A1 Refereed original research article in a scientific journal
Blood biomarker outliers and clinical events during intensive care in patients with traumatic brain injury; 
Authors: Koivikko, Pia; Posti, Jussi P.; Hossain, Iftakher; Mohammadian, Mehrbod; Tenovuo, Olli; Hutchinson, Peter; Katila, Ari J.; Maanpää, Henna-Riikka; Menon, David K.; Newcombe, Virginia F.; Sanchez, Jean-Charles; Tallus, Jussi; van Gils, Mark; Zetterberg, Henrik; Takala, Riikka SK.
Publisher: Elsevier
Publication year: 2026
Journal: Brain and spine
Article number: 106078
Volume: 6
eISSN: 2772-5294
DOI: https://doi.org/10.1016/j.bas.2026.106078
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://doi.org/10.1016/j.bas.2026.106078
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/524867045
Self-archived copy's licence: CC BY NC ND
Self-archived copy's version: Publisher`s PDF
Introduction: Monitoring and timely clinical assessment are fundamental to treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU). Proactive, individualised treatment is unavailable with the current methods.
Research question: How do outlying blood biomarker levels associate with clinical events or outcome in TBI?
Materials and methods: Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), interleukin-10 (IL-10) and total tau (t-tau) were analysed from blood plasma samples of 70 ICU-treated patients, aged ≥18, with a clinical diagnosis of TBI and an indication for a head CT scan. The blood samples were collected on arrival and on days 1, 2, 3 and 7. The biomarkers were screened for outliers and biomarker values outside Q1-1.5 × interquartile range (IQR) or Q3+1.5 × IQR on any day post-injury were considered outliers. The outlier group was compared with the non-outlier group targeting clinically significant aspects such as high intracranial pressure, seizures/status epilepticus, or mortality/poor outcome. The Glasgow Outcome Scale Extended (GOSE) was evaluated between 6 and 12 months after the injury.
Results: Difference was found in epileptic activity (n = 7 vs n = 0) and the number of performed decompressive hemicraniectomies (n = 6 vs n = 0) between the outlier and the non-outlier groups, p = 0.015 and < 0.0001, respectively. Patients in the outlier group were also more likely to have a poor outcome (GOSE 1-3) than patients in the non-outlier group, p = 0.011.
Discussion and conclusion: Biomarker outliers seem to associate with clinical events and poor outcome in ICU-treated patients with TBI, possibly due to greater severity of TBI.
Keywords:
Outliers, traumatic brain injury
Downloadable publication This is an electronic reprint of the original article. |  |
Funding information in the publication:
PK is supported by State Research Funding (Finland) (#11211), Maire Taponen Foundation and the Finnish Medical Society Duodecim. HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union's Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the Bluefield Project, Cure Alzheimer's Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Familjen Rönströms Stiftelse, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). PJH is supported by the UK NIHR (Senior Investigator Award, Cambridge BRC, NIHR Global Health Research Group on Acquired Brain and Spine Injury, Brain Injury MedTech Co-operative) and the Royal College of Surgeons of England. IH is supported by the Finnish Medical Foundation, the Paulo Foundation, the Maire Taponen Foundation, the State Research Funding (Finland) and the Orion Research Foundation. VFJN is supported by a National Institute for Health and Care Research (NIHR) Rosetrees Trust Advanced Fellowship. The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health Research, Rosetrees Trust or the Department of Health and Social Care. JPP is supported by the Research Council of Finland, Sigrid Jusélius Foundation, and State Research Funding (Finland) (#11129).
