Investigating cytokine biomarkers as early predictors of poor clinical outcome following major trauma

Despite recent advances in critical care, trauma still continues to be the leading cause ofmorbidity and mortality among individuals under 40 years of age and the third main cause ofdeath throughout the world, carrying a substantial economic burden. Globally, the mostcommon traumatic injuries are acquired through penetrating wounds, blunt injuries or burnmechanisms. Recent reports from the UK suggest a significant change in the demographicsof major trauma. The typical major trauma patient is older, with a slight predominance ofmales, and with traumatic injuries resulted from falls from less than 2m in height.Mortality due to major trauma follows a biphasic pattern. Early fatalities occur due tohaemorrhagic shock or brain injuries, whereas the late deaths (>5 days post-trauma) areattributed to progressive multiple organ failure (MOF) and sepsis postulated to result fromdysfunctions of the immune system. Depending on the severity of trauma, the immuneresponse can be over-active with uncontrolled release of pro and anti-inflammatorymediators causing multiple organ failure.This study focusses on the second-phase mortality induced due to major trauma. Thehypothesis tested is that the late mortality and morbidity results from an imbalance of thepro and anti-inflammatory immune responses (SIRS and CARS) triggered after major trauma.While a balanced response of these two arms of the immune system result in homeostasis,the hyperactivity of the compensatory anti-inflammatory response (CARS) results inimmunosuppression and increased risk of nosocomial infections and late onset MOF.The study is designed to investigate the role of IL-6, IL-10, IL-12 and IL-4 in the developmentof the late onset MOF with a view to evaluating their use as a predictive biomarker of poorclinical outcome. The data from the analysis of 80 major trauma patients show averaged IL-6 7and IL-10 levels to decrease in major trauma patients from Day 1 to Day 5 post-admission(IL-6 p=0.000; IL-10 p=0.000), while the trends for IL-4 and IL-12 increased over the sameperiod for the cohort (IL-4 p=0.031; IL-12 p<0.001). When patients were clustered on thebasis of Sequential organ failure assessment scores (SOFA) on Day 5 (cut off >3), statisticallysignificant differences were observed in the Day 1 IL-10 and IL-6 levels at the cut off >3 forthe respective SOFA score (IL-10 p=0.023, IL -6 p=0.015) indicating a strong potential fortheir use as early biomarkers of poor clinical outcomes. The trends in Day 1IL - 10 and IL- 6concentration were maintained when the SOFA cluster cut offs were increased to > 6 (IL-10p=0.037; IL-6 p<0.001). When similar analyses were carried out with IL-12 data, a reversetrend was observed with higher Day 1 IL-12 levels being observed in the <3 Day 5 SOFAcluster, suggesting that high levels of IL-12 on Day 1 post-trauma is associated with goodclinical outcomes downstream. Although the IL-12 data failed to show statistical significanceat a SOFA cut off of 3 (p=0.268), when the data was clustered more stringently on a SOFA cutoff of 6, the differences were statistically significant (p= 0.023). Similar trends weremaintained for SOFA outcomes on Day 8. Similar to IL-6 and IL-10 patterns, high IL-4 levelson Day 1 post admission showed a significant association with poor outcome patient clusterson Day 5 (SOFA cut off 6; p=0.025)When cytokine levels were defined using Day 5 serum C-reactive protein concentration as ameasure of poor outcome (rather than SOFA scores), similar trends were observed.However, the data was not statistically significant, possibly due to confounding factorsresulting from a lower cohort size (n =30) where CRP records were available. In conclusion, amultiplex panel of these 4 cytokines may be of good predictive value for the earlystratification of major trauma patients for focussed clinical intervention and improvement ofclinical outcome.

Level dc:type.qualificationlevel

Master's Level (Level 7)

Year dc:date.issued

2019

Author dc:creator

• Apreutesei, RG

Language dc:language

en

Identifier

oai:salford-repository.worktribe.com:1363099

OAI identifier oai:identifier

oai:salford-repository.worktribe.com:1363099