Systemic in utero gene editing as a treatment for cystic fibrosis.

In utero gene editing has the potential to modify disease causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. In cystic fibrosis (CF), a disease that arises from mutations in the cystic fibrosis transmembrane conductance regulator ( ) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage.

Evaluating Operative Exposure for Medical Students in the Era of Virtual Learning: A Single-Institution Experience.

Introduction: Training at a tertiary center offers clerkship students the opportunity to rotate through a wide range of surgical specialties that may not be otherwise available. At our institution, students rotate through general surgery for 3 out of 9 weeks, with the remainder offering electives. As a result, students may have limited experience with core general surgery cases which are necessary to complete by the end of the clerkship to demonstrate competency.

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations.

Ovarian Leydig Cell Tumor Associated with Recurrent Torsion and Virilization in an Adolescent Patient.

Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less than 0.1% of all ovarian tumors across all ages.

delivery of miRNA induces epigenetic alterations and corrects pulmonary pathology in congenital diaphragmatic hernia.

Structural fetal diseases, such as congenital diaphragmatic hernia (CDH) can be diagnosed prenatally. Neonates with CDH are healthy as gas exchange is managed by the placenta, but impaired lung function results in critical illness from the time a baby takes its first breath. MicroRNA (miR) 200b and its downstream targets in the TGF-β pathway are critically involved in lung branching morphogenesis.

Intra-amniotic Injection of Poly(lactic-co-glycolic Acid) Microparticles Loaded with Growth Factor: Effect on Tissue Coverage and Cellular Apoptosis in the Rat Model of Myelomeningocele.

Background: Myelomeningocele (MMC) is a devastating congenital neurologic disorder that can lead to lifelong morbidity and has limited treatment options. This study investigates the use of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) loaded with fibroblast growth factor (FGF) as a platform for in utero treatment of MMC.

Study Design: Intra-amniotic injections of PLGA MPs were performed on gestational day 17 (E17) in all-trans retinoic acid-induced MMC rat dams.

Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells.

Background: Advances in Molecular Therapy have made gene editing through systemic or topical administration of reagents a feasible strategy to treat genetic diseases in a rational manner. Encapsulation of therapeutic agents in nanoparticles can improve intracellular delivery of therapeutic agents, provided that the nanoparticles are efficiently taken up within the target cells. In prior work we had established proof-of-principle that nanoparticles carrying gene editing reagents can mediate site-specific gene editing in fetal and adult animals in vivo that results in functional disease improvement in rodent models of β-thalassemia and cystic fibrosis.

Firework-related injuries treated at emergency departments in the United States during the COVID-19 pandemic in 2020 compared to 2018-2019.

Background: Despite a national decrease in emergency department visits in the United States during the first 10 months of the pandemic, preliminary Consumer Product Safety Commission data indicate increased firework-related injuries. We hypothesized an increase in firework-related injuries during 2020 compared to years prior related to a corresponding increase in consumer firework sales.

Methods: The National Electronic Injury Surveillance System (NEISS) was queried from 2018 to 2020 for cases with product codes 1313 (firework injury) and narratives containing "fireworks".

Institutional Variation in Gastrostomy Tube Placement After Duodenal Atresia Repair in Children With Trisomy 21.

Objectives: To compare institutional practice patterns for gastrostomy tube placement in neonates with duodenal atresia (DA) and trisomy 21.

Methods: A retrospective review of the Pediatric Health Information System (PHIS) from 2015 to 2018 identified infants <10 days old with ICD-10 diagnostic codes for DA and trisomy 21, in addition to procedure codes for an intestinal bypass or duodenoduodenostomy. This cohort was then queried for gastrostomy tube procedure codes and diagnostic codes for associated co-morbidities.

Diffusion weighted imaging as a biomarker of retinoic acid induced myelomeningocele.

Neural tube defects are a common congenital anomaly involving incomplete closure of the spinal cord. Myelomeningocele (MMC) is a severe form in which there is complete exposure of neural tissue with a lack of skin, soft tissue, or bony covering to protect the spinal cord. The all-trans retinoic acid (ATRA) induced rat model of (MMC) is a reproducible, cost-effective means of studying this disease; however, there are limited modalities to objectively quantify disease severity, or potential benefits from experimental therapies.

A narrative review of in utero gene therapy: advances, challenges, and future considerations.

The field of gene therapy (IUGT) represents a crossroad of technologic advancements and medical ethical boundaries. Several strategies have been developed for IUGT focusing on either modifying endogenous genes, replacing missing genes, or modifying gene transcription products. The list of candidate diseases such as hemoglobinopathies, cystic fibrosis, lysosomal storage disorders continues to grow with new strategies being developed as our understanding of their respective underlying molecular pathogenesis increases.

Engineering alginate microparticles for optimized accumulation in fetal rat myelomeningocele.

Introduction: Intraamniotic microparticle injection is a novel technique for the treatment of myelomeningocele (MMC) in which microparticles are delivered in-utero in a minimally invasive fashion to bind to and protect the exposed spinal cord. This technique could offer earlier intervention and greater access to prenatal treatment of MMC. Here we demonstrate progress on the engineering of the microparticles to promote binding to the MMC defect.

The parental journey of fetal care: a systematic review and metasynthesis.

Objective: This study aimed to synthesize the qualitative literature on parental experiences of fetal care to reflect events that happened across the continuum of care and to better understand parents' positive and negative experiences with care delivery.

Data Sources: Eligible studies published until June 2020 were retrieved from MEDLINE, Embase, Cochrane Central Register of Controlled Trials, EBSCO CINAHL, Web of Science, and ProQuest.

Study Eligibility Criteria: Studies must have been: (1) published in English in a peer-reviewed journal or in ProQuest, (2) available in full text, (3) contained a qualitative component, and (4) focused on expectant parents' experiences of tertiary, coordinated, multidisciplinary prenatal diagnosis and care related to a fetal anomaly.

Nanoparticles for delivery of agents to fetal lungs.

Fetal treatment of congenital lung disease, such as cystic fibrosis, surfactant protein syndromes, and congenital diaphragmatic hernia, has been made possible by improvements in prenatal diagnostic and interventional technology. Delivery of therapeutic agents to fetal lungs in nanoparticles improves cellular uptake. The efficacy and safety of nanoparticle-based fetal lung therapy depends on targeting of necessary cell populations.

Outcomes following adoption of a standardized protocol for abscess drain management in pediatric appendicitis.

Background/purpose: Though evidence-based clinical pathways for the diagnosis and treatment of pediatric appendicitis have been established, protocols guiding management of percutaneous abscess drains are lacking. We hypothesized a drain management protocol utilizing drain output and clinical factors instead of fluoroscopic drain studies would reduce interventional radiologic procedures without adversely impacting clinical outcomes.

Methods: A standardized protocol was uniformly adopted at a tertiary-care children's hospital in April 2016.

The in-utero diagnosis of choledochal cyst: can postnatal imaging predict benefit from early surgical intervention?

Background: Infants prenatally suspected of having a choledochal cyst (CDC) typically undergo ultrasound imaging shortly after birth. This study sought to evaluate features on the initial postnatal ultrasound (IPU) that could identify newborns at risk for early complications.

Methods: Following IRB approval, patients from four US fetal centers with prenatal suspicion for CDC and postnatal imaging from 2000 to 2017 were reviewed.

An Evidence-Based Guideline Supporting Restricted Opioid Prescription after Pediatric Appendectomy.

Background/purpose: Surgeon overprescription of opioids is a modifiable contributor to the opioid epidemic. No clear guidelines exist for prescribing opioids to younger patients after surgery. We sought to determine postoperative opioid needs in pediatric/young adult patients after laparoscopic appendectomy.

Multicenter retrospective comparison of spontaneous intestinal perforation outcomes between primary peritoneal drain and primary laparotomy.

Purpose: The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy.

Methods: We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy.

Opioid Prescribing Habits of General Versus Pediatric Surgeons After Uncomplicated Laparoscopic Appendectomy.

Background: Adolescents who use prescription opioids have an increased risk for future drug abuse and overdose, making them a high-risk population. Appendectomy is one of the most common surgical procedures in this age group, often requires opioid analgesia, and is performed by both pediatric and general surgeons. Prescription patterns comparing these two provider groups have not yet been evaluated; we hypothesize that general surgery providers prescribe more opioids for adolescent and young adult patients than do pediatric surgery providers.

Utility of Fetal Cardiac Axis and Cardiac Position Assessment in Predicting Neonatal Respiratory Morbidity in Fetal Congenital Lung Lesions.

Objectives: To assess the diagnostic performance of the fetal cardiac axis (CA) and/or cardiac position (CP) versus the congenital pulmonary malformation volume ratio (CVR) in predicting any and severe neonatal respiratory morbidity in fetal congenital lung lesions.

Methods: This work was an 11-year retrospective cohort study. The sensitivity, specificity, positive predictive value, and negative predictive value of CA and/or CP assessment in prediction of respiratory morbidity were calculated before 24 weeks' gestation and between 24 and 32 weeks and compared to CVR cutoffs obtained from the literature.

Routine postnatal chest x-ray and intensive care admission are unnecessary for a majority of infants with congenital lung malformations.

Background: Postnatal evaluation of prenatally identified congenital lung malformations (CLMs) often includes a chest x-ray (CXR) and neonatal intensive care unit (NICU) admission for observation. With current efforts aimed at prioritizing value and resource utilization, we sought to assess the utility of this practice in infants with known CLMs. We hypothesized that CXR and NICU admission are overused and could be deferred in the majority of cases.

Alginate microparticles loaded with basic fibroblast growth factor induce tissue coverage in a rat model of myelomeningocele.

Background/purpose: We sought to develop a minimally invasive intra-amniotic therapy for prenatal treatment of myelomeningocele (MMC) in an established rat model.

Methods: Time-dated pregnant rats were gavage-fed retinoic acid to induce MMC. Groups received intraamniotic injections at E17.

In utero nanoparticle delivery for site-specific genome editing.

Genetic diseases can be diagnosed early during pregnancy, but many monogenic disorders continue to cause considerable neonatal and pediatric morbidity and mortality. Early intervention through intrauterine gene editing, however, could correct the genetic defect, potentially allowing for normal organ development, functional disease improvement, or cure. Here we demonstrate safe intravenous and intra-amniotic administration of polymeric nanoparticles to fetal mouse tissues at selected gestational ages with no effect on survival or postnatal growth.

Repair of a mycotic abdominal aortic aneurysm in a neonate using an everted jugular vein patch.

A 43-day-old boy presented with bacteremia after umbilical artery catheterization. Duplex ultrasound examination revealed a 1.1- × 1.