European Journal of Clinical Investigation最新文献

{"title":"Identification of miR-150-5p in Human Amniotic Membrane Mesenchymal Cell-Derived Extracellular Vesicles as a Novel Mechanism Driving Cardioprotection.","authors":"Nunzio Alcharani, Laura Tesoro, Javier Díez-Mata, José Luis Zamorano, Marta Saura, Maite Iglesias, Carlos Zaragoza","doi":"10.1111/eci.70212","DOIUrl":"10.1111/eci.70212","url":null,"abstract":"<p><strong>Background: </strong>Human amniotic membrane mesenchymal stem cells (hAMSCs) hold strong cardioprotective potential, yet their mechanisms of action remain largely elusive.</p><p><strong>Methods and results: </strong>C57BL/6 mice were subjected to cardiac ischemia/reperfusion (I/R) and received intravenous (IV) 2 × 10⁵ hAMSCs at 2, 7 or 14 days post-reperfusion. Cardiac function and MIAT/miR-150/HOXA4 signalling were assessed. Mice treated 2 days post-I/R markedly improved LVEF and reduced myocardial necrosis and fibrosis by Day 21. Minimal hAMSC engraftment, evidenced by SSEA-4 immunostaining, suggests paracrine rather than direct cellular effects. Guided by GWAS implicating miRNAs in myocardial infarction, we identified miR-150 as a key effector, finding that hAMSC upregulated cardiac miR-150 and suppressed HOXA4, a profibrotic target in ischemic myocardium. In parallel, hAMSC treatment reduced cardiac MIAT, a lncRNA that sequesters miR-150, uncovering a mechanism of cardioprotection via MIAT downregulation post-reperfusion. Notably, CRISPR-Cas9 miR-150-silenced hAMSC exhibited severely impaired cardioprotective effects compared to wild-type cells, confirming the functional role of miR-150. miR-150 was identified as a key extracellular vesicle (EV) cargo released by hAMSC under hypoxic conditions, both in vitro and in hAMSC-injected I/R mice. Strickingly, administration of miR-150-enriched EVs to mice recapitulated the therapeutic benefits of hAMSC, underscoring miR-150-5p as central mediator of hAMSC-iduced cardioprotection.</p><p><strong>Conclusions: </strong>hAMSCs promote cardioprotection following I/R via the MIAT/miR-150-5p/HOXA4 axis, in which miR-150-5p plays a central role. These findings provide loss-of-function evidence about the therapeutic potential of hAMSC-derived EVs as a novel cell-free exosome-based strategy for the treatment of acute myocardial infarction.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70212"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Apnoea Variability in Pacemaker Patients: A Women-Predominant Phenotype.","authors":"Philipp Spitaler, Valentin Bilgeri, Gudrun Feuchtner, Patrick Rockenschaub, Fabian Barbieri, Birkan Tugrul, Agne Adukauskaite, Markus Stühlinger, Bernhard Erich Pfeifer, Sabine Ludwig, Peter Willeit, Axel Bauer, Wolfgang Dichtl","doi":"10.1111/eci.70219","DOIUrl":"10.1111/eci.70219","url":null,"abstract":"<p><strong>Study objectives: </strong>Single-night polysomnography assumes stable sleep apnoea (SA) severity; night-to-night variability may identify clinically relevant phenotypes, particularly in women. Sex/gender-specific longitudinal phenotypes were characterised using device-detected respiratory disturbance index (RDI) and an instability metric independent of mean severity.</p><p><strong>Methods: </strong>Pacemaker patients in the prospective ACaSA study with at least 180 valid nightly RDI measurements after a 30-day post-implant period were analysed. Severity was summarised by mean RDI. Variability was summarised by an Instability Index (residual from the log-log regression of RDI standard deviation on mean RDI). Phenotypes were defined by mean RDI (< 20 vs. ≥ 20 events/h) and instability (above vs. below median).</p><p><strong>Results: </strong>About 37,260 nights from 207 patients (median age 76 years, IQR [69-81]) were analysed. Four phenotypes were identified: Mild-Stable (n = 68), Mild-Unstable (n = 67), Severe-Stable (n = 35), and Severe-Unstable (n = 37). Women comprised 37.7% of the total cohort and they were disproportionately overrepresented in the Mild-Unstable versus in the Mild-Stable phenotype (61.2% vs. 33.8%; p = 0.002). Among patients with mean RDI < 20 (n = 135), female sex/gender (adjusted OR 3.38, 95% CI 1.60-7.40; p = 0.002) and obesity (BMI ≥ 30 kg/m²; adjusted OR 3.80, 95% CI 1.31-12.53; p = 0.019) were independent predictors of the Mild-Unstable phenotype. Mild-Unstable had more severe-range nights (RDI ≥ 20/h) than Mild-Stable (7.8% vs. 2.2%; p < 0.001). Severe-Unstable recorded RDI < 20/h on 33.9% of nights versus 13.9% in Severe-Stable (p < 0.001).</p><p><strong>Conclusion: </strong>Night-to-night variability identifies longitudinal SA phenotypes not captured by mean RDI. A female- and obesity-predominant Mild-Unstable phenotype shows intermittent severe-range nights despite low average burden, while instability in severe SA increases the likelihood of underestimating severity when classification is based on a single-night test.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70219"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulse Wave Velocity, Mortality and Cardiovascular Disease in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.","authors":"Carlos Pascual-Morena, Silvana Patiño-Cardona, Miriam Garrido-Miguel, Irene Martínez-García, Maribel Lucerón-Lucas-Torres, Héctor Martínez-Martínez, Elena Moreno-Charco, José Alberto Martínez-Hortelano","doi":"10.1111/eci.70222","DOIUrl":"10.1111/eci.70222","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is mediated by arterial stiffness. Pulse wave velocity (PWV), as measured by the aortic (aPWV), brachial-ankle (baPWV) and carotid-radial (crPWV) indices or estimated by equations (ePWV), could be a powerful predictor of clinical events and mortality in this population. This study aimed to analyse the association between PWV and all-cause mortality, cardiovascular mortality, and cardiovascular disease (CVD) risk in populations with CKD.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed, Scopus, and Web of Science from inception to January 2026. Observational studies estimating the association between PWV, categorically or by an increase of 1 m/s, and the outcomes of interest were included. Random-effects meta-analyses were performed, considering the type of PWV studied. The results are presented as hazard ratios (HR) and their 95% confidence intervals (95% CI).</p><p><strong>Results: </strong>Twenty-eight studies were included in the systematic review, and 22 in the meta-analyses. Considering a 1 m/s increase in aPWV, HRs of 1.16 (95% CI: 1.06, 1.28), 1.36 (95% CI: 1.15, 1.61), and 1.20 (95% CI: 1.02, 1.41) were found for all-cause mortality, cardiovascular mortality, and CVD risk, respectively. The remaining associations for aPWV, baPWV, and ePWV were categorical and tended to be higher.</p><p><strong>Conclusions: </strong>Increased PWV was associated with an increased risk of mortality and CVD. However, given the low quality of the current evidence base, these findings should be interpreted with caution and more rigorous studies are needed to confirm their usefulness in clinical practice.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70222"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13170642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why Osteosarcopenia Matters: Clinical and Investigative Implications.","authors":"Erik Luiz Bonamigo, Marcella Nora Maia, Renata Pinheiro Cavallaro de Oliveira, Régis Gemerasca Mestriner, Ivan Aprahamian, Gustavo Duque","doi":"10.1111/eci.70221","DOIUrl":"10.1111/eci.70221","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcopenia, the combination of osteoporosis and sarcopenia, is a geriatric syndrome linked to functional decline, falls, and fragility fractures. The interaction among bone, muscle, and their shared pathophysiology is driven by mechanical, metabolic, and hormonal factors. With global population aging and increasing healthcare demands, early detection of osteosarcopenia has become essential.</p><p><strong>Methods: </strong>This narrative review summarizes current evidence on the epidemiology, pathophysiology, clinical findings, diagnosis, and treatment of osteosarcopenia, based on international consensus guidelines, large-scale population cohorts, interventional studies, and translational research.</p><p><strong>Results: </strong>The occurrence of osteosarcopenia reflects the combined impact of low bone mineral density (BMD), loss of muscle mass and strength, and age-related metabolic changes such as chronic inflammation, lipotoxicity, and disruptions in tryptophan (TRP) metabolism. Diagnostic evaluation requires combining bone assessment through Dual-energy X-ray Absorptiometry with functional and structural evaluations of sarcopenia, using criteria established by the European and global consensus on Sarcopenia. Management includes established pharmacological therapies for osteoporosis, while for sarcopenia, to date, it is mainly based on resistance exercise and adequate protein intake. Supplementation with protein, leucine, vitamin D, calcium, and creatine may further enhance outcomes. Promising emerging strategies include hormonal modulators, anti-inflammatory agents, metabolic pathway-oriented therapies, and cell-based interventions.</p><p><strong>Conclusions: </strong>Osteosarcopenia significantly raises the risk of falls, fractures, disability, and death. Effective management requires a comprehensive treatment approach that targets both bone and muscle decline. Further research is necessary to refine diagnostic criteria and assess the success of combined interventions through clinical trials.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70221"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits of Dietary Nitrate in Cognitive Decline Associated With Type 2 Diabetes: Pathways and Therapeutic Potential.","authors":"Joao S Gonçalves, Ana Marçal, João Laranjinha, Cátia F Lourenço","doi":"10.1111/eci.70223","DOIUrl":"10.1111/eci.70223","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycaemia, which are associated with a high risk of developing several complications, including cognitive dysfunction. Cognitive decline is particularly prevalent in T2DM, encompassing deficits in memory, executive function and information processing speed, which ultimately impact quality of life. The molecular mechanistic and cellular pathways linking T2DM and cognitive dysfunction are complex and multifactorial, involving hyperglycaemia-induced oxidative distress, chronic inflammation, vascular dysfunction and impaired insulin signalling in the brain.</p><p><strong>Methods: </strong>In this review, we examine how these interconnected pathways compromise key neuronal and vascular processes essential to maintaining brain proper functioning. Moreover, we explore how emerging evidence suggests that dietary nitrate, found abundantly in vegetables like beetroot and spinach, may offer innovative therapeutic benefits for individuals with T2DM. Finally, we discuss pre-clinical and clinical evidence, addressing challenges specific to T2DM populations that may influence the outcomes of nitrate interventions and highlighting future perspectives for leveraging dietary nitrate as a therapeutic innovative strategy to improve cognitive health in T2DM.</p><p><strong>Results: </strong>Emerging evidence suggests that once ingested, dietary nitrate may act as a bioprecursor of nitric oxide (˙NO), playing a pivotal role in promoting glucose homeostasis, mitigating oxidative distress and inflammation and improving vascular function, mechanisms that collectively counteract the drivers of cognitive decline in T2DM.</p><p><strong>Conclusions: </strong>Dietary nitrate represents a promising nutritional strategy to target mechanisms underlying T2DM-associated cognitive dysfunction. Nevertheless, further studies are required to clarify its therapeutic efficacy, optimal intervention protocols and long-term impact on cognitive health in T2DM.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70223"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prehospital Risk Stratification Using Unsupervised Machine Learning in STEMI.","authors":"Ana Ramos-Rodríguez, Raúl López-Izquierdo, Carlos Del Pozo Vegas, María Plaza-Martín, Cristina Tapia-Ballesteros, Juan F Delgado Benito, Ancor Sanz-García, Francisco Martín-Rodríguez","doi":"10.1111/eci.70214","DOIUrl":"10.1111/eci.70214","url":null,"abstract":"<p><strong>Background: </strong>ST-elevation myocardial infarction (STEMI) exhibits substantial clinical heterogeneity complicating prehospital risk stratification. Traditional risk assessment tools often fail to capture the complexity of this condition. Machine learning offers opportunities to identify complex clinical patterns not readily apparent during prehospital care.</p><p><strong>Aim: </strong>To identify distinct phenotypes in STEMI patients using unsupervised machine learning algorithms based on prehospital parameters, and to determine their association with short-term mortality and cardiovascular outcomes.</p><p><strong>Methods: </strong>Prospective multicenter observational cohort study including adult patients with prehospital STEMI code activation transported by emergency medical services from January 2022 to August 2025. Only EMS-transported patients were included; those who self-presented to the emergency department were excluded. Prehospital variables, including demographic, clinical, and procedural data, were used for clustering. Factor Analysis of Mixed Data and a two-step clustering: hierarchical clustering (exploring structure and number of clusters) and k-means (clustering assigning patients to phenotypes). A Random Forest classifier with SHapley Additive exPlanations values was used to identify variables contributing to cluster assignment. The primary outcome was 30-day all-cause mortality, assessed through follow-up records.</p><p><strong>Results: </strong>Among 744 patients (median age, 65 years; 76.3% male) unsupervised clustering identified three distinct phenotypes: Phenotype-1 (70.3%) characterized by hemodynamic stability, vessel locations, Killip class I presentation (70.6%), and favourable laboratory parameters; Phenotype-2 (24.3%) presented higher comorbidity burden and metabolic derangements; and Phenotype-3 (5.4%) exhibiting profound hemodynamic instability, severe respiratory failure, out-of-hospital cardiac arrest with return of spontaneous circulation (87.5%), Killip class IV presentation (67.5%), and marked metabolic derangements. The 30-day mortality rates were: 3.4% in Phenotype-1, 22.1% in Phenotype-2, and 75.0% in Phenotype-3.</p><p><strong>Conclusions: </strong>Three clinically distinct STEMI phenotypes were identified with markedly different mortality risks and treatment requirements during prehospital care. Phenotypes derived from readily available prehospital parameters may facilitate early risk stratification, optimize triage decisions, and guide individualized therapeutic strategies.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70214"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metagenomic profiling of bile in malignant cholestasis: Analysis of samples collected during EUS-guided biliary drainage.","authors":"Łukasz Krupa, Georges P Schmarz, Robert Staroń, Hartmut H Schmidt, Jacqueline Rehner, Sören L Becker, Marcin Krawczyk","doi":"10.1111/eci.70200","DOIUrl":"https://doi.org/10.1111/eci.70200","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70200"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Recommendations for Anticoagulation in Patients With Atrial Fibrillation.","authors":"Nicolas Johner, Baris Gencer","doi":"10.1111/eci.70224","DOIUrl":"10.1111/eci.70224","url":null,"abstract":"<p><strong>Background: </strong>The lifetime risk of stroke among non-anticoagulated patients with atrial fibrillation (AF) approximates 1 in 3. Oral anticoagulation (OAC) reduces stroke and systemic embolism by at least two thirds and mortality by one fourth.</p><p><strong>Methods: </strong>The present narrative review summarizes current evidence and practical recommendations on OAC in AF and highlights recent advances and remaining gaps in knowledge.</p><p><strong>Results: </strong>The threshold for net clinical benefit of OAC is met when stroke risk exceeds 1%-2% per year, typically corresponding to ≥ 1 traditional stroke risk factor (CHA₂DS₂-VA ≥ 1), with increasing risk per additional risk factor. OAC also appears beneficial in device-detected (subclinical) AF, possibly at higher CHA₂DS₂-VA scores. Direct oral anticoagulants (DOACs) reduce intracranial haemorrhage compared to vitamin K antagonists (VKAs), and meta-analyses of randomized trials showed further reduction in stroke and mortality with DOACs, including in the elderly and chronic kidney disease. VKAs are preferred in patients with mechanical heart valves, mitral stenosis, antiphospholipid syndrome and Child-Turcotte-Pugh C cirrhosis. Modifiable bleeding risk factors should be assessed periodically and mitigated. These include anti-inflammatory drugs, antiplatelet therapy, drug interactions, excessive alcohol consumption, uncontrolled hypertension, diabetes, risk factors for gastrointestinal bleeding, major organ dysfunction and frailty. There are very few contraindications to OAC and most are relative or temporary conditions. Follow-up involves reassessing adherence, thrombotic and bleeding risk, co-medication and dosing. Integrated patient-centred AF management additionally involves risk factor management, symptom control and dynamic reassessment. Lifelong OAC is currently recommended, but recent data suggested that discontinuing OAC after successful catheter ablation of AF and/or left atrial appendage closure could be safe. OAC in specific settings is discussed, including cardioversion, catheter ablation, surgery, post-operative AF, elderly patients, pregnancy and bleeding.</p><p><strong>Conclusion: </strong>OAC is the cornerstone of thromboembolism prevention in AF, but knowledge gaps remain, including on risk stratification, device-detected AF, trigger-induced AF, cardioversion, OAC resumption after major bleeding, and potential safety of OAC discontinuation after successful catheter ablation or left atrial appendage occlusion.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70224"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifelong Exercise as a Modulator of CD4⁺ T Cell Immunometabolism.","authors":"Bruna Spolador de Alencar Silva, Amanda Veiga Sardeli, Ricardo R Agostinete, Helena Batatinha, Alessandra Peres, José César Rosa-Neto, José Teixeira, Manuel J Coelho-E-Silva, Paulo J Oliveira, Fábio Santos Lira","doi":"10.1111/eci.70204","DOIUrl":"10.1111/eci.70204","url":null,"abstract":"<p><strong>Background: </strong>It is commonly assumed that aging and chronic low-grade inflammation compromise adaptive immunity, particularly the function and metabolism of CD4⁺ T cells. The preceding are key regulators of immune responses. These immunological alterations contribute to increased susceptibility to infections, diminished vaccine efficacy and the progression of age-related diseases. In contrast, adolescence and young adulthood tend to be characterized by more robust immune responses, though these are heavily influenced by modifiable lifestyle factors such as habitual physical activity, level of cardiorespiratory fitness, diet and body adiposity. Emerging evidence suggests that sustained physical activity throughout life may preserve CD4⁺ T cell competence by favourably modulating their metabolic programming.</p><p><strong>Methods: </strong>The current narrative review explores how lifelong physical exercise impacts CD4⁺ T cell metabolism, with particular emphasis on the developmental window of adolescence and the long-term benefits of early and sustained physical training across the lifespan. Molecular mechanisms linking exercise to metabolic reprogramming of T cells were summarised in parallel with attenuation of immunosenescence and inflammation over the lifespan.</p><p><strong>Results: </strong>This review suggests that lifelong exercise may reprogram CD4⁺ T cell metabolism, enhancing oxidative phosphorylation at rest and glycolytic control upon activation, thereby improving Th17/Treg balance, reducing chronic inflammation and enabling effective effector T cell responses. In this context, exercise initiated early in life may act as a critical modulator by promoting optimal immune function from childhood and establishing a functional peak that helps preserve immune competence during aging.</p><p><strong>Conclusions: </strong>Lifelong and early-life exercise may reprogram CD4⁺ T cell metabolism, strengthening immune balance and preserving immune function during aging.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70204"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplantation's Paradox: Life-Saving Procedure, Life-Changing Risks: An Editorial on 'Colorectal Cancer in Heart Transplant Recipients'.","authors":"Valentin Dupasquier, François Roubille","doi":"10.1111/eci.70229","DOIUrl":"https://doi.org/10.1111/eci.70229","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70229"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}