Characteristics of operative pediatric trauma transfer patients.

BACKGROUND: Pediatric patients treated at trauma centers demonstrate improved outcomes, but investigation of optimal resource utilization surrounding the transfer is ongoing. We evaluated characteristics of operative pediatric trauma transfer patients for resource optimization. METHODS: A retrospective review of pediatric trauma patients transferred to a level 1 pediatric trauma center from 2009 to 2019 was performed. Patients were categorized by initial operative subspecialty. RESULTS: Of 4164 transferred patients, 33.9 â€‹% required operative intervention. 65 â€‹% of operations were performed on orthopedic patients, who were significantly less injured compared to other patients. General surgery patients were more likely to undergo surgery on day of transfer compared to orthopedic patients (39.4%vs 56.3 â€‹%, OR 2.0, CI 1.4-2.8). CONCLUSIONS: One-third of pediatric trauma transfer patients required operative intervention. The majority of surgeries were on orthopedic patients, who were less likely to undergo surgery on day of transfer. Critical evaluation of this patient population is required to safely utilize a less resource-intensive transfer process.

Firearm Safety Counseling for Patients: An Interactive Curriculum for Trauma Providers.

Introduction: Firearm injuries are a major public health concern. Safe firearm storage is recommended by multiple medical organizations. However, rates of firearm safety counseling are particularly low among trauma providers. Educational initiatives for other provider groups have proven to be effective. We hypothesized that educating trauma providers to offer safety counseling would be similarly effective. Methods: We developed a didactic session around safe firearm storage counseling for trauma providers consisting of a lecture followed by an interactive session with standardized patients. Session participants completed pre- and postsurveys evaluating their knowledge about firearm storage, self-efficacy in providing firearm storage counseling, and attitudes towards firearm safety. We compared differences between pre- and postsurvey data using chi-square tests. Results: The didactic session was delivered to target trauma providers: three trauma nurse practitioners, 42 general surgery residents, and 26 emergency medicine residents. After the session, participants were more likely to know the optimal way to safely store a firearm and to be confident in effectively counseling patients about safe firearm storage. Learners were not more likely to believe that providers have a responsibility to counsel patients on firearm safety. Discussion: A didactic session on safe firearm storage counseling was associated with increased rates of knowledge and self-efficacy. The session did not change attitudes among trauma providers, although, prior to the session, most providers already believed they had a responsibility to counsel patients on safe firearm storage. Similar curricula should be piloted at other trauma centers.

Pediatric suicide by violent means: a cry for help and a call for action.

BACKGROUND: Suicide is the second most common cause of death among adolescents and young adults. In the pediatric population, gunshot wounds (GSWs) and hangings are common mechanisms of pediatric suicide. Comorbid psychiatric illness is prevalent in this population, but psychiatric resource utilization after self-inflicted traumatic injury is not well characterized. METHODS: We analyzed patients < 18 years old presenting to a level 1 pediatric trauma center after suicide attempt by GSW, hanging, or jumping from a height from 2009 to 2019. The primary outcome was psychiatric resource utilization. Secondary outcomes included prior emergency department (ED) visits to identify prior opportunities for intervention. RESULTS: Of 6538 pediatric trauma patients, there were 219 GSWs, 7 hangings, and 7 jumps from height, for a total of 233 patients. Of these, 14 presented following a suicide attempt (four GSWs, six hangings, and four jumps, total 6.0%). Half of these patients died due to their injuries. Self-inflicted GSWs had the highest mortality (75%). Most surviving patients were placed on involuntary psychiatric holds (n = 5/7, 71.4%), and three patients were discharged to an inpatient psychiatric hospital (n = 3/7, 42.9%). Five of the 14 patients had prior ED visits (35.7%), and of these, 60% were for suicidal ideation or suicide attempts. CONCLUSIONS: Among pediatric trauma patients, suicide attempts are rare, but are highly lethal, with the highest mortality rate seen in self-inflicted GSWs. Psychiatric resource utilization is high both during and after the hospitalization. Prior ED visits may represent opportunities for depression and suicidality screening in this at-risk population.

Medicaid Expansion Under the Affordable Care Act and Pediatric Trauma Patient Insurance Coverage.

INTRODUCTION: Uninsured pediatric trauma patients are at increased risk of poor outcomes. The impact of the Patient Protection and Affordable Care Act (ACA) on pediatric trauma patients has not been studied. We hypothesized that the expansion of Medicaid coverage under the ACA was associated with increased insurance coverage and improved outcomes. METHODS: Retrospective review of patients <18 y old presenting to a level 1 pediatric trauma center 2009-2019. An interrupted time series analysis was performed to assess the impact of Medicaid expansion under the ACA in January 2014. The primary outcome was rate of insurance coverage. Secondary outcomes included in-hospital mortality, disposition, 30-day readmission, length of stay (LOS), and intensive care unit (ICU) LOS. RESULTS: A total of 5645 patients were evaluated, (pre-ACA n = 2,243, post-ACA n = 3402). Expansion of Medicaid was associated with minimal changes on insurance coverage. There a decrease in mortality (RR = 0.96, P = 0.0355) and a slight increase in disposition to a rehabilitation facility (RR = 1.02, P = 0.0341). There was no association with 30-day readmission (RR = 1.02, P = 0.3498). Similarly, expansion of Medicaid was not associated with change in LOS (estimate = -0.00, P = 0.8893). There was a slight decrease in ICU LOS (estimate = -0.03, P < 0.0001). CONCLUSIONS: Medicaid expansion was associated with marginal changes in insurance coverage among pediatric trauma patients. We did not identify significant impacts on patient outcomes.

Recognition and management of traumatic fetal injuries.

Trauma during pregnancy is the leading non-obstetric cause of morbidity and mortality, and accounts for five per 1000 fetal deaths. Direct fetal injury due to trauma during pregnancy is rare, and limited information is available about how to optimize fetal outcomes after injury. Early recognition and appropriate management of direct fetal trauma may improve outcomes for the fetus. There are currently no available guidelines to direct management of the injured fetus. We provide a detailed literature review of the management and outcomes of direct fetal injury following blunt and penetrating injury during pregnancy, and describe a suggested initial approach to the injured pregnant patient with a focus on evaluation for fetal injury. We identified 45 reported cases of blunt trauma resulting in direct fetal injury, with 21 surviving past the neonatal period, and 33 of penetrating trauma resulting in direct fetal injury, with 24 surviving past the neonatal period. Prenatal imaging identified fetal injury in 19 cases of blunt trauma and was used to identify bullet location relative to the fetus in 6 cases. These reports were used to develop management algorithms for the injured fetus.

Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair.

INTRODUCTION: Fetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function. METHODS: MMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n = 3). RESULTS: Eighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p = 1). Void volumes were similar (PMSC-ECM 6.1 ml/kg vs. normal 8.8 ml/kg, p = 0.4). Resting mean anal pressures were similar between cohorts (27.0 mmHg PMSC-ECM vs. normal 23.5 mmHg, p = 0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p = 0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts. CONCLUSION: Ovine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients.

Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells.

INTRODUCTION: The Management of Myelomeningocele Study demonstrated that in utero repair of myelomeningocele improved motor outcomes compared with postnatal repair. However, even after in utero repair, many children were still unable to walk. We have previously demonstrated that augmentation of in utero repair with early-gestation placental mesenchymal stromal cells (PMSCs) improves motor outcomes in lambs compared with standard in utero repair. The neuroprotective potential of PMSCs of all gestational ages has not been evaluated previously. METHODS: PMSCs were isolated from discarded first trimester (n = 3), second trimester (n = 3), and term (n = 3) placentas by explant culture. Cytokine array analysis was performed. Secretion of two neurotrophic factors, brain-derived neurotrophic factor and hepatocyte growth factor, was evaluated by enzyme-linked immunosorbent assay. An in vitro neuroprotective assay demonstrated to be associated with in vivo function was performed. RESULTS: All cell lines secreted immunomodulatory and neuroprotective cytokines and secreted the neurotrophic factors evaluated. Increased neuroprotective capabilities relative to no PMSCs were demonstrated in two of the three first trimester cell lines (5.61, 4.96-6.85, P < 0.0001 and 2.67, 1.67-4.12, P = 0.0046), two of the three second trimester cell lines (2.82, 2.45-3.43, P = 0.0004 and 3.25, 2.62-3.93, P < 0.0001), and two of the three term cell lines (2.72, 2.32-2.92, P = 0.0033 and 2.57, 1.41-4.42, P = 0.0055). CONCLUSIONS: We demonstrated variation in neuroprotective function between cell lines and found that some cell lines from each trimester had neuroprotective properties. This potentially expands the donor pool of PMSCs for clinical use. Further in-depth studies are needed to understand potential subtle differences in cell function at different gestational ages.

Long-term safety evaluation of placental mesenchymal stromal cells for in utero repair of myelomeningocele in a novel ovine model.

PURPOSE: Augmentation of in utero myelomeningocele repair with human placental mesenchymal stromal cells seeded onto extracellular matrix (PMSC-ECM) improves motor outcomes in an ovine myelomeningocele model. This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial. METHODS: Laminectomy of L5-L6 with PMSC-ECM placement directly onto the spinal cord was performed in five fetal lambs at gestational age (GA) 100-106 days. Lambs and ewes were monitored for three months following delivery. Lambs underwent magnetic resonance imaging (MRI) of the brain and spine at birth and at three months. All organs from lambs and uteri from ewes underwent histologic evaluation. Lamb spinal cords and brains and ewe placentas were evaluated for persistence of PMSCs by polymerase chain reaction for presence of human DNA. RESULTS: MRIs demonstrated no evidence of abnormal tissue growth or spinal cord tethering. Histological analysis demonstrated no evidence of abnormal tissue growth or treatment related adverse effects. No human DNA was identified in evaluated tissues. CONCLUSION: There was no evidence of abnormal tissue growth or PMSC persistence at three months following in utero application of PMSC-ECM to the spinal cord. This supports proceeding with clinical trials of PMSC-ECM for in utero myelomeningocele repair. LEVEL OF EVIDENCE: N/A TYPE OF STUDY: Basic science.

Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair.

BACKGROUND: While fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC. METHODS: Thirty-five ovine fetuses underwent MMC defect creation at a median of 76 days gestational age, and defect repair at 101 days gestational age with application of clinical-grade PMSC-ECM (3 × 105 cells/cm2, n = 12 fetuses), research-grade PMSC-ECM (3 × 105 cells/cm2, three cell lines with n = 6 (Group 1), n = 6 (Group 2), and n = 3 (Group 3) fetuses, respectively) or ECM without PMSCs (n = 8 fetuses). Three normal lambs underwent no surgical interventions. The primary outcome was motor function measured by the Sheep Locomotor Rating scale (SLR, range 0: complete paralysis to 15: normal ambulation) at 24 h of life. Correlation of lumbar spine large neuron density with SLR was evaluated. RESULTS: Clinical-grade PMSC-ECM lambs had significantly better motor function than ECM-only lambs (SLR 14.5 vs. 6.5, p = 0.04) and were similar to normal lambs (14.5 vs. 15, p = 0.2) and research-grade PMSC-ECM lambs (Group 1: 14.5 vs. 15, p = 0.63; Group 2: 14.5 vs. 14.5, p = 0.86; Group 3: 14.5 vs. 15, p = 0.50). Lumbar spine large neuron density was strongly correlated with motor function (r = 0.753, p<0.001). CONCLUSIONS: Clinical-grade placental mesenchymal stromal cells seeded on an extracellular matrix rescued ambulation in a fetal ovine myelomeningocele model. Lumbar spine large neuron density correlated with motor function, suggesting a neuroprotective effect of the PMSC-ECM in prevention of paralysis. A first-in-human clinical trial of PMSCs in human fetal myelomeningocele repair is underway.

Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model.

INTRODUCTION: Translational models of myelomeningocele (MMC) are needed to test novel in utero interventions. An ideal animal model for MMC has locomotor function at birth and is low cost enough to allow for high throughput. The rat MMC model is limited by immature locomotor function at birth. The ovine MMC model is a costly surgical model. Guinea pigs are uniquely suited for an MMC model being a small animal model with locomotor function at birth. We aimed to develop a retinoic acid (RA) model of MMC in the guinea pig and to evaluate if pregnant guinea pigs could tolerate uterine manipulation. METHODS: Time-mated Dunkin Hartley guinea pig dams were dosed with 60 mg/kg of RA between gestation age (GA) 12 and 15 days in the development of an RA model. Fetuses were grossly evaluated for MMC lesions at Cesarean section after GA 31 days. Evaluation of the ability of pregnant guinea pig dams to tolerate uterine surgical intervention was performed by hysterotomy of a separated group of time-mated guinea pigs at GA 45, 50, and 55. RESULTS: Forty-two pregnant guinea pigs were dosed with RA, with a total of 189 fetuses. The fetal demise rate was 38% (n = 71). A total of 118 fetuses were viable, 83% (n = 98) were normal fetuses, 8% (n = 10) had a neural tube defect, and 8% (n = 10) had a hematoma or other anomalies. No fetuses developed an MMC defect. None of the fetuses that underwent hysterotomy survived to term. CONCLUSION: RA dosed at 60 mg/kg in guinea pigs between GA 12 and 15 did not result in MMC. Dunkin Hartley guinea pigs did not tolerate a hysterotomy near term in our surgical model. Further work is needed to determine if MMC can be induced in guinea pigs with alternate RA dosing.

The July Phenomenon and Pediatric Trauma.

BACKGROUND: The July Phenomenon describes concerns that patients presenting early in the academic year experience worse outcomes. Given the standardized approach to pediatric trauma patients, we hypothesized that the July Phenomenon would not impact morbidity or mortality. METHODS: A retrospective review of patients ≤16 Y presenting to a level I pediatric trauma center between March 2009 and March2019 was performed. Pediatric patients admitted during the study period were compared for differences in outcome by month of presentation. The primary outcome was mortality. Secondary outcomes were complications, and length of emergency department, hospital and Intensive Care Unit stay. Multivariable regression was used to evaluate the effect of month of admission on outcomes. RESULTS: A total of 6,135 patients were evaluated, with 605 patients presenting in July. Univariate analysis failed to demonstrate consistently increased mortality, complications, or length of emergency department, hospital or Intensive Care Unit stay in July compared to months later in the academic year. On multivariate analysis, admission in July was not an independent predictor of worse outcomes. CONCLUSIONS: In this level I pediatric trauma center, pediatric trauma patients presenting earlier in the academic year have similar outcomes to those presenting later, and there is no evidence of a July Phenomenon in this population.

Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair.

BACKGROUND: Myelomeningocele (MMC) is the congenital failure of neural tube closure in utero, for which the standard of care is prenatal surgical repair. We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor outcomes in preclinical ovine models. To evaluate the long-term safety of this product prior to use in a clinical trial, we conducted safety testing in a murine model. METHODS: Clinical grade PMSCs obtained from donor human placentas were seeded onto a 6 mm diameter ECM at a density of 3 × 105 cells/cm2. Immunodeficient mice were randomized to receive either an ECM only or PMSC-ECM administered into a subcutaneous pocket. Mice were monitored for tumor formation until two study endpoints: 4 wk and 6 mo. Pathology and histology on all tissues was performed to evaluate for tumors. Quantitative polymerase chain reaction (qPCR) was performed to evaluate for the presence of human DNA, which would indicate persistence of PMSCs. RESULTS: Fifty-four mice were included; 13 received ECM only and 14 received PMSC-ECM in both the 4-wk and 6-mo groups. No mice had gross or microscopic evidence of tumor development. A nodular focus of mature fibrous connective tissue was identified at the subcutaneous implantation pocket in the majority of mice with no significant difference between ECM only and PMSC-ECM groups (P = 0.32 at 4 wk, P > 0.99 at 6 mo). Additionally, no human DNA was detected by qPCR in any mice at either time point. CONCLUSIONS: Subcutaneous implantation of the PMSC-ECM product did not result in tumor formation and we found no evidence that PMSCs persisted. These results support the safety of the PMSC-ECM product for use in a Phase 1/2a human clinical trial evaluating fetal MMC repair augmented with PMSC-ECM.

A Novel Model of Fetal Spinal Cord Exposure Allowing for Long-Term Postnatal Survival.

BACKGROUND: The inherent morbidity associated with fetal ovine models of myelomeningocele (MMC) has created challenges for long-term survival of lambs. We aimed to develop a fetal ovine surgical spinal exposure model which could be used to evaluate long-term safety after direct spinal cord application of novel therapeutics for augmentation of in utero MMC repair. METHODS: At gestational age (GA) 100-106, fetal lambs underwent surgical intervention. Laminectomy of L5-L6 was performed, dura was removed, and an experimental product was directly applied to the spinal cord. Paraspinal muscles and skin were closed and the fetus was returned to the uterus. Lambs were delivered via cesarean section at GA 140-142. Lambs were survived for 3 months with regular evaluation of motor function by the sheep locomotor rating scale. Spinal angulation was evaluated by magnetic resonance imaging at 2 weeks and 3 months. RESULTS: Five fetal surgical intervention lambs and 6 control lambs who did not undergo surgical intervention were included. All lambs survived to the study endpoint of 3 months. No lambs had motor function abnormalities or increased spinal angulation. CONCLUSION: This model allows for long-term survival after fetal spinal cord exposure with product application directly onto the spinal cord.

Impact of Limited English Proficiency on Definitive Care in Pediatric Appendicitis.

BACKGROUND: Limited English proficiency (LEP) is associated with decreased access to healthcare. We hypothesized that LEP children with appendicitis would experience more delays in care than EP children. METHODS: Retrospective review of patients <18 y presenting to a tertiary pediatric hospital July 2014-July 2019 with appendicitis. LEP patients were compared to EP patients. The primary outcome was appendiceal perforation. Secondary outcomes included prior pediatrician or emergency department (ED) visits without definitive management, duration of symptoms, length of stay (LOS), initial operative or non-operative management, time from presentation to operation and return to the ED within 30 d. Multivariable regression was performed to evaluate LEP as a predictor of study outcomes. RESULTS: A total of 893 patients with appendicitis were identified, 15.6% (n = 140) had LEP. On multivariate regression LEP was not a significant predictor of appendiceal perforation (AOR 1.20, 95% CI 0.79, 1.80, P = 0.390). LEP was a significant predictor of a prior ED or pediatrician visit without definitive management (AOR 2.05, 95 % CI 1.05, 3.98, P= 0.034) and longer LOS (Coefficient 1.01, 95% CI 0.41, 1.61, P= 0.001). LEP was associated with a minimal increase in duration of pain prior to presentation that was not clinically significant and was not associated with initial operative or non-operative management or a significantly longer time between presentation and operation. CONCLUSIONS: LEP children did not experience higher rates of appendiceal perforation at our institution, but were more frequently initially evaluated by a pediatrician or at an ED and discharged without definitive management and had longer LOS.

Wildfire Burn Patients: A Unique Population.

In the past ten years wildfires have burned an average of 6.8 million acres per year and this is expected to increase with climate change. Wildfire burn patient outcomes have not been previously well characterized. Wildfire burn patients from the Tubbs or Camp wildfires and non-wildfire burn matched controls were identified from the burn center database and outcomes were compared. The primary outcome was mortality. Secondary outcomes included length of stay (LOS), intensive care unit (ICU) LOS, readmission and development of wound infections. Time of presentation and operating room use after wildfires was evaluated. Sixteen wildfire burn patients were identified and matched with 32 controls. Wildfire burn patients trended towards higher mortality (19% wildfire vs. 9% non-wildfire, p=0.386), longer LOS (18 days wildfire vs. 15 days non-wildfire, p=0.406), longer ICU LOS (17 days wildfire vs. 11 days non-wildfire, p=0.991), increased readmission (19% wildfire vs. 3% non-wildfire, p=0.080) and higher rates of wound infection (31% wildfire vs. 19% non-wildfire, p=0.468). The majority of wildfire patients (88%) presented within 24 hours of the wildfire reaching a residential area. Operating room time within the first week was 13 hours 44 minutes for the Tubbs Fire and 19 hours 1 minute for the Camp Fire. Patients who sustain burns in wildfires are potentially at increased risk of mortality, prolonged LOS, wound infection and readmission.

Resuscitative endovascular balloon occlusion of the aorta in combat casualties: The past, present, and future.

BACKGROUND: Noncompressible torso hemorrhage is a leading cause of preventable death on the battlefield. Intra-aortic balloon occlusion was first used in combat in the 1950s, but military use was rare before Operation Iraqi Freedom and Operation Enduring Freedom. During these wars, the combination of an increasing number of deployed vascular surgeons and a significant rise in deaths from hemorrhage resulted in novel adaptations of resuscitative endovascular balloon occlusion of the aorta (REBOA) technology, increasing its potential application in combat. We describe the background of REBOA development in response to a need for minimally invasive intervention for hemorrhage control and provide a detailed review of all published cases (n = 47) of REBOA use for combat casualties. The current limitations of REBOA are described, including distal ischemia and reperfusion injury, as well as ongoing research efforts to adapt REBOA for prolonged use in the austere setting. LEVEL OF EVIDENCE: Level V.