Dysregulation of miRNA-mRNA expression in fetal growth restriction in a caloric restricted mouse model.

Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA-mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.

The Effect of Steroids on Prenatally Diagnosed Lung Lesions.

BACKGROUND: Open fetal resection for large lung lesions has virtually been replaced by maternal steroid administration. Despite this paradigm shift, little is known about the effects steroids have on lung lesion growth in utero. METHODS: A 10-year retrospective review of all prenatally diagnosed lung lesions cared for at our fetal care center was performed. We evaluated the effects of prenatal steroids on congenital pulmonary airway malformation (CPAM)-volume-ratio (CVR), distinguishing change in CVR among CPAMs, bronchopulmonary sequestrations (BPS), and bronchial atresias. We also correlated fetal ultrasound and MRI findings with pathology to determine the accuracy of prenatal diagnosis. RESULTS: We evaluated 199 fetuses with a prenatal lung lesion. Fifty-four (27 %) were treated with prenatal steroids with a subsequent 21 % mean reduction in the CVR (2.1 ± 1.4 to 1.1 ± 0.4, p = 0.003). Fetuses with hydrops and mediastinal shift who were treated with steroids rarely had resolution of these radiographic findings. Postnatal pathology was available for 91/199 patients (45.7 %). The most common diagnosis was CPAM (42/91, 46 %), followed by BPS (30/91, 33 %), and bronchial atresia (14/91, 15 %). Fetuses who received steroids and had pathology consistent with CPAM were more likely to have a reduction in their CVR (p = 0.02). Fetal ultrasound correctly diagnosed the type of lung lesion in 75 % of cases and fetal MRI in 81 % of cases. CONCLUSIONS: Prenatally diagnosed CPAMs are more likely to respond to maternal steroids than BPS or bronchial atresias. Knowing the diagnosis in utero could aid to steward steroid usage, however, fetal imagining modalities are not perfect in distinguishing subtype. LEVEL OF EVIDENCE: III.

Surgical Necrotizing Enterocolitis - Can We Predict the Need for Gastrostomy Tube Placement?

INTRODUCTION: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement. METHODS: A single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed. RESULTS: Eighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. CONCLUSIONS: GT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.

Muscle Flap Technique Safe for On-ECMO Congenital Diaphragmatic Hernia Repair.

INTRODUCTION: Prosthetic patches (patch) and muscle flaps (flap) are techniques used for repair of congenital diaphragmatic hernia (CDH) with a large defect unamenable to primary closure. We hypothesized that the flap technique for CDH repair while on extra-corporeal membrane oxygenation (on-ECMO) would have decreased bleeding complications compared to patch due to the hemostatic advantage of native tissue. METHODS: A single-center retrospective comparative study of patients who underwent on-ECMO CDH repair between 2008 and 2022 was performed. RESULTS: Fifty-two patients met inclusion criteria: 18 patch (34.6%) and 34 flap (65.4%). There was no difference in CDH severity between groups. On univariate analysis, reoperation for surgical bleeding was lower following flap repair compared to patch (23.5% vs 55.6%, respectively; p = 0.045), 48-h postoperative blood product transfusion was lower after flap repair (132 mL/kg vs 273.5 mL/kg patch; p = 0.006), and two-year survival was increased in the flap repair group compared to patch (53.1% vs 17.7%, respectively; p = 0.036). On multivariate analysis adjusting for CDH side, day on ECMO repaired, and day of life CDH repaired, flap repair was significantly associated with lower five-day postoperative packed red blood cell transfusion amount, improved survival to hospital discharge, and improved two-year survival. CONCLUSIONS: Our experience suggests that the muscle flap technique for on-ECMO CDH repair is associated with reduced bleeding complications compared to prosthetic patch repair, which may in part be responsible for the improved survival seen in the flap repair group. These results support the flap repair technique as a favored method for on-ECMO CDH repair. LEVEL OF EVIDENCE: Level III.

Trainee educational curriculum to standardize central venous catheter repair.

INTRODUCTION: Children may require durable central venous catheters (CVCs) for various reasons. CVC-related integrity complications are common and can often be repaired at the bedside to increase lifetime. Variability in repair techniques can lead to complications, including the need for repeat repair and Central Line Associated Blood Stream Infection (CLABSI). METHODS: The impact of an educational curriculum to standardize tunneled CVC repairs for trainees on a pediatric surgery service was studied, focusing on comfort level with tunneled CVC repair and to determine the impact on complication rates. Rotating trainees studied a dedicated audiovisual educational curriculum comprised of a video, educational slides, and a practical component from November 2020 through January 2022. Experience and comfort level with tunneled CVC repairs were assessed before and after the rotation. CVCs repaired during the duration of the study were evaluated and compared to the period prior. RESULTS: Forty-nine individuals completed the pre- and post-training survey. Respondents (34.7%, n = 17) most commonly reported one year of surgical experience, and (79.6%, n = 39) had never observed or assisted in a repair previously. Following training, respondents felt more comfortable with all aspects of the CVC repair process (p < 0.001). There were no statistically significant differences in re-repair rates or CLABSI rates following the implementation of the curriculum. CONCLUSIONS: Tunneled CVC procedural repair variability can be standardized with a dedicated educational curriculum for rotating trainees, which improves knowledge and comfort with such procedures.

Angiogenic and Inflammatory microRNA Regulation in a Mouse Model of Fetal Growth Restriction.

INTRODUCTION: Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis. METHODS: Pregnant mice were provided ad libitum access to food between E1 and E8. From E9-E18, dams received either a 50% caloric restricted diet (FGR) or continued ad libitum access (controls). Placentas were harvested at E18.5 and total RNA was extracted. Gene expression levels of miRs and mRNAs were compared between FGR and control placentas. RESULTS: Placentas affected by FGR demonstrated increased expression of miR-15b. Vascular endothelial growth factor alpha, which is downregulated in response to increased levels of miR-15b, was suppressed. The anti-inflammatory miR, miR-146a, was downregulated, resulting in upregulation of proinflammatory (IL-6, IL-8, and NFkB1) and oxidative stress (HIF-1α, SOD2, and Nox2) mediators. CONCLUSIONS: Aberrant angiogenesis and chronic inflammation seen in FGR appear to be associated with dysregulated miR-15b and miR-146a gene expression, respectively. This observation suggests these miRs play a post-transcriptional regulatory role in FGR, providing an insight into possible therapeutic targets.

Evaluation and Management of Primary Spontaneous Pneumothorax in Adolescents and Young Adults: A Systematic Review From the APSA Outcomes & Evidence-Based Practice Committee.

INTRODUCTION: Controversy exists in the optimal management of adolescent and young adult primary spontaneous pneumothorax. The American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL, Elsevier Scopus, and Wiley Cochrane Central Register of Controlled Trials databases were queried for literature related to spontaneous pneumothorax between January 1, 1990, and December 31, 2020, addressing (1) initial management, (2) advanced imaging, (3) timing of surgery, (4) operative technique, (5) management of contralateral side, and (6) management of recurrence. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Seventy-nine manuscripts were included. Initial management of adolescent and young adult primary spontaneous pneumothorax should be guided by symptoms and can include observation, aspiration, or tube thoracostomy. There is no evidence of benefit for cross-sectional imaging. Patients with ongoing air leak may benefit from early operative intervention within 24-48 h. A video-assisted thoracoscopic surgery (VATS) approach with stapled blebectomy and pleural procedure should be considered. There is no evidence to support prophylactic management of the contralateral side. Recurrence after VATS can be treated with repeat VATS with intensification of pleural treatment. CONCLUSIONS: The management of adolescent and young adult primary spontaneous pneumothorax is varied. Best practices exist to optimize some aspects of care. Further prospective studies are needed to better determine optimal timing of operative intervention, the most effective operation, and management of recurrence after observation, tube thoracostomy, or operative intervention. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Systematic Review of Level 1-4 studies.

Early outcomes of a myofascial repair technique for fetal myelomeningocele.

PURPOSE: Fetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic outcomes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP. METHODS: A single-center retrospective study of patients who underwent fetal MMC or myeloschisis repair between March 2013 and February 2022 was performed. Outcomes were evaluated (n = 70 prior to July 2019, n = 34 after July 2019). Statistical significance was determined by Fisher's exact and Chi square tests (p < 0.05 significant). RESULTS: Patients who underwent myofascial closure were less likely to require a patch for skin closure (14.7% vs 58.6%, p < 0.0001). Myofascial closure was also associated with an increased rate of HBH improvement on two-week postoperative fetal MRI (93.9% vs 65.7%, p = 0.002). Surgically-treated HCP at one year was lower in the myofascial closure group (n = 21), however this did not reach statistical significance (23.8% vs 41.9%, p = 0.19). CONCLUSIONS: We conclude that the myofascial closure technique for repair of fetal MMC and myeloschisis is associated with significantly decreased need for patch closure and improvement in hindbrain herniation compared to our previous skin closure technique. These results support a surgical approach that employs a multilayer watertight closure.

The effect of single ventricle congenital heart disease on recurrence risk of pneumatosis intestinalis in neonates.

PURPOSE: Congenital heart disease (CHD) is a risk factor for the development of pneumatosis intestinalis (PI). Patients with single ventricle physiology (SVP) may be at higher risk of developing PI secondary to variations in systemic blood flow which affect bowel perfusion when compared to patients with biventricular physiology (BVP). We hypothesized that patients with SVP would have increased risk of recurrent PI. METHODS: A retrospective review was done from 10/2014 through 05/2020 with patients that met the following criteria: CHD, radiographic evidence of PI, and less than 1 year of age. Groups were divided based on ventricular physiology. Primary outcome was radiographic recurrence of PI and secondary outcomes were average antibiotic duration, NPO duration, median length of stay, need for GI operation, and death from PI. RESULTS: A total of 51 patients were included, 34 with SVP and 17 with BVP. 26.47% of SVP had recurrence of PI whereas no BVP experienced a recurrence of PI. There was no significant difference in any of the secondary outcomes. CONCLUSION: Our data suggest that patients with SVP are more likely to have recurrence of radiographic PI. We may need to consider patients with SVP that get PI as their own separate group.

Adolescent blunt solid organ injury: Differences in management strategies and outcomes between pediatric and adult trauma centers.

BACKGROUND: Adolescents with blunt solid organ injuries (BSOI) are cared for at both pediatric trauma centers (PTC) and adult trauma centers (ATC). Over the past decade, treatment strategies have shifted towards non-operative management with reported favorable outcomes. The aim of this study was to compare management strategies and outcomes between PTC and ATC. METHODS: We queried the 2016-2018 Trauma Quality Improvement Program (TQIP) datasets to identify adolescents between the ages of 16 and 19 with BSOI. Characteristics were stratified by center type (pediatric or adult) for comparative analyses. Separate logistic regressions were used to assess the association of hospital type, location of injury, age, gender, weight, Glascow Coma Score (GCS), Injury Severity Score (ISS), and intensive care unit (ICU) admissions for outcomes of interest. RESULTS: Among the 3,011,310 patients enrolled in the 2016-2018 TQIP datasets, 106,892 (3.5%) had a BSOI ICD9/10 code. Of those, 9,193 (8.6%) were between 16 and 19 years of age and included in this analysis. Within this cohort, 6,073 (66.1%) were managed at an ATC and 3,120 (33.9%) were managed at a PTC. While statistically different, there were no clinically relevant differences for age, weight, and sex between groups. A significantly higher ISS and lower GCS score were observed among those admitted to ATC compared to PTC. ICU admissions were more frequent at ATC. Number of blood transfusions by 4 h after presentation were also higher among those admitted to an ATC. Despite a lower ISS and higher GCS at presentation, mortality was higher among those treated at a PTC with an odds ratio (95% confidence interval) of 2.42 (1.31-4.53). After excluding adolescents with a traumatic brain injury, a common cause of mortality among adolescent trauma patients, these differences in outcomes persisted. CONCLUSIONS: Our data suggest that adolescents with BSOI managed at a PTC are less likely to receive blood transfusions by 4 h of admission or be admitted to the ICU than those managed at an ATC. However, this more conservative approach may come at the expense of higher overall mortality. Further work is needed to understand these differences and determine if PTC need to be more aggressive in managing BSOI.

The pediatric surgery match from the applicant perspective.

BACKGROUND: Previous studies have examined characteristics critical to make a successful applicant in the pediatric surgery match. No previous study has focused on what applicants consider important as they interview pediatric surgery training programs. STUDY DESIGN: Successfully matched applicants to our training program from 2018 to 2020 were identified and a 49-question survey sent electronically. In addition to a descriptive analysis of responses, comparisons between those who matched into one of their top three programs and those who matched outside of their top three programs were made. A Likert scale was used and data are reported as mean (95% confidence intervals). RESULTS: One hundred and thirty individuals were surveyed. Sixty-three (48%) responded. The most important characteristics identified were total index case volume 1.94 (1.87, 2.00), interactions with faculty on the interview day 1.84 (1.74, 1.94), neonatal case volume 1.75 (1.61, 1.88) and degree of autonomy 1.63 (1.50, 1.77). Respondents also placed a high importance on the in-person interview experience 1.63 (1.49, 1.77). The least important training program characteristics were quantity of vacation time -0.24 (-0.52, 0.05), opportunity to participate in medical mission trips -0.25 (-0.54, 0.06), paid accommodation at the interview -0.29 (-0.57, 0.00), and access to a simulation laboratory -0.51 (-0.78, -0.24). CONCLUSION: Clinical volume, neonatal volume, faulty interactions and the experience on the interview day are the most important characteristics to applicants. There were few, if any, characteristics applicants felt were truly unimportant as they weighed their rank lists. Applicants also placed a high level of importance on an in-person interview LEVEL OF EVIDENCE: Level IV.

Torsed ectopic intra-abdominal liver rest within an adolescent female.

Extrahepatic liver (EL) rests are rare, with a reported annual incidence of 0.24-0.47. While reports often note EL incidentally found on pathologic specimens of aberrant tissue, there has been a case report of hepatocellular carcinoma arising from one of these rests, highlighting the importance of surgical resection. EL has been reported to cause symptoms such as abdominal pain, intraperitoneal bleeding and compression of adjacent organs. Most commonly, it has been identified in the gallbladder, likely due to proximity of the gallbladder to the native liver. The paucity of diagnostic tests makes the preoperative diagnosis challenging. We present a case of a 12-year-old female presenting with severe epigastric pain secondary to incapsulated EL tissue attached to the stomach via a narrow stalk. By describing this case, we hope to improve the diagnosis and management of abdominal masses with unclear etiology.

In-utero gastric perforation from combined duodenal and esophageal atresia without consistent polyhydramnios.

We present a case in which prenatal imaging at 21-weeks' gestation suggested duodenal atresia with a double-bubble sign and enlarged stomach. Fetal magnetic resonance imaging findings demonstrated dilation of the stomach and proximal duodenum favoring duodenal atresia but no indications of esophageal atresia. Subsequent prenatal imaging demonstrated interval spontaneous decompression of the stomach without the development of polyhydramnios, obscuring the diagnosis. Postnatally, initial abdominal radiography showed a gasless abdomen, and an oral gastric tube could not pass the mid-esophagus, raising concern for pure esophageal atresia. Intraoperative findings were consistent with duodenal atresia, pure esophageal atresia and a gastric perforation due to a closed obstruction. In this case report, we review the prenatal diagnostic challenges and the limited literature pertaining to this unique pathology.

Influence of Weight Loss on Obesity-Associated Complications After Metabolic and Bariatric Surgery in Adolescents.

OBJECTIVE: Following metabolic and bariatric surgery (MBS), most adolescents experience weight loss and improvement of many obesity-associated complications (OACs). The relationship between weight loss and remission of OACs after MBS in adolescents has not been well described. METHODS: The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) is a multi-institutional prospective observational study of adolescents who underwent MBS between 2007 and 2012. Lower-weight-loss responders (LWLRs) were defined as having <20% total body weight loss (TBWL) and higher-weight-loss responders (HWLRs) were defined as having ≥20% TBWL at 5 years after MBS. The prevalence of OACs was compared at baseline and 5 years after MBS. RESULTS: Both LWLRs (n = 114) and HWLRs (n = 78) lost significant weight within the first year following MBS; however, the TBWL at 5 years for the LWLRs was 8.6% ± 9.5% compared with 33.8% ± 9.2% for the HWLRs. Those in the HWLR group were more likely to experience durable remission of composite dyslipidemia at 5 years, whereas there were no differences between groups in remission rates of all other OACs. CONCLUSIONS: Greater weight loss after MBS in adolescents was associated with greater remission of composite dyslipidemia; however, remission of other OACs was not dependent on major sustained weight loss.

Severe SARS-CoV-2 Infection in a Pediatric Patient Requiring Extracorporeal Membrane Oxygenation.

The overwhelming majority of pediatric cases of SARS-CoV-2 infection are mild or asymptomatic with only a handful of pediatric deaths reported. We present a case of severe COVID-19 infection in a pediatric patient with signs of hyperinflammation and consumptive coagulopathy requiring intubation and extracorporeal membrane oxygenation (ECMO) and eventual death due to ECMO complications.

Excess skin problems among adolescents after bariatric surgery.

BACKGROUND: Bariatric surgery results in significant and durable weight loss and improved health in severely obese adolescents. An important adverse consequence of the massive weight loss after bariatric surgery is excess skin and soft tissue. The prevalence and clinical characteristics of excess skin-related symptoms have been described in adults undergoing bariatric surgery but not in adolescents. Although the higher skin elasticity of adolescents may result in fewer excess skin problems compared with adults, this hypothesis remains untested. OBJECTIVES: The purpose of the present study was to describe the natural history of excess skin and its associated complications among severely obese adolescents undergoing bariatric surgery. SETTING: University Hospitals, United States. METHODS: We evaluated data from the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective, multiinstitutional study of adolescents (13-19 yr) undergoing bariatric surgery. Abdominal pannus severity (graded 0-5) and excess skin symptoms were evaluated preoperatively and for the first 5 years after bariatric surgery. RESULTS: Among the 217 study participants, 198 (90%) had an abdominal pannus and 16 (7%) reported pannus-related symptoms at the time of bariatric surgery. Preoperative symptoms included intertriginous infections (n = 12, 75%), recurrent cellulitis (n = 5, 31%), and superficial cutaneous ulcerations (n = 1, 6%). Participants with a higher pannus grade preoperatively experienced both a greater reduction in pannus severity (P < .0001) and a higher incidence of pannus-related symptoms (P = .002) postoperatively. Changes in pannus severity occurred during the first 24 months after bariatric surgery; mean pannus severity remained unchanged beyond 24 months. CONCLUSIONS: Severely obese adolescents who undergo bariatric surgery often present with an abdominal pannus at the time of surgery with associated symptoms. Higher preoperative pannus grade is associated with more pannus related symptoms after surgery. Counseling about need for body contouring surgery should be considered in this group.

Enhanced recovery after surgery among adolescents undergoing bariatric surgery.

Enhanced recovery after surgery (ERAS) has evolved over the past two decades. Originally aimed to standardize care among adults undergoing colorectal surgery, the tenets that developed have since been broadly accepted by a large number of adult surgical subspecialties, including bariatric surgery. This multidisciplinary, patient-centered approach involving optimizing pre-, intra-, and postoperative phases of care has resulted in shorter hospitalizations, fewer complications, and lower mortality rates. Recently, multiple pediatric surgery subspecialties have adopted ERAS principles and have documented similar favorable outcomes. Among adolescent bariatric patients, outcomes following the implementation of ERAS have not yet been described. We will review the history and goals of ERAS and detail pediatric surgery specific implementations. We will also review outcomes associated with ERAS within specific pediatric surgical subspecialties. Lastly, we will discuss the current ERAS protocol developed at Children's Hospital Colorado for adolescent bariatric surgery.