Evaluation of a biodegradable polyurethane patch for repair of diaphragmatic hernia in a rat model: A pilot study.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) repair is an area of active research. Large defects requiring patches have a hernia recurrence rate of up to 50%. We designed a biodegradable polyurethane (PU)-based elastic patch that matches the mechanical properties of native diaphragm muscle. We compared the PU patch to a non-biodegradable Gore-Tex™ (polytetrafluoroethylene) patch. METHODS: The biodegradable polyurethane was synthesized from polycaprolactone, hexadiisocyanate and putrescine, and then processed into fibrous PU patches by electrospinning. Rats underwent 4 mm diaphragmatic hernia (DH) creation via laparotomy followed by immediate repair with Gore-Tex™ (n = 6) or PU (n = 6) patches. Six rats underwent sham laparotomy without DH creation/repair. Diaphragm function was evaluated by fluoroscopy at 1 and 4 weeks. At 4 weeks, animals underwent gross inspection for recurrence and histologic evaluation for inflammatory reaction to the patch materials. RESULTS: There were no hernia recurrences in either cohort. Gore-Tex™ had limited diaphragm rise compared to sham at 4 weeks (1.3 mm vs 2.9 mm, p = 0.003), but no difference was found between PU and sham (1.7 mm vs 2.9 mm, p = 0.09). There were no differences between PU and Gore-Tex™ at any time point. Both patches formed an inflammatory capsule, with similar thicknesses between cohorts on the abdominal (Gore-Tex™ 0.07 mm vs. PU 0.13 mm, p = 0.39) and thoracic (Gore-Tex™ 0.3 mm vs. PU 0.6 mm, p = 0.09) sides. CONCLUSION: The biodegradable PU patch allowed for similar diaphragmatic excursion compared to control animals. There were similar inflammatory responses to both patches. Further work is needed to evaluate long-term functional outcomes and further optimize the properties of the novel PU patch in vitro and in vivo. LEVEL OF EVIDENCE: Level II, Prospective Comparative Study.

Chest Wall Reconstruction in Pediatric Patients with Chest Wall Tumors: A Systematic Review.

BACKGROUND: Resection of pediatric chest wall tumors can result in large defects requiring reconstruction for function and cosmesis. Multiple reconstructive methods have been described. We performed a systematic review of the literature to describe commonly used approaches and outcomes. METHODS: A systematic literature search was performed for English-language publications describing chest wall tumor resection and reconstruction using implantable materials in patients ≤21 years, excluding soft tissue resection only, sternal resection, and reconstruction by primary repair or muscle flaps alone. Data were collected on diagnoses, reconstructive method, and outcomes. Rigid chest wall reconstruction was compared to mesh reconstruction. RESULTS: There were 55 articles with 188 patients included. The median age was 12 years. Most tumors were malignant (n = 172, 91.5%), most commonly Ewing's sarcoma (n = 65, 34.6%), followed by unspecified sarcomas (n = 34, 18.1%), Askin's tumor (n = 16, 8.5%; a subset of Ewing's sarcoma) and osteosarcoma (n = 16, 8.5%). A median of 3 ribs were resected (range 1-12). Non-rigid meshes were most common (n = 138, 73.4%), followed by rigid prostheses (n = 50, 26.6%). There were 19 post-operative complications (16.8%) and 22.2% of patients developed scoliosis. There were no significant differences in complications (20.5% rigid vs. 10.6% non-rigid, p = 0.18) or scoliosis (22.7% vs. 14.0%, p = 0.23) by reconstruction method, but complications after rigid reconstruction were more likely to require surgery (90.0% vs. 53.9%, p = 0.09). The median follow-up duration was 24 months. CONCLUSIONS: In this review of the literature, there were no significant differences in overall post-operative complications or scoliosis development by reconstruction method, yet complications after rigid reconstruction were more likely to require surgical intervention. LEVEL OF EVIDENCE: Level IV.

Unintended Consequences of COVID-19 on Pediatric Falls From Windows: A Multicenter Study.

INTRODUCTION: In attempts to quell the spread of COVID-19, shelter-in-place orders were employed in most states. Increased time at home, in combination with parents potentially balancing childcare and work-from-home duties, may have had unintended consequences on pediatric falls from windows. We aimed to investigate rates of falls from windows among children during the first 6 mo of the COVID-19 pandemic. METHODS: Patients <18 y old admitted to three pediatric trauma centers (two - level 1, one - level 2) between 3/19/20 and 9/19/20 (COVID-era) were compared to a pre-COVID cohort (3/19/19 to 9/19/19). The primary outcome was the rate of falls from windows. Secondary outcomes included injury severity score (ISS), injuries sustained, and mortality. RESULTS: Of 1011 total COVID-era pediatric trauma patients, 36 (3.6%) sustained falls from windows compared to 23 of 1108 (2.1%) pre-COVID era patients (OR 1.7, P = 0.05). The median ISS was seven pre-COVID versus four COVID-era (P = 0.43). The most common injuries sustained were skull fractures (30.5%), extremity injuries (30.5%), and intracranial hemorrhage (23.7%). One-fifth of patients underwent surgery (21.7% pre-COVID versus 19.4% COVID-era, P = 1.0). There was one mortality in the COVID-era cohort and none in the pre-COVID cohort (P = 1.0). CONCLUSIONS: Despite overall fewer trauma admissions during the first 6 mo of the COVID-19 pandemic, the rate of falls from windows nearly doubled compared to the prior year, with substantial associated morbidity. These findings suggest a potential unintended consequence of shelter-in-place orders and support increased education on home safety and increased support for parents potentially juggling multiple responsibilities in the home.

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.

Child Abuse and the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has widespread effects, including enhanced psychosocial stressors and stay-at-home orders which may be associated with higher rates of child abuse. We aimed to evaluate rates of child abuse, neglect, and inadequate supervision during the COVID-19 pandemic. METHODS: Patients ≤5 y old admitted to a level one pediatric trauma center between 3/19/20-9/19/20 (COVID-era) were compared to a pre-COVID cohort (3/19/19-9/19/19). The primary outcome was the rate of child abuse, neglect, or inadequate supervision, determined by Child Protection Team and Social Work consultations. Secondary outcomes included injury severity score (ISS), mortality, and discharge disposition. RESULTS: Of 163 total COVID-era pediatric trauma patients, 22 (13.5%) sustained child abuse/neglect, compared to 17 of 206 (8.3%) pre-COVID era patients (P = 0.13). The ISS was similar between cohorts (median 9 pre-COVID versus 5 COVID-era, P = 0.23). There was one mortality in the pre-COVID era and none during COVID (P = 0.45). The rate of discharge with someone other than the primary caregiver at time of injury was significantly higher pre-COVID (94.1% versus 59.1%, P = 0.02). In addition, foster family placement rate was twice as high pre-COVID (50.0% versus 22.7%, P = 0.10). CONCLUSIONS: The rate of abuse/neglect among young pediatric trauma patients during COVID did not differ compared to pre-pandemic, but discharge to a new caregiver was significantly lower. While likely multifactorial, this data suggests that resources during COVID may have been limited and the clinical significance of this is concerning. Larger studies are warranted to further evaluate COVID-19's effect on this vulnerable population.

The Utility of Discharge Antibiotics in Pediatric Perforated Appendicitis Without Leukocytosis.

INTRODUCTION: Optimal management of pediatric perforated appendicitis remains a topic of active investigation. Our institutional clinical practice guidelines (CPGs) were modified to discontinue antibiotics on discharge for patients with normal white blood cell count (WBC) without left shift. We hypothesized that patients would receive fewer antibiotics without increased complications. METHODS: Patients <18 y old with perforated appendicitis who underwent laparoscopic appendectomy between November 1, 2016 and May 31, 2021 at a tertiary care children's hospital were included. Primary outcome was adverse events: postdischarge surgical site infection (SSI), 30-day emergency department (ED) visits, or readmissions. Outcomes were compared before and after CPG modification. Multivariable regression was performed to identify factors associated with SSI. RESULTS: There were 113 patients pre- and 97 patients post-CPG modification. 23.1% of patients in the pre-cohort had an elevated discharge WBC or left shift compared to 18.9% of patients in the post-cohort (P = 0.48). Significantly fewer patients were prescribed antibiotics on discharge in the post-cohort (70.8% pre versus 14.4% post, P < 0.0001) and for fewer days (2 pre versus 0 post, P < 0.0001). Total antibiotic days decreased significantly (6.1 pre versus 4.6 post, P < 0.0001). There was an increase in postdischarge SSIs on univariate analysis (1.8% pre versus 9.3% post, P = 0.03), ED visits (9.7% pre versus 19.6% post, P = 0.04), and readmissions (5.3% pre versus 11.3% post, P = 0.13). On multivariable analysis, being in the post-cohort was not significantly associated with post-discharge SSIs after adjusting for sex, symptom duration, initial WBC, and discharge antibiotic duration (OR 0.25, 95% CI 0.04-1.4, P = 0.11). CONCLUSIONS: Modification of a pediatric perforated appendicitis clinical practice guideline to discontinue antibiotics on discharge with a normal WBC without left shift was effective in decreasing antibiotic duration. This was associated with an increase in SSIs on univariate analysis, which did not persist on multivariable analysis and requires further investigation.

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.

The hidden mortality of pediatric firearm violence.

INTRODUCTION: Firearms and motor vehicle collisions (MVC) are leading causes of mortality in children. We hypothesized that firearm injuries would have a higher mortality than MVCs in children and a higher level of resource utilization METHODS: Trauma patients <18 years old at a Level 1 pediatric trauma center sustaining gunshot wounds (GSW) or MVCs 2009-2019 were included. The primary outcome was mortality. The secondary outcome was immediate surgery. The California Department of Public Health's Overall Injury Surveillance tool was queried for patients <18 with GSW or MVC 2006-2015 to compare statewide case fatality rates (CFRs), and analyze proportions of GSWs by intent: assault, self-inflicted, and unintentional. RESULTS: Of 13,840 pediatric trauma patients at our institution, 295 GSWs (2.1%) and 4467 MVCs (32.3%) were included. Mortality was higher for GSWs (7.5% vs. 0.8%, p<0.0001). GSW patients were more likely to require immediate surgery (34.4% vs. 11.2%, p<0.0001). On multivariable analysis, GSW patients were 7.8-times more likely to die than MVC patients (OR 7.83, 95% CI 3.68-16.66, p<0.0001), adjusted for age, sex, and injury severity. Statewide, there were 10,790 pediatric GSWs with 1586 deaths (CFR 14.7%) vs. 710 deaths in 261,363 children in MVCs (CFR 0.3%, p<0.0001). The GSW CFR rose (13.4% to 16.5%, p = 0.05) while the MVC CFR decreased (0.5% to 0.2%, p<0.0001) in 2015 vs. 2006. CONCLUSION: Firearm violence in pediatric patients is significantly more lethal than MVCs and is resource intensive. The case fatality rate for pediatric firearm violence is rising. Resources must be directed at preventing pediatric firearm injuries. LEVEL OF EVIDENCE: Prognosis study, Level II.

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.

Epidemiology of paediatric drowning hospitalisations in the USA: a population-based study.

BACKGROUND: Drowning is a leading cause of death in children ≤5 years old. Detailed data on the epidemiology of drowning in this high-risk population can inform preventative efforts. We aimed to study trends in incidence and case fatality rates (CFR) in the USA among young children hospitalised after drowning. METHODS: Children ≤5 years old hospitalised in the USA after drowning were identified from the Kids Inpatient Database 2000-2016. Incidence and CFRs by calendar year, age, sex, race/ethnicity and hospital region were calculated. Trends over time were evaluated. Factors associated with fatal drowning were assessed. RESULTS: Among 30 560 804 hospitalised children ≤5 years old, 9261 drowning cases were included. Patients were more commonly male (62.3%) and white (47.4%). Two years old had the highest incidence of hospitalisation after drowning, regardless of race/ethnicity, sex and region. Overall drowning hospitalisations decreased by 49% from 2000 to 2016 (8.38-4.25 cases per 100 000 children). The mortality rate was 11.4% (n=1060), and most occurred in children ≤3 years old (83.0%). Overall case fatality decreased between 2000 and 2016 (risk ratio (RR) 0.44, 95% CI 0.25 to 0.56). The lowest reduction in incidence and case fatality was observed among Black children (Incidence RR 0.92, 95% CI 0.75 to 1.13; case fatality RR 0.80, 95% CI 0.41 to 1.58). CONCLUSIONS: Hospitalisations and CFRs for drowning among children ≤5 years old have decreased from 2000 to 2016. Two years old are at the highest risk of both fatal and non-fatal drowning. Disparities exist for Black children in both the relative reduction in drowning hospitalisation incidence and case fatality. Interventions should focus on providing equitable preventative care measures to this population.

Fetal and neonatal outcomes following maternal aortic balloon occlusion for hemorrhage in pregnancy: A review of the literature.

BACKGROUND: Hemorrhage is a leading cause of maternal death worldwide, with increased risk in women with abnormal placentation. Aortic balloon occlusion (ABO), including resuscitative endovascular balloon occlusion, has been used for obstetrical hemorrhage for 20 years, and is associated with decreased operative blood loss, fewer transfusions, and lower rates of hysterectomy. However, the effect of aortic occlusion on fetal/neonatal outcomes is not well known. METHODS: A literature review on ABO for obstetrical or traumatic hemorrhage was performed. Cases were included if fetal/neonatal outcomes were reported. Data were collected on timing of balloon inflation (predelivery or postdelivery), fetal/neonatal mortality, and Apgar scores. Secondary maternal outcomes included blood loss, need for hysterectomy, ABO-related complications, and mortality. RESULTS: Twenty-one reports of ABO in 825 cases of obstetrical hemorrhage were reviewed (nine case reports/series and twelve comparative studies). 13.5% (111/825) had aortic occlusion prior to delivery of the fetus. Comparative cohorts included 448 patients who underwent iliac artery balloon occlusion (n = 219) or no vascular balloon occlusion (n = 229). The most common neonatal outcome reported was Apgar scores, with no difference in fetal/neonatal outcomes between ABO and non-ABO patients in any study. One neonatal mortality occurred in the sole reported case of ABO use in a pregnant trauma patient at 24 weeks gestation. One maternal mortality occurred because of aortic dissection. Five comparative studies reported significantly decreased blood loss in ABO patients compared to non-ABO patients, and four studies reported significantly lower rates of hysterectomy in ABO patients. ABO-related complications were reported in 1.6% of patients (13/825). CONCLUSION: Obstetrical hemorrhage is a devastating complication, and ABO may potentially decrease blood loss and reduce the hysterectomy rate without compromising fetal and neonatal outcomes. Further research is needed to determine the safety of predelivery aortic occlusion as this occurred in 14% of the cases.

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.

Patient selection for pediatric gastrostomy tubes: Are we placing tubes that are not being used?

INTRODUCTION: Identifying pediatric patients who may benefit from gastrostomy tube (GT) placement can be challenging. We hypothesized that many GTs would no longer be in use after 6 months. METHODS: Inpatient GT placements in patients < 18 years old at a tertiary children's hospital from 9/2014 to 2/2020 were included. The primary outcome was GT use <6 months (short-term). Secondary outcomes included age at placement, indication for GT, and operations for GT-related issues. RESULTS: Fifteen percent (22/142) of GTs were used for <6 months post-operatively. The median duration of short-term GT use was 1.6 months (IQR 0.9-3.4 months). Short-term GTs were more likely to be placed in patients with traumatic brain injury (TBI) (18.2% vs. 4.2%, p = 0.03) and adolescents (≥12 years old, 22.7% vs. 4.0%, p = 0.005). Gastrocutaneous fistula closure was required in 33.3% of short-term patients who had their GTs removed (n = 6/18), with median total hospital charges of $29,989 per patient. CONCLUSION: Fifteen percent of pediatric GTs placed as inpatients were used for <6 months, more commonly among adolescents and in TBI patients. One-third of patients with short-term GTs required gastrocutaneous fistula closure. Adolescents and TBI patients may benefit from consideration of short-term nasogastric tube (NGT) feeds rather than surgical GT placement. LEVEL OF EVIDENCE: III.

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.

Utility of Routine Head Ultrasounds in Infants on Extracorporeal Life Support: When is it Safe to Stop Scanning?

Intracranial hemorrhage (ICH) can be a devastating complication of extracorporeal life support (ECLS); however, studies on the timing of ICH detection by head ultrasound (HUS) are from 2 decades ago, suggesting ICH is diagnosed by day 5 of ECLS. Given advancements in imaging and critical care, our aim was to evaluate if the timing of ICH diagnosis in infants on ECLS support has changed. Patients <6 months old undergoing ECLS 2011-2020 at a tertiary care children's hospital were included. Primary outcome was timing of ICH diagnosis on HUS. Seventy-four infants underwent ECLS for cardiac (54%) or pulmonary (46%) indications. Venoarterial ECLS was most common (88%). Median ECLS duration was 6 days (range 1-26). Sixteen patients were diagnosed with ICH (21.6%), at a median of 2 days postcannulation (range 1-4). Nearly all were <4 weeks old at cannulation (93.8%). In conclusion, one-fifth of infants developed ICH diagnosed by HUS while on ECLS, all within the first 4 days of ECLS, consistent with previous literature. Despite advances in critical care and imaging technology, the temporality of ICH diagnosis in infants on ECLS is unchanged.

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.

Surgical Management of an Obstructive Müllerian Anomaly in a Patient with Anorectal Malformation.

Müllerian duct anomalies are rare in the general population, occurring in less than 3% of women, but much more prevalent in female patients with anorectal malformation, occurring in up to 30% of these patients. Unicornuate uterus with a rudimentary non-communicating horn is a congenital anomaly of Mullerian development which can be seen in isolation or in conjunction with other anomalies, with several case reports described in patients with VACTERL association. These anomalies may be asymptomatic until the patient develops dysmenorrhea or devastating obstetrical complications. We describe the successful surgical management of an obstructive Müllerian anomaly in a post-pubertal female patient with anorectal malformation.

Blunt Traumatic Diaphragmatic Hernia in Children: A Systematic Review.

BACKGROUND: Traumatic diaphragmatic hernia (TDH) is rare in children, most often occurring following blunt thoracoabdominal trauma from high energy mechanisms, such as motor vehicle collisions (MVC). We performed a systematic review to describe injury details and management. METHODS: Following PRISMA guidelines, a systematic literature search was performed to identify publications of blunt TDH in patients < 18 y old. Conflicts were resolved by consensus. Data were collected on demographics, TDH location, mechanism of injury, associated intraabdominal injuries (IAI), management, and outcomes. Denominators vary depending on number of patients with such information reported. RESULTS: Fifty-eight articles were reviewed with 142 patients with TDH. The median age was seven y (range 0.25-16). Most were left-sided (85 of 126, 67.5%). MVC was the most common mechanism (66 of 142, 46.5%). IAI was present in 50.0% (57 of 114), most commonly liver injuries (25 of 57, 43.9%). Delayed diagnoses occurred in 49.6% (57 of 115, range 8 h-10 y), and were more common with right-sided TDH (76.0% versus 48.5%, P = 0.02). Chest radiography was 59.0% sensitive for TDH, while computed tomography sensitivity was 65.8%. Operative repair was performed on all surviving patients, and all underwent primary diaphragm repair. The overall mortality was 11.3% (n = 16), with four attributable to the TDH. There were no reported recurrences over a median follow-up of 12 mo. CONCLUSIONS: Pediatric TDH is a rare diagnosis with a high rate of associated IAI and delayed diagnosis. Primary diaphragm repair was performed in all cases. Surgeons should maintain a high suspicion for diaphragm injury in blunt thoracoabdominal trauma.

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.