title: Circulating nucleosomes and severity of illness in children suffering from meningococcal sepsis treated with protein C.
abstract: OBJECTIVE
  Cell death leading to circulating nucleosomes and histones is a critical step in the pathogenesis of sepsis and contributes to lethality. Activated protein C was demonstrated to attenuate the harmful effects of histones. The objective of this retrospective study was to evaluate whether nucleosomes correlate with the severity of the inflammatory response and mortality in children suffering from severe meningococcal sepsis. Furthermore, we wanted to study the effects of infusion of protein C on nucleosome levels in children with septic purpura.
  
  
  METHODS
  Retrospective analysis of nucleosome levels in children suffering from meningococcal sepsis treated with either placebo or protein C.
  
  
  METHODS
  Pediatric intensive care unit of a tertiary care university center.
  
  
  METHODS
  In a randomized, placebo-controlled study, either protein C or placebo was administered to 38 children suffering from meningococcal sepsis. Nucleosome levels have been measured retrospectively in these 38 children suffering from meningococcal sepsis.
  
  
  RESULTS
  Twenty-eight children were treated with protein C and 10 received placebo. Nucleosome levels were significantly higher in nonsurvivors (n = 9) at any time point measured as compared to survivors (n = 29). Nucleosome levels significantly correlated with organ dysfunction scores, cytokines, and parameters for coagulation. Patients treated with protein C had significantly higher activated protein C levels than children receiving placebo. We could not find a clear effect of activated protein C on nucleosome levels in these patients.
  
  
  CONCLUSIONS
  Circulating nucleosomes correlated with the severity of the inflammatory response and were associated with mortality in children suffering from meningococcal sepsis. We show that protein C administration does not decrease nucleosome levels in these patients.
authors.affiliation: Department of Immunopathology, Sanquin Research at CLB and Landsteiner Laboratory of the AMC, Amsterdam, The Netherlands. s.zeerleder@sanquin.nl
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.forename: Femke
authors.initials: F
authors.lastname: Stephan
authors.forename: Marieke
authors.initials: M
authors.lastname: Emonts
authors.forename: Ester D
authors.initials: ED
authors.lastname: de Kleijn
authors.forename: Charles T
authors.initials: CT
authors.lastname: Esmon
authors.forename: Katalin
authors.initials: K
authors.lastname: Varadi
authors.forename: Cornelis Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hazelzet
mesh_terms: D000293:Adolescent; D016470:Bacteremia / Q000188:drug therapy / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008589:Meningococcal Infections / Q000188:drug therapy* / Q000378:metabolism; D009426:Netherlands; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism*; D011486:Protein C / Q000627:therapeutic use*; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D005343:Fibrinolytic Agents; D009707:Nucleosomes; D011486:Protein C