OBJECTIVE: Stratification with an effective outcome biomarker could improve the design of interventional trials in pediatric septic shock. The objective of this study was to test the usefulness of chemokine (C-C motif) ligand 4 as an outcome biomarker for mortality in pediatric septic shock. DESIGN: A cross-sectional, observational study. SETTING: Eighteen pediatric intensive care units in the United States. PATIENTS: One hundred fifty-six pediatric patients with septic shock. INTERVENTIONS: Serum samples were obtained within 24 hrs of admission to the pediatric intensive care unit. Serum levels of chemokine (C-C motif) ligand 4 were measured by enzyme-linked immunosorbent assay and compared with mortality in a training set of 34 patients. These data were used to generate a cutoff value whose usefulness was evaluated through prospective application-without post hoc modification-to a larger validation set of 122 patients. MEASUREMENTS AND MAIN RESULTS: On inspection of the training set data, a cutoff value of 140 pg/mL was chosen. When applied to the validation set, serum chemokine (C-C motif) ligand 4 levels >140 pg/mL yielded a sensitivity of 92% and a specificity of 40% for mortality. A serum level of < or =140 pg/mL had a negative predictive value for mortality of 98%. CONCLUSIONS: A serum level of chemokine (C-C motif) ligand 4 of < or =140 pg/mL, when obtained within 24 hrs of admission, predicts a very high likelihood of survival in pediatric septic shock. Exclusion of patients with a chemokine (C-C motif) ligand 4 level of < or =140 pg/mL from interventional clinical trials in pediatric septic shock could create a study population in which survival benefit from the study agent could be more readily demonstrated.
OBJECTIVE: Stratification with an effective outcome biomarker could improve the design of interventional trials in pediatric septic shock. The objective of this study was to test the usefulness of chemokine (C-C motif) ligand 4 as an outcome biomarker for mortality in pediatric septic shock. DESIGN: A cross-sectional, observational study. SETTING: Eighteen pediatric intensive care units in the United States. PATIENTS: One hundred fifty-six pediatric patients with septic shock. INTERVENTIONS: Serum samples were obtained within 24 hrs of admission to the pediatric intensive care unit. Serum levels of chemokine (C-C motif) ligand 4 were measured by enzyme-linked immunosorbent assay and compared with mortality in a training set of 34 patients. These data were used to generate a cutoff value whose usefulness was evaluated through prospective application-without post hoc modification-to a larger validation set of 122 patients. MEASUREMENTS AND MAIN RESULTS: On inspection of the training set data, a cutoff value of 140 pg/mL was chosen. When applied to the validation set, serum chemokine (C-C motif) ligand 4 levels >140 pg/mL yielded a sensitivity of 92% and a specificity of 40% for mortality. A serum level of < or =140 pg/mL had a negative predictive value for mortality of 98%. CONCLUSIONS: A serum level of chemokine (C-C motif) ligand 4 of < or =140 pg/mL, when obtained within 24 hrs of admission, predicts a very high likelihood of survival in pediatric septic shock. Exclusion of patients with a chemokine (C-C motif) ligand 4 level of < or =140 pg/mL from interventional clinical trials in pediatric septic shock could create a study population in which survival benefit from the study agent could be more readily demonstrated.
Authors: Hector R Wong; Thomas P Shanley; Bhuvaneswari Sakthivel; Natalie Cvijanovich; Richard Lin; Geoffrey L Allen; Neal J Thomas; Allan Doctor; Meena Kalyanaraman; Nancy M Tofil; Scott Penfil; Marie Monaco; Mary Ann Tagavilla; Kelli Odoms; Katherine Dunsmore; Michael Barnes; Bruce J Aronow Journal: Physiol Genomics Date: 2007-03-20 Impact factor: 3.107
Authors: Hector R Wong; Natalie Cvijanovich; Derek S Wheeler; Michael T Bigham; Marie Monaco; Kelli Odoms; William L Macias; Mark D Williams Journal: Am J Respir Crit Care Med Date: 2008-05-29 Impact factor: 21.405
Authors: Thomas P Shanley; Natalie Cvijanovich; Richard Lin; Geoffrey L Allen; Neal J Thomas; Allan Doctor; Meena Kalyanaraman; Nancy M Tofil; Scott Penfil; Marie Monaco; Kelli Odoms; Michael Barnes; Bhuvaneswari Sakthivel; Bruce J Aronow; Hector R Wong Journal: Mol Med Date: 2007 Sep-Oct Impact factor: 6.354
Authors: Hector R Wong; Natalie Z Cvijanovich; Mark Hall; Geoffrey L Allen; Neal J Thomas; Robert J Freishtat; Nick Anas; Keith Meyer; Paul A Checchia; Richard Lin; Michael T Bigham; Anita Sen; Jeffrey Nowak; Michael Quasney; Jared W Henricksen; Arun Chopra; Sharon Banschbach; Eileen Beckman; Kelli Harmon; Patrick Lahni; Thomas P Shanley Journal: Crit Care Date: 2012-10-29 Impact factor: 9.097