BackgroundHeart rate variability (HRV) has been used to assess cardiac autonomic activity in critically ill patients, driven by translational and biomarker research agendas. Several clinical and technical factors can interfere with the measurement and/or interpretation of HRV. We systematically evaluated how HRV parameters are acquired/processed in critical care medicine.MethodsPubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (1996–2016) were searched for cohort or case–control clinical studies of adult (>18 years) critically ill patients using heart variability analysis. Duplicate independent review and data abstraction. Study quality was assessed using two independent approaches: Newcastle–Ottowa scale and Downs and Black instrument. Conduct of studies was assessed in three categories: (1) study design and objectives, (2) procedures for measurement, processing and reporting of HRV, and (3) reporting of relevant confounding factors.ResultsOur search identified 31/271 eligible studies that enrolled 2090 critically ill patients. A minority of studies (15; 48%) reported both frequency and time domain HRV data, with non-normally distributed, wide ranges of values that were indistinguishable from other (non-critically ill) disease states. Significant heterogeneity in HRV measurement protocols was observed between studies; lack of adjustment for various confounders known to affect cardiac autonomic regulation was common. Comparator groups were often omitted (n = 12; 39%). This precluded meaningful meta-analysis.ConclusionsMarked differences in methodology prevent meaningful comparisons of HRV parameters between studies. A standardised set of consensus criteria relevant to critical care medicine are required to exploit advances in translational autonomic physiology.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0146-1) contains supplementary material, which is available to authorized users.

Our results indicate survival is poor after second primary glioma in this young adult population, although survival after second primary meningioma is good. Our study has clinical implications for the surveillance of childhood cancer survivors at risk of developing second primary brain tumors, in particular survivors of childhood acute lymphoblastic leukemia or childhood brain tumors.

Background: Elevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. Methods: We performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRTePCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). Results: MicroRNAs were detectable in all 59 patients (median age 67 yr [61e75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95e8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94e10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n¼48) and two (n¼11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia. Conclusions: Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.