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To assess agreement and application of Treat to Target (T2T) recommendations in Canadian practice. A survey of Canadian rheumatologists was conducted on the recommendations of T2T, an international initiative toward reaching specific therapeutic goals in rheumatoid arthritis. Agreement with each recommendation was measured on a 10-point Likert scale (1 = fully disagree, 10 = fully agree). A 4-point Likert scale (never, not very often, very often, always) assessed application of each recommendation in current practice. Responders who answered "never" or "not very often" were asked whether they were willing to change their practice according to the particular recommendation. Seventy-eight rheumatologists responded (24% of the 330 who were contacted). The average agreement scores ranged from 6.92 for recommendation #5 (the frequency of measures of disease activity) to 9.10 for recommendation #10 (the patient needs to be involved in the decision-making process). A majority of participants indicated that they apply the T2T recommendations in their practice. Recommendations dealing with frequency of visits and the use of composite measures received the highest number of "never" or "not very often" responses. Busy practices and lack of confidence in composite outcome measures were the main reasons for objections to certain components of the recommendations.

Although a majority of Canadian rheumatologists agreed with and supported the T2T recommendations, there was resistance toward specific aspects of these recommendations. Efforts are needed to better understand the reasons behind identified disagreements. Action plans to encourage the application of T2T recommendations in Canada are in development.

Type II collagen is the dominating collagen in articular cartilage. It is essential for the structural integrity and the biomechanical properties of cartilage. Using immunohistology and in situ hybridization we systematically analyzed the protein and mRNA-expression of type II collagen in cartilage/bone sections without any signs of osteoarthritis and osteoarthritic samples with various degrees of osteoarthritis. In normal articular cartilage without any histologic signs of osteoarthritis type II collagen was distributed homogeneously. An expression of the type II collagen-mRNA was not detectable in any of these samples. In cartilage sections with a roughening of the cartilage surface and a superficial loss of the safranin O staining as early histologic signs of osteoarthritis the immunohistologic staining for type II collagen was reduced in the deep cartilage zone. An expression of the type II collagen-mRNA was found in 19 of 35 preparations. This expression, however, was restricted to the middle and deep zone of cartilage. A good and reproducible correlation of the specific gene and protein expression was found in samples with more severe osteoarthritic lesions.

Detailed information on metabolic changes and the activation of chondrocytes in osteoarthritic cartilage are important to characterize certain stages of osteoarthritis and thus identify new prognostic factors. Increasing knowledge of the factors regulating the matrix synthesis and degradation in cartilage will provide the basis for new disease modifying therapies in osteoarthritis.

To examine whether components of metabolic syndrome (MetS), either singly or additively, were associated with the incidence of severe knee and hip OA, and whether these associations were independent of obesity assessed by body mass index (BMI). Twenty thousand, four hundred and thirty participants who had blood lipids, anthropometric and blood pressure measurements during 2003-2007 were selected from the Melbourne Collaborative Cohort Study. MetS was defined as central obesity assessed by waist circumference and any two of raised triglyceride level, reduced HDL cholesterol level, hypertension or impaired fasting glycaemia. The incidence of total knee and hip replacement was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Six hundred and sixty participants had knee OA and 562 had hip OA. After adjustment for age, gender, country of birth, education, physical activity and BMI, central obesity [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.25-2.01] and hypertension (1.24, 1.05-1.48) were associated with increased risk of knee OA. The accumulation of MetS components was associated with knee OA risk, independent of BMI: one component, 2.12 (1.15-3.91); two components, 2.92 (1.60-5.33) and three or more components, 3.09 (1.68-5.69). No statistically significant associations were observed for hip OA.

Cumulative number of MetS components and central obesity and hypertension were associated with increased risk of severe knee OA, independent of BMI. No associations were observed with severe hip OA. These findings suggest that the pathogenesis of knee and hip OA differ and that targeting the management of MetS may reduce the risk of knee OA.

We report a 58-year-old woman with no history of gout who subsequently developed gouty tophi around retained suture material identified 12 ½ years after repair of a ruptured Achilles tendon. The patient had intermittently developed an apparent postsurgical infection at and around the incision site. She had normal uric acid levels.

The diagnosis of gout was not confirmed until surgical exploration was performed 12 ½ years after the initial surgery. Awareness of such a rare incidence of surgical site gout would help clinicians in their management decisions.

Mechanical trauma of articular cartilage results in cell loss and cytokine-driven inflammatory response. Subsequent accumulation of reactive oxygen (ROS) and nitrogen (RNS) species enhances the enzymatic degradation of the extracellular matrix (ECM). This study aims on the therapeutic potential of N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma-model, focusing on cell- and chondroprotective features. Human full-thickness cartilage explants were subjected to a defined impact trauma (0.59 J) and treated with NAC. Efficiency of NAC administration was evaluated by following outcome parameters: cell viability, apoptosis rate, anabolic/catabolic gene expression, secretion and activity of matrix metalloproteinases (MMPs) and proteoglycan (PG) release. Continuous NAC administration increased cell viability and reduced the apoptosis rate after trauma. It also suppressed trauma-induced gene expression of ECM-destructive enzymes, such as ADAMTS-4, MMP-1, -2, -3 and -13 in a dosage- and time-depending manner. Subsequent suppression of MMP-2 and MMP-13 secretion reflected these findings on protein level. Moreover, NAC inhibited proteolytic activity of MMPs and reduced PG release.

In the context of this ex vivo study, we showed not only remarkable cell- and chondroprotective features, but also revealed new encouraging findings concerning the therapeutically effective concentration and treatment-time regimen of NAC. Its defense against chondrocyte apoptosis and catabolic enzyme secretion recommends NAC as a multifunctional add-on reagent for pharmaceutical intervention after cartilage injury. Taken together, our data increase the knowledge on the therapeutic potential of NAC after cartilage trauma and presents a basis for future in vivo studies.

Both acetabular undercoverage (hip dysplasia) and overcoverage (pincer-type femoroacetabular impingement) can result in hip osteoarthritis. In contrast to undercoverage, there is a lack of information on radiographic reference values for excessive acetabular coverage. (1) How do common radiographic hip parameters differ in hips with a deficient or an excessive acetabulum in relation to a control group; and (2) what are the reference values determined from these data for acetabular under- and overcoverage? We retrospectively compared 11 radiographic parameters describing the radiographic acetabular anatomy among hip dysplasia (26 hips undergoing periacetabular osteotomy), control hips (21 hips, requiring no rim trimming during surgical hip dislocation), hips with overcoverage (14 hips, requiring rim trimming during surgical hip dislocation), and hips with severe overcoverage (25 hips, defined as having acetabular protrusio). The hips were selected from a patient cohort of a total of 593 hips. Radiographic parameters were assessed with computerized methods on anteroposterior pelvic radiographs and corrected for neutral pelvic orientation with the help of a true lateral radiograph. All parameters except the crossover sign differed among the four study groups. From dysplasia through control and overcoverage, the lateral center-edge angle, acetabular arc, and anteroposterior/craniocaudal coverage increased. In contrast, the medial center-edge angle, extrusion/acetabular index, Sharp angle, and prevalence of the posterior wall sign decreased. The following reference values were found: lateral center-edge angle 23° to 33°, medial center-edge angle 35° to 44°, acetabular arc 61° to 65°, extrusion index 17% to 27%, acetabular index 3° to 13°, Sharp angle 38° to 42°, negative crossover sign, positive posterior wall sign, anterior femoral head coverage 15% to 26%, posterior femoral head coverage 36% to 47%, and craniocaudal coverage 70% to 83%.

These acetabular reference values define excessive and deficient coverage. They may be used for radiographic evaluation of symptomatic hips, may offer possible predictors for surgical outcomes, and serve to guide clinical decision-making.

Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs). In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence. The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n = 152) or stress reduction video (n = 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m Registered at ClinicalTrials.gov NCT02741700.

A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout.

A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs. Some variables, including the patients' preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or UTK choice is guided by skin or articular disease severity, enthesitis, and dactylitis, whereas ETN should be preferred if metabolic syndrome or high CV risk complicate PsA.

Taking in account of multiple choice driving variables, first-line biologic therapy may be optimized in patients with RA, SpA, and PsA.

To look for correlations among clinical, radiographic, and sonographic scores for enthesitis in patients with ankylosing spondylitis (AS). Prospective study of 60 patients meeting modified New York criteria for AS. The clinical evaluation relied on the BASDAI, BASFI, and ASQoL and on a visual analog scale (VAS) for entheseal pain, as well as on two specific enthesitis indices, the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Radiographs and ultrasound scans were taken of five entheses on both sides (patellar insertion of the quadriceps tendon, proximal and distal insertions of the patellar tendon, and calcaneal insertions of the Achilles tendon and superficial plantar fascia). Ultrasound scans were obtained using a Philips HD 11™ machine with a high-frequency linear probe. We studied 48 men and 12 women with a mean age of 36±11 years. The radiographic score correlated with the VAS pain score, BASDAI, and BASFI. The sonographic score for acute enthesitis correlated only with the MASES, and the sonographic score for chronic enthesitis correlated with none of the clinical scores. The Doppler score correlated with the VAS pain score, BASDAI, BASFI, and ASQoL. The overall sonographic score correlated with the MASES and SPARCC.

Good correlations were found between the clinical and sonographic scores for enthesitis. The radiographic score seemed correlated with the general AS parameters rather than with the clinical scores. Larger studies are needed to better define the role for radiographs and sonography of the entheses in the diagnosis of AS and follow-up of treated AS patients.

IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. To examine the effect of IL-4 on IL-17 production and its effect in Collagen-Induced Arthritis (CIA) mice. In this study, a chicken collagen-II-induced experimental arthritis (CIA) model was used in DBA/1 mice to investigate the relationship between IL-4 and IL-17 as well as other inflammatory factors. On the 38th day after the mice were induced with CIA, the expression of IL-17 and IL-4 as well as IFN-γ and IL-13 in sera of the mice was measured by QRT-PCR and ELISA. The result of QRT-PCR analysis of IL-17 and IL-4 mRNA levels in the spleen showed that IL-17 is increased significantly at the onset of CIA in the spleen (p<0.01). Meanwhile, IL-17 is generally reduced at the peak of CIA but IL-4 is increased significantly at this peak in the spleen when the weight of the animal was taken into consideration (p<0.05).

IL-4 can be involved in the production of IL-17 at especially the peak of CIA. These results imply that the inhibition of IL-17 may decrease the expression of IL-1β and IL-6 production which will result in the aggravation of arthritis.

To investigate the trends in the activity of rheumatoid arthritis (RA) over the past 8 years and evaluate the value of treat-to target (T2T) strategy in daily practice. All the medical records of RA patients from 2009 to 2016 were retrospectively reviewed. Disease activity scores at obtained visits were measured by DAS28-CRP, DAS28-ESR, SDAI and CDAI. To display trends over years, both mean and time-adjusted methods were applied in calculation of annual disease activity and remission rate. Disease activity and remission rate were also compared before and after the year 2011 when application of T2T strategy was initiated in our centre. Furthermore, a sub-cohort study including T2T and non-T2T period groups was conducted with outcome of cumulative percentage of remission and time to achieve first remission during the first year follow-up. In total, 1,001 patients with 6,944 clinical visits were included. Over an eight-year period, significant improvements were witnessed in disease activity and remission rate, measured by all four indices (p<0.0001). More patients achieved lower disease activity and higher remission rates after T2T adherence in 2011 compared to those in the years 2009 and 2010 (p<0.0001). Moreover, sub-cohort study revealed that more patients (49.3-73.2% vs. 19.1-34.5%, OR=2.4-3.0) achieved remission with a shorter median time compared with the non-T2T period group (p<0.0001), particularly in DAS28-CRP (21 vs. >52 weeks), DAS28-ESR (37 vs. >52 weeks).

Over the past 8 years, the RA activity has substantially decreased and T2T strategy was directly attributable to the favourable changes in clinical practice.

Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States, affecting over 1 million people. As part of the disease process, PD can cause poor bone quality and other musculoskeletal problems that can affect a patient's quality of life. With advances in treatment, PD patients can be more active and may be candidates for total hip arthroplasty (THA). However, there is a paucity of literature on the outcomes of THA in PD patients. Therefore, the purpose of this study was to evaluate the perioperative outcomes of PD patients who underwent THA. Specifically, we assessed: (1) perioperative surgical and medical complications; (2) lengths of stay (LOSs); and (3) total hospital charges. Using the Nationwide Inpatient Sample, patients who had PD and underwent THA between 2002 and 2013 were identified. With the use of propensity scores, PD patients were matched in a 1:3 ratio to patients without PD by the year of surgery, age, gender, race, Charlson/Deyo score, and insurance type. This yielded a total of 10,519 PD and 31,679 non-PD THA patients. Regression analyses were used to compare the risk of perioperative complications (any, surgical, medical), the percent differences in mean LOS, and the percent differences in total hospital charges. Compared with the matched cohort, PD patients had a 52% higher risk for any complication (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.37-1.69), a 30% higher risk for any surgical complication (OR = 1.30; 95% CI: 0.88-1.91), and a 54% higher risk for any medical complication (OR = 1.54; 95% CI, 1.38-1.71). Specifically, PD patients were more likely to have postoperative delirium (OR = 2.61; 95% CI: 1.77-3.85), altered mental status (OR = 3.01; 95% CI: 1.35-6.71), urinary tract infection (OR = 1.34; 95% CI: 1.09-1.76), and blood transfusion (OR = 1.62; 95% CI: 1.44-1.82). Also, PD patients had a mean LOS that was 8.57% longer (P < .0001), and mean total hospital charges that were 3.85% higher (P < .0001).

Orthopedic surgeons and neurologists should be involved in the preoperative counseling of PD patients regarding their potential increased risks associated with THA, which could help optimize their preoperative care. Furthermore, the risk of complications and higher costs could potentially lead to the development of different reimbursement methods in this population of patients.

We describe a new therapeutic modality for sacroiliac joint syndrome that represents an alternative to other treatment modalities. We report on four cases of sacroiliac joint syndrome with severe pain. Three patients had undergone operative treatment of the lumbar spine and one patient suffered from severe osteoarthritis of the spine. All patients were diagnosed with sacroiliac joint syndrome by means of patient history, physical examination, and intra-articular local anesthetic injection preceded by sacroiliac arthrogram. All patients received three injections of Hylan GF 20 in the sacroiliac joints 2 weeks apart. Twelve to 16 weeks after the injections, the pain was reported to be 40-67% better when measured on the visual analog scale. The duration of the beneficial effect of Hylan on arthralgia and joint function was undetermined.

Viscosupplementation of the sacroiliac joint induced a significant degree of analgesia in all four patients. This treatment modality could represent an option in the management of sacroiliac joint pain and dysfunction.

To determine if ultrasonography (US) and power Doppler (PD) may be useful in identifying polymyalgia rheumatica (PMR) patients with relapsing disease. For a mean of 41 months, 57 consecutive untreated patients with PMR were prospectively assessed for relapses/recurrences. This cohort represented all the patients diagnosed over a 18-month period in one Italian secondary referral centre. Clinical signs and symptoms as well as ESR and CRP were evaluated. US examination of the shoulders was performed in all 57 patients at diagnosis and after the onset of prednisone treatment (mean 24 +/- 3 weeks). Power Doppler ultrasonography (PDUS) was performed in 24 patients. Shoulder sonograms were obtained according to standardized techniques. Prednisone therapy significantly reduced the frequency and the degree of subacromial/subdeltoid bursitis, long head biceps tenosynovitis and glenohumeral synovitis. At diagnosis, a positive PD signal was observed more frequently in the subacromial/subdeltoid bursae (33%). Prednisone therapy significantly reduced the frequency of patients with positive PD signal. Of the 44 patients in remission or with low disease activity at the time of the second US, 26 (59%) still had evidence of persistent inflammatory lesions. There was no association between the persistence of inflammation at US and relapses/recurrences; in contrast, a positive PD signal at diagnosis was significantly associated with the occurrence of relapses/recurrences at follow-up.

Subclinical inflammation detected by US persists in most PMR patients despite glucocorticoid treatment. PDUS may be useful to detect at diagnosis the patients with most active inflammation who have a higher risk of relapses/recurrences.

The aetiology of ankylosing spondylitis (AS) remains unclear. Inflammation progresses to fibrosis and calcification of the spine and sacroiliac joints in AS development. Fibrosis results from excessive accumulations of the extracellular matrix (ECM). ECM turnover depends on the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). To evaluate the effects of the MMP-3 -1171 and TIMP-1 372 T>C polymorphisms on the modified risk of AS. Genotypes of 241 patients with AS and 241 controls were identified by PCR. Disease activity and functional status were assessed by the Bath Ankylosing Spondylitis Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Global (BAS-G) Score. MMP-3 6A/6A carriers had a 2.41-fold (95% confidence interval (CI) 1.55 to 3.74) increased risk of AS compared with 6A/5A and 5A/5A carriers. TIMP-1 C alleles had a greater risk of AS, but this was not significant (odds ratio (OR) = 1.28, 95% CI 0.92 to 1.77). Pairwise analysis of the MMP-3/TIMP-1 alleles showed that 6A/C (OR = 3.23, 95% CI 1.50 to 6.95) and 6A/T (OR = 2.55, 95% CI 1.17 to 5.54) had a significantly greater risk of AS than the 5A/T alleles. After adjustment for the effects of age, gender and disease duration, the MMP-3/TIMP-1 5A/T alleles had the lowest BASDAI (p = 0.02), BASFI (p = 0.05) and BAS-G (p = 0.02) among all MMP-3/TIMP-1 alleles.

The findings highlight the importance of the MMP-3 and TIMP-1 genes as crucial elements in AS development.

Leishmanial lipid is a strong immunosuppressor of host cells. Inhibition of the inflammatory responses of synovial cells through induction of apoptosis is one of the main targets of therapeutic intervention in rheumatoid arthritis (RA). This study was undertaken to examine the antiinflammatory and apoptosis-inducing effects of leishmanial lipid on adherent synovial fluid mononuclear cells (SFMCs) in patients with RA. Lipid was extracted from a Leishmania donovani promastigote (MHO/IN/1978/UR6) by the Bligh and Dyer method. Nitric oxide (NO) was measured using the Griess reaction, and enzyme-linked immunosorbent assays for cytokines, NF-kappaB, and cytochrome c were performed. Levels of cytokines, inducible nitric oxide synthase, caspases, Bcl-2, Bax, t-Bid, and cytochrome c in the cell lysate and of NF-kappaB p65 in the nucleus were determined by Western blotting. Microscopic analysis, nuclear staining, DNA fragmentation assay, fluorescence-activated cell sorting, colorimetric assay for caspases, and fluorescent probe for measurement of mitochondrial membrane potential were used to study the leishmanial lipid-induced apoptotic pathway in SFMCs. Leishmanial lipid inhibited the release of tumor necrosis factor alpha, interleukin-1beta, and NO in the culture, decreased their cytosolic protein levels, and decreased NF-kappaB p65 levels in SFMCs, in a dose-dependent manner. It had the reverse effect on interleukin-10 levels. Leishmanial lipid-induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the down-regulation of Bcl-2.

These results suggest that leishmanial lipid has strong antiinflammatory and apoptosis-inducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.

Both nocturnal hypertension (HT) and systemic inflammation underlying rheumatoid arthritis (RA) have been shown to be independent predictors of cardiovascular disease (CVD), although little is known on the relationship between nocturnal blood pressure (BP) and disease activity in RA patients. We performed 24-hour ambulatory BP monitoring (ABPM) in 71 RA patients to examine the relationship of nocturnal fall in BP and RA disease activity based on a disease activity score of 28 joint counts with C-reactive protein (CRP, 28-joint disease activity score (DAS28)-CRP). Among them, 25 RA patients whose consent obtained were reexamined by ABPM to assess the improvement of nocturnal fall in BP after RA therapeutic intervention. The mean DAS28-CRP level was 4.8±1.6 in 71 RA patients. The mean nocturnal fall in BP was 5.6±8.9%. DAS28-CRP was associated significantly and independently in a negative manner with the nocturnal fall in BP (β = -0.388, P = 0.004). In 25 RA patients, DAS28-CRP improved from 5.4±1.1 to 3.5±0.8 (P < 0.0001) and the nocturnal fall in BP increased significantly from 4.5±9.2% to 10.6±5.8% (P = 0.002) with the significant decrease of nighttime systolic BP (SBP) from 121.2±22.5mm Hg to 112.5±18.8mm Hg (P = 0.02) in spite of no change in daytime BP after 4 weeks of RA treatment.

The present study observed that higher RA activity was associated with lower nocturnal fall in BP, but not daytime BP, in RA patients.

Patients with medial unicompartmental osteoarthritic disease of the knee requiring arthroplasty can be treated with either Total or Unicompartmental Knee Replacement (TKR or UKR). Currently, the decision to choose one operation over another is not well defined and may depend on the profile of the surgeon consulted. We tested the hypothesis that different surgeons will select different treatment for identical patients requiring knee replacement. Four different surgeons, representing four different levels of expertise, made a forced choice decision of whether they would perform TKR or UKR based on radiographs alone and subsequent additional clinical information including gender and age, in 140 patients. Individual surgeon repeatability was tested by repeat assessment 3 months later. The knee surgeon from the UKR design centre would have performed a UKR in up to 88% of the patients. The remaining surgeons would have performed UKR in 29-48% of patients; a variation in decision making of up to 59%. Additional clinical information had little effect on decision making with surgeons maintaining their radiographic based choice in 80 to 87% of cases. The repeatability study showed high within surgeon consistency for treatment choice.

Surgeons, given identical information, do not concur on treatment for patients with the same pathology. The decision making process appears heavily influenced by radiographic findings but individual surgeons are consistent with their own treatment choice. The study shows that consensus treatment for medial osteoarthritis of the knee remains in question.

T cells from patients with systemic lupus erythematosus (SLE) display antigen receptor-mediated signaling aberrations associated with defective T cell receptor (TCR) zeta chain protein and messenger RNA (mRNA) expression. This study was undertaken to explore the possibility that coding-region mutations/polymorphisms of the TCR zeta chain could account for its decreased expression and altered signaling in SLE T cells. TCR zeta chain mRNA from 48 SLE patients, 18 disease controls, and 21 healthy volunteers was reverse transcribed, amplified by polymerase chain reaction, and cloned, and complementary DNA (cDNA) was sequenced. DNA sequences from multiple clones were analyzed for silent single-nucleotide polymorphisms, mutations, and splice variations, to promote the identification of heterozygosity. DNA sequence analysis revealed several widely distributed missense mutations and silent polymorphisms in the coding region of the TCR zeta chain, which were more frequent in SLE patients than in patients with other rheumatic diseases or healthy controls (P < 0.0001). Several of the missense mutations were located in the 3 immunoreceptor tyrosine activation motifs or the GTP binding domain, and this could lead to functional alterations in the TCR zeta chain. A splice variant of the TCR zeta chain with a codon CAG (glutamine) insertion between exons IV and V was found in half of the SLE and control samples. Two larger spliced isoforms of the TCR zeta chain, with an insertion of 145 bases and 93 bases between exons I and II, were found only in SLE T cells. We also identified various alternatively spliced forms of the TCR zeta chain resulting from the deletion of individual exons II, VI, or VII, or a combined deletion of exons V and VI; VI and VII; II, III, and IV; or V, VI, and VII in SLE T cells. The frequency of the deletion splice variants was significantly higher in SLE than in control samples (P = 0.004). These variations were observed in cDNA and may not reflect the status of the genomic DNA.

These findings demonstrate that heterogeneous mutations/polymorphisms and alternative splicing of TCR zeta chain cDNA are more frequent in SLE T cells than in T cells from non-SLE subjects and may underlie the molecular basis of known T cell signaling abnormalities in this disease.

Total wrist arthroplasty (TWA) has been described as traditionally being performed with fixation in the radius and carpus with cement. The TWA implant used in our series has been associated with promising results in studies with up to 6 years followup; however, studies evaluating survivorship, pain, and function with this implant are limited. QUESTION/PURPOSE: (1) To report ROM and pain scores after wrist reconstruction with cementless fourth-generation TWA at a mean followup of 9 years (range, 4.8-14.7 years). (2) To report complications of a cementless fourth-generation TWA and the cumulative probability of not undergoing a revision at a mean followup of 9 years. This is a retrospective case series of 69 patients who were treated for pancarpal wrist arthritis between 2002 and 2014. Of those, 31 had inflammatory arthritis (rheumatoid arthritis [n = 29], juvenile rheumatoid arthritis [n = 1], and psoriatic arthritis [n = 1]); all of these patients received TWA with the cementless implant studied in this investigation. Another 38 patients had osteoarthritis or posttraumatic arthritis; in this subgroup, 28 patients were 65 years or younger, and all underwent wrist fusion (none were offered TWA). Ten patients with osteoarthritis were older than 65 years and all were offered TWA; of those, eight underwent TWA, and two declined the procedure and instead preferred and underwent total wrist arthrodesis. The mean age of the 39 patients who had TWA was 56 ± 8.9 years (range, 31-78 years) at the time of surgery; 36 were women and three were men. The patients who underwent TWA were seen at a minimum of 4 years (mean, 9 years; range, 4-15 years), and all had been examined in 2016 as part of this study except for one patient who died 9 years after surgery. The dominant wrist was involved in 60% (25) of the patients. All patients were immobilized for 4 weeks postoperatively and then underwent hand therapy for 4 to 6 weeks. Pain and ROM were gathered before surgery as part of clinical care, and were measured again at latest followup; at latest followup, radiographs were analyzed (by the senior author) for evidence of loosening, defined as any implant migration compared with any previous radiograph with evidence of periimplant osteolysis and bone resorption. Subjective pain score was assessed by a verbal pain scale (0-10) and ROM was measured with a goniometer. Complications were determined by chart review and final examination. Kaplan Meier survival analysis was performed to estimate the cumulative probability of not undergoing a revision. The mean preoperative active ROM was 34 Level IV, therapeutic study.

Cementless fourth-generation TWA improves pain while generally preserving the preoperative arc of motion. The cumulative probability of remaining free from revision at 14.7 years after the index procedure is 77.7% (95% CI, 62.0%-91.4%). Future studies should compare alternative approaches for patients with endstage wrist arthritis; such evaluations-which might compare TWA implants, or TWAs with arthrodesis-will almost certainly need to be multicenter, as the problem is relatively uncommon.

What are people's experiences and perceived impact of physiotherapist-led exercise interventions for knee pain attributable to osteoarthritis? What barriers and facilitators to change in exercise and physical activity behaviour exist over time? A longitudinal qualitative study was undertaken; it involved face-to-face, semi-structured and longitudinal interviews. Interviews were undertaken with older adults with knee pain and who had been randomised to one of three physiotherapist-led exercise intervention arms in the Benefits of Effective Exercise for knee Pain (BEEP) trial. Thirty participants were enrolled in this qualitative study, with interviews scheduled at the end of the trial intervention period and 12 months later. A 'layered approach' to thematic analysis was used, including open coding (using constant comparison), deductive coding and within-case and cross-case longitudinal analysis of change. Different levels of exercise supervision, progression and individualisation emerged, matching the content of the intervention protocols. Barriers to exercise and general physical activity were similar across intervention arms (lack of motivation, time, physical environment, lack of supervision and/or monitoring). Despite individualising exercise programs and specifically targeting exercise, some barriers to adherence remained at 12 months. Factors facilitating longer-term exercise adherence included change in or retained knowledge about the role of exercise for knee pain and the presence and quality of a therapeutic alliance, which was also reflective of the participants' experience of the intervention, regardless of the trial arm.

Despite a focus on individualisation and exercise adherence, barriers remained in the longer term. Strong therapeutic alliance during treatment appeared to facilitate adherence to exercise and general physical activity. The findings highlight ongoing physiotherapy support and therapeutic alliance as targets for future adherence-enhancing interventions for exercise in older adults with knee pain.

Juvenile rheumatoid arthritis (JRA) can result in disability, growth disturbance, and systemic complications. This study investigated the efficacy and adverse effects of azathioprine (AZA) therapy in children with JRA. Data from the medical records of 24 children with JRA treated with oral AZA during the period from 1988 to 1998 were retrospectively analyzed. All 24 patients had received two or more nonsteroidal anti-inflammatory drugs (NSAIDs) and 12 had received disease-modifying antirheumatic drugs (DMARDs) prior to the start of AZA. Of the 24 patients, 21 were corticosteroid-dependent prior to the onset of AZA therapy. The indication for AZA therapy was lack of efficacy of the current treatment regimen. The initial and maximal doses of AZA averaged 1.7 mg.kg-1.d-1 (range, 1-3 mg. kg-1.d-1) and 1.9 mg.kg-1.d-1 (range, 1-6 mg.kg-1.d-1), respectively. The mean duration of treatment was 13 months (range, 4-37 mo). The mean duration of follow-up was 45 months (range, 7-137 mo) from the start of AZA therapy. Fifteen children (62.5%) showed clinical improvement, while the other nine (37.5%) achieved clinical remission. AZA treatment resulted in a more than 50% reduction in the required corticosteroid dose in seven children and complete discontinuation of corticosteroid administration in eight children. None of the patients treated with AZA doses of 1 to 3 mg.kg-1.d-1 developed AZA-related side-effects. Two patients suffered from AZA-related adverse effects due to AZA overdose (6 mg.kg-1.d-1). Both experienced pancytopenia and disseminated infection, which resolved following reduction of the AZA dose to 3 mg.kg-1.d-1.

AZA is an effective and well-tolerated steroid-sparing agent for JRA refractory to NSAIDs or DMARDs.

This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence.

This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

To describe the clinical features, treatment and outcomes of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children admitted to the national referral hospital in Dili, Timor-Leste. This prospective study documented cases of ARF and RHD in children aged 14 years and under who were admitted between June 2017 and May 2019. ARF was diagnosed using an adapted version of the 2015 Jones criteria and presumed (rather than proven) exposure to group A Streptococcus. Clinical and echocardiographic findings, comorbidities and discharge outcomes are reported. A total of 63 patients were admitted with ARF or RHD; 54 were diagnosed with RHD for the first time. Median age was 11 years (range 3-14); 48% were female. Of those with echocardiograms, 56/58 had RHD, 55/56 (98%) had mitral regurgitation (37/55 (67%) severe), 11/56 (20%) had mitral stenosis and 43/56 (77%) had aortic regurgitation. Left ventricular dysfunction (55%), pulmonary hypertension (64%) and cardiac failure (78%) were common. Four (6%) patients died in hospital, and 30/59 (51%) of surviving patients were lost to follow up.

Community echocardiography screening has reported a high prevalence of undetected mild to moderate cases of RHD in Timor-Leste, whereas this hospital study documents mostly severe disease among hospitalised patients with a high case fatality rate and loss to follow up. RHD is a significant health problem in Timor-Leste and improved recognition and diagnosis, as well as effective delivery of treatment and follow-up are imperative.

Disorders of coordination, strength and proprioception are frequently described after surgery of the knee joint. These muscular coordination disorders have not yet been studied sufficiently. The purpose of this study was the objective-quantitative characterization of muscular coordination disorders of the M. quadriceps femoris by means of EMG mapping in the arthrotic knee joint and their progress after the implantation of a total knee arthroplasty and after in-patient rehabilitation. The extent and pattern of activation (EMG mapping) of the M. quadriceps femoris were investigated by means of a 16-channel EMG technique in 38 patients before and after the implantation of a total knee arthroplasty (type LCS). EMG mapping permitted an objective-quantitative characterization of the extent and pattern of activation in the M. quadriceps femoris before and after the implantation of a total knee arthroplasty and therefore the objectivation of muscular coordination disorders. Muscular coordination disorders were present already before surgery and were also caused by the implantation of a total knee arthroplasty. These coordination disorders can be improved by an inpatient rehabilitation.

The development of exercise programs adequate for everyday life is necessary to remove quickly and actually the demonstrated coordination disorders.

Physical activity and diet have a positive influence on disease activity and cardiovascular risk in patients with rheumatoid arthritis (RA). We tested the feasibility and effect of a brief individualized counselling intervention on physical activity levels and fitness, and dietary intake, compared with standard of care. Thirty patients with inflammatory arthritis (<1 year duration) were assigned to standard of care or the intervention, which consisted of individualized visits with a dietetic intern and physiotherapist at two time points, to review age-specific strategies on diet and exercise. Primary outcomes included anthropometric measurements (height, weight, waist and hip circumference), nutritional intake, physical activity (pedometer steps) and physical fitness. Disease activity measures and biochemical testing (blood pressure measurement, inflammatory markers, cholesterol profile and random glucose) were collected. The changes in these outcomes from baseline to 6 months were assessed using paired t-tests between groups. Thirteen patients in the intervention group and 10 in the control group completed the study. There were non-significant trends in improvements in physical activity, low-density lipoprotein cholesterol level and nutritional intake (vitamin C, iron, fibre, vitamin A and folate) in the intervention group.

Poor enrolment and high dropout rates in this short-term study highlighted the difficulty of behavioural change. Those continuing in the study and who received the intervention demonstrated a non-significantly improved activity level and nutritional intake that may benefit long-term outcomes.

Obesity prevalence is noticeably growing, even in the elderly. Most of the studies concerning the impact of obesity in the elderly evaluated physical co-morbidities, whilst very few data are available on psychological co-morbidities in people ≥ 60 years of age. The present study aimed to compare anthropometrical measures, physical co-morbidities and psychosocial factors correlated with overweight and obesity in younger and elderly people. In 456 women in the age range of 18-59 years and 128 women in the age range of 60-80 years with body mass index (BMI) ≥ 25/kg m², body weight, height and waist and hip circumferences were measured. The presence of co-morbidities such as osteoarthritis, hypertension, type 2 diabetes and hypercholesterolaemia was assessed. The Obesity Related Well Being 97 Questionnaire (ORWELL 97), Body Uneasiness Test (BUT), Symptom Check List 90 (SCL 90) and Binge Eating Scale (BES) tests were used to evaluate psychometric variables. BMI was not significantly different between younger overweight-obese subjects and older overweight-obese subjects, whereas waist circumference and waist-to-hip ratio (WHR) were significantly higher in the elderly. Osteoarthritis, hypertension and hypercholesterolaemia were significantly more frequent in the elderly. Older overweight-obese subjects had better scores in most of the psychometric questionnaires.

Our results show that older overweight-obese subjects have generally more physical co-morbidities but a better psychological status than younger adults, despite similar BMI. These data may contribute to a better understanding of obesity consequences in the elderly and may help clinicians to differentiate obesity treatments in relation to patients' age.

To determine whether women with silicone breast prostheses have more rheumatic complaints than controls. The study included 287 women who had silicone breast prostheses implanted between 1978-90. For every patient a female control of the same age was selected who had had an aesthetic operation in the same year. A questionnaire was sent to this retrospective cohort of women with silicone breast prostheses and controls. Questionnaires were returned by 235 cases (82%) and 210 controls (73%). Patients reported more symptoms arising after surgery than controls (0.6 v 0.3 complaints per subject, p < 0.001). The average interval between surgery and onset of complaints was 5.1 years for patients and 5.9 for controls. Complaints presented by patients were: painful joints (p < 0.005), burning eyes (p < 0.01), and skin abnormalities (p < 0.005). Differences in the use of antirheumatic drugs or medical consultations related to rheumatic symptoms did not reach statistical significance. Further information obtained from the patients and controls reporting rheumatic symptoms did not reveal the presence of a specific syndrome in connection with silicone materials.

Women with silicone breast prostheses report more rheumatic complaints after silicone implantation than controls, but there is no evidence of increased prevalence of common rheumatic diseases.

To evaluate the efficacy, safety, tolerability and steroid-sparing effect of repository corticotropin injection (RCI), in an open-label clinical trial, in refractory adult polymyositis (PM) and dermatomyositis (DM). Adults with refractory PM and DM were enrolled by two centres. Inclusion criteria included refractory disease defined as failing glucocorticoid and/or ≥1 immunosuppressive agent, as well as active disease defined as significant muscle weakness and >2 additional abnormal core set measures (CSMs) or a cutaneous 10 cm Visual Analogue Scale score of ≥3 cm NCT01906372; Results.

Treatment with RCI was effective in 70% of patients, safe and tolerable, and led to a steroid dose reduction in patients with adult myositis refractory to glucocorticoid and traditional immunosuppressive drugs.

To compare fertility rates in women with RA, other chronic arthritides (OCAs) and JIA with reference women from the general population. Each woman from a Norwegian patient registry was matched by year of birth with 100 reference women randomly selected from the National Population Registry. Data linkage of patients and references with the Medical Birth Registry of Norway (MBRN) identified all offspring in patients and references until October 2007, and indirectly also nulliparous (childless) women. Groups were compared with Mann-Whitney U-test for continuous variables and chi-squared tests for categorical variables. Poisson regression analysis was applied to calculate relative fertility rates in the diagnostic groups vs references. Among 631 patients 849 children were registered in MBRN. Of these, 289 children (34.0%) were born after time of diagnosis vs 44.3% in references. Altogether, 206 of 631 patients (32.6%) were nulliparous vs 26.4% in references (P < 0.001). Among RA patients, 28.4% (96 of 338) were nulliparous vs 24.5% in references (P = 0.09), 30.7% (67 of 218) in OCA patients vs 24.5% in references (P = 0.03) and 57.3% (43 of 75) in JIA patients vs 40.9% in references (P = 0.004). Adjusted relative fertility rates in RA, OCA and JIA after diagnosis were 0.88, 0.84 and 0.84, respectively, compared with references.

A higher proportion of women with chronic inflammatory arthritides were nulliparous compared with references, and relative fertility rates were reduced in all patient groups.

In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1β-induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA. Chondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2α (EPAS1) in cartilage catabolism simulated by IL-1β (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1β-induced inflammatory conditions and their related catabolic genes expression were analyzed. Interleukin-1β (IL-1β) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10(-8) M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.

In conclusions, Ecd can reduce the IL-1β-induced inflammatory effect of the cartilage. Ecd may suppress IL-1β-induced cartilage catabolism via HIF-2α pathway.

Hemiarthroplasty for the treatment of shoulders with glenohumeral arthritis and severe rotator cuff deficiency has been reported to provide reasonable clinical results. The purposes of this study were to determine the clinical and radiographic results of hemiarthroplasty for this condition and to identify pathological and technical factors that may influence its outcome. Thirty patients (thirty-three shoulders) managed with hemiarthroplasty because of glenohumeral arthritis and a massive, irreparable tear of the rotator cuff were followed for an average of five years (range, two to eleven years). Eight shoulders had undergone a prior acromioplasty and resection of the coracoacromial ligament. A small prosthetic head was used in three shoulders; a medium head, in twenty-six; and a large head, in four. Clinical results were graded according to the limited-goals criteria of Neer et al. The mean pain score decreased from 4.2 points preoperatively to 2.2 points at the time of the most recent follow-up (p = 0.0001). However, at the time of the most recent follow-up, nine shoulders (27%) had moderate pain at rest (four shoulders) or pain with activity (five shoulders). Mean active elevation improved from 72 degrees (range, 30 degrees to 150 degrees) to 91 degrees (range, 40 degrees to 165 degrees) (p = 0.008). Anterosuperior instability occurred in seven shoulders and was associated with a history of subacromial decompression (p = 0.04). The result was graded as successful for twenty-two shoulders (67%).

Shoulder hemiarthroplasty provides marked pain relief in three-quarters of patients with glenohumeral arthritis and severe rotator cuff deficiency. It is a reconstructive option that provides durable results, but it may be complicated by instability and progressive bone loss.

To evaluate patient predictors of good outcome following total joint arthroplasty (TJA). A population cohort with hip/knee arthritis (osteoarthritis [OA] or inflammatory arthritis) ages ≥55 years was recruited between 1996 and 1998 (baseline) and assessed annually for demographics, troublesome joints, health status, and overall hip/knee arthritis severity using the Western Ontario and McMaster Universities OA Index (WOMAC). Survey data were linked with administrative databases to identify primary TJAs. Good outcome was defined as an improvement in WOMAC summary score greater than or equal to the minimal important difference (MID; 0.5 SD of the mean change). Logistic regression and Akaike's information criterion were used to determine the optimal number of predictors and the best model of that size. Log Poisson regression was used to determine the relative risk (RR) for a good outcome. Primary TJA was performed in 202 patients (mean age 71.0 years; 79.7% female; 82.7% with >1 troublesome hip/knee; 65.8% knee replacements). Mean improvement in WOMAC summary score was 10.2 points (SD 18.05; MID 9 points). Of these patients, 53.5% experienced a good outcome. Four predictors were optimal. The best 4-variable model included pre-TJA WOMAC, comorbidity, number of troublesome hips/knees, and arthritis type (C statistic 0.80). The probability of a good outcome was greater with worse (higher) pre-TJA WOMAC summary scores (adjusted RR 1.32 per 10-point increase; P < 0.0001), fewer troublesome hips/knees (adjusted RR 0.82 per joint; P = 0.002), OA (adjusted RR for rheumatoid arthritis versus OA 0.33; P = 0.009), and fewer comorbidities (adjusted RR per condition 0.88; P = 0.01).

In an OA cohort with a high prevalence of multiple troublesome joints and comorbidity, only half achieved a good TJA outcome, defined as improved pain and disability. A more comprehensive assessment of the benefits and risks of TJA is warranted.

Osteoarthritis (OA) and osteoporosis are often considered to lie at opposite ends of a spectrum of bone phenotypes. Lumbar degenerative disc disease (LDD) may be associated with low back pain (LBP) and is similar in many ways to OA. LDD is reported in small studies to be associated with increased spine bone mineral density (BMD). The present work aimed to confirm this association in a large population sample using MRI and explore the relationship further, in particular to determine whether it is mediated genetically. A population based sample (N = 908, age range 32-74 years) of UK female twins having MRI of the lumbar spine was used in this study. LDD traits and summary measures and their relationship with BMD at the lumbar spine and hip were examined using multivariate multiple regression and maximum likelihood based variance decomposition. There was a significant positive correlation between LDD and BMD at the lumbar spine and hip, which remained significant after adjustment for confounders. Both traits were highly heritable and the associations between them were mediated genetically.

A clear, significant and independent association of BMD at hip and lumbar spine with LDD was found which is, in part, genetically mediated. The association with the non-axial site, the hip, is of particular interest and suggests a systemic bone effect. This should encourage the search for pleiotropic genes to help in the understanding of the bone-cartilage relationship. Moreover, genetic variants identified could provide novel therapeutic targets in the management of LBP.

The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts. In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), rs1800896 (IL-10), rs2900180 (C5-TRAF1) and rs7528684 (FCRL3). Associations were tested in the total RA-populations and in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative subgroups per cohort, followed by meta-analyses. Furthermore, the associated region C5-TRAF1 was fine-mapped in the ACPA-negative Dutch RA-patients. No associations were found for rs1800795 (IL-6), rs1800896 (IL-10) and rs7528684 (FCRL3) in the total RA-population and after stratification for ACPA. Rs2900180 in C5-TRAF1 was associated with radiographic progression in the ACPA-negative population (P-value meta-analysis = 5.85 × 10(-7)); the minor allele was associated with more radiographic progression. Fine-mapping revealed a region of 66Kb that was associated; the lowest P-value was for rs7021880 in TRAF1. The P-value for rs7021880 in meta-analysis was 6.35 × 10(-8). Previous studies indicate that the region of rs7021880 was associated with RNA expression of TRAF1 and C5.

Variants in IL-6, IL-10 and FCRL3 were not associated with radiographic progression. Rs2900180 in C5-TRAF1 and linked variants in a 66Kb region were associated with radiographic progression in ACPA-negative RA.

This study was designed to evaluate the clinical and radiographic results of arthroscopic treatment of femoroacetabular impingement (FAI) using the technique of initial access to the peripheral compartment. It is based on a single surgeon large case series with a minimum of 2 years follow-up. Prospective longitudinal study with consecutive patients. Inclusion criteria were the presence of FAI syndrome that had failed non-operative treatment and had a hip arthroscopy with initial access to the peripheral compartment. Exclusion criteria were previous hip surgery, patients younger than 16 or older than 60 years, Tönnis grade ≥ 2 osteoarthritis, hip dysplasia based on radiographic evidence of LCEA less than 25° and workers compensation cases. One hundred and sixty hips met the inclusion criteria, 84 were female and 70 were male patients (six bilateral cases), with a median age of 36 years (range 16-59). The median alpha angle correction was 22.6º (range 5.9-46.7) (p < 0.01) and the average LCEA correction when acetabuloplasty was undertaken was 6.5º (range - 1.4-20.8) (p < 0.01). The mean NAHS at baseline was 56.1 (range 16-96) and improved to 83.2 at the last follow up (range 44-100) for the patients that had no additional procedure (p < 0.01). The mean average improvement was 27.7º points (range - 16-73). No iatrogenic labral perforation and no full-thickness chondral damage were recorded during the arthroscopic procedures. Level IV.

Favourable outcomes are reported for the arthroscopic treatment of FAI with initial access to the peripheral compartment. The technique is protective against iatrogenic chondral and labral damage, more conservative to the joint capsule, but the mean traction time was relatively long when suture anchors were used. The results are comparable to the classic initial central compartment approach.

To determine the effectiveness of nurse-led consultations in patients with stable rheumatoid arthritis (RA) in Hong Kong. This is a single-centre, randomized, open-label, non-inferiority trial. RA patients with low disease activity (LDA) were randomized in a 1:1 ratio to nurse-led consultation or rheumatologist follow-up for 2 years. The primary endpoint was the proportion of patients who remained at LDA. Secondary endpoints included the proportion of patients in disease remission and the scores of Leeds satisfaction questionnaire (LSQ) at 2 years, changes from baseline in DAS28-CRP, modified Total Sharp Score (mTSS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form 36-item (SF-36) physical component score and Compliance Questionnaire of Rheumatology 19-item (CQR-19) score. Among 280 patients who were randomized equally to either nurse-led consultation or rheumatologist follow-up, 267 patients completed the study. 92.1% and 91.4% patients remained at LDA at 2 years in nurse-led consultation and rheumatologist follow-up group, respectively. The 95% confidence intervals (CI) of the adjusted treatment difference were within the pre-defined non-inferiority margin in both the intention-to-treat analysis (95% CI -5.75, 7.15) and the per-protocol analysis (95% CI -1.67, 7.47). Although the changes in DAS28-CRP over 2 years were significantly different between the 2 treatment groups (p<0.001), there were no significant changes from baseline in mTSS, HAQ-DI, SF-36 physical component scores and CQR-19 scores. At the end of the study, more patients expressed satisfaction with nurse-led consultations.

Nurse-led consultation is not inferior to rheumatologist follow-up in patients with stable RA.

Radiography is widely accepted as the gold standard for diagnosing osteoarthritis (OA), but it has limitations when assessing early stage OA and monitoring progression. While there are improvements in the treatment of OA, the challenge is early recognition. MEDLINE and PubMed as well as professional orthopaedic and imaging websites were reviewed from 2006 to 2016. Clinical review. Level 4. Magnetic resonance imaging (MRI) can provide the most comprehensive assessment of joint injury and OA with the advantages of being noninvasive and multiplanar with excellent soft tissue contrast. However, MRI is expensive, time consuming, and not widely used for monitoring OA clinically. Computed tomography (CT) and CT arthrography (CTA) can also be used to evaluate OA, but these are also invasive and require radiation exposure. Ultrasound is particularly useful for evaluation of synovitis but not for progression of OA.

MRI, CT, and CTA are available for the diagnosis and monitoring of OA. Improvement in techniques and decrease in cost can allow some of these modalities to be effective methods of detecting early OA.

To analyse tender and swollen joint counts in three cohorts of patients with rheumatoid arthritis (RA), with a focus on the proportions of patients who had fewer than 6-12 tender or swollen joints, as possible evidence based information toward more generalisable inclusion criteria for current and future RA clinical trials. Tender and swollen joint counts were analysed in three cohorts of patients with RA: 125 in 1985, 138 in 2000, and 232 with early RA in 2001. The median numbers of tender joints were 11, 2, and 4 in 1985, 2000, and in early RA in 2001, respectively. The median numbers of swollen joints were 12, 6, and 5 in 1985, 2000, and 2001, respectively. The numbers of tender joints among 28 assessed were >or=12, >or=6, >or=4, and >or=3 in 47%, 80%, 85%, and 90% of patients in 1985; 20%, 37%, 44%, and 49% in 2000; and 17%, 37%, 50%, and 58% in early RA in 2001. The numbers of swollen joints among 28 assessed were >or=12, >or=6, >or=4, and >or=3 in 51%, 78%, 86%, and 90% of patients in 1985; 20%, 50%, 64%, and 67% in 2000; and 14%, 46%, 58%, and 72% in 2001. The number of patients with >or=6 tender or swollen joints in 1985 was greater than the number with >or=3 joints in 2000 and in early RA in 2001.

Contemporary cohorts of patients seen in standard care have smaller numbers of tender and swollen joints than in previous times. These findings suggest that revision of inclusion criteria for numbers of tender and swollen joints in contemporary RA clinical trials might improve generalisability.

Side effects of TNF neutralisation - mostly infectious complications - were recognized, the most important being pulmonary tuberculosis infections. gamma/ d T cells contribute to protective immune response against mycobacterium tuberculosis. The aim of the present study was to assess the expansion capacity of Vgamma9/Vdelta2 T cells from (tuberculin purified protein derivative (PPD) positive and PPD negative) patients with active rheumatoid arthritis (RA), and to examine the in vitro effect of infliximab on this lymphocyte subset. 28 PPD negative RA patients were studied and compared with 14 PPD positive RA patients, 45 PPD-negative and 110 PPD-positive healthy volunteers. Cell separation, expansion in vitro of Vgamma9/Vdelta2 T lymphocytes (EF) and the expression of tumor necrosis factor receptor II and IFN-gamma content by Vgamma9/Vdelta2 T lymphocytes were studied before and after infliximab in vitro addiction. The EF from PPD positive subjects was higher than that from PPD negatives. Patients with RA have the highest levels. The addition of infliximab to the cultures from PPD-positive patients determined a significant inhibition of cell expansion and TNF RII expression and a significant decrease of IFN gamma content.

In this study we have documented that gamma/ delta T lymphocytes from patients with PPD positive rheumatoid arthritis have a high capacity to respond in vitro to phosphoantingens with expansion TNF-RII expression and IFN gamma production that is inhibited by the exposure to infliximab. These results might be of relevance in view of the effect of TNF blocking on the pulmonary tuberculosis infection.

Treatment options available to patients with rheumatoid arthritis (RA) are ever-changing, and understanding the similarities and differences of efficacy and safety between different RA therapies is of key importance in order to facilitate treatment decisions by both the patient and physician. Very few head-to-head, peer-reviewed trials exist; instead, evidence for efficacy of treatments is often ascertained from placebo-controlled trials, registries and meta-analyses, which often do not sufficiently address the relative effectiveness of two medications. A targeted review of indirect comparison methods, and ongoing and published clinical studies assessing the efficacy and safety, and the comparative efficacy and safety of biologic disease modifying antirheumatic drugs in RA. Critical elements that should be considered when designing head-to head trials are described using examples of true head-to-head and placebo-controlled randomized controlled trials (RCTs). The appropriate use of head-to-head trial designs is demonstrated by reviewing different examples of well-designed clinical trials, and an overview is presented of the challenges associated with indirect comparisons. This review also examines the use of studies comparing therapies to placebo, highlighting the difficulties associated with the interpretation of these studies.

For comparative trials to contribute to evidence-based decision making in the treatment of RA, patient populations and treatment regimens as similar as possible to those used in routine clinical practice should be employed and the trial should be appropriately designed to answer the specific question asked.

. To investigate whether features associated with severe rheumatoid arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts, independent of HLA-DR3 status. A cohort of patients with RA (n = 41) who developed thrombocytopenia (platelets < 100 10(6)/l) or proteinuria (> 1.0 g/24 h) upon treatment with gold sodium thiomalate was identified from patient records and matched for age, sex, and disease duration with 41 RA controls treated with gold without development of ADR. A second group of 161 random RA patients that had received gold therapy for at least as long without development of an ADR was also compared. All patients were typed for HLA-DRB1, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA), and nodules before initiation of therapy was recorded. Association of clinical or genetic factors with ADR was investigated using the McNemar test and logistic regression analysis. Patients with ADR were more likely to have nodular disease than their matched controls (51.3% vs 25.6%; odds ratio, OR = 3.0, p = 0.02) and more likely to be HLA-DR3 positive (41.2% vs 17.6%; OR = 3.0, p = 0.045). No difference between the groups was found for RF or ANA. Nodular disease was associated with development of ADR independently of HLA-DR3, although a combination of both factors significantly increased the likelihood of an ADR.

Our data suggest that nodular disease may be a predictor of gold-induced ADR independent of HLA-DR3.

Platelets are involved in various thrombotic events, often by means of platelet-derived microparticles (PMPs). It is likely that platelets are also involved in inflammation. Because inflammatory processes play a central role in rheumatoid arthritis (RA), we sought to determine whether PMPs are present in this disease. This descriptive, cross-sectional study included 19 RA patients and 10 healthy controls. Nine of the patients had active RA (erythrocyte sedimentation rate [ESR] > or =28 mm/hour and/or C-reactive protein [CRP] level > or =28 mg/liter, > or =9 painful joints, and > or =6 swollen joints), and 10 had inactive disease (ESR < or =27 mm/hour, CRP < or =27 mg/liter, no tender joints, and no swollen joints). Platelet counts and PMP numbers were determined using cell counter and flow cytometry, respectively. Platelet counts in the 3 groups were similar. However, levels of PMPs in RA patients were significantly higher than those in healthy controls (median 616 versus 118 x 10(6)/liter; P = 0.005). PMP levels were higher in patients with active RA than in those with inactive RA (median 2,104 versus 504 x 10(6)/liter; P > 0.05). Moreover, PMP levels correlated with disease activity (r = 0.67, P = 0.05).

PMPs are associated with RA, and PMP levels are correlated with disease activity. Thus, platelets probably play a part in the inflammatory process of RA by means of PMPs. Given the importance of PMPs in cardiovascular diseases, this may be one reason for the enhanced cardiovascular morbidity and mortality in RA.

The aim of this study was to assess the effect of degree of anterior translation of the distal tibial fragment after lateral closing wedge high tibial osteotomy in patients having combined knee medial compartmental and patellofemoral osteoarthritis. A retrospective study was conducted on 64 patients who were operated on for combined knee medial compartmental and patellofemoral osteoarthritis, by lateral closing wedge high tibial osteotomy with anterior translation of the distal tibial fragment. They were divided into two groups; Group I comprising 32 patients (34 knees, mean age of 51.4±7years) whose degree of anterior translation was <1cm and Group II comprising 32 patients (33 knees, mean age of 52.2±8.3years) whose degree of anterior translation was >1.5cm. The final assessment was performed via: visual analog scale, postoperative Knee Society clinical rating system function score, active range of motion, time to union, degree of correction of mechanical axis, posterior tibial slope, and Insall-Salvati ratio. Group II patients exhibited statistically superior mean postoperative score and better return to their work than Group I (P=0.013, 0.076, respectively). Both groups showed statistically significant differences between the preoperative and postoperative evaluation parameters (P<0.001). The posterior tibial slope was decreased in both groups but with no significant difference (P=0.527).

Lateral closing wedge high tibial osteotomy combined with anterior translation of the distal tibial fragment more than 1.5cm achieved significantly better postoperative functional knee score. Both groups exhibited comparatively decreased posterior tibial slope.

To assess the reliability, validity, and responsiveness to treatment change of the single-item measure, Severity of Worst Tiredness, in patients with rheumatoid arthritis (RA). Data from two Phase 3, randomized, placebo-controlled (RA-BUILD; and active-controlled [RA-BEAM]), clinical studies of the efficacy of baricitinib in adults with moderately to severely active RA were used. The psychometric properties of the single-item measure, Severity of Worst Tiredness, were assessed, including test-retest reliability, convergent and discriminant validity, known-groups validity, and responsiveness, using other patient- and clinician-reported outcomes frequently assessed in RA patients. Test-retest reliability of the Severity of Worst Tiredness was supported through large intraclass correlation coefficients (0.89 ≤ ICC ≤ 0.91). Moderate-to-large correlations were observed between this patient-reported outcome (PRO) and other related patient- and clinician-reported assessments of RA symptoms and patient functioning, supporting construct validity of the measure (│r│ ≥ 0.41). The instrument also displayed known-groups validity through statistically significant differences between mean values of the Severity of Worst Tiredness defined using other indicators of RA severity. Finally, responsiveness was supported by large and statistically significant differences in change scores from Day 1 to Week 12 for patients comparing responders and nonresponders using the American College of Rheumatology 20 (ACR20) criteria.

The Severity of Worst Tiredness PRO demonstrated adequate reliability, validity, and responsiveness in clinical trials of adults with moderately to severely active RA and is fit for purpose in this patient population.

Juvenile idiopathic arthritis-associated uveitis (JIAU) is the most common uveitis entity in childhood. As S100A8/A9 and S100A12 proteins are valuable biomarkers in childhood arthritis, we investigated the occurrence of these proteins in childhood uveitis. Serum samples from patients with JIAU (n = 79) or idiopathic anterior uveitis (IAU, n = 24), as well as from nonuveitic controls (n = 24), were collected. Furthermore, aqueous humor samples (JIAU n = 17, nonuveitic controls n = 16, IAU n = 12) were obtained. Samples were analyzed for S100A8/A9 and S100A12 protein levels by ELISA. Intergroup comparisons were performed, involving patient data, clinical data, and S100 levels. S100A8/A9 and S100A12 serum levels were elevated in IAU and JIAU patients as compared to nonuveitic controls (all P < 0.05). S100 serum levels in JIAU patients were higher in active arthritis (not significant; P = 0.289 for S100A8/A9 and P = 0.196 for S100A12) and active uveitis (P = 0.010 for S100A8/A9 and P = 0.026 for S100A12) than in controls. No significant differences in S100 levels were found in a subgroup analysis for sex, antinuclear antibody (ANA) status, disease duration, or presence of uveitis complications. In JIAU patients, S100 serum levels correlated with age and age at onset of uveitis. A longitudinal analysis in JIAU patients showed a correlation of serum S100A8/A9 and S100A12 levels with uveitis activity (both P = 0.03). S100A8/A9 levels in aqueous humor of patients with JIAU (P = 0.001) and IAU (P = 0.0002) were increased as compared to nonuveitic controls.

Increased S100A8/A9 and S100A12 levels are found in the serum and aqueous humor of patients with autoimmune uveitis. Serum levels reflect activity of joint and eye disease.

Since the main characteristics of Rheumatoid Arthritis (RA) are joint dysfunction caused by inflammation and serious pain, anti-inflammatory agents may alleviate the clinical symptoms in RA. Pomegranate juice is rich in polyphenolic compounds that possess antioxidant and anti-inflammatory activities. This study aimed to determine the beneficial effects of pomegranate extract (POMx) in RA patients. A total of 55 RA patients were enrolled and randomly allocated to an intervention group (n=30) or a control group (n=25). The intervention group received 2 capsules of 250 mg POMx and the control group 2 capsules of 250 mg cellulose per day for 8 weeks. At the beginning of the study and after 8 weeks, Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) 28 were completed and serum concentrations of C-reactive protein (CRP), matrix metalloproteinases 3 (MMP3), malondialdehyde (MDA), glutathione peroxidase (GPx) and erythrocyte sedimentation rate (ESR) were analyzed using standard methods and compared between the two groups. Compared with the placebo group, POMx supplement significantly reduced the score of DAS28 (P<0.001) which could be related to the decrease in swollen (P<0.001) and tender joints (P=0.001) count, pain intensity (P=0.003) and ESR levels (P= 0.03). POMx consumption also decreased HAQ score (P=0.007) and morning stiffness (P=0.04) and increased GPx concentrations (P<0.001). There were no differences in the change in mean MMP3, CRP and MDA levels between two groups.

POMx alleviates disease activity and improves some blood biomarkers of inflammation and oxidative stress in RA patients.

Histone deacetylase (HDAC) inhibitor has recently been reported to have a therapeutic effect as an anti-inflammatory agent in collagen-induced arthritis (CIA). We investigated the therapeutic effect of a new selective HDAC6 inhibitor, CKD-L, compared to ITF 2357 or Tubastatin A on CIA and regulatory T (Treg) cells in patients with rheumatoid arthritis (RA). CIA was induced by bovine type II collagen (CII) in DBA/1 J mice. Mice were treated with HDAC inhibitor for 18 days. Arthritis score was assessed and histological analysis was performed by hematoxylin and eosin (H&E) stain. Cytotoxic T-lymphocyte associated protein (CTLA)-4 expression in induced Treg cells was analyzed and suppression assay was analyzed using Treg cells and effector T (Teff) cells isolated from naive C57BL/6 mice by flow cytometry. Cytokines were analyzed in peripheral blood mononuclear cells (PBMC) of five patients with RA by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Tumor necrosis factor (TNF) was analyzed using PMA- activated THP-1 cells by ELISA. Suppression assay was analyzed using Treg cells and Teff cells isolated from RA patients by flow cytometry. In the CIA model, CKD-L and Tubastatin A significantly decreased the arthritis score. CKD-L increased CTLA-4 expression in Foxp3

CKD-L decreased the arthritis score in CIA, reduced the expression of TNF and IL-1β, and increased the expression of IL-10 in PBMC from RA patients. CKD-L increased CTLA-4 expression and the suppressive function of Treg cells. These results suggest that CKD-L may have a beneficial effect in the treatment of RA.

Torque teno virus (TTV) is a highly prevalent non-pathogenic anellovirus whose plasma levels may be a biomarker of immunosuppression. The aim of this study was to assess whether specific immune-targeting with different biologic drugs may differentially modulate TTV viremia in arthritis patients. TTV DNA load was quantified by PCR in a cross-sectional sample of 79 patients with chronic arthritis on biologic therapy (abatacept, infliximab, rituximab or tocilizumab), 31 patients treated with conventional DMARDs (methotrexate and/or leflunomide), and 54 healthy individuals. Longitudinal changes in TTV load were analysed in a second group of 59 patients at baseline and 4-months after biologic therapy. Correlations between clinical or biological characteristics of recruited patients and TTV viremia were also analysed. In the cross-sectional study, TTV load was significantly higher in patients who received abatacept, infliximab or tocilizumab compared to healthy individuals. Patients treated with rituximab or conventional DMARDs showed TTV loads similar to healthy controls. In the longitudinal study, an increase in the TTV load was observed after anti-TNF, tocilizumab, abatacept and rituximab, but not after secukinumab therapy. Correlations between TTV load and clinical variables such as disease duration, concomitant glucocorticoid or DMARDs therapy, lymphocytes or previous infections were not found. A non-significant trend towards higher TTV load was observed in therapy responders.

Patients with chronic arthritis on biologic but not on conventional DMARD or anti-IL17 therapy have increased TTV viremia. This observation provides a basis to prospectively explore the potential value of TTV load as a potential pharmacodynamic biomarker.

Osteoarthritis (OA) is a leading cause of pain and disability, and the knee is one of the most commonly affected joints. Many have speculated that injury to the meniscus may play a key role in the development of knee OA; however, the exact relationship of meniscus injury and knee OA is unknown. To examine the rate of meniscus injuries in patients with and without incident radiographic knee OA and to explore how the type, size, and location of the meniscus injury affects the development of OA. Case-control study; Level of evidence, 3. A secondary case-control analysis was conducted of the Knee Osteoarthritis Initiative (OAI) database, which is a prospective, longitudinal, multicenter cohort study of knee health in patients at risk for knee OA. Eligible patients included those without radiographic OA at baseline in 1 knee. Thirty-two patients who developed radiographic OA in a previously unaffected knee after 2 years of follow-up were matched to 64 age-, sex-, and body mass index-matched patients who did not develop OA. The study analyzed the relationship between the development of OA and the presence of a meniscus tear or degenerative signal, meniscus extrusion, tear type, and size of injury on the baseline magnetic resonance imaging scans. Conditional logistic regression was used to identify significant predictors of OA. The rate of medial meniscus lesions (tear or degeneration) was not significantly higher in those who developed incident OA (85%) compared with the control patients (68%; P = .07). However, medial meniscus extrusion (odds ratio [OR], 3.03; 95% confidence interval [CI], 1.4-6.5), complex tears (OR, 5.0; 95% CI, 1.0-25), and tears with large radial involvement (OR, 5.92; 95% CI, 1.7-7.5) were more common at baseline in cases compared with controls.

Knees with meniscus tears with greater radial involvement and extrusion are at greater risk for later development of radiographic OA.

When performing total knee arthroplasty (TKA) in valgus knee deformities, a medial or lateral parapatellar approach can be performed, but the lateral approach is often considered technically more difficult. The purpose of this study was to compare intra-operative, early clinical and radiological outcomes of medial and lateral parapatellar approaches for TKA in the setting of moderate knee valgus (<10°). We prospectively analysed 424 knees with pre-operative valgus deformity between 3° and 10° that underwent TKA over an 18-year period; 109 were treated with a medial approach and 315 with a lateral approach. Intra- and post-operative outcomes and complication rates after a minimum follow-up of one year were compared. Tourniquet (p = 0.25) and surgical (p = 0.62) time were similar between groups. The popliteus tendon was released more frequently in the medial-approach group (p = 0.04), while the iliotibial band was released more frequently in the lateral-approach group (p < 0.001). A tibial tuberosity osteotomy was performed more frequently in the lateral- than medial-approach group (p = 0.003). No significant differences in limb alignment (p = 0.78), or Knee Society Score (KSS) knee (p = 0.32) and function (p = 0.47) results were noted based on surgical approach, and complication rates were similar between groups (p = 0.53).

Lateral parapatellar approach is a safe and effective surgical technique for performing TKA in moderately valgus knees. These equivalent early results are encouraging for systematic use of the lateral approach in moderately valgus knees.

C1-C2 instability or painful osteoarthritis are recognised indications for posterior atlanto-axial fixation. In the traditional trans-articular C1-C2 screw fixation, up to 20% of patients cannot have safe placement of bilateral screws in the event of a medially located vertebral artery and a straight screw trajectory in the sagittal plane. The more recently developed C1-C2 fixation technique with individual C1 lateral mass screws and converging C2 pars screws can be employed in case of a medially located vertebral artery and has comparable biomechanical strength. This is a prospective observational study to investigate the advantages, the safety, and the drawbacks of posterior atlanto-axial fixation with polyaxial C1 lateral mass screws and C2 pars screws. Twelve consecutive patients with C1-2 instability (n = 11) and painful osteoarthritis (n = 1) underwent a posterior atlanto-axial fixation with polyaxial C1 lateral mass screws and C2 pars screws. The average follow-up was 16 months and all patients reached the 12-month follow-up. No hardware failure occurred in any of the patients. Correct screw placement and construct stability was found in all 12 patients (100%) at 6 and 12 months after surgery. Mean neck pain on a visual analogue scale (VAS) was 2.1 at 6 months and 2.0 at 12 months. Only transient complications were observed: one patient presented with progressive intestinal herniation through the iliac crest scar; one suffered from severe pain at the posterior iliac crest for 3 months and three patients complained of annoying pain/dysaesthesia in the C2 dermatome for 3-6 months after surgery.

This study confirms that posterior atlanto-axial fixation with polyaxial C1 lateral mass screws and C2 pars screws is a safe and effective surgical option in the treatment of atlanto-axial instability or painful osteoarthritis.

To draw attention to and detail the features of stress fractures of the pubic rami in patients with rheumatoid arthritis (RA). Twenty two cases were collected prospectively over a four year period from patients undergoing active rheumatological surveillance in Leeds. Both old and new fractures were included. Information was obtained from the patients, clinical notes, and radiological investigations. All patients were women (mean age 68.1 years) with longstanding (mean disease duration 24.2 years) seropositive RA. Nineteen (86%) were receiving regular prednisolone treatment and all patients had radiological evidence of osteoporosis, with vertebral crush fractures in 10 (63%) of the 16 who had vertebral x ray examination. There was no biochemical evidence of osteomalacia. Nineteen (86%) presented with pain in the low back, groin, or hip and three were asymptomatic. Pain developed gradually in seven with an acute onset in the remainder. Six gave a history of a fall but only seven were x rayed at the onset of symptoms and initial radiographs were negative in five of these. In eighteen the fracture had either minimal or no effect on their mobility. Fractures affected all four pubic rami and in four all four were fractured. All but one patient (who had multiple fractures) made an uneventful recovery over two to four weeks with conservative management.

Stress fractures of the pubic rami in RA appear to be more common than had been recognised. The low grade nature of symptoms, the minimal effect on mobility, and the absence of significant trauma are typical features and suggest that many more stress fractures may go unrecognised.

In older adults, widespread pain (WP) is common, although its etiology is unclear. This study sought to identify factors associated with an increased risk of developing WP in adults age ≥50 years. A population-based prospective study was conducted. A baseline questionnaire was administered to subjects to collect data on pain, psychological status, lifestyle and health behaviors, and sociodemographic and clinical factors. Participants free of WP (as defined by the American College of Rheumatology 1990 criteria for fibromyalgia) were followed up for 3 years, and those with new-onset WP at followup were identified. Logistic regression analyses were used to test the relationship between baseline factors and new-onset WP. Multiple imputation was used to test the results for sensitivity to missing data. In this population-based study, 4,326 subjects (1,562 reporting no pain at baseline and 2,764 reporting some pain at baseline) participated at followup. Of these participants, 800 (18.5%) reported a status of new WP at followup (of whom, 121 [7.7%] had reported no pain at baseline and 679 [24.6%] had reported some pain at baseline). The majority of the study factors were associated with new-onset WP. However, only a few factors showed a persistent association with new-onset WP in the multivariate analysis, including age (odds ratio [OR] 0.97, 95% confidence interval [95% CI] 0.96-0.99), baseline pain status (OR 1.1, 95% CI 1.08-1.2), anxiety (OR 1.5, 95% CI 1.01-2.1), physical health-related quality of life (OR 1.3, 95% CI 1.1-1.5), cognitive complaint (OR 1.3, 95% CI 1.04-1.6), and nonrestorative sleep (OR 1.9, 95% CI 1.2-2.8). These associations persisted after adjustment for the presence of diffuse osteoarthritis (OA), which led to a modest increase in model fit (C-statistic 0.738, compared with 0.731 in the model excluding diffuse OA). The results were not sensitive to missing data.

Of the factors measured in this study, nonrestorative sleep was the strongest independent predictor of new-onset WP.

Although many studies have suggested that the presence of autoantibodies, such as rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) in rheumatoid arthritis (RA) are predictors of joint damage, the association with disability and quality of life questionnaires are not known. To evaluate the correlation between the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) scores with serological markers, such as RF, anti-CCP, and anti-citrullinated vimentin (anti-Sa). Sixty five patients with early RA (ERA) from the Brasília Cohort of ERA were evaluated. Serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1), and anti-Sa were performed, with the application of the HAQ and SF-36 questionnaires in the initial evaluation. The mean age was 45 years, with a female predominance (86%). At the initial evaluation, RF was positive in 32 individuals (49.23%), anti-CCP in 34 (52.3%), and anti-Sa in nine (13.8%). The initial HAQ score was 1.8. The SF-36 scores were as follow: role-emotional, 19.3; social functioning, 43.1; bodily pain, 25.43; general health, 57.6; mental health, 48.1; vitality, 49.5; role-physical, 4.6; and physical functioning, 24.7. The HAQ and SF-36 scores did not vary with autoantibody levels.

In many patients, ERA has a major impact on physical ability and health-related quality of life. Although RF and anti-CCP tests have been related with joint destruction and worse clinical prognosis, there is no correlation with the results of questionnaires of quality of life and disability.

To assess the practicability of magnetic resonance imaging (MRI) in confirming the diagnosis of clinically suspected rheumatoid arthritis (RA), when anti-cyclic citrullinated peptide antibody and radiographic erosions are absent. We prospectively involved 31 treatment-naive patients with early inflammatory arthritis. At the initial visit, X-rays and gadolinium-enhanced MRI of both hands, as well as serological examinations and acute phase reactants were performed. The scores of synovitis, bone edema, bone erosion and tenosynovitis of metacarpophalangeal and wrist joints were evaluated using the RA-MRI scoring system. For all the patients, radiographs at baseline were normal and anti-cyclic citrullinated peptide antibodies were negative. At the end of follow-up(median 15 months, range 12-20 months), 22 patients were diagnosed as having RA according to 1987 American College of Rheumatology criteria. Bone edema, erosions, synovitis and tenosynovitis were observed in all the patients. However, the frequency of symmetric synovitis in wrists was significantly higher in the RA group. Moreover this group turned out to have significantly higher MRI bone erosion score in wrists. Further, receiver operating characteristic curve analysis revealed a positive wrist bone erosion score at 5, with a specificity of 78% and a sensitivity of 68%. There was no significant difference between the two groups with respect to metacarpophalangeal synovitis, metacarpophalangeal bone erosion, bone edema or tenosynovitis.

MRI evidence of symmetric synovitis at wrist and a high bone erosion score at that site may assist in making an early diagnosis of RA in those patients who are negative for anti-cyclic citrullinated peptide antibody.

We sought to identify specific microRNA (miRNA) for systemic juvenile idiopathic arthritis (sJIA) and to determine the involvement of these miRNA in regulating the expression of cytokines. Microarray profiling was performed to identify differentially expressed miRNA in sJIA plasma. Levels of candidate miRNA and mRNA were assessed by real-time PCR, and cytokines were measured by ELISA. Dual-luciferase reporter assay was used to validate the direct interaction between miR-26a and interleukin 6 (IL-6). Forty-eight miRNA were differentially expressed in the plasma of patients with sJIA compared with healthy controls (HC). Five miRNA were selected for further validation. The expression level of miR-26a was exclusively elevated in the plasma of patients with sJIA as compared with 4 rheumatic diseases and 2 subtypes of JIA (oligoarticular and polyarticular). The levels of IL-6, IL-1β, and tumor necrosis factor-α in the plasma of patients with sJIA were increased, and only IL-6 presented a positive correlation with miR-26a (r = 0.539, p < 0.0001). After stimulation with IL-6, miR-26a expression was upregulated in THP-1 cells, while the supernatant level of IL-6 was downregulated by transfection of miR-26a mimics. Consistently, direct target relationship between miR-26a and IL-6 was confirmed.

This study demonstrates that miR-26a is expressed specifically and highly in sJIA plasma and suggests that miR-26a may regulate the levels of cytokines in sJIA. Our findings highlight miR-26a as a potential biomarker for the diagnosis as well as differential diagnosis of sJIA.

Dentofacial asymmetries are often observed in patients with juvenile idiopathic arthritis (JIA) and temporomandibular joint (TMJ) involvements. The aim of this split-face study was to associate types of radiologic TMJ abnormalities with the degree of dentofacial asymmetry in patients with unilateral TMJ involvements assessed with cone-beam computed tomography. Forty-seven JIA patients and 19 nonarthritic control subjects were included in the study. Normal condylar radiologic cone-beam computed tomography appearance in at least 1 TMJ was the inclusion criterion for all patients with JIA. The contralateral TMJ was thereafter scored as either "normal," "deformed," or "erosive," consistent with predefined criteria. Based on the bilateral radiologic TMJ appearances, 3 JIA groups were assigned: normal/normal, normal/deformed, and normal/erosive. The severity of the dentofacial asymmetry was compared between the JIA groups and control subjects. Dentofacial asymmetry was expressed as interside ratios and angular measurements. Eighty-seven percent of the JIA patients were being treated or had previously received treatment with a functional orthopedic appliance at the time of the cone-beam computed tomography. Significantly greater dentofacial asymmetries were observed in the 2 groups of JIA patients with unilateral condylar abnormalities (deformation or erosion) than in the other groups. A similar degree of dentofacial asymmetry was observed in JIA patients with bilateral normal TMJs and in the nonarthritic control group.

JIA patients with unilateral condylar abnormalities (deformation or erosion) exhibited significantly more severe dentofacial asymmetries than did the JIA patients without condylar abnormalities and the control subjects. We found the same degree of dentofacial asymmetry when dividing patients with condylar abnormalities into deformation and erosion groups.

To evaluate the correlation between the presence of antibodies to an endogenous retroviral element-encoded nuclear protein autoantigen, HRES-1, and the presence of other antinuclear antibodies and HLA class II alleles in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Antibody reactivities to native and recombinant proteins and synthetic peptides were assessed by counterimmunoelectrophoresis, enzyme-linked immunosorbent assay, and Western blotting. HLA class II alleles were determined by oligonucleotide typing. Forty-eight percent of the 153 patients with autoimmune disease, and 52% of the subgroup with SLE, had HRES-1 antibodies. In contrast, 3.6% of 111 normal donors, and none of 42 patients with the acquired immunodeficiency syndrome or 50 asymptomatic human immunodeficiency virus 1-infected patients, had HRES-1 antibodies. Chi-square analyses revealed a significant association between anti-HRES-1 and anti-RNP and an inverse correlation between HRES-1 and Ro/La autoantibodies in patients with SLE or overlap syndromes. Antigenic epitopes of HRES-1 and the retroviral gag-related region of the 70-kd protein component of U1 small nuclear RNP, which share 3 consecutive highly charged amino acids (Arg-Arg-Glu), an additional Arg, and functionally similar Arg/Lys residues, represent cross-reactive epitopes between the two proteins. Selective removal of HRES-1 antibodies from sera of HRES-1-seropositive/RNP-seropositive patients by absorption on recombinant HRES-1/glutathione-S-transferase-conjugated agarose beads had no effect on anti-RNP reactivities. A comparative multivariate analysis of HLA class II genes revealed a differential segregation of DQB1 alleles in HRES-1-seropositive versus HRES-1-seronegative patients (P = 0.04). While a relative increase of DQB1*0402 among HRES-1-seropositive patients was noted across ethnic groups (P = 0.02), a decrease of DQB1*0201 and DQB1*0301 was found in white HRES-1-seropositive patients (P = 0.04).

Autoantibodies to HRES-1 are detectable in a distinct subset of patients with autoimmune disease, primarily in those who do not have antibodies to Ro and La. Anti-HRES-1 and anti-RNP reactivities are mediated by cross-reactive but separate antibody molecules. HLA-DQB genes, rather than HLA-DRB or DQA genes, may have a more significant influence on generation of these antinuclear autoantibodies.

Dietary fibre reduces body weight and inflammation both of which are linked with knee osteoarthritis (OA). We examined the association between fibre intake and risk of knee OA. We used data from the Osteoarthritis Initiative (OAI) of 4796 participants and Framingham Offspring Osteoarthritis Study (Framingham) of 1268 persons. Dietary intake of fibre was estimated at baseline, and incident radiographic OA (ROA) and symptomatic OA (SxOA) were followed annually until 48 months in OAI and assessed 9 years later in Framingham. Knee pain worsening was also examined in OAI. Generalised estimating equations were applied in multivariable regression models. In OAI, we identified 869 knees with SxOA, 152 knees with ROA and 1964 knees with pain worsening among 4051 subjects with valid dietary intake (baseline mean age: 61.2 years; mean body mass index (BMI): 28.6). In Framingham, 143 knees with SxOA and 176 knees with ROA among 971 such subjects (baseline mean age: 53.9 years; mean BMI: 27.0) were identified. In both cohorts, dietary total fibre was inversely associated with risk of SxOA (p trend <0.03) with significantly lower risk at the highest versus lowest quartile (OR (95% CI): 0.70 (0.52, 0.94) for OAI and 0.39 (0.17, 0.88) for Framingham). Furthermore, dietary total and cereal fibre were significantly inversely associated with knee pain worsening in OAI (p trend <0.02). No apparent association was found with ROA.

Findings from two longitudinal studies consistently showed that higher total fibre intake was related to a lower risk of SxOA, while the relation to ROA was unclear.

HLA-B27/human β2 -microglobulin (hβ2 m)-transgenic (B27-transgenic) rats develop an inflammatory disorder resembling spondyloarthritis, with accumulation of proinflammatory Th17 cells. Because Treg cells and Th17 cells have opposing effects in inflammatory disorders, we sought to determine whether biased expansion of Th17 cells could result from altered Treg cell frequency and/or function in B27-transgenic rats. We characterized the phenotype and function of Treg cells from B27-transgenic rats in comparison with those from control rats, by examining their expression of cell surface markers, suppressive activity, cytokine production, and differentiation pattern. In B27-transgenic rats, the preferential accumulation of CD4+ Teff cells over Treg cells was not associated with a defect in Treg cell differentiation or suppressive activity. The expression of Treg cell markers was similar between B27-transgenic and control rats, with the exception of the inducible costimulator (ICOS) molecule, which was overexpressed in B27-transgenic rats. High levels of ICOS are considered to be a hallmark of Treg cells with heightened suppressive activity and interleukin-10 (IL-10) expression. Paradoxically, the production of IL-10 by Treg cells was reduced in B27-transgenic rats, whereas the production of IL-17 was enhanced. Moreover, the addition of anti-ICOS monoclonal antibodies during Treg cell differentiation in the presence of dendritic cells from B27-transgenic rats reversed this cytokine profile, restoring the balance between IL-10 and IL-17 in Treg cells from B27-transgenic rats.

We observed dysregulated production of IL-10 and IL-17 by Treg cells from B27-transgenic rats, which may contribute to disease development. Moreover, our data highlight a key role for ICOS signaling in the generation of imbalanced production of IL-10 and IL-17 by Treg cells in this experimental model of spondyloarthritis.

To synthesise and evaluate the current evidence investigating muscle size and composition in non-inflammatory articular hip pathology. A systematic review of five electronic databases, using three concepts; articular hip pathology (e.g., osteoarthritis (OA)); hip muscles; and outcomes (e.g., muscle size and adiposity) was undertaken. Studies addressing non-inflammatory or non-traumatic articular hip pain, using measures of muscle size and adiposity were included and appraised for risk of bias. Data was extracted to calculate standardised mean differences (SMD) and pooled where possible for meta-analysis. Thirteen cross-sectional studies were included; all studies measured muscle size and 5/13 measured adiposity. In OA, there was low to very low quality evidence of no difference in hip muscle size, compared with matched controls. In unilateral OA, there was low to very low quality evidence of smaller size in gluteus minimus (SMD -0.38; 95% confidence interval (CI) -0.74, -0.01), gluteus medius (-0.44; 95% CI: -0.83, -0.05) and gluteus maximus (-0.39; 95% CI: -0.75, -0.02) muscles in the symptomatic limb. Individual studies demonstrated non-uniform changes in muscle size in OA. No significant difference was observed in muscle size in other pathologies or in adiposity for any group.

There is some low quality evidence that specific hip muscles are smaller in unilateral hip OA. Variation in the magnitude of differences indicate changes in size are not uniform across all muscles or stage of pathology. Studies in larger cohorts investigating muscle size and composition across the spectrum of articular pathologies are required to clarify these findings.

To describe and understand the burden of out-of-pocket expenses in patients with rheumatoid arthritis (RA). We studied out-of-pocket expenses and their burden in 8,545 US patients with RA. We determined direct medical costs, out-of-pocket expenses, the burden of out-of-pocket expenses, household income, and measures of RA severity and outcome. In addition, patients were classified into 3 groups based on the level of burden caused by out-of-pocket expenses: no or limited problem (I am able to pay the bills without much problem); moderate problem (paying the bills takes away some money I need for other activities); and a great problem (I can't purchase all of the medications or medical care that I need). A total of 43.6% of patients reported problems paying medical bills after insurance payments and 9.0% reported severe or great problems. Problems with expenses were associated with measures of RA severity, but also and particularly with lower household income and absence of health insurance. The proportion of household income that was consumed by out-of-pocket spending for the 3 groups was 2.4%, 7.2%, and 19.2%, respectively, and the percentage of patients meeting the 185% poverty level for these groups was 12.3%, 24.4%, and 51.3%, respectively.

The out-of-pocket burden is substantial, particularly in those <65 years of age. Out-of-pocket expenses exert their severity predominantly on those with the most severe RA who have the least ability to pay. Household income is the primary determinant of out-of-pocket burden, followed by RA severity, and type of health insurance.

To compare baseline sociodemographic characteristics in two rheumatoid arthritis (RA) cohorts enrolled 10 years apart, and to examine differences with respect to the general population. Clinical and sociodemographic data were collected in 320 early RA patients during 1996-98 (TIRA-1) and 467 patients in 2006-09 (TIRA-2). Multivariate logistic regression tests were performed and intercohort comparisons were related to general population data, obtained from official databases. TIRA-2 patients were older than TIRA-1 (58 vs. 56 years). Women (both cohorts, 67%) were younger than men in TIRA-1 (55 vs. 59 years) and in TIRA-2 (57 vs. 61 years). Disease activity was similar but TIRA-2 women scored worse pain and worse on the HAQ. Approximately 73% were cohabiting, in both cohorts and in the general population. Education was higher in TIRA-2 than in TIRA-2 but still lower than in the general population. Women had consistently higher education than men. Education was associated with age, younger patients having higher education. In both cohorts, lower education was associated with increased disability pension and increased sick leave. Sick leave was lower in TIRA-2 than in TIRA-1 (37% vs. 50%) but disability pension was higher (16% vs. 10%). In TIRA-1, 9% of women had disability pension compared with 17% in TIRA-2. A similar decrease in sick leave and an increase in disability pension were also seen in the general population. Older age and a higher HAQ score were associated with increased sick leave and being in the TIRA-2 cohort was associated with decreased sick leave.

TIRA-2 patients were slightly older, better educated, had lower sick leave and higher disability pension than those in TIRA-1. Similar changes were seen simultaneously in the general population. Belonging to the TIRA-2 cohort was associated with decreased sick leave, indicating that societal changes are of importance.

To determine the relationship between frequent intraarticular corticosteroid injection and subsequent joint replacement surgery. A 1987 database of patients with rheumatic diseases was reviewed to find patients with rheumatoid arthritis (RA) who had received 4 or more intraarticular injections in an asymmetric pattern in a single year. A subset of 13 patients with an average of 7.4 years of followup was established as the cohort of a 5 year prospective study. In this highly selected cohort of patients with RA in a university practice who received 1622 injections, joint replacement surgery was not significantly more common in the heavily injected joints.

A strategy of frequent intraarticular steroid injection does not greatly increase, through added risk of joint replacement, the risk inherent in continued disease activity for patients with established RA. Frequent corticosteroid injection may offer some chondroprotection when the alternative is continuous disease activity.

Articular cartilage matrix synthesis and degradation are dynamic processes that must be balanced for proper maintenance of the tissue. In osteoarthritis (OA), this balance is skewed toward degradation and ultimate loss of matrix. The transcriptional and/or activity levels of hundreds of genes are dysregulated in chondrocytes from osteoarthritic cartilage, and a subset of these genes may represent pivotal factors that could be modulated if their specific role in the disease process could be identified. To investigate the role of ADAMTS-4 and ADAMTS-5 in cartilage matrix degradation by developing a chondrocyte pellet culture assay in combination with adenoviral gene expression, and to demonstrate the utility of this assay by assessing the specific functional contribution of these genes to cartilage matrix metabolism. A full-length cDNA for bovine ADAMTS-4 (bADAMTS-4) was isolated, and used to evaluate the expression, regulation, and activity of this gene in bovine cartilage. Adenoviruses expressing bADAMTS-4, human ADAMTS-5 (hADAMTS-5) or human bone morphogenetic protein 2 (BMP-2) were used to infect primary chondrocytes, and their effect on extracellular matrix metabolism was assessed by monitoring the accumulation and release of glycosaminoglycans (GAG) in three-dimensional chondrocyte pellet cultures. Analysis of bADAMTS-4 transcriptional regulation in chondrocytes revealed that interleukin-1alpha (IL-1alpha) was the most potent inducer of bADAMTS-4 mRNA and subsequent aggrecan degradation in cartilage explant cultures of those cytokines tested. bADAMTS-4 mRNA induction by IL-1alpha was greater in nasal cartilage than in articular cartilage. Chondrocytes infected with adenovirus expressing either bADAMTS-4 or hADAMTS-5 genes showed increased aggrecan degradation in newly synthesized matrix by pellet cultures while chondrocytes overexpressing BMP-2 showed increased aggrecan synthesis.

Adenoviral delivery of genes to primary bovine chondrocytes, followed by culture in three-dimensional pellet format and evaluation of extracellular matrix protein metabolism, is a useful functional assay for assessing the role of genes on cartilage matrix synthesis and degradation.

To compare 4 categories (high, moderate, and low severity, and near-remission) of RAPID3 (Routine Assessment of Patient Index Data 3), an index without formal joint counts, which is scored in < 10 seconds to 4 categories of the Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI) in patients with rheumatoid arthritis (RA). All patients complete a Multidimensional Health Assessment Questionnaire (MDHAQ) at each visit. A physician/assessor 28-joint count and erythrocyte sedimentation rate (ESR) were completed in 285 patients with RA in usual care by 3 rheumatologists to score DAS28, CDAI, and RAPID3. RAPID3 includes the 3 MDHAQ patient self-report RA Core Data Set measures for physical function, pain, and patient global estimate. Proposed RAPID3 (range 0-10) severity categories of high (> 4), moderate (2.01-4), low (1.01-2), and near-remission (< or = 1) were compared to DAS (0-10) activity categories of high (> 5.1), moderate (3.21-5.1), low (2.61-3.2), and remission (< or = 2.6), and CDAI (0-76) categories of > 22, 10.1-22.0, 2.9-10.0, and < or = 2.8. Additional RAPID scores, which add to RAPID3 a physician/assessor or patient self-report joint count and/or assessor global estimate, were also analyzed. Statistical significance was analyzed using Spearman correlations, cross-tabulations, and kappa statistics. All RAPID scores were correlated significantly with DAS28 and CDAI (rho > 0.65, p < 0.001). Overall, 78%-84% of patients who met DAS28 or CDAI moderate/high activity criteria met similar RAPID severity criteria, and 68%-77% who met DAS28 or CDAI remission/low activity criteria also met similar RAPID criteria. RAPID3 was as informative as other indices.

RAPID3 provides a feasible, informative quantitative index for busy clinical settings.

To clarify the correlation between primary gout and insulin-resistance (IR), and to observe the effect of serial gout granules (SGGs) on IR in patients with primary gout. Pearson's correlation analysis and multiple stepwise correlation analysis were conducted between 60 patients and 60 healthy volunteers in terms of blood pressure (BP), blood levels of uric acid (sUA), fasting plasma glucose (FPG), fasting insulin (FINS), fasting leptin (FL), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and C-peptide (CP), body mass index (BMI), waist-to-hip ratio (WHR), insulin resistance index (IRI) and insulin sensitivity index (ISI). Besides, the 60 primary gout patients were equally randomized into two groups, the treatment group treated with SGGs (huzhang gout granule and yinlian gout granule), and the control group treated with diclofenac sodium dual release enteric-coated capsules and Benzbromarone. bove-mentioned indexes in them were assessed before and after 12 weeks of treatment. The levels of sUA, FPG, TC, TG, LDL-C, FINS, CP, FL, IRI, BMI, and WHR were higher while the levels of HDL-C and ISI was lower in gout patients than those in healthy controls (all P < 0.05); Pearson's correlation analysis showed that level of sUA was positively correlated with levels of FPG, FINS, IRI, BMI, TC, TG, LDL-C, CP, FL, systolic pressure and diastolic pressure (r = 0.444, 0.496, 0.660, 0.542, 0.414, 0.467, 0.344, 0.470, 0.419, 0.275, 0.330 respectively, P < 0.05), but negatively correla- ted with levels of ISI and HDL-C (r = -0.569, -0.264 respectively, P < 0.05). Multiple stepwise correlation analysis showed that sUA was also positively correlated with IRI, TG and BMI (r = 5.758, 2.849, 3. 425 respectively, P < 0.05). After 12 weeks of treatment, the lowed range of TC, TG, FINS, FPG and IRI, and the increased amplitude of HDL-C and ISI in the treatment group were superior to those in the control group respectively (P < 0.05).

Patients with primary gout are low in insulin sensitivity and indicating the existence of IR. SGGs could enhance patients' insulin sensitivity and improve IR to a certain extent.

To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS). We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100). Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P<0.001), muscular (P<0.01), haematological (P<0.05), biological (P<0.05), history of arthritis (P<0.01), splenomegaly (P<0.05) and higher gamma globulin levels (P<0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P<0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS>50; 48.2%) and found that patients with dry skin had higher VAS pain (P<0.01) and drought (P<0.01) scores.

ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.

A patient self-administered questionnaire [PsA Screening and Evaluation (PASE)] has been developed and validated in English, but has not been tried in Spanish speaking populations. This study aimed to adapt and validate PASE in Spanish to screen Spanish speaking psoriasis patients for signs and symptoms of inflammatory arthritis. Initial translation from English to Spanish (forward translation) was performed by two independent translators and the resulting versions were synthesized during a consensus meeting. The questionnaire was tried in a pilot study and resulted in a change in the agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE-S)]. One hundred and eleven patients were screened with PASE-S; 25 with PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a dermatologist, and a rheumatologist determined the diagnosis of PsA or OA. Patients with PsA had statistically significant higher symptoms, function and total PASE-S scores compared with those without PsA. Receiver operator curves showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A cut-off value ≥34 showed sensitivity of 76%, and specificity of 74.4% for the diagnosis of PsA.

The validated PASE questionnaire is a self-administered tool that can be used to screen for PsA among patients with psoriasis in a Spanish speaking population. PASE was able to distinguish between symptoms of PsA and OA.

D prostanoid receptor 1 (DP1), a receptor for prostaglandin D The development of aging-associated OA and destabilization of the medial meniscus (DMM)-induced OA was compared between DP1-deficient (DP1 Compared to WT mice, DP1

These findings indicate a critical role for DP1 signaling in OA pathogenesis. Modulation of the functions of DP1 may constitute a potential therapeutic target for the development of novel OA treatments.

Albuminuria is a marker for subclinical cardiovascular disease (CVD) in the general population. It is uncertain whether this association is present in patients with rheumatoid arthritis (RA), a population with increased atherosclerosis and CVD events. Urine albumin from a spot morning collection was measured, and the urine albumin-to-creatinine ratio (uACR) was calculated for RA patients and a population-based sample of demographically matched non-RA controls. Associations of elevated uACR (≥25 mg/gm for women and ≥17 mg/gm for men) with CVD risk factors and measures of atherosclerosis (coronary artery calcification, ultrasound-determined maximal intima-media thickness of the common carotid artery and internal carotid artery [ICA], and the presence of focal plaque in the ICA) were compared cross-sectionally according to RA status. We compared 196 RA patients with 271 non-RA controls. Elevated uACR was found in 18% of the RA patients compared with 17% of the controls (P = 0.89). After adjustment, RA was associated with 57% lower odds of elevated uACR (P = 0.016). Higher serum creatinine levels and hypertension were both strongly and significantly associated with elevated uACR in the control group but not in the RA group (both P for interaction < 0.05). Among RA characteristics, the adjusted prevalence of elevated uACR among those treated with tumor necrosis factor inhibitors was less than half that among those not so treated (9% versus 20%, respectively; P = 0.047).

There was no association in the RA group of elevated uACR with measures of atherosclerosis or with several key cardiometabolic risk factors, which suggests a lower usefulness of elevated uACR as an indicator of subclinical CVD in RA.

Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are contradictory. To derive a more precise evaluation, a meta-analysis was performed. Published literatures comparing plasma/serum OPG, OCN and OPN levels between RA group and OA controls were searched in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I Nine studies including 438 RA patients and 255 OA patients were finally incorporated in the meta-analysis after examining title, type, abstracts and full text. The results showed that RA patients had higher plasma/serum OPN (pooled SMD = -2.57, 95% CI = -4.72 to -0.41) levels when compared to OA patients. No significant difference in plasma/serum OPG (pooled SMD = -0.29, 95% CI = -1.07‒0.49) and OCN (pooled SMD = -0.09, 95% CI = -0.48‒0.31) levels were found between RA patients and OA patients. Subgroup analysis indicated that plasma/serum OPG levels had no significant differences between RA patients and OA patients in Europe and Asian.

Overall, there is no significant difference in circulating OPG and OCN levels between RA patients and OA patients. However, plasma/serum OPN level is significantly higher in RA patients compared with OA patients.

Osteoarthritis (OA) is a common problem in older women that is associated with pain and disabilities. Although yoga is recommended as an exercise intervention to manage arthritis, there is limited evidence documenting its effectiveness, with little known about its long term benefits. This study's aims were to assess the feasibility and potential efficacy of a Hatha yoga exercise program in managing OA-related symptoms in older women with knee OA. Eligible participants (N=36; mean age 72 years) were randomly assigned to 8-week yoga program involving group and home-based sessions or wait-list control. The yoga intervention program was developed by a group of yoga experts (N=5). The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score that measures knee OA pain, stiffness, and function at 8 weeks. The secondary outcomes, physical function of the lower extremities, body mass index (BMI), quality of sleep (QOS), and quality of life (QOL), were measured using weight, height, the short physical performance battery (SPPB), the Pittsburgh Sleep Quality Index (PSQI), the Cantril Self-Anchoring Ladder, and the SF12v2 Health Survey. Data were collected at baseline, 4 weeks and 8 weeks, and 20 weeks. The recruitment target was met, with study retention at 95%. Based on ANCOVAs, participants in the treatment group exhibited significantly greater improvement in WOMAC pain (adjusted means [SE]) (8.3 [.67], 5.8 [.67]; p=.01), stiffness (4.7 [.28], 3.4 [.28]; p=.002) and SPPB (repeated chair stands) (2.0 [.23], 2.8 [.23]; p=.03) at 8 weeks. Significant treatment and time effects were seen in WOMAC pain (7.0 [.46], 5.4 [.54]; p=.03), function (24.5 [1.8], 19.9 [1.6]; p=.01) and total scores (35.4 [2.3], 28.6 [2.1]; p=.01) from 4 to 20 weeks. Sleep disturbance was improved but the PSQI total score declined significantly at 20 weeks. Changes in BMI and QOL were not significant. No yoga related adverse events were observed. ClinicalTrials.gov: NCT01832155.

A weekly yoga program with home practice is feasible, acceptable, and safe for older women with knee OA, and shows therapeutic benefits.

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc). Although pulmonary function tests (PFTs) are commonly used to screen for ILD in patients with SSc, studies have shown that they lack sensitivity for the detection of ILD in general SSc cohorts. This study was undertaken to assess the performance characteristics of PFTs for the detection of ILD in patients with early diffuse cutaneous SSc (dcSSc), a population at high risk for the development of ILD. We performed a retrospective cohort study of patients enrolled in the Prospective Registry of Early Systemic Sclerosis at 11 sites in the US between April 2012 and January 2019. Patients were included if they underwent spirometry and high-resolution computed tomography (HRCT) of the chest. We calculated the performance characteristics of PFTs for the detection of ILD on HRCT. The study included 212 patients, 54% of whom had radiographic ILD. For the detection of ILD on HRCT imaging, a forced vital capacity (FVC) <80% predicted had a sensitivity of 63%. The combination of FVC <80% predicted or diffusing capacity for carbon monoxide (DLco) <80% predicted improved the sensitivity to 85%. An FVC <80% predicted had a negative predictive value (NPV) of 61%, while the combination of FVC <80% predicted or DLco <80% predicted had an NPV of 70%.

PFTs alone are an inadequate screening tool for the diagnosis of ILD in patients with early dcSSc. HRCT should be part of the ILD screening algorithm in patients with dcSSc.

A patient with arthritis usually experiences the progression of symptoms over time. At some stage, the patient may decide that the symptoms have reached a level of severity that leads him or her to elect to proceed with joint replacement; we refer to this degree of symptom severity as the "tipping point." Our goal was to study the factors that influenced the tipping point for patients undergoing elective shoulder arthroplasty. We analyzed the characteristics of 931 patients undergoing shoulder arthroplasty to determine the factors affecting the tipping point as characterized by the patients' comfort and function at the time they determined their symptoms had progressed to the point when this elective surgery was merited. The preoperative Simple Shoulder Test (SST) score for all patients averaged 3.6 ± 2.7. The average tipping points were different for the ream-and-run procedure (mean SST score, 5.0 ± 2.5), hemiarthroplasty (mean SST score, 3.1 ± 3.3), total shoulder arthroplasty (mean SST score, 3.0 ± 2.4), cuff tear arthropathy arthroplasty (mean SST score, 2.8 ± 2.5), and reverse total shoulder arthroplasty (mean SST score, 1.5 ± 1.8). A number of other factors were significantly associated with a higher tipping point: younger age, better health, male sex, commercial insurance, married, nonuse of narcotics, use of alcohol, and shoulder problem not related to work.

Analysis of the tipping point-the patients' self-assessed comfort and function at the point they decide to undergo shoulder joint replacement-provides a means by which surgeons can understand the factors influencing the indications for these procedures.

Hemorrhagic arthritis (HA) is a common disease of the musculoskeletal system caused by hemorrhage in the joints, leading to damages in the synovium and cartilage. Pure platelet-rich plasma (P-PRP) has been recently demonstrated to have anti-inflammatory and regenerative potential attributed to the various cytokines and growth factors that it contains. The aim of this study was to investigate the efficacy of P-PRP for the treatment of patients with mild and severe HA. Autologous blood was withdrawn from the New Zealand rabbits and injected into their left and right knees to establish the HA models. The injection was performed once a week and repeated for 8 weeks to establish the mild HA models and for 16 weeks to establish the severe HA models. One hundred microliters of P-PRP was injected into the left HA knees, and the same volume of sterile 0.9% saline was injected into the corresponding right knees. MRI examination, H&E staining, and toluidine blue staining were respectively performed to evaluate the histological difference of synovium and cartilage between the P-PRP treated and untreated mild and severe groups. Normal knees were set as the control group. Pathological changes including tissue color, joint effusion, and synovium inflammation in the mild treated group were less severe compared to the other three experimental groups based on gross observation. The difference of joint cavity diameter between the mild treated and untreated groups was 2.67 ± 0.75 mm (95%CI, 1.20-4.14 mm), which was significantly larger than that between the severe treated and untreated groups (1.50 mm ± 0.48, 95%CI, 0.56-2.44 mm) (mean difference in joint cavity, 1.17 ± 0.32 mm; 95%CI, 0.49-1.85 mm; P < 0.01). MRI examination showed the synovitis and bone marrow edema were less severe in the treated groups compared to the corresponding untreated groups. H&E staining of the synovium suggested that the inflammation was much less and the cell number was much smaller in the treated than in the untreated HA knees in regard to both the mild and severe groups. The mean difference of cell number between the mild treated and untreated groups was 307.40 ± 14.23 (95%CI, 241.54-343.26; P < 0.001), which was 699.20 ± 82.80 (95%CI, 508.26-890.14; P < 0.001) between the severe treated and untreated groups. H&E staining and toluidine blue staining of the cartilage exhibited an obvious amelioration of inflammation and cartilage matrix loss after being treated with P-PRP for both groups, especially the mild group.

P-PRP was effective for the treatment of HA by inhibiting the development of synovitis and cartilage matrix loss in the affected joints, which was particularly obvious in the early-stage HA. This study supports the view that there is a great potential of P-PRP to be considered and used as a non-operative treatment for hemorrhagic arthritis at its early stage.

Mucormycosis (zygomycosis) is a rare, aggressive, invasive fungal infection that usually afflicts immunosuppressed patients. Indolent presentations are rare, especially in the setting of immune suppression. Case report and review of the pertinent English-language literature. A 64-year-old male patient with diabetes mellitus and rheumatoid arthritis, treated chronically with infliximab, presented with toothache, headache, and right facial numbness. Therapy with intravenous glucocorticoids and antibiotics resulted in transitory improvement before his referral to a tertiary-care center, where imaging studies and biopsy revealed rhinocerebral mucormycosis. Four weeks after initial presentation, a radical right maxillectomy, followed by long-term therapy with amphotericin B lipid complex, resulted in clinical improvement. Five reconstructive procedures were required to obliterate the facial defect and restore contour. Although biopsies during the reconstructive procedures revealed persistent fungal colonization, there was no clinical recurrence during nearly five years of followup.

Indolent rhinocerebral mucormycosis is rare and is seldom survived by immunosuppressed patients. Multimodal therapy with surgical debridement and antifungal chemotherapy is required for an optimal outcome. Discontinuance of immunosuppressive therapy, if possible, is a cornerstone of management.

Cross-sectional study. To evaluate the association between lumbar spine facet joint orientation, facet joint tropism, and spondylolysis identified by multidetector computed tomography (CT) in the community-based Framingham Heart Study. The association between lumbar spondylolysis and facet orientation and tropism remains unclear. This study was an ancillary project to the Framingham Heart Study. Three thousand five hundred twenty-nine participants of the Framingham Heart Study aged 40 to 80 years underwent multidetector CT imaging to assess aortic calcification. One hundred ninety-one subjects were included in this ancillary study. Facet joint features and spondylolysis were evaluated on CT scans. The final analyzed sample included 104 men with mean age 51.90+/-11.25 years and 84 women with mean age 53.61+/-10.20 years. The association between spondylolysis and facet orientation and tropism was examined using univariate and multivariate analyses. Spondylolysis was prevalent in 11.5% of the total population. chi2 test demonstrated a significant sex difference in prevalence of spondylolysis (P=0.0154), with almost 3 times higher prevalence among men. There was no statistically significant difference in facet orientation and continuous facet tropism between individuals with and without spondylolysis at the L5 level (P=0.49 to 0.91). After adjustment for age, sex, and body mass index, no significant association between the occurrence of spondylolysis and facet orientation and tropism was found. In the studied sample the prevalence of facet joint osteoarthritis was significantly higher in individuals with spondylolysis than in those without spondylolysis at both sides of L4-L5 spinal level (P=0.044 at the right side and P=0.003 at the left side) and at left side of L5-S1 level (P=0.038).

We did not find an association between facet orientation, facet tropism, and spondylolysis. One of the possible explanations for this is that the high prevalence of facet joint osteoarthritis in individuals with spondylolysis in the studied sample might have led to diminished differences in facet orientation.

To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02).

In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.

Aldehyde dehydrogenase 1 family member A1 (RALDH1)-producing dermal dendritic cells (DCs), a conventional DC subset regulating skin fibrosis, are decreased in the involved skin of patients with systemic sclerosis (SSc). In this study, we investigated the contribution of Fli1 deficiency, a potential predisposing factor of SSc, to the phenotypical alteration of RALDH1-producing dermal DCs by using SSc model mice and SSc skin samples. Bleomycin (BLM)-induced skin fibrosis was generated with Fli1 RALDH activity of dermal DCs was significantly decreased in BLM-treated Fli1

Fli1 deficiency inhibits RALDH1 activity of CD103

Fc receptors for IgG (FcyR) modulate immune responses. FcyR are expressed on various leukocytes and contain allelic polymorphisms with different capacity for IgG binding and phagocytosis. We investigated the distribution of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB polymorphisms in rheumatoid arthritis (RA) and whether they were related to disease expression and severity. Ninety-six controls and 114 patients fulfilling American College of Rheumatology (ACR) criteria for RA were genotyped for FcgammaRIIA, IIIA, and IIIB using polymerase chain reaction. Physician's global assessment of RA type estimated RA disease expression. In addition, usual measures of disease activity were recorded. The genotype and allele frequencies did not differ significantly between the RA patients and the controls. Patients homo or heterozygous for the FcgammaRIIA arginine (R) allele had significantly more aggressive RA and swollen joints than patients homozygous for the FcgammaRIIA histidine (H) allele. Although there was a tendency of more severe disease among patients homo or heterozygous for the FcgammaRIIIA valine allele, there were no significant findings with the disease activity for the FcgammaRIIIA and FcgammaRIIIB genotypes.

FcgammaRIIA is implicated as a possible disease modifying gene in RA. Individuals homozygous for the FcgammaRIIA R allele have less efficient binding of IgG2 subclasses than individuals homozygous for the H allele. Less effective processing of circulating immune complexes in RA patients homozygous for the FcgammaRIIA R allele may therefore contribute to a more unfavorable course.

To evaluate the cost effectiveness of TNF-alpha antagonist therapies for rheumatoid arthritis (RA) in the United Kingdom using data from the British Society for Rheumatology Biologics Registry (BSRBR). A simulation model is constructed to quantify the cost effectiveness of the TNF-alpha antagonist therapies (infliximab, etanercept and adalimumab) as a group versus traditional disease-modifying anti-rheumatic drugs, with a time horizon over the full patient lifetime. Participants are UK NHS patients in the BSRBR with RA who have failed at least two traditional disease-modifying anti-rheumatic drugs. The BSRBR aims to recruit all RA patients starting on a TNF-alpha antagonist agent and follows them 6 monthly via consultant and patient administered questionnaires. Data collected include disease activity scores (DAS28), the Health Assessment Questionnaire and the SF-36. Costs include drug, monitoring and hospitalisations. Benefits are measured in disability and quality of life improvements. The main outcome measure is the incremental cost per quality adjusted life-year gained (discounted). The basecase cost per quality adjusted life-year gained by using TNF-alpha antagonist therapies is estimated at pound23 882, with probabilistic uncertainty analysis suggesting that the probability that treatments are below 30,000 pounds per QALY is around 84%. The results are most sensitive to assumptions concerning long-term disability progression, discount rates and the validity or otherwise of SF6D derived utility measures. Subgroup analysis, monotherapy versus combination with methotrexate, and a limited analysis of sequential therapy with two TNF-alpha antagonist agents, suggest cost-effectiveness ratios around 20,000 pounds to 30,000 pounds.

The BSRBR data provide valuable evidence for estimating cost-effectiveness. The analysis concludes that current policies and practice for the use of TNF-alpha antagonist therapies, after RA patients have failed at least two traditional disease-modifying anti-rheumatic drugs, appear cost-effective in the context of the NICE re-appraisal of 2006 for England and Wales, thus supporting their decision to continue their reimbursement. Decision-makers worldwide might adapt this analysis because differential costs, discount rates and other factors could affect results. There remains uncertainty, particularly on long-term disease progression. Further data collection using the BSRBR is recommended, together with a revision to this analysis when data become available.

To identify the somatostatin receptor-expressing cells in rheumatoid synovium using a recently developed antiserum directed against the somatostatin receptor subtype 2A (sst2A). We carried out immunohistochemical studies of synovial biopsies from 7 patients with rheumatoid arthritis (RA) and one non-RA patient, using a rabbit polyclonal antiserum directed against sst2A and monoclonal antibodies directed against phenotypic markers. SSt2A was expressed by the endothelial cells of the synovial venules but also by a subset of synovial macrophages.

The identification of somatostatin receptors on macrophages, which are thought to be important effector cells in RA, may offer mechanistic insights into the potential therapeutic effect of somatostatin (analogs) in RA.

To investigate the effect of Qingre Huoxue decoction, (QRHX) on radiographic progression in patients with rheumatoid arthritis (RA) with X-ray imaging. From July 2007 to March 2009, 86 patients with active RA who were diagnosed as damp-heat and blood stasis syndrome were randomly divided into QRHX group and QRHX plus methotrexate (MTX) group, 43 cases in each group. Patients in the QRHX group were treated with QRHX decoction [composed of Huangbai, Chishao, Bixie, Danshen, Ezhu, Qingfengteng, raw Huangqi, Jinyinhua, Tufuling, Wugong, Fengfang, raw Yiyiren, which was cooked with water as 400 ml liquid); while patients in the other group were treated with QRHX decoction plus MTX. After one-year observation, 21 patients in each group (42 in total) were evaluated,with 19 females in QRHX group, average age of (43.0 +/- 11.3) years, and the course of the disease was 2 (1,3) years; and 18 females in QRHX+MTX group, average age of (44.5 +/- 14.0) years, and the course of the disease was 3 (1.7, 5) years. Radiographs of hands were obtained at baseline and 12 months after treatment. Images were evaluated by investigators blinded to chronology and clinical data, and assessed according to Sharp/van der Heijde methods. High intrareader agreements were reached (mean intraobserver intraclass coefficients: 0.95). No significant change in any imaging parameters of joint destruction was observed at 12 months after treatment in both groups; and there were no statistical differences between the two groups (P > 0.05). The severity of progress in two groups was also similar (P = 0.46), 7 patients without radiographic progress in QRHX group and 8 patients in QRHX+MTX group,3 patients with obvious radiographic progress in QRHX group and 1 patient in QRHX+MTX group.

Radiographic progress of RA patients in two groups is similar, indicating QRHX decoction has a potential role in preventing bone destruction.

The aim of this paper is to investigate sensitivity to change (SRM), predictive validity and discriminative ability of a quantitative (QS) and a semi-quantitative (SQS) Doppler ultrasound scoring systems in patients with rheumatoid arthritis (RA) treated with anti-TNF-α therapy. RA patients with wrist joint affection treated with TNF-α inhibitor were followed for one year. The wrist was examined with Doppler before initiating therapy and after one year. DAS28 was determined at both visits. One person trained in the SQS system and one in the QS system evaluated the anonymised images. The SRM, predictive validity and discriminative ability for both systems were calculated using DAS28 as the measure of disease improvement. Fourty-six patients with RA (80% females) were included. The mean Doppler activity at baseline was QS:24.4% (SD=17.7%) and SQS:2.0 (SD=0.6). A decrease in Doppler activity was seen for both systems after anti-TNF-α therapy. Sensitivity to change was seen, SRM=-0.52 (95%CI; -0.83 to -0.21; QS) and -0.24 (-0.53 to -0.05; SQS). Predictive value was poor (QS rs=-0.24; SQS rs=-0.05). Construct validity was; QS: rs=0.29, SQS: rs=0.23.

Both systems were to some extent sensitive to change. Predictive validity and discriminate capacity of both systems showed only a weak association to DAS 28 in the study population. The QS was a little superior to the SQS. The results do not necessarily reflect Doppler evaluation as being ineffective, but may be caused by DAS28 not being a perfect marker of inflammation.

Excess weight is a known risk factor for functional limitation and common in adults with knee osteoarthritis (OA). We asked to what extent high waist circumference was linked with developing difficulty with walking speed and distance over 4 years in adults with or at risk of knee OA. Using data from the Osteoarthritis Initiative (OAI), we employed World Health Organization (WHO) categories for Body Mass Index (BMI) and waist circumference (small/medium and large). Difficulty with speed was defined by slow gait: <1.2 m/s during a 20-m walk, and difficulty with distance was defined by an inability to walk 400 m. We calculated risk ratios (RR) to examine the likelihood of developing difficulty with distance and speed using obesity and waist circumference as predictors with RRs adjusted for potential confounders (i.e., age, sex, race, education, physical activity, and OA status). Participants with obesity and large waists were 2.2 times more likely to have difficulty with speed at 4 years compared to healthy weight and small/medium waisted participants (Adjusted RR 2.2 [95% Confidence interval (CI) 1.6, 3.1], P < .0001). Participants with obesity and a large waist circumference had 2.4 times the risk of developing the inability to walk 400 m compared with those with a healthy BMI and small/medium waist circumference (Adjusted RR 0.9 [95% CI 1.6, 3.7], P < .0001).

Waist circumference may be a main risk factor for developing difficulty with speed in adults with or at risk of knee OA.

Dickkopf-1 (DKK-1), an inhibitor of the Wnt pathway, has recently emerged as an important player in several critical aspects of bone biology. We performed an extensive internet search (MEDLINE) using the key words Dickkopf-1 and the abbreviation DKK-1. DKK-1 is a regulator of bone mass with increased expression linked to osteopenia and decreased expression to high bone mass. Moreover, it appears to actively participate in joint remodeling in animal models of arthritis, with increased levels related to bone resorption and decreased levels to new bone formation. Recent studies indicate its possible involvement in the remodeling process of human systemic rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis. DKK-1 may also play a role in osteoarthritis, metabolic bone disease (osteoporosis and Paget's disease), as well as multiple myeloma-associated bone disease and prostate cancer bone metastases.

DKK-1 is a regulator of bone mass and joint remodeling. It may be a promising therapeutic target in osteoporosis; monoclonal antibody-based inhibition of Dkk-1 is already under development for osteoporosis treatment. Its role as a regulator of joint remodeling in animal models requires further exploration in humans.

To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years.

Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage, and it may present with comorbidities at the systemic level. The Th1/Th2/Th17 CD4 Peripheral blood mononuclear cells (PBMCs) of RA patients and healthy donors were exposed to atorvastatin in different concentrations following a cytotoxicity assay. Th1, Th2, and Th17 cytokines profiles were evaluated in the culture supernatant by cytometric bead array (CBA). Data were analyzed using the Wilcoxon test, and differences were considered significant when p < 0.05. Atorvastatin showed no toxicity at the tested doses in RA PBMC cultures, and at 10μM, it showed the most significant results, reducing IL-17A (p = 0.002), TNF (p = 0.002), and IL-6 (p = 0.008) supernatant levels. The outcomes also revealed that only patients with more severe disease activity and those sensitive to corticoid treatments were responders to atorvastatin in vitro.

These findings suggest the potential immunomodulatory action of atorvastatin as a mechanism in rheumatoid arthritis treatment.

To evaluate racial and ethnic disparities in utilization of total knee arthroplasty (TKA) in relation to demographic, health, and socioeconomic status variables. Prospective study of 102,767 Women's Health Initiative postmenopausal women initially aged 50-79, examining utilization rates of primary TKA between non-Hispanic Black/African American, non-Hispanic White, and Hispanic/Latina women (hereafter referred to as Black, White, and Hispanic). A total of 8,942 Black, 3,405 Hispanic, and 90,420 White women with linked Medicare claims data were followed until time of TKA, death, or transition from fee-for-service coverage. Absolute disparities were determined using utilization rates by racial/ethnic group and relative disparities quantified using multivariable hazards models in adjusting for age, arthritis, joint pain, mobility disability, body mass index, number of comorbidities, income, education, neighborhood socioeconomic status (SES), and geographic region. TKA utilization was higher among White women (10.7/1,000 person-years) compared to Black (8.5/1,000 person-years) and Hispanic women (7.6/1,000 person-years). Among women with health indicators for TKA including diagnosis of arthritis, moderate to severe joint pain, and mobility disability, Black and Hispanic women were significantly less likely to undergo TKA after adjusting for age [Black: HR (95% confidence interval) = 0.70 (0.63-0.79); Hispanic: HR = 0.58 (0.44-0.77)]. Adjustment for SES modestly attenuated the measured disparity, but significant differences remained [Black: HR = 0.75 (0.67-0.89); Hispanic: HR = 0.65 (0.47-0.89)].

Compared to White women, Black and Hispanic women were significantly less likely to undergo TKA after considering need and appropriateness for TKA and SES. Further investigation into personal-level and provider-level factors that may explain these disparities is warranted.

In osteoarthritis (OA), changes occur in both cartilage and subchondral bone. The subchondral bone plate facilitates normal cross-talk between articular cartilage and trabecular subchondral bone, and adaptive changes in the plate due to OA may therefore disturb cross-talk homeostasis. To investigate these changes over time, we examined the cartilage-subchondral bone interface using a combined approach of histologic analysis and in vivo microfocal computed tomography. Sixteen-week-old male C57BL/6 mice (n=32) received intraarticular injections of collagenase in 1 joint to induce instability-related OA and received saline injections in the contralateral knee joint (control joint). At 2, 4, 6, 10, and 14 weeks after injection, changes in the tibial subchondral bone plate and subchondral trabeculae were analyzed. Two weeks after injection, collagenase-injected joints had significantly more cartilage damage and osteophytosis than did control joints. Osteoclast activity directly underneath the subchondral bone plate was significantly elevated in collagenase-injected joints compared to control joints (mean±SEM osteoclast surface/bone surface 11.07±0.79% versus 7.60±0.81%), causing the plate to become thinner and creating a large increase in subchondral bone plate porosity (mean±SEM cumulative porosity volume 0.05±0.04×10(-3) mm3 in control joints versus 2.52±0.69×10(-3) mm3 in collagenase-injected joints). Four weeks after injection, the previously formed perforations disappeared, coinciding with a significant rise in osteoblast activity in the subchondral trabecular bone in collagenase-injected joints compared to control joints (mean ± SEM bone formation rate/bone surface 0.62±0.13 μm3/μm2 per day versus 0.30±0.03 μm3/μm2 per day).

The current study is the first to provide quantitative longitudinal data on the dynamic changes in the subchondral bone plate after OA induction. The development of plate perforations may enhance mutual interaction between subchondral trabeculae, bone marrow cells, and the articular cartilage in OA.

Mutations in the TNFRSF1A gene, encoding tumor necrosis factor receptor 1 (TNF-R1), are associated with the autosomal dominant autoinflammatory disorder, called TNF receptor associated periodic syndrome (TRAPS). TRAPS is clinically characterized by recurrent episodes of long-lasting fever and systemic inflammation. A novel mutation (c.262 T > C; S59P) in the TNFRSF1A gene at residue 88 of the mature protein was recently identified in our laboratory in an adult TRAPS patient. The aim of this study was to functionally characterize this novel TNFRSF1A mutation evaluating its effects on the TNF-R1-associated signaling pathways, firstly NF-κB, under particular conditions and comparing the results with suitable control mutations. HEK-293 cell line was transfected with pCMV6-AC construct expressing wild-type (WT) or c.262 T > C (S59P), c.362G > A (R92Q), c.236C > T (T50M) TNFRSF1A mutants. Peripheral blood mononuclear cells (PBMCs) were instead isolated from two TRAPS patients carrying S59P and R92Q mutations and from five healthy subjects. Both transfected HEK-293 and PBMCs were stimulated with tumor necrosis factor (TNF) or interleukin 1β (IL-1β) to evaluate the expression of TNF-R1, the activation of TNF-R1-associated downstream pathways and the pro-inflammatory cytokines by means of immunofluorescent assay, array-based technique, immunoblotting and immunometric assay, respectively. TNF induced cytoplasmic accumulation of TNF-R1 in all mutant cells. Furthermore, all mutants presented a particular set of active TNF-R1 downstream pathways. S59P constitutively activated IL-1β, MAPK and SRC/JAK/STAT3 pathways and inhibited apoptosis. Also, NF-κB pathway involvement was demonstrated in vitro by the enhancement of p-IκB-α and p65 nuclear subunit of NF-κB expression in all mutants in the presence of TNF or IL-1β stimulation. These in vitro results correlated with patients' data from PBMCs. Concerning the pro-inflammatory cytokines secretion, mainly IL-1β induced a significant and persistent enhancement of IL-6 and IL-8 in PBMCs carrying the S59P mutation.

The novel S59P mutation leads to defective cellular trafficking and to constitutive activation of TNF-R1. This mutation also determines constitutive activation of the IL-1R pathway, inhibition of apoptosis and enhanced and persistent NF-κB activation and cytokine secretion in response to IL-1β stimulation.

The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline. RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant. 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.

Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events.

Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.

To analyse the current evidence for the management of lupus nephritis (LN) informing the 2019 update of the EULAR/European Renal Association-European Dialysis and Transplant Association recommendations. According to the EULAR standardised operating procedures, a PubMed systematic literature review was performed, from January 1, 2012 to December 31, 2018. Since this was an update of the 2012 recommendations, the final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including literature prior to 2012. We identified 387 relevant articles. High-quality randomised evidence supports the use of immunosuppressive treatment for class III and class IV LN (LoE 1a), and moderate-level evidence supports the use of immunosuppressive treatment for pure class V LN with nephrotic-range proteinuria (LoE 2b). Treatment should aim for at least 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (<500-700 mg/day) at 12 months (LoE 2a-2b). High-quality evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) as initial treatment of active class III/IV LN (LoE 1a). Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a). There is low-quality level evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease, all methods of kidney replacement treatment can be used, with transplantation having the most favourable outcomes (LoE 2b).

There is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment, but low-to-moderate quality evidence to guide treatment of class V LN, monitoring and optimal duration of immunosuppression.

Zonal T2 mapping and dGEMRIC (delayed gadolinium-enhanced magnetic resonance imaging of cartilage) are diagnostic quantitative techniques to evaluate the biochemical health of articular cartilage. We adapted these techniques to investigate the results of osteochondral allograft transplantation and correlated the findings with patient-reported outcomes. Nine patients with contained ICRS (International Cartilage Repair Society) grade-4 defects of the articular portion of a femoral condyle were treated with fresh osteochondral allografts and were evaluated prospectively with dGEMRIC and T2 mapping before and after gadolinium administration. The KOOS (Knee Injury Osteoarthritis Outcome Score) and IKDC (International Knee Documentation Committee) subjective scores were obtained at baseline and at one and two years postoperatively. For quantitative T2 mapping, regions of interest were drawn in the deep and superficial layers of allograft and control cartilage. For dGEMRIC analyses, the relaxation rate, post-gadolinium change in relaxation rate, and ratio between changes in the allograft and control regions of interest were calculated from T1 values. The mean ratio between the post-gadolinium changes in the allograft and control cartilage was 1.13 at one year and 1.55 at two years, and the ratio increased in eight of nine patients from one to two years. There was no difference between the mean T2 values in the deep zone of the allograft and control cartilage at one or two years (p > 0.05), but mean T2 values were higher in the superficial zone of the allograft cartilage at one (p < 0.0001) and two (p < 0.028) years. The mean improvement from baseline was significant at one and two years for the IKDC and all five KOOS subdomains (p < 0.05). All or nearly all patients showed improvements in all clinical outcomes scores at one year.

Functional MRI techniques can be applied to noninvasively assess the biochemical health of cartilage after osteochondral allograft transplantation. The MRI findings correlated with certain patient-reported outcomes in the early postoperative period. Relative glycosaminoglycan content and the collagen structure of allograft cartilage may undergo time-dependent degeneration. A patient's perception of clinical outcome and quality of life is likely multifactorial and is impacted by more than the health of the allograft cartilage.

The use of hip arthroscopy (HA) has substantially increased over the last decade. However, while the benefits of HA after 1 year in patients with femoroacetabular impingement (FAI) are well documented, long-term data on the progression of osteoarthritis (OA) or patient-reported outcomes (PROMs) are lacking. To evaluate long-term clinical and radiological outcomes after HA. Preoperative clinical records, operative notes, and radiographs from all patients who underwent HA at our hospital between 1998 and 2006 were reviewed. Exclusion criteria were previous hip surgery or diagnostic HA. Primary endpoints were subsequent total hip arthroplasty (THA) or other hip surgery. Secondary endpoints were OA progression and PROMs. HA was performed in 92 consecutive patients from 1998 to 2006. Indications for HA were FAI, labral lesions, early OA, and focal osteochondral defects. Mean follow-up was 11.2 years (SD 2.5, range 7.9-16). Data from 43 patients were available for analysis; 38 patients were excluded, and 11 were lost to follow-up. 20 patients had subsequent hip surgery, of which 11 patients required THA. 33 patients (77%) stated that they would undergo HA again under the same circumstances. Longitudinal radiological analysis showed no significant OA progression in patients without THA. The Forgotten Joint Score-12 was the only PROM to significantly differ between patients who had no further surgery and patients who had undergone revision (p = 0.037).

There was no significant OA progression on plain radiography at an average of 11 years post-HA. Sound indication criteria is essential, as 45% of patients required subsequent surgery.

Chronic inflammation of rheumatoid arthritis (RA) is associated with disturbances in muscle and bone metabolism. The purpose of this study was to investigate whether endocrine regulators of myogenesis and bone metabolism in patients with rheumatoid arthritis (RA) in remission differed from unaffected healthy controls. An additional point was whether these were associated with patients' health-related functioning or particular bodily functions of the International Classification of Functioning, Disability and Health (ICF). Bone turnover and the markers for muscle, i.e. myostatin (MSTN), follistatin (FSTN), growth differentiation factor (GDF-15) and for bone, i.e. sclerostin (SOST), dickkopf 1 (Dkk1), periostin (PSTN) metabolism were determined in 24 female RA patients and matched healthy controls. The chair rising test (CRT), timed up and go test (TUG), 6 min walking test, maximum hand grip and back extensor strength tests were used to assess patients' health-related functions. Additionally, bone mineral density of the lumbar spine and the hip region was measured. For the bone turnover markers no differences were observed between patients and controls. In contrast, the markers MSTN and Dkk1 were significantly lower and FSTN and PSTN significantly higher in patients than controls. Patients performed worse in the CRT and TUG. Some correlations reflected associations between these endocrine factors and physical function.

Anti-inflammatory therapy may be responsible for the positive effect on endocrine factors influencing myogenesis. Elevation of PSTN probably reflects the increased risk of fragility fractures in RA patients.

To test the validity of a second-generation appropriateness system in a cohort of patients undergoing total knee arthroplasty (TKA). We applied the RAND/UCLA Appropriateness Method to derive our second-generation system and conducted a prospective study of patients diagnosed with knee osteoarthritis in eight public hospitals in Spain. Main outcome questionnaires were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short-Form-12 (SF-12), and the Knee Society Score satisfaction scale (KSS), completed before and 6 months after TKA. Baseline, changes from baseline to 6 months (journey outcome), and 6-month scores (destination outcome) were compared according to appropriateness category. Percentage of patients attaining the minimal clinically important difference (MCID) and responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society (OMERACT-OARSI) criteria were also reported. A total of 282 patients completed baseline and 6-month questionnaires. Of these, 142 (50.4%) were classified as Appropriate, 90 (31.9%) as Uncertain, and 50 (17.7%) as Inappropriate. Patients classified as Appropriate had worse preoperative pain, function, and satisfaction (p < 0.001) and had greater improvements (i.e., journey scores) than those classified as Inappropriate (p < 0.001). At 6 months, destination scores for pain, function, or satisfaction were not significantly different across appropriateness categories. The percentage of patients meeting responder criteria (p < 0.001) and attaining MCID was statistically higher in Appropriate versus Inappropriate groups in pain (p = 0.04) and function (p = 0.004).

The validity of our second-generation appropriateness system was generally supported. The findings highlight a critical issue in TKA healthcare: whether TKA appropriateness should be driven by the extent of improvement, by patient final state, or by both.