Orthopaedic Management of Gout.

Gout is characterized by the deposition of monosodium urate crystals in patients with chronically elevated blood levels of uric acid. It is the most common form of inflammatory arthritis in the United States and is often comorbid with hypertension, obesity, and chronic kidney disease. Initial presentation is usually an acutely warm, swollen joint, most commonly the first metatarsophalangeal joint, but a variety of locations may be affected. The main treatment for gout is medical management of acute inflammation and chronic uric acid levels, but surgical treatment may be indicated in cases of damage to the surrounding soft tissue, concomitant septic arthritis, symptomatic cartilage loss, or neurologic deficits. Based on the literature to date, gout does not seem to independently affect outcomes after total hip, knee, and ankle arthroplasty, but associated comorbidities affecting outcomes in these patients should be considered.

Serum amyloid A impairs the antiinflammatory properties of HDL.

HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO3 fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO3-injected mice lacking Saa1.1 and Saa2.1 exhibited a partial restoration of antiinflammatory and cholesterol efflux properties in adipocytes. Conversely, incorporation of SAA into HDL preparations reduced antiinflammatory properties but not to the same extent as HDL from AgNO3-injected mice. SAA-enriched HDL colocalized with cell surface-associated extracellular matrix (ECM) of adipocytes, suggesting impaired access to the plasma membrane. Enzymatic digestion of proteoglycans in the ECM restored the ability of SAA-containing HDL to inhibit palmitate-induced inflammation and cholesterol efflux. Collectively, these findings indicate that inflammation results in a loss of the antiinflammatory properties of HDL on adipocytes, which appears to partially result from the SAA component of HDL binding to cell-surface proteoglycans, thereby preventing access of HDL to the plasma membrane.