{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:32:54Z","timestamp":1779366774019,"version":"3.53.0"},"reference-count":59,"publisher":"SAGE Publications","issue":"1-2","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n                    Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo\/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo\/sTBI (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200985) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-tau), amyloid \u03b240 (A\u03b240) and amyloid \u03b242 (A\u03b242), within 24\u2009h of admission. Similar analyses were conducted for controls (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200940) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20099\/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5\u20138) versus unfavorable (GOSE &lt;5) (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200938\/42, 5 missing) outcome. Outliers were sought individually from all subgroups from and the whole TBI patient population. Biomarker levels outside Q1\u2009\u2212\u20091.5 interquartile range (IQR) or Q3\u2009+\u20091.5 IQR were considered as outliers. The medical records of each outlier patient were reviewed in a team meeting to determine possible reasons for outlier values. A total of 29 patients (34%) combined from all subgroups and 12 patients (30%) among the controls showed outlier values for one or more of the eight biomarkers. Nine patients with TBI and five control patients had outlier values in more than one biomarker (up to 4). All outlier values were &gt; Q3\u2009+\u20091.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo\/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B).\n                  <\/jats:p>","DOI":"10.1089\/neu.2023.0120","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T13:17:52Z","timestamp":1695129472000},"page":"91-105","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Outlier Analysis for Acute Blood Biomarkers of Moderate and Severe Traumatic Brain Injury"],"prefix":"10.1177","volume":"41","author":[{"given":"Otto","family":"Korhonen","sequence":"first","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malla","family":"Mononen","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrbod","family":"Mohammadian","sequence":"additional","affiliation":[{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Tenovuo","sequence":"additional","affiliation":[{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden."},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iftakher","family":"Hossain","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henna-Riikka","family":"Maanp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Menon","sequence":"additional","affiliation":[{"name":"Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia F.","family":"Newcombe","sequence":"additional","affiliation":[{"name":"Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Specialities of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka S.K.","family":"Takala","sequence":"additional","affiliation":[{"name":"Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Tallus","sequence":"additional","affiliation":[{"name":"Turku Brain Injury Center, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Clinical Neurosciences, Turku University Hospital and University of Turku, Turko, Finland."},{"name":"Department of Radiology, Turku University Hospital and University of Turku, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"van Gils","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, 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