Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
Abstract Background Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identification of those at risk of death and persistent organ dysfunctions is necessary to enrich patients for future trials of sepsis therapeutics. Here, we sough...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Critical Care |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13054-022-04070-5 |
| _version_ | 1818510796862259200 |
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| author | Mihir R. Atreya Natalie Z. Cvijanovich Julie C. Fitzgerald Scott L. Weiss Michael T. Bigham Parag N. Jain Adam J. Schwarz Riad Lutfi Jeffrey Nowak Geoffrey L. Allen Neal J. Thomas Jocelyn R. Grunwell Torrey Baines Michael Quasney Bereketeab Haileselassie Christopher J. Lindsell Matthew N. Alder Hector R. Wong |
| author_facet | Mihir R. Atreya Natalie Z. Cvijanovich Julie C. Fitzgerald Scott L. Weiss Michael T. Bigham Parag N. Jain Adam J. Schwarz Riad Lutfi Jeffrey Nowak Geoffrey L. Allen Neal J. Thomas Jocelyn R. Grunwell Torrey Baines Michael Quasney Bereketeab Haileselassie Christopher J. Lindsell Matthew N. Alder Hector R. Wong |
| author_sort | Mihir R. Atreya |
| collection | DOAJ |
| description | Abstract Background Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identification of those at risk of death and persistent organ dysfunctions is necessary to enrich patients for future trials of sepsis therapeutics. Here, we sought to integrate endothelial and PERSEVERE biomarkers to estimate the composite risk of death or organ dysfunctions on day 7 of septic shock. Methods We measured endothelial dysfunction markers from day 1 serum among those with existing PERSEVERE data. TreeNet® classification model was derived incorporating 22 clinical and biological variables to estimate risk. Based on relative variable importance, a simplified 6-biomarker model was developed thereafter. Results Among 502 patients, 49 patients died before day 7 and 124 patients had persistence of MODS on day 7 of septic shock. Area under the receiver operator characteristic curve (AUROC) for the newly derived PERSEVEREnce model to predict death or day 7 MODS was 0.93 (0.91–0.95) with a summary AUROC of 0.80 (0.76–0.84) upon tenfold cross-validation. The simplified model, based on IL-8, HSP70, ICAM-1, Angpt2/Tie2, Angpt2/Angpt1, and Thrombomodulin, performed similarly. Interaction between variables—ICAM-1 with IL-8 and Thrombomodulin with Angpt2/Angpt1—contributed to the models’ predictive capabilities. Model performance varied when estimating risk of individual organ dysfunctions with AUROCS ranging from 0.91 to 0.97 and 0.68 to 0.89 in training and test sets, respectively. Conclusions The newly derived PERSEVEREnce biomarker model reliably estimates risk of death or persistent organ dysfunctions on day 7 of septic shock. If validated, this tool can be used for prognostic enrichment in future pediatric trials of sepsis therapeutics. Graphical abstract |
| first_indexed | 2024-12-10T23:24:57Z |
| format | Article |
| id | doaj.art-3458c844990943b98a33a6e14c2f4a95 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-12-10T23:24:57Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-3458c844990943b98a33a6e14c2f4a952022-12-22T01:29:37ZengBMCCritical Care1364-85352022-07-012611910.1186/s13054-022-04070-5Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational studyMihir R. Atreya0Natalie Z. Cvijanovich1Julie C. Fitzgerald2Scott L. Weiss3Michael T. Bigham4Parag N. Jain5Adam J. Schwarz6Riad Lutfi7Jeffrey Nowak8Geoffrey L. Allen9Neal J. Thomas10Jocelyn R. Grunwell11Torrey Baines12Michael Quasney13Bereketeab Haileselassie14Christopher J. Lindsell15Matthew N. Alder16Hector R. Wong17Division of Critical Care Medicine, MLC2005, Cincinnati Children’s Hospital Medical Center, Cincinnati Children’s Research FoundationUCSF Benioff Children’s Hospital OaklandChildren’s Hospital of PhiladelphiaChildren’s Hospital of PhiladelphiaAkron Children’s HospitalTexas Children’s Hospital and Baylor College of MedicineChildren’s Hospital of Orange CountyRiley Hospital for ChildrenChildren’s Hospital and Clinics of MinnesotaChildren’s Mercy HospitalPenn State Hershey Children’s HospitalChildren’s Healthcare of Atlanta at EglestonUniversity of Florida Health Shands Children’s HospitalCS Mott Children’s Hospital at the University of MichiganLucile Packard Children’s Hospital StanfordDepartment of Biostatistics, Vanderbilt University Medical CenterDivision of Critical Care Medicine, MLC2005, Cincinnati Children’s Hospital Medical Center, Cincinnati Children’s Research FoundationDivision of Critical Care Medicine, MLC2005, Cincinnati Children’s Hospital Medical Center, Cincinnati Children’s Research FoundationAbstract Background Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identification of those at risk of death and persistent organ dysfunctions is necessary to enrich patients for future trials of sepsis therapeutics. Here, we sought to integrate endothelial and PERSEVERE biomarkers to estimate the composite risk of death or organ dysfunctions on day 7 of septic shock. Methods We measured endothelial dysfunction markers from day 1 serum among those with existing PERSEVERE data. TreeNet® classification model was derived incorporating 22 clinical and biological variables to estimate risk. Based on relative variable importance, a simplified 6-biomarker model was developed thereafter. Results Among 502 patients, 49 patients died before day 7 and 124 patients had persistence of MODS on day 7 of septic shock. Area under the receiver operator characteristic curve (AUROC) for the newly derived PERSEVEREnce model to predict death or day 7 MODS was 0.93 (0.91–0.95) with a summary AUROC of 0.80 (0.76–0.84) upon tenfold cross-validation. The simplified model, based on IL-8, HSP70, ICAM-1, Angpt2/Tie2, Angpt2/Angpt1, and Thrombomodulin, performed similarly. Interaction between variables—ICAM-1 with IL-8 and Thrombomodulin with Angpt2/Angpt1—contributed to the models’ predictive capabilities. Model performance varied when estimating risk of individual organ dysfunctions with AUROCS ranging from 0.91 to 0.97 and 0.68 to 0.89 in training and test sets, respectively. Conclusions The newly derived PERSEVEREnce biomarker model reliably estimates risk of death or persistent organ dysfunctions on day 7 of septic shock. If validated, this tool can be used for prognostic enrichment in future pediatric trials of sepsis therapeutics. Graphical abstracthttps://doi.org/10.1186/s13054-022-04070-5SepsisSeptic shockMultiple organ dysfunction syndromeEndothelial dysfunctionPrecision medicineBiomarkers |
| spellingShingle | Mihir R. Atreya Natalie Z. Cvijanovich Julie C. Fitzgerald Scott L. Weiss Michael T. Bigham Parag N. Jain Adam J. Schwarz Riad Lutfi Jeffrey Nowak Geoffrey L. Allen Neal J. Thomas Jocelyn R. Grunwell Torrey Baines Michael Quasney Bereketeab Haileselassie Christopher J. Lindsell Matthew N. Alder Hector R. Wong Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study Critical Care Sepsis Septic shock Multiple organ dysfunction syndrome Endothelial dysfunction Precision medicine Biomarkers |
| title | Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study |
| title_full | Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study |
| title_fullStr | Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study |
| title_full_unstemmed | Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study |
| title_short | Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study |
| title_sort | integrated persevere and endothelial biomarker risk model predicts death and persistent mods in pediatric septic shock a secondary analysis of a prospective observational study |
| topic | Sepsis Septic shock Multiple organ dysfunction syndrome Endothelial dysfunction Precision medicine Biomarkers |
| url | https://doi.org/10.1186/s13054-022-04070-5 |
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