title: HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis.
abstract: OBJECTIVE
  To study the predictive value of high mobility group box-1 protein (HMGB1) and hospital mortality in adult patients with severe sepsis.
  
  
  METHODS
  Prospective observational cohort study in 24 ICUs in Finland.
  
  
  METHODS
  Two hundred and forty-seven adult patients with severe sepsis.
  
  
  RESULTS
  Blood samples for HMGB1 analyses were drawn from 247 patients at baseline and from 210 patients 72 h later. The mean APACHE II and SAPS II scores were 24 (SD 9) and 44 (SD 17), respectively. The hospital mortality was 26%. The serum HMGB1 concentrations were measured first by semi-quantitative Western immunoblotting (WB) analysis. The median HMGB1 concentration on day 0 was 108% (IQR 98.5-119) and after 72 h 107% (IQR 98.8-120), which differed from healthy controls (97.5%, IQR 91.3-106.5; p=0.028 and 0.019, respectively). The samples were re-analysed by ELISA (in a subgroup of 170 patients) to confirm the results by WB. The median concentration in healthy controls was 0.65 ng/ml (IQR 0.51-1.0). This was lower than in patients with severe sepsis (3.6 ng/ml, IQR 1.9-6.5, p< 0.001). HMGB1 concentrations (WB and ELISA) did not differ between hospital survivors and non-survivors. In ROC analyses for HMGB1 levels (WB) on day 0 and 72 h with respect to hospital mortality, the areas under the curve were 0.51 and 0.56 (95% CI 0.40-0.61 and 0.47-0.65).
  
  
  CONCLUSIONS
  Serum HMGB1 concentrations were elevated in patients with severe sepsis, but did not differ between survivors and non-survivors and did not predict hospital mortality.
authors.affiliation: Department of Intensive Care Medicine, Tampere University Hospital, Teiskontie 35, Tampere, Finland. sari.karlsson@pshp.fi
authors.forename: Sari
authors.initials: S
authors.lastname: Karlsson
authors.forename: Ville
authors.initials: V
authors.lastname: Pettilä
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
authors.forename: Raili
authors.initials: R
authors.lastname: Laru-Sompa
authors.forename: Marja
authors.initials: M
authors.lastname: Hynninen
authors.forename: Esko
authors.initials: E
authors.lastname: Ruokonen
mesh_terms: D018806:APACHE; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D015153:Blotting, Western; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005387:Finland / Q000453:epidemiology; D024243:HMGB1 Protein / Q000097:blood*; D017052:Hospital Mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D018805:Sepsis / Q000097:blood* / Q000150:complications* / Q000401:mortality / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein