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Background In primary Total Knee Arthroplasty (TKA), it is still not clear if cemented or uncemented fixation has the best long-term survival. The Low Contact Stress (LCS) mobile-bearing (MB) knee system was introduced in 1977. The aim of this study is to investigate the long-term survival of this design with a minimum of 15-year follow-up. Methods A retrospective analysis was performed, with the primary endpoint for survival defined as revision. Cox regression analysis was performed to assess the association between type of fixation and the risk of revision, while correcting for potential confounders (diagnosis, design, age and sex). Results 1271 cases were included with inflammatory joint disease (IJD) (657 cases) and non-IJD (614 cases). TKAs were performed cemented in 522 cases and uncemented in 749 cases. A bicruciate retaining design was used in 180 cases, a rotating platform design in 174 cases and an anterior posterior glide posterior cruciate-retaining (PCR) design in 916 cases. Cumulative incidence of component revision at 15 years was 2.7% (95% CI 1.6; 4.5) for cemented and 10% (95% CI 8.1; 12.4) for uncemented TKA, respectively. The 20-year cumulative incidence was 2.9% (95% CI 1.7; 4.7) for cemented and 10.9% (95% CI 8.8; 13.4) for uncemented TKA, respectively. Age, non-IJD and PCR design were associated with a significantly higher risk of revision, regardless of the type of fixation. Conclusion Long-term survival for patients undergoing cemented or uncemented TKA using the LCS MB system revealed lower revision rates for cemented fixation. Revision risk was higher in younger, non-IJD patients who had the PCR design, regardless of the type of fixation. For the LCS MB TKA design, it is recommended to use cemented fixation.

Objectives:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.Methods:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.Results:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.Conclusion:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.

A meta-analysis of previous genome-wide association studies of Crohn’s disease and ulcerative colitis, the two most common forms of inflammatory bowel disease, with a combined total of more than 75,000 cases and controls, finds that most loci contribute to both phenotypes and other immune-mediated disorders. Pathogenesis of inflammatory bowel disease Genetic studies have implicated unsuspected mechanisms in the pathogenesis of Crohn's disease and ulcerative colitis, two of the most common forms of inflammatory bowel disease. This paper presents a meta-analysis of published genome-wide association studies, together with validation in more than 75,000 cases and controls. In addition to several new associations, the authors find that most loci contribute to both phenotypes, but also to other immune-mediated disorders. The data reveal an overlap between susceptibility loci for inflammatory bowel disease and mycobacterial infection, and between the pathways that govern host responses to mycobacteria and those predisposing to inflammatory bowel disease. Crohn’s disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations 1 . Genome-wide association studies and subsequent meta-analyses of these two diseases 2 , 3 as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy 4 , in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases 5 . Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases. The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed. The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease. Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine.

The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality. Rheumatoid arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications, early death, and socioeconomic costs. 1 The cause of rheumatoid arthritis is unknown, and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. However, several unmet needs remain. Current conventional and biologic disease-modifying therapies sometimes fail or produce only . . .

Objective To determine the magnitude of the risk of incident cardiovascular disease (CVD; fatal and non-fatal), including acute myocardial infarction (MI), cerebrovascular accidents (CVA) and congestive heart failure (CHF), in patients with rheumatoid arthritis (RA) compared to the general population through a meta-analysis of controlled observational studies. Methods The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic. Results Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)). Conclusions Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.

Gout is a common arthritis caused by deposition of monosodium urate crystals within joints after chronic hyperuricaemia. It affects 1–2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Diet and genetic polymorphisms of renal transporters of urate seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended drugs to treat acute attacks. Oral corticosteroids could be an alternative to these drugs. Interleukin 1β is a pivotal mediator of acute gout and could become a therapeutic target. When serum uric acid concentrations are lowered below monosodium urate saturation point, the crystals dissolve and gout can be cured. Patient education, appropriate lifestyle advice, and treatment of comorbidities are an important part of management of patients with gout.

Ankylosing spondylitis is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain, which can lead to structural and functional impairments and a decrease in quality of life. New imaging techniques and therapies have substantially changed the management of this disease in the past decade. Whether inhibition of radiographic progression and structural damage can be reached with available drugs is as yet unclear. Furthermore, treatment with non-steroidal anti-inflammatory agents and physiotherapy remains an important approach to long-term management of patients with ankylosing spondylitis. The new treatment options with tumour necrosis factor blockers seems a breakthrough for patients refractory to conventional treatment.

In a randomized trial involving children with severe systemic juvenile idiopathic arthritis, the anti–interleukin-6 receptor antibody tocilizumab was effective (response rate, 85% with tocilizumab vs. 24% with placebo). Adverse events included serious infections and neutropenia. Systemic juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis, systemic manifestations (spiking fever, rash, hepatosplenomegaly, lymphadenopathy, and serositis), and substantially elevated inflammatory markers. 1 It is the most severe subtype of JIA; approximately half the patients have an unremitting course of chronic polyarthritis (with or without persistent systemic features). Substantial joint damage and disability often develop in these patients. 2 , 3 Treatment remains challenging because of the limited efficacy of methotrexate 4 and tumor necrosis factor inhibitors 5 , 6 and because of the major toxicity of high-dose glucocorticoids. Efficacy of the interleukin-1 inhibitor anakinra has been reported in a subset of patients. 7 – . . .

Both giant-cell arteritis and polymyalgia rheumatica are immune-mediated diseases that are treated with glucocorticoids, with higher doses used for giant-cell arteritis. Prompt initiation of high doses and a biopsy are recommended when ischemic optic neuropathy is suspected. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage A 79-year-old woman presents with new-onset pain in her neck and both shoulders. She takes 7.5 mg of prednisone per day for giant-cell arteritis. Occipital tenderness and diplopia developed 11 months before presentation. At that time, her erythrocyte sedimentation rate was elevated, at 78 mm per hour, and a temporal-artery biopsy revealed granulomatous arteritis. The diplopia resolved after 6 days of treatment with 60 mg of prednisone daily. Neither headache nor visual symptoms developed when the glucocorticoids were tapered. How should this patient's care be managed? The Clinical Problem Giant-cell arteritis is an inflammatory vasculopathy that typically occurs in . . .