersen and other disease-modifying therapies in spinal muscular atrophy (SMA), patients may still experience clinical manifestations of the disease. Here we assessed the potential for high-dose nusinersen to rapidly slow neurodegeneration and lead to improved outcomes for patients. The global, three-part, phase 2/3 DEVOTE trial evaluated the efficacy and safety of high-dose nusinersen (50-mg loading dose; 28-mg maintenance dose) in individuals with SMA. In Part B, treatment-naive individuals (n = 75) were randomized 2:1 to 50/28 mg or 12/12 mg nusinersen. In a supportive open-label cohort (Part C), nusinersen-experienced individuals (12/12 mg for more than 1 year) were enrolled. The primary endpoint (Part B infantile-onset participants) was a 6-month change in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score comparing 50/28 mg with matched ENDEAR participants (n = 20) who received sham. DEVOTE met its primary endpoint: at day 183, the CHOP-INTEND total score significantly improved (+15.1 points) in those who received 50/28 mg nusinersen and worsened (−11.1 points) in matched ENDEAR participants who received sham (difference, 26.19 (95% confidence interval = 20.7 to 31.74); statistical testing was performed using the joint-rank test where the difference in ranks was 26.06 (95% confidence interval = 17.9 to 34.2; P < 0.0001). The safety profile of 50/28 mg nusinersen was similar to the 12/12 mg regimen. The data support that high-dose nusinersen provides benefit in patients with SMA, with a generally well-tolerated safety profile. ClinicalTrials.gov registration: https://clinicaltrials.gov/study/NCT04089566. EudraCT no: 2019-002663-10.
{"title":"High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial","authors":"Richard S. Finkel, Thomas O. Crawford, Eugenio Mercuri, Charlotte J. Sumner, Maria del Mar Garcia Romero, John W. Day, Jacqueline Montes, Peng Sun, Ben Tichler, Angela D. Paradis, Emily Boesch, Jennifer Inra, Ross Littauer, Jihee Sohn, Michael Monine, Giulia Gambino, Richard Foster, Raechel Farewell, Stephanie Fradette","doi":"10.1038/s41591-025-04193-6","DOIUrl":"https://doi.org/10.1038/s41591-025-04193-6","url":null,"abstract":"Despite the remarkable benefits of nusinersen and other disease-modifying therapies in spinal muscular atrophy (SMA), patients may still experience clinical manifestations of the disease. Here we assessed the potential for high-dose nusinersen to rapidly slow neurodegeneration and lead to improved outcomes for patients. The global, three-part, phase 2/3 DEVOTE trial evaluated the efficacy and safety of high-dose nusinersen (50-mg loading dose; 28-mg maintenance dose) in individuals with SMA. In Part B, treatment-naive individuals (n = 75) were randomized 2:1 to 50/28 mg or 12/12 mg nusinersen. In a supportive open-label cohort (Part C), nusinersen-experienced individuals (12/12 mg for more than 1 year) were enrolled. The primary endpoint (Part B infantile-onset participants) was a 6-month change in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score comparing 50/28 mg with matched ENDEAR participants (n = 20) who received sham. DEVOTE met its primary endpoint: at day 183, the CHOP-INTEND total score significantly improved (+15.1 points) in those who received 50/28 mg nusinersen and worsened (−11.1 points) in matched ENDEAR participants who received sham (difference, 26.19 (95% confidence interval = 20.7 to 31.74); statistical testing was performed using the joint-rank test where the difference in ranks was 26.06 (95% confidence interval = 17.9 to 34.2; P < 0.0001). The safety profile of 50/28 mg nusinersen was similar to the 12/12 mg regimen. The data support that high-dose nusinersen provides benefit in patients with SMA, with a generally well-tolerated safety profile. ClinicalTrials.gov registration: https://clinicaltrials.gov/study/NCT04089566. EudraCT no: 2019-002663-10.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102152","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}
Pub Date : 2026-02-03DOI: 10.1038/s41591-025-04184-7
Michelle M Li, Ben Y Reis, Adam Rodman, Tianxi Cai, Noa Dagan, Ran D Balicer, Joseph Loscalzo, Isaac S Kohane, Marinka Zitnik
Medical artificial intelligence (AI) tools, including clinical language models, vision-language models and multimodal health record models, are used to summarize clinical notes, answer questions and support decisions. Their adaptation to new populations, specialties or care settings often relies on fine-tuning, prompting or retrieval from external knowledge bases. These strategies can scale poorly and risk contextual errors-outputs that appear plausible but miss critical patient or situational information. We envision context switching as an emergent solution. Context switching adjusts model reasoning at inference, without retraining. Generative models can tailor outputs to patient biology, care setting or disease. Multimodal models can switch between notes, laboratory results, imaging and genomics, even when some data are missing or delayed. Agent models can coordinate tools and roles based on task and user context. In each case, context switching enables medical AI to adapt across specialties, populations and geographies. This approach requires advances in data design, model architectures and evaluation frameworks, and establishes a foundation for medical AI that scales to an infinite number of contexts, while remaining reliable and suited to real-world care.
{"title":"Scaling medical AI across clinical contexts.","authors":"Michelle M Li, Ben Y Reis, Adam Rodman, Tianxi Cai, Noa Dagan, Ran D Balicer, Joseph Loscalzo, Isaac S Kohane, Marinka Zitnik","doi":"10.1038/s41591-025-04184-7","DOIUrl":"https://doi.org/10.1038/s41591-025-04184-7","url":null,"abstract":"<p><p>Medical artificial intelligence (AI) tools, including clinical language models, vision-language models and multimodal health record models, are used to summarize clinical notes, answer questions and support decisions. Their adaptation to new populations, specialties or care settings often relies on fine-tuning, prompting or retrieval from external knowledge bases. These strategies can scale poorly and risk contextual errors-outputs that appear plausible but miss critical patient or situational information. We envision context switching as an emergent solution. Context switching adjusts model reasoning at inference, without retraining. Generative models can tailor outputs to patient biology, care setting or disease. Multimodal models can switch between notes, laboratory results, imaging and genomics, even when some data are missing or delayed. Agent models can coordinate tools and roles based on task and user context. In each case, context switching enables medical AI to adapt across specialties, populations and geographies. This approach requires advances in data design, model architectures and evaluation frameworks, and establishes a foundation for medical AI that scales to an infinite number of contexts, while remaining reliable and suited to real-world care.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113699","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}
Pub Date : 2026-02-03DOI: 10.1038/s41591-026-04199-8
Paul Adepoju
{"title":"Fault lines in a global promise.","authors":"Paul Adepoju","doi":"10.1038/s41591-026-04199-8","DOIUrl":"https://doi.org/10.1038/s41591-026-04199-8","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113586","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}
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