Presence of calcified carotid plaque predicts vascular events: The Northern Manhattan Study

The prognostic implications of carotid plaque calcification (CPC) relative to subsequent vascular events are unclear. Our aim was to determine the association between CPC and risk of vascular events in a prospective multi-ethnic cohort. CPC was assessed among 1118 stroke-free subjects (mean age 68 ± 8 years; 59% women; 59% Hispanic, 22% black, 19% white) from the Northern Manhattan Study using high-resolution B-mode ultrasound. CPC was defined by presence of any acoustic shadowing associated with carotid plaque, producing a reduction in echo amplitude due to intervening structures with high attenuation. Using Cox proportional hazards models, hazard ratios (HR) were estimated for the combined vascular outcome, defined as ischemic stroke (IS), myocardial infarction (MI) or vascular death (VD). Carotid plaque was present in 637 (57%) subjects. CPC was present in 225 subjects (20% of total cohort; 35% of those with plaque). During a mean follow-up time of 2.7 years, the combined vascular outcome occurred among 52 subjects (20 IS, 22 MI, and 24 VD). Adjusting for demographics, major vascular risk factors, and carotid intima media thickness, those with CPC (in comparison to those without plaque) had a significantly increased risk of the combined vascular outcome (HR 2.5, 95% CI 1.0–5.8). In this population-based cohort, the presence of calcified carotid plaque, as assessed by high-resolution B-mode ultrasound, was an independent predictor of vascular events. It may serve as a simple and non-invasive marker of increased atherosclerotic risk and further aid in vascular risk stratification

Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients with rheumatoid arthritis and an inadequate response to methotrexate: the ASSET randomised controlled trial

This randomised, double-blind, placebo-controlled phase IIIb study evaluated the impact of abatacept on MRI pathology as a primary outcome in methotrexate (MTX)-refractory patients with rheumatoid arthritis. Patients received intravenous abatacept (∼10 mg/kg) or placebo, on background MTX, for 4 months, followed by an 8-month open-label extension (OLE; all patients received abatacept plus MTX). Patients had 1.5T MRI with intravenous contrast at baseline, Months 4 and 12; wrist synovitis (three locations assessed), and wrist and hand (15 and eight locations assessed, respectively) osteitis and erosion were scored using OMERACT-RAMRIS. 26/27 abatacept- and 23/23 placebo-randomised patients completed Month 4 and entered the OLE; 26 and 21 completed Month 12. The primary endpoint was not achieved; mean change (SD) from baseline in synovitis was -0.44 (1.47) for abatacept versus 0.52 (1.38) for placebo (p=0.103) at Month 4. For mean change in synovitis adjusted for baseline score (sensitivity analysis), the difference between groups was -0.69, p=0.078. Adjusted mean changes (SE) in osteitis and erosion were -1.94 (0.86) and 0.45 (0.43) for abatacept, and 1.54 (0.90) and 0.95 (0.45) for placebo. Further MRI improvements were observed up to Month 12 for abatacept and from Months 4 to 12 for placebo-treated patients switched to abatacept at Month 4. Clinical efficacy was shown with abatacept and sustained to Month 12. Despite small patient numbers, MRI detected structural and synovial benefit, sustained to Month 12 in abatacept+MTX-treated patients, and improvements in structural and inflammatory outcomes for placebo+MTX-treated patients following addition of abatacept. Clinicaltrials.gov NCT0042019

A Fluorogenic Labeling of Live Viruses

Viruses are an important class of pathogens that can cause serious infectious diseases. The ability to directly analyze viral particles in real time is essential to understand their pathological functions. In this work, we developed a strategy for fluorogenic labeling of live viruses by using an optimal tetrazolate-functionalized AIEgen (Aggregation-induced emission luminogen), named PBET. Due to its AIE activities, this dye fluoresces weakly when dissolved in aqueous solution, thus providing dark fluorescence background. The fluorescence turn-on labeling is achieved by binding of PBET molecules into the outmost viral proteins (e.g., structural Capsid protein VP1), which triggers protein-induced fluorescence enhancement (PIFE) of PBET. Probably due to this PIFE/AIE-based sensing strategy, these PBET-labeled viruses can retain infectivity to a large extent, which is a great advantage for biologically friendly labeling. This fluorogenic labeling may find uses in imaging studies to combat virus-associated infectious diseases, especially those associated with previously unknown wild-type viruses