BackgroundTo identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA.MethodsPersons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates. Groups were compared using mixed models. Bivariate associations were assessed with Spearman correlation.ResultsCompared to controls, patients with RA had 75% greater muscle concentrations of IL-6 protein (p = 0.006). In patients with RA, muscle concentrations of inflammatory markers were positively associated (p < 0.05 for all) with disease activity (IL-1β, IL-8), disability (IL-1β, IL-6), pain (IL-1β, TNF-α, toll-like receptor (TLR)-4), and physical inactivity (IL-1β, IL-6). Muscle cytokines were not related to corresponding systemic cytokines. Prominent among the gene sets differentially expressed in muscles in RA versus controls were those involved in skeletal muscle repair processes and glycolytic metabolism. Metabolic profiling revealed 46% higher concentrations of pyruvate in muscle in RA (p < 0.05), and strong positive correlation between levels of amino acids involved in fibrosis (arginine, ornithine, proline, and glycine) and disability (p < 0.05).ConclusionRA is accompanied by broad-ranging molecular alterations in skeletal muscle. Analysis of inflammatory markers, gene expression, and metabolic intermediates linked disease-related disruptions in muscle inflammatory signaling, remodeling, and metabolic programming to physical inactivity and disability. Thus, skeletal muscle dysfunction might contribute to a viscous cycle of RA disease activity, physical inactivity, and disability.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1215-7) contains supplementary material, which is available to authorized users.

BACKGROUND Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of glycoprotein acetylation (GlycA)—a novel serum inflammatory biomarker that is an aggregate measure of enzymatically glycosylated acute phase proteins—and HDL subclasses on adverse events in a retrospective observational study of a secondary prevention population and to understand a priori defined potential interactions between GlycA and HDL subclasses. METHODS GlycA and HDL subclasses were measured using proton nuclear magnetic resonance spectroscopy in 7617 individuals in the CATHGEN (CATHeterization GENetics) cardiac catheterization biorepository. RESULTS GlycA was associated with presence [odds ratio (OR) 1.07 (1.02–1.13), P = 0.01] and extent [OR 1.08 (1.03, 1.12) P < 0.0005] of coronary artery disease and with all-cause mortality [hazard ratio (HR) 1.34 (1.29–1.39), P < 0.0001], cardiovascular mortality [1.37 (1.30–1.45), P < 0.0001] and noncardiovascular mortality [1.46 (1.39–1.54) P <0.0001] in models adjusted for 10 cardiovascular risk factors. GlycA and smaller HDL subclasses had independent but opposite effects on mortality risk prediction, with smaller HDL subclasses being protective [HR 0.69 (0.66–0.72), P < 0.0001]. There was an interaction between GlycA and smaller HDL subclasses—increasing GlycA concentrations attenuated the inverse association of smaller HDL subclasses with mortality. Adding GlycA and smaller HDL subclasses into the GRACE (Global Registry of Acute Coronary Events) and Framingham Heart Study Risk Scores improved mortality risk prediction, discrimination and reclassification. CONCLUSIONS These findings highlight the interaction of systemic inflammation and HDL with clinical outcomes and may increase precision for clinical risk assessment in secondary prevention populations.

Although heart failure (HF) and osteoporosis are common diseases, particularly in elderly populations, patients with HF have an increased risk for osteoporosis. The relationship of HF with osteoporosis is modified by gender and the severity of HF. In addition, shared risk factors, medication use, and common pathogenic mechanisms affect both HF and osteoporosis. Shared risk factors for these 2 conditions include advanced age, hypovitaminosis D, renal disease, and diabetes mellitus. Medications used to treat HF, including spironolactone, thiazide diuretics, nitric oxide donors, and aspirin, may protect against osteoporosis. In contrast, loop diuretics may make osteoporosis worse. HF and osteoporosis appear to share common pathogenic mechanisms, including activation of the renin-angiotensin-aldosterone system, increased parathyroid hormone levels, and/or oxidative/nitrosative stress. HF is a major risk factor for mortality following fractures. Thus, in HF patients, it is important to carefully assess osteoporosis and take measures to reduce the risk of osteoporotic fractures.

Rheumatoid meningitis typically presents as a late manifestation of rheumatoid arthritis, and its pathogenesis remains uncertain. We describe a patient with neurological symptoms, subsequently found to have a brain mass of unclear etiology. The findings from imaging and histological analysis led to a diagnosis of rheumatoid meningitis. Surprisingly, this case presented in the absence of a history of arthritis or other systemic signs typically seen in RA. This case highlights the fact that rheumatoid meningitis can be the initial presenting symptom of rheumatologic disease and should be kept in the differential in patients with or without a history of RA.

No abstract