| 1. |
- Brophy, Gretchen M., et al.
(author)
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Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids
- 2011
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 28:6, s. 861-870
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Journal article (peer-reviewed)abstract
- Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ≤ 8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (r(s)=0.59, p<0.001), AUC (r(s)=0.3, p=0.027), Tmax (r(s)=0.68, p<0.001), and MRT (r(s)=0.65, p<0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax((0-24h)) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.
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| 2. |
- Büki, Andras, 1966-, et al.
(author)
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Minor and repetitive head injury
- 2014
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In: Advances and Technical Standards in Neurosurgery. - Cham : Springer. - 9783319090658 - 9783319090665 ; , s. 147-192
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Book chapter (peer-reviewed)abstract
- Traumatic brain injury (TBI) is the leading cause of death and disability in the young, active population and expected to be the third leading cause of death in the whole world until 2020. The disease is frequently referred to as the silent epidemic, and many authors highlight the "unmet medical need" associated with TBI.The term traumatically evoked brain injury covers a heterogeneous group ranging from mild/minor/minimal to severe/non-salvageable damages. Severe TBI has long been recognized to be a major socioeconomical health-care issue as saving young lives and sometimes entirely restituting health with a timely intervention can indeed be extremely cost efficient.Recently it has been recognized that mild or minor TBI should be considered similarly important because of the magnitude of the patient population affected. Other reasons behind this recognition are the association of mild head injury with transient cognitive disturbances as well as long-term sequelae primarily linked to repeat (sport-related) injuries.The incidence of TBI in developed countries can be as high as 2-300/100,000 inhabitants; however, if we consider the injury pyramid, it turns out that severe and moderate TBI represents only 25-30 % of all cases, while the overwhelming majority of TBI cases consists of mild head injury. On top of that, or at the base of the pyramid, are the cases that never show up at the ER - the unreported injuries.Special attention is turned to mild TBI as in recent military conflicts it is recognized as "signature injury."This chapter aims to summarize the most important features of mild and repetitive traumatic brain injury providing definitions, stratifications, and triage options while also focusing on contemporary knowledge gathered by imaging and biomarker research.Mild traumatic brain injury is an enigmatic lesion; the classification, significance, and its consequences are all far less defined and explored than in more severe forms of brain injury.Understanding the pathobiology and pathomechanisms may aid a more targeted approach in triage as well as selection of cases with possible late complications while also identifying the target patient population where preventive measures and therapeutic tools should be applied in an attempt to avoid secondary brain injury and late complications.
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| 3. |
- Mondello, Stefania, et al.
(author)
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Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury : a case control study
- 2011
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In: Critical Care. - London : Springer Nature. - 1364-8535 .- 1466-609X. ; 15:3
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Journal article (peer-reviewed)abstract
- Introduction: Authors of several studies have studied biomarkers and computed tomography (CT) findings in the acute phase after severe traumatic brain injury (TBI). However, the correlation between structural damage as assessed by neuroimaging and biomarkers has not been elucidated. The aim of this study was to investigate the relationships among neuronal (Ubiquitin carboxy-terminal hydrolase L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels in serum, neuroradiological findings and outcomes after severe TBI.Methods: The study recruited patients from four neurotrauma centers. Serum samples for UCH-L1 and GFAP were obtained at the time of hospital admission and every 6 hours thereafter. CT scans of the brain were obtained within 24hrs of injury. Outcome was assessed by Glasgow Outcome Scale (GOS) at discharge and at 6 months.Results: 81 severe TBI patients and 167 controls were enrolled. The mean serum levels of UCH-L1 and GFAP were higher (p < 0.001) in TBI patients compared to controls. UCH-L1 and GFAP serum levels correlated significantly with Glasgow Coma Scale (GCS) and CT findings. GFAP levels were higher in patients with mass lesions than in those with diffuse injury (2.95 +/- 0.48 ng/ml versus 0.74 +/- 0.11 ng/ml) while UCH-L1 levels were higher in patients with diffuse injury (1.55 +/- 0.18 ng/ml versus 1.21 +/- 0.15 ng/ml, p = 0.0031 and 0.0103, respectively). A multivariate logistic regression showed that UCH-L1 was the only independent predictor of death at discharge [adjusted odds ratios 2.95; 95% confidence interval, 1.46-5.97], but both UCH-L1 and GFAP levels strongly predicted death 6 months post-injury.Conclusions: Relationships between structural changes detected by neuroimaging and biomarkers indicate each biomarker may reflect a different injury pathway. These results suggest that protein biomarkers could provide better characterization of subjects at risk for specific types of cellular damage than that obtained with neuroimaging alone, as well as provide valuable information about injury severity and outcome after severe TBI.
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| 4. |
- Mondello, Stefania, et al.
(author)
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The Challenge of Mild Traumatic Brain Injury : Role of Biochemical Markers in Diagnosis of Brain Damage
- 2013
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In: Medicinal research reviews (Print). - : John Wiley & Sons. - 0198-6325 .- 1098-1128. ; 34:3, s. 503-531
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Research review (peer-reviewed)abstract
- During the past decade there has been an increasing recognition of the incidence of mildtraumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficitsthat may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteriafor mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detectbrain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss thecurrent research on serum biomarkers for mTBI including their rationale and diagnostic performances.Sensitive and specific biomarkers reflecting brain injury can provide important information regardingTBI pathophysiology and serve as candidate markers for predicting abnormal computed tomographyfindings and/or the development of residual deficits in patients who sustain an mTBI. We also outline theroles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and militaryinjuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emergingproteomics-based strategies for identifying novel markers will be discussed.
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| 5. |
- Welch, Robert D, et al.
(author)
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Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B to Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.
- 2016
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 33:2, s. 203-214
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Journal article (peer-reviewed)abstract
- Head Computed Tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multi-center observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (Glial Fibrillary Acidic Protein [GFAP], Ubiquitin C-Terminal Hydrolase-L1 [UCH-L1] and S100B measured within 6-hours of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury), was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value > 40 pg/ml. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/ml) and S100B had a specificity of only 2% (cutoff value 30 pg/ml). All three biomarkers had similar values for areas under the receiver operator characteristic curve; 0.79 (95% CI; 0.70 to 0.88) for GFAP, 0.80 (0.71 to 0.89) for UCH-L1, and 0.75 (0.65 to 0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p=0.21 and p=0.77 respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values < 40 pg/ml could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
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| 6. |
- Welch, Robert D., et al.
(author)
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Ability of serum glial fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B to differentiate normal and abnormal head computed tomography findings in patients with suspected mild or moderate traumatic brain injury
- 2016
-
In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 33:2, s. 203-214
-
Journal article (peer-reviewed)abstract
- Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
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