Search

Major trauma frequently occurs in the deployed, combat setting and is especially applicable in the recent conflicts with explosives dominating the combat wounded. In future near-peer conflicts, we will likely face even more profound weapons including mortars and artillery. As such, the number of severely wounded will likely increase. Hypocalcemia frequently occurs after blood transfusions, secondary to the preservatives in the blood products; however, recent data suggests major trauma in and of itself is a risk factor for hypocalcemia. Calcium is a major ion involved in heart contractility; thus, hypocalcemia can lead to poor contractility. Smaller studies have linked hypocalcemia to worse outcomes, but it remains unclear what causes hypocalcemia and if intervening could potentially save lives. The objective of this study is to determine the incidence of hypocalcemia on hospital arrival and the association with survival. We are seeking to address the following scientific questions, (1) Is hypocalcemia present following traumatic injury prior to transfusion during resuscitation? (2) Does hypocalcemia influence the amount of blood products transfused? (3) To what extent is hypocalcemia further exacerbated by transfusion? (4) What is the relationship between hypocalcemia following traumatic injury and mortality? We will conduct a multicenter, prospective, observational study. We will gather ionized calcium levels at 0, 3, 6, 12, 18, and 24 hours as part of scheduled calcium measurements. This will ensure we have accurate data to assess the early and late effects of hypocalcemia throughout the course of resuscitation and hemorrhage control. These data will be captured by a trained study team at every site. Our findings will inform clinical practice guidelines and optimize the care delivered in the combat and civilian trauma setting. We are seeking 391 patients with complete data to meet our a priori inclusion criteria. Our study will have major immediate short-term findings including risk prediction modeling to assess who is at risk for hypocalcemia, data assessing interventions associated with the incidence of hypocalcemia, and outcome data including mortality and its link to early hypocalcemia.

Limited literature exists examining outcomes associated with alternative thresholds for massive transfusion outside of the historical definition of 10 units of packed red blood cells (PRBC) in 24 hours. This study reports the predictive accuracy of alternative thresholds for 24-hour mortality and explores implications for Role 1 care supply requirements.We conducted a secondary analysis of data from the Department of Defense Trauma Registry (DODTR) spanning encounters from 1 January 2007 through 17 March 2020. We included all casualties who received at least 1 unit of either PRBC or whole blood. We calculated area under the receiver operator curve (AUROC) of blood product quantity received, including both PRBC and whole blood, as a predictor for mortality within 24 hours of arrival to a military treatment facility. We identified optimal predictive thresholds per Youden's index.We identified 28,950 encounters of which 2,608 (9.0%) entailed receipt of at least 1 unit of PRBC or whole blood. Most casualties sustained battle injuries (2,437, 93.4%) with explosives as the most common mechanism (1,900, 72.8%) followed by firearms (609, 23.3%). The AUROC for blood product received within 24 hours was 0.59. The optimal threshold for predicting 24-hour mortality per Youden's Index was 20 units (sensitivity of 34.9% and specificity of 78.6%). The threshold exceeding 90% sensitivity was 2 units; whereas, the threshold exceeding 90% specificity was 33 units.We identified a wide range of numbers of received blood products associated with short-term mortality based upon prioritization of sensitivity or specificity. This study found only 2 units of blood product received had a 90% sensitivity for predicting 24-hour mortality, highlighting the resource mobilization challenges that confront healthcare providers during resuscitation at the Role 1.

Previous studies have found that intravenous fluid administration within the first 24 h may be associated with prolonged mechanical ventilation (PMV). We examined the association between initial 24 h fluids and PMV in combat casualties.This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry (DODTR). We included casualties with at least 24 h on the ventilator and no significant traumatic brain injury. The definition of PMV and associations were constructed using univariable and multivariable logistic regression models.We identified 1508 casualties available for analysis for this study - 1275 in the non-PMV cohort (9 days on ventilator vs. 233 in the PMV cohort (≥9 days on ventilator). Explosives comprised the most common mechanism of injury for both groups (72% vs. 75%) followed by firearms (21% vs. 16%). The composite injury severity score (ISS) was lower in the non-PMV cohort (18 vs. 30, p .001). There were lower volumes of all resuscitation fluid within the first 24 h in the non-PMV cohort. When adjusting for composite ISS and mechanism of injury in a multivariable logistic regression model with PMV as the outcome, crystalloid volume (unit odds ratio [UOR] 1.07) and colloid volume (UOR 1.03) were both associated with PMV.We found that volume of resuscitation fluids were substantially higher in the PMV cohort. Our findings suggest the need for caution with the routine use of crystalloid and colloid in the first 24 h of resuscitation.

Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure. Recent studies have shown that VPA has cellular protective effects in preclinical models following severe hemorrhage. This study investigated the effects of VPA on coagulation and survival in pigs after traumatic hemorrhage and hypotensive resuscitation.Following baseline measurements, femur fracture was performed in 20 anesthetized and instrumented pigs (41 ± 2 kg), followed by hemorrhage of 55% of the estimated blood volume and a 10-minute shock period. Pigs were then resuscitated for 30 minutes with normal saline (NS) alone (NS group, n = 10, 4 mL/kg) or VPA solution (VPA group, n = 10, 90 mg/kg, 2 mL/kg of 45 mg VPA/mL, plus 2 mL NS/kg). All pigs were then monitored for 2 hours or until death. Hemodynamics were recorded, and blood samples were taken for blood and coagulation analysis (Rotem) at baseline, after hemorrhage, resuscitation, and 2 hours or death.Femur fracture and hemorrhage caused similar reductions in mean arterial pressure and cardiac output, and increase in heart rate in both groups. Resuscitation with NS or VPA did not return these measurements to baseline. No differences were observed in hematocrit, pH, lactate, base excess, or total protein between the groups. Compared with NS, resuscitation with VPA decreased platelet counts and prolonged activated partial thromboplastin time, with no differences in fibrinogen levels, prothrombin time, or any of the Rotem measurements between the two groups. Neither survival rates (NS, 7 of 10 pigs; VPA, 7 of 10 pigs) nor survival times after resuscitation (NS, 97 ± 40 minutes; VPA, 98 ± 43 minutes) differed between the groups.Following traumatic hemorrhage and hypotensive resuscitation in pigs, VPA provides no benefit toward improving coagulation function or survival times.

Hemorrhage is the leading cause of potentially preventable death on the battlefield. Blood transfusions are used as treatment to restore circulating volume until the hemorrhage can be surgically controlled. Research has shown earlier transfusion of blood products has better casualty outcomes, so blood products have been pushed forward to the point of injury. Currently, there is a mixed use of blood components and whole blood in the prehospital setting-both of which have challenging supply chain requirements. Alternative blood products offer several potential advantages, as they are easier to mass produce, obviating the need for donor recruitment. They also have improved shelf-life stability, potentially remove cold-chain storage, and even cross-matching requirements. In this limited review, we sought to provide a narrative review of current promising developments including hemoglobin-based oxygen carriers, polyhemoglobin, platelet like cells, dried plasma, liquid plasma, fibrinogen concentrates, enzyme concentrates, nanoparticles, and perfluorocarbon-based artificial oxygen carriers.

Introduction: During multi-domain combat operations, logistical constraints may compel forward medical personnel to decide whether to use expired blood products. The incidence of expired blood product usage in recent conflicts is unknown.We queried the Armed Services Blood Program (ASBP) database of all blood administered in theater from 2002-2019. We categorized any administration of blood product with a transfusion date of 1-30 days after the expiration date for this analysis. We excluded any documented transfusions more than 30 days after the expiration date as likely represents clerical error based on study team experience.There were 1,491 (0.4% of the total transfusion dataset) units that met inclusion for this analysis. Of the 1,491, 86% (n=1,278 transfusions) will occur within 1-3 days post-expiration. These 1,491 units were transfused into 741 patients. The majority of expired blood product recipients were male (87%). Afghans were most frequent (46%), followed by US forces (22%) with most occurring during Operation Enduring Freedom (64%). Trauma was the most common mechanism of injury for these patients (70%). The most common blood type transfused to recipients was O positive (28%). The most frequently transfused expired unit was red blood cells (n=899), followed by platelets (n=299), followed by whole blood (n=152).Expired red blood cell and platelet use suggests a need for better methods for extending the lifespan of whole blood and further development of longer stability cold-stored platelets to meet the needs of our end-users. Our data arises from mature theaters during counterinsurgency operations. The incidence of transfusion of expired blood products may increase in future multi-domain operations where medical personnel are likely to operate under more resource constrained settings.

Emergency department (ED) utilization continues to climb nationwide resulting in overcrowding, increasing wait times, and a surge in patients with non-urgent conditions. Patients frequently choose the ED for apparent non-emergent medical issues or injuries that after-the-fact could be cared for in a primary care setting. We seek to better understand the reasons why patients choose the ED over their primary care managers.We prospectively surveyed patients that signed into the ED at the Brooke Army Medical Center as an emergency severity index of 4 or 5 (non-emergent triage) regarding their visit. We then linked their survey data to their ED visit including interventions, diagnoses, diagnostics, and disposition by using their electronic medical record. We defined their visit to be non-urgent and more appropriate for primary care, or primary care eligible, if they were discharged home and received no computed tomography (CT) imaging, ultrasound, magnetic resonance imaging (MRI), intravenous (IV) medications, or intramuscular (IM) controlled substances.During the 2-month period, we collected data on 208 participants out of a total of 252 people offered a survey (82.5%). There were 92% (n=191) that were primary care eligible within our respondent pool. Most reported very good (38%) or excellent (21%) health at baseline. On survey assessing why they came, inability to get a timely appointment (n=73), and a self-reported emergency (n=58) were the most common reported reasons. Most would have utilized primary care if they had a next-morning appointment available (n=86), but many reported they would have utilized the ED regardless of primary care availability (n=77). The most common suggestion for improving access to care was more primary care appointment availability (n=96). X-rays were the most frequent study (37%) followed by laboratory studies (20%). Before coming to the ED, 38% (n=78) reported trying to contact their primary care for an appointment. Before coming to the ED, 22% (n=46) reported contacting the nurse advice line. Based on our predefined model, 92% (n=191) of our respondents were primary care eligible within our respondent pool.Patient perceptions of difficulty obtaining appointments appear to be a major component of the ED use for non-emergent visits. Within our dataset, most patients surveyed stated they had difficulty obtaining a timely appointment or self-reported as an emergency. Data suggests most patients surveyed could be managed in the primary care setting.

Most battlefield deaths occur in the prehospital setting prior to reaching surgical and hospital care. Described are casualties captured by the Joint Trauma System (JTS) in the Prehospital Trauma Registry (PHTR) module of the Department of Defense Trauma Registry (DoDTR), from inception through May 2019.The JTS was queried for all PHTR encounters and associated data from inception (January 2003) through May 2019. The PHTR captures data on Role 1 prehospital care which encompasses treatment prior to arrival at a Role 2 with or without forward surgical team or Role 3 combat support hospital. Two unique patient identifiers were used to link DODTR outcome data to each PHTR encounter. Descriptive statistics were used to analyze the data.We obtained a total of 1,357 encounters from the PHTR. Of these encounters, we successfully linked 52.2% (709/1357) to the DODTR for outcome data. Encounters spanned from 2003 to 2019, with most (69.5%) occurring from 2012 to 2014. Many casualties were in the 18-25 (25.5%) or 26-33 (27.0%) age ranges, male (99.2%), injured by explosive (47.1%) or firearm (34.8%), enlisted (44.8%), and US military conventional (24.1%) and special operations (23.9%) forces. Of those linked to the DODTR, demographics were similar, most casualties sustained battle injuries (87.1%), the majority of which survived (99.1%).We described 1,357 encounters within the PHTR, most of which were US casualties and casualties injured by explosives. This renewed effort by the JTS to capture more casualties for inclusion into the registry has nearly doubled the proportion of available encounters for analysis. This analysis lays the foundation for in-depth analyses targeting areas for optimizing Role 1 prehospital combat casualty care.

Blood products are often a life-saving intervention for both traumatic and medical indications. The United States Indo-Pacific Command (INDOPACOM) is the largest Geographic Combat Command (GCC). Procurement of blood products that meet the US military healthcare standards throughout this region is challenging. Yet, the frequency to which this life-saving intervention is administered remains unclear. We seek to describe blood product administration throughout INDOPACOM.This is a secondary analysis of a previously described dataset from the US Transportation Command (TRANSCOM) Regulating Command and Control and Evacuation System (TRAC2ES) from 2008 to 2018.Between 2008 and 2018, there were 4,217 cases in TRAC2ES originating within INDOPACOM, of which 173 (4%) cases involved blood product transfusion. The largest percentage for patients receiving a blood transfusion was 19-29 years old (29%), followed by patients under a year (21%). Most (66%) of the patients classified as male. Almost half of the patients (49%) were dependents of members of service in parallel with the young patient ages. Anemia (23%) and trauma (20%) , mostly non-combat related, were the largest proportions of indications. The common blood product used was packed red cells (72%) followed by fresh frozen plasma (16%).Blood products were administered to nearly 1 out of every 25 patients transported within INDOPACOM, which highlights the need for reliable methods for obtaining and maintaining blood products. Given INDOPACOM's vast area of responsibility and possibility for a peer-to-peer war, finding optimal methods to transport and store blood and blood products is imperative.

Personal protective equipment (PPE) is crucial to force protection and preservation. Innovation in PPE has shifted injury patterns, with protected body regions accounting for decreased proportions of battlefield trauma relative to unprotected regions. Little is known regarding the PPE in use by warfighters at the time of injury.We queried the Prehospital Trauma Registry (PHTR) for all encounters from 2003-2019. This is a sub-analysis of casualties with documented PPE at the time of medical encounter. When possible, encounters were linked to the Department of Defense Trauma Registry (DODTR) for outcome data. Serious injuries are defined as an abbreviated injury scale of 3 or greater.Of 1,357 total casualty encounters in the PHTR, 83 were US military with documented PPE. We link 62 of this cohort to DODTR. The median composite Injury Severity Score (ISS) was 6 (Interquartile range (IQR) 4-21), and 11 casualties (18%) had an ISS25. The most seriously injured body regions were the extremities (21%), head/neck (16%), thorax (16%), and abdomen (10%). PPE worn at time of injury included helmet (91%), eye protection (73%), front (75%) and rear plates (77%), left/right plates (65%), tactical vest (46%), groin protection (12%), neck protection (6%), pelvic shield (3%), and deltoid protection (3%).Our data set demonstrates that the extremities were the most commonly injured body region, followed by head/neck, and thorax. PPE designed for the extremities and neck are also among the least commonly worn protective equipment.

Introduction: Hemorrhage is the leading cause of potentially preventable death on the battlefield. After hemorrhage control, the resuscitation with blood products is essential to restore circulating volume and prevent coagulopathy. While massive transfusion (MT) occurs frequently after major trauma, it remains unclear who the subset of casualties is that define a super massive transfusion which would require mobilization of additional resources. We seek to determine what defines a super MT as this would help allocate resources. Methods: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry. In this analysis, we isolated US and Coalition casualties that received at least 1 unit of packed red cells or whole blood. To describe the super MT, we sought the top quartile of total products administered within the first 24 hours. Results: Out of the 28222 casualties within our dataset, we identified 2204 US military and 498 Coalition that met inclusion for this analysis. The median number of total products administered within the first 24 hours was 16 with 39 total product units at the 75th percentile, which included 691 casualties. Of those in the super MT group, their median injury severity score was higher (29 versus 18, p Conclusions: In our dataset, we identified the top 25th percentile of total product administration within the first 24 hours at 39 total product units. More data is needed to define this population early in their clinical course to better mobile resources early when needed. Disclosures No relevant conflicts of interest to declare.

Introduction: Hemorrhage is the leading cause of potentially preventable death on the battlefield. We previously published data defining the pediatric massive transfusion at 40mL/kg of total blood products. However, there is a subset of casualties that require large volumes of blood products - super massive transfusions - which remains unclear. We seek to determine what defines a super massive transfusion within the pediatric population as understanding this unique group would help mobilize resources early in their clinical course. Methods: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry. In this analysis, we sought all casualties within our dataset that met inclusion for MT. To describe the super MT, we sought the top quartile of total products administered within the first 24 hours on a volume per weight basis. Results: Within our original dataset of 3439 pediatric casualties, we identified 543 that met inclusion for massive transfusion, with the 75th percentile at 120.6 mL/kg - we rounded this to 120mL/kg for simplicity which left 137 for analysis. Most of the casualties were in the 5-9 and 10-14 age groups (24% and 39%, respectively) and were most frequently injured by explosive (71%). Those in the super MT group had lower survival (75% versus 84%, p=0.015), longer ventilator courses (median 3 days versus 2 days, p=0.029) despite similar median injury severity scores (17 versus 17, p=0.100). However, they more frequently had serious injuries to the extremities (62% versus 35%, p Conclusions: In our analysis, we found that 120 mL/kg of total blood products administered within the first 24 hours was the threshold for the top 25th percentile of pediatric blood product consumers. More data is needed to define this unique population that requires mobilization of extensive resources. Disclosures No relevant conflicts of interest to declare.

Introduction: We have recently shown that severe trauma and hemorrhage lead to inhibition of platelet aggregation and an elevation in cyclic adenosine monophosphate (cAMP). Adenosine is one of the few humoral agents known to stimulate cAMP in platelets. Because adenosine is released from damaged tissue, it may contribute to the platelet dysfunction seen after severe trauma. Platelets have four adenosine receptors (A1, A2a, A2b and A3). These receptors are G-Protein Coupled Receptors and have been proposed to stimulate adenylyl cyclase and increase intracellular cAMP. Although studies have shown that stimulate A2a can inhibit platelet aggregation and elevate cAMP, there is little data elucidating the function of the other receptors. Objective: Define which adenosine receptors affects platelet aggregation and cAMP production. Methods: Platelet-rich plasma (PRP) was isolated from whole blood of human volunteers, and centrifuged at 200g for 10min. Light transmission aggregometry was performed using a plate reader (Synergy Neo2 Multimode Reader, BioTek) with constant agitation. PRP was stimulated with adenosine diphosphate (ADP) with or without various adenosine agonists or antagonists, including the non-metabolizable adenosine agonist 5-(N-ethyl-carboxamido) adenosine (NECA), antagonists to receptors A1 (DPCPX), A2a (Sch 58261), A2b (GS 6201) and A3 (MRS 1220), or agonists for A2a (CGS 21680) A2b (BAY 60-6583) or agonist A1 (CCPA), A2a (CGS 21680), A2b (Bay 60-6583), A3 (2-Cl-IB-Meca). Cyclic AMP was extracted from 100ul of PRP after adding 1ml of EtOH, 10mM ammonium formate, with 10ug/ml cGMP-Br as an internal control. Samples were centrifuged at 20K g for 10min, and supernatant dried. Samples were brought up in 200ul of 0.1% formic acid for analysis by Reverse Phase liquid chromatography/ Tandem Mass Spectroscopy (Quantiva, ThrermoFisher). N-8/group. Results: Adenosine diphosphate (100uM) leads to platelet aggregation (change in mAbsorbance units, Table 1). The adenosine agonist NECA inhibited aggregation to ADP and elevated cAMP in a dose dependent manner (pg/ml per 1000 plt, Table 1). Platelet aggregation was inhibited and cAMP was elevated after stimulation with agonists for adenosine receptor A2a agonist, but not A1, A2b, or A3 (Table 2). Antagonists for A2a, but not A1, A2b, A3, blocked NECA inhibition of ADP aggregation (Table 3). Agonist for adenosine receptor A2a inhibited the ADP-induced aggregation and elevated cAMP in a dose response manner (Table 4). Discussion: Adenosine inhibits platelet aggregation to ADP. The mechanism appears to be due to elevation in intracellular cAMP, and works through the A2a receptor. These data suggest that the A2a receptor could be potential target for a resuscitation strategy that could attenuate or prevent platelet dysfunction after trauma by preventing stimulation of adenylate cyclase and synthesis of cAMP. This study was funded by the US Army medical Research and Development Command. Disclosures No relevant conflicts of interest to declare.

The striking and affecting 1986 opera, X: The Life and Times of Malcolm X, composed by Anthony Davis, uses clever theatrical devices in concert with Malcolm X's own doctrines to realize its objectives. The opera draws upon events as they were posited by the memoirs of Malcolm X, coauthored by Pulitzer Prize–winner Alex Haley, as well as additional historical sources. Composed by Anthony Davis, with a book by his brother, actor-director Christopher Davis, and a libretto by his cousin, poet Thulani Davis, X, The Life and Times of Malcolm X premiered professionally in 1986 at the New York City Opera. The work inaugurated a new genre: the opera based on a contemporary political subject. Davis's score is composed of an effortless blending of swing, bebop, gospel, hip-hop, traditional West Africans rhythms, classical Western music, and improvised sections. The piece is successful at examining from several innovative angles the seminal association between Malcolm X and Elijah Muhammad and inevitability of the re...

Cellular damage from oxidative stress, in particular following ischemic injury, occurs during heart attack, stroke, or traumatic injury, and is potentially reducible with appropriate drug treatment. We previously reported that caffeic acid phenethyl ester (CAPE), a plant-derived polyphenolic compound, protected human umbilical vein endothelial cells (HUVEC) from menadione-induced oxidative stress and that this cytoprotective effect was correlated with the capacity to induce heme oxygenase-1 (HMOX1) and its protein product, a phase II cytoprotective enzyme. To further improve this cytoprotective effect, we studied a synthetic triterpenoid, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), which is known as a potent phase II enzyme inducer with antitumor and anti-inflammatory activities, and compared it to CAPE. CDDO-Im at 200 nM provided more protection to HUVEC against oxidative stress than 20 μM CAPE. We explored the mechanism of CDDO-Im cytoprotection with gene expression profiling and pathway analysis and compared to that of CAPE. In addition to potent up-regulation of HMOX1, heat shock proteins (HSP) were also found to be highly induced by CDDO-Im in HUVEC. Pathway analysis results showed that transcription factor Nrf2-mediated oxidative stress response was among the top canonical pathways commonly activated by both CDDO-Im and CAPE. Compared to CAPE, CDDO-Im up-regulated more HSP and some of them to a much higher extent. In addition, CDDO-Im treatment affected Nrf2 pathway more significantly. These findings may provide an explanation why CDDO-Im is a more potent cytoprotectant than CAPE against oxidative stress in HUVEC.

We conducted a small retrospective study of rates of early complications associated with external fixation of pediatric femur fractures and compared rates at our institution with those reported in the literature. In our series of 22 patients, early complications included 12 pin-track infections (54.5%), 2 cases of loss of reduction (9.1%), 1 pin-track abscess (4.5%), and 1 refracture (4.5%). Overall rates (ours combined with those reported by other investigators) were 4.7% (34/719) for refractures and 33.1% (224/677) for pin-track infections. Factors that correlated with refractures were open fracture, bilateral fracture, and longer time in fixator. Factors with inconclusive correlations were fracture pattern, dynamization status, fixator type, pin size, and number of pins.