Primary caregiver employment status is associated with traumatic brain injury in children in the USA.

BACKGROUND: Traumatic brain injury (TBI) is a common injury in children. Previous literature has demonstrated that TBI may be associated with supervision level. We hypothesised that primary caregiver employment would be associated with child TBI. METHODS: A retrospective cross-sectional study was performed for children aged 0-17 using the National Survey of Children's Health (NSCH) 2018-2019. The NSCH contains survey data on children's health completed by adult caregivers from randomly selected households across the USA. We compared current TBI prevalence between children from households of different employment statuses. Current TBI was defined by survey responses indicating a healthcare provider diagnosed TBI or concussion for the child and the condition was present at the time of survey completion. Household employment status was categorised as two caregivers employed, two caregivers unemployed, one of two caregivers unemployed, single caregiver employed and single caregiver unemployed. Multivariable logistic regression was performed, controlling for sociodemographic factors. RESULTS: Of 56 865 children, median age was 10 years (IQR: 5-14), and 0.6% (n=332) had a current TBI. Children with TBI were older than children without TBI (median 12 years vs 10 years, p<0.001). On multivariable regression, children with at least one caregiver unemployed had increased odds of current TBI compared with children with both caregivers employed. CONCLUSIONS: Children with at least one caregiver unemployed had increased TBI odds compared with children with both caregivers employed. These findings highlight a population of families that may benefit from injury prevention education and intervention.

Opioid consumption before discharge predicts outpatient opioid use in adolescents undergoing surgery.

BACKGROUND: The majority of adolescents undergoing surgery report unused prescription opioids after surgery, increasing the risk of diversion, misuse, and addiction. Adult studies have demonstrated that opioid use 24 hours before discharge corresponds with opioid use at home. We hypothesized that inpatient opioid consumption is associated with outpatient opioid use in adolescents. METHODS: Adolescents aged 13-20 years undergoing elective surgery associated with an opioid prescription were prospectively recruited. Parent-adolescent dyads were surveyed preoperatively to assess sociodemographics, health literacy, and baseline substance use, and opioid use was measured at 30- and 90-days postoperatively. Medical records were reviewed to calculate cumulative opioid use during hospitalization. Inpatient and postoperative opioid use was converted to oral morphine equivalents. Adjusting for age, sex, race, health literacy, alcohol use, pain score, and surgery, multivariable linear regression identified factors associated with outpatient oral morphine equivalent use 90 days postoperatively. RESULTS: Overall, 103 adolescents were enrolled. Median oral morphine equivalents used from 24 and 48 hours before discharge and throughout the hospitalization were 30.8 (interquartile range:11.7-45.0), 67.5 (interquartile range:37.5-94.3), and 97.5 (interquartile range:18.0-152.7), respectively. Regression analysis demonstrated that adolescent-reported pain at discharge (P = .028) and cumulative oral morphine equivalents used 24 hours (P < .001) and 48 hours (P = .003) before discharge were significantly associated with postoperative oral morphine equivalents use at home. Oral morphine equivalents consumption 24 hours before discharge estimated cumulative oral morphine equivalents use 90 days postoperatively at a 1-to-5 ratio in 94.1% of patients. CONCLUSION: For adolescents undergoing surgery, patient-reported pain at discharge and oral morphine equivalents administered 24 hours before discharge are associated with cumulative outpatient opioid use. Tailoring outpatient prescriptions to total oral morphine equivalent consumption 24 hours before discharge could reduce excess opioid prescribing.

Differential RNA Expression Between Metastatic and Primary Neuroblastoma Cells.

INTRODUCTION: Neuroblastoma (NB) is the most common extra-cranial malignancy in children. Poor survival in high-risk NB is attributed to recurrent metastatic disease. To better study metastatic disease, we used a novel mouse model to investigate differential gene expression between primary tumor cells and metastatic cells. We hypothesized that metastatic NB cells have a different gene expression profile from primary tumor cells and cultured cells. METHODS: Using three human NB cell lines (NGP, CHLA255, and SH-SY5Y), orthotopic xenografts were established in immunodeficient nod/scid gamma mice via subcapsular renal injection. Mice were sacrificed and NB cells were isolated from the primary tumor and from sites of metastasis (bone marrow, liver). RNA sequencing, gene set analysis, and pathway analysis were performed to identify differentially expressed genes and molecular pathways in the metastatic cells compared to primary tumor cells. RESULTS: There were 266 differentially expressed genes in metastatic tumor cells (bone marrow and liver combined) compared to primary tumor cells. The top upregulated gene was KCNK1 and the top downregulated genes were PDE7B and NEBL. Top upregulated pathways in the metastatic cells were involved in ion transport, cell signaling, and cell proliferation. Top downregulated pathways were involved in DNA synthesis, transcription, and cellular metabolism. CONCLUSIONS: In metastatic NB cells, our study identified the upregulation of biologic processes involved in cell cycle regulation, cell proliferation, migration, and invasion. Ongoing studies aim to validate downstream translation of these genomic alterations, as well as target these pathways to more effectively suppress and inhibit recurrent metastatic disease in NB.

Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Childhood opportunity and appropriate use of child safety restraints in motor vehicle collisions.

Objectives: Safety restraints reduce injuries from motor vehicle collisions (MVCs) but are often improperly applied or not used. The Childhood Opportunity Index (COI) reflects social determinants of health and its study in pediatric trauma is limited. We hypothesized that MVC patients from low-opportunity neighborhoods are less likely to be appropriately restrained. Methods: A retrospective cross-sectional study was performed on children/adolescents ≤18 years old in MVCs between January 1, 2011 and December 31, 2021. Patients were identified from the Children's Hospital Los Angeles trauma registry. The outcome was safety restraint use (appropriately restrained, not appropriately restrained). COI levels by home zip codes were stratified as very low, low, moderate, high, and very high. Multivariable regression controlling for age identified factors associated with safety restraint use. Results: Of 337 patients, 73.9% were appropriately restrained and 26.1% were not appropriately restrained. Compared with appropriately restrained patients, more not appropriately restrained patients were from low-COI (26.1% vs 20.9%), high-COI (14.8% vs 10.8%) and very high-COI (10.2% vs 3.6%) neighborhoods. Multivariable analysis demonstrated no significant associations in appropriate restraint use and COI. There was a non-significant trend that children/adolescents from moderate-COI neighborhoods were more likely than those from very low-COI neighborhoods to be appropriately restrained (OR=1.82, 95% CI 0.78, 4.28). Conclusion: Injury prevention initiatives focused on safety restraints should target families of children from all neighborhood types. Level of evidence: III.

A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation.

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

The impact of COVID-19 on racial and ethnic disparities in presentation with perforated appendicitis in children: A retrospective cohort study.

Background: Children from racial and ethnic minority groups have higher prevalence of perforated appendicitis, and the COVID-19 pandemic worsened racial and ethnic health-related disparities. We hypothesized that the incidence of perforated appendicitis worsened for children from racial and ethnic minorities during the COVID-19 pandemic. Methods: We performed a retrospective cohort study of the Pediatric Health Information System for children ages 2-18y undergoing appendectomy pre-pandemic (3/19/2019-3/18/2020) and intra-pandemic (3/19/2020-3/30/2021). The primary outcome was presentation with perforated appendicitis. Multivariable logistic regression with mixed effects estimated the likelihood of presentation with perforated appendicitis. Covariates included race, ethnicity, pandemic status, Child Opportunity Index, gender, insurance, age, and hospital region. Results: Overall, 33,727 children underwent appendectomy: 16,048 (47.6 %) were Non-Hispanic White, 12,709 (37.7 %) were Hispanic, 2261 (6.7 %) were Non-Hispanic Black, 960 (2.8 %) were Asian, and 1749 (5.2 %) Other. Overall perforated appendicitis rates were unchanged during the pandemic (37.4 % intra-pandemic, 36.4 % pre-pandemic, p = 0.06). Hispanic children were more likely to present with perforated appendicitis intra-pandemic versus pre-pandemic (OR 1.18, 95%CI: 1.07, 1.13). Hispanic children had higher odds of perforated appendicitis versus Non-Hispanic White children pre-pandemic (OR 1.10, 95%CI: 1.00, 1.20) which increased intra-pandemic (OR 1.19, 95%CI: 1.09, 1.30). Publicly-insured children had increased odds of perforated appendicitis intra-pandemic versus pre-pandemic (OR 1.14, 95%CI: 1.03, 1.25), and had increased odds of perforated appendicitis versus privately-insured children (intra-pandemic OR 1.26, 95%CI: 1.16, 1.36; pre-pandemic OR 1.12, 95%CI: 1.04, 1.22). Conclusions: During the COVID-19 pandemic, Hispanic and publicly-insured children were more likely to present with perforated appendicitis, suggesting that the pandemic exacerbated existing disparities in healthcare for children with appendicitis. Key message: We found that Hispanic children and children with public insurance were more likely to present with perforated appendicitis during the COVID-19 pandemic. Public health efforts aimed at ameliorating racial and ethnic disparities created during the COVID-19 pandemic should consider increasing healthcare access for Hispanic children to address bias, racism, and systemic barriers that may prevent families from seeking care.

Optimizing the Postoperative Management of Children Undergoing Resection of High-Risk Abdominal Neuroblastoma.

BACKGROUND: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB. METHODS: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS). RESULTS: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery (P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter (P < .01) for a longer duration (P = .02), with no difference in total opioid utilization (P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use (P = .68) or use of neuraxial anesthesia (P = .89). CONCLUSION: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization.

Comparison of Outcomes Between Surveillance Ultrasound and Completion Lymph Node Dissection in Children and Adolescents With Sentinel Lymph Node-Positive Cutaneous Melanoma.

OBJECTIVE: To determine the impact of nodal basin ultrasound (US) surveillance versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma. BACKGROUND: Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma. METHODS: Patients ≤18 years diagnosed with cutaneous melanoma between 2010 and 2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information. RESULTS: Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. A total of 67 patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 y) than CLND (median age 11.3 y; P =0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P =0.28) or death from disease (2.2% vs 9.7%; P =0.36) for those who underwent US versus CLND, respectively. CONCLUSIONS: Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.

Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.