Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L variant and study of organoids towards treatment.

Autosomal dominant Fanconi syndrome due to a variant (GATM-FS), causes accumulation of misfolded arginine-glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM-FS presents during childhood and progresses to end-stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known variant and the effect of creatine supplementation in kidney organoids.

The development and validation of a conceptual definition of avoidable transitions from long-term care to the emergency department: A mixed methods study.

Background/objectives: Transitions to and from Emergency Departments (EDs) can be detrimental to long-term care (LTC) residents and burden the healthcare system. While reducing avoidable transfers is imperative, various terms are used interchangeably including inappropriate, preventable, or unnecessary transitions. Our study objectives were to develop a conceptual definition of avoidable LTC-ED transitions and to verify the level of stakeholder agreement with this definition.

Sex- and Gender-Based Reporting in Antihypertensive Medication Literature Informing Hypertension Guidelines.

Background: Hypertension is the leading modifiable cardiovascular risk factor with recognized sex- and gender-based differences. We assessed the incorporation of sex and gender reporting in the antihypertensive medication literature informing hypertension guidelines.

Methods And Results: Literature cited in the International Society of Hypertension (2020), European Society of Cardiology/European Society of Hypertension (2018), American College of Cardiology/American Heart Association (2017), Latin American Society of Hypertension (2017), Pan-African Society of Cardiology (2020), and Hypertension Canada (2020) guidelines was systematically reviewed.

Prognostic Utility of Cardiovascular Magnetic Resonance-Based Phenotyping in Patients With Muscular Dystrophy.

Background The prognostic utility of cardiovascular magnetic resonance imaging, including strain analysis and tissue characterization, has not been comprehensively investigated in adult patients with muscular dystrophy. Methods and Results We prospectively enrolled 148 patients with dystrophinopathies (including heterozygotes), limb-girdle muscular dystrophy, and type 1 myotonic dystrophy (median age, 36.0 [interquartile range, 23.

Late laryngeal dysfunction in head and neck cancer survivors.

Objectives: Head and neck cancer (HNC) survivorship issues are areas of increasing research interest. Laryngeal dysfunction in HNC patients is particularly important given the importance of the larynx in voice, swallowing, and airway protection. The objective of our study is to characterize late laryngeal dysfunction in a cohort of long-term HNC survivors.

Gait in Cerebral Amyloid Angiopathy.

Background Gait is a complex task requiring coordinated efforts of multiple brain networks. To date, there is little evidence on whether gait is altered in cerebral amyloid angiopathy (CAA). We aimed to identify impairments in gait performance and associations between gait impairment and neuroimaging markers of CAA, cognition, and falls.

Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans.

Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non-invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non-failing control (NFC, n=46) explanted human hearts.

Use of medium chain triglyceride (MCT) oil in subjects with Alzheimer's disease: A randomized, double-blind, placebo-controlled, crossover study, with an open-label extension.

Introduction: Cerebral glucose and insulin metabolism is impaired in Alzheimer's disease (AD). Ketones provide alternative energy. Will medium chain triglyceride (MCT) oil, a nutritional source of ketones, impact cognition in AD?

Methods: This was a 6-month randomized, double-blind, placebo-controlled, crossover study, with 6-month open-label extension in probable AD subjects, on stable medications.

SNPs for Genes Encoding the Mitochondrial Proteins Sirtuin3 and Uncoupling Protein 2 Are Associated With Disease Severity, Type 2 Diabetes, and Outcomes in Patients With Pulmonary Arterial Hypertension and This Is Recapitulated in a New Mouse Model Lacking Both Genes.

Background Isolated loss-of-function single nucleotide polymorphisms (SNPs) for (a mitochondrial deacetylase) and (an atypical uncoupling protein enabling mitochondrial calcium entry) have been associated with both pulmonary arterial hypertension (PAH) and insulin resistance, but their collective role in animal models and patients is unknown. Methods and Results In a prospective cohort of patients with PAH (n=60), we measured SNPs for both and along with several clinical features (including invasive hemodynamic data) and outcomes. We found and SNPs often both in the same patient in a homozygous or heterozygous manner, correlating positively with PAH severity and associated with the presence of type 2 diabetes and 10-year outcomes (death and transplantation).

Statins and SARS-CoV-2 Infection: Results of a Population-Based Prospective Cohort Study of 469 749 Adults From 2 Canadian Provinces.

Background Small observational studies have suggested that statin users have a lower risk of dying with COVID-19. We tested this hypothesis in a large, population-based cohort of adults in 2 of Canada's most populous provinces: Ontario and Alberta. Methods and Results We examined reverse transcriptase-polymerase chain reaction swab positivity rates for SARS-CoV-2 in adults using statins compared with nonusers.

Emergency physician perspectives on initiating buprenorphine/naloxone in the emergency department: A qualitative study.

Objectives: The objective of this study was to examine the perspectives of Canadian emergency physicians on the care of patients with opioid use disorders in the emergency department (ED), in particular the real-world facilitators to prescribing buprenorphine/naloxone (BUP) in the ED.

Methods: We conducted semistructured qualitative interviews using a multi-site-focused ethnographic design. Purposive sampling via an existing national research network was used to recruit ED physicians.

Comparison of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Management Strategies Before Cardiac Surgery: A Pilot Randomized Controlled Registry Trial.

Background Postoperative clinical outcomes associated with the preoperative continuation or discontinuation of angiotensin-converting enzyme inhibitors ( ACEIs ) or angiotensin receptor blockers ( ARBs ) before cardiac surgery remain unclear. Methods and Results In a single-center, open-label, randomized, registry-based clinical trial, patients undergoing nonemergent cardiac surgery were assigned to ACEI / ARB continuation or discontinuation 2 days before surgery. Among the 584 patients screened, 261 met study criteria and 126 (48.