Introduction: The COVID-19 pandemic led to perceived increases in the rates of complicated appendicitis. Multiple studies have shown, both in adults and children, higher rates of complicated appendicitis among patients with Medicaid insurance. At our institution, we previously found that, contrary to statewide and nationwide findings, no differences in complicated appendicitis rates existed based on age, sex, race, insurance status, socioeconomic status, and income level. The purpose of this study was to determine if the COVID-19 pandemic altered our previous findings. Methods: The electronic medical record of a large tertiary children’s hospital was queried for all patients with ICD 10 appendicitis codes from 1/1/2017-12/31/2020. Patient records were reviewed to determine complicated (defined as having either a hole in the appendix, extraluminal fecalith, well-formed abscess, or frank stool in the abdomen) vs. uncomplicated appendicitis. Demographic information including age, sex, race, ethnicity, and insurance type were collected. Rates of complicated appendicitis were compared across years. Correlation between rates of complicated appendicitis and demographic variables was determined both within and across years. Results: The rate of complicated appendicitis was not significantly different across years from 2017-2020. There was no significant difference in the rate of complicated appendicitis based on age, sex, race, ethnicity, or insurance type. Conclusion: While some U.S. centers and those abroad found a significantly higher rate of complicated appendicitis in 2020 compared to prior years, the rate of complicated appendicitis at a large tertiary children’s hospital did not change during the pandemic. No disparities exist based on age, sex, race, ethnicity, or insurance type.

Introduction: Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients are often reliant on pulmonary and sys-temic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population.Methods: We utilized International Classification of Diseases (ICD) codes to identify high risk congenital cardiac disease patients <= 6 mo of age, cared for at a tertiary children's hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmo-nary vasodilators, systemic vasodilators) was compared to controls in a multivariate analysis.Results: Of the 352 patients, who met inclusion criteria, 77.6% had ductal dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 37.5% received other vasodilatory drugs. The overall NEC rate was 15.1%. On univariate analysis, DD-S, iNO use, and systemic va-sodilators was associated with a significantly higher risk of NEC, while DD-P was associ-ated with lower NEC risk. On multivariate analysis, only iNO (odds ratio 2.725, confidence interval [1.36-5.44]) and DD-S (odds ratio 2.279, confidence interval [1.02-5.11]) were inde-pendent risk factors for NEC.Conclusions: In patients with at-risk congenital cardiac disease lesions, a ductus dependent systemic circulation or iNO treatment is associated with an increased risk of developing NEC. The presence of iNO or DD-S should be utilized as markers of increased risk both in the prevention and workup of suspected NEC.(c) 2023 Elsevier Inc. All rights reserved.

Introduction: We compared strategy outcomes and financial impact over the first two years of life (F2YOL) for patients with giant omphaloceles undergoing early repair (ER) (primary or staged) versus delayed repair (DR). Methods: A retrospective review of giant omphaloceles (fascial defect > 5 cm/> 50% liver herniation) at a tertiary children's hospital between 1/1/2010 and 12/31/2019 was performed. Survival, length of stay, age at repair, ventilation days (VD), time to full enteral feeds, readmissions during the F2YOL, incidence of major associated anomalies, and total hospitalization charges during the F2YOL were compared. A subanalysis removing potential confounders and only including patients who underwent fascial closure within the F2YOL was also conducted. Results: Thirty four giant omphaloceles (23DR and 11ER) were identified. The median age (days) at repair was 289 [148, 399] DR versus 10 [5, 21] ER, P < 0.001. Total cohort two-year survival was significantly higher in the DR group (95.7% versus 63.6%, P = 0.03). Including patients with a tracheostomy there was no significant difference in VD during the index hospitalization. Excluding tracheostomy patients, the DR group had significantly fewer VD during the index hospitalization, 15 [0, 15] versus 18 [10, 54], P = 0.02 and over the F2YOL 6.5 [ 0, 21] versus 18 [14, 43], P = 0.03. There were no significant differences in the incidence/ type of major associated anomalies, time to full enteral feeds, index length of stay, total hospital days, total admissions, or associated hospital charges. On subanalysis, there was no significant difference in VD or survival at any time. Conclusions: Delayed and early repair strategies for giant omphaloceles have equivalent outcomes in the index hospitalization and over the course of the first two years of life. These findings are useful for family counseling and expectation setting.

Introduction: This study's purpose was to (1)determine the effect of locally administered serum amyloid P (SAP) on the development of hypertrophic scars (HTS) in porcine and rabbit HTS models and (2)determine the pharmacokinetics of systemically administered SAP and its effect on circulating fibrocyte quantities.Methods: Two large animal (New Zealand White Rabbit and Female Red Duroc Pigs) HTS models were utilized to study the effects of daily local injections of SAP immediately post wounding (x5 din rabbits; x7 din pigs) on HTS development as measured by scar elevation index , scar area, wound closure, and molecular expression studies of scar components. For SAP pharmacokinetics, total and human SAP levels in porcine blood were measured at regular intervals following intravenous administration of human SAP. Fibrocyte quantities were determined prior to and 1 h following human SAP intravenous administration.Results: In the rabbit model, local SAP significantly decreased the level of tissue inhibitor of metalloproteinases-1 mRNA expression and maintained matrix mettaloproteinase-9 expression, while control and vehicle groups significantly declined. In the pig model, there was a significant decrease in the trend of scar elevation indexes treated with local SAP versus controls over the study period. This decrease was statistically significant at days 14 and 84. Human SAP administered intravenously is degraded within 24 h and does not influence circulating fibrocyte quantities.Conclusions: This is the first study to demonstrate attenuation of HTS formation using locally administered SAP in large animal HTS models. Local SAP administration reduces HTS formation by maintaining matrix mettaloproteinase-9 and decreasing tissue inhibitor of metalloproteinases-1. Intravenous administration of SAP is not as effective.& COPY; 2023 Published by Elsevier Inc.

Introduction: Covered abdominal wall defects (CAWD) can be categorized into giant omphaloceles (GOs), nongiant omphaloceles (NGOs), and umbilical cord hernias (UCHs). We sought to evaluate differences in management and outcomes of the different CAWD, treated at a large tertiary children's hospital, with regards to survival and association with other major congenital anomalies. Methods: A retrospective review of CAWD patients between January 2010 and January 2021 was conducted. GO was defined as a fascial defect >5 cm or >50% liver herniation. UCH were defined as fascial defects < 2 cm. All others were classified as NGO. Type of repair, time to fascial closure, index hospitalization length of stay (LOS), and survival rates were compared. Four major anomaly categories were identified: cardiac, midline, BeckwithWeidemann Syndrome, and other genetic anomalies. Results: We identified 105 CAWD patients (UCH n = 40; GO n = 34; and NGO n = 31). Ninety percent of UCH underwent primary repair, 10% were never repaired. NGOs were repaired by primary or staged methods in 92.9% of cases and 7.1% by delayed repair. Primary or staged repair occurred in 32.4% of GOs and delayed repair occurred in 67.6%. The median days to repair was 181 [24,427] GO, 1 [1,3] NGO, and 1 [0,1] UCHs (P < 0.01). Index hospitalization median LOS (days) was 90 [55,157] GO, 23 [10,48] NGO, 9 [5,22] UCH, (P < 0.01). There were no statistical differences in survival rates, number of patients with major anomalies (GO 35.4%, NGO 51.5%, UCH 50%), or types of anomalies. Conclusions: UCHs and omphaloceles have similar incidences of major associated anomalies. Thus, all patients with a covered abdominal wall defect should undergo workup for associated anomalies.(c) 2022 Elsevier Inc. All rights reserved.

Introduction: It has been reported that pediatric patients experienced a delay in treatment for acute appendicitis during the pandemic, resulting in increased rates of complicated appendicitis. We investigated the association of the COVID-19 pandemic and the incidence and severity of acute appendicitis among pediatric Medicaid patients using a population based approach. Methods: The claims database of Partners For Kids, a pediatric Medicaid accountable care organization (ACO) in Ohio, was queried for cases of acute appendicitis from April to August 2017-2020. The monthly rate of acute appendicitis/100,000 covered lives was calculated each year and compared over time. Rates of complicated appendicitis were also compared. Diagnosis code validation for classification as complicated or uncomplicated appendicitis was performed for patients treated at our hospital. Results: During the study period, 465 unique cases of acute appendicitis were identified. Forty percent (186/465) were coded as complicated. No significant difference in the incidence of acute appendicitis cases was observed across the 4 y, either in an overall comparison or in pairwise comparisons (P > 0.15 for all). The proportion of acute appendicitis cases that were coded as complicated did vary significantly over the 4-year study period (P = 0.005); this was due to this proportion being significantly higher in 2018 than in either 2019 (P = 0.005 versus 2018) or 2020 (P = 0.03 versus 2018). Conclusions: The COVID-19 pandemic was not associated with reduced access to treatment for acute appendicitis among patients in a pediatric Medicaid ACO. This suggests that an ACO may promote continued healthcare access for their covered population during an unexpected crisis. 2023 Elsevier Inc. All rights reserved.

Objective To study the role of fetal endoscopic tracheal occlusion (FETO) on resolution of pulmonary hypertension (PH) in fetuses with isolated moderate left-sided diaphragmatic hernia (CDH). Methods This retrospective study included fetuses with CDH evaluated between February 2004 and July 2017. Using the tracheal occlusion to accelerate lung growth (TOTAL) trial definition, we classified fetuses into moderate left CDH if O/E-LHR (observed/expected-lung head ratio) was 25-34.9% regardless of liver position or O/E-LHR of 35-44.9% if liver was in the chest. Postnatal echocardiograms were used to diagnose PH. Logistic regression analyses were performed to determine the relationship of FETO with study outcomes. Results Of 184 cases with no other major anomalies, 30 (16%) met criteria. There were nine FETO and 21 non-FETO cases. By hospital discharge, a higher proportion of infants in the FETO group had resolution of PH (87.5 (7/8) vs. 40% (8/20); p=.013). FETO was associated with adjusted odds ratio of 17.3 (95% CI: 1.75-171; p=.015) to resolve PH by hospital discharge. No significant differences were noted in need for ECMO or survival to discharge between groups. Conclusions Infants with moderate left-sided CDH according to O/E-LHR, FETO is associated with resolution of PH by the time of hospital discharge.

We present a rare case of congenital diaphragmatic hernia (CDH) with intrathoracic stomach associated with a congenital short esophagus (CSE) prenatally diagnosed in a male fetus. The unusual hernia appeared right-sided but did not contain liver, instead containing stomach, small and large bowel, and spleen. The infant was delivered preterm at 32 weeks gestation. At 9 days of age, the spleen, small bowel, and large bowel were reduced into the abdominal cavity. The stomach was only partially reduced because of the CSE. Gastropexy and a gastrostomy were also performed. The diaphragmatic defect was fixed around the stomach, which later presented problems requiring another surgery. Additional operations: 1. Tracheostomy placed (3 months) 2. Stomach repositioned more into the abdominal cavity and gastrostomy redone (8 months) 3. Duodenoplasty (postoperative small bowel obstruction) (9 months). Outcome: The patient is currently alive at 11 years old and continues with a gastrostomy tube (g-tube) and tracheostomy dependent. Lessons: To the best of our knowledge, this patient is the longest surviving patient with CDH and intrathoracic stomach caused by CSE. Early diagnosis and continued monitoring remain a key feature to survival.

INTRODUCTION: Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients with these lesions are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. METHODS: We used ICD codes to identify high-risk congenital cardiac disease patients ≤6 months of age, cared for at a tertiary children’s hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal-dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared with controls in a multivariate analysis. RESULTS: Of the 353 patients who met inclusion criteria, 77.6% had ductal-dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 51.8% received other vasodilatory drugs. The overall NEC rate was 15.3%. On univariate analysis, DD-S, iNO use, and systemic vasodilators had a significantly higher risk of NEC, and DD-P was associated with lower NEC risk (Figure). On multivariate analysis, only iNO (odds ratio 2.725 [CI 1.36 to 5.44]) and DD-S (odds ratio 2.279 [CI 1.02 to 5.11]) were independent risk factors for NEC.FigureCONCLUSION: In patients with at-risk congenital cardiac disease lesions, a ductus-dependent systemic circulation and/or iNO treatment increases the risk of developing NEC. The presence of iNO or DD-S should be used as a marker of increased risk both in the prevention and workup of suspected NEC.

Background Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets. Methods Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or parenteral nutrition (PN) prepared from a soybean oil-based emulsion containing either 24.0% (depleted [DEP]), 100% (Intralipid; normal phytosterol [NP] concentration), or 144% (enriched [ENR]) total phytosterol concentration. Results At the end of the study, plasma and liver phytosterol concentrations were highest in the ENR group, followed by NP and then DEP and ENT. Serum direct bilirubin, serum bile acids, and gamma-glutamyltransferase were higher in the ENR and NP groups compared with either DEP or ENT groups. All PN lipid groups showed evidence of mild hepatic steatosis but no change in hepatic expression of proinflammatory cytokines or Farnesoid X receptor target genes. Conclusion The increase in serum direct bilirubin was lower in the DEP group vs the lipid emulsions with normal or ENR phytosterols. Our results provide additional evidence that phytosterols are linked to an increase in serum markers of cholestasis in preterm PN-fed pigs.

Introduction: We sought to investigate whether hydroxyurea therapy is associated with the need for surgical splenectomy among patients with sickle cell disease (SCD). We hypothesized that as hydroxyurea gained widespread use, surgical splenectomy among pediatric patients with SCD occurred at a higher rate and older age among those taking hydroxyurea. Methods: In this retrospective cross-sectional study, the Pediatric Health Information System was queried for all SCD International Classification of Diseases 9/10 diagnosis codes and splenectomy procedure codes from January 1, 2005, to December 31, 2020. Hydroxyurea use was defined as at least one hospital admission with hydroxyurea listed as a medication. The rates of surgical splenectomy, age at splenectomy, hospital length of stay, and incidence of blood transfusion during the splenectomy admission were compared among patients receiving hydroxyurea versus those not receiving hydroxyurea. Additional subanalysis was performed in the Hemoglobin-SS, Hemoglobin-SC, and Other cohorts separately. Results: During the study period, 28,520 patients were identified. All patients with SCD receiving hydroxyurea had a significantly higher rate of surgical splenectomy compared with the nontreatment group (7.2% versus 3.2%, P = 0.01). The age at surgical splenectomy was significantly younger among Hemoglobin-SS patients receiving hydroxyurea (5.7 [5.1, 6.4] y versus 6.6 [5.8, 7.4] y; P < 0.01). There were no significant differences in length of stay or incidence of blood transfusion during the surgical splenectomy admission between treatment groups.Conclusions: Hydroxyurea use in children is associated with higher rates of surgical sple-nectomy and occurs at a younger age in the Hemoglobin-SS population. Although these findings warrant further investigation for causality, it provides useful information to cli-nicians and patients alike, allowing for more informed decision-making. 2022 Elsevier Inc. All rights reserved.

INTRODUCTION: This study compares the morbidity and mortality associated with delayed vs primary/staged closure of giant omphaloceles. METHODS: We performed a retrospective review of giant omphaloceles (fascial defect >5 cm or a majority of liver in the omphalocele sac) managed at a tertiary children’s hospital between January 2010 and October 2021. Survival, length of stay, ventilation days (VD), and gastrointestinal (GI) or bronchopulmonary dysplasia (BPD) readmissions for those who underwent primary/staged repair (PSR) or delayed repair (DR) were compared for the initial and all subsequent hospitalizations in the first 2 years of life. RESULTS: Twenty-three DR and 11 PSR patients were identified. Hospital stay (days) was higher for the DR group in the initial hospitalization (104 [65,172] vs 71 [45,213], p = 0.220) and more than 2 years (135.5 [69,299] vs 76 [53, 290] p = 0.429). The DR median age (days) of repair was 302 [163,675] vs 10 [5,21] in the PSR group. DR babies had significantly fewer VD in the initial hospitalization (1.5 [0,14] vs 18 days [10,54] p = 0.02) but not in the first 2 years of life (16 [1,45] vs 18 days [12,43] p = 0.42). No significant differences were seen in the number of GI or BPD readmissions. Two-year survival was higher in the DR group (95.7% vs 63.6%, p = 0.03; Fig. 1).CONCLUSION: Repair of giant omphaloceles at the initial hospitalization is associated with higher mortality that may be averted by delayed repair. Primary/staged and delayed repair of giant omphaloceles had equivalent hospital length of stay, GI or BPD readmissions, and total ventilatory days in the first 2 years of life.

With advances in ultrasound, birth defects are increasingly detected during pregnancy and may be amenable to surgical correction before delivery, to improve outcomes. This essential book discusses the different birth defects that can be treated during pregnancy and the important anesthetic considerations for the mother and fetus undergoing these procedures. Experts in the fields of anesthesiology, maternal fetal medicine, surgery, and pediatrics have come together to develop the content of this book. Enhanced throughout with full color images and illustrations, the book covers important topics such as spina bifida, twin-twin transfusion syndrome, sacrococcygeal teratoma, and lung masses, as well as fetal cardiac intervention, intrauterine transfusion, ex utero intrapartum treatment, and multidisciplinary approaches to fetal surgery. An invaluable guide for pediatric and obstetric anesthesiologists, anesthesiology, obstetrics, and surgical trainees, nurse anesthetists, and maternal-fetal medicine specialists.

Optimizing enteral nutrition for premature infants may help mitigate extrauterine growth restriction and adverse chronic health outcomes. Previously, we showed in neonatal pigs born at term that lean growth is enhanced by intermittent bolus compared with continuous feeding. The objective was to determine if prematurity impacts how body composition, muscle protein synthesis, and myonuclear accretion respond to feeding modality. Following preterm delivery, pigs were fed equivalent amounts of formula delivered either as intermittent boluses (INT; n = 30) or continuously (CONT; n = 14) for 21 days. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and muscle growth was assessed by morphometry, myonuclear accretion, and satellite cell abundance. Tissue anabolic signaling and fractional protein synthesis rates were determined in INT pigs in postabsorptive (INT-PA) and postprandial (INT-PP) states and in CONT pigs. Body weight gain and composition did not differ between INT and CONT pigs. Longissimus dorsi (LD) protein synthesis was 34% greater in INT-PP than INT-PA pigs (P < 0.05) but was not different between INT-PP and CONT pigs. Phosphorylation of 4EBP1 and S6K1 and eIF4E·eIF4G abundance in LD paralleled changes in LD protein synthesis. Satellite cell abundance, myonuclear accretion, and fiber cross-sectional area in LD did not differ between groups. These results suggest that, unlike pigs born at term, intermittent bolus feeding does not enhance lean growth more than continuous feeding in pigs born preterm. Premature birth attenuates the capacity of skeletal muscle to respond to cyclical surges in insulin and amino acids with intermittent feeding in early postnatal life.NEW & NOTEWORTHY Extrauterine growth restriction often occurs in premature infants but may be mitigated by optimizing enteral feeding strategies. We show that intermittent bolus feeding does not increase skeletal muscle protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in preterm pigs. This attenuated anabolic response of muscle to intermittent bolus feeding, compared with previous observations in pigs born at term, may contribute to deficits in lean mass that many premature infants exhibit into adulthood.

Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days, n = 25) or at term (T; 112 days, n = 26) were subject to euinsulinemic-euaminoacidemic-euglycemic (FAST), hyperinsulinemic-euaminoacidemic-euglycemic (INS), or euinsulinemic-hyperaminoacidemic-euglycemic (AA) clamps four days after delivery. Indices of mechanistic target of rapamycin complex 1 (mTORC1) signaling and fractional protein synthesis rates were measured after 2 h. Although longissimus dorsi (LD) muscle protein synthesis increased in response to both INS and AA, the increase was 28% lower in PT than in T. Upstream of mTORC1, Akt phosphorylation, an index of insulin signaling, was increased with INS but was 40% less in PT than in T. The abundances of mTOR·RagA and mTOR·RagC, indices of amino acid signaling, increased with AA but were 25% less in PT than in T. Downstream of mTORC1, eIF4E·eIF4G abundance was increased by both INS and AA but attenuated by prematurity. These results suggest that preterm birth blunts both insulin- and amino acid-induced activation of mTORC1 and protein synthesis in skeletal muscle, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the high prevalence of extrauterine growth restriction in prematurity.NEW & NOTEWORTHY Extrauterine growth faltering is a major complication of premature birth, but the underlying cause is poorly understood. Our results demonstrate that preterm birth blunts both the insulin-and amino acid-induced activation of mTORC1-dependent translation initiation and protein synthesis in skeletal muscle, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced accretion of lean mass and extrauterine growth restriction of premature infants.

Style, Candace C. MD, MS; Menchaca, Alicia D. MD; Kyhl, Tyler A. BS; Olutoye, Oluyinka O. MD, PhD, FACS Author Information

Surgery during pregnancy occurs when maternal or fetal needs outweigh the status quo, yet much uncertainty remains regarding the effects of anesthesia and surgery on fetal neurodevelopment. This article will review common maternal and fetal indications for invasive procedures, along with contemporary research on fetal neurodevelopment following anesthesia and surgery, focusing on future areas of investigation.

Significance: This body of work gives a concise and comprehensive overview for the clinician and scientist on the latest treatment modalities for hypertrophic scars (HTS) and keloids in the pediatric population, as well as the most promising methods of prevention currently being investigated. This review will serve as a guide to the clinician for treatment selection and as an efficient tool for the scientist to achieve a comprehensive overview of the scientific literature to guide their future experiments aimed at pathologic scar prevention. Recent Advances: Current studies in the literature suggest carbon dioxide (CO2) laser and E-light (bipolar radiofrequency, intense pulsed light, and cooling) are two of the most effective treatment modalities for HTS, while surgical excision+CO2 laser+triamcinolone injection was one of the most successful treatments for keloids. In animal models, drug impregnated electrospun nanofiber dressings offer encouraging results for HTS prevention, while Kelulut honey showed promising results for keloid prevention. Critical Issues: Treatment outcome reproducibility is hindered by small cohorts of patients, inadequate-follow up, and variability in assessment tools. Prevention studies show multiple ways of achieving the same result, yet fall short of complete prevention. Furthermore, some studies that have purported full prevention have not been validated. Future Directions: To establish a standard of care, large clinical trials of the most successful modalities in small cohorts are needed. The key for prevention will be validation in animal models of the most successful methods, followed by translational and clinical studies.