Comparison of latest generation supra-annular and intra-annular self-expanding transcatheter heart valves

BackgroundThis study compares two latest-generation self-expanding transcatheter heart valves (THV), the supra-annular ACURATE neo (Boston Scientific) and the intra-annular Centera THV (Edwards Lifesciences).MethodsIn this single center observational cohort trial 317 patients treated with the ACURATE neo and 78 patients treated with the Centera TVH were included. The main endpoints were device success and the early safety endpoint at 30 days.ResultsBesides higher incidence of diabetes mellitus and higher body mass index in patients treated with the ACURATE neo THV, there were no baseline differences between the groups. Device success was similar in both groups (neo: 91.8% vs. Centera: 93.6%; P=0.598), with numerically higher rates of moderate to severe paravalvular leakage in the ACURATE neo group (4.7% vs. 1.3%; P=0.214). At 30 days all-cause mortality rates were low in both groups (0.3% vs. 0%; P=0.620) and no difference occurred in the early safety at 30 days (19.3% vs. 16.7%; P=0.599). However, all-cause stroke rates were significantly higher in patients treated with the Centera THV (6.4 vs. 1.6%; P=0.015).ConclusionsThe ACURATE neo and the Centera THV show low mortality rates as well as comparable, favorable hemodynamics. The finding of higher stroke rates at 30 days with the repositionable Centera SE-THV needs further assessment.     

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan-Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.