Communications medicine最新文献

{"title":"Bayesian multistate modelling of prefrailty and frailty using microsimulation with weight management interventions for prevention in Asian settings.","authors":"Xinyu Zhang, Shihui Jin, Haolong Song, Johnathan Hong-Hui Yeo, Borame Lee Dickens","doi":"10.1038/s43856-026-01756-7","DOIUrl":"10.1038/s43856-026-01756-7","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of pre-frailty and frailty is increasing in Asia, resulting in substantial morbidity and mortality in older populations. Modelling frameworks are required to estimate the prevalence of frailty and potential impacts of ongoing population-level nutritional interventions.</p><p><strong>Methods: </strong>Using a microsimulation sociodemographic model of 3,353,032 individuals from 2011 to 2050, and published estimates from the Singapore Longitudinal Ageing Study 2 of 3270 participants, we developed a Bayesian multistate model of robust, pre-frail, and frail stages with estimated transition probabilities by age, ethnicity, gender, and body mass index category. We then explored four scenarios where weight management interventions are applied that modify the annual distribution of underweight, normal weight, overweight, obese I and obese II individuals.</p><p><strong>Results: </strong>Here we show that, between 2011 and 2050, the projected overall prevalence of pre-frailty and frailty increases from 44.2% to 49.57% (95% credible interval: 47.60-51.00%), and from 3.2% to 11.97% (7.34-15.60%), respectively. Reductions range from 22,045 (18,430-23,487) to 3,599 (2554-4621) pre-frail individuals and from 62,847 (40,165-91,517) to 15,802 (13,238-17,133) frail individuals when 100% to 5% of both underweight individuals shift to normal weight and obese II individuals move to obese I, respectively. Total healthcare utilisation decreases by 7.1% (3.9-9.4%) to 0.3% (0.2-0.5%) under 100% to 5% intervention coverage.</p><p><strong>Conclusions: </strong>Frailty prevalence in Singapore is projected to substantially increase by 2050, while population-level weight management interventions could avert cases of both pre-frailty and frailty in older individuals, even at modest real-world effectiveness.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388491","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 wearable device dataset for mental health assessment using laser Doppler flowmetry and fluorescence spectroscopy sensors.","authors":"Minh Ngoc Nguyen, Khai Le-Duc, Tan-Hanh Pham, Trong Nhan Nguyen, Trang Nguyen, Ba Kien Tran, Viktor Dremin, Sergei Sokolovsky, Edik Rafailov, Truong-Son Hy","doi":"10.1038/s43856-026-01766-5","DOIUrl":"10.1038/s43856-026-01766-5","url":null,"abstract":"<p><strong>Background: </strong>Mental health conditions such as depression, anxiety, and stress are commonly assessed using self-reported questionnaires and limited wearable physiological measures. However, reliance on subjective reporting, restricted sensor modalities such as heart rate variability and electrodermal activity, and small or homogeneous datasets may limit generalizability. We aimed to evaluate whether wearable optical sensing of microcirculation and tissue metabolism enables objective assessment of stress-related mental health states.</p><p><strong>Methods: </strong>We conducted a prospective observational study including 132 adults aged 18 to 94 years (58% female) from 19 countries. Participants underwent repeated fingertip measurements using a non-invasive wearable device combining laser Doppler flowmetry and fluorescence spectroscopy to capture microvascular perfusion and metabolic signals. Frequency-domain features were extracted using wavelet analysis. Depression, anxiety, and stress levels were assessed using a standardized 21-item questionnaire. Multiple machine learning models were evaluated under subject-wise validation, and model interpretability was assessed using Shapley-based feature attribution.</p><p><strong>Results: </strong>Here we show that ensemble-based models distinguish individuals with stress-related symptoms from those without with a receiver operating characteristic area under the curve of 0.72 and a precision-recall area under the curve of 0.89 under subject-wise validation. Microcirculatory variability and metabolic fluorescence features contribute substantially to prediction performance. Demographic variables, including sex, age, body mass index, and heart rate, are associated with increased stress-related risk.</p><p><strong>Conclusions: </strong>Wearable optical sensing combined with interpretable machine learning provides physiological signatures associated with stress-related mental health conditions. This framework supports development of scalable and data-driven tools for objective mental health monitoring.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388493","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":"Human papillomavirus 68 subtypes among people with human immunodeficiency virus and implications for anal screening.","authors":"M Bello-Perez, A Gutiérrez-Ortiz de la Tabla, P Mascarell, J A García, A Galiana, M Fernández-González, J García-Abellán, S Padilla, F Gutiérrez, M Masiá","doi":"10.1038/s43856-026-01717-0","DOIUrl":"10.1038/s43856-026-01717-0","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) infection is a key risk factor for anal cancer. While HPV16's carcinogenic role is well established, the contribution of other high-prevalence genotypes in people with HIV (PWH), such as HPV68 is less defined. This study examines the prevalence of HPV68 subtypes, their oncogene expression, and association with histologically confirmed high-grade squamous intraepithelial lesions (HSIL).</p><p><strong>Methods: </strong>Two hundred PWH with abnormal anal cytology underwent HPV genotyping and mRNA analysis for the E6/E7 oncogenes of HPV16 and HPV68. Statistical analyses evaluated associations between HPV genotypes, oncogene expression, and HSIL.</p><p><strong>Results: </strong>The cohort had a median age of 50 (IQR, 43-57) years, with 83% male participants and 93.9% virologically suppressed. HSIL was confirmed by histology in 25% of participants. HPV68 (28.5%) and HPV16 (24.5%) were the most prevalent genotypes, with HPV68a detected in 65.3% of HPV68-positive cases. Among HSIL cases, HPV16 (42%) and HPV68 (34%) were most common. HPV68a was significantly associated with HSIL in participants without HPV16. mRNA expression levels of E6 and E7 from HPV68a were significantly higher in the HSIL group (142.0 vs 12.9, p = 0.007 and 82.5 vs 9.1, p = 0.014, respectively). Differences remained significant after adjusting for the number of HPV genotypes and HPV16.</p><p><strong>Conclusions: </strong>These findings suggest that HPV68a drives anal HSIL and warrants inclusion in screening and vaccination for high-risk groups.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13710971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383287","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":"A memory retrieval-aversive conditioning procedure durably reduces gaming craving and fronto-insular activation in internet gaming disorder: a randomized controlled trial.","authors":"Shuang Li, Menghui Li, Xuefeng Xu, Anhang Jiang, Guang-Heng Dong","doi":"10.1038/s43856-026-01705-4","DOIUrl":"https://doi.org/10.1038/s43856-026-01705-4","url":null,"abstract":"<p><strong>Background: </strong>Internet gaming disorder (IGD) is a growing mental health concern worldwide, yet effective interventions remain limited. Inspired by memory reconsolidation theory, conditioning, and previous work on retrieval-extinction procedures in substance addiction, this study developed a retrieval-aversive conditioning (R-AC) training protocol to target addiction-related memories in IGD.</p><p><strong>Methods: </strong>The trial was registered with the Chinese Clinical Trial Registry (ChiCTR; registration number: ChiCTR2500095444; https://www.chictr.org.cn/) on January 7, 2025. This was a single-center randomized controlled trial conducted in Hangzhou, China. Sixty-two individuals with IGD were randomly assigned to an R-AC group (n = 30) or a control group (n = 32). The R-AC group underwent five days of training involving memory reactivation via gaming cues followed by aversive conditioning within the reconsolidation window. Participants were blinded to the existence of the other group. The primary outcome was neuroimaging measures derived from task-based fMRI, specifically changes in brain activation associated with cue-induced craving following the intervention. Secondary outcomes included behavioral measures obtained from questionnaire assessments, including scores on the Internet Addiction Test (IAT), DSM-5 proposed criteria for IGD, and the gaming craving scale. Exploratory outcomes comprised correlation analyses examining the relationships between changes in brain activation (BOLD signals) and changes in behavioral measures.</p><p><strong>Results: </strong>The primary outcome shows decreased activation in the left insula and middle frontal gyrus, and increased activation in the left postcentral gyrus. Secondary outcomes show that R-AC training significantly reduces addiction severity scores and self-reported craving. Exploratory outcomes show that changes in frontal activation are negatively correlated with reductions in addiction severity. No adverse events are reported.</p><p><strong>Conclusions: </strong>These findings suggest that R-AC training effectively attenuates gaming craving and modulates neural circuits involved in craving and executive control, offering a promising behavioral intervention for IGD.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383282","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":"Troponin release and mechanism-dependent myocardial injury in a lightning-induced mass casualty incident.","authors":"Marcin Waligóra, Tomasz Sanak, Maciej Mikiewicz, Ryan Blumenthal, Klaudia Zaczyńska, Sylweriusz Kosiński","doi":"10.1038/s43856-026-01739-8","DOIUrl":"10.1038/s43856-026-01739-8","url":null,"abstract":"<p><strong>Background: </strong>Systematic data on cardiac involvement after lightning strikes are limited and mostly derived from case reports. On 22 August 2019, a cloud-to-ground lightning event on Mt. Giewont (Poland) caused a mass casualty incident, providing a unique opportunity to characterize myocardial injury in a large cohort. This study aimed to quantify high-sensitivity cardiac troponin (hs-cTnT) release after lightning strike and its relationship with injury mechanisms.</p><p><strong>Methods: </strong>Individuals from the MT Giewont incident with available troponin measurements were analyzed. Injury mechanisms were predefined, and the location on the trail at the time of the strike was determined. Peak hs-cTnT measured in the emergency department was the primary biomarker of myocardial injury. Among 131 exposed hikers, 59 underwent hs-cTnT testing. The cohort comprised 27 (45.8%) females, and median age of individuals was 29.5 years (IQR 23-41).</p><p><strong>Results: </strong>Overall, 27 (45.8%) exceeded the upper reference limit of hs-cTnT (URL; 14 ng/L). Median peak hs-cTnT was 13 ng/L (IQR 7.6-25.6). Individuals with direct strike/side-flash exposure had significantly greater troponin levels (median 25.6 vs 10.7 ng/L; p = 0.004). In multivariable analysis, direct/side flash exposure was the only independent predictor of increased troponin (β = 0.90 p = 0.014; relative change +146%). Contact injury, ground current, and blast injury were not significant. ECG abnormalities were uncommon despite frequent biomarker elevation. Individuals with hs-cTnT above the upper reference limit were more frequently admitted to hospital (63% vs 34.4%; p = 0.03), with a 60% increase in odds of admission per doubling of troponin (95% CI 1.01-2.5; p = 0.048). Discrimination for admission was moderate (AUC 0.66, 95% CI 0.52-0.78); a threshold >16 ng/L provided 53.6% sensitivity and 77.4% specificity.</p><p><strong>Conclusions: </strong>Among individuals who underwent cardiac troponin testing, nearly half demonstrated elevated hs-cTnT levels. Troponin release was significantly greater in individuals exposed to direct strike/side flash.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382415","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":"The landscape of artificial intelligence in neurodegenerative diseases: a systematic review.","authors":"Walter Endrizzi, Flavio Ragni, Stefano Bovo, Avinash Chandra, Monica Moroni, Giuseppe Jurman, Venet Osmani","doi":"10.1038/s43856-026-01669-5","DOIUrl":"10.1038/s43856-026-01669-5","url":null,"abstract":"<p><strong>Background: </strong>The rising global burden of neurodegenerative diseases underscores an urgent need for advanced research in diagnosis, prognosis, and treatment. Artificial Intelligence (AI) methods, particularly when applied to multimodal data, offer a powerful tool to address these challenges. However, a comprehensive overview and critique of the current landscape of AI methods is lacking.</p><p><strong>Methods: </strong>4,685 records of peer-reviewed, primary research articles were screened and 1,956 articles reviewed in full text, yielding 1,186 included studies. For each included study, clinical objectives, disease focus, data modalities, modelling approach, evaluation strategy, and reporting practices were extracted.</p><p><strong>Results: </strong>Fewer than 5% of studies integrated pharmacological treatments into their predictive models, limiting the extent to which models can directly inform clinical decision-making. Neuroimaging was the predominant input modality, while integration of other clinically relevant data types was relatively rare. Reproducibility rates remain critically low at 35%, and external validation practices fail to use geographically and demographically diverse datasets.</p><p><strong>Conclusions: </strong>Overall, AI research in neurodegenerative diseases suffers from significant limitations in reproducibility, data inclusivity, and clinical translatability. We provide a set of recommendations that can be adopted to address these issues and improve reliability and downstream clinical utility.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382468","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":"Integrating a national crisis counseling hotline into Iran's primary health care network to provide rapid mental health support during armed conflict.","authors":"Alireza Raeisi, Mohammadreza Shalbafan, Sedigheh Khadem, Babak Farrokhi, Mohammadreza Rahbar, Maryam Chegini, Seyed Ebrahim Ghoddousi, Hadi Zarafshan","doi":"10.1038/s43856-026-01772-7","DOIUrl":"10.1038/s43856-026-01772-7","url":null,"abstract":"","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383106","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":"Integrative proteogenomic analyses identify plasma proteins that impact the risk of ischemic stroke.","authors":"Lazaros Belbasis, Adam von Ende, Parag Gajendragadkar, Elsa Valdes-Marquez, Federico Murgia, Cornelia van Duijn, Jemma C Hopewell","doi":"10.1038/s43856-026-01734-z","DOIUrl":"10.1038/s43856-026-01734-z","url":null,"abstract":"<p><strong>Background: </strong>Understanding the proteins implicated in the pathogenesis of ischemic stroke is important for elucidating disease mechanisms and informing prevention strategies. In this study, we aim to identify plasma proteins with a potentially causal effect on risk of ischemic stroke by integrating the largest available genetic data sources for plasma proteins, ischemic stroke and its risk factors.</p><p><strong>Methods: </strong>We use genome-wide association (GWA) statistics to identify cis protein quantitative trait loci for over 3,500 proteins across two proteomic platforms. Subsequently, we perform two-sample Mendelian randomization (MR) to assess the potentially causal relationships between plasma proteins and a) risk of ischemic stroke and its subtypes, and b) well-established cardiovascular risk factors. Downstream analyses include Bayesian colocalization, phenome-wide associations and interrogation of biological databases.</p><p><strong>Results: </strong>We identify 21 proteins with evidence of potentially causal associations with risk of ischemic stroke or its subtypes at 5% false discovery rate, with 16 supported further by colocalization. Four proteins (CEP85, KNG1, MMUT, SPATA20) represent findings not previously implicated in ischemic stroke through MR, or through cognate genes in GWA studies. Integration of evidence from phenome-wide MR, animal models and tissue-specific gene expression highlights agonists of MMUT, CEP85 and GRK5, and inhibitors of F11 and KNG1 as the most promising for further consideration as targets for prevention of ischemic stroke.</p><p><strong>Conclusions: </strong>Our study provides the most comprehensive data integration to date supporting the identification and causal relevance of plasma proteins for ischemic stroke and implicating a number of potential therapeutic targets.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383180","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":"Intraoperative dexmedetomidine reduces postoperative sleep disturbance in older adults undergoing major abdominal surgery: a single-center, randomized, double-blind, placebo-controlled trial.","authors":"Hui-Ping Peng, Jing-Hui Hu, Li-Ping Fan, Xiu Yang, Hua-Yue Liu, Xi-Sheng Shan, Hong Liu, Nazneen Sudhan, Fu-Hai Ji, Ke Peng","doi":"10.1038/s43856-026-01769-2","DOIUrl":"10.1038/s43856-026-01769-2","url":null,"abstract":"<p><strong>Background: </strong>Postoperative sleep disturbance (PSD) after major abdominal surgery in older adults is common and impairs recovery. Dexmedetomidine is a selective α₂-adrenergic agonist with sedative, analgesic, and anti-inflammatory properties that promotes natural sleep. We hypothesized that intraoperative dexmedetomidine would reduce PSD in this population.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled trial, 210 older adults undergoing major abdominal surgery were randomly assigned (1:1:1) to receive intraoperative normal saline, dexmedetomidine 0.3 μg/kg/h, or 0.6 μg/kg/h. The primary outcome was PSD on the first postoperative night (Athens Insomnia Scale score ≥ 6). Secondary outcomes included PSD on until nights 30; pain at 24 and 48 h; delirium and depressive symptoms within 7 days; and recovery quality on postoperative days 1‒3. Sleep patterns on nights 1 and 2 were assessed using wrist actigraphy. This trial was registered on the Chinese Clinical Trial Registry (Identifier: ChiCTR2300073163; principal investigator: Ke Peng; dated July 23, 2023; https://www.chictr.org.cn/showproj.html?proj=199410 ).</p><p><strong>Results: </strong>203 patients (median age 71 years; 67.5% male) completed this trial. Compared with normal saline (n = 67), both low-dose (n = 68) and high-dose dexmedetomidine (n = 68) significantly reduced first-night PSD (20.6% vs 65.7%; relative risk 0.31, 95% CI 0.19-0.50; NNT 2.2; P < 0.001; and 11.8% vs 65.7%; relative risk 0.18, 95% CI 0.09-0.34; NNT 1.8; P < 0.001, respectively). The two doses did not differ. Dexmedetomidine was associated with lower sleep disturbance on night 2 and higher recovery quality, without between-group differences in hypotension, bradycardia, delirium, or 30-day mortality. Exploratory actigraphy analysis (n = 20 per group) showed longer total sleep time and lower wake-time percentage associated with dexmedetomidine.</p><p><strong>Conclusions: </strong>Intraoperative dexmedetomidine infusion reduced the relative risk of first-night PSD by 70-80% among older adults undergoing major abdominal surgery. These findings require confirmation in multicenter trials.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13710947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383327","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":"Endomyocardial Gremlin-1 is associated with structural remodeling and adverse clinical outcomes in non-ischemic cardiomyopathy.","authors":"Tobias Harm, Karin Klingel, Patrick Krumm, David Heinzmann, Livia Dingemann, Ioannis Toskas, Peter Seizer, Jörg Kumbrink, Thomas Kirchner, Oliver Borst, Jürgen Schreieck, Tobias Geisler, Simon Greulich, Meinrad Paul Gawaz, Karin Anne Lydia Müller","doi":"10.1038/s43856-026-01762-9","DOIUrl":"10.1038/s43856-026-01762-9","url":null,"abstract":"<p><strong>Background: </strong>Risk stratification in non-ischemic cardiomyopathies (NICM) remains challenging despite guideline-based phenotypic classification using multimodal diagnostics including endomyocardial biopsy (EMB). We aimed to identify EMB-derived histological and molecular markers that improve phenotypic characterization and long-term risk stratification in patients with NICM.</p><p><strong>Methods: </strong>In this prospective cohort study, 703 consecutive patients with symptomatic NICM underwent standardized multimodal evaluation, including clinical assessment, cardiac imaging, and endomyocardial biopsy. Biopsy specimens were analyzed using histology, immunohistochemistry, and targeted myocardial mRNA profiling. Associations between endomyocardial markers, and fibroinflammatory remodeling, imaging parameters, and molecular signatures were assessed cross-sectionally. Long-term prognostic relevance was evaluated using survival and multivariable prediction analyses during follow-up of up to fifteen years for all-cause mortality, cardiovascular mortality, implantable cardioverter-defibrillator (ICD) implantation, and appropriate ICD discharge.</p><p><strong>Results: </strong>Elevated myocardial Gremlin-1 expression was associated with increased fibrosis, adverse cardiac remodelling, reduced left ventricular function, and enrichment of pro-fibrotic and inflammatory mRNA signalling pathways. Myocardial and circulating Gremlin-1 expression was independently associated with all-cause and cardiovascular mortality, and ICD implantation and discharge. Machine learning-based phenotyping using histological EMB data identified Gremlin-1 as a key predictive feature of poor prognosis. Incorporation of Gremlin-1 into predictive models significantly improved long-term cardiovascular risk stratification in NICM patients.</p><p><strong>Conclusion: </strong>Our results unveil that Gremlin-1 is associated with inflammation and cardiac remodelling in patients with NICM, and patients with Gremlin-1⁺ EMB and high plasmatic Gremlin-1 concentrations are at elevated risk to develop adverse cardiovascular events. Thus, the histological evaluation of Gremlin-1 may help to improve risk discrimination and management of NICM and HF patients.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378277","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}