Data_Sheet_1_Supplemental oxygen did not significantly affect two-year mortality in patients at-risk for cardiovascular complications undergoing moderate- to high-risk abdominal surgery–A follow-up analysis of a prospective randomized clinical trial.docx

BackgroundIn relatively healthy middle-aged patients, recent studies have shown that supplemental oxygen did not significantly increase one-year mortality after noncardiac surgery. If supplemental oxygen influences long-term mortality, specifically in elderly patients with cardiovascular risk-factors, remains unknown. Thus, we evaluated the effect of supplemental oxygen on two-year mortality in patients with cardiovascular risk factors undergoing moderate- to high-risk major abdominal surgery.MethodsThis is a follow-up study of a prospective, randomized, double-blinded, clinical trial. Two hundred fifty-eight patients, who were at least 45 years of age and at-risk for cardiovascular complications were randomly assigned to receive 80 vs. 30% oxygen during surgery and for the first two postoperative hours. Vital status was obtained from all patients 2 years after surgery using the national registry. Preoperative and postoperative maximum concentrations of NT-proBNP, Troponin T (TnT), Copeptin, von Willebrand Factor (vWF), static oxidation-reduction potential (sORP) and oxidation-reduction potential capacity (cORP) were tested for association with two-year mortality.ResultsThe median age of patients was 74 years (25th-75th percentile 70–78 years). 25.8% (95% CI: 17.3–32.4%) of patients in the 80% oxygen group and 22.3% (95% CI: 14.8–29.1%) in the 30% oxygen group died within 2 years after surgery. No significant difference in two-year mortality was found between patients, who received 80% oxygen concentration, versus patients, who received 30% oxygen concentration (estimated hazard ratio 1.145; 95% CI 0.693–1.893; p = 0.597). Preoperative Copeptin concentrations and postoperative maximum vWF activity were significantly associated with two-year mortality (p ConclusionOur results are consistent with previous studies, that showed that supplemental oxygen did not increase long-term mortality. Therefore, it is becoming more evident that supplemental oxygen may not have a significant effect on long-term outcome in patients undergoing major abdominal surgery.</p

A novel <i>HSD17B10</i> mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression

<p>We report a Caucasian boy with intractable epilepsy and global developmental delay. Whole-exome sequencing identified the likely genetic etiology as a novel p.K212E mutation in the X-linked gene <i>HSD17B10</i> for mitochondrial short-chain dehydrogenase/reductase SDR5C1. Mutations in <i>HSD17B10</i> cause the HSD10 disease, traditionally classified as a metabolic disorder due to the role of SDR5C1 in fatty and amino acid metabolism. However, SDR5C1 is also an essential subunit of human mitochondrial RNase P, the enzyme responsible for 5′-processing and methylation of purine-9 of mitochondrial tRNAs. Here we show that the p.K212E mutation impairs the SDR5C1-dependent mitochondrial RNase P activities, and suggest that the pathogenicity of p.K212E is due to a general mitochondrial dysfunction caused by reduction in SDR5C1-dependent maturation of mitochondrial tRNAs.</p