Med最新文献

{"title":"Moving beyond associations: The role of mechanistic evidence in prenatal paracetamol safety.","authors":"Athina Samara, Asma Khalil","doi":"10.1016/j.medj.2026.101142","DOIUrl":"10.1016/j.medj.2026.101142","url":null,"abstract":"<p><p>Prenatal paracetamol safety has been debated due to inconsistent observational findings and inherent confounding. Here we argue that epidemiology alone cannot resolve biological plausibility. Human-relevant mechanistic models, including organoid and microphysiological systems, can complement population studies by testing causal pathways, refining interpretation, and enabling integrated evidence triangulation to better inform clinical guidance.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 6","pages":"101142"},"PeriodicalIF":13.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240368","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":"Rethinking healthcare data interoperability in the age of large language models.","authors":"Georg von Arnim, Severin Kohler, Stefan Hegselmann, Michael Marschollek, Roland Eils, Benjamin Wild","doi":"10.1016/j.medj.2026.101146","DOIUrl":"10.1016/j.medj.2026.101146","url":null,"abstract":"<p><p>Electronic health records contain extensive real-world clinical data, but their effective use is hindered by data heterogeneity and interoperability challenges. Traditional post hoc standardization is costly and labor-intensive and reduces data granularity. Large language models enable analysis of unstructured data without full harmonization but lack precision for some tasks. We propose a hybrid strategy that combines large-language-model-based analysis of legacy data with prospectively standardized data, offering a scalable alternative that challenges the need for retrospective data harmonization and improves interoperability.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101146"},"PeriodicalIF":13.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057013","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":"Therapeutic development in MASH: From accelerated approval to cirrhosis trial innovation.","authors":"Winston Dunn, Naim Alkhouri","doi":"10.1016/j.medj.2026.101172","DOIUrl":"10.1016/j.medj.2026.101172","url":null,"abstract":"<p><p>Therapeutic development in MASH is rapidly evolving, with accelerated approvals (resmetirom, semaglutide) based on histology in non-cirrhosis and event-driven trials in cirrhosis. Emerging paradigms include noninvasive biomarkers, hybrid endpoints, and combination therapies, aiming to improve outcomes and streamline trials while addressing disease heterogeneity and systemic cardiometabolic risk.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 6","pages":"101172"},"PeriodicalIF":13.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240387","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":"Entering a new age of innovation in IBD clinical trial design.","authors":"Joana Roseira, Irene Marafini, Gülden Bilican, Beatriz Gros, Nurulamin M Noor","doi":"10.1016/j.medj.2026.101178","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101178","url":null,"abstract":"<p><p>With a growing number of molecules to investigate as potential treatments for inflammatory bowel disease, an important advance has been through the use of more innovative and novel trial designs. This includes the VIBRATO and PIZZICATO umbrella trials, which efficiently provided novel insights for both ulcerative colitis and Crohn's disease.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 6","pages":"101178"},"PeriodicalIF":11.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240345","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":"Impact of baseline medications on real-world overall survival in immune checkpoint inhibitor-treated patients with cancer in the RADIOHEAD cohort.","authors":"Samantha Stone, Muhammad Zaki Fadlullah, Yuxin Zhao, Enjun Yang, Jordan McPherson, Roberta Florido, Grace Watkins, Aik Choon Tan, John E Connolly, Ben J Brintz, Samantha I Liang, Zoe Quandt, Arabella Young","doi":"10.1016/j.medj.2026.101100","DOIUrl":"10.1016/j.medj.2026.101100","url":null,"abstract":"<p><strong>Background: </strong>The benefits of immune checkpoint inhibitors (ICIs) observed in clinical trials often fail to translate to patients with cancer treated in a real-world setting. The identification of modifiable or monitorable exposures, such as baseline medication status, that may influence patient outcomes is necessary to reconcile disparities between clinical trial and real-world ICI efficacy.</p><p><strong>Methods: </strong>We analyzed baseline medication use obtained through electronic data capture (EDC) from the real-world RADIOHEAD cohort, a prospective, pan-cancer collection of immunotherapy-naive patients receiving standard-of-care ICI treatment across the United States. Survival analyses were performed to evaluate associations between both individual and cumulative medication exposures and real-world overall survival (rwOS).</p><p><strong>Findings: </strong>Of 1,024 patients from the RADIOHEAD cohort, 55% (n = 564/1,024) were exposed to polypharmacy, defined as more than five drug classes, at ICI initiation. Polypharmacy, explored as a continuous variable of cumulative medication exposure, was significantly associated with worse rwOS (hazard ratio [HR] 1.06 [95% confidence interval [CI] 1.03-1.10], p < 0.001, q = 0.005). Among individual medication class exposures, there was a strong association between opioids and worse rwOS (HR 1.79 [95% CI 1.43-2.24], p < 0.001), as well as beta-blocker use (HR 1.38 [95% CI, 1.10-1.72], p = 0.005), after adjusting for clinically relevant covariates and patterns of co-prescription. The association between opioid exposure and worse rwOS was independent of additional palliative medication use (HR 1.61 [95% CI 1.09-2.36], p = 0.016, p for interaction = 0.4) and persisted in patients with early-stage and non-metastatic disease (p = 0.044).</p><p><strong>Conclusions: </strong>Polypharmacy and baseline medication exposures, particularly opioid and beta-blocker use, have prognostic significance for rwOS in patients with cancer receiving ICI treatment. This study evaluates the influence of baseline medications on ICI efficacy within the context of cumulative medication exposures reflective of co-prescription.</p><p><strong>Funding: </strong>This study was supported in part by the National Institutes of Health and the Parker Institute for Cancer Immunotherapy (PICI).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101100"},"PeriodicalIF":13.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717849","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":"Five trials reshaping multiple myeloma.","authors":"Alexis Talbot, Arthur Bobin, Cyrille Touzeau, Bertrand Arnulf, Salomon Manier, Aurore Perrot, Xavier Leleu","doi":"10.1016/j.medj.2026.101177","DOIUrl":"10.1016/j.medj.2026.101177","url":null,"abstract":"<p><p>Emerging therapies in multiple myeloma are challenging the long-standing paradigm of continuous disease control and raising the possibility of durable remission. Five pivotal clinical trials are evaluating transformative strategies, including replacement of transplantation, MRD-guided treatment, finite therapy, multi-target immune redirection, and early interception. Together, these studies may establish biology-driven, immune-based treatment frameworks aimed at achieving treatment-free remission and, ultimately, cure.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 6","pages":"101177"},"PeriodicalIF":13.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240377","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":"Chemoimmunotherapy enables adaptive strategies in locally advanced MSS colorectal cancer.","authors":"Filippo Ghelardi, Filippo Pietrantonio","doi":"10.1016/j.medj.2026.101145","DOIUrl":"https://doi.org/10.1016/j.medj.2026.101145","url":null,"abstract":"<p><p>Early exposure to checkpoint blockade restores immune-sensitivity in localized, immune-excluded cancers. In this issue of Med, Zhang et al. reported promising pathological activity of 3-month preoperative cadonilimab (bispecific anti-PD-1/CTLA-4 antibody) with modified FOLFOXIRI triplet intensive chemotherapy in patients with locally advanced MSS colorectal adenocarcinoma, hinting to new adaptive strategies of radiotherapy-sparing and organ preservation.¹.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 6","pages":"101145"},"PeriodicalIF":11.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240352","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":"Ferroptosis in MASLD: From molecular mechanisms to therapeutic opportunities.","authors":"Xiao-Dong Zhou, Qiong-Yue Fan, Giovanni Targher, Christopher D Byrne, Wei Xie, Qin-Fen Chen, Yuxing Dong, Fudi Wang, Daolin Tang, Ming-Hua Zheng","doi":"10.1016/j.medj.2026.101099","DOIUrl":"10.1016/j.medj.2026.101099","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver conditions, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, and cirrhosis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key pathogenic mechanism in MASLD. Given the liver's pivotal role in iron and lipid metabolism, hepatocytes are highly susceptible to ferroptotic injury, which amplifies hepatic oxidative stress, inflammation, and fibrogenesis. Beyond the liver, ferroptosis has also been linked to systemic metabolic dysfunction and extrahepatic organ involvement in MASLD. This review summarizes the molecular pathways linking ferroptosis to disease progression across the MASLD spectrum, integrating evidence from preclinical and clinical studies. We further discuss emerging biomarkers and the therapeutic strategies targeting ferroptosis, including iron chelation, antioxidants, and lipid peroxidation inhibitors. Understanding how metabolic stress and ferroptotic signaling interact may open new avenues for treating MASLD and its systemic complications.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101099"},"PeriodicalIF":11.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692576","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":"Resectability redefined: Lessons from quadruple therapy in HCC.","authors":"Nan Jiang, Bin-Yan Zhong","doi":"10.1016/j.medj.2026.101136","DOIUrl":"10.1016/j.medj.2026.101136","url":null,"abstract":"<p><p>Qiu et al. report a phase II trial (PLATIC) evaluating sintilimab, lenvatinib, and transarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC) as conversion therapy for unresectable hepatocellular carcinoma (uHCC).¹ While these results represent a substantial advance in conversion therapy, they also raise critical questions about how to optimally integrate locoregional and systemic therapies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"7 6","pages":"101136"},"PeriodicalIF":11.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240400","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":"First human decedent model of orthotopic multi-organ xenotransplantation: Whole liver and bilateral kidneys from a six-gene-edited pig.","authors":"Jixiang Liao, Sanqi An, Jianhui Dong, ShihJung Li, Jianhui Li, Lei Dong, Ziyang Luo, Liugen Lan, Ning Wen, Jihua Wu, Jiqiu Wen, Zhiying Lei, Dongge Yang, Haibin Li, Minghu Li, Yan Mo, Luying Chen, Zhao Gao, Xuyang Liu, Haisong Qin, Xiang Wang, Yajing Chen, Wenli Yin, Bihui Huang, Wenxing Li, Gabriel Oniscu, Wenshi Jiang, Dengke Pan, Zhengxin Wang, Zhijun Zhu, Jinzhen Cai, Haitao Li, Juntao Gao, Xiaocong Kuang, Xuyong Sun","doi":"10.1016/j.medj.2026.101148","DOIUrl":"10.1016/j.medj.2026.101148","url":null,"abstract":"<p><strong>Background: </strong>We report orthotopic combined whole-liver and bilateral-kidney xenotransplantation (xeno-CLKT) from a six-gene-edited pig into a 53-year-old human decedent recipient.</p><p><strong>Methods: </strong>After simultaneous implantation and reperfusion, graft function was monitored for nearly 5 days using continuous clinical assessments. Host responses were further characterized with single-cell RNA sequencing, proteomics, and metabolomics of blood and graft tissues collected before and after transplantation.</p><p><strong>Findings: </strong>All grafts maintained basic physiological function throughout the observation period, with no evidence of hyperacute rejection. Early post-transplant immune analysis showed expansion of S100A12⁺ neutrophils, which emerged as central hubs in inferred intercellular communication networks. Systems-level metabolomic profiling indicated that post-transplant metabolic patterns remained positively correlated with the recipient's pre-transplant baseline, with generally higher magnitudes.</p><p><strong>Conclusions: </strong>This study provides initial evidence for the feasibility of pig-to-human orthotopic whole-liver plus bilateral-kidney transplantation and identifies early immune and metabolic features that may inform perioperative management and future clinical translation.</p><p><strong>Funding: </strong>The research was supported by the Guangxi Key Research and Development Program (AB24010059), the Shenzhen Medical Research Fund (SMAF) (B2302008), and the Guangdong Province Guangdong-Shenzhen Joint Key Project (2023B1515120083).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"101148"},"PeriodicalIF":13.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057292","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}