Publications by authors named "Andrew P Cap"

229 Publications

Fluid Resuscitation in Tactical Combat Casualty Care; TCCC Guidelines Change 21-01. 4 November 2021.

J Spec Oper Med 2021 ;21(4):126-137

Hemorrhagic shock in combat trauma remains the greatest life threat to casualties with potentially survivable injuries. Advances in external hemorrhage control and the increasing use of damage control resuscitation have demonstrated significant success in decreasing mortality in combat casualties. Presently, an expanding body of literature suggests that fluid resuscitation strategies for casualties in hemorrhagic shock that include the prehospital use of cold-stored or fresh whole blood when available, or blood components when whole blood is not available, are superior to crystalloid and colloid fluids. On the basis of this recent evidence, the Committee on Tactical Combat Casualty Care (TCCC) has conducted a review of fluid resuscitation for the combat casualty who is in hemorrhagic shock and made the following new recommendations: (1) cold stored low-titer group O whole blood (CS-LTOWB) has been designated as the preferred resuscitation fluid, with fresh LTOWB identified as the first alternate if CS-LTOWB is not available; (2) crystalloids and Hextend are no longer recommended as fluid resuscitation options in hemorrhagic shock; (3) target systolic blood pressure (SBP) resuscitation goals have been redefined for casualties with and without traumatic brain injury (TBI) coexisting with their hemorrhagic shock; and (4) empiric prehospital calcium administration is now recommended whenever blood product resuscitation is required.
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January 2022

Joint Trauma System Clinical Practice Guideline (JTS CPG): Prehospital Blood Transfusion. 30 October 2020.

J Spec Oper Med 2021 ;21(4):11-21

This Clinical Practice Guideline (CPG) provides a brief summary of the scientific literature for prehospital blood use, with an emphasis on the en route care environment. Updates include the importance of calcium administration to counteract the deleterious effects of hypocalcemia, minimal to no use of crystalloid, and stresses the importance of involved and educated en route care medical directors alongside at a competent prehospital and en route care providers (see Table 1). With the paradigm shift to use FDA-approved cold stored low titer group O whole blood (CS-LTOWB) along with the operational need for continued use of walking blood banks (WBB) and point of injury (POI) transfusion, there must be focused, deliberate training incorporating the different whole blood options. Appropriate supervision of autologous blood transfusion training is important for execution of this task in support of deployed combat operations as well as other operations in which traumatic injuries will occur. Command emphasis on the importance of this effort as well as appropriate logistical support are essential elements of a prehospital blood program as part of a prehospital/en route combat casualty care system.
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January 2022

Suppression of fibrin(ogen)-driven pathologies through controlled knockdown by lipid nanoparticle delivery of siRNA.

Blood 2021 Dec 27. Epub 2021 Dec 27.

University of British Columbia, Canada.

Fibrinogen plays a pathologic role in multiple diseases. It contributes to thrombosis and modifies inflammatory and immune responses, supported by studies in mice expressing fibrinogen variants with altered function or with a germline fibrinogen deficiency. However, therapeutic strategies to safely and effectively tailor plasma fibrinogen concentration are lacking. Here, we developed a strategy to tune fibrinogen expression by administering lipid nanoparticle (LNP)-encapsulated siRNA targeting the fibrinogen α chain (siFga). Three distinct LNP-siFga reagents reduced both hepatic Fga mRNA and fibrinogen levels in platelets and plasma, with plasma levels decreased to 42%, 16% and 4% of normal within one-week of administration. Using the most potent siFga, circulating fibrinogen was controllably decreased to 32%, 14%, and 5% of baseline with a 0.5, 1, and 2 mg/kg dose, respectively. Whole blood from mice treated with siFga formed clots with significantly decreased clot strength ex vivo, but siFga treatment did not compromise hemostasis following saphenous vein puncture or tail transection. In an endotoxemia model, siFga suppressed the acute phase response and decreased plasma fibrinogen, D-dimer, and proinflammatory cytokine levels. In a sterile peritonitis model, siFga restored normal macrophage migration in plasminogen-deficient mice. Finally, treatment of mice with siFga decreased the metastatic potential of tumour cells in a manner comparable to that observed in fibrinogen-deficient mice. The results indicate that siFga causes robust and controllable depletion of fibrinogen and provide the proof-of-concept that this strategy can modulate the pleiotropic effects of fibrinogen in relevant disease models.
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http://dx.doi.org/10.1182/blood.2021014559DOI Listing
December 2021

Intravenous administration of mesenchymal stromal cells leads to a dose dependent coagulopathy and is unable to attenuate acute traumatic coagulopathy in rats.

J Trauma Acute Care Surg 2021 Nov 17. Epub 2021 Nov 17.

Blood and Shock Resuscitation, United States Army Institute of Surgical Research, Fort Sam Houston, TX 78234.

Background: Mesenchymal stromal cells (MSC) express surface tissue factor (TF), which may affect hemostasis and detract from therapeutic outcomes of MSCs if administered intravenously (IV). In this study, we determine a safe dose of MSCs for IV administration, and further demonstrate the impact of IV-MSC on acute traumatic coagulopathy (ATC) in rats.

Methods: TF expression of rat bone marrow derived MSC (BMSC) or adipose derived MSC (AMSC) was detected by immunohistochemistry and ELISA. The coagulation properties were measured in MSC-treated rat whole blood, and blood samples collected from rats after IV administration of MSCs. ATC-rats underwent polytrauma and 40% hemorrhage, followed by IV administration of 5 or 10million/kg BMSCs (BMSC-5, BMSC-10), or vehicle at 1 hr after trauma.

Results: Rat MSCs expressed TF, and incubation of rat BMSCs or AMSCs with whole blood in vitro led to a significantly shortened clotting time (CT). However, a dose-dependent prolongation of prothrombin time (PT) with reduction in platelet counts and fibrinogen was found in healthy rat treated with IV-MSCs. BMSCs at 5 million/kg or less led to minimal effect on hemostasis. MSCs were not found in circulation, but in the lungs after IV administration regardless of the dosage. ATC with prolonged PT was not significantly affected by 5 or 10million/kg BMSCs. BMSC-10 led to significantly lower fibrinogen and platelet counts; while significantly higher levels of lactate, wet/dry weight ratio and leukocyte infiltration in the lung were present compared to BMSC-5 or vehicle. No differences were seen in immune or inflammatory profiles with BMSC treatment in ATC-rats, at least in the acute timeframe.

Conclusions: Intravenous administration of MSCs leads to a risk of coagulopathy associated with a dose-dependent reduction in platelet counts and fibrinogen, and is incapable of restoring hemostasis of rats with ATC after polytrauma and hemorrhagic shock.

Level Of Evidence: Animal and laboratory studies; Study type: therapeutic.
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http://dx.doi.org/10.1097/TA.0000000000003476DOI Listing
November 2021

Blood Product Administration During Transport Throughout the US Africa Command Theater of Operation.

J Spec Oper Med 2021 ;21(3):66-70

Background: United States Africa Command (US AFRICOM) is one of six US Defense Department's geographic combatant commands and is responsible to the Secretary of Defense for military relations with African nations, the African Union, and African regional security organizations. A full-spectrum combatant command, US AFRICOM is responsible for all US Department of Defense operations, exercises, and security cooperation on the African continent, its island nations, and surrounding waters. We seek to characterize blood product administration within AFRICOM using the in-transit visibility tracking tool known as TRAC2ES (TRANSCOM Regulating and Command & Control Evacuation System).

Methods: We performed a retrospective review of TRAC2ES medical evacuations from the AFRICOM theater of operations conducted between 1 January 2008 and 31 December 2018.

Results: During this time, there were 963 cases recorded in TRAC2ES originating within AFRICOM, of which 10 (1%) cases received blood products. All patients were males. One was a Department of State employee, one was a military working dog, and the remainder were military personnel. Of the ten humans, seven were the result of trauma, most by way of gunshot wound, and three were due to medical causes. Among human subjects receiving blood products for traumatic injuries, a total of 5 units of type O negative whole blood, 29 units of packed red blood cells (pRBCs), and 9 units of fresh frozen plasma (FFP) were transfused. No subjects underwent massive transfusion of blood products, and only one subject received pRBCs and FFP in 1:1 fashion. All subjects survived until evacuation.

Conclusions: Within the TRAC2ES database, blood product administration within AFRICOM was infrequent, with some cases highlighting lack of access to adequate blood products. Furthermore, the limitations within this database highlight the need for systems designed to capture medical care performance improvement, as this database is not designed to support such analyses. A mandate for performance improvement within AFRICOM that is similar to that of the US Central Command would be beneficial if major improvements are to occur.
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September 2021

The rebirth of the cool: a narrative review of the clinical outcomes of cold stored low titer group O whole blood recipients compared to conventional component recipients in trauma.

Hematology 2021 Dec;26(1):601-611

Vitalant, Pittsburgh, PA, USA.

There has been renewed interest in the use of low titer group O whole blood (LTOWB) for the resuscitation of civilian casualties. LTOWB offers several advantages over conventional components such as providing balanced resuscitation in one bag that contains less additive/preservative solution than an equivalent volume of conventional components, is easier and faster to transfuse than multiple components, avoids blood product ratio confusion, contains cold stored platelets, and reduces donor exposures. The resurgence in its use in the resuscitation of civilian trauma patients has led to the publication of an increasing number of studies on its use, primarily amongst adult recipients but also in pediatric patients. These studies have indicated that hemolysis does not occur amongst adult and pediatric non-group O recipients of a modest quantity of LTOWB. The published studies to date on mortality have shown conflicting results with some demonstrating a reduction following LTOWB transfusion while most others have not shown a reduction; there have not been any studies to date that have found significantly increased overall mortality amongst LTOWB recipients. Similarly, when other clinical outcomes, such as venous thromboembolism, sepsis, hospital or intensive care unit lengths of stay are evaluated, LTOWB recipients have not demonstrated worse outcomes compared to conventional component recipients. While definitive proof of the trends in these morbidity and mortality outcomes awaits confirmation in randomized controlled trials, the evidence to date indicates the safety of transfusing LTOWB to injured civilians.
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http://dx.doi.org/10.1080/16078454.2021.1967257DOI Listing
December 2021

Whole blood resuscitation restores intestinal perfusion and influences gut microbiome diversity.

J Trauma Acute Care Surg 2021 12;91(6):1002-1009

From the Department of Surgery (J.Y., S.S., S.E.N.), UT Health San Antonio, San Antonio; Coagulation and Blood Research, US Army Institute of Surgical Research (W.M., X.W., D.D., D.Z., A.P.C., J.B., S.E.N.), Fort Sam Houston, Texas; Department of Medicine, Uniformed Services University of the Health Sciences (D.B.), Bethesda, Maryland; and Department of Molecular Medicine (Z.L.), Greehey Children's Cancer Research Institute, UT Health San Antonio, San Antonio, Texas.

Objective: Gut dysbiosis, an imbalance in the gut microbiome, occurs after trauma, which may be ameliorated with transfusion. We hypothesized that gut hypoperfusion following trauma causes dysbiosis and that whole blood (WB) resuscitation mitigates these effects.

Methods: Anesthetized rats underwent sham (S; laparotomy only, n = 6); multiple injuries (T; laparotomy, liver and skeletal muscle crush injuries, and femur fracture, n = 5); multiple injuries and 40% hemorrhage (H; n = 7); and multiple injuries, hemorrhage, and WB resuscitation (R; n = 7), which was given as 20% estimated blood volume from donor rats 1 hour posttrauma. Baseline cecal mesenteric tissue oxygen (O2) concentration was measured following laparotomy and at 1 hour and 2 hours posttrauma. Fecal samples were collected preinjury and at euthanasia (2 hours). 16S rRNA sequencing was performed on purified DNA, and diversity and phylogeny were analyzed with QIIME (Knight Lab, La Jolla, CA; Caporaso Lab, Flagstaff, AZ) using the Greengenes 16S rRNA database (operational taxonomic units; 97% similarity). α and β diversities were estimated using observed species metrics. Permutational analysis of variance was performed for overall significance.

Results: In H rats, an average decline of 36% ± 3.6% was seen in the mesenteric O2 concentration at 1 hour without improvement by 2 hours postinjury, which was reversed following resuscitation at 2 hours postinjury (4.1% ± 3.1% difference from baseline). There was no change in tissue O2 concentration in the S or T rats. β Diversity differed among groups for all measured indices except Bray-Curtis, with the spatial median of the S and R rats more similar compared with S and H rats (p < 0.05). While there was no difference in α diversity found among the groups, indices were significantly correlated with mesenteric O2 concentration. Members of the family Enterobacteriaceae were significantly enriched in only 2 hours.

Conclusion: Mesenteric perfusion after trauma and hemorrhage is restored with WB resuscitation, which influences β diversity of the gut microbiome. Whole blood resuscitation may also mitigate the effects of hemorrhage on intestinal dysbiosis, thereby influencing outcomes.
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http://dx.doi.org/10.1097/TA.0000000000003381DOI Listing
December 2021

Synthetic blood and blood products for combat casualty care and beyond.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S26-S32

From the US Army Institute of Surgical Research (A.P.C.), For Sam Houston, Texas; Uniformed Services University (A.P.C., J.W.C.), Bethesda, Maryland; Division of Traumatology, Surgical Critical Care & Emergency Surgery (J.W.C.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Joint Health Command (M.C.R.), Australian Defence Force, Canberra; Faculty of Medicine (M.C.R.), University of Queensland, Brisbane; and Royal Brisbane and Women's Hospital (M.C.R.), Brisbane, Australia.

Abstract: Synthetic biology adopts an engineering design approach to create innovative treatments that are reliable, scalable, and customizable to individual patients. Interest in substitutes for allogenic blood components, primarily red blood cells and platelets, increased in the 1980s because of concerns over infectious disease transmission. However, only now, with emerging synthetic approaches, are such substitutes showing genuine promise. Affordable alternatives to donated blood would be of enormous benefit worldwide. Several approaches to replacing the oxygen-carrying function of red cells are under advanced investigation. Hemoglobin-based oxygen carriers incorporate modifications to reduce the renal toxicity and nitric oxide scavenging of free hemoglobin. While use of earlier-generation hemoglobin-based oxygen carriers may be limited to circumstances in which blood transfusion is not an option, recent advances in chemical modification of hemoglobin may eventually overcome such problems. Another approach encases hemoglobin molecules in biocompatible synthetic nanoparticles. An alternative is the ex vivo production of red cells in bioreactors, with or without genetic manipulation, that offers the potential of a universal donor product. Various strategies to manufacture synthetic platelets are also underway, ranging from simple phospholipid liposomes encapsulating adenosine diphosphate and decorated with fibrinogen fragments, to more complex capsules with multiple receptor peptide sequences. Ex vivo production of platelets in bioreactors is also possible including, for example, platelets derived from induced pluripotent stem cells that are differentiated into a megakaryocytic lineage. Prior to clinical use, trials assessing synthetic blood components must evaluate meaningful safety and effectiveness outcomes in relatively large numbers of critically ill patients. Overcoming these challenges may be as much a hurdle as product design. This article reviews the state of the science of the synthetic biology approach to developing blood component substitutes.
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http://dx.doi.org/10.1097/TA.0000000000003248DOI Listing
August 2021

A prehospital scoring system for predicting the need for emergent blood product transfusion.

Transfusion 2021 07;61 Suppl 1:S195-S205

The Trauma and Combat Medicine Branch, Surgeon General's Headquarters, Israel Defense Forces, Ramat Gan, Israel.

Background: Several tools have been proven to predict the need for massive transfusion in trauma casualties, yet tools that are easily applicable in the prehospital setting for predicting the need for any blood product transfusion in the emergency department (ED) are lacking.

Methods: A retrospective analysis of the cross-referenced Israeli Defense Forces Trauma Registry and the Israeli National Trauma Registry databases was performed to identify predictors for any blood product transfusion in the ED. A scoring system was developed after internally validating the prediction model. Division to risk groups was performed.

Results: Seven variables (systolic blood pressure, heart rate, arterial oxygen saturation, trunk involvement, mechanism of injury, chest decompression, and tourniquet application) were included in the scoring system, ranging from 0 to 11.5. Risk groups for ED transfusion included very low (0.8%), low (3.2%), intermediate (8.5%), and high (31.2%) risk.

Conclusion: A scoring system for predicting the need for any blood product transfusion in the ED was developed, based on information readily available in the early stages of prehospital resuscitation, allowing the receiving medical facility to prepare for that need.
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http://dx.doi.org/10.1111/trf.16529DOI Listing
July 2021

Coagulation function of never frozen liquid plasma stored for 40 days.

Transfusion 2021 07;61 Suppl 1:S111-S118

U.S. Army Institute of Surgical Research, JBSA-Fort Sam Houston, Texas, USA.

Background: Never frozen liquid plasma (LP) has limited shelf life versus fresh frozen plasma (FFP) or plasma frozen within 24 h (PF24). Previous studies showed decreasing factor activities after Day (D)14 in thawed FFP but no differences between LP and FFP until D10. This study examined LP function through D40.

Study Design And Methods: FFP and PF24 were stored at -20°C until assaying. LP was assayed on D5 then stored (4°C) for testing through D40. A clinical coagulation analyzer measured Factor (F)V, FVIII, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT). Thromboelastography (TEG) and thrombogram measured functional coagulation. Ristocetin cofactor assay quantified von Willebrand factor (vWF) activity. Residual platelets were counted.

Results: FV/FVIII showed diminished activity over time in LP, while PT and aPTT both increased over time. LP vWF declined significantly by D7. Fibrinogen remained high through D40. Thrombin lagtime was delayed in LP but consistent to D40, while peak thrombin was significantly lower in LP but did not significantly decline over time. TEG R-time and angle remained constant. LP and PF24 (with residual platelets) had initially higher TEG maximum amplitudes (MA), but by D14 LP was similar to FFP.

Conclusion: Despite significant declines in some factors in D40 LP, fibrinogen concentration and TEG MA were stable suggesting stored LP provides fibrinogen similarly to frozen plasmas even at D40. LP is easier to store and prepare for prehospital transfusion, important benefits when the alternative is crystalloid.
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http://dx.doi.org/10.1111/trf.16526DOI Listing
July 2021

Intraoperative blood transfusions in burn patients.

Transfusion 2021 07;61 Suppl 1:S183-S187

U.S. Army Institute of Surgical Research, Research Directorate, Fort Sam Houston, Texas, USA.

Background: Donated blood is a valuable and limited resource. Excision of burn wounds often leads to significant blood loss requiring transfusion. Accurately estimating blood loss is difficult, so examining the amount of blood products given intraoperatively is a clinically relevant way to measure utilization of this valuable resource. In this study, we examined the factors that influenced the amount of blood given intraoperatively during burn wound excisions.

Study Design And Methods: A retrospective analysis of patients admitted to a single burn center over 5 years who underwent excision of their burn wounds and received intraoperative blood products was performed. Patient and burn characteristics as well as pertinent surgical data and laboratory values on the day of surgery and postoperatively were gathered. A linear regression analysis examined factors influencing the number of units of products given and a predictive model was generated.

Results: A total of 563 operations performed on 166 patients were included. The amount of burn excised was the most influential variable on the amount of blood products given. Hemoglobin level, international normalized ratio, and platelet count on the day of surgery were associated with transfusion of different blood products. A predictive model was generated to aid in preoperative ordering of blood products.

Conclusion: The amount of burn excised and common hematology and coagulation lab values were associated with the amount of different blood products administered during burn surgery. The predictive model generated needs to be validated prospectively to aid in preoperative planning for burn excisions.
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http://dx.doi.org/10.1111/trf.16505DOI Listing
July 2021

Civilian walking blood bank emergency preparedness plan.

Transfusion 2021 07;61 Suppl 1:S313-S325

University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place.

Methods And Materials: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage.

Results And Conclusions: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.
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http://dx.doi.org/10.1111/trf.16458DOI Listing
July 2021

Joint Trauma System, Defense Committee on Trauma, and Armed Services Blood Program consensus statement on whole blood.

Transfusion 2021 07;61 Suppl 1:S333-S335

Uniformed Services University, Bethesda, Maryland, USA.

Hemorrhage is the most common mechanism of death in battlefield casualties with potentially survivable injuries. There is evidence that early blood product transfusion saves lives among combat casualties. When compared to component therapy, fresh whole blood transfusion improves outcomes in military settings. Cold-stored whole blood also improves outcomes in trauma patients. Whole blood has the advantage of providing red cells, plasma, and platelets together in a single unit, which simplifies and speeds the process of resuscitation, particularly in austere environments. The Joint Trauma System, the Defense Committee on Trauma, and the Armed Services Blood Program endorse the following: (1) whole blood should be used to treat hemorrhagic shock; (2) low-titer group O whole blood is the resuscitation product of choice for the treatment of hemorrhagic shock for all casualties at all roles of care; (3) whole blood should be available within 30 min of casualty wounding, on all medical evacuation platforms, and at all resuscitation and surgical team locations; (4) when whole blood is not available, component therapy should be available within 30 min of casualty wounding; (5) all prehospital medical providers should be trained and logistically supported to screen donors, collect fresh whole blood from designated donors, transfuse blood products, recognize and treat transfusion reactions, and complete the minimum documentation requirements; (6) all deploying military personnel should undergo walking blood bank prescreen laboratory testing for transfusion transmitted disease immediately prior to deployment. Those who are blood group O should undergo anti-A/anti-B antibody titer testing.
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http://dx.doi.org/10.1111/trf.16454DOI Listing
July 2021

Evaluation of KP-1199: a novel acetaminophen analog for hemostatic function and antinociceptive effects.

Transfusion 2021 07;61 Suppl 1:S234-S242

United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA.

Background: Acetaminophen (APAP) is a widely self-prescribed analgesic for mild to moderate pain, but overdose or repeat doses can lead to liver injury and death. Kalyra Pharmaceuticals has developed a novel APAP analog, KP-1199, currently in Phase 1 clinical studies, which lacks hepatotoxicity. In this study, the authors evaluated the antinociceptive effect of KP-1199 on thermal injury-induced nociceptive behaviors as well as hemostatic parameters using human blood samples.

Methods: Full-thickness thermal injury was induced in anesthetized adult male Sprague-Dawley rats. On day 7 post-injury, KP-1199 (30 and 60 mg/kg) or APAP (60 mg/kg) was administered orally. Antinociception of KP-1199 and APAP were assessed at multiple time points using Hargreaves' test. In separate experiments, human whole blood was collected and treated with either KP-1199, APAP, or Vehicle (citrate buffer) at 1× (214 μg/ml) and 10× (2140 μg/ml) concentrations. The treated blood samples were assessed for: clotting function, thrombin generation, and platelet activation.

Results: APAP did not produce antinociceptive activity. KP-1199 treatment significantly increased the nociceptive threshold, and the antinociceptive activity persisted up to 3 h post-treatment. In human samples, 10× APAP caused significantly prolonged clotting times and increased platelet activation, whereas KP-1199 had caused no negative effects on either parameter tested.

Conclusion: These results suggest that KP-1199 possesses antinociceptive activity in a rat model of thermal injury. Since KP-1199 does not induce platelet activation or inhibit coagulation, it presents an attractive alternative to APAP for analgesia, especially for battlefield or surgical scenarios where blood loss and blood clotting are of concern.
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http://dx.doi.org/10.1111/trf.16497DOI Listing
July 2021

Cold-stored platelets have better preserved contractile function in comparison with room temperature-stored platelets over 21 days.

Transfusion 2021 07;61 Suppl 1:S68-S79

Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA.

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.
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http://dx.doi.org/10.1111/trf.16530DOI Listing
July 2021

Whole blood at the tip of the spear: A retrospective cohort analysis of warm fresh whole blood resuscitation versus component therapy in severely injured combat casualties.

Surgery 2021 Jul 9. Epub 2021 Jul 9.

Uniformed Services University of the Health Sciences, Bethesda, MD; Department of Surgery, Scripps Mercy Hospital, San Diego, CA. Electronic address: https://twitter.com/docmartin22.

Background: Death from uncontrolled hemorrhage occurs rapidly, particularly among combat casualties. The US military has used warm fresh whole blood during combat operations owing to clinical and operational exigencies, but published outcomes data are limited. We compared early mortality between casualties who received warm fresh whole blood versus no warm fresh whole blood.

Methods: Casualties injured in Afghanistan from 2008 to 2014 who received ≥2 red blood cell containing units were reviewed using records from the Joint Trauma System Role 2 Database. The primary outcome was 6-hour mortality. Patients who received red blood cells solely from component therapy were categorized as the non-warm fresh whole blood group. Non- warm fresh whole blood patients were frequency-matched to warm fresh whole blood patients on identical strata by injury type, patient affiliation, tourniquet use, prehospital transfusion, and average hourly unit red blood cell transfusion rates, creating clinically unique strata. Multilevel mixed effects logistic regression adjusted for the matching, immortal time bias, and other covariates.

Results: The 1,105 study patients (221 warm fresh whole blood, 884 non-warm fresh whole blood) were classified into 29 unique clinical strata. The adjusted odds ratio of 6-hour mortality was 0.27 (95% confidence interval 0.13-0.58) for the warm fresh whole blood versus non-warm fresh whole blood group. The reduction in mortality increased in magnitude (odds ratio = 0.15, P = .024) among the subgroup of 422 patients with complete data allowing adjustment for seven additional covariates. There was a dose-dependent effect of warm fresh whole blood, with patients receiving higher warm fresh whole blood dose (>33% of red blood cell-containing units) having significantly lower mortality versus the non-warm fresh whole blood group.

Conclusion: Warm fresh whole blood resuscitation was associated with a significant reduction in 6-hour mortality versus non-warm fresh whole blood in combat casualties, with a dose-dependent effect. These findings support warm fresh whole blood use for hemorrhage control as well as expanded study in military and civilian trauma settings.
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http://dx.doi.org/10.1016/j.surg.2021.05.051DOI Listing
July 2021

Extracellular vesicles derived from cardiosphere-derived cells as a potential antishock therapeutic.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S81-S88

From the Coagulation and Blood Research (Blood) (T.C.C., X.W., J.D.K., J.G.-M., C.L.S., B.L., A.P.C., J.A.B.), United States Army Institute of Surgical Research, San Antonio, Texas; Capricor Therapeutics Institute (J.J.M., K.A.P., L.R.-B., N.A.A., L.S.M.), Beverly Hills, California; Department of Biological Chemistry (S.J.G.), Johns Hopkins, Baltimore, Maryland; and Department of Biomedical Engineering (C.R.R.), The University of Texas at San Antonio, San Antonio, Texas.

Background: Extracellular vesicles (EVs) isolated from cardiosphere-derived cells (CDC-EVs) are coming to light as a unique cell-free therapeutic. Because of their novelty, however, there still exist prominent gaps in knowledge regarding their therapeutic potential. Herein the therapeutic potential of CDC-EVs in a rat model of acute traumatic coagulopathy induced by multiple injuries and hemorrhagic shock is outlined.

Methods: Extracellular vesicle surface expression of procoagulant molecules (tissue factor and phosphatidylserine) was evaluated by flow cytometry. Extracellular vesicle thrombogenicity was tested using calibrated thrombogram, and clotting parameters were assessed using a flow-based adhesion model simulating blood flow over a collagen-expressing surface. The therapeutic efficacy of EVs was then determined in a rat model of acute traumatic coagulopathy induced by multiple injuries and hemorrhagic shock.

Results: Extracellular vesicles isolated from cardiosphere-derived cells are not functionally procoagulant and do not interfere with platelet function. In a rat model of multiple injuries and hemorrhagic shock, early administration of EVs significantly reduced the elevation of lactate and creatinine and did not significantly enhance coagulopathy in rats with acute traumatic coagulopathy.

Conclusion: The results of this study are of great relevance to the development of EV products for use in combat casualty care, as our studies show that CDC-EVs have the potential to be an antishock therapeutic if administered early. These results demonstrate that research using CDC-EVs in trauma care needs to be considered and expanded beyond their reported cardioprotective benefits.
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http://dx.doi.org/10.1097/TA.0000000000003218DOI Listing
August 2021

Michael A. Dubick, PhD: A man devoted to advancing the care of combat wounded.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S6-S8

From the United States Army Institute of Surgical Research (A.P.C.), Fort Sam Houston, Texas; Department of Medicine (A.P.C.), F. Edward Hébert School of Medicine at the Uniformed Services University, Bethesda, Maryland; Division of Traumatology, Surgical Critical Care & Emergency Surgery, Department of Surgery (J.W.C.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics (J.W.C.), University of Pennsylvania, Philadelphia, PA; Office of the Assistant Secretary of Defense for Health Affairs (J.W.C.), Falls Church, VA; and Department of Surgery (J.W.C.), F. Edward Hébert School of Medicine at the Uniformed Services University, Bethesda, Maryland.

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http://dx.doi.org/10.1097/TA.0000000000003303DOI Listing
August 2021

Charting a new path after two decades of war and a global pandemic.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S1-S5

From the United States Army Institute of Surgical Research (A.P.C.), Fort Sam Houston, Texas; Department of Medicine (A.P.C.), F. Edward Hébert School of Medicine at the Uniformed Services University, Bethesda; US Army Medical Research & Development Command (T.M.P.), Fort Detrick; Department of Surgery (T.M.P., J.W.C.), F. Edward Hébert School of Medicine at the Uniformed Services University, Bethesda, Maryland; Division of Traumatology, Surgical Critical Care & Emergency Surgery, Department of Surgery (J.W.C.), Perelman School of Medicine at the University of Pennsylvania; Leonard Davis Institute of Health Economics (J.W.C.), University of Pennsylvania, Philadelphia, Pennsylvania; and Office of the Assistant Secretary of Defense for Health Affairs (J.W.C.), Falls Church, Virginia.

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August 2021

Role of albumin on endothelial basement membrane and hemostasis in a rat model of hemorrhagic shock.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S65-S73

From the Tactical Combat Casualty Care Research Department, US Army Institute of Surgical Research, Joint Base San Antonio-Fort Sam Houston, Texas.

Background: We sought to determine the extent of loss of endothelial basement membrane (BM), leukocyte recruitment, and changes in coagulation after hemorrhagic shock, followed by limited-volume resuscitation (LVR) with 5% albumin (ALB).

Methods: Anesthetized rats were bled 40% of blood volume and assigned to treatment groups: untreated (n = 6), LVR with normal saline (NS; n = 8), or LVR with ALB (n = 8). Sham rats (n = 6) underwent all procedures except hemorrhage or resuscitation. Blood samples were assayed for active proteases, such as metalloproteinase 9 (MMP-9) and a disintegrin and metalloproteinase 10 (ADAM-10), BM-type heparan sulfate proteoglycan (perlecan), cell count, and coagulation function. Leukocyte transmigration was used to estimate the net efficiency of leukocyte recruitment in cremaster venules.

Results: Hemorrhage significantly lowered red cell count, but white cell and platelet counts did not change (vs. sham). Ionized calcium in plasma was significantly reduced in untreated and remained so after NS. In contrast, ionized calcium was normalized after ALB. Plasma expansion after NS and ALB further reduced leukocyte and platelet counts. Metalloproteinase 9, ADAM-10, and perlecan were significantly higher in untreated rats (vs. sham). Albumin normalized MMP-9, ADAM-10, and perlecan levels, while NS further increased MMP-9, ADAM-10, and perlecan (vs. sham). Transmigrated leukocytes doubled in the untreated group and remained elevated after NS (vs. sham) but normalized after ALB. Albumin reduced every stage of the leukocyte recruitment process to sham levels.

Conclusion: Despite similar plasma expansion, NS weakened platelet function contrary to ALB. Plasma expansion with ALB resulted in restoration of BM integrity and attenuation of leukocyte recruitment to tissues, in contrast to NS. Albumin plays a critical role in restoring BM integrity, attenuating leukocyte recruitment to tissues, and optimizing hemostasis by increasing ionized calcium in plasma.
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http://dx.doi.org/10.1097/TA.0000000000003298DOI Listing
August 2021

Recommended primary outcomes for clinical trials evaluating hemostatic blood products and agents in patients with bleeding: Proceedings of a National Heart Lung and Blood Institute and US Department of Defense Consensus Conference.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S19-S25

From the Division of Critical Care, Department of Pediatrics (P.C.S.), Washington University School of Medicine, St. Louis, Missouri; National Heart Lung and Blood Institute (N.E.K., A.L.K.), National Institutes of Health, Bethesda, Maryland; US Army Institute of Surgical Research (A.P.C.), Fort Sam Houston, Texas; Heart Failure Service, Cardiac Anti-coagulation Service, Lucile Packard Children's Hospital Stanford, Stanford University School of Medicine (C.S.A.), Palo Alto, California; Division of Gastroenterology (A.B.), McGill University Health Centre, McGill University, Montréal, Québec, Canada; Division of Hematology (T.B.G.), University of Washington, Seattle, Washington; Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Surgery (J.B.H.), Center for Injury Science, Division of Acute Care Surgery, University of Alabama at Birmingham, Birmingham, Alabama; Division of Hematology and Thromboembolism, Department of Medicine (A.I.), and Department of Health Research Methods, Evidence, and Impact (A.I.), McMaster University, Hamilton, Ontario, Canada; Division of Gastroenterology, Department of Medicine (D.M.J.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Division of Hematology and Blood Research Center, Department of Medicine (N.S.K.), University of North Carolina, Chapel Hill, North Carolina; Department of Anesthesiology and Critical Care (J.H.L.), Duke University Medical Center, Durham, North Carolina; Department of Neurology (S.A.M.), and Department of Neurosurgery (S.A.M.), Westchester Medical Center, New York Medical College, Valhalla, New York; Department of Surgery (E.E.M.), Ernest E Moore Shock Trauma Center at Denver Health, University of Colorado Denver, Denver, Colorado; Transfusion Medicine, NHS Blood and Transplant (S.J.S.), Oxford, United Kingdom; Department of Haematology, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust (S.J.S.), Oxford, United Kingdom; Radcliffe Department of Medicine, University of Oxford, and Oxford BRC Haematology Theme (S.J.S.), Oxford, United Kingdom; Berry Consultants LLC (R.J.L.), Austin, Texas; Department of Emergency Medicine (R.J.L.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; and Division of Pediatric Hematology and Oncology (M.E.S.), and Division of Pediatric Critical Care Medicine (M.E.S.), Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota.

Abstract: High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.
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August 2021

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine - Part 2: Transfusion Advances.

Front Vet Sci 2021 7;8:571370. Epub 2021 May 7.

U.S. Army Institute of Surgical Research, Joint Base San Antonio, San Antonio, TX, United States.

Since the inception of recent conflicts in Afghanistan and Iraq, transfusion practices in human military medicine have advanced considerably. Today, US military physicians recognize the need to replace the functionality of lost blood in traumatic hemorrhagic shock and whole blood is now the trauma resuscitation product of choice on the battlefield. Building on wartime experiences, military medicine is now one of the country's strongest advocates for the principle of hemostatic resuscitation using whole blood or balanced blood components as the primary means of resuscitation as early as possibly following severe trauma. Based on strong evidence to support this practice in human combat casualties and in civilian trauma care, military veterinarians strive to practice similar hemostatic resuscitation for injured Military Working Dogs. To this end, canine whole blood has become increasingly available in forward environments, and non-traditional storage options for canine blood and blood components are being explored for use in canine trauma. Blood products with improved shelf-life and ease of use are not only useful for military applications, but may also enable civilian general and specialty practices to more easily incorporate hemostatic resuscitation approaches to canine trauma care.
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http://dx.doi.org/10.3389/fvets.2021.571370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138582PMC
May 2021

Increasing hemoglobin concentration with an artificial oxygen carrier improves severe anemia-induced degraded cognitive function.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S182-S185

From the Department of Anesthesia and Perioperative Care, University of California (R.B.W.), San Francisco, California; Department of Pathology (R.D.), University of Michigan Medical School; US Army Institute of Surgical Research (A.P.C.), JBSA-Ft Sam Houston, San Antonio, Texas; Department of Medicine (A.P.C.), Uniformed Services University of the Health Sciences, Bethesda, Maryland; Pulmonary and Critical Care Medicine (V.R.), Wellstar Health System, Marietta, Georgia; Department of Anesthesiology and Perioperative Medicine and Bioengineering (J.H.W.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Laboratory Medicine Program (C.C.-G.) and Department of Medical Oncology and Hematology (C.C.-G.), University Health Network, University of Toronto, Toronto, Ontario, Canada.

Abstract: Before death, patients commonly experience impaired consciousness for a significant period, frequently preventing family and others from final interactions with the patient. Some of these episodes of cognitive impairment may be treatable, with treatment not offered owing to the perception of ultimate futility or expense, or both. One of the causes of terminal loss of consciousness or decreased lucidity can be inadequate cerebral oxygen delivery. We report five cases from four institutions where an infusion of a hemoglobin-based oxygen carrier to patients who were unconscious or not lucid owing to acute severe anemia (hemoglobin range, 2.1-5.2 g/dL) resulted in awakening or lucidity. We review briefly human cognitive function and anemia and remark about the use of a hemoglobin-based oxygen carrier for acute severe anemia when red cell transfusion is not an option.
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http://dx.doi.org/10.1097/TA.0000000000003261DOI Listing
August 2021

Hemostatic capacity of canine chilled whole blood over time.

J Vet Emerg Crit Care (San Antonio) 2021 Mar 11;31(2):239-246. Epub 2021 Mar 11.

US Army Institute of Surgical Research, Joint Base San Antonio, Fort Sam Houston, Texas, USA.

Objective: To determine the hemostatic potential of canine chilled whole blood maintained at clinically relevant storage conditions.

Design: In vitro experimental study.

Setting: Government blood and coagulation research laboratory and government referral veterinary hospital.

Animals: Ten healthy Department of Defense military working dogs.

Interventions: One unit of fresh whole blood was collected from each of 10 military working dogs using aseptic technique. Blood was maintained in a medical-grade refrigerator for 28 days at 4°C (39°F) and analyzed before refrigeration (day 0) and after (days 2, 4, 7, 9, 11, 14, 21, and 28).

Measurements And Main Results: Ten units of canine blood were analyzed with whole blood platelet aggregation, thromboelastography, CBC, biochemical analysis, blood gas, and prothrombin/activated partial thromboplastin/fibrinogen assay. Clotting strength of chilled blood was maintained up to 21 days despite significant decreases in platelet aggregation to ADP, collagen, or γ-thrombin, significant prolongation of prothrombin and activated partial thromboplastin times, and reduced speed of clot formation (K time, alpha angle). Fibrinogen concentration, WBC, RBC, and platelet counts did not change over time.

Conclusions: Chilled canine whole blood loses a small percentage of clot strength through 21 days of refrigerated storage. Further research is needed to determine if this hemostatic potential is clinically relevant in hemorrhaging dogs who require surgical intervention or are exposed to traumatic events.
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http://dx.doi.org/10.1111/vec.13055DOI Listing
March 2021

Interactions of human mesenchymal stromal cells with peripheral blood mononuclear cells in a Mitogenic proliferation assay.

J Immunol Methods 2021 05 18;492:113000. Epub 2021 Feb 18.

Blood and Coagulation Research, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, United States of America. Electronic address:

Background: Immunomodulation by mesenchymal stromal cells (MSCs) is a potentially important therapeutic modality. MSCs suppress peripheral blood mononuclear cell (PBMC) proliferation in vitro, suggesting a mechanism for suppressing inflammatory responses in vivo. This study details the interactions of PBMCs and MSCs.

Methods: Pooled human PBMCs and MSCs were co-cultured at different MSC:PBMC ratios and harvested from 0 to 120 h, with and without phytohaemagglutin A (PHA) stimulation. Proliferation of adherent MSCs and non-adherent PBMCs was assessed by quantitation of ATP levels. PBMC surface marker expression was analyzed by flow cytometry. Indoleamine 2,3-dioxygenase (IDO) activity was determined by kynurenine assay and IDO mRNA by RT-PCR. Cytokine release was measured by ELISA. Immunofluorescent microscopy detected MSC, PBMC, monocyte (CD14+) and apoptotic events.

Results: PBMC proliferation in response to PHA gave a robust ATP signal by 72 h, which was suppressed by co-culture with densely plated MSCs. Very low level MSC seeding densities relative to PBMC number reproducibly stimulated PBMC proliferation. The CD4+/CD3+ population significantly decreased over time while the CD8+/CD3+ population significantly increased. No change in CD4+/CD8+ ratio is seen with high density MSC co-culture; very low density MSCs augment the changes seen in PHA stimulated PBMCs alone. IDO activity in MSCs co-cultured with PBMCs correlated with PBMC suppression. MSCs increased the secretion of IL-10 and IL-6 from stimulated co-cultures and decreased TNF-α secretion. In stimulated co-culture, low density MSCs decreased in number; fluorescence immunomicroscopy detected association of PBMC with MSC and phosphatidyl serine externalization in both cell populations.

Conclusions: A bidirectional interaction between MSCs and PBMCs occurs during co-culture. High numbers of MSCs inhibit PHA-stimulated PBMC proliferation and the PBMC response to stimulation; low numbers of MSCs augment these responses. Low density MSCs are susceptible to attrition, apparently by PBMC-induced apoptosis. These results may have direct application when considering therapeutic dosing of patients; low MSC doses may have unintended detrimental consequences.
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http://dx.doi.org/10.1016/j.jim.2021.113000DOI Listing
May 2021

Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application.

Stem Cells Transl Med 2021 06 1;10(6):883-894. Epub 2021 Feb 1.

Sentien Biotechnologies, Inc, Lexington, Massachusetts, USA.

While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. In this system, MSCs are seeded on the exterior of a hollow-fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore-size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against directly injected "free" MSCs, a model of systemic administration. Our results showed that restricting MSCs exposure to plasma via a bioreactor extends the time necessary for clot formation to occur when compared with "free" MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Furthermore, application of this technology in two in vivo models did not require additional heparin in fully anticoagulated experimental animals to maintain target activated clotting time levels relative to heparin anticoagulated controls. Taken together the clinical use of bioreactor housed MSCs could offer a novel method to control systemic MSC exposure and prolong clot formation time.
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http://dx.doi.org/10.1002/sctm.20-0454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133341PMC
June 2021

Hypocalcemia in Military Casualties From Point of Injury to Surgical Teams in Afghanistan.

Mil Med 2021 01;186(Suppl 1):300-304

Joint Trauma System, Joint Base San Antonio-Fort Sam Houston, TX 78234, USA.

Introduction: Hypocalcemia is a known sequela of citrated blood product transfusion. Civilian data suggest hypocalcemia on hospital admission is associated with worse outcomes. Initial calcium levels in military casualties have not previously been analyzed. The objective of this retrospective review aimed to assess the initial calcium levels in military trauma casualties at different Forward Surgical Teams (FST) locations in Afghanistan and describe the effects of prehospital blood product administration on arrival calcium levels.

Materials And Methods: This is a retrospective cohort analysis of military casualties arriving from point of injury to one of two FSTs in Afghanistan from August 2018 to February 2019 split into four locations. The primary outcome was incidence of hypocalcemia (ionized calcium < 1.20 mmol/L).

Results: There were 101 patients included; 55 (54.5%) experienced hypocalcemia on arrival to the FST with a mean calcium of 1.16 mmol/L (95% confidence interval [CI], 1.14 to 1.18). The predominant mechanism of injury consisted of blast patterns, 46 (45.5%), which conferred an increased risk of hypocalcemia compared to all other patterns of injury (odds ratio = 2.42, P = .042). Thirty-eight (37.6%) patients required blood product transfusion. Thirty-three (86.8%) of the patients requiring blood product transfusion were hypocalcemic on arrival. Mean initial calcium of patients receiving blood product was 1.13 mmol/L (95% CI, 1.08 to 1.18), which was significantly lower than those who did not require transfusion (P = .01). Eight (7.9%) of the patients received blood products before arrival, with 6/8 (75%) presenting with hypocalcemia.

Conclusions: Hypocalcemia develops rapidly in military casualties and is prevalent on admission even before transfusion of citrated blood products. Blast injuries may confer an increased risk of developing hypocalcemia. This data support earlier use of calcium supplementation during resuscitation.
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http://dx.doi.org/10.1093/milmed/usaa267DOI Listing
January 2021

Neglected No More: Emerging Cellular Therapies in Traumatic Injury.

Stem Cell Rev Rep 2021 08 8;17(4):1194-1214. Epub 2021 Jan 8.

Blood & Coagulation Research Department, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA.

Traumatic injuries are a leading cause of death and disability in both military and civilian populations. Given the complexity and diversity of traumatic injuries, novel and individualized treatment strategies are required to optimize outcomes. Cellular therapies have potential benefit for the treatment of acute or chronic injuries, and various cell-based pharmaceuticals are currently being tested in preclinical studies or in clinical trials. Cellular therapeutics may have the ability to complement existing therapies, especially in restoring organ function lost due to tissue disruption, prolonged hypoxia or inflammatory damage. In this article we highlight the current status and discuss future directions of cellular therapies for the treatment of traumatic injury. Both published research and ongoing clinical trials are discussed here.
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http://dx.doi.org/10.1007/s12015-020-10086-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793620PMC
August 2021
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