This prospective observational study investigated the prognostic value of the hemoglobin-to-red cell distribution width ratio (HRR) in 278 patients hospitalized with decompensated heart failure (HF). The primary endpoint was a composite of all-cause mortality or HF rehospitalization at 12 months. Multivariable Cox regression was employed to adjust for risk factors including age, sex, NT-proBNP, LVEF, and eGFR.

The median HRR was 0.89. During follow-up, the primary endpoint occurred in 167 (60.1%) patients. Unadjusted analysis showed a lower HRR was significantly associated with reduced event-free survival (log-rank p = 0.027). However, after multivariable adjustment, this association was no longer statistically significant (p = 0.240). Older age and male sex remained independent predictors.

In patients with decompensated HF, a lower baseline HRR correlates with increased risk but does not maintain independent prognostic value after adjusting for powerful confounders. HRR may serve as a simple, initial marker of risk rather than an independent predictor.

Objectives: Cardiovascular diseases (CVDs) represent the main global burden of morbidity and mortality, with an accelerated epidemiological transition in regions such as Latin America. The university environment constitutes a period of critical vulnerability due to increased sedentary lifestyles and cardiometabolic risk factors. The objective of this study was to evaluate the cardiovascular risk profile in a university community in the central Andean region of Colombia using anthropometric, haemodynamic and biochemical indicators. Methods: A cross-sectional, observational, and analytical study was conducted on a sample of n = 143 participants (students, teachers, and administrators) aged between 18 and 80 years. Haemodynamic parameters (SBP, DBP, MAP), anthropometric parameters (BMI, % body fat, waist-to-height ratio [WC/W]) and lipid profile were evaluated. Statistical analysis included multiple linear regression models to determine predictors of systolic blood pressure (SBP). Results: Significantly higher levels of SBP were found in the older age groups compared with the younger age groups, reaching stage 1 hypertension levels in the sixth decade. The biochemical profile revealed metabolic deterioration with an atherogenic index (TC/HDL) consistently above the clinical threshold (>4.5) in all groups. The regression model BMI was identified as the statistical predictor with the strongest association with SBP variability in the sample (β = 1.18), followed by age (β = 0.28). A marked sexual dimorphism was observed, with men presenting early haemodynamic risk, while women experienced an accelerated post-menopausal tension and metabolic crisis. Conclusions: The university community presents latent cardiometabolic vulnerability closely linked to modifiable anthropometric factors. These findings underscore the urgency of implementing institutional preventive health policies and weight control intervention programmes to mitigate the future burden of chronic diseases on campus.

Background: RASopathies represent a clinically and genetically diverse group of syndromes resulting from germline mutations in genes regulating the RAS/mitogen-activated protein kinase (MAPK) signaling cascade. Methods: The aim of this study was to describe the clinical features and genetic variants identified in patients with genetically confirmed Noonan syndrome (NS) in a limited cohort from Romania. A total of 25 patients with positive genetic testing for NS-associated genes were included. Genetic testing was performed primarily using next-generation sequencing. Results: A total of twenty-six variants were identified in twenty-five patients, as one patient carried two pathogenic variants in the PTPN11 gene (c.188A>G and c.922A>G). Of these variants, twenty-four (92.31%) were classified as pathogenic and two (7.69%) as variants of uncertain significance (VUS). Pathogenic variants were found in different genes, including PTPN11, LZTR1, SOS1, and RAF1, with PTPN11 being the most frequently affected gene. Males predominated (17/25), with a male-to-female ratio of approximately 2:1. Two patients inherited the pathogenic variant from an affected parent. Cardiovascular involvement was present in 21 patients (84%), with pulmonary valve stenosis (PVS) being the most common finding (48%), followed by hypertrophic cardiomyopathy (16%). Additional cardiac anomalies included atrial septal defect, valvular regurgitation, dysplastic valves, coarctation of the aorta, and sinotubular junction narrowing. Short stature was observed in 64% of patients, and craniofacial dysmorphism was present in 96%. Cutaneous, ectodermal, dental, ophthalmologic, and auditory manifestations were variably observed. Conclusions: Although based on a limited cohort from Romania, this study provides insights into clinical features suggestive of NS. Our findings highlight the genetic heterogeneity of NS and emphasize the importance of comprehensive genetic testing for confirming diagnosis, guiding clinical management, and supporting family counseling.

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by microvascular dysfunction, immune activation, and progressive fibrosis affecting multiple organs, including the heart. Myocardial involvement represents an important but frequently underrecognized manifestation of SSc and may develop even in the absence of overt clinical symptoms. Cardiac manifestations include ventricular dysfunction, arrhythmias, conduction abnormalities, and heart failure, contributing substantially to morbidity and mortality. The underlying pathophysiology involves coronary microvascular dysfunction, immune-mediated myocardial inflammation, and progressive myocardial fibrosis, which often precede clinically apparent cardiac disease. This review aims to summarize the current understanding of myocardial involvement in SSc and to provide a comprehensive overview of contemporary multimodality cardiovascular imaging techniques for its detection, characterization, and risk stratification. A comprehensive overview of the current literature was conducted focusing on established and emerging cardiovascular imaging modalities for the evaluation of myocardial involvement in SSc. Particular attention was given to echocardiography, cardiac magnetic resonance (CMR), nuclear imaging techniques including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), and cardiac computed tomography (CT). Recent advances in imaging biomarkers, parametric mapping, myocardial strain analysis, and emerging technologies such as artificial intelligence (AI), radiomics, and molecular imaging were also considered. Multimodality cardiovascular imaging plays a central role in the early detection and comprehensive assessment of myocardial involvement in SSc. Advanced imaging techniques enable improved identification of subclinical myocardial dysfunction, microvascular impairment, inflammation, and fibrosis. An integrated imaging approach combining echocardiography, CMR, nuclear imaging, and CT may facilitate earlier diagnosis, enhance risk stratification, and ultimately improve cardiovascular outcomes in patients with SSc.

Background: Women face underdiagnosed cardiovascular disease (CVD)/stroke risks due to sex-specific pathophysiological mechanisms, including hormonal variations such as oestrogen decline, adverse pregnancy outcomes (APOs), endothelial dysfunction, autoimmune-mediated factors, and sexual dimorphism in cardiac remodelling. Conventional risk assessment tools, predominantly calibrated to male pathophysiology, lack sensitivity in detecting these female-specific determinants. We hypothesise that artificial intelligence (AI), machine learning (ML) and deep learning (DL) may offer a transformative approach by integrating multimodal data, including pathological biomarkers, clinical history, and vascular imaging, to enable precision CVD/stroke risk stratification, pending rigorous external validation in sex-stratified cohorts. Method: This narrative review adopts a PRISMA-informed study selection framework and oversees gender-specific biomarkers, including vasoactive peptides (adrenomedullin), adipocytokines (adiponectin), inflammatory mediators (hs-CRP, IL-6), and thrombogenic factors (homocysteine, D-dimer), alongside clinical variables (APOs, autoimmune disorders) and ultrasonographic markers, carotid intima-media thickness (cIMT), plaque burden and plaque area (PA). Advanced ML/DL algorithms were employed to synthesise these heterogeneous datasets, identifying nonlinear interactions for better outcomes. Findings: Key insights reveal that hormonal dynamics (e.g., hypoestrogenism post-menopause) modulate CVD risk, while APOs induce persistent endothelial dysfunction and subclinical atherosclerosis. Biomarker sexual dimorphism is evident; hs-CRP exhibits higher baseline levels in women, whereas adiponectin declines with metabolic dysfunction. Radiomic features (cIMT progression, plaque morphology) are a well-established biomarker for CVD risk stratification. Conclusions: The integration of AI-driven multimodal systems holds the potential to enable a paradigm shift from population-based to personalised risk assessment, addressing critical gaps in female CVD health. However, this potential is currently at the early validation stage, and widespread clinical implementation requires prospective, externally validated, and ethnically diverse studies. Future applications should incorporate longitudinal biomarker profiling and advanced imaging, namely shear wave elastography and plaque radiomics, to optimise predictive models.

Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder with high morbidity and mortality, despite advances in aneurysm securing and neurocritical care. Clinical outcomes are determined by early brain injury (EBI), delayed cerebral ischemia (DCI), hydrocephalus, and long-term cognitive impairment, extending beyond the traditional focus on large-vessel vasospasm alone. Emerging evidence identifies the dysfunction of the glymphatic system and meningeal lymphatic pathway, the brain's primary clearance pathways, as a central and unifying mechanism linking acute hemorrhagic injury to delayed and chronic neurological sequelae. Following SAH, acute intracranial pressure elevation, subarachnoid blood clot burden, loss of arterial pulsatility, venous congestion, astrocytic aquaporin-4 perivascular depolarization, and neuroinflammation converge to suppress cerebrospinal fluid-interstitial fluid exchange and outflow in glymphatic system and subsequent meningeal lymphatic drainage. Persistent clearance failure promotes the retention of blood breakdown products, inflammatory mediators, and metabolic waste, amplifying microvascular dysfunction, cortical spreading depolarizations, blood-brain barrier disruption, and secondary ischemic injury. Importantly, accumulating data highlight venous pathology and meningeal lymphatic impairment as critical, yet underappreciated, contributors to delayed injury and post-SAH hydrocephalus. In this review, we synthesize the current knowledge of the physiological organization of glymphatic and meningeal lymphatic systems, delineate the mechanistic and molecular drivers of their dysfunction after SAH, and discuss clinical implications for EBI, DCI, hydrocephalus, and long-term cognitive outcomes. We further outline future directions, including translational imaging, biomarker development, and therapeutic strategies targeting clearance pathways, to advance disease-modifying approaches in SAH.

Acute kidney injury (AKI) continues to pose a significant clinical challenge due to its high morbidity rates and limited therapeutic options. Recent evidence suggests that natural compounds may provide renoprotective benefits by modulating oxidative stress and inflammation. This study examines the protective effects of a novel polysaccharide peptide extracted from Ganoderma lucidum (GL-PPQ1) against renal ischemia-reperfusion (I/R) injury, with particular emphasis on the integrin β3/Fibronectin 1 (Fn1) signaling axis. A murine model of renal I/R injury was established, and GL-PPQ1 was administered orally for seven days before surgery. The assessment included renal function, histopathology, oxidative stress markers, and inflammatory cytokines. Additionally, transcriptomic profiling and protein expression analyses were conducted to elucidate the underlying mechanisms. The results revealed that GL-PPQ1 pretreatment significantly reduced renal tubular damage, lowered serum creatinine and blood urea nitrogen levels, and diminished oxidative stress and inflammatory responses. RNA sequencing revealed that GL-PPQ1 affected gene sets associated with extracellular matrix remodeling and cell adhesion. Western blot and immunohistochemistry further confirmed that GL-PPQ1 decreased the expression of integrin β3 and Fn1, suggesting a regulatory effect on their interaction during I/R injury. These findings demonstrate that GL-PPQ1 offers substantial kidney protection by mitigating oxidative stress, inflammation, and dysregulation of the integrin β3/Fn1 signaling pathway. Thus, this study supports that polysaccharide peptides derived from Ganoderma lucidum could have the potential to serve as both a dietary supplement and a therapeutic agent in the treatment of AKI.

Vascular diseases (VD) remain a leading global cause of morbidity and mortality, often developing silently before manifesting as severe complications like stroke or ischemia. Traditional diagnostic imaging provides essential anatomical data but frequently fails to capture the dynamic molecular processes underlying vascular pathology. This narrative review summarizes current evidence regarding Extracellular Vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, as emerging biomarkers and mediators in vascular conditions. The review evaluates the biological mechanisms of EVs across several disorders, including arterial aneurysms, peripheral artery disease, carotid stenosis, and venous thromboembolism. Findings indicate that EVs concentration and molecular cargo, particularly microRNAs and proteins, reflect the physiological state of parent cells, offering a "liquid biopsy" for vascular inflammation, endothelial dysfunction, and plaque vulnerability. Furthermore, the review explores the therapeutic potential of stem cell-derived EVs in promoting angiogenesis and tissue repair in chronic vascular ulcers. Despite these advances, the review concludes that the clinical implementation of EV-based diagnostics faces significant hurdles, primarily due to the lack of standardized isolation and characterization methods. Addressing these methodological challenges is crucial for translating EV research into routine clinical practice.

Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context.

Hypertension continues to be a major global public health challenge. Dopamine generated in the kidney is a vital coordinator of sodium homeostasis and blood pressure control. Dopamine exerts its effects by activating its receptors, which are divided into the D₁-like receptor family (D₁R and D₅R) and the D₂-like receptor family (D₂R, D₃R, and D₄R). All five dopamine receptor subtypes are differentially expressed along the nephron. Dopamine receptors inhibit the activities and/or expression of renal tubular sodium transporters/exchangers/channels, decrease renal oxidative stress, and interact with other receptors, including angiotensin II receptors. Many studies have demonstrated that renal dopamine receptors play an important role in the regulation of blood pressure. The germline deletion or renal-selective silencing of any of the five dopamine receptor subtypes may impair sodium excretion and increase blood pressure. In addition, renal dopamine receptor expression and/or function are regulated by some factors such as G protein-coupled receptor kinases, oxidative stress, and sorting nexins. In this article, we summarize the role of each dopamine receptor subtype in the pathogenesis of hypertension and discuss the potential regulatory mechanisms of their expression and function. These may lead to the development of novel therapeutic approaches to the prevention and treatment of hypertension.