Seminars in arthritis and rheumatism
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Urate is the end-product of the purine metabolism in humans. The dominant source of urate is endogenous purines and the remainder comes through diet. Approximately two thirds of urate is eliminated via the kidney with the rest excreted in the feces. ⋯ Hyperuricemia can result in the formation of monosodium urate (MSU) crystals that may be recognized as danger signals by the immune system. This immune response results in the activation of the NLRP3 inflammasome and ultimately in the production and release of interleukin-1β, and IL-18, that mediate both inflammation, pyroptotic cell death, and necroinflammation. It has also been demonstrated that soluble urate mediates effects on the kidney to induce hypertension and can induce long term epigenetic reprogramming in myeloid cells to induce "trained immunity." Together, these sequelae of urate are thought to mediate most of the physiological effects of hyperuricemia and gout, illustrating this biologically active molecule is more than just an "end-product" of purine metabolism.
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Semin. Arthritis Rheum. · Jun 2020
Randomized Controlled TrialOnset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: A 16-week dose-titration study.
To examine the onset and maintenance of efficacy of subcutaneous tanezumab for pain relief and functional improvement in difficult-to-treat patients with moderate-to-severe osteoarthritis (OA) in a 16-week dose-titration study (NCT02697773). ⋯ Subcutaneous tanezumab provided statistically significant improvements compared with placebo in average daily index joint pain within the first week and WOMAC Pain and Physical Function (week 2) that were generally maintained throughout the 16-week treatment period. Tanezumab 5 mg provided only modest additional efficacy over tanezumab 2.5 mg.
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Musculoskeletal (MSK) involvement of the hands is a significant source of morbidity, impacting on quality of life in patients with systemic sclerosis (SSc). MSK complications are common in SSc and can affect the whole of the MSK system. MSK hand involvement can occur early in the course of the disease. ⋯ Other important manifestations include (but are not limited to) calcinosis, acro-osteolysis and carpal tunnel syndrome. MSK imaging is an important tool that allows insight into both disease pathogenesis and to inform the clinical management of MSK complications. The purpose of this review is to provide an overview of the MSK hand complications in patients with SSc, highlighting the breadth and burden of pathology relevant to clinical practice.
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Semin. Arthritis Rheum. · Feb 2020
Comparative Study Observational StudyComparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naïve patients with rheumatoid arthritis.
To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). ⋯ In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.
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Semin. Arthritis Rheum. · Feb 2020
Risk of medical complications following total hip or knee arthroplasty in patients with rheumatoid arthritis: A register-based cohort study from Denmark.
To investigate the risk of medical complications following total hip and knee arthroplasty (THA/TKA) among rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients; and, to assess the risk of complications among biologics-treated RA patients. ⋯ In this study, RA was a risk factor for infection after THA/TKA, and RA patients treated with biologics had a slightly increased risk compared with non-biologics treated RA patients. Compared with OA, RA patients had a lower risk of VTE following THA/TKA, but our finding of increased incidences of VTE in biologics-treated patients warrants further studies.