Proteome- and Transcriptome-Wide Genetic Analysis Identifies Biological Pathways and Candidate Drug Targets for Preeclampsia.

Background: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. However, the current understanding of its underlying biological pathways remains limited.

Methods: In this study, we performed a cross-platform proteome- and transcriptome-wide genetic analysis aimed at evaluating the causal relevance of >2000 circulating proteins with preeclampsia, supported by data on the expression of over 15 000 genes across 36 tissues leveraging large-scale preeclampsia genetic association data from women of European ancestry.

Mechanical circulatory support in patients with congenital heart disease: a European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study.

Objectives: This study aims to explore characteristics and clinical outcomes of patients with congenital heart disease (CHD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS).

Methods: This is a retrospective study of EUROMACS participants receiving MCS as bridge-to-transplant, possible bridge-to-transplant, or rescue therapy/bridge-to-recovery from 2011 to 2023 (n = 5340). Adult and paediatric cohorts were analysed separately.

Genetically proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations.

Aims: Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is increasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL-lowering, overall and through PCSK9 drug targets, on congenital malformations.

Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association.

Background And Aims: Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects).

Effects of intensive induction and consolidation chemotherapy with idarubicin and high dose cytarabine on minimal residual disease levels in newly diagnosed adult precursor-B acute lymphoblastic leukemia.

An intensive induction regimen, consisting of idarubicin and high dose cytarabine, was assessed in 19 adult patients, median age 44 years, with newly diagnosed precursor-B acute lymphoblastic leukemia (ALL). Patients achieving a complete response (CR) were given an attenuated consolidation course. The primary endpoints were induction death rate and incidence of serious non-hematological toxicity.