title: Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study.
abstract: BACKGROUND
  The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED).
  
  
  METHODS
  In total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients.
  
  
  RESULTS
  The median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days' follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group.
  
  
  CONCLUSIONS
  NGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.
authors.affiliation: Emergency Department, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Beijing, Chao-yang District, 100020, China. wmm0327@126.com.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Emergency Department, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Beijing, Chao-yang District, 100020, China. zqian604@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Emergency Department, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Beijing, Chao-yang District, 100020, China. zhaoxin4190@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Emergency Department, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Beijing, Chao-yang District, 100020, China. donggj1981@sina.com.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Dong
authors.affiliation: Emergency Department, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Beijing, Chao-yang District, 100020, China. lcscyyy@163.com.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004636:Emergency Service, Hospital / Q000592:standards; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9