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Background: Traumatic pancreatic laceration with ductal injury in children can be managed non-operatively (NOM); however, variable management affects outcomes. We hypothesized that a standardized management approach with early feeding and limited resource utilization is safe and improves outcomes., Method: Prospective, multicenter study of 13 pediatric trauma centers (2018-2022). Children with blunt pancreatic trauma with ductal injury were managed per a standard NOM pathway. Outcomes were compared to a historical NOM cohort with variable management., Results: Of 22 patients, the median age was 7.5 years (range 1-14 years). Low-fat diet was started at median 4 days [IQR 2-7] and median hospital stay was 8 days [IQR 4-10]. One patient failed NOM and underwent distal pancreatectomy. Of the rest, most (17/21, 81%) had early recovery and discharged in median 6 days [IQR 4-8.25] while 4 (19%) had prolonged recovery (median stay 24 days, IQR 19.8-30.5) and higher peri-pancreatic cyst development (early 23.5% vs prolonged 75%,p = 0.05). Pancreatic ascites at presentation correlated with cyst development (p < 0.0001). Endoscopic stent (optional) was placed in 33% and did not prevent cyst development. Delayed exocrine pancreatic insufficiency was noted in 1 patient. Compared to the historic cohort (32 patients), TPN use was lower (pre-protocol 56% vs post 23%, p = 0.02), days to diet was shorter (pre-protocol 7 vs post 4; p = 0.03), and cyst development was lower (pre-protocol 81% vs post 33%, p < 0.001)., Conclusion: Children with traumatic pancreatic ductal injury can be safely managed per the PTS NOM clinical pathway and most recover rapidly. Pancreatic ascites may predict pseudocyst formation., Levels of Evidence: IV., Study Type: therapeutic, comparative., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Burn injuries remain one of the leading causes of injury and death in children. Studies have demonstrated a higher mortality for pediatric burns associated with non-accidental injury. Using data from a burn registry, our study aimed to discern potential factors associated with non-accidental burn injuries., Methods: We utilized the American Burn Association database from 2016 to 2018, which collects data from over one hundred burn centers across the United States, to evaluate a large pediatric burn population. Patients aged ≤14 years were analyzed. The population was then divided into suspected non-accidental versus accidental burn injuries. A multivariable logistic regression model was utilized to evaluate for predictors of burn injuries. Additional models were used to assess the relationship between suspected non-accidental burn injury and mortality, intensive care unit (ICU) stay, and hospital length of stay., Results: 16,671 pediatric patients were included. Of those, 1228 (7.4%) patients suffered non-accidental burn injury. A majority of children who sustained non-accidental burn injury were younger, non-white, and sustained scald burns. The regression model demonstrated predictors for non-accidental burn injuries included younger age, Black race, chemical/corrosion burns, government insurance, and increased total body surface area (TBSA) burn. Overall mortality for the population was 0.5%., Conclusion: This evaluation of a national burn registry reveals differences in pediatric patients sustaining non-accidental burns compared to accidental burns. The findings in this study identify pediatric populations at risk for suspected non-accidental burn injuries which may assist in preparing the families for expectations after admission for a burn injury., Level of Evidence: III., Competing Interests: Conflicts of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs., Methods: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05., Results: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04)., Conclusions: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Firearm injury is the leading cause of death in children. The recent rise has coincided with the COVID-19 pandemic. The purpose of this study was to evaluate the trends of pediatric firearm injury over a 6-y period, to include the COVID-19 pandemic, at our pediatric trauma center., Methods: A retrospective review of the trauma registry at a free-standing children's hospital from January 2018 to December 2023 was performed. The variables evaluated included year of injury, age of injury, race, gender, admission requirements, need for blood products, need for operation, mortality, insurance type, and reason for injury., Results: There were 397 firearm injury presentations identified over the 6-y period. The median age of injury was 13 y with an interquartile range of 6-15 y. Most were male (72.3%) and of Black race (74.6%). A majority of children who sustained a firearm injury had Medicaid (77.8%). During the years of 2018 and 2019, we evaluated 40 and 39 patients, respectively. Over the next 2 y, there was a dramatic increase in pediatric firearm injuries with an increase of 65% (N = 66) in 2020 and 102.5% (N = 81) in 2021. Although there was less of an increase above baseline in 2022, there was still an elevation of 82.5% (N = 73). By the end of 2023, there had been a 145% rise (N = 98) in pediatric firearm injuries above the baseline year of 2018. The mortality rate was 7.6% (N = 30), which is 2.5 times higher than the all-cause trauma mortality of 3.1% at our facility., Conclusions: The number of firearm injuries dramatically increased during the COVID-19 pandemic and these increases have been sustained. Most of the victims have been male, of Black race, and publicly insured. While the state population of Alabama is 26.4% Black race, Black children account for 74.6% of all firearm-injured pediatric patients in our trauma registry. The reason for this disparity is not well-understood. Through ongoing research, we hope to gain insight into the reasons behind pediatric firearm injury and the best ways to mitigate them through both the medical and public health arenas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Neonatal renal replacement therapy (RRT) is a treatment modality used for severe kidney failure. Historically, its use has been limited in small infants due to circuits with large extra-corporeal volumes that require large double lumen vascular catheters. We sought to review our institution's experience with vascular access and overall survival in infants who receive RRT., Methods: A retrospective chart review of infants less than 5 kg (kg) was performed at our free-standing children's hospital from January 2016 to July 2023. We assessed the number of catheters used per patient, location of catheter placements, size of catheter, duration of treatment, reasons for line removal, and mortality., Results: A total of 93 neonatal patients were identified who underwent RRT. Thirty-two patients (34.4%) required more than one catheter, with a total of 145 catheters placed for this cohort. The median (IQR) weight at insertion was 3.3 kg (2.7-4.0). The most common location for placement was the right internal jugular vein (n = 114, 78.6%). Patients required catheters for RRT for a median (IQR) of 16 days (7-39). Six patients underwent catheter placement at a weight of less than 2 kg. Nineteen total patients went on to peritoneal dialysis (20.4%). Fifty-three patients died during their admission (57.0%)., Conclusion: To our knowledge this is the largest review of catheter use for RRT in infants within an intensive care unit and it reveals the success in treating renal failure in even the smallest infants., Level of Evidence: IV, Treatment Study., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The benefit of targeting high ratio fresh frozen plasma (FFP)/red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP/RBC transfusion and the association with outcomes in children presenting in shock., Methods: A post hoc analysis of a 24-institution prospective observational study (April 2018 to September 2019) of injured children younger than 18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (≥1:2) ratio FFP/RBC. Nonparametric Kruskal-Wallis and χ 2 were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths., Results: Of 135 children with median (interquartile range) age 10 (5-14) years and weight 40 (20-64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (low-38%, high-46%, p = 0.34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low-25, high-33, p = 0.01); however, hospital mortality was similar (low-24%, high-20%, p = 0.65) as was the risk of extended ventilator, intensive care unit, and hospital days (all p > 0.05)., Conclusion: Despite increased injury severity, patients who received a high ratio of FFP/RBC had comparable rates of mortality. These data suggest high ratio FFP/RBC resuscitation is not associated with worst outcomes in children who present in shock. Massive transfusion protocol activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Burn injuries are among the top ten leading causes of unintentional death in pediatric patients and are encountered by pediatric surgeons in all practice settings. There is a lack of literature evaluating mortality in pediatric burn injuries in regard to nonaccidental burns and potential disparities. Our study aims to determine the risk factors associated with mortality in pediatric burn injuries and highlight the characteristics of this patient population., Methods: We utilized the Trauma Quality Improvement Program database from 2017 to 2019 to identify primary burn injuries in children ≤14 y old. Physical abuse descriptors were used to identify patients with suspected nonaccidental injuries. Further demographics, including age, race, ethnicity, and insurance type, were evaluated. Descriptive statistics were generated and a multivariable logistic regression analysis was utilized to evaluate risk factors for mortality., Results: 13,472 pediatric burn patients (≤14 y old) were identified. The overall mortality was low (<1%). Children with burns to multiple body regions had the highest independent risk of mortality in this cohort. All older age groups had an independent risk of mortality compared to the youngest patients, but those from ages 5 to <10 y old had the highest risk of mortality (OR = 11.40; 95% confidence interval: 4.41-29.43, P < 0.001). Black children had a significantly higher mortality compared to White children. Nonaccidental burns carried a mortality that was twice that of accidental burns. Government insurance type was the primary insurance type for a majority of patients who died., Conclusions: Risk factors for mortality in pediatric burn include Black race, multiple affected body regions, and nonaccidental burns. This study identified an increased mortality risk in the older age groups in contrast to previous studies that showed increased mortality in younger patients suffering from burn injuries., (Published by Elsevier Inc.)

Objective: To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the 2 most common antibiotic regimens with and without antipseudomonal activity [piperacillin-tazobactam (PT) and ceftriaxone with metronidazole (CM)]., Background: Variation in the use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes., Methods: A retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed-effects regression to adjust for clustering after propensity matching on measures of disease severity., Results: In all, 1002 children met the criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall [PT: 11.8%, CM: 12.1%; odds ratio (OR): 1.44 (OR: 0.71-2.94)] and higher rates of drainage associated with the growth of any organism [PT: 7.7%, CM: 4.6%; OR: 2.41 (95% CI: 1.08-5.39)] and Escherichia coli [PT: 4.6%, CM: 1.8%; OR: 3.42 (95% CI: 1.07-10.92)] compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms [PT: 2.6%, CM: 1.5%; OR: 3.81 (95% CI: 0.96-15.08)] and Pseudomonas [PT: 1.0%, CM: 1.3%; OR: 3.42 (95% CI: 0.55-21.28)]., Conclusions and Relevance: The use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Gangrenous, suppurative, and exudative (GSE) findings have been associated with increased surgical site infection (SSI) risk and resource use in children with nonperforated appendicitis. Establishing the role for postoperative antibiotics may have important implications for infection prevention and antimicrobial stewardship., Objective: To compare SSI rates in children with nonperforated appendicitis with GSE findings who did and did not receive postoperative antibiotics., Design, Setting, and Participants: This was a retrospective cohort study using American College of Surgeons' National Surgical Quality Improvement Program (NSQIP)-Pediatric Appendectomy Targeted data from 16 hospitals participating in a regional research consortium. NSQIP data were augmented with operative report and antibiotic use data obtained through supplemental medical record review. Children with nonperforated appendicitis with GSE findings who underwent appendectomy between July 1, 2015, and June 30, 2020, were identified using previously validated intraoperative criteria. Data were analyzed from October 2022 to July 2023., Exposure: Continuation of antibiotics after appendectomy., Main Outcomes and Measures: Rate of 30-day postoperative SSI including both incisional and organ space infections. Complementary hospital and patient-level analyses were conducted to explore the association between postoperative antibiotic use and severity-adjusted outcomes. The hospital-level analysis explored the correlation between postoperative antibiotic use and observed to expected (O/E) SSI rate ratios after adjusting for differences in disease severity (presence of gangrene and postoperative length of stay) among hospital populations. In the patient-level analysis, propensity score matching was used to balance groups on disease severity, and outcomes were compared using mixed-effects logistic regression to adjust for hospital-level clustering., Results: A total of 958 children (mean [SD] age, 10.7 [3.7] years; 567 male [59.2%]) were included in the hospital-level analysis, of which 573 (59.8%) received postoperative antibiotics. No correlation was found between hospital-level SSI O/E ratios and postoperative antibiotic use when analyzed by either overall rate of use (hospital median, 53.6%; range, 31.6%-100%; Spearman ρ = -0.10; P = .71) or by postoperative antibiotic duration (hospital median, 1 day; range, 0-7 days; Spearman ρ = -0.07; P = .79). In the propensity-matched patient-level analysis including 404 patients, children who received postoperative antibiotics had similar rates of SSI compared with children who did not receive postoperative antibiotics (3 of 202 [1.5%] vs 4 of 202 [2.0%]; odds ratio, 0.75; 95% CI, 0.16-3.39; P = .70)., Conclusions and Relevance: Use of postoperative antibiotics did not improve outcomes in children with nonperforated appendicitis with gangrenous, suppurative, or exudative findings.

Purpose: Balanced blood product resuscitation with red blood cells, plasma, and platelets can be achieved using whole blood (WB) or component therapy (CT). However, balanced resuscitation of younger children with severe traumatic hemorrhage may be complicated by delays in delivering all blood components and concerns regarding multiple product exposures. We hypothesized that WB achieves balanced resuscitation faster than CT, with fewer product exposures and improved clinical outcomes., Methods: Children younger than 12 years receiving balanced resuscitation within 4 hours of arrival were identified from the 2017 to 2019 Trauma Quality Improvement Program database. Time to balanced resuscitation was defined as the time of initiation of WB or all three components. Patient characteristics, resuscitation details, and outcomes were compared between WB and CT groups. Time to balanced resuscitation was compared using Kaplan-Meier analysis and Cox regression modeling to adjust for covariates. Additional multivariable regression models compared number of transfusion exposures, intensive care unit (ICU) length of stay, and mortality., Results: There were 390 patients (109 WB, 281 CT) with median age 7 years, 12% penetrating mechanism, 42% severe traumatic brain injury, and 49% in-hospital mortality. Time to balanced resuscitation was shorter for WB versus CT (median, 28 vs. 87 minutes; hazard ratio [HR], 2.93; 95% confidence interval [CI], 2.31-3.72; p < 0.0001). Whole blood patients received fewer transfusion exposures (mean, 3.2 vs. 3.9; adjusted incidence rate ratio, 0.82; 95% CI, 0.72-0.92; p = 0.001) and lower total product volumes (50 vs. 85 mL/kg; p = 0.01). Intensive care unit stays trended shorter for WB versus CT (median, 10 vs. 12 days; adjusted HR, 1.32; 95% CI, 0.93-1.86), while in-hospital mortality was similar (50% vs. 45%; adjusted odds ratio, 1.11; 95% CI, 0.65-1.88)., Conclusion: In critically injured preadolescent children receiving emergent transfusion, WB was associated with faster time to balanced resuscitation, fewer transfusion exposures, lower blood product volumes, and a trend toward shorter ICU stays than CT., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Intestinal atresia is a common cause of neonatal bowel obstruction. Atresias are often associated with other congenital anomalies. The purpose of the study was to evaluate associated anomalies, operative management, and postoperative outcomes of infants with intestinal atresia., Methods: A review of patients presenting to a single free-standing children's hospital from March 2012 through February 2022 was performed. The variables examined were type of atresia, additional congenital anomalies, type of operative intervention, and postoperative outcomes. Standard statistical methods were utilized., Results: A total of 75 patients with intestinal atresia were identified and several of these patients had multiple atresias. Isolated duodenal atresia patients were the most common (49.3%), followed by jejunal (32%) and ileal (12%). Mixed atresias were rare at 4%, with isolated pyloric and colonic also rare at 1.3% each. Malrotation was associated with 13% of patients and equally associated with duodenal and jejunoileal atresias. A low percentage (3%) of intestinal atresias was seen in conjunction with gastroschisis and concomitant malrotation. A majority of infants with duodenal atresia underwent standard duodenoduodenostomy (19% laparoscopic, 81% open). In infants with jejunoileal atresia, most underwent resection with primary anastomosis. A tapering enteroplasty was performed primarily in 13% of atresias. There were no significant differences noted in time to first feed or length of stay between those with and without tapering enteroplasty. Eleven percent of patients required subsequent intervention for stricture or small bowel obstruction. There was one death in this series., Conclusions: Consistent with other literature, duodenal atresia was the most common type of intestinal atresia. However, we demonstrated that malrotation was equally associated with duodenal and jejunoileal atresias while prior reports had shown a higher association with duodenal atresia. In our patient population, the use of tapering enteroplasty did not appear to be associated with outcomes. Overall, these infants have a low morbidity and mortality rate with a rare need for reoperation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis., Background: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis., Methods: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0., Results: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures., Conclusions: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis., Background: Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing before incision., Methods: This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from July 2016 to June 2020 who received antibiotics upon diagnosis of appendicitis between 1 and 6 hours before incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within 1 hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events., Results: A total of 3533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P <0.001) and iSSI rates were similar between groups [redosed: 1.2% vs non-redosed: 1.3%; odds ratio (OR) 0.84, (95%,CI, 0.39-1.83)]. In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs nonredosed: 2.5%; OR: 0.38, (95% CI, 0.17-0.84)], but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity., Conclusions: Redosing of antibiotics within 1 hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Damage-control resuscitation (DCR) consists of rapid control of bleeding, avoidance of hemodilution, acidosis, and hypothermia; early empiric balanced transfusions with red blood cells, plasma and platelets, or whole blood when available, and the use of intravenous or mechanical hemostatic adjuncts when indicated. The principles used in pediatric and adult trauma patients are quite similar. There are very important recognized physiologic differences in children with traumatic hemorrhagic shock that warrant slight variations in DCR. In pediatric trauma patients, early physiologic signs of shock may be different from adults and the early recognition of this is critical to enable prompt resuscitation and utilization of damage control principles. This review details the current principles of pediatric DCR based on the best available literature, expert consensus recommendations, and also describes a practical guide for implementation of DCR strategies for pediatric trauma patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Injured children with severe hemorrhage often receive blood product transfusions with ratios of plasma and platelets to packed red blood cells (PRBCs) approaching 1:1:1. Whether blood product ratios vary during pediatric resuscitation is unknown. This study (1) described precise timing of pediatric blood product administration, (2) characterized changes in blood product ratios over time, and (3) evaluated the association of blood products with early mortality while incorporating time-varying factors., Methods: Pediatric (younger than 18 years) trauma patients receiving high-volume transfusion (>40 mL/kg total products or >2 U PRBC or whole blood, during first 4 hours) were obtained from the 2017 to 2019 Trauma Quality Improvement Program database. The time of each individual product transfusion was recorded, along with demographics, injury details, and times of death. Patients were assigned to blood product groups at 15-minute intervals: high plasma/PRBC ratio (>1:1) with platelets, high plasma/PRBC ratio (>1:1) without platelets, low plasma/PRBC ratio (<1:1), PRBC only, and whole blood. Cox proportional hazards modeling for 24-hour mortality was performed, including blood product group as a time-varying variable and adjusting for relevant covariates., Results: Of 1,152 included patients (median age, 15 years; 32% penetrating, 28% severe traumatic brain injury [sTBI]), 18% died within 24 hours. During the resuscitation period, the number of patients in high-ratio groups increased over time, and patients switched blood product groups up to six times. There was no significant difference in mortality by blood product group. Among patients with sTBI, there was a strong trend toward lower mortality among high plasma/PRBC without platelets versus high plasma/PRBC with platelets (hazard ratio, 0.55; p = 0.07)., Conclusion: No significant association of high ratios or whole blood with mortality was seen when time-varying factors were incorporated. The impact of balanced resuscitation strategies, particularly platelet transfusion, may be greatest among patients with sTBI. Optimizing balanced resuscitation for children requires appropriately designed prospective studies., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Non-operative management of blunt liver and spleen injuries was championed initially in children with the first management guideline published in 2000 by the American Pediatric Surgical Association (APSA). Multiple articles have expanded on the original guidelines and additional therapy has been investigated to improve care for these patients. Based on a literature review and current consensus, the management guidelines for the treatment of blunt liver and spleen injuries are presented., Methods: A recent literature review by the APSA Outcomes committee [2] was utilized as the basis for the guideline recommendations. A task force was assembled from the APSA Committee on Trauma to review the original guidelines, the literature reported by the Outcomes Committee and then to develop an easy to implement guideline., Results: The updated guidelines for the management of blunt liver and spleen injuries are divided into 4 sections: Admission, Procedures, Set Free and Aftercare. Admission to the intensive care unit is based on abnormal vital signs after resuscitation with stable patients admitted to the ward with minimal restrictions. Procedure recommendations include transfusions for low hemoglobin (<7 mg/dL) or signs of ongoing bleeding. Angioembolization and operative exploration is limited to those patients with clinical signs of continued bleeding after resuscitation. Discharge is based on clinical condition and not grade of injury. Activity restrictions remain the same while follow-up imaging is only indicated for symptomatic patients., Conclusion: The updated APSA guidelines for the management of blunt liver and spleen injuries present an easy-to-follow management strategy for children., Level of Evidence: Level 5., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: This study examined differences in clinical and resuscitation characteristics between injured children with and without severe traumatic brain injury (sTBI) and aimed to identify resuscitation characteristics associated with improved outcomes following sTBI., Methods: This is a post hoc analysis of a prospective observational study of injured children younger than 18 years (2018-2019) transported from the scene, with elevated shock index pediatric-adjusted on arrival and head Abbreviated Injury Scale score of ≥3. Timing and volume of resuscitation products were assessed using χ 2t test, Fisher's exact t test, Kruskal-Wallis, and multivariable logistic regression analyses., Results: There were 142 patients with sTBI and 547 with non-sTBI injuries. Severe traumatic brain injury patients had lower initial hemoglobin (11.3 vs. 12.4, p < 0.001), greater initial international normalized ratio (1.4 vs. 1.1, p < 0.001), greater Injury Severity Score (25 vs. 5, p < 0.001), greater rates of ventilator (59% vs. 11%, p < 0.001) and intensive care unit (ICU) requirement (79% vs. 27%, p < 0.001), and more inpatient complications (18% vs. 3.3%, p < 0.001). Severe traumatic brain injury patients received more prehospital crystalloid (25% vs. 15%, p = 0.008), ≥1 crystalloid boluses (52% vs. 24%, p < 0.001), and blood transfusion (44% vs. 12%, p < 0.001) than non-sTBI patients. Among sTBI patients, receipt of ≥1 crystalloid bolus (n = 75) was associated with greater ICU need (92% vs. 64%, p < 0.001), longer median ICU (6 vs. 4 days, p = 0.027) and hospital stay (9 vs. 4 days, p < 0.001), and more in-hospital complications (31% vs. 7.5%, p = 0.003) than those who received <1 bolus (n = 67). These findings persisted after adjustment for Injury Severity Score (odds ratio, 3.4-4.4; all p < 0.010)., Conclusion: Pediatric trauma patients with sTBI received more crystalloid than those without sTBI despite having a greater international normalized ratio at presentation and more frequently requiring blood products. Excessive crystalloid may be associated with worsened outcomes, including in-hospital mortality, seen among pediatric sTBI patients who received ≥1 crystalloid bolus. Further attention to a crystalloid sparing, early transfusion approach to resuscitation of children with sTBI is needed., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Introduction: Endoscopic surveillance guidelines for patients with repaired esophageal atresia (EA) rely primarily on expert opinion. Prior to embarking on a prospective EA surveillance registry, we sought to understand EA surveillance practices within the Eastern Pediatric Surgery Network (EPSN)., Methods: An anonymous, 23-question Qualtrics survey was emailed to 181 physicians (surgeons and gastroenterologists) at 19 member institutions. Likert scale questions gauged agreement with international EA surveillance guideline-derived statements. Multiple-choice questions assessed individual and institutional practices., Results: The response rate was 77%. Most respondents (80%) strongly agree or agree that EA surveillance endoscopy should follow a set schedule, while only 36% claimed to perform routine upper GI endoscopy regardless of symptoms. Many institutions (77%) have an aerodigestive clinic, even if some lack a multi-disciplinary EA team. Most physicians (72%) expressed strong interest in helping develop evidence-based guidelines., Conclusions: Our survey reveals physician agreement with current guidelines but weak adherence. Surveillance methods vary greatly, underscoring the lack of evidence-based data to guide EA care. Aerodigestive clinics may help implement surveillance schedules. Respondents support evidence-based protocols, which bodes well for care standardization. Results will inform the first multi-institutional EA databases in the United States (US), which will be essential for evidence-based care., Level of Evidence: This is a prognosis study with level 4 evidence., Competing Interests: Conflicts of interest Author has no competing interests or financial conflicts. This study has institutional financial support only that has allowed access to research staff., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to evaluate the clinical utility of a routine predischarge WBC count (RPD-WBC) for predicting postdischarge organ space infection (OSI) in children with complicated appendicitis., Study Design: This was a multicenter study using NSQIP-Pediatric data from 14 hospitals augmented with RPD-WBC data obtained through supplemental chart review. Children with fever or surgical site infection diagnosed during the index admission were excluded. The positive predictive value (PPV) for postdischarge OSI was calculated for RPD-WBC values of persistent leukocytosis (≥9.0 × 10 3 cells/μL), increasing leukocytosis (RPD-WBC > preoperative WBC), quartiles of absolute RPD-WBC, and quartiles of relative proportional change from preoperative WBC. Logistic regression was used to calculate predictive values adjusted for patient age, appendicitis severity, and use of postdischarge antibiotics., Results: A total of 1,264 children were included, of which 348 (27.5%) had a RPD-WBC obtained (hospital range: 0.8 to 100%, p < 0.01). The median RPD-WBC was similar between children who did and did not develop a postdischarge OSI (9.0 vs 8.9; p = 0.57), and leukocytosis was absent in 50% of children who developed a postdischarge OSI. The PPV of RPD-WBC was poor for both persistent and increasing leukocytosis (3.9% and 9.8%, respectively) and for thresholds based on the quartiles of highest RPD-WBC values (>11.1, PPV: 6.4%) and greatest proportional change (<32% decrease from preoperative WBC; PPV: 7.8%)., Conclusions: Routine predischarge WBC data have poor predictive value for identifying children at risk for postdischarge OSI after appendectomy for complicated appendicitis., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The objective was to explore the hospital-level relationship between routine pre-discharge WBC utilization (RPD-WBC) and outcomes in children with complicated appendicitis., Methods: Multicenter analysis of NSQIP-Pediatric data from 14 consortium hospitals augmented with RPD-WBC data. WBC were considered routine if obtained within one day of discharge in children who did not develop an organ space infection (OSI) or fever during the index admission. Hospital-level observed-to-expected ratios (O/E) for 30-day outcomes (antibiotic days, imaging utilization, healthcare days, and OSI) were calculated after adjusting for appendicitis severity and patient characteristics. Spearman correlation was used to explore the relationship between hospital-level RPD-WBC utilization and O/E's for each outcome., Results: 1528 children were included. Significant variation was found across hospitals in RPD-WBC use (range: 0.7-100%; p < 0.01) and all outcomes (mean antibiotic days: 9.9 [O/E range: 0.56-1.44, p < 0.01]; imaging: 21.9% [O/E range: 0.40-2.75, p < 0.01]; mean healthcare visit days: 5.7 [O/E 0.74-1.27, p < 0.01]); OSI: 14.1% [O/E range: 0.43-3.64, p < 0.01]). No correlation was found between RPD-WBC use and antibiotic days (r = +0.14, p = 0.64), imaging (r = -0.07, p = 0.82), healthcare days (r = +0.35, p = 0.23) or OSI (r = -0.13, p = 0.65)., Conclusions: Increased RPD-WBC utilization in pediatric complicated appendicitis did not correlate with improved outcomes or resource utilization at the hospital level., Level of Evidence: III., Type of Study: Clinical Research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis., Objective: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization., Design, Setting, and Participants: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020., Exposures: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports., Main Outcomes and Measures: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals., Results: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P < .001). Reviewers agreed on presence or absence of GSE findings in 93.3% of cases (weighted κ, 0.89; 95% CI, 0.86-0.92). In multivariable analysis, GSE findings were associated with increased odds of any surgical site infection (4.3% vs 2.2%; odds ratio [OR], 1.91; 95% CI, 1.35-2.71; P < .001), organ space infection (2.8% vs 1.1%; OR, 2.18; 95% CI, 1.30-3.67; P = .003), postoperative imaging (5.8% vs 3.7%; OR, 1.70; 95% CI, 1.23-2.36; P = .002), and prolonged mean postoperative length of stay (1.6 vs 0.9 days; rate ratio, 1.43; 95% CI, 1.32-1.54; P < .001)., Conclusions and Relevance: In children with nonperforated appendicitis, findings of gangrene, suppuration, or exudate are associated with increased surgical site infections and resource utilization. Further investigation is needed to establish the role and duration of postoperative antibiotics and inpatient management to optimize outcomes in this cohort of children.

Peroxiredoxin-2 (Prx-2) is a critical antioxidant protein in red blood cells (RBC). Prx-2 is oxidized to a disulfide covalently-bound dimer by H 2 O 2 , and then reduced back by the NADPH-dependent thioredoxin-thioredoxin reductase system. The reduction of oxidized Prx-2 is relatively slow in RBCs. Since Prx-2 is highly abundant, Prx-2s' peroxidase catalytic cycle is not considered to be limiting under normal conditions. However, whether Prx-2 recycling becomes limiting when RBCs are exposed to stress is not known. Using three different model systems characterized by increased oxidative damage to RBCs spanning the physiologic (endogenous RBCs of different ages), therapeutic (cold-stored RBCs in blood banks) and pathologic (RBCs from sickle cell disease (SCD) patients and humanized SCD mice) spectrum, basal levels of Prx-2 oxidation and Prx-2 recycling kinetics after addition of H 2 O 2 were determined. The reduction of oxidized Prx-2 was significantly slower in older versuin older versus younger RBCs, in RBCs stored for 4-5 weeks compared to 1 week, and in RBC from pediatric SCD patients compared to RBCs from control non-SCD patients. Similarly, the rate of Prx-2 recycling was slower in humanized SCD mice compared to WT mice. Treatment of RBC with carbon monoxide (CO) to limit heme-peroxidase activity had no effect on Prx-2 recycling kinetics. Treatment with glucose attenuated slowed Prx-2 recycling in older RBCs and SCD RBCs, but not stored RBCs. In conclusion, the reduction of oxidized Prx-2 can be further slowed in RBCs, which may limit the protection afforded by this antioxidant protein in settings associated with erythrocyte stress., (© 2022 Federation of American Societies for Experimental Biology.)

Background: Pediatric trauma patients sustaining blunt abdominal trauma (BAT) with intra-abdominal injury (IAI) are frequently admitted to the intensive care unit (ICU). This study was performed to identify predictors for ICU admission following BAT., Methods: Prospective study of children (< 16 years) who presented to 14 Level-One Pediatric Trauma Centers following BAT over a 1-year period. Patients were categorized as ICU or non-ICU patients. Data collected included vitals, physical exam findings, laboratory results, imaging, and traumatic injuries. A multivariable hierarchical logistic regression model was used to identify predictors of ICU admission. Predictive ability of the model was assessed via tenfold cross-validated area under the receiver operating characteristic curves (cvAUC)., Results: Included were 2,182 children with 21% (n = 463) admitted to the ICU. On univariate analysis, ICU patients were associated with abnormal age-adjusted shock index, increased injury severity scores (ISS), lower Glasgow coma scores (GCS), traumatic brain injury (TBI), and severe solid organ injury (SOI). With multivariable logistic regression, factors associated with ICU admission were severe trauma (ISS > 15), anemia (hematocrit < 30), severe TBI (GCS < 8), cervical spine injury, skull fracture, and severe solid organ injury. The cvAUC for the multivariable model was 0.91 (95% CI 0.88-0.92)., Conclusion: Severe solid organ injury and traumatic brain injury, in association with multisystem trauma, appear to drive ICU admission in pediatric patients with BAT. These results may inform the design of a trauma bay prediction rule to assist in optimizing ICU resource utilization after BAT., Study Design: Prognosis study., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients., Design: Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB])., Setting: Not applicable., Patients: Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions., Interventions: None., Measurements and Main Results: A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients., Conclusions: The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners., Competing Interests: Drs. Nellis, Bateman, Bembea, and Russell received support for article research from the National Institutes of Health. Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorders and Stroke (R01NS106292), the National Institute of Child Health and Human Development, and Grifols Investigator Sponsored Research Grant. Dr. Nishijima received funding from Bristol Myers Squibb. Dr. Emani received funding from Cheisi Pharmaceuticals. Dr. Haas received funding from Octapharma. Dr. Goel received funding from the National Heart, Lung, and Blood Institute and Rigel Pharmaceuticals. Dr. Crighton disclosed that she is employed by Royal Children’s Hospital of Melbourne, Australia and that she was the Australian and New Zealand Society of Blood Transfusion President. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children following noncardiac surgery and critically ill children undergoing invasive procedures outside the operating room from the Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding., Design: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children., Setting: Not applicable., Patients: Critically ill children undergoing invasive procedures outside of the operating room or noncardiac surgery., Interventions: None., Measurements and Main Results: A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill children following noncardiac surgery or undergoing invasive procedures outside of the operating room. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed eight expert consensus statements focused on the critically ill child following noncardiac surgery and 10 expert consensus statements on the critically ill child undergoing invasive procedures outside the operating room., Conclusions: Evidence regarding plasma and platelet transfusion in critically ill children in this area is very limited. The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding Consensus Conference developed 18 pediatric specific consensus statements regarding plasma and platelet transfusion management in these critically ill pediatric populations., Competing Interests: Dr. Crighton disclosed that she is employed by Royal Children’s Hospital of Melbourne, Australia, and that she was the Australian and New Zealand Society of Blood Transfusion President. Drs. Russel and Nellis received support for article research from the National Institutes of Health. Dr. Haas received funding from Octapharma. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To present a list of high-priority research initiatives for the study of plasma and platelet transfusions in critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding., Design: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children., Setting: Not applicable., Patients: Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions., Interventions: None., Measurements and Main Results: A panel of 13 experts developed research priorities for the study of plasma and platelet transfusions in critically ill children which were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. The specific priorities focused on the following subpopulations: severe trauma, traumatic brain injury, intracranial hemorrhage, cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, oncologic diagnosis or stem cell transplantation, acute liver failure and/or liver transplantation, noncardiac surgery, invasive procedures outside of the operating room, and sepsis and/or disseminated intravascular coagulation. In addition, tests to guide plasma and platelet transfusion, as well as component selection and processing, were addressed. We developed four general overarching themes and 14 specific research priorities using modified Research and Development/University of California, Los Angeles methodology., Conclusions: Studies are needed to focus on the efficacy/harm, dosing, timing, and outcomes of critically ill children who receive plasma and/or platelet transfusions. The completion of these studies will facilitate the development of evidence-based recommendations., Competing Interests: Dr. Bembea’s institution received funding from the National Institute of Neurological Disorders and Stroke (R01NS106292), the National Institute of Child Health and Human Development, and Grifols Investigator Sponsored Research Grant. Drs. Bembea and Russell received support for article research from the National Institutes of Health. Dr. Steiner received funding from Pumps for Kids, Infants, and Neonates (PumpKIN) Data Safety and Monitoring Board and HealthCore. Dr. Crighton disclosed that she is employed by the Royal Children’s Hospital of Melbourne, Australia and was the Australian and New Zealand Society of Blood Transfusion President. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Introduction: Coronavirus Disease-19 (COVID-19) was declared a pandemic in March 2020. States issued stay-at-home orders and hospitals cancelled non-emergent surgeries. During this time, we anecdotally noticed more admissions for perforated appendicitis. Therefore, we hypothesized that during the months following the COVID-19 pandemic declaration, more children were presenting with perforated appendicitis., Materials and Methods: This is a retrospective cohort study reviewing pediatric patients admitted at a single institution with acute and/or perforated appendicitis between October 2019 to May 2020. Interval appendectomies were excluded. COVID-19 months were designated as March, April, and May 2020. Additional analysis of March, April, and May 2019 was performed for comparison purposes. Analyzed data included demographics, symptoms, white blood cell count, imaging findings, procedures performed, and perforation status. Statistical analysis was performed., Results: During the study period, 285 patients were admitted with the diagnosis of acute appendicitis with 95 patients being perforated. We identified a significant increase in perforated appendicitis cases in the three COVID-19 months compared with the preceding five months (45.6% vs 26.4%; P <0.001). In addition, a similar significant increase was identified when comparing to the same months a year prior (P = 0.003). No significant difference in duration of pain was identified (P=0.926)., Conclusion: The COVID-19 pandemic and its associated stay-at-home orders have had downstream effects on healthcare. Our review has demonstrated a significant increase in the number of children presenting with perforated appendicitis following these stay-at-home ordinances. These results demonstrate that further investigations into the issues surrounding access to healthcare, especially during this pandemic, are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/purpose: Continuous renal replacement therapy (CRRT) is difficult in neonates for several reasons, including problems with catheter placement and maintenance. We sought to compare outcomes between standard hemodialysis catheters (HDC) and 6Fr-tunneled central venous catheters (TC-6Fr)., Methods: We evaluated neonates who received CRRT from December 2013 - January 2018. All patients received CRRT with the Aquadex (Baxter Corporation, Minneapolis, Minnesota) circuit. Data regarding patient demographics, CRRT indication, catheter days, reason for removal, and catheter-specific complications were analyzed., Results: Forty-six catheters were placed in 26 neonates; nine of these were 6Fr-tunneled catheters. The median age and mean weight at CRRT initiation was 9.5 days (IQR 4-31) and 3.5 kg (+/- 0.6 kg), respectively. TC-6Fr lasted longer (median of 28 days vs 10 days, p = 0.02), required fewer revisions (0 vs 0.16/10 catheter days) and were less commonly removed due to bleeding complications (0% vs 10.8%), occlusion (11.1% vs 18.9%), or malposition (0% vs 8.1%); none of these differences were statistically significant. TC-6Fr were associated with higher infection rates (33.3% vs 0%, p = 0.01) than HDC., Conclusions: TC-6Fr use resulted in less need for catheter revisions and provided longer-lasting vascular access, which may influence infection rates. This catheter provides neonates in need of CRRT more reliable vascular access., Level of Evidence: III., Competing Interests: Declaration of Competing Interest All authors declare no real or perceived conflicts of interest that could affect the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit for publication. For full disclosure, we provide here an additional list of other author's commitments and funding sources that are not directly related to this study: David J Askenazi serves on the speaker board for Baxter (Baxter, USA), and the Acute Kidney Injury (AKI) Foundation (Cincinnati, OH, USA); he also receives grant funding for studies not related to this manuscript from Octapharma AG (Switzerland), CHF solutions, Baxter and the National Institutes of Health - National Institutes of Diabetes and Digestive and Kidney Diseases (NIHNIDDK, R01 DK103608) and consults for CHF solutions. None of these commitments are related to the scope of the current study., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The Accreditation Council for Graduate Medical Education (ACGME) monitors fellow case numbers. Previous literature has shown new fellowships detrimentally affecting general surgery residency case numbers. We hypothesize that an increase in pediatric otolaryngology and pediatric urology fellowships would decrease overlapping case numbers in pediatric surgery fellowships., Materials and Methods: A review of each specialties' fellowship match results was performed. Publicly available pediatric surgery cases logs were reviewed for overlapping cases including thyroidectomy, parathyroidectomy, branchial cleft cyst excision, thyroglossal duct cyst excision, major neck tumor excision, nephrectomy, orchidopexy, inguinal hernia, and testicular torsion. Analyzed data included average case numbers and number of fellows each year. Linear regression analysis was performed., Results: We identified a significant increase in fellowship graduates from 2003 to 2018 (p < 0.006). Reviewed cases showed little fluctuation despite an increase in graduates. A decrease in tumor-related nephrectomies and orchidopexies was identified for pediatric surgery fellows (p < 0.001; p < 0.004). Though significant, nephrectomy fluctuation was between 2 and 4 cases. Similarly, we identified a significant rise in thyroidectomies (p < 0.001). Again, the increase was by 3 cases each year., Conclusions: Despite the increase in number of fellowships, there has been a minimal overall effect on pediatric surgery case volume. Continuing to monitor these trends will help ensure adequate training for all pediatric surgical subspecialties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Diversity in the physician workforce remains a priority in healthcare as it has been shown to improve outcomes. Decisions for choosing specific fields in medicine are partly influenced by mentors, which tend to be the same sex or ethnicity. Females are starting to outnumber males in medical school and minorities are targeted for recruitment. We hypothesized that diversity in pediatric surgery has increased over time., Methods: The recently published A Genealogy of North American Pediatric Surgery was utilized to identify graduating pediatric surgery fellows from 1981 to 2018. Organization websites were used to identify past and current leaders. A web-based analysis, including online facial recognition software, was performed. A year-to-year and decade-to-decade demographic comparison was completed., Results: 1217 pediatric surgery fellows graduated between 1981 and 2018. When comparing graduates from the first and last decades, an increase from 16.9% to 39.5% for female graduates was observed (p = 0.046). A significant increase in nonwhite graduates was seen for all races (p < 0.05). Representation in leadership was White and male dominant., Conclusion: There was a significant increase in diversity in pediatric surgery fellowship graduates. There were increasing trends in female graduates and all nonwhite racial groups. Focusing on enhancing the pipeline and mentoring underrepresented minorities will continue to enhance this trend for the field of pediatric surgery., Level of Evidence: III; Retrospective Review., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The Accreditation Council for Graduate Medical Education (ACGME) regulates the general surgery residency curriculum. Case volume remains a priority as recent concerns surrounding a lack of proficiency for certain surgical cases have circulated. We hypothesize that there is a significant decrease in pediatric surgery case numbers during general surgery residency despite residents meeting the minimum case requirements., Methods: We reviewed publicly available ACGME case reports for general surgery residency from 1999 to 2018. Cases are classified as Surgeon Chief or Surgeon Junior. Analyzed data included case classifications, number of residents, and number of residency programs. Simple linear regression analysis was performed., Results: We identified a significant decrease in total number of logged pediatric surgery cases over the past 20 years (p<0.001). Nearly 60% of cases were logged under a single category - inguinal/umbilical hernia. From the past five years, pyloric stenosis was the only other category with an average of greater than two cases logged (range 2.1-2.8)., Conclusion: We identified a significant decrease in total pediatric surgery case numbers during general surgery residency from 1999 to 2018. Though meeting set requirements, overall case variety was limited. With minimal number of cases required by the ACGME, graduating general surgery residents may lack proficiency in simple pediatric surgery cases., (Copyright © 2021. Published by Elsevier Inc.)

Massive transfusion in pediatric patients is infrequent but associated with much higher mortality than in adults. Blood transfusion and hematology has conceptualized ideas such as blood failure and the interplay of the blood-endothelium interface to understand coagulopathy in the context of hemorrhagic shock. Researchers are still searching for an appropriate definition of what constitutes a pediatric massive transfusion. There is no universally accepted protocol for massive transfusion and how to address the many complications that can arise. Pharmacologic adjuncts to resuscitation may prove beneficial in reducing coagulopathy during pediatric massive transfusion, but high-quality evidence has not yet emerged., Competing Interests: Disclosure P.C. Spinella: consultant for Secure Transfusion Services, Cerus, and Octapharma. J.W. Cannon: DOD funding on resuscitation/decision support, UpToDate royalties on REBOA (resuscitative endovascular balloon occlusion of the aorta). The other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia., Background: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators., Methods: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability., Conclusions: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes., Competing Interests: Deborah J. del Junco received no funding support or conflicts of interest to disclose and Hemanext. Brohi K reports no active or recent relevant conflicts of interests. Funding support from Barts Health NHS Trust, Barts Charity, National Institute of Health Research UK, Medical Research Council UK. Andrew P. Cap is an active duty officer in the US Army and has no conflicts of interest to disclose. Newgard C has no conflicts of interest to report. Funding for trauma research from NICHD and HRSA. Anthony E. Pusateri is a US Government employee and has no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Trauma is the leading cause of pediatric and adolescent morbidity and mortality. Firearm-related injuries and deaths contribute substantially to the overall disease burden. This study described the intent, location, demographics, and outcomes of a nationally representative pediatric population with firearm injuries. We hypothesized that younger patients would have a higher percentage of unintentional and self-inflicted injuries with associated higher mortality rates., Materials and Methods: The National Trauma Data Bank, maintained by the American College of Surgeons, from 2010 to 2016 was utilized. All pediatric patients (0-19 y) with firearm injuries who had complete data were analyzed for mechanism, location, demographics, and outcomes. Basic descriptive statistics were used to compare subgroups. Multivariable logistic regression analysis was applied to investigate risk factors for firearm injury-caused mortality., Results: In the study period, 46,039 pediatric patients sustained firearm injuries (median age = 17 y). Males, Blacks, ages 15-19, and the Southern region were the most common injured demographics. However, subgroup analysis showed the demographics differ for self-inflicted and unintentional firearm injuries, which had significantly higher White patients (66.6% and 47.9%, respectively; P < 0.001). Nearly 76% of injuries were related to assaults, 14% were unintentional, 5% were self-inflicted, and 5% were undetermined. The overall mortality was nearly 12%. The youngest population had higher proportion of unintentional injuries and highest mortality rate when compared with other classifications of intent (P < 0.001)., Conclusions: Pediatric firearm injuries have high mortality, especially in the youngest populations. Age-tailored prevention strategies, such as strict child access prevention laws and enforced gun storage violations, may help in reducing firearm injuries and improving health outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Pediatric foreign body ingestion remains a common reason for emergency department (ED) visits. Button battery ingestion is an established surgical emergency, requiring immediate removal. Timing of removal for other foreign bodies remains controversial. We hypothesize that there is no difference in complication rate or successful removal of esophageal foreign bodies that wait until the following morning for removal. Materials and Methods: A retrospective review for cases involving esophageal foreign body removal by pediatric surgery or pediatric gastroenterology from November 2015 to November 2019 was performed. Patients were divided into two groups based on ED arrival-daytime (05:00-16:59); nighttime (17:00-04:59). Imaging confirmed an esophageal foreign body. Data collected included basic demographics, time of presentation, time of procedure, symptoms, location of the foreign body, and complications within 30 days. Statistical analysis was performed. Results: After excluding button batteries, 273 children underwent esophageal foreign body removal. Two-thirds presented at night. A significant difference was identified in the median time from ED to the operating room when comparing daytime (194.8 minutes; interquartile range [IQR]: 108.5-347) versus nighttime groups (643 minutes; IQR: 471.5-745; P  < .001). Nine children had a complication or readmission within 30 days of their procedure and 25 patients had migration of their foreign body into the stomach, both with no significant difference ( P  = .94; P  = .98, respectively). Conclusion: We found that waiting until the following morning had minimal impact on complications or success rate when removing esophageal foreign bodies. By waiting, institutions with limited personnel can keep resources and staff available for more pressing emergencies.

Background: Case number requirements by the Accreditation Council for Graduate Medical Education (ACGME) have recently changed in general surgery residency and pediatric surgery fellowship. Overall, pediatric surgery fellowship case volumes remain high, but there may be limited exposure to many index cases. We hypothesize that pediatric antireflux surgery is decreasing nationally, and this trend is independent of the fluctuating number of pediatric surgery fellows., Materials and Methods: A review of publicly available ACGME case reports from 2003 to 2018 was performed. Both open and laparoscopic antireflux surgery cases were evaluated. Analyzed data included average case number per fellow, minimum and maximum case numbers, and number of fellows each year. Simple and multiple linear regression analyses were performed., Results: We identified a significant relationship (P < 0.001) between the total number of antireflux procedures and the years of operation. The slope coefficient was -1.45, meaning the number of operations decreased by an average of 1.45 per year from 2003 to 2018 . The number of fellows fluctuated during this time period (range: 24-45). With multiple linear regression analysis, we found that the number of fellows did not affect the decline of antireflux surgery seen over the years (P = 0.91)., Conclusions: Case numbers continue to be an important topic in ACGME discussions for surgical residency and subspecialty fellowships. Our review has shown a national decline in the number of pediatric antireflux surgeries performed in pediatric surgery fellowship. Identifying additional trends in surgical management of diseases may aid in the evolution of the pediatric surgery curriculum., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine the relationship between timing and volume of crystalloid before blood products and mortality, hypothesizing that earlier transfusion and decreased crystalloid before transfusion would be associated with improved outcomes., Methods: A multi-institutional prospective observational study of pediatric trauma patients younger than 18 years, transported from the scene of injury with elevated age-adjusted shock index on arrival, was performed from April 2018 to September 2019. Volume and timing of prehospital, emergency department, and initial admission resuscitation were assessed including calculation of 20 ± 10 mL/kg crystalloid boluses overall and before transfusion. Multivariable Cox proportional hazards and logistic regression models identified factors associated with mortality and extended intensive care, ventilator, and hospital days., Results: In 712 children at 24 trauma centers, mean age was 7.6 years, median (interquartile range) Injury Severity Score was 9 (2-20), and in-hospital mortality was 5.3% (n = 38). There were 311 patients(43.7%) who received at least one crystalloid bolus and 149 (20.9%) who received blood including 65 (9.6%) with massive transfusion activation. Half (53.3%) of patients who received greater than one crystalloid bolus required transfusion. Patients who received blood first (n = 41) had shorter median time to transfusion (19.8 vs. 78.0 minutes, p = 0.005) and less total fluid volume (50.4 vs. 86.6 mL/kg, p = 0.033) than those who received crystalloid first despite similar Injury Severity Score (median, 22 vs. 27, p = 0.40). On multivariable analysis, there was no association with mortality (p = 0.51); however, each crystalloid bolus after the first was incrementally associated with increased odds of extended ventilator, intensive care unit, and hospital days (all p < 0.05). Longer time to transfusion was associated with extended ventilator duration (odds ratio, 1.11; p = 0.04)., Conclusion: Resuscitation with greater than one crystalloid bolus was associated with increased need for transfusion and worse outcomes including extended duration of mechanical ventilation and hospitalization in this prospective study. These data support a crystalloid-sparing, early transfusion approach for resuscitation of injured children., Level of Evidence: Therapeutic, level IV.

Background: Malnutrition in critically ill patients is common in neonates and children, including those that receive extracorporeal life support (ECLS). We hypothesize that nutritional adequacy is highly variable, overall nutritional adequacy is poor, and enteral nutrition is underutilized in this population., Materials and Methods: A retrospective study of neonates and children (age<18 y) receiving ECLS at 5 centers from 2012 to 2014 was performed. Demographic, clinical, and outcome data were analyzed. Continuous variables are presented as median [IQR]. Adequate nutrition was defined as meeting 66% of daily caloric goals during ECLS support., Results: Two hundred and eighty three patients received ECLS; the median age was 12 d [3 d, 16.4 y] and 47% were male. ECLS categories were neonatal pulmonary 33.9%, neonatal cardiac 25.1%, pediatric pulmonary 17.7%, and pediatric cardiac 23.3%. The predominant mode was venoarterial (70%). Mortality was 41%. Pre-ECLS enteral and parenteral nutrition was present in 80% and 71.5% of patients, respectively. The median percentage days of adequate caloric and protein nutrition were 50% [0, 78] and 67% [22, 86], respectively. The median percentage days with adequate caloric and protein nutrition by the enteral route alone was 22% [0, 65] and 0 [0, 50], respectively. Gastrointestinal complications occurred in 19.7% of patients including hemorrhage (4.2%), enterocolitis (2.5%), intra-abdominal hypertension or compartment syndrome (0.7%), and perforation (0.4%)., Conclusions: Although nutritional delivery during ECLS is adequate, the use of enteral nutrition is low despite relatively infrequent observed gastrointestinal complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Although bleeding frequently occurs in critical illness, no published definition to date describes the severity of bleeding accurately in critically ill children. We sought to develop diagnostic criteria for bleeding severity in critically ill children., Design: Delphi consensus process of multidisciplinary experts in bleeding/hemostasis in critically ill children, followed by prospective cohort study to test internal validity., Setting: PICU., Patients: Children at risk of bleeding in PICUs., Interventions: None., Measurements and Main Results: Twenty-four physicians worldwide (10 on a steering committee and 14 on an expert committee) from disciplines related to bleeding participated in development of a definition for clinically relevant bleeding. A provisional definition was created from 35 descriptors of bleeding. Using a modified online Delphi process and conference calls, the final definition resulted after seven rounds of voting. The Bleeding Assessment Scale in Critically Ill Children definition categorizes bleeding into severe, moderate, and minimal, using organ dysfunction, proportional changes in vital signs, anemia, and quantifiable bleeding. The criteria do not include treatments such as red cell transfusion or surgical interventions performed in response to the bleed. The definition was prospectively applied to 40 critically ill children with 46 distinct bleeding episodes. The kappa statistic between the two observers was 0.74 (95% CI, 0.57-0.91) representing substantial inter-rater reliability., Conclusions: The Bleeding Assessment Scale in Critically Ill Children definition of clinically relevant bleeding severity is the first physician-driven definition applicable for bleeding in critically ill children derived via international expert consensus. The Bleeding Assessment Scale in Critically Ill Children definition includes clear criteria for bleeding severity in critically ill children. We anticipate that it will facilitate clinical communication among pediatric intensivists pertaining to bleeding and serve in the design of future epidemiologic studies if it is validated with patient outcomes.

Background: Hepatoblastoma and Wilms tumor are the most common primary liver and kidney tumor in children, respectively, and little is documented about patient outcomes in the immediate perioperative period. The aim of this study was to analyze the short-term outcomes of pediatric patients after surgical resection for hepatoblastoma and Wilms tumor., Methods: We queried the 2012-2016 ACS National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database for patients with hepatoblastoma who underwent liver resection and patients with Wilms tumor who underwent a partial or total nephrectomy. Patient demographics, preoperative, intraoperative, and postoperative characteristics were analyzed. Multivariate logistic regression was used to determine independent risk factors for unplanned reoperations., Results: There were a total of 189 patients with hepatoblastoma and 586 patients with Wilms in National Surgical Quality Improvement Program-Pediatric. The mean age of patients with hepatoblastoma was 3.1 y and 4.2 y in the Wilms group. Nine percent (n = 17) of patients underwent an unplanned reoperation after hepatectomy, and 4.1% (n = 24) of patients with Wilms experienced an unplanned reoperation. Over half of patients with hepatoblastoma (59.8%, n = 113) and 29.7% (n = 174) patients with Wilms tumor received a blood transfusion in the perioperative period. Patients in both groups demonstrated low rates of surgical site infections, but 6.3% (n = 12) of hepatoblastoma patients showed evidence of sepsis., Conclusions: This study will allow providers to more effectively counsel families of the common morbidities in the associated perioperative period following surgical resection of either solid tumor type including the substantial risk of blood transfusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors because of an error involving the dataset which doubled the reported sample size, thereby invalidating the analysis. The authors reported this error immediately upon discovering the problem. The authors regret the error., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pancreatic islet cell tumors are rare in adolescents, and most studies published to date focus on older patients. We utilized a national database to describe the histology and clinical pattern of pancreatic islet cell tumors in adolescent and young adult (AYA) patients, and to compare AYAs to older adults. We hypothesized that AYAs with pancreatic islet cell tumors would have better overall survival., Methods: The National Cancer Data Base (NCDB, 1998-2012) was queried for AYA patients (15-39 years) with a pancreatic islet cell tumor diagnosis. Demographics, tumor characteristics, treatment modalities, and outcomes were abstracted and compared to adults (≥40 years)., Results: 383 patients (56.4% female, 65% non-Hispanic Whites) were identified, with a median age of 27 (IQR 16-34) years. Islet cell carcinoma was the most common histology. Of patients with known stage of disease, 49% presented with early stage (I or II). Seventy percent of patients underwent surgical resection, including local excision 44%, Whipple procedure 37.5%, or total pancreatectomy 19%. Chemotherapy was utilized in 27% and radiotherapy in 7%. All-cause mortality was 36%. AYA patients underwent more extensive resections (p = 0.001) and had lower mortality rates (p < 0.001), with no differences in tumor stage or use of adjuvant therapies, when compared to adults., Conclusions: AYA patients with pancreatic islet cell tumors had comparable utilization of adjuvant therapies but underwent more extensive resections and demonstrated a higher overall survival rate than adult counterparts. Further investigation into approaches to earlier diagnosis and tailoring of multimodality therapy of these neoplasms in the AYA population is needed., Levels of Evidence: Prognostic Study, Level II - retrospective study., (Copyright © 2019. Published by Elsevier Inc.)

Background: Solid pseudopapillary neoplasms (SPPNs) comprise the majority of pediatric pancreatic neoplasms. We queried the National Cancer Database to compare pediatric and adult patients with SSPNs to examine differences in demographics, tumor characteristics, treatment, and overall survival. We aimed to determine if survival differences existed between adult and pediatric patients with SPPN., Methods: The National Cancer Database (2004-2014) was reviewed, and patients were stratified by age at diagnosis: pediatric (≤21 y) and adult (≥22 y). Demographics, comorbidities, tumor characteristics, diagnostic periods, treatments, and survival rates were compared using pooled variance t-tests and chi-square, followed by multivariate Cox proportional hazard model (α = 0.05). Log-rank test was used to compare survival., Results: A total of 468 patients were analyzed and categorized according to age group. Four hundred and fourteen patients were included in the survival analysis. The pediatric patients were primarily female, Caucasian, had no comorbidities, and presented with stage I disease. Race/ethnicity, gender, socioeconomic status, comorbidities, and disease stage at presentation were similar between the groups. There was no difference in time to initiation of therapy or to surgical intervention. No significant difference was found in type of surgical resection, chemotherapy, or radiotherapy utilization. Despite the similarities between groups, comparison of overall survival demonstrated improved survival of pediatric SPPN compared with adult SPPN in every pathologic stage., Conclusions: These results suggest that pediatric and adult SPPNs are similar with regards to demographics, tumor characteristics, and treatment modalities. However, survival was better in children with SPPNs, which may be due to differences in tumor biology and may serve for risk stratification of prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)