Not All in Your Head (and Neck): Stroke after Blunt Cerebrovascular Injury Is Associated with Systemic Hypercoagulability BACKGROUND Stroke secondary to blunt cerebrovascular injury (BCVI) most often occurs before initiation of antithrombotic therapy. Earlier treatment, especially in multiply injured patients with relative contraindications to antithrombotic agents, could be facilitated with improved risk stratification; furthermore, the relationship between BCVI-attributed stroke and hypercoagulability remains unknown. We hypothesized that patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who do not stroke. METHODS Rapid thromboelastography (TEG) was evaluated for patients with BCVI-attributed stroke at an urban Level I trauma center from 2011 to 2018. Contemporary controls who had BCVI but did not stroke were selected for comparison using propensity-score matching with 20% caliper that accounted for age, sex, injury severity, and BCVI location and grade. RESULTS 15,347 patients were admitted following blunt trauma. BCVI was identified in 435 patients (3%), of whom 28 experienced associated stroke and had a TEG within 24 hours of arrival. 49 patients who had BCVI but did not stroke served as matched controls. Stroke patients formed clots faster as evident in their larger angle (77.5 vs 74.6 degrees, p=0.03) and had greater clot strength as indicated by their higher maximum amplitude (MA; 66.9 vs 61.9 mm, p<0.01). Activated clotting time was shorter among stroke patients but not significantly (113 vs 121 s, p>0.05). Increased angle and elevated MA were significant predictors of stroke with odds ratios of 2.97 for angle >77.3 degrees and 4.30 for MA >63.0 mm. CONCLUSIONS Patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who remain asymptomatic. Increased angle or MA should be considered when assessing the risk of thrombosis and determining the optimal time to initiate antithrombotic therapy in patients with BCVI. LEVEL OF EVIDENCE III TYPE OF STUDY: Prognostic Corresponding Author Joshua J. Sumislawski, MD, Department of Surgery, Denver Health Medical Center, 777 Bannock Street, MC 0206, Denver, Colorado 80204, (615) 504-2711 (phone), (303) 436-6572 (fax). joshua.sumislawski@ucdenver.edu; Address for Reprints Clay Cothren Burlew, MD, Department of Surgery, Denver Health Medical Center, 777 Bannock Street, MC 0206, Denver, Colorado 80204, (303) 602-1830 (phone), (303) 436-6572 (fax). clay.cothren@dhha.org Conflicts of Interest The authors declare no conflicts of interest. Disclosures The authors receive research support from Haemonetics Corporation and Instrumentation Laboratory in the form of consumables. Presentation History This study was presented at the 49th annual meeting of the Western Trauma Association; March 3–8, 2019; in Snowmass, Colorado; and was awarded second place for the Earl G. Young Resident Prize for Clinical Research. © 2019 Lippincott Williams & Wilkins, Inc.

Traumatic cardiac dislocation – A case report and review of the literature including a new classification system Traumatic pericardial ruptures and cardiac dislocations are rare injuries after blunt trauma to the thorax or abdomen. Even using spiral computed tomography (CT), these injuries can be missed. We present a case report of a patient with a traumatic heart dislocation who was treated in our trauma center. Moreover, we performed a review of the literature on these injuries to suggest diagnostic and therapeutic consequences. We describe a 33-year-old male patient who sustained a motorcycle accident in 2016. Prehospitalization, the patient was intubated, left chest-tube placement was performed on suspicion of a unilateral pneumothorax, and he was airlifted to a level II trauma center. There, whole-body CT revealed multiple injuries, such as cardiac dislocation outside the pericardium and traumatic aortic injury, accounting for an Injury Severity Score of 59. The patient was transferred to our level I trauma center. After stenting of the traumatic aortic injury and cardiopulmonary stabilization, the heart was operatively repositioned and the pericardium closed with sutures seven days after the accident. After eight weeks, the patient was discharged in a good general state of health. Analysis of 58 case reports revealed that heart dislocations can be subdivided into primary and secondary dislocations. Primary heart dislocations occur immediately after trauma. Secondary dislocations are preceded by an isolated traumatic pericardial rupture and can occur even months after the initial trauma. We established the following classification system: I° pericardial rupture without cardiac dislocation, II° pericardial rupture with cardiac subluxation, III° complete cardiac dislocation outside the pericardium, III°b complete cardiac dislocation and malrotation, and III°c complete cardiac dislocation with myocardial tearing/rupture. Of all 58 patients, only one was treated conservatively. The gold standard in cardiac dislocations and traumatic pericardial ruptures is operative treatment. Conservative treatments for these injuries bear risks such as myocardial strangulation through the pericardial tear. Study Type Review article Level of Evidence Not applicable Corresponding Author: Frank Graef, MD, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: +49-30 450 615083, Fax: +49-30 450 552901. Email: frank.graef@charite.de Conflicts of interest: None Meetings the paper was presented at: None Fundings received for this work: None © 2019 Lippincott Williams & Wilkins, Inc.

Protective effects of plasma products on the endothelial-glycocalyx barrier following trauma-hemorrhagic shock: is sphingosine-1 phosphate responsible? Background Plasma is an important component of resuscitation after trauma and hemorrhagic shock (T/HS). The specific plasma proteins and the impact of storage conditions is uncertain. Utilizing a microfluidic device system, we studied the effect of various types of plasma on the endothelial barrier function following T/HS. Methods Human umbilical vein endothelial cells (HUVEC) were cultured in microfluidic plates. The microfluidic plates were subjected to control or shock conditions (hypoxia/reoxygenation+ epinephrine, 103 μM). Fresh plasma, one day thawed plasma, five-day thawed plasma and lyophilized plasma were then added. Supplementation of sphingosine-1 phosphate (S-1P) was done in a subset of experiments. Effect on the endothelial glycocalyx was indexed by shedding of syndecan-1, and hyaluronic acid. Endothelial injury/activation was indexed by soluble thrombomodulin (sTM), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1). Vascular permeability determined by the ratio of angiopoetin-2 to angiopoetin-1 (ang-2/1). Concentration of S-1P and adiponectin in the different plasma groups was measured. Results HUVEC exposed to shock conditions increased shedding of syndecan-1 and hyaluronic acid. Administration of the various types of plasma decreased shedding, except for 5-day thawed plasma. Shocked HUVEC cells demonstrated a profibrinolytic phenotype, this normalized with all plasma types except for 5-day thawed plasma. The concentration of S-1P was significantly less in the 5-day thawed plasma compared to the other plasma types. Addition of S-1P to 5-day thawed plasma returned the benefits lost with storage Conclusion A biomimetic model of the microcirculation following T/HS demonstrated endothelial glycocalyx and endothelial cellular injury/activation as well as a profibrinolytic phenotype. These effects were abrogated by all plasma products except the 5-day thawed plasma. Plasma thawed > 5 days had diminished S1-P concentrations. Our data suggest that S1-P protein is critical to the protective effect of plasma products on the endothelial-glycocalyx barrier following T/HS. Basic Science Correspondence: Lawrence N. Diebel MD, Michael and Marian Ilitch Department of Surgery, 6C-University Health Center, 4201 St. Antoine, Detroit, MI 48210, Phone: 313-577-5005, Fax: 313-577-5310. Email: ldiebel@med.wayne.edu Conflicts of interest: none. This study was presented at the 49th annual meeting of the Western Trauma Association, March 3-March 8, 2019, in Snowmass, CO. © 2019 Lippincott Williams & Wilkins, Inc.

Propranolol Attenuates Cognitive, Learning and Memory Deficits in a Murine Model of Traumatic Brain Injury Introduction β-blockers have been shown to improve survival after traumatic brain injury (TBI), however, the impact of continuous dosage of β-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning and cognitive function following TBI. Study Design Twenty male-C57BL-mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the β-blocker-group (n=10) or the placebo-group (n=10). Mice in the β-blocker-group received intraperitoneal 4mg/Kg propranolol every 24 hours for seven days while the placebo group received 4mg/Kg normal saline. Baseline novel-object-recognition (NOR) and classic-maze-tests were done prior to TBI and then daily from day one through seven after TBI. Animals were sacrificed on day seven. Serum biomarkers were measured using ELISA and brain-sections were analyzed using western-blot and H&E-staining. Results Both the β-blocker and placebo groups had lower recognition index scores compared to the baseline following TBI. β-blocker mice had significantly higher NOR-scores compared to placebo mice two days after TBI. The β-blocker group required less time to complete the maze-test compared to placebo-group after day 4. There was no difference regarding the serum levels of IL-1β, IL-6, and TNF-α. The β-blocker-group had lower levels of UCHL-1 and higher levels of Hsp-70 in brain-lysate. H&E-staining revealed that more neurons in the hippocampal-CA1 area underwent apoptosis in the placebo-group compared to the β-blocker-group. Conclusion Post-injury propranolol administration results in improved memory, learning and cognitive functions in a murine model of moderate TBI. Propranolol increases the expression of anti-apoptotic-protein (Hsp-70) and decreases cell death in the hippocampal-CA1 area compared to the placebo. Level of Evidence Basic Science Oral presentation for the EE Moore Resident Research Paper Competition at the 49th Annual Meeting of Western Trauma Association, March 3rd -March 8th, 2019, Snowmass, Colorado. Presentation Category: EE Moore Resident Prize for Basic Science Research There are no identifiable conflicts of interests to report. The authors have no financial or proprietary interest in the subject matter or materials discussed in the manuscript. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Address for correspondence: Bellal Joseph, MD, University of Arizona, Department of Surgery, Division of Trauma, Critical Care, and Emergency Surgery. 1501 N. Campbell Ave, Room.5411, P.O. Box 245063, Tucson, AZ 85727. E-mail: bjoseph@surgery.arizona.edu. Tel 520-626-5056, Fax 520-626-5016 © 2019 Lippincott Williams & Wilkins, Inc.

Random Forest Modeling Can Predict Infectious Complications Following Trauma Laparotomy Background Identifying clinical and biomarker profiles of trauma patients may facilitate the creation of models that predict postoperative complications. We sought to determine the utility of modeling for predicting severe sepsis (SS) and organ space infections (OSI) following laparotomy for abdominal trauma. Methods Clinical and molecular biomarker data were collected prospectively from patients undergoing exploratory laparotomy for abdominal trauma at a Level 1 trauma center between 2014 and 2017. Machine learning algorithms were used to develop models predicting SS and OSI. Random forest (RF) was performed and features were selected using backwards elimination. The SS model was trained on 117 records and validated using the leave-one-out method on the remaining 15 records. The OSI model was trained on 113 records and validated on the remaining 19. Models were assessed using areas under curve (AUC). Results One hundred and thirty-two patients were included (median age 30 (23-42), 68.9% penetrating injury, median ISS 18 (10-27)). Of these, 10.6% (14/132) developed SS and 13.6% (18/132) developed OSI. The final RF model resulted in five variables for SS (Penetrating Abdominal Trauma Index (PATI), serum EGF, MCP-1, IL-6, and eotaxin) and four variables for OSI (Penetrating Abdominal Trauma Index (PATI), serum EGF, MCP-1, and IL-8). The RF models predicted SS and OSI with AUCs of .798 and .774, respectively. Conclusions Random forests with RFE can help identify clinical and biomarker profiles predictive of SS and OSI after trauma laparotomy. Once validated, these models could be used as clinical decision support tools for earlier detection and treatment of infectious complications following injury. Level of Evidence Level III, prognostic Address correspondence & reprints to: Rondi B Gelbard, MD, 60 Jesse Hill Jr Dr SW, Glenn Memorial Bldg, Room 310, Atlanta, GA 30303. rondi.beth.gelbard@emory.edu Meetings: Presented as a podium presentation at the 49th Annual Western Trauma Association Meeting, March 3-8th, 2019, Snowmass, Colorado. Conflicts of interest disclosure: The authors have no conflicts of interest to disclose. Funding disclosure: Research activities leading to the development of this manuscript were funded by the Department of Defense’s Defense Health Program-USU Cooperative Agreement (HU0001-15-2-0001). © 2019 Lippincott Williams & Wilkins, Inc.

The Utility of MRI in Pediatric Trauma Patients Suspected of Having Cervical Spine Injuries BACKGROUND Pediatric cervical spine injuries (CSI) are rare but potentially devastating sequelae of blunt trauma. Existing protocols to evaluate children at risk for CSI frequently incorporate computerized topography (CT) and magnetic resonance imaging (MRI); however, the clinical value of performing both remains unclear. METHODS Single center retrospective review of pediatric trauma patients who underwent both CT and MRI of the cervical spine between 2001 and 2015. Based on radiographic findings, CT and MRI results were grouped into one of three categories: no injury, stable injury, or unstable injury. Radiographic instability was defined by disruption of two or more contiguous spinal columns while radiographic stability was defined by any other acute cervical spine abnormality on imaging. Clinical instability was defined by the need for surgical intervention (halo or spinal fusion), with the remaining patients, including children discharged in a cervical collar, considered clinically stable. RESULTS In total, 221 children met inclusion criteria, with a median age of 9 (IQR 3, 14). The Glasgow Coma Score (GCS) of the cohort was 9 (IQR 4, 15). Thirty-three children (14.9%) had clinically unstable injuries, requiring surgical intervention. Among the 160 children (72.4%) with no injury on CT, MRI identified no injury in 84 cases (52.5%), a stable injury in 76 cases (47.5%), and an unstable injury in none. Among the 21 children with stable injuries on CT, MRI findings were concordant in 17 cases (81.0%). In four cases (19.0%), a spinal column injury was identified on CT and appeared to be stable, but later deemed unstable on MRI. Forty patients (18.1%) had an unstable injury on CT with 100% MRI concordance. CONCLUSION In pediatric trauma patients suspected of having a CSI, a normal cervical spine CT is sufficient to rule out a clinically significant CSI as no child with a normal cervical CT was found to be radiographically or clinically unstable. Level of Evidence III Diagnostic Test The authors have no conflict of interest or funding disclosures to report This data has been presented at the Western Pediatric Trauma Conference, Park City, Utah, July 18-22, 2018 Address correspondence/reprint requests to: Michael H Handler, MD, Children’s Hospital Colorado, University of Colorado School of Medicine, 13123 E 16th Ave, Box 330, Aurora, CO 8004. Office: 720-777-6100. Email: michael.handler@childrenscolorado.org © 2019 Lippincott Williams & Wilkins, Inc.

Delayed inter-hospital transfer of critically ill patients with surgical sepsis Background Suboptimal triage of critically ill patients with surgical sepsis may contribute to adverse outcomes. Patients transferred to a tertiary care center after spending ≥24 hours at an outside facility were compared with patients who had early triage to a tertiary care center with the null hypothesis that management parameters and outcomes would be similar between groups. Methods This prospective observational cohort study included 308 patients treated for surgical sepsis in a surgical intensive care unit at a tertiary care center. Patients transferred after spending more than 24 hours at an outside facility (n=69) were compared with patients who were directly admitted or transferred within 24 hours (n=239). Patient characteristics, management parameters, and outcomes were compared between groups. This study was registered at ClinicalTrials.gov (NCT02276066). Results Average outside facility length of stay in the delayed transfer group was 43 hours. Delayed transfer patients had higher SOFA (7 vs. 5, p=0.003) and APACHE II scores (19 vs. 16, p=0.007) on admission. The interval between admission and source control was significantly longer in the delayed transfer group (12.1 vs. 1.0 hours, p=0.009). The incidence of nosocomial infection was significantly higher in the delayed transfer group (41% vs. 23%, p=0.005). Delayed transfer was independently associated with a 10-day increase in hospital length of stay. Delayed transfer patients were less likely to be discharged home (22% vs. 59%, p<0.001) and suffered two-fold higher in-hospital mortality (14.5% vs. 7.1%, p=0.056). Conclusion Patients with surgical sepsis who spent more than 24 hours at an outside facility prior to transfer had greater initial illness severity, longer intervals between admission and source control, and more nosocomial infections compared with patients who had early triage to a tertiary care center. Level of evidence Level III prognostic study Please address correspondence to: Scott C. Brakenridge, MD, MSCS, University of Florida Health, Gainesville, FL, 1600 SW Archer Road Room M-602, Gainesville, Florida, 32610-3003, 972-415-2447. Scott.Brakenridge@surgery.ufl.edu This work will be presented at the 78th Annual Meeting of the American Association for the Surgery of Trauma and Clinical Congress of Acute Care Surgery, September 18-21, 2019 in Dallas, Texas. This manuscript has not been submitted elsewhere. The authors have no relevant conflicts of interest or financial disclosures. This work was supported in part by grants R01 GM110240 (AB), R01 GM113945 (PAE), R01 GM105893 (AMM), and P50 GM111152 (QU, ZW, FAM, AB, PAE, AMM, SCB) awarded by the National Institute of General Medical Sciences (NIGMS). TJL was supported by a post-graduate training grant (T32 GM-008721) in burns, trauma and perioperative injury by NIGMS. © 2019 Lippincott Williams & Wilkins, Inc.

Ketamine Infusion for Pain Control in Elderly Patients with Multiple Rib Fractures: Results of a Randomized Controlled Trial Introduction Rib fractures are associated with increased mortality, particularly in the elderly. While opiate-based pain regimens remain the cornerstone of rib fracture management, issues related to opioids have driven research into alternative analgesics. Adjunctive ketamine use in lieu of opioids continues to increase but little evidence exists to support its efficacy or safety within the elderly trauma population. Methods A prospective, randomized, double-blind placebo-controlled trial of elderly patients (age ≥65) with ≥3 rib fractures admitted to a Level 1 trauma center was conducted. Exclusion criteria included GCS <14, and chronic opiate use. Groups were randomized to either low dose ketamine (LDK) at 2 mcg/kg/min or an equivalent rate of 0.9% normal saline. The primary outcome was reduction in numeric pain scores (NPS). Secondary outcomes included oral morphine equivalent (OME) utilization, epidural rates, pulmonary complications, and adverse events. Results Thirty of 59 (50.8%) were randomized to the experimental arm. Groups were similar in makeup. LDK failed to reduce 24-hour NPS or OME totals. Subgroup analysis of 24 patients with ISS >15 demonstrated that LDK was associated with a reduction in OME utilization the first 24-hours (25.6 vs. 42.6mg, p=0.04) but at no other time points. No difference in other secondary outcomes or adverse events was noted. Conclusion LDK failed to affect NPS or OME within the overall cohort, but a decrease in OME was observed in those with an ISS >15. Additional studies are necessary to confirm whether LDK benefits severely injured elderly patients. Level of Evidence Level I. RCT with no negative criteria. Meeting Presentation: 49th Annual Meeting of the Western Trauma Association March 3-8, 2019 in Snowmass, CO. Corresponding Author: Thomas W Carver MD, FACS, Societal Memberships: AAST, Medical College of Wisconsin, Department of Surgery, Division of Trauma and Acute Care Surgery, 8701 Watertown Plank Rd. Milwaukee, Wisconsin 53226 United States, Cell: 1 (847) 977-4896, Office: 1 (414) 955-1733, Fax: 1 (414) 955-0072 Conflict of Interest Statement: There are no conflicts of interests to report for any of the authors of this study. Source of Funding: This trial was funded through internal support from the Department of Surgery at the Medical College of Wisconsin. Financial Disclosures: Drs. Carver and Kugler are paid consultant for InnoVital Systems Inc but these are not relevant to this study. The remaining authors have no financial disclosures. Disclosure: None of the authors have any financial and personal relationships with other people or organizations that could potentially and inappropriately influence their work and conclusions on this topic. © 2019 Lippincott Williams & Wilkins, Inc.

Letter to the editor (Infection after penetrating brain injury) No abstract available

The IDF Experience with Freeze Dried Plasma For The Resuscitation of Traumatized Pediatric Patients Introduction With the growing recognition of the disadvantages of crystalloid and colloid based resuscitation and the advantages of using blood products as the preferred resuscitation fluid, the Israel Defense Forces Medical Corps (IDF-MC) adopted plasma as the primary volume resuscitation regimen in 2013. While data are accumulating for prehospital plasma transfusion, little to no data exists regarding using plasma as a pre-hospital resuscitation fluid for traumatized pediatric patients. Methods All patients treated by the IDF-MC personnel are recorded in the IDF trauma registry (ITR), a unique prehospital trauma registry. All patients treated by the IDF ALS providers with FDP at the point of injury between April 2013 and June 2018 who were under the age of 18 years at the time of injury were included. Results 679 children were treated by IDF medical providers, of whom 33 (5%)were identified in the ITR as having received FDP at the point of injury. Most patients (80%) were treated for penetrating injuries. Most patients received one plasma unit. 54% of patients were also treated by TXA and 48% were transfused with crystalloids. In 33% of patients additional life saving interventions were performed. Discussion While the ideal resuscitation fluid for the pediatric population remains to be determined, it seems reasonable to pursue a similar approach to that of applied that for adults. In the IDF-MC, the resuscitation fluid of choice for trauma patients in hemorrhagic shock is freeze-dried plasma transfused at the point of injury. The current study demonstrates the feasibility of FDP administration in the prehospital scenario for injured children and further supports the growing confidence in the use of FDP for the treatment of pediatric trauma patients Retrospective descriptive study Level of evidence IV Roy Nadler and Mozer-Glassberg Yael declare equal contribution Corresponding author: Roy Nadler, MD, The Trauma and Combat Medicine Branch, Medical Corps, Surgeon General’s Headquarters. Military POB 02149. Israel Defense Forces. roynadlerr@gmail.com. Israel, +972-3-737-9284 (phone) Conflicts of Interest and Source of Funding: For all authors, no conflicts of interest or funding were declared. © 2019 Lippincott Williams & Wilkins, Inc.