Home Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL1) as blood biomarkers of mild acute traumatic brain injury (mTBI) or sport-related concussion (SRC) in adult subjects
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Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL1) as blood biomarkers of mild acute traumatic brain injury (mTBI) or sport-related concussion (SRC) in adult subjects

  • Paolo Mastandrea ORCID logo EMAIL logo , Silvia Mengozzi and Sergio Bernardini
Published/Copyright: August 20, 2024
Diagnosis
From the journal Diagnosis Volume 12 Issue 1

Abstract

Introduction

Neurotrauma is the leading cause of death in individuals <45 years old. Many of the published articles on UCHL1 and GFAP lack rigorous methods and reporting.

Content

Due to the high heterogeneity between studies, we evaluated blood GFAP and UCHL1 levels in the same subjects. We determined the biomarker congruence among areas under the ROC curves (AUCs), sensitivities, specificities, and laboratory values in ng/L to avoid spurious results. The definitive meta-analysis included 1,880 subjects in eight studies. The items with the highest risk of bias were as follows: cut-off not prespecified and case-control design not avoided. The AUC of GFAP was greater than the AUC of UCHL1, with a lower prediction interval (PI) limit of 50.1 % for GFAP and 37.3 % for UCHL1, and a significantly greater percentage of GFAP Sp. The PI of laboratory results for GFAP and UCHL1 were 0.517–7,518 ng/L (diseased), 1.2–255 ng/L (nondiseased), and 3–4,180 vs. 3.2–1,297 ng/L, respectively.

Summary

Only the GFAP positive cut-off (255 ng/L) appears to be reliable. The negative COs appear unreliable.

Outlook

GFAP needs better standardization. However, the AUCs of the phospho-Tau and phospho-Tau/Tau proteins resulted not significantly lower than AUC of GFAP, but this result needs further verifications.

Corresponding author: Paolo Mastandrea, Department of Clinical Pathology, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità San Giuseppe Moscati, Discesa Campanile 52, 84085 Mercato S. Severino, Salerno, Italy, E-mail:

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: (1) Substantial contributions to the conception, design, acquisition, analysis and interpretation of data of the work: Mastandrea, Mengozzi, Bernardini; (2) drafting of the work and revising it critically for important intellectual content: Mastandrea, Mengozzi, Bernardini; (3) final approval of the version to be published: Mastandrea, Mengozzi Bernardini; (4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: Mastandrea, Mengozzi, Bernardini. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: Not applicable.

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Received: 2024-04-23
Accepted: 2024-07-14
Published Online: 2024-08-20

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL1) as blood biomarkers of mild acute traumatic brain injury (mTBI) or sport-related concussion (SRC) in adult subjects
  4. Opinion Papers
  5. From stable teamwork to dynamic teaming in the ambulatory care diagnostic process
  6. Bringing team science to the ambulatory diagnostic process: how do patients and clinicians develop shared mental models?
  7. Vitamin D assay and supplementation: still debatable issues
  8. Original Articles
  9. Developing a framework for understanding diagnostic reconciliation based on evidence review, stakeholder engagement, and practice evaluation
  10. Validity and reliability of Brier scoring for assessment of probabilistic diagnostic reasoning
  11. Impact of disclosing a working diagnosis during simulated patient handoff presentation in the emergency department: correctness matters
  12. Implementation of a bundle to improve diagnosis in hospitalized patients: lessons learned
  13. Time pressure in diagnosing written clinical cases: an experimental study on time constraints and perceived time pressure
  14. A decision support system to increase the compliance of diagnostic imaging examinations with imaging guidelines: focused on cerebrovascular diseases
  15. Bridging the divide: addressing discrepancies between clinical guidelines, policy guidelines, and biomarker utilization
  16. Unnecessary repetitions of C-reactive protein and leukocyte count at the emergency department observation unit contribute to higher hospital admission rates
  17. Quality control of ultrasonography markers for Down’s syndrome screening: a retrospective study by the laboratory
  18. Short Communications
  19. Unclassified green dots on nucleated red blood cells (nRBC) plot in DxH900 from a patient with hyperviscosity syndrome
  20. Bayesian intelligence for medical diagnosis: a pilot study on patient disposition for emergency medicine chest pain
  21. Case Report – Lessons in Clinical Reasoning
  22. A delayed diagnosis of hyperthyroidism in a patient with persistent vomiting in the presence of Chiari type 1 malformation
  23. Letters to the Editor
  24. Mpox (monkeypox) diagnostic kits – September 2024
  25. Barriers to diagnostic error reduction in Japan
  26. Superwarfarin poisoning: a challenging diagnosis
  27. Reviewer Acknowledgment
  28. Reviewer Acknowledgment
https://doi.org/10.1515/dx-2024-0078

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Systematic review and meta-analysis of observational studies evaluating glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL1) as blood biomarkers of mild acute traumatic brain injury (mTBI) or sport-related concussion (SRC) in adult subjects
  4. Opinion Papers
  5. From stable teamwork to dynamic teaming in the ambulatory care diagnostic process
  6. Bringing team science to the ambulatory diagnostic process: how do patients and clinicians develop shared mental models?
  7. Vitamin D assay and supplementation: still debatable issues
  8. Original Articles
  9. Developing a framework for understanding diagnostic reconciliation based on evidence review, stakeholder engagement, and practice evaluation
  10. Validity and reliability of Brier scoring for assessment of probabilistic diagnostic reasoning
  11. Impact of disclosing a working diagnosis during simulated patient handoff presentation in the emergency department: correctness matters
  12. Implementation of a bundle to improve diagnosis in hospitalized patients: lessons learned
  13. Time pressure in diagnosing written clinical cases: an experimental study on time constraints and perceived time pressure
  14. A decision support system to increase the compliance of diagnostic imaging examinations with imaging guidelines: focused on cerebrovascular diseases
  15. Bridging the divide: addressing discrepancies between clinical guidelines, policy guidelines, and biomarker utilization
  16. Unnecessary repetitions of C-reactive protein and leukocyte count at the emergency department observation unit contribute to higher hospital admission rates
  17. Quality control of ultrasonography markers for Down’s syndrome screening: a retrospective study by the laboratory
  18. Short Communications
  19. Unclassified green dots on nucleated red blood cells (nRBC) plot in DxH900 from a patient with hyperviscosity syndrome
  20. Bayesian intelligence for medical diagnosis: a pilot study on patient disposition for emergency medicine chest pain
  21. Case Report – Lessons in Clinical Reasoning
  22. A delayed diagnosis of hyperthyroidism in a patient with persistent vomiting in the presence of Chiari type 1 malformation
  23. Letters to the Editor
  24. Mpox (monkeypox) diagnostic kits – September 2024
  25. Barriers to diagnostic error reduction in Japan
  26. Superwarfarin poisoning: a challenging diagnosis
  27. Reviewer Acknowledgment
  28. Reviewer Acknowledgment
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