Evolution and Variations of the Ovine Model of Spina Bifida.

Spina bifida is the most common congenital anomaly of the central nervous system and the first non-fatal fetal lesions to be addressed by fetal intervention. While research in spina bifida has been performed in rodent, nonhuman primate, and canine models, sheep have been a model organism for the disease. This review summarizes the history of development of the ovine model of spina bifida, previous applications, and translation into clinical studies. Initially used by Meuli et al. [Nat Med. 1995;1(4):342-7], fetal myelomeningocele defect creation and in utero repair demonstrated motor function preservation. The addition of myelotomy in this model can reproduce hindbrain herniation malformations, which is the leading cause of mortality and morbidity in humans. Since inception, the ovine models have been validated numerous times as the ideal large animal model for fetal repair, with both locomotive scoring and spina bifida defect scoring adding to the rigor of this model. The ovine model has been used to study different methods of myelomeningocele defect repair, the application of various tissue engineering techniques for neuroprotection and bowel and bladder function. The results of these large animal studies have been translated into human clinical trials including Management of Meningocele Study (MOMS) trial that established current standard of care for prenatal repair of spina bifida defects, and the ongoing trials including the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) trial using a stem cell patch for repair. The advancement of these life savings and life-altering therapies began in sheep models, and this notable model continues to be used to further the field including current work with stem cell therapy.

Prenatal Rupture of Hydrocolpos in a Cloacal Malformation.

INTRODUCTION: Cloacal dysgenesis occurs from failure of embryological division of urogenital sinus and hindgut, leading to a single common perineal opening for genitourinary and gastrointestinal tracts. The prenatal diagnosis of cloacal malformation is imprecise, but the clinical correlation of postnatal findings to prenatal history can help reveal explanations for unusual pathological findings in patients with urogenital abnormalities. CASE PRESENTATION: A 21-year-old woman was referred after her 20-week ultrasound demonstrated anhydramnios and concern for dilated fetal bowel. Fetal MRI confirmed anhydramnios and a dilated fetal colon, in addition to hydronephrosis and a pelvic cyst. Repeat ultrasound at 27 weeks showed unexpected complete resolution of her anhydramnios but new fetal ascites. The newborn girl was postnatally diagnosed with a cloacal malformation and an unusual near-complete fusion of her labia. She underwent proximal sigmoid colostomy and a tube vaginostomy at birth followed by cloacal reconstruction at 1.5 years old. CONCLUSION: In female fetus with a pelvic cyst, one should have a high index of suspicion for cloacal anomaly and consider the possibility of urinary obstruction leading to alteration in amniotic fluid.

Centers of Excellence: If We Build It, Will They Come?

Pediatric surgeons have been pursuing high quality, affordable care or value-based care for over 50 years. One approach to streamlining the clinical care for a complex problem was the development of a center of excellence (COE). The concept of COE focuses on a shared vision of providing high quality care through a multidisciplinary approach. The goal is to improve diagnostic accuracy as well as therapeutic outcomes using focused expertise within a group. COEs are often resource intensive before becoming fiscally viable and therefore require initial support from hospital leadership. This review discusses the key steps to consider before building a COE, strategies to help build one, and how to keep one successful as defined by quality, accessibility, equity, training, and maintaining teams within the group.

Management of Congenital Lung Malformations.

Congenital lung malformations represent a spectrum of lesions, each with a distinct cause and tailored clinical approach. This article will focus on the following malformations: congenital pulmonary airway malformations, formally known as congenital cystic adenomatoid malformations, bronchopulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst. Each of these malformations will be defined and examined from an embryologic, pathophysiologic, and clinical management perspective unique to that specific lesion. A review of current recommendations in both medical and surgical management of these lesions will be discussed as well as widely accepted treatment algorithms.

Care Levels for Fetal Therapy Centers.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.

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.

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.

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.

Novel Use of a Bronchial Blocker in a Challenging Case of Congenital Diaphragmatic Hernia-A Case Report.

The diagnosis of congenital diaphragmatic hernia (CDH) is associated with significant morbidity and mortality. Survival of neonates with CDH has improved recently, although the clinical course is complicated by sequelae of hypoplastic pulmonary parenchyma and vasculature, pulmonary hypertension, ventilation/perfusion (V/Q) mismatch, reduced pulmonary function and poor somatic growth. In this case report, we describe an infant with an antenatal diagnosis of CDH with a poor prognosis who underwent initial surgery followed by a tracheostomy but had a worsening clinical course due to a large area of ventilated but poorly perfused lung based on a V/Q nuclear scintigraphy scan. The emphysematous left lung was causing mediastinal shift and compression of the right lung, further compromising gas exchange. The infant had clinical improvement following bronchial blockade of the under-perfused left lung. This paved the way for further management with resection of the under-perfused lung lobe and continued clinical improvement. We present the novel use of selective bronchial blockade in a challenging case of CDH to determine if surgical lung resection may benefit the infant. We also review the physiology of gas exchange during the use of a bronchial occluder and the relevant literature.

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.

Causes of early mortality in pediatric trauma patients.

BACKGROUND: Trauma is the leading cause of death in children, and most deaths occur within 24 hours of injury. A better understanding of the causes of death in the immediate period of hospital care is needed. METHODS: Trauma admissions younger than 18 years from 2009 to 2019 at a Level I pediatric trauma center were reviewed for deaths (n = 7,145). Patients were stratified into ages 0-6, 7-12, and 13-17 years old. The primary outcome was cause of death, with early death defined as less than 24 hours after trauma center arrival. RESULTS: There were 134 (2%) deaths with a median age of 7 years. The median time from arrival to death was 14.4 hours (interquartile range, 0.5-87.8 hours). Half (54%) occurred within 24 hours. However, most patients who survived initial resuscitation in the emergency department died longer than 24 hours after arrival (69%). Traumatic brain injury was the most common cause of death (66%), followed by anoxia (9.7%) and hemorrhage (8%). Deaths from hemorrhage were most often in patients sustaining gunshot wounds (73% vs. 11% of all other deaths, p < 0.0001), more likely to occur early (100% vs. 50% of all other deaths, p = 0.0009), and all died within 6 hours of arrival. Death from hemorrhage was more common in adolescents (21.4% of children aged 13-17 vs. 6.3% of children aged 0-6, and 0% of children aged 7-12 p = 0.03). The highest case fatality rates were seen in hangings (38.5%) and gunshot wounds (9.6%). CONCLUSION: Half of pediatric trauma deaths occurred within 24 hours. Death from hemorrhage was rare, but all occurred within 6 hours of arrival. This is a critical time for interventions for bleeding control to prevent death from hemorrhage in children. Analysis of these deaths can focus efforts on the urgent need for development of new hemorrhage control adjuncts in children. LEVEL OF EVIDENCE: Epidemiological study, level IV.

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.

Total gastrectomy with delayed Hunt-Lawrence pouch reconstruction for neonatal gastric perforation presenting with hematemesis.

The differential for neonatal hematoma sis ranges from benign etiologies to life-threatening emergencies. Neonatal gastric perforation is a rare cause of neonatal hematoma sis but is a deadly condition, requiring prompt diagnosis and treatment. The etiology is usually related to conditions predisposing to over distension of the stomach, such as positive pressure ventilation or distal obstruction, but in some cases cannot be determined. Patients generally present with abdominal distension and respiratory distress. We present a case of a 1-day old term baby girl who developed sudden onset hematoma sis and clinical deterioration, who was found to have a large proximal gastric perforation requiring emergent total gastrectomy with delayed reconstruction.

Interprofessional/interdisciplinary teamwork during the early COVID-19 pandemic: experience from a children's hospital within an academic health center.

The COVID-19 pandemic has created multiple, complex and intense demands on hospitals, including the need for surge planning in the many locations outside epicenters such as northern Italy or New York City. We here describe such surge planning in an Academic Health Center that encompasses a children's hospital. Interprofessional teams from every aspect of inpatient care and hospital operations worked to prepare for a COVID-19 surge. In so doing, they successfully innovated ways to integrate pediatric and adult care and maximize bed capacity. The success of this intense collaborative effort offers an opportunity for ongoing teamwork to enhance efficient, effective, and high-quality patient care.

Malignant primitive epithelioid sarcoma with features of rhabdoid tumor presenting in utero with diffusely metastatic disease.

Diagnosis of a tumor in utero is a rare occurrence and poses diagnostic and therapeutic challenges. In cases of tumor-associated hydrops, there is significant risk of fetal demise, and prenatal intervention may be considered to avoid this outcome when possible. When fetal intervention is unlikely to improve survival, information can be useful for counseling families. We present a rare case of fetal diagnosis of a primary renal malignancy with widespread metastases and hydrops, with unique immunohistochemical findings consistent with malignant primitive epithelioid sarcoma with features of rhabdoid tumor.

Necrotizing enterocolitis following diazoxide therapy for persistent neonatal hypoglycemia.

Recalcitrant neonatal hypoglycemia poses a treatment challenge for clinicians. When a patient's hypoglycemia does not respond to dextrose infusion, several medication options are available, including diazoxide(1,2). Several side effects of diazoxide are described in the literature, including fluid retention with the risk of development of congestive heart failure(3,4). We describe a case of necrotizing enterocolitis in a patient with Beckwith-Wiedemann Syndrome with persistent neonatal hypoglycemia who was treated with increasing doses of diazoxide.

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.

Outcomes for Prenatally Diagnosed Right Congenital Diaphragmatic Hernia.

BACKGROUND: Right congenital diaphragmatic hernia (CDH) occurs less frequently than left CDH. Therefore, prognostic indicators for right CDH are not as well studied as for left CDH. METHODS: A retrospective review from a single, tertiary referral center (from 1994 until July 2013) of patients with unilateral right CDH was conducted. Prenatal characteristics were evaluated and correlated with survival to discharge and need for extracorporeal membranous oxygen (ECMO). RESULTS: In total, 34 patients were identified. There were 12 postnatal deaths and 2 fetal demises (6%), representing an overall mortality of 41%. Six patients required ECMO. Nine patients underwent fetal intervention and were analyzed separately. For patients not undergoing fetal intervention, the survival rate was 52% and a higher mean (±SD) lung-to-head ratio (LHR) was associated with survival (1.1 ± 0.4 vs. 0.8 ± 0.2, p = 0.03). There were no deaths or need for ECMO in any patient with an LHR ≥1.0. Of the 9 patients who underwent fetal intervention, survival was 78% and only 1 patient required ECMO. Fetal intervention was primarily tracheal occlusion (n = 8). CONCLUSIONS: An LHR <1.0 is associated with worse survival for right CDH and may also reflect the need for ECMO.

Resection of a thoracoabdominal ganglioneuroma via a retroperitoneal minimally invasive approach.

A 10-year-old girl presented to her pediatrician with a history of cough and fever. A chest radiograph revealed a paraspinal mass. On cross-sectional imaging, the mass traversed the diaphragm, extending from T9 to L1 spinal levels with involvement of the T10-12 neural foramen. Vanillylmandelic and homovanillic acid levels were normal. On review of historical radiographs, the mass had increased in size. Thus, surgical resection was recommended for diagnosis and treatment. The patient was placed in left lateral decubitus position. The retroperitoneal space was accessed inferior to the twelfth rib. One 12 mm and two 5 mm ports were used. Development of the retroperitoneal space was achieved with both blunt dissection and a vessel-sealing device. The diaphragm was incised to resect the thoracic component of the mass. The tumor was adherent at the neural foramen and was resected flush with the spine. The diaphragm repaired primarily. She was discharged home on post-operative day four without complication. Pathology demonstrated a ganglioneuroma. The patient was well at her follow-up, and imaging one year postoperatively was without recurrence. No additional treatment was required. A laparoscopic retroperitoneal approach allows for a safe, minimally invasive resection of a thoracoabdominal mass without violation of the abdominal cavity.

Fetal myelomeningocele repair.

Myelomeningocele is a congenital malformation that causes a spectrum of morbidity. With the standard of care now being in utero repair, the spectrum of morbidity has changed. The purpose of this article is to review the diagnosis, workup and treatment options of fetal myelomeningocele. We also review the obstetrical, neurological, gastrointestinal, urinary, and orthopedic outcomes of the in utero myelomeningocele repair.