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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.

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.

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., (© 2016 S. Karger AG, Basel.)

OBJECTIVE Xiao et al. and other investigators have studied an intradural somatic-to-autonomic (e.g., L-5 to S3-4) nerve transfer as a method to create a reflex arc to allow bladder emptying in response to cutaneous stimulation (the Xiao procedure). In previous clinical studies of patients with spinal dysraphism who underwent the Xiao procedure, high success rates (70%-85%) were reported for the establishment of a "skin-CNS-bladder" reflex arc that allows spontaneous, controlled voiding in children with neurogenic bladder dysfunction. However, many of these studies did not use blinded observers, did not have control groups, and/or featured only limited follow-up durations. METHODS A randomized, prospective, double-blind trial was initiated in March 2009, enrolling children with myelomeningocele (MM), lipomyelomeningocele (LMM), and neurogenic bladder dysfunction who were scheduled for spinal cord detethering (DT) for the usual indications. At the time of DT, patients were randomized between 2 arms of the study: half of the patients underwent a standard spinal cord DT procedure alone (DT group) and half underwent DT as well as the Xiao procedure (DT+X group). Patients, families, and study investigators, all of whom were blinded to the surgical details, analyzed the patients' strength, sensory function, mobility, voiding, and urodynamic bladder function before surgery and at regular intervals during the 3-year follow-up. RESULTS Twenty patients were enrolled in the study: 10 underwent only DT and the other 10 underwent DT+X. The addition of the Xiao procedure to spinal cord DT resulted in longer operative times (p = 0.024) and a greater chance of wound infection (p = 0.03). Patients in both treatment arms could intermittently void or dribble small amounts of urine (< 20% total bladder capacity) in response to scratching in dermatomes T-9 through S-2 using a standardized protocol, but the voiding was not reproducible and the volume voided was not clinically useful in any patient. Voiding in response to scratching was not more frequent in patients who underwent DT+X compared with those who underwent only DT. Bladder contractions in response to scratching occurred in both treatment arms at various intervals after surgery, but they were not more reproducible or more frequent in the patients who underwent the Xiao procedure than in the patients who did not. No patient in either treatment arm was continent of urine before, during, or after the study. CONCLUSIONS Patients with MM and LMM who underwent the Xiao procedure during spinal cord DT were no more likely to be able to void, to control their urination, to achieve continence, or to have a demonstrable urodynamic bladder contraction in response to cutaneous stimulation than patients who underwent only spinal cord DT. This study, in the context of disappointing results reported in other recent studies of the Xiao procedure, raises doubts about the clinical applicability of this procedure in humans until further basic science research is performed.

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., (© 2015 WILEY PERIODICALS, INC.)

Hospital-associated venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is increasing in pediatric centers. The objective of this work was to systematically review literature on pediatric hospital-acquired venous thromboembolism risk factors and risk-assessment models, to inform future prevention research. We conducted a literature search on pediatric venous thromboembolism risk via PubMed (1946-2014) and Embase (1980-2014). Data on risk factors and risk-assessment models were extracted from case-control studies, while prevalence data on clinical characteristics were obtained from registries, large (n>40) retrospective case series, and cohort studies. Meta-analyses were conducted for risk factors or clinical characteristics reported in at least three studies. Heterogeneity among studies was assessed with the Cochran Q test and quantified by the I(2) statistic. From 394 initial articles, 60 met the final inclusion criteria (20 case-control studies and 40 registries/large case series/cohort studies). Significant risk factors among case-control studies were: intensive care unit stay (OR: 2.14, 95% CI: 1.97-2.32); central venous catheter (OR: 2.12, 95% CI: 2.00-2.25); mechanical ventilation (OR: 1.56, 95%CI: 1.42-1.72); and length of stay in hospital (per each additional day, OR: 1.03, 95% CI: 1.03-1.03). Three studies developed/applied risk-assessment models from a combination of these risk factors. Fourteen significant clinical characteristics were identified through non-case-control studies. This meta-analysis confirms central venous catheter, intensive care unit stay, mechanical ventilation, and length of stay as risk factors. A few pediatric hospital-acquired venous thromboembolism risk scores have emerged employing these factors. Prospective validation is necessary to inform risk-stratified prevention trials., (Copyright© Ferrata Storti Foundation.)

Background: Previous studies have suggested that children with pre-formed anti-HLA antibodies (PRA) undergoing orthotopic heart transplantation (OHT) have increased risk for rejection, coronary artery vasculopathy (CAV) and death. In 2005, our program started utilizing aggressive desensitization (including plasmapheresis, IVIg, pulse cytoxan and rituximab) with the goal of improving outcomes for these patients. The purpose of this study was to compare outcomes with this new strategy in recipients with pre-OHT high PRA (>10%) vs low PRA ≤10%)., Methods: A retrospective study of 70 consecutive pediatric OHT patients was undertaken between January 2005 and July 2013 to identify patients with pre-OHT PRA >10% (high PRA), or PRA ≤10% (low PRA). Demographic/data information and detailed post-OHT outcomes, including rejection, 30-day and overall mortality, freedom from significant rejection, and CAV, were analyzed., Results: Fourteen (20%) patients had high PRA and 56 (80%) did not. There was a significant decrease in PRA values before and after desensitization. Thirty-day and overall mortality and the proportion of patients with rejections or CAV were lower in the high PRA group, although the difference was not statistically significant. Kaplan-Meier survival analysis revealed no significant difference in survival between the two groups. There was a significant difference in survival in our sensitized patients before 2005 vs after 2005., Conclusions: We identified no significant differences in outcomes between high or low PRA patients. These preliminary findings may suggest improvement in OHT outcomes for high PRA patients as a result of aggressive desensitization. A larger study is warranted to confirm these findings., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (P(heterogeneity)≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; P(trend) = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; P(trend)≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)≤0.003), age at diagnosis (P(interaction) = 0.04), and year of diagnosis (P(interaction) = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.