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Expression of High Mobility Group Box 1 Protein
                             in a Polytrauma Model During Ground Transport and
                                        Simulated High-Altitude Evacuation




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                              Jae Hyek Choi, PhD, DVSc ; Teryn R. Roberts, PhD ; Kyle Sieck, BS ;
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                George T. Harea, BS ; Vitali Karaliou, MD ; Daniel S. Wendorff, BS ; Brendan M. Beely, RRT, BS ;
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                          Leopoldo C. Cancio, MD ; Valerie G. Sams, MD ; Andriy I. Batchinsky, MD  10
              ABSTRACT
              Background: We investigated the expression of high mobility   capabilities carried out via drones are being developed. New
              group box 1 (HMGB1) protein in a combat-relevant poly-  critical care capabilities and diagnostic tools to help guide tri-
              trauma/acute respiratory distress syndrome (ARDS) model. We   age and management of casualties will need to be validated to
              hypothesized that systemic HMGB1 expression is increased af-  avoid increased mortality on future battlefields.
              ter injury and during aeromedical evacuation (AE) at altitude.
              Methods: Female Yorkshire swine (n =15) were anesthetized   Among the injury mechanisms that are likely to cause increased
              and cannulated with a 23Fr dual-lumen catheter. Venovenous   mortality in future conflicts is chest trauma complicated by
              extracorporeal life support (VV ECLS) was initiated via the   ARDS.  Data from the USAISR Joint Theater Trauma Reg-
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              right jugular vein and carried out with animals uninjured on   istry from 2003-2011 during Operations Enduring Freedom
              day 1 and injured by bilateral pulmonary contusion on day   and Iraqi Freedom (OEF/OIF) showed that among the 6,030
              2. On both days, animals underwent transport and simulated   thoracic  injuries, pneumothorax and  pulmonary contusions
              AE. Systemic HMGB1 expression was measured in plasma   were the most common (51.8% and 50.2%, respectively).
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              by ELISA. Plasma-free Hb (pfHb) was measured with the use   Pulmonary contusion (PC) is one of the common consequences
              of spectrophotometric methods. Results: Plasma HMGB1 on   of thoracic trauma and may lead to early-onset ARDS. 5,7,8  PC
              day 1 was transiently higher at arrival to the AE chambers,   is an independent risk factor for pneumonia and ARDS and
              increased significantly after injury, reaching highest values at   carries a 10%–25% mortality, as well as the possibility of sig-
              8,000 ft on day 2, after which levels decreased but remained   nificant long-term disability. 9,10
              elevated versus baseline at each time point. pfHb decreased on
              day 1 at 30,000 ft and significantly increased on day 2 at 8,000   Diagnosis of injury severity following PC and during early
              ft and postflight. Conclusions: Systemic HMGB1 demonstrated   ARDS is a challenging task especially for combat medics and
              sustained elevation after trauma and altitude transport and may   Special Operations Forces (SOF). To ease diagnosis of injury se-
              provide a useful monitoring capability during en route care.  verity for SOF, a novel metric, HMGB1 protein, has been identi-
                                                                 fied as a mediator of ARDS and is expressed in blood following
              Keywords: acute respiratory distress syndrome; polytrauma;   activation of damaged cells after chest trauma or smoke inhala-
              evacuation; altitude physiology; HMGB1             tion injury. 11–13  In this study, we investigate HMGB1 expression
                                                                 in systemic blood samples obtained from uninjured and injured
                                                                 animals that undergo ECLS and AE as part of a larger combat
                                                                 relevant study. This is the first report of HMGB1 analysis from
              Introduction
                                                                 a severely injured animal model, which mimics human combat
              Ground and high-altitude evacuation of combat casualties is   injuries and subsequent AE with extracorporeal life support
              at the forefront of military research as it presents therapeu-  (ECLS). This marker may enable the SOF medic to grade injury
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              tic and logistical challenges.  Future anti-access area denial   severity and prognosis of possible multiorgan failure (MOF) at
              operations will prohibit immediate evacuation of casualties   or near the point of injury or while in transit during evacuation.
              because of contested airspace. This delay in evacuation, ne-  This first report aims to inform future efforts toward mobile
              cessitating extended care-in-place for combat casualties may   laboratory capability, potentially down to a “lab-on-a-chip” for
              last from hours to days and mandate changes in practice,   far-forward use by SOF. We aim to eventually provide the SOF
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              to include prolonged field care (PFC) of casualties.  Deliv-  medic with this vital tool to monitor injury severity and inflam-
              ery of medical supplies to PFC environments and evacuation   matory reaction of patients during PFC scenarios.
              *Correspondence to Jae Hyek Choi, PhD, DVSc, The Geneva Foundation, 2509 Kennedy Circle, Building 125, San Antonio, TX 78235 or
              jae-hyek.choi.ctr@mail.mil
              1 Dr Choi is affiliated with the Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Insti-
              tute of Surgical Research, JBSA Ft. Sam Houston, TX.  Dr Roberts is affiliated with the Autonomous Reanimation and Evacuation Program,
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              The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX.  Mr Sieck is affiliated with
              The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX.  Mr Harea is affiliated with the
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              Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA.  Dr Karaliou is affiliated with University of Texas
              Health Science Center at San Antonio, Department of Surgery, San Antonio, TX.  Mr Wendorff is affiliated with the Autonomous Reanimation
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              and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX.  Mr
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              Beely is affiliated with the Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Institute
              of Surgical Research, JBSA Ft. Sam Houston, TX.  COL (Ret) Cancio is affiliated with US Army Institute of Surgical Research, JBSA Ft. Sam
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              Houston, TX.  Lt Col Sams is affiliated with San Antonio Military Medical Center, JBSA Ft. Sam Houston, TX.  Dr Batchinsky is affiliated with
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              the Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research,
              JBSA Ft. Sam Houston, TX
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