Nature Medicine最新文献_第5页

Phenome-wide associations of sleep characteristics in the Human Phenotype Project

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-27 DOI: 10.1038/s41591-024-03481-x

Sarah Kohn, Alon Diament, Anastasia Godneva, Raja Dhir, Adina Weinberger, Yotam Reisner, Hagai Rossman, Eran Segal

{"title":"Phenome-wide associations of sleep characteristics in the Human Phenotype Project","authors":"Sarah Kohn, Alon Diament, Anastasia Godneva, Raja Dhir, Adina Weinberger, Yotam Reisner, Hagai Rossman, Eran Segal","doi":"10.1038/s41591-024-03481-x","DOIUrl":"https://doi.org/10.1038/s41591-024-03481-x","url":null,"abstract":"Sleep tests commonly diagnose sleep disorders, but the diverse sleep-related biomarkers recorded by such tests can also provide broader health insights. In this study, we leveraged the uniquely comprehensive data from the Human Phenotype Project cohort, which includes 448 sleep characteristics collected from 16,812 nights of home sleep apnea test monitoring in 6,366 adults (3,043 male and 3,323 female participants), to study associations between sleep traits and body characteristics across 16 body systems. In this analysis, which identified thousands of significant associations, visceral adipose tissue (VAT) was the body characteristic that was most strongly correlated with the peripheral apnea–hypopnea index, as adjusted by sex, age and body mass index (BMI). Moreover, using sleep characteristics, we could predict over 15% of body characteristics, spanning 15 of the 16 body systems, in a held-out set of individuals. Notably, sleep characteristics contributed more to the prediction of certain insulin resistance, blood lipids (such as triglycerides) and cardiovascular measurements than to the characteristics of other body systems. This contribution was independent of VAT, as sleep characteristics outperformed age, BMI and VAT as predictors for these measurements in both male and female participants. Gut microbiome-related pathways and diet (especially for female participants) were notably predictive of clinical obstructive sleep apnea symptoms, particularly sleepiness, surpassing the prediction power of age, BMI and VAT on these symptoms. Together, lifestyle factors contributed to the prediction of over 50% of the sleep characteristics. This work lays the groundwork for exploring the associations of sleep traits with body characteristics and developing predictive models based on sleep monitoring.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"4 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044091","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

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-27 DOI: 10.1038/s41591-024-03480-y

Ali Aminian, Abdullah Aljabri, Sarah Wang, James Bena, Daniela S. Allende, Hana Rosen, Eileen Arnold, Rickesha Wilson, Alex Milinovich, Rohit Loomba, Arun J. Sanyal, Naim Alkhouri, Jamile Wakim-Fleming, Sobia N. Laique, Srinivasan Dasarathy, Arthur J. McCullough, Steven E. Nissen

{"title":"Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis","authors":"Ali Aminian, Abdullah Aljabri, Sarah Wang, James Bena, Daniela S. Allende, Hana Rosen, Eileen Arnold, Rickesha Wilson, Alex Milinovich, Rohit Loomba, Arun J. Sanyal, Naim Alkhouri, Jamile Wakim-Fleming, Sobia N. Laique, Srinivasan Dasarathy, Arthur J. McCullough, Steven E. Nissen","doi":"10.1038/s41591-024-03480-y","DOIUrl":"https://doi.org/10.1038/s41591-024-03480-y","url":null,"abstract":"No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.0 ± 4.5 years. The 15 year cumulative incidence of MALO was 20.9% (95% confidence interval (CI), 2.5–35.9%) in the surgical group compared with 46.4% (95% CI, 25.6–61.3%) in the nonsurgical group, with an adjusted hazard ratio of 0.28 (95% CI, 0.12–0.64), P = 0.003. The 15 year cumulative incidence of decompensated cirrhosis was 15.6% (95% CI, 0–31.3%) in the surgical group compared with 30.7% (95% CI, 12.9–44.8%) in the nonsurgical group, with an adjusted hazard ratio of 0.20 (95% CI, 0.06–0.68), P = 0.01. Among patients with compensated MASH-related cirrhosis and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MALO. In the absence of approved medical therapies for compensated MASH-related cirrhosis, metabolic surgery may represent a safe and effective therapeutic option to influence the trajectory of cirrhosis.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"174 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044090","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

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-25 DOI: 10.1038/s41591-024-03443-3

Scott Kopetz, Takayuki Yoshino, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S. Maughan, Elena Beyzarov, Xiaoxi Zhang, Graham Ferrier, Xiaosong Zhang, Josep Tabernero

{"title":"Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial","authors":"Scott Kopetz, Takayuki Yoshino, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S. Maughan, Elena Beyzarov, Xiaoxi Zhang, Graham Ferrier, Xiaosong Zhang, Josep Tabernero","doi":"10.1038/s41591-024-03443-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03443-3","url":null,"abstract":"Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403–4.253; 99.8% CI: 1.019–5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318–0.691; repeated CI: 0.166–1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"10 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035159","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

Author Correction: Propagative α-synuclein seeds as serum biomarkers for synucleinopathies

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-24 DOI: 10.1038/s41591-025-03521-0

Ayami Okuzumi, Taku Hatano, Gen Matsumoto, Shuko Nojiri, Shin-ichi Ueno, Yoko Imamichi-Tatano, Haruka Kimura, Soichiro Kakuta, Akihide Kondo, Takeshi Fukuhara, Yuanzhe Li, Manabu Funayama, Shinji Saiki, Daisuke Taniguchi, Taiji Tsunemi, Deborah McIntyre, Jean-Jacques Gérardy, Michel Mittelbronn, Rejko Kruger, Yasuo Uchiyama, Nobuyuki Nukina, Nobutaka Hattori

引用次数: 0

Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-24 DOI: 10.1038/s41591-024-03486-6

Christian Kurzeder, Bich Doan Nguyen-Sträuli, Ilona Krol, Alexander Ring, Francesc Castro-Giner, Manuel Nüesch, Simran Asawa, Yu Wei Zhang, Selina Budinjas, Ana Gvozdenovic, Maren Vogel, Angela Kohler, Cvetka Grašič Kuhar, Fabienne D. Schwab, Viola Heinzelmann-Schwarz, Walter Paul Weber, Christoph Rochlitz, Denise Vorburger, Heike Frauchiger-Heuer, Isabell Witzel, Andreas Wicki, Gabriela M. Kuster, Marcus Vetter, Nicola Aceto

{"title":"Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial","authors":"Christian Kurzeder, Bich Doan Nguyen-Sträuli, Ilona Krol, Alexander Ring, Francesc Castro-Giner, Manuel Nüesch, Simran Asawa, Yu Wei Zhang, Selina Budinjas, Ana Gvozdenovic, Maren Vogel, Angela Kohler, Cvetka Grašič Kuhar, Fabienne D. Schwab, Viola Heinzelmann-Schwarz, Walter Paul Weber, Christoph Rochlitz, Denise Vorburger, Heike Frauchiger-Heuer, Isabell Witzel, Andreas Wicki, Gabriela M. Kuster, Marcus Vetter, Nicola Aceto","doi":"10.1038/s41591-024-03486-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03486-6","url":null,"abstract":"The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na+/K+ ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na+/K+ ATPase inhibitor digoxin could reduce mean CTC cluster size. An analysis of nine patients treated daily with a maintenance digoxin dose (0.7–1.4 ng ml−1 serum level) revealed a mean cluster size reduction of −2.2 cells per cluster upon treatment (P = 0.003), meeting the primary endpoint of the study. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell–cell adhesion and cell-cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. No treatment-related adverse events occurred. Thus, our data provide a first-in-human proof of principle that digoxin treatment leads to a partial CTC cluster dissolution, encouraging larger follow-up studies with refined Na+/K+ ATPase inhibitors and that include clinical outcome endpoints. ClinicalTrials.gov identifier: NCT03928210.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"2 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026968","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

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-24 DOI: 10.1038/s41591-024-03430-8

Caitlin Bond, Olivia J. Bednarski, Dibyadyuti Datta, Ruth Namazzi, Robert O. Opoka, Giselle Lima-Cooper, Anthony Batte, Keerthi Udumula, Deepali Balasubramani, Marilyn Vasquez, Ana Rodriguez, Claire Liepmann, Paul Bangirana, Marco Abreu, Tae-Hwi Schwantes-An, Yi Zhao, Tarek M. El-Achkar, Nathan W. Schmidt, Chandy C. John, Andrea L. Conroy

{"title":"Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria","authors":"Caitlin Bond, Olivia J. Bednarski, Dibyadyuti Datta, Ruth Namazzi, Robert O. Opoka, Giselle Lima-Cooper, Anthony Batte, Keerthi Udumula, Deepali Balasubramani, Marilyn Vasquez, Ana Rodriguez, Claire Liepmann, Paul Bangirana, Marco Abreu, Tae-Hwi Schwantes-An, Yi Zhao, Tarek M. El-Achkar, Nathan W. Schmidt, Chandy C. John, Andrea L. Conroy","doi":"10.1038/s41591-024-03430-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03430-8","url":null,"abstract":"We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl−1) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026989","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

Imatinib and the dawn of precision cancer therapy 伊马替尼和精准癌症治疗的曙光

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-23 DOI: 10.1038/s41591-024-03436-2

引用次数: 0

Unlocking the broad health benefits and risks of GLP-1 receptor agonist drugs 揭示GLP-1受体激动剂药物的广泛健康益处和风险

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-01-23 DOI: 10.1038/s41591-024-03476-8

引用次数: 0

The Access to Dialysis in Low- and Middle-Income Countries Commission: lessons for universal health coverage 低收入和中等收入国家获得透析委员会：全民健康覆盖的经验教训

IF 58.7 1区医学

Nature Medicine Pub Date : 2025-01-22 DOI: 10.1038/s41591-024-03448-y

Yot Teerawattananon, Kinanti Khansa Chavarina, Jeerath Phannajit, Jiratorn Sutawong, Natcha Yongphiphatwong, Sydney C. W. Tang, Talerngsak Kanjanabuch, Tanainan Chuanchaiyakul, Thunyarat Anothaisintawee, Valerie Luyckx, Wanrudee Isaranuwatchai, Kearkiat Praditpornsilpa, Kriang Tungsanga, Vivekanand Jha

引用次数: 0

The Future of Medicine 医学的未来

IF 58.7 1区医学

Nature Medicine Pub Date : 2025-01-22 DOI: 10.1038/s41591-024-03464-y

引用次数: 0