Exposure to a Virtual Reality Mass-Casualty Simulation Elicits a Differential Sympathetic Response in Medical Trainees and Attending Physicians.

BACKGROUND: Previous studies have demonstrated the use of virtual reality (VR) in mass-casualty incident (MCI) simulation; however, it is uncertain if VR simulations can be a substitute for in-person disaster training. Demonstrating that VR MCI scenarios can elicit the same desired stress response achieved in live-action exercises is a first step in showing non-inferiority. The primary objective of this study was to measure changes in sympathetic nervous system (SNS) response via a decrease in heart rate variability (HRV) in subjects participating in a VR MCI scenario. METHODS: An MCI simulation was filmed with a 360º camera and shown to participants on a VR headset while simultaneously recording electrocardiography (EKG) and HRV activity. Baseline HRV was measured during a calm VR scenario immediately prior to exposure to the MCI scenarios, and SNS activation was captured as a decrease in HRV compared to baseline. Cognitive stress was measured using a validated questionnaire. Wilcoxon matched pairs signed rank analysis, Welch's t-test, and multivariate logistic regression were performed with statistical significance established at P <.05. RESULTS: Thirty-five subjects were enrolled: eight attending physicians (two surgeons, six Emergency Medicine [EM] specialists); 13 residents (five Surgery, eight EM); and 14 medical students (six pre-clinical, eight clinical-year students). Sympathetic nervous system activation was observed in all groups during the MCI compared to baseline (P <.0001) and occurred independent of age, sex, years of experience, or prior MCI response experience. Overall, 23/35 subjects (65.7%) reported increased cognitive stress in the MCI (11/14 medical students, 9/13 residents, and 3/8 attendings). Resident and attending physicians had higher odds of discordance between SNS activation and cognitive stress compared to medical students (OR = 8.297; 95% CI, 1.408-64.60; P = .030). CONCLUSIONS: Live-actor VR MCI simulation elicited a strong sympathetic response across all groups. Thus, VR MCI training has the potential to guide acquisition of confidence in disaster response.

Physiologic Fidelity as a Domain in Assessing Mixed Reality Trauma Simulation.

INTRODUCTION: Mixed reality has been used in trauma and emergency medicine simulation for more than a decade. As mixed reality potential in trauma simulation continues to expand, so too does the need to validate it as a surrogate for real-life emergency scenarios. Validation of these simulations can occur by measuring fidelity, or the degree to which a computing system can reproduce real-world experiences. After performing a literature review, we determined that most fidelity assessments of trauma and emergency simulations focus on how the user subjectively experiences the simulation. Although subjective user assessment is an important component of determining fidelity, we pose an introductory three-part framework that may assess mixed reality trauma simulation more adequately. MATERIALS AND METHODS: A literature review was conducted using Google Scholar, PubMed, and the Uniformed Services University PowerER search database. Relevant articles were assessed to identify how studies measured fidelity in trauma simulation. We then designed the three-part framework to aid researchers in assessing the fidelity of mixed reality trauma simulations. RESULTS: The domains we determined to best assess mixed reality emergency simulation are as follows:1. Continue assessing fidelity via subjective user assessments. This allows the researcher to know how real the simulation looked and felt to the user based on their individual report.2. Determine whether the trauma simulation changes the medical decision-making capacity of the user. If the user's decision-making capacity changes with a stress-inducing trauma simulation versus a non-stress-inducing simulation, then the stress-inducing trauma environment would be approaching greater fidelity.3. Study the domain of our newly proposed concept: physiologic fidelity. We define physiologic fidelity as the degree to which the simulation elicits a measurable, autonomic response independent of observed emotion or perceived affect. Recreating objective autonomic arousal may be the best way to ensure a trauma simulation reaches fidelity. CONCLUSION: We propose a methodology to assess mixed reality trauma simulation fidelity. Once fidelity is more fully known to the researcher and the simulation user, adjustments can be made to approach reality more closely. Improved simulators may enrich the preparedness of both junior and senior learners for real-life emergencies. We believe assessing the three domains using the Wide Area Virtual Experience at the Val G. Hemming simulation center in Bethesda, MD, will validate mixed reality-trauma simulators as invaluable surrogates for real-life emergency scenarios and ultimately contribute to improved clinical outcomes for clinicians and their patients.

Anti-Fn14-Conjugated Prussian Blue Nanoparticles as a Targeted Photothermal Therapy Agent for Glioblastoma.

Prussian blue nanoparticles (PBNPs) are effective photothermal therapy (PTT) agents: they absorb near-infrared radiation and reemit it as heat via phonon-phonon relaxations that, in the presence of tumors, can induce thermal and immunogenic cell death. However, in the context of central nervous system (CNS) tumors, the off-target effects of PTT have the potential to result in injury to healthy CNS tissue. Motivated by this need for targeted PTT agents for CNS tumors, we present a PBNP formulation that targets fibroblast growth factor-inducible 14 (Fn14)-expressing glioblastoma cell lines. We conjugated an antibody targeting Fn14, a receptor abundantly expressed on many glioblastomas but near absent on healthy CNS tissue, to PBNPs (aFn14-PBNPs). We measured the attachment efficiency of aFn14 onto PBNPs, the size and stability of aFn14-PBNPs, and the ability of aFn14-PBNPs to induce thermal and immunogenic cell death and target and treat glioblastoma tumor cells in vitro. aFn14 remained stably conjugated to the PBNPs for at least 21 days. Further, PTT with aFn14-PBNPs induced thermal and immunogenic cell death in glioblastoma tumor cells. However, in a targeted treatment assay, PTT was only effective in killing glioblastoma tumor cells when using aFn14-PBNPs, not when using PBNPs alone. Our methodology is novel in its targeting moiety, tumor application, and combination with PTT. To the best of our knowledge, PBNPs have not been investigated as a targeted PTT agent in glioblastoma via conjugation to aFn14. Our results demonstrate a novel and effective method for delivering targeted PTT to aFn14-expressing tumor cells via aFn14 conjugation to PBNPs.

Pediatric Blast Trauma: A Systematic Review and Meta-Analysis of Factors Associated with Mortality and Description of Injury Profiles.

INTRODUCTION: Blast polytrauma is among the most serious mechanisms of injury confronted by medical providers. There are currently no specific studies or guidelines that define risk factors for mortality in the context of pediatric blast injuries or describe pediatric blast injury profiles. OBJECTIVE: The objectives of this study were to evaluate risk factors for pediatric mortality and to describe differences in injury profiles between explosions related to terrorism versus unrelated to terrorism within the pediatric population. METHODS: A PRISMA systematic review and meta-analysis was performed where articles published from the years 2000-2021 were extracted from PubMed. Mortality and injury profile data were extracted from articles that met inclusion criteria. A bivariant unadjusted odds ratio (OR) analysis was performed to establish protective and harmful factors associated with mortality and to describe the injury profiles of blasts related to terrorism. Statistical significance was established at P < .05. RESULTS: Thirty-eight articles were included and described a total of 222,638 unique injuries. Factors associated with increased mortality included if the explosion was related to terrorism (OR = 32.73; 95% CI, 28.80-37.21; P < .05) and if the explosion involved high-grade explosives utilized in the Global War on Terror ([GWOT] OR = 1.28; 95% CI, 1.04-1.44; P < .05). Factors associated with decreased mortality included if the patient was resuscitated in a North Atlantic Treaty Organization (NATO)-affiliated combat trauma hospital (OR = 0.48; 95% CI, 0.37-0.62; P < .05); if the explosive was fireworks (OR = 3.20×10-5; 95% CI, 2.00×10-6-5.16×10-4; P < .05); and if the explosion occurred in the United States (OR = 2.40×10-5; 95% CI, 1.51×10-6-3.87×10-4; P < .05). On average, victims of explosions related to terrorism were 10.30 years old (SD = 2.73) with 68.96% (SD = 17.58%) of victims reported as male. Comparison of victims of explosions related to terrorism revealed a higher incidence of thoracoabdominal trauma (30.2% versus 8.6%), similar incidence of craniocerebral trauma (39.5% versus 43.1%), and lower incidence of extremity trauma (31.8% versus 48.3%) compared to victims of explosions unrelated to terrorism. CONCLUSION: Explosions related to terrorism are associated with increased mortality and unique injury profiles compared to explosions unrelated to terrorism in the pediatric population. Such findings are important for optimizing disaster medical education of pediatric providers in preparation for and management of acute sequelae of blast injuries-terror-related and otherwise.

Disasters on campus: A cross-sectional survey of college EMS systems' preparedness to respond to mass casualty incidents.

OBJECTIVE: The objective of this study was to assess the training and readiness levels of Collegiate Emergency Medical Service (EMS) providers to respond to mass casualty incidents (MCIs). METHODS: An anonymous cross-sectional survey of Collegiate EMS providers was performed. PARTICIPANTS: Participants were US-based EMS providers affiliated with the National Collegiate Emergency Medical Services Foundation. OUTCOME MEASURES: The main outcome measures were levels of EMS experience and MCI training, subjective readiness levels for responding to various MCI scenarios, and analyzing the effect of the COVID-19 pandemic on MCI response capabilities. RESULTS: Respondents had a median age of 21 years (interquartile range IQR 20, 22), with 86 percent (n = 96/112) being trained to the Emergency Medical Technician-Basic level. Providers reported participating in an average of 1.6 MCI trainings over the last four years (IQR, 1.0, 2.2). Subjective MCI response readiness levels were highest with active assailant attacks followed by large event evacuations, natural disasters, hazardous material (HAZMAT) incidents, targeted automobile ramming attacks, explosions, and finally bioweapons release. Disparate to this, only 18 percent of participants reported training in the fundamentals of tactical and disaster medicine. With respect to the effect of the COVID-19 pandemic on MCI readiness, 27 percent of respondents reported being less prepared, and there was a statistically significant decrease in subjective readiness to respond to HAZMAT incidents. CONCLUSION: Given low rates of MCI training but high rates of self-assessed MCI preparedness, respondents may overestimate their readiness to adequately respond to the complexity of a real-world MCI. More objective assessment measures are needed to evaluate provider preparedness.

Robot-assisted and augmented reality-assisted spinal instrumentation: a systematic review and meta-analysis of screw accuracy and outcomes over the last decade.

OBJECTIVE: The use of technology-enhanced methods in spine surgery has increased immensely over the past decade. Here, the authors present the largest systematic review and meta-analysis to date that specifically addresses patient-centered outcomes, including the risk of inaccurate screw placement and perioperative outcomes in spinal surgeries using robotic instrumentation and/or augmented reality surgical navigation (ARSN). METHODS: A systematic review of the literature in the PubMed, EMBASE, Web of Science, and Cochrane Library databases spanning the last decade (January 2011-November 2021) was performed to present all clinical studies comparing robot-assisted instrumentation and ARSN with conventional instrumentation techniques in lumbar spine surgery. The authors compared these two technologies as they relate to screw accuracy, estimated blood loss (EBL), intraoperative time, length of stay (LOS), perioperative complications, radiation dose and time, and the rate of reoperation. RESULTS: A total of 64 studies were analyzed that included 11,113 patients receiving 20,547 screws. Robot-assisted instrumentation was associated with less risk of inaccurate screw placement (p < 0.0001) regardless of control arm approach (freehand, fluoroscopy guided, or navigation guided), fewer reoperations (p < 0.0001), fewer perioperative complications (p < 0.0001), lower EBL (p = 0.0005), decreased LOS (p < 0.0001), and increased intraoperative time (p = 0.0003). ARSN was associated with decreased radiation exposure compared with robotic instrumentation (p = 0.0091) and fluoroscopy-guided (p < 0.0001) techniques. CONCLUSIONS: Altogether, the pooled data suggest that technology-enhanced thoracolumbar instrumentation is advantageous for both patients and surgeons. As the technology progresses and indications expand, it remains essential to continue investigations of both robotic instrumentation and ARSN to validate meaningful benefit over conventional instrumentation techniques in spine surgery.

Epidemiology of Blast Neurotrauma: A Meta-analysis of Blast Injury Patterns in the Military and Civilian Populations.

BACKGROUND: Mass casualty incidents (MCIs) due to bombing-related terrorism remain an omnipresent threat to our global society. The aim of this study was to elucidate differences in blast injury patterns between military and civilian victims affected by terrorist bombings. METHODS: An analysis of the Global Terrorism Database (GTD) and a PubMed literature search of casualty reports of bombing attacks from 2010-2020 was performed (main key words: blast injuries/therapy, terrorism, military personnel) with key epidemiological and injury pattern data extracted and statistically analyzed. RESULTS: Demographic analysis of casualties revealed that military casualties tend to be younger and predominantly male (P < 0.05) compared with civilians. Military casualties also reported higher amounts of head/neck injury (P < 0.01) compared with civilians. The proportion of instantaneous fatalities along with injuries affecting the thoracoabdominal and extremity regions remained approximately equal across both groups. CONCLUSIONS: Though the increased number of head/neck injuries was unexpected, we also found that the number of nonlethal head injuries also increased, predicating that more military blast neurotrauma patients survived their injuries. These data can be used to increase blast MCI preparation and education throughout the international neurosurgical community.

NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations.

Natural killer (NK) cells, the primary effector cells of the innate immune system, utilize multiple strategies to recognize tumor cells by (1) detecting the presence of activating receptor ligands, which are often upregulated in cancer; (2) targeting cells that have a loss of major histocompatibility complex (MHC); and (3) binding to antibodies that bind to tumor-specific antigens on the tumor cell surface. All these strategies have been successfully harnessed in adoptive NK cell immunotherapies targeting cancer. In this review, we review the applications of NK cell therapies across different tumor types. Similar to other forms of immunotherapy, tumor-induced immune escape and immune suppression can limit NK cell therapies' efficacy. Therefore, we also discuss how these limitations can be overcome by conferring NK cells with the ability to redirect their tumor-targeting capabilities and survive the immune-suppressive tumor microenvironment. Finally, we also discuss how future iterations can benefit from combination therapies with other immunotherapeutic agents.

Synthesis of a superparamagnetic iron oxide based nano-complex for targeted cell death of glioblastoma cells.

In the last ten years, there has been little advancement in the treatment of the aggressive brain cancer Glioblastoma Multiforme (GBM). This research describes the synthesis of a superparamagnetic iron oxide (SPION)-based nanotheraputic complex for use in targeting and killing aggressive mesenchymal GBM cells. The average sizes and magnetic properties of the synthesized SPIONs are tailored via a novel time-controlled approach to a previously described electrochemical reaction. Through this synthetic method, the optimal particle size where maximal thermal energy is released upon stimulation with an external magnetic field was determined to be 21 nm. The nano-complex was further modified to selectively target GBM cells by adding a heterobifunctional poly(ethylene) glycol polymer crosslinked to TWEAK (a GBM targeting peptide). Preliminary investigation with FITC Annexin V/propidium iodide fluorescent probes and transmission electron microscopy revealed biochemical and morphological evidence of both SPION internalization and cytotoxic effects over the course of three hours. Thus, these nano-complexes hold promise as a potential treatment agent for an otherwise untreatable disease.