Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.

Objective: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau.

Miniaturized electromagnetic tracking enables efficient ultrasound-navigated needle insertions.

Ultrasound (US) has gained popularity as a guidance modality for percutaneous needle insertions because it is widely available and non-ionizing. However, coordinating scanning and needle insertion still requires significant experience. Current assistance solutions utilize optical or electromagnetic tracking (EMT) technology directly integrated into the US device or probe.

CNS Inflammation as the First Sign of Complement Factor I Deficiency: A Severe Myelitis Treated With Intense Immunotherapy and Eculizumab.

Objectives: Complement factor I (CFI) deficiency is a rare autosomal recessive inborn error of immunity. In this report, we highlight that complete CFI deficiency may present with isolated and severe CNS inflammation without associated systemic features nor prior non-CNS episodes. This inflammation may respond to complement blockade therapy.

The Experience of Parents of Children With Genetically Determined Leukoencephalopathies With the Health Care System: A Qualitative Study.

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. We sought to gain a better understanding of their experience with the public health care system in Quebec, Canada, to obtain suggestions for improving their services, and to identify modifiable factors to improve their quality of life. We conducted interviews with 13 parents.

A Single-Center 10-Year Experience of 180 Transmasculine Patients Undergoing Gender-Affirming Mastectomy While Continuing Masculinizing Hormone Replacement Therapy.

Background: Gender-affirming mastectomy is a fundamental step in the transition process of transmasculine patients following the initiation of hormone replacement therapy. Its perioperative management, however, remains underreported and controversial. In this study, a large series of mastectomies in transmen maintaining hormonal therapy is presented.

Long-Term Survival of Patients After Total Pharyngolaryngoesophagectomy With Gastric Pull-Up Reconstruction for Hypopharyngeal or Laryngeal Cancer Invading Cervical Esophagus.

Objectives: Hypopharyngeal and laryngeal cancers are aggressive and usually diagnosed at advanced stage with esophagus invasion. Total pharyngolaryngoesophagectomy with gastric pull-up reconstruction has been a common surgery for these cancers but long-term outcomes are still questionable. This study aimed to investigate short-term and long-term outcomes of patients who underwent this surgery.

Variants in impair LSM complexes assembly, neurodevelopment in zebrafish and may be associated with an ultra-rare neurological disease.

Leukodystrophies, genetic neurodevelopmental and/or neurodegenerative disorders of cerebral white matter, result from impaired myelin homeostasis and metabolism. Numerous genes have been implicated in these heterogeneous disorders; however, many individuals remain without a molecular diagnosis. Using whole-exome sequencing, biallelic variants in were uncovered in two unrelated individuals, one with a leukodystrophy and the other who died .

Experience of Parents of Children with Genetically Determined Leukoencephalopathies Regarding the Adapted Health Care Services During the COVID-19 Pandemic.

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopathies during the pandemic given the adapted health care services.

Hematologic safety of Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer.

Background: Myelosuppression is a potential dose-limiting factor in radioligand therapy (RLT). This study aims to investigate occurrence, severity and reversibility of hematotoxic adverse events in patients undergoing RLT with Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC). The contribution of pretreatment risk factors and cumulative treatment activity is taken into account specifically.

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial.

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD).

Objective: This international, randomized 2 : 1, placebo-controlled, phase 3 study in patients ≥4 - < 8 years old with DMD due to any dystrophin mutation examined the effect of edasalonexent (100 mg/kg/day) compared to placebo over 52 weeks.

Methods: Endpoints were changes in the North Star Ambulatory Assessment (NSAA; primary) and timed function tests (TFTs; secondary).

Impact of a Pharmacist Intervention in the Emergency Department on the Appropriateness of Direct Oral Anticoagulants Prescribed in Venous Thromboembolism Patients.

Background: It is now widely accepted to manage low risk acute venous thromboembolism (VTE) in the outpatient setting with direct oral anticoagulants (DOACs). Although DOACs are straightforward to dose, they are high risk medications and not immune to medication errors. There is limited evidence that pharmacists' intervention has an impact on DOAC discharge medication errors in the ED.

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

Background: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype.

A Phenotypic Description of Congenital Myotonic Dystrophy using PhenoStacks.

Background: Congenital Myotonic Dystrophy (CDM1) is a rare neuromuscular condition caused by a triplet repeat expansion in the DMPK gene. Despite there being a well-recognized clinical syndrome, there has not been an effort to use a standardized ontology system to describe the disease characteristics in existing literature. Thus, comparing or contrasting different cohorts from the literature can be challenging, and coding disease features for clinical research or for registry data items is not uniform.

Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy.

Purpose: Skeletal muscle growth and regeneration rely on muscle stem cells, called satellite cells. Specific transcription factors, particularly PAX7, are key regulators of the function of these cells. Knockout of this factor in mice leads to poor postnatal survival; however, the consequences of a lack of PAX7 in humans have not been established.

Further delineation of TBCK - Infantile hypotonia with psychomotor retardation and characteristic facies type 3.

Deleterious homozygous or compound heterozygous mutations in the TBCK (TBC1-domain-containing kinase) gene (implicated in the MTOR pathway) produce profound hypotonia, global developmental delay, facial dysmorphic features, and brain abnormalities. The disorder has been named "infantile hypotonia with psychomotor retardation and characteristic facies-3" (IHPRF3). Here we present two sisters with a novel mutation in TBCK (NM_001163435.

A natural history study of X-linked myotubular myopathy.

Objective: To define the natural history of X-linked myotubular myopathy (MTM).

Methods: We performed a cross-sectional study that included an online survey (n = 35) and a prospective, 1-year longitudinal investigation using a phone survey (n = 33).

Results: We ascertained data from 50 male patients with MTM and performed longitudinal assessments on 33 affected individuals.

Developmental Milestones and Quality of Life Assessment in a Congenital Myotonic Dystrophy Cohort.

Background: Congenital myotonic dystrophy (CDM) is a neuromuscular disorder caused by a CTG triplet repeat expansion in the DMPK gene. In addition to the expected motor delay, affected children often have significant developmental disability in language and cognitive realms, which ultimately impacts on quality of life.

Objective: In a prospective cohort of children with CDM to 1) present the profile of language and motor developmental milestones, and 2) describe their early childhood health related quality of life (HRQOL).

Pharmacological therapy for the prevention and management of cardiomyopathy in Duchenne muscular dystrophy: A systematic review.

Cardiomyopathy is a major source of morbidity and mortality in Duchenne muscular dystrophy (DMD) patients now that respiratory care has improved. There is currently no definitive evidence guiding the management of DMD-associated cardiomyopathy (DMD-CM). The objective of this systematic review was to evaluate the effectiveness of pharmacotherapies for the prevention and/or management of DMD-CM and to determine the optimal timing to commence these interventions.

Echocardiographic guidance for diagnostic and therapeutic percutaneous procedures.

Echocardiographic guidance has an important role in percutaneous cardiovascular procedures and vascular access. The advantages include real time imaging, portability, and availability, which make it an effective imaging modality. This article will review the role of echocardiographic guidance for diagnostic and therapeutic percutaneous procedures, specifically, transvenous and transarterial access, pericardiocentesis, endomyocardial biopsy, transcatheter pulmonary valve replacement, pulmonary valve repair, transcatheter aortic valve implantation, and percutaneous mitral valve repair.