title: Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype.
abstract: OBJECTIVE
  The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF).
  
  
  METHODS
  PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts.
  
  
  METHODS
  Multiple PICUs in the United States.
  
  
  METHODS
  Standard care.
  
  
  RESULTS
  PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase. PERSEVERE-II had an AUC of 0.89 (0.85-0.93) and performed equally well across TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly enrolled subjects. Sample size calculations for a clinical trial testing the efficacy of plasma exchange for children with septic shock and TAMOF indicated PERSEVERE-II-based stratification could substantially reduce the number of patients necessary, when compared with no stratification.
  
  
  CONCLUSIONS
  Testing PERSEVERE in the context of septic shock phenotypes prompted a revision incorporating platelet count. PERSEVERE-II performs well upon testing, independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a prognostic enrichment tool.
authors: 1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, OH. 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH. 3UCSF Benioff Children's Hospital Oakland, Oakland, CA. 4Children's Hospital of Orange County, Orange, CA. 5Children's Mercy Hospital, Kansas City, MO. 6Penn State Hershey Children's Hospital, Hershey, PA. 7Akron Children's Hospital, Akron, OH. 8The Children's Hospital of Philadelphia, Philadelphia, PA. 9Texas Children's Hospital and Baylor College of Medicine, Houston, TX. 10Miami Children's Hospital, Miami, FL. 11CS Mott Children's Hospital at the University of Michigan, Ann Arbor, MI. 12Nationwide Children's Hospital, Columbus, OH. 13Children's Hospital of Wisconsin, Milwaukee, WI. 14Children's National Medical Center, Washington, DC. 15Children's Hospital and Clinics of Minnesota, Minneapolis, MN. 16Riley Hospital for Children, Indianapolis, IN. 17Hackensack University Medical Center, Joseph M. Sanzari Children's Hospital, Hackensack, NJ. 18Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
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mesh_terms: D015415:Biomarkers / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D053804:Granzymes / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D015233:Models, Statistical; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality; D010976:Platelet Count; D011379:Prognosis; D018570:Risk Assessment; D012772:Shock, Septic / Q000097:blood* / Q000401:mortality; D013921:Thrombocytopenia / Q000150:complications; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D054405:Chemokine CCL3; D018840:HSP70 Heat-Shock Proteins; D016209:Interleukin-8; D053804:Granzymes; D020784:Matrix Metalloproteinase 8