Nature Medicine最新文献

{"title":"Human outbreaks of a novel reassortant Oropouche virus in the Brazilian Amazon region","authors":"Felipe Gomes Naveca, Tatiana Amaral Pires de Almeida, Victor Souza, Valdinete Nascimento, Dejanane Silva, Fernanda Nascimento, Matilde Mejía, Yasmin Silva de Oliveira, Luisa Rocha, Natana Xavier, Janis Lopes, Rodrigo Maito, Cátia Meneses, Tatyana Amorim, Luciana Fé, Fernanda Sindeaux Camelo, Samyly Coutinho de Aguiar Silva, Alexsandro Xavier de Melo, Leíse Gomes Fernandes, Marco Aurélio Almeida de Oliveira, Ana Ruth Arcanjo, Guilherme Araújo, Walter André Júnior, Renata Lia Coragem de Carvalho, Rosiane Rodrigues, Stella Albuquerque, Cristiane Mattos, Ciciléia Silva, Aline Linhares, Taynã Rodrigues, Francy Mariscal, Márcia Andréa Morais, Mayra Marinho Presibella, Nelson Fernando Quallio Marques, Anne Paiva, Karina Ribeiro, Deusilene Vieira, Jackson Alves da Silva Queiroz, Ana Maísa Passos-Silva, Lígia Abdalla, João Hugo Santos, Regina Maria Pinto de Figueiredo, Ana Cecília Ribeiro Cruz, Livia Neves Casseb, Jannifer Oliveira Chiang, Livia Vinhal Frutuoso, Agata Rossi, Lucas Freitas, Túlio de Lima Campos, Gabriel Luz Wallau, Emerson Moreira, Roberto Dias Lins Neto, Laura W. Alexander, Yining Sun, Ana Maria Bispo de Filippis, Tiago Gräf, Ighor Arantes, Ana I. Bento, Edson Delatorre, Gonzalo Bello","doi":"10.1038/s41591-024-03300-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03300-3","url":null,"abstract":"<p>The Brazilian western Amazon is experiencing its largest laboratory-confirmed Oropouche virus (OROV) outbreak, with more than 6,300 reported cases between 2022 and 2024. Here, we sequenced and analyzed 382 OROV genomes from human samples collected in Amazonas, Acre, Rondônia, and Roraima states, between August 2022 and February 2024, to uncover the origin and genetic evolution of OROV in the current outbreak. Genomic analyses revealed that the upsurge of OROV cases in the Brazilian Amazon coincides with spread of a novel reassortant lineage containing the M segment of viruses detected in the eastern Amazon region (2009-2018) and the L and S segments of viruses detected in Peru, Colombia, and Ecuador (2008-2021). The novel reassortant likely emerged in the Amazonas state between 2010 and 2014 and spread through long-range dispersion events during the second half of the 2010s. Phylodynamics reconstructions showed that the current OROV spread was mainly driven by short-range (&lt; 2 km) movements consistent with the flight range of vectors. Nevertheless, a substantial proportion (22%) of long-range (&gt; 10 km) OROV migrations were also detected, consistent with viral dispersion by humans. Our data provides a view of the unprecedented spread and evolution of OROV in Brazilian western Amazon region.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236144","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":"Navigating treatment combinations in small-cell lung cancer","authors":"Ning Li, Si-Yu Wang","doi":"10.1038/s41591-024-03255-5","DOIUrl":"https://doi.org/10.1038/s41591-024-03255-5","url":null,"abstract":"The ETER701 trial demonstrates that a four-drug regimen, involving the addition of anti-angiogenesis therapy to immuno-chemotherapy, improves survival outcomes for extensive-stage small-cell lung cancer — but is more indeed better when it comes to treating this intractable disease?","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236149","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":"Improving primary healthcare with generative AI","authors":"Winnie Yip","doi":"10.1038/s41591-024-03257-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03257-3","url":null,"abstract":"Studies in China show how large language models can improve primary healthcare systems, but equitably scaling this technology will require attention to rural, low-resource settings and the companion policies that support its implementation.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236142","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":"Countering the impact of the climate crisis on health will require data","authors":"","doi":"10.1038/s41591-024-03276-0","DOIUrl":"10.1038/s41591-024-03276-0","url":null,"abstract":"As drastically rising global temperatures threaten the health and wellbeing of populations, solutions that drive policy action must be based on scientific evidence of which strategies work in different scenarios.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03276-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236097","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}

{"title":"Data-driven risk stratification and precision management of pulmonary nodules detected on chest computed tomography","authors":"Chengdi Wang, Jun Shao, Yichu He, Jiaojiao Wu, Xingting Liu, Liuqing Yang, Ying Wei, Xiang Sean Zhou, Yiqiang Zhan, Feng Shi, Dinggang Shen, Weimin Li","doi":"10.1038/s41591-024-03211-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03211-3","url":null,"abstract":"<p>The widespread implementation of low-dose computed tomography (LDCT) in lung cancer screening has led to the increasing detection of pulmonary nodules. However, precisely evaluating the malignancy risk of pulmonary nodules remains a formidable challenge. Here we propose a triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) utilizing a medical checkup cohort of 45,064 cases. The system was operated in a stepwise fashion, initially distinguishing low-, mid-, high- and extremely high-risk nodules based on their size and density. Subsequently, it progressively integrated imaging information, demographic characteristics and follow-up data to pinpoint suspicious malignant nodules and refine the risk scale. The multidimensional system achieved a state-of-the-art performance with an area under the curve (AUC) of 0.918 (95% confidence interval (CI) 0.918–0.919) on the internal testing dataset, outperforming the single-dimensional approach (AUC of 0.881, 95% CI 0.880–0.882). Moreover, C-Lung-RADS exhibited a superior sensitivity compared with Lung-RADS v2022 (87.1% versus 63.3%) in an independent cohort, which was screened using mobile computed tomography scanners to broaden screening accessibility in resource-constrained settings. With its foundation in precise risk stratification and tailored management, this system has minimized unnecessary invasive procedures for low-risk cases and recommended prompt intervention for extremely high-risk nodules to avert diagnostic delays. This approach has the potential to enhance the decision-making paradigm and facilitate a more efficient diagnosis of lung cancer during routine checkups as well as screening scenarios.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236145","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":"Exposure to extreme heat increases perinatal mortality in sub-Saharan Africa","authors":"","doi":"10.1038/s41591-024-03251-9","DOIUrl":"https://doi.org/10.1038/s41591-024-03251-9","url":null,"abstract":"Extreme heat events are expected to become more frequent because of climate change. Our analysis of almost 140,000 births across 16 hospitals in four countries in sub-Saharan Africa indicates 34% higher odds of perinatal mortality (stillbirth or death up to 24 hours after birth) if extreme heat occurred in the week preceding childbirth.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236146","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":"Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors","authors":"Yoshiaki Nakamura, Hiroshi Ozaki, Makoto Ueno, Yoshito Komatsu, Satoshi Yuki, Taito Esaki, Hiroya Taniguchi, Yu Sunakawa, Kensei Yamaguchi, Ken Kato, Tadamichi Denda, Tomohiro Nishina, Naoki Takahashi, Taroh Satoh, Hisateru Yasui, Hironaga Satake, Eiji Oki, Takeshi Kato, Takashi Ohta, Nobuhisa Matsuhashi, Masahiro Goto, Naohiro Okano, Koushiro Ohtsubo, Kentaro Yamazaki, Riu Yamashita, Naoko Iida, Mihoko Yuasa, Hideaki Bando, Takayuki Yoshino","doi":"10.1038/s41591-024-03244-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03244-8","url":null,"abstract":"<p>Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234483","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":"ctDNA-based molecular residual disease and survival in resectable colorectal cancer","authors":"Yoshiaki Nakamura, Jun Watanabe, Naoya Akazawa, Keiji Hirata, Kozo Kataoka, Mitsuru Yokota, Kentaro Kato, Masahito Kotaka, Yoshinori Kagawa, Kun-Huei Yeh, Saori Mishima, Hiroki Yukami, Koji Ando, Masaaki Miyo, Toshihiro Misumi, Kentaro Yamazaki, Hiromichi Ebi, Kenji Okita, Atsushi Hamabe, Hiroki Sokuoka, Satoshi Kobayashi, George Laliotis, Vasily N. Aushev, Shruti Sharma, Adham Jurdi, Minetta C. Liu, Alexey Aleshin, Matthew Rabinowitz, Hideaki Bando, Hiroya Taniguchi, Ichiro Takemasa, Takeshi Kato, Daisuke Kotani, Masaki Mori, Takayuki Yoshino, Eiji Oki","doi":"10.1038/s41591-024-03254-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03254-6","url":null,"abstract":"<p>The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II–III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, <i>P</i> &lt; 0.0001) and overall survival (OS; HR: 9.68, <i>P</i> &lt; 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, <i>P</i> &lt; 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234481","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":"Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial","authors":"Iris Nederlof, Olga I. Isaeva, Manon de Graaf, Robbert C. A. M. Gielen, Noor A. M. Bakker, Adrianne L. Rolfes, Hannah Garner, Bram Boeckx, Joleen J. H. Traets, Ingrid A. M. Mandjes, Michiel de Maaker, Thomas van Brussel, Maksim Chelushkin, Elisa Champanhet, Marta Lopez-Yurda, Koen van de Vijver, José G. van den Berg, Ingrid Hofland, Natasja Klioueva, Ritse M. Mann, Claudette E. Loo, Frederieke H. van Duijnhoven, Victoria Skinner, Sylvia Luykx, Emile Kerver, Ekaterina Kalashnikova, Marloes G. J. van Dongen, Gabe S. Sonke, Sabine C. Linn, Christian U. Blank, Karin E. de Visser, Roberto Salgado, Lodewyk F. A. Wessels, Caroline A. Drukker, Ton N. Schumacher, Hugo M. Horlings, Diether Lambrechts, Marleen Kok","doi":"10.1038/s41591-024-03249-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03249-3","url":null,"abstract":"<p>Immune checkpoint inhibition (ICI) with chemotherapy is now the standard of care for stage II–III triple-negative breast cancer; however, it is largely unknown for which patients ICI without chemotherapy could be an option and what the benefit of combination ICI could be. The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary end point, twofold increase in CD8⁺ T cells or <i>IFNG</i>), providing a rationale for neoadjuvant ICI without chemotherapy. Here, in window-of-opportunity cohorts A (4 weeks of anti-PD-1) and B (4 weeks of anti-PD-1 + anti-CTLA4), we observed immune activation in 53% (8 of 15) and 60% (9 of 15) of patients, respectively. High levels of tumor-infiltrating lymphocytes correlated with response. Single-cell RNA sequencing revealed that higher pretreatment tumor-reactive CD8⁺ T cells, follicular helper T cells and shorter distances between tumor and CD8⁺ T cells correlated with response. Higher levels of regulatory T cells after treatment were associated with nonresponse. Based on these data, we opened cohort C for patients with high levels of tumor-infiltrating lymphocytes (≥50%) who received 6 weeks of neoadjuvant anti-PD-1 + anti-CTLA4 followed by surgery (primary end point, pathological complete response). Overall, 53% (8 of 15) of patients had a major pathological response (&lt;10% viable tumor) at resection, with 33% (5 of 15) having a pathological complete response. All cohorts met Simon’s two-stage threshold for expansion to stage II. We observed grade ≥3 adverse events for 17% of patients and a high rate (57%) of immune-mediated endocrinopathies. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early triple-negative breast cancer. ClinicalTrials.gov registration: NCT03815890.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234487","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":"Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial","authors":"Peter G. M. de Gooyer, Yara L. Verschoor, Lauren D. W. van den Dungen, Sara Balduzzi, Hendrik A. Marsman, Marnix H. Geukes Foppen, Cecile Grootscholten, Simone Dokter, Anne G. den Hartog, Wieke H. M. Verbeek, Karlijn Woensdregt, Joris J. van den Broek, Steven J. Oosterling, Ton N. Schumacher, Koert F. D. Kuhlmann, Regina G. H. Beets-Tan, John B. A. G. Haanen, Monique E. van Leerdam, Jose G. van den Berg, Myriam Chalabi","doi":"10.1038/s41591-024-03250-w","DOIUrl":"https://doi.org/10.1038/s41591-024-03250-w","url":null,"abstract":"<p>Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by a defective DNA mismatch repair system, resulting in hypermutated and highly immunogenic tumors. Although patients with dMMR CC have limited benefit from chemotherapy, these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses. Here, based on data from melanoma studies, we postulated a high efficacy and favorable toxicity profile of anti-PD-1 plus anti-LAG-3. In the NICHE-3 study, a total of 59 patients with locally advanced dMMR CC were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 57 of 59 (97%; 95% confidence interval (CI): 88–100%) patients, meeting the primary endpoint. Responses included 54 (92%; 95% CI: 81–97%) major pathologic responses (≤10% residual viable tumor) and 40 (68%; 95% CI: 54–79%) pathologic complete responses. With a median follow-up of 8 months (range, 2–19), one patient had recurrence of disease. The treatment displayed an acceptable safety profile, with all-grade and grade 3–4 immune-related adverse events (irAEs) occurring in 80% and 10% of patients, respectively. The most common irAEs were infusion-related reactions (29%), thyroid dysfunction (22%) and fatigue (20%). In conclusion, our results show that neoadjuvant nivolumab/relatlimab induces high rates of pathologic responses and that further investigation of this treatment in larger studies is warranted. These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233351","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}