title: Circadian Variation of Plasminogen-Activator-Inhibitor-1 Levels in Children with Meningococcal Sepsis.
abstract: OBJECTIVE
  To study whether the circadian variation of plasminogen-activator-inhibitor-1 (PAI-1) levels, with high morning levels, is associated with poor outcome of children with meningococcal sepsis presenting in the morning hours.
  
  
  METHODS
  Retrospective analysis of prospectively collected clinical and laboratory data.
  
  
  METHODS
  Single center study at Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
  
  
  METHODS
  184 patients aged 3 weeks to 18 years with meningococcal sepsis. In 36 of these children, PAI-1 levels at admission to the PICU were measured in plasma by ELISA.
  
  
  METHODS
  None.
  
  
  RESULTS
  Circadian variation was studied by dividing one day in blocks of 6 hours. Patients admitted between 6:00 am and 12:00 am had increased illness severity scores and higher PAI-1 levels (n = 9, median 6912 ng/mL, IQR 5808-15600) compared to patients admitted at night (P = 0.019, n = 9, median 3546 ng/mL, IQR 1668-6118) or in the afternoon (P = 0.007, n = 7, median 4224 ng/mL, IQR 1804-5790). In 184 patients, analysis of circadian variation in relation to outcome showed more deaths, amputations and need for skin grafts in patients admitted to the PICU between 6:00 am and 12:00 am than patients admitted during the rest of the day (P = 0.009).
  
  
  CONCLUSIONS
  Circadian variation of PAI-1 levels is present in children with meningococcal sepsis and is associated with illness severity, with a peak level in the morning. Whether circadian variation is an independent risk factor for morbidity and mortality in meningococcal sepsis needs to be explored in future studies.
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.|Department of Pediatrics, Division of Pediatric Infectious Diseases & Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Navin P
authors.initials: NP
authors.lastname: Boeddha
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases & Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Gertjan J
authors.initials: GJ
authors.lastname: Driessen
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Marjon H
authors.initials: MH
authors.lastname: Cnossen
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hazelzet
authors.affiliation: Paediatric Infectious Diseases and Immunology Department, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.|Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Marieke
authors.initials: M
authors.lastname: Emonts
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008585:Meningitis, Meningococcal / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D009345:Neisseria meningitidis / Q000302:isolation & purification; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human