Nature MedicinePub Date : 2025-03-31DOI: 10.1038/s41591-025-03617-7
Kanta Horie, Gemma Salvadó, Rama K. Koppisetti, Shorena Janelidze, Nicolas R. Barthélemy, Yingxin He, Chihiro Sato, Brian A. Gordon, Hong Jiang, Tammie L. S. Benzinger, Erik Stomrud, David M. Holtzman, Niklas Mattsson-Carlgren, John C. Morris, Sebastian Palmqvist, Rik Ossenkoppele, Suzanne E. Schindler, Oskar Hansson, Randall J. Bateman
{"title":"Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease","authors":"Kanta Horie, Gemma Salvadó, Rama K. Koppisetti, Shorena Janelidze, Nicolas R. Barthélemy, Yingxin He, Chihiro Sato, Brian A. Gordon, Hong Jiang, Tammie L. S. Benzinger, Erik Stomrud, David M. Holtzman, Niklas Mattsson-Carlgren, John C. Morris, Sebastian Palmqvist, Rik Ossenkoppele, Suzanne E. Schindler, Oskar Hansson, Randall J. Bateman","doi":"10.1038/s41591-025-03617-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03617-7","url":null,"abstract":"<p>Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer’s disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (<i>n</i> = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma eMTBR-tau243 showed strong associations with tau positron emission tomography binding (<i>β</i> = 0.72, <i>R</i><sup>2</sup> = 0.56) and cognitive performance (<i>β</i> = 0.60, <i>R</i><sup>2</sup> = 0.40), outperforming other plasma tau (%p-tau217 and %p-tau205) biomarkers. These results suggest that plasma eMTBR-tau243 may be useful for estimating the tauopathy load in AD, thereby improving the diagnostic evaluation of AD in clinical practice and monitoring the efficacy of tau-targeted therapies in clinical trials.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"38 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736655","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}
Nature MedicinePub Date : 2025-03-31DOI: 10.1038/s41591-025-03607-9
Yosef Ellenbogen, Gelareh Zadeh
{"title":"A new paradigm for immunotherapy in glioblastoma","authors":"Yosef Ellenbogen, Gelareh Zadeh","doi":"10.1038/s41591-025-03607-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03607-9","url":null,"abstract":"A detailed case report shows that neoadjuvant combination immunotherapy can activate antitumor immunity and drive clinical benefit in newly diagnosed glioblastoma, revealing avenues for further research that could shift the treatment landscape to improve survival.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"183 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736774","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}
Nature MedicinePub Date : 2025-03-31DOI: 10.1038/s41591-025-03675-x
Alexander J. Nihart, Marcus A. Garcia, Eliane El Hayek, Rui Liu, Marian Olewine, Josiah D. Kingston, Eliseo F. Castillo, Rama R. Gullapalli, Tamara Howard, Barry Bleske, Justin Scott, Jorge Gonzalez-Estrella, Jessica M. Gross, Michael Spilde, Natalie L. Adolphi, Daniel F. Gallego, Heather S. Jarrell, Gabrielle Dvorscak, Maria E. Zuluaga-Ruiz, Andrew B. West, Matthew J. Campen
{"title":"Author Correction: Bioaccumulation of microplastics in decedent human brains","authors":"Alexander J. Nihart, Marcus A. Garcia, Eliane El Hayek, Rui Liu, Marian Olewine, Josiah D. Kingston, Eliseo F. Castillo, Rama R. Gullapalli, Tamara Howard, Barry Bleske, Justin Scott, Jorge Gonzalez-Estrella, Jessica M. Gross, Michael Spilde, Natalie L. Adolphi, Daniel F. Gallego, Heather S. Jarrell, Gabrielle Dvorscak, Maria E. Zuluaga-Ruiz, Andrew B. West, Matthew J. Campen","doi":"10.1038/s41591-025-03675-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03675-x","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-024-03453-1, published online 3 February 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"25 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744757","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}
Nature MedicinePub Date : 2025-03-30DOI: 10.1038/s41591-025-03671-1
Stefan D. Anker, Mahir Karakas, Robert J. Mentz, Piotr Ponikowski, Javed Butler, Muhammad Shahzeb Khan, Khawaja M. Talha, Paul R. Kalra, Adrian F. Hernandez, Hillary Mulder, Frank W. Rockhold, Marius Placzek, Christian Röver, John G. F. Cleland, Tim Friede
{"title":"Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency","authors":"Stefan D. Anker, Mahir Karakas, Robert J. Mentz, Piotr Ponikowski, Javed Butler, Muhammad Shahzeb Khan, Khawaja M. Talha, Paul R. Kalra, Adrian F. Hernandez, Hillary Mulder, Frank W. Rockhold, Marius Placzek, Christian Röver, John G. F. Cleland, Tim Friede","doi":"10.1038/s41591-025-03671-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03671-1","url":null,"abstract":"<p>Uncertainty remains about the effect of intravenous (IV) iron on outcomes for heart failure (HF) with iron deficiency. Here, we summarize the efficacy and safety of IV iron from six trials (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID, and FAIR-HF2) including 7,175 patients. In comparison to prior analyses, this meta-analysis adds new data from FAIR-HF2, uses a harmonized and robust Bayesian approach, and includes individual participant data from 5 trials. Patients assigned to IV iron, as compared to those assigned to placebo, had lower rates for the composite endpoint of recurrent HF hospitalizations and cardiovascular mortality at 12 months (RR 0.72 [95% CI 0.55–0.89]) and for the complete length of follow up (RR 0.81 [95% CI 0.63–0.97]). Each component of the primary endpoint contributed to the beneficial effect of IV iron at both 12 months and for the complete length of follow up: recurrent HF hospitalizations (RR 0.69 [95% CI 0.48–0.88] and RR 0.78 [95% CI 0.55–0.98], respectively) and cardiovascular mortality (HR 0.80 [95% CI 0.61–1.03] and HR 0.87 [95% CI 0.73–1.04], respectively). All-cause mortality at 12 months and for the complete length of follow up (HR: 0.82 [95% CI 0.65–1.03]) and 0.92 [95% CI 0.80–1.07], respectively) indicated the overall safety of IV iron treatment. Treatment effects were greatest in the first year after randomization when doses of IV iron provided are highest. These findings suggest that treating iron deficiency in patients with HF significantly reduces cardiovascular events and suggests further investigation of optimal dosing of IV iron.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"70 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736326","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}
Nature MedicinePub Date : 2025-03-30DOI: 10.1038/s41591-025-03628-4
Job J. Herrmann, Hans-Peter Brunner-La Rocca, Lisette E. H. J. M. Baltussen, Fabienne Beckers-Wesche, Sebastiaan C. A. M. Bekkers, Louise Bellersen, J. W. Martijn van Eck, H. Carlijne Hassing, Tiny Jaarsma, Gerard C. M. Linssen, Ron Pisters, Sandra Sanders-van Wijk, Marjolein H. I. Verdijk, M. Louis Handoko, Peter van der Meer, Frederik H. Verbrugge, James L. Januzzi, Antoni Bayés-Genís, Robby Nieuwlaat, Laura Rodwell, D. H. Frank Gommans, Roland R. J. van Kimmenade
{"title":"Liberal fluid intake versus fluid restriction in chronic heart failure: a randomized clinical trial","authors":"Job J. Herrmann, Hans-Peter Brunner-La Rocca, Lisette E. H. J. M. Baltussen, Fabienne Beckers-Wesche, Sebastiaan C. A. M. Bekkers, Louise Bellersen, J. W. Martijn van Eck, H. Carlijne Hassing, Tiny Jaarsma, Gerard C. M. Linssen, Ron Pisters, Sandra Sanders-van Wijk, Marjolein H. I. Verdijk, M. Louis Handoko, Peter van der Meer, Frederik H. Verbrugge, James L. Januzzi, Antoni Bayés-Genís, Robby Nieuwlaat, Laura Rodwell, D. H. Frank Gommans, Roland R. J. van Kimmenade","doi":"10.1038/s41591-025-03628-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03628-4","url":null,"abstract":"<p>Fluid restriction is frequently recommended to patients with chronic heart failure, but randomized clinical trials assessing the effects of fluid restriction remain scarce. In this multicenter open-label trial, outpatients with chronic heart failure were randomized to receiving advice for liberal fluid intake versus receiving advice for fluid restriction, up to 1,500 ml per day of fluid intake. The primary outcome of the trial was health status after 3 months, as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS). Secondary outcomes included thirst distress and safety events. Among 504 randomized patients (67.3% male), the KCCQ-OSS after 3 months was 74.0 in the liberal fluid intake group versus 72.2 in the fluid restriction group, with a mean difference after adjustment for baseline scores of 2.17 (95% confidence interval −0.06 to 4.39; <i>P</i> = 0.06), indicating that the primary outcome was not met. Thirst distress was higher in the fluid restriction group and no differences were observed for safety events between the two groups. These findings question the benefit of fluid restriction in chronic heart failure. ClinicalTrials.gov registration: NCT04551729.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"216 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736474","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}
Nature MedicinePub Date : 2025-03-28DOI: 10.1038/s41591-025-03665-z
Johanna Klughammer, Daniel L. Abravanel, Åsa Segerstolpe, Timothy R. Blosser, Yury Goltsev, Yi Cui, Daniel R. Goodwin, Anubhav Sinha, Orr Ashenberg, Michal Slyper, Sébastien Vigneau, Judit Jané‐Valbuena, Shahar Alon, Chiara Caraccio, Judy Chen, Ofir Cohen, Nicole Cullen, Laura K. DelloStritto, Danielle Dionne, Janet Files, Allison Frangieh, Karla Helvie, Melissa E. Hughes, Stephanie Inga, Abhay Kanodia, Ana Lako, Colin MacKichan, Simon Mages, Noa Moriel, Evan Murray, Sara Napolitano, Kyleen Nguyen, Mor Nitzan, Rebecca Ortiz, Miraj Patel, Kathleen L. Pfaff, Caroline B. M. Porter, Asaf Rotem, Sarah Strauss, Robert Strasser, Aaron R. Thorner, Madison Turner, Isaac Wakiro, Julia Waldman, Jingyi Wu, Jorge Gómez Tejeda Zañudo, Diane Zhang, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Edward S. Boyden, Fei Chen, Garry P. Nolan, Scott J. Rodig, Xiaowei Zhuang, Orit Rozenblatt-Rosen, Bruce E. Johnson, Aviv Regev, Nikhil Wagle
{"title":"Author Correction: A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features","authors":"Johanna Klughammer, Daniel L. Abravanel, Åsa Segerstolpe, Timothy R. Blosser, Yury Goltsev, Yi Cui, Daniel R. Goodwin, Anubhav Sinha, Orr Ashenberg, Michal Slyper, Sébastien Vigneau, Judit Jané‐Valbuena, Shahar Alon, Chiara Caraccio, Judy Chen, Ofir Cohen, Nicole Cullen, Laura K. DelloStritto, Danielle Dionne, Janet Files, Allison Frangieh, Karla Helvie, Melissa E. Hughes, Stephanie Inga, Abhay Kanodia, Ana Lako, Colin MacKichan, Simon Mages, Noa Moriel, Evan Murray, Sara Napolitano, Kyleen Nguyen, Mor Nitzan, Rebecca Ortiz, Miraj Patel, Kathleen L. Pfaff, Caroline B. M. Porter, Asaf Rotem, Sarah Strauss, Robert Strasser, Aaron R. Thorner, Madison Turner, Isaac Wakiro, Julia Waldman, Jingyi Wu, Jorge Gómez Tejeda Zañudo, Diane Zhang, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Edward S. Boyden, Fei Chen, Garry P. Nolan, Scott J. Rodig, Xiaowei Zhuang, Orit Rozenblatt-Rosen, Bruce E. Johnson, Aviv Regev, Nikhil Wagle","doi":"10.1038/s41591-025-03665-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03665-z","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-024-03215-z, published online 30 October 2024.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"183 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723279","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}
Nature MedicinePub Date : 2025-03-28DOI: 10.1038/s41591-025-03664-0
Lynn van Olst, Brooke Simonton, Alex J. Edwards, Anne V. Forsyth, Jake Boles, Pouya Jamshidi, Thomas Watson, Nate Shepard, Talia Krainc, Benney MR Argue, Ziyang Zhang, Joshua Kuruvilla, Lily Camp, Mengwei Li, Hang Xu, Jeanette L. Norman, Joshua Cahan, Robert Vassar, Jinmiao Chen, Rudolph J. Castellani, James AR Nicoll, Delphine Boche, David Gate
{"title":"Author Correction: Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease","authors":"Lynn van Olst, Brooke Simonton, Alex J. Edwards, Anne V. Forsyth, Jake Boles, Pouya Jamshidi, Thomas Watson, Nate Shepard, Talia Krainc, Benney MR Argue, Ziyang Zhang, Joshua Kuruvilla, Lily Camp, Mengwei Li, Hang Xu, Jeanette L. Norman, Joshua Cahan, Robert Vassar, Jinmiao Chen, Rudolph J. Castellani, James AR Nicoll, Delphine Boche, David Gate","doi":"10.1038/s41591-025-03664-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03664-0","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-025-03574-1, published online 6 March 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"72 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723379","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}
Nature MedicinePub Date : 2025-03-28DOI: 10.1038/s41591-025-03557-2
Louise Y. Cheng, Jayesh Desai, Paul J. Neeson
{"title":"Targeting GDF-15 in cancer cachexia and immunity","authors":"Louise Y. Cheng, Jayesh Desai, Paul J. Neeson","doi":"10.1038/s41591-025-03557-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03557-2","url":null,"abstract":"Two recent, early-phase trials evaluating antibodies that target GDF-15 show positive effects on immunotherapy response and cachexia symptoms; further work to unravel the multifaceted biology of GDF-15 in cancer could lead to transformative treatment strategies.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"61 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723140","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}
Nature MedicinePub Date : 2025-03-28DOI: 10.1038/d41591-025-00022-y
{"title":"The health consequences of foreign policy sanctions","authors":"","doi":"10.1038/d41591-025-00022-y","DOIUrl":"https://doi.org/10.1038/d41591-025-00022-y","url":null,"abstract":"Foreign aid sanctions reverse progress on child and maternal health and increase mortality rates, according to an analysis of three decades’ worth of data from 113 countries.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"183 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723141","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}
Nature MedicinePub Date : 2025-03-28DOI: 10.1038/s41591-025-03528-7
Francis Vergunst, Massimiliano Orri, Alberto Forte, Marie-Claude Geoffroy
{"title":"Links between climate change and suicidal behavior risks","authors":"Francis Vergunst, Massimiliano Orri, Alberto Forte, Marie-Claude Geoffroy","doi":"10.1038/s41591-025-03528-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03528-7","url":null,"abstract":"Climate change is altering the frequency and intensity of weather-related hazards, which can harm mental health and wellbeing and thus elevate risks for suicidal behaviors.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"22 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723142","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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