Hereditary Angioedema Attacks in Patients Receiving Long-Term Prophylaxis: A Systematic Review.

Long-term prophylaxis (LTP) has been shown to reduce the frequency of hereditary angioedema (HAE) attacks; however, attacks occurring in patients receiving LTP have not been well characterized. The objective of this systematic review was to evaluate the proportion of type I/II HAE (HAE-C1INH) patients who experience attacks while receiving LTP, the characteristics of these attacks, and associated on-demand therapy use. A systematic search was conducted in PubMed to identify studies reporting LTP use with plasma-derived C1 inhibitor (pdC1INH), lanadelumab, berotralstat, androgens, or antifibrinolytics in patients with HAE-C1INH.

Brain Volumes in Opsoclonus-Myoclonus Ataxia Syndrome: A Longitudinal Study.

Introduction: Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain volumes in pediatric opsoclonus-myoclonus ataxia syndrome patients compared with age- and sex-matched healthy children.

Patients And Methods: This longitudinal case-control study included brain magnetic resonance imaging (MRI) scans from consecutive pediatric opsoclonus-myoclonus ataxia syndrome patients (2009-2020) and age- and sex-matched healthy control children.

Clinical features and outcomes in children with seronegative autoimmune encephalitis.

Aim: To characterize the presenting features and outcomes in children with seronegative autoimmune encephalitis, and to evaluate whether scores at nadir for the Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) or its paediatric-specific modification (ped-CASE) are predictive of outcomes.

Method: This observational study included children younger than 18 years of age with seronegative autoimmune encephalitis. Demographics and clinical data were collected.

Evaluation of patient-reported outcome measures for on-demand treatment of hereditary angioedema attacks and design of KONFIDENT, a phase 3 trial of sebetralstat.

Background: Hereditary angioedema (HAE) with C1-inhibitor deficiency (HAE-C1-INH) is characterized by recurrent, debilitating episodes of swelling. Sebetralstat, an investigational oral plasma kallikrein inhibitor, demonstrated promising efficacy for on-demand treatment of HAE-C1-INH in a phase 2 trial. We describe the multipronged approach informing the design of KONFIDENT, a phase 3 randomized, placebo-controlled, three-way crossover trial evaluating the efficacy and safety of sebetralstat in patients aged ≥12 years with HAE-C1-INH.

An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial.

Background: Guidelines recommend effective on-demand therapy for all individuals with hereditary angioedema. We aimed to assess the novel oral plasma kallikrein inhibitor, sebetralstat, which is in development, for on-demand treatment of hereditary angioedema attacks.

Methods: In this two-part phase 2 trial, individuals with type 1 or 2 hereditary angioedema aged 18 years or older were recruited from 25 sites, consisting of specialty outpatient centres, across nine countries in Europe and the USA.

Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

Objectives: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition.

Study Design: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition.

Results: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

Objective: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection.

Design: Multicentre retrospective cohort study.

Setting: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

Purpose: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection.

Methods: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome.

Machine learning classification of multiple sclerosis in children using optical coherence tomography.

Background: In children, multiple sclerosis (MS) is the ultimate diagnosis in only 1/5 to 1/3 of cases after a first episode of central nervous system (CNS) demyelination. As the visual pathway is frequently affected in MS and other CNS demyelinating disorders (DDs), structural retinal imaging such as optical coherence tomography (OCT) can be used to differentiate MS.

Objective: This study aimed to investigate the utility of machine learning (ML) based on OCT features to identify distinct structural retinal features in children with DDs.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

Introduction: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited.

Methods: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021.

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

Background: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time.

Methods: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar.

Pharmacological suppression of the kallikrein kinin system with KVD900: An orally available plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare genetic disease that leads to recurrent episodes of swelling and pain caused by uncontrolled plasma kallikrein (PKa) activity. Current guidelines recommend ready availability of on-demand HAE treatments that can be administered early upon attack onset. This report describes the pharmacological and pharmacodynamic properties of the novel oral small-molecule PKa inhibitor KVD900 as a potential on-demand treatment for HAE.

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals.

Outcomes in influenza and RANBP2 mutation-associated acute necrotizing encephalopathy of childhood.

Aim: To evaluate clinical and imaging features in patients with acute necrotizing encephalopathy of childhood (ANEC) to identify predictors of RANBP2 mutations, influenza association, and long-term outcomes.

Method: A retrospective chart review in patients with ANEC (2012-2020) seen at a tertiary pediatric center was performed. Children were included if they had acute inflammatory lesions in the basal ganglia and pons.

KVD900, an oral on-demand treatment for hereditary angioedema: Phase 1 study results.

Background: Attacks of hereditary angioedema are attributed to excessive plasma kallikrein (PKa) activity, which cleaves high-molecular-weight kininogen to generate the proinflammatory hormone bradykinin.

Objective: We evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KVD900, an orally administered inhibitor of PKa in healthy adults.

Methods: KVD900 was administered in 2 clinical studies.

Infection-Related Myelopathies.

Recent years have seen growing attention to inflammatory and infectious disorders of the spinal cord, not only due to the discovery of autoantibody-mediated disorders of the spinal cord [e.g., aquaporin-4 immunoglobulin G (IgG) antibodies and myelin oligodendrocyte glycoprotein IgG antibodies], but also due to the emergence of clusters of infection-related myelopathy, now known as acute flaccid myelitis.

Impact of COVID-19 public health measures on myelin oligodendrocyte glycoprotein IgG-associated disorders in children.

Background: Despite better characterization of the spectrum of MOG-IgG-associated disorders (MOGAD) in children, the role of infection in its pathophysiology remains unclear. The goal of this study was to evaluate if public health measures put in place to prevent the spread of SARS-CoV-2 in March 2020 in Ontario (Canada) have been associated with a change in the incidence of MOGAD and other neuroinflammatory disorders in children.

Methodology: We reviewed a single-centre cohort of children referred for a suspicion of neuroinflammatory disorder between January 2015 and March 2021.

Rituximab in children with myelin oligodendrocyte glycoprotein antibody and relapsing neuroinflammatory disease.

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol.

An upfront immunomodulatory therapy protocol for pediatric opsoclonus-myoclonus syndrome.

Background: Treatment of opsoclonus-myoclonus syndrome (OMS) has historically involved corticosteroids and intravenous immunoglobulin (IVIG) for a duration of 6-12 months or longer. This study evaluated whether a brief upfront immunomodulatory therapy protocol with rituximab reduces the duration of OMS therapy without adversely affecting OMS outcomes.

Procedure: Retrospective chart review was performed for consecutive children diagnosed with OMS from 2006 to 2019 at The Hospital for Sick Children (Toronto, Canada).

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada.

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively.

In situ label-free quantification of human pluripotent stem cells with electrochemical potential.

Conventional methods for quantification of undifferentiated pluripotent stem cells such as fluorescence-activated cell sorting and real-time PCR analysis have technical limitations in terms of their sensitivity and recyclability. Herein, we designed a real-time in situ label-free monitoring system on the basis of a specific electrochemical signature of human pluripotent stem cells in vitro. The intensity of the signal of hPSCs highly corresponded to the cell number and remained consistent in a mixed population with differentiated cells.