Med (New York, N.y.)最新文献

{"title":"One size fits all: The story of SGLT2 inhibitors in heart failure.","authors":"Subodh Verma,&nbsp;Nitish K Dhingra,&nbsp;Deepak L Bhatt,&nbsp;Nikolaus Marx,&nbsp;Francesco Cosentino","doi":"10.1016/j.medj.2022.10.001","DOIUrl":"https://doi.org/10.1016/j.medj.2022.10.001","url":null,"abstract":"<p><p>EMPEROR-Preserved and DELIVER have ushered in a new era for the treatment of heart failure with a preserved ejection fraction (HFpEF). In this commentary, we compare the characteristics and findings of these two trials and assess their implications for the broader management of the heart failure syndrome.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"735-739"},"PeriodicalIF":17.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40456573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy and sustainable diets.","authors":"","doi":"10.1016/j.medj.2022.10.007","DOIUrl":"https://doi.org/10.1016/j.medj.2022.10.007","url":null,"abstract":"<p><p>Global food systems are under increasing stress due to climate change, environmental pollution, biodiversity loss, international conflicts, and pandemics, while billions of people continue to lack access to healthy and nutritious food. A series of expert voices address the transformations needed to ensure healthy, affordable, and sustainable diets for all.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"723-726"},"PeriodicalIF":17.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40463324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating human mutation databases for \"treatability\" using patient-customized therapy.","authors":"Swapnil Mittal,&nbsp;Isaac Tang,&nbsp;Joseph G Gleeson","doi":"10.1016/j.medj.2022.08.006","DOIUrl":"https://doi.org/10.1016/j.medj.2022.08.006","url":null,"abstract":"<p><p>Genome sequencing in the clinic often allows patients to receive a molecular diagnosis. However, variants are most often evaluated for pathogenicity, neglecting potential treatability and thus often yielding limited clinical benefit. Antisense oligonucleotides (ASOs), among others, offer attractive programmable and relatively safe platforms for customized therapy based upon the causative genetic variant. The landscape of ASO-treatable variants is largely uncharted, with new developments emerging for loss-of-function, haploinsufficient, and gain-of-function effects. ASOs can access the transcriptome to target splice-gain variants, poison exons, untranslated/regulatory regions, and naturally occurring antisense transcripts. Here we assess public variant databases and find that approximately half of pathogenic variants have one or more viable avenues for ASO therapy. The future might see medical teams considering \"treatability\" when interpreting genomic sequencing results to fully realize benefits for patients.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"740-759"},"PeriodicalIF":17.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40465569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fields to fermentors: Brewing botanical chemotherapeutic precursors using genetically engineered yeast.","authors":"Prashanth Srinivasan,&nbsp;Christina D Smolke","doi":"10.1016/j.medj.2022.10.006","DOIUrl":"https://doi.org/10.1016/j.medj.2022.10.006","url":null,"abstract":"<p><p>Plants are a rich source of chemotherapeutics and other essential medicines, but plant-based drug supply chains are unsustainable. Writing in Nature, Zhang et al.¹ demonstrated a proof-of-concept alternate source of the anticancer drug vinblastine by engineering yeast to convert sugar and amino acids into its direct precursors, catharanthine and vindoline.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"727-729"},"PeriodicalIF":17.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40463325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically oriented prediction of patient response to targeted and immunotherapies from the tumor transcriptome","authors":"Gal Dinstag, E. Shulman, Efrat Elis, Doreen S. Ben-Zvi, O. Tirosh, Eden Maimon, I. Meilijson, Emmanuel Elalouf, Boris Temkin, Philipp Vitkovsky, Eyal Schiff, Danh-Tai Hoang, Sanju Sinha, N. Nair, Joo Sang Lee, A. Schäffer, Z. Ronai, D. Juric, A. Apolo, W. Dahut, S. Lipkowitz, R. Berger, R. Kurzrock, A. Papanicolau‐Sengos, F. Karzai, M. Gilbert, Kenneth Aldape, P. Rajagopal, T. Beker, E. Ruppin, R. Aharonov","doi":"10.1101/2022.02.27.481627","DOIUrl":"https://doi.org/10.1101/2022.02.27.481627","url":null,"abstract":"Background Precision oncology is gradually advancing into mainstream clinical practice, demonstrating significant survival benefits. However, eligibility and response rates remain limited in many cases, calling for better predictive biomarkers. Methods We present ENLIGHT, a transcriptomics-based computational approach that identifies clinically relevant genetic interactions and uses them to predict a patient’s response to a variety of therapies in multiple cancer types, without training on previous treatment response data. We study ENLIGHT in two translationally oriented scenarios: Personalized Oncology (PO), aimed at prioritizing treatments for a single patient, and Clinical Trial Design (CTD), selecting the most likely responders in a patient cohort. Findings Evaluating ENLIGHT’s performance on 21 blinded clinical trial datasets in the PO setting, we show that it can effectively predict a patient’s treatment response across multiple therapies and cancer types. Its prediction accuracy is better than previously published transcriptomics-based signatures and is comparable to that of supervised predictors developed for specific indications and drugs. In combination with the IFN-γsignature, ENLIGHT achieves an odds ratio larger than 4 in predicting response to immune checkpoint therapy. In the CTD scenario, ENLIGHT can potentially enhance clinical trial success for immunotherapies and other monoclonal antibodies by excluding non-responders, while overall achieving more than 90% of the response rate attainable under an optimal exclusion strategy. Conclusion ENLIGHT demonstrably enhances the ability to predict therapeutic response across multiple cancer types from the bulk tumor transcriptome. Funding This research was supported in part by the Intramural Research Program, NIH and by the Israeli Innovation Authority.","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":"45 6-7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133005978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next generation T cell therapies for solid cancers.","authors":"John B Haanen,&nbsp;Ton N Schumacher","doi":"10.1016/j.medj.2022.09.008","DOIUrl":"https://doi.org/10.1016/j.medj.2022.09.008","url":null,"abstract":"<p><p>Tumor-infiltrating lymphocytes show consistent clinical benefit in metastatic melanoma, but they are a poorly defined product with variable antitumor activity. In this issue, Palmer et al.¹ create for clinical testing a cell product consisting of highly functional tumor-reactive T cells by knocking out CISH, an inhibitor of T cell activation.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"645-647"},"PeriodicalIF":17.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33513992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gemcitabine combined with apatinib and toripalimab in recurrent or metastatic nasopharyngeal carcinoma.","authors":"Rui You,&nbsp;Xiong Zou,&nbsp;Xi Ding,&nbsp;Wei-Jing Zhang,&nbsp;Meng-Xia Zhang,&nbsp;Xiao Wang,&nbsp;Han-Shi Xu,&nbsp;Yong-Long Liu,&nbsp;Yan-Feng Ouyang,&nbsp;Chong-Yang Duan,&nbsp;Chen-Mei Gu,&nbsp;Zhi-Qiang Wang,&nbsp;You-Ping Liu,&nbsp;Yi-Jun Hua,&nbsp;Pei Yu Huang,&nbsp;Ming-Yuan Chen","doi":"10.1016/j.medj.2022.07.009","DOIUrl":"https://doi.org/10.1016/j.medj.2022.07.009","url":null,"abstract":"<p><strong>Background: </strong>The role of a triple combination of gemcitabine (chemotherapy) plus apatinib (anti-vascular endothelial growth factor [VEGFR]) and toripalimab (anti-PD-1) (GAT) in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) is unclear.</p><p><strong>Methods: </strong>Between August 2019 and April 2020, 41 patients with RM-NPC were enrolled and received GAT for up to 6 cycles followed by apatinib and toripalimab. The primary endpoint was the safety. The secondary endpoints included the objective response rate (ORR) and progression-free survival (PFS). Integrated genomic and transcriptional analyses were conducted to identify the patients who benefited in response to this novel combination therapy.</p><p><strong>Findings: </strong>As of April 1, 2022, treatment-related grade 3 or 4 adverse events (AEs) occurred in 23 of 41 patients (56.1%, 95% confidence interval [CI] 41%-70.1%). G3-4 nasopharyngeal necrosis was observed in 9 (9/41, 21.9%) patients. High-risk factors for necrosis included repeated radiotherapy and an interval of less than 12 months from the last radiotherapy. The ORR was 90.2% (95% CI: 76.9%-97.2%). The median PFS was 25.8 months (95% CI: not reached (NR)-NR), and the 24-month PFS rate was 50.7% (95% CI: 34.0%-67.4%). MAS-related GPR family member F (MRGPRF) high expression in tumors correlated with poor PFS from the GAT therapy, characterized by high epithelial mesenchymal transition signatures. Serial circulating tumor DNA (ctDNA) sequencing could predict PFS outcomes to combination therapy.</p><p><strong>Conclusions: </strong>GAT therapy exhibits a promising antitumor activity and manageable toxicities in patients with RM-NPC. Patients with repeated radiotherapy and an interval of less than 12 months from the last radiotherapy should be carefully selected for antiangiogenic therapies. MRGPRF expression and serial ctDNA monitoring could identify patients that derive benefits from the combination therapy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT04073784.</p><p><strong>Funding: </strong>This research was funded by the National Natural Science Foundation of China (nos. 81772895 and 82002857), the Key-Area Research and Development of Guangdong Province (2020B1111190001), the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project (202103010001), and the National \"Ten Thousand Talents Program\" Science and Technology Innovation Leading Talents (84000-41180005).</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"664-681.e6"},"PeriodicalIF":17.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40329437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extreme temperatures and mortality in Latin America: Voices are needed from the Global South.","authors":"Yuming Guo,&nbsp;Bo Wen,&nbsp;Yao Wu,&nbsp;Rongbin Xu,&nbsp;Shanshan Li","doi":"10.1016/j.medj.2022.09.004","DOIUrl":"https://doi.org/10.1016/j.medj.2022.09.004","url":null,"abstract":"<p><p>Recent work by Kephart et al.¹ updates estimates for mortality burden attributable to non-optimal ambient temperatures in Latin America, which helps to understand the climate-related health risks and burden in less-developed areas. Here, we discuss the main findings and focus on methodology that remains controversial in heat health field.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"656-660"},"PeriodicalIF":17.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33513994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic genomic mosaicism in the brain: Identified mutations provide challenges and opportunities for the clinic.","authors":"Jerold Chun","doi":"10.1016/j.medj.2022.09.009","DOIUrl":"https://doi.org/10.1016/j.medj.2022.09.009","url":null,"abstract":"<p><p>Recent work by Bae et al.¹ represents a major next-generation sequencing effort to identify somatic genomic mosaicism in normal and diseased human brains. Some samples displayed age-associated hypermutability, and the general possibility that somatic mutations can drive brain disease has implications for new therapeutic strategies, disease staging, biomarkers, and cohort selection for clinical trials.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"648-650"},"PeriodicalIF":17.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33513993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The promise of tenecteplase in acute stroke: Within reach or beyond approval?","authors":"Kori S Zachrison,&nbsp;Lee H Schwamm","doi":"10.1016/j.medj.2022.09.005","DOIUrl":"https://doi.org/10.1016/j.medj.2022.09.005","url":null,"abstract":"<p><p>Reperfusion is critical for improving outcomes of patients experiencing ischemic stroke. Increasing evidence supports tenecteplase as an alternative to alteplase, with many potential benefits. This article discusses the current state of the evidence for intravenous reperfusion and considers strategies for improving access, including possible modifications to efficacy-related regulatory updates.</p>","PeriodicalId":272244,"journal":{"name":"Med (New York, N.y.)","volume":" ","pages":"651-655"},"PeriodicalIF":17.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33491024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}