Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Metal complexes of ursodeoxycholic acid and its metal complexes as potential antitumor agents against colon cancer

Colorectal cancer (CRC) takes the third place among the most commonly diagnosed cancer in males and the sec­ond in females. It is the second leading cause of death among neoplastic diseases worldwide.The physiological role of bile acids (BAs) is well known. The prevalence and clinical application of ursodeoxycho­lic acid (UDCA) as well as the data on participation of BAs in the pathogenesis of several liver diseases and gas­trointestinal (colon) tumorigenesis provoke interest in the relationship between UDCA and cancer. Experimen­tal evidence (in vitro and animal studies) suggests that ursodeoxycholic acid may have chemopreventive actions in colorectal cancer.The aim of our study was to evaluate the influence of Cu(II), Zn(II) and Ni(II) complexes of ursodeoxycholic ac­ids on viability and proliferation of cultured human colon cancer cells.In our investigations, we used the permanent cell line HT29 (human colorectal carcinoma) as a model system. The compounds tested were applied at concentrations of 10-200 μg/mL for 24-96 h (for short-term experiments with monolayer cell cultures) and 30 days (for long-term experiments with 3D cell colonies) and their effect on cell viability and proliferation was evaluated by the MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, trypan blue dye exclusion technique, double staining with acridine orange and propidium iodide and colony-forming method.Our results showed that the compounds investigated decreased viability and proliferation of the treated cells in a time- and concentration-dependent manner. Metal complexes expressed more pronounced cytotoxic/cytostatic activity compared to the corresponding ligand ursodeoxycholic acid.The metal complexes examined exhibited promising cytotoxic/antiproliferative properties against HT29 colon cancer cells and deserve further studies to clarify better their anti-tumor potential.Acknowledgements: This study was funded by Grant DFNP-17-89/28.07.2017 from the Program `Support of Young Scientists at the Bulgarian Academy of Sciences` and by a mutual project between the Bulgarian Academy of Sciences and the Romanian Academy

Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE.

Purpose Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)-positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. Methods Patients were randomly assigned (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI versus TRAS + AI. Secondary end points were PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety. Results Three hundred fifty-five patients were included in this analysis: LAP + TRAS + AI (n = 120), TRAS + AI (n = 117), and LAP + AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP + TRAS + AI versus TRAS + AI (median PFS, 11 v 5.7 months; hazard ratio, 0.62; 95% CI, 0.45 to 0.88; P = .0064). Consistent PFS benefit was observed in predefined subgroups. Overall response rate, clinical benefit rate, and overall survival also favored LAP + TRAS + AI. The median PFS with LAP + AI versus TRAS + AI was 8.3 versus 5.7 months (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = .0361). Common adverse events (AEs; ≥ 15%) with LAP + TRAS + AI, TRAS + AI, and LAP + AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the three groups, and AEs leading to discontinuation were lower with LAP + TRAS + AI. Conclusion Dual HER2 blockade with LAP + TRAS + AI showed superior PFS benefit versus TRAS + AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population