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Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study
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 int...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275255/ https://www.ncbi.nlm.nih.gov/pubmed/35818064 http://dx.doi.org/10.1186/s13054-022-04070-5 |
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author | Atreya, Mihir R. Cvijanovich, Natalie Z. Fitzgerald, Julie C. Weiss, Scott L. Bigham, Michael T. Jain, Parag N. Schwarz, Adam J. Lutfi, Riad Nowak, Jeffrey Allen, Geoffrey L. Thomas, Neal J. Grunwell, Jocelyn R. Baines, Torrey Quasney, Michael Haileselassie, Bereketeab Lindsell, Christopher J. Alder, Matthew N. Wong, Hector R. |
author_facet | Atreya, Mihir R. Cvijanovich, Natalie Z. Fitzgerald, Julie C. Weiss, Scott L. Bigham, Michael T. Jain, Parag N. Schwarz, Adam J. Lutfi, Riad Nowak, Jeffrey Allen, Geoffrey L. Thomas, Neal J. Grunwell, Jocelyn R. Baines, Torrey Quasney, Michael Haileselassie, Bereketeab Lindsell, Christopher J. Alder, Matthew N. Wong, Hector R. |
author_sort | Atreya, Mihir R. |
collection | PubMed |
description | 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-04070-5. |
format | Online Article Text |
id | pubmed-9275255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92752552022-07-13 Integrated PERSEVERE and endothelial biomarker risk model predicts death and persistent MODS in pediatric septic shock: a secondary analysis of a prospective observational study Atreya, Mihir R. Cvijanovich, Natalie Z. Fitzgerald, Julie C. Weiss, Scott L. Bigham, Michael T. Jain, Parag N. Schwarz, Adam J. Lutfi, Riad Nowak, Jeffrey Allen, Geoffrey L. Thomas, Neal J. Grunwell, Jocelyn R. Baines, Torrey Quasney, Michael Haileselassie, Bereketeab Lindsell, Christopher J. Alder, Matthew N. Wong, Hector R. Crit Care Research 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-04070-5. BioMed Central 2022-07-11 /pmc/articles/PMC9275255/ /pubmed/35818064 http://dx.doi.org/10.1186/s13054-022-04070-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Atreya, Mihir R. Cvijanovich, Natalie Z. Fitzgerald, Julie C. Weiss, Scott L. Bigham, Michael T. Jain, Parag N. Schwarz, Adam J. Lutfi, Riad Nowak, Jeffrey Allen, Geoffrey L. Thomas, Neal J. Grunwell, Jocelyn R. Baines, Torrey Quasney, Michael Haileselassie, Bereketeab Lindsell, Christopher J. Alder, Matthew N. Wong, Hector R. 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 | 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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275255/ https://www.ncbi.nlm.nih.gov/pubmed/35818064 http://dx.doi.org/10.1186/s13054-022-04070-5 |
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