A Pilot, Double-Blind, Randomized, Controlled Trial of High-Dose Intravenous Vitamin C for Vasoplegia After Cardiac Surgery.

OBJECTIVE: To conduct a pilot feasibility and physiologic efficacy study of high-dose vitamin C in patients with vasoplegia after cardiac surgery. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Two tertiary intensive care units (ICUs). PARTICIPANTS: Post-cardiac surgery patients with vasoplegia. INTERVENTIONS: The authors randomly assigned the patients to receive either high-dose intravenous vitamin C (1,500 mg every 6 hours) or placebo. The primary outcome was time from randomization to resolution of vasoplegia. Secondary outcomes included total norepinephrine equivalent dose in the first 2 days, ICU length of stay, ICU mortality, and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: The authors studied 50 patients (25 patients in each arms). The mean (standard deviation) time to resolution of vasoplegia was 27.0 (16.5) hours in the vitamin C group versus 34.7 (41.1) hours in the placebo group (mean decrease with vitamin C of 7.7 hours, 95% confidence interval -10.5 to 25.9, p = 0.40). The median (interquartile range) norepinephrine equivalent dose in the first 2 days was 64.9 (23.5-236.5) µg/kg versus 47.4 (21.4-265.9) µg/kg in the vitamin C and placebo group (p = 0.75). The median duration of ICU admission was similar (1.4 [0.5-2.5] days and 1.5 [0.5-3.3] days in the vitamin C and placebo group; p = 0.36). Only 1 patient, in the vitamin C arm, died. CONCLUSION: In patients with post-cardiac surgery vasoplegia, high-dose vitamin C infusion was feasible, appeared safe, and, within the limitations of a pilot study, did not achieve statistically faster resolution of vasoplegia.

Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders.

BACKGROUND: APOL1 variants G1 and G2 are common in populations with recent African ancestry. They are associated with protection from African sleeping sickness, however homozygosity or compound heterozygosity for these variants is associated with chronic kidney disease (CKD) and related conditions. What is not clear is the extent of associations with non-kidney-related disorders, and whether there are clusters of diseases associated with individual APOL1 genotypes. METHODS: Using a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes. FINDINGS: We identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were specifically associated with 26 of these conditions (all deleteriously), with an over-representation of infectious diseases (including hospitalisation and death resulting from COVID-19). The analysis also exposed complexities in the relationship between APOL1 and CKD that are not evident when risk variants are grouped together: G1 homozygosity, G2 homozygosity, and G1/G2 compound heterozygosity were each shown to be associated with distinct CKD phenotypes. The multi-locus nature of the G1/G2 genotype means that its associations would go undetected in a standard genome-wide association study. INTERPRETATION: Our findings have implications for understanding health risks and better-targeted detection, intervention, and therapeutic strategies, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora. FUNDING: This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).