Nature Medicine最新文献

Dual immunotherapy benefits certain patients with metastatic colorectal cancer

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-21 DOI: 10.1038/d41591-025-00014-y

引用次数: 0

Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-21 DOI: 10.1038/s41591-025-03499-9

Till Braun, Michael Rade, Maximilian Merz, Hanna Klepzig, Florian Große, David Fandrei, Nhu-Nguyen Pham, Markus Kreuz, Christina Katharina Kuhn, Florian Kuschel, Dennis Löffler, Jörn Meinel, Eva Heger, Viola Schweinsberg, Natali Pflug, Uwe Platzbecker, Michael Hallek, Udo Holtick, Ulrike Köhl, Christof Scheid, Kristin Reiche, Marco Herling, Tim Richardson

{"title":"Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody","authors":"Till Braun, Michael Rade, Maximilian Merz, Hanna Klepzig, Florian Große, David Fandrei, Nhu-Nguyen Pham, Markus Kreuz, Christina Katharina Kuhn, Florian Kuschel, Dennis Löffler, Jörn Meinel, Eva Heger, Viola Schweinsberg, Natali Pflug, Uwe Platzbecker, Michael Hallek, Udo Holtick, Ulrike Köhl, Christof Scheid, Kristin Reiche, Marco Herling, Tim Richardson","doi":"10.1038/s41591-025-03499-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03499-9","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells and bispecific T cell engagers have become integral components in the treatment of relapsed/refractory multiple myeloma. We report a 63-year-old male who received ciltacabtagene autoleucel CAR T cells and the GPRC5D × CD3 bispecific talquetamab for early relapse of his multiple myeloma. Nine months after CAR T therapy, he developed a symptomatic leukemic peripheral T cell lymphoma with cutaneous and intestinal involvement. Longitudinal single-cell RNA and T cell receptor sequencing of peripheral blood and bone marrow revealed two hyperexpanded CAR-carrying T cell clones. These expanded clones exhibited an exhausted effector-memory T cell transcriptional signature, and the neoplasm itself was sensitive to dexamethasone treatment. The immunophenotypic and transcriptional alterations of these abnormal T cells resembled those of T-large granular lymphocytic leukemia. Spatial transcriptomes of skin lesions confirmed the aberrant CAR-expressing T cells. Whole-genome sequencing revealed three distinct integration sites, within the introns of ZGPAT, KPNA4 and polycomb-associated noncoding RNAs. Before and after CAR T whole-genome analyses implicated clonal outgrowth of a TET2-mutated precursor propelled by additional subclone-specific loss of heterozygosity and other secondary mechanisms. This case highlights the evolution of a CAR-carrying peripheral T cell lymphoma following CAR T cell and bispecific T cell engager therapy, offering critical insights into the clonal evolution from a predisposed hematopoietic precursor to a mature neoplasm.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"84 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462299","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}

引用次数: 0

Telemedicine-based integrated management of atrial fibrillation in village clinics: a cluster randomized trial

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-21 DOI: 10.1038/s41591-025-03511-2

Ming Chu, Shimeng Zhang, Jinlong Gong, Shu Yang, Gang Yang, Xingxing Sun, Dan Wu, Yaodongqin Xia, Jincheng Jiao, Xiafeng Peng, Zhihang Peng, Li Hong, Zhirong Wang, Mingfang Li, Gregory Y. H. Lip, Minglong Chen

{"title":"Telemedicine-based integrated management of atrial fibrillation in village clinics: a cluster randomized trial","authors":"Ming Chu, Shimeng Zhang, Jinlong Gong, Shu Yang, Gang Yang, Xingxing Sun, Dan Wu, Yaodongqin Xia, Jincheng Jiao, Xiafeng Peng, Zhihang Peng, Li Hong, Zhirong Wang, Mingfang Li, Gregory Y. H. Lip, Minglong Chen","doi":"10.1038/s41591-025-03511-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03511-2","url":null,"abstract":"In rural China, where healthcare relies on village doctors (nonspecialized practitioners who work exclusively in their village clinics), delivering integrated atrial fibrillation (AF) management poses challenges. We developed a telemedicine-based, village doctor-led integrated care model and conducted a cluster randomized clinical trial to assess its efficacy compared to usual care. A total of 30 village clinics were randomly assigned (1:1) to the intervention or control group, with 1,039 village residents aged ≥65 years with AF (44.3% women) recruited. The primary outcome in stage 1 is adherence to integrated AF care at 12 months. In stage 2, the primary outcome is a composite of cardiovascular death, all strokes, heart failure or acute coronary syndrome hospitalization, and AF emergency visits over 36 months. Both primary outcomes were met. At 12 months, 33.1% in the telemedicine-based, village doctor-led care group and 8.7% in the usual care group met all criteria for integrated AF care (between-group difference, 24.4% (95% confidence interval (CI), 18.3–30.5%); P < 0.001). Over 34.0 months, 41.8% in the telemedicine-based, village doctor-led care group and 10.3% in the usual care group met all criteria for integrated AF care (P < 0.001). The rate of the composite cardiovascular event outcome was lower in the telemedicine-based, village doctor-led care group than in the usual care group (6.2% versus 9.6% per year; hazard ratio, 0.64 (95% CI, 0.50–0.82); P < 0.001). Our trial intervention by this telemedicine-based integrated care delivery model of AF care in rural villages demonstrates better adherence and improved clinical outcomes compared to usual care. ClinicalTrials.gov registration: NCT04622514.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"176 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462300","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}

引用次数: 0

Epigenetic footprints in prenatal cell-free DNA reveal risk of preeclampsia

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-19 DOI: 10.1038/s41591-025-03536-7

引用次数: 0

Reduced-energy diet in women with gestational diabetes: the dietary intervention in gestational diabetes DiGest randomized clinical trial

IF 58.7 1区医学

Nature Medicine Pub Date : 2025-02-19 DOI: 10.1038/s41591-024-03356-1

Laura C. Kusinski, Danielle Jones, Nooria Atta, Elizabeth Turner, Suzanne Smith, Linda M. Oude Griep, Kirsten Rennie, Emanuella De Lucia Rolfe, Stephen J. Sharp, Vern Farewell, Helen R. Murphy, Roy Taylor, Claire L. Meek

{"title":"Reduced-energy diet in women with gestational diabetes: the dietary intervention in gestational diabetes DiGest randomized clinical trial","authors":"Laura C. Kusinski, Danielle Jones, Nooria Atta, Elizabeth Turner, Suzanne Smith, Linda M. Oude Griep, Kirsten Rennie, Emanuella De Lucia Rolfe, Stephen J. Sharp, Vern Farewell, Helen R. Murphy, Roy Taylor, Claire L. Meek","doi":"10.1038/s41591-024-03356-1","DOIUrl":"10.1038/s41591-024-03356-1","url":null,"abstract":"Reduced-energy diets promote weight loss and improve long-term outcomes in type 2 diabetes but are untested in gestational diabetes. We aimed to identify if weight loss in pregnancy improves perinatal outcomes in gestational diabetes. We performed a multicentre parallel, randomized, controlled, double-blind trial of energy restriction in women with singleton pregnancies, gestational diabetes and body mass index ≥25 kg m−2. Participants were randomized to receive a standard-energy control diet (2,000 kcal d−1) or reduced-energy intervention diet (1,200 kcal d−1) from enrollment (29 weeks) until delivery, provided as weekly diet boxes (40% carbohydrate, 35% fat, 25% protein). The randomization was performed in a 1:1 ratio, stratified by center and blinded to the participants and study team. Primary outcomes were maternal weight change from enrollment to 36 weeks and offspring birth weight. In total, 425 participants were randomized to the control (n = 211) or intervention (n = 214). Outcome data were available for 388 of 425 (90.1%) participants at 36 weeks and 382 of 425 (89.8%) at delivery. There was no evidence of a difference in maternal weight change to 36 weeks between groups (intervention effect −0.20 (95% confidence interval −1.01, 0.61); P > 0.1) and offspring standardized birth weight (intervention effect 0.005 (−0.19, 0.20); P > 0.1). A reduced-energy diet was safe in pregnancy. ISRCTN registration no. 65152174 . In a clinical trial in pregnant women with gestational diabetes, a dietary intervention for energy restriction was safe and did not result in any difference in maternal weight or offspring standardized birth weight outcomes compared to the control arm.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 2","pages":"514-523"},"PeriodicalIF":58.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03356-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443718","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}

引用次数: 0

Integrating the environmental and genetic architectures of aging and mortality

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-19 DOI: 10.1038/s41591-024-03483-9

M. Austin Argentieri, Najaf Amin, Alejo J. Nevado-Holgado, William Sproviero, Jennifer A. Collister, Sarai M. Keestra, Midas M. Kuilman, Bigina N. R. Ginos, Mohsen Ghanbari, Aiden Doherty, David J. Hunter, Alexandra Alvergne, Cornelia M. van Duijn

{"title":"Integrating the environmental and genetic architectures of aging and mortality","authors":"M. Austin Argentieri, Najaf Amin, Alejo J. Nevado-Holgado, William Sproviero, Jennifer A. Collister, Sarai M. Keestra, Midas M. Kuilman, Bigina N. R. Ginos, Mohsen Ghanbari, Aiden Doherty, David J. Hunter, Alexandra Alvergne, Cornelia M. van Duijn","doi":"10.1038/s41591-024-03483-9","DOIUrl":"https://doi.org/10.1038/s41591-024-03483-9","url":null,"abstract":"Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3–26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5–49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"24 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443720","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}

引用次数: 0

Dementia prevention needs clinical trials

IF 58.7 1区医学

Nature Medicine Pub Date : 2025-02-19 DOI: 10.1038/s41591-025-03552-7

引用次数: 0

Engineered heart muscle reinvigorates failing hearts

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-18 DOI: 10.1038/d41591-025-00013-z

引用次数: 0

Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-17 DOI: 10.1038/s41591-025-03513-0

Che-Hsing Li, Sandhya Sharma, Andras A. Heczey, Mae L. Woods, David H. M. Steffin, Chrystal U. Louis, Bambi J. Grilley, Sachin G. Thakkar, Mengfen Wu, Tao Wang, Cliona M. Rooney, Malcolm K. Brenner, Helen E. Heslop

{"title":"Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma","authors":"Che-Hsing Li, Sandhya Sharma, Andras A. Heczey, Mae L. Woods, David H. M. Steffin, Chrystal U. Louis, Bambi J. Grilley, Sachin G. Thakkar, Mengfen Wu, Tao Wang, Cliona M. Rooney, Malcolm K. Brenner, Helen E. Heslop","doi":"10.1038/s41591-025-03513-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03513-0","url":null,"abstract":"In a phase 1 clinical trial open to accrual from 2004 to 2009, we treated children with neuroblastoma with Epstein–Barr virus (EBV)-specific T lymphocytes and CD3-activated T cells—each expressing chimeric antigen receptors (CARs) targeting GD2 but without an embedded co-stimulatory sequence (first-generation CARs). These CARs incorporated barcoded sequences to track each infused population. We previously reported outcomes up to 5 years and now report long-term outcomes up to 18 years. Of 11 patients with active disease at infusion, three achieved a complete response that was sustained in two patients, one for 8 years until lost to follow-up and one for more than 18 years. Of eight patients with no evidence of disease at the time of CAR-T administration, five are disease free at their last follow-up between 10 years and 15 years after infusion. Intermittent low levels of transgene were detected during the follow-up period with significantly greater persistence in those who were long-term survivors. Despite using first-generation vectors that are no longer employed because of the lack of co-stimulatory domains, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy, including one patient now in remission of relapsed disease for more than 18 years.ClinicalTrials.gov identifier: NCT00085930.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"12 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435121","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}

引用次数: 0

Publisher Correction: GPT-4 assistance for improvement of physician performance on patient care tasks: a randomized controlled trial

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-02-17 DOI: 10.1038/s41591-025-03586-x

Ethan Goh, Robert J. Gallo, Eric Strong, Yingjie Weng, Hannah Kerman, Jason A. Freed, Joséphine A. Cool, Zahir Kanjee, Kathleen P. Lane, Andrew S. Parsons, Neera Ahuja, Eric Horvitz, Daniel Yang, Arnold Milstein, Andrew P. J. Olson, Jason Hom, Jonathan H. Chen, Adam Rodman

引用次数: 0