title: TIMP1 and MMP9 are predictors of mortality in septic patients in the emergency department and intensive care unit unlike MMP9/TIMP1 ratio: Multivariate model.
abstract: BACKGROUND
  Matrix metalloproteinases and tissue inhibitors of metalloproteinases could be promising biomarkers for establishing prognosis during the development of sepsis. It is necessary to clarify the relationship between matrix metalloproteinases and their tissue inhibitors. We conducted a cohort study with 563 septic patients, in order to elucidate the biological role and significance of these inflammatory biomarkers and their relationship to the severity and mortality of patients with sepsis.
  
  
  METHODS
  A multicentric prospective cohort was performed. The sample was composed of patients who had sepsis as defined by the International Conference 2001. Serum procalcitonin, creatinine, urea nitrogen, C-Reactive protein, TIMP1, TIMP2, MMP2 and MMP9 were quantified; each patient was followed until death or up to 30 days. A descriptive analysis was performed by calculating the mean and the 95% confidence interval for continuous variables and proportions for categorical variables. A multivariate logistic regression model was constructed by the method of intentional selection of covariates with mortality at 30 days as dependent variable and all the other variables as predictors.
  
  
  RESULTS
  Of the 563 patients, 68 patients (12.1%) died within the first 30 days of hospitalization in the ICU. The mean values for TIMP1, TIMP2 and MMP2 were lower in survivors, MMP9 was higher in survivors. Multivariate logistic regression showed that age, SOFA and Charlson scores, along with TIMP1 concentration, were statistically associated with mortality at 30 days of septic patients; serum MMP9 was not statistically associated with mortality of patients, but was a confounder of the TIMP1 variable.
  
  
  CONCLUSIONS
  It could be argued that plasma levels of TIMP1 should be considered as a promising prognostic biomarker in the setting of sepsis. Additionally, this study, like other studies with large numbers of septic patients does not support the predictive value of TIMP1 / MMP9.
authors.affiliation: Department of Public Health, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Niño
authors.affiliation: Department of Public Health, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Sergio Eduardo
authors.initials: SE
authors.lastname: Serrano
authors.affiliation: Department of Pharmacology, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Daniela Camila
authors.initials: DC
authors.lastname: Niño
authors.affiliation: Department of Pharmacology, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Diana Margarita
authors.initials: DM
authors.lastname: McCosham
authors.affiliation: Microbiology and Inmunology Department, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Cardenas
authors.affiliation: Department of Pharmacology, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Vivian Poleth
authors.initials: VP
authors.lastname: Villareal
authors.affiliation: Biotechnology Department, Enterprise Technology Center, Fundación Cardiovascular de Colombia, Bucaramanga, Santander, Colombia.
authors.forename: Marcos
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Department of Medical Clinics, Emergency unit, Faculty of Medicine, Universidade de Sao Paulo, Ribeirao preto, Sao Paulo, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazin-Filho
authors.affiliation: Department of Internal Medicine, School Of Medicine, Universidad de Antioquia, Medellin, Antioquia, Colombia.
authors.forename: Fabian Alberto
authors.initials: FA
authors.lastname: Jaimes
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universidade de Sao Paulo, Ribeirao preto, Sao Paulo, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cunha
authors.affiliation: Departments of Pediatrics and Pharmacology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Department of Pharmacology, Medicine Program, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Santander, Colombia.
authors.forename: Diego
authors.identifier: http://orcid.org/0000-0002-8006-7461
authors.initials: D
authors.lastname: Torres-Dueñas
mesh_terms: D000368:Aged; D001806:Blood Urea Nitrogen; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D003404:Creatinine / Q000097:blood; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D002116:Calcitonin; D002097:C-Reactive Protein; D003404:Creatinine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9