Hospital Admissions for Abusive Head Trauma Before and During the COVID-19 Pandemic.

Importance: Several studies have demonstrated a decrease in the occurrence of child abuse in the US since the start of the COVID-19 pandemic. This finding has generated concern for missed cases due to the initial lockdowns and lack of childcare resources. Determining the association of the pandemic on hospitalizations for severe forms of abuse is essential to focus preventive efforts. Objective: To examine trends in abusive head trauma (AHT) before and during the COVID-19 pandemic. Design, Setting, and Participants: Retrospective, multicenter, repeated cross-sectional study, conducted January 1, 2016, through April 30, 2022, with data from tertiary care children's hospitals and contributors to the Pediatric Health Information System. Data were obtained for 2380 hospitalizations of children younger than 5 years with International Classification of Diseases, Tenth Revision, Clinical Modification codes for both abuse and head trauma. Main Outcomes and Measures: Monthly hospitalizations were analyzed using interrupted time-series analysis. Hospitalization severity (eg, intensive care unit stay) and clinical characteristics (subdural hemorrhages and retinal hemorrhages) were compared before and after the start of the pandemic. Results: We identified 2380 hospitalizations due to AHT (median age, 140 [IQR, 75.0-325.5] days) from 45 hospitals. The mean (SD) monthly incidence of AHT was 34.3 (5.8) before the COVID-19 pandemic compared with 25.6 (4.2) during COVID-19 (a 25.4% decrease). When the pre-COVID-19 and during COVID-19 periods were compared, there were no significant differences in severity or clinical characteristics. On interrupted time-series analysis, there was a significant decrease in the number of monthly hospitalizations (-8.1; 95% CI, -12.41 to -3.72; P < .001) in the first month of the pandemic. In the subgroup of children younger than 1 year, there was a significant decrease in monthly hospitalizations at the onset of the pandemic (-8.2; 95% CI, -12.02 to -4.43; P < .001) followed by a significant temporal increase across the COVID-19 period (P = .01). Conclusions and Relevance: The findings of this cross-sectional study suggest there was a significant decrease in monthly hospitalizations for AHT following the start of the pandemic in March 2020. Although there was no corresponding increase in hospitalization severity, the decrease during the pandemic may have been transient, as monthly hospitalizations for children younger than 1 year increased significantly over time during COVID-19, after the initial decrease.

In utero 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 in utero 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-ß pathway are critically involved in lung branching morphogenesis. Here, we characterize the expression of miR200b and the TGF-ß pathway at different gestational times using a rat model of CDH. Fetal rats with CDH are deficient in miR200b at gestational day 18. We demonstrate that novel polymeric nanoparticles loaded with miR200b, delivered in utero via vitelline vein injection to fetal rats with CDH results in changes in the TGF-ß pathway as measured by qRT-PCR; these epigenetic changes improve lung size and lung morphology, and lead to favorable pulmonary vascular remodeling on histology. This is the first demonstration of in utero epigenetic therapy to improve lung growth and development in a pre-clinical model. With refinement, this technique could be applied to fetal cases of CDH or other forms of impaired lung development in a minimally invasive fashion.

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. MPs loaded with fluorescent dye (DiO) were evaluated 3 hours after injection to determine incidence of binding to the MMC defect. Fetuses were then treated with PBS or PLGA particles loaded with DiO, bovine serum albumin, or FGF and evaluated at term (E21). Fetuses with MMC defects were evaluated for gross and histologic evidence of soft tissue coverage. The effect of PLGA-FGF treatment on spinal cord cell death was evaluated using an in situ cell death kit. RESULTS: PLGA-DiO MPs had a binding incidence of 86% and 94% 3 hours after injection at E17 for doses of 0.1 mg and 1.2 mg, respectively. Incidence of soft tissue coverage at term was 19% (4 of 21), 22% (2 of 9), and 83% (5 of 6) for PLGA-DiO, PLGA-BSA, and PLGA-FGF, respectively. At E21, the percentage of spinal cord cells positive for in situ cell death was significantly higher in MMC controls compared with wild-type controls or MMC pups treated with PLGA-FGF. CONCLUSION: PLGA MPs are an innovative minimally invasive platform for induction of soft tissue coverage in the rat model of MMC and may reduce cellular apoptosis.

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. RESULTS: Two hundred and nine infants were identified with DA, trisomy 21, and an intestinal bypass. Fifty-seven (27%) underwent gastrostomy placement. Baseline characteristics of those with and without gastrostomy tubes were similar. Patients from 16 hospitals that placed no gastrostomy tubes (No-G-tube-Hospitals) were compared to children from 30 hospitals that placed at least one gastrostomy tube (G-tube-Hospitals). Open atresia repairs occurred more frequently at G-tube-Hospitals, but patients were otherwise similar. There was no difference in readmission at 12 months for gastrostomy placement between children from No-G-tube-Hospitals and those from G-tube-Hospitals that did not undergo gastrostomy during their index admission. CONCLUSIONS: One-third of institutions in this study did not place gastrostomy tubes during index admissions for neonates with trisomy 21 and DA, yet this did not negatively impact the length of stay or incidence of subsequent gastrostomy placement as a result. Future research is needed to determine factors that predispose patients to failure without gastrostomy, as well as best practices for post-operative management in these patients to reduce unnecessary tube placement.

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

The field of in utero 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. Treatment in utero has several distinct advantages to postnatal treatment. Biologic and physiologic phenomena enable the delivery of a higher effective dose, generation of immune tolerance, and the prevention of phenotypic onset for genetic diseases. Therapeutic technology for IUGT including CRISPR-Cas9 systems, zinc finger nucleases (ZFN), and peptide nucleic acids (PNAs) has already shown promise in animal models and early postnatal clinical trials. While the ability to detect fetal diagnoses has dramatically improved with developments in ultrasound and next-generation sequencing, treatment options remain experimental, with several translational gaps remaining prior to implementation in the clinical realm. Complicating this issue, the potential diseases targeted by this approach are often debilitating and would otherwise prove fatal if not treated in some manner. The leap from small animals to large animals, and subsequently, to humans will require further vigorous testing of safety and efficacy.

Trends in fundoplication volume for pediatric gastroesophageal reflux disease.

INTRODUCTION: Fundoplication for gastro-esophageal reflux disease (GERD) has been commonly performed by pediatric surgeons, however there are no recent data documenting fundoplication trends. Changes in fundoplication volume impact pediatric surgical training and may reflect changes in care for children with severe GERD. MATERIALS & METHODS: The Pediatric Health Information System (PHIS) was queried from 2010-2019 for children with ICD-9/ICD-10 codes for GERD, fundoplication, and gastrostomy. Institutional surgical volume and patient demographics were examined over time. A secondary analysis using the Accreditation Council for Graduate Medical Education case logs for pediatric surgery fellows was performed across the same years to assess effects upon surgical volume for trainees. RESULTS: Mean institutional fundoplication case volume decreased from 50 in 2010 to 17 in 2019. Trends were similar between institutions with and without fellowship programs when corrected by total operative volume. Patient characteristics were relatively unchanged between 2010 and 2019. Fundoplication volume reported in fellow case logs decreased from 46 in 2010 to 26 in 2019, mirroring national data. CONCLUSIONS: Institutional volume for fundoplication in children with GERD has seen a 3-fold decrease over the last decade, mirrored by an almost 2-fold decrease in case volume reported by pediatric surgery fellows.

Laparoscopy is increasingly used for pediatric inguinal hernia repair.

INTRODUCTION: Inguinal hernia repairs (IHR) are commonly performed by pediatric surgeons in the United States. The operative approach depends on surgeon preference with no definitive prospective studies comparing laparoscopic inguinal hernia repair (LIHR) versus traditional inguinal hernia repair (TIHR). We aim to assess current practice, hypothesizing that laparoscopy is increasingly used for pediatric IHR. MATERIAL & METHODS: The Children's Hospital Association (CHA) Pediatric Health Information System was queried for IHRs performed between 01/01/2009 and 12/31/2018. Demographics, procedure type, hernia laterality, and cost were obtained. Patients were grouped by procedure type (laparoscopic/traditional). RESULTS: 125,249 IHRs were performed at 32 CHA hospitals during the ten-year study period. 115,782 (92.4%) were TIHR and 9467 (7.6%) LIHR. Use of laparoscopy increased 5-fold from 3% to 15% over the study period. When comparing laparoscopic to traditional IHR groups, there were more females (28.3% vs 12.6%), African-Americans (19.7% vs 14.4%), government-insured (50% vs 45.2%), younger patients (4.2 vs 4.4 years), bilateral IHRs (11.4% vs 7.9%), and higher adjusted total hospital cost ($3,791 vs $2995) in the laparoscopic group (p<0.0001, all comparisons). CONCLUSIONS: Laparoscopy for pediatric IHR is increasing at CHA hospitals where nearly 1 in 6 children currently undergoes a laparoscopic repair. The long-term outcomes with laparoscopic repair are worthy of future study.

Establishing a National Rate of Rectal Biopsy Positivity in the Diagnosis of Hirschsprung Disease.

OBJECTIVES: Although rectal biopsy has long been established as the criterion standard for the diagnosis of Hirschsprung disease, little to no information exists regarding nationwide rates of rectal biopsy positivity or interinstitutional variability. We sought to determine the national rate of rectal biopsy positivity and factors contributing to institutional variability. METHODS: A retrospective review of the Children's Hospital Association's (CHA) Pediatric Health Information System from 2009 to 2018 identified infants <100 days old with ICD-9/ICD-10 procedural codes for rectal biopsy in addition to codes for pull-through procedures within 500 days of life as a proxy for positive biopsy. A subgroup analysis of only patients biopsied at institutions with positive biopsy rates 1 standard deviation above or below the mean positive biopsy rate (deemed high and low outliers) was performed to better delineate these populations. RESULTS: A total of 7225 children underwent rectal biopsies between 2009 and 2018 at 52 Children's Hospital Association Hospitals. Mean positive biopsy rate for individual institutions was 21.5% (standard deviation ±â€Š6.4%). Linear regression to predict the effect of hospital surgical volume on positive biopsy rate demonstrated no volume outcome relationship (R2 = 0.049). Patients at high outlier hospitals for biopsy positivity were found to travel significantly further to the hospital (232.5 vs 123.1 miles, P < 0.0001) when compared to patients presenting at low outlier hospitals. CONCLUSIONS: There appears to be little interinstitutional variability in the rate of surgery following rectal biopsy for presumed Hirschsprung and no significant relationship to surgical volume. About 1 in every 4 infants undergoing biopsy proceeds to surgery.

Model for End-Stage Liver Disease Sodium as a Predictor of Surgical Risk in Cirrhotic Patients With Ascites.

BACKGROUND: The Model for End-Stage Liver Disease Sodium (MELD-Na) incorporates hyponatremia into the MELD score and has been shown to correlate with surgical outcomes. The pathophysiology of hyponatremia parallels that of ascites, which purports greater surgical risk. This study investigates whether MELD-Na accurately predicts morbidity and mortality in patients with ascites undergoing general surgery procedures. MATERIALS AND METHODS: We used the National Surgical Quality Improvement Program database (2005-2014) to examine the adjusted risk of morbidity and mortality of cirrhotic patients with and without ascites undergoing inguinal or ventral hernia repair, cholecystectomy, and lysis of adhesions for bowel obstruction. Patients were stratified by the MELD-Na score and ascites. Outcomes were compared between patients with and without ascites for each stratum using low MELD-Na and no ascites group as a reference. RESULTS: A total of 30,391 patients were analyzed. Within each MELD-Na stratum, patients with ascites had an increased risk of complications compared with the reference group (low MELD-Na and no ascites): low MELD-Na with ascites odds ratio (OR) 4.33 (95% confidence interval [CI] 1.96-9.59), moderate MELD-Na no ascites OR 1.70 (95% CI 1.52-1.9), moderate MELD-Na with ascites OR 3.69 (95% CI 2.49-5.46), high MELD-Na no ascites OR 3.51 (95% CI 3.07-4.01), and high MELD-Na ascites OR 7.18 (95% CI 5.33-9.67). Similarly, mortality risk was increased in patients with ascites compared with the reference: moderate MELD-Na no ascites OR 3.55 (95% CI 2.22-5.67), moderate MELD-Na ascites OR 13.80 (95% CI 5.65-33.71), high MELD-Na no ascites OR 8.34 (95% CI 5.15-13.51), and high MELD-Na ascites OR 43.97 (95% CI 23.76-81.39). CONCLUSIONS: MELD-Na underestimates morbidity and mortality risk for general surgery patients with ascites.

Preoperative Venoarterial Extracorporeal Membrane Oxygenation Slashes Risk Score in Advanced Structural Heart Disease.

BACKGROUND: Cardiac surgery for structural heart disease has poor outcomes in the presence of cardiogenic shock or advanced heart failure. We applied venoarterial extracorporeal membrane oxygenation (ECMO) to restore end-organ function and resuscitate patients before high-risk cardiac operation. METHODS: Twelve patients with cardiogenic shock and end-organ failure were evaluated for cardiac surgery. The average Society of Thoracic Surgeons mortality risk was 24% ± 13%. Patients were peripherally cannulated on ECMO for 7 ± 4 days, before undergoing operation for prosthetic mitral stenosis (n = 4), ruptured papillary muscle (n = 4), ischemic ventricular septal defect (n = 3), or severe aortic stenosis (n = 1). RESULTS: Mean age was 61 ± 8 years. Comorbidities included acute renal failure (n = 11), inotrope requirement (n = 10), intraaortic balloon pump (n = 8), severe acidosis (n = 6), high-dose vasopressor requirement (n = 8), and cardiac arrest (n = 1). With ECMO support, vasopressor requirement, central venous pressure, creatinine, lactate, pH, pulmonary hypertension, and The Society of Thoracic Surgeons mortality risk and EuroSCORE (European System for Cardiac Operative Risk Evaluation) II all improved significantly. Care was withdrawn in 1 patient on ECMO with initially unknown anoxic brain injury. No patients required dialysis at discharge. Complications included 1 permanent stroke. All operative patients survived to hospital discharge. Average length of follow-up was 420 days, with 2 patient deaths at 76 and 230 days and 6 patients surviving over 1 year. CONCLUSIONS: ECMO can be used as a bridge to heart valve or septal defect surgery in severely decompensated patients. Through recovery of end-organ function, ECMO may allow surgical correction of structural heart disease in patients considered inoperable or convert a salvage situation to an elective operation.

Programmatic and Surgeon Specialization Improves Mortality in Isolated Coronary Bypass Grafting.

BACKGROUND: Throughout surgery, specialization in a procedure has been shown to improve outcomes. Currently, there is no evidence for or against subspecialization in coronary surgery. Tasked with the goal of improving outcomes after isolated coronary artery bypass grafting (CABG), our institution sought to determine whether the development of a subspecialized coronary surgery program would improve morbidity and mortality. METHODS: All isolated CABG operations at a single institution were retrospectively examined in two distinct periods, 2002 to 2013 and 2013 to 2016, before and after the implementation of a subspecialized coronary surgery program. Improved policies included leadership and subspecialization of a program director, standardization of surgical technique and postoperative care, and monthly multidisciplinary quality review. Outcomes were collected and compared. RESULTS: Between 2002 and 2013, 3,256 CABG operations were done by 16 surgeons, the most frequent surgeon doing 33%. Between 2013 and 2016, 1,283 operations were done by 10 surgeons, 70% by the coronary program director. CABGs done in the specialized era had shorter bypass and clamps times and increased use of bilateral internal mammary arteries. Blood transfusion and complication rates, including permanent stroke and prolonged ventilation, were significantly decreased after implementation of the coronary program. Likewise, overall operative mortality (2.67% vs 1.48%, p = 0.02) was significantly reduced. CONCLUSIONS: Subspecialization in CABG and dedicated coronary surgery programs may lead to faster operations, increased use of bilateral internal mammary arteries, fewer complications, and improved survival after isolated CABG.