Hypolipidaemia among patients with PMM2-CDG is associated with low circulating PCSK9 levels: a case report followed by observational and experimental studies.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel therapeutics for reducing low-density lipoprotein cholesterol (LDLc). While serious side-effects have not been observed in short-term clinical trials, there remain concerns that long-term PCSK9 inhibition may cause neurocognitive side-effects.

Methods And Results: An adult male with childhood-onset global developmental delay, cerebellar atrophy and severe hypolipidaemia underwent extensive biochemical and genetic investigations.

Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis.

Aims: To determine whether a restrictive strategy of red blood cell (RBC) transfusion at lower haemoglobin concentrations is inferior to a liberal strategy of RBC transfusion at higher haemoglobin concentrations in patients undergoing cardiac surgery.

Methods And Results: We conducted a systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials of the effect of restrictive and liberal RBC transfusion strategies on mortality within 30 days of surgery as the primary outcome. Secondary outcomes were those potentially resulting from anaemia-induced tissue hypoxia and transfusion outcomes.

Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial.

Objectives: To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity.

Design: Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898).

PON1 Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics, pharmacodynamics, and a meta-analysis of clinical outcomes.

Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support.

Genetic determinants of dabigatran plasma levels and their relation to bleeding.

Background: Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.

Methods And Results: We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants.