Med最新文献

{"title":"Nivolumab plus ipilimumab: A promising first-line therapy for hepatocellular carcinoma.","authors":"Bernardo Stefanini, Fabio Piscaglia","doi":"10.1016/j.medj.2025.100783","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100783","url":null,"abstract":"<p><p>Recently published in The Lancet, CheckMate 9DW evaluated the efficacy and safety of dual immune checkpoint blockade nivolumab plus ipilimumab (Nivo/Ipi) compared to either sorafenib or lenvatinib in treatment-naive patients with unresectable hepatocellular carcinoma. This open-label, randomized phase 3 trial demonstrated that Nivo/Ipi provides an overall survival benefit versus lenvatinib or sorafenib.¹.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100783"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812433","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":"Burden of neurological disorders in China and its provinces, 1990-2021: Findings from the global burden of disease study 2021.","authors":"Chen Zhang, Xuan Yang, Dongshan Wan, Qingfeng Ma, Peng Yin, Maigeng Zhou, Junwei Hao","doi":"10.1016/j.medj.2025.100692","DOIUrl":"10.1016/j.medj.2025.100692","url":null,"abstract":"<p><strong>Background: </strong>The burden of neurological disorders in China has not been systematically analyzed. We aim to provide a comprehensive estimation of the national and subnational neurological burden across China from the Global Burden of Disease Study (GBD) 2021.</p><p><strong>Methods: </strong>We assessed burden estimates for 16 neurological disorders by age, sex, and province from 1990 to 2021, with prevalence, death, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs). We performed decomposition analysis to determine contributing factors for DALYs and used the socio-demographic index (SDI) to assess relations with development level.</p><p><strong>Findings: </strong>In 2021, there were 468.29 million prevalent cases of neurological disorders in China, corresponding to 78.10 million DALYs. Intracerebral hemorrhage was the leading cause of DALYs, followed by ischemic stroke, dementias, and migraine. DALYs of neurological disorders were higher in males than females, peaking at 70-74 years. From 1990 to 2021, the number and age-standardized rate of DALYs significantly decreased for idiopathic epilepsy and subarachnoid hemorrhage, primarily attributed to the reduction in YLLs, while the number of DALYs disproportionately increased for dementias, Parkinson's disease, and ischemic stroke contributed by population aging. The age-standardized DALY rates of seven neurological disorders had more than 5-fold variation between western and eastern provinces, despite reduced burdens with rising SDI.</p><p><strong>Conclusions: </strong>Neurological disorders pose a large and growing burden on public health, primarily driven by population aging. Our findings could inform priority setting and targeted strategies to optimize neurological service delivery.</p><p><strong>Funding: </strong>The funding information is presented in the acknowledgments.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100692"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055808","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":"Advances in TIL therapy: Expanding the horizons beyond melanoma.","authors":"Pauline Wiertsema, Ya Hwee Tan, John B A G Haanen, Tom T P Seijkens, Inge Jedema","doi":"10.1016/j.medj.2025.100702","DOIUrl":"10.1016/j.medj.2025.100702","url":null,"abstract":"<p><p>Tumor-infiltrating lymphocyte (TIL) therapy represents a breakthrough in solid tumor treatment, addressing unmet needs for patients with limited options. While its efficacy is established in advanced melanoma, TIL therapy shows early promise in non-small cell lung cancer, breast cancer, gynecological cancers, and head and neck cancers. However, challenges such as reduced T cell infiltration, lower tumor mutational burden (TMB), immunosuppressive tumor microenvironments (TME), and toxicity associated with the TIL therapy regimen hinder its broader application in these patient groups, compared with melanoma. To address these challenges, new approaches focus on the selection of tumor-reactive TIL, optimization of TIL expansion, combination of immune checkpoint inhibitors with TIL therapy to counteract immunosuppressive microenvironments, and genetic modification of TIL to enhance persistence and functionality. Larger clinical trials are essential to validate these innovations and standardize protocols. With continued advancements, TIL therapy has the potential to redefine the treatment landscape for advanced solid cancers.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100702"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095076","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":"SOUL searching in GLP-1 therapy: Oral semaglutide confirms cardioprotection in type 2 diabetes.","authors":"Christine Rode Schwarz, Tina Vilsbøll","doi":"10.1016/j.medj.2025.100774","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100774","url":null,"abstract":"<p><p>Semaglutide's evolution from weekly injections to an SNAC-enabled tablet preserved its metabolic and cardiovascular efficacy. Large injectable CVOTs have demonstrated robust cardioprotection, and the SOUL trial now shows a 14% reduction in major adverse cardiovascular events with the oral formulation.¹ These data confirm formulation-independent benefit, positioning oral semaglutide as the only cardioprotective, non-injectable, GLP-1RA for high-risk type 2 diabetes.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100774"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812516","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":"CD70-targeted cancer theranostics: Progress and challenges.","authors":"Weijun Wei, Viktor Grünwald, Ken Herrmann","doi":"10.1016/j.medj.2025.100671","DOIUrl":"10.1016/j.medj.2025.100671","url":null,"abstract":"<p><p>CD70, a tumor-associated antigen, exhibits elevated expression in clear cell renal cell carcinoma (ccRCC), nasopharyngeal carcinoma, and lymphoma, among others, with minimal presence in healthy tissues. CD70 has emerged as a promising biomarker for molecular imaging, targeted therapies, and immunotherapies. ImmunoPET imaging with single-domain antibody-derived tracers, such as [¹⁸F]RCCB6 and [⁶⁸Ga]Ga-NOTA-RCCB6, demonstrates exceptional diagnostic precision, identifying both common and rare metastases from ccRCC. This capability enhances staging accuracy and further enables early intervention. Beyond diagnostics, CD70-targeted imaging optimizes patient selection for emerging therapies, such as CAR-T cells and antibody-drug conjugates, by stratifying candidates based on their CD70 expression levels. It also supports real-time monitoring of therapeutic responses, enabling dynamic adjustments to treatment. The integration of these imaging tools into clinical workflows enhances personalized treatment efficacy for CD70-expressing cancers. Radiotheranostic strategies can further allow the simultaneous diagnosis and treatment of malignancies, opening new horizons for the precise management of CD70⁺ tumors.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100671"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052658","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":"Gradual recovery of auditory brainstem responses in the first DFNB9 patients with successful virus-mediated gene therapy.","authors":"Barbara Vona, Nicola Strenzke","doi":"10.1016/j.medj.2025.100775","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100775","url":null,"abstract":"<p><p>A bit more than one year ago, there was a major breakthrough in the treatment of sensorineural hearing loss: three publications¹^,²^,³ reported on the first successful gene therapy trials to restore hearing function in children with autosomal recessive prelingual deafness DFNB9. In their recent publication in Med, Zhang et al.⁴ report follow-up data regarding objective measures of hearing function.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100775"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812431","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 genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI/PRIMO.","authors":"Asma Essat, Anaïs Chapel, Kahina Amokrane, Valérie Monceaux, Céline Didier, Adeline Melard, Elise Gardiennet, Véronique Avettand-Fenoel, Sylvie Orr, Faroudy Boufassa, Olivier Lambotte, Michaela Müller-Trutwin, Camille Lécuroux, Antoine Chéret, Cécile Goujard, Christine Rouzioux, Sophie Caillat-Zucman, Laurent Hocqueloux, Daniel Scott-Algara, Laurence Meyer, Asier Sáez-Cirión","doi":"10.1016/j.medj.2025.100670","DOIUrl":"10.1016/j.medj.2025.100670","url":null,"abstract":"<p><strong>Background: </strong>There is currently no curative treatment for HIV-1 infection. However, some individuals (defined as posttreatment controllers) durably control viremia after the discontinuation of antiretroviral therapy (ART). Although the ability to achieve this HIV-1 remission status is enhanced by early treatment initiation, the mechanisms leading to posttreatment HIV-1 control remain unclear.</p><p><strong>Methods: </strong>We retrospectively explored the immunogenetic characteristics of long-term posttreatment controllers from the ANRS VISCONTI study and persons monitored since primary HIV-1 infection in the ANRS PRIMO cohort and evaluated their influence on clinical parameters and outcome after ART discontinuation.</p><p><strong>Findings: </strong>We identified a major histocompatibility complex (MHC)-related fingerprint favoring sustained HIV-1 remission. HLA-B∗35 alleles, which are associated with rapid progression to AIDS during natural HIV-1 infection, were paradoxically overrepresented among posttreatment controllers and had a positive impact on outcome after treatment discontinuation in people who began therapy during primary infection. Specifically, the influence of HLA-B∗35 alleles was observed when they were carried in combination with other HLA class I alleles expressing Bw4 and C2 ligands of killer immunoglobulin-like receptors (KIRs) in a genetic context that favors KIR education of natural killer (NK) cells (Bw4TTC2 genotype). Accordingly, posttreatment controllers with HLA-B∗35 alleles carry distinct KIR genotypes and NK cells.</p><p><strong>Conclusions: </strong>The combination of HLA-B∗35 with Bw4TTC2 genotype, associated with KIR education of NK cells, was abundant among posttreatment HIV-1 controllers and promoted viral control after interruption of early-initiated antiretroviral treatment. These results support a role of NK cells in sustained HIV-1 remission.</p><p><strong>Funding: </strong>The VISCONTI study and the PRIMO cohort are funded by the ANRS-MIE.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100670"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy without resolution: A critical appraisal of mepolizumab in eosinophilic COPD.","authors":"Mario Cazzola, Maria Gabriella Matera","doi":"10.1016/j.medj.2025.100784","DOIUrl":"10.1016/j.medj.2025.100784","url":null,"abstract":"<p><p>Mepolizumab reduces exacerbations in eosinophilic COPD but shows limited effects on symptoms, lung function, or quality of life. The MATINEE trial supports a precision medicine approach targeting high blood eosinophil counts.¹ However, IL-5 blockade alone may be insufficient due to complex, overlapping inflammatory pathways and persistent lung-resident eosinophils.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 8","pages":"100784"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812430","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":"HRS-5965, a small-molecule factor B inhibitor, in healthy participants and participants with renal insufficiency: A first-in-human, phase 1 trial.","authors":"Yi Xu, Fen Tian, Hong Ren, Xian Yu, Xiaoyu Chen, Kun Ye, Feifei Sun, Lin Fang, Yuan Li, Rongxin Ban, Xin Jiang, Chenjing Wang, Yaping Ma, Fu Kuang, Xin Li, Zhigao Zhang, Chaobaihui Ye, Min Hu, Feng He, Chang Shu, Yanfang Zou, Rong Huang, Kai Shen, Guangqun Xing, Yu Cao","doi":"10.1016/j.medj.2025.100698","DOIUrl":"10.1016/j.medj.2025.100698","url":null,"abstract":"<p><strong>Background: </strong>HRS-5965 is an oral selective small-molecule inhibitor of complement factor B, a key component of the alternative pathway. This study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of HRS-5965 in healthy participants and participants with renal insufficiency.</p><p><strong>Methods: </strong>The first-in-human, phase 1 study consisted of 3 parts (ClinicalTrials.gov: NCT05505955). Part 1 was a single-ascending-dose, randomized, double-blind study with 5 dose groups preset, including a food effect evaluation. Part 2 was a multiple-ascending-dose, randomized, double-blind study with 9 dose groups preset. Part 3 was an open-label, single-dose study on severe renal insufficiency. The primary endpoints were safety and tolerability.</p><p><strong>Findings: </strong>A total of 82 participants were enrolled and received either HRS-5965 or placebo (26 in part 1, 40 in part 2, and 16 in part 3). HRS-5965 was well tolerated. Treatment-emergent adverse events were comparable between the HRS-5965 groups and placebo groups in part 1 (17/20 [85.0%] vs. 6/6 [100.0%]) and part 2 (27/30 [90.0%] vs. 10/10 [100.0%]). No deaths were reported. HRS-5965 was absorbed rapidly, with a median time to reach peak concentration (T_max) ranging from 0.75 to 1.50 h in fasted states and 2.00 h in fed states. Pharmacokinetics was nonlinear, and food delayed the absorption of HRS-5965 but did not impact the exposure. Alternative pathway activity was inhibited by over 80% with HRS-5965, compared to less than 20% with placebo.</p><p><strong>Conclusion: </strong>HRS-5965 demonstrated favorable safety and robust inhibition of alternative pathway activity, supporting further clinical development.</p><p><strong>Funding: </strong>The study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100698"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086163","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":"Early immune system changes in amyotrophic lateral sclerosis correlate with later disease progression.","authors":"Benjamin J Murdock, Bangyao Zhao, Ian F Webber-Davis, Samuel J Teener, Kristen D Pawlowski, Joshua P Famie, Caroline E Piecuch, Dae Gyu Jang, Eva L Feldman, Lili Zhao, Stephen A Goutman","doi":"10.1016/j.medj.2025.100673","DOIUrl":"10.1016/j.medj.2025.100673","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no cure and limited treatment options. The immune system is implicated in disease pathology, unlocking a potential therapeutic avenue. However, it is unclear whether immune changes are a cause or consequence of disease progression.</p><p><strong>Methods: </strong>Peripheral immune cells were longitudinally measured at monthly intervals in 55 ALS and 50 control participants. 22 peripheral immune markers in the blood were assessed using flow cytometry, and clinical progression was assessed using the revised ALS functional rating scale (ALSFRS-R). Individual immune markers, their trajectories, and overall variability were compared in ALS versus control participants; ALS participants were also stratified by clinical progression rates and assessed similarly across progression groups. Finally, a novel, lagged linear regression model correlated the rate of immune changes to subsequent downstream ALSFRS-R changes.</p><p><strong>Findings: </strong>Numerous immune markers were dysregulated in ALS versus control participants, with altered levels, trajectories, or variability in immune populations and surface markers. ALS participants had increased immune variability relative to control participants; within ALS participants, faster progressors overall had decreased marker variability. Finally, natural killer (NK) cell numbers, NK cell subpopulations, and NK cell surface markers were significantly associated with downstream ALS progression.</p><p><strong>Conclusions: </strong>The immune system is dysregulated in ALS and more consistently dysregulated in faster ALS progression, and immune dysregulation occurs upstream of clinical changes. These findings suggest that the immune system is a causal factor of ALS progression in human patients.</p><p><strong>Funding: </strong>CReATe Consortium, NIH, Target ALS, DoD, ALSA.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100673"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}