Abdominal Aortic Junctional Tourniquet - Stabilized (AAJTS) can be applied both successfully and rapidly by Combat Medical Technicians (CMTs).

BACKGROUND: 'Non-compressible' haemorrhage is the leading cause of preventable battlefield death, often requiring surgical or radiological intervention, which is precluded in the pre-hospital environment. One-fifth of such bleeds are junctional and therefore potentially survivable. We examine the use of the Abdominal Aortic Junctional Tourniquet - Stabilized (AAJTS) among UK Combat Medical Technicians (CMTs) as a device to control junctional haemorrhage with external compression of the abdominal aorta-compression of junctional haemorrhage previously considered 'non-compressible.' This follows animal studies showing that the AAJTS achieves control of haemorrhage and improves physiological parameters. METHODS: CMTs were selected and applied the AAJTS to each other following a 1-hour training package. A consultant radiologist-operated hand-held ultrasound monitored flow changes in the subjects' common femoral artery. CMTs were then surveyed for their opinions as to utility and function. RESULTS: 21 CMTs were screened and 17 CMTs participated with 34 total applications (16 day and 18 low-light). 27/34 (79%) achieved a successful application. The median application time was 75 s in daylight and 57 s in low-light conditions. There was no significant difference in Body Mass Index (p=0.23), median systolic blood pressure (p=0.19), nor class of CMT (p=0.10) between successful and unsuccessful applications. Higher systolic blood pressure was associated with longer application times (p=0.03). Users deemed the device easy to use (median score 4.4 on a 5-point Likert scale). CONCLUSION: CMTs can use AAJTS successfully after a 1-hour training session in the majority of applications. Application was successful in both daylight and low-light conditions. Self-reported usability ratings were high.

Interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity.

Infections caused by enveloped viruses require fusion with cellular membranes for viral genome entry. Viral entry occurs following an interaction of viral and cellular membranes allowing the formation of fusion pores, by which the virus accesses the cytoplasm. Here, we focus on interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity. IFITM3 is predicted to block or stall viral fusion at an intermediate state, causing viral propagation to fail. After introducing IFITM3, we describe the generalized lipid membrane fusion pathway and how it can be stalled, particularly with respect to IFITM3, and current questions regarding IFITM3's topology, with specific emphasis on IFITM3's amphipathic α-helix (AAH) 59V-68M, which is necessary for the antiviral activity. We report new hydrophobicity and hydrophobic moment calculations for this peptide and a variety of active site peptides from known membrane-remodeling proteins. Finally, we discuss the effects of posttranslational modifications and localization, how IFITM3's AAH may block viral fusion, and possible ramifications of membrane composition.

Secure app-based secondary healthcare clinical decision support to deployed forces in the UK Defence Medical Services.

BACKGROUND: Modern instant messaging systems facilitate reach-back medical support for Defence Medical Services (DMS) by connecting deployed clinicians to remote specialists. The mobile app Pando (Forward Clinical, UK) has been used for this purpose by the DMS via the 'Ask Advice' function. We aimed to investigate the usage statistics for this technology in its first 1000 days to better understand its role in the DMS. METHODS: An observational study was undertaken using metadata extracted from the prospective database within the application server for clinical queries between June 2019 and February 2022. These data included details regarding number and name of specialties, timings, active users per day and the number of conversations. RESULTS: There were 29 specialties, with 298 specialist users and 553 requests for advice. The highest volume of requests were for trauma and orthopaedics (n=116; 21.0%), ear, nose and throat (n=67; 12.1%) and dermatology (n=50; 9.0%). There was a median of 164 (IQR 82-257) users logged in per day (range 2-697). The number of requests during each day correlated with the number of users on that day (r=0.221 (95% CI 0.159 to 0.281); p<0.001). There were more daily users on weekdays than weekends (215 (IQR 123-277) vs 88 (IQR 58-121), respectively; p<0.001). For the top 10 specialties, the median first response time was 9 (IQR 3-42) min and the median time to resolution was 105 (IQR 21-1086) min. CONCLUSION: In the first 1000 days of secure app-based reach-back by the DMS there have been over 500 conversations, responded to within minutes by multiple specialists. This represents a maturing reach-back capability that may enhance the force multiplying effect of defence healthcare while minimising the deployed 'medical footprint'. Further discussions should address how this technology can be used to provide appropriately responsive clinical advice within DMS consultant job-planned time.

Thirty-Day Mortality for Proximal Femoral Fractures Treated at a U.K. Elective Center with a Site-Streaming Policy During the COVID-19 Pandemic.

COVID-19 led to the reconfiguration of U.K. orthopaedic trauma services because surgical capacity was threatened in acute centers. We report the 30-day mortality of proximal femoral fractures in older adults treated at an elective orthopaedic center. METHODS: Patients >60 years old who presented with a proximal femoral fracture to any of 4 sites in the regional trauma network were transferred to our elective center for emergency surgery. Care was modeled according to the National Institute for Health and Care Excellence guidelines, and efforts were made to treat all patients within 36 hours. Data were collected prospectively, and mortality outcomes were recorded. RESULTS: Of the 192 patients who presented to the elective orthopaedic center, 167 were treated there. The median age of the latter patients was 88 years (interquartile range, 83 to 79 years). The median Charlson Comorbidity Index was 4 (interquartile range, 4 to 6). The median time from emergency department admission to surgical treatment was 24.5 hours (interquartile range, 18.8 to 34.7 hours). The 30-day rate of mortality was 10.2%. A total of 29 (17.4%) tested positive for COVID-19 during their admission, of whom 10 died, for a case-fatality rate of 34.5%. There were no significant differences in age (p = 0.33) or Charlson Comorbidity Index (p = 0.13) between patients who tested positive and those who did not. There was no significant difference in age between those who tested positive and died and those who tested positive and did not die (p = 0.13), but there was a significant difference in Charlson Comorbidity Index between those subgroups (p = 0.03). CONCLUSIONS: During a pandemic, an elective orthopaedic center can be reconfigured to a surgical center for older patients with proximal femoral fractures with acceptable health-care quality outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Highly realistic cadaveric trauma simulation of the multiply injured battlefield casualty: an international, multidisciplinary exercise in far-forward surgical management.

INTRODUCTION: We designed an ultra-high-fidelity military cadaveric surgical simulation course to train military medical teams for specific battlefield injuries. Our aim was to deliver a highly realistic, immersive simulation training experience, teaching both technical and non-technical skills necessary for the management of war-injuries in the austere environment of a far forward surgical facility. We designed an educational cohort study around the course to measure its learning impact. METHODS: 25 personnel participated in 15 non-continuous hours of simulation that included 12 patient scenarios. Participants were given previously piloted questionnaires pre- and post-simulation to assess their confidence with managing battlefield injuries by body area, their views on the realism of the simulation, and their perceptions of training benefit. All questions were assessed using a Likert scale of 1-10 (10=best). RESULTS: The response rate for complete questionnaires was 95%. Baseline confidence scores were; abdomen (5.5), pelvis (5.7), chest (6.2), airway (6.3), extremity (7.3). Confidence gains following training were; abdomen (+1.7), pelvis (+ 1.6), chest (+1.6), airway (+1.2), extremity (+0.8). The most realistic aspects of the simulation were; injury replication (9.1), the cadaver as a multiply injured casualty (9.1) and the multidisciplinary team (9.2). The mean ratings for technical and non-technical skill acquisition were 9.1 and 9.0 respectively. Cadaveric simulation was reported to be ideal for learning military medical skills (9.3), and participants strongly recommended that provision should be increased (9.7). CONCLUSION: We have demonstrated an ability to recreate highly realistic injuries in an ultra-high-fidelity simulation of a multiply injured military casualty. There was a measurable increase in confidence for both technical skills in all major body areas, and non-technical skills. Multinational and multidisciplinary working strongly enhanced learning.

Quantifying the uncertainty of transfer of Cronobacter spp. between fomites and floors and touch points in dairy processing plants.

Cronobacter spp. are opportunistic pathogens that must be controlled in infant powder manufacturing plants. This study evaluated the spread of Cronobacter cells via contact surfaces within a dairy manufacturing environment. Transfer rates of Cronobacter spp. were determined from vectors for transmission including moveable fomites (e.g. trolley wheels and boots) and gloved hands to various types of recipient surfaces (stainless steel, linoleum and resin-coated concrete) typical for dairy manufacturing environments. Overall, with a starting inoculum of 106 CFU/mL, approximately 104 CFU/mL Cronobacter cells were transferred from each fomite onto each recipient surface during the initial transfer event. Gloved hands transferred the highest number of Cronobacter cells, followed by polyvinylchloride boots and then polyurethane trolley wheels. We demonstrate, using a combination of experimental data and uncertainty analysis, that if a movable fomite (boots or trolley wheels), or gloves became contaminated, Cronobacter could be spread over a wide area within a manufacturing plant. To the authors' knowledge, this is the first quantitative estimation of the spread of Cronobacter within a dairy manufacturing plant, that can also be practically applied as a tool for providing information in making risk management decisions. In particular, the estimation of spread suggests areas for cleaning and sanitation within a dairy manufacturing environment during a contamination event.

The Combat Application Tourniquet Versus the Tactical Mechanical Tourniquet.

BACKGROUND: Exsanguination from limb injury is an important battlefield consideration that is mitigated with the use of emergency tourniquets. The Combat Application Tourniquet (C-A-T®) is the current British military standard tourniquet. METHODS: We tested the self-application of a newer tourniquet system, the Tactical Mechanical Tourniquet (TMT), against self-application of the C-A-T. A total of 24 healthy British military volunteers self-applied the C-A-T and the TMT to their mid thigh in a randomized, sequential manner. Popliteal artery flow was monitored with a portable ultrasound machine, and time until arterial occlusion was measured. Pain scores were also recorded. Results The volunteers allowed testing on their lower limbs (n = 48 legs). The C-A-T was applied successfully to 22 volunteers (92%), and the TMT was successfully applied to 17 (71%). Median time to reach complete arterial occlusion was 37.5 (interquartile range [IQR], 27-52) seconds with the C-A-T, and 35 (IQR, 29-42) seconds with the TMT. The 2.5-second difference in median times was not significant (ρ = .589). The 1-in-10 difference in median pain score was also not significant (ρ = .656). The success or failure of self-application between the two tourniquet models as assessed by contingency table was not significant (p= .137). CONCLUSION: The TMT is effective when self-applied at the mid thigh. It does not offer an efficacy advantage over the C-A-T.

Non-battle injury among repatriated UK armed forces since cessation of combat operations: a prospective observational study.

AIM: To describe the mechanisms, burden of injury, inpatient management and rehabilitation requirements of wounded military personnel at the UK Role 4 (R4) facility within the first 12 months following cessation of combat operations in Afghanistan. METHODS: All aeromedical evacuations were recorded prospectively between October 2014 and October 2015. Demographic, logistical and clinical data were derived manually from referring medical unit and patient movement requests in addition to host nation and R4 medical records. RESULTS: Ninety-five patients were repatriated to R4 following traumatic injury: 98.9% (n=94) were male, and median age was 27 years (IQR 25-36 years). The most common mechanisms of injury (MOIs) were sports 26.3% (n=25), falls <2 m 11.6% (n=11) and road traffic collisions 9.8% (n=9). The most common anatomical regions of injury were isolated lower limb 24.1% (n=22), isolated hand 20.0% (n=19) and polytrauma 14.7% (n=14). Median Injury Severity Score was 4 (IQR 4-9), mean 8 (range 1-41). Eleven patients (11.6%) were discharged to rehabilitation units, of whom 7 (63.6%) required neurorehabilitation. CONCLUSION: Although service personnel sustain civilian-type injuries, the specific rehabilitation goals and shift in the acute rehabilitation requirements for military personnel must be considered in the absence of enduring combat operations. It is notable that permanent medical downgrading secondary to trauma still occurs outside of warfare. The colocation of civilian major trauma services and R4 has ensured a mutually beneficial partnership that contributes to institutional memory and improves the coordination of patient pathways. The importance of relevant resource allocation, training, support and logistical considerations remain, even during the current scale of military activity overseas.

Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy.

PURPOSE: Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP5+, MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients. METHODS: A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE. A dose reduction study was performed to establish the maximum tolerated dose (MTD) of MnBuOE. The safety and PK of a multi-dosing protocol was assessed. RESULTS: Peak plasma drug concentration occurred 30 min post-injection. The t 1/2 was defined as 7 h. MnBuOE induced an anaphylactic reaction and prolonged tachycardia. The MTD was defined as 0.25 mg/kg. The dogs were given MTD 3×/week for 2-3 weeks. The highest recorded tissue drug levels were in the lymph nodes (4-6 µM), followed by kidney and liver (2.5, 2.0 uM, respectively). CONCLUSIONS: We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.

Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma.

Positron emission tomography (PET) in conjunction with computed tomography is a frequently used modality for staging patients with lymphoma. Utility of PET-computed tomography before or early following auto-SCT has not been as rigorously evaluated. We retrospectively analyzed patients who received auto-SCT for treatment of relapsed or refractory non-Hodgkins lymphoma or Hodgkins disease between the years of 1996 and 2007. Patients who had either a PET scan following salvage chemotherapy within 14 weeks of transplantation (pre-PET), and/or a PET scan 6-14 weeks following transplantation (post-PET) were included. A total of 90 patients were identified for analysis. The median follow-up time is 3.3 years, with a range of 0.13-12.0 years. The median PFS was 4.6 years, and median OS was 5.1 years. At the time of this analysis, 34 patients (37%) experienced disease relapse, and 25 (27%) of the patients died from disease progression. In multivariate Cox proportional hazards analysis, post-PET did not predict for outcome, pre-PET positivity predicted for decrease in PFS. In conclusion, post-PET scan did not predict for PFS or OS in multivariate analysis. Positive pre-PET scan did predict for PFS as seen in previous studies, and may help identify patients who would benefit from innovative post transplant therapies.

Endoscopic evaluation of a complex ballistic injury.

The current conflict in Afghanistan is characterised by significant injuries resulting from the use of Improvised Explosive Devices. Increasing survivability from battlefield injury, escalating musculoskeletal ballistic trauma and the use of blast weaponry combine to produce an injury profile which defines contemporary combat casualty care. Such complex multi-system trauma challenges current wound care rationale. Ballistic injury of the perineum, often associated with proximal femoral injury and significant tissue loss, raises particular management difficulties. These cases demand an individualised, flexible approach due both to the extent of their wounds, logistical issues with positioning and often limited surgical approaches. Routine positioning and approaches around the pelvis may not be available to the surgical team due to presence of external fixators and tenuous skin bridges. The availability of donor skin to cover soft tissue defects is limited and as such, approaches to wounds with minimal additional tissue trauma are of particular use. We describe the benefits of endoscopic techniques and equipment in the evaluation and management of such an injury.

The impact of radiation therapy in patients with diffuse large B-cell lymphoma with positive post-chemotherapy FDG-PET or gallium-67 scans.

BACKGROUND: 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (PET) and gallium-67 citrate (gallium) response after chemotherapy are powerful prognostic factors in diffuse large B-cell lymphoma (DLBCL). However, clinical outcomes when consolidation radiation therapy (RT) is administered are less defined. PATIENTS AND METHODS: We reviewed 99 patients diagnosed with DLBCL from 1996 to 2007 at Duke University who had a post-chemotherapy response assessment with either PET or gallium and who subsequently received consolidation RT. Clinical outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Median follow-up was 4.4 years. Stage distribution was I-II in 70% and III-IV in 30%. Chemotherapy was R-CHOP or CHOP in 88%. Median RT dose was 30 Gy. Post-chemotherapy PET (n = 79) or gallium (n = 20) was positive in 21 of 99 patients and negative in 78 of 99 patients. Five-year in-field control was 95% with a negative PET/gallium scan versus 71% with a positive scan (P < 0.01). Five-year event-free survival (EFS; 83% versus 65%, P = 0.04) and overall survival (89% versus 73%, P = 0.04) were also significantly better when the post-chemotherapy PET/gallium was negative. CONCLUSIONS: A positive PET/gallium scan after chemotherapy is associated with an increased risk of local failure and death. Consolidation RT, however, still results in long-term EFS in 65% of patients.

Acidification of the phagosome in Crassostrea virginica hemocytes following engulfment of zymosan.

Phagocytic hemocytes are responsible for engulfing and internally degrading foreign organisms within the hemolymph and tissue of the eastern oyster, Crassostrea virginica. Since rapid acidification of the phagosome lumen is typically essential for activation of hydrolytic and reactive oxygen intermediate (ROI) producing enzymes in vertebrate cells, we measured phagosomal pH in oyster hemocytes by using the emission fluorescence of two fluorescent probes, rhodamine and Oregon Green 488 (OG 488), conjugated to zymosan to determine whether oyster hemocyte phagosomes become acidified after phagocytosis of zymosan. The average pH of 1079 phagosomes within 277 hemocytes 1 h after phagocytosis of zymosan was 3.9 +/- 0.03. Observations of 141 hemocytes with internalized zymosan by light microscopy revealed that, over a 60-min time period, 51% of highly granular hemocytes became partially granular, and 29% became agranular. In addition, 83% of partially granular hemocytes containing zymosan at time = 0 became agranular within 60 min. A comparison revealed that the phagosomes of agranular hemocytes were much more acidic (pH 3.1 +/- 0.02) than those of highly granular hemocytes (4.9 +/- 0.02; P < 0.05). These values are significantly lower than most reported in the literature for blood cells from metazoan organisms.