Discussion
MODS, endotoxemia, organ dysfunction, infection, organ failure, sepsis
ENDOTOXEMIA, DISEASE, INFECTION, MODS, DYSREGULATED HOST RESPONSE, SEPSIS, DYSFUNCTION
In this study, we statistically uncovered the heterogeneity in treatment effects of PMX-HA and identified a potential target phenotype of sepsis responsive to PMX-HA using a novel machine learning-based method (i.e., causal forest). Specifically, to streamline the use of PMX-HA on patients with sepsis, we estimated the individual treatment effects of PMX-HA on 28-day survival and identified patients with PT-INR > 1.4 or lactate > 3 mmol/L to be an optimal target of PMX-HA in the JSEPTIC-DIC study cohort. These derived criteria were validated in the EUPHRATES trial cohort which already used biomarker-guided enrichment with EAA.Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [Identification of patients for any therapy combines clinical phenotyping with diagnostic testing. As PMX-HA targets endotoxin, the identification of endotoxemia using EAA is essential. However, high EAA without clinical evidence of organ failure for example using Multiple Organ Dysfunction Score (MODS) or SOFA score may not identify patients with sufficient disease burden to benefit from PMX-HA [