Assessment of genetic variant burden in epilepsy-associated brain lesions.

It is challenging to estimate genetic variant burden across different subtypes of epilepsy. Herein, we used a comparative approach to assess the genetic variant burden and genotype-phenotype correlations in four most common brain lesions in patients with drug-resistant focal epilepsy. Targeted sequencing analysis was performed for a panel of 161 genes with a mean coverage of >400×.

ICAR: endoscopic skull-base surgery.

Background: Endoscopic skull-base surgery (ESBS) is employed in the management of diverse skull-base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature.

CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development.

Objective: The cyclin-dependent kinase like 5 (CDKL5) gene is a known cause of early onset developmental and epileptic encephalopathy, also known as CDKL5 deficiency disorder (CDD). We sought to (1) provide a description of seizure types in patients with CDD, (2) provide an assessment of the frequency of seizure-free periods and cortical visual impairment (CVI), (3) correlate these features with genotype and gender, and (4) correlate these features with developmental milestones.

Methods: This is a cohort study of patients with CDD.

Paternal-age-related de novo mutations and risk for five disorders.

There are established associations between advanced paternal age and offspring risk for psychiatric and developmental disorders. These are commonly attributed to genetic mutations, especially de novo single nucleotide variants (dnSNVs), that accumulate with increasing paternal age. However, the actual magnitude of risk from such mutations in the male germline is unknown.

Multi-institutional trial of non-operative management and surgery for uncomplicated appendicitis in children: Design and rationale.

Traditionally, children presenting with appendicitis are referred for urgent appendectomy. Recent improvements in the quality and availability of diagnostic imaging allow for better pre-operative characterization of appendicitis, including severity of inflammation; size of the appendix; and presence of extra-luminal inflammation, phlegmon, or abscess. These imaging advances, in conjunction with the availability of broad spectrum oral antibiotics, allow for the identification of a subset of patients with uncomplicated appendicitis that can be successfully treated with antibiotics alone.

Evaluating narrative operative reports for endoscopic sinus surgery in a residency training program.

Objective: The narrative operative report (NR) bears testimony to critical elements of patient care. Residents' NRs also provide insights into their comprehension of the procedure. NR documentation is an informal element of surgical residency training but data regarding quality of such training are scant.

Factors Associated With Management of Pediatric Ovarian Neoplasms.

Background: Available evidence supports ovary-sparing surgery for benign ovarian neoplasms; however, preoperative risk stratification of pediatric ovarian masses can be difficult. Our objective of this study was to characterize the surgical management of pediatric ovarian neoplasms across 10 children's hospitals and to identify factors that could potentially aid in the preoperative risk stratification of these lesions.

Methods: A retrospective review of girls and women aged 2 to 21 years who underwent surgery for an ovarian neoplasm between 2010 and 2016 at 10 children's hospitals was performed.

Clinical Consensus Statement: Balloon Dilation of the Eustachian Tube.

Objective: To develop a clinical consensus statement on the use of balloon dilation of the eustachian tube (BDET).

Methods: An expert panel of otolaryngologists was assembled with nominated representatives of general otolaryngology and relevant subspecialty societies. The target population was adults 18 years or older who are candidates for BDET because of obstructive eustachian tube dysfunction (OETD) in 1 or both ears for 3 months or longer that significantly affects quality of life or functional health status.

Simple ClinVar: an interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database.

Clinical genetic testing has exponentially expanded in recent years, leading to an overwhelming amount of patient variants with high variability in pathogenicity and heterogeneous phenotypes. A large part of the variant level data is aggregated in public databases such as ClinVar. However, the ability to explore this rich resource and answer general questions such as 'How many genes inside ClinVar are associated with a specific disease? or 'In which part of the protein are patient variants located?' is limited and requires advanced bioinformatics processing.

Variant Score Ranker-a web application for intuitive missense variant prioritization.

Motivation: The correct classification of missense variants as benign or pathogenic remains challenging. Pathogenic variants are expected to have higher deleterious prediction scores than benign variants in the same gene. However, most of the existing variant annotation tools do not reference the score range of benign population variants on gene level.

Targeted gene sequencing in 6994 individuals with neurodevelopmental disorder with epilepsy.

Purpose: We aimed to gain insight into frequencies of genetic variants in genes implicated in neurodevelopmental disorder with epilepsy (NDD+E) by investigating large cohorts of patients in a diagnostic setting.

Methods: We analyzed variants in NDD+E using epilepsy gene panel sequencing performed between 2013 and 2017 by two large diagnostic companies. We compared variant frequencies in 6994 panels with another 8588 recently published panels as well as exome-wide de novo variants in 1942 individuals with NDD+E and 10,937 controls.

Diseases, Injuries, and Risk Factors in Child and Adolescent Health, 1990 to 2017: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2017 Study.

Importance: Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies.

Objective: To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories.

Design, Setting, And Participants: This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis.

The spectrum of intermediate SCN8A-related epilepsy.

Objective: Pathogenic variants in SCN8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID) or movement disorders without epilepsy have been reported. The vast majority of the published SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE).

The management of pilonidal disease: A systematic review.

Objective: The goal of this systematic review by the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee was to derive recommendations from the medical literature regarding the management of pilonidal disease.

Methods: The PubMed, Cochrane, Embase, Web of Science, and Scopus databases from 1965 through June 2017 were queried for any papers addressing operative or non-operative management of pilonidal disease. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed.

Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene CDKL5. This unique disorder includes early infantile onset refractory epilepsy, hypotonia, developmental intellectual and motor disabilities, and cortical visual impairment. We review the clinical presentations and genetic variations in CDD based on a systematic literature review and experience in the CDKL5 Centers of Excellence.

Current operative management of congenital lobar emphysema in children: A report from the Midwest Pediatric Surgery Consortium.

Purpose: The purpose of this study was to evaluate the clinical presentation and operative outcomes of patients with congenital lobar emphysema (CLE) within a large multicenter research consortium.

Methods: After central reliance IRB-approval, a retrospective cohort study was performed on all operatively managed lung malformations at eleven participating children's hospitals (2009-2015).

Results: Fifty-three (10.

Development of a multi-institutional registry for children with operative congenital lung malformations.

Introduction: The purpose of this study was to develop a multi-institutional registry to characterize the demographics, management, and outcomes of a contemporary cohort of children undergoing congenital lung malformation (CLM) resection.

Methods: After central reliance IRB approval, a web-based, secure database was created to capture retrospective cohort data on pathologically-confirmed CLMs performed between 2009 and 2015 within a multi-institutional research collaborative.

Results: Eleven children's hospitals contributed 506 patients.

Diagnostic implications of genetic copy number variation in epilepsy plus.

Objective: Copy number variations (CNVs) represent a significant genetic risk for several neurodevelopmental disorders including epilepsy. As knowledge increases, reanalysis of existing data is essential. Reliable estimates of the contribution of CNVs to epilepsies from sizeable populations are not available.

Management of long gap esophageal atresia: A systematic review and evidence-based guidelines from the APSA Outcomes and Evidence Based Practice Committee.

Background: Treatment of the neonate with long gap esophageal atresia (LGEA) is one of the most challenging scenarios facing pediatric surgeons today. Contributing to this challenge is the variability in case definition, multiple approaches to management, and heterogeneity of the reported outcomes. This necessitates a clear summary of existing evidence and delineation of treatment controversies.

A comprehensive clinico-pathological and genetic evaluation of bottom-of-sulcus focal cortical dysplasia in patients with difficult-to-localize focal epilepsy.

We comprehensively studied the clinical presentation, stereo-EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug-resistant patients with difficult-to-localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS-FCD). We identified 10 patients with BOS-FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video-EEG monitoring. Brain MRI, including voxel-based morphometric analysis and surgical tissue submitted for histopathology, was reviewed.

Non-operative management of solid organ injuries in children: An American Pediatric Surgical Association Outcomes and Evidence Based Practice Committee systematic review.

Purpose: The American Pediatric Surgical Association (APSA) guidelines for the treatment of isolated solid organ injury (SOI) in children were published in 2000 and have been widely adopted. The aim of this systematic review by the APSA Outcomes and Evidence Based Practice Committee was to evaluate the published evidence regarding treatment of solid organ injuries in children.

Methods: A comprehensive search strategy was crafted and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were utilized to identify, review, and report salient articles.

Developing standardized competencies to strengthen immunization systems and workforce.

Despite global support for immunization as a core component of the human right to health and the maturity of immunization programs in low- and middle-income countries throughout the world, there is no comprehensive description of the standardized competencies needed for immunization programs at the national, multiple sub-national, and community levels. The lack of defined and standardized competencies means countries have few guidelines to help them address immunization workforce planning, program management, and performance monitoring. Potential consequences resulting from the lack of defined competencies include inadequate or inefficient distribution of resources to support the required functions and difficulties in adequately managing the health workforce.

Clinical spectrum of -related epileptic disorders.

Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to , encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.

Methods: We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases.

Spectrum of neurodevelopmental disease associated with the GNAO1 guanosine triphosphate-binding region.

Objective: To characterize the phenotypic spectrum associated with GNAO1 variants and establish genotype-protein structure-phenotype relationships.

Methods: We evaluated the phenotypes of 14 patients with GNAO1 variants, analyzed their variants for potential pathogenicity, and mapped them, along with those in the literature, on a three-dimensional structural protein model.

Results: The 14 patients in our cohort, including one sibling pair, had 13 distinct, heterozygous GNAO1 variants classified as pathogenic or likely pathogenic.