Nature Medicine最新文献

{"title":"A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults.","authors":"Barbara McGowan, Andreea Ciudin, Jennifer L Baker, Luca Busetto, Dror Dicker, Gema Frühbeck, Gijs H Goossens, Matteo Monami, Paolo Sbraccia, Borja Martinez-Tellez, Euan Woodward, Volkan Yumuk","doi":"10.1038/s41591-025-03978-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03978-z","url":null,"abstract":"<p><p>This systematic review and network meta-analysis evaluated the efficacy and safety of obesity management medications (OMMs) in terms of reducing body weight and impact on obesity-related complications. Here a Medline and Embase search was performed up to 31 January 2025 for randomized controlled trials comparing OMMs versus placebo/active comparators in adults. Primary endpoint was percentage of total body weight loss (TBWL%) at the end of the study. Secondary endpoints were TBWL% at 1, 2 and ≥3 years, lipid profile, blood pressure, hemoglobin A1c, fasting plasma glucose, mental health, serious adverse events, quality of life, cardiovascular morbidity and mortality, remission of obesity-related complications and all-cause mortality. Fifty-six clinical trials were identified-orlistat (22), semaglutide (14), liraglutide (11), tirzepatide (6), naltrexone/bupropion (5) and phentermine/topiramate (2)-enrolling 60,307 patients (32,598 OMM and 27,709 placebo). All OMMs showed a significantly greater TBWL% versus placebo (P < 0.0001), more than 10% for semaglutide and tirzepatide. Both tirzepatide and semaglutide showed normoglycemia restoration, remission of type 2 diabetes and reduction in hospitalization due to heart failure. Semaglutide was effective in reducing major adverse cardiovascular events and reducing pain in knee osteoarthritis. Tirzepatide was effective in remission of obstructive sleep apnea syndrome and metabolic dysfunction-associated steatohepatitis. These results support the need to individualize the selection of OMMs.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213252","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: Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function.","authors":"Yuxi Liu, Xiao Gu, Yanping Li, Fenglei Wang, Chirag M Vyas, Cheng Peng, Danyue Dong, Yuhan Li, Yu Zhang, Yin Zhang, Oana A Zeleznik, Jae H Kang, Molin Wang, Frank B Hu, Walter C Willett, Olivia I Okereke, A Heather Eliassen, Peter Kraft, Meir J Stampfer, Dong D Wang","doi":"10.1038/s41591-025-04025-7","DOIUrl":"https://doi.org/10.1038/s41591-025-04025-7","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213206","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":"Framework for the pharmacological treatment of obesity and its complications from the European Association for the Study of Obesity (EASO).","authors":"Barbara McGowan, Andreea Ciudin, Jennifer L Baker, Luca Busetto, Dror Dicker, Gema Frühbeck, Gijs H Goossens, Matteo Monami, Paolo Sbraccia, Borja Martinez-Tellez, Euan Woodward, Volkan Yumuk","doi":"10.1038/s41591-025-03765-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03765-w","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213237","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":"In defense of Brazil's resolution on transgender healthcare.","authors":"Raphael Camara Medeiros Parente, Bruno Leandro de Souza, Francisco Eduardo Cardoso Alves, Jose Hiran da Silva Gallo","doi":"10.1038/s41591-025-03946-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03946-7","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206964","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 consensus immune dysregulation framework for sepsis and critical illnesses.","authors":"Andrew R Moore, Hong Zheng, Ananthakrishnan Ganesan, Yehudit Hasin-Brumshtein, Manoj V Maddali, Joseph E Levitt, Tom van der Poll, Jingyi Lu, Hjalmar R Bouma, Brendon P Scicluna, Evangelos J Giamarellos-Bourboulis, Antigone Kotsaki, Ignacio Martin-Loeches, Alexis Garduno, Richard E Rothman, Jonathan Sevransky, David W Wright, Mihir R Atreya, Lyle L Moldawer, Philip A Efron, Marcela Kralovcova, Thomas Karvunidis, Heather M Giannini, Nuala J Meyer, Timothy E Sweeney, Angela J Rogers, Purvesh Khatri","doi":"10.1038/s41591-025-03956-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03956-5","url":null,"abstract":"<p><p>Critical care syndromes such as sepsis, acute respiratory distress syndrome (ARDS) and trauma continue to have unacceptably high morbidity and mortality, with progress limited by the inherent heterogeneity within syndromic illnesses. Although numerous immune endotypes have been proposed for sepsis and critical care, the similarities and differences between these endotypes remain unclear, hindering clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine in critical care through the sharing of transcriptomic data. Here, evaluating the overlap of existing immune endotypes in sepsis across >7,074 samples from 37 independent cohorts, we developed cell-type-specific gene expression signatures to quantify dysregulation within immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. Importantly, this dysregulation was also observed in patients with ARDS, trauma and burns, suggesting a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation are associated with differential mortality in patients treated with anakinra in the SAVE-MORE trial (n = 452) and corticosteroids in the VICTAS (n = 89) and VANISH (n = 117) trials, underscoring their prognostic and therapeutic implications. In conclusion, our proposed immunology-based framework for quantifying cellular compartment dysregulation offers a potentially valuable tool for understanding immune dysregulation in critical illness with prognostic and therapeutic significance.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200083","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":"Clinical validation of an AI-based blood testing device for diagnosis and prognosis of acute infection and sepsis.","authors":"Oliver Liesenfeld, Sanjay Arora, Tom P Aufderheide, Casey M Clements, Elizabeth DeVos, Miriam Fischer, Evangelos J Giamarellos-Bourboulis, Stacey House, Roger L Humphries, Jasreen Kaur Gill, Edward Liu, Sharon E Mace, Larissa May, Edward Michelson, Tiffany M Osborn, Edward Panacek, Richard E Rothman, Wesley H Self, Howard A Smithline, Jay Steingrub, Paul Van Heukelom, Alexandra Weissman, Matthew Wilson, Donna M Wolk, David W Wright, Ljubomir Buturovic, Yehudit Hasin-Brumshtein, Nandita Damaraju, Cici Lu, Joshua R Shak, Natalie N Whitfield, Purvesh Khatri, Timothy E Sweeney, Nathan I Shapiro","doi":"10.1038/s41591-025-03933-y","DOIUrl":"https://doi.org/10.1038/s41591-025-03933-y","url":null,"abstract":"<p><p>Lack of reliable diagnostics for the presence, type and severity of infection in patients presenting to emergency departments with non-specific symptoms poses considerable challenges. We developed TriVerity, which uses isothermal amplification of 29 mRNAs and machine learning algorithms on the Myrna instrument to determine likelihoods of bacterial infection, viral infection and need for critical care interventions within 7 days. To validate TriVerity, the SEPSIS-SHIELD study enrolled 1,222 patients with clinically adjudicated infection status and need for critical care intervention within 7 days as endpoints. The TriVerity Bacterial and Viral scores had higher accuracy than C-reactive protein, procalcitonin or white blood cell count for the diagnosis of bacterial infection with area under the receiver operating characteristic (AUROC) of 0.83, and viral infection (AUROC = 0.91). The TriVerity Severity score had an AUROC of 0.78 for predicting illness severity and allowed reclassification of risk for critical care interventions compared to clinical assessment (quick Sequential Organ Failure Assessment) alone. Each of the three scores had rule-in specificity >92% and rule-out sensitivity >95%. Comparison of antibiotics administration at presentation with post-follow-up adjudication found that TriVerity could potentially reduce false positives and false negatives for inappropriate antibiotics use by 60-70%. Further clinical testing in an interventional setting is needed to prove actionability and clinical benefit of TriVerity.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200159","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 damage done.","authors":"Marianne Guenot","doi":"10.1038/s41591-025-03994-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03994-z","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200199","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 consensus blood transcriptomic framework for sepsis.","authors":"Brendon P Scicluna, Kiki Cano-Gamez, Katie L Burnham, Emma E Davenport, Andrew Reese Moore, Soumen Khan, Charles J Hinds, Olaf L Cremer, Purvesh Khatri, Timothy E Sweeney, Julian C Knight, Tom van der Poll","doi":"10.1038/s41591-025-03964-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03964-5","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition driven by a maladaptive host response to infection. To establish a standardized blood transcriptomic subtype model, we aggregated blood transcriptomics data from two major sepsis cohorts: the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project (n = 678 sampled on intensive care unit admission; ClinicalTrials.gov registration no. NCT01905033 ) and the Genomic Advances in Sepsis (GAinS) study (n = 444 sampled on intensive care unit admission and n = 817 follow-up samples; ClinicalTrials.gov registration no. NCT00131196 ). We demonstrate a strong interconnection across three separate classification methods, resulting in the proposed groupings of three consensus transcriptomic subtypes (CTSs). The distinguishing characteristics of CTS1 included gene activation of typical inflammatory pathways, more pronounced endothelial activation and an overall immature neutrophil theme. CTS2 was characterized by gene activation of a heme metabolism pathway, fibrinolytic disturbances and platelet and eosinophil signatures. CTS3 was associated with genes involved in the activation of allograft rejection, interferon signaling and anticoagulation functions, together with lymphocyte and nonclassical monocyte features. Evaluating CTS classification in independent patient cohorts, specifically the vasopressin vs noradrenaline as initial therapy in septic shock (VANISH) randomized controlled trial (n = 176; ISRCTN registration no. ISRCTN20769191 ) and patients hospitalized with suspected sepsis at a district hospital in Uganda (n = 128), ascertained the robustness of our approach. Notably, post hoc analysis of a pseudo-randomized cohort, along with a reanalysis of the VANISH trial data, unmasked a harmful signal in CTS2-assigned patients treated with corticosteroids. The CTS classification method aligns diverse sepsis transcriptomic subgroupings into a robust, reproducible framework, thereby enabling biological interpretation and potentially assisting aspects of clinical trial design to advance precision medicine in sepsis.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200445","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":"Dietary profiles and associated metabolic risk factors in India from the ICMR-INDIAB survey-21.","authors":"Ranjit Mohan Anjana, Vasudevan Sudha, Kuzhandaivelu Abirami, Rajagopal Gayathri, Valangaiman Sriram Manasa, Mohan Deepa, Rajendra Pradeepa, Ranjit Unnikrishnan, Shashank Joshi, Banshi Saboo, Arvind Gupta, Prashant P Joshi, Prabha Adhikari, Puthiyaveettil Kottayam Jabbar, Sunil M Jain, Subhankar Chowdhury, Anil J Purty, Saroj Kumar Tripathy, Sarita Behera, Jagdish Mahanta, Avula Laxmaiah, Kamala Krishnaswamy, Anura Viswanath Kurpad, Ashok Kumar Das, Rupinder Singh Dhaliwal, Tanvir Kaur, Shilpa N Bhupathiraju, Viswanathan Mohan","doi":"10.1038/s41591-025-03949-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03949-4","url":null,"abstract":"<p><p>Rapid dietary transitions in India have been associated with an alarming rise in cardiometabolic diseases. Using data from the national Indian Council of Medical Research-India Diabetes survey (18,090 adults), we examined India's dietary profile and the effect of isocaloric substitution of carbohydrates with other macronutrients on metabolic risk. Indian diets are characterized by high intakes of low-quality carbohydrates (white rice, milled whole grains and added sugar), high levels of saturated fat and low intakes of protein. Compared to those with the least carbohydrate intakes, those with the highest intakes had higher risk of newly diagnosed type 2 diabetes (T2D; odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.14,1.47), prediabetes (OR = 1.20, 95% CI = 1.06,1.33), generalized obesity (OR = 1.22, 95% CI = 1.07,1.37) and abdominal obesity (OR = 1.15, 95% CI = 1.01, 1.30). Replacing refined cereals with whole wheat or millet flour without decreasing overall carbohydrate quantity was not associated with lower risk for T2D (OR = 0.94, 95% CI = 0.57, 1.56) or abdominal obesity (OR = 1.08, 95% CI = 0.66, 1.76). Modeled isocaloric substitution of carbohydrates for plant, dairy, egg or fish protein was associated with lower likelihood of T2D (ranging from OR = 0.89, 95% CI = 0.83, 0.95-for dairy to OR = 0.91, 95% CI = 0.82, 0.99-egg) and prediabetes (ranging from OR = 0.82, 95% CI = 0.72, 0.92-for dairy to OR = 0.94, 95% CI = 0.89, 0.99-for fish). Public health strategies that reduce overall carbohydrates and saturated fat while increasing intake of plant and dairy proteins could mitigate the risk of metabolic diseases in India.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200121","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":"Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.","authors":"Paolo Marchetti, Giuseppe Curigliano, Mauro Biffoni, Sara Lonardi, Simone Scagnoli, Lorenzo Fornaro, Valentina Guarneri, Ugo De Giorgi, Paolo Antonio Ascierto, Giovanni Blandino, Giulia D'Amati, Massimo Aglietta, Chiara Cremolini, Pierfranco Conte, Edoardo Crimini, Maurizio Ceracchi, Simona Pisegna, Sofia Verkhovskaia, Roberto Bordonaro, Sergio Bracarda, Giovanni Butturini, Lucia Del Mastro, Andrea DeCensi, Agnese Fabbri, Elisabetta Fenocchio, Stefania Gori, Giulio Metro, Annamaria Pessino, Daniele Pozzessere, Fabio Puglisi, Stefano Tamberi, Alberto Zambelli, Donatella Marino, Ettore Capoluongo, Federico Cappuzzo, Bruna Cerbelli, Giuseppe Giannini, Umberto Malapelle, Federica Mazzuca, Marianna Nuti, Giancarlo Pruneri, Maurizio Simmaco, Lidia Strigari, Giuseppe Tonini, Nello Martini, Andrea Botticelli","doi":"10.1038/s41591-025-03918-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03918-x","url":null,"abstract":"<p><p>Despite recent advancements demonstrating the potential of tumor-agnostic biomarkers to guide effective therapies, randomized evidence supporting the clinical superiority of precision oncology approaches compared to standard therapies remains limited. The ROME trial was a multicenter, randomized, open-label phase 2 study comparing tailored treatment (TT) to standard of care (SoC) in patients with advanced solid tumors progressing after one or two lines of therapy. Comprehensive genomic profiling on tissue and blood was performed to identify actionable alterations. Overall response rate (ORR) was the primary endpoint, and progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), time to next treatment (TTNT) and safety were the secondary endpoints. Between November 2020 and August 2023, 1,794 patients were screened, 897 were evaluated by the molecular tumor board (MTB) and 400 were randomized to TT or SoC. TT achieved a significantly higher ORR (17.5% versus 10%; P = 0.0294) and improved median PFS (3.5 months versus 2.8 months; hazard ratio = 0.66 (0.53-0.82), P = 0.0002). TT also showed superior 12-month PFS rates (22.0% versus 8.3%). Median OS was similar, with a 52% crossover rate. Grade 3/4 adverse events were also similar (40% TT versus 52% SoC). These results highlight the potential of TT to improve outcomes for patients with diverse actionable genomic alterations. These results also provide relevant evidence supporting a tumor-agnostic precision oncology strategy and highlight the potential of TTs, guided by genomic profiling and MTB recommendations, to significantly improve outcomes for patients with diverse actionable genomic alterations. ClinicalTrials.gov identifier: NCT04591431 .</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192199","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}