US physician perspective on the use of biomarker and ctDNA testing in patients with melanoma.

New treatments have increased survival of patients with melanoma, and methods to monitor patients throughout the disease process are needed. Circulating tumor DNA (ctDNA) is a predictive and prognostic biomarker that may allow routine, real-time monitoring of disease status. We surveyed 44 US physicians to understand their preferences and practice patterns for biomarker and ctDNA testing in their patients with melanoma. Tumor biomarker testing was often ordered in stage IIIA-IV patients. Barriers to biomarker testing include insufficient tissue (60%) and lack of insurance coverage (54%). ctDNA testing was ordered by 16-18% of physicians for stages II-IV. Reasons for not using ctDNA testing included lack of prospective data (41%), ctDNA testing used for research only (18%), and others. Physicians (≥74%) believed that ctDNA assays could help with monitoring and treatment selection throughout the disease process. Physicians consider ctDNA testing potentially valuable for clinical decision-making but cited concerns that should be addressed.

Bioprosthetic versus mechanical valves for mitral valve replacement in patients < 70 years: an updated pairwise meta-analysis.

BACKGROUND: The ideal conduit for mitral valve replacement (MVR) remains elusive, particularly among younger patients due to increased life expectancy. We perform a pairwise meta-analysis comparing the use of bioprosthetic valves (BPV) and mechanical mitral valves (MMV) in patients < 70 years old undergoing MVR. METHODS: We comprehensively searched medical databases to identify studies comparing the use of BPV and MMV in patients < 70 years old undergoing MVR. Pairwise meta-analysis was performed using the Mantel-Haenszel method in R version 4.0.2. Outcomes were pooled using the random effect model as risk ratios (RR) with their 95% confidence intervals (95% CI). RESULTS: 16,879 patients from 15 studies were pooled. Compared to MMV, BPV was associated with significantly higher rates of 30-day mortality (RR 1.53, p = 0.0006) but no difference in 30-day stroke (RR 0.70, p = 0.43). At a weighted mean follow-up duration of 14.1 years, BPV was associated with higher rates of long-term mortality (RR 1.28, p = 0.0054). No difference was seen between the two groups for risk of long-term stroke (RR 0.92, p = 0.67), reoperation(RR 1.72, p = 0.12), or major-bleeding (RR 0.57, p = 0.10) at a weighted mean follow-up duration of 11.7, 11.3, and 11.9 years, respectively. CONCLUSION: The use of MMV in patients < 70 undergoing MVR is associated with lower rates of 30-day/long-term mortality compared to BPV. No significant differences were observed for risk of 30-day/long-term stroke, long-term reoperation, and long-term major bleeding. These findings support the use of MMV in younger patients, although prospective, randomized trials are still needed.

Molecular targets of statins and their potential side effects: Not all the glitter is gold.

Statins are a class of drugs widely used worldwide to manage hypercholesterolemia and the prevention of secondary heart attacks. Currently, available statins vary in terms of their pharmacokinetic and pharmacodynamic profiles. Although the primary target of statins is the inhibition of HMG-CoA reductase (HMGR), the rate-limiting enzyme in cholesterol biosynthesis, statins exhibit many pleiotropic effects downstream of the mevalonate pathway. These pleiotropic effects include the ability to reduce myocardial fibrosis, pathologic cardiac disease states, hypertension, promote bone differentiation, anti-inflammatory, and antitumor effects through multiple mechanisms. Although these pleiotropic effects of statins may be a cause for enthusiasm, there are many adverse effects that, for the most part, are unappreciated and need to be highlighted. These adverse effects include myopathy, new-onset type 2 diabetes, renal and hepatic dysfunction. Although these adverse effects may be relatively uncommon, considering the number of people worldwide who use statins daily, the actual number of people affected becomes quite large. Also, co-administration of statins with several other medications, herbal agents, and foods, which interact through common enzymatic pathways, can have untoward clinical consequences. In this review, we address these concerns.