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Adipokines are related to knee osteoarthritis, but their exact role is not well known. The aim of this study was to evaluate the association between adipokines in synovial fluid and clinical severity in patients with knee osteoarthritis with joint effusion. Cross-sectional study with systematic inclusion of female patients with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, physical exercise, knee osteoarthritis symptoms duration, classical cardiovascular risk factors and different anthropometric measurements were collected. Metabolic syndrome was defined in accordance to National Cholesterol Education Program-Adult Treatment Panel III. Radiographic severity was evaluated according to Kellgren-Lawrence scale and Lequesne index was used to assess clinical severity. Seven adipokines (leptin, adiponectin, resistin, visfatin, osteopontin, omentin and chemerin) and three inflammatory markers (tumor necrosis factor α, interleukin 6 and high sensitivity C-reactive protein) were measured by enzyme-linked immunosorbent assay in synovial fluid. Kellgren-Lawrence grade, physical exercise, all anthropometric measurements (especially waist circumference), tumor necrosis factor α, and high levels of leptin, resistin, and ostepontin were related to knee osteoarthritis severity. After adjustment for clinical confounders (age, symptom duration, and radiology), anthropometric measurements, inflammatory markers, and all evaluated adipokines, there were independent associations with clinical severity for resistin (directly associated) and visfatin (inversely associated). No other adipokines or inflammatory markers were independently associated with Lequesne index. The association of radiological parameters, physical exercise, and waist circumference with Lequesne index remained after adjustment.

Resistin was directly associated, and visfatin was inversely associated, with clinical severity in female patients with knee osteoarthritis with joint effusion. These associations were more important after adjustment for confounders, especially when all adipokines were evaluated.

The aims of the total knee arthroplasty are to reduce or completely relieve pain and improve mobility of the affected joint. In the last decade navigation systems based on computer and infrared camera technology are developing quickly as an alternative to conventional surgical navigation techniques. We compare post-operative results in 2 groups of patients after total knee arthroplasty. The groups consist of patients operated with the navigation system performing total knee arthroplasty compared with another group patients where we implanted the total knee arthroplasty using mechanical navigation system for bone resection. All patients suffered from gonarthrosis grade III or IV and had pre-operative axial deformity of the mechanical axis in the knee more than 10 degrees. Post-operative follow up X-ray was aimed to establish the mechanical axis of the limb (Mikulicz line). Statistical analysis was directed on testing the difference between two groups using the method of Mann-Whitney non-parametric test. Using the computerised navigation system we achieved excellent or good result in as much as 94% patients; whereas using the conventional navigation such results were in 87%. It was delightful to find that using the computerised navigation system we did not have any dissatisfactory result and the range of axial deformities deviating from the ideal Mikulicz line was significantly reduced.

Results of our study show advantage in using the optoelectronic navigation system in total knee arthroplasty. Computerised navigation system enables exact insertion of knee components which results in longer life-span of the prosthesis (Tab. 2, Fig. 6, Ref. 19).

Glycogen synthase kinase 3β (GSK-3β) has been demonstrated to be involved in immune and inflammatory responses via multiple signaling pathways, leading to the production of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK-3β in the pathogenesis of lupus nephritis in 2 mouse models. Thiadiazolidinone 8 (TDZD-8), a selective inhibitor of GSK-3β, was administered intraperitoneally to 12-week-old MRL/lpr mice for 8 weeks or to 22-week-old (NZB × NZW)F1 mice for 12 weeks. The expression of GSK-3β and NLRP3 inflammasome components was analyzed. Proteinuria, biochemical parameters, proinflammatory cytokines, anti-double-stranded DNA (anti-dsDNA) antibody levels, and renal pathology were examined. In vitro, the effect of GSK-3β-directed small interfering RNA (siRNA) on NLRP3 inflammasome activation was evaluated in bone marrow-derived macrophages (BMMs) from the mice and in the J774A.1 macrophage cell line. The incidence of severe proteinuria and renal inflammation was significantly attenuated in both models, with a significant reduction in anti-dsDNA antibody production, immune complex deposition in the kidney, and circulating proinflammatory cytokine levels. TDZD-8 inhibited the activation of GSK-3β and caspase 1, with a concomitant decrease in interleukin-1β (IL-1β) synthesis. In vitro, GSK-3β siRNA transfection of mouse BMMs and the J774A.1 cell line with GSK-3β siRNA inhibited the expression of GSK-3β, the activation of caspase 1, and the production of IL-1β.

These results show that GSK-3β promotes lupus nephritis at least partly by activating the NLRP3/IL-1β pathway. The linking of GSK-3β to the NLRP3/IL-1β pathway is a novel observation in our study. Our results suggest that the GSK-3β/NLRP3/IL-1β pathway may be a potential therapeutic target for lupus in humans.

The burden of disability, analgesia, and health services use associated with knee pain and osteoarthritis (OA) in developing countries is relatively unknown, despite a high proportion of these populations required to be engaged in heavy occupational physical activity throughout their life span. The aim of this survey was to estimate the burden of disability, analgesia, and health services use associated with knee pain in rural China. This was a population-based cross-sectional survey among residents, aged 50 years and older, of Wuchuan County, Inner Mongolia. Participants completed an interviewer-based questionnaire, evaluating knee pain and associated disability, analgesia, and health services use, and obtained bilateral standardized weight-bearing knee radiographs. Of the 1,027 participants, 513 (50%) reported knee pain on most days of at least 1 month in the past year, with 109 (21%) also demonstrating radiographic OA (Kellgren-Lawrence grade ≥2) in the symptomatic knee. Adjusting for age, gender, body mass index (BMI), education, and back pain, the presence of knee pain was associated with significantly greater difficulty in walking, climbing 10 steps, stooping, completing cleaning chores, and preparing meals. Among the 513 subjects with knee pain, the additional presence of radiographic evidence of OA was significantly associated with more occasions of "unbearable" pain (59% versus 36%) and restricted activity (64% versus 39%), as well as increased use of nonsteroidal antiinflammatory drugs (NSAIDs) (88% versus 78%) and the reported number of doctor visits (59% versus 33%) in the past year. The use of paracetamol for knee pain was rare (6% versus 2%).

Knee pain is highly prevalent in rural northern China. The associated significant disability and marked preferential use of NSAIDs as analgesia should be of concern in these communities reliant on heavy occupational physical activity for their livelihood. The findings will be useful to guide the distribution of future health care resources and preventive strategies.

To describe a new short-term treatment for pain in rheumatoid arthritis (RA)-affected temporomandibular joint (TMJ). We investigated four female patients (age 42.8+/-26.0 yr) with chronic rheumatoid arthritis affecting a single TMJ. Patients had received antirheumatic drugs such as sodium aurothiomalate, and as a result showed no symptoms in other body joints. Linear polarized near infrared radiation using Super Lizer was applied weekly with and/or without jaw movement to the unilateral skin areas overlying the mandibular fossa, anterior articular tubercle, masseter muscle and posterior margin of the ramus of the mandible. The duration of irradiation to each point was two seconds on and ten seconds off per cycle and the intensity at each point was approximately 138 J x cm(-2) at a wavelength of 830 nm. Interincisal distance was measured with maximal mouth opening in the absence and presence of pain before and after each treatment. Additionally, subjective TMJ pain scores assessed using a visual analog scale were performed for painful maximal mouth opening before and after each irradiation. TMJ pain disappeared after only four treatments. Moreover, painless maximal mouth opening without pain after irradiation in three patients was on average improved to 5.3+/-2.1 mm. However, one case was observed where the opening length prior to irradiation did not improve, despite the fact that the RA-affected TMJ pain had disappeared.

Application of linear polarized near infrared irradiation to patients with RA-affected TMJ pain is an effective and non-invasive short-term treatment.

To assess the efficacy of anakinra treatment in patients with adult-onset Still's disease (AOSD) that is refractory to corticosteroids, methotrexate (MTX), and etanercept. Four patients with AOSD were treated with prednisone and MTX and 2 patients were also treated with etanercept for worsening symptoms and indicators of systemic inflammation. White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in 1 patient, serum creatinine levels were determined. Treatment with anakinra at 100 mg/day was initiated. The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal </=200), and a CRP level of 86 mg/liter (normal <8). Levels of interleukin-1beta (IL-1beta), IL-1alpha, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, the WBC count was 14,600/mm(3), the CRP level was 86 mg/liter, and the ferritin level was 573 ng/ml, with daily spiking fevers to 104 degrees F, rash, and swollen joints. Within hours of the first injection, the patient was afebrile and asymptomatic; within days, the WBC count, ferritin level, and CRP level decreased into the normal range. On 2 occasions, anakinra was withheld. Within a few days, the WBC count rose to >20,000/mm(3) with prominent neutrophilia, the CRP level rose to >200 mg/liter, and the ferritin level rose to >3,000 ng/ml. Upon restarting anakinra, the patient became afebrile, the WBC count fell to 8,000/mm(3), the CRP level fell to <3 mg/liter, and the ferritin level fell to <300 ng/ml. Three additional patients with refractory AOSD who experienced rapid reductions in fever, symptoms, and markers of inflammation when treated with anakinra are reported.

Refractory AOSD appears to be IL-1-mediated since anakinra decreases hematologic, biochemical, and cytokine markers and also produces rapid reductions in systemic and local inflammation. Reported efficacy of tumor necrosis factor-blocking therapies in AOSD may be due to a reduction in IL-1.

To investigate whether molecules found to be up-regulated within hours of surgical joint destabilization in the mouse are also elevated in the analogous human setting of acute knee injury, how this molecular response varies between individuals, and whether it is related to patient-reported outcomes in the 3 months after injury. Seven candidate molecules were analyzed in blood and synovial fluid (SF) from 150 participants with recent structural knee injury at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following baseline. Knee Injury and Osteoarthritis Outcome Score 4 (KOOS4 ) was obtained at baseline and 3 months. Patient and control samples were compared using Meso Scale Discovery platform assays or enzyme-linked immunosorbent assay. Six of the 7 molecules were significantly elevated in human SF immediately after injury: interleukin-6 (IL-6), monocyte chemotactic protein 1, matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), activin A, and tumor necrosis factor-stimulated gene 6 (TSG-6). There was low-to-moderate correlation with blood measurements. Three of the 6 molecules were significantly associated with baseline KOOS4 (those with higher SF IL-6, TIMP-1, or TSG-6 had lower KOOS4 ). These 3 molecules, MMP-3, and activin A were all significantly associated with greater improvement in KOOS4 over 3 months, after adjustment for other relevant factors. Of these, IL-6 alone significantly accounted for the molecular contribution to baseline KOOS4 and change in KOOS4 over 3 months.

Our findings validate relevant human biomarkers of tissue injury identified in a mouse model. Analysis of SF rather than blood more accurately reflects this response. The response is associated with patient-reported outcomes over this early period, with SF IL-6 acting as a single representative marker. Longitudinal outcomes will determine if these molecules are biomarkers of subsequent disease risk.

To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis. The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies.

This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Scleritis is a rare, progressive and serious disease, the signs of which are inflammation and edema of episcleral and scleral tissues and is greatly associated with systemic rheumatoid diseases. To perform a prospective and comparative study between ophthalmologic manifestations, serologic findings and therapeutic response of patients with isolated scleritis and scleritis associated with systemic rheumatoid disease. Thirty-two outpatients with non-infectious scleritis were studied, from March 2006 to March 2008. The treatment was corticoid eye drops associated with anti-inflammatory agents, followed by systemic corticoids and immunosuppressive drugs if necessary, was considered successful after six months without scleritis recurrence. Fourteen of 32 patients had scleritis associated with systemic rheumatoid disease, of which nine had rheumatoid arthritis, two systemic lupus erythematosus, one Crohn's disease, one Behçet's disease and one gout. There were no difference in relation to involvement and ocular complications, there was predominance of nodular anterior scleritis and scleral thinning was the most frequent complication. The scleritis associated with systemic rheumatoid disease group had 64.3% of autoantibodies, versus 27.8% among those with isolated scleritis and this difference was statistically significant. In the isolated scleritis group 16.7% used anti-inflammatory, 33.3% corticosteroids, 27.8% corticosteroids with one immunosuppressive drug, 5.5% two immunosuppressive drugs, 16.7% corticosteroids with two immunosuppressive drugs and 33.3% pulse of immunosuppressive drugs, there was remission in 88.9%. In the scleritis associated with systemic rheumatoid disease group 7.1% used anti-inflammatory, 7.1% corticosteroids, 50% corticosteroids with one immunosuppressive drug, 7.1% two immunosuppressive drugs and 22.2% pulse of immunosuppressive drugs, 100% had treatment success.

Prevalence of unilateral nodular scleritis was noted in both groups and higher rates of all the parameters tested were noted in the scleritis associated with systemic rheumatoid disease group. There were no differences between the groups with respect to the use of immunosuppressive drugs and therapeutic response, which was fully satisfactory in the scleritis associated with systemic rheumatoid disease group and satisfactory in the isolated scleritis group.

The association between vasculitis and large granular lymphocyte (LGL) leukemia has rarely been reported or investigated. Thus, we assessed the clinical and biological phenotypes of LGL leukemia associated with vasculitis. We studied a series of 11 patients displaying LGL leukemia associated with vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there were nine women and two men. The mean follow-up period was 45 months. The main LGL lineage was T-LGL (10 patients), and only one NK-LGL was identified. Clinical and biological features of T-LGL leukemia were compared with those from the 2009 French T-LGL registry. We did not find any relevant differences except that patients with LAV were predominantly female (p < 0.05). The most frequently observed vasculitis was cryoglobulinemia (n = 5). Three patients presented with cutaneous leukocytoclastic angiitis, two patients had ANCA-negative microscopic polyangiitis, and one patient had giant cell arteritis. The main clinical features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic finding was leucocytoclastic vasculitis (54%). The rate of complete remission was high; i.e., 80%. A minority of patients had a vasculitis relapse (27%). Three patients (27%) died; one death was related to LGL leukemia (acute infection) and the two other deaths were related to vasculitis (both with heart failure).

We conclude that vasculitis is overrepresented in the population of LGL patients, LAV predominantly affects women, vasculitis preferentially affects the small vessels, and LAV has high rate of complete response.

Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment.

Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).

The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

The purpose of this study was to review the literature to provide a comprehensive description of the Level of Evidence (LOE) available to support the operative technique of distraction ankle arthroplasty for the current generally accepted indications and make a grade of recommendation for each. A comprehensive review of the literature was performed (November 2010 to January 2011) using the PubMed database. The abstracts from these searches were reviewed to isolate literature that described therapeutic studies investigating the results of distraction ankle arthroplasty. All articles were reviewed and assigned a classification (I-V) of Level of Evidence. An analysis of the literature reviewed was used to assign a Grade of Recommendation for each current generally accepted indication for distraction ankle arthroplasty. There is insufficient evidence based literature (Grade I) to support or refute the procedure for either: post-traumatic ankle arthritis, arthritis associated with ligamentous instability, primary degenerative joint disease, chondrolysis, deformity associated with arthritis, osteochondral defects and congenital ankle abnormalities.

Inadequate evidence based literature exists to support or refute all currently accepted indications for distraction ankle arthroplasty and further high quality, scientific studies are needed upgrade to these recommendations.

To determine whether a combination of anti-rheumatic drugs is associated with the risk of coronary artery diseases (CAD) in incident rheumatoid arthritis (RA) patients. This population-based cohort study used administrative data to identify 6260 newly-diagnosed patients with RA (age ≥20 years) as the study group. The study end-point was occurrence of CAD according to the ICD-9-CM codes. Exposure to different combinations of drugs and the risk of CAD was assessed. These included different combinatiosn of celecoxib (Cx), hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SSZ). Patients who never used Cx, HCQ, MTX, or SSZ were used as a reference group. A Cox proportional hazards model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption was violated, the spline curve of the Scaled Schoenfeld residuals was fitted to demonstrate the estimated effect on CAD over time for drug usage. Among RA patients, the adjusted HR (95% confidence interval) of CAD for "Cx only", "Cx and HCQ ever", and "Cx, HCQ, MTX, and SSZ ever", were 0.29 (0.19-0.44), 0.46 (0.24-0.88), and 0.42 (0.24- 0.75), respectively, during the first period of 0-3, 4, or 7 years. However, they became 1.04 (0.78-1.38), 1.16 (0.62-2.19), and 0.59 (0.32-1.08), respectively, during the second time period of 3, 4, or 7-10 years. The adjusted HR (95% CI) of CAD for "Cx, MTX, and SSZ ever" remains constant at 0.12 (0.02-0.89).

Celecoxib-DMARDs drug combinations were associated with reduced CAD risk on incident RA patients, and some of them exhibited the time-varying drug effect.

Insufficient soft-tissue coverage following total knee arthroplasty jeopardizes prosthesis retention and may lead to significant complications. The aim of this study was to evaluate the natural history of total knee arthroplasty following flap reconstruction of soft-tissue defects. A retrospective review of patients treated with flaps after failed total knee arthroplasty between 1998 and 2013 was conducted. Patients with preexisting soft-tissue defects who required reactive flap reconstruction were included in group 1. Patients with no preexisting soft-tissue defects, but with extensive débridement during revision total knee arthroplasty requiring immediate proactive flap coverage, were included in group 2. Fifty-eight patients in group 1 were treated with 86 flaps, and 15 patients in group 2 were treated with 17 flaps. Mean length of follow-up was 67.0 and 54.7 months, respectively (p = 0.21). Flap-related complications and number of subsequent flap revisions were comparable in both groups. Patients in group 1 had a higher rate of implant reinfection (58 percent versus 27 percent; p < 0.05), amputations (25 percent versus 0 percent; p < 0.05), and subsequent prosthesis revisions (2.2 versus 0.9; p < 0.05). Functional joint was preserved in 54 percent and 80 percent of cases, respectively. Mean gain in range of motion and quality of life were significantly better in group 2 (p < 0.05). Therapeutic, III.

Early proactive soft-tissue coverage of total-knee arthroplasty is critical to long-term success. In cases where reactive treatment is required, significantly worse outcomes and a high rate of complications should be expected.

To (i) devise a new semi-quantitative scoring system known as Early Rheumatoid Arthritis Magnetic Resonance Score (ERAMRS) to assess inflammation of the wrist on magnetic resonance imaging in early rheumatoid arthritis and to (ii) test ERAMRS and other MR scoring systems against everyday used clinical scorings. One hundred six treatment-naïve patients (81 females, 25 males, mean age 53 ± 12 years) with early rheumatoid arthritis (ERA) underwent clinical/serological testing as well as 3-T MRI examination of the most symptomatic wrist. Clinical assessment included Disease Activity Score-28 and Health Assessment Questionnaire; erythrocyte sedimentation rate and C-reactive protein were measured. MR imaging data was scored in all patients using three devised MR semi-quantitative scoring systems, namely, the (a) ERAMRS system, (b) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) system, and the (c) McQueen Score system. Synovitis was present in 106 (100%), tenosynovitis in 98 (92%), and bone marrow edema in 84 (79%) of 106 ERA wrists. ERAMRS had the highest correlation with clinical disease activity scores (r = 0.476, p < 0.001) and serological parameters (r = 0.562, p < 0.001). RAMRIS system had the lowest correlation (r = 0.369, p < 0.001 for clinical disease activity; r = 0.436, p < 0.001 for serological parameters). RAMRIS synovitis subscore had a lower correlation than ERAMRS for clinical disease activity (r = 0.410, p < 0.001) and for serological parameters (r = 0.456, p < 0.001). • We devised a clinically relevant, easy-to-use semi-quantitative scoring system for scoring inflammation on MRI of the wrist in patients with early rheumatoid arthritis. • ERAMRS system showed better correlation with all clinical and serological assessment of inflammation in patients with early rheumatoid arthritis indicating its improved clinical relevance over other MR scoring systems.

The ERAMRS system, designed to grade inflammation on wrist MRI in ERA, provided the best correlation with all clinical scoring systems and serological parameters, indicating its improved clinical relevance over other MR scoring systems.

Molecular information derived from dynamic [ Eleven healthy volunteers and twenty OA subjects were included. Both knees of all subjects were scanned simultaneously using a 3T hybrid PET/MRI system. MRI MOAKS assessment was performed to score the presence and size of osteophytes, bone marrow lesions, and cartilage lesions. Subchondral bone kinetic parameters of bone perfusion (K Mean and maximum SUV and kinetic parameters K

Results suggest that bone metabolism is altered in OA subjects, including bone regions with and without structural findings, compared to healthy subjects. Kinetic parameters of [

To investigate the interaction between nuclear factor kappa-B (NF-κB) and inflammatory cytokines in synovial cell inflammatory responses induced by sodium urate, and to evaluate the efficacy of Xixiancao (Herba Siegesbeckiae Orientalis) on these interactions. The interactions between NF-κB and inflammatory cytokines/mediators in synovial cells in acute gouty arthritis were investigated. We observed the expressions of NF-κB, interleukin (IL)-1β, IL-8, and tumor necrosis factor alpha (TNF-α) in synovial cells at different timepoints in an in vitro model of synovial cell inflammatory responses induced by sodium urate and in an in vivo model of gouty arthritis. Changes in the expressions of NF-κB, IL-1β, IL-8, and TNF- in synovial cells of all experimental groups were compared and observed after treatment with different doses of Xixiancao (Herba Siegesbeckiae Orientalis) and colchicine. The interactions between NF-κB and IL-1β, IL-8, and TNF-α were analyzed. Pathological changes in synovial tissues were observed in rats with acute gouty arthritis. Compared with the blank group, the expression levels of NF-κB, IL-1β, IL-8, and TNF-α were increased significantly at different timepoints in the in vitro model of synovial cell inflammatory responses induced by sodium urate, and in the in vivo model of gouty arthritis. Compared with the model group, the expressions of NF-κB, IL-1β, IL-8, and TNF-α in synovial cells induced by sodium urate were decreased in the different Xixiancao (Herba Siegesbeckiae Orientalis) dose groups and the colchicine group. The effect was more obvious in the high dose Xixiancao (Herba Siegesbeckiae Orientalis) group. The expression of NF-κB in synovial cells was positively correlated with the expressions of IL-1β, IL-8, and TNF-. Histopathological examination of synovial tissues in the high dose Xixiancao (Herba Siegesbeckiae Orientalis) group and Colchicine group showed that the characteristics of acute gouty arthritis were reduced, and there was a trend towards a positive correlation between NF-κB and inflammatory cytokine expressions.

The activation of NF-κB is associated with the activation of IL-1β, IL-8, and TNF-α during the pathogenesis of acute gouty arthritis, leading to the continuation and enhancement of the inflammatory response. Expressions of IL-1β, IL-8, and TNF-α in synoviocytes during acute gouty arthritis effectively inhibit local inflammation.

To investigate whether plain radiography is useful for assessing the changes in gouty tophi size following hypouricemic therapy. Gout was diagnosed according to the American College of Rheumatology criteria. Before and after hypouricemic treatment, serum uric acid level was measured, and plain radiography was performed to measure gouty tophi size. The tophi were graded by measuring the maximum vertical and horizontal diameters, and they were scored by adding up the scores of the grades. The vertical diameter was measured on both sides of the proximal phalanges (PPs). The horizontal diameter was measured on the lateral side of the PPs. The maximum vertical diameter measurement was graded 0-4. The maximum horizontal diameter measurement was graded 0-3. Seven hundred first metatarsal phalangeal joints (MTPJ) of 350 patients with gout were assessed for gouty tophi. Tophi were observed using plain radiography in 174 MTPJs (24.9%) of 109 patients (31.1%). Follow-up plain radiography was performed in 60 of these patients. Before the treatment, the average serum uric acid level of these patients was 8.3 ± 1.9 mg/dL, and the average tophi score was 3.7 ± 2.5. After hypouricemic treatment, the uric acid level decreased to 5.9 ± 1.6 mg/dL (P < 0.05), and the average tophi score decreased to 1.5 ± 1.8 (P < 0.05).

This new method for measuring gouty tophi using plain radiography may be useful for evaluating changes in gouty tophi size following hypouricemic treatment.

To examine the impact of the Affordable Care Act on preventable hospitalizations and associated charges for patients living with systemic lupus erythematosus, before and after Medicaid expansion. A retrospective, quasi-experimental study, using an interrupted time series research design, was conducted to analyze data for 8 states from the Healthcare Cost and Utilization Project state inpatient databases. Lupus hospitalizations with a principal diagnosis of predetermined ambulatory-care sensitive (ACS) conditions were the unit of primary analysis. The primary outcome variable was access to care measured by preventable hospitalizations caused by an ACS condition. There were 204,150 lupus hospitalizations in the final analysis, with the majority (53.5%) of lupus hospitalizations in states that did not expand Medicaid. In unadjusted analysis, Medicaid expansion states had significantly lower odds of having preventable lupus hospitalizations (odds ratio [OR] 0.958); however, after adjusting for several covariates, Medicaid expansion states had increased odds of having preventable lupus hospitalizations (OR 1.302). Adjusted analysis showed that those individuals with increased age, public insurance (Medicare or Medicaid), no health insurance, rural residence, or low income had significantly higher odds of having a preventable lupus hospitalization. States that expanded Medicaid had $523 significantly more charges than states that did not expand Medicaid. Older age and rural residence were associated with significantly higher charges.

Our findings suggest that while Medicaid expansion increased health insurance coverage, it did not address other issues related to access to care that could reduce the number of preventable hospitalizations.

The Disease Activity Score 28 (DAS28) and its versions have been used to measure rheumatoid arthritis (RA) activity, but there is no consensus about which one is the best. Determine the correlation among indexes (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata using different cutoff points. Rheumatoid arthritis patients were cross-sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP), SDAI and CDAI, using different cut-offs for defining remission, mild, moderate and high activity. Pearson correlations were calculated for continuous measures and agreement (kappa test) for the strata (remission, mild, moderate and high activity). Of 111 patients included, 108 were women, age 55.6 years, 11-year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0 vs. 3.5; p<0.001) and the values remained higher after stratification by age, gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI. Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut-off point for the remission of 2.3 underestimated disease activity by 45.8% compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four indexes were associated with disease duration and HAQ.

Although the activity indexes show good correlation, they show discrepancies in activity strata, thus requiring more researches to define a better index and better cutoff points.

To observe the therapeutic efficacy of Qianggu Granule (QGG), Diacerein Capsule (DC), and QGG + DC in treating knee osteoarthritis (KOA, belonging to Gan-Shen insufficiency induced vein stasis syndrome), and to explore the clinical advantages of QGG + DC. Ninety patients in line with the diagnosis standard were randomly assigned to three groups, i. e., the QGG group (30 case, treated by QGG), the Western medicine treatment group (30 case, treated by DC), and the combination therapy group (30 case, treated by QGG +DC). Then the patients' symptoms and signs were scored. Meanwhile, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor alpha (TNF-alpha), comprehensive efficacy, and adverse reactions, etc. were assessed. The ache could be obviously alleviated, the patients' joint function could be improved, and their quality of daily activities could be elevated in all the 3 groups. There was statistical difference in the symptoms and signs scores, CRP, ESR, and TNF-alpha before and after treatment (P < 0.05). Better effects were obtained in the combination therapy group (P < 0.05). As for the comprehensive efficacy, it was better in the QGG + DC group than in the QGG group and the DC group, showing statistical difference (P < 0.01).

The comprehensive therapeutic efficacy of applying QGG + DC in treating KOA (belonging to Gan-Shen insufficiency induced vein stasis syndrome) was superior to using QGG or DC alone. Besides, no obvious adverse reaction occurred.

To review and analyze the clinical features, treatment, and outcome of macrophage activation syndrome (MAS) in children with systemic onset juvennil rheumatoid arthritis (SOJRA). Retrospective review and analysis were performed on cases with MAS from a prospectively collected database of children with SOJRA from the year of 2003 to 2006 in the Hospital. Twenty four patients (21 boys, 3 girls) were diagnosed as having MAS with SOJRA. Mean age of the patients with MAS at diagnosis was 7 years, and the duration prior to diagnosis of MAS was 12 months. No trigger factors were found except in one case whose MAS was triggered by use of methotrexate and in another by parvovirus B19 infection. High grade fever, new onset hepatosplenomegaly and lymphadenopathy, pancytopenia, liver dysfunction were common clinical features in all the 24 cases (100%). Bleeding from skin, mucous membrane and gastrointestinal tract were noted in 9 cases (38%). Twelve (50%) cases had CNS dysfunction (high intracranial pressure, seizure and coma). Six cases (25%) developed ARDS. One patient suffered from renal damage. The laboratory test revealed elevated live enzymes and ferritin, decreased value of ESR, albumin, complete blood count and fibrinogen in all the 24 cases. Bone marrow examination supported the diagnosis of definite hemophagocytosis in the 24 cases. Lymph node biopsy was done for one case and histopathological examination showed that the node was full of activated macrophage. As to treatment, five cases only received high dose steroids (three of them died), 14 cases were treated with high dose steroids plus cyclosporine (one died), two were treated with steroids plus cyclosporine and etoposide (none died). The causes of deaths were ARDS and CNS involvement. In three of the cases who died, treatment was given up by their parents.

MAS is a rare and potentially fatal complication of SOJRA. Most of our patients were male. Bone marrow studies support the diagnosis. CNS involvement and ARDS were poor prognostic signs. Early diagnosis and aggressive therapy are essential.

To evaluate the presence of sicca symptoms and secondary Sjögren's syndrome (SS) and the association with clinical characteristics, functional tests and patient-reported outcomes in patients with rheumatoid arthritis (RA) at baseline and after 10 years of follow-up. A cohort of RA patients was evaluated in 2008 and re-evaluated in 2018 with respect to sicca symptoms, presence of secondary SS according to AECG classification criteria, disease activity of RA and patient-reported outcomes. Patient characteristics were compared between the RA-non-sicca, RA-sicca and RA-SS groups. Of the original 2008 cohort of 96 RA patients, 32 (33%) had sicca symptoms and 6 (6.3%) secondary SS. Of the 36 patients who agreed to be re-evaluated in 2018, 6 (17%) had sicca symptoms and 2 (6%) developed secondary SS. In the majority of patients, sicca symptoms were reversible while the functional tests of salivary and lacrimal glands significantly decreased. 67% of RA-sicca patients had no sicca complaints at the second screening, while only two RA-sicca patients developed secondary SS. RA-SS patients and, to a slightly lesser extent, RA-sicca patients had significantly higher RA disease activity (DAS-28), lower lacrimal (Schirmer's test) and salivary gland function, more limitations in daily activities (HAQ), worse health-related quality of life (RAND-36), more fatigue (MFI) and more patient symptoms (ESSPRI) compared to RA-non-sicca patients.

Secondary SS was found in a minor subset of the RA patients. Sicca symptoms of the eyes or mouth were more frequent, but their presence varied over time. Higher RA disease activity was associated with SS and sicca symptoms. These patients had lower gland function and worse patient-reported outcomes.

The purpose of this study was to assess the effect of continuous compression stimulation on pressure-pain threshold and muscle spasms in older adults with knee osteoarthritis. Thirty-two older adults with knee osteoarthritis on outpatient visits were randomly divided into 2 groups. Those in the treatment group (n = 16) received 5-minute massage therapy (continuous compression stimulation), and those in the control group (n = 16) received sham massage therapy (touch without compression). Immediately before and after single-intervention sessions, the pressure-pain threshold, muscle spasm, and pain were quantified. The change in pain on walking in the treatment group exceeded 1.9 cm, corresponding to the minimum clinically important difference. In the treatment group, the pressure-pain threshold improved significantly for pain both at rest and while walking, but the improvement in muscle spasm was not significant.

Massage therapy resulted in minimal clinically important changes for pain relief. There was an increase in the pressure-pain threshold in the older adults with knee osteoarthritis. We propose that the improvements in pain may be related to the medial thigh muscle rather than knee osteoarthritis.

To describe and compare the prevalence of lifetime and current self-reported comorbidity and associated quality of life in 4 rheumatic diseases, and to investigate comorbid conditions in light of the overlap between the index condition and comorbid conditions (CC), and in the context of symptom-type diagnoses. We studied comorbidity in 11,704 patients with fibromyalgia (FM), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and noninflammatory rheumatic disorders (NIRD). Patients completed semiannual self-reports relating to 22 present and past illnesses and completed the EuroQol (EQ-5D) utility index. CC were most common in FM, followed by SLE. FM comorbidity was dominated by depression, mental illness, and symptom-type comorbidity (e.g., gastrointestinal and genitourinary disorders). In SLE, there were substantial increases in hypertension, depression, cataract, fractures, and cardiovascular and cerebrovascular, neurologic, lung, gall bladder and endocrine disorders compared with RA. Any current CC reduced the EQ-5D utility by 0.08 to 0.16 units. The lowest EQ-5D score was noted for current psychiatric illness (0.55) and current depression (0.60).

Four patterns of comorbidity emerged: that associated with aging; that associated with aging but enhanced by the index condition, as in SLE and cardiovascular disease; comorbidity that is part of the symptoms complex of the index condition; and CC that represent lifetime traits or manifestations of the underlying illness. Depression was the most strongly associated correlate of EQ-5D quality of life, and current depression was present in about 15% of patients with RA or NIRD and 34% to 39% of those with SLE and FM.

In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure.

The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

To identify methylation quantitative trait loci (mQTLs) correlating with osteoarthritis (OA) risk alleles and to undertake mechanistic characterization as a means of target gene prioritization. We used genome-wide genotyping and cartilage DNA methylation array data in a discovery screen of novel OA risk loci. This was followed by methylation, gene expression analysis, and genotyping studies in additional cartilage samples, accompanied by in silico analyses. We identified 4 novel OA mQTLs. The most significant mQTL contained 9 CpG sites where methylation correlated with OA risk genotype, with 5 of the CpG sites having P values <1 × 10

PLEC encodes plectin, a cytoskeletal protein that maintains tissue integrity by regulating intracellular signaling in response to mechanical stimuli. GRINA encodes the ionotropic glutamate receptor TMBIM3 (transmembrane BAX inhibitor 1 motif-containing protein family member 3), which regulates cell survival. Based on our results, we hypothesize that in a joint predisposed to OA, expression of these genes alters in order to combat aberrant biomechanics, and that this is epigenetically regulated. However, carriage of the OA risk-conferring allele at this locus hinders this response and contributes to disease development.

To investigate the contribution of cold induced pulmonary vasospasm by peripheral and central cold stimulus in exacerbating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis undergoing cardiac catheterisation. In a prospective pilot study, 21 patients with systemic sclerosis and catheter proven PAH had mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) measured before and after peripheral (hand immersion into cold water at 10-15 degrees C for two minutes if tolerated) and central (direct cold water at 4 degrees C injected into the right atrium) cold pressor challenge. Markers of endothelial activation, platelet function, and nitric oxide degradation were measured in blood sampled from the pulmonary artery. 19 of the patients (mean (SD) age, 56 (4) years; baseline mPAP, 34 (8) mm Hg; PVR, 420 (87) dyne.s.cm(-5); CO, 6.4 (1.8) l/min) tolerated cold hand immersion for the maximum two minute duration. All 21 tolerated central cold pressor challenge (three to five injections of 10 ml saline boluses at 4 degrees C). There was no significant change in haemodynamics after cold challenge by either route of provocation. Levels of endothelin-1, von Willebrand factor, fibrinogen, and 3-nitrotyrosine were raised compared with control values in patients with systemic sclerosis but without PAH, but did not change significantly after peripheral cold challenge.

Pulmonary vasospasm in response to peripheral and centrally administered cold pressor challenge is unlikely to contribute to persistence of pulmonary arterial hypertension in patients with systemic sclerosis.

To investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs). PubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patients with RA receiving Jakinibs, from inception to October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs). OR and 95% CI were calculated using the Mantel-Haenszel fixed-effect method. 26 RCTs randomising 11 799 patients were included. No significant difference was observed regarding all CVEs risk following Jakinibs usage in general (OR 1.04 (0.61 to 1.76), p = 0.89), tofacitinib (OR 0.63 (0.26 to 1.54), p = 0.31), baricitinib (OR 1.21 (0.51 to 2.83), p = 0.66), upadacitinib (OR 3.29 (0.59 to 18.44), p = 0.18), peficitinib (OR 0.43 (0.07 to 2.54), p = 0.35) or decernotinib (OR 1.12 (0.13 to 10.11), p = 0.92). Likewise, there was no significant difference for Jakinibs treatment overall regarding occurrence of MACEs (OR 0.80 (0.36 to 1.75), p = 0.57) or VTEs (OR 1.16 (0.48 to 2.81), p = 0.74). Dose-dependent impact of Jakinibs on the risks of all CVEs, MACEs and VTEs was not observed in tofacitinib (5 mg vs 10 mg), upadacitinib (15 mg vs 30 mg), whereas baricitinib at 2 mg was found to be safer than 4 mg in all CVEs incidence (OR 0.19 (0.04 to 0.88), p = 0.03).

The existing evidence from RCTs indicated no significant change in cardiovascular risk for Jakinib-treated patients with RA in a short-term perspective, but postmarketing data are sorely needed to ascertain their cardiovascular safety, especially at the higher dose, due to increased risk of thromboembolism events for both tofacitinib and baricitinib at higher dosage.

Osteoarthritis (OA) is a disorder involving deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. Glucosamine is a component of articular cartilage naturally synthesized in the body from glucose and incorporated into substances contained in the cartilage. It has been suggested that consumption of glucosamine may reduce the pain of OA and may have favorable effects on structural changes in the cartilage. This article presents a systematic review and meta-analysis of the effectiveness of orally consumed glucosamine sulfate (GS) on OA-related pain and joint structural changes. PubMed and Ovid Embase were searched using specific search terms to find randomized, double-blinded, placebo-controlled trials on the effects of GS on pain and/or joint-space narrowing. The outcome measure was the standardized mean difference (SMD), which was the improvement in the placebo groups minus the improvement in the GS groups divided by the pooled standard deviation. There were 17 studies meeting the review criteria for pain, and the summary SMD was -0.35, with a 95% confidence interval (95% CI) = -0.54 to -0.16 (negative SMD is in favor of GS). Of the 17 studies, 7 showed a statistically significant reduction in pain from GS use. Four studies met the review criteria for joint space narrowing with a summary SMD = -0.10 (95% CI = -0.23 to +0.04). Studies without involvement of the commercial glucosamine industry had a lower (but still significant) pain reduction efficacy (summary SMD = -0.19, 95% CI = -0.39 to -0.02) than those with industry involvement. Several smaller dosages throughout the day had larger pain reduction effects than a single daily large dose (1500 mg).

These data indicate that GS may have a small to moderate effect in reducing OA-related pain but little effect on joint-space narrowing. Until there is more definitive evidence, healthcare providers should be cautious in recommending use of GS to their patients. Because GS dosages used in studies to date resulted in mild and transient adverse effects, and these were similar to that experienced by patients receiving placebos, larger GS doses possibly could be investigated in future studies.

Coronary artery disease (CAD) is the leading cause of excess deaths in rheumatoid arthritis (RA). However, identification of features denoting patients with a risk of developing CAD is lacking. The composition of circulating peripheral blood mononuclear cell (PBMC) subsets in RA patients differs markedly from that in healthy controls with regard to the extent of T cell activation, with clonal expansion and differentiation to effector memory status, and presence of inflammatory monocytes. In this study, we sought to evaluate whether elevations in these PBMC subpopulations in RA patients could denote those with an increased risk of subclinical CAD, as determined by the presence of coronary artery calcification (CAC). The study cohort comprised 72 patients with RA who underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and the presence of CAC. Among the 72 patients with RA, 33% had CAC and exhibited significant increases in the levels of circulating CD4 T cell subsets denoting activation and differentiation to the effector memory phenotypes. Analogous increases in the levels of CD8 T cell subsets, as well as in the CD14(high)CD16+ intermediate monocyte subset, were also present in these patients, as compared to those without CAC. The increases in the CD4 and CD8 T cell subsets were highly intercorrelated, whereas the increases in CD14(high)CD16+ monocytes were independent of elevations in the CD4 T cell subsets. After adjustments for relevant confounders, the levels of CD4+CD56+CD57+ T cells and CD14(high)CD16+ monocytes remained associated with the presence of CAC.

These findings indicate that PBMC subsets are markers for the presence of CAC and suggest that mechanisms of atherogenesis in RA may operate in part through the elevations in these subsets, raising further questions about the mechanisms underlying the presence of such alterations in cell composition in patients with RA and the potential for shared etiologic pathways between RA and cardiovascular disease.

To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). Randomized, blinded study. Fifteen geriatric cats weighing 4.5 ± 1.0 kg. Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM.

Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.

Physical activity reduces mobility impairments in elders. We examined the association of physical activity on risk of subjective and objective physical function in adults with and at risk for osteoarthritis (OA). Adults aged ≥ 60 years from the longitudinal Osteoarthritis Initiative, a prospective observational study of knee OA, were classified by sex-specific quartiles of Physical Activity Score for the Elderly scores. Using linear mixed models, we assessed 6-year data on self-reported health, gait speed, Late-Life Function and Disability Index (LLFDI) and chair stand. Of 2252 subjects, mean age ranged from 66 to 70 years. Within each quartile, physical component (PCS) of the Short Form-12 and gait speed decreased from baseline to follow-up in both sexes (all P < .001), yet the overall changes across PASE quartiles between these 2 time points were no different (P = .40 and .69, males and females, respectively). Decline in PCS occurred in the younger age group, but rates of change between quartiles over time were no different in any outcomes in either sex. LLFDI scores declined in the 70+ age group. Adjusting for knee extensor strength reduced the strength of association.

Higher physical activity is associated with maintained physical function and is mediated by muscle strength, highlighting the importance of encouraging physical activity in older adults with and at risk for OA.

This prospective cohort study (ClinicalTrials.gov identifier: NCT02674386) evaluated the postoperative outcomes of patients who had undergone total joint replacement (TJR) while participating in one of three tanezumab (a nerve growth factor inhibitor) randomized phase 3 osteoarthritis (OA) studies. Eligible patients were those who underwent TJR (knee, hip, or shoulder) at any time during any of three tanezumab randomized phase 3 OA studies. Consenting patients were followed for 24 weeks post-surgery. Patients undergoing sub-total arthroplasty procedures were not eligible; there were no further protocol-defined exclusion criteria. Outcomes assessed in relation to joint adjudication outcome and prior tanezumab treatment included: 1) surgeon's assessment of procedural difficulty (uneventful, minor complications, major complications) at the time of the TJR; 2) postsurgical complications (clinically significant events attributable to the TJR, derived from adverse events) up to week 24; and 3) additional/corrective procedures (procedures or investigations related to the TJR) up to week 24. The 150 patients had received placebo (n=20), tanezumab 2.5mg (n=52), tanezumab 2.5mg titrated to 5mg (tanezumab 2.5/5mg, n=8), tanezumab 5mg (n=53), or a nonsteroidal anti-inflammatory drug (n=17) in the parent studies. The 150 patients were adjudicated to have primary osteonecrosis (n=1), rapidly progressive OA (RPOA) type 2 (n=8), RPOA type 1 (n=3), other joint outcome (n=6), normal progression of OA (NPOA) (n=130), or insufficient information to determine RPOA versus NPOA (n=2). Surgeon's assessment of procedural difficulty was uneventful for 95.1% (116/122) of patients. Through the 24-week study, there were no postsurgical complications for 96.0% (144/150) of patients; the 6 patients who had complications were all adjudicated as NPOA (tanezumab 2.5mg, n=2; tanezumab 5mg, n=4). There were no additional/corrective procedures for 93.3% (140/150) of patients.

Procedural difficulty of minor complications during surgery, postsurgical complications, and additional/corrective procedures were infrequent, although more common with tanezumab 5mg, typically occurring in patients adjudicated as NPOA. Adjudication outcome (RPOA/primary osteonecrosis vs. NPOA) was not associated with postoperative outcome.

Patients with fibromyalgia syndrome (FM) complain of inadequate sleep, which could contribute to common symptoms including sleepiness, fatigue, or pain. However, measures that consistently and objectively distinguish FM patients remain elusive. Fifteen women with FM and 15 age- and gender-matched controls underwent 3 nights of polysomnography; Multiple Sleep Latency Tests to assess sleepiness; testing of auditory arousal thresholds during non-REM stage 2 and stage 4 sleep; overnight assessment of urinary free cortisol; and analysis of 24-hour heart rate variability. On the second night of polysomnography, women with FM in comparison to controls showed more stage shifts (p = 0.04) but did not differ significantly on any other standard polysomnographic measure or on the Multiple Sleep Latency Tests. Alpha EEG power during deep non-REM sleep, alone or as a proportion of alpha power during remaining sleep stages, also failed to distinguish the groups, as did auditory arousal thresholds. Urinary free cortisol did not differ between FM and control subjects in a consistent manner. However, decreased short-term heart rate variability (HRV) and especially ratio-based HRV among FM subjects suggested diminished parasympathetic and increased sympathetic activity, respectively. Other HRV measures suggested decreased complexity of HRV among the FM subjects.

Standard measures of sleep, a gold-standard measure of sleepiness, quantified alpha-delta EEG power, auditory arousal thresholds, and urinary free cortisol largely failed to distinguish FM and control subjects. However, HRV analyses showed more promise, as they suggested both increased sympathetic activity and decreased complexity of autonomic nervous system function in FM.

The purpose of this study was to translate the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), which is a tool for measuring disease activity in rheumatoid arthritis (RA) patients, into Turkish language and prove its validity, reliability and sensitivity to changes. Translation from the original German version was performed according to the standardized methods. One hundred and two patients with RA completed in the Turkish RADAI-5 twice within 3 days interval. Internal consistency and test-retest reliability was investigated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC), respectively. Validity was assessed by analyzing the correlations between the Turkish RADAI-5 and some measurement tools evaluating the disease activity, functional status and quality of life. To test the scale's responsiveness to the changes, another 23 patients with uncontrolled disease activity and three newly diagnosed RA patients completed the RADAI-5 before and after a biologic agent or methotrexate treatment. There were no floor or ceiling effects. Cronbach's alpha (0.91) and ICC (0.997) values certified the Turkish version's reliability. Strong correlations between the Turkish questionnaire and Disease Activity Score-28 (DAS28), DAS28-CRP, DAS28-three variables, Health Assessment Questionnaire, Rheumatoid Arthritis Quality of Life questionnaire, patient's and doctor's global assessments, tender joint count proved the convergent validity of the scale. Effect size (3.08) demonstrated that the Turkish RADAI-5 is sensitive to the changes.

The Turkish RADAI-5 is a feasible, reliable and valid questionnaire and sensitive to changes; thus it can be used to monitor disease activity in Turkish RA patients.

Rheumatoid arthritis (RA) has seriously affected the quality of life of patients with its refractory, recurrent, and disabled characteristics, and has become a major public health problem. Previous studies have confirmed that acupuncture and moxibustion have a reliable effect on RA, but there are many forms of acupuncture and moxibustion, and the efficacy of each form is different. This study is to evaluate the clinical efficacy of different acupuncture-related therapies in the treatment of RA by means of network meta-analysis. According to the retrieval strategy, we retrieved the randomized controlled studies on acupuncture-related therapy for RA from China National Knowledge Infrastructure, Wanfang, VIP, China Biomedicine, PubMed, Embase, Web of Science, and The Cochrane Library databases from the establishment of the database to July 2021. We assessed the quality of the studies using the Cochrane Risk Bias Assessment Tool and assessed the strength of the evidence using the Grading of Recommendation Assessment, Development, and Evaluation methodology. All data analyses were performed by Revman5.3, Gemtc 0.14.3, and Stata 14.0. This study is to evaluate the efficacy of different acupuncture-related therapies in the treatment of RA by evaluating the total effective rate, pain scores, joint function scores, quality of life scores, laboratory indicators, adverse reactions, etc. Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

This study will provide a reliable evidence-based basis for the selection of the best acupuncture form for the treatment of RA.

Osteoarthritis is an age-related disorder of bone-joint that causes pain and disability in middle and older people. This study aimed to investigate the potential effects of long non-coding RNA (lncRNA) THRIL on lipopolysaccharide (LPS)-induced osteoarthritis cell injury model (ATDC5 cell inflammatory injury), as well as the possible internal molecular mechanisms. Cell viability and apoptosis were assessed using CCK-8 assay and Guava Nexin assay, respectively. Cell transfection was conducted to change the expression of THRIL and microRNA-125b (miR-125b) in ATDC5 cells. qRT-PCR was performed to detect the expression of THRIL, miR-125b and pro-inflammatory cytokines IL-6, TNF-α and monocyte chemotactic protein 1 (MCP-1) in ATDC5 cells. ELISA was used to measure the concentrations of IL-6, TNF-α and MCP-1 in culture supernatant of ATDC5 cells. Finally, the protein expression of key factors involved in cell apoptosis, inflammatory response, JAK1/STAT3 and NF-κB pathways were evaluated using western blotting. LPS significantly induced ATDC5 cell inflammatory injury and up-regulated the expression of THRIL. Overexpression of THRIL aggravated the LPS-induced ATDC5 cell inflammatory injury. Suppression of THRIL had opposite effects. Moreover, THRIL negatively regulated the expression of miR-125b in ATDC5 cells. miR-125b participated in the effects of THRIL overexpression on LPS-induced ATDC5 cell inflammatory injury. Furthermore, overexpression of THRIL enhanced the LPS-induced JAK1/STAT3 and NF-κB pathways activation by down-regulating miR-125b.

THRIL exerted pro-inflammatory roles in LPS-induced osteoarthritis cell injury model. Overexpression of THRIL promoted LPS-induced ATDC5 cell inflammatory injury by down-regulating miR-125b and then activating JAK1/STAT3 and NF-κB pathways.

Recent studies have indicated that piperlongumine (PLM) may exert anti-inflammatory effects. In the present study, we determined the effect of PLM on the proliferation, apoptosis, migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) (referred to herein as RA FLS). We further explored the mechanisms by which the studied compound inhibits the functions of RA FLS. RA FLS viability and apoptosis were tested using MTT and Annexin V/PI assays, respectively. We performed an EDU assay to examine the proliferation of RA FLS. The migration and invasion of these cells were measured using a transwell chamber method and wound closure assay. The MMP-1, MMP-3, and MMP-13 levels in the culture supernatants of RA FLS were detected using a Luminex Assay kit. The intracellular ROS levels were detected using DCFH-DA. The expression levels of signal transduction proteins were measured using western blot. We found that PLM induced apoptosis in RA FLS at concentrations of 15 and 20 μM. The proliferation of RA FLS was downregulated by PLM at concentrations of 1, 5 and 10 μM. Migration and invasion of RA FLS were reduced by PLM at concentrations of 1, 5 and 10 μM. PLM also inhibited cytoskeletal reorganization in migrating RA FLS and decreased TNF-α-induced intracellular ROS production. Moreover, we demonstrated the inhibitory effect of PLM on activation of the p38, JNK, NF-κB and STAT3 pathways.

Our findings suggest that PLM can inhibit proliferation, migration and invasion of RA FLS. Moreover, these data suggests that PLM might have therapeutic potential for the treatment of RA.

Soluble E-selectin (sE-selectin) is a marker of activation of vascular endothelium. To examine serum levels of sE-selectin in a cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five years. sE-selectin levels were assessed annually using an enzyme linked immunosorbent assay (ELISA) and related to simultaneously obtained clinical and laboratory measures. Joint inflammation was evaluated by active joint count, functional status by Health Assessment Questionnaire (HAQ), and radiographic findings in hands and feet by the Larsen method. Laboratory tests included serum C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin level, white blood cell count (WBC), and platelet count. Area under the curve (AUC) was calculated for each variable, and Jonckheere's test for ordered alternatives was applied to assess significance of association between sE-selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were related to change in Larsen score and HAQ score at five years. Odds ratios (OR) with 95% confidence interval (CI) were calculated using univariate and multivariate logistic regression. sE-selectin levels were associated with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019), progression of joint destruction (p=0.038), and HAQ score at five years (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE-selectin levels in the third tertile predicted the HAQ score at five years (OR 4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ significantly from those of healthy control subjects.

The degree of activation of vascular endothelium is associated with activity and outcome of early RA.

To assess and analyse nutritional status in patients with systemic sclerosis (SSc) and identify possible associations with clinical symptoms and its prognostic value. Body mass index (BMI) and parameters of bioelectrical impedance analysis (BIA) were assessed in 124 patients with SSc and 295 healthy donors and matched for sex, age and BMI for comparisons. In patients with SSc, BMI and BIA values were compared with clinical symptoms in a cross-sectional study. In a prospective open analysis, survival and changes in the nutritional status and energy uptake induced by nutritional treatment were evaluated. Patients with SSc had reduced phase angle (PhA) values, body cell mass (BCM), percentages of cells, increased extracellular mass (ECM) and ECM/BCM values compared with healthy donors. Malnutrition was best reflected by the PhA values. Of the patients with SSc, 69 (55.7%) had malnutrition that was associated with severe disease and activity. As assessed by multivariate analysis, low predicted forced vital capacity and high N-terminal(NT)-proBNP values discriminated best between good and bad nutritional status. Among different clinical parameters, low PhA values were the best predictors for SSc-related mortality. BMI values were not related to disease symptoms or mortality. Fifty per cent of patients with SSc had a lower energy uptake related to their energy requirement, 19.8% related to their basal metabolism. Nutritional treatment improved the patients' nutritional status.

In patients with SSc, malnutrition is common and not identified by BMI. BIA parameters reflect disease severity and provide best predictors for patient survival. Therefore, an assessment of nutritional status should be performed in patients with SSc.

Glial fibrillary acidic protein (GFAP) immunoglobulin G is a recently discovered biomarker of an autoimmune central nervous system disorder characterized by a steroid-responsive meningoencephalomyelitis. A 63-year-old man with rheumatoid arthritis on etanercept presented with steroid-responsive subacute encephalopathy and foot drop. Brain and sural nerve biopsies demonstrated a T-cell perivascular infiltrate. Cerebrospinal fluid studies 18 months into the course of the illness demonstrated a GFAP antibody on mouse tissue immunofluorescence confirmed by cell-based assay. The patient was treated with steroids and cyclophosphamide leading to resolution of his symptoms.

This case expands on the previously reported cases of GFAP immunoglobulin G autoimmunity by describing an associated inflammatory large fiber peripheral neuropathy.

The purpose of this retrospective study was to evaluate clinical outcomes of osteochondral autograft transplantation (OAT) for isolated patellofemoral (PF) osteoarthritis (OA). OAT was performed in seven patients (six men, one woman; mean age, 61.1years) with isolated PF OA. The mean duration of follow up was 46.9months (range, 24-84months). Clinical outcomes were evaluated preoperatively and postoperatively according to the International Knee Documentation Committee (IKDC) objective score and the knee scoring system of the Japanese Orthopaedic Association (JOA) score. The International Cartilage Repair Society (ICRS) score was recorded in three cases that underwent second-look arthroscopies postoperatively. For morphological evaluation, the Kellgren and Lawrence (KL) classification and the modified magnetic resonance observation of cartilage repair tissue (MOCART) score were used. The mean IKDC and JOA scores were both significantly improved. The percentage of normal and nearly normal on the IKDC score was increased from 28.6% (2/7) to 85.7% (6/7) (P=0.05). The mean JOA score was improved from 80.0 (range, 65.0-85.0) to 95.0 (range, 90.0-100) (P=0.0008). The mean ICRS scores were 10.3 (nearly normal) in the three cases that underwent second-look arthroscopies postoperatively. Regarding KL classification, the grade was unchanged in five cases (two cases in grade 1, three cases in grade 2) and improved in two cases (from grade 3 to 2, from grade 4 to 3). The mean modified MOCART score was 67.9 (range, 60.0-75) at 12-month follow up. There were no complications, and satisfaction was obtained in all cases. The study design was case series: level IV.

All clinical scores improved significantly postoperatively. Osteochondral plugs were transplanted perpendicular to the articular surface to obtain good congruity of the repaired articular surface. In this way, OAT is an effective procedure to prevent progression of isolated PF OA.

We evaluated the presence of Porphyromonas gingivalis (Pg) DNA in the synovial tissue through synovial biopsy and in other compartments of rheumatoid arthritis (RA) patients in comparison with patients affected by other arthritides. Possible links with clinical, immunologic and genetic features were assessed. Peripheral blood (PB), sub-gingival dental plaque, synovial fluid (SF) and synovial tissue samples were collected from 69 patients with active knee arthritis (32 with RA and 37 with other arthritides, of which 14 had undifferentiated peripheral inflammatory arthritis - UPIA). Demographic, clinical, laboratory and immunological data were recorded. The presence of Pg DNA was evaluated through PCR. The HLA-DR haplotype was assessed for 45 patients with RA and UPIA. No differences arose in the positivity for Pg DNA in the sub-gingival plaque, PB and SF samples between RA and the cohort of other arthritides. Full PB samples showed a higher positivity for Pg DNA than plasma samples (11.8% vs. 1.5%, P = 0.04). Patients with RA showed a higher positivity for Pg DNA in the synovial tissue compared to controls (33.3% vs. 5.9%, P <0.01). UPIA and RA patients carrying the HLA DRB1*04 allele showed a higher positivity for Pg DNA in the synovial tissue compared to patients negative for the allele (57.1% vs. 16.7%, P = 0.04). RA patients positive for Pg DNA in the sub-gingival plaque had a lower disease duration and a higher peripheral blood leucocyte and neutrophil count. The presence of Pg DNA did not influence disease activity, disease disability or positivity for autoantibodies.

The presence of Pg DNA in the synovial tissue of RA patients suggests a pathogenic role of the bacterium. The higher positivity of Pg DNA in full peripheral blood and synovial tissue samples compared to plasma and synovial fluid suggests a possible intracellular localization of Pg, in particular in patients positive for HLA-DR4.

An inverted labrum is an acknowledged but often elusive cause of osteoarthritis. The study goals were to define the characteristic radiographic features of secondary osteoarthritis of the hip due to an inverted labrum and report the results of arthroscopic treatment. This is a case series study. From 220 consecutive arthroscopic hip procedures, 9 patients were identified who had had secondary osteoarthritis caused by an inverted labrum and who underwent a minimum 2 years follow-up. All were prospectively assessed with a modified Harris hip score. All patients underwent excision of a torn inverted labrum and chondroplasty. Three patients who had well- circumscribed grade IV acetabular lesions also underwent microfracture of the subchondral bone. Characteristic anteroposterior radiographic features included isolated narrowing of the superolateral joint space. This narrowing caused a lateral convergence in the normally parallel lines created by the radius of curvature of the subchondral bone of the acetabulum and the convex surface of the femoral head. These 2 features created a false appearance of dysplasia (pseudodysplasia), because the center edge angle of Weiberg was normal in 6 cases (range, 24 degrees to 41 degrees; average, 29 degrees ) and was indicative of true dysplasia in only 3 cases (17 degrees ). The median preoperative score was 51, and the postoperative hip score was 56. Only 4 patients showed significant improvement. The best results were in the group with microfracture; the average improvement in this group was 36.

An inverted labrum is an occasionally encountered cause of osteoarthritis of the hip. The radiographic features seen with this disorder are quite characteristic and essentially pathognomonic. Recognizing these features in this population may help the physician avoid an unnecessarily extensive work-up for poorly explained hip pain. The 3 patients with microfracture responded well to the arthroscopic technique; otherwise the results of arthroscopic treatment were poor. The outcomes were no better than those previously reported for arthritis of all causes.

In patients with knee pain due to gonarthrosis, we have treatments that are not free of side effects. to evaluate the analgesic efficacy of radiofrequency (pulsed and conventional) on the saphenous nerve at the subsartorial level and the genicular nerves of the knee, by ultrasonography. Prospective, randomized, double-blind clinical trial. G1 (RDF1): subjects subjected to radiofrequency, G2 (PLCB): subjects subjected to placebo. A decrease ≥30% of the pain was considered clinically relevant, according to numerical rating scale and in the Western Ontario and McMaster Universities Osteoarthritis Index, global patient impression questionnaire (PGIC) and health status questionnaire (SF-12) in the evaluation at month, three months and six months after the completion of the technique. 28 patients (G1: 12, G2: 16), 72% women, age: 75.2±9.1 years, body mass index: 29.9±4.64. The analysis did not show a pain reduction, neither statistically significant, not clinically relevant, at one month, three, or six months with respect to the start of treatment, in the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire and numerical rating scale (rest, movement). Regarding PGIC and the SF-12 questionnaire, there were no statistically significant differences between G1 and G2 either before or after treatment.

The combination of two radiofrequency techniques, does not cause a reduction in the intensity of the knee pain, at month, three, or at six months after its completion. It is necessary to change the radiofrequency technique and include more variables to continue with the efficacy study.

Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-μCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-μCT X-ray attenuation, sGAG content and collagen content was assessed. CTa X-ray attenuation correlated well with EPIC-μCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36).

Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research.

To evaluate whether patient characteristics and/or radiographic disease patterns predict symptomatic response to treatment with glucosamine in osteoarthritis (OA) of the knee. Exploratory prospective correlational study. Institutional. 39 participants with chronic knee pain from the local community. Glucosamine sulphate (1.5 g/day) for 12 weeks. Pain and physical function were assessed with visual analogue scales (VASs) and participant-perceived global change scores (GCSs). Regression modelling evaluated the relationship between treatment outcome and age, body mass index (BMI), pain and function self-efficacy and presence/absence of osteophytes in the medial and lateral tibiofemoral joint (TFJ) and patellofemoral joint (PFJ) compartments. 13 (33%) participants were men. The mean (SD) age and BMI were 53.6 (13.1) years and 27.9 (4.6) kg/m(2), respectively. 13 (33%), 19 (49%) and 24 (62%) participants had medial TFJ, lateral TFJ and PFJ osteophytes, respectively. Glucosamine significantly improved pain (mean change on VAS = -1.4, 95% CI -0.6 to -2.2; p = 0.002) and activity restriction (-1.9, 95% CI -1.0 to -2.8; p<0.001). At 12 weeks, 30 (77%) and 27 (69%) participants reported improvement in pain and physical function, respectively. Regression modelling showed that no evaluated variables predicted change in pain on VAS. Decreased function self-efficacy, presence of PFJ osteophytes and absence of medial TFJ osteophytes predicted functional improvement on VAS. BMI, pain self-efficacy and function self-efficacy predicted improvement in pain by GCS.

Although glucosamine significantly improved symptoms, most of the variance in outcome at 12 weeks was unexplained by the predictors evaluated. However, glucosamine may be more effective at improving symptoms in patients with knee OA who have a lower BMI, PFJ osteophytes and lower functional self-efficacy.

To evaluate the social functioning and health related quality of life (HRQoL) in patients with juvenile idiopathic arthritis (JIA) in early adulthood. The patient files of the Rheumatism Foundation Hospital were screened to identify patients born in 1976-1980 diagnosed as having JIA. HRQoL was measured by the RAND 36-item health survey 1.0; spousal relationships and educational and employment status were assessed by questionnaire. The patients were invited to a follow up study. Age and sex matched controls from the community were identified in the Finnish population registry. Of 187 patients identified, 123 participated. Spousal relationships, educational level, and employment status were similar to controls. HRQoL in JIA patients was similar to controls except on the physical functioning scale. At follow up 35% of patients were in remission. Patients with active disease had poorer HRQoL in the physical component than those in remission or controls. The extended oligoarthritis group had the lowest physical and mental score in HRQoL compared with the other JIA subgroups. The patient's own evaluation was the explanatory factor in both the physical and mental component of HRQoL.

Social functioning and HRQoL were similar in JIA patients and age, sex, and municipality matched controls. However, patients with extended oligoarthritis attained significantly lower scores in the physical and mental component of HRQoL than oligo- or polyarthritis patients. Special attention in everyday care should be paid to those patients who have active disease or the extended oligoarthritis type of disease.

Uric acid may be linked to bone health through its antioxidant or prooxidant effects, thereby affecting bone resorption and formation, or through its dual inhibition of vitamin D activation and parathyroid hormone production. Results of prior studies on the relationship between uric acid and bone mineral density have been conflicting. This prospective study was undertaken to examine the relationship between gout, a disease characterized by hyperuricemia and inflammation, and risk of hip or wrist fracture in women. We conducted a prospective observational study of gout and risk of incident wrist and hip fracture in women participating in the Nurses' Health Study (n = 103,799 at baseline, with 14 years of follow-up for the wrist fracture analysis and 22 years of follow-up for the hip fracture analysis). Gout history and incident cases of wrist and hip fracture were assessed by biennial questionnaire. Cox proportional hazards models were used to simultaneously adjust for potential confounders. In this cohort, there were 3,769 incident wrist fractures (1990-2004) and 2,147 incident hip fractures (1990-2012), with 107 wrist fractures and 117 hip fractures occurring in participants with gout. In those women with a history of gout compared with women without gout, the multivariable-adjusted relative risk of wrist fracture was 1.12 (95% confidence interval [95% CI] 0.92-1.36) and the multivariable-adjusted relative risk of hip fracture was 1.38 (95% CI 1.14-1.68).

In women, a history of gout is associated with a modestly increased risk of hip fracture, but not significantly associated with a risk of wrist fracture.

In the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis. The aim of this study was to assess joint damage progression and clinical outcomes over 2 years. Patients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed. At 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone (57% vs 37%; p<0.0001). Contrary to 1-year results, exploratory analysis of rituximab 2×500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61% versus placebo+MTX (mTSS, exploratory p=0.0041). Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2. Safety profiles were similar between groups.

Treatment with rituximab 2×1000 mg+MTX was associated with sustained improvements in radiographic, clinical and functional outcomes over 2 years. Clinical trials.gov identifier NCT00299104.

To determine whether there is any evidence that there are spatial clusters of rheumatoid arthritis in particular, and inflammatory arthritis in general. Setting was a population based incidence register of inflammatory arthritis: the Norfolk Arthritis Register (NOAR). All cases identified between 1990-1995 were mapped to place of residence. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. Three clusters were identified including one small area (population 85) where five unrelated cases developed during this time period. There was no obvious greater disease homogeneity within clusters and no common environmental factors were identified.

Rare clusters of inflammatory polyarthritis do occur. Their significance and cause remain to be elucidated.

Osteoarthritis is a chronic debilitating condition affecting many adults in the United States. This study was to compare pharmacologic treatments and costs for newly diagnosed and existing osteoarthritis patients to assess unmet medication treatment needs and economic burden. This retrospective analysis of de-identified medical and pharmacy insurance claims from the MarketScan(®) databases identified adult patients with an osteoarthritis claim in 2007. The date of the first osteoarthritis claim in 2007 served as the index. Patients were stratified into newly diagnosed and existing cohorts, based on the presence of osteoarthritis claim(s) over the 12-month pre-index period. Utilization of pain-related medications and healthcare costs was assessed in the 12-month postindex period. Multivariate analysis was conducted to adjust costs controlling for cross-cohort differences. Newly diagnosed osteoarthritis patients (n = 134,584) were younger (66.0 vs. 68.0, P < 0.001), had a higher proportion of men (37.4% vs. 33.9%, P < 0.001) but lower rates of comorbidities than existing patients (n = 123,653). Significantly higher proportions of newly diagnosed patients had an inpatient admission and outpatient office visit. Higher proportions of existing patients utilized a majority of the medication classes examined. Total adjusted osteoarthritis-related costs for newly diagnosed patients were $6,811 annually (95% confidence interval [CI] $6,743 to $6,887), compared to $6,407 (95% CI $6,327 to $6,477) for existing patients. Costs of pain-related prescription drugs associated with osteoarthritis were $965 (95% CI $955 to $975) among new patients, less than the $1,117 (95% CI $1,107 to $1,129) among existing patients.

Newly diagnosed osteoarthritis patients incurred higher annual costs, but lower pain-related prescription drug costs in the year following diagnosis than patients with existing osteoarthritis.

We assessed the morphological differences in the knee joint related to knee rotation angle in patients with hip dysplasia. These results may explain the anatomy of the knee in patients with hip dysplasia and aid in planning knee surgery. We enrolled 73 women (146 legs, 35.6 ± 9.0 years) with bilateral hip dysplasia and 45 healthy women (90 legs, 49.0 ± 18.9 years) without lumbago, knee symptoms, or osteoarthritic findings of the knee or spine on plain radiographs. We examined the parameters affecting knee rotation angle, such as the condylar twist angle and femoral condyle measurements with a three-dimensional bone model using the correlation coefficients of each parameter. The condylar twist angle and the length of the posterior part of the lateral femoral condyle were statistically positively correlated with knee rotation angle in both the normal (condylar twist angle: r = 0.286, p = 0.007, posterolateral: r = 0.429, p < 0.001) and developmental dysplasia of the hip groups (condylar twist angle: r = 0.230, p = 0.033, posterolateral: r = 0.272, p = 0.005). Knee rotation angle had no statistical correlation with femoral neck anteversion in the developmental dysplasia of the hip group (r = 0.094, p = 0.264), but had a statistical correlation with femoral neck anteversion in the normal group (r = 0.243, p = 0.039).

Knee joint morphology is affected by hip dysplasia. We found that the length of the posterior part of the lateral femoral condyle was significantly positively correlated with knee rotation angle in both the normal and developmental dysplasia of the hip groups, and this finding indicates that a greater posterolateral dimension was associated with a greater knee rotation angle. These morphological knee joint differences in patients with hip dysplasia may help determine the alignment of prostheses in total knee arthroplasty.

To analyze the safety of methotrexate (MTX) in rheumatoid arthritis (RA) regarding the reproductive system (fertility, pregnancy, and breastfeeding). Systematic review of studies retrieved by a sensitive search strategy in Medline (1961 - October 2007), Embase (1961 - October 2007), Cochrane Library (up to October 2007), and from the abstracts of the ACR (2005, 2006) and EULAR (2005 - 2007) annual scientific meetings. a) population: studies had to include patients with RA; b) intervention and control: discontinuation of MTX or elective abortion versus continuation of MTX or continuing pregnancy; and c) outcomes: infertility, oligospermia, reversibility, miscarriages, malformations, premature babies, healthy newborn, percent of the dose of MTX that passes to human milk, adverse effects in the lactating child. There was no limitation regarding study design, except for case reports, or language. MTX and pregnancy: we selected 6 articles for detailed evaluation from 847 initial ones from the literature search. They were descriptions of cases obtained from searching retrospectively clinical databases of individual centers or from surveys. Patients had been exposed to MTX at doses used in rheumatology (5-25 mg/w), from conception to first trimester of pregnancy. Total number of MTX exposed pregnancies is 101, and the pooled outcomes (elective abortion not included): 19 miscarriages (23% of pregnancies); 55 live births (66% of pregnancies); and 5 of them had minor neonatal malformations (5% of pregnancies). The rate of induced abortions is 18%. MTX and lactation and fertility: no articles fulfilled the selection criteria. There is indirect evidence on the excretion of MTX in human milk and probably of reversible infertility from case reports.

This review exposes the shortage of data on the safety and risks of MTX during conception, pregnancy and lactation at the doses commonly used in rheumatology. MTX and pregnancy: there is not sufficient evidence to support whether it is MTX or the disease what underlies miscarriage in these patients. Pooling the data from the studies included, the rates of miscarriages and of birth defects are similar to the rates observed in healthy population. MTX and lactation and fertility: there is absence of confirming evidence.

To examine the validity, reliability and sensitivity to change of the Activity Participation Questionnaire (APaQ), a simple measure of activity participation for patients with RA. The questionnaire contained two items: (i) number of days in the past month of being unable to perform one's usual activities because of RA; and (ii) a score measuring how often one's usual activities could be completed. The APaQ was administered to 1043 RA patients in two clinical trials of abatacept. Construct validity was evaluated by examining changes from baseline in activity scores by clinical response measured by the European League Against Rheumatism (EULAR) and ACR criteria and minimal disease activity (MDA) state and by correlations with patient-reported outcome measures of physical function, disease activity, pain and fatigue at study end-point. Internal consistency, test-retest reliability and sensitivity to change were assessed. Both activity participation items were significantly associated with levels of EULAR and ACR response and the achievement of MDA state (P < 0.0005 for all comparisons). Moderate correlations with patient-reported outcomes were consistently found (correlations 0.5-0.6). Cronbach's alpha was 0.7 indicating good internal consistency, the intraclass correlation coefficient of 0.6 suggesting acceptable test-retest reliability. Sensitivity to change was demonstrated by the treatment differences and the standardized response mean (0.39 and 0.30) for the two activity items.

The APaQ is a simple, reliable and valid measure of patient activity, which is sensitive to change, suggesting its suitability for use in clinical trials.

To investigate whether radiographic osteoarthritis (OA) is asymmetric and greater on the right side than on the left side in the hands, hips, and knees. Participants were 489 individuals with posteroanterior hand radiographs from a family study of nodal OA, 1,715 community-derived individuals who had undergone intravenous urography with views of both hips, and 1,729 community-derived individuals with weight-bearing fully extended tibiofemoral (TF) joint and skyline patellofemoral (PF) joint radiographs. All radiographs were evaluated for global OA grade, osteophytes, and joint space narrowing (JSN). Minimum joint space width (JSW) was measured at the hip and knee. Odds ratios (ORs) for global OA on the right side versus the left side were calculated. Osteophytes and JSN were compared by Wilcoxon's signed rank test, and the JSW was compared by paired t-test. Global OA was more prevalent on the right side at the distal interphalangeal joints (OR 1.57; 95% confidence interval 1.22, 2.02) and the TF joint (OR 1.24; 95% confidence interval 1.01, 1.52). Osteophyte scores for the fingers were greater on the right side, but JSN was symmetric. At the hip, there were no right-left differences in osteophytosis or JSN, but the JSW was smaller on the left. At the TF joint, the medial compartment was narrower and the lateral compartment wider on the right side, and osteophyte scores were greater on the right side. At the PF joint, there were no right-left differences in osteophytes, and for lone PF joint OA, there were no differences in JSN or the JSW.

This discordance in symmetry suggests that the relative importance of biomechanical factors in the pathogenesis of OA is site-specific and may be discordant for cartilage and bone.

To explore the transitional needs of adolescents with juvenile idiopathic arthritis (JIA), as perceived by a range of professionals, and to examine how these needs may be addressed within a structured programme of transitional care. Postal surveys (n = 1670) were distributed to key professionals employed in health, social support, education and vocation. Surveys were completed by 478 individuals. The majority of respondents (91%) were currently active in the care of adolescents with JIA. Planning for transitional care was perceived to be important for both adolescents and parents and to require multidisciplinary involvement. Respondents rated a wide range of resources to be important in supporting adolescents, including self-medication teaching packages and social skills training. A number of barriers to providing transitional care were identified, including inadequate resources, coordination and training.

Transitional care in the context of JIA is perceived as necessary by a wide variety of professionals.

To review the pharmacology, pharmacokinetics, efficacy and safety, dosage administration, and adverse effects of tofacitinib for rheumatoid arthritis (RA) treatment. Primary sources of information were obtained from clinical studies, which were identified through PubMed (1966 to June 2013) and International Pharmaceutical Abstracts (1970 to March 2013) using terms: tofacitinib, tasocitinib, CP-690550, and CP-690,550. Information was used from tofacitinib package insert, guidelines, and published abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism. Data search was limited to include publications in English language and from human subjects. Tofacitinib is the first oral Janus kinase inhibitor indicated for treatment of moderate to severe RA. Tofacitinib demonstrated efficacy and safety comparable to other disease-modifying antirheumatic drugs (DMARDs). Tofacitinib was efficacious in RA patients, indicated by achievements of ACR20, ACR50, and ACR70 criteria. Similar improvements were observed in patients who met remission criteria based on the Disease Activity Scores 28 criteria and quality of life as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Tofacitinib was associated with infections and malignancies; and elevations in serum creatinine and lipids were observed. Drug interactions with inducers and inhibitors of the cytochrome P-450 3A4 and 2C9 isoenzymes were reported.

Tofacitinib is an oral treatment option for RA patients who have inadequate response or intolerance to methotrexate. Postmarket surveillance will provide further insight to tofacitinib's role in RA therapy, especially in patients who may require different types of combination therapy with DMARDS.

Physical activity can improve osteoarthritis-related symptoms; however, many people with osteoarthritis (PWOA) are insufficiently active. Social support for physical activity from an intimate partner can help PWOA increase activity, but managing multiple, chronic physical or mental health conditions (i.e., multimorbidity) may influence provision and receipt of that support. Data from a 1-year longitudinal observational study was used to examine associations between multimorbidity and three dimensions of partner support for physical activity-companionship partner support (doing activity together), enacted partner support, and social support effectiveness-in 169 insufficiently active PWOA and their partners. Multivariable-adjusted multi-level models indicated baseline differences in support by multimorbidity status: when partners had multimorbidity, PWOA reported receiving less companionship support and less effective support from partners; when PWOA had multimorbidity, partners reported providing less enacted support and both partners and PWOA reported less effective partner support. Broad trends (p < .05) indicate initial increases and subsequent decreases in companionship and enacted partner support when PWOA had multimorbidity, and among partners with and without multimorbidity. When PWOA had multimorbidity, an initial increase in support effectiveness was followed by no significant change; a similar trend was seen among partners with and without multimorbidity.

Multimorbidity may generally contribute to less partner support for physical activity or less effective support, although influences on support over time are less clear. Physical activity interventions for couples experiencing multimorbidity would likely benefit from attention to the impact of multiple chronic health conditions on physical activity and physical activity-related partner support.

Rheumatoid arthritis (RA) is an inflammatory chronic disease characterized by inflammation, pain, swelling and disability, and radiosynovectomy is one of the disease treatment lines. In this study, the possibility of providing rhenium-186/rhenium-188 chitosan radiopharmaceuticals, optimization of conditions for their production and bio-distribution are reported. In order to build perrhenic acid for labeling, natural rhenium was exposed to radiation. Radionuclidic and radiochemical purities of (186/188Re)-NaReO4 were examined by gamma spectroscopy and paper chromatography methods, respectively. Labeling of chitosan with rhenium was done in different acidic situations. The radiochemical purity 186/188Re-chitosan was applied by radio thin layer chromatography (RTLC). Lastly, the bio-distribution of the radiolabeled chitosan was studied in various organs after intra articular injection of the complex to lab rats. Gamma spectrometry confirmed the high rhenium radionuclidic purity. Chromatography results showed that perrhenic acid was produced with purity greater than 97% and rhenium chitosan labeling was done over 98% in pH = 3. Dissection results showed a high bio-distribution of 186/188Re-chitosan after injection into the joint with no leakage to surrounding organs.

According to the results, there is a possibility of labeling rhenium with chitosan in very high radiochemical purity. Regarding the high retention of these radiopharmaceuticals in joints with no leakage to surrounding organs, 186/188Re-chitosan can be applied as new radiosynovectomy drugs for rheumatoid arthritis treatment.

The objective of this study was to compare the total costs associated with the administration of two different tumour necrosis factor (TNF) strategies used in the treatment of rheumatoid arthritis (RA): etanercept, a soluble TNF receptor that can be administered at home by subcutaneous injection, versus infliximab, an antibody that requires an intravenous infusion in a hospital outpatient setting. The main analytical framework of the study was a cost-cost analysis comparing the total annual costs associated with the administration of etanercept and infliximab in adult RA patients. The perspective of the study was that of the Dutch society. An economic model was constructed to determine the costs of both treatments. The cost evaluation included direct medical costs, direct nonmedical costs and indirect costs. The base-case analysis compared monotherapy with etanercept versus a combination therapy with infliximab and methotrexate. Data for the economic model came from published literature, expert opinion and official price and tariff lists. All costs were in 1999 values. The analysis was performed for the adult RA population eligible for treatment with etanercept or infliximab in The Netherlands. The analysis showed that the total annual drug costs per patient do not differ substantially between infliximab and etanercept, with costs of Netherland guilders (NLG)31,526 (12,610 US dollars) and NLG31,334 (12,534 US dollars), respectively. However, the other medical costs (i.e. excluding the costs of the two drugs themselves) are substantially higher for infliximab due to the additional costs associated with administration in an outpatient clinic and the use of methotrexate [NLG 12,621 (5048 US dollars) versus NLG269 (107 US dollars) for etanercept]. The impact of direct nonmedical costs (transportation) and indirect costs were negligible. Overall treatment with infliximab is more expensive than treatment with etanercept with total costs of NLG45 115 (18,046 US dollars) and NLG3I,621 (12,648 US dollars), respectively (42.7% increase).

Based on the assumptions used in the model, we may conclude that the use of etanercept compares favourably with infliximab from a budgetary and health economic perspective: the total costs are substantially lower when the efficacy of etanercept is assumed to be at least equivalent to the efficacy of infliximab.

To evaluate the effect of infrared radiation and magnetic field therapy on cartilage damage in rabbits with knee osteoarthritis. Knee osteoarthritis was induced in 24 adult New Zealand rabbits by prolonged fixation of the knee joint in extension for 6 weeks. The rabbits were subsequently randomized into control group (without treatment), infrared therapy group, magnetic field therapy group and the combined infrared and magnetic field therapy group. At the end of the first, second and third weeks of the therapy, respectively, 2 rabbits from each group were sacrificed to observe the general changes and histopathology of the condylar cartilage of the femur, and the findings were assessed using Mankin scores. Compared with other groups, the rabbits in the combined therapy group showed significantly milder cartilage damage (including injury of the cartilage surface and chondrocyte's proliferation and disarrangement) with significantly lower Mankin scores (P<0.05). No significant differences were found in the findings between the two groups with exclusive infrared or magnetic field therapy (P>0.1).

Combined infrared and magnetic field therapy can effectively alleviate cartilage destruction, shortens the disease course and enhance the therapeutic effects in rabbits with knee osteoarthritis.

Erdheim-Chester disease (ECD) is a rare inflammatory disorder characterised by organ infiltration by non-Langerhans' histiocytes. Although rare, ECD is clearly an overlooked diagnosis. No data specifically addressing the most frequent presentations of ECD at the time of onset in a large cohort of patients are currently available. We reviewed all the published cases in the English literature of histologically-confirmed ECD. We excluded reports in which data regarding onset and diagnosis were not univocal, as well as repeated reports of the same case(s). We also included in the analysis 10 new unpublished patients from our cohort. We analysed the disease presentation with particular regard to the manifestations that induced patients to seek medical attention and their subsequent evolution. In the cumulative cohort of 259 cases, ECD predominantly presented with skeletal symptoms, diabetes insipidus, neurological and constitutional symptoms. Diabetes insipidus and constitutional symptoms, if not present at onset, seemed to only seldom develop. There were differences in ECD presentation and course among different age groups of patients.

Physicians should be aware of the extraordinarily heterogeneous clinical presentations and manifestations of ECD in order to include ECD in the differential diagnosis of several conditions.

The phenotype of patients who remain naive of glucocorticosteroids has not been described, and the type and rate of their damage accrual remains largely unknown. The objective of this study was to compare the type, amount, rate, and nature of organ damage accrual, mortality, and atherosclerotic comorbidities in glucocorticosteroid-naive and glucocorticosteroid-exposed patients with systemic lupus erythematosus (SLE). Inception patients from the University of Toronto Lupus Clinic who had never taken glucocorticosteroids and had a minimum of 3 years of followup were compared to patients who received glucocorticosteroids within the first 6 months of SLE diagnosis and for at least 3 years. All patients had no damage at inception. A total of 86 glucocorticosteroid-naive and 173 glucocorticosteroid-exposed patients were included. There were more females and whites among the glucocorticosteroid-naive patients, whereas the glucocorticosteroid-exposed patients had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores on first examination. Overall mortality was higher in the glucocorticosteroid-exposed group, but the deaths occurred late. There was no difference in the frequency of coronary artery disease overall or at each of the time points. Damage accrual was higher in glucocorticosteroid-exposed patients overall and at 5 and 8 years. Individual damage items that were higher in glucocorticosteroid-exposed patients included ocular (cataracts) and musculoskeletal (osteoporosis with fragility fractures, and osteonecrosis) components.

Mortality is more frequent in patients taking glucocorticosteroids for at least the first 3 years of their lupus compared to patients who are glucocorticosteroid-naive. In addition, patients taking glucocorticosteroids accumulate more damage by 5 years of disease, and damage tends to be glucocorticosteroid related, including cataracts and musculoskeletal components.

Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counselling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. The studied cohort was 37% overweight, 34% obese (average body mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgiasymptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the "Diet adherence" (85%). "Satisfaction with improvement of symptoms" (76%), showed correlating with "diet adherence" (r = 0.65; p < 0.01).

Results are highly encouraging, showing low fermentable oligo-di-mono-saccharides and polyols diets as a nutritionally balanced approach, contributing to weight loss and reducing the severity of FM fibromyalgiasymptoms.

Nitrergic and prostanoid pathways have both been implicated in inflammatory processes. To investigate their respective contributions in a rat model of chronic arthritis. Male Wistar rats (n = 4-6/group) received either an intra-articular injection of 2% carrageenan/4% kaolin (C/K) or intra- and periarticular injections of Freund's complete adjuvant (FCA; 10 mg/ml M tuberculosis). Joint diameter, urinary nitric oxide metabolites (NO(x)), and prostaglandin E(2) (PGE(2)) levels were measured as indices of the inflammatory process. A prophylactic and therapeutic (day 5) dose ranging study of an inducible nitric oxide synthase inhibitor, L-N-(1-iminoethyl)-lysine (L-NIL), and a cyclo-oxygenase-2 (COX-2) inhibitor, SC-236, was performed with the drugs given subcutaneously. Submaximal doses were identified and used for combination studies. Appropriate vehicle controls were included. L-NIL and SC-236 dose dependently inhibited C/K induced acute joint swelling, the magnitude being greatest when they were given in combination. Both prophylactic and therapeutic administration of SC-236 in the FCA induced model of chronic arthritis produced a dose dependent reduction in all the measures assessed. However, although L-NIL demonstrated similar dose dependent inhibition of urinary NO(x) and PGE(2) levels, joint swelling was significantly exacerbated in this model. Co-administration of the inhibitors nullified the benefits of SC-236.

Whereas COX-2 derived prostaglandins are proinflammatory in both acute and chronic joint inflammation, NO seems to have divergent roles, being anti-inflammatory in chronic and proinflammatory in acute joint inflammation.

Biologic glenoid resurfacing was developed in 1988 as an alternative to total shoulder arthroplasty in selected (usually younger) patients with primary, posttraumatic, or postreconstructive glenohumeral arthritis. A variety of biologic surfaces, including anterior capsule, autogenous fascia lata, and Achilles tendon allograft, have been combined with a humeral hemiarthroplasty. From November 1988 to November 2003, thirty-four patients (thirty-six shoulders) who were managed with biologic glenoid resurfacing and humeral head replacement either with cement (ten shoulders) or without cement (twenty-six shoulders) were followed prospectively. The study group included thirty men and four women with an average age of fifty-one years. The diagnoses included primary glenohumeral osteoarthritis (eighteen shoulders), postreconstructive arthritis (twelve), posttraumatic arthritis (five), and osteonecrosis (one). Anterior capsule was used for seven shoulders, autogenous fascia lata for eleven, and Achilles tendon allograft for eighteen. All shoulders were assessed clinically and with serial radiographs. The mean American Shoulder and Elbow Surgeons score was 39 points preoperatively and 91 points at the time of the most recent follow-up. According to Neer's criteria, the result was excellent for eighteen shoulders, satisfactory for thirteen, and unsatisfactory for five. Glenoid erosion averaged 7.2 mm and appeared to stabilize at five years. There were no revisions for humeral component loosening. Complications included infection (two patients), instability (three patients), brachial plexitis (one patient), and deep-vein thrombosis (one patient). Factors that appeared to be associated with unsatisfactory results were the use of capsular tissue as the resurfacing material and infection.

Biologic resurfacing of the glenoid can provide pain relief similar to total shoulder arthroplasty. It allows selected younger patients to maintain an active lifestyle, including weight-lifting and manual work, without the risk of polyethylene wear. On the basis of this and previous reviews, we currently recommend Achilles tendon allograft as the preferred resurfacing material when this option is chosen.

Treat-to-target therapy is effective for patients with rheumatoid arthritis (RA), but long-term results of continued targeted treatment are lacking. To evaluate long-term outcomes in patients with early RA after 10 years of targeted treatment in 4 treatment strategies. Randomized trial. (Nederlands Trial Register: NTR262 and NTR265). The Netherlands. 508 patients with early active RA. Sequential monotherapy (strategy 1), step-up combination therapy (strategy 2), or initial combination therapy with prednisone (strategy 3) or with infliximab (strategy 4), all followed by targeted treatment aiming at low disease activity. Functional ability (Health Assessment Questionnaire [HAQ] score) and radiographic progression (Sharp-van der Heijde score) were primary end points. Survival in the study population was compared with the general population using the standardized mortality ratio. 195 of 508 of patients (38%) dropped out of the study (28% in strategy 4 vs. 40% to 45% in strategies 1 to 3, respectively). At year 10, mean HAQ score (SD) was 0.57 (0.56); 53% and 14% of patients were in remission and drug-free remission, respectively, without differences among the strategies. Over 10 years, mean HAQ scores were 0.69, 0.72, 0.64, and 0.58 in strategies 1 to 4, respectively (differences not clinically relevant). Radiographic damage was limited for all strategies, with mean Sharp-van der Heijde estimates during follow-up of 11, 8, 8, and 6 in strategies 1 to 4, respectively (P = 0.15). Standardized mortality ratio was 1.16 (95% CI, 0.92 to 1.46) based on 72 observed and 62 expected deaths, with similar survival among the 4 strategies (P = 0.81). Dropout rate varied by strategy. Dutch College of Health Insurance Companies, Schering-Plough, and Janssen.

In patients with early RA, initial (temporary) combination therapy results in faster clinical improvement and targeted treatment determines long-term outcomes. Drug-free remission, with prevention of functional deterioration and clinically relevant radiographic damage, and normalized survival are realistic outcomes.

The purpose of this study was to evaluate the effect of obesity on intermediate- to long-term implant failure rates and survivorship after total ankle arthroplasty. A chart review was performed for all patients who underwent primary total ankle arthroplasty between 2004 and 2009 with a minimum 5-year follow-up. Patients were separated into a reference group with a body mass index less than 30 kg/m2 and an obese group with an index greater than or equal to 30 kg/m2. Minimum 5-year follow-up outcomes were available for 49 patients in the obese group and 48 patients in the nonobese group. Mean follow-up was 8.2 ± 2.0 years (range, 5.1-11.5 years) in the reference group and 7.7 ± 2.0 years (range, 5.0-11.9 years) in the obese group (P = .26). Based on multivariable logistic regression, obese patients had a significantly greater probability of implant failure by final follow-up (adjusted odds ratio, 2.8 [95% CI, 1.04-7.53]; P = .04). Cox regression analysis of 5-year implant survivorship showed no significant difference between the 2 groups (adjusted hazard ratio, 1.89 [95% CI, 0.77-4.65]; P = .17). When compared with obese patients with inflammatory or posttraumatic arthritis, obese patients with osteoarthritis demonstrated a significantly decreased 5-year survivorship (adjusted hazard ratio, 3.73 [95% CI, 1.05-10.43]; P = .04). Level III, retrospective comparative series.

This study demonstrated an increased long-term risk of implant failure among obese patients that was not seen in the intermediate term. Furthermore, obese patients with primary osteoarthritis were found to have a significantly decreased 5-year implant survivorship after ankle arthroplasty as compared with obese patients with inflammatory or posttraumatic arthritis and therefore should be counseled appropriately when deciding between arthroplasty and arthrodesis.

To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc) by testing the hypothesis that platelets contribute to skin fibrosis via the activation of human dermal microvascular endothelial cells (HDMECs) and subsequent production of profibrotic mediators. A total of 203 SSc patients and 30 healthy donors were prospectively enrolled between 2012 and 2015 at the University Hospital of Bordeaux. Immunohistochemistry and immunofluorescence analyses were performed on skin biopsy sections from 18 SSc patients and 5 healthy donors. Serum thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay in the entire cohort. HDMECs and fibroblasts were purified from biopsy sections. Extracellular matrix production by cultured fibroblasts was assessed by real-time quantitative polymerase chain reaction. Serum TSLP levels were significantly increased in SSc patients compared to healthy donors (P < 0.0001) and were associated with a higher frequency of vasculopathy (P = 0.02). The proportion of TSLP-positive dermal cells was increased in the skin of SSc patients compared with healthy donors (P < 0.0001) and was correlated with fibrosis (modified Rodnan skin thickness score) (r = 0.6146, P = 0.0001). In SSc dermis, TSLP was mainly expressed by CD31-positive endothelial cells. In vitro, activated platelets induced TSLP production by HDMECs in an interleukin-1β-dependent manner. SSc fibroblasts responded differently according to their original TSLP environment.

Taken together, these results identify HDMECs as contributors to TSLP production in SSc and suggest a potential mechanism by which platelets may profoundly affect the fibrotic process in SSc.

The predictive role of patient-specific characteristics and radiographic parameters on medial unicompartmental knee arthroplasty (UKA) outcomes is well known, but knowledge of these predictors is lacking in lateral UKA. Therefore, purpose of this study was to assess the predictive role of these parameters on short-term functional outcomes of lateral UKA. In this retrospective cohort study, Western Ontario and McMaster Universities Arthritis Index scores were collected at 2-year follow-up (median 2.2 years, range 2.0-4.0 years) in 39 patients who underwent lateral UKA. Patient-specific characteristics included age, BMI and gender, while radiographic parameters included osteoarthritis severity of all three compartments and both preoperative and postoperative hip-knee-ankle alignment. BMI, gender, age and preoperative valgus alignment were not correlated with functional outcomes, while postoperative valgus alignment was correlated with functional outcomes (0.561; p = 0.001). Postoperative valgus of 3°-7° was correlated with better outcomes than more neutral (-2° to 3° valgus) alignment (96.7 vs. 85.6; p = 0.011). Postoperative alignment was a predictor when corrected for patient-specific characteristics (regression coefficient 4.1; p < 0.001) and radiological parameters (regression coefficient 3.8; p = 0.002). Prognostic study, Level II.

Postoperative valgus alignment of 3°-7° was correlated with the best short-term functional outcomes in lateral UKA surgery, while patient-specific parameters and preoperative alignment were not correlated with functional outcomes. Based on these findings, a surgeon should aim for valgus alignment of 3°-7° when performing lateral UKA surgery for optimal functional outcomes.

Increased impact loading is implicated in knee osteoarthritis development and progression. This study examined the impact ground reaction force (GRF) peak, its loading rate, its relative timing to stance phase timing, and walking speed during unilateral and bilateral use of laterally wedged insoles with arch supports. Within-subject design. Thirty-three female patients with medial knee osteoarthritis were examined with (unilateral 6° and 11°, and bilateral 0°, 6°, and 11°) and without insole use. Repeated measures MANOVA revealed that the impact force increased significantly in bilateral 11° versus unilateral 6° and without-insole conditions. The loading rate decreased significantly in unilateral 11° versus bilateral 6° insoles. The relative timing increased significantly in each of bilateral 6°, bilateral 11°, and unilateral 11° versus bilateral 0° insoles and in each of bilateral 11° and unilateral 11° versus without-insole condition. There were significant positive correlations between the walking speed and each of the force and loading rate. The Chi-square test revealed insignificant association between the insole condition and the presence of impact forces. Unilaterally applied 11° laterally wedged insoles are capable of reducing and delaying the initial impact ground reaction forces and reducing their loading rates during walking in patients with medial knee osteoarthritis, thus reducing osteoarthritis progression. Walking slowly could also be used as a strategy to reduce impact loading.

Unilateral 11° insoles are capable of reducing impact loading possibly through increasing foot pronation. Walking slowly is another possible strategy to reduce loading.

In autologous chondrocyte implantation (ACI), the periosteum patch which is sutured over the cartilage defect has been identified as a major source of complications such as periosteal hypertrophy. In the present retrospective study, we compared midterm results of first-generation ACI with a periosteal patch to second generation ACI using a biodegradable collagen fleece (BioSeed-C) in 82 patients suffering from chronic posttraumatic and degenerative cartilage lesions of the knee. Clinical outcome was assessed in 42 patients of group 1 and in 40 patients of group 2 before implantation of the autologous chondrocytes and at a minimum follow-up of 2 years using the ICRS score, the modified Cincinnati score and the Lysholm score. Although patients treated with BioSeed-C had more previous surgical procedures on their respective knees, highly significant improvements (P < 0.001) were assessed in both groups at comparable outcome levels: the ICRS score improved from grade D (poor) preoperatively to grade C (fair); the modified Cincinnati knee score from 3.26 to 6.4 (group 1) and 3.3 and 6.88 (group 2). Lysholm score improved from 33 to 70 points (group 1) and from 47 to 78 points (group 2), respectively. Revision surgery was due to symptomatic periosteal hypertrophy (n = 4), graft failure (n = 3), plica syndrome (n = 2) synovectomy (n = 1) (group 1); and graft failure (n = 2), debridement (n = 1), synovectomy (n = 2) (group 2).

These results suggest that BioSeed-C is an equally effective treatment option for focal degenerative chondral lesions of the knee in this challenging and complex patient profile.

To evaluate whether hinge position affects the change in posterior tibial slope in medial open-wedge high tibial osteotomy (HTO). We retrospectively evaluated 19 knees from 17 patients who underwent medial open-wedge HTO by 3-dimensional computed tomography scan before and after surgery. A 3-dimensional image model was constructed by applying reverse-engineering software to the computed tomography DICOM (Digital Imaging and Communications in Medicine) files. The hinge axis (i.e., the position of the hinge compared with the anteroposterior axis on an axial view), posterior tibial slope, medial-proximal tibial angle, and gap ratio (i.e., the ratio of anterior gap to posterior gap in the opened wedge) were measured. The mean hinge axis was 4.92° ± 3.86°. Posterior tibial slope increased from 7.29° ± 2.56° preoperatively to 10.48° ± 3.01° postoperatively (P = .001). The mean medial-proximal tibial angle was 85.96° ± 1.97° preoperatively and 93.13° ± 3.17° postoperatively (P = .001). The mean gap ratio was 62.48% ± 7.26%. Linear regression analysis determined that the hinge axis (P = .0001) was a significant factor changing posterior tibial slope. Level IV, therapeutic study.

Hinge position affected the change in posterior tibial slope in medial open-wedge HTO; in particular, a posterolateral hinge position led to an increase in posterior tibial slope.

Studies linking health literacy to outcomes in rheumatoid arthritis (RA) have been underpowered and have not adequately accounted for confounders. We examined the association of health literacy with functional status in 6,052 subjects participating in a prospective observational study, controlling for numerous important covariates. Using linear regression, we analyzed the cross-sectional association of health literacy, as measured by 2 validated single-item literacy screening questions (SILS1 and SILS2), and functional status, assessed by the Health Assessment Questionnaire (HAQ) disability index. Subjects reported demographics, comorbidities, social support, educational attainment, visual problems, and memory problems, as well as use of prednisone, disease-modifying antirheumatic drugs, and biologic agents. Each SILS measure was forced into the final model. Low health literacy was present in 7.0% and 4.3% of subjects (per SILS1 and SILS2, respectively). When controlling for all covariates, low health literacy was associated with a 0.376-point greater HAQ score, compared to subjects with adequate health literacy (95% confidence interval 0.306, 0.447; P < 0.001). This relationship persisted, even after modeling educational attainment. Results were similar for the 2 SILS instruments. Low health literacy was also associated with poorer self-reported adherence to RA medications. Visual and memory problems were associated with worse functional status.

Health literacy was more strongly associated with functional status than prednisone use, smoking history, and biologic agent use, and independent of educational attainment. Health literacy may play an important role in understanding functional status in RA patients. Single-item questions amenable to use in the clinical setting may identify subjects with low health literacy, who are at risk for poor RA outcomes.

Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury-related lncRNAs (lncRNA-CIR) in OA. To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA-CIR was specifically, differentially, and highly expressed. The function of lncRNA-CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)-related molecules were detected by qPCR, Western blot, and immunofluorescence analyses. Up to 152 lncRNAs were found to be differentially expressed (>8-fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA-CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA-CIR increased in chondrocytes with in vitro treatment with interleukin-1β and tumor necrosis factor α. Silencing of lncRNA-CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrix-degrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix-degrading enzymes was increased, after overexpression of lncRNA-CIR.

The results indicate that lncRNA-CIR contributes to ECM degradation and plays a key role in the pathogenesis of OA. We propose that lncRNA-CIR could be used as a potential target in OA therapy.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by peripheral and symmetrical polyarthritis. It can be divided into Very Early Rheumatoid Arthritis (VERA) diagnosed up to 3 months of symptoms and late onset (Late Early Rheumatoid Arthritis - LERA), diagnosed between 3 and 12 months. Currently, it is recommended to evaluate the patient with joint symptoms as early as possible, and the first 12 weeks of manifestations represent the ideal phase for the diagnosis, favoring a better evolution of the treatment. The present study aimed to determine the prevalence of early diagnosis of rheumatoid arthritis, mean time of diagnosis and to determine possible associated factors in the municipality of Blumenau, Santa Catarina, Brazil. A cross-sectional study using the 1987 American College of Rheumatology diagnostic criteria to select patients attended at primary or secondary health care units in Blumenau, Santa Catarina, southern Brazil, in 2014. Diagnostic time was verified by self-report of the time elapsed between the onset of symptoms and the diagnosis made by a rheumatologist. To test the associations, the chi-square test, the Wald linear trend test and the Poisson regression analysis were used. The mean time of diagnosis was 28 months. The prevalence of diagnosis up to 3 and 12 months was 27.7% and 64.8%, respectively. Obesity was associated with time diagnosis in both periods. The 0-4 years category of the variable education was associated only with the period up to 12 months.

The mean time of diagnosis was similar to the national context. Among socioeconomic factors, lower education was associated with the diagnosis of late onset RA. The anthropometric variable presented a progressive increase in the prevalence due to the longer time to diagnosis.

Sjögren's syndrome (SS) is an autoimmune disease characterized by an inflammatory infiltrate of exocrine salivary and lachrymal glands. Diagnosis is complex, and minor salivary gland biopsy and subsequent focus score (FS) calculation appear of extreme importance in the diagnostic work-up of the disease. Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique, which is gaining an increasingly important role in intraoral imaging. This study aims at exploring the usefulness of UHFUS for obtaining valuable labial salivary gland samples to assess the histopathological features of SS patients. Patients with clinical suspect of SS and eligible for minor salivary gland biopsy were enrolled. UHFUS scan of the lower lip was performed. Glandular echostructure was classified according to Outcome Measures in Rheumatology (OMERACT) scoring system. The glands to be sampled were selected on the basis of UHFUS evaluation and biopsied. The areas of the samples were recorded and compared with those obtained without UHFUS guidance. The correlation between UHFUS grade and labial gland FS was also assessed. The areas of the samples obtained with UHFUS guidance were significantly higher (7.25 ± 3.98 mm

UHFUS seems a promising tool in SS diagnostic algorithm, being able to provide a valuable support to the biopsy procedure. Further studies are mandatory to confirm the role of UHFUS in SS.

To examine the association of disease activity and disability with rehabilitation utilization in African American adults with rheumatoid arthritis (RA). We analyzed cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR) I and CLEAR II registry. Disease activity was quantified with the Disease Activity Score in 28 joints using the C-reactive protein level. Disability was measured with the Health Assessment Questionnaire. Rehabilitation utilization was determined by self-reported recall of physical therapy or occupational therapy visits in the prior 6 months or ever. We examined the association of disease activity and disability with rehabilitation utilization using separate binary logistic regression models to estimate odds ratios and 95% confidence intervals and adjusted for potential confounders. We repeated the analyses with the sample stratified by disease duration (early RA and established RA). Of 1,067 participants, 14% reported utilizing rehabilitation in the prior 6 months, and 41% reported ever utilizing rehabilitation. Rehabilitation utilization in the prior 6 months was similar among those with early and established RA (12% versus 16%). A greater proportion of those with established RA reported any past rehabilitation utilization (28% versus 50%). Among those with established RA but not early RA, worse disability was associated with rehabilitation utilization in the prior 6 months. Disease activity was not associated with either outcome.

Among African American adults with RA, rehabilitation utilization in the 6 months prior to assessment was low and associated with disability but not disease activity. Factors driving rehabilitation utilization are unclear.

To clarify the mechanism by which interleukin?22 (IL?22) promotes the proliferation of fibroblast?like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). FLS were isolated from the synovial tissues of patients with RA and identified by immunohistochemistry for vimentin/CD68. The cells were subcultured and incubated with different concentrations of IL?22 for 24, 48, or 72 h, and their proliferation was examined using MTT assay. After treatment of the cells with IL?22 and AG490, alone or in combination, the expressions of the total and phosphorylated proteins of STAT3, ERK1/2 and P38 were detected with Western blotting. IL?22 significantly increased the proliferation of FLS in a dose?dependent manner (P<0.05). The total protein of STAT3 in the cells showed no significant changes with extended time of IL?22 treatment (P=0.68), but the expression of phosphorylated STAT3 protein increased significantly (P<0.001). The total and phosphorylated proteins of ERK1/2 and P38 underwent no significant changes after IL?22 treatment (P>0.05). A combined treatment with 50 ng/mL IL?22 and 100 µmol/L AG490 resulted in a significant decrease in the proliferation of FLS as compared with IL?22 treatment alone (P<0.01).

IL?22 can dose?dependently promote the proliferation of FLS from patients with RA by inducing phosphorylation of STAT3 protein but not through ERK1/2 or P38 signal pathway.

To compare the long-term clinical and radiological results of metal-on-polyethylene hybrid total hip replacement (THA) with metal-on-metal Birmingham hip resurfacing (BHR) in young, active patients. From the 1st consecutive 63 hips in young, active patients who underwent BHR by the senior author, 54 (51 patients) were matched to patients who had undergone THA with regard to age, gender, body mass index and preoperative levels of activity. Radiologically, all hips were assessed for migration and osteolysis, THAs for polyethylene wear and BHRs for a pedestal sign. Patient-reported outcomes, mortality and revision rates were compared. The mean follow-up of the patients with a hybrid THR was 19.9 years and for those with a BHR, 17.6 years. 13 patients with a hybrid THR and 5 with a BHR had died. 1 hybrid THR and 3 BHRs were lost to follow-up. The revision rate of the hybrid THRs was 14/54 and of the BHRs 6/54. Log rank comparison of Kaplan-Meier survival estimates demonstrated a significantly lower mortality in the BHR group (

After 18 years, patients with BHRs remained more active with a lower mortality rate but demonstrated no significant difference in revision rates. Both groups demonstrated progressive radiological changes at long-term follow-up.

Innate immune responses in the rheumatoid synovium contribute to inflammation and joint destruction in RA. Two IκB kinase (IKK)-related kinases, TNF receptor associated factor (TRAF) family member-associated nuclear factor κ-light-chain enhancer of activated B cells (NF-κB) activator (TANK)-binding kinase 1 (TBK1) and IKKε, potentially regulate synovitis by activating IFN response genes. These kinases induce the expression of inflammatory mediators such as C-X-C motif ligand 10 (CXCL10)/IFN-γ-induced protein 10 kDa (IP-10) in fibroblast-like synoviocytes (FLS). Since IP-10 is a promising therapeutic target in RA, we evaluated whether blocking TBK1 might be an effective way to modulate IP-10 expression. Wild-type (WT) and IKKε(-/-) FLS were transfected with TBK1 or control small interfering RNA (siRNA) and stimulated with polyinosinic acid : polycytidylic acid [poly(I:C)]. Gene expression was assayed using quantitative PCR. Cytokine production in culture supernatants was measured by Luminex multiplex analysis. IFN-regulatory factor (IRF3) dimerization was determined by native PAGE. IFN-β and IP-10 promoter activity was measured using luciferase reporter constructs. Initial studies showed that siRNA markedly decreased TBK1 expression in cultured FLS. Poly(I:C)-induced IRF7 gene expression was inhibited in the absence of TBK1, but not IKKε. IRF3 gene expression was similar to WT cells in TBK1 or IKKε-deficient FLS. IRF3 dimerization required both TBK1 and IKKε. Surprisingly, IRF3-mediated gene and protein expression of IFN-β and IP-10 was dependent on TBK1, not IKKε. Promoter constructs showed that TBK1 decreased IP-10 gene transcription and IP-10 mRNA stability was unaffected by TBK1 deficiency.

Based on the selective regulation of IP-10 in FLS, TBK1 appears to be the optimal IKK-related kinase to target in RA.

We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes. We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: self-reported quality of life [Short Form-12 (SF-12)], physical function [Physical Activity Scale for the Elderly (PASE)] and disability [Late-life Disability Index (LLDI)]. Linear regression analyses predicted 6-year outcomes based on WC quartile category (lowest = referent), adjusted for age, sex, race, education, knee pain, smoking status, a modified Charlson co-morbidity index and baseline scores, where available. We identified 2,182 subjects meeting our inclusion criteria and stratified the study cohort by quartiles of WC. Mean age ranged from 67.5-68.7 years, 60-71% were female and 80-86% were white. The highest WC quartile compared to 50-75th, 25-50th or lowest quartile, was associated with a greater number of medications (4.3, 4.0, 3.6 and 3.4 [p < 0.001]), lower gait speeds (1.23, 1.27, 1.32, and 1.34 m/s[p < 0.001]), higher rates of knee osteoarthritis (70.2, 62.2, 60.2, 48.6;p < 0.001), higher Charlson co-morbidity scores and greater knee pain (WOMAC scores) (all p < 0.001). At follow-up, adjusted SF-12 physical function subscale and PASE scores, were lowest in the highest WC quartile as compared to the 50-75%, 25-50%, and lowest quartiles [(SF-12 scores: 45.5, 46.7, 47.6, and 47.9), and (PASE scores: 109.6, 128.7, 126.6, and 131.0). The LLDI limitation subscale for disability demonstrated lower scores in the high WC quartile as opposed to the referent group.

Elevated WC is associated with lower quality of life, a decline in physical function, and a slightly higher risk of disability over time. Intervention studies are needed to prevent functional decline in this high-risk population.

This population-based study investigated the subsequent cardiovascular risk of patients with knee osteoarthritis underwent total knee arthroplasty in Taiwan. This was a population-based follow-up study of 22931 patients diagnosed with knee osteoarthritis between 2008 and 2011. Each patient was followed for 3 years or until death. Treatment was dichotomized into conservative treatment and TKA. The association between TKA and cardiovascular disease (CVD) events was analyzed using propensity score analysis and instrumental variable analysis and two-stage least-squares regression model. Patients with knee osteoarthritis who underwent TKA had a lower 3-year cumulative risk of stroke and acute myocardial infarction (AMI). After adjusting for measured risk and confounding factors, propensity score showed a 0.56 fold (adjusted OR = 0.56; 95% CI, 0.51-0.61; p<0.001) risk for CVD in those with TKA. Use of instrumental variable analysis for adjusting measured and unmeasured factors and two-stage least squares regression model revealed that the average treatment effect of TKA was statistically associated with a decreased 7% risk of CVD events (95% CI, 0.2%-13.6%).

Our study revealed that patients with knee osteoarthritis who underwent TKA had a lower risk of suffering from a future severe cardiovascular event. This benefit may be attributed to an improvement in physical activity, reduction of psychosocial stress, and/or a decreased use of NSAIDs as a result of having undergone TKA.

Unicompartmental knee replacement (UKR) is widely considered to be a pre-total knee replacement (TKR) particularly in the young. The implication of this is that it is sensible to do a UKR, even though it will be revised at some stage, as it will delay the need for a TKR. The chance of a UKR being revised during a patient's life time has not previously been calculated. The aim of this study was to estimate this lifetime revision risks for patients of different ages undergoing UKR. Calculations were based on data from a designer series of 1000 medial Oxford UKR with mean 10-year follow up. These UKR were implanted for the recommended indications using the recommended surgical technique. Parametric survival models were developed for patients of different ages based on observed data, and were extrapolated using a Markov model to estimate lifetime revision risk. The estimated lifetime revision risk reduced with increasing age at surgery. Lifetime revision risk at age 55 was 15% (95% CI 12-19), at 65 it was 11% (8-13), at 75 it was 7% (5-9), and at 85 it was 4% (3-5). III.

Provided UKR is used appropriately, the lifetime revision risk is markedly lower than expected. UKR should be considered to be a definitive knee replacement rather than a Pre-TKR even in the young. These lifetime estimates, alongside established benefits for UKR in speed of recovery, morbidity, mortality and function, can be discussed with appropriate patients when considering whether to implant a UKR or TKR.

Annexin A1 (AnxA1) is an endogenous anti-inflammatory protein and agonist of the formyl peptide receptor 2 (FPR2). However, the potential for therapeutic FPR ligands to modify immune-mediated disease has been little explored. We investigated the effects of a synthetic FPR agonist on joint disease in the K/BxN model of rheumatoid arthritis (RA) and RA fibroblast-like synoviocytes (FLS). Arthritis was induced by injection of K/BxN serum at day 0 and 2 in wild-type (WT) or AnxA1(-/-) mice and clinical and histopathological manifestations measured 8-11 days later. WT mice were given the FPR agonist compound 43 (Cpd43) (6 or 30 mg·kg(-1) i.p.) for 4 days. Effects of AnxA1 and Cpd43 on RANKL-induced osteoclastogenesis were assessed in RAW 264.7 cells and human RA FLS and macrophages. Treatment with Cpd43 before or after the onset of arthritis reduced clinical disease severity and attenuated synovial TNF-α and osteoclast-associated gene expression. Deletion of AnxA1 in mice exacerbated arthritis severity in the K/BxN model. In vitro, Cpd43 suppressed osteoclastogenesis and NFAT activity elicited by RANKL, and inhibited IL-6 secretion by mouse macrophages. In human RA joint-derived FLS and monocyte-derived macrophages, Cpd43 treatment inhibited IL-6 release, while blocking FPR2 or silencing AnxA1 increased this release.

The FPR agonist Cpd43 reduced osteoclastogenesis and inflammation in a mouse model of RA and exhibited anti-inflammatory effects in relevant human cells. These data suggest that FPR ligands may represent novel therapeutic agents capable of ameliorating inflammation and bone damage in RA.

The purpose of this prospective study was to assess changes in gait parameters after unilateral total hip arthroplasty and to correlate these objective changes with the results of subjective analyses. Thirty-eight patients (21 women, 17 men; mean age 61 years) with unilateral degenerative hip disease were evaluated in order to investigate preoperative and postoperative gait characteristics with the use of a gait evaluation mat (Gait Rite, USA). Each patient underwent at least two postoperative gait evaluations in the sixth and twelfth months, respectively. Gait evaluations were also made in a control group of 50 individuals without any neuromuscular and skeletal disease. Clinical evaluations were made using the Harris hip scoring system. All patients exhibited poor subjective evaluations preoperatively (Harris hip score <70). Compared to controls, patients had decreased step length and velocity, but increased stance, step, double support and swing times. Postoperatively, gait characteristics did not differ from those elicited prior to surgery in the first six months; however, patients attained near-normal velocity in the twelfth month. The recorded values for step length, step time, and double support time were similar to those of controls in both extremities.

This study showed that total hip arthroplasty considerably improved the gait characteristics of patients with degenerative arthritis, and that this improvement could be measured and recorded quantitatively with the use of a walking band.

Mobile-bearing total ankle arthroplasty designs have achieved good clinical results for the treatment of ankle osteoarthritis. However, no direct comparison of the outcomes of total ankle arthroplasty has been made between post-traumatic and primary osteoarthritis. The purpose of the present study was to compare the clinical and radiographic outcomes of total ankle arthroplasty in patients with post-traumatic and primary osteoarthritis. The HINTEGRA total ankle arthroplasty was carried out in 65 patients (67 ankles) with symptomatic ankle osteoarthritis. Group A included 37 patients (37 ankles) with post-traumatic osteoarthritis, whereas Group B included 28 patients (30 ankles) with primary osteoarthritis. Patients were assessed clinically and radiographically at a mean followup of 38 months. No significant differences were found between the two study groups in terms of American Orthopaedic Foot and Ankle Society ankle-hindfoot scales, range of motion, or radiographic values at final followup (p > 0.05). The incidence of complications (38% in Group A, 27% in Group B) and additional procedures (54% in Group A, 27% in Group B) was significantly higher in Group A (p = 0.014 for complications, p = 0.013 for additional procedures). One ankle was revised in Group A for a deep infection.

The clinical and radiographic outcomes of total ankle arthroplasty for post-traumatic and primary osteoarthritis were comparable, although the incidence of complications after total ankle arthroplasty was higher in the post-traumatic osteoarthritis group. More preceding or concomitant surgeries were required in order to make the post-traumatic cases suitable for total ankle arthroplasty.

Osteoarthritis (OA) of the knee is a secondary inflammatory, painful disease of the knee joint with increasing destruction of the articular cartilage. In the inflammatory process the formation of free radicals (reactive oxygen species, ROS) plays a major role in progression of disease and in the subsequent destruction of joint cartilage. The aim of this pilot study was to examine the antioxidative potency of the non-steroidal anti-inflammatory drug (NSAID) nimesulide on glutathione S-transferase (GST), an enzymatic free radical scavenger. In addition, the effects on matrix metalloproteinase MMP-3 and its antagonist tissue inhibitor of matrix-metalloproteinase 3 (TIMP-1) were determined. This was an open-pilot study on 20 patients (aged 41-71 years old) suffering from painful OA of the knee, treated for 3 weeks with nimesulide 100 mg b.i.d. Twenty-three healthy subjects (aged 23-57 years), not age matched, served as a comparison group. GST, MMP-3 and TIMP-1 were measured by enzyme-immunoassays. Clinical symptoms and joint function were measured using the WOMAC Index. During the 3-week treatment period with nimesulide 100 mg b.i.d., both scavenger GST and the TIMP-1/MMP-3 ratio significantly increased. This change was accompanied by significant clinical improvement in terms of pain reduction, stiffness and joint function. Two adverse events occurred possibly related to nimesulide treatment: one case of moderate eyelid swelling, and one case of moderate diarrhea with no abnormality in the endoscopic examination.

These results confirm the antioxidative properties of the study drug, indicating that nimesulide, beside its known anti-inflammatory properties, also shows an evident antioxidative activity that adds further supportive evidence to its key role in the treatment of OA patients (thanks to the absence of degenerative effects on cartilage).

To evaluate the long-term effectiveness and tolerability of adalimumab in the treatment of psoriatic arthritis (PsA). Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible to enroll in an open-label extension study and receive adalimumab 40 mg subcutaneously every other week for up to an additional 120 weeks. At the time of this analysis, available efficacy evaluations throughout 2 years of treatment (n = 245) included American College of Rheumatology (ACR) 20%, 50% and 70% improvement scores, measures of joint disease and skin disease, disability and quality of life; modified total Sharp scores (mTSS) were available for 2.75 years of treatment for patients who received adalimumab in the 24-week study. After 24 weeks of double-blind treatment, the mean change in mTSS was -0.2 for the adalimumab group (N = 144) and 1.0 for the placebo group (N = 152; p<0.001), and outcomes for all individual ACR component variables were significantly improved in adalimumab compared with placebo-treated patients. Compared with 24-week responses, inhibition of radiographic progression and improvements in joint disease were maintained in most patients during long-term, open-label adalimumab treatment. Also, improvements in skin disease were maintained, with >20% of patients achieving the strict criterion of psoriasis area and severity index 100. The nature and frequency of adverse events during long-term adalimumab treatment were consistent with the safety profile during short-term treatment. NCT00195689.

The clinical and radiographic efficacy of adalimumab demonstrated during short-term treatment was sustained during long-term treatment. Adalimumab has a favourable risk-benefit profile in patients with PsA.

To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part I) addresses additional conditions. The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. We estimated that among US adults, nearly 27 million have clinical osteoarthritis (up from the estimate of 21 million for 1995), 711,000 have polymyalgia rheumatica, 228,000 have giant cell arteritis, up to 3.0 million have had self-reported gout in the past year (up from the estimate of 2.1 million for 1995), 5.0 million have fibromyalgia, 4-10 million have carpal tunnel syndrome, 59 million have had low back pain in the past 3 months, and 30.1 million have had neck pain in the past 3 months.

Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions more studies generalizable to the US or addressing understudied populations are needed.

To assess the responsiveness of the Intermittent and Constant Osteoarthritis Pain (ICOAP) measure, Hip Disability and Osteoarthritis Outcome Score Physical Function Short Form (HOOS-PS), and the Knee Disability and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) in a pharmacological trial. Data were obtained from a randomized double-blind trial comparing naproxcinod with naproxen and ibuprofen in individuals with hip or knee osteoarthritis (OA) (NCT00662896). Participants completed the ICOAP, HOOS-PS/KOOS-PS, and Western Ontario and McMaster Universities OA Index (WOMAC) Likert version 3.0 before and 13 weeks after treatment. In hip and knee OA participants separately, the mean pre-post treatment change in scores, effect size (ES) and standardized response mean (SRM) were determined for each measure by treatment arm, and for all arms combined. Of 349 trial participants, 156 with knee OA and 48 with hip OA completed all measures at both time-points and were included (mean age 61 years; two-thirds female). Although there was both within treatment and between treatment variability in response, among knee OA participants, ICOAP intermittent, constant, and total scores and KOOS-PS scores showed, on average, moderate effects, with ESs ranging from 0.46 to 0.54 and SRMs from 0.49 to 0.56. Similar changes were seen for the WOMAC pain and function subscales (0.58 and 0.58, respectively). In those with hip OA, no significant improvement in symptoms was seen for any measure.

Responsiveness to pharmaceutical intervention was demonstrated for ICOAP and KOOS-PS among participants with knee OA. Absence of treatment response precluded assessment of responsiveness in hip OA.

To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a decrease of hazard for new relapse of 93%.

A high number of patients with inactive uveitis relapse quickly after the withdrawal of MTX. Our results suggest that a longer period of inactivity prior to withdrawal and a longer treatment period with MTX reduce the chance of relapse after withdrawal.

Spironolactone (SPL) is a reversible mineralocorticoid receptor (MR) and androgen receptor (AR) antagonist which attracts pharmacotherapeutic interest not only because of its beneficial effects in heart failure but also because of the pathogenetic roles of MR and AR activities in neuropsychiatric diseases. Recently, beneficial and rapid-onset effects of SPL have been documented in a case series of women with fibromyalgia syndrome (FMS). To reaffirm this observation, we performed a double-blind placebo-controlled randomized clinical trial (RCT). A total of 69 patients were screened, 56 patients were eligible and randomized to SPL or placebo (each n = 28). Forty-three patients completed the clinical trial to the last visit (n = 21 and n = 22). After a run-in phase of 50 and 100 mg/day, 200 mg/day SPL or placebo were applied between days 7 and 28. Primary outcome was the change in the FIQ-G score (Fibromyalgia Impact Questionnaire, German version). Secondary outcome parameters were the changes in pain (numeric rating scale, NRS), mood (ADS), quality of life (SF-36) and change in FIQ scores 14 days after the end of the medication. SPL of 200 mg/day did not change significantly either the primary or the secondary end points. SPL evoked a transient rise in serum potassium and a transient fall in GFR maximal after 2 weeks, but without clinical relevance. The mineralocorticoid receptor and androgen receptor antagonist spironolactone is repeatedly tested for its therapeutic effectivity against neuropsychiatric disorders. The present RCT demonstrated that 200 mg spironolactone does not change the symptoms of the fibromyalgia syndrome (FMS) in adult women. Between 2 and 4 weeks, spironolactone evokes a transient decrease in GFR and increase in serum potassium. Spironolactone cannot be recommended for the treatment of FMS.

SPL at 200 mg/day does not improve symptoms in women with FMS, but was considered not to cause harm.

To investigate the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors, compared to a standard RA population. Patients were recruited from a regional register, which includes over 90% of patients with RA started on TNF blockers in 1999 or later, and a local community based cohort of RA patients, established in 1997. Of a total of 983 patients in the combined cohort, 531 received treatment with etanercept or infliximab during the study period. The total cohort (n = 983) was linked with national registers for inpatient care and cause of death through December 31, 2001. CVD was defined as the first inpatient care or death from CVD without inpatient care for CVD prior to study entry. First CVD events in those treated versus not treated with TNF blockers were estimated, using age and sex adjusted incidence density computations with treatment and disease severity markers as time-dependent covariates. In the anti-TNF-treated patients, the age-sex adjusted incidence rate of first CVD event was 14.0/1000 person-years at risk (95% CI 5.7-22.4), compared with 35.4/1000 person-years (95% CI 16.5-54.4) in those not treated. Controlling for disability, the age-sex adjusted rate ratio was 0.46 (95% CI 0.25-0.85, p = 0.013) in anti-TNF-treated versus not treated.

These findings suggest that the risk of developing CVD is lower in patients with RA treated with TNF blockers. This is compatible with the hypothesis that inflammation contributes to the development of cardiovascular events.

The present study was undertaken to conduct a phase IV, open-label, prospective study to characterize the long-term safety of rituximab in a 4-year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the US. Patients initiating treatment with rituximab were evaluated every 6 months for up to 4 years. Outcomes included the incidence of serious adverse events (SAEs), infusion-related reactions (IRRs), and SAEs of specific interest, including serious infections, serious cardiac events, serious vascular events, and malignancies. Overall, 97 patients (72 with GPA and 25 with MPA) received rituximab through a median of 8 (range 1-28) infusions and were followed up for a median of 3.94 years (range 0.05-4.32 years). The estimated incidence rates (95% confidence interval [95% CI]) of serious infections, serious cardiac events, and serious vascular events were 7.11 (4.55-10.58), 5.03 (2.93-8.06), and 2.37 (1.02-4.67) per 100 patient-years (PYs), respectively. No IRRs or SAEs occurred within 24 hours of an infusion of rituximab. None of the 9 deaths reported (crude mortality rate 2.67 [95% CI 1.22-5.06] per 100 PYs) were considered to be related to use of rituximab.

The safety profile of long-term treatment with rituximab in patients with GPA or MPA was consistent with that of rituximab administered for shorter durations and with rituximab's known safety profile in other autoimmune diseases for which it has received regulatory approval. These findings provide clinicians with long-term, practice-level safety data for rituximab in the treatment of GPA or MPA.

Syndecan-4 (sdc4) is a cell-anchored proteoglycan that consists of a transmembrane core protein and glucosaminoglycan (GAG) side chains. Binding of soluble factors to the GAG chains of sdc4 may result in the dimerisation of sdc4 and the initiation of downstream signalling cascades. However, the question of how sdc4 dimerisation and signalling affects the response of cells to inflammatory stimuli is unknown. Sdc4 immunostaining was performed on rheumatoid arthritis (RA) tissue sections. Interleukin (IL)-1 induced extracellular signal-regulated kinases (ERK) phosphorylation and matrix metalloproteinase-3 production was investigated. Il-1 binding to sdc4 was investigated using immunoprecipitation. IL-1 receptor (IL1R1) staining on wild-type, sdc4 and IL1R1 knockout fibroblasts was performed in fluorescence-activated cell sorting analyses. A blocking sdc4 antibody was used to investigate sdc4 dimerisation, IL1R1 expression and the histological paw destruction in the human tumour necrosis factor-alpha transgenic mouse. We show that in fibroblasts, the loss of sdc4 or the antibody-mediated inhibition of sdc4 dimerisation reduces the cell surface expression of the IL-1R and regulates the sensitivity of fibroblasts to IL-1. We demonstrate that IL-1 directly binds to sdc4 and in an IL-1R-independent manner leads to its dimerisation. IL-1-induced dimerisation of sdc4 regulates caveolin vesicle-mediated trafficking of the IL1R1, which in turn determines the responsiveness to IL-1. Administration of antibodies (Ab) against the dimerisation domain of sdc4, thus, strongly reduces the expression IL1R1 on arthritic fibroblasts both in vitro and an animal model of human RA.

Collectively, our data suggest that Ab that specifically inhibit sdc4 dimerisation may support anti-IL-1 strategies in diseases such as inflammatory arthritis.

Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers. We have retrospectively examined the effect of therapy with the prostaglandin E1 analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy. All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2-10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5-16.8) g/dL (95% confidence intervals 10.06, 11.82); P = 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5-10.6) g/dL to 8.1 (5.6-14.7) g/dL (P = N.S.).

Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.