HerpesDRG: a comprehensive resource for human herpesvirus antiviral drug resistance genotyping.

The prevention and treatment of many herpesvirus associated diseases is based on the utilization of antiviral therapies, however therapeutic success is limited by the development of drug resistance. Currently no single database cataloguing resistance mutations exists, which hampers the use of sequence data for patient management. We therefore developed HerpesDRG, a drug resistance mutation database that incorporates all the known resistance genes and current treatment options, built from a systematic review of available genotype to phenotype literature.

Caplacizumab in pediatric immune thrombotic thrombocytopenic purpura: the UK TTP Registry experience.

Pediatric thrombotic thrombocytopenic purpura (TTP) is an ultrarare disease. Immune TTP (iTTP) is driven by anti-ADAMTS13 autoantibodies causing an imbalanced von Willebrand factor (VWF):ADAMTS13 axis, and rarer still in children, but potentially life-threatening. Caplacizumab is licensed for iTTP treatment in adults and adolescents aged ≥12 years who weigh ≥40 kg.

Determinants of Functional Outcome after Pediatric Hemispherotomy.

Objective: We aimed to evaluate determinants of functional outcome after pediatric hemispherotomy in a large and recent multicenter cohort.

Methods: We retrospectively investigated the functional outcomes of 455 children who underwent hemispherotomy at 5 epilepsy centers in 2000-2016. We identified determinants of unaided walking, voluntary grasping with the hemiplegic hand, and speaking through Bayesian multivariable regression modeling using missing data imputation.

Genomic and geographical structure of human cytomegalovirus.

Human cytomegalovirus (CMV) has infected humans since the origin of our species and currently infects most of the world's population. Variability between CMV genomes is the highest of any human herpesvirus, yet large portions of the genome are conserved. Here, we show that the genome encodes 74 regions of relatively high variability each with 2 to 8 alleles.

Machine Learning to Identify Genetic Salt-Losing Tubulopathies in Hypokalemic Patients.

Introduction: Clinically distinguishing patients with the inherited salt-losing tubulopathies (SLTs), Gitelman or Bartter syndrome (GS or BS) from other causes of hypokalemia (LK) patients is difficult, and genotyping is costly. We decided to identify clinical characteristics that differentiate SLTs from LK.

Methods: A total of 66 hypokalemic patients with possible SLTs were recruited to a prospective observational cohort study at the University College London Renal Tubular Clinic, London.

Expanding the Spectrum of Early Neuroradiologic Findings in β Propeller Protein-Associated Neurodegeneration.

Background And Purpose: β propeller protein-associated neurodegeneration (BPAN) is the most common neurodegeneration with brain iron accumulation disorder. Typical radiologic findings are T2 hypointensity in the substantia nigra and globus pallidus, as well as a T1 halolike substantia nigra hyperintense signal surrounding a hypointense central area. However, these findings are often subtle or absent on initial scans, risking diagnostic delay.

The Cochlea in Branchio-Oto-Renal Syndrome: An Objective Method for the Diagnosis of Offset Cochlear Turns.

Background And Purpose: An "unwound" or "offset" cochlea has been described as a characteristic imaging feature in patients with branchio-oto-renal syndrome, and recently recognized to be associated in particular to those with gene mutations. Determination of this feature has traditionally relied on subjective visual assessment. Our aim was to establish an objective assessment method for cochlear offset (the cochlear turn alignment ratio) and determine an optimal cutoff turn alignment ratio value that separates individuals with -branchio-oto-renal syndrome from those with -branchio-oto-renal syndrome and healthy controls.

Refining the Neuroimaging Definition of the Dandy-Walker Phenotype.

Background And Purpose: The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to establish updated imaging criteria for Dandy-Walker malformation on the basis of cerebellar development.

Materials And Methods: In this multicenter study, retrospective MR imaging examinations from fetuses and children previously diagnosed with Dandy-Walker malformation or vermian hypoplasia were re-evaluated, using the choroid plexus/tela choroidea location and the fastigial recess shape to differentiate Dandy-Walker malformation from vermian hypoplasia.

A Network Meta-Analysis of Retreatment Rates following Bevacizumab, Ranibizumab, Aflibercept, and Laser for Retinopathy of Prematurity.

Topic: To compare bevacizumab, ranibizumab, aflibercept, and laser treatment as primary therapies for retinopathy of prematurity (ROP) in terms of retreatment rate.

Clinical Relevance: Anti-VEGF agents are increasingly used as primary treatment for ROP and may provide superior outcomes compared with laser in posterior disease. Head-to-head comparisons between different anti-VEGFs are lacking.

The Feasibility and Acceptability of Remote Videoconference Use of the Brief Developmental Assessment Tool for Young Children with Congenital Heart Disease.

Young children with congenital heart disease (CHD) are at heightened risk of developmental delay. The outbreak of COVID-19 and the ensuing lockdowns presented an opportunity to test the feasibility of using a short neurodevelopmental assessment tool-the Brief Developmental Assessment (BDA)-remotely via new technologies. We tested the feasibility and acceptability of remote testing of the tool's 6 domains of development with 30 children younger than 5 years with CHD and 10 healthy controls.

Twenty-Year Experience and Outcomes in a National Pediatric Pulmonary Hypertension Service.

Pediatric pulmonary hypertension is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases, contributions of different pulmonary hypertension subtypes, therapeutic strategies, and clinical outcomes in children. To report the 20-year experience of a large UK National Pediatric Pulmonary Hypertension Service focusing on epidemiology and clinical outcomes. Consecutive patients presenting between 2001 and 2021 were included, and survival analysis was performed for incident patients.

Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies.

The genetic interferonopathies are a heterogeneous group of disorders thought to be caused by the dysregulated expression of interferons and are now commonly considered in the differential diagnosis of children presenting with recurrent or persistent inflammatory phenotypes. With emerging therapeutic options, recognition of these disorders is increasingly important, and neuroimaging plays a vital role. In this article, we discuss the wide spectrum of neuroradiologic features associated with monogenic interferonopathies by reviewing the literature and illustrate these with cases from our institutions.

Recommendations for uniform definitions used in newborn screening for severe combined immunodeficiency.

Background: Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia.

Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit.

A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data.

Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy.

Introduction: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults and is a leading cause of end-stage renal disease due to glomerulonephritis. Primary MN has a strong male predominance, accounting for approximately 65% of cases; yet, currently associated genetic loci are all located on autosomes. Previous reports of familial MN have suggested the existence of a potential X-linked susceptibility locus.

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).

Objectives: This study sought to characterize HCT outcomes in APDS.

Methods: Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.

Calcium isotope fractionation by osteoblasts and osteoclasts, across endothelial and epithelial cell barriers, and with binding to proteins.

Timely and accurate diagnosis of osteoporosis is essential for adequate therapy. Calcium isotope ratio (δCa) determination has been suggested as a sensitive, noninvasive, and radiation-free biomarker for the diagnosis of osteoporosis, reflecting bone calcium balance. The quantitative diagnostic is based on the calculation of the δCa difference between blood, urine, and bone.

Compassionate Use of Remdesivir in Children With Severe COVID-19.

Objectives: Remdesivir shortens time to recovery in adults with severe coronavirus disease 2019 (COVID-19), but its efficacy and safety in children are unknown. We describe outcomes in children with severe COVID-19 treated with remdesivir.

Methods: Seventy-seven hospitalized patients <18 years old with confirmed severe acute respiratory syndrome coronavirus 2 infection received remdesivir through a compassionate-use program between March 21 and April 22, 2020.

Associations between Deprivation, Geographic Location, and Access to Pediatric Kidney Care in the United Kingdom.

Background And Objectives: Pre-emptive kidney transplantation is advocated as best practice for children with kidney failure who are transplant eligible; however, it is limited by late presentation. We aimed to determine whether socioeconomic deprivation and/or geographic location (distance to the center and rural/urban residence) are associated with late presentation, and to what degree these factors could explain differences in accessing pre-emptive transplantation.

Design, Setting, Participants, & Measurements: A cohort study using prospectively collected United Kingdom Renal Registry and National Health Service Blood and Transplant data from January 1, 1996 to December 31, 2016 was performed.