title: Association between serum tissue inhibitor of matrix metalloproteinase-1 levels and mortality in patients with severe brain trauma injury.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality. Thus, the aim of this study was to determine whether serum TIMP-1 and MMP-9 levels are associated with mortality in patients with severe TBI.
  
  
  METHODS
  This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of TIMP-1, MMP-9 and tumor necrosis factor (TNF)-alpha, and plasma levels of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 plasma were measured in 100 patients with severe TBI at admission. Endpoint was 30-day mortality.
  
  
  RESULTS
  Non-surviving TBI patients (n = 27) showed higher serum TIMP-1 levels than survivor ones (n = 73). We did not find differences in MMP-9 serum levels. Logistic regression analysis showed that serum TIMP-1 levels were associated 30-day mortality (OR = 1.01; 95% CI = 1.001-1.013; P = 0.03). Survival analysis showed that patients with serum TIMP-1 higher than 220 ng/mL presented increased 30-day mortality than patients with lower levels (Chi-square = 5.50; P = 0.02). The area under the curve (AUC) for TIMP-1 as predictor of 30-day mortality was 0.73 (95% CI = 0.624-0.844; P<0.001). An association between TIMP-1 levels and APACHE-II score, TNF- alpha and TF was found.
  
  
  CONCLUSIONS
  The most relevant and new findings of our study, the largest series reporting data on TIMP-1 and MMP-9 levels in patients with severe TBI, were that serum TIMP-1 levels were associated with TBI mortality and could be used as a prognostic biomarker of mortality in TBI patients.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.affiliation: Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.affiliation: Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Intensive Care Unit, Hospital General La Palma, La Palma, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Ramos
authors.affiliation: Intensive Care Unit, Hospital Clínico Universitario de Valencia, Fundación INCLIVA, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Blanquer
authors.affiliation: Intensive Care Unit, Hospital Insular, Las Palmas de Gran Canaria, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Cáceres
authors.affiliation: Intensive Care Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.affiliation: Deparment of Anesthesiology and Reanimation, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Solera
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Cabrera
authors.affiliation: Intensive Care Unit, Hospital Clínico Universitario de Valencia, Fundación INCLIVA, Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Argueso
authors.affiliation: Intensive Care Unit, Hospital General La Palma, La Palma, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ortiz
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Mora
authors.affiliation: Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Lubillo
authors.affiliation: Research Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
authors.affiliation: Laboratory Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Borreguero-León
authors.affiliation: Laboratory Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: González
authors.affiliation: Atherosclerosis Research Laboratory, CIMA-University of Navarra, Pamplona, Spain.
authors.forename: Josune
authors.initials: J
authors.lastname: Orbe
authors.affiliation: Atherosclerosis Research Laboratory, CIMA-University of Navarra, Pamplona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez
authors.affiliation: Atherosclerosis Research Laboratory, CIMA-University of Navarra, Pamplona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Páramo
mesh_terms: D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000097:blood* / Q000201:enzymology / Q000401:mortality*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D017741:Survivors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1
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