ABSTRACTThree Forward Aeromedical Evacuation platforms operate in Southern AfghanistanUK Medical Emergency Response Team (MERT), US Air Force Expeditionary Rescue Squadron (PEDRO), and US Army ...Medical Evacuation Squadrons (DUSTOFF), each with a different clinical capability. Recent evidence suggests that retrieval by a platform with a greater clinical capability (MERT) is associated with improved mortality in critical patients when compared with platforms with less clinical capability (PEDRO and DUSTOFF). It is unclear whether this is due to en route resuscitation or the dispatch procedure. The aim of this study was to compare prehospital Shock Index (SI = heart rate / systolic blood pressure) with admission values as a measure of resuscitation, across these platforms. Patients were identified from the Department of Defense Trauma Registry, who were evacuated between June 2009 and June 2011 in Southern Afghanistan. Data on platform type, physiology, and injury severity was extracted. Overall, 865 patients were identified478 MERT, 291 PEDRO, and 96 DUSTOFF patients and groups were compared across three injury severity scoring (ISS) bins1 to 9, 10 to 25, and 26 or greater. An improvement in the admission SI was observed across all platforms in the lowest ISS bin. Within the middle bin, both the MERT and PEDRO groups saw improved SI on admission, but not the DUSTOFF group. This trend was continued only in the MERT group for the highest ISS bin (1.39 ± 0.62 vs. 1.09 ± 0.42; P = 0.001), whereas a deterioration was identified in the PEDRO group (0.88 ± 0.37 vs. 1.02 ± 0.43; P = 0.440). The use of a Forward Aeromedical Evacuation platform with a greater clinical capability is associated with an improved hemodynamic status in critical casualties. The ideal prehospital triage should endeavor to match patient need with clinical capability.
Determine if a higher level of Army flight medic (AFM) training was associated with improved physiological state on arrival to a combat support hospital (CSH).
A retrospective study comparing ...casualties who were evacuated by two AFM units with only Emergency Medical Technicians-Basic (EMT-Bs) to an Army National Guard unit with Critical Care Flight Paramedics (CCFPs) in Afghanistan with an injury severity score >16 in different time periods looking at their 48-hour mortality, hematocrit (HCT), base deficit (BD), oxygen saturation (SpO2), and physiological parameters on arrival to the CSH.
The CCFP group had better HCT 36.5 (8.8) than the EMT-B group 33.1 (11.4); p ≤ 0.001. BD and SpO2 were better in the CCFP group -3.2 (4.7)/97.8 (4.8) than the EMT-B group -4.4 (5.5)/96.3 (10.9) p ≤ 0.014. The CCFP group had a 72% lower estimated risk ratio of mortality with an associated improvement in 48-hour survivability of 4.9% versus 15.8% for the EMT-B-group.
There is a statistically significant improvement in the HCT, BD, SpO2, and 48-hour survivability at the CSH in the cohort transported by the CCFP group when compared to the cohort transported by the EMT-B group.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
OBJECTIVE To evaluate battlefield survival in a novel command-directed casualty response system that comprehensively integrates Tactical Combat Casualty Care guidelines and a prehospital trauma ...registry. DESIGN Analysis of battle injury data collected during combat deployments. SETTING Afghanistan and Iraq from October 1, 2001, through March 31, 2010. PATIENTS Casualties from the 75th Ranger Regiment, US Army Special Operations Command. MAIN OUTCOME MEASURES Casualties were scrutinized for preventable adverse outcomes and opportunities to improve care. Comparisons were made with Department of Defense casualty data for the military as a whole. RESULTS A total of 419 battle injury casualties were incurred during 7 years of continuous combat in Iraq and 8.5 years in Afghanistan. Despite higher casualty severity indicated by return-to-duty rates, the regiment's rates of 10.7% killed in action and 1.7% who died of wounds were lower than the Department of Defense rates of 16.4% and 5.8%, respectively, for the larger US military population (P = .04 and P = .02, respectively). Of 32 fatalities incurred by the regiment, none died of wounds from infection, none were potentially survivable through additional prehospital medical intervention, and 1 was potentially survivable in the hospital setting. Substantial prehospital care was provided by nonmedical personnel. CONCLUSIONS A command-directed casualty response system that trains all personnel in Tactical Combat Casualty Care and receives continuous feedback from prehospital trauma registry data facilitated Tactical Combat Casualty Care performance improvements centered on clinical outcomes that resulted in unprecedented reduction of killed-in-action deaths, casualties who died of wounds, and preventable combat death. This data-driven approach is the model for improving prehospital trauma care and casualty outcomes on the battlefield and has considerable implications for civilian trauma systems.
Background Ex vivo generated chimeric antigen receptor (CAR) T cell therapies have shown tremendous success in treating hematologic malignancies. However, this modality has significant limitations to ...providing treatment to a broader population: high cost of goods (COGS) and associated care, impractical redosability, requirement of cytotoxic lymphodepletion protocols, and insufficient accessibility to cell therapy centers for a large number of cancer patients who qualify for this treatment. LNP-mediated delivery of long coding RNA has been clinically validated for protein replacement, vaccines and gene editing.MethodsWe have been developing a novel, synthetic, circular coding RNA platform (oRNA technology) which exhibits significant improvements in production, expression and formulation compared to mRNAs. We have combined oRNA technology with novel immunotropic LNPs to address the limitations of ex vivo CAR-T therapies by creating off-the-shelf, yet ‘autologous’, in situ CAR (isCAR™) therapies. The anti-CD19 isCAR candidates were evaluated for in vitro cell killing and tumor regression in a Nalm6CD19+ mouse model.ResultsOur immunotropic LNPs show preferential biodistribution to the spleen, with oRNA reporter expression detected in multiple immune cell subsets, including T cells, macrophage and NK cells. Delivery to immune cells is preserved across mice, rats and non-human primates. In vitro, expanding human T cells expressing an anti-human CD19 CAR oRNA show potent and sustained cytotoxicity and pro-inflammatory cytokine production compared to controls. Sequence optimization of our oRNA construct drove high levels of CAR expression and cytotoxicity in primary human T cells that were significantly elevated compared to modified mRNA. These optimized IRES elements and coding sequences translated into a 20-fold increase in efficacy in mice treated with the corresponding LNP-oRNAs in a human PBMC-engrafted NALM6 tumor-bearing mouse model. The optimized LNP-oCAR enabled q2w dosing at clinically relevant dose levels producing well-tolerated, robust, and reproducible efficacy across multiple PBMC donors (figure 1).ConclusionsoRNA-enabled isCAR therapies promise a transient, re-dosable and scalable immune cell therapy without requiring immunodepletion for the treatment of cancer. We believe the ability to deliver to multiple immune cell types and large cargo space for multi-targeting provides a differentiated strategy in both hematological malignancies as well as solid tumors.Abstract 1205 Figure 1ORN-101 effectively controls leukemia growth when dosed every other week. NSG-MHC I/II double knockout mice were engrafted with Nalm6-fLUC B-ALL cells at D0. On D4, human peripheral blood mononuclear cells (PBMC) were engrafted, followed by LNP-oRNA dosing starting at D5. Animals received 4 doses, every other week, of LNP-CD19CAR at either 0.1 mg/kg or 0.3 mg/kg, or HER2 CAR 0.3 mg/kg (negative control). Animals were imaged twice weekly to monitor Nalm6 burden. Graphs show Nalm6 leukemia burden, based on tumor flux value, in ORN-101 or control treated individual mice.
On the battlefield, a properly applied tourniquet can be an extremely effective means of controlling severe extremity wound hemorrhage. However, a great deal of confusion exists among soldiers, ...medics, and military medical officers on a number of tourniquet-related issues. What is an appropriate combat tourniquet? When is it appropriate to use a tourniquet? When and by whom should a tourniquet be removed? Under what conditions should a tourniquet not be released or removed? What are the most effective ways to increase limb salvage while using a tourniquet? These and other issues were addressed by a panel of experts at the 2003 Advanced Technology Applications for Combat Casualty Care Conference, August 21 and 23, 2003, St. Pete Beach, Florida. Here we review those issues and present a summary of the panel's recommendations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The purpose of the present study is to introduce a laboratory model of hemorrhage with data comparing gauze wound packing and medical device use to better understand out-of-hospital hemorrhage ...control. The manikin trainer (Combat Ready Clamp Trainer Manikin; Operative Experience, Inc, North East, MD) had a gunshot wound of the right groin that bled water from the common femoral artery; the wound track went through the thigh posterior to anterior.
Abstract
Introduction. Airway compromise is the third leading cause of potentially preventable death on the battlefield. An understanding of the injuries associated with fatal airway compromise is ...necessary to develop improvements in equipment, training, and prehospital management strategies in order to maximize survival. Objective. To determine injury patters resulting in airway compromise in the combat setting. Methods. This was a subgroup analysis of cases previously examined by Kelly and colleagues, who reviewed autopsies of military personnel who died in combat in Iraq and Afghanistan between 2003 and 2006. Casualties with potentially survivable (PS) injuries and deaths related to airway compromise previously identified by Kelly et al. were reviewed in depth by a second panel of military physicians. Results. There were 982 cases that met the inclusion criteria. Of these, 232 cases had PS injuries. Eighteen (1.8%%) cases were found to have airway compromise as the likely cause of primary death. All had penetrating injuries to the face or neck. Twelve deaths (67%%) were caused by gunshot wounds, while six deaths (33%%) were caused by explosions. Nine cases had concomitant injury to major vascular structures, and eight had significant airway hemorrhage. Cricothyroidotomy was attempted in five cases; all were unsuccessful. Conclusion. Airway compromise from battlefield trauma results in a small number of PS fatalities. Penetrating trauma to the face or neck may be accompanied by significant hemorrhage, severe and multiple facial fractures, and airway disruption, leading to death from airway compromise. Cricothyroidotomy may be required to salvage these patients, but the procedure failed in all instances in this series of cases. Further studies are warranted to determine the appropriate algorithm of airway management in combat casualties sustaining traumatic airway injuries.
Brucella melitensis is a highly infectious animal pathogen able to cause a recurring debilitating disease in humans and is therefore high on the list of biological warfare agents. Immunoglobulin ...genes from mice immunized with gamma-irradiated
B. melitensis strain 16M were used to construct a library that was screened by phage display against similarly prepared bacteria. The selected phage particles afforded a strong enzyme-linked immunosorbent assay (ELISA) signal against gamma-irradiated
B. melitensis cells. However, extensive efforts to express the respective single chain antibody variable region fragment (scFv) in soluble form failed due to: (i) poor solubility and (ii) in vivo degradation of the c-myc tag used for the detection of the recombinant antibodies. Both problems could be addressed by: (i) fusing a human kappa light chain constant domain (Ck) chain to the scFv to generate single chain antibody fragment (scAb) antibody fragments and (ii) by co-expression of the periplasmic chaperone Skp. While soluble, functional antibodies could be produced in this manner, phage-displaying scFvs or scAbs were still found to be superior ELISA reagents for immunoassays, due to the large signal amplification afforded by anti-phage antibodies. The isolated phage antibodies were shown to be highly specific to
B. melitensis and did not recognize
Yersinia pseudotuberculosis in contrast to the existing diagnostic monoclonal YST 9.2.1.
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