Effects of blood-brain barrier opening using ultrasound on tauopathies: A systematic review.

Unlabelled: Blood-brain barrier opening with ultrasound can potentiate drug efficacy in the treatment of brain pathologies and also provides therapeutic effects on its own. It is an innovative tool to transiently, repeatedly and safely open the barrier, with studies showing beneficial effects in both preclinical models for Alzheimer's disease and recent clinical studies. The first preclinical and clinical work has mainly shown a decrease in amyloid burden in mice models and in patients.

Endothelial Response to Blood-Brain Barrier Disruption in the Human Brain.

Cerebral endothelial cell (EC) injury and blood-brain barrier (BBB) permeability contribute to neuronal injury in acute neurological disease states. Preclinical experiments have used animal models to study this phenomenon, yet the response of human cerebral ECs to BBB disruption remains unclear. In our Phase 1 clinical trial (NCT04528680), we used low-intensity pulsed ultrasound with microbubbles (LIPU/MB) to induce transient BBB disruption of peri-tumoral brain in patients with recurrent glioblastoma.

Glucocorticoid Minimization in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An International Survey of Clinicians.

Rationale & Objective: Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on reducing treatment toxicities, notably through reduction of exposure to glucocorticoids. Glucocorticoid-sparing therapies such as avacopan are not widely available in many countries, and patients are exposed to high glucocorticoid doses. There is little data concerning what clinicians should accept as the lowest glucocorticoid dosing that can be used in induction therapy for AAV.

Effect of ultrasound-mediated blood-spinal cord barrier opening on survival and motor function in females in an amyotrophic lateral sclerosis mouse model.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB).

Methods: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.

Cardiovascular Risk in Patients With Glomerular Disease: A Narrative Review of the Epidemiology, Mechanisms, Management, and Patient Priorities.

Purpose Of Review: Cardiovascular (CV) disease is a major cause of morbidity and mortality for patients with glomerular disease. Despite the fact that mechanisms underpinning CV disease risk in this population are likely distinct from other forms of kidney disease, treatment and preventive strategies tend to be extrapolated from studies of patients with undifferentiated chronic kidney disease (CKD). There is an unmet need to delineate the pathophysiology of CV disease in patients with glomerular disease, establish unique risk factors, and identify novel therapeutic targets for disease prevention.

Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion.

Assessing Discharge Communication and Follow-up of Acute Kidney Injury in British Columbia: A Retrospective Chart Review.

Background And Objective: Acute kidney injury (AKI) affects up to 20% of hospitalizations and is associated with chronic kidney disease, cardiovascular disease, increased mortality, and increased health care costs. Proper documentation of AKI in discharge summaries is critical for optimal monitoring and treatment of these patients once discharged. Currently, there is limited literature evaluating the quality of discharge communication after AKI.

The Association Between Serum Vancomycin Level and Clinical Outcome in Patients With Peritoneal Dialysis Associated Peritonitis.

Introduction: Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum levels correlate with clinical outcomes remains unclear.

Methods: We conducted a retrospective single-center adult cohort study of 98 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022.

Are patients with primary glomerular disease at increased risk of malignancy?

Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases and the development of malignancies, with an estimated risk ranging from 5 to 11%. These malignancies include solid organ tumours as well as haematologic malignancies such as lymphoma and leukaemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of glomerular disease cases that were potentially secondary to an underlying malignancy, misclassification of glomerular disease type and ascertainment bias arising from an increased likelihood of physician encounters compared with the general population.

Stroke Subtype Among Individuals With Chronic Kidney Disease.

Background: It is widely accepted that there is a stepwise increase in the risk of acute ischemic stroke with chronic kidney disease (CKD). However, whether the risk of specific ischemic stroke subtypes varies with CKD remains unclear.

Objective: To assess the association between ischemic stroke subtypes (cardioembolic, arterial, lacunar, and other) classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and CKD stage.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

Background: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown.

Objectives: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+).

Unveiling the enigma of the blood-brain barrier in glioblastoma: current advances from preclinical and clinical studies.

Purpose Of Review: Glioblastoma (GBM), the most prevalent primary brain malignancy in adults, poses significant challenges in terms of treatment. Current therapeutic strategies for GBM patients involve maximal safe resection, followed by radiotherapy with concurrent and adjuvant temozolomide. However, despite this multimodal approach for GBM, the prognosis of GBM patients remains dismal because of their inherent primary and secondary resistances to treatments.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study.

Rationale & Objective: Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease.

Study Design: Observational cohort study.

Managing Hyperkalemia in the Modern Era: A Case-Based Approach.

The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format.

Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study.

Objective: To study age specific associations of modest reductions in estimated glomerular filtration rate (eGFR) with adverse outcomes.

Design: Retrospective, population based cohort study.

Setting: Linked healthcare administrative datasets in Ontario, Canada.

Risk of venous thromboembolism or hemorrhage among individuals with chronic kidney disease on prophylactic anticoagulant after hip or knee arthroplasty.

Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada.