Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium.

OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children. DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry. SETTING: PICUs within U.S. CHAT Consortium participating centers. PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE. CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.

Effects of Cumulative Head Impact Exposure in Adolescent Male Contact and Collision Sport Student Athletes.

OBJECTIVE: This prospective cohort study aimed to investigate the association between head impact exposure (HIE) and neuropsychological sequelae in high school football and ice hockey players over 1 year. SETTING: Community sample. PARTICIPANTS: A cohort of 52 adolescent American football and ice hockey players were enrolled in the study, with a final study sample of 35 included in analyses. DESIGN: The study followed a prospective cohort design, with participants undergoing neuropsychological screening and accelerometer-based measurement of HIE over 1 season. MAIN MEASURES: Changes in cognition, emotions, behavior, and reported symptoms were assessed using standardized neuropsychological tests and self-reported questionnaires. RESULTS: Cumulative HIE was not consistently associated with changes in cognition, emotions, behavior, or reported symptoms. However, it was linked to an isolated measure of processing speed, showing inconsistent results based on the type of HIE. History of previous concussion was associated with worsened verbal memory recognition (ImPACT Verbal Memory) but not on a more robust measure of verbal memory (California Verbal Learning Test [CVLT]). Reported attention-deficit/hyperactivity disorder history predicted improved neurocognitive change scores. No associations were found between reported history of anxiety/depression or headaches/migraines and neuropsychological change scores. CONCLUSION: Overall, our findings do not support the hypothesis that greater HIE is associated with an increase in neuropsychological sequelae over time in adolescent football and ice hockey players. The results align with the existing literature, indicating that HIE over 1 season of youth sports is not consistently associated with significant neuropsychological changes. However, the study is limited by a small sample size, attrition over time, and the absence of performance validity testing for neurocognitive measures. Future studies with larger and more diverse samples, longer follow-up, and integration of advanced imaging and biomarkers are needed to comprehensively understand the relationship between HIE and neurobehavioral outcomes. Findings can inform guidelines for safe youth participation in contact sports while promoting the associated health and psychosocial benefits.

Defining the Healthy Infant Metabolome: Liquid Chromatography Tandem-Mass Spectrometry Analysis of Dried Blood Spot Extracts from the Prospective Research on Early Determinants of Illness and Children's Health Trajectories Birth Cohort Study.

Newborn screening using dried plasma spots offers preanalytical advantages over conventional cards for plasma-associated targets of interest. Herein we present dried plasma spot-based methods for measuring metabolites using a 250+ compound liquid chromatography tandem mass spectrometry library. Quality assurance reduced this library to 134, and from these, 30 compounds determined the normal newborn reference ranges.

A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children's Hospital-Acquired Thrombosis Consortium.

OBJECTIVES: To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU. DESIGN: Case-control study. SETTING: ICUs from eight children's hospitals throughout the United States. SUBJECTS: Critically ill children with hospital-acquired venous thromboembolism (cases) 0-21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The multi-institutional Children's Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1-10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2-8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7-7.1), immobility (odds ratio 3.6, 95% CI, 2.1-6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1-5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2-3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73-0.84). CONCLUSIONS: Using the multicenter Children's Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospital-acquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.

Comparison of general endotracheal anesthesia versus sedation without endotracheal intubation during initial percutaneous endoscopic gastrostomy insertion for infants: A retrospective cohort study.

BACKGROUND: Critical airway incidents are a major cause of morbidity and mortality during anesthesia. Delayed management of airway obstruction quickly leads to severe complications due to the reduced apnea tolerance in infants and neonates. The decision of whether to intubate the trachea during anesthesia is therefore of great importance, particularly as an increasing number of procedures are performed outside of the operating room. AIM: In this retrospective cohort study, we evaluated airway management for infants below 6 months of age undergoing percutaneous endoscopic gastrostomy insertion. We compared demographic, procedural, and health outcome-related data for infants undergoing percutaneous endoscopic gastrostomy insertion under general endotracheal anesthesia (n = 105) to those receiving monitored anesthesia care (n = 44) without endotracheal intubation. METHODS: A retrospective chart review was completed for all infants <6 months of age who underwent percutaneous endoscopic gastrostomy insertion in our institution's endoscopy suite between January 2002 and January 2017. Descriptive statistics summarized numeric variables using medians and corresponding ranges (minimum-maximum), and categorical variables using frequencies and percentages. Differences in study outcomes between patients undergoing general anesthesia or monitored anesthesia care were evaluated with univariate quantile or Firth logistic regression for numerical and categorical outcomes, respectively. Results are presented as ß [95% confidence interval] or odds ratio [95% confidence interval] along with corresponding p-values. RESULTS: Both groups were similar in distribution of age, race, and gender. However, patients selected for general anesthesia had lower median body weights (3.9 kg [range: 2.0-6.7] vs. 4.4 kg [range: 2.6-6.9]), higher percentages of cardiac (95.2% vs. 84.1%), and/or neurologic comorbidities (74.3% vs. 56.8%) and were more frequently given American Society of Anesthesiologists level IV classifications (41.9% vs. 29.6%) indicating that these infants may have had more severe disease than patients selected for monitored anesthesia care. Three monitored-anesthesia-care patients required intraoperative conversion to general anesthesia. General anesthesia patients experienced greater odds of intraoperative hypoxemia (45.2% vs. 29.0%; odds ratio: 2.0 [0.9-4.3], p-value: .09) and required postoperative airway intervention more frequently than monitored-anesthesia-care patients (13.03% vs. 2.3%; odds ratio: 4.6 [0.8-25.6], p-value: .08). Procedure times were identical in both groups (6 min), but general anesthesia resulted in longer median anesthesia times (44 min [range: 22-292] vs. 12 min [range:19-136]; ß:13 [95% 6.9-19.1], p-value: < .001). CONCLUSION: Study results suggest that providers selected general anesthesia over monitored anesthesia care for infants and neonates with low body weights, cardiac comorbidities, and neurologic comorbidities. Increased rates of airway intervention, and increased length of stay may be at least partially related to more severe patient comorbidity, as indicated by higher American Society of Anesthesiologists classifications. However, due to the exploratory nature of these analyses, further confirmatory studies are needed to evaluate the impact of airway selection during PEG on postoperative patient outcomes.

Volatile anesthetic agents for life-threatening pediatric asthma: A multicenter retrospective cohort study and narrative review.

BACKGROUND: Volatile anesthetic agents are described as rescue therapy for children invasively ventilated for critical asthma. Yet, data are currently limited to case series. AIMS: Using the Virtual Pediatric Systems database, we assessed children admitted to a pediatric intensive care unit invasively ventilated for life-threatening asthma and hypothesized ventilation duration and mortality rates would be lower for subjects exposed to volatile anesthetics compared with those without exposure. METHODS: We performed a multicenter retrospective cohort study among nine institutions including children 5-17 years of age invasively ventilated for asthma from 2013 to 2019 with and without exposure to volatile anesthetics. Primary outcomes were ventilation duration and mortality. Secondary outcomes included patient characteristics, length of stay, and anesthetic-related adverse events. A subgroup analysis was performed evaluating children intubated ≥2 days. RESULTS: Of 203 children included in study, there were 29 (14.3%) with and 174 (85.7%) without exposure to volatiles. No differences in odds of mortality (1.1, 95% CI: 0.3-3.9, p > .999) were observed. Subjects receiving volatiles experienced greater median difference in length of stay (4.8, 95% CI: 1.9-7.8 days, p < .001), ventilation duration (2.3, 95% CI: 1-3.3 days, p < .001), and odds of extracorporeal life support (9.1, 95% CI: 1.9-43.2, p = .009) than those without volatile exposure. For those ventilated ≥2 days, no differences were detected in mortality, ventilation duration, length of stay, arrhythmias, or acute renal failure. However, the odds of extracorporeal life support remained greater for those receiving volatiles (7.6, 95% CI: 1.3-44.5, p = .027). No children experienced malignant hyperthermia or hepatic failure after volatile exposure. CONCLUSIONS: For intubated children for asthma, no differences in mechanical ventilation duration or mortality between those with and without volatile anesthetic exposure were observed. Although volatiles may represent a viable rescue therapy for severe cases of asthma, definitive, and prospective trials are still needed.

Comparison of Tolerance and Complication Rates Between Early and Delayed Feeding After Percutaneous Endoscopic Gastrostomy Placement in Children.

BACKGROUND: Enteral nutrition is commonly initiated 24 hours after percutaneous endoscopic gastrostomy (PEG) in children. Adult studies report safe refeeding within 1 to 6 hours of PEG, and these findings have been cautiously applied to children. Comparative studies assessing early versus next-day refeeding in children are currently lacking. This study evaluates feeding tolerance and complications following early versus next-day refeeding in children. METHODS: This is a single-center, pre-post study. In June 2015 our clinical practice changed to begin refeeding within 6 hours of PEG. Children receiving early refeeding from December 2015 to August 2017 were included. A retrospective cohort from February 2013 to April 2015 was used for comparison. RESULTS: Forty-six children received early refeeding after PEG and 37 received next-day refeeding. Gender distribution was similar in the 2 groups. Early refeeding patients were slightly older (3.5 vs 2.2 years) and heavier (15.5 vs 11.5 kg) at PEG placement compared to next-day refeeding patients. Early refeeding patients experienced greater postprocedural nausea and/or vomiting (19% vs 8%, P < 0.001) and leakage, irritation, and infection around the stoma (19% vs 0.0%, P < 0.001). Compared to early refeeders, next-day refeeding patients experienced higher occurrence of fever (35% vs 13%, P = 0.021), longer nutritional disruption (24.6 vs 3.7 hours, P < 0.001), and longer length of stay (51 vs 27 hours; P < 0.001). One next-day refeeding patient experienced peritonitis. One early refeeding patient experienced cellulitis requiring hospitalization and a second experienced gastrostomy tube migration into the peritoneal cavity requiring removal. CONCLUSION: Early refeeders experienced higher rates of postprocedural nausea or vomiting and irritation, leakage, or infection around the stoma; but experienced lower rates of postoperative fever. Early refeeding resulted in reduced nutritional interruption and hospital length of stay.

Instituting a New Central Line Policy to Decrease Central Line-associated Blood Stream Infection Rates During Induction Therapy in Pediatric Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) require central lines to facilitate their care. Peripherally inserted central catheters (PICCs) may have lower rates of central line-associated bloodstream infections (CLABSIs) versus other central lines. OBJECTIVES: The objective of this study was to compare the CLABSI rate in the first month of therapy after initiating a policy to place PICCs in new patients with severe neutropenia (SN) and Mediports in those with moderate-to-no neutropenia. We also examined thrombosis rates. DESIGN/METHOD: We prospectively gathered data on new patients for 2.5 years following the policy change and retrospectively for the 2 years prior and compared rates of CLABSIs and thrombosis. RESULTS: CLABSIs decreased in SN patients from 7.52/1000 to 3.11/1000 line days (P=0.33). The CLABSI rate for all patients with SN who had a Mediport was 13.39/1000 versus 4.08/1000 line days for those that received PICCs (P=0.15). The thrombosis rate for Mediport patients was 3.13 clots/1000 versus 7.65/1000 line days for PICC patients, but the difference was not significant (P= 0.11). CONCLUSION: The differences observed suggest that placing PICCs versus Mediports in new ALL patients with SN may result in a lower incidence of CLABSIs in the first month of therapy without a significant increase in thrombosis.

Incidentally found brain tumors in the pediatric population: a case series and proposed treatment algorithm.

PURPOSE: With the increasing use of imaging, there has been an increase in the number of incidentally found brain lesions in pediatric patients resulting in a treatment dilemma for physicians and emotional strain for patients and families. Adult studies support initial surveillance of incidentally found low grade appearing lesions as the most appropriate approach. The aim of this study was to evaluate incidental lesions in the pediatric population and propose an initial treatment algorithm for such lesions. METHODS: Pediatric records were retrospectively reviewed at Johns Hopkins All Children's Hospital for incidentally found brain tumors between 2000 and 2017. Demographic data, presenting symptoms, treatment approach, and outcomes were reviewed for 55 patients, age 0-18. RESULTS: Of the 55 patients included in the study, 14 underwent surgical resection, 3 underwent biopsy, and 38 with benign imaging characteristics at presentation were monitored with radiology alone. Only one patient, out of the 17 that underwent resection or biopsy, had pathology consistent with a high grade glioma. Of the patients monitored radiographically 10 total patients showed an increase in the overall size of the lesion; however after a median follow up of 34.2 months only 2 increased to a degree that required surgical intervention. CONCLUSIONS: The majority of incidentally found brain lesions with benign imaging characteristics at presentation may be managed conservatively. Surveillance is an important part of the initial management of incidental lesions in the pediatric population, but careful scrutiny must be paid to the potential for higher grade lesions or malignant transformation.

Coagulative function assessed preoperatively via the clot formation and lysis assay as a prognostic factor for blood loss in adolescents undergoing posterior spinal fusion for idiopathic scoliosis.

BACKGROUND: Posterior spinal fusion for adolescent idiopathic scoliosis is a complex surgery often associated with clinically significant blood loss leading to perioperative blood transfusion. Knowledge of risk factors for blood loss and transfusion stems mostly from retrospective studies. AIM: We sought to prospectively investigate putative prognostic factors for intraoperative blood loss and perioperative blood transfusion in adolescent idiopathic scoliosis patients undergoing posterior spine fusion, including clinical characteristics, surgical factors, and preoperative assessment of overall coagulative and fibrinolytic functions in plasma using the clot formation and lysis (CloFAL) assay. METHODS: Following Internal Review Board approval, adolescents 10 to <21 years old with idiopathic scoliosis undergoing posterior spine fusion were enrolled preoperatively in a single-institutional prospective cohort and biobanking study. Clinical data were collected on patient characteristics, surgical approach, perioperative management, intraoperative estimated blood loss, and blood transfusion through hospital discharge. Coagulative and fibrinolytic functions in plasma were measured on preoperative samples by CloFAL assay (Coagulation Index and modified Fibrinolytic Index). Univariate linear regression and multivariable linear regression were performed to identify predictors of weight-indexed intraoperative estimated blood loss EBL (EBL/kg). RESULTS: The final study population included 74 patients. Median age was 14.8 years (SD = 2.2). After adjustment for other putative prognostic factors via multivariable linear regression, coagulative function as determined preoperatively by CloFAL Coagulation Index was an independent predictor of intraoperative (EBL)/kg. Specifically, each 10% increase in CloFAL CI was associated with 3% decrease in the geometric mean of EBL/kg (OR 0.97, 95%CI 0.94-0.99, P = .01). CONCLUSION: In adolescents undergoing posterior spinal fusion for idiopathic scoliosis, increased coagulative function measured preoperatively using the CloFAL assay is independently associated with decreased intraoperative blood loss. Future studies should expand upon these investigations of plasma coagulative and fibrinolytic capacities in combination with clinical factors, to guide precise preventive strategies against blood loss and blood transfusion in this patient population.

Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas.

BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution. RESULTS: Sixteen patients (median age 13.5 years, range 3-19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with nonhematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no complete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2-19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression-free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. CONCLUSIONS: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic toxicities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway.

Implications of non-accidental trauma on resource utilization and outcomes.

PURPOSE: The purpose was to compare the resource utilization and outcomes between patients with suspected (SUSP) and confirmed (CONF) non-accidental trauma (NAT). METHODS: The institutional trauma registry was reviewed for patients aged 0-18 years presenting from 2007 to 2012 with a diagnosis of suspicion for NAT. Patients with suspected and confirmed NAT were compared. RESULTS: There were 281 patients included. CONF presented with a higher heart rate (142 ± 27 vs 128 ± 23 bpm, p < 0.01), lower systolic blood pressure (100 ± 18 vs 105 ± 16 mm Hg, p = 0.03), and higher Injury Severity Score (15 ± 11 vs 9 ± 5, p < 0.01). SUSP received fewer consultations (1.6 ± 0.7 vs 2.4 ± 1.1, 95% CI - 0.58 to - 0.09, p < 0.01) and had a shorter length of stay (1.6 ± 1.3 vs 7.8 ± 9.8 days, 95% CI - 4.58 to - 0.72, p < 0.01). SUSP were more often discharged home (OR 94.22, 95% CI: 21.26-417.476, p < 0.01). CONF had a higher mortality rate (8.2 vs 0%, p < 0.01). CONCLUSIONS: Patients with confirmed NAT present with more severe injuries and require more hospital resources compared to patients in whom NAT is suspected and ruled out.

Helicopter Transport From the Scene of Injury: Are There Improved Outcomes for Pediatric Trauma Patients?

BACKGROUND: There is conflicting data to support the routine use of helicopter transport (HT) for the transfer of trauma patients. The purpose of this study was to evaluate outcomes for trauma patients transported via helicopter from the scene of injury to a regional pediatric trauma center. METHODS: The institutional trauma registry was queried for trauma patients presenting from January 2000 through March 2012. Of 9119 patients, 1709 patients who presented from the scene were selected for further evaluation. This cohort was stratified into HT and ground transport (GT) for analysis. Associations between mode of transport and outcomes were estimated using odds ratios and 95% confidence intervals from multivariable logistic regression models. RESULTS: Seven hundred twenty-five patients (42.4%) presented via HT, whereas 984 (57.6%) presented via GT. Patients arriving by HT had a higher Injury Severity Score, lower Glasgow Coma Scale, were less likely to undergo surgery within 3 hours, more likely to present after motorized trauma, and had longer intensive care unit (ICU) and hospital length of stay (LOS). Multivariate analysis controlling for Injury Severity Score, Glasgow Coma Scale, mechanism of injury, scene distance, and time to arrive to the hospital revealed that patients arriving by HT were more likely to have longer hospital LOS compared with those arriving by GT (odds ratios = 2.3, 95% confidence interval = 1.00-5.28, P = 0.049). However, no statistically significant association was observed for prehospital intubation, surgery within 3 hours, ICU admissions, or ICU LOS. CONCLUSIONS: Although patients arriving by helicopter are more severely injured and arrive from greater distances, when controlling for injuries, scene distance, and time to hospital arrival, only hospital LOS was significantly affected by HT.

A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia.

Acute leukemia is the most common childhood cancer diagnosis and leading cause of cancer-related death among children and adolescents. Despite substantial improvements in the survival rate of childhood acute leukemia, approximately 20-40% of the patients who undergo treatment develop relapse, with a dismal one third of these patients surviving in the long term. Epigenetics plays an important role in the progression of cancer, and existing evidence suggests a role in childhood acute leukemia relapse. A better understanding of the epigenetic mechanisms in recurrent acute leukemia could potentially lead to novel therapeutic regimens to prevent or treat disease recurrences. In this review, we summarize existing evidence on two of the most studied epigenetic mechanisms, DNA methylation and microRNA expression, in recurrent pediatric acute leukemia.

Enhancing recovery after minimally invasive repair of pectus excavatum.

PURPOSE: There are variations in the perioperative management of patients who undergo minimally invasive repair of pectus excavatum (MIRPE). The purpose is to analyze the change in resource utilization after implementation of a standardized practice plan and describe an enhanced recovery pathway. METHODS: A standardized practice plan was implemented in 2013. A retrospective review of patients who underwent MIRPE from 2012 to 2015 was performed to evaluate the trends in resource utilization. A pain management protocol was implemented and a retrospective review was performed of patients who underwent repair before (2010-2012) and after (2014-2015) implementation. RESULTS: There were 71 patients included in the review of resource utilization. After implementation, there was a decrease in intensive care unit length of stay (LOS), and laboratory and radiologic studies ordered. There were 64 patients included in the pain protocol analysis. After implementation, postoperative morphine equivalents (3.3 ± 1.4 vs 1.2 ± 0.5 mg/kg, p < 0.01), urinary retention requiring catheterization (33 vs 14%, p = 0.07), and LOS (4 ± 1 vs 2.8 ± 0.8 days, p < 0.01) decreased. CONCLUSION: The implementation of an enhanced recovery pathway is a feasible and effective way to reduce resource utilization and improve outcomes in pediatric patients who undergo minimally invasive repair of pectus excavatum.

Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.

Urological Outcome of the Xiao Procedure in Children with Myelomeningocele and Lipomyelomeningocele Undergoing Spinal Cord Detethering.

PURPOSE: Although previous studies have revealed high success rates (70% to 85%) after an intradural somatic-to-autonomic nerve transfer procedure in children with spinal dysraphism, no study has had a control group or blinded observers. We report a rigorously designed study to investigate the effectiveness of the Xiao procedure. MATERIALS AND METHODS: Children with neurogenic bladder dysfunction related to myelomeningocele or lipomyelomeningocele who required spinal cord detethering were randomized to 2 groups at surgery, with half undergoing only spinal cord detethering and half undergoing the Xiao procedure in addition to detethering. Double-blind evaluations were performed at regular intervals during the 3-year followup. RESULTS: A total of 10 patients underwent spinal cord detethering only and 10 underwent detethering plus the Xiao procedure. The Xiao procedure did not result in voluntary voiding or continence in any patient, but patients undergoing spinal cord detethering plus the Xiao procedure were more likely to have greater improvements in total bladder capacity, bladder overactivity and overall quality of life than those who underwent detethering only. By the end of the study no participant or evaluator was able to accurately predict to which group the patients had been assigned. CONCLUSIONS: The results of this randomized controlled trial are in agreement with recently published similarly poor results of the Xiao procedure in patients with spinal cord injury. Improvements in bladder parameters observed in this study may be related to sacral nerve root section, a necessary portion of the Xiao procedure, instead of reinnervation. Confirmatory animal studies are recommended before further clinical trials of the Xiao procedure are performed in humans.

Oxygen requirement as a screening tool for the detection of late pulmonary hypertension in extremely low birth weight infants.

BACKGROUND: Many extremely low birth weight infants develop pulmonary hypertension late in their clinical course, and over 60% go undetected by early screening echocardiography. At present, no standardised screening protocol exists for detecting late pulmonary hypertension in extremely low birth weight infants. We assessed the utility of oxygen supplementation as a predictor of late pulmonary hypertension. METHODS: A retrospective single-centre review of extremely low birth weight infants with no evidence of CHD and those surviving for >30 days was performed. The association between oxygen ⩾30% at day of life 30 and diagnosis of late pulmonary hypertension was estimated with an odds ratio and 95% confidence interval using logistic regression. Doppler echocardiography was used to diagnose pulmonary hypertension in the infants. RESULTS: A total of 230 infants met the study criteria. The incidence of late pulmonary hypertension was 8.3% (19/230). Infants with late pulmonary hypertension were more likely to have a lower mean birth weight (667.1±144 versus 799.3±140 g, p=0.001) and more likely to be small for gestational age (47.4 versus 14.2%, p=0.004). Oxygen requirement ⩾30% at day of life 30 was associated with increased risk of late pulmonary hypertension (odds ratio=3.77, 95% confidence interval=1.42-10.00, p=0.008) in univariate analysis and after adjusting for birth weight (odds ratio=2.47, 95% confidence interval=0.89-6.84, p=0.08). CONCLUSIONS: The need of oxygen supplementation ⩾30% at day of life 30 may be a good screening tool for detecting late pulmonary hypertension in extremely low birth weight infants.

Assessment of Weight Bias Among Pediatric Nurses and Clinical Support Staff Toward Obese Patients and Their Caregivers.

The increasing burden of obesity is prevalent in the pediatric populations. Pediatric nurses are spending increasing amounts of time and effort caring for obese patients however no prior studies have explored how nurses perceive obese patients. The purpose of this study is to identify weight bias in pediatric nurses (RNs) and clinical support staff (CSS) working in a pediatric hospital setting. A convenience sample of RNs and CSS from an urban, pediatric hospital were surveyed using the Nurses' Attitudes toward Obesity and Obese Patients Scale (NATOOPS), which consists of 6 patient-care factors with an additional factor added to assess bias towards the patient's caregiver. Mean factor scores ≥50 indicated bias. Data were summarized using descriptive statistics and means were compared using independent t tests. Multivariate logistic regression models were used to determine the association between putative risk factors and weight bias. RNs and CSS (N=308) demonstrated weight bias toward obese patient characteristics (mean=61.9) and perceived controllability of obesity (mean=65.8). CSS felt negatively about their supportive roles in caring for obese patients (mean=52.5). Respondent weight status and professional title resulted in variability of biased attitudes. Race, employment status, number of obese patients cared for daily, and department were predictive of biased attitudes. Weight biased attitudes toward obese pediatric patients and their caregivers were found among RNs and CSS. Future qualitative research will assist in the understanding the factors that cause nurse weight bias.

Interleukin polymorphisms associated with overall survival, disease-free survival, and recurrence in non-small cell lung cancer patients.

Biomarkers based on germline DNA variations could have translational implications by identifying prognostic factors and sub-classifying patients to tailored, patient-specific treatment. To investigate the association between germline variations in interleukin (IL) genes and lung cancer outcomes, we genotyped 251 single nucleotide polymorphisms (SNPs) from 33 different IL genes in 651 non-small cell lung cancer (NSCLC) patients. Analyses were performed to investigate overall survival, disease-free survival, and recurrence. Our analyses revealed 24 different IL SNPs significantly associated with one or more of the lung cancer outcomes of interest. The GG genotype of IL16:rs7170924 was significantly associated with disease-free survival (HR = 0.65; 95% CI 0.50-0.83) and was the only SNP that produced a false discovery rate (FDR) of modest confidence that the association is unlikely to represent a false-positive result (FDR = 0.142). Classification and regression tree (CART) analyses were used to identify potential higher-order interactions. We restricted the CART analyses to the five SNPs that were significantly associated with multiple endpoints (IL1A:rs1800587, IL1B:rs1143634, IL8:s12506479, IL12A:rs662959, and IL13:rs1881457) and IL16:rs7170924 which had the lowest FDR. CART analyses did not yield a tree structure for overall survival; separate CART tree structures were identified for recurrence, based on three SNPs (IL13:rs1881457, IL1B:rs1143634, and IL12A:rs662959), and for disease-free survival, based on two SNPs (IL12A:rs662959 and IL16:rs7170924), which may suggest that these candidate IL SNPs have a specific impact on lung cancer progression and recurrence. These data suggest that germline variations in IL genes are associated with clinical outcomes in NSCLC patients.