Andrew M Penn1, Maximilian B Bibok2, Viera K Saly1, Shelagh B Coutts3, Mary L Lesperance4, Robert F Balshaw5, Kristine Votova2,6, Nicole S Croteau2,4, Anurag Trivedi1, Angela M Jackson7, Janka Hegedus3, Evgenia Klourfeld3, Amy Y X Yu8, Charlotte Zerna3, Christoph H Borchers9,10,11. 1. a Neurosciences, Stroke Rapid Assessment Clinic , Island Health Authority , Victoria , BC , Canada. 2. b Department of Research and Capacity Building , Island Health Authority , Victoria , BC , Canada. 3. c Departments of Clinical Neurosciences, Radiology, and Community Health Services , University of Calgary, Hotchkiss Brain Institute, C1242, Foothills Medical Centre , Calgary , AB , Canada. 4. d Department of Mathematics and Statistics , University of Victoria , Victoria , BC , Canada. 5. e British Columbia Centre for Disease Control , Vancouver , BC , Canada. 6. f Division of Medical Sciences , University of Victoria , Victoria , BC , Canada. 7. g University of Victoria - Genome British Columbia Proteomics Centre, Vancouver Island Technology Park , Victoria , BC , Canada. 8. h Department of Medicine , University of Toronto Sunnybrook Health Sciences Centre , Toronto , ON , Canada. 9. i Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , Canada. 10. j Gerald Bronfman Department of Oncology , Jewish General Hospital McGill University , Montreal , QC , Canada. 11. k Proteomics Centre, Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University , Montreal , QC , Canada.
Abstract
OBJECTIVE: To derive a plasma biomarker protein panel from a list of 141 candidate proteins which can differentiate transient ischaemic attack (TIA)/minor stroke from non-cerebrovascular (mimic) conditions in emergency department (ED) settings. DESIGN: Prospective clinical study (#NCT03050099) with up to three timed blood draws no more than 36 h following symptom onset. Plasma samples analysed by multiple reaction monitoring-mass spectrometry (MRM-MS). PARTICIPANTS: Totally 545 participants suspected of TIA enrolled in the EDs of two urban medical centres. OUTCOMES: 90-day, neurologist-adjudicated diagnosis of TIA informed by clinical and radiological investigations. RESULTS: The final protein panel consists of 16 proteins whose patterns show differential abundance between TIA and mimic patients. Nine of the proteins were significant univariate predictors of TIA [odds ratio (95% confidence interval)]: L-selectin [0.726 (0.596-0.883)]; Insulin-like growth factor-binding protein 3 [0.727 (0.594-0.889)]; Coagulation factor X [0.740 (0.603-0.908)]; Serum paraoxonase/lactonase 3 [0.763 (0.630-0.924)]; Thrombospondin-1 [1.313 (1.081-1.595)]; Hyaluronan-binding protein 2 [0.776 (0.637-0.945)]; Heparin cofactor 2 [0.775 (0.634-0.947)]; Apolipoprotein B-100 [1.249 (1.037-1.503)]; and von Willebrand factor [1.256 (1.034-1.527)]. The scientific plausibility of the panel proteins is discussed. CONCLUSIONS: Our panel has the potential to assist ED physicians in distinguishing TIA from mimic patients.
OBJECTIVE: To derive a plasma biomarker protein panel from a list of 141 candidate proteins which can differentiate transient ischaemic attack (TIA)/minor stroke from non-cerebrovascular (mimic) conditions in emergency department (ED) settings. DESIGN: Prospective clinical study (#NCT03050099) with up to three timed blood draws no more than 36 h following symptom onset. Plasma samples analysed by multiple reaction monitoring-mass spectrometry (MRM-MS). PARTICIPANTS: Totally 545 participants suspected of TIA enrolled in the EDs of two urban medical centres. OUTCOMES: 90-day, neurologist-adjudicated diagnosis of TIA informed by clinical and radiological investigations. RESULTS: The final protein panel consists of 16 proteins whose patterns show differential abundance between TIA and mimic patients. Nine of the proteins were significant univariate predictors of TIA [odds ratio (95% confidence interval)]: L-selectin [0.726 (0.596-0.883)]; Insulin-like growth factor-binding protein 3 [0.727 (0.594-0.889)]; Coagulation factor X [0.740 (0.603-0.908)]; Serum paraoxonase/lactonase 3 [0.763 (0.630-0.924)]; Thrombospondin-1 [1.313 (1.081-1.595)]; Hyaluronan-binding protein 2 [0.776 (0.637-0.945)]; Heparin cofactor 2 [0.775 (0.634-0.947)]; Apolipoprotein B-100 [1.249 (1.037-1.503)]; and von Willebrand factor [1.256 (1.034-1.527)]. The scientific plausibility of the panel proteins is discussed. CONCLUSIONS: Our panel has the potential to assist ED physicians in distinguishing TIA from mimic patients.
Authors: Johann Otto Pelz; Katharina Kubitz; Manja Kamprad-Lachmann; Kristian Harms; Martin Federbusch; Carsten Hobohm; Dominik Michalski Journal: Front Neurol Date: 2021-11-08 Impact factor: 4.003
Authors: Austin G Milton; Stephan Lau; Karlea L Kremer; Sushma R Rao; Emilie Mas; Marten F Snel; Paul J Trim; Deeksha Sharma; Suzanne Edwards; Mark Jenkinson; Timothy Kleinig; Erik Noschka; Monica Anne Hamilton-Bruce; Simon A Koblar Journal: BMJ Open Date: 2022-04-01 Impact factor: 2.692