SIMPLIFIED IMMUNE-DYSREGULATION INDEX: A NOVEL MARKER PREDICTS 28-DAY MORTALITY OF INTENSIVE CARE PATIENTS WITH SEPSIS.

Abstract

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. There is currently no simple immune-imbalance-driven indicator for patients with sepsis. Methods: This study was conducted in Peking Union Medical College Hospital. Patients with sepsis were identified according to Sepsis 3.0 after reviewing patient data from May 2018 through October 2022. Least absolute shrinkage and selection operator logistic regression was used for features selection. Receiver operating characteristic curves for 28-day mortality were used to compare the predictive performance of level of interleukin 6 (IL-6) and lymphocyte count (LY#) with that of the combined ratio, namely, the IL-6/LY# ratio. A Cox hazard model was also used to test the predictive performance of IL-6/LY# versus several other measurements. The dynamic trend of IL-6/LY# based on day 1 IL-6/LY# level was analyzed. Results: The mortality rate was 24.5% (220/898) in the study cohort. The LY#, IL-6 level, blood platelet count, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, heart rate, age and Fi o2 level were identified as key factors for predicting 28-day mortality. IL-6/LY# was identified as a core indicator according to Least absolute shrinkage and selection operator logistic regression analysis. IL-6/LY# was significantly higher in nonsurvivors than in survivors (348 [154.6-1371.7] vs. 42.3 [15.4-117.1]). IL-6/LY# yielded a higher area under the curve (0.852 [95% CI = 0.820-0.879]) than the level of IL-6 (0.776 [95% CI = 0.738-0.809]) and LY# (0.719 [95% CI = 0.677-0.755]) separately. Survival analysis of mortality risk versus the IL-6/LY# ratio suggested that IL-6/LY# was significantly more predictive of patient risk than the Sequential Organ Failure Assessment score or the other factors ( P = 1.5 × 10 -33 ). In trend analysis, as the trend of D1-D3-D7 IL-6/LY# decreases, the morality rate is lower than increase or fluctuate group (42.1% vs. 58.3%, 37.9% vs. 43.8%, 37.5% vs. 38.5% in high, moderate, and low D1 IL-6/LY# group separately). Conclusion: IL-6/LY# examined on first day in intensive care unit can be used as an immune-imbalance alert to identify sepsis patients with higher risk of 28-day mortality. Decreasing trend of IL-6/LY# suggests a lower 28-day mortality rate of sepsis patients.