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

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

WSES classification and guidelines for liver trauma

The severity of liver injuries has been universally classified according to the American Association for the Surgery of Trauma (AAST) grading scale. In determining the optimal treatment strategy, however, the haemodynamic status and associated injuries should be considered. Thus the management of liver trauma is ultimately based on the anatomy of the injury and the physiology of the patient. This paper presents the World Society of Emergency Surgery (WSES) classification of liver trauma and the management Guidelines

Spontaneous Splenic Rupture: A Rare Complication of Acute Pancreatitis in a Patient with Crohn's Disease

Crohn's disease (CD) is an idiopathic inflammatory bowel disease which can involve any part of the gastrointestinal tract. It frequently involves the ileum, colon and the anorectum. Although rare, acute pancreatitis as a complication of CD involving the duodenum has been described in the literature. We describe a 37-year-old male with CD presenting with acute pancreatitis and spontaneous splenic rupture. The potential mechanisms associated with acute pancreatitis along with spontaneous rupture of the spleen in this patient population and its treatment will be discussed. Common complaints such as upper abdominal pain in a patient with CD should undergo workup to exclude less commonly involved sites such as the pancreas and spleen. Close monitoring in the critical care setting is recommended in carefully selected and hemodynamically stable patients with splenic rupture. Surgical treatment is considered as the standard of care in hemodynamically unstable patients

Oesophageal injuries: Position paper, WSES, 2013

Peer reviewe

Impact of Splenic Artery Embolization on the Success Rate of Nonoperative Management for Blunt Splenic Injury

Introduction Nonoperative management (NOM) has become the treatment of choice for hemodynamically stable patients with blunt splenic injury. Results of outcome after NOM are predominantly based on large-volume studies from level 1 trauma centers in the United States. This study was designed to assess the results of NOM in a relatively low-volume Dutch level 1 trauma center. Methods An analysis of a prospective trauma registry was performed for a 6-year period before (period 1) and after the introduction and implementation of splenic artery embolization (SAE) (period 2). Primary outcome was the failure rate of initial treatment. Results A total of 151 patients were reviewed. An increased use of SAE and a reduction of splenic operations during the second period was observed. Compared with period 1, the failure rate after observation in period 2 decreased from 25% to 10%. The failure rate after SAE in period 2 was 18%. The splenic salvage rate (SSR) after observation increased from 79% in the first period to 100% in the second period. During the second period, all patients with failure after observation were successfully treated with SAE. The SSR after SAE in periods 1 and 2 was respectively 100% and 86%. Conclusions SAE of patients with blunt splenic injuries is associated with a reduction in splenic operations. The failure and splenic salvage rates in this current study were comparable with the results from large-volume studies of level 1 trauma centers. Nonoperative management also is feasible in a relatively low-volume level 1 trauma center outside the United State

P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

Prevention of Hypovolemic Circulatory Collapse by IL-6 Activated Stat3

Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT) 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3β, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients