| Autor: |
Swaney EEK; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Victoria, Australia., Babl FE; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Emergency Department, Royal Children's Hospital, Melbourne, Victoria, Australia., Rausa VC; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Anderson N; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Hearps SJC; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Parkin G; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Hart-Smith G; Australian Proteomics Analysis Facility, Macquarie University, Sydney, New South Wales, Australia., Zaw T; Australian Proteomics Analysis Facility, Macquarie University, Sydney, New South Wales, Australia., Carroll L; Australian Proteomics Analysis Facility, Macquarie University, Sydney, New South Wales, Australia., Takagi M; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; School of Psychological Sciences, University of Melbourne, Victoria, Australia., Seal ML; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Victoria, Australia., Davis GA; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Neurosurgery, Austin and Cabrini Hospitals, Melbourne, Victoria, Australia., Anderson V; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; School of Psychological Sciences, University of Melbourne, Victoria, Australia.; Psychology Service, Royal Children's Hospital, Melbourne, Victoria, Australia., Ignjatovic V; Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Victoria, Australia.; Johns Hopkins All Children's Institute for Clinical and Translational Research, St. Petersburg, FL, USA.; Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. |
| Abstrakt: |
Of the four million children who experience a concussion each year, 30-50% of children will experience delayed recovery, where they will continue to experience symptoms more than two weeks after their injury. Delayed recovery from concussion encompasses emotional, behavioral, physical, and cognitive symptoms, and as such, there is an increased focus on developing an objective tool to determine risk of delayed recovery. This study aimed to identify a blood protein signature predictive of delayed recovery from concussion in children. Plasma samples were collected from children who presented to the Emergency Department at the Royal Children's Hospital, Melbourne, within 48h post-concussion. This study involved a discovery and validation phase. For the discovery phase, untargeted proteomics analysis was performed using single window acquisition of all theoretical mass spectra to identify blood proteins differentially abundant in samples from children with and without delayed recovery from concussion. A subset of these proteins was then validated in a separate participant cohort using multiple reaction monitoring and enzyme linked immunosorbent assay. A blood protein signature predictive of delayed recovery from concussion was modeled using a Support Vector Machine, a machine learning approach. In the discovery phase, 22 blood proteins were differentially abundant in age- and sex-matched samples from children with ( n = 9) and without ( n = 9) delayed recovery from concussion, six of whom were chosen for validation. In the validation phase, alpha-1-ACT was shown to be significantly lower in children with delayed recovery ( n = 12) compared with those without delayed recovery ( n = 28), those with orthopedic injuries ( n = 7) and healthy controls ( n = 33). A model consisting of alpha-1-ACT concentration stratified children based on recovery from concussion with an 0.88 area under the curve. We have identified that alpha-1-ACT differentiates between children at risk of delayed recovery from those without delayed recovery from concussion. To our knowledge, this is the first study to identify alpha-1-ACT as a potential marker of delayed recovery from concussion in children. Multi-site studies are required to further validate this finding before use in a clinical setting. |
