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{"title":"Audiological characteristics following gene therapy in patients with autosomal recessive deafness 9.","authors":"Longlong Zhang, Dingding Dong, Yanbo Yin, Honghai Tang, Jun Lv, Qi Cao, Wuqing Wang, Bing Chen, Yunfeng Wang, Huawei Li, Daqi Wang, Yilai Shu","doi":"10.1016/j.medj.2025.100696","DOIUrl":"10.1016/j.medj.2025.100696","url":null,"abstract":"<p><strong>Background: </strong>Gene therapy shows promising potential for patients with autosomal recessive deafness 9 (DFNB9), with ongoing clinical trials (ChiCTR2200063181). A deeper understanding of changes in audiological characteristics is crucial for optimizing the monitoring and evaluation of patients' recovery post-treatment.</p><p><strong>Methods: </strong>Audiological data were collected from 10 DFNB9 patients who underwent gene therapy, including auditory brain stem response (ABR), auditory steady-state response (ASSR), distortion product otoacoustic emission (DPOAE), and pure-tone audiometry (PTA) tests.</p><p><strong>Findings: </strong>A clear ABR wave V was observed in all participants by 13 weeks. By 52 weeks, distinct ABR waves I and III were visible in some participants. The 1-kHz ABR wave V latency at 85 dB decreased significantly from 9.220 (range 9.015-9.810) ms at 4 weeks to 8.190 (range 7.780-8.530) ms at 52 weeks (p = 0.004), with a trend toward increased wave V amplitude (p = 0.055). Significant correlations were observed between PTA, ABR, and ASSR thresholds at 0.5-4 kHz. The DPOAE signal-to-noise ratio (SNR) at 26 weeks post-treatment showed no significant difference compared with pre-treatment SNR values, nor were there significant correlations between the pre-treatment SNR values and the post-treatment ABR thresholds.</p><p><strong>Conclusions: </strong>The study demonstrates that ABR and ASSR are reliable objective tools for assessing hearing recovery in DFNB9 patients after gene therapy. ABR reveals positive changes in the auditory pathway over time after gene therapy, enhancing our understanding of the impact of gene therapy on auditory pathway recovery.</p><p><strong>Funding: </strong>This work was funded by the National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100696"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133102","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":"Microbiota-derived metabolites: Key modulators of cancer immunotherapies.","authors":"Markus Perl, Matthias A Fante, Konstantin Herfeld, Julian N Scherer, Hendrik Poeck, Erik Thiele Orberg","doi":"10.1016/j.medj.2025.100773","DOIUrl":"10.1016/j.medj.2025.100773","url":null,"abstract":"<p><p>The human gut microbiome shapes local and systemic immune responses and influences cancer immunotherapy outcomes. Microbial metabolites, including short-chain and branched-chain fatty acids, bile acids, tryptophan derivatives, and others, influence anti-tumor immunity by modulating immune cells, tumor growth, and the tumor microenvironment. These metabolites impact the efficacy of immune checkpoint inhibitors, allogeneic stem cell transplantation, chimeric antigen receptor T cell therapies, and immune-related adverse events. However, interindividual microbiome variability, antibiotic exposure, and the context-dependent pro- and anti-inflammatory effects of metabolites present significant challenges for clinical translation. Microbiome-based therapies, including live biotherapeutic products, dietary modifications (such as prebiotics), and synthetic metabolite compounds (postbiotics), are being developed for use in combination with immunotherapy. This review outlines how metabolites influence immunotherapy outcomes and discusses translational approaches to harness them for clinical practice. Future research should focus on validating metabolite-based biomarkers and tailoring metabolite-based interventions to enhance efficacy and reduce toxicity across different immunotherapies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100773"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691804","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":"Alzheimer's disease: Clinical trials to watch.","authors":"Marwan Noel Sabbagh, Jessica Kennedy, Jad Majeed, Boris Decourt","doi":"10.1016/j.medj.2025.100771","DOIUrl":"10.1016/j.medj.2025.100771","url":null,"abstract":"<p><p>Second-generation anti-amyloid therapies (ATTs) offer new options for early Alzheimer's disease treatment, but with modest efficacy and documented adverse events. Here we highlight several ongoing clinical trials, aiming to develop therapeutic agents with higher efficacy and better safety profiles including third-generation ATTs, aggregation inhibitors, Sigma-1 receptor agonists, anti-tau antisense oligonucleotides, and GLP-1 receptor agonists.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100771"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812429","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":"DiabetesLiver score: A non-invasive algorithm for advanced liver fibrosis and liver-related outcomes in type 2 diabetes mellitus population.","authors":"Chuan Liu, Jie Shen, Jie Li, Zhihui Li, Ming-Hua Zheng, Hua Bian, Xiqiao Zhou, Wenjing Ni, Zhongji Meng, Jiaojian Lv, Yijun Tang, Xuan Liang, Min Li, Taolong Zhou, Heng Wan, Yuping Chen, Yuxia Qi, Yuli Ge, Yan Wang, Wen-Yue Liu, Mingxing Huang, Shanghao Liu, Xiaomei Wang, Mingfeng Xia, Xuefeng Li, Yuehua Wang, Xinjie Li, Xiaoxiong Hu, Yan Wu, Huimin Ying, Jing He, Fengmei Wang, Wei Yan, Huili Wu, Qingge Zhang, Weimin Jiang, Yan Huang, Yudong Zhang, Hongliang He, Xiaofeng Wu, Yuwei Zhang, Ling Li, Terry Cheuk-Fung Yip, Gao-Jun Teng, Xiaolong Qi","doi":"10.1016/j.medj.2025.100700","DOIUrl":"10.1016/j.medj.2025.100700","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop and validate a non-invasive model for screening advanced liver fibrosis and predicting liver-related outcomes in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>This study included patients with T2DM from five tertiary hospitals for the development and internal validation of a non-invasive model. Advanced liver fibrosis was defined as a liver stiffness measurement ≥12 kPa. An external validation cohort was obtained from the National Health and Nutrition Examination Survey (NHANES), and the model's predictive performance for hepatocellular carcinoma (HCC) and liver-related mortality was assessed in the UK Biobank.</p><p><strong>Findings: </strong>In total, 28,197 patients with T2DM were enrolled. In the derivation cohort (n = 1,129), waist circumference, alanine aminotransferase, aspartate aminotransferase, platelet count, and albumin were identified as independent risk factors for advanced fibrosis and were fit to develop the \"DiabetesLiver score.\" The area under the curve (AUC) was 0.835 (95% confidence interval [CI]: 0.781-0.890), significantly higher than the AUCs of non-invasive tests (all p < 0.01). It maintained high AUCs of 0.870 and 0.823 in the internal validation (n = 1,000), and NHANES cross-sectional (n = 1,432) cohorts, respectively. A dual cutoff of 2.39 and 3.99 with sensitivity ≥90% and specificity ≥90%, respectively, was used to classify patients into low-, middle-, and high-risk groups. In the UK Biobank cohort (n = 24,636), the high-risk group had an elevated risk of liver-related outcomes.</p><p><strong>Conclusions: </strong>The DiabetesLiver score demonstrated good performance in identifying advanced liver fibrosis and the development of liver-related events in the T2DM population.</p><p><strong>Funding: </strong>National Natural Science Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100700"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128876","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":"CD19 CAR-T cell therapy in a pediatric patient with MDA5⁺ dermatomyositis and rapidly progressive interstitial lung disease.","authors":"Andrés París-Muñoz, Rosa M Alcobendas-Rueda, Cristina Verdú-Sánchez, Clara Udaondo, Víctor Galán-Gómez, Berta González-Martínez, Juan J Menéndez, Isabel Martínez-Romera, Jordi Minguillón, Lidia Pertíñez, Cristina de Manuel-Gómez, Ana de la Cruz-Benito, Alejandro Sanz-Rupérez, Agustín Remesal, Carmen Cámara, Elena Sánchez-Zapardiel, Lucía Del Pino-Molina, Ana Gómez-Zamora, María G Serrano-Olmedo, Marta Español-Rego, Marta Ruiz de Valbuena, Francisco Climent, Paloma Dorao, Juan J Ríos-Blanco, José D Andrade, Gonzalo Ruiz-Zurita, Miguel A Fernández-García, Antonio Pérez-Martínez","doi":"10.1016/j.medj.2025.100676","DOIUrl":"10.1016/j.medj.2025.100676","url":null,"abstract":"<p><strong>Background: </strong>Anti-melanoma differentiation-associated protein 5 dermatomyositis (MDA5⁺DM) is a potentially fatal subtype of dermatomyositis. The most severe cases are characterized by rapidly progressive interstitial lung disease (RPILD), the leading cause of death in these patients. There is currently no curative treatment for these patients, and indeed, MDA5⁺DM-RPILD is considered one of the most challenging pathologies in medicine. Nevertheless, the recent introduction of CD19 chimeric antigen receptor (CAR)-T cell therapies appears to offer a serious opportunity to develop solutions for complex autoimmune diseases refractory to multiple immunosuppressant treatments, mainly rheumatic diseases such as rheumatoid arthritis, dermatomyositis, and systemic lupus erythematosus.</p><p><strong>Methods: </strong>In this report, we describe the first use of a second-generation CD19 CAR-T cell therapy (ARI-0001) in a pediatric patient with severe MDA5⁺DM-RPILD.</p><p><strong>Findings: </strong>Conventional treatments stabilized MDA5⁺DM-RPILD before CAR-T cell inoculation (-34 days). The presence of CD19⁺ B lymphocytes that might serve as target cells in deeper tissues was suspected due to CAR-T cell expansion in a context of B cell aplasia. No fever or cytokine release syndrome/cell-associated neurotoxicity syndrome was evident. In global terms, B cell reconstitution and cutaneous, motor, respiratory, and neurological improvements were observed gradually in the patient in an immunosuppressant-free context (-7 to +325 days).</p><p><strong>Conclusions: </strong>A pediatric patient with aggressive MDA5⁺DM-RPILD achieved progressive long-term improvement and immunosuppressant-free remission over 11 months after compassionate use of a CD19 CAR-T cell therapy (ARI-0001).</p><p><strong>Funding: </strong>This work was supported by the Programa Investigo (PI_SEPE_APM) and grants from the ISC-III (PI22/01226) from the Comunidad de Madrid (S2022/BMD-7225) and from the CRIS Cancer Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100676"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988983","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":"Tecovirimat at a crossroads: What the PALM007 trial tells us.","authors":"Olivier Segeral, Yazdan Yazdanpanah, Alexandra Calmy","doi":"10.1016/j.medj.2025.100779","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100779","url":null,"abstract":"<p><p>The double-blind, randomized, placebo-controlled PALM007 trial did not report any significant differences between placebo and tecovirimat regarding the time-to-lesion resolution or the virological clearance for the treatment of clade I Mpox virus infection in the Democratic Republic of Congo.¹ We discuss how these results compare with other clinical trials and what lessons can be drawn for future therapeutics strategies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100779"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812517","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":"Obicetrapib and CETP inhibition: An exception to the rule?","authors":"Bertrand Cariou, Philippe Moulin","doi":"10.1016/j.medj.2025.100780","DOIUrl":"10.1016/j.medj.2025.100780","url":null,"abstract":"<p><p>Obicetrapib is the latest CETP inhibitor, a drug class blocking lipid transfer between LDL and HDL. In two phase 3 trials, BROADWAY¹ and TANDEM,² obicetrapib alone or with ezetimibe lowered LDL-C, apolipoprotein B, and Lp(a) levels in patients with high cardiovascular risk. Given previous CETP inhibitor failures, results of the ongoing cardiovascular outcome study are needed to confirm obicetrapib's cardiovascular benefits.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100780"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812515","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":"IMforte: A new starting point and new challenges.","authors":"Ying Cheng, Shuang Zhang","doi":"10.1016/j.medj.2025.100777","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100777","url":null,"abstract":"<p><p>The IMforte study¹ demonstrated that maintenance treatment with atezolizumab plus lurbinectedin significantly improved progression-free survival and overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC). This phase 3 study is the first to report a positive result in first-line maintenance therapy for ES-SCLC, representing another milestone that is likely to establish a new standard of care for this condition.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100777"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812432","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":"Immune-related adverse events associated with cancer immunotherapy.","authors":"Smith Kungwankiattichai, Amrita Desai, Shelby Koppinger, Richard T Maziarz","doi":"10.1016/j.medj.2025.100800","DOIUrl":"10.1016/j.medj.2025.100800","url":null,"abstract":"<p><p>Immunotherapy has become central to cancer care, whether in combination with traditional chemotherapy, as adjuvant therapy, or as primary therapy, and has been demonstrated to be central to treatment of newly diagnosed or relapsed disease in multiple randomized control trials. Antibody-based immunotherapy initiated the treatment revolution, but now immune effector cellular therapy is rapidly emerging and expanding its indications. Efficacy determinations have led to multiple international regulatory approvals, but unique significant toxicities have also been identified. It remains critical to understand risk factors that predict for adverse events that are encountered after administration of cancer immunotherapy. Similarly, identification of patient-related factors that enhance or diminish therapeutic efficacy, independent of the underlying malignancy, is critical for balancing the benefit and risk of immunotherapy. This review addresses the multiple new cellular therapy initiatives and addresses the importance of appropriate patient selection that will ultimately maximize the treatment benefit.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100800"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769162","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":"Efficacy and safety of anti-PD-1 versus anti-PD-L1 in perioperative immunotherapy: A comprehensive reanalysis of randomized controlled trials.","authors":"Chaoqi Zhang, Peng Wu, Dongyu Li, Junhan Zhou, Chuqi Lin, Xuanyu Gu, Dexin Shang, Ruijie Ma, Jingjing Liu, Guochao Zhang, Pan Wang, Yun Che, Qingpeng Zeng, Jilin Peng, Bohui Zhao, Nan Sun, Jie He","doi":"10.1016/j.medj.2025.100669","DOIUrl":"10.1016/j.medj.2025.100669","url":null,"abstract":"<p><strong>Background: </strong>Perioperative anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint inhibitors improve outcomes, but optimal selection between agents remains debated. We compared the efficacy and safety of anti-PD-1 versus anti-PD-L1 in neoadjuvant/adjuvant settings.</p><p><strong>Methods: </strong>PubMed, Embase, Cochrane CENTRAL, and major oncology conferences (up to May 20, 2024) were systematically searched for randomized trials comparing anti-PD-1/PD-L1 with standard perioperative therapy. Data extraction followed PRISMA guidelines, including trial characteristics, efficacy outcomes (pathological response and survival outcome), and safety profiles. Indirect comparisons between agents were conducted through network meta-analysis employing the mirror principle, utilizing both frequentist and Bayesian methodologies.</p><p><strong>Findings: </strong>Thirty-one trials (14,974 patients) were analyzed. Anti-PD-1 demonstrated superior pathological complete response (relative risk [RR]: 1.65, 95% confidence interval [CI]: 1.18-2.29, p = 0.003), major pathological response (RR: 1.43, 95% CI: 1.04-1.96, p = 0.026), and disease-free survival (hazard ratio [HR] = 0.82, 95% CI: 0.71-0.96, p = 0.0106) versus anti-PD-L1. Safety profiles were comparable overall, though anti-PD-1 correlated with higher grade 3-5 immune-related adverse events (irAEs). Frequentist and Bayesian analyses yielded consistent results.</p><p><strong>Conclusions: </strong>Perioperative anti-PD-1 therapy shows enhanced efficacy but increased severe irAEs compared to anti-PD-L1, supporting agent-specific considerations in clinical practice. Further tumor-specific evaluations and mature data are warranted.</p><p><strong>Funding: </strong>This work is supported in part by the CAMS Innovation Fund for Medical Sciences (2024-I2M-ZD-004) and so on.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100669"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051005","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}