Med最新文献

{"title":"Multisystem health comorbidity networks of metabolic dysfunction-associated steatotic liver disease.","authors":"Fangyuan Jiang, Lijuan Wang, Haochao Ying, Jing Sun, Jianhui Zhao, Ying Lu, Zilong Bian, Jie Chen, Aiping Fang, Xuehong Zhang, Susanna C Larsson, Christos S Mantzoros, Weilin Wang, Shuai Yuan, Yuan Ding, Xue Li","doi":"10.1016/j.medj.2024.07.013","DOIUrl":"10.1016/j.medj.2024.07.013","url":null,"abstract":"<p><strong>Background: </strong>The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing, but its subsequent health consequences have not been thoroughly examined.</p><p><strong>Methods: </strong>A phenome-wide association study was conducted to map the associations of MASLD with 948 unique clinical outcomes among 361,021 Europeans in the UK Biobank. Disease trajectory and comorbidity analyses were applied to visualize the sequential patterns of multiple comorbidities related to the occurrence of MASLD. The associations jointly verified by observational and polygenic phenome-wide analyses were further replicated by two-sample Mendelian randomization analysis using data from the FinnGen study and international consortia.</p><p><strong>Findings: </strong>The observational and polygenic phenome-wide association study revealed the associations of MASLD with 96 intrahepatic and extrahepatic diseases, including circulatory, metabolic, genitourinary, neurological, gastrointestinal, and hematologic diseases. Sequential patterns of MASLD-related extrahepatic comorbidities were primarily found in circulatory, metabolic, and inflammatory diseases. Mendelian randomization analyses supported the causal associations between MASLD and the risk of several intrahepatic disorders, metabolic diseases, cardio-cerebrovascular disease, and ascites but found no associations with neurological diseases.</p><p><strong>Conclusions: </strong>This study elucidated multisystem comorbidities and health consequences of MASLD, contributing to the development of combination interventions targeting distinct pathways for health promotion among patients with MASLD.</p><p><strong>Funding: </strong>X.L. was funded by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019) and Y.D. was funded by the Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (GZY-ZJ-KJ-24077) and the National Natural Science Foundation of China (82001673 and 82272860).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1413-1423.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907819","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":"Preoperative camrelizumab combined with chemotherapy for borderline resectable ESCC: A single-arm, prospective, phase 2 study.","authors":"Guoqing Zhang, Teng Mu, Yan Zhang, Jia Jiao, Zheng Ding, Hang Yang, Dabo Pan, Jia Zhao, Jindong Li, Xiangnan Li","doi":"10.1016/j.medj.2024.07.015","DOIUrl":"10.1016/j.medj.2024.07.015","url":null,"abstract":"<p><strong>Background: </strong>We investigated the safety and efficacy of preoperative camrelizumab combined with chemotherapy for treating thoracic borderline resectable esophageal squamous cell carcinoma (Br-ESCC) (ChiCTR2200056728).</p><p><strong>Methods: </strong>Patients with thoracic Br-ESCC received intravenous camrelizumab plus chemotherapy and underwent esophagectomy. The primary endpoint was the pathologic complete response (pCR) rate. We introduced computed tomography and endoscopic examination into the diagnostic criteria to increase its reproducibility. Additionally, we defined a new resection status, Rbr^+/-, for Br-ESCC.</p><p><strong>Findings: </strong>Thirty-one patients with Br-ESCC were ultimately enrolled in this study. Overall, 71.0% (22/31) of the patients underwent esophagectomy. R0 resection was achieved in 81.8% of patients (18/22). pCR and major pathological response were observed in 40.9% (9/22) and 63.6% (14/22) of the resected patients, respectively. Eighteen R0 resection patients were redefined according to our Rbr definition; 61.1% (11/18) were classified as Rbr⁺ resection, and 38.9% (7/18) were classified as Rbr^- resection. With a median postoperative follow-up of 17.9 months, 4 patients out of 11 who underwent Rbr⁺ resection experienced local recurrence (2 of whom achieved pCR). However, no patients (0/7) who underwent Rbr^- resection experienced local recurrence.</p><p><strong>Conclusions: </strong>Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for Br-ESCC. R0 resection was achieved in 81.8% of patients, and a pCR was observed in 40.9% of resected patients. Even after complete excision, Rbr⁺ resection leads to a higher rate of local recurrence in patients with Br-ESCC.</p><p><strong>Funding: </strong>This study was supported by the Key Scientific Research Projects of the Institutions of Higher Learning in Henan Province (no. 21A320032).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1424-1432.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914183","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":"Lingering impact: Maternal SARS-CoV-2 infection during early pregnancy results in fetal situs inversus.","authors":"Kjersti M Aagaard, Alireza A Shamshirsaz","doi":"10.1016/j.medj.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.medj.2024.10.010","url":null,"abstract":"<p><p>In this issue of Med, Guo et al.¹ describe their observed association of maternal SARS-CoV-2 infection in early (4-6 weeks) pregnancy with a confirmed fetal diagnosis of situs inversus congenital heart disease. Using sophisticated genomic tools and population-based statistical modeling, the study's authors present a very convincing argument causally linking maternal SARS-CoV-2 infection and resultant fetal situs inversus.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 11","pages":"1338-1339"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629418","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":"A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma.","authors":"Kaiyang Ding, Hailing Liu, Haiyan Yang, Huayuan Zhu, Jie Ma, Hongling Peng, Hongming Huang, Wei Shi, Lei Cao, Wei Wu, Xiaoli Zhao, Xiao Shi, Jianyong Li, Xiaohui Zhang, Lei Fan","doi":"10.1016/j.medj.2024.07.007","DOIUrl":"10.1016/j.medj.2024.07.007","url":null,"abstract":"<p><strong>Background: </strong>Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients.</p><p><strong>Methods: </strong>We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate.</p><p><strong>Findings: </strong>As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%).</p><p><strong>Conclusions: </strong>The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies.</p><p><strong>Funding: </strong>This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1393-1401.e2"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861129","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":"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}