Precision Medicine for High-Risk Gene Fusions in Paediatric AML: a focus on KMT2A, NUP98, and GLIS2 Rearrangements.

Robust genetic characterization of paediatric AML has demonstrated that fusion oncogenes are highly prevalent drivers of AML leukemogenesis in young children. Identification of fusion oncogenes associated with adverse outcomes has facilitated risk stratification of patients, although successful development of precision medicine approaches for most fusion-driven AML subtypes have been historically challenging. This knowledge gap has been in part due to difficulties in targeting structural alterations involving transcription factors and in identification of a therapeutic window for selective inhibition of the oncofusion without deleterious effects upon essential wild-type proteins.

Hip displacement in children with cerebral palsy: surveillance to surgery - a current concepts review.

This review brings together a multidisciplinary, multinational team of experts to discuss the current state of knowledge in the detection and treatment of hip displacement in cerebral palsy (CP), a global public health problem with a high disease burden. Though common themes are pervasive, different views are also represented, reflecting the confluence of traditional thinking regarding the aetiology and treatment of hip displacement in CP with emerging research that challenges these tried-and-true principles. The development of hip displacement is most closely related to gross motor function, with radiographic surveillance programs based on the Gross Motor Function Classification System (GMFCS), the goal being early detection and timely treatment.

Pediatric Esophageal Button Battery Protocol Reduces Time From Presentation to Removal.

Objective: Evaluate implementation of an institutional protocol to reduce the time to removal of esophageal button battery (BB) and increase use of mitigation strategies.

Methods: We developed a protocol for esophageal BB management [Zakai's Protocol (ZP)]. All cases of esophageal BB impaction managed at a tertiary care center before and after implementation from 2011 to 2023 were reviewed.

Comparing Leadership Skills of Senior Emergency Medicine Residents in 3-Year Versus 4-Year Programs During Simulated Pediatric Resuscitation: A Pilot Study.

Objectives: The majority of pediatric patients in the United States (US) are evaluated and treated at general emergency departments. It is possible that discrepancies in length of emergency medicine (EM) residency training may allow for variable exposure to pediatric patients, critical resuscitations, and didactic events. The goal of this pilot study was to compare leadership skills of graduating EM residents from 3- to 4-year programs during simulated pediatric resuscitations using a previously validated leadership assessment tool, the Concise Assessment of Leader Management (CALM).

A novel deep intronic variant in LAMA2 identified by RNA sequencing.

LAMA2-related muscular dystrophy is caused by pathogenic variants of the alpha2 subunit of Laminin. This common form of muscular dystrophy is characterized by elevated CK >1000IU/L, dystrophic changes on muscle biopsy, complete or partial absence of merosin staining, and both central and peripheral nervous system involvement. Advancements in genomic testing using NGS and wider application of RNA sequencing has expanded our knowledge of novel non-coding pathogenic variants in LAMA2.

Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage.

Objective: Intraventricular hemorrhage (IVH) is a common cause of preterm brain injury. Fresh parent's own milk (POM) contains pluripotent stem cells (SCs) that produce neuronal cells in-vitro. The permeable neonatal blood brain barrier potentially allows SC delivery.

Public knowledge of button battery ingestions: A social media based cross-sectional analysis.

Introduction: Button battery (BB) ingestion injuries are a devastating and preventable event within the pediatric population. Efforts to reduce the prevalence of esophageal button battery ingestion injuries include primary preventative measures. It is integral to assess the public's baseline knowledge about BB injuries to tailor future primary prevention efforts.

Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease.

Background: Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard-of-care treatment is suboptimal for these children.

Methods And Results: The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416).

Assessing the quality and value of metabolic chart data for capturing core outcomes for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

Background: Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits.

Methods: We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes.

Intractable abdominal pain as the sole symptom of Varicella Zoster reactivation after allogeneic stem cell transplantation: brief case report and review of the literature.

After primary infection, Varicella Zoster (VZV) persists in sensory dorsal root ganglia and may be reactivated in periods of diminished T-cell immunity. Varicella Zoster reactivation post allogenic stem cell transplantation (HSCT) can be challenging to diagnose as it does not always present with characteristic skin lesions. We describe a pediatric patient who presented with isolated severe abdominal pain with no other symptoms.

Understanding the Clinical Utility of Genome Sequencing in Critically Ill Newborns.

Diagnostic genome sequencing (GS) in newborns may have many benefits. More accurate diagnosis could spur the development of innovative genomic therapies. A precise diagnosis could help doctors and parents anticipate clinical problems and inform a family's future reproductive choices.

Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 inhibitor, trametinib, has been approved in select BRAF V600-mutant solid tumors.

The Epilepsy Surgery Experience in Children With Infantile Epileptic Spasms Syndrome at a Tertiary Care Center in Canada.

Infantile epileptic spasms syndrome is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. Appropriately selected patients with infantile epileptic spasms syndrome may be candidates for epilepsy surgery. This is a single-center retrospective case series of children 0-18 years with a current or previous diagnosis of infantile epileptic spasms syndrome with a lesion on magnetic resonance imaging (MRI) and/or positron emission tomography scan who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada.

Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric V600-Mutant Low-Grade Glioma.

Purpose: V600 mutations occur in many childhood cancers, including approximately 20% of low-grade gliomas (LGGs). Here, we describe a phase I/II study establishing pediatric dosing and pharmacokinetics of trametinib with or without dabrafenib, as well as efficacy and safety in a disease-specific cohort with V600-mutant LGG; other cohorts will be reported elsewhere.

Methods: This is a four-part, phase I/II study (ClinicalTrials.

Mechanical Ventilation in ARDS With an Automatic Resuscitator.

Background: The Oxylator is an automatic resuscitator, powered only by an oxygen cylinder with no electricity required, that could be used in acute respiratory failure in situations in which standard mechanical ventilation is not available or feasible. We aimed to assess the feasibility and safety of mechanical ventilation by using this automatic resuscitator in an animal model of ARDS.

Methods: A randomized experimental study in a porcine ARDS model with 12 pigs randomized to the Oxylator group or the control group (6 per group) and ventilated for 4 h.

Educators Describe the "Best Things" About Students with Autism at School.

This study examined educators' descriptions of the positive character traits of students with autism spectrum disorder at ages 7-8 and 10-11, using an adapted version of the Values in Action (VIA) Classification of Strengths. The most commonly endorsed strengths at both age intervals were kindness, specific skills, self-regulation, and perseverance. Higher scores for challenging behavior were associated with a lower likelihood of endorsement for Happiness and Courage traits.

Workload Measurement in Subspecialty Placental Pathology in Canada.

Background: Workload measurement is important to help determine optimal staffing and workload distribution for pathology laboratories. The Level 4 Equivalent (L4E) System is the most widely used Anatomical Pathology (AP) workload measurement tool in Canada. However, it was initially not developed with subspecialties in mind.