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

Abstract

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.

Percutaneous transforaminal endoscopic discectomy ameliorates postoperative reactive pain in patients with lumbar disc herniation

“…Different from the open discectomy, PTED is performed under the water boundary during the operation [9,19,20], which may effectively prevent the aggregation of local in ammatory substances thorough continuous irrigation. Furthermore, previous studies demonstrated that in ammatory substances may also be released by the locally damaged tissue around the surgical site [21,22], that may also stimulate the nerve roots and cause reactive pain. Therefore, less in ammatory exudation at the surgical site caused by smaller surgical wounds in PTED may be another reason for reduced aggregation of local in ammatory substances around nerve roots.…”

Percutaneous transforaminal endoscopic discectomy ameliorates postoperative reactive pain in patients with lumbar disc herniation

“…Different from the open discectomy, PTED is performed under the water boundary during the operation [9,21,22], which may effectively prevent the aggregation of local in ammatory substances thorough continuous irrigation. Furthermore, previous studies demonstrated that in ammatory substances may also be released by the locally damaged tissue around the surgical site [23,24], that may also stimulate the nerve roots and cause reactive pain. Therefore, less in ammatory exudation at the surgical site caused by smaller surgical wounds in PTED may be another reason for reduced aggregation of local in ammatory substances around nerve roots.…”

Why the lungs became a target organ due to ischemic-reperfusion syndrome of the limb, caused by the use of haemostatic tourniquet

“…Due to the direct pressure of the tourniquet on the skin and muscles, there is a local violation of microcirculation in the skin and muscles, followed by reinfusion of hypoxic tissues with degeneration of axons, [28]. Though, as a result of a significant increase in the concentration of rhabdomyolysis products and the triggering of local oxidative stress, lipid peroxidation products enter the systemic bloodstream, cytokines are activated [29][30][31]. In particular, in these cases, the use of a tourniquet is already a recognized factor that causes changes in the activity of neurophiles, activation of monocytes, stimulates neutrophil transendothelial migration, followed by the likelihood of tissue damage [32].…”