Early increase in anti-inflammatory biomarkers is associated with the development of multiple organ dysfunction syndrome in severely injured trauma patients

Abstract

BackgroundAs a result of improvements in the early resuscitation phase of trauma, mortality is largely driven by later mortality due to multiple organ dysfunction syndrome (MODS), which may be mediated by an early overdrive in the host immune response. If patients at risk for MODS could be identified early, preventive treatment measures could be taken. The aim of this study is to investigate whether specific biomarkers are associated with MODS.MethodsMultiple trauma patients presenting to the Amsterdam University Medical Centers, location Academic Medical Center, between 2012 and 2018 with an Injury Severity Score of 16 or higher were sampled on arrival at the emergency department. A wide variety of inflammatory cytokines, endothelial and lung-specific markers were determined. Comparisons were made between patients with and without MODS. Univariate and multivariate logistic regression was used to determine associations between specific biomarkers and MODS. A p value of 0.05 was considered to be statistically significant.ResultsIn total, 147 multiple trauma patients were included. Of these, 32 patients developed MODS (21.7%). Patients who developed MODS were more severely injured, had more traumatic brain injury and showed more deranged markers of coagulation when compared with patients without MODS. Overall, both proinflammatory and anti-inflammatory cytokines were higher in patients with MODS, indicative of a host immune reaction. In the multivariate analysis, the combination of anti-inflammatory proteins interleukin 1 receptor antagonist (IL-1RA) (OR 1.27 (1.07–1.51), p=0.002) and Clara cell protein 16 (CC-16) (1.06 (1.01–1.05), p=0.031) was most strongly associated with the development MODS.ConclusionsIn trauma, anti-inflammatory proteins IL-1RA and CC-16 have the potential to early identify patients at risk for development of MODS. Further research is warranted to prospectively validate these results.Level of evidencePrognostic study, level III.

Alarming Cargo: The Role of Exosomes in Trauma-Induced Inflammation

“…Identification of early biological signatures to predict development, progression, and clinical outcome of severe inflammation-mediated immune dysfunction is critical for timely intervention and mitigation of downstream effects. Prior research efforts have largely focused on individual or small numbers of classic systemic inflammatory markers as biological signatures [ 4 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ]. A combinatorial signature involving genome-wide multi-plexed analyses of interlinked pathways may have a greater predictive value at any given point.…”

A Nomogram Based on Clinical Characteristics for Predicting Multiple Organ Dysfunction Syndrome(MODS) Following Multiple Trauma Patients

“…To date,despite enhanced understanding of MODS pathogenesis,there have been no effective therapy,and prevention is still crucial for MODS [4] .Therefore,early identi cation of multiple trauma patients who were at risk of developing MODS can help to timely prevention and intervention,and may improve these patient's prognosis.Recently studies showed several speci c biomarkers could be useful in predicting high risk patients to develop posttraumatic MODS.A study by Haasper [5] showed procalcitonin(PCT) had a high sensitivity for predicting the development of MODS(sensitivity was 0.88).Kleinveld [6] found that the combination of anti-in ammatory proteins interleukin 1receptor antagonist(IL-1RA) and Clara cell protein 16(CC-16) was most strongly associated with the development MODS by multivariate analysis.A retrospective cohort study [7] showed plasma levels of Neutrophil gelatinase-associated lipocalin(NGAL), paracrine osteoprtegerin(OPG) and IL-6 were signi cantly elevated in MODS+ group,and these biomarkers positively correlated with MODS score and diagnosis of MODS.Kong et al [8] found that delta neutrophil index (DNI)values of >3.25% and >5.3% at 12h post-admission were signi cant predictors of the development of MODS and 30-days mortality,respectively,in trauma patients.In addition,the AUC of combined detection of NF-κB 1.20,IL-6 25.1 ug/L and TNF-α 2.20 ng/ml in peripheral blood in predicting MODS was 0.853,95%CI(0.659,0.977) [9] . These above speci c biomarkers had a certain guiding signi cance for predicting developing of MODS in patients with multiple trauma.However,these biomarkers were not routinely performed in clinical particularly in emergency room,because of cumbersome laboratory techniques or high cost associated with these approaches currently inhibited their clinical implementation.Therefore,it is quite necessary to explore a easy-to-use and reliable predictive model for MODS following multiple trauma patients.…”