GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask

Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools

Nearshore wave forecasting and hindcasting by dynamical and statistical downscaling

A high-resolution nested WAM/SWAN wave model suite aimed at rapidly establishing nearshore wave forecasts as well as a climatology and return values of the local wave conditions with Rapid Enviromental Assessment (REA) in mind is described. The system is targeted at regions where local wave growth and partial exposure to complex open-ocean wave conditions makes diagnostic wave modelling difficult. SWAN is set up on 500 m resolution and is nested in a 10 km version of WAM. A model integration of more than one year is carried out to map the spatial distribution of the wave field. The model correlates well with wave buoy observations (0.96) but overestimates the wave height somewhat (18%, bias 0.29 m). To estimate wave height return values a much longer time series is required and running SWAN for such a period is unrealistic in a REA setting. Instead we establish a direction-dependent transfer function between an already existing coarse open-ocean hindcast dataset and the high-resolution nested SWAN model. Return values are estimated using ensemble estimates of two different extreme-value distributions based on the full 52 years of statistically downscaled hindcast data. We find good agreement between downscaled wave height and wave buoy observations. The cost of generating the statistically downscaled hindcast time series is negligible and can be redone for arbitrary locations within the SWAN domain, although the sectors must be carefully chosen for each new location. The method is found to be well suited to rapidly providing detailed wave forecasts as well as hindcasts and return values estimates of partly sheltered coastal regions.Comment: 20 pages, 7 figures and 2 tables, MREA07 special issue on Marine rapid environmental assessmen

Psychosocial correlates with depressive symptoms six years after a first episode of psychosis as compared with findings from a general population sample

BACKGROUND: Depression is frequently occurring during and after psychosis. The aim of this study was to analyze if the psychosocial characteristics associated with depression/depressive symptoms in the late phase of a first episode psychosis (FEP) population were different compared to persons from the general population. METHODS: A questionnaire was sent out to all individuals six years after their FEP and to a general population sample. Depressive symptoms were recorded using a self-rating scale, the Major Depression Inventory. RESULTS: Formerly FEP persons had a higher representation of depressive symptoms/depression, unemployment, financial problems and insufficient social network. Depressive symptoms/depression were found to be associated with psychosocial problems. An age and gender effect was found in the general population, but not in the FEP sample. When the psychosocial characteristics were taken into account there were no association between having had FEP and depressive symptoms. CONCLUSIONS: The association between having been a FEP patient and depressive symptoms/depression disappeared when negative social aspects were taken into account

GFAP and S100B : What You Always Wanted to Know and Never Dared to Ask

Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools

Clinical significance of serum S100B levels in neurointensive care

Objective S100B is viewed as the most promising biomarker for brain damage. It has been proposed that this marker is useful in a Neurointensive Care Unit (NICU) as a monitoring parameter. This study aims to examine the clinical usefulness of daily serum S100B measurements in this setting. Design Prospective consecutive inclusion of patients. Patients A total of 79 patients with confirmed or suspected head injury or cerebrovascular insults (CVIs) (based upon patient history, computed tomography (CT) and/or magnetic resonance imaging (MRI) and neurological examination including coma scoring) who required neurointensive care were included in the study. Interventions Sampling for S100B was performed at admission and daily until patients were discharged from the NICU. S100B measurements were statistically compared to occurrence of secondary complications and outcome according to Glasgow Outcome Scale (GOS), with focus on clinical prediction. Measurements and main results 17 of 79 patients (22%) had secondary neurological complications. Mean S100B levels were found to be an independent parameter associated with these complications (P = 0.03). Mean S100B levels were higher in patients with complications compared to those without on both the complication day (P = 0.033) and the day after (P = 0.015), but not the day prior to the complication (P = 0.62). S100B did not predict secondary neurological complication. Neither mean (P = 0.182) nor peak (P = 0.370) S100B levels were associated with or predicted outcome according to dichotornised GOS. Conclusion Daily S100B measurements are associated with secondary complications but not to outcome. However, daily S100B levels do not predict secondary complications, which limit the usefulness of this brain biomarker in this setting

Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016

Protocolised reduction of non-resuscitation fluids versus usual care in patients with septic shock (REDUSE) : a protocol for a multicentre feasibility trial

INTRODUCTION: Administration of large volumes of fluids is associated with poor outcome in septic shock. Recent data suggest that non-resuscitation fluids are the major source of fluids in the intensive care unit (ICU) patients suffering from septic shock. The present trial is designed to test the hypothesis that a protocol targeting this source of fluids can reduce fluid administration compared with usual care. METHODS AND ANALYSIS: The design will be a multicentre, randomised, feasibility trial. Adult patients admitted to ICUs with septic shock will be randomised within 12 hours of admission to receive non-resuscitation fluids either according to a restrictive protocol or to receive usual care. The healthcare providers involved in the care of participants will not be blinded. The participants, outcome assessors at the 6-month follow-up and statisticians will be blinded. Primary outcome will be litres of fluids administered within 3 days of randomisation. Secondary outcomes will be proportion of randomised participants with outcome data on all-cause mortality; days alive and free of mechanical ventilation within 90 days of inclusion; any acute kidney injury and ischaemic events in the ICU (cerebral, cardiac, intestinal or limb ischaemia); proportion of surviving randomised patients who were assessed by European Quality of Life 5-Dimensions 5-Level questionnaire and Montreal Cognitive Assessment; proportion of all eligible patients who were randomised and proportion of participants experiencing at least one protocol violation. ETHICS AND DISSEMINATION: Ethics approval has been obtained in Sweden. Results of the primary and secondary outcomes will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05249088