Modifiable Preoperative Risk Factors to Mitigate Postoperative Site Infection Following Pediatric Gastrostomy.

PURPOSE: There are limited studies assessing modifiable preoperative risk factors for pediatric laparoscopic gastrostomy tubes (LGT) and percutaneous endoscopic gastrostomy (PEG) tubes. We sought to evaluate the effect of demographics and surgical/infectious history on the superficial infection rate following gastrostomy tube (GT) placement. METHODS: After IRB approval, we conducted a single-institution retrospective cohort study from 2015 to 2021 of pediatric patients undergoing LGT or PEG tube. The primary outcome was cellulitis or abscess formation within 30-days and 90-days postoperatively. Statistical analyses were performed with t-tests, Chi-squared, and logistic regression(p ≤ 0.05). RESULTS: There were 382 patients, with 181 (47%) LGT and 201 (53%) PEGs. LGT patients were younger (5.9 vs. 12.3 months, p < 0.001) and more likely to be admitted to the neonatal or cardiac intensive care unit prior to their GT. There were similar rates of prior surgical intervention (58% vs. 66%, p = 0.29) and previous infection (37% vs. 38%, p = 0.87) in both LGT and PEG patients. Within 30-days postoperatively, LGT patients had a higher superficial infection rate (12% vs. 6%, p = 0.04). On multivariate regression, Black race (Odds Ratio 0.10, p = 0.03) was protective and prior Staphylococcus colonization (OR 2.35, p = 0.04) increased the odds of infection. In those patients colonized with Staphylococcus, 21% developed a superficial site infection compared to 9% in those not colonized (p = 0.01). CONCLUSION: These data suggest prior Staphylococcus colonization is a significant risk factor for superficial infection following GT. Further work into preoperative decolonization strategies may provide an avenue to decrease the high infection rate in this common pediatric procedure. LEVEL OF EVIDENCE: Level III.

Post-operative Opioid Reduction Protocol Reduces Racial Disparity in Clinical Outcomes in Children.

INTRODUCTION: Racial disparities in health outcomes continue to exist for children requiring surgery. Previous investigations suggest that clinical protocols may reduce racial disparities. A post-operative opioid reduction protocol was implemented in children undergoing abdominal surgery who were less than 1 years old at a tertiary level hospital. The purpose of this investigation was to determine if the clinical protocol was associated with a reduction in racial disparity in post-operative opioid prescribing patterns and associated clinical outcomes. METHODS: A post-operative opioid reduction protocol based on standing intravenous acetaminophen, educational sessions with nursing staff, and standardized post-operative sign-out between the surgical and NICU teams was implemented in children under 1 year old in 2016. A time series and before and after analysis was conducted using a historical pre-intervention cohort (Jan 2011-Dec 2015) and prospectively collected post-intervention cohort (Jan 2016-Jan 2021). Primary outcomes included post-operative opioid use and post-operative pain scores stratified by race. Secondary outcomes included associated clinical outcomes also stratified by race. RESULTS: A total of 249 children were included in the investigation, 117 in the pre-intervention group and 132 in the post intervention group. The majority of patients in both cohorts were either White or Black. The two cohorts were equally matched in terms of pre-operative clinical variables. In the pre-intervention cohort, the median post-operative morphine equivalents in White children was 2.1 mg/kg (IQR 0.2, 11.1) while in Black children it was 13.1 mg/kg (IQR 2.4, 65.3), p-value = 0.0352. In the post-intervention cohort, the median value for White children and Black children was statistically identical (0.05 mg/kg (IQR 0, 0.5) and 0.0 mg/kg (IQR 0, 0.3), respectively, p-value = 0.237). This pattern was also demonstrated in clinical variables including length of stay, intubation length and total parenteral nutrition use. In the pre-intervention cohort, the total length of stay for white children was 16 days while for black children it was 45 days (p = 0.007). In the postintervention cohort the length of stay for both White and Black children were identical at 8 days (p = 0.748). CONCLUSION: The use of a clinical opioid reduction protocol implemented at a tertiary medical center was associated with a reduction in racial disparity in opioid prescribing habits in children. Prior to the protocol, there was a racial disparity in clinical variables associated with prolonged opioid use including length of stay, TPN use, and intubation length. The clinical protocol reduced variability in opioid prescribing patterns in all racial groups which was associated with a reduction in variability in associated clinical variables. LEVEL OF EVIDENCE: Level III.

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

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

Long-term outcomes of congenital diaphragmatic hernia: A single institution experience.

BACKGROUND/PURPOSE: As survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic. METHODS: A retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020. RESULTS: A total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3-6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8-50.0). Median length of follow up was 49 months (IQR 17.8-95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%). CONCLUSION: As survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes.

High-Frequency Positive Pressure Ventilation as Primary Rescue Strategy for Patients with Congenital Diaphragmatic Hernia: A Comparison to High-Frequency Oscillatory Ventilation.

OBJECTIVE: The aim of this article was to evaluate high-frequency positive pressure ventilation (HFPPV) compared with high-frequency oscillatory ventilation (HFOV) as a rescue ventilation strategy for patients with congenital diaphragmatic hernia (CDH). HFPPV is a pressure-controlled conventional ventilation method utilizing high respiratory rate and low positive end-expiratory pressure. STUDY DESIGN: Seventy-seven patients diagnosed with CDH from January 2005 to September 2019 who were treated with stepwise progression from HFPPV to HFOV versus only HFOV were included. Fisher's exact test and the Kruskal-Wallis test were used to compare outcomes. RESULTS: Patients treated with HFPPV + HFOV had higher survival to discharge (80 vs. 50%, p = 0.007) and to surgical intervention (95.6 vs. 68.8%, p = 0.003), with average age at repair 2 days earlier (p = 0.004). Need for extracorporeal membrane oxygenation (p = 0.490), inhaled nitric oxide (p = 0.585), supplemental oxygen (p = 0.341), and pulmonary hypertension medications (p = 0.381) were similar. CONCLUSION: In CDH patients who fail respiratory support with conventional ventilation, HFPPV may be used as an intermediary mode of rescue ventilation prior to HFOV without adverse effects. KEY POINTS: · HFPPV may be used as an intermediary mode of rescue ventilation prior to HFOV without adverse effect.. · HFPPV is more widely available and can mitigate the limitations faced when using HFOV.. · HFPPV allows for intra- or interhospital transfer of neonates with CDH..

Primary gastrojejunostomy tube placement using laparoscopy with endoscopic assistance: A novel technique.

BACKGROUND: Gastrojejunostomy (GJ) tubes are commonly used to provide postpyloric enteral nutrition in pediatric patients who cannot tolerate gastric feeds. Most techniques depend on a preexisting gastrostomy tube (GT) site to convert to a gastrojejunostomy. Several minimally invasive techniques have been described; however, their risk profile varies widely. DESCRIPTION OF THE OPERATIVE TECHNIQUE: We present a technique for primary laparoscopic GJ tube placement that minimizes the risk of hollow viscus injury and the use of fluoroscopy through endoscopic assistance. RESULTS: Eleven GJ tubes were placed using this technique in patients ranging from 5 months to 17 years of age and weighing 6.3 to 46.0 kg. Endoscopy through the gastrostomy site allowed direct visualization of wire and tube placement. There were no intraoperative or postoperative complications within 30 days of operation. Use of fluoroscopy was limited with minimal total radiation exposure. CONCLUSION: The described technique of laparoscopic primary gastrojejunostomy tube placement with endoscopic assistance was associated with a low complication rate and minimal use of fluoroscopy. LEVEL OF EVIDENCE: IV.

Delayed presentation and sub-optimal outcomes of pediatric patients with acute appendicitis during the COVID-19 pandemic.

OBJECTIVE: Early presentation and prompt diagnosis of acute appendicitis are necessary to prevent progression of disease leading to complicated appendicitis. We hypothesize that patients had a delayed presentation of acute appendicitis during the COVID-19 pandemic, which affected severity of disease on presentation and outcomes. PATIENTS AND METHODS: We conducted a retrospective review of all patients who were treated for acute appendicitis at Morgan Stanley Children's Hospital (MSCH) between March 1, 2020 and May 31, 2020 when the COVID-19 pandemic was at its peak in New York City (NYC). For comparison, we reviewed patients treated from March 1, 2019 to May 31, 2019, prior to the pandemic. Demographics and baseline patient characteristics were analyzed for potential confounding variables. Outcomes were collected and grouped into those quantifying severity of illness on presentation to our ED, type of treatment, and associated post-treatment outcomes. Fisher's Exact Test and Kruskal-Wallis Test were used for univariate analysis while cox regression with calculation of hazard ratios was used for multivariate analysis. RESULTS: A total of 89 patients were included in this study, 41 patients were treated for appendicitis from March 1 to May 31 of 2019 (non-pandemic) and 48 were treated during the same time period in 2020 (pandemic). Duration of symptoms prior to presentation to the ED was significantly longer in patients treated in 2020, with a median of 2 days compared to 1 day (p = 0.003). Additionally, these patients were more likely to present with reported fever (52.1% vs 24.4%, p = 0.009) and had a higher heart rate on presentation with a median of 101 beats per minute (bpm) compared to 91 bpm (p = 0.040). Findings of complicated appendicitis on radiographic imaging including suspicion of perforation (41.7% vs 9.8%, p < 0.001) and intra-abdominal abscess (27.1% vs 7.3%, p = 0.025) were higher in patients presenting in 2020. Patients treated during the pandemic had higher rates of non-operative treatment (25.0% vs 7.3%, p = 0.044) requiring increased antibiotic use and image-guided percutaneous drain placement. They also had longer hospital length of stay by a median of 1 day (p = 0.001) and longer duration until symptom resolution by a median of 1 day (p = 0.004). Type of treatment was not a predictor of LOS (HR = 0.565, 95% CI = 0.357-0.894, p = 0.015) or duration until symptom resolution (HR = 0.630, 95% CI = 0.405-0.979, p = 0.040). CONCLUSION: Patients treated for acute appendicitis at our children's hospital during the peak of the COVID-19 pandemic presented with more severe disease and experienced suboptimal outcomes compared to those who presented during the same time period in 2019. LEVEL OF EVIDENCE: III.

Development of pediatric surgical decision-making guidelines for COVID-19 in a New York City children's hospital.

OBJECTIVE: During the COVID-19 pandemic, experience-based guidelines are needed in the pediatric population in order to deliver high quality care in a new way that keeps patients and healthcare workers safe and maximizes hospital resource utilization. BACKGROUND: The COVID-19 pandemic has created an unprecedented strain on national health care resources, particularly in New York City, the epicenter of the outbreak in the United States. Prudent allocation of surgical resources during the pandemic quickly became essential, and there is an unprecedented need to weigh the risks of operating versus delaying intervention in our pediatric patients. METHODS: Here we describe our experience in surgical decision-making in the pediatric surgical population at Morgan Stanley Children's Hospital of New York-Presbyterian (MSCHONY), which has served as a major urban catchment area for COVID-19 positive pediatric patients. We describe how we have adjusted our current treatment of multiple facets of pediatric surgery including oncology, trauma, minimally invasive procedures, and extracorporeal membrane oxygenation (ECMO). CONCLUSIONS: Our pediatric surgery department had to creatively and expeditiously adjust our protocols, guidelines, and workforce to not only serve our pediatric population but merge ourselves with our adult hospital system during the COVID pandemic. TYPE OF STUDY: Clinical research paper LEVEL OF EVIDENCE: Level V.

Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation.

BACKGROUND: Despite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation. METHODS: From June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed. RESULTS: After a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance. CONCLUSIONS: Favorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.

High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele.

PURPOSE: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. METHODS: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm2) (n = 8), PMSC-ECM (167 K cells/cm2) (n = 7), or PMSC-ECM (250-300 K cells/cm2) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30-70 µm) were counted manually and density calculated per mm2 gray matter. RESULTS: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5-15]) than ECM alone (6.5 [IQR 4-12.75], p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm2) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250-300 K/cm2) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). CONCLUSIONS: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. TYPE OF STUDY: Basic science. LEVEL OF EVIDENCE: N/A.

Fetal Surgery for Myelomeningocele: A Systematic Review and Meta-Analysis of Outcomes in Fetoscopic versus Open Repair.

BACKGROUND/OBJECTIVES: The Management of Myelomeningocele (MMC) Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes but was associated with high rates of obstetrical complications. This study compares outcomes of open and fetoscopic MMC repair. DATA SOURCES: PubMed and Embase studies reporting outcomes of fetal MMC repair published since the completion of the MOMS. RESULTS: We analyzed 11 studies and found no difference in mortality or the rate of shunt placement for hydrocephalus. Percutaneous fetoscopic repair was associated with higher rates of premature rupture of membranes (91 vs. 36%, p < 0.01) and preterm birth (96 vs. 81%, p = 0.04) compared to open repair, whereas fetoscopic repair via maternal laparotomy reduced preterm birth. The rate of dehiscence and leakage from the MMC repair site was higher after both types of fetoscopic surgery (30 vs. 7%, p < 0.01), while the rate of uterine dehiscence was higher after open repair (11 vs. 0%, p < 0.01). DISCUSSION: Fetoscopic repair is a promising alternative to open fetal MMC repair with a lower risk of uterine dehiscence; however, fetoscopic techniques should be optimized to overcome the high rate of dehiscence and leakage at the MMC repair site. A fetoscopic approach via maternal laparotomy reduces the risk of preterm birth.

Lessons from the Barn to the Operating Suite: A Comprehensive Review of Animal Models for Fetal Surgery.

The International Fetal Medicine and Surgery Society was created in 1982 and proposed guidelines for fetal interventions that required demonstrations of the safety and feasibility of intended interventions in animal models prior to application in humans. Because of their short gestation and low cost, small animal models are useful in early investigation of fetal strategies. However, owing to the anatomic and physiologic differences between small animals and humans, repeated studies in large animal models are usually needed to facilitate translation to humans. Ovine (sheep) models have been used the most extensively to study the pathophysiology of congenital abnormalities and to develop techniques for fetal interventions. However, nonhuman primates have uterine and placental structures that most closely resemble those of humans. Thus, the nonhuman primate is the ideal model to develop surgical and anesthetic techniques that minimize obstetrical complications.

Subcutaneous local anesthetic infusion could eliminate use of epidural analgesia after the Nuss procedure.

AIM: To compare outcomes of continuous subcutaneous infusion of local anesthetic and epidural analgesia following the Nuss procedure. PATIENTS & METHODS: A retrospective chart review compared patients managed with subcutaneous local anesthetic infusion (n = 12) versus thoracic epidural (n = 19) following the Nuss procedure from March 2013 to June 2015. RESULTS: There was no difference in hospital length of stay or days on intravenous narcotics. Epidural catheter placement prolonged operating room time (146.58 ± 28.30 vs 121.42 ± 21.98 min, p = 0.01). Average pain scores were slightly higher in the subcutaneous infusion group (3.72 ± 1.62 vs 2.35 ± 0.95, p = 0.02), but of negligible clinical significance. CONCLUSION: Continuous subcutaneous infusion of local anesthetic could eliminate the need for thoracic epidural for pain management after the Nuss procedure.

Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele.

PURPOSE: The purpose of this study was to investigate the effects of placental mesenchymal stromal cells (PMSCs) seeded on a clinical grade porcine small intestinal submucosa (SIS)-derived extracellular matrix (ECM) on hindlimb motor function in an ovine fetal repair model of myelomeningocele (MMC). METHODS: MMC defects were surgically created in 21 fetuses at median gestational age 78 (range 76-83) days. Fetuses were randomly assigned to repair 25days later with ECM only or PMSC-ECM. Surviving fetuses were delivered at term. Motor function was evaluated using the Sheep Locomotor Rating (SLR) scale (0-15). Histologic analysis of the spinal cord (SC) was completed. RESULTS: Fetal viability was 71%. 5 of 8 (63%) lambs repaired with PMSC-ECM ambulated independently versus only 1 of 6 (17%) repaired with ECM only (p=0.04, χ2 test). SLR scores and large neuron densities were higher in the PMSC-ECM group. The cross-sectional areas of the SC and the gray matter were equally preserved. CONCLUSIONS: Fetal repair of MMC with PMSCs seeded on SIS-ECM improves hindlimb motor function in lambs. Using ECM helps to preserve the architecture of the SC, but adding PMSCs improves the lamb's ability to walk and increases large neuron density. Clinical studies are needed to show benefits in humans. LEVELS OF EVIDENCE/TYPE OF STUDY: Basic Science.

Fetal surgical repair with placenta-derived mesenchymal stromal cell engineered patch in a rodent model of myelomeningocele.

PURPOSE: The purpose of this study is to determine the feasibility of fetal surgical repair of myelomeningocele (MMC) in a rodent model using human placental mesenchymal stromal cells (PMSCs) seeded onto extracellular matrix (ECM) and to characterize the resulting changes in spinal cord tissue. METHODS: Fetal rodents with retinoic acid (RA) induced MMC underwent surgical repair of the MMC defect using an ECM patch on embryonic age (EA) 19 and were collected via caesarean section on EA 21. Various seeding densities of PMSC-ECM and ECM only controls were evaluated. Cross-sectional compression (width/height) and apoptotic cell density of the lumbosacral spinal cord were analyzed. RESULTS: 67 dams treated with 40mg/kg of RA resulted in 352 pups with MMC defects. 121 pups underwent MMC repair, and 105 (86.8%) survived to term. Unrepaired MMC pups had significantly greater cord compression and apoptotic cell density compared to normal non-MMC pups. Pups treated with PMSC-ECM had significantly less cord compression and demonstrated a trend towards decreased apoptotic cell density compared to pups treated with ECM only. CONCLUSION: Surgical repair of MMC with a PMSC-seeded ECM disc is feasible with a postoperative survival rate of 86.8%. Fetal rodents repaired with PMSC-ECM have significantly less cord deformity and decreased histological evidence of apoptosis compared to ECM only controls.

Isolation of myogenic progenitor cell population from human placenta: A pilot study.

PURPOSE: The purpose of this study was to demonstrate a method of isolating myogenic progenitor cells from human placenta chorionic villi and to confirm the myogenic characteristics of the isolated cells. METHODS: Cells were isolated from chorionic villi of a second trimester male placenta via a combined enzymatic digestion and explant culture. A morphologically distinct subpopulation of elongated and multinucleated cells was identified. This subpopulation was manually passaged from the explant culture, expanded, and analyzed by fluorescence in situ hybridization (FISH) assay, immunocytochemistry, and flow cytometry. Myogenic characteristics including alignment and fusion were tested by growing these cells on aligned polylactic acid microfibrous scaffold in a fusion media composed of 2% horse serum in Dulbecco's modified Eagle medium/high glucose. RESULTS: The expanded subpopulation was uniformly positive for integrin α-7. Presence of Y-chromosome by FISH analysis confirmed chorionic villus origin rather than maternal cell contamination. Isolated cells grew, aligned, and fused on the microfibrous scaffold, and they expressed myogenin, desmin, and MHC confirming their myogenic identity. CONCLUSION: Myogenic progenitor cells can be isolated from human chorionic villi. This opens the possibility for translational and clinical applications using autologous myogenic cells for possible engraftment in treatment of chest and abdominal wall defects.

New directions in fetal surgery for myelomeningocele.

The treatment of children with myelomeningocele (MMC) has improved over time, from supportive management to early postnatal closure to prenatal repair of the defect. The Management of Myelomeningocele Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes compared to postnatal closure. Follow-up studies showed that prenatal repair was, as with any other fetal intervention, associated with higher rates of obstetrical complications. There was no significant difference in urological outcomes. Long-term follow-up of ambulatory status, executive functioning, and urological outcomes is needed to determine the durable effects of fetal MMC repair on mobility, functional independence, and the prevalence of renal insufficiency in patients with MMC who survive to adulthood. The future of fetal MMC repair consists of developing strategies to reduce maternal morbidity and improve infant outcomes. Fetoscopic MMC repair has been suggested as an alternative to open repair that may reduce obstetrical complications and the need for cesarean delivery in subsequent pregnancies. Translational research using mesenchymal stromal cells to augment fetal repair of ovine MMC has shown improvement in motor function.

Effect of 2-octylcyanoacrylate on placenta derived mesenchymal stromal cells on extracellular matrix.

PURPOSE: Determine the effect of 2-octylcyanoacrylate on placenta derived mesenchymal stromal cells (PMSCs) seeded onto extracellular matrix (ECM) in order to assess its biocompatibility as a potential adhesive for in-vivo fetal cell delivery. METHODS: PMSCs isolated from chorionic villus tissue were seeded onto ECM. A MTS proliferation assay assessed cellular metabolic activity at various time points in PMSC-ECM with direct, indirect, and no glue contact. Conditioned media collected prior to and 24 hours after glue exposure was analyzed for secretion of human brain-derived neurotrophic factor, hepatocyte growth factor, and vascular endothelial growth factor. RESULTS: Direct and indirect contact with 2-octylcyanoacrylate results in progressively decreased cellular metabolic activity over 24 hours compared to no glue controls. Cells with direct contact are less metabolically active than cells with indirect contact. 24 hours of glue exposure resulted in suppression of growth factor secretion that is near complete with direct contact. DISCUSSION: Exposure to 2-octylcyanoacrylate results in decreased metabolic activity and decreased measurable secretion of growth factors by PMSCs seeded onto ECM. Thus, the application of 2-octylcyanoacrylate glue should be limited when working with cell-engineered scaffolds as its inhibitory effects on cell growth and secretory function can limit the therapeutic potential of cell-based interventions.

Fetal surgery for myelomeningocele: current clinical practice and translational research.

INTRODUCTION: The Management of Myelomeningocele Study (MOMS) showed that prenatal repair of myelomeningocele (MMC) resulted in better neurological outcomes than postnatal closure but was, by necessity, associated with higher rates of obstetrical complications. Fetoscopic MMC repair has been explored as an alternative to reduce complications of the open approach used in MOMS. This review summarizes the trends in fetoscopic and open fetal repair of MMC. EVIDENCE ACQUISITION: We searched PubMed and Embase® for studies on fetal repair of MMC published since the completion of the MOMS trial. EVIDENCE SYNTHESIS: Fetoscopic MMC repair was temporarily halted in the United States (US) prior to the initiation of the MOMS trial. The German Center for Fetal Surgery has reported the largest series of fetoscopic MMC repair. The other largest series is the Brazilian Cirurgia Endoscopica para Correcao Antenatal da Meningomielocele (CECAM) trial. Both groups demonstrate the feasibility of minimally invasive fetal MMC repair, but also report high rates of premature rupture of membranes, preterm births, and persistent cerebrospinal fluid (CSF) leakage that requires postnatal revision of the MMC repair. In addition, these groups have yet to report long term cognitive, behavioral, and functional outcomes of fetoscopic MMC repair. CONCLUSIONS: The fetoscopic approach to fetal MMC repair is a promising alternative to the open approach if preterm birth and persistent CSF leakage can be overcome.