Pharmacokinetics of tranexamic acid (TXA) delivered by expeditious routes in a swine model of polytrauma and hemorrhagic shock.

OBJECTIVE: Hemorrhage is the leading cause of preventable death in civilian trauma centers and on the battlefield. One of the emerging treatment options for hemorrhage in austere environments is tranexamic acid (TXA). However, the landscape is not amenable to the current delivery standard. This study compared the pharmacokinetics of TXA via a standard 10-minute intravenous infusion (IV infusion), intravenous rapid push over 10 s (IV push), and intramuscular injection (IM) in a swine polytrauma and hemorrhagic shock model (trauma group) compared to uninjured controls (control group). METHODS: Thirty swine were randomized to the trauma or control group. Following anesthesia, the trauma group experienced a simulated blast injury and 40% controlled hemorrhage. Subjects in both groups were then randomized to receive 1 g/10 mL TXA via IV infusion, IV push, or IM. Animals were monitored for four hours with serial blood sampling. Serum TXA concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and analyzed. RESULTS: The time to maximum TXA concentration (Tmax) was not affected by trauma in IV infusion or IV push, but was affected in the IM administration with Tmax significantly slower than the control group (p = 0.016). The minimum effective serum concentration of TXA (Ceff, 10 µg/mL) was reached in less than one minute with IV infusion and instantaneously with IV push. Despite lower bioavailability, the time to reach Ceff (Teff) was achieved via IM administration in less than 10 minutes for both groups (6.4 minutes trauma vs. 2.1 minutes control). CONCLUSIONS: In austere prehospital environments, an alternative to intravenous infusion of a life-saving medication is desired. Administration of TXA via all three methods reached the level needed to cause substantial inhibition of fibrinolysis within 10 minutes. The IV push method showed similar pharmacokinetics to IV infusion of TXA but can be delivered quickly without sacrificing an access site for 10 minutes.

Neurocutaneous Disorders in Pregnancy.

Importance: Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population. Objective: This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient. Evidence Acquisition: A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms "pregnancy," "Sturge -Weber," "Neurofibromatosis Type 1," "neurofibromatosis type 2," "von Hippel Lindau," "Tuberous Sclerosis," "neurocutaneous disorder," "treatment," "congenital malformations," "neurodevelopmental defects," "miscarriage," "breastfeeding," "autoimmune," "pathophysiology," and "management." References of included articles were searched to identify any articles that may have been missed after the above method was used. Results: Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder. Conclusion and Relevance: Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients.

Substrate-Selective Adhesion of Metal Nanoparticles to Graphene Devices.

Nanostructured electronic devices, such as those based on graphene, are typically grown on top of the insulator SiO2. Their exposure to a flux of small size-selected silver nanoparticles has revealed remarkably selective adhesion: the graphene channel can be made fully metallized, while the insulating substrate remains coverage-free. This conspicuous contrast derives from the low binding energy between the metal nanoparticles and a contaminant-free passivated silica surface. In addition to providing physical insight into nanoparticle adhesion, this effect may be of value in applications involving deposition of metallic layers on device working surfaces: it eliminates the need for masking the insulating region and the associated extensive and potentially deleterious pre- and postprocessing.

Ultrasound Localization of Resuscitative Endovascular Balloon Occlusion of the Aorta in a Human Cadaver Model.

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a method of gaining proximal control of noncompressible torso hemorrhage (NCTH). Catheter placement is traditionally confirmed with fluoroscopy, but few studies have evaluated whether ultrasound (US) can be used. METHODS: Using a pressurized human cadaver model, a certified REBOA placer was shown one of four randomized cards that instructed them to place the REBOA either correctly or incorrectly in Zone 1 (the distal thoracic aorta extending from the celiac artery to the left subclavian artery) or Zone 3 (in the distal abdominal aorta, from the aortic bifurcation to the lowest renal artery). Once the REBOA was placed, 10 US-trained locators were asked to confirm balloon placement via US. The participants were given 3 minutes to determine whether the catheter had been correctly placed, repeating this 20 times on two cadavers. RESULTS: Overall, US exhibited an average sensitivity of 83%, specificity of 76%, and accuracy of 80%. For Zone 1, US showed a sensitivity of 78% and specificity of 83%, and for Zone 3, a sensitivity of 88% and specificity of 76%. In addition, US exhibited a likelihood positive ratio (LR+) of 3.73 and a likelihood negative ratio (LR-) of 0.22 for either position, with similar numbers for Zone 1 (+4.57, -0.26) and Zone 3 (+3.16, -0.16). CONCLUSION: Ultrasound could prove to be a useful tool for confirming placement of a REBOA catheter, especially in austere environments.

Fetal effects of mild maternal COVID-19 infection: metabolomic profiling of cord blood.

INTRODUCTION: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. OBJECTIVES: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. METHODS: Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure. RESULTS: Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95% CI) = 0.841 (0.725-0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response. CONCLUSION: We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population.

Cric in the Dark: Surgical Cricothyrotomy in Low Light Tactical Environments.

BACKGROUND: Surgical cricothyrotomy (SC) is a difficult procedure with high failure rates in the battlefield environment. The difficulty of this procedure is compounded in a low-light tactical environment in which white light cannot be used. This study compared the use of red-green (RG) light and red (R) light in the performance of SC in a low-light environment. MATERIALS AND METHODS: Tactical Combat Casualty Care-certified navy corpsmen (n = 33) were provided 15 minutes of standardized instruction followed by hands-on practice with the Tactical CricKit and the H&H bougie-assisted Emergency Cricothyrotomy Kit. Participants acclimated to a dark environment for 30 minutes before performing SC on a mannequin with both devices using both R and RG light in a randomized order. Application time, success, participant preference, and participant confidence were analyzed. RESULTS: There were similarly high levels of successful placement (>87.5%) in all four cohorts. Light choice did not appear to affect placement time with either of the two kits. On Likert-scale surveys, participants reported that RG decreased difficulty (p < .0001) and increased confidence (p < .0001) in performing the procedure. CONCLUSION: RG light increased confidence and decreased perceived difficulty when performing SC, though no differences in placement time or success were observed.

iTClamp-Mediated Wound Closure Speeds Control of Arterial Hemorrhage With or Without Additional Hemostatic Agents.

BACKGROUND: Exsanguination is the leading cause of preventable posttraumatic death, especially in the prehospital arena. Traditional hemorrhage control methods involve packing the wound with hemostatic agents, providing manual pressure, and then applying a pressure dressing to stabilize the treatment. This is a lengthy process that frequently destabilizes upon patient transport. Conversely, the iTClamp, a compact wound closure device, is designed to rapidly seal wound edges mechanically, expediting clot formation at the site of injury. OBJECTIVES: To determine the efficacy of the iTClamp with and without wound packing in the control of a lethal junction hemorrhage. METHODS: Given the limited available information regarding the efficacy of the iTClamp in conjunction with traditional hemostatic agents, this study used a swine model of severe junctional hemorrhage. The goal was to compare a multiagent strategy using the iTClamp in conjunction with XSTAT to the traditional method of Combat Gauze packing with pressure dressing application. Readouts include application time, blood loss, and rebleed occurrence. RESULTS: Mean application times of the iTClamp treatment alone or in conjunction with other hemostatic agents were at least 75% faster than the application time of Combat Gauze with pressure dressing. Percent blood loss was not significantly different between groups but trended the highest for Combat Gauze treated swine, followed by iTClamp plus XSTAT, iTClamp alone and finally iTClamp plus Combat Gauze. CONCLUSION: The results from this study demonstrate that the iTClamp can be effectively utilized in conjunction with hemostatic packing to control junctional hemorrhages.

Speed, Skill Retention, and End User Perceptions of iTClamp Application by Navy Corpsmen on a Manikin Model of Femoral Hemorrhage.

INTRODUCTION: Tactical Combat Casualty Care guidelines recommend packing junctional wounds with gauze, applying direct pressure for 3 minutes, and then securing with an external pressure dressing. This method is time-consuming, which can be problematic in a combat environment. Alternatively, the iTClamp has documented efficacy and rapid application. However, no studies have evaluated device application by military prehospital medical providers, such as Navy corpsmen, or their user experience with the device. MATERIALS AND METHODS: Research data derived from a protocol were approved by the Naval Medical Center Portsmouth's Institutional Review Board in compliance with all applicable federal regulations governing the protection of human subjects. Navy corpsmen with the current Tactical Combat Casualty Care certification applied the iTClamp or standard pressure dressing on a manikin model of femoral hemorrhage in a crossover study design. Each participant used both devices in a randomized fashion. Time to application was recorded, and participants completed Likert scale surveys to evaluate both devices for preference, ease of use, and physical assessment. A repeat assessment was performed 1 month later to assess skill atrophy. Repeated-measures ANOVA was used to compare application time. Likert scale survey data were analyzed using Mann-Whitney and Wilcoxon tests to compare survey data within and between time points, respectively. RESULTS: The application of the iTClamp was more than twice as fast as the application of pressure dressings at both the initial and follow-up evaluations. There was no statistically significant difference in application times between the first evaluation and the 30-day assessment of either device, indicating no atrophy in skill. While 65% and 52% of the participants expressed preference in for the iTClamp in their surveys during the initial and follow-up respective visits, the difference in preference was not statistically significant for either the initial or the follow-up survey. Open-ended survey responses yielded both perceived advantages and disadvantages for each treatment option. CONCLUSIONS: In austere or hostile environments, speed of treatment and extrication can have significant implications for the safety of both the patient and the medical providers. Hemorrhage control interventions must be both effective and easy to use for a prehospital provider to ensure its efficacy in a live battlefield situation. The iTClamp is small, simple, and fast to use, but its wide adoption in the field may be based on limitations perceived by participants, including narrow indications for use. However, based on our findings, it is reasonable to field the iTClamp depending on provider preference.

Drive-Through Medicine: A Novel Health Care Delivery Mechanism for the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) placed additional strain on an already struggling health care system. In response, novel solutions such as telehealth have been explored, however, there is significant room for innovation in health care delivery. OBJECTIVES: The aim of our study was to evaluate the effectiveness of a drive-through medical treatment system for evaluating patients with COVID-like symptoms. METHODS: We designed a prototype drive-through medical treatment facility (DMF) to triage large volumes of patients quickly and efficiently, while fully evaluating, treating, and discharging low-risk patients. A retrospective chart review was performed to extract clinical and logistical metrics. RESULTS: A total of 2164 patients were evaluated between May 1 and July 1, 2020. Overall accuracy for patient classification was 92.4% (95% confidence interval [CI] 91.2-93.5%). Screening criteria resulted in a return with need for workup or admission rate of 0.25%, yielding a sensitivity of 83.3% (95% CI 65.3-94.4%). Of those presenting to the DMF, 179 patients (8.3%) were diverted to the main emergency department (ED) for further evaluation, of which 14% received diagnostic workups and 5% subsequent admission to an inpatient service, yielding a specificity of 92.8% (95% CI 91.7- 93.9%). Length of stays for those seen in the DMF vs. the main ED (M = 38 min vs 149 min) yielded a mean difference of 111 min per encounter and a total time savings of 3762 h. CONCLUSION: Drive-through medical systems can accurately triage patients presenting with potential COVID-19 and effectively treat lower-risk patients, thereby reducing ED utilization.

Patient Perceptions of Drive-through Medical Treatment Facilities During the COVID-19 Pandemic.

INTRODUCTION: The cumulative burden of coronavirus disease 2019 (COVID-19) on the United States' healthcare system is substantial. To help mitigate this burden, novel solutions including telehealth and dedicated screening facilities have been used. However, there is limited data on the efficacy of such models and none assessing patient comfort levels with these changes in healthcare delivery. The aim of our study was to evaluate patients' perceptions of a drive-through medical treatment system in the setting of the COVID-19 pandemic. METHOD: Patients presenting to a drive-through COVID-19 medical treatment facility were surveyed about their experience following their visit. An anonymous questionnaire consisting of five questions, using a five-point Likert scale was distributed via electronic tablet. RESULTS: We obtained 827 responses over two months. Three quarters of respondents believed care received was similar to that in a traditional emergency department (ED). Overall positive impression of the drive-through was 86.6%, and 95% believed that it was more convenient. CONCLUSION: Overall, the drive-through medical system was perceived as more convenient than the ED and was viewed as a positive experience. While representing a dramatic change in the delivery model of medical care, if such systems can provide comparable levels of care, they may be a viable option for sustained and surge healthcare delivery.

A comparison of efficacy, efficiency, and durability in novel tourniquet designs.

BACKGROUND: Exsanguination due to extremity hemorrhage is a major cause of preventable traumatic deaths. Extremity tourniquet use has been shown to be safe and improve survival. The purpose of this study was to compare the efficacy, efficiency, and durability of the Generation 7 Combat Application Tourniquet (CAT; North American Rescue, Greer, SC), the Tactical Mechanical Tourniquet (TMT; Combat Medical Systems, Harrisburg, NC), and the SOF Tactical Tourniquet-Wide (SOFTT-W; Tactical Medical Solutions, Anderson, SC). METHODS: This study was a three-phase randomized, cross-over trial. In successive trials, subjects were timed during the application of each tourniquet to the upper and lower extremity. Following successful lower extremity application, subjects low crawled 25 ft and then were dragged 25 ft, after which effectiveness was reassessed, as defined by the cessation of distal pulses by Doppler ultrasound. RESULTS: In arm application, both the CAT and TMT had significantly less failure rates than the SOFTT-W (5.56%, 19.44%, 58.33%), with the CAT being the fastest tourniquet when compared with TMT and SOFTT-W (37.8 seconds, 65.01 seconds, 63.07 seconds). In leg application, the CAT had significantly less rates of failure when compared with the SOFTT-W, but there was no other significant difference between the tourniquets (27.78%, 44.44%, 61.11%). In addition, the CAT was significantly faster than both the TMT and SOFTT-W when applied to the leg (8.33 seconds, 40.96 seconds, 34.5 seconds). There was no significant difference in tourniquet failure rates between the three tourniquets after subject maneuvers in phase 3 (34.29%, 42.86%, 45.45%). DISCUSSION: The CAT is as effective as the TMT and significantly more effective than the SOFTT-W. In addition, the CAT demonstrated shorter application times than either the TMT or SOFTT-W. However, there was no significant difference between the three tourniquets in their ability to maintain pulselessness after subject maneuvers. LEVEL OF EVIDENCE: Care management, level II.

Efficacy of Hemostatic Gauzes in a Swine Model of Prolonged Field Care with Limb Movement.

INTRODUCTION: Prolonged field care for junctional wounds is challenging and involves limb movement to facilitate transport. No studies to date have explored the efficacy of gauze products to limit rebleeding in these scenarios. MATERIALS AND METHODS: We randomly assigned 48 swine to QuikClot Combat Gauze, ChitoGauze, NuStat Tactical, or Kerlix treatment groups (12 each) and then inflicted a severe groin injury by utilizing a modified Kheirabadi model of a 6-mm femoral artery punch followed by unrestricted bleeding for 60 seconds. We reassessed rebleed following limb movement at 30 minutes of stabilization and 4 hours after stabilization. RESULTS: Swine treated with Combat Gauze proved to have the lowest incidence of rebleeding, and conversely, NuStat Tactical had the highest incidence of rebleeding at wounds after limb movement. Importantly, rebleeds occurred at a rate of 25%-58% across all swine treatment groups at 30 minutes postinjury and 0%-42% at 270 minutes postinjury demonstrating that limb movements universally challenge hemostatic junctional wounds. CONCLUSIONS: Our findings highlight the difficulty of controlling hemorrhage from junctional wounds with hemostatic gauze in the context of prolonged field care and casualty transport. Our research can guide selection of hemorrhage control gauze when patients have prolonged field extraction or difficult transport. Our data demonstrates the frequency of junctional wound rebleeding after movement and thus the importance of frequent patient reassessment.

Development and growth of corrosion features on protected silver mirrors during accelerated environmental exposure.

Various layer schemes have been developed to protect thin film silver mirrors from tarnish and corrosion. However, the mechanisms by which these additional layers improve mirror durability are not fully understood. Accelerated environmental exposure testing of protected silver mirrors was used to investigate the effects of layer composition on the mechanisms of corrosion feature development and growth. Two model mirror coatings were analyzed in which the composition of the base layer below the silver and the adhesion layer above the silver were varied. Large circular corrosion features formed preferentially along the silver-chromium interfaces, regardless of where this interface was located within the layered structure of the mirror. The corrosion features originated at coating defects in the dielectric protection layer, and their growth was likely driven by the oxidation and chloridation of both silver and chromium at the Ag-Cr interfaces.

Wrist Injury in Deployed U.S. Marine-How to Maintain the Mission.

Wrist pain commonly affects military members and while most instances are benign, some require urgent orthopedic attention to prevent permanent loss of function. A 27-year-old male Marine while deployed presented with wrist pain after a seemingly benign fall during recreation. Radiographs were initially read as unremarkable and treated as a sprain. Though when reviewed by the Shock Trauma Platoon physicians, a perilunate dislocation was noted. After unsuccessful closed attempts to reduce injury, the Marine was sent to orthopedic surgery and underwent open reduction internal fixation and required a subsequent closed reduction and percutaneous pinning. Perilunate dislocations are uncommon but are among the most severe types of wrist injuries. This case is a reminder that proper evaluation of all injuries is critical. Proper evaluation of wrist injuries includes an attentive physical exam and careful examination of the radiographs; paying close attention to Gilula arcs and collinearity of the radius, lunate, and capitate. Prompt recognition and referral to specialty care for definitive treatment are important to maximize functional outcomes.

Pilot Study of a Novel Swine Model for Controlling Junctional Hemorrhage Using the iTClamp in Conjunction With Hemostatic Agents.

Exsanguinating hemorrhage is a primary cause of battlefield death. The iTClamp is a relatively new device (FDA approval in 2013) that takes a different approach to hemorrhage control by applying mechanism wound closure. However, no previous studies have explored the feasibility of utilizing the iTClamp in conjunction with hemostatic packing. To fill this important gap in the literature, a novel swine model was developed, and a total of 12 trials were performed using QuikClot Combat Gauze or XSTAT sponges in conjunction with the iTClamp to treat arterial injuries through 5 cm or 10 cm skin incisions in the groin, axilla, or neck. First-attempt application success rate, application time, and blood loss were recorded. Hemostasis was achieved on all wounds, though reapplication was required in one Combat Gauze and three XSTAT applications. Application averaged ~50% slower for Combat Gauze (M = 41 seconds, 95%CI: 22-32 seconds) than for XSTAT (M = 27 seconds, 95%CI: 35-47 seconds). XSTAT application was faster than Combat Gauze for each wound location and size. The 10 cm wounds took ~10 seconds (36%) longer to close (M = 27 seconds, 95%CI: 35-47 seconds) than the 5 cm wounds (M = 27 seconds, 95%CI: 35-47 seconds). Blood loss was similar for Combat Gauze (M = 51 mL, 95%CI: 25-76 mL) and XSTAT (M = 60 mL, 95%CI: 30-90 mL). Blood loss was roughly twice as great for 10 cm wounds (M = 73 mL, 95%CI: 47-100 mL) than for 5 cm wounds (M = 38 mL, 95%CI: 18-57 mL). This pilot study supports the feasibility of a novel model for testing the iTClamp in conjunction with hemostatic packing towards controlling junctional hemorrhage.

A rare seizure: Tumor lysis syndrome after radiation therapy of a solid tumor.

Tumor lysis syndrome (TLS) is an uncommon but life threatening condition seen in oncology patients. Due to its underlying pathophysiology, it is classically associated with hematologic malignancies following chemotherapeutic treatment. In this article, we present a case of TLS in the setting of two rare features: a solid tumor malignancy and the absence of recent chemotherapy. We briefly review risk factors and the diagnosis of this potentially fatal but treatable condition.