BMC Medicine最新文献

{"title":"Behavior change support in the new era of obesity care.","authors":"Brunna Boaventura, Stuart W Flint","doi":"10.1186/s12916-026-05167-2","DOIUrl":"10.1186/s12916-026-05167-2","url":null,"abstract":"","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-155-5p drives coordinated tumor and macrophage reprogramming across multiple cancer entities.","authors":"Theresa Kordaß, Ann-Katrin Schlosser, Marijan Czygan, Luisa Vieira Codeco Marques, Melisa Wartusch, Eric Nerenz, Vincencia Stefanie Muliawan, Stephan Kersting, Wolfram Osen, Stefan B Eichmüller","doi":"10.1186/s12916-026-05146-7","DOIUrl":"10.1186/s12916-026-05146-7","url":null,"abstract":"<p><strong>Background: </strong>T cell-based immunotherapies have improved cancer treatment, however their efficacy is frequently limited by tumor-intrinsic resistance mechanisms and by the immune suppressive tumor microenvironment, counteracting tumor specific immune responses through impaired antigen presentation and the accumulation of M2-like tumor-associated macrophages. MicroRNAs have emerged as regulators of tumor cell - immune cell interactions, yet the miRNAs' capacity to coordinate anti-tumor effects across different cell types is poorly understood. This study aimed to investigate whether miR-155-5p and miR-3535 represent regulators capable of driving coordinated functional reprogramming of both, tumor cells and macrophages.</p><p><strong>Methods: </strong>Human tumor cell lines of various cancer entities were transfected with miR-155-5p or miR-3535 and the resulting effects on immune checkpoint molecule expression and tumor cell proliferation were assessed on transcriptional and functional level. Similarly, human PBMC-derived M2 polarized macrophages were transfected with the same microRNAs, followed by analysis of the cytokine secretion patterns and by transcriptomic profiling to evaluate the macrophage polarization states and the immune-regulatory pathways involved. Transcription factor activity and pathway enrichment analyses were performed to identify the regulatory mechanisms affected.</p><p><strong>Results: </strong>Both miR-155-5p and miR-3535 reduced expression of the immune checkpoint molecule CD73 (NT5E) in tumor cells, while miR-155-5p additionally suppressed PD-L1 (CD274) expression. At the same time, both microRNAs reprogrammed M2-like macrophages toward a pro-inflammatory M1-like phenotype, characterized by increased TNFα and CXCL10 secretion and the induction of M1-associated gene expression. Transcriptomic analysis revealed activation of STAT1/IRF-driven inflammatory pathways and a reduced activity of ZNF703, representing a transcriptional hub associated with M2 macrophage infiltration and poor prognosis. Both microRNAs increased TAP1 expression, suggesting enhanced antigen-processing capacity. Furthermore, miR-155-5p and miR-3535 exerted anti-proliferative effects across cell lines of various tumor entities.</p><p><strong>Conclusions: </strong>miR-155-5p and miR-3535 modulate tumor-intrinsic immune checkpoint expression and functional macrophage polarization in a coordinated way, linking tumor cell plasticity to neutralization of the immunosuppressive tumor environment. These findings highlight the potential of coordinated microRNA-mediated regulation via different cell types to overcome immune resistance mechanisms in tumors and support further investigation of microRNA-based strategies in cancer immunotherapy.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conflicting evidence for continuous glucose monitoring in gestational diabetes: current challenges and the imperative for individual participant data meta-analysis.","authors":"Ina Geerts, Catherine Yu, Nina Embo, Katrien Benhalima","doi":"10.1186/s12916-026-05191-2","DOIUrl":"10.1186/s12916-026-05191-2","url":null,"abstract":"<p><strong>Background: </strong>The incidence of gestational diabetes mellitus (GDM) is rising along with rates of obesity and type 2 diabetes. GDM is associated with an increased risk of various short- and long-term complications for both mother and child, including type 2 diabetes. Managing GDM requires a multidisciplinary approach that includes dietary guidance, promoting regular physical activity, and performing self-monitoring of blood glucose (SMBG). Continuous glucose monitoring (CGM) has transformed pregnancy care in women with type 1 diabetes and is increasingly being proposed as a strategy to improve glycaemic management in GDM. By capturing postprandial glucose excursions, glycaemic variability, and time in range, CGM provides a more detailed picture of glycaemia and has raised expectations of improved metabolic control and pregnancy outcomes.</p><p><strong>Main body: </strong>Despite these theoretical advantages, evidence for CGM in GDM remains conflicting. More recently, several large randomized controlled trials (RCT's) show conflicting data: some studies show modest improvements in glycaemic measures, whereas others report no clear benefit for key maternal or neonatal outcomes, leaving the clinical value and cost-effectiveness of CGM unclear. A major limitation is the absence of validated CGM-based glycaemic targets specific to GDM, and current guidelines offer little direction beyond conventional SMBG guidelines. Future research should prioritize adequately powered large RCT's representing a broad population, and, importantly, individual participant data meta-analyses to reconcile inconsistent findings, identify subgroups most likely to benefit, establish pregnancy-specific CGM thresholds, and evaluate the impact on both obstetric outcomes and long-term postpartum metabolic risk.</p><p><strong>Conclusions: </strong>This ongoing debate underscores the need to critically appraise the role of CGM in GDM, summarize results from completed RCT's and meta-analyses, recognize key methodological and clinical evidence gaps, and outline the steps required for CGM to become fully integrated into standard GDM care.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-suicidal self-injury and other key predictors of suicide deaths among children and adolescents in England: a population-based case-control study.","authors":"Ben Hoi-Ching Wong, David Odd, Karen Luyt, Vicky Sleap, Sylvia Stoianova, Tom Williams, Samantha Drew, Camilla Parker, Joan Asarnow, Dennis Ougrin","doi":"10.1186/s12916-026-05170-7","DOIUrl":"10.1186/s12916-026-05170-7","url":null,"abstract":"<p><strong>Background: </strong>Suicide is a leading cause of mortality in young people globally. A history of prior self-harm, with or without suicidal intent, is associated with increased risks of future suicide attempts (SAs) or suicides. While non-suicidal self-injury (NSSI) is likely a predictor of SA, its particular association to suicide deaths remains unexplored.</p><p><strong>Methods: </strong>This is a population-based case-control study in England. Cases were all individuals who died by suicide before their 18th birthday (n = 240), between April 2019 and March 2021. Controls (n = 240) were age- and sex-matched individuals who died from other unexpected causes. Conditional logistic regression was used to estimate odds ratios for self-harm history and other risk factors, adjusting for ethnicity and socioeconomic deprivation. A fully adjusted multivariable model was formed to estimate associations between each risk factor and suicide death, adjusting for all measured factors.</p><p><strong>Results: </strong>A history of NSSI was strongly associated with subsequent suicide death (partially adjusted OR, 27.8; 95% CI, 9.5-81.0; fully adjusted OR, 9.2; 95% CI, 2.1-39.5). The association remained significant in sensitivity analyses restricted to those with only NSSI history without SA (partially adjusted OR, 7.7; 95% CI, 3.6-16.5). History of SA was also significant (adjusted OR, 64.2; 95% CI, 8.8-468; fully adjusted OR, 12.3; 95% CI, 0.4-357). Notably, 42.6% of suicides occurred in individuals without previous self-harm, and 71% of suicides occurred on the first documented act of intentional self-injury or self-poisoning. MDMA was recorded in 14 suicide cases, and alcohol use in 34 suicide cases, regardless of whether the intake resulted in overdose. Fully adjusted model found that known NSSI history, known suicidal ideation history, and bullying victimization remained independently associated with suicide death.</p><p><strong>Conclusions: </strong>NSSI and SA are both major predictors for suicide in young people. Risk assessments should aim to include all significant factors. These findings highlight the need for holistic clinical screening for all forms of self-harm regardless of intent, indicated suicide prevention intervention for those identified, and enhanced access to mental health services.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic immune activation in hereditary cancer predisposition syndromes: a cross-sectional study.","authors":"István Kelemen, Klaudia Horti-Oravecz, Anikó Bozsik, Tímea Pócza, János Papp, István Likó, Patrícia Neuperger, Fanni Balogh, Ágnes Kemény, Petra Nagy, Viktória Vereczki, Szonja Polett Pósa, Lőrinc Sándor Pongor, Dorottya Kövesdi, Henriett Butz, Attila Patócs, Gábor János Szebeni, Vince Kornél Grolmusz","doi":"10.1186/s12916-026-05188-x","DOIUrl":"10.1186/s12916-026-05188-x","url":null,"abstract":"<p><strong>Background: </strong>Immune surveillance mechanisms contribute to the elimination of precancerous lesions in hereditary cancer predisposition syndromes (HCPSs).</p><p><strong>Methods: </strong>By combining single-cell transcriptomics, multiparametric mass cytometry and cytokine profiling of the systemic immune environment in 391 individuals among whom 227 are living with HCPSs we investigated phenotypic alterations in cancer-free individuals with HCPS.</p><p><strong>Results: </strong>A decrease in peripheral B cell abundance and their more differentiated phenotype have been confirmed both in breast cancer patients with germline pathogenic variants in BRCA1 (gpath(BRCA1)) and in patients living with Lynch syndrome (LS). Pre-cancer women with gpath(BRCA1) exhibited an activated phenotype of multiple immune cell lineages, similar to those with manifest disease. In LS, B cell phenotypes exhibited the largest changes in response to cancer eradication, while increased peripheral IL-6 levels was detected even in presymptomatic individuals with LS.</p><p><strong>Conclusions: </strong>HCPS-specific differences in the phenotype of the systemic immune system might be leveraged in future risk-reducing strategies.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JP1 peptide modulates oxidative stress and autophagy via Keap1-Nrf2-ARE in ALS model mice.","authors":"Yu Zhang, Yaxi Liu, Shiyu Shi, Qingyang Li, Yani Huo, Pan You, Mingzhu Shu, Xi Cheng, Jun Zhang, Dong Liang, Aihua Zhang, Chao Lu, Bin Shen, Jianwei Zhou, Qi Niu","doi":"10.1186/s12916-026-05119-w","DOIUrl":"10.1186/s12916-026-05119-w","url":null,"abstract":"<p><strong>Background: </strong>The simultaneous modulation of oxidative stress and autophagy represents a potential therapeutic strategy for amyotrophic lateral sclerosis (ALS), yet agents capable of coordinately regulating both processes remain scarce. The Keap1‑Nrf2‑ARE pathway serves as a critical hub linking redox homeostasis and autophagic regulation, making it an attractive target for ALS intervention. JWA is a stress‑responsive protein involved in cellular protection against oxidative injury, and its neuroprotective effects have been shown to depend on activation of the MEK/ERK‑Nrf2 axis. JP1 is a functional oligopeptide derived from the JWA protein that has been engineered to cross the blood-brain barrier and specifically target integrin αVβ3. Based on the link between JWA and Nrf2 signaling, we hypothesized that JP1 activates the Keap1‑Nrf2‑ARE pathway to coordinate antioxidant defense and autophagic clearance. Here, we evaluated this hypothesis in the SOD1‑G93A mouse model, a well‑established transgenic model of familial ALS, and elucidated the underlying mechanisms.</p><p><strong>Methods: </strong>We evaluated the efficacy of JP1 in the SOD1-G93A mice model using behavioral phenotyping and survival analysis. The coordinated mechanism was investigated in spinal cord tissues by profiling the Keap1-Nrf2-ARE pathway and oxidative stress, quantifying autophagic flux (by Western blotting and transmission electron microscopy) and neuronal apoptosis, and evaluating histology (by Nissl staining and immunofluorescence). Integrated transcriptomic and proteomic analyses further elucidated the global molecular landscape underlying the therapeutic effects of JP1.</p><p><strong>Results: </strong>JP1 treatment ameliorated motor deficits and extended survival in SOD1-G93A mice without adversely affecting liver or kidney function. JP1 crossed the blood-brain barrier, targeted motor neurons expressing integrin αVβ3, and activated the ERK pathway. This promoted Keap1/Cul3 degradation and Nrf2 nuclear translocation, thereby activating the Keap1-Nrf2-ARE pathway to alleviate oxidative stress. Concurrently, JP1 restored autophagic flux, increased autophagic activity, attenuated motor neuron injury, suppressed neuronal apoptosis, and preserved neuronal structural integrity. The Nrf2 inhibitor ML385 reversed the protective effects of JP1 on survival, motor function, autophagy, oxidative stress, and neuronal apoptosis, which confirms that JP1 acts via the Nrf2 pathway.</p><p><strong>Conclusions: </strong>JP1 acts as a promising coordinator of antioxidant and autophagic processes by targeting the Keap1-Nrf2-ARE pathway, thus highlighting its therapeutic potential for ALS.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postpartum GLP-1 receptor agonists and SGLT-2 therapies in women with prior gestational diabetes: current evidence and uncertainties.","authors":"Yana Vanlaer, Ester Van de Cauter, Nina Embo, Katrien Benhalima","doi":"10.1186/s12916-026-05182-3","DOIUrl":"10.1186/s12916-026-05182-3","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies and is associated with adverse pregnancy outcomes and a substantially increased risk of long-term cardiometabolic disease. Although glucose levels often normalise postpartum, women with prior GDM have a ten-fold increased risk of developing type 2 diabetes mellitus (T2DM), particularly when early postpartum prediabetes is present. Current prevention strategies, including lifestyle modification and metformin, have in general shown limited effectiveness in this high-risk population.</p><p><strong>Main body: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve glycaemic control, promote weight loss, and reduce cardiovascular risk in people with T2DM and/or obesity. Given the central role of insulin resistance and weight retention in progression from GDM to T2DM, these therapies represent a promising strategy for postpartum diabetes prevention. However, available evidence in women with prior GDM is limited and largely derived from small, short-term studies not adequately powered to assess sustained diabetes prevention or long-term outcomes. Whether GLP-1 RA therapy should be considered an early preventive strategy in this high risk population remains therefore uncertain. The evidence base is now evolving, with the first large multicentre randomised controlled trial (RCT) with a potent GLP-1 RA in women with early postpartum prediabetes following GDM currently underway. In parallel, sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated robust cardiovascular and renal benefits in T2DM, independent of glycaemic status, and may offer additional preventive potential. Their insulin-independent mechanism and favourable cardiovascular profile are particularly attractive in women with prior GDM, who face elevated long-term cardiometabolic risk. However, uncertainties persist regarding safety in women of reproductive age, use during lactation, optimal timing, and patient selection, highlighting the gap between therapeutic promise and dedicated postpartum trial data.</p><p><strong>Conclusion: </strong>This Debate examines the emerging role of GLP-1 RA and SGLT-2 inhibitors in preventing T2DM after GDM. Despite their potential, important uncertainties remain regarding long-term efficacy and safety. While these therapies may provide a shift beyond lifestyle intervention and metformin, robust trial data and careful consideration of reproductive factors are required before routine implementation. We discuss how pharmacological prevention strategies could be integrated into postpartum care for this high-risk population.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific signatures of fetal programming for gestational diabetes mellitus in umbilical cord: A cohort study from Tanzania.","authors":"Gad Hatem, Jonas Andersson, Line Hjort, Daniel T R Minja, Francesca Catellani, Sofie Lykke Møller, Olof Asplund, Dirk Lund Christensen, Birgitte Bruun Nielsen, Thor G Theander, Isabella Artner, Nael Shaat, John P A Lusingu, Allan Vaag, Ib Christian Bygbjerg, Christentze Schmiegelow, Louise Groth Grunnet, Rashmi B Prasad","doi":"10.1186/s12916-026-05158-3","DOIUrl":"10.1186/s12916-026-05158-3","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. Offspring of GDM mothers have an increased risk of developing type 2 diabetes (T2D), obesity, and other metabolic disorders later in life.</p><p><strong>Methods: </strong>We analyzed metabolic, genetic, epigenetic, and transcriptional profiles in umbilical cord blood (UCB) from male and female offspring of GDM mothers versus normoglycemic controls in Tanzania. We constructed polygenic and methylation risk scores for T2D and GDM to assess whether diabetes-related susceptibility is detectable at birth. We identified differentially expressed genes (DEGs) and corresponding epigenome-wide alterations in GDM-exposed UCB. We then integrated genetic (PGS), epigenetic (MRS), and transcriptomic (DEG) data to identify convergent molecular signatures of GDM exposure. We examined their associations with neonatal anthropometry and cord insulin levels to infer potential effects on early growth. We further assessed DEG relevance by examining expression in human fetal and adult islets and by reviewing mouse-knockout data to explore possible roles in β-cell development or function.</p><p><strong>Results: </strong>Offspring of GDM mothers showed sex-specific differences in neonatal anthropometry, particularly among females, who exhibited greater adiposity and growth measures. Female offspring also displayed higher PGS for T2D, especially β-cell dysfunction, and a MRS for GDM/T2D associated with elevated cord insulin. We identified 36 DEGs in GDM-exposed UCB overall, with a striking sex-specific pattern (273 DEGs in females vs. 4 in males). Several DEGs and associated DNA methylation (DNAm) sites correlated with neonatal anthropometry, particularly in females, indicating putative fetal programming signatures. These signals showed convergence across genetic risk, DNA methylation, and gene expression layers. The expression of SESN3, HMBS, NUTM2D, and MAN2A2 associated with insulin levels. MAN2A2 expression also associated with birth weight and length in female offspring. The SLC4A1 gene showed fetal pancreas-specific expression and co-expression with key pancreatic developmental genes, suggesting a role in pancreatic development.</p><p><strong>Conclusions: </strong>We identified integrated multi-omic signatures of GDM exposure in offspring at birth, with markedly stronger effects in females. These genes and pathways may contribute to fetal metabolic programming in this understudied Tanzanian population, offering new insights into biological mechanisms that may influence early development.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT02191683 Registered 2 July 2014.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microvascular remodeling and endothelial dysfunction across the post-COVID-19 spectrum: a prospective observational case-control study.","authors":"Timon Wallraven, Roman Günthner, Isabelle Lethen, Andrea Ribeiro, Maciej Lech, Frederike Cosima Oertel, Lukas Gabriel Reeß, Bernhard Haller, Lukas Streese, Henner Hanssen, Michael Basta-Wunderle, Christoph Schmaderer","doi":"10.1186/s12916-026-05144-9","DOIUrl":"10.1186/s12916-026-05144-9","url":null,"abstract":"<p><strong>Background: </strong>Post-viral diseases, including post-COVID-19 syndrome (PCS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), cause substantial long-term morbidity. Persistent cardiovascular (CV) risk after acute infection highlights the need for accessible tools to quantify microvascular health.</p><p><strong>Methods: </strong>The \"All Eyes on PCS\" is a prospective observational study assessing the microcirculation using retinal vessel analysis (RVA). Both dynamic and static parameters (DVA and SVA) were compared across never SARS-CoV-2 infected individuals (NI, n = 96), SARS-CoV-2 recovered individuals (n = 102), and PCS patients (n = 102), including a subgroup fulfilling ME/CFS criteria (n = 62). Analyses were complemented by propensity score-based weighting and multivariable adjustment. Associations with symptom severity and circulating biomarkers of endothelial dysfunction and inflammation were examined.</p><p><strong>Results: </strong>PCS patients showed reduced venular flicker-induced dilation compared with recovered individuals (3.7% ± 2.2 vs. 4.8% ± 3.0, p = 0.006) and narrower retinal arterioles (CRAE) compared with both recovered (178.3 ± 15.5 μm vs. 186.1 ± 15.7 μm, p = 0.001) and NI individuals (184.4 ± 14.3 μm, p = 0.009). Arteriolar-to-venular ratio (AVR) was lower in PCS compared with NI (0.83 ± 0.06 vs. 0.87 ± 0.06, p < 0.001) and recovered participants (0.86 ± 0.07, p = 0.034). Findings remained largely consistent after age and sex balancing and adjustment for CV risk factors, although the association for AVR was attenuated. PCS patients fulfilling ME/CFS criteria showed the most pronounced retinal microvascular alterations, and a combined model discriminated ME/CFS patients with good accuracy (AUC = 0.79). Higher symptom burden was associated with lower AVR (r = - 0.21, p = 0.037), particularly for neurocognitive symptoms. IL-6, ICAM-1, and VCAM-1 were elevated in PCS and ME/CFS, and lower AVR was associated with inflammatory and iron-related markers (all adjusted p < 0.01).</p><p><strong>Conclusions: </strong>PCS is associated with persistent endothelial dysfunction, most pronounced in ME/CFS patients and linked to symptom severity and ongoing inflammation. These findings support the potential use of RVA as a non-invasive tool for assessing and monitoring endothelial health in post-viral syndromes, with implications for cardiovascular risk stratification.</p><p><strong>Trial registration: </strong>The All Eyes on PCS Study has previously been registered at ClinicalTrials.gov (NCT05635552).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-enhanced management system for secondary prevention of coronary heart disease: a randomized clinical trial.","authors":"Zhengqing Ba, Jing Yuan, Sheng Zhao, Mengyuan Liu, Guangzhi Chen, Xiaodan Lian, Fei Yu, Yajing Su, Zuoxiang Wang, Lanshu Yang, Ximei Wang, Yang Wang, Xue Zhang, Wei Zhao, Xiaojin Gao, Yongjian Wu","doi":"10.1186/s12916-026-05135-w","DOIUrl":"10.1186/s12916-026-05135-w","url":null,"abstract":"<p><strong>Background: </strong>Secondary prevention of coronary heart disease (CHD) remains suboptimal due to fragmented care and therapeutic inertia. While digital health interventions offer a promising strategy, few existing tools provide comprehensive, closed-loop management of multidimensional risk factors without increasing clinician workload. This study aimed to evaluate the efficacy of an artificial intelligence (AI)-enhanced management system (AIM-CHD) in improving multidimensional risk factor control among patients with CHD.</p><p><strong>Methods: </strong>This single-center, open-label, parallel-group, randomized clinical trial was conducted from November 2024 to June 2025 in China. A total of 1100 adults with confirmed CHD were randomized 1:1 to receive either the AIM-CHD intervention (n = 549) or usual care (n = 551) for 3 months. The AIM-CHD system featured automated multi-source data capture, guideline-directed risk stratification, and closed-loop feedback via smartphone. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) level at 3 months. Secondary outcomes included goal attainment rates for LDL-C (< 70 mg/dL) and blood pressure (BP, < 130/80 mm Hg), glycated hemoglobin, smoking cessation, body mass index (BMI), medication adherence, and a composite cardiovascular endpoint at 3 months. Analysis was performed on an intention-to-treat (ITT) basis.</p><p><strong>Results: </strong>Of 1100 randomized participants (mean age 61 years; 75.3% male), 943 (85.7%) completed the 3-month follow-up. The intervention group achieved a significantly lower mean LDL-C level compared with the control group (60.4 ± 23.4 vs. 63.7 ± 26.0 mg/dL), with an adjusted mean difference of - 3.2 mg/dL (95% CI, - 6.2 to - 0.3; p = 0.03). Furthermore, participants in the intervention group were more likely to achieve the LDL-C target (71% vs. 64%; RR, 1.10; 95% CI, 1.01-1.20; p = 0.03) and the BP target (45% vs. 35%; RR, 1.27; 95% CI, 1.09-1.48; p = 0.002). No significant differences were observed for HbA1c, BMI, or medication adherence.</p><p><strong>Conclusions: </strong>The AIM-CHD system significantly improved short-term lipid and BP control compared with usual care. These findings support interoperable, low-burden digital management systems as a scalable strategy in routine secondary prevention.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT06686056. Registered on 11 November 2024.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}