Temporal response profiles of serum ubiquitin C-terminal hydrolase-L1 and the 145-kDa alpha II-spectrin breakdown product after severe traumatic brain injury in children
| Autor: | Ryan R. Metzger, Michelle E. Schober, Xiaoming Sheng, Brandon A. Zielinski, Denise C. Morita, Kimberly Statler Bennett, Christian M. Niedzwecki |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty Adolescent Traumatic brain injury Alpha (ethology) Ubiquitin C-Terminal Hydrolase Pilot Projects 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid Ubiquitin Internal medicine Brain Injuries Traumatic Medicine Humans Spectrin Child biology business.industry Infant General Medicine medicine.disease ICP - Intracranial pressure 030104 developmental biology Child Preschool biology.protein Biomarker (medicine) Female business Ubiquitin Thiolesterase 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Journal of neurosurgery. Pediatrics. 22(4) |
| ISSN: | 1933-0715 |
| Popis: | OBJECTIVETraumatic brain injury (TBI) is the leading cause of acquired disability among children. Brain injury biomarkers may serve as useful diagnostic and prognostic indicators for TBI. Levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and the 145-kDa alpha II-spectrin breakdown product (SBDP-145) correlate with outcome in adults after severe TBI. The authors conducted a pilot study of these biomarkers in children after severe TBI to inform future research exploring their utility in this population.METHODSThe levels of UCH-L1 and SBDP-145 were measured in serum, and UCH-L1 in CSF from pediatric patients after severe TBI over 5 days after injury. Both biomarkers were also measured in age-matched control serum and CSF.RESULTSAdequate numbers of samples were obtained in serum, but not CSF, to assess biomarker temporal response profiles. Using patients with samples from all time points, UCH-L1 levels increased rapidly and transiently, peaking at 12 hours after injury. SBDP-145 levels showed a more gradual and sustained response, peaking at 48 hours. The median serum UCH-L1 concentration was greater in patients with TBI than in controls (median [IQR] = 361 [187, 1330] vs 147 [50, 241] pg/ml, respectively; p < 0.001). Receiver operating characteristic (ROC) analysis revealed an AUC of 0.77. Similarly, serum SBDP-145 was greater in children with TBI than in controls (median [IQR] = 172 [124, 257] vs 69 [40, 99] pg/ml, respectively; p < 0.001), with an ROC AUC of 0.85. When only time points of peak levels were used for ROC analysis, the discriminability of each serum biomarker increased (AUC for UCH-L1 at 12 hours = 1.0 and for SBDP-145 at 48 hours = 0.91). Serum and CSF UCH-L1 levels correlated well in patients with TBI (r = 0.70, p < 0.001).CONCLUSIONSFindings from this exploratory study reveal robust increases of UCH-L1 and SBDP-145 in serum and UCH-L1 in CSF obtained from children after severe TBI. In addition, important temporal profile differences were found between these biomarkers that can help guide optimal time point selection for future investigations of their potential to characterize injury or predict outcomes after pediatric TBI. |
| Databáze: | OpenAIRE |
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