Sleep in hospitalized children and adolescents: A scoping review.

Hospitalized children and adolescents are at risk of short sleep and subsequent adverse health effects, but little is known about actual sleep duration, the factors that cause sleep disturbances in an inpatient pediatric setting, and what has been done to promote sleep in this population. The aim of this review was to systematically identify, categorize, and synthesize the literature on sleep in children and adolescents in an inpatient setting. We searched five electronic databases (PubMed, CENTRAL, CINAHL, PsycINFO, and Scopus) and of the 3770 references identified, 28 were eligible for inclusion. From studies reporting age-specific sleep durations, we found that four out of nineteen fell within the National Sleep Foundations recommendations for age-specific sleep durations. Reported causes of sleep disturbances were primarily related to modifiable, external factors, e.g., nursing care activities and noise from equipment and other patients. Sleep-promoting interventions seemed acceptable to patients, parents, and healthcare professionals. However, the literature in this area is heterogeneous regarding methodology, reporting, and population characteristics. Our findings underline the importance of prioritizing and optimizing sleep in hospitalized pediatric patients and highlight the need for standardization in the planning and reporting of studies within this field.

Distinct circular RNA expression profiles in pediatric ependymomas.

Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non-specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric ependymomas. To advance our molecular understanding of ependymomas, we performed Next Generation Sequencing of rRNA-depleted total RNA of 10 primary ependymoma and three control samples. CircRNA expression patterns were correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ-FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, NanoString nCounter experiments were performed, using a custom-designed panel targeting 66 selected circRNAs, on a larger cohort that also included medulloblastomas and pilocytic astrocytomas. These experiments indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRNAs derived from RMST, LRBA, WDR78, DRC1 and BBS9 genes were specifically upregulated in ependymomas. In conclusion, circRNAs have different expression profiles in ependymomas relative to controls and between survivors and patients with a dismal outcome, suggesting that circRNAs could be exerted as diagnostic and prognostic biomarkers in the future if further validated in larger cohorts.

Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.

Purpose: Pediatric cancers are often difficult to classify and can be complex to treat. To ensure precise diagnostics and identify relevant treatment targets, we implemented comprehensive molecular profiling of consecutive pediatric patients with cancer relapse. We evaluated the clinical impact of extensive molecular profiling by assessing the frequency of identified biological onco-drivers, altered diagnosis, and/or identification of new relevant targeted therapies. Patients and Methods: Forty-six tumor samples (44 fresh-frozen; two formalin-fixed paraffin embedded), two bone marrow aspirates, three cerebrospinal fluid samples, and one archived DNA were obtained from 48 children (0-17 years; median 9.5) with relapsed or refractory cancer, where the disease was rapidly progressing in spite of their current treatment or they had exhausted all treatment options. The samples were analyzed by whole-exome sequencing (WES), RNA sequencing (RNAseq), transcriptome arrays, and SNP arrays. Final reports were available within 3-4 weeks after patient inclusion and included mutation status, a description of copy number alterations, differentially expressed genes, and gene fusions, as well as suggestions for targeted treatment. Results: Of the 48 patients, 33 had actionable findings. The most efficient method for the identification of actionable findings was WES (39%), followed by SNP array (37%). Of note, gene fusions were identified by RNAseq in 21% of the samples. Eleven findings led to clinical intervention, i.e., oncogenetic counseling, targeted treatment, and treatment based on changed diagnosis. Four patients received compassionate use targeted therapy. Six patients experienced direct benefits in the form of stable disease or response. Conclusion: The application of comprehensive genetic diagnostics in children with recurrent cancers allowed for discovery and implementation of effective targeted therapies and hereby improvement of outcome in some patients.