To examine the epidemiology of stroke and transient ischaemic attack (TIA), and quality of care provided to Aboriginal and Torres Strait Islander ('Indigenous') patients presenting to emergency medical services (EMSs) with stroke or TIA.

Retrospective population-based data linkage study.

Victoria, Australia. Patients aged ≥ 18 years with hospital-confirmed stroke or TIA who presented to EMSs between 1 January 2015 and 30 June 2019 and were successfully linked with hospital or mortality datasets.

Thirty- and 90-day mortality, crude and age-standardised incidence rates, EMS quality of care.

Among 32,163 patients, 287 (0.9%) were Indigenous. Indigenous patients were younger than non-Indigenous patients (median age, 62 vs. 77 years, p < 0.001). Age-standardised incidence of EMS attendance was higher within the Indigenous population (343 vs. 144 per 100,000 person-years; incidence rate ratio, 2.383 [95% confidence interval (CI), 2.084-2.711]). Rates of call-taker identification of stroke or TIA and hospital diagnoses were comparable; however, Indigenous patients were less likely to receive a stroke assessment from paramedics (166/285 [58.2%] vs. 21,271/31,605 [67.3%]; p = 0.001) and more frequently taken to stroke-capable hospitals (257/275 [93.5%] vs. 27,371/30,647 [89.3%]; p = 0.027), but less frequently taken to endovascular thrombectomy-capable hospitals (67/275 [24.4%] vs. 10,015/30,647 [32.7%]; p = 0.003). Adjusted mortality was similar between groups (30 days: hazard ratio, 0.814 [95% CI, 0.518-1.279]; 90 days: hazard ratio, 0.805 [95% CI, 0.534-1.214]). However, age-standardised incidence of 90-day mortality was higher within the Indigenous population (39 vs. 24 per 100,000 person-years; incidence rate ratio, 1.621 [95% CI, 1.031-2.398]). Indigenous patients also more often recontacted EMSs for any reason within 90 days (subdistribution hazard ratio, 1.548 [95% CI, 1.194-2.007]).

The age-standardised incidence of EMS attendance for stroke in the Indigenous population was more than double that for the non-Indigenous population. Although there was no difference in stroke identification at the time of the emergency call, Indigenous patients were less likely to be evaluated by paramedics for stroke.

Transcatheter aortic valve replacement (TAVR) in nonagenarians with extensive aortic valve calcification is associated with a substantial risk of intraprocedural circulatory collapse.

This case report describes a structured pre-procedural risk mitigation strategy integrating a balloon-expandable valve system and a pre-emptive, "wet-prepared" extracorporeal membrane oxygenation (ECMO) backup. A 97-year-old man with severe symptomatic aortic stenosis (peak velocity = 4.76 m/s; aortic valve calcium volume = 1178 mm³) underwent transfemoral TAVR using a structured approach incorporating precision imaging, careful device selection using a domestic Chinese balloon-expandable valve system (Prizvalve^® TAV23), proactive ECMO preparedness, and multidisciplinary team coordination. Immediately after valve deployment, the patient developed circulatory collapse (blood pressure = 40/20 mmHg). A predefined emergency protocol was promptly activated. Following chest compressions, vasopressor administration, and pacing optimization, spontaneous circulation was restored within minutes. Angiography confirmed stable valve positioning with satisfactory expansion. At 3-month follow-up, echocardiography demonstrated absence of paravalvular leakage and preserved left ventricular systolic function.

This case demonstrates the feasibility of a structured, pre-procedural risk mitigation strategy for TAVR in an exceptionally high-risk patient. The approach enabled the management of intraprocedural circulatory collapse. In this setting, the balloon-expandable valve platform demonstrated procedural characteristics that were well suited for this complex anatomy.

Acute Coronary Syndrome (ACS) imposes substantial psychological and cardiovascular disease-related distress, influenced by socioeconomic and psychosocial determinants. Identifying these determinants is essential for improving patient outcomes and delivering holistic patient-centered care.

This study aimed to assess cardiovascular disease-related distress among patients with Acute Coronary Syndrome (ACS) and examine its association with psychosocial and socioeconomic determinants.

A prospective observational study was conducted over five months at a tertiary care hospital after obtaining ethical approval. A total of 105 adult patients diagnosed with ACS by a cardiologist were enrolled. Patients aged ≥ 18 years, of either gender, who provided written informed consent were included in the study. Socio-demographic characteristics, clinical parameters, and cardiovascular disease-related distress were assessed using a structured distress assessment tool comprising domains including Fear and Uncertainty, Changes to Role and Responsibilities, Economic Impact, and Overwhelm and Depletion. Data regarding psychosocial and socioeconomic determinants were collected and analyzed to evaluate their association with distress levels.

The highest distress scores were observed in the domains of changes in roles and relationships, overwhelm and depletion, and fear and uncertainty. Significant associations were identified between cardiovascular distress and socioeconomic status, age, gender, and polypharmacy (p < 0.05). Patients from lower socioeconomic classes and rural areas demonstrated higher psychosocial and economic distress, while female participants reported significantly greater distress in role-related and medication-management domains. No significant association was observed between distress and ACS subtype or comorbidity burden.

Cardiovascular disease-related distress among ACS patients varied across specific psychosocial domains rather than uniformly affecting all aspects of patient well-being. Distinct patterns of distress were observed across socioeconomic groups, highlighting the influence of psychosocial and socioeconomic determinants on cardiovascular distress. These findings emphasize the importance of identifying domain-specific distress to facilitate targeted and individualized patient care.

Coronary artery bypass grafting (CABG) carries a risk for serious adverse events. The Prognostic Nutritional Index (PNI) and Neutrophil-to-Lymphocyte Ratio (NLR), are simple measures of nutritional and inflammatory statuses, have been proposed as a potential predictor of postoperative outcomes. This study aimed to assess the predictive performance of preoperative PNI and NLR and their dynamic changes for post-CABG outcomes.

The study investigated the medical records of 327 patients who underwent CABG between February 20, 2020, and February 19, 2025.

The overall complication and mortality rates were 15%, and 3.36% respectively. The preoperative PNI decreased significantly (P1 < 0.001) at 24-h postoperative and at the time of discharge. At the time of discharge, the mean PNI value increased significantly (P2 < 0.001) compared to that determined at 24-h postoperative. The magnitude of ∆PNI at discharge was significantly smaller than that at 24-h postoperatively (P3 < 0.001). Multivariate binary logistic regression identified preoperative PNI as an independent predictor of 1-month mortality, while ΔPNI at 24 h was independently associated with 1-month mortality.

PNI is a simple and inexpensive marker that may serve as a potential predictor of short-term outcomes after CABG. Lower preoperative PNI and greater early postoperative PNI decline were associated with adverse short-term outcomes after CABG, whereas preoperative NLR did not retain independent significance after multivariable adjustment; however, further prospective multicenter studies are required to confirm these findings.

Hypertension is a highly prevalent clinical condition and a major contributor to global cardiovascular morbidity and mortality. Despite extensive research, its complex and multifaceted pathogenesis is yet to be fully elucidated. This paper explores the updated understanding of primary hypertension as a systemic disorder rather than an isolated vascular or renal abnormality. At the center of this multifactorial disease lie three primary and interrelated pathophysiological mechanisms: dysregulation of the renin-angiotensin-aldosterone system, dysfunction of the central nervous system, and activation of inflammatory and oxidative stress pathways. These core drivers not only interact with each other in a self-reinforcing cycle but also serve as convergence points for a range of additional contributors. Specifically, suboptimal dietary patterns, salt sensitivity, gut microbiota dysbiosis, circadian rhythm disruption, and insulin resistance act by modulating these central processes, thereby perpetuating blood pressure elevation. This review further elaborates on how these mechanisms span across multiple organ systems, driving vascular, renal, neurohumoral, and immune dysfunction. Taken together, this perspective underscores the need for integrated, upstream-targeted therapeutic strategies. By highlighting the interconnected nature of these drivers and contributors, this paper provides a comprehensive framework to inform future research and guide more effective preventive and management approaches for hypertension.

Acute kidney injury (AKI) is a prevalent clinical syndrome associated with high mortality and lacking effective therapies, largely due to incomplete understanding of its pathogenic mechanisms. Proximal tubular epithelial cells (PTECs), with their high metabolic demand, represent the primary targets of injury in AKI. We identified β-ureidopropionase 1 (Upb1), a key enzyme in pyrimidine catabolism, as being specifically enriched in PTECs but markedly downregulated upon AKI. Genetic silencing of Upb1 exacerbated IR-induced AKI. Targeted metabolomics revealed that loss of renal Upb1 drives accumulation of 3-ureidopropionate (3-UPA), a pyrimidine catabolic intermediate. Integrated multi-omics analyses and functional validation demonstrated that 3-UPA impairs fatty acid oxidation through DNMT1-mediated DNA methylation, leading to mitochondrial structural and functional defects. Transcription factor analysis further revealed that myeloid ecotropic viral integration site 1 (Meis1) transcriptionally represses Upb1. Tubule-specific Meis1 overexpression aggravated folic acid (FA)- and ischemia/reperfusion injury (IR)-induced AKI, whereas pharmacological inhibition of Meis1 alleviated tubular damage. Notably, Meis1 overexpression induced marked 3-UPA accumulation, reinforcing its role as an upstream regulator of this metabolic axis. Collectively, these results demonstrate that Meis1/Upb1/3-UPA axis exerted a detrimental role in AKI, and targeting this axis (inhibiting Meis1 or activating Upb1) has therapeutic potential for AKI.

The receptor for advanced glycation end products (RAGE) is a multiligand pattern-recognition receptor involved in inflammation, oxidative stress, and cardiometabolic disease. In acute myocardial infarction (AMI), activation of the AGE-RAGE signaling axis contributes to ischemia-reperfusion injury and post-infarction cardiac remodeling. Its soluble isoform (sRAGE) has emerged as a potential circulating biomarker related to RAGE pathway activity. Experimental studies support a role for RAGE in amplifying myocardial injury through inflammatory and oxidative mechanisms. In clinical settings, circulating sRAGE levels have been associated with markers of myocardial damage and disease severity; however, findings remain inconsistent, with both direct and inverse associations reported. Interpretation is further complicated by differences in sRAGE isoforms, heterogeneity in study design, timing of measurement, and lack of standardized analytical methods. Consequently, no validated cut-off values or clinical applications have been established. Limited longitudinal evidence suggests that the clinical significance of sRAGE may vary over the course of AMI. Higher acute-phase levels have been associated with myocardial injury and adverse outcomes in some cohorts, whereas longitudinal changes may reflect distinct biological processes and carry different prognostic information. These observations support further investigation of sRAGE kinetics as a potential complement to single time-point measurements, although prospective longitudinal validation is required before clinical implementation.

Acute heart failure (AHF) is a clinical syndrome characterized by the rapid or gradual onset of symptoms and signs of heart failure that are severe enough to require urgent evaluation and treatment. It may represent de novo heart failure or acute decompensation of pre-existing chronic heart failure. Natriuretic peptides remain the cornerstone biomarkers for diagnosis and risk assessment, but predominantly reflect hemodynamic stress and incompletely capture inflammation, oxidative injury, cellular damage, and multiorgan dysfunction. Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine of the transforming growth factor-beta superfamily, may complement natriuretic peptides by reflecting these non-hemodynamic pathways. We conducted a targeted PubMed search from database inception to January 2025 and identified 16 original mechanistic and clinical studies relevant to GDF-15 in AHF. In cultured cardiomyocytes, biomechanical stretch increased GDF-15 expression approximately 24.8-fold, while recombinant GDF-15 reduced ischemia/reperfusion-related necrosis and apoptosis through phosphoinositide 3-kinase/Akt signaling and attenuated agonist-induced hypertrophy through SMAD2/3-associated pathways. In animal models, GDF-15 deficiency increased infarct size and cardiomyocyte apoptosis after ischemia/reperfusion and produced greater hypertrophy and an 84% reduction in contractile performance after 2 weeks of pressure overload, compared with a 25% reduction in wild-type mice. Clinical studies generally showed that higher admission or discharge GDF-15 concentrations and increasing serial levels were associated with mortality or heart-failure rehospitalization. For example, serial GDF-15 remained independently associated with adverse outcomes after simultaneous modelling with established biomarkers (adjusted hazard ratio 1.44 per 1-SD increase in log GDF-15), and a multimarker model incorporating GDF-15, NT-proBNP, and troponin I achieved an area under the curve of 0.785. GDF-15 is not currently recommended for routine heart-failure management since assays and thresholds are not standardized and no prospective trial has shown that GDF-15-guided treatment improves outcomes. Its most plausible near-term role is therefore as one component of a multimarker risk-stratification strategy.

Ginseng dripping pills (GDPs), a traditional Chinese patent medicine, are extensively used for cardiovascular diseases (CVDs), but their active components and underlying mechanisms remain unclear. This study aimed to identify the chemical constituents of GDP and to explore their potential mechanisms in treating myocardial infarction (MI) and atherosclerosis (AS). Chemical profiling was performed using ultra-high-performance liquid chromatography coupled with Q-Exactive^TM hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) and the Global Natural Products Social Molecular Networking (GNPS), leading to the identification of 113 compounds, and 13 blood-absorbed components were identified, with ginsenosides identified as the predominant bioactive constituents. Network pharmacology was then used to predict the key therapeutic targets and associated signaling pathways, and a comprehensive "GDP-component-target-pathway" interaction network was constructed. 18 targets were identified as core targets of GDP in treating CVD. The main pathways involved included PI3K-Akt, RAS, cAMP, Rap1, and calcium signaling. Molecular docking showed that 13 blood-absorbed components of GDP, including ginsenoside Ro, ginsenoside Rs1 and ginsenoside Ra3, had strong binding affinities with MAPK3, MMP9, and PTGS2. These findings suggest that GDP may exert cardioprotective effects through a multicomponent, multitarget, and multipathway mode of action, providing a scientific basis for its clinical application in CVD treatment.

Exosomes are nanoscale vesicles abundantly distributed across biological fluids, serving as crucial mediators of intercellular communication by carrying bioactive molecules such as proteins, nucleic acids, and lipids. They exert pivotal functions in various physiological and pathological processes. Mesenchymal stem cell-derived exosomes (MSC-exos) exhibit low immunogenicity, minimal tumorigenic risk, abundant sources, and amenability to engineering modifications. Through the targeted delivery of bioactive molecules, MSC-exos exert multifaceted therapeutic effects in heart failure (HF) repair. They not only protect cardiomyocytes, thereby maintaining structural integrity, but also modulate immune and inflammatory responses, thereby improving the myocardial microenvironment. Additionally, they inhibit fibrosis, promote angiogenesis, and optimize myocardial metabolism, offering novel strategies and tools for the treatment of HF. This review aims to systematically elucidate the biological characteristics of MSC-exos, provide an in-depth analysis of their molecular mechanisms in HF therapy, summarize optimization strategies, and explore their potential in drug delivery and clinical applications. Furthermore, it discusses the challenges and future directions for clinical translation, thereby offering a comprehensive reference for both basic research and clinical practice regarding MSC-exos as a therapeutic tool for HF repair.