Author: "Yang, Zhihui" / Topic: brain injuries - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Yang, Zhihui"' showing total 37 results

Start Over Author "Yang, Zhihui" Topic brain injuries

37 results on '"Yang, Zhihui"'

1. MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

Author: Dakroub F, Kobeissy F, Mondello S, Yang Z, Xu H, Sura L, Rossignol C, Albayram M, Rajderkar D, Wang K, and Weiss MD
Subjects: Infant, Newborn, Infant, Humans, Retrospective Studies, Biomarkers, Cohort Studies, Gene Expression Profiling methods, MicroRNAs genetics, MicroRNAs metabolism, Brain Injuries diagnosis, Brain Injuries genetics, Infant, Newborn, Diseases
Abstract: Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

2. Temporal Profiles of P-Tau, T-Tau, and P-Tau:Tau Ratios in Cerebrospinal Fluid and Blood from Moderate-Severe Traumatic Brain Injury Patients and Relationship to 6-12 Month Global Outcomes.

Author: Rubenstein R, McQuillan L, Wang KKW, Robertson C, Chang B, Yang Z, Xu H, Williamson J, and Wagner AK
Subjects: Humans, Biomarkers, Glasgow Outcome Scale, Longitudinal Studies, Brain Injuries, Brain Injuries, Traumatic
Abstract: Traumatic brain injury (TBI) can initiate progressive injury responses, which are linked to increased risk of neurodegenerative diseases known as "tauopathies." Increased post-TBI tau hyperphosphorylation has been reported in brain tissue and biofluids. Acute-to-chronic TBI total (T)-tau and phosphorylated (P)-tau temporal profiles in the cerebrospinal fluid (CSF) and serum and their relationship to global outcome is unknown. Our multi-site longitudinal study examines these concurrent profiles acutely (CSF and serum) and also characterizes the acute- to-chronic serum patterns. Serial serum and CSF samples from individuals with moderate-to-severe TBI were obtained from two cohorts (acute, subacute, and chronic samples from University of Pittsburgh [UPitt] [ n = 286 unique subjects] and acute samples from Baylor College of Medicine [BCM] [ n = 114 unique subjects]) and assayed for T-tau and P-tau using the Rolling Circle Amplification-Surround Optical Fiber ImmunoAssay platform. Biokinetic analyses described serum T-tau and P-tau temporal patterns. T-tau and P-tau levels are compared with those in healthy controls ( n = 89 for both CSF and serum), and univariate/multivariable associations are made with global outcome, including the Disability Rating Scale (DRS) and the Glasgow Outcome Scale-Extended (GOS-E) scores at 3 and 6 months post-TBI (BCM cohort) and at 6 and 12 months post-TBI (UPitt cohort). For both the UPitt and BCM cohorts, temporal increases in median serum and CSF T-tau and P-tau levels occurred over the first 5 days post-injury, while the initial increases of P-tau:T-tau ratio plateaued by day 4 post-injury (UPitt: n = 99, BCM: n = 48). Biokinetic analyses with UPitt data showed novel findings that T-tau ( n = 74) and P-tau ( n = 87) reached delayed maximum levels at 4.5 and 5.1 days, while exhibiting long serum half-lives (152 and 123 days), respectively. The post-TBI rise in acute (days 2-6) serum P-tau (up to 276-fold) far outpaced that of T-tau (7.3-fold), leading to a P-tau:T-tau increase of up to 267-fold, suggesting a shift toward tau hyperphosphorylation. BCM analyses showed that days 0-6 mean CSF T-tau and P-tau levels and P-tau:T-tau ratios were associated with greater disability (DRS) ( n = 48) and worse global outcome (GOS-E) ( n = 48) 6 months post-injury. Days 0-6 mean serum T-tau, P-tau, and P-tau:T-tau ratio were not associated with outcome in either cohort (UPitt: n = 145 [DRS], n = 154 [GOS-E], BCM: n = 99 [DRS and GOS-E]). UPitt multivariate models showed that higher chronic (months 1-6) mean P-tau levels and P-tau:T-tau ratio, but not T-tau levels, are associated with greater disability (DRS: n = 119) and worse global outcomes (GOS-E: n = 117) 12 months post-injury. This work shows the potential importance of monitoring post-TBI T-tau and P-tau levels over time. This multi-site longitudinal study features concurrent acute TBI T-tau and P-tau profiles in CSF and serum, and also characterizes acute-to-chronic serum profiles. Longitudinal profiles, along with no temporal concordance between trajectory groups over time, imply a sustained post-TBI shift in tau phosphorylation dynamics that may favor tauopathy development chronically.
Published: 2024
Full Text: View/download PDF

3. Combined GFAP, NFL, Tau, and UCH-L1 panel increases prediction of outcomes in neonatal encephalopathy.

Author: Yang Z, Xu H, Sura L, Arja RD, Patterson RL, Rossignol C, Albayram M, Rajderkar D, Ghosh S, Wang K, and Weiss MD
Subjects: Infant, Newborn, Humans, Glial Fibrillary Acidic Protein, Ubiquitin Thiolesterase, Biomarkers, Intermediate Filaments, Brain Injuries
Abstract: Background: Neuroprognostication in neonates with neonatal encephalopathy (NE) may be enhanced by early serial measurement of a panel of four brain-specific biomarkers., Methods: To evaluate serum biomarkers, 40 NE samples and 37 healthy neonates from a biorepository were analyzed. Blood samples were collected at 0-6, 12, 24, 48, and 96 h of life. MRI provided a short-term measure of injury. Long-term outcomes included death or a Bayley III score at 17-24 months of age., Results: Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), and Tau peaked at 0-6 h of life, while neurofilament light chain (NFL) peaked at 96 h of life. These four marker concentrations at 96 h of life differentiated moderate/severe from none/mild brain injury by MRI, while GFAP and Tau showed early discrimination. For long-term outcomes, GFAP, NFL, Tau, and UCH-L1 could differentiate a poor outcome vs good outcome as early as 0-6 h of life, depending on the Bayley domain, and a combination of the four markers enhanced the sensitivity and specificity. Machine learning trajectory analyses identified upward trajectory patients with a high concordance to poor outcomes., Conclusion: GFAP, NFL, Tau, and UCH-L1 may be of neuroprognostic significance after NE., Impact: Serial measurements of GFAP, NFL, Tau, and UCH-L1 show promise in aiding the bedside clinician in making treatment decisions in neonatal encephalopathy. The panel of four neuroproteins increased the ability to predict neurodevelopmental outcomes. The study utilized a trajectory analysis that enabled predictive modeling. A panel approach provides the bedside clinician with objective data to individualize care. This study provides the foundation to develop a point of care device in the future., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
Published: 2023
Full Text: View/download PDF

4. Neurobiochemical, Peptidomic, and Bioinformatic Approaches to Characterize Tauopathy Peptidome Biomarker Candidates in Experimental Mouse Model of Traumatic Brain Injury.

Author: Yadikar H, Johnson C, Pafundi N, Nguyen L, Kurup M, Torres I, Al-Enezy A, Yang Z, Yost R, Kobeissy FH, and Wang KKW
Subjects: Mice, Animals, Humans, tau Proteins metabolism, Disease Models, Animal, Peptide Hydrolases, Peptides, Biomarkers, Brain Injuries, Traumatic pathology, Tauopathies, Brain Injuries metabolism
Abstract: Traumatic brain injury (TBI) is a multidimensional damage, and currently, no FDA-approved medicine is available. Multiple pathways in the cell are triggered through a head injury (e.g., calpain and caspase activation), which truncate tau and generate variable fragment sizes (MW 400-45,000 K). In this study, we used an open-head TBI mouse model generated by controlled cortical impact (CCI) and collected ipsilateral (IC) and contralateral (CC) mice htau brain cortices at one (D1) three (D3), and seven (D7) days post-injury. We implemented immunological (antibody-based detection) and peptidomic approaches (nano-reversed-phase liquid chromatography/tandem mass spectrometry) to investigate proteolytic tau peptidome (low molecular weight (LMW) < 10 K)) and pathological phosphorylation sites (high-molecular-weight (HMW); > 10 K) derived from CCI-TBI animal models. Our immunoblotting analysis verified tau hyperphosphorylation, HMW, and HMW breakdown products (HMW-BDP) formation of tau (e.g., pSer 202 , pThr 181 , pThr 231 , pSer 396 , and pSer 404 ), following CCI-TBI. Peptidomic data revealed unique sequences of injury-dependent proteolytic peptides generated from human tau protein. Among the N-terminal tau peptides, EIPEGTTAEEAGIGDTPSLEDEAAGHVTQA (a.a. 96-125) and AQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARM (a.a. 91-127). Examples of tau C-terminal peptides identified include NVSSTGSIDMVDSPQLATLADEVSASLAKQGL (a.a. 410-441) and QLATLADEVSASLAKQGL (a.a. 424-441). Our peptidomic bioinformatic tools showed the association of proteases, such as CAPN1, CAPN2, and CTSL; CASP1, MMP7, and MMP9; and ELANE, GZMA, and MEP1A, in CCI-TBI tau peptidome. In clinical trials for novel TBI treatments, it might be useful to monitor a subset of tau peptidome as targets for biomarker utility and use them for a "theranostic" approach., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2023
Full Text: View/download PDF

5. Characterization of Calpain and Caspase-6-Generated Glial Fibrillary Acidic Protein Breakdown Products Following Traumatic Brain Injury and Astroglial Cell Injury.

Author: Yang Z, Arja RD, Zhu T, Sarkis GA, Patterson RL, Romo P, Rathore DS, Moghieb A, Abbatiello S, Robertson CS, Haskins WE, Kobeissy F, and Wang KKW
Subjects: Animals, Astrocytes metabolism, Biomarkers, Calpain metabolism, Caspase 6, Glial Fibrillary Acidic Protein metabolism, Humans, Intermediate Filaments metabolism, Mice, Peptide Hydrolases, Peptides, Brain Injuries, Brain Injuries, Traumatic
Abstract: Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites at A-56*A-61 and (ii) major C-terminal cleavage sites at T-383*Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78/R-79 and D-225/A-226, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.
Published: 2022
Full Text: View/download PDF

6. The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries.

Author: Sarkis GA, Mangaonkar MD, Moghieb A, Lelling B, Guertin M, Yadikar H, Yang Z, Kobeissy F, and Wang KK
Subjects: Animals, Biomarkers, Comorbidity, Disease Models, Animal, Humans, Mass Spectrometry, Brain metabolism, Brain Injuries metabolism, Proteomics, Spinal Cord Injuries metabolism
Abstract: Traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), collectively termed neurotrauma, are two parallel neurological conditions that can cause long-lasting neurological impairment and other comorbidities in patients, while at the same time, can create a high burden to society. To date, there are still no FDA-approved therapeutic interventions for either TBI or SCI. Recent advances in proteomic technologies, including tandem mass spectrometry, as well as imaging mass spectrometry, have enabled new approaches to study the differential proteome in TBI and SCI with the use of either animal disease models and/or biosamples from clinical observational studies. Thus, the applications of state-of-the-art proteomic method hold promises in shedding light on identifying clinically useful neurotrauma "biomarkers" and/or in identifying distinct and, otherwise, unobvious systems pathways or "key drivers" that can be further exploited as new therapeutic intervention targets.
Published: 2017
Full Text: View/download PDF

7. A Repetitive Concussive Head Injury Model in Mice.

Author: Yang Z, Lin F, Weissman AS, Jaalouk E, Xue QS, and Wang KK
Subjects: Animals, Humans, Mice, Brain Concussion, Brain Injuries, Disease Models, Animal
Abstract: Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.
Published: 2016
Full Text: View/download PDF

8. The functional and structural changes in the basilar artery due to overpressure blast injury.

Author: Toklu HZ, Muller-Delp J, Yang Z, Oktay Ş, Sakarya Y, Strang K, Ghosh P, Delp MD, Scarpace PJ, Wang KK, and Tümer N
Subjects: Animals, Capillaries pathology, Male, Muscle Contraction drug effects, Muscle, Smooth, Vascular drug effects, Nitric Oxide Synthase Type III drug effects, Nitric Oxide Synthase Type III metabolism, Pressure, Rats, Rats, Sprague-Dawley, Receptor, Endothelin A drug effects, Receptor, Endothelin A metabolism, Vasoconstrictor Agents pharmacology, Vasodilator Agents pharmacology, Basilar Artery pathology, Blast Injuries pathology, Brain Injuries pathology
Abstract: Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10(-12) to 10(-7) mol/L), acetylcholine (ACh) (10(-10) to 10(-4) mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10(-10) to 10(-4) mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ET(A)) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI.
Published: 2015
Full Text: View/download PDF

9. Degradation of βII-Spectrin Protein by Calpain-2 and Caspase-3 Under Neurotoxic and Traumatic Brain Injury Conditions.

Author: Kobeissy FH, Liu MC, Yang Z, Zhang Z, Zheng W, Glushakova O, Mondello S, Anagli J, Hayes RL, and Wang KK
Subjects: Animals, Apoptosis drug effects, Brain Injuries pathology, Cells, Cultured, Cerebral Cortex pathology, Hippocampus pathology, Humans, Immunoblotting, Male, Necrosis, Neurotoxicity Syndromes pathology, Neurotoxins toxicity, Protease Inhibitors pharmacology, Rats, Sprague-Dawley, Time Factors, Brain Injuries metabolism, Calpain metabolism, Caspase 3 metabolism, Neurotoxicity Syndromes metabolism, Proteolysis drug effects, Spectrin metabolism
Abstract: A major consequence of traumatic brain injury (TBI) is the rapid proteolytic degradation of structural cytoskeletal proteins. This process is largely reflected by the interruption of axonal transport as a result of extensive axonal injury leading to neuronal cell injury. Previous work from our group has described the extensive degradation of the axonally enriched cytoskeletal αII-spectrin protein which results in molecular signature breakdown products (BDPs) indicative of injury mechanisms and to specific protease activation both in vitro and in vivo. In the current study, we investigated the integrity of βII-spectrin protein and its proteolytic profile both in primary rat cerebrocortical cell culture under apoptotic, necrotic, and excitotoxic challenge and extended to in vivo rat model of experimental TBI (controlled cortical impact model). Interestingly, our results revealed that the intact 260-kDa βII-spectrin is degraded into major fragments (βII-spectrin breakdown products (βsBDPs)) of 110, 108, 85, and 80 kDa in rat brain (hippocampus and cortex) 48 h post-injury. These βsBDP profiles were further characterized and compared to an in vitro βII-spectrin fragmentation pattern of naive rat cortex lysate digested by calpain-2 and caspase-3. Results revealed that βII-spectrin was degraded into major fragments of 110/85 kDa by calpain-2 activation and 108/80 kDa by caspase-3 activation. These data strongly support the hypothesis that in vivo activation of multiple protease system induces structural protein proteolysis involving βII-spectrin proteolysis via a specific calpain and/or caspase-mediated pathway resulting in a signature, protease-specific βsBDPs that are dependent upon the type of neural injury mechanism. This work extends on previous published work that discusses the interplay spectrin family (αII-spectrin and βII-spectrin) and their susceptibility to protease proteolysis and their implication to neuronal cell death mechanisms.
Published: 2015
Full Text: View/download PDF

10. Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury.

Author: Yang Z, Lin F, Robertson CS, and Wang KK
Subjects: Animals, Brain Injuries pathology, Cells, Cultured, Cerebral Cortex metabolism, Cerebral Cortex pathology, Disease Models, Animal, Female, Humans, Male, Mice, Neurons metabolism, Neurons pathology, Rats, Brain Injuries cerebrospinal fluid, Calpain cerebrospinal fluid, Caspase 3 cerebrospinal fluid, DNA-Binding Proteins cerebrospinal fluid, Proteolysis
Abstract: Transactivation response DNA-binding protein 43 (TDP-43) proteinopathy has recently been reported in chronic traumatic encephalopathy, a neurodegenerative condition linked to prior history of traumatic brain injury (TBI). While TDP-43 appears to be vulnerable to proteolytic modifications under neurodegenerative conditions, the mechanism underlying the contribution of TDP-43 to the pathogenesis of TBI remains unknown. In this study, we first mapped out the calpain or caspase-3 TDP-43 fragmentation patterns by in vitro protease digestion. Concurrently, in cultured cerebrocortical neurons subjected to cell death challenges, we identified distinct TDP-43 breakdown products (BDPs) of 35, 33, and 12 kDa that were indicative of dual calpain/caspase attack. Cerebrocortical culture incubated with calpain and caspase-fragmented TDP-43 resulted in neuronal injury. Furthermore, increased TDP-43 BDPs as well as redistributed TDP-43 from the nucleus to the cytoplasm were observed in the mouse cortex in two TBI models: controlled cortical impact injury and overpressure blast-wave-induced brain injury. Finally, TDP-43 and its 35 kDa fragment levels were also elevated in the cerebrospinal fluid (CSF) of severe TBI patients. This is the first evidence that TDP-43 might be involved in acute neuroinjury and TBI pathology, and that TDP-43 and its fragments may have biomarker utilities in TBI patients.
Published: 2014
Full Text: View/download PDF

11. Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury.

Author: Schober ME, Requena DF, Davis LJ, Metzger RR, Bennett KS, Morita D, Niedzwecki C, Yang Z, and Wang KK
Subjects: Animals, Cell Death physiology, Cerebral Cortex growth & development, Disease Models, Animal, Functional Laterality, Hippocampus growth & development, Immunoblotting, Male, Random Allocation, Rats, Sprague-Dawley, Time Factors, Brain Injuries physiopathology, Cerebral Cortex physiopathology, Hippocampus physiopathology, Spectrin metabolism
Abstract: After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI., (Copyright © 2014 Elsevier B.V. All rights reserved.)
Published: 2014
Full Text: View/download PDF

12. Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.

Author: Zhang Z, Zoltewicz JS, Mondello S, Newsom KJ, Yang Z, Yang B, Kobeissy F, Guingab J, Glushakova O, Robicsek S, Heaton S, Buki A, Hannay J, Gold MS, Rubenstein R, Lu XC, Dave JR, Schmid K, Tortella F, Robertson CS, and Wang KK
Subjects: Adult, Animals, Astrocytes immunology, Astrocytes metabolism, Astrocytes pathology, Brain Injuries pathology, Female, Humans, Male, Rats, Rats, Sprague-Dawley, Time Factors, Autoantibodies blood, Autoantibodies immunology, Brain Injuries blood, Brain Injuries immunology, Glial Fibrillary Acidic Protein immunology, Immunoglobulin G blood, Immunoglobulin G immunology
Abstract: The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.
Published: 2014
Full Text: View/download PDF

13. Characterization and standardization of multiassay platforms for four commonly studied traumatic brain injury protein biomarkers: a TBI Endpoints Development Study

Author: Sarkis, George Anis, Zhu, Tian, Yang, Zhihui, Li, Xue, Shi, Yuan, Rubenstein, Richard, Yost, Richard A, Manley, Geoffrey T, and Wang, Kevin K
Subjects: Physical Injury - Accidents and Adverse Effects, Traumatic Brain Injury (TBI), Brain Disorders, Dementia, Traumatic Head and Spine Injury, Neurosciences, Acquired Cognitive Impairment, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Antigens, Biological Assay, Biomarkers, Brain Injuries, Traumatic, Case-Control Studies, Endpoint Determination, Glial Fibrillary Acidic Protein, Humans, Recombinant Proteins, Reference Standards, S100 Calcium Binding Protein beta Subunit, Ubiquitin Thiolesterase, tau Proteins, biomarker qualification, GFAP, neurodegeneration, protein biomarkers, S100B, Tau, traumatic brain injury, UCH-L1, Medicinal and Biomolecular Chemistry, Medical Biochemistry and Metabolomics, Clinical Sciences, Oncology & Carcinogenesis
Abstract: Aim: There is a critical need to validate biofluid-based biomarkers as diagnostic and drug development tools for traumatic brain injury (TBI). As part of the TBI Endpoints Development Initiative, we identified four potentially predictive and pharmacodynamic biomarkers for TBI: astroglial markers GFAP and S100B and the neuronal markers UCH-L1 and Tau. Materials & methods: Several commonly used platforms for these four biomarkers were identified and compared on analytic performance and ability to detect gold standard recombinant protein antigens and to pool control versus TBI cerebrospinal fluid (CSF). Results: For each marker, only some assay formats could differentiate TBI CSF from the control CSF. Also, different assays for the same biomarker reported divergent biomarker values for the same biosamples. Conclusion: Due to the variability of TBI marker assay in performance and reported values, standardization strategies are recommended when comparing reported biomarker levels across assay platforms.
Published: 2021

14. Penetrating Traumatic Brain Injury Triggers Dysregulation of Cathepsin B Protein Levels Independent of Cysteine Protease Activity in Brain and Cerebral Spinal Fluid

Author: Boutté, Angela M, Hook, Vivian, Thangavelu, Bharani, Sarkis, George Anis, Abbatiello, Brittany N, Hook, Gregory, Jacobsen, J Steven, Robertson, Claudia S, Gilsdorf, Janice, Yang, Zhihui, Wang, Kevin KW, and Shear, Deborah A
Subjects: Biomedical and Clinical Sciences, Neurosciences, Physical Injury - Accidents and Adverse Effects, Traumatic Head and Spine Injury, Traumatic Brain Injury (TBI), Brain Disorders, Animals, Biomarkers, Brain, Brain Injuries, Traumatic, Cathepsin B, Craniotomy, Cysteine Proteases, Enzyme Activation, Head Injuries, Penetrating, Humans, Male, Rats, Rats, Sprague-Dawley, biomarkers, cathepsin B, clinical TBI, cysteine protease, head trauma, penetrating ballistic-like brain injury, translational rodent models, traumatic brain injury, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract: Cathepsin B (CatB), a lysosomal cysteine protease, is important to brain function and may have dual utility as a peripheral biomarker of moderate-severe traumatic brain injury (TBI). The present study determined levels of pro- and mature (mat) CatB protein as well as cysteine protease activity within the frontal cortex (FC; proximal injury site), hippocampus (HC; distal injury site), and cerebral spinal fluid (CSF) collected 1-7 days after craniotomy and penetrating ballistic-like brain injury (PBBI) in rats. Values were compared with naïve controls. Further, the utility of CatB protein as a translational biomarker was determined in CSF derived from patients with severe TBI. Craniotomy increased matCatB levels in the FC and HC, and led to elevation of HC activity at day 7. PBBI caused an even greater elevation in matCatB within the FC and HC within 3-7 days. After PBBI, cysteine protease activity peaked at 3 days in the FC and was elevated at 1 day and 7 days, but not 3 days, in the HC. In rat CSF, proCatB, matCatB, and cysteine protease activity peaked at 3 days after craniotomy and PBBI. Addition of CA-074, a CatB-specific inhibitor, confirmed that protease activity was due to active matCatB in rat brain tissues and CSF at all time-points. In patients, CatB protein was detectable from 6 h through 10 days after TBI. Notably, CatB levels were significantly higher in CSF collected within 3 days after TBI compared with non-TBI controls. Collectively, this work indicates that CatB and its cysteine protease activity may serve as collective molecular signatures of TBI progression that differentially vary within both proximal and distal brain regions. CatB and its protease activity may have utility as a surrogate, translational biomarker of acute-subacute TBI.
Published: 2020

15. An update on diagnostic and prognostic biomarkers for traumatic brain injury

Author: Wang, Kevin K, Yang, Zhihui, Zhu, Tian, Shi, Yuan, Rubenstein, Richard, Tyndall, J Adrian, and Manley, Geoff T
Subjects: Autoimmune Disease, Physical Injury - Accidents and Adverse Effects, Neurodegenerative, Brain Disorders, Dementia, Neurosciences, Traumatic Brain Injury (TBI), Acquired Cognitive Impairment, Clinical Research, Traumatic Head and Spine Injury, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Injuries and accidents, Neurological, Good Health and Well Being, Biomarkers, Brain Injuries, Traumatic, Humans, Liquid Biopsy, Neuroimaging, Prognosis, Severity of Illness Index, traumatic brain injury, diagnostics, theranostics, neurotrauma, Clinical Sciences
Abstract: IntroductionTraumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring.
Published: 2018

16. Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

Author: Rubenstein, Richard, Chang, Binggong, Yue, John K, Chiu, Allen, Winkler, Ethan A, Puccio, Ava M, Diaz-Arrastia, Ramon, Yuh, Esther L, Mukherjee, Pratik, Valadka, Alex B, Gordon, Wayne A, Okonkwo, David O, Davies, Peter, Agarwal, Sanjeev, Lin, Fan, Sarkis, George, Yadikar, Hamad, Yang, Zhihui, Manley, Geoffrey T, Wang, Kevin KW, Cooper, Shelly R, Dams-O’Connor, Kristen, Borrasso, Allison J, Inoue, Tomoo, Maas, Andrew IR, Menon, David K, Schnyer, David M, and Vassar, Mary J
Subjects: Brain Disorders, Neurosciences, Clinical Research, Traumatic Brain Injury (TBI), Traumatic Head and Spine Injury, Physical Injury - Accidents and Adverse Effects, Acquired Cognitive Impairment, Injuries and accidents, Good Health and Well Being, Acute Disease, Adult, Biomarkers, Brain Injuries, Traumatic, Chronic Disease, Female, Glasgow Coma Scale, Glasgow Outcome Scale, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Trauma Centers, Young Adult, tau Proteins, the TRACK-TBI Investigators, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract: ImportanceAnnually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated.ObjectiveTo examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI.Design, setting, and participantsIn the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau-T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively).Conclusions and relevancePlasma P-tau levels and P-tau-T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau-T-tau ratios show more robust and sustained elevations among patients with chronic TBI.
Published: 2017

17. Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study

Author: Wang, Kevin KW, Yang, Zhihui, Yue, John K, Zhang, Zhiqun, Winkler, Ethan A, Puccio, Ava M, Diaz-Arrastia, Ramon, Lingsma, Hester F, Yuh, Esther L, Mukherjee, Pratik, Valadka, Alex B, Gordon, Wayne A, Okonkwo, David O, Manley, Geoffrey T, Cooper, Shelly R, Dams-O'Connor, Kristen, Hricik, Allison J, Inoue, Tomoo, Maas, Andrew IR, Menon, David K, Schnyer, David M, Sinha, Tuhin K, and Vassar, Mary J
Subjects: Physical Injury - Accidents and Adverse Effects, Clinical Research, Neurosciences, Traumatic Head and Spine Injury, Brain Disorders, Traumatic Brain Injury (TBI), Injuries and accidents, Acute Disease, Adolescent, Adult, Aged, Aged, 80 and over, Autoantibodies, Brain Injuries, Traumatic, Chronic Disease, Female, Glial Fibrillary Acidic Protein, Humans, Male, Middle Aged, Pilot Projects, Young Adult, autoantibody, autoimmunity, biomarkers, glia, traumatic brain injury, Clinical Sciences, Neurology & Neurosurgery
Abstract: We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (
Published: 2016

18. Health care utilization and outcomes in older adults after Traumatic Brain Injury: A CENTER-TBI study

Author: van der Vlegel, Marjolein, Mikolić, Ana, Wilson, Lindsay, Gomez, Pedro A., Lagares, Alfonso, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Vargiolu, Alessia, Ceyisakar, Iris, Gravesteijn, Benjamin, Haagsma, Juanita A., Huijben, Jilske, Maas, Andrew I. R., Lingsma, Hester, Nieboer, Daan, Mikolic, Ana, Polinder, Suzanne, Sewalt, Charlie, Steyerberg, Ewout W., Velt, Kimberley, Voormolen, Daphne, Wiegers, Eveline, Peul, Wilco, van Dijck, Jeroen T. J. M., van Essen, Thomas A., van Wijk, Roel P. J., Clusmann, Hans, Coburn, Mark, Kowark, Ana, Rossaint, Rolf, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čovid, Amra, von Steinbüchel, Nicole, Curry, Nicola, Stanworth, Simon, Dahyot-Fizelier, Claire, Dark, Paul, Johnson, Faye, Dawes, Helen, Esser, Patrick, van Heugten, Caroline, CENTER-TBI Participants and Investigators, De Keyser, Véronique, Menovsky, Tomas, Van der Steen, Gregory, Della Corte, Francesco, Grossi, Francesca, Depreitere, Bart, Đilvesi, Đula, Golubovic, Jagoš, Karan, Mladen, Åkerlund, Cecilia, Vulekovic, Petar, Dreier, Jens, Vajkoczy, Peter, Wolf, Stefan, Dulière, Guy-Loup, Maréchal, Hugues, Fabricius, Martin, Kondziella, Daniel, Feigin, Valery L., Jones, Kelly, George, Pradeep, Ao, Braden Te, Theadom, Alice, Foks, Kelly, Haitsma, Iain, Volovici, Victor, Furmanov, Alex, Rosenthal, Guy, Gagliardo, Pablo, Gao, Guoyi, Jiang, Ji-yao, Lanyon, Linda, Ghuysen, Alexandre, Giga, Lelde, Valeinis, Egils, Ziverte, Agate, Glocker, Ben, Rueckert, Daniel, Gratz, Johannes, Gruen, Russell L., Gupta, Deepak, Roe, Cecilie, Muraleedharan, Visakh, Helseth, Eirik, Roise, Olav, Horton, Lindsay, Hutchinson, Peter J., Kolias, Angelos G., Jacobs, Bram, van der Naalt, Joukje, Jankowski, Stefan, Kompanje, Erwin, Nelson, David, Timmers, Marjolein, Laureys, Steven, Ledoux, Didier, Misset, Benoit, Lecky, Fiona, Olubukola, Otesile, Lefering, Rolf, Schäfer, Nadine, Legrand, Valerie, Lejeune, Aurelie, Lee Hee, Quentin, Amrein, Krisztina, Vega, Emmanuel, Mattern, Julia, Levi, Leon, Lightfoot, Roger, Maegele, Marc, Manara, Alex, Thomas, Matt, Manley, Geoffrey, Martino, Costanza, Sakowitz, Oliver, Ezer, Erzsébet, Sanchez-Porras, Renan, Younsi, Alexander, McMahon, Catherine, Negru, Ancuta, Oresic, Matej, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Persona, Paolo, Piippo-Karjalainen, Anna, Kovács, Noémi, Pirinen, Matti, Ples, Horia, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Melegh, Béla, Ripatti, Samuli, Rocka, Saulius, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rossi, Sandra, Rusnák, Martin, Sahuquillo, Juan, Sandor, Janos, Schmidt, Silke, Schoechl, Herbert, Nyirádi, József, Schoonman, Guus, Skandsen, Toril, Stevens, Robert, Stewart, William, Takala, Riikka, Tamosuitis, Tomas, Tenovuo, Olli, Tibboel, Dick, Tolias, Christos, Tudora, Cristina Maria, Tamás, Viktória, van der Jagt, Mathieu, Van Hecke, Wim, Van Praag, Dominique, Vyvere, Thijs Vande, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Wang, Kevin K. W., Yang, Zhihui, Vámos, Zoltán, Ylén, Peter, Sorinola, Abayomi, Andelic, Nada, Andreassen, Lasse, Kaplan, Z. L. Rana, Anke, Audny, Frisvold, Shirin, Antoni, Anna, Schwendenwein, Elisabeth, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Beretta, Luigi, Calvi, Maria Rosa, Bartels, Ronald, Retel Helmrich, Isabel R. A., Boogert, Hugo den, Barzó, Pál, Beauvais, Romuald, Perera, Natascha, Beer, Ronny, Helbok, Raimund, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Degos, Vincent, van Veen, Ernest, Galanaud, Damien, Perlbarg, Vincent, Berardino, Maurizio, Cavallo, Simona, Blaabjerg, Morten, Rosenlund, Christina, Schou, Rico Frederik, Bragge, Peter, Brazinova, Alexandra, Majdan, Marek, Taylor, Mark Steven, Zelinkova, Veronika, Brinck, Vibeke, Jarrett, Mike, Brooker, Joanne, Donoghue, Emma, Synnot, Anneliese, Brorsson, Camilla, Koskinen, Lars-Owe, Sundström, Nina, Steinbuechel, Nicole V., Buki, Andras, Czeiter, Endre, Bullinger, Monika, Cabeleira, Manuel, Czosnyka, Marek, Dixit, Abhishek, Ercole, Ari, Koraropoulos, Evgenios, Menon, David, Newcombe, Virginia, Plass, Anne Marie, Richter, Sophie, Smielewski, Peter, Stamatakis, Emmanuel, Williams, Guy, Winzeck, Stefan, Zeiler, Frederick A., Caccioppola, Alessio, Calappi, Emiliana, Carbonara, Marco, Ortolano, Fabrizio, Zeldovich, Marina, Zoerle, Tommaso, Stocchetti, Nino, Cameron, Peter, Gantner, Dashiell, Murray, Lynnette, Trapani, Tony, Vallance, Shirley, Lozano, Guillermo Carbayo, Pomposo, Inigo, Castaño-León, Ana M., Molecular Neuroscience and Ageing Research (MOLAR), CENTER-TBI Participants and Investigators, van der Vlegel, M, Mikolić, A, Hee, Q, Kaplan, Z, Helmrich, I, van Veen, E, Andelic, N, Steinbuechel, N, Plass, A, Zeldovich, M, Wilson, L, Maas, A, Haagsma, J, Polinder, S, Åkerlund, C, George, P, Lanyon, L, Muraleedharan, V, Nelson, D, Amrein, K, Ezer, E, Kovács, N, Melegh, B, Nyirádi, J, Tamás, V, Vámos, Z, Sorinola, A, Andreassen, L, Anke, A, Frisvold, S, Antoni, A, Schwendenwein, E, Audibert, G, Azouvi, P, Azzolini, M, Beretta, L, Calvi, M, Bartels, R, Boogert, H, Barzó, P, Beauvais, R, Perera, N, Beer, R, Helbok, R, Bellander, B, Belli, A, Benali, H, Degos, V, Galanaud, D, Perlbarg, V, Berardino, M, Cavallo, S, Blaabjerg, M, Rosenlund, C, Schou, R, Bragge, P, Brazinova, A, Majdan, M, Taylor, M, Zelinkova, V, Brinck, V, Jarrett, M, Brooker, J, Donoghue, E, Synnot, A, Brorsson, C, Koskinen, L, Sundström, N, Buki, A, Czeiter, E, Bullinger, M, Cabeleira, M, Czosnyka, M, Dixit, A, Ercole, A, Koraropoulos, E, Menon, D, Newcombe, V, Richter, S, Smielewski, P, Stamatakis, E, Williams, G, Winzeck, S, Zeiler, F, Caccioppola, A, Calappi, E, Carbonara, M, Ortolano, F, Zoerle, T, Stocchetti, N, Cameron, P, Gantner, D, Murray, L, Trapani, T, Vallance, S, Lozano, G, Pomposo, I, Castaño-León, A, Gomez, P, Lagares, A, Chevallard, G, Chieregato, A, Citerio, G, Vargiolu, A, Ceyisakar, I, Gravesteijn, B, Huijben, J, Lingsma, H, Nieboer, D, Mikolic, A, Sewalt, C, Steyerberg, E, Velt, K, Voormolen, D, Wiegers, E, Peul, W, van Dijck, J, van Essen, T, van Wijk, R, Clusmann, H, Coburn, M, Kowark, A, Rossaint, R, Coles, J, Cooper, J, Correia, M, Čovid, A, von Steinbüchel, N, Curry, N, Stanworth, S, Dahyot-Fizelier, C, Dark, P, Johnson, F, Dawes, H, Esser, P, van Heugten, C, De Keyser, V, Menovsky, T, Van der Steen, G, Corte, F, Grossi, F, Depreitere, B, Đilvesi, Đ, Golubovic, J, Karan, M, Vulekovic, P, Dreier, J, Vajkoczy, P, Wolf, S, Dulière, G, Maréchal, H, Fabricius, M, Kondziella, D, Feigin, V, Jones, K, Ao, B, Theadom, A, Foks, K, Haitsma, I, Volovici, V, Furmanov, A, Rosenthal, G, Gagliardo, P, Gao, G, Jiang, J, Ghuysen, A, Giga, L, Valeinis, E, Ziverte, A, Glocker, B, Rueckert, D, Gratz, J, Gruen, R, Gupta, D, Roe, C, Helseth, E, Roise, O, Horton, L, Hutchinson, P, Kolias, A, Jacobs, B, van der Naalt, J, Jankowski, S, Kompanje, E, Timmers, M, Laureys, S, Ledoux, D, Misset, B, Lecky, F, Olubukola, O, Lefering, R, Schäfer, N, Legrand, V, Lejeune, A, Vega, E, Mattern, J, Levi, L, Lightfoot, R, Maegele, M, Manara, A, Thomas, M, Manley, G, Martino, C, Sakowitz, O, Sanchez-Porras, R, Younsi, A, Mcmahon, C, Negru, A, Oresic, M, Palotie, A, Parizel, P, Payen, J, Persona, P, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Ripatti, S, Rocka, S, Rosand, J, Rosenfeld, J, Rossi, S, Rusnák, M, Sahuquillo, J, Sandor, J, Schmidt, S, Schoechl, H, Schoonman, G, Skandsen, T, Stevens, R, Stewart, W, Takala, R, Tamosuitis, T, Tenovuo, O, Tibboel, D, Tolias, C, Tudora, C, van der Jagt, M, Van Hecke, W, Van Praag, D, Vyvere, T, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Wang, K, Yang, Z, Ylén, P, Public Health, Otorhinolaryngology and Head and Neck Surgery, Intensive Care, Neurology, Neurosurgery, Pediatric Surgery, University of Helsinki, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Department of Mathematics and Statistics, Helsinki Institute for Information Technology, Statistical and population genetics, Clinicum, Helsinki University Hospital Area, Neurokirurgian yksikkö, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics
Subjects: Traumatic, Quality of Life/psychology, Traumatic Brain Injury, Health-related quality of life, Health care utilization, 3112 Neurosciences, Glasgow Outcome Scale, Outcomes, Patient Acceptance of Health Care, SDG 3 - Good Health and Well-being, Older adults, Brain Injuries, Brain Injuries, Traumatic, Quality of Life, Humans, General Earth and Planetary Sciences, Mental health, 3111 Biomedicine, Prospective Studies, Human medicine, Older adult, Aged, Outcome, General Environmental Science
Abstract: Injury : international journal of the care of the injured 53(8), 2774-2782 (2022). doi:10.1016/j.injury.2022.05.009, Published by Elsevier Science, Amsterdam [u.a.]
Published: 2022

19. Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury

Author: Bockhop, Fabian, Zeldovich, Marina, Cunitz, Katrin, Van Praag, Dominique, van der Vlegel, Marjolein, Beissbarth, Tim, Hagmayer, York, von Steinbuechel, Nicole, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, L. Gruen, Russell, Gupta, Deepak, A. Haagsma, Juanita, Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, G. Kolias, Angelos, Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, I.R. Maas, Andrew, Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Røe, Cecilie, Røise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, RueckertMartin Rusnák, Daniel, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Steven Taylor, Mark, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Maria Tudora, Cristina, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, Naalt, Joukje van der, T.J.M. van Dijck, Jeroen, van Erp, Inge A. M., van Essen, Thomas A., Hecke, Wim Van, van Heugten, Caroline, van Veen, Ernest, Vande Vyvere, Thijs, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, K.W. Wang, Kevin, Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Apollo - University of Cambridge Repository, Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, „Springer Nature' grupė, Ročka, Saulius, Tamošuitis, Tomas, CTR-TBI Participants Investigators, Molecular Neuroscience and Ageing Research (MOLAR), Public Health, Amrein, Krisztina, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Andelic, Nada, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Andreassen, Lasse, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Anke, Audny, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Antoni, Anna, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Audibert, Gérard, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Azouvi, Philippe, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Retel Helmrich, Isabel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Azzolini, Maria Luisa, Ripatti, Samuli, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Bartels, Ronald, Rueckert, Martin, Rusnák, Daniel, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Barzó, Pál, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Beauvais, Romuald, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Taylor, Mark Steven, Te Ao, Braden, Tenovuo, Olli, Beer, Ronny, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Bellander, Bo-Michael, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Erp, Inge A. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Belli, Antonio, Van Praag, Dominique, van Veen, Ernest, Vande Vyvere, Thijs, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Benali, Habib, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Berardino, Maurizio, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Åkerlund, Cecilia, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Bockhop, F, Zeldovich, M, Cunitz, K, Van Praag, D, van der Vlegel, M, Beissbarth, T, Hagmayer, Y, von Steinbuechel, N, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini Maria, L, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi Maria, R, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper Jamie, D, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin Valery, L, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Guoyi Gao, N, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, A., G, Gratz, J, Gravesteijn, B, Grossi, F, L., G, Gupta, D, A., H, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, J., H, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, G., K, Kompanje, E, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, I. R., M, Castaño-León Ana, M, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Maréchal, H, Mattern, J, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyirádi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel Paul, M, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti Jussi, P, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Helmrich Isabel, R, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld Jeffrey, V, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, RueckertMartin Rusnák, D, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schäfer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou Rico, F, Schwendenwein, E, Sewalt, C, Singh Ranjit, D, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg Ewout, W, Stocchetti, N, Sundström, N, Takala, R, Tamás, V, Tamosuitis, T, Steven Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Maria Tudora, C, Unterberg, A, Vajkoczy, P, Vallance, S, Valeinis, E, Vámos, Z, van der Jagt, M, Van der Steen, G, Naalt Joukje van, D, T. J. M., V, van Erp Inge, A, van Essen Thomas, A, Hecke Wim, V, van Heugten, C, van Veen, E, Vande Vyvere, T, van Wijk Roel, P, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa Paul, M, Vik, A, Vilcinis, R, Volovici, V, von Steinbüchel, N, Voormolen, D, Vulekovic, P, K. W., W, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Younsi, A, Zeiler Frederick, A, Zelinkova, V, Ziverte, A, Zoerle, T, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Statistical and population genetics, Clinicum, Helsinki University Hospital Area, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics
Subjects: Post-Traumatic/psychology, Multidisciplinary, Traumatic/complications, Brain Injuries, Traumatic/complications, 3124 Neurology and psychiatry, Diagnostic and Statistical Manual of Mental Disorder, Stress Disorders, Post-Traumatic/psychology, Checklist, Diagnostic and Statistical Manual of Mental Disorders, Stress Disorders, Post-Traumatic, Brain Injuries, Brain Injuries, Traumatic, Humans, Human medicine, Human, Stress Disorders, Language
Abstract: Scientific reports 12, 16571 (2022). doi:10.1038/s41598-022-20170-2, Published by Macmillan Publishers Limited, part of Springer Nature, [London]
Published: 2022

20. Serum metabolome associated with severity of acute traumatic brain injury

Author: Thomas, Ilias, Dickens, Alex M., Posti, Jussi P., Czeiter, Endre, Duberg, Daniel, Sinioja, Tim, Kråkström, Matilda, Retel Helmrich, Isabel R. A., Wang, Kevin K. W., Maas, Andrew I. R., Steyerberg, Ewout W., Menon, David K., Tenovuo, Olli, Hyötyläinen, Tuulia, Büki, András, Orešič, Matej, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Røe, Cecilie, Røise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Te Ao, Braden, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Åkerlund, Cecilia, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Amrein, Krisztina, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Andelic, Nada, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Andreassen, Lasse, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Anke, Audny, Te Ao, Braden, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Antoni, Anna, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Audibert, Gérard, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Azouvi, Philippe, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Azzolini, Maria Luisa, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Molecular Neuroscience and Ageing Research (MOLAR), Psychology 3, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Posti, Jussi P [0000-0002-5925-5193], Czeiter, Endre [0000-0002-9578-6944], Maas, Andrew IR [0000-0003-1612-1264], Steyerberg, Ewout W [0000-0002-7787-0122], Menon, David [0000-0002-3228-9692], Orešič, Matej [0000-0002-2856-9165], Apollo - University of Cambridge Repository, CENTER-TBI Participants Investigators, Menon, David K [0000-0002-3228-9692], Public Health, Neurology, Neurosurgery, Intensive Care, Pediatric Surgery, Thomas, I, Dickens, A, Posti, J, Czeiter, E, Duberg, D, Sinioja, T, Kråkström, M, Retel Helmrich, I, Wang, K, Maas, A, Steyerberg, E, Menon, D, Citerio, G, „Springer Nature' grupė, Ročka, Saulius, and Tamošuitis, Tomas
Subjects: Traumatic, IMPACT, BIOMARKERS, General Physics and Astronomy, acute traumatic brain injury, General Biochemistry, Genetics and Molecular Biology, CHAIN AMINO-ACIDS, MYOINOSITOL, Cohort Studies, GLUTAMATE, 692/53, Brain Injuries, Traumatic, Metabolomics/methods, TOOL, Humans, Metabolomics, Serum metabolome, 692/699/375/1345, 631/378/1689, OUTCOMES, Multidisciplinary, article, General Chemistry, MAGNETIC-RESONANCE-SPECTROSCOPY, 140/58, nervous system diseases, nervous system, Brain Injuries, Metabolome, MODERATE, CHOLINE, Human medicine
Abstract: Nature Communications 13, 2545 (2022). doi:10.1038/s41467-022-30227-5, Published by Nature Publishing Group UK, [London]
Published: 2022

21. Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations

Author: J. Russell Huie, Stefania Mondello, Christopher J. Lindsell, Luca Antiga, Esther L. Yuh, Elisa R. Zanier, Serge Masson, Bedda L. Rosario, Adam R. Ferguson, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Sonia Jain, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, David Okonkwo, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, David Schnyer, Seth Seabury, Murray Stein, Sabrina Taylor, Nancy Temkin, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, Ross Zafonte, Cecilia Ackerlund, Hadie Adams, Vanni Agnoletti, Judith Allanson, Krisztina Amrein, Norberto Andaluz, Nada Andelic, Lasse Andreassen, Audny Anke, Azasevac Antun, Anna Antoni, Hilko Ardon, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Camelia Baciu, Rafael Badenes, Ronald Bartels, Pál Barzó, Ursula Bauerfeind, Romuald Beauvais, Ronny Beer, Francisco Javier Belda, Bo Michael Bellander, Antonio Belli, Rémy Bellier, Habib Benali, Thierry Benard, Maurizio Berardino, Luigi Beretta, Christopher Beynon, Federico Bilotta, Harald Binder, Erta Biqiri, Morten Blaabjerg, Hugo den Boogert, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Lozano Guillermo Carbayo, Marco Carbonara, Elsa Carise, K. Carpenter, Ana M. Castaño León, Francesco Causin, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Maryse Cnossen, Mark Coburn, Jonathan Coles, Lizzie Coles-Kemp, Johnny Collett, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot Fizelier, François Damas, Pierre Damas, Helen Dawes, Véronique De Keyser, Francesco Della Corte, Bart Depreitere, Godard C.W. de Ruiter, Dula Dilvesi, Shenghao Ding, Diederik Dippel, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy Loup Dulière, Heiko Engemann, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Junfeng Feng, Kelly Foks, Francesca Fossi, Gilles Francony, Ulderico Freo, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Karin Geleijns, Pradeep George, Alexandre Ghuysen, Lelde Giga, Benoit Giraud, Ben Glocker, Jagos Golubovic, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Asta Kristine Håberg, Bram Jacobs, Iain Haitsma, Jed A. Hartings, Raimund Helbok, Eirik Helseth, Daniel Hertle, Astrid Hoedemaekers, Stefan Hoefer, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Mike Jarrett, Bojan Jelaca, Ji yao Jiang, Kelly Jones, Konstantinos Kamnitsas, Mladen Karan, Ari Katila, Maija Kaukonen, Thomas Kerforne, Riku Kivisaari, Angelos G. Kolias, Bálint Kolumbán, Erwin Kompanje, Ksenija Kolundzija, Daniel Kondziella, Lars Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Christian Ledig, Rolf Lefering, Valerie Legrand, Jin Lei, Leon Levi, Roger Lightfoot, Hester Lingsma, Dirk Loeckx, Angels Lozano, Andrew I.R. Maas, Stephen MacDonald, Marc Maegele, Majdan Marek, Sebastian Major, Alex Manara, Geoffrey Manley, Didier Martin, Leon Francisco Martin, Costanza Martino, Hugues Maréchal, Armando Maruenda, Alessandro Masala, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Cristina Morganti Kossmann, Davide Mulazzi, Holger Mühlan, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Annemarie Oldenbeuving, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Adriana Patruno, Jean François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Floury Sébastien Pili, Matti Pirinen, Horia Ples, Maria Antonia Poca, Suzanne Polinder, Inigo Pomposo, Jussi Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Veronika Rehorčíková, Jonathan Rhodes, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Gerwin Roks, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Marco Sacchi, Barbara Sahakian, Juan Sahuquillo, Oliver Sakowitz, Francesca Sala, Renan Sanchez Porras, Janos Sandor, Edgar Santos, Luminita Sasu, Davide Savo, Nadine Schäffer, Inger Schipper, Barbara Schlößer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Michael Schöll, Charlie Sewalt, Özcan Sir, Toril Skandsen, Lidwien Smakman, Dirk Smeets, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Nicole Steinbüchel, Ana Stevanovic, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Fabio Silvio Taccone, Riikka Takala, Viktória Tamás, Päivi Tanskanen, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Ralph Telgmann, Guido Teodorani, Alice Theadom, Matt Thomas, Dick Tibboel, Christos Tolias, Jean Flory Luaba Tshibanda, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Gregory Van der Steen, Mathieu van der Jagt, JV de Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Julia Van Waesberghe, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Giacinta Vizzino, Carmen Vleggeert Lankamp, Victor Volovici, Daphne Voormolen, Peter Vulekovic, Zoltán Vámos, Derick Wade, Kevin K.W. Wang, Lei Wang, Lars Wessels, Eveline Wiegers, Eno Wildschut, Guy Williams, Lindsay Wilson, Maren K.L. Winkler, Stefan Wolf, Peter Ylén, Alexander Younsi, Menashe Zaaroor, Frederik Zeiler, Yang Zhihui, Agate Ziverte, Fabrizio Zumbo, Huie, J Russell, Mondello, Stefania, Lindsell, Christopher J, Antiga, Luca, Yuh, Esther L, Zanier, Elisa R, Masson, Serge, Rosario, Bedda L, Ferguson, Adam R (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators), Beretta, Luigi, Huie, J, Mondello, S, Lindsell, C, Antiga, L, Yuh, E, Zanier, E, Masson, S, Rosario, B, Ferguson, A, Citerio, G, and Molecular Neuroscience and Ageing Research (MOLAR)
Subjects: Traumatic, 030506 rehabilitation, Data Interpretation, Data management, data sharing, TERMINAL HYDROLASE-L1, Big data, Poison control, 0302 clinical medicine, Brain Injuries, Traumatic, TBI, Medicine, Biomarker discovery, Common Data Elements, traumatic brain injury, Injuries and accidents, Statistical, Reference Standards, NET RECLASSIFICATION INDEX, Data Interpretation, Statistical, Biomarker (medicine), biomarker, 0305 other medical science, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, CT, The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, medicine.medical_specialty, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Context (language use), Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Traumatic Brain Injury (TBI), Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators, 03 medical and health sciences, MICROARRAY, Special Section: Statistical Methods in Tbi Research, Humans, biomarkers, Intensive care medicine, Traumatic Head and Spine Injury, Neurology & Neurosurgery, business.industry, Information Dissemination, OUTCOME PREDICTION, Neurosciences, COMMON DATA ELEMENTS, Precision medicine, Brain Disorders, DIFFUSE AXONAL INJURY, Data sharing, Good Health and Well Being, Brain Injuries, DISCOVERY, TRACK, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.
Published: 2021

22. Evaluation of Diffusion Tensor Imaging and Fluid Based Biomarkers in a Large Animal Trial of Cyclosporine in Focal Traumatic Brain Injury.

Author: Karlsson, Michael, Yang, Zhihui, Chawla, Sanjeev, Delso, Nile, Pukenas, Bryan, Elmér, Eskil, Hugerth, Matilda, Margulies, Susan S., Ehinger, Johannes, Hansson, Magnus J., Wang, Kevin K.W., and Kilbaugh, Todd J.
Subjects: *DIFFUSION tensor imaging, *BRAIN injuries, *MAGNETIC resonance imaging, *GLIAL fibrillary acidic protein, *CYCLOSPORINE
Abstract: All phase III trials evaluating medical treatments for traumatic brain injury (TBI), performed to date, have failed. To facilitate future success there is a need for novel outcome metrics that can bridge pre-clinical studies to clinical proof of concept trials. Our objective was to assess diffusion tensor imaging (DTI) and biofluid-based biomarkers as efficacy outcome metrics in a large animal study evaluating the efficacy of cyclosporine in TBI. This work builds on our previously published study that demonstrated a reduced volume of injury by 35% with cyclosporine treatment based on magnetic resonance imaging (MRI) results. A focal contusion injury was induced in piglets using a controlled cortical impact (CCI) device. Cyclosporine in a novel Cremophor/Kolliphor EL-free lipid emulsion, NeuroSTAT, was administered by continuous intravenous infusion for 5 days. The animals underwent DTI on day 5. Glial fibrillary acidic protein (GFAP), as a measure of astroglia injury, and neurofilament light (NF-L), as a measure of axonal injury, were measured in blood on days 1, 2, and 5, and in cerebrospinal fluid (CSF) on day 5 post-injury. Normalized fractional anisotropy (FA) was significantly (p = 0.027) higher in in the treatment group, indicating preserved tissue integrity with treatment. For the biomarkers, we observed a statistical trend of a decreased level of NF-L in CSF (p = 0.051), in the treatment group relative to placebo, indicating less axonal injury. Our findings suggest that DTI, and possibly CSF NF-L, may be feasible as translational end-points assessing neuroprotective drugs in TBI. [ABSTRACT FROM AUTHOR]
Published: 2021
Full Text: View/download PDF

23. Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

Author: Rubenstein, Richard, Chang, Binggong, Yue, John K, Chiu, Allen, Winkler, Ethan A, Puccio, Ava M, Diaz-Arrastia, Ramon, Yuh, Esther L, Mukherjee, Pratik, Valadka, Alex B, Gordon, Wayne A, Okonkwo, David O, Davies, Peter, Agarwal, Sanjeev, Lin, Fan, Sarkis, George, Yadikar, Hamad, Yang, Zhihui, Manley, Geoffrey T, Wang, Kevin KW, the TRACK-TBI Investigators, Cooper, Shelly R, Dams-O'Connor, Kristen, Borrasso, Allison J, Inoue, Tomoo, Maas, Andrew IR, Menon, David K, Schnyer, David M, Vassar, Mary J, Menon, David [0000-0002-3228-9692], and Apollo - University of Cambridge Repository
Subjects: Traumatic, Adult, Male, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Glasgow Outcome Scale, Pilot Projects, tau Proteins, the TRACK-TBI Investigators, Traumatic Brain Injury (TBI), Young Adult, Trauma Centers, Clinical Research, mental disorders, Brain Injuries, Traumatic, Acquired Cognitive Impairment, Humans, Glasgow Coma Scale, Prospective Studies, Traumatic Head and Spine Injury, Neurology & Neurosurgery, Neurosciences, Injuries and accidents, Middle Aged, Brain Disorders, Good Health and Well Being, Brain Injuries, Acute Disease, Chronic Disease, Cognitive Sciences, Female, Biomarkers
Abstract: Importance: Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. Objective: To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. Design, Setting, and Participants: In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau-T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively). Conclusions and Relevance: Plasma P-tau levels and P-tau-T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau-T-tau ratios show more robust and sustained elevations among patients with chronic TBI., This study was supported in part by the Office of the Assistant Secretary of Defense for Health Affairs through the Department of Defense (DOD) Broad Agency Announcement under award numbers W81XWH-11-2-0069 (Dr Rubenstein) and W81XWH-14-2-0166 (Dr Rubenstein). It was also supported in part by National Institutes of Health (NIH) grant RC2 NS069409 (Dr Manley), NIH grant 1U01 NS086090-01 (Dr Manley), US DOD grant W81XWH-14-2-0176 (Dr Manley), US DOD grant W81XWH-13-1-04 (Dr Manley), NIH grant R21NS085455-01 (Dr Wang), and University of Florida McKnight Brain Institute BSCIRTF fund (Dr Wang).
Published: 2018
Full Text: View/download PDF

24. Circulating GFAP and Iba-1 levels are associated with pathophysiological sequelae in the thalamus in a pig model of mild TBI.

Author: Lafrenaye, Audrey D., Mondello, Stefania, Wang, Kevin K., Yang, Zhihui, Povlishock, John T., Gorse, Karen, Walker, Susan, Hayes, Ronald L., and Kochanek, Patrick M.
Subjects: BRAIN injuries, PATHOLOGICAL physiology, ANIMAL models in research, HISTOPATHOLOGY, BIOMARKERS
Abstract: Serum biomarkers are promising tools for evaluating patients following traumatic brain injury (TBI). However, their relationship with diffuse histopathology remains unclear. Additionally, translatability is a focus of neurotrauma research, however, studies using translational animal models are limited. Here, we evaluated associations between circulating biomarkers and acute thalamic histopathology in a translational micro pig model of mTBI. Serum samples were collected pre-injury, and 1 min-6 h following mTBI. Markers of neuronal injury (Ubiquitin Carboxy-terminal Hydrolase L1 [UCH-L1]), microglial/macrophage activation (Ionized calcium binding adaptor molecule-1 [Iba-1]) and interleukin-6 [IL-6]) and astrogliosis/astrocyte damage (glial fibrillary acidic protein [GFAP]) were measured. Axonal injury and histological features of neurons and glia were also investigated using immunofluorescent labeling and correlated to serum levels of the associated biomarkers. Consistent with prior experimental and human studies, GFAP, was highest at 6 h post-injury, while no substantial changes were observed in UCH-L1, Iba-1 or IL-6 over 6 h. This study also found promising associations between thalamic glial histological signatures and ensuing release of Iba-1 and GFAP into the circulation. Our findings suggest that in diffuse injury, monitoring serum Iba-1 and GFAP levels can provide clinically relevant insight into the underlying acute pathophysiology and biomarker release kinetics following mTBI, providing previously underappreciated diagnostic capability. [ABSTRACT FROM AUTHOR]
Published: 2020
Full Text: View/download PDF

25. Anti-Pituitary and Anti-Hypothalamus Autoantibody Associations with Inflammation and Persistent Hypogonadotropic Hypogonadism in Men with Traumatic Brain Injury.

Author: Vijapur, Sushupta M., Yang, Zhihui, Barton, David J., Vaughan, Leah, Awan, Nabil, Kumar, Raj G., Oh, Byung-Mo, Berga, Sarah L., Wang, Kevin K., and Wagner, Amy K.
Subjects: *BRAIN injuries, *IMMUNOGLOBULIN M, *BLOOD groups, *HYPOGONADISM, *PATHOLOGY, *HYPOPITUITARISM
Abstract: Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n = 143) were compared with healthy men (n = 39). The TBI group provided blood samples 1–12 months post-injury (n = 1225). TBI and healthy control (n = 39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1–6 months post-injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin G (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG than controls (p < 0.0001 all comparisons). However, only APA IgM (p = 0.03) and AHA IgM (p = 0.03) levels were lower in the PHH than in the non-PHH group in multivariate analysis. There were no differences in IgG levels by PHH status. Multiple inflammatory markers were positively correlated with IgM autoantibody production. PHH was associated with higher soluble tumor-necrosis-factor receptors I/II, (sTNFRI, sTNFRII), regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble interleukin-2-receptor-alpha (sIL-2Rα) levels. Higher IgM APA, and AHA, but not AGA, in the absence of PHH may suggest a beneficial or reparative role for neuroendocrine tissue-specific IgM autoantibody production against PHH development post-TBI. [ABSTRACT FROM AUTHOR]
Published: 2020
Full Text: View/download PDF

26. Serum-Based Phospho-Neurofilament-Heavy Protein as Theranostic Biomarker in Three Models of Traumatic Brain Injury: An Operation Brain Trauma Therapy Study.

Author: Yang, Zhihui, Zhu, Tian, Mondello, Stefania, Akel, Miis, Wong, Aaron T., Kothari, Isha M., Lin, Fan, Shear, Deborah A., Gilsdorf, Janice S., Leung, Lai Yee, Bramlett, Helen M., Dixon, C. Edward, Dietrich, W. Dalton, Hayes, Ronald L., Povlishock, John T., Tortella, Frank C., Kochanek, Patrick M., and Wang, Kevin K.W.
Subjects: *TRAUMA therapy, *CEREBROSPINAL fluid, *BRAIN injuries, *GLIAL fibrillary acidic protein, *PROTEINS
Abstract: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), markers of glial and neuronal cell body injury, respectively, have been previously selected by the Operation Brain Trauma Therapy (OBTT) pre-clinical therapy and biomarker screening consortium as drug development tools. However, traumatic axonal injury (TAI) also represents a major consequence and determinant of adverse outcomes after traumatic brain injury (TBI). Thus, biomarkers capable of assessing TAI are much needed. Neurofilaments (NFs) are found exclusively in axons. Here, we evaluated phospho-neurofilament-H (pNF-H) protein as a possible new TAI marker in serum and cerebrospinal fluid (CSF) across three rat TBI models in studies carried out by the OBTT consortium, namely, controlled cortical impact (CCI), parasagittal fluid percussion (FPI), and penetrating ballistics-like brain injury (PBBI). We indeed found that CSF and serum pNF-H levels are robustly elevated by 24 h post-injury in all three models. Further, in previous studies by OBTT, levetiracetam showed the most promising benefits, whereas nicotinamide showed limited benefit only at high dose (500 mg/kg). Thus, serum samples from the same repository collected by OBTT were evaluated. Treatment with 54 mg/kg intravenously of levetiracetam in the CCI model and 170 mg/kg in the PBBI model significantly attenuated pNF-H levels at 24 h post-injury as compared to respective vehicle groups. In contrast, nicotinamide (50 or 500 mg/kg) showed no reduction of pNF-H levels in CCI or PBBI models. Our current study suggests that pNF-H is a useful theranostic blood-based biomarker for TAI across different rodent TBI models. In addition, our data support levetiracetam as the most promising TBI drug candidate screened by OBTT to date. [ABSTRACT FROM AUTHOR]
Published: 2019
Full Text: View/download PDF

27. The diagnostic values of UCH-L1 in traumatic brain injury: A meta-analysis.

Author: Shahjouei, Shima, Sadeghi-Naini, Mohsen, Yang, Zhihui, Kobeissy, Firas, Rathore, Disa, Shokraneh, Farhad, Blackburn, Spiros, Manley, Geoff T, and Wang, Kevin K.W.
Subjects: BRAIN injuries, BIOMARKERS, COMPUTED tomography, DIAGNOSIS, MEDICAL information storage & retrieval systems, MEDLINE, META-analysis, SYSTEMATIC reviews
Abstract: Traumatic brain injury (TBI) is a major health concern. The purpose of this study is to identify the diagnostic accuracy of ubiquitin C-terminal hydrolase-L1 (UCH-L1)—a protein biomarker—in comparison with CT-scan findings post-TBI. Accordingly, we conducted a systematic review of eligible studies and assessed the risk of bias according to the QUADAS-2 checklist. A total of 13 reports from 10 original studies were included. Based on our analysis, serum UCH-L1 has a high accuracy in predicting CT findings in mild to moderate TBI. Based on the QUADAS-2 checklist, this result has a high risk of bias affecting its applicability. The plasma level of UCH-L1 has moderate accuracy in predicting CT findings when assessed in all GCS levels. This result has a low risk of bias and low concerns regarding applicability. Pooled analysis suggests that the plasma/serum UCH-L1 level has high accuracy in predicting CT findings in a wide range of GCS in patients with TBI. This result has a high risk of bias and high concern about its applicability. The heterogeneity in approaching TBI biomarker interferes with drawing a definitive conclusion. Therefore, although UCH-L1 is a promising blood-based diagnostic biomarker for TBI, but due to differences in reported diagnostic accuracy, further studies are needed to recommend UCH-L1 as an alternative to CT scanning. [ABSTRACT FROM PUBLISHER]
Published: 2018
Full Text: View/download PDF

28. Early Signs of Elevated Intracranial Pressure on Computed Tomography Correlate With Measured Intracranial Pressure in the Intensive Care Unit and Six-Month Outcome After Moderate to Severe Traumatic Brain Injury.

Author: Harder, Tyler J., Leary, Owen P., Yang, Zhihui, Lucke-Wold, Brandon, Liu, David D., Still, Megan E.H., Zhang, Miao, Yeatts, Sharon D., Allen, Jason W., Wright, David W., Merck, Derek, and Merck, Lisa H.
Subjects: *INTRACRANIAL hypertension, *BRAIN injuries, *INTRACRANIAL pressure, *COMPUTED tomography, *INTENSIVE care units, *INTRAVENTRICULAR hemorrhage, *PRESSURE ulcers
Abstract: Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Early triage and treatment after TBI have been shown to improve outcome. Identifying patients at risk for increased intracranial pressure (ICP) via baseline computed tomography (CT) , however, has not been validated previously in a prospective dataset. We hypothesized that acute CT findings of elevated ICP, combined with direct ICP measurement, hold prognostic value in terms of six-month patient outcome after TBI. Data were obtained from the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECTIII) multi-center clinical trial. Baseline CT scans for 881 participants were individually reviewed by a blinded central neuroradiologist. Five signs of elevated ICP were measured (sulcal obliteration, lateral ventricle compression, third ventricle compression, midline shift, and herniation). Associations between signs of increased ICP and outcomes (six-month functional outcome and death) were assessed. Secondary analyses of 354 patients with recorded ICP monitoring data available explored the relationships between hemorrhage phenotype/anatomic location, sustained ICP ≥20 mm Hg, and surgical intervention(s). Univariate and multi-variate logistic/linear regressions were performed; p < 0.05 is defined as statistically significant. Imaging characteristics associated with ICP in this cohort include sulcal obliteration (p = 0.029) and third ventricular compression (p = 0.039). Univariate regression analyses indicated that increasing combinations of the five defined signs of elevated ICP were associated with death, poor functional outcome, and time to death. There was also an increased likelihood of death if patients required craniotomy (odds ratio [OR] = 4.318, 95% confidence interval [1.330–16.030]) or hemicraniectomy (OR = 2.993 [1.109–8.482]). On multi-variate regression analyses, hemorrhage location was associated with death (posterior fossa, OR = 3.208 [1.120–9.188] and basal ganglia, OR = 3.079 [1.178–8.077]). Volume of hemorrhage >30 cc was also associated with increased death, OR = 3.702 [1.575–8.956]). The proportion of patient hours with sustained ICP ≥20 mm Hg, and maximum ICP ≥20 mm Hg were also directly correlated with increased death (OR = 6 4.99 [7.731–635.51]; and OR = 1.025 [1.004–1.047]), but not with functional outcome. Poor functional outcome was predicted by concurrent presence of all five radiographic signs of elevated ICP (OR = 4.44 [1.514–14.183]) and presence of frontal lobe (OR = 2.951 [1.265–7.067]), subarachnoid (OR = 2.231 [1.067–4.717]), or intraventricular (OR = 2.249 [1.159–4.508]) hemorrhage. Time to death was modulated by total patient days of elevated ICP ≥20 mm Hg (effect size = 3.424 [1.500, 5.439]) in the first two weeks of hospitalization. Sulcal obliteration and third ventricular compression, radiographic signs of elevated ICP, were significantly associated with measurements of ICP ≥20 mm Hg. These radiographic biomarkers were significantly associated with patient outcome. There is potential utility of ICP-related imaging variables in triage and prognostication for patients after moderate-severe TBI. [ABSTRACT FROM AUTHOR]
Published: 2023
Full Text: View/download PDF

29. Parallel Cerebrospinal Fluid and Serum Temporal Profile Assessment of Axonal Injury Biomarkers Neurofilament-Light Chain and Phosphorylated Neurofilament-Heavy Chain: Associations With Patient Outcome in Moderate-Severe Traumatic Brain Injury.

Author: Wang, Kevin K.W., Barton, David J., McQuillan, Leah E., Kobeissy, Firas, Cai, Guangzheng, Xu, Haiyan, Yang, Zhihui, Trifilio, Erin, Williamson, John B., Rubenstein, Richard, Robertson, Claudia S., and Wagner, Amy K.
Subjects: *BRAIN injuries, *CEREBROSPINAL fluid, *PROGNOSIS, *BLOOD proteins, *BIOMARKERS, *BLOOD platelet transfusion, *GLASGOW Coma Scale
Abstract: Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n = 277 unique subjects) and CSF (n = 95 unique subjects) daily for 1 week, and serum every 2 weeks for 6 months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n = 99 unique subjects) and CSF (n = 54 unique subjects) NF-L and pNF-H levels were measured at least daily during Days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r = 0.44-0.48; p < 0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (Months [M]2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p < 0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p < 0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and Glasgow Coma Scale. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed. [ABSTRACT FROM AUTHOR]
Published: 2024
Full Text: View/download PDF

30. Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study.

Author: Helmrich, Isabel R A Retel, Czeiter, Endre, Amrein, Krisztina, Büki, András, Lingsma, Hester F, Menon, David K, Mondello, Stefania, Steyerberg, Ewout W, von Steinbüchel, Nicole, Wang, Kevin K W, Wilson, Lindsay, Xu, Haiyan, Yang, Zhihui, van Klaveren, David, Maas, Andrew I R, and CENTER-TBI participants and investigators
Subjects: *BRAIN injuries, *GLIAL fibrillary acidic protein, *PROGNOSIS, *TAU proteins, *BIOMARKERS, *ESTERASES, *LONGITUDINAL method
Abstract: Background: Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome.Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.Findings: Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models.Interpretation: Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.Funding: European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences. [ABSTRACT FROM AUTHOR]
Published: 2022
Full Text: View/download PDF

31. Kollidon VA64 Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Author: Osier, Nicole D., Bramlett, Helen M., Shear, Deborah A., Mondello, Stefania, Carlson, Shaun W., Dietrich, W. Dalton, Deng-Bryant, Ying, Wang, Kevin K.W., Hayes, Ronald L., Yang, Zhihui, Empey, Philip E., Poloyac, Samuel M., Lafrenaye, Audrey D., Povlishock, John T., Gilsdorf, Janice S., Kochanek, Patrick M., and Dixon, C. Edward
Subjects: *BRAIN injuries, *GLIAL fibrillary acidic protein, *TRAUMA therapy, *TOTAL body irradiation, *GLASGOW Coma Scale, *HISTOPATHOLOGY, *FUNCTIONAL assessment
Abstract: Loss of plasmalemmal integrity may mediate cell death after traumatic brain injury (TBI). Prior studies in controlled cortical impact (CCI) indicated that the membrane resealing agent Kollidon VA64 improved histopathological and functional outcomes. Kollidon VA64 was therefore selected as the seventh therapy tested by the Operation Brain Trauma Therapy consortium, across three pre-clinical TBI rat models: parasagittal fluid percussion injury (FPI), CCI, and penetrating ballistic-like brain injury (PBBI). In each model, rats were randomized to one of four exposures (7–15/group): (1) sham; (2) TBI+vehicle; (3) TBI+Kollidon VA64 low-dose (0.4 g/kg); and (4) TBI+Kollidon VA64 high-dose (0.8 g/kg). A single intravenous VA64 bolus was given 15 min post-injury. Behavioral, histopathological, and serum biomarker outcomes were assessed over 21 days generating a 22-point scoring matrix per model. In FPI, low-dose VA64 produced zero points across behavior and histopathology. High-dose VA64 worsened motor performance compared with TBI-vehicle, producing -2.5 points. In CCI, low-dose VA64 produced intermediate benefit on beam balance and the Morris water maze (MWM), generating +3.5 points, whereas high-dose VA64 showed no effects on behavior or histopathology. In PBBI, neither dose altered behavior or histopathology. Regarding biomarkers, significant increases in glial fibrillary acidic protein (GFAP) levels were seen in TBI versus sham at 4 h and 24 h across models. Benefit of low-dose VA64 on GFAP was seen at 24 h only in FPI. Ubiquitin C-terminal hydrolase-L1 (UCH-L1) was increased in TBI compared with vehicle across models at 4 h but not at 24 h, without treatment effects. Overall, low dose VA64 generated +4.5 points (+3.5 in CCI) whereas high dose generated -2.0 points. The modest/inconsistent benefit observed reduced enthusiasm to pursue further testing. [ABSTRACT FROM AUTHOR]
Published: 2021
Full Text: View/download PDF

32. Glibenclamide Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Author: Jha, Ruchira M., Mondello, Stefania, Bramlett, Helen M., Dixon, C. Edward, Shear, Deborah A., Dietrich, W. Dalton, Wang, Kevin K.W., Yang, Zhihui, Hayes, Ronald L., Poloyac, Samuel M., Empey, Philip E., Lafrenaye, Audrey D., Yan, Hong Q., Carlson, Shaun W., Povlishock, John T., Gilsdorf, Janice S., and Kochanek, Patrick M.
Subjects: *BRAIN injuries, *TRAUMA therapy, *MAZE tests, *GLIAL fibrillary acidic protein, *GLIBENCLAMIDE, *BRUISES
Abstract: Glibenclamide (GLY) is the sixth drug tested by the Operation Brain Trauma Therapy (OBTT) consortium based on substantial pre-clinical evidence of benefit in traumatic brain injury (TBI). Adult Sprague-Dawley rats underwent fluid percussion injury (FPI; n = 45), controlled cortical impact (CCI; n = 30), or penetrating ballistic-like brain injury (PBBI; n = 36). Efficacy of GLY treatment (10-μg/kg intraperitoneal loading dose at 10 min post-injury, followed by a continuous 7-day subcutaneous infusion [0.2 μg/h]) on motor, cognitive, neuropathological, and biomarker outcomes was assessed across models. GLY improved motor outcome versus vehicle in FPI (cylinder task, p < 0.05) and CCI (beam balance, p < 0.05; beam walk, p < 0.05). In FPI, GLY did not benefit any other outcome, whereas in CCI, it reduced 21-day lesion volume versus vehicle (p < 0.05). On Morris water maze testing in CCI, GLY worsened performance on hidden platform latency testing versus sham (p < 0.05), but not versus TBI vehicle. In PBBI, GLY did not improve any outcome. Blood levels of glial fibrillary acidic protein and ubiquitin carboxyl terminal hydrolase-1 at 24 h did not show significant treatment-induced changes. In summary, GLY showed the greatest benefit in CCI, with positive effects on motor and neuropathological outcomes. GLY is the second-highest–scoring agent overall tested by OBTT and the only drug to reduce lesion volume after CCI. Our findings suggest that leveraging the use of a TBI model-based phenotype to guide treatment (i.e., GLY in contusion) might represent a strategic choice to accelerate drug development in clinical trials and, ultimately, achieve precision medicine in TBI. [ABSTRACT FROM AUTHOR]
Published: 2021
Full Text: View/download PDF

33. Copenhagen Head Injury Ciclosporin Study: A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients.

Author: Kelsen, Jesper, Karlsson, Michael, Hansson, Magnus J., Yang, Zhihui, Fischer, Walter, Hugerth, Matilda, Nordström, Carl-Henrik, Åstrand, Ramona, Keep, Marcus F., Kilbaugh, Todd, Wang, Kevin K.W., Møller, Kirsten, Juhler, Marianne, and Elmér, Eskil
Subjects: *BRAIN injuries, *GLIAL fibrillary acidic protein, *HEAD injuries, *MICRODIALYSIS, *GLASGOW Coma Scale
Abstract: Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4–8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood–brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy. [ABSTRACT FROM AUTHOR]
Published: 2019
Full Text: View/download PDF

34. Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients

Author: van Veen, Ernest, Van Der Jagt, Mathieu, Citerio, Giuseppe, Stocchetti, Nino, Gommers, Diederik, Burdorf, Alex, Menon, David, Maas, Andrew I. R., Kompanje, Erwin J. O., Lingsma, Hester F., Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Frisvold, Shirin, Helseth, Eirik, Røe, Cecilie, Røise, Olav, Skandsen, Toril, Vik, Anne, Åkerlund, Cecilia, Amrein, Krisztina, Antoni, Anna, Audibert, Gerard, Azouvi, Philippe, Azzolini, Maria luisa, Bartels, Ronald, Barzo, Pal, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria rosa, Cameron, Peter, Lozano, Guillermo carbayo, Carbonara, Marco, Chevallard, Giorgio, Chieregato, Arturo, Molecular Neuroscience and Ageing Research (MOLAR), Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, „Springer' grupė, van Veen, E, van der Jagt, M, Citerio, G, Stocchetti, N, Gommers, D, Burdorf, A, Menon, D, Maas, A, Kompanje, E, Lingsma, H, Apollo - University of Cambridge Repository, van Veen, Ernest, van der Jagt, Mathieu, Citerio, Giuseppe, Stocchetti, Nino, Gommers, Diederik, Burdorf, Alex, Menon, David K, Maas, Andrew I R, Kompanje, Erwin J O, Lingsma, Hester F (CENTER-TBI investigators and participants), Beretta, L, Ročka, Saulius, Tamošuitis, Tomas, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, CTR-TBI Investigators Participants, Public Health, Intensive Care, Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji Yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Åkerlund, Cecilia, Kornaropoulos, Evgenios, Koskinen, Lars Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Amrein, Krisztina, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño, Ana M. León, Maegele, Marc, Majdan, Marek, Manara, Alex, Andelic, Nada, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Andreassen, Lasse, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Anke, Audny, Palotie, Aarno, Parizel, Paul M., Payen, Jean François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Antoni, Anna, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Audibert, Gérard, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Azouvi, Philippe, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Porras, Renan Sanchez, Sandor, Janos, Schäfer, Nadine, Azzolini, Maria Luisa, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Bartels, Ronald, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Sundström, Nina, Takala, Riikka, Tamás, Viktória, Taylo, Mark Steven, Barzó, Pál, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Beauvais, Romuald, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, Beer, Ronny, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Bellander, Bo-Michael, Vik, Anne, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Belli, Antonio, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Covic, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Fizelier, Claire Dahyot, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, den Boogert, Hugo, Depreitere, Bart, Ðilvesi, Ðula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, and Hutchinson, Peter J.
Subjects: Traumatic, medicine.medical_specialty, Pediatrics, WLSM, Traumatic brain injury, Original, MULTICENTER, LARGE COHORT, DECISION-MAKING, Critical Care and Intensive Care Medicine, THERAPY, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Anesthesiology, SUPPORT, Brain Injuries, Traumatic, Medicine, Humans, Intensive care unit, Glasgow Coma Scale, 030212 general & internal medicine, Prospective Studies, ORGAN DONATION, OUTCOMES, business.industry, 030208 emergency & critical care medicine, Odds ratio, medicine.disease, INTENSIVE-CARE UNITS, Confidence interval, 1ST 72 HOURS, 3. Good health, Critical care, Intensive Care Units, Brain Injuries, traumatic brain injury, critical care, intensive care unit, END, Injury Severity Score, Human medicine, business, Cohort study
Abstract: Intensive care medicine 47(10), 1115-1129 (2021). doi:10.1007/s00134-021-06484-1, Published by Springer, Berlin
Published: 2021

35. Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis

Author: Böhm J. K., Schaeben V., Schäfer N., Güting H., Lefering R., Thorn S., Schöchl H., Zipperle J., Grottke O., Rossaint R., Stanworth S., Curry N., Maegele M., Åkerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzó P., Beauvais R., Beer R., Bellander B. M., Belli A., Benali H., Berardino M., Beretta L., Blaabjerg M., Bragge P., Brazinova A., Brinck V., Brooker J., Brorsson C., Buki A., Bullinger M., Cabeleira M., Caccioppola A., Calappi E., Calvi M. R., Cameron P., Lozano G. C., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Ceyisakar I., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Čović A., Czeiter E., Czosnyka M., Dahyot-Fizelier C., Dark P., Dawes H., De Keyser V., Degos V., Corte F. D., Boogert H. d., Depreitere B., Đilvesi Đ., Dixit A., Donoghue E., Dreier J., Dulière G. L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., Foks K., Frisvold S., Furmanov A., Gagliardo P., Galanaud D., Gantner D., Gao G., George P., Ghuysen A., Giga L., Glocker B., Golubovic J., Gomez P. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Molecular Neuroscience and Ageing Research (MOLAR), Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Koraropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Åkerlund, Cecilia, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Amrein, Krisztina, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Andelic, Nada, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Andreassen, Lasse, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Anke, Audny, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Antoni, Anna, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Audibert, Gérard, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Synnot, Anneliese, Takala, Riikka, Azouvi, Philippe, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Azzolini, Maria Luisa, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, Naalt, Joukje van der, Bartels, Ronald, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Barzó, Pál, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Wiegers, Eveline, Beauvais, Romuald, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Beer, Ronny, Zoerle, Tommaso, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Ceyisakar, Iris, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, „Springer' grupė, Ročka, Saulius, Tamošuitis, Tomas, Böhm, Julia K, Schaeben, Victoria, Güting, Helge, Thorn, Sophie, Schöchl, Herbert, Zipperle, Johanne, Grottke, Oliver, Maegele, Marc (CENTER-TBI Participants and Investigators), Beretta, L, Apollo - University of Cambridge Repository, Böhm, J, Schaeben, V, Schäfer, N, Güting, H, Lefering, R, Thorn, S, Schöchl, H, Zipperle, J, Grottke, O, Rossaint, R, Stanworth, S, Curry, N, Maegele, M, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Corte, F, Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Section Neuropsychology, and RS: FPN NPPP I
Subjects: Thrombin generation, THROMBIN ACTIVATABLE FIBRINOLYSIS, CENTER-TBI, HEMORRHAGIC PROGRESSION, Progressive intracranial hemorrhage, Critical Care and Intensive Care Medicine, Traumatic brain injury, Coagulopathy, Fibrin monomers, Brain Injuries, Traumatic, Humans, Prospective Studies, coagulopathy, fibrin monomers, progressive intracranial hemorrhage, thrombin generation, traumatic brain injury, Traumatic/epidemiology, HYPOPERFUSION, Brain Injuries, Traumatic/epidemiology, Thrombin, INHIBITOR, PATHWAYS, Plasminogen, CARE, Blood Coagulation Disorders, Fibrin monomer, Brain Injuries, Neurology (clinical), Protein C
Abstract: Neurocritical care 36(3), 927-941 (2022). doi:10.1007/s12028-021-01400-3, Published by Springer, New York, NY
Published: 2022

36. A genome-wide association study of outcome from traumatic brain injury

Author: Mart Kals, Kevin Kunzmann, Livia Parodi, Farid Radmanesh, Lindsay Wilson, Saef Izzy, Christopher D. Anderson, Ava M. Puccio, David O. Okonkwo, Nancy Temkin, Ewout W. Steyerberg, Murray B. Stein, Geoff T. Manley, Andrew I.R. Maas, Sylvia Richardson, Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, David K. Menon, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan P. Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire DahyotFizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, GuyLoup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J.A. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, LarsOwe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. CastañoLeón, Marc Maegele, Marek Majdan, Alex Manara, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia F.J. Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Paul M. Parizel, JeanFrançois Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan SanchezPorras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Janek Frantzén, Ari Katila, Henna-Rikka Maanpää, Jussi Tallus, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Sonia Jain, Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, John K. Yue, Esther Yuh, Ross Zafonte, Public Health, Cell biology, Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J. A., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David K., Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia F. J., Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Åkerlund, Cecilia, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Amrein, Krisztina, Ziverte, Agate, Zoerle, Tommaso, Izzy, Saef, Radmanesh, Farid, Frantzén, Janek, Katila, Ari, Maanpää, Henna-Rikka, Tallus, Jussi, Adeoye, Opeolu, Badjatia, Neeraj, Andelic, Nada, Boase, Kim, Barber, Jason, Bodien, Yelena, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Andreassen, Lasse, Feeser, Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Anke, Audny, Hemphill, Claude, Hotz, Gillian, Jain, Sonia, Keene, Dirk, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Antoni, Anna, Madden, Christopher, Manley, Geoffrey T., Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B., Noel, Florence, Audibert, Gérard, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Azouvi, Philippe, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Yue, John K., Azzolini, Maria Luisa, Yuh, Esther, Zafonte, Ross, Carroll, Ellen, Chatfield, Doris A., Coles, Jonathan P., Helmy, Adel, Manktelow, Anne, Outtrim, Joanne G., Bartels, Ronald, Takala, Rikka, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Molecular Neuroscience and Ageing Research (MOLAR), Kals, M, Kunzmann, K, Parodi, L, Radmanesh, F, Wilson, L, Izzy, S, Anderson, C, Puccio, A, Okonkwo, D, Temkin, N, Steyerberg, E, Stein, M, Manley, G, Citerio, G, Genetic Associations In Neurotrauma (GAIN) Consortium, CENTER-TBI, CABI, MGB, TBIcare Studies, TRACK-TBI, „Elsevier Science' grupė, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Complex Disease Genetics, Research Programs Unit, Centre of Excellence in Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, and Biostatistics Helsinki
Subjects: Traumatic, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, LOCI, SUSCEPTIBILITY, Traumatic Brain Injury (TBI), Mannose-Binding Lectin, DISEASE, General Biochemistry, Genetics and Molecular Biology, Traumatic brain injury, Consortia, Recovery, Brain Injuries, Traumatic, Genetics, 2.1 Biological and endogenous factors, Humans, Prospective Studies, Aetiology, Traumatic Head and Spine Injury, Outcome, Human Genome, 3112 Neurosciences, Neurosciences, General Medicine, LECTIN, Brain Disorders, Good Health and Well Being, consortia, genome-wide association study, outcome, recovery, traumatic brain injury, Brain Injuries, Genetic Associations In Neurotrauma (GAIN) Consortium, Public Health and Health Services, Human medicine, Transcriptome, Genome-Wide association study
Abstract: EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]
Published: 2022

37. Can We Cluster ICU Treatment Strategies for Traumatic Brain Injury by Hospital Treatment Preferences?

Author: Ceyisakar, Iris, Huijben, Jilske A., Maas, Andrew I. R., Lingsma, Hester F., van Leeuwen, Nikki, Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Frisvold, Shirin, Helseth, Eirik, Røe, Cecilie, Røise, Olav, Skandsen, Toril, Vik, Anne, Åkerlund, Cecilia, Amrein, Krisztina, Antoni, Anna, Audibert, Gerard, Azouvi, Philippe, Azzolini, Maria luisa, Bartels, Ronald, Barzo, Pal, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria rosa, Cameron, Peter, Lozano, Guillermo carbayo, Carbonara, Marco, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Cnossen, Maryse, Coburn, Mark, Molecular Neuroscience and Ageing Research (MOLAR), Anke, Audny, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Antoni, Anna, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Audibert, Gérard, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Azouvi, Philippe, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Azzolini, Maria Luisa, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Bartels, Ronald, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Barzó, Pál, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Beauvais, Romuald, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Beer, Ronny, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Bellander, Bo-Michael, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Belli, Antonio, Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Benali, Habib, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, Berardino, Maurizio, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Erp, Inge A., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Beretta, Luigi, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, Blaabjerg, Morten, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Bragge, Peter, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Åkerlund, Cecilia, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Amrein, Krisztina, Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Andelic, Nada, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Andreassen, Lasse, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Ceyisakar, I, Huijben, J, Maas, A, Lingsma, H, van Leeuwen, N, Citerio, G, Ročka, Saulius, Tamošuitis, Tomas, Ceyisakar, Iris E [0000-0002-9081-6278], Apollo - University of Cambridge Repository, Ceyisakar, Iris E, Huijben, Jilske A, Maas, Andrew I R, Lingsma, Hester F, van Leeuwen, Nikki (CENTER-TBI participants and investigators), Public Health, Neurology, Neurosurgery, Intensive Care, Pediatric Surgery, „Springer' grupė, Section Neuropsychology, RS: FPN NPPP I, and CENTER-TBI participants and investigators
Subjects: Traumatic/therapy, Neurologi, CENTER-TBI, Critical Care and Intensive Care Medicine, 01 natural sciences, Provider profiling, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Traumatic brain injury, Trauma Centers, Surveys and Questionnaires, Brain Injuries, Traumatic, MANAGEMENT, Humans, 0101 mathematics, Comparative effectiveness research, provider profiling, between-hospital variation, comparative effectiveness research, traumatic brain injury, Brain Injuries, Traumatic/therapy, Between-hospital variation, CARE, Hospitals, 3. Good health, Intensive Care Units, Neurology, Brain Injuries, Human medicine, Neurology (clinical), 030217 neurology & neurosurgery
Abstract: Neurocritical care 36(3), 846-856 (2022). doi:10.1007/s12028-021-01386-y, Published by Springer, New York, NY
Published: 2022

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

37 results on '"Yang, Zhihui"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources