Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology (original) (raw)
Related papers
The pediatric sepsis biomarker risk model
Critical Care, 2012
Introduction: The intrinsic heterogeneity of clinical septic shock is a major challenge. For clinical trials, individual patient management, and quality improvement efforts, it is unclear which patients are least likely to survive and thus benefit from alternative treatment approaches. A robust risk stratification tool would greatly aid decisionmaking. The objective of our study was to derive and test a multi-biomarker-based risk model to predict outcome in pediatric septic shock.
Testing the Prognostic Accuracy of the Updated Pediatric Sepsis Biomarker Risk Model
PLoS ONE, 2014
Background: We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort.
2022
Background: Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identi cation of those at risk of 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 risk of day 7 MODS and individual organ dysfunctions on day 7 of pediatric septic shock. Methods: We measured endothelial dysfunction markers from day 1 serum among those with existing PERSEVERE data. TreeNet® classi cation model was derived incorporating 22 clinical and biological variables to estimate risk. Based on relative variable importance, a simpli ed 6 biomarker model was developed thereafter. Results: Among 502 patients, 173 (34.5%) patients had MODS on day 7. Area under the receiver operator characteristic curve (AUROC) for the newly derived PERSEVEREnce model to predict day 7 MODS was 0.93 (0.91-0.95) with a summary AUROC of 0.80 (0.76-0.84) upon 10-fold cross validation. The simpli ed 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 between 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 day 7 MODS and individual organ dysfunctions in pediatric septic shock. If validated, this tool can be used for prognostic enrichment in future pediatric trials of sepsis therapeutics.
American journal of respiratory and critical care medicine, 2017
We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins, selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered. Determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and provide biological information regarding the pathophysiology of septic shock. We reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using Classification and Regression Tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n =77). Variable reductio...
Early prediction of impending septic shock in children using age-adjusted Sepsis-3 criteria
Sepsis is a syndrome which afflicts both adults and children, with many disease courses and diverse outcomes. Understanding of sepsis pathophysiology has changed over time; the Sepsis-3 criteria define sepsis in adults as organ dysfunction, quantified by SOFA score, caused by dysregulated immune response to infection. However, pediatric consensus definitions still utilize the SIRS-based Sepsis-2 criteria, though individual groups have attempted to adapt the Sepsis-3 criteria for children. We evaluate age-adjusted Sepsis-3 criteria on 2,384 pediatric patients admitted to the Johns Hopkins PICU, and apply previously-published methods for early prediction of septic shock. We obtain best early prediction performance of 0.96 AUC, 49.9% overall PPV, and a 5.8-hour median EWT using Sepsis-3 labels based on age-adjusted SOFA score. Through analyses of risk score evolution over time, we corroborate our past finding of an abrupt transition preceding onset of septic shock in children, and are ...
Critical Care
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 ...
Predictor Prognosis of Pediatric Septic Shock : Literature review
Critical & Medical Surgical Nursing Journal, 2022
Introduction: The unpredictability of body response to organ dysfunction needs an effective tool to predict the prognosis of shock septic. Early recognition and treatment of septic shock improved prognosis and reduced mortality, especially in pediatrics. This review aimed to identify the predictor of mortality in pediatric septic shock. Methods: We performed a literature review of the predictor of mortality in pediatric septic shock conducted between 2015 and 2020 in ProQuest, Google Scholar, PubMed, and Science Direct. We used keywords (predictor or predictive) and (septic shock or septic), and (prognostic or prognosis) and (pediatric or children). The study selection was using the Preferred Reporting Items for Systematic Review and Meta-Analysis PRISMA framework. Results: 944 articles identified in ProQuest, 720 articles in Science Direct, 339 articles in Google Scholar, and 67 in Pubmed. Equally, the total articles were 2,070 articles, and there were 414 duplicates. After review of the complete texts was performed for 35 potential studies. In the full-text review, we excluded review articles (n = 3), different populations (n=8), and of poor quality (n = 20). Eventually, four papers were reviewed in this study. We found PELOD, PELOD-2, PIM, PIM 2, PIM 3, PMODS, PRISM, PRISM-III, PRISM-IV, and pSOFA as a predictor of sepsis in pediatrics. Conclusion: In conclusion, pSOFA is a more accurate screening result for estimating the risk of death by being 10 times more sensitive and specific. However, adding biomarkers to pSOFA will improve the accuracy of the predictor prognosis of pediatric sepsis.
Frontiers in Pediatrics
Objectives: Innovative Cell Population Data (CPD) have been used as early biomarkers for diagnosing sepsis in adults. We assessed the usefulness of CPD in pediatric patients with sepsis/septic shock, in terms of early recognition and outcome prediction. We revised 54 patients (0–15 y) admitted to our Pediatric Intensive Care Unit (PICU) for sepsis/septic shock during a 4-year period. Twenty-eight patients were excluded, 26 septic patients were enrolled (G1). Forty children admitted for elective surgery served as controls (G2). Data on five selected CPD parameters, namely neutrophils fluorescence intensity (NE-SFL), monocytes cells complexity (MO-X), monocytes fluorescence intensity (MO-Y), monocytes complexity and width of dispersion of events measured (MO-WX), and monocytes cells size and width dispersion (MO-WZ), were obtained at time of PICU admission (t0) by a hematological analyzer (Sysmex XN 9000®). As the primary outcome we evaluated the relevance of CPD for diagnosing sepsis...