A phase 2a, randomized, double-blind, placebo-controlled, three-arm, parallel-group study to assess the efficacy, safety, tolerability and pharmacodynamics of PF-06835919 in patients with non-alcoholic fatty liver disease and type 2 diabetes.

Aim: To assess the safety, tolerability and pharmacodynamics (PD) of the ketohexokinase inhibitor PF-06835919 in participants with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D).

Materials And Methods: This double-blind, placebo-controlled, parallel-group study enrolled adults with NAFLD (≥ 8% whole liver fat [WLF] using MRI proton density fat fraction [MRI-PDFF]) and T2D on stable doses of metformin (≥ 500 mg/day). Participants received once-daily placebo, PF-06835919 150 or 300 mg for 16 weeks.

Risk of venous thromboembolism in immune-mediated inflammatory diseases: a UK matched cohort study.

Objectives: To describe the risk of venous thromboembolism (VTE), and risk factors for VTE, in people with immune-mediated inflammatory diseases (IMID) (ulcerative colitis, Crohn's disease (CD), rheumatoid arthritis (RA) and psoriatic arthritis (PsA)), compared with a matched control population.

Methods: A total of 53 378 people with an IMID were identified over 1999-2019 in the UK Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database and were matched to 213 512 people without an IMID. The association between the presence of any IMID, and each IMID separately, and risk of VTE was estimated using unadjusted and multivariable-adjusted Cox proportional hazards models.

Cardiovascular risk factors and outcomes in early rheumatoid arthritis: a population-based study.

Objective: To assess the burden of cardiovascular disease (CVD) at and prior to diagnosis in people with early rheumatoid arthritis (RA) and subsequent CVD in these patients.

Methods: A retrospective case-control study using a large English primary care database. People with RA (n=6591) diagnosed between 2004 and 2016 (inclusive) were identified using a validated algorithm, matched 1:1 by age and gender to those without RA (n=6591) and followed for a median of 5.

"A Step and a Ceiling": mechanical properties of Ca spark vasoregulation in resistance arteries by pressure-induced oxidative activation of PKG.

We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to oxidative activation were studied using wire and pressure myography. Ca sparks and Ca transients within vascular smooth muscle cells of intact arteries were characterized using high-speed confocal microscopy of intact arteries.