Iron is essential for cellular function and cancer growth. While iron imbalance has been implicated in cancer development, epidemiological evidence remains inconsistent. Erythropoietin (EPO) may influence tumour progression. We aimed to investigate the associations between iron status, EPO levels, and cancer incidence in the general population. Data were obtained from 6109 participants (mean age 52 ± 12 years; 49% male) in the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort. Iron biomarkers, including ferritin, transferrin saturation, soluble transferrin receptor (sTfR), hepcidin and EPO levels, were measured at baseline. Over a median 18.5 year follow-up, 1090 participants developed cancer. Multivariable Cox regression revealed that higher EPO (HR 1.26; 95% CI 1.07-1.47; p = 0.005) was associated with increased overall cancer risk, while elevated hepcidin levels were associated with a lower risk (HR 0.88; 95% CI 0.80-0.96; p = 0.006). Higher sTfR (HR 1.35; 95% CI 1.01-1.80; p = 0.043) was suggestive for an increased risk of overall cancer. After excluding early diagnoses, the increased risk associated with higher EPO levels and decreased risk associated with higher hepcidin levels remained significant. Lower transferrin saturation was associated with increased haematological cancer risk, while higher hepcidin was associated with reduced gastrointestinal cancer risk, especially in women and those with BMI < 25 kg/m2. In non-smokers, higher sTfR and EPO were associated with increased overall and kidney cancer. These findings underscore the putative roles of iron metabolism and EPO in cancer, with consistently decreased risks associated with elevated hepcidin levels, particularly among women and individuals with lower BMI.

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. The present narrative review summarizes current evidence and practical recommendations on OAC in AF and highlights recent advances and remaining gaps in knowledge. 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. 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.

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. 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. 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. 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.

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. 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. 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. Lifelong and early-life exercise may reprogram CD4+ T cell metabolism, strengthening immune balance and preserving immune function during aging.

Single-cell analysis of human heart failure identifies a fibroblast-enriched ferroptosis signature that distinguishes DCM from controls and reveals a pseudotime trajectory linking ferroptotic stress to progressive fibroblast activation and pro-fibrotic remodelling.

Despite being a common reason for Emergency Department (ED) admission, information about the management of acute pericarditis is limited in this setting. In this retrospective study conducted at the ED of Ospedale di Circolo in Varese (Italy) from 2019 to 2023, patients with acute pericarditis were included. The primary endpoint was the occurrence of the 12-month composite outcome (treatment failure, recurrent pericarditis, cardiac tamponade, constrictive pericarditis or death). One-hundred and sixty-nine patients were included (median age 54 years, 65.1% males). Chest pain was the main symptom (96.4%). On admission, aspirin was more frequently given over non-steroidal anti-inflammatory drugs (NSAIDs), and colchicine was prescribed in 40% of patients. At discharge, more patients were prescribed ibuprofen, and colchicine prescription significantly increased to 71%. Drug doses were compliant with guidelines in a limited number of patients at admission and increased at discharge. The composite outcome occurred in 20.1% of patients (n = 34), mainly driven by recurrences (n = 18) and treatment failure. Patients with a complicated course were older, of female sex, with a larger proportion of comorbidities and higher CRP levels. Diabetes (HR 3.9, 95% CI 1.7-9.1), COPD (HR 6.2, 95% CI 2.3-17.1), recent percutaneous cardiac procedures (HR 6.5, 95% CI 2.1-19.6), and recent SARS-CoV-2 vaccination (HR 3.0, 95% CI 1.1-8.2) were independent risk factors for the composite outcome. A significant proportion of patients with acute pericarditis experience long-term complications. Sub-optimal adherence to guideline-recommended doses of anti-inflammatory drugs was commonly observed, suggesting an area for improvement in the management of these patients.

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. 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. 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. 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.

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. 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). 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). 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.

Late adverse events after percutaneous coronary intervention continue to occur beyond the first year with last-generation drug-eluting stents (DES). The coronary bioadaptor marks a new approach with an uncaging beginning at approximately 6 months after implantation. We conducted a pairwise meta-analysis of bioadaptor versus DES in randomised trials with complementary single-arm 6-12 and 6-24 landmark analyses. The systematic review and meta-analysis was conducted according to PRISMA 2020 Guidelines. PubMed, Embase, CENTRAL and Google Scholar were searched for studies reporting clinical outcomes after bioadaptor implantation. The primary outcome was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularisation at 1 year. Secondary outcomes were TLF and individual components at landmark intervals 6-12 and 6-24 months. Single-arm pooled event rates and pairwise comparisons were estimated using generalised linear mixed-effects models. Three randomised trials (n = 2892; 1448 bioadaptor, 1444 DES) were included in pairwise analyses. 1-year TLF showed no significant difference between bioadaptor and DES (OR 0.81, 95% CI 0.51-1.31, I2 = 0.0%, p = 0.3943). Likewise, individual components of TLF and device thrombosis did not differ between groups. Ten studies (1753 patients; 1900 lesions) were included in single-arm analyses. Landmark TLF was 0.57% (95% CI 0.07-4.29; I2 = 4.6%) from 6 to 12 months and 2.01% (95% CI 0.81-4.92; I2 = 74.2%) from 6 to 24 months. Event rates for other endpoints were generally low. No significant differences in safety and efficacy outcomes were observed between bioadaptor and DES. Complementary single-arm landmark analyses suggested low late event rates, but these findings should be interpreted as exploratory. Further randomised trials are warranted.