Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the “inflammatory reflex,” is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases.
The ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.
Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX 'beta' versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height) 2 ) and age were considered alongside femoral neck BMD (FN-BMD, g/cm 2 ) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSAderived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p50.001, deLong's test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more proactive approach to identifying women at high risk of hip fracture in the community.
Aims: Although considered as a feature of inflammatory rheumatic diseases, there is a lot of controversy around low bone mass in patients with psoriatic arthritis. The aim of this cross-sectional study was to analyze bone mineral density in patients with psoriatic arthritis, as well as to investigate its possible association with some measures of disease activity and functional capacity. Subjects and Methods:Sixty-nine patients with established psoriatic arthritis (mean age 56.20±12.23 years) and who has not been treated with specific antiosteoporotic drugs were recruited from the outpatient clinic database. Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and at the left hip. Disease activity measures included: duration of morning stiffness, tender and swollen joint count, patient's and physician's global assessment, presence of dactylitis and enthesitis, ESR, CRP and Disease Activity Score 28. Health Assessment Questionnaire was used to assess functional status.Results: According to WHO definition, spinal osteoporosis was found in 7.2% of patients, total hip osteoporosis in 1.4% of patients and femoral neck osteoporosis in 2.9% of patients. There was no significant association of any of the measures of disease activity with BMD at any site. Higher HAQ scores were associated with lower total hip BMD.Conclusions: In our sample of patients with psoriatic arthritis we did not find increased prevalence of osteoporosis. There was no association of BMD with indices of disease activity, while negative correlation was found between HAQ and total hip BMD.
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