Journal Article

Computational evidence for an early, amplified systemic inflammation program in polytrauma patients with severe extremity injuries

Vodovotz, Yoram, Sperry, Jason, Billiar, Timothy R., Almahmoud, Khalid, Gaski, Greg E., Zamora, Ruben, McKinley, Todd O., Abboud, Andrew, Peitzman, Andrew B., Namas, Rami A., Truitt, Michael S.

2019

Overview

Extremity and soft tissue injuries contribute significantly to inflammation and adverse in-hospital outcomes for trauma survivors; accordingly, we examined the complex association between clinical outcomes inflammatory responses in this setting using in silico tools. Two stringently propensity-matched, moderately/severely injured (Injury Severity Score > 16) patient sub-cohorts of ~30 patients each were derived retrospectively from a cohort of 472 blunt trauma survivors and segregated based on their degree of extremity injury severity (above or below 3 on the Abbreviated Injury Scale). Serial blood samples were analyzed for 31 plasma inflammatory mediators. In addition to standard statistical analyses, Dynamic Network Analysis (DyNA) and Principal Component Analysis (PCA) were used to model systemic inflammation following trauma. Patients in the severe extremity injury sub-cohort experienced longer intensive care unit length of stay (LOS), total LOS, and days on a mechanical ventilator, with higher Marshall Multiple Organ Dysfunction (MOD) Scores over the first 7 days post-injury as compared to the mild/moderate extremity injury sub-cohort. The higher severity cohort had statistically significant elevated lactate, base deficit, and creatine phosphokinase on first blood draw, along with significant changes in multiple circulating inflammatory mediators. DyNA pointed to a sustained role for type 17 immunity in both sub-cohorts, along with IFN-γ in the severe extremity injury group. DyNA network complexity increased over 7 days post-injury in the severe injury group, while generally decreasing over this same time period in the mild/moderate injury group. PCA suggested a more robust activation of multiple pathways in the severe extremity injury group as compared to the mild/moderate injury group. These studies thus point to the possibility of self-sustaining inflammation following severe extremity injury vs. resolving inflammation following less severe extremity injury.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Area Under Curve / Arm injuries / Biology and Life Sciences / Biomarkers - metabolism / Blood / Blood circulation / Blunt trauma / Bone surgery / Care and treatment / Cohort Studies / Complexity / Computer applications / Computer Simulation / Creatine / Creatine kinase / Critical care / Cytokines / Diagnosis / Extremities - injuries / Female / Fractures / Health aspects / Humans / Immune response / Immune system / Immunity / Inflammation / Inflammation - complications / Injuries / Injury analysis / Injury Severity Score / Lactic acid / Leg injuries / Male / Medical education / Medicine / Medicine and Health Sciences / Middle Aged / Multiple Trauma - complications / Network analysis / Orthopedics / Patient outcomes / Patients / Physical Sciences / Principal Component Analysis / Principal components analysis / Research and Analysis Methods / Soft tissues / Statistical analysis / Statistical methods / String matching / Time Factors / Trauma / Treatment Outcome / γ-Interferon