Rethinking Prehospital Response to Mass Casualty Events: Move, Treat, and Transport.

Herein, we present a simplified approach to prehospital mass casualty event (MASCAL) management called "Move, Treat, and Transport." Prior publications demonstrate a disconnect between MASCAL response training and actions taken during real-world incidents. Overly complex algorithms, infrequent training on their use, and chaotic events all contribute to the low utilization of formal triage systems in the real world. A review of published studies on prehospital MASCAL management and a recent series of military prehospital MASCAL responses highlight the need for an intuitive MASCAL management system that accounts for expected resource limitations and tactical constraints. "Move, Treat, and Transport" is a simple and pragmatic approach that emphasizes speed and efficiency of response; considers time, tactics, and scale of the event; and focuses on interventions and evacuation to definitive care if needed.

Limitations of Triage in Military Mass Casualty Response: A Case Series.

INTRODUCTION: Mass casualty events (MASCALs) in the combat environment, which involve large numbers of casualties that overwhelm immediately available resources, are fundamentally chaotic and dynamic and inherently dangerous. Formal triage systems use diagnostic algorithms, colored markers, and four or more named categories. We hypothesized that formal triage systems are inadequately trained and practiced and too complex to successfully implement in true MASCAL events. This retrospective analysis evaluates the real-world application of triage systems in prehospital military MASCALs and other aspects of MASCAL management. METHODS: We surveyed Special Operations Forces (SOF) medics known to us who have participated in military prehospital MASCALs and analyzed them. Aggregated data describing the scope of the incidents, the use of formal triage algorithms and colored markers, the number of categories, and the interventions on scene were analyzed using descriptive statistics, and lessons learned were consolidated. RESULTS: From 1996 to 2022 we identified 29 MASCALs that were managed by military medics in the prehospital setting. There was a median of three providers (range 1-85) and 15 casualties (range 6-519) per event. Four or more formal triage categories were used in only one event. Colored markers and formal algorithms were not used. Life-saving interventions were performed in 27 of 29 (93%) missions and blood transfusions were performed in four (17%) MASCALs. The top lessons learned were: 1) security and accountability are cornerstones of MASCAL management; 2) casualty movement is a priority; 3) intuitive triage categories are the default; 4)life-saving interventions are performed as time and tacticspermit. CONCLUSION: Formal triage systems requiring the use ofdiagnostic algorithms, colored tags, and four or five categories are seldom implemented in real-world military prehospitalMASCAL management. The training of field triage should besimplified and pragmatic, as exemplified by these instances.

Lessons Learned From a Large-Scale Military Mass Casualty Incident: Reevaluation of the Response to the Khobar Towers Bombing.

The 1996 Khobar Towers bombing, a large-scale mass casualty incident (MASCAL) at a coalition forces housing complex, resulted in 519 casualties. Key lessons learned include the importance of MASCAL exercises, self-aid and buddy care, and casualty triage, all critical to preparation for future terrorist attacks or near-peer combat operations MASCALs.

The Effect of Critical Task Auto-failure Criteria on Medical Evaluation Methods in the Pararescue Schoolhouse.

BACKGROUND: Medical training and evaluation are important for mission readiness in the pararescue career field. Because evaluation methods are not standardized, evaluation methods must align with training objectives. We propose an alternative evaluation method and discuss relevant factors when designing military medical evaluation metrics. METHODS: We compared two evaluation methods, the traditional checklist (TC) method used in the pararescue apprentice course and an alternative weighted checklist (AWC) method like that used at the U.S. Army static line jumpmaster course. The AWC allows up to two minor errors, while critical task errors result in autofailure. We recorded 168 medical scenarios during two Apprentice course classes and retroactively compared the two evaluation methods. RESULTS: Despite the possibility of auto-failure with the AWC, there was no significant difference between the two evaluation methods, and both showed similar overall pass rates (TC=50% pass, AWC=48.8% pass, p=.41). The two evaluation methods yielded the same result for 147 out of 168 scenarios (87.5%). CONCLUSIONS: The AWC method strongly emphasizes critical tasks without significantly increasing failures. It may provide additional benefits by being more closely aligned with our training objectives while providing quantifiable data for a longitudinal review of student performance.

Roxadustat and Oral Iron Absorption in Chinese Patients with Anemia of Chronic Kidney Disease: A Randomized, Open-Label, Phase 4 Study (ALTAI).

INTRODUCTION: Anemia of chronic kidney disease (CKD) has a high incidence and is associated with many disease conditions. Iron dysmetabolism is an important contributor to anemia in CKD patients. METHODS: ALTAI, a randomized, active-controlled, phase 4 trial, investigated the efficacy of roxadustat versus recombinant human erythropoietin (rHuEPO) on gastrointestinal iron absorption in patients with anemia of CKD (stage 4/5). The primary endpoint was change from baseline to day 15 in gastrointestinal iron absorption (serum iron area under the concentration-time curve; AUC0-3h) following single-dose oral iron. RESULTS: Twenty-five patients with a mean age of 55.1 years were randomized 1:1 to roxadustat (n = 13) or rHuEPO (n = 12). Baseline iron profiles were similar between treatment groups. Change from baseline to day 15 in serum iron AUC0-3h was not statistically significantly different between the roxadustat and rHuEPO groups. Mean (SD) change from baseline in serum iron AUC0-3h was 11.3 (28.2) g × 3 h/dl in the roxadustat group and - 0.3 (9.7) g × 3 h/dl in the rHuEPO group. Roxadustat treatment was associated with decreased hepcidin and also increased transferrin, soluble transferrin receptor, and total iron-binding capacity (TIBC), with nominal significance. The proportion of patients experiencing one or more adverse events was 38.5% when treated with roxadustat and 16.7% with rHuEPO. CONCLUSIONS: The study showed no significant difference between roxadustat and rHuEPO in iron absorption but was underpowered because of recruitment challenges. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04655027.

Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is associated with polyneuropathy, cardiomyopathy, or both. The effects of eplontersen on cardiac structure and function were assessed. METHODS AND RESULTS: NEURO-TTRansform was an open-label trial involving 144 adults with ATTRv polyneuropathy (49 patients [34%] with cardiomyopathy) receiving eplontersen throughout and compared with a historical placebo group (n = 60; 30 patients [50%] with cardiomyopathy) from the NEURO-TTR trial at week 65. Treatment effect (eplontersen vs placebo), presented as mean difference (95% confidence interval) was analyzed after adjusting for age, sex, region, baseline value, ATTRv disease stage, previous ATTRv treatment, and V30M transthyretin variant. There were notable differences at baseline between the eplontersen group and historical placebo. In the cardiomyopathy subgroup, 65 weeks of eplontersen treatment was associated with improvement from baseline relative to placebo in left ventricular ejection fraction of 4.3% (95% confidence interval 1.40-21.01; P = .049) and stroke volume 10.64 mL (95% confidence interval 3.99-17.29; P = .002) while the remainder of echocardiographic parameters remained stable. CONCLUSIONS: Eplontersen was associated with stable or improved measures of cardiac structure and function vs historical placebo in patients with ATTRv polyneuropathy and cardiomyopathy. Further investigation into eplontersen's effect on transthyretin amyloid cardiomyopathy is being conducted in the CARDIO-TTRansform trial.

How message appeals and prior product use influence information processing, risk perceptions, trust, attitudes, and genetic test purchase intentions.

Within the direct-to-consumer (DTC) genetic test industry, attracting customers can be difficult especially due to the highly sensitive nature of these products. How these tests are communicated to consumers may be one avenue in which companies can impact customer purchase intentions. A 2 (message sidedness: one-way vs. two-way refutational) x 2 (hedging: present vs. absent) between-subjects experiment was conducted to understand how message features and prior product use influence information processing, risk and trust perceptions, and attitude toward the genetic test, which in turn, may influence direct-to-consumer (DTC) genetic test purchase intentions. Results demonstrated that having used a genetic test in the past predicted participants' trust in the company, information processing, and risk judgments; however, among those who used a genetic test, viewing a message that included hedging tended to increase their trust in the message. Trust in the message and company, information processing, and risk judgments significantly predicted participants' attitudes toward genetic testing, which in turn predicted their purchase intentions. The results suggest that in the context of DTC genetic test messaging, practitioners should strive to increase consumer trust in the message and the company and facilitate information processing, and they should work to diminish perceived risk. These results suggest opportunities for identifying other message features that may influence message and company trust, information processing, risk judgments, and attitudes related to DTC genetic testing.

Effectiveness of and Adherence to Triage Algorithms During Prehospital Response to Mass Casualty Incidents.

Mass casualty incidents (MCIs) can rapidly exhaust available resources and demand the prioritization of medical response efforts and materials. Principles of triage (i.e., sorting) from the 18th century have evolved into a number of modern-day triage algorithms designed to systematically train responders managing these chaotic events. We reviewed reports and studies of MCIs to determine the use and efficacy of triage algorithms. Despite efforts to standardize MCI responses and improve the triage process, studies and recent experience demonstrate that these methods have limited accuracy and are infrequently used.

Threat Appraisal, Recovery Operations, and PTSD Symptoms Among US Air Force Rescue Personnel.

BACKGROUND: Research among military personnel and veterans indicates that subjective appraisal of warzone stressors explains the relation of combat exposure to posttraumatic stress disorder (PTSD), but not the relation of exposure to injury and death to PTSD. Studies have primarily been limited to conventional forces using aggregate measures of warzone stressor exposure. Threat appraisal may play a different role in the emergence of PTSD among military personnel for whom dangerous deployment experiences are more closely associated with exposure to injury and death, such as US Air Force Pararescuemen and Combat Rescue officers. MATERIALS AND METHODS: In a sample of 207 rescue personnel, correlations among various types of warzone stressor exposure, threat appraisal, and postdeployment PTSD symptoms were examined. RESULTS: The relative strongest correlates of threat appraisal were stressors related to injury, death, and human remains. Although exposure to these stressors was also correlated with PTSD symptom severity, partial correlations of stressor exposure and PTSD symptoms were no longer significant when adjusting for threat appraisal. CONCLUSION: Results support the contributing role of threat appraisal to PTSD among military personnel whose primary duties entail exposure to injury and death under hostile and dangerous conditions.

Fecal Supernatants from Patients with Crohn's Disease Induce Inflammatory Alterations in M2 Macrophages and Fibroblasts.

Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn's disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFß superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.

Evidence-based principles of time, triage and treatment: Refining the initial medical response to massive casualty incidents.

BACKGROUND: The overall approach to massive casualty triage has changed little in the past 200 years. As the military and civilian organizations prepare for the possibility of future large-scale combat operations, terrorist attacks and natural disasters, potentially involving hundreds or even thousands of casualties, a modified approach is needed to conduct effective triage, initiate treatment, and save as many lives as possible. METHODS: Military experience and review of analyses from the Department of Defense Trauma Registry are combined to introduce new concepts in triage and initial casualty management. RESULTS: The classification of the scale of massive casualty (MASCAL) incidents, timeline of life-saving interventions, immediate first pass actions prior to formal triage decisions during the first hour after injury, simplification of triage decisions, and the understanding that ultra-MASCAL will primarily require casualty movement and survival needs with few prehospital life-saving medical interventions are discussed. CONCLUSION: Self aid, bystander, and first responder interventions are paramount and should be trained and planned extensively. Military and disaster planning should not only train these concepts, but should seek innovations to extend the timelines of effectiveness and to deliver novel capabilities within the timelines to the greatest extent possible.

Conditional correlation network data from the financial sector.

This data set contains rolling conditional correlation networks estimated from stock returns and the volume synchronized probability of informed trading. Only the largest 104 financial firms are included for the period of 1996 through 2012. The data was used to analyze banking sector systemic risk in Borochin and Rush (2022)[1].

MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn´s Disease Patients.

Inflammasomes are intracellular protein complexes whose activation results in proinflammatory cytokines. Inflammasomes are implicated in Crohn´s disease (CD) pathogenesis, yet the contribution of inflammasomes in intestinal epithelial cells (IECs) versus lamina propria (LP) macrophages is poorly understood. Whether inflammasome expression in intestinal tissue reflects the serum inflammatory protein profile of patients is also not known. We aimed to determine the intestinal cell types where inflammasome expression is increased in CD and if they correlate with the serum protein profile. RT-PCR and NanoString nCounter technology were used to characterize inflammasome gene expression in CD patients and controls. The mucosa, LP and IEC cell fractions and FACS-sorted cells were analyzed. Proximity extension assay with a 92-protein panel was used to determine the serum inflammatory protein profile. Compositional analysis was used to correlate ileum inflammasome gene expression with intestinal mononuclear phagocyte populations. We show that NLRP3 and MEFV inflammasome sensors and downstream effector expression including IL-1ß are increased in inflamed mucosa of IBD patients and correlate with disease activity. Inflammasome gene expression increased with the abundance of immature intestinal macrophages, and increased IL-1ß released by CD LP cells correlated with immature macrophage frequency. Inflammasome gene expression was also increased in circulating monocytes, the precursors of immature intestinal macrophages. Finally, the serum inflammatory profile of CD patients correlates with ileal expression of genes related to NLRP3 and MEFV inflammasomes. Overall, we show that MEFV and NLRP3 inflammasome expression in CD intestine is attributed to the accumulation of immature macrophages and correlates with serum inflammatory proteins.

Prehospital Iliac Crest Intraosseous Whole Blood Infusion.

Low-titer cold-stored O-positive whole blood (LTCSO+WB) resuscitation therapy is the cornerstone of military hemorrhagic shock resuscitation. During the past 19 years, improved patient outcomes have shown the importance of this intervention in shock treatment. Iliac crest intraosseous (IO) placement is an alternative when peripheral sites such as the humeral head and tibia are not available options. To date, no study has explored the administration of LTCSO+WB through an iliac crest IO in the military prehospital setting. Contingency procedures for vascular access are necessary for casualties with severe trauma to all four extremities, and the iliac crest is a viable option. The literature supports situational advantages over other peripheral IO sites.

Systemic Inflammation in Preclinical Ulcerative Colitis.

BACKGROUND & AIMS: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. METHODS: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. CONCLUSIONS: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.

23.4% Hypertonic Saline: A Tactical Option for the Management of Severe Traumatic Brain Injury With Impending or Ongoing Herniation.

There are limited options available to the combat medic for management of traumatic brain injury (TBI) with impending or ongoing herniation. Current pararescue and Tactical Combat Casualty Care (TCCC) guidelines prescribe a bolus of 3% or 5% hypertonic saline. However, this fluid bears a tactical burden of weight (~570g) and pack volume (~500cm3). Thus, 23.4% hypertonic saline is an attractive option, because it has a lighter weight (80g) and pack volume (55cm3), and it provides a similar osmotic load per dose. Current literature supports the use of 23.4% hypertonic saline in the management of acute TBI, and evidence indicates that it is safe to administer via peripheral and intraosseous cannulas. Current combat medic TBI treatment algorithms should be updated to include the use of 23.4% hypertonic saline as an alternative to 3% and 5% solutions, given its effectiveness and tactical advantages.

Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation.

BACKGROUND: Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. METHODS: We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. RESULTS: We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. CONCLUSIONS: Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.

Rationale and Implementation of a Novel Special Operations Medical Officer Course.

BACKGROUND: The Air Force Special Warfare Medical Officer Course was created to address the lack of operationally focused, job-specific clinical training for medical officers (MOs). This course addresses the gap in knowledge, skill, and application of operational medicine, as well as the behavioral health, human performance, education, and medical oversight of Operators. METHODS: The course was designed around the senior author's decade of experience piecing together training for his own role as a pararescue flight surgeon and informed by 5 years of flight surgeon courses, lessons learned from case studies of ill-prepared deployed physicians, and input from prehospital medicine subject matter experts. RESULTS: Air Force pararescue and special tactics flight surgeons, physician assistants, and an independent duty medical technician (IDMT) attended. The course consisted of 10 full weekdays of didactics and skills sessions covering theory and application of operational medicine, human performance optimization, behavioral health for Operators, adult education theory, principles of prehospital clinical oversight, and other expeditionary concepts. The course culminated with combat casualty care scenario-based exercises, in which the providers performed operational medicine in full kit with weapons and simulation rounds. DISCUSSION: For many logistical and practical reasons, civilian medical experience, traditional military medical training, existing special operations medical courses, and "merit badge" card classes are not adequate preparation for this specialized role. Focused, job-specific training should be provided to Special Operations Forces Medical Officers (SOFMO) and, ultimately, to any MO deploying in support of medics or combatants. The goal is to maximize the success of military medical operations while reducing the morbidity and mortality of combat and training casualties. CONCLUSION: This operationally focused MO course can serve as a model for the future training of SOFMO and has stimulated discussion for consideration of a joint approach to prehospital medical training.

Commercial and Improvised Pelvic Compression Devices: Applied Force and Implications for Hemorrhage Control.

Uncontrolled hemorrhage secondary to unstable pelvic fractures is a preventable cause of prehospital death in the military and civilian sectors. Because the mortality rate associated with unstable pelvic ring injuries exceeds 50%, the use of external compression devices for associated hemorrhage control is paramount. During mass casualty incidents and in austere settings, the need for multiple external compression devices may arise. In assessing the efficacy of these devices, the magnitude of applied force has been offered as a surrogate measure of pubic symphysis diastasis reduction and subsequent hemostasis. This study offers a sensor-circuit assessment of applied force for a convenience sample of pelvic compression devices. The SAM® (structural aluminum malleable) Pelvic Sling II (SAM Medical) and improvised compression devices, including a SAM Splint tightened by a Combat Application Tourniquet® (C-A-T; North American Rescue) and a SAM® Splint tightened by a cravat, as well as two joined cravats and a standard-issue military belt, were assessed in male and female subjects. As hypothesized, compressive forces applied to the pelvis did not vary significantly based on device operator, subject sex, and subject body fat percentage. The use of the military belt as an improvised method to obtain pelvic stabilization is not advised.

Ketamine Administration by Special Operations Medical Personnel During Training Mishaps.

BACKGROUND: Opioids can have adverse effects on casualties in hemorrhagic shock. In 2014, the Committee on Tactical Combat Casualty Care (CoTCCC) recommended the use of ketamine at the point of injury (POI). Despite these recommendations the adherence is moderate at best. Poor use may stem from a lack of access to use ketamine during training. The United States Special Operations Command (USSOCOM) is often in a unique position, they maintain narcotics for use during all training events and operations. The goal of this work is to demonstrate that ketamine is safe and effective in both training and operational environments. METHODS: This was a retrospective, observational performance improvement project within United States Special Operations Command and Air Combat Command that included the US Army's 75th Ranger Regiment, 160th Special Operations Aviation Regiment, and US Air Force Pararescue. Descriptive statistics were used to calculate the doses per administration to include the interquartile range (IQR), standard deviation (SD) and the range of likely doses using a 95% confidence interval (CI). A Wilcoxon signed-rank test was used to compare the mean pre-ketamine pain scores to the mean post-ketamine on a 0-to-10 pain scale. RESULTS: From July 2010 to October 2017, there was a total of 34 patients; all were male. A total of 22 (64.7%) received intravenous ketamine and 12 (35.3%) received intramuscular ketamine and 8 (23.5%) received intranasal ketamine. The mean number of ketamine doses via all routes administered to patients was 1.88 (SD 1.094) and the mean total dose of all ketamine administration was 90.29mg (95% CI, 70.09-110.49). The mean initial dose of all ketamine administration was 47.35mg (95% CI, 38.52-56.18). The median preketamine pain scale for casualties was noted to be 8.0 (IQR 3) and the median post-ketamine pain scale was 0.0 (IQR 3). CONCLUSION: Ketamine appears to be safe and effective for use during military training accidents. Military units should consider allowing their medics to carry and use as needed.