Background: Melanoma patients stop responding to targeted therapies mainly due to mitogen activated protein kinase (MAPK) pathway re-activation, phosphoinositide 3 kinase/the mechanistic target of rapamycin (PI3K/mTOR) pathway activation or stromal cell influence. The future of melanoma treatment lies in combinational approaches. To address this, our in vitro study evaluated if lower concentrations of Celecoxib (IC₅₀ in nM range) could still preserve the chemopreventive effect on melanoma cells treated with trametinib. Materials and Methods: All experiments were conducted on SK-MEL-28 human melanoma cells and BJ human fibroblasts, used as co-culture. Co-culture cells were subjected to a celecoxib and trametinib drug combination for 72 h. We focused on the evaluation of cell death mechanisms, melanogenesis, angiogenesis, inflammation and resistance pathways. Results: Low-dose celecoxib significantly enhanced the melanoma response to trametinib. The therapeutic combination reduced nuclear transcription factor (NF)–kB (p < 0.0001) and caspase-8/caspase-3 activation (p < 0.0001), inhibited microphthalmia transcription factor (MITF) and tyrosinase (p < 0.05) expression and strongly down-regulated the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway more significantly than the control or trametinib group (p < 0.0001). Conclusion: Low concentrations of celecoxib (IC₅₀ in nM range) sufficed to exert antineoplastic capabilities and enhanced the therapeutic response of metastatic melanoma treated with trametinib.

Background and Objectives: ST elevation myocardial infarction (STEMI), particularly when complicated by cardiogenic shock (CS), is a critical condition associated with high mortality rates. Identifying predictors of in-hospital mortality can enhance patient management and outcomes. Materials and Methods: This observational, retrospective case–control study included STEMI patients, both complicated and uncomplicated by CS. Additionally, demographics, clinical characteristics, laboratory data and in-hospital mortality rates were analysed for STEMI patients with CS and those without CS. Results: This study included a total of 101 patients with STEMI, of whom 51 (50.5%) had STEMI without CS and 50 (49.5%) had STEMI with CS. No significant differences were observed in demographic characteristics or STEMI risk factors between the two groups. Emergency coronarography was performed in 90.1% of the patients, with successful thrombolysis achieved in 24.5%. Patients with CS exhibited a significantly higher mortality (52%) than those without CS (11.76%). Univariate analysis identified white blood cell counts, CK-MB, CK levels, elevated creatinine and uric acid levels and a reduced left ventricular ejection fraction (LVEF) as predictors of mortality. Logistic regression analysis revealed that LVEF and CK-MB were independent predictors of in-hospital mortality in patients with STEMI and CS. Each 1% increase in LVEF was associated with a reduced mortality risk (HR = 0.89; 95% CI 0.81–0.98; p = 0.018), while elevated CK-MB levels were linked to an increased mortality risk (HR = 1; 95% CI 1–1.01; p = 0.014). Conclusions: Reduced systolic function and elevated CK-MB levels are key predictors of in-hospital mortality and outcomes in STEMI patients with CS. These findings underscore the importance of early identification and support the development of targeted management strategies aimed at improving outcomes in this high-risk population.

Iron interactions with the cardiovascular system were proposed about half a century ago, yet a clear-cut understanding of this micronutrient and its intricacies with acute and chronic events is still lacking. In chronic heart failure, patients with decreased iron stores appear to benefit from intravenous administration of metallic formulations, whereas acute diseases (e.g., myocardial infarction, stroke) are barely studied in randomized controlled trials in humans. However, proof-of-concept studies have indicated that the dual redox characteristics of iron could be involved in atherosclerosis, necrosis, and ferroptosis. To this end, we sought to review the currently available body of literature pertaining to these temporal profiles of heart diseases, as well as the pathophysiologic mechanism by which iron enacts, underlining key points related to treatment options.

Objectives: To evaluate the individual and combined impact of sarcopenia (SARC) and heart failure (HF) on functional performance, systemic biomarkers, and structural cardiac changes in hospitalized older adults. A total of 598 patients aged ≥65 years admitted to a geriatric unit between January 2023 and December 2024, stratified into four groups based on the presence or absence of sarcopenia and HF. Methods: Muscle strength (handgrip), gait speed, SPPB score, and calf circumference were assessed, along with inflammatory/nutritional markers and echocardiographic parameters. Sarcopenia was diagnosed according to EWGSOP2 criteria and HF was diagnosed according to ESC 2021 guidelines. Results: Functional impairment was the most severe in the SARC+/HF+ group, with significantly lower handgrip strength, gait speed, and SPPB scores (p < 0.001). Sarcopenia alone was associated with greater functional decline than HF alone. Serum hemoglobin and albumin levels were reduced in sarcopenic groups, while NT-proBNP and cardiac remodeling indices (IVS and LVEDD) were highest in patients with both conditions. Conclusions: Sarcopenia exerts a significant impact on physical performance in older adults, surpassing that of HF in isolation. The coexistence of sarcopenia and HF amplifies vulnerability and clinical decline, supporting the need for integrated assessment and early muscle-targeted interventions in geriatric cardiology.

Cardiovascular diseases are the main cause of death in the world, with ischemic heart disease (i.e., myocardial infarction) and cerebrovascular disease (i.e., stroke) taking the highest toll. Advances in diagnosis and treatment have led to a significant alleviation of ischemic complications, specifically in the realm of pharmacotherapy and interventional devices, while pharmacogenomics has yet to be fully leveraged to improve the burden of disease. Atherothrombotic events might occur earlier or respond worse to treatment in patients with genetic variants of GP IIb/IIIa. Therefore, we aimed to quantitate the involvement of the PlA2 variant in the risk of cerebral stroke events. A systematic search and meta-analysis were performed by pooling the risks of individual studies. A total of 31 studies comprising 5985 stroke patients and 7886 controls were analyzed. A meta-analysis of four studies on hemorrhagic stroke patients showed no association with the PIA2 rs5918(C) polymorphism in both fixed-effect (OR = 0.90 95%CI [0.71; 1.14]; p = 0.398) and random-effect models (OR = 0.86 95%CI [0.62; 1.20]; p-value = 0.386). The power of this analysis was below 80%. The PIA2 allele was associated with an increased risk of ischemic stroke. No association was found with hemorrhagic stroke, most likely due to the small number of available studies, which resulted in a lack of power.