Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease.

Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity.

Risk of Recurrent Hypoglycemia and Long-term Survival after total Pancreatectomy: A Prospective Observational Study.

Objective: To evaluate risk of severe hypoglycemia after total pancreatectomy (TP).

Background: Historically, TP was feared due to loss of insulin and counter-regulatory hormones, as well as the risk of severe hypoglycemic events (SHE). While TP with islet auto-transplant (TPIAT) can preserve endocrine function, past studies reported 41% SHE incidence post-operatively.

Sequential islet transplants for type 1 diabetes are not associated with sustained or cumulative increases in hepatic portal venous pressure.

Islet transplantation (ITx) is advancing rapidly, with clinical trials of stem cell derived islets demonstrating short-term insulin independence. However, long-term insulin independence may still require multiple infusions. We examined the effects of sequential ITx on portal venous pressure and factors influencing acute pressure changes across 693 intraportal ITx procedures in 298 adults (44% M); who received up to 5 procedures, at the University of Alberta Hospital over 24 years.

High-dose Hook Effect in a Case of Giant Prolactinoma Confounded by Acute Kidney Injury.

A 21-year-old man admitted to the hospital for acute kidney injury developed blindness 5 days after admission. Workup included magnetic resonance imaging, which was terminated prematurely due to a ball bearing/air gun pellet in his neck causing pain. His incomplete scan revealed a large sellar mass causing significant compression of the optic chiasm.

Cardiotoxicity Associated with Venlafaxine-Defining Features in a Series of Five Cases and a Call for Proactive Monitoring.

Venlafaxine (VEN) is a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant. Arterial hypertension (HTN), heart failure (HF), and arrhythmias are side effects of VEN. Cardiotoxicity (CTOX) as a feature of VEN-associated side-effects has only rarely been described.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Evaluating Islet Cell Isolation and Transplantation From Donors Following Medical Assistance in Dying.

Background: Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors.

Methods: ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023.

Incidental Arrhythmias During Atrial Fibrillation Screening With Repeat 7-Day Holter ECGs in a Hospital-Based Patient Population.

Background: Screening for atrial fibrillation (AF) may reveal incidental arrhythmias of relevance. The aim of this study was to describe incidental arrhythmias detected during screening for AF in the STAR-FIB (Predicting SilenT AtRial FIBrillation in Patients at High Thrombembolic Risk) cohort study.

Methods And Results: In the STAR-FIB cohort study, we screened hospitalized patients for AF with 3 repeat 7-day Holter ECGs.

Epicardial adipose tissue dispersion at CT and recurrent atrial fibrillation after pulmonary vein isolation.

Objectives: Epicardial adipose tissue (EAT) remodeling is associated with atrial fibrillation (AF). Left atrial (LA) EAT dispersion on cardiac CT is a non-invasive imaging biomarker reflecting EAT heterogeneity. We aimed to investigate the association of LA EAT dispersion with AF recurrence after pulmonary vein isolation (PVI).

Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.

Background: In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types.

C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis.

Background: Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes.

Acute and long-term outcomes of quadripolar IS-4 versus bipolar IS-1 left ventricular leads in cardiac resynchronization therapy: A retrospective registry study.

Background: The implantation procedure of left ventricular (LV) leads and the management of cardiac resynchronization therapy (CRT) patients can be challenging. The IS-4 standard for CRT offers additional pacing vectors compared to bipolar leads (IS-1). IS-4 leads improve procedural outcome and may also result in lower adverse events during follow-up (FU) and improve clinical outcome in CRT patients.

Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials.

Background: Elexacaftor-tezacaftor-ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.

Methods: We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor-tezacaftor-deutivacaftor in participants with cystic fibrosis who were aged 18 years or older.

Acetylsalicylic Acid (Aspirin) for Primary Prevention of Cardiovascular Events in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Evidence regarding using acetylsalicylic acid (aspirin) for the prevention of cardiovascular (CV) events in patients with diabetes mellitus (DM) is inconsistent. Therefore, we performed a meta-analysis.

Methods: A literature search was performed (January 1990 to February 2022) and publications meeting the inclusion criteria were reviewed, and a meta-analysis was performed using RevMan software.

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years.

Objective: To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation.

Summary Background Data: Studies describing long-term outcomes with ITx and PTx are scarce.

Methods: We included adults undergoing ITx (n=266) and PTx (n=146) at the University of Alberta from January 1999 to October 2019.

Improved Glycemia and Quality of Life Among Loop Users: Analysis of Real-world Data From a Single Center.

Background: Despite do-it-yourself automated insulin delivery being an unapproved method of insulin delivery, an increasing number of people with type 1 diabetes (T1D) worldwide are choosing to use Loop, a do-it-yourself automated insulin delivery system.

Objective: In this study, we aimed to assess glycemic outcomes, safety, and the perceived impact on quality of life (QOL) in a local Edmonton cohort of known Loop users.

Methods: An observational study of adults with T1D who used Loop was performed.

C-peptide Targets and Patient-centered Outcomes of Relevance to Cellular Transplantation for Diabetes.

Background: C-peptide levels are a key measure of beta-cell mass following islet transplantation, but threshold values required to achieve clinically relevant patient-centered outcomes are not yet established.

Methods: We conducted a cross-sectional retrospective cohort study evaluating patients undergoing islet transplantation at a single center from 1999 to 2018. Cohorts included patients achieving insulin independence without hypoglycemia, those with insulin dependence without hypoglycemia, and those with recurrent symptomatic hypoglycemia.

A Novel MIP-1-Expressing Macrophage Subtype in BAL Fluid from Healthy Volunteers.

Tissue availability remains an important limitation of single-cell genomic technologies for investigating cellular heterogeneity in human health and disease. BAL represents a minimally invasive approach to assessing an individual's lung cellular environment for diagnosis and research. However, the lack of high-quality, healthy lung reference data is a major obstacle to using single-cell approaches to study a plethora of lung diseases.

A scoping review of Do-It-Yourself Automated Insulin Delivery system (DIY AID) use in people with type 1 diabetes.

Introduction: User designed Automated Insulin Delivery systems (AID), termed Do-It-Yourself (DIY) AID include; AndroidAPS, OpenAPS and Loop. These unregulated systems provide challenges for healthcare providers worldwide, with potential legal and ethical barriers to supporting their use. We performed a scoping review of the currently available literature surrounding DIY AID systems, specifically to highlight the evidence available to facilitate healthcare providers to support persons with diabetes who may benefit from DIY AID.

Do-It-Yourself and Commercial Automated Insulin Delivery Systems in Type 1 Diabetes: An Uncertain Area for Canadian Health-care Providers.

In the past century, since the discovery of insulin, methods of insulin delivery and glucose monitoring have advanced technologically. In particular, the introduction of insulin pumps, providing continuous subcutaneous insulin infusion (CSII), and continuous glucose monitors (CGMs) have been revolutionary for people living with type 1 diabetes. In this review, we have focussed on automated insulin delivery (AID) systems and discuss the implications of both approved and off-label options for the user and health-care providers.

Estimation of Early Graft Function Using the BETA-2 Score Following Clinical Islet Transplantation.

Little is known about how early islet graft function evolves in the clinical setting. The BETA-2 score is a validated index of islet function that can be calculated from a single blood sample and lends itself to frequent monitoring of graft function. In this study, we characterized early graft function by calculating weekly BETA-2 score in recipients who achieved insulin independence after single transplant (group 1, = 8) compared to recipients who required a second transplant before achieving insulin independence (group 2, = 7).

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study.

Background: Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited.

Methods: This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018.

The Relationship between Enhancing Left Atrial Adipose Tissue at CT and Recurrent Atrial Fibrillation.

Background The association of epicardial adipose tissue (EAT) and its metabolic activity with atrial fibrillation (AF) is an area of active investigation. Left atrial (LA) enhancing EAT (e-EAT) at cardiac CT may be a noninvasive surrogate marker for the metabolic activity of EAT. Purpose To determine the relationship between LA e-EAT and recurrence after AF ablation.

Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada.

Background: Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation.

Differences in Atrial Remodeling in Hypertrophic Cardiomyopathy Compared to Hypertensive Heart Disease and Athletes' Hearts.

Background: Hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD) and athletes’ heart share an increased prevalence of atrial fibrillation. Atrial cardiomyopathy in these patients may have different characteristics and help to distinguish these conditions. Methods: In this single-center study, we prospectively collected and analyzed electrocardiographic (12-lead ECG, signal-averaged ECG (SAECG), 24 h Holter ECG) and echocardiographic data in patients with HCM and HHD and in endurance athletes.