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Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury
  1. Pia Koivikko1,2,
  2. Jussi P Posti3,4,
  3. Mehrbod Mohammadian4,5,
  4. Linnea Lagerstedt6,
  5. Leire Azurmendi6,
  6. Iftakher Hossain3,7,
  7. Ari J Katila1,2,
  8. David Menon8,
  9. Virginia F J Newcombe8,
  10. Peter John Hutchinson7,
  11. Henna-Riikka Maanpää3,4,
  12. Jussi Tallus5,9,
  13. Henrik Zetterberg10,11,
  14. Kaj Blennow10,12,
  15. Olli Tenovuo4,5,
  16. Jean-Charles Sanchez6,
  17. Riikka S K Takala1,2
  1. 1Perioperative Services, Intensive Care Medicine, and Pain Management, Turku University Hospital, Turku, Finland
  2. 2Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland
  3. 3Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital, Turku, Finland
  4. 4Department of Clinical Neurosciences, University of Turku, Turku, Finland
  5. 5Neurocenter, Turku Brain Injury Center, Turku University Hospital, Turku, Finland
  6. 6Department of Specialities of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
  7. 7Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Cambridge, UK
  8. 8Department of Anaesthesia, University of Cambridge, Cambridge, UK
  9. 9Department of Radiology, University of Turku, Turku, Finland
  10. 10Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg Sahlgrenska Academy, Mölndal, Sweden
  11. 11UK Dementia Research Institute, UCL, London, UK
  12. 12Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
  1. Correspondence to Dr Pia Koivikko, Perioperative Services, Intensive Care Medicine, and Pain Management, TYKS Turku University Hospital, Turku, Finland; piaknuu{at}utu.fi

Abstract

Background There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting.

Methods Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011–2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13–15 was classified as mild (mTBI); GCS 9–12 as moderate (moTBI) and GCS 3–8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed.

Results Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls.

Conclusions S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.

  • assessment
  • acute care

Data availability statement

Data are available on reasonable request. De-identified clinical, imaging and biochemical data not published within the article can be shared with a qualified investigator by request.

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Data availability statement

Data are available on reasonable request. De-identified clinical, imaging and biochemical data not published within the article can be shared with a qualified investigator by request.

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Footnotes

  • Handling editor Ellen J Weber

  • Contributors PK, JPP and RSKT conceived and designed the current study. JPP, RSKT, AJK, H-RM, JT and OT recruited the patients. JPP, RSKT, AJK, MM, IH, HRM, JT, PK and OT collected and curated the data. MM, LA and LL conducted the statistical analyses. HZ, KB and J-CS supervised the biomarker analyses. PH, DM, VFJN and OT supervised the TBI care study. PK drafted the manuscript with critical contributions from JPP and RSKT. All authors substantially contributed to the revision of the manuscript. RSKT is the author responsible for the overall content as the guarantor.

  • Funding This study was a part of the EU-funded TBI care project (Evidence-based Diagnostic and Treatment Planning Solution for Traumatic Brain Injuries). This work was partially funded by Academy of Finland (Grant #17379, JPP), Finnish Government’s Special Financial Transfer tied to academic research in Health Sciences (Grant #11129, JPP). VFJN is supported by an Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 860197 (MIRIADE), the UK Dementia Research Institute at UCL and Centrum för Idrottsforskning (#P2019-0198). KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, and is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243) and a grant (#ALFGBG-715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF agreement.

  • Competing interests DM reports grants from European Union, during the conduct of the study; grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Pfizer, personal fees from NeuroTrauma Sciences, personal fees from Calico, grants and personal fees from PressuraNeuro, grants and personal fees from Integra Neurosciences, grants and personal fees from Lantmannen, outside the submitted work; VFJN reports grants from Roche, outside the submitted work; HZ reports that he has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg (BBS), which is a part of the GU Ventures Incubator Program; KB served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg (BBS), which is a part of the GU Ventures Incubator Program.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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