Yerevan State Medical University

Heart failure with preserved ejection fraction (HFpEF) is a cardiometabolic syndrome strongly associated with aging, systemic inflammation and endothelial dysfunction, in which impaired endothelial nitric oxide synthase (eNOS) signaling plays a central role. This study aimed to identify circulating proteins associated with HFpEF and to explore their relationship with endothelial alterations under metabolic stress. A total of 109 HFpEF patients and 49 control subjects underwent clinical, laboratory, and echocardiographic assessment. HFpEF patients exhibited a high burden of cardiometabolic comorbidities and significantly increased NT-proBNP (2851.2 ± 1565.5 vs 156.0 ± 85.2 pg/mL) and C-reactive protein levels (2.9 ± 4.5 vs 0.31 ± 0.33 mg/dL). Echocardiography revealed elevated filling pressures (E/e′ 16.5 ± 3.8 vs 7.0 ± 1.9), a higher prevalence of high-probability pulmonary hypertension, and impaired right ventricular–pulmonary artery coupling. Exploratory proteomic profiling identified galectin-3 binding protein (LGALS3BP) as increased in plasma from HFpEF patients, a finding confirmed by ELISA showing significantly higher circulating levels compared with controls (8.65 ± 0.66 vs 2.36 ± 0.26 ng/mL, p < 0.001). Pathway analysis suggested a potential association between LGALS3BP and activation of nitric oxide synthase 2 (NOS2)-related inflammatory pathways. In vitro, metabolic stress conditions increased LGALS3BP expression in murine endothelial cells, with a more pronounced response in eNOS⁻/⁻ cells. In addition, eNOS deficiency was associated with the appearance of a lower-molecular weight LGALS3BP form and with increased markers of endothelial senescence and autophagy. LGALS3BP is elevated in HFpEF and is associated with endothelial alterations linked to impaired eNOS signaling under metabolic stress. These findings suggest a potential connection between endothelial stress responses and LGALS3BP expression in HFpEF, supporting further investigation of this protein as a biomarker of endothelial dysfunction in age-related cardiometabolic disease.

The aim of this study was to evaluate differences in safety and efficacy outcomes of PCNL between elderly and non-elderly patients, with special focus on commonly applied age cut-off values. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Comparative studies evaluating outcomes of PCNL in elderly versus non-elderly patients were identified through comprehensive searches of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library up to February 2026. Primary outcomes included overall, minor, and major complications, as well as stone-free rate (SFR). Subgroup analyses were performed according to different age thresholds used to define elderly populations (60, 65, and 70 years). Seventeen studies encompassing 45,603 patients, including 10,745 elderly individuals, were included. When pooled across all age definitions, rates of overall complications (OR 1.20, 95

This study evaluated the diagnostic and prognostic value of serum bone metabolism markers—osteocalcin and β-Cross-Laps—in patients with type 2 diabetes mellitus (T2DM) undergoing intraosseous dental implantation. A blind randomized prospective clinical study was conducted between 2023 and 2025 involving 73 patients with partial or complete edentulism. Patients were randomly assigned to two groups: (1) Group A: 37 patients received UV-photofunctionalized implants (154 implants). (2) Group B: 36 patients received non-UV-photofunctionalized implants (148 implants). Serum osteocalcin and β-Cross-Laps were measured preoperatively, 1 month postoperatively, and 3 months after implantation using enzyme-linked immunosorbent assay (ELISA). Clinical and radiological outcomes included implant survival, marginal bone loss (MBL), probing pocket depth (PPD), bleeding on probing (BOP), resonance frequency analysis (RFA), and prosthetic success. Significant correlations were observed between serum osteocalcin and β-Cross-Laps concentrations and implant success rates. Implant failure occurred more frequently in patients with low osteocalcin and elevated β-Cross-Laps. Implant survival over 3 years was 95.2

Recent advancements in oncology have markedly enhanced cancer survival rates; however, anticancer therapies, particularly anthracyclines, pose significant cardiovascular (CV) risks, collectively referred to as cancer therapy-related cardiovascular toxicity (CTR-CVT). This review consolidates evidence on strategies to mitigate CTR-CVT especially associated with anthracyclines. Neurohormonal blockers, including ACE inhibitors, ARBs, and β-blockers, constitute the foundation of prevention, although their efficacy varies: combinations such as ACEi/ARB with βB yield mixed outcomes, whereas carvedilol offers antioxidant benefits beyond β-blockade. Sacubitril/valsartan (ARNI) has demonstrated improvements in global longitudinal strain and LVEF preservation in the SARAH trial, albeit with associated hypotension risks. Aldosterone antagonists show potential, with spironolactone preserving LVEF and diastolic function, though eplerenone has not shown significant effects. Statins present conflicting data; the STOP-CA trial supports atorvastatin for LVEF preservation, while the PREVENT and SPARE-HF trials found no benefit. Emerging evidence suggests sodium-glucose cotransporter-2 inhibitors (SGLT2i), such as dapagliflozin and empagliflozin, as promising agents, with preclinical and early clinical data indicating cardioprotection through metabolic modulation, anti-inflammatory effects, and reduced oxidative stress. Gaps remain in understanding CTR-CVT pathophysiology, risk stratification, and the translation of preclinical findings. Future efforts should prioritize personalized approaches, dynamic risk assessment (e.g., HFA-ICOS tool), and a paradigm shift from oxidative stress to cardiometabolic dysfunction. Multidisciplinary collaboration is essential to optimize oncological outcomes while minimizing CV toxicity, with SGLT2i representing a key frontier for validation in ongoing trials.

BACKGROUND:Long-term survival for high-risk neuroblastoma has increased from 40% to 60% by optimizing chemotherapy, surgery, radiation therapy, and the addition of anti-GD2 antibody therapy. However, the high cost of this antibody presents access issues globally. This study evaluates the availability, financial coverage, and barriers to accessing these therapies across diverse healthcare settings. METHODS:An online survey collected data on demographics, treatment practices, financial coverage, regulatory status, and barriers to anti-GD2 therapy. Fisher's exact test was used to compare categorical variables between high-income countries (HICs) and low- and middle-income countries (LMICs). A retrospective cost analysis estimated the financial burden of anti-GD2 therapies using standardized dosing for a representative 3-year-old patient. RESULTS:Responses came from 100 facilities in 80 cities and 59 countries. Anti-GD2 therapy for frontline maintenance was available in 93% of HIC centers, but only 21% of LMIC centers; 65% of LMIC centers reported no access, while the remainder had limited or irregular availability (p < 0.0001, Fisher's exact test). When unavailable, isotretinoin was most often used alone. Financial coverage differed significantly: HICs relied on government or insurance funding, while LMICs depended on out-of-pocket or non-profit support. Cost analysis showed a full treatment course would cost approximately $192,750 for dinutuximab, $142,695 for dinutuximab beta, and $610,800 for naxitamab, highlighting the substantial financial burden these therapies impose. CONCLUSION:Global access to anti-GD2 therapy is highly unequal. Strategic measures, including negotiations for reduced drug costs, research-based access, and WHO Essential Medicines List inclusion, could help address these disparities.