PMID- 37460257
OWN - NLM
STAT- MEDLINE
DCOM- 20230719
LR  - 20230722
IS  - 2044-6055 (Electronic)
IS  - 2044-6055 (Linking)
VI  - 13
IP  - 7
DP  - 2023 Jul 17
TI  - Study protocol for investigating the clinical performance of an automated blood 
      test for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase 
      L1 blood concentrations in elderly patients with mild traumatic BRAIN Injury and 
      reference values (BRAINI-2 Elderly European study): a prospective multicentre 
      observational study.
PG  - e071467
LID - 10.1136/bmjopen-2022-071467 [doi]
LID - e071467
AB  - INTRODUCTION: Two blood brain-derived biomarkers, glial fibrillar acidic protein 
      (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out 
      intracranial lesions in patients with mild traumatic brain injury (mTBI) when 
      assessed within the first 12 hours. Most elderly patients were excluded from 
      previous studies due to comorbidities. Biomarker use in elderly population could 
      be affected by increased basal levels. This study will assess the performance of 
      an automated test for measuring serum GFAP and UCH-L1 in elderly patients to 
      predict the absence of intracranial lesions on head CT scans after mTBI, and 
      determine both biomarkers reference values in a non-TBI elderly population. 
      METHODS AND ANALYSIS: This is a prospective multicentre observational study on 
      elderly patients (>/=65 years) that will be performed in Spain, France and Germany. 
      Two patient groups will be included in two independent substudies. (1) A cohort 
      of 2370 elderly patients (1185<80 years and 1185>/=80 years; BRAINI2-ELDERLY 
      DIAGNOSTIC AND PROGNOSTIC STUDY) with mTBI and a brain CT scan that will undergo 
      blood sampling within 12 hours after mTBI. The primary outcome measure is the 
      diagnostic performance of GFAP and UCH-L1 measured using an automated assay for 
      discriminating between patients with positive and negative findings on brain CT 
      scans. Secondary outcome measures include the performance of both biomarkers in 
      predicting early (1 week) and midterm (3 months) neurological status and quality 
      of life after trauma. (2) A cohort of 480 elderly reference participants 
      (BRAINI2-ELDERLY REFERENCE STUDY) in whom reference values for GFAP and UCHL1 
      will be determined. ETHICS AND DISSEMINATION: Ethical approval was obtained from 
      the Institutional Review Boards of Hospital 12 de Octubre in Spain (Re#22/027) 
      and Southeast VI (Clermont Ferrand Hospital) (Re# 22.01782.000095) in France. The 
      study's results will be presented at scientific meetings and published in 
      peer-review publications. TRIAL REGISTRATION NUMBER: NCT05425251.
CI  - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Lagares, Alfonso
AU  - Lagares A
AD  - Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain 
      alfonlag@ucm.es.
AD  - Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Cirugia, 
      Madrid, Spain.
AD  - Instituto de Investigacion Sanitaria imas12, Hospital Universitario 12 de 
      Octubre, Madrid, Spain.
FAU - Payen, Jean-Francois
AU  - Payen JF
AD  - Department of Anaesthesia and Intensive Care, Univ. Grenoble Alpes, Centre 
      Hospitalier Universitaire de Grenoble, Grenoble Alpes, France.
AD  - Grenoble Institut des Neurosciences, INSERM, U1216, Grenoble, France.
FAU - Biberthaler, Peter
AU  - Biberthaler P
AD  - Department of Trauma Surgery, School of Medicine, Klinikum Rechts der Isar, 
      Technical University of Munich, Munich, Germany.
FAU - Poca, M Antonia
AU  - Poca MA
AD  - Department of Neurosurgery, Vall d'Hebron Hospital Universitari; Neurotrauma and 
      Neurosurgery Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall 
      d'Hebron Barcelona Hospital Campus, Department of Surgery, Universitat Autonoma 
      de Barcelona, Barcelona, Spain.
FAU - Mejan, Odile
AU  - Mejan O
AD  - bioMerieux, Clinical Unit, Chemin de l'Orme, Marcy l'Etoile, France.
FAU - Pavlov, Vladislav
AU  - Pavlov V
AD  - bioMerieux, Medical Affairs, Chemin de l'Orme, Marcy l'Etoile, France.
FAU - Viglino, Damien
AU  - Viglino D
AD  - Emergency Department, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, 
      France.
AD  - HP2 Laboratory INSERM U1800, Grenoble, France.
FAU - Sapin, Vincent
AU  - Sapin V
AD  - Department of Biochemistry and Molecular Genetics, University Hospital, 
      Clermont-Ferrand, Clermont Auvergne University, CNRS, INSERM, iGReD, 
      Clermont-Ferrand, France.
FAU - Lassaletta, Aurora
AU  - Lassaletta A
AD  - Asociacion Dano Cerebral Invisible, Madrid, Spain.
FAU - de la Cruz, Javier
AU  - de la Cruz J
AD  - Instituto de Investigacion imas12, Hospital Universitario 12 de Octubre, SAMID, 
      Madrid, Spain.
CN  - Braini2_elderly_investigators Collaborative group
LA  - eng
SI  - ClinicalTrials.gov/NCT05425251
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230717
PL  - England
TA  - BMJ Open
JT  - BMJ open
JID - 101552874
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - Aged
MH  - *Brain Concussion/diagnosis
MH  - Prospective Studies
MH  - Glial Fibrillary Acidic Protein
MH  - Ubiquitin Thiolesterase
MH  - Quality of Life
MH  - Reference Values
MH  - Biomarkers
MH  - Hematologic Tests
MH  - *Brain Injuries, Traumatic/diagnostic imaging
MH  - Observational Studies as Topic
MH  - Multicenter Studies as Topic
PMC - PMC10357305
OTO - NOTNLM
OT  - ACCIDENT & EMERGENCY MEDICINE
OT  - Computed tomography
OT  - Neurosurgery
OT  - Trauma management
COIS- Competing interests: OM and VP are employees of bioMerieux.
FIR - Castano-Leon, Ana Maria
IR  - Castano-Leon AM
FIR - Baciu, Andreea
IR  - Baciu A
FIR - Maldonado, Monica
IR  - Maldonado M
FIR - Posadas, Guillermo Garcia
IR  - Posadas GG
FIR - Esteban, Olga
IR  - Esteban O
FIR - Moreno, Luis Miguel
IR  - Moreno LM
FIR - Salvador, Elena
IR  - Salvador E
FIR - Cuesta, Maite
IR  - Cuesta M
FIR - Garcia, Tamara
IR  - Garcia T
FIR - Trillo, Elena Sanchez
IR  - Trillo ES
FIR - Morales, Julian
IR  - Morales J
FIR - Gamiz, Mercedes Garcia
IR  - Gamiz MG
FIR - Anchustegui, Alejandro Yanez
IR  - Anchustegui AY
FIR - Sanchez, Jorge Sanchez-Tembleque
IR  - Sanchez JS
FIR - Martinez Barquero Santelices, Joliette Maybe
IR  - Martinez Barquero Santelices JM
FIR - Alen, Jose A Fernandez
IR  - Alen JAF
FIR - Garcia de Andoain, Guillermo Blasco
IR  - Garcia de Andoain GB
FIR - Luordo, Davide
IR  - Luordo D
FIR - Garcia Sanchez, Francisco
IR  - Garcia Sanchez F
FIR - Diez, Sergio Gamez
IR  - Diez SG
FIR - Barcenilla, Gonzalo Latorre
IR  - Barcenilla GL
FIR - Blanco Cabello, Juan Antonio
IR  - Blanco Cabello JA
FIR - Pacios, Maria Elena
IR  - Pacios ME
FIR - Rosas, Katiusca
IR  - Rosas K
FIR - Calvo, Helena
IR  - Calvo H
FIR - Lopez-Bermeo, Diego
IR  - Lopez-Bermeo D
FIR - Cabrera, Andres
IR  - Cabrera A
FIR - Figueroa, Margarita
IR  - Figueroa M
FIR - Sanchez-Raya, Judith
IR  - Sanchez-Raya J
FIR - Leon, Ana
IR  - Leon A
FIR - Petriman, Eladi-Madalina
IR  - Petriman EM
FIR - Sahuquillo, Juan
IR  - Sahuquillo J
FIR - Montoya, Noelia
IR  - Montoya N
FIR - Peris, Marta
IR  - Peris M
FIR - Duch, Paula
IR  - Duch P
FIR - Sanchez-Mancheno, Angel
IR  - Sanchez-Mancheno A
FIR - Sahuquillo, Aasma
IR  - Sahuquillo A
FIR - Barcena, Juan Perez
IR  - Barcena JP
FIR - Pascual, Maria Clara
IR  - Pascual MC
FIR - Jacquin, Laurent
IR  - Jacquin L
FIR - Douplat, Marion
IR  - Douplat M
FIR - Bouillon, Jean Baptiste
IR  - Bouillon JB
EDAT- 2023/07/18 01:09
MHDA- 2023/07/19 06:43
PMCR- 2023/07/17
CRDT- 2023/07/17 21:42
PHST- 2023/07/19 06:43 [medline]
PHST- 2023/07/18 01:09 [pubmed]
PHST- 2023/07/17 21:42 [entrez]
PHST- 2023/07/17 00:00 [pmc-release]
AID - bmjopen-2022-071467 [pii]
AID - 10.1136/bmjopen-2022-071467 [doi]
PST - epublish
SO  - BMJ Open. 2023 Jul 17;13(7):e071467. doi: 10.1136/bmjopen-2022-071467.