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.

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.

Impact of prescription drug monitoring program mandate on postoperative opioid prescriptions in children.

PURPOSE: Prescription drug monitoring programs (PDMPs) have been established to combat the opioid epidemic, but there is no data on their efficacy in children. We hypothesized that a statewide PDMP mandate would be associated with fewer opioid prescriptions in pediatric surgical patients. METHODS: Patients < 18 undergoing inguinal hernia repair, orchiopexy, orchiectomy, appendectomy, or cholecystectomy at a tertiary children's hospital were included. The primary outcome, discharge opioid prescription, was compared for 10 months pre-PDMP (n = 158) to 10 months post-PDMP (n = 228). Interrupted time series analysis was performed to determine the effect of the PDMP on opioid prescribing. RESULTS: Over the 20-month study period, there was an overall decrease in the rate of opioid prescriptions per month (- 3.6% change, p < 0.001). On interrupted time series analysis, PDMP implementation was not associated with a significant decrease in the monthly rate of opioid prescriptions (1.27% change post-PDMP, p = 0.4). However, PDMP implementation was associated with a reduction in opioid prescriptions of greater than 5 days' supply (- 2.7% per month, p = 0.03). CONCLUSION: Opioid prescriptions declined in pediatric surgical patients over the study time period. State-wide PDMP implementation was associated with a reduction in postoperative opioid prescriptions of more than 5 days' duration.

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.

A Decade of Experience with the Ovine Model of Myelomeningocele: Risk Factors for Fetal Loss.

INTRODUCTION: The ovine model is the gold standard large animal model of myelomeningocele (MMC); however, it has a high rate of fetal loss. We reviewed our experience with the model to determine risk factors for fetal loss. METHODS: We performed a retrospective review from 2009 to 2018 to identify operative factors associated with fetal loss (early fetal demise, abortion, or stillbirth). Operative risk factors included gestational age at operation, operative time, reduction of multiple gestations, amount of replaced amniotic fluid, ambient temperature, and method of delivery. RESULTS: MMC defects were created in 232 lambs with an overall survival rate of 43%. Of the 128 fetuses that died, 53 (42%) had demise prior to repair, 61 (48%) aborted, and 14 (11%) were stillborn. Selective reduction of multiple gestations in the same uterine horn was associated with increased fetal demise (OR 3.03 [95% CI 1.29-7.05], p = 0.01). Later gestational age at MMC repair and Cesarean delivery were associated with decreased abortion/stillbirth (OR 0.90 [95% CI 0.83-0.90], p = 0.03, and OR 0.37 [95% CI 0.16-0.31], p = 0.02), respectively. CONCLUSION: Avoiding selective reduction, repairing MMC later in gestation, and performing Cesarean delivery decreases the rate of fetal loss in the ovine MMC model.

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.

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.

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.

Fetal myelomeningocele repair: a narrative review of the history, current controversies and future directions.

Fetal surgery is a relatively new field of medicine. The purpose of this narrative review is to present the history of how fetal surgery became the standard of care for myelomeningocele (MMC), the current controversies of this treatment, and active areas of research that may change how MMC is treated. Fetal surgery for MMC emerged out of the University of California, San Francisco in the 1980s in the laboratory of Dr. Michael Harrison. Initial research focused on testing the hypothesis that the in utero repair of MMC could improve outcomes in the ovine model. Evidence from this model suggested that in utero repair decreases the secondary damage to the exposed neural tissue and improves post-natal neurologic outcomes, opening the door for human intervention. This was followed by the Management of Myelomeningocele Study (MOMS), which was a multicenter randomized controlled trial comparing the prenatal versus postnatal MMC repair. The MOMS trial was stopped early due to the improved outcomes of the prenatal repair, establishing the open fetal MMC repair as the standard of care. Since the MOMS trial, two primary areas of controversy have arisen: the operative approach and criteria for the repair. The three operative approaches include open, endoscopic and a hybrid approach combining open and endoscopic. Several of the inclusion and exclusion criteria from the MOMS trial have been challenged, to include body mass index, gestational diabetes, other fetal abnormalities, maternal infections and Rh alloimmunization. New areas of research have also emerged, exploring cell based therapies to improve fetal outcomes, alternatives to fetal surgery and alternatives to primary skin closure of the fetus.

Increased mortality in very young children with traumatic brain injury due to abuse: A nationwide analysis of 10,965 patients.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in young children; however, the impact of mechanism on outcomes has not been fully evaluated. We hypothesized that children with TBI due to abuse would have a higher mortality than children with accidental TBI due to motor vehicle collisions (MVC). METHODS: We performed a retrospective review of the National Kids' Inpatient (KID) hospitalizations database of children <2 years old with TBI due to abuse or MVC (2000-2016). The primary outcome was mortality. Secondary outcomes were length of stay (LOS) and hospital charges. We investigated predictors of mortality with multivariable regression. RESULTS: Of 10,965 children with TBI, 65.2% were due to abuse. Overall mortality was 9.8% (n = 1074). Abused children had longer LOS (5.7 vs 1.6 days, p < 0.0001) and higher hospital charges ($34,314 vs $19,360, p < 0.0001) than children with TBI due to MVC. The odds of mortality were 42% higher in children with abusive head trauma (OR 1.42, 95% CI 1.10-1.83, p = 0.007) compared to MVCs after adjusting for age, race, sex, neurosurgical intervention, injury severity, and insurance. CONCLUSION: Children with abusive traumatic brain injury have increased risk of mortality, longer LOS, and higher hospital charges compared to children with TBI due to motor vehicle collision after adjusting for relevant confounders. Resources must be directed at prevention and early identification of abuse.

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.

Quantifying the need for pediatric REBOA: A gap analysis.

BACKGROUND: Trauma is the leading cause of death in children. Resuscitative endovascular balloon occlusion of the aorta (REBOA) provides temporary hemorrhage control, but its potential benefit has not been assessed in children. We hypothesized that there are pediatric patients who may benefit from REBOA. METHODS: Trauma patients <18 years old at a level 1 pediatric trauma center between 2009 and 2019 were queried for deaths, pre-hospital cardiac arrest, massive transfusion protocol activation, transfusion requirement, or hemorrhage control surgery. These patients defined the cohort of severely injured patients. From this cohort, patients with intraabdominal injuries for which REBOA may provide temporary hemorrhage control were identified, including solid organ injury necessitating intervention, vascular injury, or pelvic hemorrhage. RESULTS: There were 239 severely injured patients out of 6538 pediatric traumas. Of these, 38 had REBOA-amenable injuries (15.9%) with 34.2% mortality, accounting for 10.2% of all pediatric trauma deaths at one center. Eleven patients with REBOA-amenable injuries had TBI (28.9%). Patients with REBOA-amenable injuries represented 0.6% of all pediatric traumas. CONCLUSION: Nearly 20% of severely injured pediatric patients could potentially benefit from REBOA. The overall proportion of pediatric patients with REBOA-amenable injuries is similar to adult studies. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

Minimizing the risk of occupational Q fever exposure: A protocol for ensuring Coxiella burnetii-negative pregnant ewes are used for medical research.

Q fever is a worldwide zoonosis caused by Coxiella burnetii that can lead to abortion, endocarditis, and death in humans. Researchers utilizing parturient domestic ruminants, including sheep, have an increased risk of occupational exposure. This study evaluated the effectiveness of our screening protocol in eliminating C. burnetii-positive sheep from our facility. From August 2010 to May 2018, all ewes (N = 306) and select lambs (N = 272; ovis aries) were screened twice for C. burnetii utilizing a serum Phase I and Phase II antibody immunofluorescence assay (IFA). The first screen was performed by the vendor prior to breeding, and the second screen was performed on arrival to the research facility. Ewes that were positive on arrival screening were quarantined and retested using repeat IFA serology, enzyme-linked immunosorbent assay, buffy coat polymerase chain reaction (PCR), and amniotic fluid PCR. The overall individual seroprevalence of C. burnetii in the flocks tested by the vendor was 14.2%. Ewes with negative Phase I and Phase II IFA results were selected for transport to the research facility. Upon arrival to the facility, two (0.7%) ewes had positive Phase I IFA results. Repeat testing demonstrated seropositivity in one of these two ewes, though amniotic fluid PCR was negative in both. The repeat seropositive ewe was euthanized prior to use in a research protocol. No Q fever was reported among husbandry, laboratory or veterinary staff during the study period. Serologic testing for C. burnetii with IFA prior to transport and following arrival to a research facility limits potential exposure to research staff.

Design and In Vivo Evaluation of a Non-Invasive Transabdominal Fetal Pulse Oximeter.

OBJECTIVE: Current intrapartum fetal monitoring technology is unable to provide physicians with an objective metric of fetal well-being, leading to degraded patient outcomes and increased litigation costs. Fetal oxygen saturation (SpO2) is a more suitable measure of fetal distress, but the inaccessibility of the fetus prior to birth makes this impossible to capture through current means. In this paper, we present a fully non-invasive, transabdominal fetal oximetry (TFO) system that provides in utero measures of fetal SpO2. METHODS: TFO is performed by placing a reflectance-mode optode on the maternal abdomen and sending photons into the body to investigate the underlying fetal tissue. The proposed TFO system design consists of a multi-detector optode, an embedded optode control system, and custom user-interface software. To evaluate the developed TFO system, we utilized an in utero hypoxic fetal lamb model and performed controlled desaturation experiments while capturing gold standard arterial blood gases (SaO2). RESULTS: Various degrees of fetal hypoxia were induced with true SaO2 values ranging between 10.5% and 66%. The non-invasive TFO system was able to accurately measure these fetal SpO2 values, supported by a root mean-squared error of 6.37% and strong measures of agreement with the gold standard. CONCLUSION: The results support the efficacy of the presented TFO system to non-invasively measure a wide-range of fetal SpO2 values and identify critical levels of fetal hypoxia. SIGNIFICANCE: TFO has the potential to improve fetal outcomes by providing obstetricians with a non-invasive measure of fetal oxygen saturation prior to delivery.

Does the pediatric hemodynamic cliff exist in response to hemorrhagic shock?

BACKGROUND: The paradigm that children maintain normal blood pressure during hemorrhagic shock until 30%-45% hemorrhage is widely accepted. There are minimal data supporting when decompensation occurs and how a child's vasculature compensates up to that point. We aimed to observe the arterial response to hemorrhage and when mean arterial pressure (MAP) decreased from baseline in pediatric swine. METHODS: Piglets were hemorrhaged in 20% increments of their total blood volume to 60%. MAP and angiograms of the thoracic aorta (TA) and abdominal arteries were obtained. Percent change in area of the vessels from baseline was calculated. RESULTS: Piglets (n = 8) had a differential vasoconstriction starting at 20% hemorrhage (celiac artery 36.3% [31.4-44.6] vs TA 16.7% [10.7-19.1] p = 0.0012). At 40% hemorrhage, the differential vasoconstriction favored shunting blood away from the abdominal visceral branches to the TA (celiac artery 54.7% [36.9-60.6] vs TA 29.5% [23.9-36.2] p = 0.0056 superior mesenteric artery 46.7% [43.9-68.6] vs TA 29.5% [23.9-36.2] p = 0.0100). This was exacerbated at 60% hemorrhage. MAP decreased from baseline at 20% hemorrhage (66.4 ±â€¯6.0 mmHg vs 41.4 ±â€¯10.4 mmHg, p < 0.0001), and worsened at 40% and 60% hemorrhage. CONCLUSION: In piglets, a differential vasocontriction shunting blood proximally occurred in response to hemorrhage. This did not maintain normal MAP at 20%, 40% or 60% hemorrhage. LEVEL OF EVIDENCE: Level II.

Resuscitative endovascular balloon occlusion of the aorta in a pediatric swine model: Is 60 minutes too long?

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is recommended in adults with a noncompressible torso hemorrhage with occlusion times of less than 60 minutes. The tolerable duration in children is unknown. We used a pediatric swine controlled hemorrhage model to evaluate the physiologic effects of 30 minutes and 60 minutes of REBOA. METHODS: Pediatric swine weighing 20 kg to 30 kg underwent a splenectomy and a controlled 60% total blood volume hemorrhage over 30 minutes, followed by either zone 1 REBOA for 30 minutes (30R) or 60 minutes (60R). Swine were then resuscitated with shed blood and received critical care for 240 minutes. RESULTS: During critical care, the 30R group's (n = 3) pH, bicarbonate, base excess, and lactate were no different than baseline, while at the end of critical care, these variables continued to differ from baseline in the 60R group (n = 5) and were worsening (7.4 vs. 7.2, p < 0.001, 30.4 mmol/L vs. 18.4 mmol/L, p < 0.0001, 5.6 mmol/L vs. -8.5 mmol/L, p < 0.0001, 2.4 mmol/L vs. 5.7 mmol/L, p < 0.001, respectively). Compared with baseline, end creatinine and creatinine kinase were elevated in 60R swine (1.0 mg/dL vs. 1.7 mg/dL, p < 0.01 and 335.4 U/L vs. 961.0 U/L, p < 0.001, respectively), but not 30R swine (0.9 mg/dL vs. 1.2 mg/dL, p = 0.06 and 423.7 U/L vs. 769.5 U/L, p = 0.15, respectively). There was no difference in survival time between the 30R and 60R pediatric swine, p = 0.99. CONCLUSION: The physiologic effects of 30 minutes of zone 1 REBOA in pediatric swine mostly resolved during the subsequent 4 hours of critical care, whereas the effects of 60 minutes of REBOA persisted and worsened after 4 hours of critical care. Sixty minutes of zone 1 REBOA may create an irreversible physiologic insult in a pediatric population.

Validation of a Novel Transabdominal Fetal Oximeter in a Hypoxic Fetal Lamb Model.

Current intrapartum fetal oxygen saturation (SaO2) monitoring methodologies are limited, mostly consisting of fetal heart rate monitoring which is a poor predictor of fetal hypoxia. A newly developed transabdominal fetal oximeter (TFO) may be able to determine fetal SaO2 non-invasively. This study is to validate a novel TFO in determining fetal SaO2 in a hypoxic fetal lamb model. Fetal hypoxia was induced in at-term pregnant ewe by placing an aortic occlusion balloon infrarenally and inflating it in a stepwise fashion to decrease blood flow to the uterine artery. The inflation was held at each step for 10 min, and fetal arterial blood gases (ABGs) were intermittently recorded from the fetal carotid artery. The balloon catheter was deflated when fetal SaO2 fell below 15%, and the fetus was recovered. A total of three desaturation experiments were performed. The average fetal SpO2 reported by the TFO was derived at each hypoxic level and correlated with the ABG measures. Fetal SaO2 from the ABGs ranged from 10.5 to 66%. The TFO SpO2 correlated with the ABG fetal SaO2 (r-squared = 0.856) with no significant differences (p > 0.5). The fetal SpO2 measurements from TFO were significantly different than the maternal SpO2 (p < 0.01), which suggests that the transcutaneous measurements are penetrating through the maternal abdomen sufficiently and are expressing the underlying fetal tissue physiology. The recently developed TFO system was able to non-invasively report the fetal SpO2, which showed strong correlation with ABG measures and showed no significant differences.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) in a pediatric swine liver injury model: A pilot study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has not been studied in children. We hypothesized that REBOA was feasible and would improve hemorrhage control and survival time, compared to no aortic occlusion, in a pediatric swine liver injury model. METHODS: Pediatric swine were randomized to Zone 1 REBOA or no intervention (control). Piglets underwent a partial liver amputation and free hemorrhage followed by either REBOA or no intervention for 30 min, then a damage control laparotomy and critical care for 4 h. RESULTS: Compared to control piglets (n = 5), REBOA piglets (n = 6) had less blood loss (34.0 ±â€¯1.6 vs 61.3 ±â€¯2.5 mL/kg, p < 0.01), higher end hematocrit (28.1 ±â€¯2.1 vs 17.1 ±â€¯4.1%, p = 0.03), higher end creatinine (1.4 ±â€¯0.1 vs 1.2 ±â€¯0.1 mg/dL, p = 0.05), higher end ALT and AST (56 ±â€¯4 vs 32 ±â€¯6 U/L, p = 0.01 and 155 ±â€¯26 vs 69 ±â€¯25 U/L, p = 0.05) and required more norepinephrine during critical care (1.4 ±â€¯0.3 vs 0.3 ±â€¯0.3 mg/kg, p = 0.04). All REBOA piglets survived, whereas 2 control piglets died, p = 0.10. CONCLUSION: In pediatric swine, 30 min of REBOA is feasible, decreases blood loss after liver injury and may improve survival. LEVEL OF EVIDENCE: Level 1.

In utero treatment of myelomeningocele with placental mesenchymal stromal cells - Selection of an optimal cell line in preparation for clinical trials.

BACKGROUND: We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model. METHODS: PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model. In vivo, myelomeningocele defects were created in 28 fetuses and repaired with PMSCs at 3 × 105 cells/cm2 of scaffold from Line A (n = 6), Line B (n = 7) and Line C (n = 5) and compared to no PMSCs (n = 10). Ambulation was scored as ≥13 on the Sheep Locomotor Rating Scale. RESULTS: In vitro, Line A and B had higher neuroprotective capability than no PMSCs (1.7 and 1.8 respectively vs 1, p = 0.02, ANOVA). In vivo, Line A and B had higher large neuron densities than no PMSCs (25.2 and 27.9 respectively vs 4.8, p = 0.03, ANOVA). Line C did not have higher neuroprotection or larger neuron density than no PMSCs. In vivo, Line A and B had ambulation rates of 83% and 71%, respectively, compared to 60% with Line C and 20% with no PMSCs. CONCLUSION: The in vitro neuroprotection assay will facilitate selection of optimal PMSC lines for clinical use. LEVEL OF EVIDENCE: n/a. TYPE OF STUDY: Basic science.