Perioperative extracorporeal membrane oxygenation in liver transplantation-bridge to transplantation, intraoperative salvage, and postoperative support: outcomes and predictors for survival in a large-volume liver transplant center.

Data on perioperative extracorporeal membrane oxygenation (ECMO) in liver transplantation (LT) are scarce. ECMO has been used preoperatively, intraoperatively, and postoperatively for a variety of indications at our center. This retrospective, single-center study of ECMO use peri-LT aimed to describe predictors for successful outcome in this highly select cohort of patients.

Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial.

Background: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment.

Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022).

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of oesophageal varices: study protocol for a randomised controlled trial.

Background: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality.

Macrophage activation markers are associated with infection and mortality in patients with acute liver failure.

Background And Aims: Acute liver failure is a multisystem disorder with a high mortality and frequent need for emergency liver transplantation. Following massive innate immune system activation, soluble markers of macrophage activation are released during liver damage and their association with disease severity and prognosis requires exploration.

Methods: Patients ALF from the United States Acute Liver Failure Study Group (USALFSG, n = 224) and King's College Hospital (n = 40) together with healthy controls (HC, n = 50) were recruited.

Immunopathogenesis of acute on chronic liver failure.

Acute-on-chronic liver failure is a well-established description of a high-mortality syndrome of chronic liver disease (usually cirrhosis) with organ failure. While the exact definition is under refinement, the accepted understanding of this entity is in patients with chronic liver disease and various organs in failure and where systemic inflammation is a major component of the pathobiology. There are limited therapies for a disease with such a poor prognosis, and while improvements in the critical care management and for very few patients, liver transplantation, mean 50% can survive to hospital discharge, rapid application of new therapies is required.

Liver Elastography in Acute Liver Failure: A Pilot Study.

Objectives: We aimed to assess the feasibility and reliability of sequential ultrasonographic and elastographic monitoring in acute liver failure (ALF).

Design: Observational study.

Setting: ALF is a rare, life-threatening disease that requires intensive care admission and often liver transplant, where the accurate selection of patients is crucial.

Computed Tomography (CT) Calcium Scoring in Primary Prevention of Acute Coronary Syndrome and Future Cardiac Events in Patients With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex and chronic autoimmune disease that impacts multiple organ systems and presents with varying symptomatology that makes targeting treatment extremely difficult. The cardiovascular system and more specifically the coronary arteries are heavily affected by SLE causing increased atherosclerosis and subsequently increased acute coronary syndrome (ACS) and increased future cardiac events. ACS is a common occurrence in patients with SLE due to the premature development of atherosclerosis due to the dysregulation of pro-inflammatory cytokines.

Should Canada adopt managed access agreements in Canada for expensive drugs?

Drugs are increasingly authorized based on less mature evidence, leaving payors faced with significant clinical and cost-effectiveness uncertainties. As a result, payors must often choose between reimbursing a drug that may not turn out to be cost-effective (or may even be unsafe) or delaying the reimbursement of a drug that is cost-effective and offers clinical benefit to patients. Novel reimbursement decision models and frameworks, such as managed access agreements (MAAs), may address this decision challenge.

Aeroacoustic source prediction using material surfaces bounding the flow.

This article presents an extension of Liepmann's characterization of an aeroacoustic source in terms of the motion of a bounding surface containing the source region. Rather than using an arbitrary surface, we express the problem in terms of bounding material surfaces, identified by Lagrangian Coherent Structures (LCS), which demarcate flow into regions with distinct dynamics. The sound generation of the flow is written in terms of the motion of these material surfaces using the Kirchhoff integral equation, so that the flow noise problem now appears like that of a deforming body.

Usage of Tranexamic Acid for Treatment of Subdural Hematomas.

The collection of blood in the subdural layer within the cranium is classified as a subdural hematoma. Prevalence of subdural hematomas is most common among older populations with the current standard of treatment being invasive surgical evacuation for patients presenting with acute subdural hematomas with a midline shift greater than 5 mm on computed tomography (CT).Tranexamic acid (TXA) has been identified as an alternative, non-invasive option to treat patients presenting with subdural hematoma who are not suitable for surgical intervention.

Lessons from Canada's notice of compliance with conditions policy for the life-cycle regulation of drugs.

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada's regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market clinical trials, finding that most NOC/c authorizations are based on one, single-arm clinical trial using a surrogate endpoint.

Potential therapies for acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that develops in approximately 30% of patients hospitalised with cirrhosis and is characterised by an acute decompensation of liver function associated with extra-hepatic organ failures and a high short-term mortality. At present, no specific therapies are available for ACLF, and current management is limited to treatment of the precipitating event and organ support. Given the high prevalence and high mortality of this severe liver disease, there is an urgent need for targeted treatments.

Can Managed Access Agreements Mitigate Evidentiary, Economic and Ethical Issues with Access to Expensive Drugs for Rare Diseases in the Canadian Context?

Expensive drugs for rare diseases (EDRDs) pose challenges for regulatory and reimbursement decision makers. Managed access agreements (MAAs), conditional reimbursement schemes that use a variety of price and evidence generation mechanisms to support value-based decision making, have the potential to address the evidentiary, economic and ethical issues associated with EDRDs. Several jurisdictions have successfully used MAAs to manage budget impact and evidentiary uncertainties, demonstrating the promise of this approach.

Lysophosphatidylcholines modulate immunoregulatory checkpoints in peripheral monocytes and are associated with mortality in people with acute liver failure.

Background & Aims: Acute liver failure (ALF) is a life-threatening disease characterised by high-grade inflammation and immunoparesis, which is associated with a high incidence of death from sepsis. Herein, we aimed to describe the metabolic dysregulation in ALF and determine whether systemic immune responses are modulated via the lysophosphatidylcholine (LPC)-autotaxin (ATX)-lysophosphatidylcholinic acid (LPA) pathway.

Methods: Ninety-six individuals with ALF, 104 with cirrhosis, 31 with sepsis and 71 healthy controls (HCs) were recruited.

Trilayered Hydrogel Scaffold for Vocal Fold Tissue Engineering.

The lamina propria within the vocal fold (VF) is a complex multilayered tissue that increases in stiffness from the superficial to deep layer, where this characteristic is crucial for VF sound production. Tissue-engineered scaffolds designed for VF repair must mimic the biophysical nature of the native vocal fold and promote cell viability, cell spreading, and vibration with air flow. In this study, we present a unique trilayered, partially degradable hydrogel scaffold that mimics the multilayered structure of the VF lamina propria.

A perspective on life-cycle health technology assessment and real-world evidence for precision oncology in Canada.

Health technology assessment (HTA) can be used to make healthcare systems more equitable and efficient. Advances in precision oncology are challenging conventional thinking about HTA. Precision oncology advances are rapid, involve small patient groups, and are frequently evaluated without a randomized comparison group.