Radical Resection of Pediatric Fibrosarcoma Is Not Associated With Survival Benefit: A Nationwide Database Analysis.

INTRODUCTION: Fibrosarcoma is one of the most common nonrhabdomyosarcoma soft tissue sarcomas in the pediatric population. Surgical resection is the cornerstone of treatment; however, optimal factors regarding the extent of fibrosarcoma resection in localized versus regional disease is poorly understood. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients who are 19 y old or younger with a diagnosis of fibrosarcoma from 1975 to 2016. Kaplan-Meier analyses were performed for disease-specific survival on clinical and pathologic variables. Multivariate analysis was performed based on significant predictors of disease-specific survival. RESULTS: There were 1290 patients (median age 13 [7-17] y) identified with fibrosarcoma. The overall survival rate at 20 y was 93%. Radical resection was performed on 22%, 40%, and 52% of patients with localized, regional, and distant Surveillance, Epidemiology, and End Results disease stage, respectively. Chemotherapy (P < 0.001), radiation (P < 0.001), histology (P < 0.001), and stage (P = 0.004) were significant predictors of increased mortality using univariate Kaplan-Meier analysis. Most patients (86%) with localized or regional stage who underwent radiation had fibrosarcomas of nondermatofibrosarcoma histology (P < 0.001). Dermatofibrosarcoma subtype comprised most radical resections (41%). Excluding distant stage, nondermatofibroma histology (hazard ratio 16.94, 95% confidence interval 3.77-76.01) and regional stage (hazard ratio 8.15, 95% confidence interval 2.93-22.69) were independent prognostic factors of mortality (both P < 0.001). Radical resection was not a significant independent prognostic indicator of survival. CONCLUSIONS: Nondermatofibrosarcoma subtype is independently associated with increased mortality. Although surgery remains the mainstay of treatment, the extent of resection is not a predictor of survival for patients with the localized and regional stage of disease.

National burden of pediatric abusive injuries: patterns vary by age.

PURPOSE: Child abuse is often unrecognized by healthcare practitioners. This study sought to characterize pediatric abuse injury patterns and associated mortality rates in a nationwide cohort. METHODS: The Kids' Inpatient Database (1997-2012) was queried for patients < 18 years old with a diagnosis of child abuse (utilizing ICD-9 codes for abusive head trauma [AHT], neglect, physical, emotional, sexual, and other abuse). Demographic factors, mortality, and injury patterns were compared with demographic factors using standard statistical tests. RESULTS: > 39,000 children were hospitalized for abuse from 1997 to 2012. The majority were Caucasian (36%), male (51%) and < 4 years old (70%). Most sustained physical abuse (53%), followed by AHT (14%), sexual (9%) and emotional abuse (2%). Multiple injuries were sustained by 44% of patients. Mortality was 4% (n = 1476). Burns (2%) and intrathoracic (2%) injuries had the highest mortality compared to other injuries (21% and 19%, respectively; both P < 0.001). Emotional abuse (5%) and neglect (1%) were highest in those ≥ 13 years old (both P  = 0.001). CONCLUSION: Physical injuries are less common in adolescents (13-18 years) hospitalized for abuse. However, they are more likely to report emotional abuse and neglect, which has not been compared in previous studies. Intrathoracic injuries and AHT are associated with significant mortality.

Liquid Nitrogen Applied at Point of Sale: A New Presentation of Gastric Perforation in Children.

ABSTRACT: The August 30, 2018, US Food and Drug Administration advisory warned consumers to avoid eating, drinking, or handling food products prepared with liquid nitrogen (LN) (US FDA. Safety Alerts & Advisories: FDA Advises Consumers to Avoid Eating, Drinking, or Handling Food Products Prepared with Liquid Nitrogen at the Point of Sale. US Food and Drug Administration). We report on the case of a pediatric patient sustaining gastric perforation after ingestion of LN applied to food at the point of sale in the United States. "Dragon's Breath" is a popular snack of cereal puffs coated in LN giving the allusion of breathing smoke on ingestion. Instructions provided by vendors include avoidance of touching or drinking the liquid in the bottom of the cup. We report on a case of a 9-year-old girl presenting with peritonitis and gross pneumoperitoneum after consumption of Dragon's Breath with injury conferred secondary to LN ingestion. Intraoperative finding of a large perforation along the lesser curvature of the stomach was repaired primarily with an omental overlay. Her postoperative course was complicated by pneumonia and a surgical site infection. She was discharged 13 days after admission. A review of the literature of previous case reports of LN ingestion by intentional or accidental means is provided. This case report and review of the literature bring awareness of the dangers posed to pediatric patients exposed to LN applied at the point of sale.

Chronic illness in childhood and early adolescence: A longitudinal exploration of co-occurring mental illness.

Chronic health conditions are hypothesized to disrupt the typical trajectory of child and adolescent development, and subsequently lead to increased levels of mental illness. However, due to methodological limitations in existing studies, this theory remains to be fully substantiated by empirical research. This study aimed to more thoroughly test hypotheses in the field. This study used data from the Avon Longitudinal Study of Parents and Children to examine the co-occurrence of mental illness among children with chronic illness in late childhood into early adolescence and explore mediating factors in these outcomes. Children with chronic health problems presented with a disproportionate rate of psychiatric illness at 10 years, and these chronic health problems continued to be associated with poor mental health outcomes at 13 years and 15 years. These outcomes were mediated by high levels of peer victimization and health-related school absenteeism. This study suggests that chronic illness may impact on functioning and social development in early adolescence, and consequently lead to increased rates of mental illness. Examining rates of school absenteeism and peer victimization may be key to identifying children at risk over time.

Protocol-Driven Surgical Care of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

BACKGROUND: There is no clear consensus on the optimal operative management of premature infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP); thus, a protocol was developed to guide surgical decision making regarding initial peritoneal drainage (PD) versus initial laparotomy (LAP). We sought to evaluate outcomes after implementation of the protocol. METHODS: Pre-post study including multiple urban hospitals. Premature infants with sNEC/SIP were accrued after implementation of surgical protocol-directed care (June 2014-June 2019). Patients with a birth weight of <750 g and less than 2 wk of age without pneumatosis or portal venous gas were treated with PD on perforation. PD patients received subsequent LAP for clinical deterioration or continued meconium/bilious drainage. Postprotocol characteristics and outcomes were compared with institutional historical controls. Significance set at P < 0.05. RESULTS: Preprotocol and postprotocol cohorts comprise 35 and 73 patients, respectively. There was a statistically significant difference in age at intervention between historical control PD (14 ± 13 d) and postprotocol PD (9 ± 4 d) groups (P = 0.01), PD patient's birth weight (716 ± 212 g versus 610 ± 141 g, P = 0.02) and estimated gestational age of LAP patients (27 ± 1.7 wk versus 31 ± 4 wk, P = 0.002). PD was definitive surgery in 27% (12 of 44) of postprotocol patients compared with 13% (3 of 23) historical controls. A trend in improved survival postprotocol occurred in all PD infants (73% versus 65%), all LAP (75% versus 70%), and for initial PD and subsequent LAP (82% versus 67%). CONCLUSIONS: Utilization of a surgical protocol in sNEC/SIP is associated with improved success of PD as definitive surgery and improved survival.

Lymph Node Sampling and Survival in Child and Adolescent Extremity Soft-Tissue Sarcoma.

BACKGROUND: The significance of lymph node sampling (LNS) on disease-specific survival (DSS) of extremity soft tissue sarcomas (STS) is unknown. We investigated the effect of LNS on DSS in child and adolescent extremity STS. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results registry was queried for patients aged <20 y with extremity STS who underwent surgery. Patient demographics were collected and analyzed. RESULTS: A total of 1550 patients were included, with findings of 10-y DSS of 74% for all extremity STS and 49% for rhabdoymyosarcoma (RMS) (P < 0.005). LNS was associated with worse DSS in patients with extremity nonrhabdomyosacrcoma soft tissue sarcomas (79% versus 84%, P = 0.036). Conversely, LNS was associated with an improved DSS in patients with extremity RMS (64% versus 49%, P = 0.005). CONCLUSIONS: LNS is positively associated with an improved DSS in child and adolescent extremity RMS. Multivariate analysis found no correlation between DSS and LNS in child and adolescent extremity nonrhabdomyosarcoma soft tissue sarcomas.

Psychiatric outcomes associated with chronic illness in adolescence: A systematic review.

Recent years have seen an increased focus on the high rates of psychiatric comorbidities in adults with chronic illness. This systematic review explored whether chronic illness in adolescents was similarly associated with poor psychiatric outcomes. The literature search identified 129 articles, only 5 of which were indicated to be at a low risk of methodological bias. Four of these articles found a strong relationship between asthma in adolescence and an increase in the prevalence of anxiety and depressive disorders, while the remaining article, which focused on diabetes mellitus, indicated similarly increased rates of psychiatric illness. Trends among the remaining studies suggested that many illnesses were not associated with poor adolescent mental health. Please note that chronic conditions with a neurological aetiology were excluded from the main review due to indications of qualitative differences in comorbidities. Findings highlight that the well-being of adolescents with chronic illness warrants a specific research focus.

Implementation of a Three-Way Comparability Assessment for a Bioanalytical Anti-Drug Antibody Method.

Immunogenicity evaluation is a critical part of drug development. Regulatory guidelines from multiple health agencies provide recommendations for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity in clinical trials. These recommendations primarily describe an ADA method run in one bioanalytical laboratory supporting a biotherapeutic molecule; however, there are increasing instances that may necessitate the support of the ADA method being run in more than one laboratory. A program can rapidly expand into multiple clinical studies within one or multiple countries, where the most appropriate way to support the program is by having multiple laboratories perform ADA sample analysis. In addition, there may be certain country-specific challenges that may make it infeasible to transport samples outside of the country for analysis. China for example has a lengthy sample exportation process that has potential to negatively impact study timelines. If multiple laboratories analyze samples using the same ADA method, comparable method performance should be established. Here, we describe a three-way assessment of ADA assay comparability between two US-based bioanalytical laboratories and one based in China.

Endoscopic Management of a Double Duodenal Web: A Case Report of a Rare Alimentary Anomaly.

Duodenal webs are a rare clinical entity with the presentation of a double duodenal web being exceedingly uncommon. Management of duodenal webs traditionally involves duodenal web excision with duodenoduodenostomy, which is usually performed via a laparoscopic or an open approach. We report the case of a 6-month-old child who presented with progressively worsening bilious emesis with imaging findings concerning for a duodenal web. Endoscopic evaluation was performed that identified 2 webs in the fourth portion of the duodenum. These were managed completely endoscopically with balloon dilation. Although surgery is the mainstay of treatment of duodenal webs, this patient was successfully managed by endoscopic intervention without the need for open or laparoscopic excision, which has not been previously described for double duodenal webs. This work demonstrates the safety and efficacy of endoscopic management for infants with this anomaly.

Pediatric Pedestrian Injuries: Striking Too Close to Home.

BACKGROUND: Pediatric pedestrian injuries (PPI) are a major public health concern. This study utilized geospatial analysis to characterize the risk and injury severity of PPI. METHODS: A retrospective chart review of PPI patients (age < 18) from a level 1 trauma center was performed (2013-2020). A geographic information system geocoded injury location to home and other public landmarks. Incidents were aggregated to zip codes and the Local Indicators of Spatial Association statistic tested for spatial clustering of injury rates per 10,000 children. Predictors for increased injury severity were assessed by logistic regression. RESULTS: PPI encompassed 6% (n = 188) of pediatric traumas. Most patients were black (54%), male (58%), >13 years (56%), and with Medicaid insurance (68%). Nine zip codes comprised a statistically significant cluster of PPI. Nearly half (40%) occurred within a quarter mile of home; 7% occurred at home. Most (65%) PPI occurred within 1 mile of a school, and 45% occurred within a quarter mile of a park. Nearly all (99%) PPI occurred within a quarter mile of a major intersection and/or roadway. Using admission to ICU as a marker for injury severity, farther distance from home (OR 1.060, 95% CI 1.001-1.121, p = 0.045) and age <13 years (3.662, 95% CI 1.854-7.231, p < 0.001) were independent predictors of injury severity. CONCLUSIONS: There are significant sociodemographic disparities in PPI. Most injuries occur near patients' homes and other public landmarks. Multidisciplinary injury prevention collaboration can help inform policymakers, direct local safety programs, and provide a model for PPI prevention at the national level. LEVEL OF EVIDENCE: Level IV.

Association of endogenous anti-interferon-α autoantibodies with decreased interferon-pathway and disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: Numerous observations implicate interferon-α (IFNα) in the pathophysiology of systemic lupus erythematosus (SLE); however, the potential impact of endogenous anti-IFNα autoantibodies (AIAAs) on IFN-pathway and disease activity is unclear. The aim of this study was to characterize IFN-pathway activity and the serologic and clinical profiles of AIAA-positive patients with SLE. METHODS: Sera obtained from patients with SLE (n = 49), patients with rheumatoid arthritis (n = 25), and healthy control subjects (n = 25) were examined for the presence of AIAAs, using a biosensor immunoassay. Serum type I IFN bioactivity and the ability of AIAA-positive sera to neutralize IFNα activity were determined using U937 cells. Levels of IFN-regulated gene expression in peripheral blood were determined by microarray, and serum levels of BAFF, IFN-inducible chemokines, and other autoantibodies were measured using immunoassays. RESULTS: AIAAs were detected in 27% of the serum samples from patients with SLE, using a biosensor immunoassay. Unsupervised hierarchical clustering analysis identified 2 subgroups of patients, IFN(low) and IFN(high) , that differed in the levels of serum type I IFN bioactivity, IFN-regulated gene expression, BAFF, anti-ribosomal P, and anti-chromatin autoantibodies, and in AIAA status. The majority of AIAA-positive patients had significantly lower levels of serum type I IFN bioactivity, reduced downstream IFN-pathway activity, and lower disease activity compared with the IFN(high) patients. AIAA-positive sera were able to effectively neutralize type I IFN activity in vitro. CONCLUSION: Patients with SLE commonly harbor AIAAs. AIAA-positive patients have lower levels of serum type I IFN bioactivity and evidence for reduced downstream IFN-pathway and disease activity. AIAAs may influence the clinical course in SLE by blunting the effects produced by IFNα.

A Fit-for-Purpose Method to Measure Circulating Levels of the mRNA Component of a Liposomal-Formulated Individualized Neoantigen-Specific Therapy for Cancer.

Autogene cevumeran is an individualized neoantigen-specific therapy (iNeST) under development for the treatment of various solid tumors. It consists of an RNA-Lipoplex (RNA-LPX) in which the encapsulated mRNA molecule encodes up to ten neoepitopes identified from each individual patient. In association with major histocompatibility complex (MHC) class I and MHC class II, these neoantigens can potentially stimulate and expand neoantigen-specific CD4+ and CD8+ T cells, leading to antitumor responses. As part of the pharmacokinetic (PK) property assessment of Autogene cevumeran in patients, both the lipid and mRNA content in circulation are measured. This work focused on our efforts to establish a sensitive and robust method for the measurement of mRNA levels of RNA-LPX in plasma. Due to the chemical characteristics of mRNA, extra precautions are required in order to effectively preserve mRNA integrity in human plasma during sample collection, handling and storage. To this end, a number of sample collection tubes and storage conditions were evaluated in order to inform the most optimal and operationally feasible conditions by which to preserve mRNA integrity during sample collection and upon freeze-thaw. PAXgene Blood ccfDNA tubes successfully prevented mRNA degradation and were subsequently selected for patient sample collection in the clinical trial. A branched DNA (bDNA)-based mRNA PK assay was developed to achieve the desired assay performance. Here, we discuss the evaluation of various sample collection and processing conditions as well as the optimization of the work flow during bDNA PK method development.

Quest for a realistic in vivo test method for antimicrobial hand-rub agents: introduction of a low-volume hand contamination procedure.

A novel method has been developed for the evaluation of alcohol-based hand rubs (ABHR) that employs a hand contamination procedure that more closely simulates the in-use conditions of ABHR. Hands of human subjects were contaminated with 0.2 ml of a concentrated suspension of Serratia marcescens (ATCC 14756) to achieve baseline contamination between 8 and 9 log10 CFU/hand while allowing product to be applied to dry hands with minimal soil load. Evaluation of 1.5 ml of an ABHR gel containing 62% ethanol produced log10 reductions of 2.66 ± 0.96, 2.40 ± 0.50, 2.41 ± 0.61, and 2.33 ± 0.49 (means ± standard deviations) after 1, 3, 7, and 10 successive contamination/product application cycles. In a study comparing this low-volume contamination (LVC) method to ASTM E1174, product dry times were more realistic and log10 reductions achieved by the ABHR were significantly greater when LVC was employed (P < 0.05). These results indicate that a novel low-volume hand contamination procedure, which more closely represents ABHR use conditions, provides more realistic estimates of in-use ABHR efficacies. Based on the LVC method, log10 reductions produced by ABHR were strongly dependent on the test product application volume (P < 0.0001) but were not influenced by the alcohol concentration when it was within the range of 62 to 85% (P = 0.378).

The limited role of ultrasound in the surgical assessment of solid pediatric breast lesions.

INTRODUCTION: Ultrasound (US) is an adjunct to history and clinical exam (CE) in the assessment of pediatric breast lesions. We sought to investigate the reliability of US and CE to predict final pathologic diameter (P). METHODS: A single institutional retrospective analysis of patients aged ≤18 years who underwent breast mass resection was performed. Data was collected and analyzed using SPSS. RESULTS: 88 patients met inclusion criteria with an average age at surgery of 16 ± 1.5 years. No malignancies were encountered. The largest mean diameter measured by final pathology (MPØ) for all lesions was 4.1 ± 2.6 cm. Pathology encountered were fibroadenoma (83%, MPØ 3.7 ± 1.7 cm), juvenile fibroadenoma (10%, MPØ 7.0 ± 5.4 cm), and low-grade phyllodes tumor (3%, MPØ 6.2 ± 3.8 cm). 67 patients had documented CE measurement with a mean diameter of 3.4 ± 1.8 cm. 62 patients underwent US with a mean diameter of 3.3 ± 1.6 cm. US and CE were accurate in determining P by Cronbach Alpha reliability testing. CONCLUSION: US and CE are reliable measurements of P. The surgical utility of US when considering pediatric breast lesions is limited and should be individualized following pediatric surgical evaluation and CE.

AAMC Data Shows Effect of Surgery Faculty Diversity on General Surgery Resident Attrition Rate at Programs Sponsored by LCME-Accredited Medical Schools.

OBJECTIVE: General surgery resident (GSR) 5-year attrition rates of 12% to 20% are currently reported. This study explores the impact of full-time surgery faculty (FSF) diversity on GSR attrition. DESIGN: Deidentified data were obtained from the Association of American Medical Colleges (AAMC) for FSF at US Liaison Committee on Medical Education (LCME)-accredited medical schools and GSR at the affiliated general surgery residency programs (2001-2016). Data included annual GSR attrition rate and the number, gender, and race of FSF and GSR. Data were analyzed using linear and logarithmic regression. SETTING: The study was conducted at the University of Miami Leonard M. Miller School of Medicine in Miami, Florida. PARTICIPANTS: The data obtained included FSF from US LCME-accredited medical schools and GSR from those residency programs affiliated with US LCME-accredited medical schools. Data were included only if available for both FSF and GSR at a single institution. There were 107,300 annual FSF positions and 39,504 annual GSR positions from 61 U.S. LCME-accredited medical schools included in the analysis. RESULTS: Data included 107,300 FSF positions (26% non-white; 20% female) and 39,504 GSR positions (41% non-white; 33% female) summed across 1034 institution years. Increased female FSF is associated with decreased GSR attrition (R2 = 0.009, p = 0.002, Fig. 1). For every 1% increase in female FSF, GSR programs were 4% less likely to have an attrition rate in the top quartile (odds ratio 0.96, confidence interval 0.94-0.98). CONCLUSIONS: Gender diversity of FSF has an impact on GSR attrition; more female FSF correlates with lower GSR attrition rates.

A retrospective comparison of outcomes for open vs. laparoscopic surgical techniques in pediatric ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an aggressive disease in the pediatric population and a cause of significant, lifelong morbidity. The aim of this study is to compare surgical complications in pediatric patients undergoing laparoscopic vs. open surgical treatment for UC. METHODS: We queried the Kids' Inpatient Database (KID) for all cases of UC undergoing surgical treatment in 2009 and 2012. We identified patients who received total colectomy without proctectomy (n=413) or total proctocolectomy (n=196) and performed univariate and multivariate analyses comparing laparoscopic vs. open procedures. RESULTS: In pediatric UC patients undergoing total colectomy without proctectomy, open procedures were associated with more complications than laparoscopic, including fluid and electrolyte disorders (40% vs. 28%), surgical wound dehiscence (6% vs. 2%), septicemia (18% vs. 2%), and gastrointestinal disorders (16% vs. 7%) among others, all P<0.05. Likewise, in patients with UC undergoing total proctocolectomy, there were more complications in open vs. laparoscopic technique, including increased transfusion requirements (25% vs. 7%, P=0.001) and significantly more gastrointestinal upset, including nausea, vomiting, and diarrhea (11% vs. 1%, P=0.003). In multivariate analysis, patients who underwent total colectomy with or without proctectomy had an increased risk of experiencing any complication when their procedure was performed in an open or non-elective fashion (all odds ratio >2.4; all P<0.001). CONCLUSIONS: The laparoscopic approach was associated with significantly lower rates of surgical complications in pediatric patients undergoing total colectomy with or without proctectomy for UC. These findings demonstrate that laparoscopic technique compares favorably, and may be preferable, to the open approach in selected pediatric patients with UC.

Laparoscopic-assisted Open Pyloroduodenostomy Repair of Pyloric Atresia in an Infant: A Rare Congenital Anomaly.

PURPOSE: Pyloric atresia is an uncommon congenital anomaly that may present with emesis and dehydration early in infancy. Definitive therapy consists of pyloroplasty or gastroduodenostomy depending on the subtype of atresia involved. CASE PRESENTATION: We report the case of a 2-day-old girl infant who presented with nonbilious emesis with feeds. Abdominal ultrasound and upper gastrointestinal series were performed and demonstrated a dilated, air-filled stomach with no distal air or passage of contrast. The patient was successfully treated by laparoscopic-assisted open pyloroduodenostomy of a type 2 pyloric atresia. CONCLUSION: Type 2 pyloric atresia is a rare clinical entity that can present with symptoms of gastric outlet obstruction. The patient described was treated by laparoscopic-assisted open pyloroduodenostomy, which has not been previously described for pyloric atresia. This work demonstrates an example of the safety and efficacy of laparoscopic surgery for infants with this anomaly.

Low-Grade Appendiceal Mucinous Neoplasm in an Adolescent Patient With Untreated Crohn's Disease.

Appendiceal mucinous neoplasms are rarely diagnosed in pediatric patients. We present a 16-year-old adolescent boy with severe Crohn's disease who was not on maintenance medication for his underlying diagnosis. He was referred for nutritional optimization and small bowel obstruction. An emergent laparoscopic ileocecectomy with primary ileocolonic anastomosis was carried out secondary to acute peritonitis. Small bowel pathologic findings were consistent with Crohn's disease with low-grade appendiceal mucinous neoplasm (LAMN) of the appendix.