Characterisation of a compound in-cis GATA2 germline mutation in a pedigree presenting with myelodysplastic syndrome/acute myeloid leukemia with concurrent thrombocytopenia

Letter to the editorC N Hahn, P J Brautigan, C-E Chong, A Janssan, P Venugopal, Y Lee, A E Tims, M S Horwitz, M Klingler-Hoffmann, and H S Scot

High-density lipoprotein cholesterol associated with change in coronary plaque lipid burden assessed by near infrared spectroscopy

Abstract not availableSatoshi Honda, Samuel L. Sidharta, Daisuke Shishikura, Kohei Takata, Giuseppe A. Di Giovanni, Tracy Nguyen, Alex Janssan, Susan W. Kim, Jordan Andrews, Peter J. Psaltis, Matthew I. Worthley, Stephen J. Nicholl

Effect of Serial Infusions of CER-001, a Pre-β High-Density Lipoprotein Mimetic on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes: The CARAT Trial

Background: CER - 001 is a negatively charged, engineered pre - HDL mimetic containing apolipoprotein A - I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER - 001 on cholesterol efflux and vascular inflammation. In a post hoc re - analy sis of a previously completed study of intravenous infusion of CER - 001 3 mg/kg in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasound (IVUS) . Objective: To determine the effect of infusing CER - 001 on cor onary atherosclerosis progression in statin - treated patients. Design: A double - blind, randomized, multicenter trial evaluated the effect of ten weekly intravenous in fusions of CER - 001 3 mg/kg (n=135) or placebo (n=137 ) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) >30% in the proximal segment of an epicardial artery by IVUS . Settings and participants: 34 academic and community hospitals in Australia, Hungary, The Netherlands and United States in patients wit h ACS presenting for coronary angiography. Intervention: Participants were randomized to receive weekly CER - 001 3 mg/kg or placebo for ten weeks, in addition to statins. Main outcome measures: The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to day 78 measured by serial intravascular ultrasonography (IVUS) imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of Nicholls et al 5 patients demonstrating plaque re gression. Safety and tolerability were also evaluated. Results: Among 293 treated patients, 29 % had statin use prior to the index ACS and 272 had evaluable imaging at follow - up. The placebo and CER - 001 groups had similar post - treatment median levels of LDL - C (74 vs 79 mg/dL (P=0.15) and HDL - C (43 vs 44 mg/dL, P=0.66). The primary efficacy measure, PAV, decreased 0.41 % with placebo (P=0.005 compared with baseli ne), but not with CER - 001 ( - 0.09 %, P=0.67 compared with baseline; between group differences P=0.15) . Similar percentages of patients in the placebo and CER - 001 groups demonstrated regression of PAV (57.7% vs. 53.3%, P=0.49). Infusions were well tolerated with no differences in clinical and laboratory adverse events observed between treatment groups. Co nclusion: Infusion of CER - 001 did not promote regression of coronary atherosclerosis in statin - treated patients with ACS and high plaque burden. (Funded by Cerenis Pharmaceuticals , ClinicalTrials.gov identifier – NCT 2484378