BMC Medicine最新文献

{"title":"Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies.","authors":"Michael Siebers, Dana Huvermann, Christoph Siebers, Deborah Canales-Romero, Alexandra Florea-Ghile, Lina Keite, Lucas John, Moritz Munk, Roman Bizjak, Jens Witzel, Sebastian Schulz, Johannes Kirsten, Laura Bindila, Anke Hinney, Marijke Grau, Daniel A Bizjak, Harald Engler, Johannes Fuss","doi":"10.1186/s12916-026-05186-z","DOIUrl":"10.1186/s12916-026-05186-z","url":null,"abstract":"<p><strong>Background: </strong>Endocannabinoid (eCB) signaling has been implicated in the physiological and affective responses to endurance exercise, including phenomena such as the runner's high. However, although humans have the capacity to run for several hours and even days, evidence regarding eCB signaling is largely limited to exercise bouts shorter than 60 min. Consequently, the temporal dynamics of eCB signaling during prolonged running and the accompanying acute affective responses remain unclear.</p><p><strong>Methods: </strong>This study investigated eCB signaling during long-distance running and following a 45-minute break. Two studies were conducted: In Study 1, 19 trained runners completed both a marathon and a duration-matched walking session, with repeated blood sampling every 14 km during the marathon and after a 45-minute recovery. In Study 2, 36 ultramarathon runners completed races of 100 km, 160 km, or 230 km and provided blood samples before and after their respective races. Plasma concentrations of anandamide (AEA), 2-arachidonoylglycerol (2-AG), 1-AG, arachidonic acid (AA), and palmitoylethanolamide (PEA) were quantified by a standardized liquid chromatography/multiple reaction monitoring assay. Euphoria, anxiety, and pain were assessed as core features of the runner's high using visual analog scales.</p><p><strong>Results: </strong>AEA increased progressively throughout the marathon and remained elevated after 45 min, whereas walking elicited only modest changes. In line, after all ultramarathon distances AEA levels were increased compared with baseline. By contrast, an increase in 2-AG during exercise was observed only in the regular marathon, where concentrations rose significantly during the later stages of running and into early recovery. Elevated post-race 2-AG levels were also observed following all ultramarathon distances, consistent with a delayed, recovery-related response. Marathon running was associated with higher euphoria and lower anxiety than walking, while pain increased after 28 km of running. Ultramarathon running increased pain, reduced anxiety, and did not significantly alter euphoria post-exercise.</p><p><strong>Conclusions: </strong>Together, these findings show robust, time-dependent changes in circulating eCB concentrations during and after prolonged endurance running, as well as gradual increases in AEA during walking. These eCB dynamics occurred alongside acute affective changes during sustained endurance exercise.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872912","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":"Bladder cancer precision-cut tumor slices (PCTS) preserve functional immune microenvironment enabling ex vivo drug evaluation.","authors":"Sarah Richtmann, Maja Radak, Viktor Sincic, Jenny Hugoson, Nadja Werner, Valeriia Skoryk, Darcy Wagner, Fredrik Liedberg, Kristina Lundberg","doi":"10.1186/s12916-026-05173-4","DOIUrl":"10.1186/s12916-026-05173-4","url":null,"abstract":"<p><strong>Background: </strong>The development of effective cancer immunotherapies is hindered by the lack of preclinical models that faithfully preserve tumor-immune interactions. Current approaches provide limited representation of immune components, creating a critical translational gap between laboratory findings and clinical outcomes. Precision Cut Tumor Slices (PCTS) offer a promising solution by maintaining complete tumor architecture including native immune cell populations and spatial organization.</p><p><strong>Methods: </strong>We established a PCTS platform using fresh bladder cancer specimens and optimized culture conditions to preserve tissue integrity and cell viability. Comprehensive phenotyping was performed using flow cytometry to characterize tumor and immune cell populations. Immune functionality was validated through CD3/CD28 stimulation experiments measuring activation markers (CD69, CD137, HLA-DR) and cytokine secretion. Nine patient samples were treated with the PD-1 checkpoint inhibitor nivolumab to assess ex vivo effects. Additionally, multiplex immunofluorescence microscopy was employed on fixed PCTS as a readout for spatial distribution and cytotoxic effects of chemotherapy agents.</p><p><strong>Results: </strong>PCTS maintained viability of both cancer cells and diverse immune populations for up to six days. Functional validation demonstrated immune responsiveness upon T cell stimulation, with elevated activation markers and significantly increased secretion of inflammatory mediators including IFNγ and CXCL10, in treated as compared to control samples. The platform successfully addressed intra-tumor heterogeneity while maintaining experimental reproducibility across patient samples. Treatment with nivolumab revealed heterogeneous responses, with two out of nine samples (22%) demonstrating dose-dependent immune activation in the PCTS model, consistent with published response rates. Multiplex immunofluorescence analysis confirmed the ability to capture both immune-mediated responses and direct cytotoxic effects on cancer cells, enabling comprehensive evaluation of combination therapies.</p><p><strong>Conclusions: </strong>This validated PCTS platform represents a versatile human-derived tool for evaluating cancer immunotherapies while maintaining physiological tumor microenvironment complexity. The technical foundation established here enables future prospective studies correlating ex vivo responses with patient clinical outcomes, potentially advancing personalized treatment selection and reducing reliance on animal models in immunotherapy development.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872856","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":"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":"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":"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":"https://doi.org/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":"https://doi.org/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}

{"title":"Risk-adapted intervals for colorectal cancer screening using fecal immunochemical tests: a modelling study based on the BLITZ cohort.","authors":"Thomas Heisser, Teresa Seum, Michael Hoffmeister, Hermann Brenner","doi":"10.1186/s12916-026-05138-7","DOIUrl":"https://doi.org/10.1186/s12916-026-05138-7","url":null,"abstract":"<p><strong>Background: </strong>Established screening programs for colorectal cancer (CRC) based on fecal immunochemical tests (FITs) employ fixed screening intervals of either one year or two years for all participants. We aimed to assess the potential design of risk-adapted FIT screening intervals based on quantitative values of the fecal hemoglobin concentration among FIT negative participants.</p><p><strong>Methods: </strong>Using COSIMO, a previously validated simulation tool, we compared CRC risks in subgroups with initially negative FIT. Subgroups were stratified by stool hemoglobin levels at screening (< 8 (low), 8-<10 (medium), 10-<17 µg (high) Hb/g stool), a routinely available measure in FIT-based screening programs. Colorectal neoplasia prevalences at model start were informed by 6,661 screening colonoscopy participants in Germany at average CRC risk with negative FIT and available colonoscopy results (BLITZ study). Simulations were run for hypothetical cohorts of 100,000 individuals.</p><p><strong>Results: </strong>Of 6,661 FIT-negative participants, 6,016 (90%), 273 (4%), and 372 (6%) were in the low, medium, and high-negative subgroups, respectively. In those low-negative, expected cancer detection rates were 0.17%, 0.30%, 0.42%, 0.53%, and 0.62%, after screening intervals of 1, 2, 3, 4, and 5 years, respectively. Cancer detection rates among the small groups of medium- and high-negative patients were up to six times higher and exceeded the expected 2-year detection rates of the low-negative group already after 1 year of follow-up.</p><p><strong>Conclusions: </strong>Fecal hemoglobin concentrations among FIT negative participants may be a readily available, highly informative tool for defining risk-adapted annual or biennial FIT screening intervals.</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/PMC13488231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788322","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}