Effectiveness of a specific trauma training on war-related truncal injury management: A pre-post study.

BACKGROUND: Non-Compressible Torso Hemorrhage (NCTH) is the leading cause of preventable death in combat casualty care. To enhance the French military surgeons' preparedness, the French Military Health Service designed the Advanced Course for Deployment Surgery (ACDS) in 2008. This study evaluates behavioral changes in war surgery practice since its implementation. METHODS: Data were extracted from the OPEX® registry, which recorded all surgical activity during deployment from 2003 to 2021. All patients treated in French Role 2 or 3 Medical Treatment Facilities (MTFs) deployed in Afghanistan, Mali, or Chad requiring emergency surgery for NCTH were included. The mechanism of injury, severity, and surgical procedures were noted. Surgical care produced before (Control group) and after the implementation of the ACDS course (ACDS group) were compared. RESULTS: We included 189 trauma patients; 99 in the ACDS group and 90 in the Control group. Most injuries were combat-related (88 % of the ACDS and 82 % of the Control group). The ACDS group had more polytrauma (42% vs. 27 %; p= 0.034) and more e-FAST detailed patients (35% vs. 21 %; p= 0.044). Basics in surgical trauma care were similar between both groups, with a tendency in the ACDS group toward less digestive diversion (n= 6 [6 %] vs. n= 12 [13 %]; p= 0.128), more temporary closure with abdominal packing (n= 17 [17 %] vs. n= 10 [11 %]; p= 0.327), and less re-operation for bleeding (n= 0 [0 %] vs. n= 5 [6 %]; p= 0.046). CONCLUSION: The French model of war trauma course succeeded in keeping specialized surgeons aware of the basics of damage control surgery. The main improvements were better use of preoperative imaging and better management of seriously injured patients.

The variant hERG/R148W associated with LQTS is a mutation that reduces current density on co-expression with the WT.

BACKGROUND: A variant of the ether-à-go-go related channel (hERG), p.Arg148Trp (R148W) was found at heterozygous state in two infants who died from sudden infant death syndrome (SIDS), one with documented prolonged QTc and Torsade de Pointes (TdP), and in an adult woman with QTc >500 ms, atrioventricular block and TdP. This variant was previously reported in cases of severe ventricular arrhythmia but very rarely in control subjects. Its classification as mutation or polymorphism awaited electrophysiological characterization. METHODS: The properties of this N-terminal, proximal domain, hERG variant were explored in Xenopus oocytes injected with the same amount of RNA encoding for either hERG/WT or hERG/R148W or their equimolar mixture. The human ventricular cell (TNNP) model was used to test the effects of changes in hERG current. RESULTS: R148W alone produced a current similar to the WT (369 ± 76 nA (mean ± SEM), n=13 versus 342 ± 55 nA in WT, n=13), while the co-expression of 1/2 WT+1/2 R148W lowered the current by 29% versus WT (243 ± 35 nA, n=13, p<0.05). The voltage dependencies of steady-state activation and inactivation were not changed in the variant alone or in co-expression with the WT. The time constants of fast recovery from inactivation and of fast and slow deactivation analyzed between -120 and +20 mV were not changed. The voltage-dependent distribution of the current amplitudes among fast-, slow- and non-deactivating fractions was unaltered. A 6.6% increase in APD90 from 323.5 ms to 345 ms was observed using the human cardiac ventricular myocyte model. CONCLUSIONS: Such a decrease in hERG current as evidenced here when co-expressing the hERG/R148W variant with the WT may have predisposed to the observed long QT syndrome and associated TdP. Therefore, the heterozygous carriers of hERG/R148W may be at risk of cardiac sudden death.

Sodium overload due to a persistent current that attenuates the arrhythmogenic potential of a novel LQT3 mutation.

Long QT syndrome (LQTS) is a congenital abnormality of cardiac repolarization that manifests as a prolonged QT interval on 12-lead electrocardiograms (ECGs). The syndrome may lead to syncope and sudden death from ventricular tachyarrhythmias known as torsades de pointes. An increased persistent Na(+) current is known to cause a Ca(2+) overload in case of ischemia for example. Such increased Na(+) persistent current is also usually associated to the LQT3 syndrome. The purpose of this study was to investigate the pathological consequences of a novel mutation in a family affected by LQTS. The impact of biophysical defects on cellular homeostasis are also investigated. Genomic DNA was extracted from blood samples, and a combination of PCR and DNA sequencing of several LQTS-linked genes was used to identify mutations. The mutation was reproduced in vitro and was characterized using the patch clamp technique and in silico quantitative analysis. A novel mutation (Q1476R) was identified on the SCN5A gene encoding the cardiac Na(+) channel. Cells expressing the Q1476R mutation exhibited biophysical alterations, including a shift of SS inactivation and a significant increase in the persistent Na(+) current. The in silico analysis confirmed the arrhythmogenic character of the Q1476R mutation. It further revealed that the increase in persistent Na(+) current causes a frequency-dependent Na(+) overload in cardiomyocytes co-expressing WT and mutant Nav1.5 channels that, in turn, exerts a moderating effect on the lengthening of the action potential (AP) duration caused by the mutation. The Q1476R mutation in SCN5A results in a three-fold increase in the window current and a persistent inward Na(+) current. These biophysical defects may expose the carrier of the mutation to arrhythmias that occur preferentially in the patient at rest or during tachycardia. However, the Na(+) overload counterbalances the gain-of-function of the mutation and is beneficial in that it prevents severe arrhythmias at intermediate heart rates.