Human Neural stem cell (HNSC) Transplant Location dependent neuroprotection and motor deficit amelioration in rats with penetrating TBI (PTBI) BACKGROUND Penetrating traumatic brain injury (PTBI) induced chronic inflammation that drives persistent tissue loss long after injury. Absence of endogenous reparative neurogenesis and effective neuroprotective therapies render injury-induced disability an unmet need. Cell replacement via neural stem cell transplantation could potentially rebuild the tissue and alleviate PTBI disability. The optimal transplant location remains to be determined. METHODS To test if subacute human neural stem cells (hNSCs) transplant location influences engraftment, lesion expansion, and motor deficits, rats (n=10/group) were randomized to following four groups (uninjured and three injured). Gr1: uninjured rats with cell transplants (sham+hNSCs), one-week post-unilateral pTBI, after establishing motor deficit, Gr2 was treated with vehicle (media, no cells), Gr3 hNSCs were transplanted into lesion core (intra), or in Gr4, tissue surrounding the lesion (peri). All animals were immunosuppressed for twelve weeks and euthanized following motor assessment. RESULTS In Gr2, pTBI injury effect manifest as porencephalic cyst, 22.53±2.87 (% of intact hemisphere), with p-value <0.0001 compared to uninjured Gr1. Gr3 lesion volume at 17.44±2.11 did not differ significantly from Gr2 (p=0.36) while Gr4 value, 9.17±1.53 differed significantly (p=0.0001). Engraftment and neuronal differentiation were significantly lower in the uninjured Gr1 (p<0.05), compared to injured groups. However, there were no differences between Gr3 and G4. Significant increase in cortical tissue sparing (p=0.03), including motor cortex (p=0.005) was observed in Gr4 but not Gr3. Presence of transplant within lesion or in penumbra attenuated motor deficit development (p<0.05) compared to Gr2. CONCLUSIONS In aggregate, injury milieu supports transplanted cell proliferation and differentiation independent of location. Unexpectedly, cortical sparing is transplant location dependent. Thus, apart from cell replacement and transplant mediated deficit amelioration, transplant location dependent neuroprotection may be key to delaying onset or preventing development of injury-induced disability. LEVEL OF EVIDENCE Preclinical study evaluation of therapeutic intervention, Level VI Authors contributed equally: Zhen Hu, Markus S. Spurlock Corresponding Author contact information for SG: Shyam Gajavelli, PhD, Telephone: 305 243 4926, Fax: 305 243 3914, Email: shyam@miami.edu ORCID iD: 0000-0002-5947-6973 Conflict Of Interest Statement: All authors have no conflicts of interest. Meeting presentation: This study was presented at 25th annual meeting of Military Health System Research Symposium, August 27, 2017, in Kissimmee, Florida. (Portions of this study were presented at National Neurotrauma Symposium, June 2017, in Louisville, KY, and Society for Neuroscience, Nov 13, 2017, Washington DC. KNR presented part of this work at New England Science Symposium, Harvard in 2018 and is recipient of Asclepius Laboratories Stem Cell and Regenerative Medicine Award. Disclosure of funding: The opinions or assertions contained in this article are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the US Army, or the US Department of Defense, or the US government. Funding for research was provided by the United States Army Medical Research and Material Command, Combat Casualty Care Research Program, Fort Detrick MD, Grant number W81XWH-16-2-0008, BA150111 CDMRP JPC-6. Howard Hughes Medical Institute (HHMI) grant number 52008118 to Prof. M.S. Gaines facilitated GRG participation through University of Miami-HHMI partnership, NIH Shared and High-End Instrumentation Awards to Dr Armando Mendez, S10OD023579 for Olympus VS120 Fluorescence and Brightfield Slide Scanner for High-Throughput Image Acquisition at the University of Miami. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 Lippincott Williams & Wilkins, Inc.

A Comprehensive Review of Topical Hemostatic Agents: The Good, The Bad, and the Novel Exsanguination remains the leading cause of preventable death for trauma patients, many of whom die in the pre-hospital setting. Without expedient intervention, trauma-associated hemorrhage induces a host of systemic responses, including the acute coagulopathy of trauma. For this reason, healthcare providers and pre-hospital personnel face the challenge of rapid, effective hemorrhage control. The utilization of adjuncts to facilitate hemostasis was first recorded in 1886. Commercial products have since expanded to include topical hemostats, surgical sealants, and adhesives. The ideal product balances efficacy, safety, practicality, and cost-effectiveness. This review of hemostatic agents provides a guide for successful implementation and simultaneously highlights future opportunities. CORRESPONDING AUTHOR: Allison J. Tompeck, MD, 7025 East Via Soleri Drive, Apt 3052, Scottsdale, AZ 85251. allisontompeck@gmail.com. 908-227-7062 CONFLICT OF INTEREST Matt Dowling PhD, is Chief Scientific Officer and Director of gel-e. Mayur Narayan MD, MBA and David King MD, LTC are members of the gel-e clinical advisory board. PRESENTATIONS: None DISCLOSURES: No funding disclosures to report. © 2019 Lippincott Williams & Wilkins, Inc.

PERCEIVED LOSS OF SOCIAL SUPPORT AFTER NON-NEUROLOGIC INJURY NEGATIVELY IMPACTS RECOVERY Background Traumatic injury is not only physically devastating, but also psychologically isolating, potentially leading to poor quality of life, depression and post-traumatic stress disorder (PTSD). Perceived social support (PSS) is associated with better outcomes in some populations. What is not known is if changes in PSS influence long-term outcomes following non-neurologic injury. We hypothesized that a single drop in PSS during recovery would be associated with worse quality of life. Methods This is a post-hoc analysis of a prospectively collected database that included patients ≥18 years old admitted to a Level 1 trauma center with injury severity score (ISS) of >10, and no traumatic brain or spinal cord injury. Demographic and injury data were collected at the initial hospital admission. Screening for depression, PTSD, and Medical Outcomes Study Short Form 36 Mental Composite Score (MCS) were obtained at the initial hospitalization, 1, 2, 4, and 12 months post-injury. The Multidimensional Scale of Perceived Social Support (MSPSS) was obtained at similar time points. Patients with high MSPSS (>5) at baseline were included and grouped by those that ever reported a score ≤ 5 (DROP), and those that remained high (STABLE). Outcomes were determined at 4 and 12 months. Results 411 patients were included with 96 meeting DROP criteria at 4mo, and 97 at 1yr. There were no differences in gender, race, or injury mechanism. DROP patients were more likely to be single (p=0.012 at 4mo, p=0.0006 at 1yr) and unemployed (p=0.016 at 4mo, and p=0.026 at 1yr) compared to STABLE patients. At 4mo and 1yr, DROP patients were more likely to have PTSD, depression, and a lower MCS (p=0.0006, p<0.0001). Conclusion Patients who have a drop in PSS during the first year of recovery have significantly higher odds of poor psychological outcomes. Identifying these socially frail patients provides an opportunity for intervention to positively influence an otherwise poor quality of life. Level of Evidence IV Study Type Prognostic and Epidemiological Corresponding Author: Ben L. Zarzaur, MD, MPH, 600 Highland Avenue, G5/335, Madison, WI 53792-3236. Office Phone Number: 608-263-2284. Administrative Assistant’s (Tricia) Office Phone Number: 608-265-9574. Fax Number: 608-252-0936 COI Statement: no author involved in this study has any conflicts of interest to disclose Presented during the Raymond H. Alexander Resident Paper Competition at the 32nd Annual Scientific Assembly of the Eastern Association for the Surgery of Trauma held from January 15-19, 2019. Austin, TX. Funding Statement: This project was funded by a grant from the National Institute of General Medical Science at the National Institute of Health, award number K23GM084427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No authors have any financial conflicts of interest to declare for this work This study was funded by National Institutes of Health. Award number K23GM084427 © 2019 Lippincott Williams & Wilkins, Inc.

Fall Prevention Initiative: A Fall Screening and Intervention Pilot Study on the Ambulatory Setting Objective Falling is the most common cause of trauma in the geriatric population. To identify patients that were at-risk for falling, we implemented a provider-directed fall prevention screening initiative in the ambulatory setting of a large tertiary care referral center. We used 3 clinician-directed questions from the STEADI toolkit. Our goal was to intervene on patients who were screened as at-risk for falling by referring them to our physical therapy program and evaluating its effects to these patients. Method Patients ≥ 55 yo who live in the community were screened from 6/2017-6/2018. Patients who answered yes to any of the 3 questions were identified as at-risk for falling, and referred to the Fall Prevention Initiative Physical Therapy Program (FPIPTP). The FPIPTP is a program that establishes a quantifiable fall risk using the Time Up and Go test (TUG), which then initiates PT treatments, designed to prevent future falls by improving, gait, balance, and fitness. The Wilcoxon signed rank test was used to determine significance (p<0.05). Results We identified 112 patients with a median age of 76.5 yo (IQR 68-82) to be at-risk for falling. The initial median TUG score in this group of patients is 15.85 sec (12-20.33), which is consistent with a high fall-risk (time > 12 sec). After completing the FPIPTP, the median TUG score significantly improved to 12sec (9-15, p<0.0001). Conclusion We conclude that a provider can use the 3 specific questions from the STEADI toolkit to identify patients (≥55 yo) that are at-risk for falling. Additionally, the FPIPTP is able to significantly improve the TUG score in this group. We will need to confirm this conclusion with a larger population study. Level IV evidence diagnostic/therapeutic study Corresponding Author: Susan Kartiko MD PhD FACS, University of Massachusetts-Baystate Medical Center, 2 Medical Center Dr. Ste. 301, Springfield, MA 01107, USA, Tel: 413-794-4022, Fax: 413-794-2165, Email: susan.kartikomd@baystatehealth.org The authors have no conflict of interests and there is no funding source for this study. This study was presented at the 32nd EAST Annual Scientific Assembly, January 15-19, 2019 in Austin, TX. © 2019 Lippincott Williams & Wilkins, Inc.

Truth Behind the Appearances: Translating New Drug Therapies to Humans No abstract available

Analysis of Blunt Cerebrovascular Injury in Pediatric Trauma Background Blunt cerebrovascular injury (BCVI) occurs in <1% of pediatric patients. The two principal screening criteria for BCVI in children are the Utah and McGovern Score with motor vehicle accident (MVA) considered to be a predictor for BCVI. We sought to confirm previously reported risk factors and identify novel associations with BCVI in pediatric patients. Methods The Pediatric Trauma Quality Improvement Program (2014-2016) was queried for patients age<16 years presenting after blunt trauma. A multivariable logistic regression was used to determine risk of BCVI. Results From 69,149 pediatric patients, 109 (<0.2%) had BCVI. The median age was 13 years and the median injury severity score was 25. More than half the patients were involved in MVAs (53.2%) and had a skull-base fracture (53.2%). Factors independently associated with BCVI include skull-base fracture (OR 3.84, CI 2.40-6.14, p<0.001), cervical-spine fracture (OR 3.15, CI 1.91-5.18, p<0.001), intracranial hemorrhage (OR 3.11, CI 1.89-5.14, p<0.001), GCS<8 (OR 2.11, 1.33-3.54, p=0.003), and mandible fracture (OR 1.99, 1.05-3.84, p=0.04). MVA was not an independent predictor for BCVI (p=0.07). Conclusion In the largest analysis of pediatric BCVI to date, skull-base fracture had the strongest association with BCVI. Other associations to pediatric BCVI included cervical-spine and mandible fracture. MVA, previously identified to be associated with BCVI, was not an independent risk factor in our analysis. A future multicenter study incorporating newly identified variables in a scoring system to screen for BCVI is warranted. Level of Evidence IV (Prognostic/Epidemiologic) This work was presented at the 90th Annual Meetings of the Pacific Coast Surgical Association, February 15-18, 2019 in Tucson, Arizona Correspondence: Areg Grigorian, MD, Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, University of California, Irvine Medical Center, 333 The City Blvd West, Suite 1600; Orange, CA, USA 92868-3298, Email: agrigori@uci.edu, Tel: (818) 438-9093, Fax: (714) 456-6070 The authors report no conflicts of interest. © 2019 Lippincott Williams & Wilkins, Inc.

RE: End Tidal Carbon Dioxide Underestimates Plasma Carbon Dioxide During Emergent Trauma Laparotomy Leading to Hypoventilation and Misguided Resuscitation: A Western Trauma Association Multicenter Study No abstract available

Reply: The Beers Criteria: Not Just for Geriatrics Anymore? Analysis of Beers Criteria Medications in Non-Geriatric Trauma Patients and Their Association with Falls No abstract available

Commentary on Challenges in Acute Care Surgery – Blunt Celiac Artery Injury No abstract available

Development and Validation of a Revised Trauma-Specific Quality of Life (RT-QoL) Instrument Background The National Academies of Science has called for routine collection of long-term outcomes after injury. One of the main barriers for this is the lack of practical trauma-specific tools to collect such outcomes. The only trauma-specific long-term outcomes measure that applies a biopsychosocial view of patient care, the Trauma Quality-of-Life (T-QoL), has not been adopted due to its length, lack of composite scores, and unknown validity. Our objective was to develop a shorter version of the T-QoL measure that is reliable, valid, specific, and generalizable to all trauma populations. Methods We used two random samples selected from a prospective registry developed to follow long-term outcomes of adult trauma survivors (Injury Severity Score ≥9) admitted to three Level-I trauma centers. First, we validated the original T-QoL instrument using the SF-12 and Breslau PTSD-screening (B-PTSD) tools. Second, we conducted a confirmatory factor analysis (CFA) to reduce the length of the original T-QoL instrument; and using a different sample, we scored and performed internal consistency and validity assessments of the revised T-QoL (RT-QoL) components. Results All components of the original T-QoL were significantly correlated negatively with the B-PTSD and positively with the SF-12 mental and physical composite scores. After CFA, a three-component structure using 18-items (6-items/component) most appropriately represented the data. Each component in the revised instrument demonstrated a high level of internal consistency (Cronbach’s alpha ≥0.8) and correlated negatively with the B-PTSD and positively with the SF-12, demonstrating concurrent validity. Additionally, each of the RT-QoL components were able to distinguish between individuals based on their work status, with those who have returned to work reporting better health. Conclusions This more practical RT-QoL measure greatly increases the ability to evaluate long-term outcomes in trauma more efficiently and meaningfully, without sacrificing the validity and psychometric properties of the original instrument. Level of Evidence Level III – Prognostic and Epidemiological Sources of Financial Support: None. The present original work was funded by the Center for Surgery and Public Health own resources. Corresponding author: Juan P. Herrera-Escobar, Center for Surgery and Public Health, 1620 Tremont Street, Suite 4-020, Boston, MA 02120. Phone: (617) 525 3075. Email: jherreraescobar@bwh.harvard.edu © 2019 Lippincott Williams & Wilkins, Inc.