Obesity and hypertension are interdependent chronic conditions that substantially elevate global cardiovascular risk. Rising obesity prevalence has led to a parallel increase in hypertension, driven by complex physiological disturbances that extend beyond excess body weight alone. This review synthesizes current evidence on the mechanisms linking adiposity to blood pressure elevation, emphasizing the roles of sympathetic nervous system overactivity, insulin resistance, renal sodium retention, and adipose-derived hormonal and inflammatory dysregulation. Particular attention is given to visceral adiposity, which exerts adverse vascular, renal, and metabolic effects that accelerate development of hypertension-mediated organ damage, including left ventricular hypertrophy, arterial stiffness, and early renal injury. The manuscript also evaluates therapeutic strategies for obesity-related hypertension. Lifestyle interventions-caloric restriction, structured physical activity, and behavioral therapy-remain the cornerstone of management, producing clinically meaningful reductions in body weight and blood pressure. However, sustained weight loss is difficult for many individuals, necessitating adjunctive approaches. Contemporary pharmacotherapies, particularly glucagon-like peptide-1 receptor agonists such as semaglutide, have demonstrated substantial benefits in both weight reduction and blood pressure control. For patients with severe obesity or inadequate response to medical therapy, metabolic and bariatric procedures offer the most durable outcomes, improving cardiometabolic profiles and reducing antihypertensive medication burden.
Cardiac amyloidosis (CA) represents an increasingly recognized but historically underdiagnosed cause of restrictive cardiomyopathy and heart failure. CA is now understood to be more prevalent, particularly in older adults, as advancements in imaging and biomarker technologies have improved detection. The disease results from the misfolding of precursor proteins, primarily immunoglobulin light chains (in light chain (AL) amyloidosis) or transthyretin (in transthyretin (ATTR) amyloidosis), into insoluble fibrils that deposit in myocardial tissue. These deposits cause structural and functional cardiac impairment through both physical infiltration and cytotoxic mechanisms, leading to diastolic dysfunction, arrhythmias, and progressive heart failure. Understanding the molecular basis of amyloid formation and deposition has revealed subtype-specific mechanisms of toxicity and tissue tropism, highlighting the central role of protein instability, proteolytic cleavage, and oxidative stress in disease progression. Furthermore, increasing awareness of phenotypic variability and sex- or ethnicity-based diagnostic disparities has called for earlier recognition and differentiation of CA subtypes. Diagnostic precision is enhanced by a multimodal approach incorporating histopathology, biomarker staging, and advanced imaging techniques such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy. This review addresses our contemporary understanding of the molecular mechanisms, pathophysiologic cascade, and diagnostic evolution of AL and ATTR CA, emphasizing clinical progress. By delineating the biological mechanisms and tools for early identification, this paper aims to strengthen the framework for diagnosing and managing a disease that was once overlooked but is now at the forefront of modern cardiovascular medicine.
BACKGROUND:Fluorouracil (5-FU) remains a cornerstone of systemic therapy for metastatic colorectal cancer (mCRC). Leucovorin enhances fluorouracil cytotoxicity through thymidylate synthase modulation. Although randomized trials established the benefit of leucovorin modulation, real-world survival and toxicity outcomes remain incompletely characterized. METHODS:We conducted a retrospective cohort study using the TriNetX US Collaborative Network, which includes electronic health record data from 67 healthcare organizations. Adult patients with mCRC receiving intravenous fluorouracil between January 2000 and January 2026 were included. Patients were stratified by leucovorin exposure. Propensity score matching (1:1 nearest neighbor) balanced demographics, comorbidities, treatment exposures, surgical history, and genomic alterations. The primary outcome was all-cause mortality. Secondary outcomes included hospitalization, granulocyte colony-stimulating factor use, blood transfusion, sepsis, thrombocytopenia, and gastrointestinal toxicity. Kaplan-Meier and Cox proportional hazards analyses were performed. RESULTS:After propensity score matching, 2,403 patients were included in each cohort. Survival analysis included 2,385 patients in the leucovorin cohort and 2,391 patients in the fluorouracil-alone cohort after exclusions. Mortality occurred in 38.8% of patients receiving fluorouracil with leucovorin compared with 47.1% receiving fluorouracil alone (hazard ratio 0.752, 95% CI 0.690-0.821). Median survival was longer in the leucovorin cohort (964 vs. 718 days). Leucovorin use was associated with increased hospitalization (HR 1.222), granulocyte colony-stimulating factor use (HR 1.360), blood transfusion (HR 1.593), and gastrointestinal toxicity. CONCLUSIONS:In this large real-world cohort, leucovorin significantly improved survival in patients with metastatic colorectal cancer receiving fluorouracil but was associated with increased treatment-related toxicity. These findings support the continued use of leucovorin as a key component of fluorouracil-based chemotherapy regimens.
Chimeric antigen receptor T-cell therapy has revolutionized the treatment of hematological malignancies but is associated with significant immune-mediated toxicities, particularly cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, driven by an exaggerated inflammatory response involving cytokines such as interleukin (IL)-6, IL-1, and tumor necrosis factor-alpha. These processes contribute to endothelial dysfunction and a spectrum of cardiovascular complications, including hypotension, arrhythmias, myocardial dysfunction, and heart failure. The underlying pathophysiology involves complex interactions between immune activation and vascular injury, often progressing rapidly and necessitating early recognition. Contemporary management is shifting from reactive treatment to proactive strategies, emphasizing early risk stratification using clinical parameters, biomarkers, and imaging, alongside timely intervention with cytokine-directed therapies such as IL-6 and IL-1 inhibitors. Integration of cardiology within multidisciplinary care teams is essential for optimizing outcomes through tailored monitoring and management of cardiovascular complications. As chimeric antigen receptor T-cell therapy expands to broader and higher-risk populations, including those with pre-existing cardiovascular disease, a structured cardio-oncology approach and further prospective research are critical to improving safety and long-term outcomes.
