Med最新文献

{"title":"ADRIATIC: When face value is enough.","authors":"Alfredo Addeo, Stephen V Liu","doi":"10.1016/j.medj.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.004","url":null,"abstract":"<p><p>The ADRIATIC¹ study marks a major advancement in limited-stage small cell lung cancer (LS-SCLC), showing that consolidation therapy with durvalumab after chemoradiation significantly improves overall survival (OS) and progression-free survival (PFS). This establishes durvalumab as the new standard of care for LS-SCLC.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 11","pages":"1348-1350"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629409","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 impact of OCEANIC-AF and the future of factor XIa inhibitors.","authors":"Lina Palaiodimou, Georgios Tsivgoulis","doi":"10.1016/j.medj.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.001","url":null,"abstract":"<p><p>The OCEANIC-AF trial was terminated early due to inferiority of asundexian compared with apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation.¹ However, the promisingly low bleeding rates support continued exploration of factor XIa inhibitors. Future efforts should focus on achieving greater factor XIa inhibition and identifying patient populations that may benefit most from these therapies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 11","pages":"1342-1344"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629419","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":"Tumor microenvironment RNA test to predict immunotherapy outcomes in advanced gastric cancer: The TIMES001 trial.","authors":"Min Shi, Dongqiang Zeng, Huiyan Luo, Jian Xiao, Yongqiang Li, Xia Yuan, Na Huang, Jiani Wu, Siting Zheng, Jianhua Wu, Shaowei Li, Xiaoxiang Rong, Chunlin Wang, Luyang Jiang, Qianqian Mao, Wenjun Qiu, Jian Guo, Qiong Deng, Huiying Sun, Xiansheng Lu, Yunfang Yu, Yonghong Lai, Yiran Fang, Rui Zhou, Ling Wang, Xiatong Huang, Yuyun Kong, Jun Li, Li Liang, Jianping Bin, Yulin Liao, Wangjun Liao","doi":"10.1016/j.medj.2024.07.006","DOIUrl":"10.1016/j.medj.2024.07.006","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). To identify the determinants of response, we developed a TMEscore model to assess tumor microenvironment (TME), which was previously proven to be a biomarker for ICBs.</p><p><strong>Methods: </strong>A reference database of TMEscore assays was established using PCR assay kits containing 30 TME genes. This multi-center prospective clinical trial (NCT#04850716) included patients with mGC who were administered ICB combined with chemotherapy as a first-line regimen. Eighty-six tumor samples extracted from five medical centers before treatment were used to estimate the TMEscore, PD-L1 (CPS), and mismatch repair deficiency.</p><p><strong>Findings: </strong>The objective response rate (ORR) and median PFS of the cohort were 31.4% and six months. Enhanced ORR was observed in TMEscore-high mGC patients (ORR = 59%). The survival analysis demonstrated that high TMEscore was significantly associated with a more favorable PFS and OS. Moreover, TMEscore was found to be a predictive biomarker that surpassed MSI and CPS (AUC = 0.873, 0.511, and 0.524, respectively). By integrating the TMEscore and clinical variables, the fused model further enhances the predictive efficiency and translational application in a clinical setting.</p><p><strong>Conclusions: </strong>This prospective clinical study indicates that the TMEscore assay is a robust biomarker for screening patients with mGC who may derive survival benefits from ICB plus chemotherapy.</p><p><strong>Funding: </strong>Guangdong Basic and Applied Basic Research Foundation (2023A1515011214), Science and Technology Program of Guangzhou (202206080011), and Guangzhou Science and Technology Project (2023A03J0722 and 2023A04J2357).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1378-1392.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876229","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":"[⁸⁹Zr]Zr-girentuximab PET-CT imaging to diagnose, characterize, and differentiate clear-cell renal cell carcinoma.","authors":"Chadi Hage Chehade, Georges Gebrael, Neeraj Agarwal","doi":"10.1016/j.medj.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.003","url":null,"abstract":"<p><p>In the phase 3 ZIRCON trial, [⁸⁹Zr]Zr-girentuximab positron emission tomography-computed tomography (PET-CT) detected the presence of clear-cell renal cell carcinoma (ccRCC) with a sensitivity of 86% and a specificity of 87% in patients with an indeterminate renal mass undergoing nephrectomy.¹ This imaging technique could be a promising tool that could revolutionize the management of small renal masses (SRMs) and ccRCC.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 11","pages":"1345-1347"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629230","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":"Association between situs inversus and maternal SARS-CoV-2 infection at gestational age 4-6 weeks.","authors":"Zhenming Guo, Yingchun Luo, Yan Bi, Liangjie Liu, Yuan Qi, Jin Yan, Chunhai Cai, Chenxiang Xi, Yihan Tan, Shifa Yao, Yanhui Qu, Ping Chen, Jiayu Chen, Yanlin Wang, Xiao Mao, Baoying Ye, Shaorong Gao, Guang He, Shan Bian","doi":"10.1016/j.medj.2024.07.009","DOIUrl":"10.1016/j.medj.2024.07.009","url":null,"abstract":"<p><strong>Background: </strong>A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus.</p><p><strong>Methods: </strong>In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement. Relevant information, including SARS-CoV-2 infection, and other potential risk factors were collected. Conditional logistic regression was used to test possible associations between fetal situs inversus and SARS-CoV-2 infection at different gestational weeks as well as individual risk factors.</p><p><strong>Findings: </strong>A total of 52 pregnant women diagnosed with fetal situs inversus between January 1 and October 31, 2023 and 208 matched controls with normal fetuses were enrolled. We found no association between an increased risk of fetal situs inversus with gestational SARS-CoV-2 infection or with other risk factors. However, fetal situs inversus was significantly associated with SARS-CoV-2 infection specifically in gestational weeks 4-6 (adjusted odds ratio [aOR] 6.54 [95% confidence interval 1.76-24.34]), but not with infection at other gestational ages, after adjusting for covariates.</p><p><strong>Conclusions: </strong>Increased risk of fetal situs inversus is significantly associated with maternal SARS-CoV-2 infection at gestational weeks 4-6, corresponding to the fetal developmental window for visceral lateralization in humans.</p><p><strong>Funding: </strong>National Key R&D Program of China, etc.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1433-1441.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879594","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":"ARCADIA trials: Can nemolizumab be a valid alternative to the therapies currently available?","authors":"Maddalena Napolitano, Cataldo Patruno","doi":"10.1016/j.medj.2024.09.008","DOIUrl":"10.1016/j.medj.2024.09.008","url":null,"abstract":"<p><p>ARCADIA 1 and ARCADIA 2 were two randomized, placebo-controlled phase 3 trials showing the effectiveness of nemolizumab with concomitant use of low-to-medium potency topical corticosteroids, and/or with or without topical calcineurin inhibitors, in adults and adolescents with moderate-to-severe atopic dermatitis. Coprimary endpoints were met in the nemolizumab plus background therapy groups in both trials, with significant differences versus placebo.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 11","pages":"1340-1341"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629410","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":"Body ownership alterations in stroke emerge from reduced proprioceptive precision and damage to the frontoparietal network.","authors":"Giulio Mastria, Tommaso Bertoni, Henri Perrin, Nikita Akulenko, Gaia Risso, Michel Akselrod, Eleonora Guanziroli, Franco Molteni, Patric Hagmann, Michela Bassolino, Andrea Serino","doi":"10.1016/j.medj.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.013","url":null,"abstract":"<p><strong>Background: </strong>Stroke patients often experience alterations in their subjective feeling of ownership for the affected limb, which can hinder motor function and interfere with rehabilitation. In this study, we aimed at disentangling the complex relationship between sensory impairment, body ownership (BO), and motor control in stroke patients.</p><p><strong>Methods: </strong>We recruited 20 stroke patients with unilateral upper limb sensory deficits and 35 age-matched controls. Participants performed a virtual reality reaching task with a varying displacement between their real unseen hand and a visible virtual hand. We measured reaching errors and subjective ownership ratings as indicators of hand ownership. Reaching errors were modeled using a probabilistic causal inference model, in which ownership for the virtual hand is inferred from the level of congruency between visual and proprioceptive inputs and used to weigh the amount of visual adjustment to reaching movements.</p><p><strong>Findings: </strong>Stroke patients were more likely to experience ownership over an incongruent virtual hand and integrate it into their motor plans. The model explained this tendency in terms of a decreased capability of detecting visuo-proprioceptive incongruences, proportionally to the amount of proprioceptive deficit. Lesion analysis further revealed that BO alterations, not fully explained by the proprioceptive deficit, are linked to frontoparietal network damage, suggesting a disruption in higher-level multisensory integration functions.</p><p><strong>Conclusions: </strong>Collectively, our results show that BO alterations in stroke patients can be quantitatively predicted and explained in a computational framework as the result of sensory loss and higher-level multisensory integration deficits.</p><p><strong>Funding: </strong>Swiss National Science Foundation (163951).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629099","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":"No association between the early-life gut microbiota and childhood body mass index and body composition.","authors":"Christina Egeø Poulsen, Rebecca Vinding, Morten A Rasmussen, Shiraz Shah, Urvish Trivedi, Cristina Leal Rodriguez, Michael L Widdowson, Jie Jiang, Casper S Poulsen, Anders Eliasen, Bo Chawes, Klaus Bønnelykke, Camilla H F Hansen, Søren J Sørensen, Jonathan Thorsen, Jakob Stokholm","doi":"10.1016/j.medj.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.015","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota has been implicated in adult obesity, but the causality is still unclear. It has been hypothesized that an obesity-prone gut microbiota can be established in infancy, but only few studies have examined the early-life gut microbiota in relation to obesity in childhood, and no consistent associations have been reported. Here, we examine the association between the early-life gut microbiota and body mass index (BMI) development and body composition throughout childhood.</p><p><strong>Methods: </strong>Gut microbiota from stool were collected from 700 children in the Copenhagen Prospective Studies on Asthma in Childhood₂₀₁₀ (COPSAC₂₀₁₀) cohort at ages of 1 week, 1month, 1 year, 4 years, and 6 years and analyzed by 16S rRNA gene sequencing. Outcomes included BMI World Health Organization (WHO) Z scores (zBMI), overweight (zBMI > 1.04) and obesity (zBMI > 1.64) (0-10 years), and adiposity rebound and body composition from dual-energy X-ray absorptiometry at 6 years.</p><p><strong>Findings: </strong>The early-life gut microbiota diversity, overall composition, and individual taxon abundances in unsupervised and supervised models were not consistently associated with either current or later BMI Z scores, overweight, obesity, adiposity rebound, or body composition in childhood.</p><p><strong>Conclusions: </strong>In a deeply characterized longitudinal birth cohort, we did not observe any consistent associations between the early-life gut microbiota and BMI or risk of obesity in later childhood. While this does not conclusively rule out a relationship, it suggests that if such associations exist, they may be more complex and potentially influenced by factors emerging later in life, including lifestyle changes.</p><p><strong>Funding: </strong>COPSAC is funded by private and public research funds (all listed on www.copsac.com).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629140","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":"DHDH-mediated D-xylose metabolism induces immune evasion in triple-negative breast cancer.","authors":"Huai-Liang Wu, Yue Gong, Yun-Xiao Ling, Si-Yu Wu, Peng Ji, Qian Zhao, Li-Hua He, Zhi-Ming Shao, Yi-Zhou Jiang, Guang-Yu Liu","doi":"10.1016/j.medj.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.012","url":null,"abstract":"<p><strong>Background: </strong>Although the prognosis of triple-negative breast cancer (TNBC) has significantly improved in the era of immunotherapy, many TNBC patients are resistant to therapies, and their disease progresses rapidly. Deciphering the metabolic mechanisms regulating anticancer immunity will provide new insights into therapeutic strategies for TNBC.</p><p><strong>Methods: </strong>In this study, we performed bioinformatics analysis in our multi-omics TNBC database and identified that a metabolic enzyme, dihydrodiol dehydrogenase (DHDH), might promote the phenotype of \"cold tumor\" in TNBC. The biological function of DHDH was verified by in vitro and in vivo functional experiments, and the potential molecular mechanism of DHDH promoting TNBC immune escape was further explored.</p><p><strong>Findings: </strong>Mechanistically, DHDH mediated the synthesis and depletion of the substrate D-xylose and inhibited the activation of the proteasome subunit beta type 9 (PSMB9) and further induction of the immune response. We demonstrated that D-xylose supplementation could enhance the proliferation of CD8⁺ T cells and the expression of cytotoxic markers against cocultured DHDH-wild type (WT) cells. Consistently, D-xylose supplementation in vivo promoted CD8⁺ T cell infiltration and the expression of cytotoxic markers and increased the sensitivity of DHDH-overexpressing tumors to immune checkpoint blockade (ICB).</p><p><strong>Conclusions: </strong>Our findings reveal that a D-xylose-regulated PSMB9-dependent pathway governs tumor-intrinsic immunogenicity and, hence, the sensitivity to ICB, which may provide approaches to promote the \"cold-to-hot\" transition in TNBC.</p><p><strong>Funding: </strong>This study was funded by the National Key Research and Development Plan of China, Shanghai Science and Technology Commission, National Natural Science Foundation of China, and China Postdoctoral Science Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629128","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":"Precision phenotyping for curating research cohorts of patients with unexplained post-acute sequelae of COVID-19.","authors":"Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri","doi":"10.1016/j.medj.2024.10.009","DOIUrl":"10.1016/j.medj.2024.10.009","url":null,"abstract":"<p><strong>Background: </strong>Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.</p><p><strong>Methods: </strong>In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews to tune and validate the algorithm.</p><p><strong>Findings: </strong>The PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying PASC cohorts compared to the ICD-10-CM code U09.9. The algorithm identified a cohort of over 24,000 patients with 79.9% precision. Our estimated prevalence of PASC was 22.8%, which is close to the national estimates for the region. We also provide in-depth analyses, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC.</p><p><strong>Conclusions: </strong>PASC precision phenotyping boasts superior precision and prevalence estimation while exhibiting less bias in identifying patients with PASC. The cohort derived from this algorithm will serve as a springboard for delving into the genetic, metabolomic, and clinical intricacies of PASC, surmounting the constraints of prior PASC cohort studies.</p><p><strong>Funding: </strong>This research was funded by the US National Institute of Allergy and Infectious Diseases (NIAID).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629209","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}