The Pediatric Sepsis Biomarker Risk Model (PERSEVERE) Biomarkers Predict Clinical Deterioration and Mortality in Immunocompromised Children Evaluated for Infection

L Jacobs, Z Berrens, E K Stenson, M W Zackoff, L A Danziger, P Lahni, H R Wong, L Jacobs, Z Berrens, E K Stenson, M W Zackoff, L A Danziger, P Lahni, H R Wong

Abstract

Pediatric sepsis and bacterial infection cause significant morbidity and mortality worldwide, with immunocompromised patients being at particularly high risk of rapid deterioration and death. This study evaluated if PERSEVERE, PERSEVERE-II, or the PERSEVERE biomarkers, can reliably estimate the risk of clinical deterioration and 28-day mortality among immunocompromised pediatric patients. This is a single-center prospective cohort study conducted from July 2016 through September 2017 incorporating 400 episodes of suspected bacterial infection from the inpatient units at Cincinnati Children's Hospital Medical Center, a large, tertiary care children's hospital. The primary analysis assessed clinical deterioration within 72 hours of evaluation for infection. Secondarily, we assessed 28-day mortality. Clinical deterioration was seen in 15% of subjects. Twenty-eight day mortality was 5%, but significantly higher among critically ill patients. Neither PERSEVERE nor PERSEVERE-II performed well to predict clinical deterioration or 28-day mortality, thus we derived new stratification models using the PERSEVERE biomarkers with both high sensitivity and negative predictive value. In conclusion, we evaluated previously validated biomarker risk models in a novel population of largely non-critically ill immunocompromised pediatric patients, and attempted to stratify patients based on a new outcome metric, clinical deterioration. The new highly predictive models indicate common physiologic pathways to clinical deterioration or death from bacterial infection.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
New Classification and Regression Tree to Predict Clinical Deterioration. The classification tree consists of four biomarker-based decision rules with five terminal daughter nodes. The tree incorporates four of five PERSEVERE biomarkers: interleukin-8 (IL8), heat shock protein 70 kDa 1B (HSPA1B), chemokine ligand 3 (CCL3), and matrix metalloproteinase-8 (MMP8). Each node denotes the number of subjects in the node, the serum concentration of a given biomarker determining the branch point (pg/mL), and both the total number and accompanying rate of subjects with clinical deterioration or clinical stability. Terminal Nodes 1 and 3 are considered low risk terminal nodes; terminal nodes 2, 4, and 5 are high risk. The AUROC for this model was 0.81.
Figure 2
Figure 2
New Classification and Regression Tree to Predict 28-Day Mortality. The classification tree consists of four biomarker-based decision rules with five terminal daughter nodes. The tree incorporates three of five PERSEVERE biomarkers: interleukin-8 (IL8), heat shock protein 70 kDa 1B (HSPA1B), and chemokine ligand 3 (CCL3). Each node denotes the number of subjects in the node, the serum concentration of a given biomarker determining the branch point (pg/mL), and both the total number and accompanying rate of survivors and non-survivors. Terminal nodes 1, 2, and 4 are low risk nodes. Terminal node 3 is higher risk, with terminal node 5 being the highest risk node. The AUROC for this model was 0.87.

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Source: PubMed

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