To Örebro University

oru.seÖrebro University Publications
Change search
Link to record
Permanent link

Direct link
Büki, Andras, ProfessorORCID iD iconorcid.org/0000-0002-2190-9278
Alternative names
Publications (10 of 141) Show all publications
Whitehouse, D. P., Wilson, L., Czeiter, E., Büki, A., Wang, K. K. W., von Steinbüchel, N., . . . Newcombe, V. F. J. (2025). Association of Blood-Based Biomarkers and 6-Month Patient-Reported Outcomes in Patients With Mild TBI: A CENTER-TBI Analysis. Neurology, 104(1), Article ID e210040.
Open this publication in new window or tab >>Association of Blood-Based Biomarkers and 6-Month Patient-Reported Outcomes in Patients With Mild TBI: A CENTER-TBI Analysis
Show others...
2025 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 104, no 1, article id e210040Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND OBJECTIVES: There is seemingly contradictory evidence concerning relationships between day-of-injury biomarkers and outcomes after mild traumatic brain injury (mTBI). To address this issue, we examined the association between a panel of biomarkers and multidimensional TBI outcomes.

METHODS: Participants with mTBI (Glasgow coma scores [GCSs] 13-15) were selected from Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury, a European observational study recruiting patients with TBI with indication for brain CT and presentation within 24 hours. Exclusion criteria for this secondary analysis were age younger than 16 years, incomplete biomarker panel, death, or no recorded outcomes. Participants were separated into 2 groups, CT-negative and CT-positive. Multivariable binary logistic regression was used to assess the relation between the log biomarker level (glial fibrillary acidic protein [GFAP], neurofilament light [NfL], neuron-specific enolase [NSE], S100 calcium-binding protein B [S100B], tau, ubiquitin C-terminal hydrolase L1 [UCH-L1]) and dichotomized 6-month outcomes (functional outcomes [GOSE score <8], health-related quality of life [HRQoL; Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) score <52, Short-Form 12-Item Survey version 2 Mental Component Summary (SF12v2 MCS) score <40, Short-Form 12-Item Survey version 2 Physical Component Summary (SF12v2 PCS) score <40], persistent postconcussion symptoms [Rivermead Post-Concussion Symptoms Questionnaire score ≥16], anxiety disorder [Generalized Anxiety Disorder-7 (GAD-7) score ≥8], depression [Patient Health Questionnaire-9 (PHQ-9) score ≥10], and post-traumatic stress disorder [PTSD Checklist for DSM-5 (PCL-5) score ≥33]).

RESULTS: A total of 1,589 participants (865 CT-negative, 724 CT-positive) were included (77% GCS 15, median age 52 years, 66% male). Higher biomarker levels were associated with a GOSE score <8: CT-negative: S100B (odds ratio [OR] 1.78, 95% CI 1.43-2.23) and UCH-L1 (OR 1.16, 95% CI 1.01-1.33); CT-positive: GFAP (OR 1.22, 95% CI 1.11-1.36), NfL (OR 1.30, 95% CI 1.11-1.52), S100B (OR 1.51, 95% CI 1.23-1.86), tau (OR 1.36, 95% CI 1.17-1.59), and UCH-L1 (OR 1.34, 95% CI 1.17-1.53). In CT-positive participants, positive association was seen between NfL (OR 1.3, 95% CI 1.06-1.60) and UCH-L1 (OR 1.28, 95% CI 1.07-1.54) with QOLIBRI-OS; S100B (OR 1.32, 95% CI 1.02-1.70) with SF12v2 PCS; and NSE (OR 1.52, 95% CI 1.06-2.18) and UCH-L1 (OR 1.21, 95% CI 1.01-1.46) with the GAD-7. However, in CT-negative participants only, negative associations were seen between GFAP and impairment on the QOLIBRI-OS (OR 0.76, 95% CI 0.66-0.88), SF12v2 MCS (OR 0.71, 95% CI 0.61-0.82), SF12v2 PCS (OR 0.79, 95% CI 0.68-0.91), GAD-7 (OR 0.80, 0.68-0.95), PHQ-9 (OR 0.80, 95% CI 0.68-0.93), and PCL-5 (OR 0.80, 95% CI 0.66-0.97). DISCUSSION: Participants with higher biomarker levels had greater odds of impaired functional recovery. However, in CT-negative participants, higher GFAP concentrations were associated with better HRQoL and less impaired mental health. Further exploration is required of the patient phenotypes that may explain the relationships observed in this analysis.

Place, publisher, year, edition, pages
Wolters Kluwer, 2025
National Category
Neurosciences
Identifiers
urn:nbn:se:oru:diva-117738 (URN)10.1212/WNL.0000000000210040 (DOI)001375598700001 ()39652812 (PubMedID)2-s2.0-85212245301 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 602150
Note

Funding Agencies:

CENTER-TBI was supported by the European Union 7thFramework program (EC grant 602150). Additional fundingwas obtained from the Hannelore Kohl Stiftung (Germany),OneMind (USA), Integra LifeSciences Corporation (USA),and NeuroTrauma Sciences (USA). D.P. Whitehouse issupported by the Royal College of Emergency Medicine(RCEM) Doctoral Research Fellowship. V.F.J. Newcombe issupported by a NIHR Rosetrees Trust Advanced Fellowship,NIHR302544, which is funded in partnership by the NIHRand Rosetrees Trust. 

Available from: 2024-12-11 Created: 2024-12-11 Last updated: 2025-01-14Bibliographically approved
Tallroth, M., Östlundh, L., Büki, A., Cao, Y., von Euler, M. & Ström, J. O. (2025). Reversal treatment and clinical outcomes in acute intracranial haemorrhage associated with oral anticoagulant use: protocol of a planned systematic review and meta-analysis. BMJ Open, 15(2), Article ID e090357.
Open this publication in new window or tab >>Reversal treatment and clinical outcomes in acute intracranial haemorrhage associated with oral anticoagulant use: protocol of a planned systematic review and meta-analysis
Show others...
2025 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 15, no 2, article id e090357Article, review/survey (Refereed) Published
Abstract [en]

INTRODUCTION: Reversal treatment is commonly used for managing oral anticoagulant (OAC)-associated intracranial haemorrhages. Its effects on mortality are still understudied, particularly in various subtypes of intracranial haemorrhages. This systematic review and meta-analysis aims to synthesise the available data to study the impact of reversal therapies on mortality following various OAC-associated acute intracranial haemorrhages.

METHODS AND ANALYSIS: This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Protocols, and the final review will be reported in accordance with the PRISMA reporting guidelines. This systematic review and meta-analysis will include studies that assess contemporary reversal treatment in comparison to no reversal treatment, in cases of OAC-associated intracranial haemorrhage. Stratification will be performed for the types of bleeding as well as OAC at bleeding onset. Preliminary searches to determine search term inclusions were conducted in May-August 2024 in the electronic databases Embase, PubMed, Scopus and Web of Science without language and publication date restrictions. Randomised controlled studies, non-randomised controlled trials, and observational studies will be considered for the final meta-analysis. Three reviewers (MT, JOS and AB) will screen titles and abstracts, and one reviewer (MT) will subsequently conduct full-text screening. Risks of bias will be assessed by MT using tools such as Risk of Bias 2, Risk Of Bias In Non-randomised Studies - of Interventions and the Newcastle-Ottawa Scale. Heterogeneity among the study results will be assessed using the I² statistic. If appropriate, a random-effects meta-analysis model will be performed. Subgroup analyses and meta-regression (if applicable) will be performed to assess sources of heterogeneity among (1) intracranial haemorrhage types, (2) OAC drugs and (3) study types, with randomised controlled trials being the primary focus.

ETHICS AND DISSEMINATION: Ethical approval is not needed as this project involves previously published data. We intend to publish the results in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42024556420.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2025
Keywords
Intracerebral Haemorrhage, NEUROLOGY, NEUROSURGERY
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-119362 (URN)39965957 (PubMedID)
Note

Study protocol

Funding Agencies:

This work was supported by funds from the Swedish Stroke Foundation and grants provided by the Swedish state according to the ‘Avtal om Läkarutbildning och Forskning agreement’ (ALF grants).

Available from: 2025-02-19 Created: 2025-02-19 Last updated: 2025-02-19Bibliographically approved
Magyar-Sumegi, Z. D., Stankovics, L., Lendvai-Emmert, D., Czigler, A., Hegedus, E., Csendes, M., . . . Toth, P. (2024). Acute neuroendocrine changes after traumatic brain injury. Brain & spine, 4, Article ID 102830.
Open this publication in new window or tab >>Acute neuroendocrine changes after traumatic brain injury
Show others...
2024 (English)In: Brain & spine, E-ISSN 2772-5294, Vol. 4, article id 102830Article, review/survey (Refereed) Published
Abstract [en]

INTRODUCTION: Post-traumatic hypopituitarism (PTHP) is a significant, but often neglected consequence of traumatic brain injury (TBI).

RESEARCH QUESTION: We aimed to provide a comprehensive overview of epidemiology, pathophysiology, clinical features and diagnostic approaches of PTHP.

MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Library and Web of Science were searched. 45 articles of human studies evaluating acute endocrine changes following mild, moderate and severe TBI were selected.

RESULTS: Severity of TBI seems to be the most important risk factor of PTHP. Adrenal insufficiency (AI) was present in 10% of TBI patients (prevalence can be as high as 50% after severe TBI), and hypocortisolemia is a predictor of mortality and long-term hypopituitarism. Suppression of the thyroid axis in 2-33% of TBI patients may be an independent predictor of adverse neurological outcome, as well. 9-36% of patients with severe TBI exhibit decreased function of the somatotrophic axis with a divergent effect on the central nervous system. Arginine-Vasopressin (AVP) deficiency is present in 15-51% of patients, associated with increased mortality and unfavorable outcome. Due to shear and injury of the stalk hyperprolactinemia is relatively common (2-50%), but it bears little clinical significance. Sex hormone levels remain within normal values.

DISCUSSION AND CONCLUSION: PTHP occurs frequently after TBI, affecting various axis and determining patients' outcome. However, evidence is scarce regarding exact epidemiology, diagnosis, and effective clinical application of hormone substitution. Future studies are needed to identify patients at-risk, determine the optimal timing for endocrine testing, and refine diagnostic and treatment approaches to improve outcome.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Acute pituitary disfunction, Neuroendocrine changes, Post-traumatic hypopituitarism, Traumatic brain injury
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-113748 (URN)10.1016/j.bas.2024.102830 (DOI)001240730600001 ()38764890 (PubMedID)2-s2.0-85192702165 (Scopus ID)
Note

This work was supported by grants from the National Research, Development and Innovation Office (OTKA K-134555, OTKA FK-146334 to PT), National Clinical Neuroscience Laboratory (RRF-2.3.1-21-2022-00011), the Thematic Excellence Program 2021 Health sub-programme of the Ministry for Innovation and Technology in Hungary, within the framework of the EGA-16 project of the University of Pecs (to PT). Project no. TKP2021-NKTA-47 was implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme. Funding through the National Cardiovascular Laboratory Program (RRF-2.3.1-21-2022-00003) was provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund; Project no. 135784 was implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the K_20 funding scheme and the European University for Well-Being (EUniWell) program (grant agreement number: 101004093/EUniWell/EAC-A02-2019/EAC-A02-2019-1).

Available from: 2024-05-22 Created: 2024-05-22 Last updated: 2024-07-29Bibliographically approved
Tallroth, M., Udumyan, R., Büki, A. & von Euler, M. (2024). Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 13(10), Article ID e034716.
Open this publication in new window or tab >>Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register
2024 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, E-ISSN 2047-9980, Vol. 13, no 10, article id e034716Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH.

METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence.

CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
Antithrombotic drugs, death, functional outcome, intracerebral hemorrhage, oral anticoagulants
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-113689 (URN)10.1161/JAHA.123.034716 (DOI)001228221200017 ()38726922 (PubMedID)2-s2.0-85194013585 (Scopus ID)
Funder
The Swedish Stroke Association
Note

The study was funded by the Swedish Stroke Foundation and by grants provided by the “Avtal om Läkarutbildning och Forskning agreement,” an agreement between the Swedish government and the Region Örebro Council. 

Available from: 2024-05-23 Created: 2024-05-23 Last updated: 2024-07-04Bibliographically approved
Hossain, I., Marklund, N., Czeiter, E., Hutchinson, P. & Büki, A. (2024). Blood biomarkers for traumatic brain injury: A narrative review of current evidence. Brain and Spine, 4, Article ID 102735.
Open this publication in new window or tab >>Blood biomarkers for traumatic brain injury: A narrative review of current evidence
Show others...
2024 (English)In: Brain and Spine, E-ISSN 2772-5294, Vol. 4, article id 102735Article, review/survey (Refereed) Published
Abstract [en]

Introduction: A blood-based biomarker (BBBM) test could help to better stratify patients with traumatic brain injury (TBI), reduce unnecessary imaging, to detect and treat secondary insults, predict outcomes, and monitor treatment effects and quality of care.

Research question: What evidence is available for clinical applications of BBBMs in TBI and how to advance this field?

Material and methods: This narrative review discusses the potential clinical applications of core BBBMs in TBI. A literature search in PubMed, Scopus, and ISI Web of Knowledge focused on articles in English with the words "traumatic brain injury" together with the words "blood biomarkers", "diagnostics", "outcome prediction", "extracranial injury" and "assay method" alone-, or in combination.

Results: Glial fibrillary acidic protein (GFAP) combined with Ubiquitin C-terminal hydrolase-L1(UCH-L1) has received FDA clearance to aid computed tomography (CT)-detection of brain lesions in mild (m) TBI. Application of S100B led to reduction of head CT scans. GFAP may also predict magnetic resonance imaging (MRI) abnormalities in CT-negative cases of TBI. Further, UCH-L1, S100B, Neurofilament light (NF-L), and total tau showed value for predicting mortality or unfavourable outcome. Nevertheless, biomarkers have less role in outcome prediction in mTBI. S100B could serve as a tool in the multimodality monitoring of patients in the neurointensive care unit.

Discussion and conclusion: Largescale systematic studies are required to explore the kinetics of BBBMs and their use in multiple clinical groups. Assay development/cross validation should advance the generalizability of those results which implicated GFAP, S100B and NF-L as most promising biomarkers in the diagnostics of TBI.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Traumatic brain injury, Blood biomarkers, Diagnostics, Outcome prediction
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-111346 (URN)10.1016/j.bas.2023.102735 (DOI)001141836900001 ()38510630 (PubMedID)2-s2.0-85180350517 (Scopus ID)
Funder
The Swedish Brain Foundation
Note

Funding: The Finnish Medical Foundation (IH), The Päivikki and Sakari Sohlberg Foundation (IH), The Paulo Foundation (IH), The Finnish Cultural Foundation (IH), Skåne University Hospital ALF funds (NM), Hans-Gabriel af Trolle Wachtmeister Foundation (NM) and Swedish Brain Foundation (NM).

Available from: 2024-02-02 Created: 2024-02-02 Last updated: 2024-09-04Bibliographically approved
Iaccarino, C., Chibbaro, S., Sauvigny, T., Timofeev, I., Zaed, I., Franchetti, S., . . . Servadei, F. (2024). Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel. Brain & spine, 4, Article ID 102761.
Open this publication in new window or tab >>Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel
Show others...
2024 (English)In: Brain & spine, E-ISSN 2772-5294, Vol. 4, article id 102761Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance.

RESEARCH QUESTION: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems.

METHODS: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction."

RESULTS: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain."

DISCUSSION AND CONCLUSION: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Cranioplasty, Diagnosis, Post-traumatic hydrocephalus, Surgical strategy
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-112511 (URN)10.1016/j.bas.2024.102761 (DOI)001197849600001 ()38510640 (PubMedID)2-s2.0-85185576973 (Scopus ID)
Note

This project was conducted with the non-conditioning assistance of Integra LifeSciences.

Available from: 2024-03-21 Created: 2024-03-21 Last updated: 2024-09-04Bibliographically approved
Picetti, E., Büki, A. & Robba, C. (2024). Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS). World Journal of Emergency Surgery, 19(1), Article ID 4.
Open this publication in new window or tab >>Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)
2024 (English)In: World Journal of Emergency Surgery, E-ISSN 1749-7922, Vol. 19, no 1, article id 4Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.

METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.

RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak).

CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Management, Polytrauma, Traumatic spinal cord injury
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-111044 (URN)10.1186/s13017-023-00525-4 (DOI)001187894300001 ()38238783 (PubMedID)2-s2.0-85182635691 (Scopus ID)
Available from: 2024-01-31 Created: 2024-01-31 Last updated: 2024-09-04Bibliographically approved
Büki, A., d'Avella, D. & Germanò, A. (2024). Obituary Ronald L. Hayes. Acta Neurochirurgica, 166(1), Article ID 119.
Open this publication in new window or tab >>Obituary Ronald L. Hayes
2024 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 166, no 1, article id 119Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2024
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-112078 (URN)10.1007/s00701-024-06001-5 (DOI)001174885100002 ()38427122 (PubMedID)
Available from: 2024-03-04 Created: 2024-03-04 Last updated: 2024-03-15Bibliographically approved
Richter, S., Winzeck, S., Correia, M. M., Czeiter, E., Whitehouse, D., Kornaropoulos, E. N., . . . Newcombe, V. F. J. (2024). Predicting recovery in patients with mild traumatic brain injury and a normal CT using serum biomarkers and diffusion tensor imaging (CENTER-TBI): an observational cohort study. eClinicalMedicine, 75, Article ID 102751.
Open this publication in new window or tab >>Predicting recovery in patients with mild traumatic brain injury and a normal CT using serum biomarkers and diffusion tensor imaging (CENTER-TBI): an observational cohort study
Show others...
2024 (English)In: eClinicalMedicine, E-ISSN 2589-5370, Vol. 75, article id 102751Article in journal (Refereed) Published
Abstract [en]

Background: Even patients with normal computed tomography (CT) head imaging may experience persistent symptoms for months to years after mild traumatic brain injury (mTBI). There is currently no good way to predict recovery and triage patients who may benefit fi t from early follow-up and targeted intervention. We aimed to assess if existing prognostic models can be improved by serum biomarkers or diffusion tensor imaging metrics (DTI) from MRI, and if serum biomarkers can identify patients for DTI.

Methods: We included 1025 patients aged >18 years with a Glasgow Coma Score >12 and normal CT from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study which recruited between December 19,2014 and December 17, 2017 (NCT02210221). Biomarkers (GFAP, NFL, S100B) were obtained at a median of 8.8 h (Q1-Q3 - Q3 4.2-16.7) - 16.7) and DTI at 13 days (3-19) - 19) after injury. DTI metrics were available in 153 patients for 48 white matter tracts (ICBM-DTI-81 atlas). Incomplete recovery at three months was defined fi ned as an extended Glasgow Outcome Scale score <8. Existing prognostic models were fi tted with and without biomarkers, or with and without DTI, and internally validated using bootstrapping.

Findings: 385 (38%) patients had incomplete recovery. Adding biomarkers did not improve performance beyond the best existing clinical prognostic model [optimism-corrected AUC 0.69 (95% CI 0.65-0.72) - 0.72) and R2 2 17% (11-22)]. - 22)]. Adding DTI metrics significantly fi cantly enhanced all models [best optimism-corrected AUC 0.82 (0.79-0.85) - 0.85) and R2 2 75% (39-100)]. - 100)]. The top three prognostic tracts were the left posterior thalamic radiation, left superior cerebellar peduncle and right uncinate fasciculus. Serum biomarkers could have avoided 1 in 5 DTI scans, with GFAP <12 h and NFL 12-24 - 24 h from injury performing best.

Interpretation: DTI substantially improved existing prognostic models for functional outcome in patients with mTBI and a normal CT, and biomarkers could help select patients for MRI. If validated, DTI could allow for targeted follow- up and enrichment of clinical trials of early interventions to improve outcome.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Traumatic brain injury, Concussion, Imaging, Biomarkers, Prognostication, Outcome
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-116768 (URN)10.1016/j.eclinm.2024.102751 (DOI)001325330400001 ()39720677 (PubMedID)2-s2.0-85202063072 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme
Note

Funding: EU Seventh Framework Programme, Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, NeuroTrauma Sciences.

Available from: 2024-10-15 Created: 2024-10-15 Last updated: 2025-01-09Bibliographically approved
Trivedi, D., Forssten, M. P., Cao, Y., Mohammad Ismail, A., Czeiter, E., Amrein, K., . . . Mohseni, S. (2024). Screening Performance of S100 Calcium-Binding Protein B, Glial Fibrillary Acidic Protein, and Ubiquitin C-Terminal Hydrolase L1 for Intracranial Injury Within Six Hours of Injury and Beyond. Journal of Neurotrauma, 41(3-4), 349-358
Open this publication in new window or tab >>Screening Performance of S100 Calcium-Binding Protein B, Glial Fibrillary Acidic Protein, and Ubiquitin C-Terminal Hydrolase L1 for Intracranial Injury Within Six Hours of Injury and Beyond
Show others...
2024 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 41, no 3-4, p. 349-358Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The Scandinavian NeuroTrauma Committee (SNC) guidelines recommend S100B as a screening tool for early detection of Traumatic brain injury (TBI) in patients presenting with an initial Glasgow coma scale (GCS) of 14-15. The objective of the current study was to compare S100B's diagnostic performance within the recommended 6-hour window after injury, compared to GFAP and UCH-L1. The secondary outcome of interest was the ability of these biomarkers in detecting traumatic intracranial pathology beyond the 6-hour mark.

METHODS: The Center-TBI core database (2014-2017) was queried for data pertaining to all TBI patients with an initial GCS of 14-15 who had a blood sample taken within 6 hours of injury in which the levels of S100B, GFAP, and UCH-L1 were measured. As a subgroup analysis, data involving patients with blood samples taken within 6-9 hours, and 9-12 hours were analyzed separately for diagnostic ability. The diagnostic ability of these biomarkers for detecting any intracranial injury was evaluated based on the area under the receiver operating characteristic curve (AUC). Each biomarker's sensitivity, specificity, and accuracy were also reported at the cutoff that maximized Youden's index.

RESULTS: A total of 531 TBI patients with GCS 14-15 on admission had a blood sample taken within 6 hours, of whom 24.9% (N = 132) had radiologically confirmed intracranial injury. The AUCs of GFAP (0.86, 95% confidence interval (CI): 0.82-0.90) and UCH-L1 (0.81, 95% CI: 0.76-0.85) were statistically significantly higher than that of S100B (0.74, 95% CI: 0.69-0.79) during this time. There was no statistically significant difference in the predictive ability of S100B when sampled within 6 hours, 6-9 hours, and 9-12 hours of injury, as the p-values were >0.05 when comparing the AUCs. Overlapping AUC 95% CI suggests no benefit of a combined GFAP and UCH-L1 screening tool over GFAP during the time periods studied [ 0.87 (0.83-0.90) vs 0.86 (0.82-0.90) when sampled within 6 hours of injury, 0.83 (0.78-0.88) vs 0.83 (0.78-0.89) within 6-to-9 hours and 0.81 (0.73-0.88) vs 0.79 (0.72-0.87) within 9-12 hours].

CONCLUSIONS: Targeted analysis of the CENTER-TBI core database, with focus on the patient category for which biomarker testing is recommended by the SNC guidelines, revealed that GFAP and UCH-L1 perform superior to S100B in predicting CT-positive intracranial lesions within 6 hours of injury. GFAP continued to exhibit superior predictive ability to S100B during the time periods studied. S100B displayed relatively unaltered screening performance beyond the diagnostic timeline provided by SNC guidelines. These findings suggest the need for a re-evaluation of the current SNC TBI guidelines.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2024
Keywords
biomarkers, head trauma, screening, traumatic brain injury
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-110462 (URN)10.1089/neu.2023.0322 (DOI)001155701500005 ()38115670 (PubMedID)2-s2.0-85184280856 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, FP7/2007-2013
Note

The research leading to these results was supported by the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement no 602150 (CENTER-TBI). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from One Mind(USA), Integra Life Sciences (USA), and Neuro Trauma Sciences (US) and, Stroke for bundet, (SE).

Available from: 2023-12-21 Created: 2023-12-21 Last updated: 2024-04-02Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2190-9278

Search in DiVA

Show all publications