Search Results (349)

Atezolizumab–bevacizumab is established as first-line therapy for unresectable hepatocellular carcinoma (HCC) based on phase III randomized evidence. Although overall safety outcomes were acceptable in the registration trial, the risk of gastrointestinal (GI) and variceal bleeding remains a clinically relevant concern, particularly in patients with cirrhosis and portal hypertension. Differences between trial-based safety estimates and observational data necessitate a focused evaluation of hemorrhagic risk in this setting. Randomized trial data indicate low rates of high-grade bleeding under protocol-driven endoscopic screening and predefined eligibility criteria. In contrast, real-world cohorts report higher incidences of GI and variceal hemorrhage, especially among patients with prior bleeding, untreated or high-risk varices, reduced hepatic reserve, and extensive portal vein tumor thrombosis. Pooled analyses confirm an increased prevalence of bleeding with atezolizumab–bevacizumab compared with non-antiangiogenic systemic therapies, although event rates vary across studies due to differences in patient selection and bleeding definitions. Severe and fatal hemorrhage occurs in a minority of cases and is concentrated in clinically high-risk subgroups. Bleeding during atezolizumab–bevacizumab therapy is influenced by baseline portal hypertension severity, hepatic functional status, and tumor-related vascular involvement. Trial-derived safety data reflect outcomes under controlled conditions and may underestimate risk in broader populations. Structured baseline assessment, endoscopic evaluation, and risk-adapted portal hypertension management are integral to clinical implementation. Prospective studies incorporating standardized hemorrhage definitions and predefined risk stratification frameworks are required to refine patient selection and optimize safety in routine practice. Full article

Background: The optimal method of starting maintenance haemodialysis (HD) in patients with kidney failure is not known. We have compared early treatment characteristics, blood pressure trajectories, and selected dialysis-related safety events in patients who started HD using a stepped and phased approach, with those who received conventional care. Method: A single-centre cohort feasibility study was conducted. Participants with kidney failure, about to start maintenance HD, were enrolled prospectively (intervention arm). They started treatment on a novel regime comprising four pre-specified incremental steps (Phases 1 to 4) over 14 weeks. They were matched using propensity scores with historical controls: patients who had previously started HD on a three-times weekly basis from the outset (control arm). Results: The final cohort comprised 15 and 29 participants in the intervention and control arms respectively (1:2 ratio; one control excluded after matching). Intervention group participants were slightly older with a higher proportion of men. The rate of decline in blood pressure was slower in the intervention group. There were also signals for fewer events of intra-dialytic hypotension (211 vs. 379 per 100 person-year), infections not requiring admission (56 vs. 114 per 100 person-year) and loss of vascular access (56 vs. 79 per 100 person-year) in intervention group. There was a signal for higher incidence of severe hypertension (systolic BP ≥ 180 or diastolic BP ≥ 110 mmHg) in the intervention group. Hospitalisation rates were similar; there were no deaths and one non-fatal major cardiac event (MACE) in the intervention group, and one death and no MACE in the control group. Conclusions: Implementing a short transitional regime of incremental HD may be possible in clinical settings, potentially helping to reduce the gradient of physiological change and burden of early treatment. The findings of this feasibility study are exploratory, and fully powered randomised controlled trials are needed to establish the efficacy and safety of such a programme. Full article

The global burden of hypertension continues to rise, highlighting an urgent need for effective therapeutic strategies. Angiotensin-converting enzyme (ACE) is central to blood pressure regulation, but commonly used synthetic ACE inhibitors often have adverse side effects, spurring the search for safer natural alternatives. The aim of this study was to investigate Yanbian cattle hemoglobin as a novel precursor for ACE inhibitory peptides. The <1 kDa fraction was identified as exhibiting the highest inhibitory activity through the systematic screening of hydrolysates across multiple molecular weight ranges. LC-MS/MS analysis identified 1980 peptides, of which four were selected for further experiments. Solid-phase synthesis confirmed that NFGYDL exhibited the strongest ACE inhibition (IC₅₀ = 54.95 μM). Inhibition kinetics showed FHDYL acted as a mixed-type inhibitor, DLGHF and NFGYDL as competitive inhibitors and GFHLD as a non-competitive inhibitor. Molecular dynamics simulations validated the stable binding of these bovine blood-derived peptides to the ACE complex. HUVEC functional assays demonstrated that four peptides significantly increased angiotensin II-induced nitric oxide production and endothelin-1 levels, suggesting their potential antihypertensive activity. These findings suggested that bovine blood is a promising natural source of ACE-inhibitory peptides and holds potential for application as a functional component in functional foods targeting hypertension management. Full article

Background: Hypertension remains one of the leading causes of cardiovascular morbidity and mortality in South Africa. Although extensive evidence exists on modifiable risk factors, the translation of this evidence into strategic and equitable health investments remains limited. Current models such as the Global Burden of Disease (GBD) and WHO “Best Buys” identify key exposures, but lack operational mechanisms for context-specific prioritisation and dynamic resource allocation. The aim of this study is to develop and validate an integrated decision-support model that links evidence-based risk factor prioritisation with dynamic budget allocation to improve hypertension prevention and control in South Africa. Methods: This study adopts a two-phase mixed-methods design. Phase 1 develops a Risk Factor Prioritisation Model that ranks modifiable exposures using composite indices for the causality strength, implementation feasibility, policy integration, and equity. Phase 2 constructs a Dynamic Resource Allocation Model that distributes health budgets across interventions to maximise Disability-Adjusted Life Years (DALYs) averted, subject to budget and equity constraints. The model integrates data from systematic reviews, GBD 2019 estimates, WHO-CHOICE cost data, and national health expenditure databases. A validated quantitative Risk Priority Score (RPS) for major hypertension risk factors, an optimisation model for resource allocation, and an interactive dashboard that visualises efficiency and equity trade-offs under varying budget scenarios are expected. Conclusions: This study will provide a reproducible model for transforming epidemiological and economic evidence into actionable policy guidance. It bridges the gap between evidence generation and health planning, supporting more equitable and data-driven decision making in noncommunicable disease control. Full article

Background and Clinical Significance: Left atrial myxoma is the most common benign primary cardiac tumor and is associated with embolic and hemodynamic complications. Complete surgical excision is the treatment of choice, while postoperative cardiovascular rehabilitation is essential for functional recovery. Case Presentation: We report the case of a 75-year-old woman with arterial hypertension, dyslipidemia, and chronic venous insufficiency (Clinical–Etiological–Anatomical–Pathophysiological (CEAP) class 2), and chronic hepatitis B virus (HBV) infection who underwent surgical excision of a left atrial myxoma and was subsequently admitted three weeks postoperatively for phase II cardiovascular rehabilitation. The postoperative course was complicated by transient atrial fibrillation, peripheral edema, pleural effusion, and progressive purpuric lesions of the lower limbs. Laboratory and immunological evaluation revealed positive cryoglobulins, markedly elevated rheumatoid factor (1058 UI/mL) and IgM levels (715 mg/dL), reduced complement levels (C3, C4), normocytic normochromic anemia, microscopic hematuria, and elevated ALT (156 U/L), AST (142 U/L), total bilirubin (1.4 mg/dL), and INR (1.6), suggestive of hepatic inflammatory activity. HBV status was scheduled for evaluation through Gastroenterology referral (HBV DNA viral load, serological markers: HBsAg, HBeAg, anti-HBe), as our Cardiology Rehabilitation Clinic lacks the possibility of evaluation. After systematic exclusion of alternative etiologies, secondary cryoglobulinemic vasculitis in the context of chronic HBV infection with biochemical evidence of hepatic activity was considered the most plausible diagnosis. Conclusions: This case highlights the complexity of managing elderly patients after cardiac tumor surgery, particularly in the presence of systemic comorbidities. Early recognition of extracardiac complications and an individualized, multidisciplinary strategy are essential to optimize outcomes. Full article

Background: Changes in body composition, such as decreased muscle mass and increased adipose tissue, are significant in older adults, impacting health, functional capacity, and increasing the risk of metabolic diseases, functional decline, and frailty. Bioelectrical Impedance Analysis (BIA) is a non-invasive tool for assessing body composition, including fat-free mass (FFM), skeletal muscle mass (SMM), and fluid distribution (e.g., ECW/TBW ratio). Complementing BIA, the Mini Nutritional Assessment (MNA) serves as a validated tool for identifying malnutrition risk in the elderly. This study aimed to understand the correlation between BIA-derived parameters, MNA scores and clinical outcomes. Methods: This cross-sectional study involved 195 older adults (mean age 72.8 ± 5.4 years), divided into two groups based on body composition profiles determined by cluster analysis. Data collected included demographics, comprehensive BIA parameters (BMI, fat mass, FFM, SMM, ECW/TBW, phase angle), MNA scores, self-assessed health, chronic disease prevalence, frailty index (TFI), and functional limitations (EQ-5D). Statistical analyses included descriptive statistics, t-tests/ANOVA, chi-square tests, Pearson’s/Spearman’s correlations, point-biserial correlations, regression analyses, and ROC curve analysis to compare groups, explore variable relationships, and assess predictive abilities for malnutrition risk. Results: The first group had significantly higher BMI, AFM (AFM), FFM, and SMM, but a lower ECW/TBW ratio compared to Group 2 (N = 115), which was predominantly female and had higher frailty scores. MNA scores showed significant positive correlations with FFM (rho = 0.165, p = 0.021) and SMM (rho = 0.182, p = 0.011), and a negative correlation with ECW/TBW (rho = −0.188, p = 0.008). Higher adiposity (BMI, fat mass) correlated positively with arterial hypertension and obesity. Lower FFM and SMM were negatively correlated with gastroesophageal reflux disease. Skeletal muscle mass (AUC = 0.634, cut-off ≤ 17.3 kg) and ECW/TBW ratio (AUC = 0.626, cut-off ≥ 49.7%) showed modest discriminatory capacity to identify malnutrition risk. Individuals at risk of malnutrition reported greater functional limitations and lower self-assessed health. Numerous BIA parameters, including segmental muscle mass, total body water, phase angle, and impedance values, significantly correlated with MNA scores. Conclusions: The study highlights the importance of body composition analysis, particularly BIA, in correlation with MNA, for assessing nutritional status, functional limitations, and chronic disease associations in older adults. Integrating BIA and MNA into geriatric assessments provides a complementary profile of nutritional and functional vulnerability. Full article

Background/Objectives: There is little information on the definition and management of dyslipidemia in patients and survivors of childhood, adolescent and young adult (CAYA) cancer. However, it is known that this population is at higher risk of developing cardiovascular disease (CVD). Dyslipidemia, hypertension, and metabolic syndrome are common among CAYA cancer survivors due to the cancer itself or the treatment received. Therefore, managing dyslipidemia in this population is crucial to mitigate the risk of long-term CVD. The aim of this systematic review was to summarize currently used definitions and cutoffs for dyslipidemia, its prevalence, and management strategies in CAYA cancer survivors. This review further describes reported pharmacological and lifestyle interventions and their impact on lipid levels. Methods: We conducted a systematic literature search in PubMed, including studies published in English, German or French between January 2015 and February 2025. The population included individuals diagnosed with any type of CAYA cancer prior to 25 years of age and either receiving cancer treatment or in follow-up care. We considered all types of publications except for Phase I and II studies. We followed PRISMA guidelines, assessed the quality of the eligible studies according to the respective Joanna Briggs Institute’s Critical Appraisal Tools, and reported the results descriptively. Results: Of 575 identified publications, 53 fulfilled the inclusion criteria. Forty-three studies reported on the definitions of abnormal lipid values, 40 stated the prevalence of abnormal lipid values, and 17 studies described management approaches, of which 12 were case reports and small case series. For all three outcomes, the results were very heterogeneous. Using the example of triglycerides (TGs), the cutoff values for high TGs ranged from 5.17 mmol/L to 6.2 mmol/L and the reported prevalence of high TGs ranged from 0% to 75%, with an average of 31%. The only reported intervention to prevent dyslipidemia in CAYA cancer survivors was lifestyle modification. Preventive strategies that started during treatment were lifestyle modifications and fish oil supplements. Conclusions: Our systematic review provides a comprehensive overview of existing definitions, prevalences, and management of abnormal lipid values in CAYA cancer patients and survivors. However, the identified heterogeneities indicate that reported prevalences and results of interventions must be interpreted cautiously. An internationally harmonized approach to defining and reporting lipid values in CAYA cancer survivors is urgently needed to enable tailored screening and treatment strategies. Full article

Background and Objectives: The objectives of this study were to determine the prevalence of diabetes mellitus (DM) and major cardiometabolic comorbidities in adults living in El Trébol, Argentina, and to evaluate their associations using laboratory-confirmed, community-based data. Methods: A cross-sectional, probabilistic, two-phase design was implemented, combining a household survey with clinical and biochemical assessments. Of 1112 surveyed adults aged 20–79 years, 860 completed the clinical phase and formed the effective sample. Cardiometabolic risk factors, including obesity, hypertension, dyslipidemia, and physical inactivity, were assessed through standardized measurements and questionnaires. Multivariate logistic regression explored independent associations with DM. Results: Crude DM prevalence was 10.47%, higher in men and increasing markedly with age; the age-standardized prevalence for the Argentine population was 9.87%. Of all diabetes cases, 23% were previously undiagnosed. Obesity (35.62%), hypertension (38.83%), dyslipidemia, and physical inactivity (83.84%) were highly prevalent. DM was independently associated with older age, higher BMI, elevated triglycerides, lower HDL cholesterol, and insufficient physical activity. Conclusions: This study reveals a substantial cardiometabolic burden in a small urban Argentine population and suggests that self-report-based national surveys may misestimate true DM prevalence. Laboratory-confirmed, community-based surveillance is essential to strengthen early detection, guide targeted interventions, and inform equitable public health strategies. Full article

Background/Objectives: Limited health literacy among older adults with noncommunicable diseases (NCDs) remains a major challenge in community and primary-care settings. This action research aimed to develop and evaluate a community-based health literacy training model for volunteer caregivers for the elderly (VCEs) to support the prevention and control of diabetes and hypertension among older adults in the community. Materials and Methods: This study was conducted in a primary care-based community setting and comprised two phases: Phase 1 (model development) and Phase 2 (implementation and evaluation). The primary analytic sample consisted of 38 volunteer caregivers for the elderly, each providing home-based health education to one older adult (n = 38). The intervention combined structured health literacy education based on the K-shape framework (Knowledge, Comprehension, Thoughtful Inquiry, Decision-making, and Implementation) with SKT meditation/exercise. The program was delivered weekly over 8 weeks. Outcomes included health literacy (20-item scale) and disease prevention and control behaviors (12-item scale), assessed at baseline, immediately post-intervention, and 1 month after program completion. Results: Among VCEs, mean health literacy scores increased significantly from baseline to post-intervention and were further improved at 1-month follow-up (p < 0.001), indicating sustained gains in health literacy. Preventive behavior scores also increased significantly from baseline to post-intervention (p < 0.001); however, no additional improvement was observed at 1 month compared with immediately after the program (p > 0.05). The magnitude of improvement suggested a meaningful effect of the intervention on health literacy, while behavioral changes appeared to plateau after program completion. Conclusions: The community-based training model effectively and sustainably improved health literacy among volunteer caregivers for the elderly. Although preventive health behaviors improved immediately after the intervention, no further gains were observed at 1 month, suggesting that ongoing reinforcement may be required to sustain behavioral change. This model supports the role of community participation in primary care-based NCD prevention among older adults. Full article

Background/Objectives: Postoperative atrial fibrillation (POAF) is a common and serious complication after coronary artery bypass grafting (CABG), leading to increased morbidity and healthcare utilization. Although systemic inflammation is a well-established driver of POAF pathogenesis, no composite preoperative inflammatory biomarker has been validated for risk stratification in this population. This study aimed to evaluate the novel Inflammatory Burden Index (IBI)—the first composite biomarker combining acute-phase (C-reactive protein, CRP) and chronic cellular (neutrophil-to-lymphocyte ratio, NLR) inflammation—as a preoperative predictor of POAF after CABG. Methods: In this large retrospective cohort study, we included 3481 consecutive patients who underwent isolated CABG at a high-volume cardiac center between 2019 and 2024. Preoperative IBI was calculated as CRP (mg/dL) × NLR. The primary outcome was new-onset POAF within the first 7 postoperative days, confirmed by continuous telemetry on 12-lead ECG. Predictive performance was assessed using multivariable logistic regression, receiver operating characteristic (ROC) curve analysis (area under the curve, AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and internal validation via bootstrapping (1000 resamples). Results: POAF developed in 866 patients (24.9%). Patients with POAF exhibited significantly higher preoperative IBI levels (39.4 ± 18.6 vs. 26.3 ± 16.7, p < 0.01). In multivariable analysis adjusted for age, hypertension, left atrial diameter, and other clinical covariates, IBI emerged as a strong independent predictor of POAF (adjusted OR 1.041, 95% CI 1.036-1.046, p < 0.01). The IBI alone demonstrated moderate-to-good discriminative performance (AUC 0.72, 95% CI 0.70–0.74), significantly outperforming the Systemic Immune/Inflammation Index (SII; AUC 0.61, DeLong test p < 0.001) and providing superior reclassification (NRI 0.150, IDI 0.032) and model fit (lower AIC). Combining IBI with established clinical risk factors further improved predictive accuracy (combined AUC 0.74, specificity 72.4%). Tertile-based stratification revealed a clear graded relationship with POAF incidence (low IBI: 16.6%, medium: 21.3%, high: 35.1%; p = 0.02). Notably, the medium IBI stratum (11.18-25.44) displayed the highest discriminative power (AUC 0.87, 95% CI 0.85-0.88), with bootstrap validation confirming model stability (minimal bias, robust 95% CI). Conclusions: This study establishes the preoperative Inflammatory Burden Index (IBI) as the first validated composite inflammatory biomarker independently associated with POAF following CABG. Its superior performance over existing indices (SII), graded risk stratification, and peak accuracy in the moderate inflammation window highlight its potential for personalized preoperative risk assessment and targeted perioperative intervention strategies. Full article

Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) involves a sudden onset of a perfusion-pressure injury from the initial insult combined with a secondary injury phase produced by delayed cerebral ischemia, cerebrospinal fluid circulation disturbances, and generalized instability of the patient’s physiological state. The situation may be further complicated when there has been rupture of the aneurysm at the site of the carotid–posterior communicating (PCom) artery junction that occurs in conjunction with a fetal configuration of the posterior cerebral artery (fPCA), thereby making definitive treatment dependent on preserving the critical nature of the branches of the posterior circulation since the aneurysm’s neck plane coincides with the dominant posterior circulation conduit. Case Presentation: A 65-year-old female patient who was obese (Grade III BMI = 42), had chronic bronchial asthma, and arterial hypertension experienced a “thunderclap” type of headache in the right retro-orbital area followed by a syncopal episode and developed acute confusion with agitation. Upon admission to the hospital, her Glasgow Coma Scale (GCS) was 13, her FOUR score was 15, her Montreal Cognitive Assessment (MoCA) score was 12/30, her Hunt–Hess grade was 3, WFNS grade 2, and Fisher grade 4 SAH with intraventricular extension. Digital subtraction angiography (DSA) and three-dimensional rotational angiography revealed a posteriorly directed right carotid communicating aneurysm that had a relatively compact neck (approximately 2.5 mm) and sac size of approximately 7.7 × 6.6 mm, with the fPCA originating at the neck plane. Microsurgical treatment was performed with junction-preserving reconstruction with skull base refinement, temporary occlusion of the internal carotid artery for a few minutes, placement of clips reconstructing the carotid–PCom interface, and micro-Doppler verification of patent vessel. Postoperatively, the blood pressure was kept within the range of 110–130 mmHg with nimodipine and closely monitored. The neurological recovery was sequential (GCS of 15 by POD 2; MoCA of 22 by POD 5). By POD 5 CT scan, the clip remained positioned in a stable fashion without evidence of infarct, hemorrhage, or hydrocephalus; at three months she was neurologically intact (mRS 0; Barthel 100; MoCA 28/30), and CTA confirmed persistent exclusion of the aneurysm and preservation of fPCA flow. Conclusions: In cases where the ruptured aneurysm is located at the carotid communicating junction with the PCom artery in a configuration of the posterior cerebral artery that is described as fetal, clip treatment should be viewed as a form of branch-preserving junction reconstruction of the carotid–PCom junction supported by adherence to controlled postoperative physiology and close ppostoperativesurveillance. Full article

Ketones are metabolites primarily produced by the liver and are utilized by various organs outside of the liver. Recent advances have demonstrated that ketones serve not only as alternative energy sources but also as signaling molecules. Research indicates that ketones can influence cancer development and metastasis, cardiac metabolic and structural remodeling, physical performance, vascular function, inflammation, and the aging process. Emerging evidence from preclinical and early-phase clinical studies suggests that strategies such as ketone salts, ketone esters, and the ketogenic diet may offer therapeutic benefits for conditions like heart failure, acute cardiac injury, diabetic cardiomyopathy, vascular complications, atherosclerosis, hypertension, and aortic aneurysm. This literature review updates the current understanding of ketone metabolism and its contributions to cardiovascular health and diseases. We highlight the underlying molecular mechanism with post-translational modification known as β-hydroxybutyrylation, which affects the fate and function of target proteins. Additionally, we discuss the therapeutic challenges associated with ketone therapy, the potential of using ketone levels as biomarkers for cardiovascular diseases, as well as gender- and age-specific differences in ketone treatment. Finally, we explore future research directions and what is needed to translate these new insights into cardiovascular medicine. Full article

The acute phase of pulmonary embolism (PE) may be a severe and potentially life-threatening condition. Moreover, long-term consequences following the acute phase can significantly impact a patient’s daily life. A systematic approach to PE follow-up can identify potential complications following acute PE. Post-PE syndrome (PPES) is a common occurrence among survivors experiencing persistent dyspnea and impaired functional status. While the exact definition is evolving, it encompasses a spectrum of disease phenotypes that may occur following an acute PE, which ranges from dyspnea, functional limitation, or cardiac impairment to chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. This review will describe the different PPES phenotypes, including their physiological basis, diagnosis and workup, and management following acute PE. Full article

Background: Hemodynamic overload induces left ventricular remodeling and heart failure across various clinical presentations. While geometric remodeling is classically associated with increased vascular resistance in hypertension, distinct patterns emerge under the mechanical stress of aortic stenosis (AS). Concept: The “Stress Septal Sign” (Triple S) represents a marker of stress-mediated hemodynamic overload driven by diverse stimuli, ranging from mechanical stress in AS to emotional triggers in acute stress cardiomyopathy. Within this spectrum, Stressed Heart Morphology describes a specific phenotype characterized by a predominant and hyperdynamic LV septal base. Results: Chronic hemodynamic stress in severe AS results in prominent basal septal hypertrophy. This remodeling is characterized by distinct tissue energetics: hypermetabolic activity at the basal septum contrasted with reduced metabolic activity or hypokinesis in the apical regions. These findings on myocardial geometry, function, and energetics align with the adaptive phase of LV remodeling. Conclusions: The presence of adaptive myocardial basal tissue suggests an advanced remodeling stage that may require timely therapeutic intervention in severe AS. Therefore, identifying these specific tissue characteristics offers a unifying imaging paradigm (Triple S) for assessing cardiac stress, independent of the primary etiology. Full article

Pulmonary arterial hypertension (PAH) is a severe, progressive vasculopathy characterized by endothelial dysfunction, medial hypertrophy, and maladaptive vascular and cardiac remodelling that ultimately leads to right-heart failure and premature death. Despite advances in vasodilator therapies targeting endothelin, nitric oxide, and prostacyclin pathways, a substantial proportion of patients fail to achieve or maintain a low-risk profile, highlighting the need for disease-modifying strategies. Dysregulation of transforming growth factor-β (TGF-β) superfamily signalling, with excessive activin and growth differentiation factor activity and impaired bone morphogenetic protein signalling, plays a central role in PAH pathobiology. Sotatercept, a first-in-class activin signalling inhibitor, restores this imbalance by selectively trapping pro-proliferative ligands, thereby addressing a key molecular driver of pulmonary vascular remodelling. Evidence from pivotal phase II and III trials—PULSAR, STELLAR, ZENITH, and HYPERION—demonstrates that sotatercept significantly improves exercise capacity, haemodynamics, and risk status when added to background therapy. This review summarises the molecular mechanisms underlying sotatercept’s therapeutic effects, synthesises the current clinical evidence, and discusses its emerging role as a disease-modifying agent capable of promoting reverse pulmonary vascular remodelling within contemporary PAH management. Full article