Prolonged but not short-duration blast waves elicit acute inflammation in a rodent model of primary blast limb trauma

BackgroundBlast injuries from conventional and improvised explosive devices account for 75% of injuries from current conflicts; over 70% of injuries involve the limbs. Variable duration and magnitude of blast wave loading occurs in real-life explosions and is hypothesised to cause different injuries. While a number of in vivo models report the inflammatory response to blast injuries, the extent of this response has not been investigated with respect to the duration of the primary blast wave. The relevance is that explosions in open air are of short duration compared to those in confined spaces.MethodsHindlimbs of adult Sprauge-Dawley rats were subjected to focal isolated primary blast waves of varying overpressure (1.8–3.65 kPa) and duration (3.0–11.5 ms), utilising a shock tube and purpose-built experimental rig. Rats were monitored during and after the blast. At 6 and 24 h after exposure, blood, lungs, liver and muscle tissues were collected and prepared for histology and flow cytometry.ResultsAt 6 h, increases in circulating neutrophils and CD43Lo/His48Hi monocytes were observed in rats subjected to longer-duration blast waves. This was accompanied by increases in circulating pro-inflammatory chemo/cytokines KC and IL-6. No changes were observed with shorter-duration blast waves irrespective of overpressure. In all cases, no histological damage was observed in muscle, lung or liver. By 24 h post-blast, all inflammatory parameters had normalised.ConclusionsWe report the development of a rodent model of primary blast limb trauma that is the first to highlight an important role played by blast wave duration and magnitude in initiating acute inflammatory response following limb injury in the absence of limb fracture or penetrating trauma. The combined biological and mechanical method developed can be used to further understand the complex effects of blast waves in a range of different tissues and organs in vivo

Combat vascular injury: influence of mechanism of injury on outcome

Background: Haemorrhage is the leading cause of death on the battlefield. Seventy percent of injuries are due to explosive mechanisms. Anecdotally, these patients have had poorer outcomes when compared to those with penetrating mechanisms of injury (MOI). We wished to test the hypothesis that outcomes following vascular reconstruction were worse in blast-injured than non blast-injured patients.Methods: Retrospective cohort study. British and American combat casualties with arterial injuries sustained in Iraq or Afghanistan (2003-2014) were identified from the UK Joint Theatre Trauma Registry (JTTR). Eligibility included explosive or penetrating MOI with follow-up to UK hospital discharge, or death. Outcomes were mortality, amputation, graft thrombosis, haemorrhage, and infection. Statistical analysis was performed using Pearson Chi-Square test, t-tests, ANOVA or non-parametric equivalent, and survival analyses.Results: One hundred and fifteen patients were included, 80 injured by explosive and 35 by penetrating mechanisms. Evacuation time, ISS, number of arterial injuries, age and gender were comparable between groups. Seventy percent of arterial injuries resulted from an explosive MOT The explosive injuries group received more blood products (p = 0.008) and suffered more regions injured (p < 0.0001). Early surgical interventions in both were ligation (n = 36, 31%), vein graft (n = 33, 29%) and shunting (n = 9, 8%). Mortality (n= 12, 10%) was similar between groups. Differences in limb salvage rates following explosive (n= 17, 53%) vs penetrating (n = 13, 76.47%) mechanisms approached statistical significance (p = 0.056). Nine (28%) vein grafted patients developed complications. No evidence of a difference in the incidence of vein graft thrombosis was found when comparing explosive with non-explosive cohorts (p = 0.154).Conclusions: The recorded numbers of vein grafts following combat arterial trauma in are small in the JTTR. No statistically-significant differences in complications, including vein graft thrombosis, were found between cohorts injured by explosive and non-explosive mechanisms. Crown Copyright (C) 2018 Published by Elsevier Ltd. All rights reserved

Predicting the Outcome of Limb Revascularization in Patients With Lower-extremity Arterial Trauma: Development and External Validation of a Supervised Machine-learning Algorithm to Support Surgical Decisions.

Objectives: Estimating the likely success of limb revascularization in patients with lower-extremity arterial trauma is central to decisions between attempting limb salvage and amputation. However, the projected outcome is often unclear at the time these decisions need to be made, making them difficult and threatening sound judgement. The objective of this study was to develop and validate a prediction model that can quantify an individual patient's risk of failed revascularization. Methods: A BN prognostic model was developed using domain knowledge and data from the US joint trauma system. Performance (discrimination, calibration, and accuracy) was tested using ten-fold cross validation and externally validated on data from the UK Joint Theatre Trauma Registry. BN performance was compared to the mangled extremity severity score. Results: Rates of amputation performed because of nonviable limb tissue were 12.2% and 19.6% in the US joint trauma system (n = 508) and UK Joint Theatre Trauma Registry (n = 51) populations respectively. A 10-predictor BN accurately predicted failed revascularization: area under the receiver operating characteristic curve (AUROC) 0.95, calibration slope 1.96, Brier score (BS) 0.05, and Brier skill score 0.50. The model maintained excellent performance in an external validation population: AUROC 0.97, calibration slope 1.72, Brier score 0.08, Brier skill score 0.58, and had significantly better performance than mangled extremity severity score at predicting the need for amputation [AUROC 0.95 (0.92–0.98) vs 0.74 (0.67–0.80); P < 0.0001]. Conclusions: A BN (https://www.traumamodels.com) can accurately predict the outcome of limb revascularization at the time of initial wound evaluation. This information may complement clinical judgement, support rational and shared treatment decisions, and establish sensible treatment expectations

Stability and haplotype analysis of the FRAXE region

FRAXE full mutations are rare and appear to be associated with mild mental retardation. As part of a screening survey of boys with learning difficulties to determine the frequency of full and premutations, we have collected data on the frequency of instability at FRAXE for about 4000 transmissions and the haplotype for over 7000 chromosomes. The distribution of FRAXE repeats was similar to other English populations but differed from two North American Caucasian series. Observed instability at FRAXE was rare but increased with increasing repeat number, and there were no expansions into the full mutation range, except in pedigrees ascertained through a full mutation. Haplotype analysis suggested division into five groups with each group having a characteristic distribution of FRAXE repeats. Fourteen of the 15 full mutations occurred on a single haplotype and this haplotype also had a significant excess of intermediate-sized alleles, suggesting that full mutations originate from large normal alleles. However, a related haplotype also had a significant excess of intermediates but we observed no full mutations on this haplotype, suggesting either loss or gain of stability determinants on it. We suggest that whilst triplet repeat size is a significant predisposing factor for expansion at FRAXE other genetic determinants are also likely to be important. <br/