Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipidomics and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of submaximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy metabolism compared to young adults with comparable activity levels. Here we found that 50% of these age-related differences were absent in trained older adults, resulting in profiles resembling those of young adults. Although all participants displayed transcriptional immune and stress responses upon acute exercise, the magnitude of these responses in older adults was positively correlated with their physical fitness. Integrated multiomic analyses further revealed links among mitochondrial respiration, lipid metabolism, stress responses and NAD⁺ biology. These findings demonstrate that sustained physical training transforms age-related molecular profiles and provide a molecular atlas for study of fitness-dependent aging mechanisms.

Identifying serum biomarkers that accurately reflect the progression of coronary artery disease (CAD) remains a major challenge. Integrative proteomic and metabolomic profiling can provide novel insights into disease pathogenesis and improve clinical prediction. We conducted a four-phase study. In the discovery phase, serum from 40 patients (controls, stable CAD, and acute coronary syndrome (ACS)) was analyzed using data-independent acquisition (DIA) proteomics and liquid chromatography-tandem mass spectrometry (LC-MS)/gas chromatography-mass spectrometry (GC-MS) metabolomics to identify differentially expressed proteins (DEPs) and metabolites. In the verification phase, selected DEPs were validated by parallel reaction monitoring (PRM) in an independent 40-patient cohort. In the derivation phase, six validated proteins were measured by ELISA in 207 angina patients to assess their association with coronary obstruction (≥ 50% stenosis). In the validation phase, a support vector machine (SVM) model incorporating clinical risk factors and these biomarkers was developed in the derivation cohort and tested in an independent 97-patient cohort. Model performance was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. Coronary obstruction is defined as ≥ 50% luminal diameter stenosis in at least one major coronary artery on angiography. Proteomic analysis identified 97 DEPs, and metabolomic profiling revealed 322 DEMs (including 289 from LC-MS and 33 from GC-MS analyses). Seven proteins showed consistent changes in both DIA and PRM validation. Among these, thrombospondin-1 (TSP-1) was significantly upregulated in stable CAD compared with controls, while serum amyloid A1 (SAA1) was markedly elevated in ACS compared with stable CAD. In an independent angina cohort (n = 207), serum levels of TSP-1 and SAA1 were significantly higher in patients with coronary obstruction. Multivariate logistic regression adjusted for conventional cardiovascular risk factors (including age, sex, homocysteine, and other clinical variables) demonstrated that TSP-1 remained independently associated with coronary artery occlusion (OR = 1.424, 95% CI 1.057-1.918, P = 0.020). A support vector machine (SVM) model incorporating conventional clinical risk factors was constructed, and the addition of TSP-1 and SAA1 significantly improved diagnostic performance for CAD severity (AUC = 0.919 in derivation, 0.992 in validation). In conclusion, our dual-omics approach identified novel biomarkers and pathways in CAD progression. The SVM-based prediction model offers a promising non-invasive tool for early CAD detection, potentially reducing unnecessary invasive procedures.

The complement system is crucial in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) pathogenesis. Extracellular vesicles (EVs) serve as carriers of bioactive substances, influencing the immune system. We aimed to investigate myeloperoxidase-positive EVs (MPO⁺EVs) exposing complement components (C3a, C4d), terminal complement complex (TCC) and complement factor B (CFB) in relation to disease activity and kidney involvement.

Plasma MPO⁺EVs carrying complement products, C3a, C4d, TCC or CFB, were analysed by flow cytometry. Clinical data, including kidney biopsy findings, were retrieved. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS).

Eighty-one patients with AAV with granulomatosis with polyangiitis (n=59) or microscopic polyangiitis (n=22) were included. Active disease was noted in 73 (90.1%) patients and 50 (68.5%) had kidney involvement. Patients with kidney involvement had higher concentrations of MPO⁺, MPO⁺C3a⁺, MPO⁺C4d⁺ and MPO⁺TCC⁺EVs compared to patients without, and concentrations correlated positively with BVAS (p<0.05), respectively. Levels of EVs showed a negative correlation with estimated glomerular filtration rate, and a positive correlation with the proportions of necrosis and crescents in kidney biopsies. ROC curve analysis indicated that MPO⁺EVs could distinguish patients with kidney involvement from non-renal AAV. A binary multivariable logistic regression confirmed an independent association between levels of EV subsets and kidney involvement.

Elevated levels of MPO⁺EVs exposing complement components in patients with kidney involvement indicate activation of the classical or lectin and common complement pathways in renal AAV. Furthermore, the association between levels of MPO⁺EVs with the presence of crescents and necrotic lesions in kidney tissue supports a role in renal inflammatory activity.

The cardiovascular intensive care unit (CVICU) presents unique opportunities and challenges for integrating palliative care. A growing population of patients living longer with advanced cardiac disease, persistent symptoms, and functional limitations may benefit from early palliative involvement. With increasing use of advanced therapies such as mechanical circulatory support, many patients die in the CVICU, while survivors often experience long-term physical and psychosocial burdens. Despite evidence that early palliative care improves quality of life and reduces nonbeneficial interventions, it remains underutilized because of prognostic uncertainty and inconsistent referral guidance. This review explores therapies, palliative roles, and end-of-life practices in the CVICU.

Heart transplantation is the definitive treatment for end-stage heart failure. Post-transplant care is dynamic and complex, requiring a thoughtful multidisciplinary approach. Invasive hemodynamic monitoring is central to guiding inotrope and vasopressor titration to optimize allograft function and end-organ perfusion. Vigilant assessment for primary graft dysfunction is essential and informs escalation to mechanical circulatory support when needed. As hemodynamics and graft function stabilize, patients are liberated from mechanical ventilation, volume status is optimized, nutrition and mobility are prioritized, and pharmacologic and mechanical supports are weaned. Concurrently, immunosuppression is titrated and patients are monitored closely for infection.

Postcardiotomy shock (PCS) is a complex, high-mortality complication following cardiac surgery, driven by cardiopulmonary bypass-related inflammation, vasoplegia, myocardial dysfunction, and pulmonary hypertension. Conventional shock definitions are poorly applicable to this population; a vasoactive inotropic score greater than 20 to 25 with evidence of hypoperfusion is proposed as a practical operational definition. Overlapping PCS phenotypes (cardiogenic, vasoplegic, obstructive, arrhythmic, mixed) necessitate multimodal hemodynamic profiling incorporating pulmonary artery catheter data, echocardiography, and dynamic perfusion indices. Management focuses on judicious fluid and blood product administration, phenotype-directed inotropes and vasopressors, lung-protective ventilation, and early initiation of temporary mechanical circulatory support.

Surgical or endovascular repair is the cornerstone of interventional management for acute ascending aortic dissection and complicated descending aortic dissection. However, perioperative medical therapy plays a decisive role in stabilizing patients, preventing propagation of dissection and mitigating end-organ injury. Perioperative clinicians must navigate competing priorities: reducing aortic shear stress while maintaining adequate perfusion, managing severe pain and sympathetic activation, addressing malperfusion syndromes, and preparing patients for urgent or emergent intervention. This article outlines a practical framework for perioperative medical management across the continuum of care.

Valvular heart disease is an uncommon but high-risk cause of cardiogenic shock requiring rapid, multidisciplinary management aimed at bridging patients to definitive surgical or transcatheter valve intervention. Early comprehensive Doppler echocardiography is essential, as clinical signs may be subtle. Distinguishing decompensated chronic valvular disease from acute unstable lesions guides urgency and treatment strategy. Medical stabilization and mechanical circulatory support vary markedly between stenotic and regurgitant lesions, and standard shock therapies may be harmful in specific contexts. Transcatheter approaches are preferred when feasible, though their expanding use introduces added complexity in cardiac intensive care.

Management of venoarterial-extracorporeal membrane oxygenation for cardiogenic shock requires prompt diagnosis, rapid intervention with individualized cannulation, adherence to clear device and anticoagulation management protocols, and close hemodynamic and end-organ monitoring. Assessment of left ventricular unloading and oxygen delivery is essential to prevent complications such as malperfusion of end organs, limb ischemia, pulmonary edema, and Harlequin (North-South) syndrome. Daily evaluation guides weaning for myocardial recovery and transition to durable support, transplant, or palliative care. Multidisciplinary coordination with critical care clinicians, early involvement of advanced heart failure and transplant teams, and clear communication with families are crucial to align therapy with patient.

Cardiogenic Shock remains one of the deadliest clinical conditions in the world. Despite technological advances, mortality rates remain unacceptably high. While recently published data in acute myocardial infarction-cardiogenic shock (AMI-CS) suggest improved outcomes with protocolized use of early temporary mechanical circulatory support (tMCS) real-world observational and registry data in both AMI-CS and heart failure-related CS suggest opportunities to improve survival through use of shock teams, early escalation to tMCS and use of hemodynamic and hemometabolic monitoring. Here we review current literature on escalation of care in cardiogenic shock and provide recommendations for optimal escalation through organized systems of care.