Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): A Prospective Longitudinal Observational Study

BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management

Effect of Genetic Variations in Syntaxin-Binding Protein-5 and Syntaxin-2 on von Willebrand Factor Concentration and Cardiovascular Risk

Background - Elevated von Willebrand factor (VWF) plasma levels are associated with an increased risk of cardiovascular disease. A meta-analysis of genomewide association studies on VWF identified novel candidate genes, that is, syntaxin-binding protein 5 (STXBP5) and syntaxin 2 (STX2), which are possibly involved in the secretion of VWF. We investigated whether VWF antigen levels (VWF:Ag), VWF collagen-binding activity (VWF:CB) and the risk of arterial thrombosis are affected by common genetic variations in these genes. Methods and Results - In 463 young white subjects (men ≤45 years of age and women ≤55 years of age), who were included 1 to 3 months after a first event of arterial thrombosis, and 406 control subjects, we measured VWF:Ag and VWF:CB. Nine haplotype tagging single-nucleotide polymorphisms of STXBP5 and STX2 were selected and subsequently analyzed using linear regression with additive genetic models adjusted for age, sex, and ABO blood group. The minor alleles of rs9399599 and rs1039084 in STXBP5 were associated with lower VWF plasma levels and activity, whereas the minor allele of rs7978987 in STX2 was associated with higher VWF plasma levels and activity. The minor alleles of the single-nucleotide polymorphisms in STX2 were associated with a reduced risk of arterial thrombosis (rs1236

European Stroke Organisation (ESO) guidelines for the management of temperature in patients with acute ischemic stroke

Background: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke. Methods: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. Results: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke. Conclusions: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future. © 2015 World Stroke Organization

The time course and determinants of temperature within the first 48 h after ischaemic stroke

Background and Purpose: Previous research has attempted to analyze the relationship between post-stroke hyperthermia and prognosis. These analyses have been hindered by a lack of information about the time course and determinants of temperature change after stroke. Methods: Serial temperatures were measured until 48 h after ischaemic stroke in a prospectively recruited cohort. Potential determinants of temperature, including stroke severity [measured using the National Institutes of Health Stroke Scale (NIHSS)], infection and paracetamol use were recorded. Mixed-effects models were used to model serial temperature measurements over time, adjusted for significant determinants. Results: In 155 patients the mean temperature rose from 36.5 degrees C at the time of stroke to 36.7 degrees C approximately 36 h later. The factors with significant multivariable associations with serial temperatures were: first- and second-order time components, infection, paracetamol administration and the interaction between stroke severity (NIHSS >= 6) and time ( all p = 6 had a mean temperature rise of 0.35 degrees C during the first 36 h after stroke, compared with a rise of 0.17 degrees C in those with NIHS