Pub Date : 2026-02-13DOI: 10.1038/s41591-026-04232-w
Johanna M C Blom, Ciara Staunton, Sophie Tascedda, Neil Slabbert, Luca Pani, Melodie Labuschaigne
{"title":"Embedding equity in clinical research governance.","authors":"Johanna M C Blom, Ciara Staunton, Sophie Tascedda, Neil Slabbert, Luca Pani, Melodie Labuschaigne","doi":"10.1038/s41591-026-04232-w","DOIUrl":"https://doi.org/10.1038/s41591-026-04232-w","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195055","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 role of strategy units in guiding research institutions through complexity.","authors":"Michela Giulia Bertero, Katrine Sonne-Hansen, Anna-Lynn Wegener, Teresa Sanchis","doi":"10.1038/s41591-026-04218-8","DOIUrl":"https://doi.org/10.1038/s41591-026-04218-8","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195078","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 : 2026-02-12DOI: 10.1038/s41591-025-04139-y
Aarthi Talla, Joao L. L. C. Azevedo, Muhammad Bilal Latif, Ana B. Enriquez, Gabriela Pacheco Sanchez, Adam N. Pelletier, Saswat Kumar Bal, Sangeeta Kumari, Viviane Schuch, Khader Ghneim, Ajantha Rhodes, Frank Maldarelli, Robert Yarchoan, Kathryn Lurain, Ramya Ramaswami, Elad Sharon, Bruce W. Hess, Leonard D’Amico, Javier Martinez-Picado, Nicolas Chomont, Sharon R. Lewin, Steven G. Deeks, Steven P. Fling, Martin A. Cheever, Thomas S. Uldrick, Ashish A. Sharma, Rafick-Pierre Sekaly
Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear. We performed a prespecified exploratory, longitudinal multiomic profiling of 30 PLWH (29 males and one female) with cancer in the phase 1 CITN-12 clinical trial, in which pembrolizumab was evaluated for safety and preliminary antitumor activity. The therapy was generally well tolerated, with most adverse events graded 1–2 and objective antitumor response observed in five participants (one complete response and four partial responses). Within 24 hours of treatment, we observed an expansion of proliferating HIV-specific effector CD8+ T cells and a decline in plasma TGFβ. Furthermore, among the 14 participants tracked to the end of treatment (ranging from 44 to 315 days after therapy initiation), nine display early induction and sustained expression of interferon-stimulated genes (ISGs), antiviral restriction factors and Toll-like receptor (TLR) signaling and a reduction in the HIV reservoir. Mapping these transcriptomic signatures across more than 1,000 public single-cell RNA sequencing datasets reveals that anti-PD-1-induced programs are present in subsets of across subsets of disease states, indicating that some people already display a heightened antiviral state. Together, these findings define immune pathways that help identify PLWH most likely to experience reservoir decay with anti-PD-1 therapy and suggest that sustained ISG activation may contribute to reservoir reduction and prevention of viral rebound upon ART interruption. ClinicalTrials.gov registration: NCT02595866 . A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.
{"title":"Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy","authors":"Aarthi Talla, Joao L. L. C. Azevedo, Muhammad Bilal Latif, Ana B. Enriquez, Gabriela Pacheco Sanchez, Adam N. Pelletier, Saswat Kumar Bal, Sangeeta Kumari, Viviane Schuch, Khader Ghneim, Ajantha Rhodes, Frank Maldarelli, Robert Yarchoan, Kathryn Lurain, Ramya Ramaswami, Elad Sharon, Bruce W. Hess, Leonard D’Amico, Javier Martinez-Picado, Nicolas Chomont, Sharon R. Lewin, Steven G. Deeks, Steven P. Fling, Martin A. Cheever, Thomas S. Uldrick, Ashish A. Sharma, Rafick-Pierre Sekaly","doi":"10.1038/s41591-025-04139-y","DOIUrl":"10.1038/s41591-025-04139-y","url":null,"abstract":"Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear. We performed a prespecified exploratory, longitudinal multiomic profiling of 30 PLWH (29 males and one female) with cancer in the phase 1 CITN-12 clinical trial, in which pembrolizumab was evaluated for safety and preliminary antitumor activity. The therapy was generally well tolerated, with most adverse events graded 1–2 and objective antitumor response observed in five participants (one complete response and four partial responses). Within 24 hours of treatment, we observed an expansion of proliferating HIV-specific effector CD8+ T cells and a decline in plasma TGFβ. Furthermore, among the 14 participants tracked to the end of treatment (ranging from 44 to 315 days after therapy initiation), nine display early induction and sustained expression of interferon-stimulated genes (ISGs), antiviral restriction factors and Toll-like receptor (TLR) signaling and a reduction in the HIV reservoir. Mapping these transcriptomic signatures across more than 1,000 public single-cell RNA sequencing datasets reveals that anti-PD-1-induced programs are present in subsets of across subsets of disease states, indicating that some people already display a heightened antiviral state. Together, these findings define immune pathways that help identify PLWH most likely to experience reservoir decay with anti-PD-1 therapy and suggest that sustained ISG activation may contribute to reservoir reduction and prevention of viral rebound upon ART interruption. ClinicalTrials.gov registration: NCT02595866 . A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"505-517"},"PeriodicalIF":50.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-04139-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180935","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}
Pub Date : 2026-02-12DOI: 10.1038/s41591-025-04152-1
PD-1 blockade reprograms both innate and adaptive immunity in people living with HIV and cancer, inducing interferon-driven antiviral responses that reduce the HIV reservoir. A pre-existing type I interferon signature predicts reservoir decline, whereas high TGFβ signaling opposes it, defining immune states that influence the outcome of PD-1 therapy.
{"title":"PD-1 blockade reprograms antiviral immunity and reduces the HIV reservoir","authors":"","doi":"10.1038/s41591-025-04152-1","DOIUrl":"10.1038/s41591-025-04152-1","url":null,"abstract":"PD-1 blockade reprograms both innate and adaptive immunity in people living with HIV and cancer, inducing interferon-driven antiviral responses that reduce the HIV reservoir. A pre-existing type I interferon signature predicts reservoir decline, whereas high TGFβ signaling opposes it, defining immune states that influence the outcome of PD-1 therapy.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"425-426"},"PeriodicalIF":50.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181077","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 : 2026-02-11DOI: 10.1038/s41591-026-04216-w
Capillary blood sampling for the Alzheimer’s disease biomarkers p-tau217, NfL and GFAP correlates with venous measures for the same biomarkers. As capillary p-tau217 accurately classified amyloid burden, it might support remote assessment in large-scale epidemiology to estimate the prevalence of Alzheimer’s disease and enable triage into clinical services and trials.
{"title":"Capillary blood sampling for detecting biomarkers of Alzheimer’s disease","authors":"","doi":"10.1038/s41591-026-04216-w","DOIUrl":"10.1038/s41591-026-04216-w","url":null,"abstract":"Capillary blood sampling for the Alzheimer’s disease biomarkers p-tau217, NfL and GFAP correlates with venous measures for the same biomarkers. As capillary p-tau217 accurately classified amyloid burden, it might support remote assessment in large-scale epidemiology to estimate the prevalence of Alzheimer’s disease and enable triage into clinical services and trials.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"429-430"},"PeriodicalIF":50.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165278","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 : 2026-02-09DOI: 10.1038/s41591-025-04074-y
Andrew M. Bean, Rebecca Elizabeth Payne, Guy Parsons, Hannah Rose Kirk, Juan Ciro, Rafael Mosquera-Gómez, Sara Hincapié M, Aruna S. Ekanayaka, Lionel Tarassenko, Luc Rocher, Adam Mahdi
Global healthcare providers are exploring the use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested whether LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in fewer than 34.5% of cases and disposition in fewer than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities before public deployments in healthcare. In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment.
{"title":"Reliability of LLMs as medical assistants for the general public: a randomized preregistered study","authors":"Andrew M. Bean, Rebecca Elizabeth Payne, Guy Parsons, Hannah Rose Kirk, Juan Ciro, Rafael Mosquera-Gómez, Sara Hincapié M, Aruna S. Ekanayaka, Lionel Tarassenko, Luc Rocher, Adam Mahdi","doi":"10.1038/s41591-025-04074-y","DOIUrl":"10.1038/s41591-025-04074-y","url":null,"abstract":"Global healthcare providers are exploring the use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested whether LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in fewer than 34.5% of cases and disposition in fewer than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities before public deployments in healthcare. In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"609-615"},"PeriodicalIF":50.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-04074-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149740","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}
Pub Date : 2026-02-06DOI: 10.1038/s41591-026-04246-4
Vivek Y Reddy, Edward P Gerstenfeld, Stavros E Mountantonakis, Chinmay Patel, Kenneth A Ellenbogen, John D Harding, Douglas N Gibson, Andrea Natale, Jonathan W Waks, Hugh Calkins, Sanjaya K Gupta, Christopher E Woods, William Whang, Marcos Daccarett, Frank A Cuoco, David B Delurgio, Elizabeth Richards, Matthew D Martens, Brad Sutton, Moussa Mansour
Pulsed field ablation (PFA) has proven to be a safe and effective non-thermal ablation modality for the treatment of atrial fibrillation (AF), but little outcome data beyond 1 year have been reported. Here we present results from the ADVENT-LTO study, which provides extended follow-up of the ADVENT trial, the first randomized trial comparing PFA with conventional thermal ablation. In ADVENT-LTO, 364 patients with paroxysmal AF (183 PFA, 181 thermal; 237 men, 127 women) participated and were followed for 1,332 ± 147 days. For the primary endpoint of 4-year treatment success, PFA demonstrated preserved effectiveness compared to thermal ablation (72.8% PFA, 64.3% thermal; P = 0.12). Moreover, there was a trend favoring PFA as compared to thermal ablation for the prespecified outcome of freedom from hospital-based arrhythmia intervention (85.6% PFA, 78.6% thermal; hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.38-1.05), including fewer repeat ablations (10.4% PFA, 17.7% thermal; P = 0.04) as well as a trend favoring PFA as compared to thermal ablation for the prespecified outcome of progression to persistent AF (2.6% PFA, 4.6% thermal; HR = 0.55, 95% CI: 0.16-1.88). Taken together, these data demonstrate that the favorable outcomes of PFA are maintained over the course of 4 years. Coupled with the safety advantages of PFA over thermal ablation, these long-term data support widespread adoption of PFA for the treatment of AF. ClinicalTrials.gov registration: NCT06526546 .
{"title":"Pulsed field ablation versus conventional thermal ablation for paroxysmal atrial fibrillation: 4-year outcomes in the ADVENT-LTO study.","authors":"Vivek Y Reddy, Edward P Gerstenfeld, Stavros E Mountantonakis, Chinmay Patel, Kenneth A Ellenbogen, John D Harding, Douglas N Gibson, Andrea Natale, Jonathan W Waks, Hugh Calkins, Sanjaya K Gupta, Christopher E Woods, William Whang, Marcos Daccarett, Frank A Cuoco, David B Delurgio, Elizabeth Richards, Matthew D Martens, Brad Sutton, Moussa Mansour","doi":"10.1038/s41591-026-04246-4","DOIUrl":"10.1038/s41591-026-04246-4","url":null,"abstract":"<p><p>Pulsed field ablation (PFA) has proven to be a safe and effective non-thermal ablation modality for the treatment of atrial fibrillation (AF), but little outcome data beyond 1 year have been reported. Here we present results from the ADVENT-LTO study, which provides extended follow-up of the ADVENT trial, the first randomized trial comparing PFA with conventional thermal ablation. In ADVENT-LTO, 364 patients with paroxysmal AF (183 PFA, 181 thermal; 237 men, 127 women) participated and were followed for 1,332 ± 147 days. For the primary endpoint of 4-year treatment success, PFA demonstrated preserved effectiveness compared to thermal ablation (72.8% PFA, 64.3% thermal; P = 0.12). Moreover, there was a trend favoring PFA as compared to thermal ablation for the prespecified outcome of freedom from hospital-based arrhythmia intervention (85.6% PFA, 78.6% thermal; hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.38-1.05), including fewer repeat ablations (10.4% PFA, 17.7% thermal; P = 0.04) as well as a trend favoring PFA as compared to thermal ablation for the prespecified outcome of progression to persistent AF (2.6% PFA, 4.6% thermal; HR = 0.55, 95% CI: 0.16-1.88). Taken together, these data demonstrate that the favorable outcomes of PFA are maintained over the course of 4 years. Coupled with the safety advantages of PFA over thermal ablation, these long-term data support widespread adoption of PFA for the treatment of AF. ClinicalTrials.gov registration: NCT06526546 .</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132412","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 : 2026-02-06DOI: 10.1038/s41591-026-04227-7
Annesa Flentje, Brian Mustanski
{"title":"Surviving as a health equity researcher amidst a shifting political climate.","authors":"Annesa Flentje, Brian Mustanski","doi":"10.1038/s41591-026-04227-7","DOIUrl":"https://doi.org/10.1038/s41591-026-04227-7","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132495","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 : 2026-02-06DOI: 10.1038/s41591-026-04205-z
Nerys Astbury, Elizabeth Morris
Data suggest that primary care practices could help deliver effective weight management — but only with robust implementation strategies that acknowledge the realities and pressures of primary care settings.
{"title":"Practical solutions to weight management in primary care","authors":"Nerys Astbury, Elizabeth Morris","doi":"10.1038/s41591-026-04205-z","DOIUrl":"10.1038/s41591-026-04205-z","url":null,"abstract":"Data suggest that primary care practices could help deliver effective weight management — but only with robust implementation strategies that acknowledge the realities and pressures of primary care settings.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"418-419"},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132401","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：