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We assessed the level of maintained effectiveness and associated healthcare costs in stabilised rheumatoid arthritis (RA) patients who reduced doses of adalimumab or etanercept. Eligible patients were identified from a U.S. commercial insurance database using the following criteria: adults with ≥2 RA diagnoses; effectively treated on standard dose of adalimumab or etanercept for a 6-month baseline period; and ≥3 months of dose reduction within a 6-month assessment period following the index date (date of the first reduced dose). Effectiveness was estimated using a validated claims-based algorithm. Multivariate regression models were used to assess maintained effectiveness and healthcare costs in the short-term (months 7-12) and long-term (months 13-24) following the index date, while adjusting for baseline characteristics. Cost per patient maintaining effective treatment (CPME) was calculated as the average total healthcare costs divided by the proportion of patients with maintained effectiveness. Both groups (etanercept=375; adalimumab=610) had 70% females and a mean age of 48 years. Adjusted rates of maintained effectiveness for etanercept vs. adalimumab were 57.5% vs. 64.7% (p=0.028) in the short-term and 44.3% vs. 51.9% (p=0.047) in the long-term. Adjusted healthcare costs were similar for etanercept- and adalimumab-treated patients (short-term: $15,043 vs. $15,041; long-term: $31,461 vs. $30,449). The CPME was $2,915 higher with etanercept-treated patients in short-term and $12,349 higher in long-term compared with adalimumab-treated patients.

Among stabilised RA patients who reduced biologic dosing, a greater proportion of adalimumab-treated patients maintained effectiveness than etanercept-treated patients. Adalimumab was associated with a lower total CPME than etanercept.

Articular cartilage is the target tissue of osteoarthritis (OA), and because it lacks capillary networks, the microenvironment is hypoxic. Hypoxia inducible factor-1 alpha (HIF-1α) regulates the homeostasis of this tissue. The aim of this study was to investigate whether genetic polymorphisms of the HIF-1α signaling pathway are involved in the development of knee OA. We performed a case-control association study and genotyped 134 knee OA patients and 267 healthy controls. All participants were genotyped in order to evaluate 42 SNPs from 22 genes involved in the HIF-1α signaling pathway using the OpenArray technology. Gene-gene interactions (epistasis) were analyzed using the multifactor dimensionality reduction (MDR) method. The MDR analysis showed epistasis between AKT2 (rs8100018) and IGF1 (rs2288377), AKT2 (rs8100018) and IGF1 (rs35767), IGF1 (rs35767) and COL2A1 (rs1793953), and between GSK3B (rs6438552) and IGF1 (rs35767) polymorphisms, with information gain values of 21.24%, 8.37%, 9.93%, and 5.73%, respectively. Additionally, our model allowed us to identify high- and low-risk genotypes among COL2A1 rs1793953, GSK3B rs6438552, AKT2 rs8100018, and IGF1 rs35767 polymorphisms.

Knowing the interactions of these polymorphisms involved in HIF-1α signaling pathway could provide a new diagnostic support tool to identify individuals at high risk of developing knee OA.

To determine and illustrate the causes of unproductive arthrocentesis of the knee. Consecutive patients were studied who had inflammatory (rheumatoid or psoriatic) arthritis affecting the knees and experienced unproductive arthrocentesis during a randomized, controlled trial. Magnetic resonance imaging (MRI) was used, supplemented first by intravenous gadolinium contrast and subsequently by manual mixing of the diffused contrast to outline the furthest possible penetration of contrast within the joint cavity. In 4 out of 5 patients studied, failed arthrocentesis was due to combinations of inspirated joint fluid too viscous to be withdrawn or to mix with contrast, adipose tissue, and lipoma arborescens (thickened synovium with fat replacement). One MRI exam was normal. More free synovial fluid was imaged on the lateral side.

Failure to aspirate synovial fluid from the knee is explicable to anatomic terms; in particular, fluid viscosity and lipoma arborescens play a role in chronic effusions. Although surface anatomic landmarks for knee arthrocentesis may be more visible medially, the lateral approach is more likely to yield fluid for synovial analysis in difficult cases. Internal medicine trainees should be taught the lateral approach.

Utilization of unicompartmental knee arthroplasty (UKA) and patellofemoral arthroplasty (PFA) as alternatives to total knee arthroplasty (TKA) for unicompartmental knee osteoarthritis (OA) has increased. However, no single resource consolidates survivorship data between TKA and partial resurfacing options for each variant of unicompartmental OA. This meta-analysis compared survivorship between TKA and medial UKA (MUKA), lateral UKA (LUKA) and PFA using annual revision rate as a standardized metric. A systematic literature search was performed for studies quantifying TKA, MUKA, LUKA and/or PFA implant survivorship. Studies were classified by evidence level and assessed for bias using the MINORS and PEDro instruments. Annual revision rates were calculated for each arthroplasty procedure as percentages/observed component-year, based on a Poisson-normal model with random effects using the R-statistical software package. One hundred and twenty-four studies (113 cohort and 11 registry-based studies) met inclusion/exclusion criteria, providing data for 374,934 arthroplasties and 14,991 revisions. The overall evidence level was low, with 96.7% of studies classified as level III-IV. Annual revision rates were lowest for TKA (0.49%, CI 0.41 to 0.58), followed by MUKA (1.07%, CI 0.87 to 1.31), LUKA (1.13%, CI 0.69 to 1.83) and PFA (1.75%, CI 1.19 to 2.57). No difference was detected between revision rates for MUKA and LUKA (p=0.222).

Revisions of MUKA, LUKA and PFA occur at an annual rate of 2.18, 2.31 and 3.57-fold that of TKA, respectively. These estimates may be used to inform clinical decision-making, guide patient expectations and evaluate the cost-effectiveness of total versus partial knee replacement in the setting of unicompartmental OA.

Tendon disease is a significant global healthcare burden whereby patients experience pain and disability; however, the mechanisms that underlie inflammation and pain are poorly understood. Herein, we investigated the role of prostaglandins as important mediators of inflammation and pain in tissues and cells derived from patients with tendinopathy. We studied supraspinatus and Achilles tendon biopsies from symptomatic patients with tendinopathy or rupture. Tendon-derived stromal cells (CD45 Diseased tendon tissues showed increased expression of prostacyclin receptor (IP) and enzymes catalyzing the biosynthesis of prostaglandins, including cyclooxygenase-1 (COX-1), COX-2, prostacyclin synthase (PGIS), and microsomal prostaglandin E synthase-1 (mPGES-1). PGIS co-localized with cells expressing Podoplanin, a marker of stromal fibroblast activation, and the nociceptive neuromodulator NMDAR-1. Treatment with IL-1β induced release of the prostacyclin metabolite 6-keto PGF

Our results suggest that PGE

The purpose of this study was to assess the MRI features of the all-inside repaired meniscus in the long-term. Among 27 consecutive all-inside arthroscopic meniscal repairs, 23 patients aged 25 ± 5 years at the time of surgery were reviewed at a median follow-up of 10 ± 1 years. Retrospective clinical examinations and imaging assessments using a 1.5-T MRI after all-inside arthroscopic meniscal repair were conducted. At follow-up, Lysholm and IKDC averaged 89 ± 11 and 95 ± 8, respectively. MRI examinations revealed no meniscal signal alteration in three patients (13%), a vertical signal located in the previously torn area in seven (30%), a horizontal grade 3 in nine (39%), and a complex tear (grade 4) in four (17.5%). There were no differences between medial and lateral menisci (p = 0.15), stable and stabilised knees (p = 0.56).

Several abnormal vertical and/or horizontal hypersignals are still present on MRI examination ten years after arthroscopic all-inside meniscal repair. The appearance of early signs of osteoarthritis is rare, suggesting a chondroprotective effect of the repaired meniscus.

This study had a twofold aim: first, to gather knowledge about the prevalence of radiologic signs of temporomandibular joint osteoarthritis (TMJ-OA) and possible risk factors in patients who had worn an implant prosthesis for between 2.5 and 10 years; and second, to investigate the diagnostic value of radiologic TMJ-OA signs for orofacial pain in a non-temporomandibular disorders group. Two hundred thirty patients (134 women, 96 men) answered a questionnaire regarding orofacial pain. In mean, they were 64 years old and wore 98 fixed and 132 removable implant dentures. The effect of age, gender, state of the dentition, time span after prosthesis placement, parafunction, and TMJ sounds on radiologic TMJ-OA signs was estimated through multiple logistic regression. The predictive values were calculated to assess the diagnostic value of severe TMJ-OA signs to predict orofacial pain. Prevalence of TMJ-OA signs was 70% for flattening, 23% for osteophytes, and 24% for erosion. Some effect on radiologic TMJ-OA signs of gender and state of the dentition was found. The predictive values for orofacial pain from radiologic TMJ-OA ranged from 0.22 to 0.81.

Radiologic signs of TMJ-OA were common findings. The study gave no indication that long-term wearing of an implant prosthesis has a negative effect on TMJ-OA. It was not possible to predict orofacial pain from radiologic TMJ-OA signs.

To investigate whether Abatacept could regulate the occurrence and progression of rheumatoid arthritis (RA) by mediating cell migration of fibroblast-like synoviocytes (FLS) via mitogen-activated protein kinase (MAPK) pathway. Levels of MMP1, MMP3 and MMP13 in RA-FLS treated with Abatacept or MAPK pathway inhibitor were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The regulatory effect of Abatacept on MAPK pathway was detected by Western blot. Transwell assay was performed to access the role of Abatacept in regulating cell migration of RA-FLS. Abatacept treatment remarkably downregulated levels of MMP1, MMP3 and MMP13 in FLS, which were confirmed by qRT-PCR and ELISA. Migratory ability of FLS was inhibited by Abatacept treatment. Western blot results suggested that Abatacept treatment downregulated MAPK pathway-related genes in FLS. The effects of Abatacept on MMPs expressions and cell migration were partially reversed by SB203580 treatment, the MAPK pathway inhibitor.

Abatacept inhibits FLS migration and MMPs expressions via inhibiting MAPK pathway, thereby inhibiting RA development.

To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups.

To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

To examine the macroscopic vascular pattern of early synovitis in psoriatic arthritis (PsA), reactive arthritis (ReA), and rheumatoid arthritis (RA) and to assess the reliability of the grading features for synovitis. Forty-four patients (14 PsA, 12 ReA, and 18 RA) with knee synovitis who were undergoing arthroscopy were assessed. Video recordings of the examination were scored independently by 3 arthroscopists who were blinded to the patient's identity and clinical details. Features of vascularity, villous formation, pannus, granularity, and capillary hyperemia were recorded and kappa values (-1<kappa<1) were calculated to assess interobserver reliability. The interobserver reliability between experienced observers was high (kappa> or =0.8) for features of vascularity, villous hypertrophy, and pannus. Seventy-three percent of the PsA and ReA patients had predominantly tortuous, bushy vessels; 89% of the RA patients had mainly straight, branching vessels.

The distinct vascular patterns in PsA and ReA compared with those in RA may reflect different specific vascular factors in the pathogenesis of these arthritides. Vascularity and villous hypertrophy are the most reliable features of synovitis grading.

Resolvin D1 (RvD1), an important member of resolvins, exerts a wide spectrum of biological effects, including resolution of inflammation, tissue repair, and preservation of cell viability. The aim of the present study is to investigate the anti-arthritic potential and clarify the bone protective actions of RvD1 in vitro and in vivo. RAW264.7 cells were treated with 50 ng/ml LPS for 72 h in the presence or absence of RvD1 (0-500 nM). Primary human monocytes were treated with M-CSF + RANKL for 14 days ± RvD1 (0-500 nM) with or without siRNA against RvD1 receptor FPR2. Expressions of inflammatory mediators, degrading enzymes, osteoclasts (OC) formation, and bone resorption were analyzed. The therapeutic effect of RvD1 (0-1000 ng) was carried out in murine collagen antibody-induced arthritis. Arthritis scoring, joint histology, and inflammatory and bone turnover markers were measured. RvD1 is not toxic and inhibits OC differentiation and activation. It decreases bone resorption, as assessed by the inhibition of TRAP and cathepsin K expression, hydroxyapatite matrix resorption, and bone loss. In addition, RvD1 reduces TNF-α, IL-1β, IFN-γ, PGE

Our results provide additional evidence that RvD1 plays a key role in preventing bone resorption and other pathophysiological changes associated with arthritis. The study highlights the clinical relevance of RvD1 as a potential compound for the treatment of inflammatory arthritis and related bone disorders.

TNFalpha blockers have been shown to be highly efficacious in patients with active ankylosing spondylitis (AS). To identify parameters predicting the clinical response to TNF blockers in AS. Patients with active AS participated in two placebo controlled, randomised trials conducted in Germany with infliximab (n = 69) and etanercept (n = 30), respectively. For inclusion in either trial patients had to have high disease activity (BASDAI >or=4) and a spinal pain score (numerical rating scale 0-10) >or=4 despite treatment with NSAIDs. A major clinical response was defined as a 50% improvement of the initial BASDAI (BASDAI 50) after 12 weeks' treatment with active drug. Logistic regression likelihood ratio tests (univariate and multivariate), Student's t test, and chi(2) tests were performed. Univariate analysis showed the following to be predictors of a major response (BASDAI 50) to treatment: shorter disease duration (p = 0.003); lower BASFI (p = 0.007); younger age (p = 0.009); raised ESR (p = 0.033); raised CRP (p = 0.035). After adjustment for disease duration, BASFI, ESR, and CRP, but not age, remained significantly associated. After adjustment for disease duration and for BASFI, ESR, CRP, and in addition, a higher BASDAI were significantly associated with response. The best multivariate model built by stepwise regression contained the covariables disease duration, BASFI, BASDAI, and CRP.

A shorter disease duration, younger age, and a lower BASFI are predictors of a major clinical response to TNF blockers in active AS. Raised CRP and a higher BASDAI may also be valuable predictors. These data need to be confirmed in further studies.

The goal of the work was to evaluate the mid-term results of the Rubis II® trapeziometacarpal prosthesis for the treatment of basal thumb osteoarthritis. From 1997 to 2003, 118 trapeziometacarpal prostheses Rubis II® were implanted at Saint-Quentin's Hospital. Seventy-seven have been clinically and radiologically reviewed. The average follow-up was of 88 months. Sixteen patients were reviewed by phone. Fourteen patients were lost to contact and two died (13.5% of cases). Nine prostheses were removed (7.6% of cases). Among the reviewed prostheses, 76.6% of patients had no pain, the others had moderate pain. Postoperatively, the average opposition according to Kapandji's scale was 9.52. The average key-pinch force was similar on both sides. All reviewed patients were satisfied or very satisfied. No radiological loosening was noted. Nine removals were necessary; for post-traumatic dislocation in six cases, post-traumatic fracture of the trapezium in two cases, and inflammatory reaction with no infection in one case. The survival rate of the prosthesis was 93% at five years.

The Rubis II® prosthesis presents a satisfactory survival rate after five years and good clinical results. The design of the implant could explain the absence of loosening. The main risk of the Rubis II prosthesis seems to be the post-traumatic dislocation occurring mostly during the first two years after surgery.

To compare the analgesic effect of IM ketorolac tromethamine with that of oral indomethacin in the treatment of acute gouty arthritis. Prospective, randomized, double-blind, controlled, parallel group clinical trial. Two urban emergency departments. Twenty consecutive patients who presented to the ED with acute gout. Each patient was randomly assigned to receive in the ED (1) 60 mg of IM ketorolac and oral placebo or (2) 50 mg of oral indomethacin and IM placebo. The patients rated the intensity of their pain on a Wong-Baker pain scale (which runs from 0 to 5) before treatment and 30, 60, 90, and 120 minutes after treatment. All the patients were discharged with instructions to take oral indomethacin and to complete pain score cards at home at 6, 12, and 24 hours. The 10 patients in each group were similar with regard to age, sex, race, and initial mean pain score. After 2 hours, the mean pain scores (+/- SD) for the ketorolac group had decreased from 4.5 +/- .71 to 1.4 +/- 1.43 (P < .05), and the mean score for the indomethacin group had decreased from 4.4 +/- .70 to 1.5 +/- 1.18 (P < .05). The difference between the two groups was not significant. At 6 hours, there was some pain rebound in the ketorolac group.

IM ketorolac and oral indomethacin are similar in the relief of the pain of acute gouty arthritis in the ED.

Lead (Pb) is known to affect bone, and recent evidence suggests that it has effects on cartilage as well. As osteoarthritis (OA) is a highly prevalent disease affecting bone and cartilage, we undertook the present analysis to determine whether whole blood Pb levels are associated with radiographic and symptomatic OA (rOA and sxOA, respectively) of the knee. The analysis was conducted using cross-sectional data from the Johnston County Osteoarthritis Project, a rural, population-based study, including whole blood Pb levels, bilateral posteroanterior weight-bearing knee radiography and knee symptom data. rOA assessment included joint-based presence (Kellgren-Lawrence (K-L) grade 2 or higher) and severity (none, K-L grade 0 or 1; mild, K-L grade 2; moderate or severe, K-L grade 3 or 4), as well as person-based laterality (unilateral or bilateral). SxOA was deemed present (joint-based) in a knee on the basis of K-L grade 2 or higher with symptoms, with symptoms rated based on severity (0, rOA without symptoms; 1, rOA with mild symptoms; 2, rOA with moderate or severe symptoms) and in person-based analyses was either unilateral or bilateral. Generalized logit or proportional odds regression models were used to examine associations between the knee OA status variables and natural log-transformed blood Pb (ln Pb), continuously and in quartiles, controlling for age, race, sex, body mass index (BMI), smoking and alcohol drinking. Those individuals with whole blood Pb data (N = 1,669) had a mean (±SD) age of 65.4 (±11.0) years and a mean BMI of 31.2 (±7.1) kg/m2, including 66.6% women and 35.4% African-Americans, with a median blood Pb level of 1.8 μg/dl (range, 0.3 to 42.0 μg/dl). In joint-based analyses, for every 1-U increase in ln Pb, the odds of prevalent knee rOA were 20% higher (aOR, 1.20; 95% CI, 1.01 to 1.44), while the odds of more severe rOA were 26% higher (aOR, 1.26; 95% CI, 1.05 to 1.50, under proportional odds). In person-based analyses, the odds of bilateral rOA were 32% higher for each 1-U increase in ln Pb (aOR, 1.32; 95% CI, 1.03 to 1.70). Similarly for knee sxOA, for each 1-U increase in ln Pb, the odds of having sxOA were 16% higher, the odds of having more severe symptoms were 17% higher and the odds of having bilateral knee symptoms were 25% higher. Similar findings were obtained with regard to ln Pb in quartiles.

Increases in the prevalence and severity measures for both radiographically and symptomatically confirmed knee OA (although statistically significant only for rOA) were observed with increasing levels of blood Pb, suggesting that Pb may be a potentially modifiable environmental risk factor for OA.

The objective was to analyse the ability of Lactobacillus strains isolated from supragingival plaque of subjects with hyposalivation and from healthy controls to ferment sugars and sugar alcohols. Fifty strains isolated from interproximal plaque from subjects with radiation-induced hyposalivation (25 strains), subjects with primary Sjögren's syndrome (16 strains) and from subjects with normal salivary secretion rate (9 strains) were tested. Growth and pH were determined after 24 and 48 h of anaerobic incubation in vials containing basal media with 1 % of glucose, fructose, sucrose, mannitol, sorbitol or xylitol. No differences between strains isolated from hyposalivated subjects and controls were detected. All strains lowered the pH to <5.0 from fructose and the majority of the strains from glucose and sucrose. A pH of <5.5 was seen for 52 % of the strains using mannitol, 50 % using sorbitol and 36 % using xylitol. The ability to produce acids from sugars and sugar alcohols was highest among strains of Lactobacillus rhamnosus, Lactobacillus casei and Lactobacillus paracasei and lowest among Lactobacillus fermentum strains. Our findings suggest that products containing mannitol, sorbitol and/or xylitol may contribute to the acidogenic potential of the dental plaque and especially in hyposalivated subjects with high numbers of lactobacilli.

A large number of Lactobacillus strains are able to ferment not only sugars but also the sugar substitutes mannitol, sorbitol and xylitol to pH levels critical for enamel demineralisation.

Tolerogenic dendritic cells (tDCs) are immunosuppressive cells with potent tolerogenic ability and are promising immunotherapeutic tools for treating rheumatoid arthritis (RA). However, it is currently unknown whether allogeneic tDCs (allo-tDCs) induce tolerance in RA, and whether the numbers of adoptively transferred allo-tDCs, or the requirement for pulsing with relevant auto-antigens are important. tDCs were derived from bone marrow precursors of C57BL/B6 mice, which were induced in vitro by GM-CSF, IL-10 and TGF-β1. Collagen-induced arthritis (CIA) was modeled in D1 mice by immunization with type II collagen (CII) to test the therapeutic ability of allo-tDCs against CIA. Clinical and histopathologic scores, arthritic incidence, cytokine and anti-CII antibody secretion, and CD4(+)Th subsets were analyzed. tDCs were characterized in vitro by a stable immature phonotype and a potent immunosuppressive ability. Following adoptive transfer of low doses (5×10(5)) of CII-loaded allo-tDCs, a remarkable anti-arthritic activity, improved clinical scores and histological end-points were found. Serological levels of inflammatory cytokines and anti-CII antibodies were also significantly lower in CIA mice treated with CII-pulsed allo-tDCs as compared with allo-tDCs. Moreover, treatment with allo-tDCs altered the proportion of Treg/Th17 cells.

These findings suggested that allo-tDCs, especially following antigen loading, reduced the severity of CIA in a dose-dependent manner. The dampening of CIA was associated with modulated cytokine secretion, Treg/Th17 polarization and inhibition of anti-CII secretion. This study highlights the potential therapeutic utility of allo-tDCs in autoimmune arthritis and should facilitate the future design of allo-tDC immunotherapeutic strategies against RA.

Tibial proximal osteotomy is one of the treatments for patients with knee compartment osteoarthritis. Studies showed 80% good prognosis in five years follow up after osteotomy. Almost always this method is used for pure medial knee compartment osteoarthritis that has a varus deformity. THE AIM of all methods is reforming varus deformity and lower limb alignment to gain 3 to 5 degree extra reformation and take knee in 10 degree valgus. One of the main etiologies for patients inconvenience and no decreasing in their pain is overcorrection or undercorrection, but unfortunately these can't be noticed. Therefore we must make sure that additional stress on the medial joint line was eliminated and regeneration of cartilage was facilitated or at least occurrence of osteochondritis was decreased. So we aimed to determine the efficacy of tibial proximal osteotomy in lower limb alignment indexes in patients with osteoarthritis in medial compartment of knee. This study is a clinical trial study that has done in Alzahra University Hospital of Isfahan Medical Science University in Iran since June 2010 till February in 2011. Patients had pain, pure medial knee compartment osteoarthritis and varus deformities were determined for study. Patients who wouldn't come for control, those who had no convenience for giving their data or osteoarthritis of all three compartments were excluded from study. Number of patients has determined 40 persons according to previous studies. Sampling occurred convenient. Before any surgical processes, the AP x-ray radiography was applied for alignment view. The demographic and radiographic data was registered. Six months later we applied AP x-ray radiography again and obtained data and analysis them with SPSS software and T-Paired statistical method. The mean of anatomical limb angle before and after surgical process were 5.1 +/- 3.4 varus and 11.9 +/- 3.4 degree valgus, respectively,so with T-test there was a significant difference between them (P < 0.001). The mean of mechanical limb angle before and after surgical process were 12.6 +/- 3.4 varus and 4.75 +/- 3.5 degree valgus, respectively. Therefor with T-test, there was significant difference between them (P < 0.001).

Results were achieved from this study showed that Tibial proximal osteotomy is appropriate treatment for young and middle age patients with progressive deformity, symptomatic varus knee. Key words: Tibial proximal osteotomy, Knee, Osteoarthritis, Varus deformity.

Because juvenile idiopathic inflammatory myopathies (IIMs) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for juvenile IIM mortality. Mortality status was available for 405 patients (329 with juvenile dermatomyositis [DM], 30 with juvenile polymyositis [PM], and 46 with juvenile connective tissue disease-associated myositis [CTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMRs) were calculated using US population statistics. Cox regression analysis was used to assess univariable associations with mortality, and random survival forest (RSF) classification and Cox regression analysis were used for multivariable associations. Of 17 deaths (4.2% overall mortality), 8 (2.4%) were in juvenile DM patients. Death was related to the pulmonary system (primarily interstitial lung disease [ILD]) in 7 patients, gastrointestinal system in 3, and multisystem in 3, and of unknown etiology in 4 patients. The SMR for juvenile IIMs overall was 14.4 (95% confidence interval [95% CI] 12.2-16.5) and was 8.3 (95% CI 6.4-10.3) for juvenile DM. The top mortality risk factors in the univariable analysis included clinical subgroup (juvenile CTM, juvenile PM), antisynthetase autoantibodies, older age at diagnosis, ILD, and Raynaud's phenomenon at diagnosis. In multivariable analyses, clinical subgroup, illness severity at onset, age at diagnosis, weight loss, and delay to diagnosis were the most important predictors from RSF; clinical subgroup and illness severity at onset were confirmed by multivariable Cox regression analysis.

Overall mortality was higher in juvenile IIM patients, and several early illness features were identified as risk factors. Clinical subgroup, antisynthetase autoantibodies, older age at diagnosis, and ILD are also recognized as mortality risk factors in adult myositis.

Documentation on secondary prevention with statins in RA patients with coronary heart disease (CHD) is limited, despite the increased risk of CHD in RA. Our objective was to describe the effect of statin treatment on lipid levels and cardiovascular disease (CVD) events in patients with RA who participated in the incremental decrease in endpoints through aggressive lipid lowering (IDEAL) study. Patients with previous myocardial infarction (MI) were randomly assigned to atorvastatin 80 mg daily or simvastatin 20-40 mg daily and followed for 4.8 years. We focused on changes in lipid levels in the current exploratory analyses and used the composite secondary endpoint in the IDEAL study: any CVD event. Out of the 8888 patients in the IDEAL study, 87 had RA. RA patients had significantly lower baseline levels of total- and low-density lipoprotein (LDL) cholesterol than patients without RA; 4.8 + 1.0 vs 5.1 + 1.0 (P = 0.023) and 2.9 + 0.9 vs 3.1 + 0.9 mmol/l (P = 0.034) for total cholesterol and LDL, respectively. The lipid reductions with either simvastatin or atorvastatin were comparable. Cardiovascular events occurred in 23/87 (26.4%) of the RA patients compared with 2523/8801 (28.7%; P = 0.70) in the general IDEAL population. The occurrence of these events was not related to the duration of RA, age, gender or treatment assignment.

Patients with RA and previous MI had comparable lipid-lowering effect and similar rates of cardiovascular events as those without RA, although the RA patients had lower baseline cholesterol levels than patients without RA.

The treatment of painful osteoarthritis of the hip in cerebral palsy requires a therapy concept that considers the pathoanatomical features and adapts the treatment to the individual physical and mental abilities. Femoral head resection has been proven be effective in severely dislocated hip joints in completely immobilized patients, whereas no satisfactory outcome is achieved in those patients with sufficient walking ability and moderate expression of spasticity. The following study investigates the results of total hip replacement (THR) in patients with tetraspastic cerebral palsy. Between 1992 and 2004, 19 total hip arthroplasties were performed in 175 patients with an average follow-up of 4,6 years. In all patients the walking ability improved significantly; 84% of the patients were pain free. Aseptic loosening of the femoral component was registered in one patient. A periprosthetic fracture in another patient required the implantation of a modular non-cemented femoral component.

In this study total hip arthroplasty represents an important expansion of operative treatment options in secondary osteoarthritis of cerebral palsy in selected and cooperative patients. Taking the contradictions into consideration (severe athetosis, absence of adequate weight bearing, severe pelvic obliquity), THR promises to be an effective alternative to femoral head resection with significant pain reduction and improvement of walking abilities.

To investigate the relationship of psychological distress and associated factors with continuation of tumor necrosis factor (TNF) antagonist therapy in patients with rheumatoid arthritis (RA). Patients about to start therapy with TNF antagonists (n = 166) were assessed for psychological distress using the Hospital Anxiety and Depression Scale (HADS). A core set of demographic and clinical variables, including comorbidities from medical records and cigarette smoking history by questionnaire, were recorded at baseline and regular intervals thereafter. Cox proportional hazards regression analysis was used to assess the likelihood of patients discontinuing therapy over a 36-month followup period. The number of years smoked was associated with anxiety (HADS-A; p for trend = 0.008) and general psychological distress (HADS-Total; p for trend = 0.03). In univariate analyses, earlier discontinuation was associated with these variables at baseline: anxiety (HADS-A), depression (HADS-D), abnormal mood (HADS-Total), smoking history (> 30 pack-yrs), years smoked (> 30 yrs), current smoking, high Disease Activity Score 28-joint count (DAS28), poor patient global assessment, and evidence of cardio/cerebrovascular disease (CVD). In multivariate analyses, the strongest predictors of discontinuation were HADS-Total, smoking history (> 30 pack-yrs), DAS28, and evidence of CVD at baseline.

Discontinuation of therapy with TNF antagonists is independently associated with psychological distress, heavy smoking, and CVD at baseline.

This patient survey evaluated the return to previous sports activities in Swiss patients up to five years after reverse shoulder arthroplasty (RSA). We screened our local shoulder arthroplasty registry for patients registered with a unilateral RSA due to rotator cuff deficiency between May 2010 and May 2015. Revision cases and patients already known as unwilling or unable to complete a German language questionnaire were excluded. Eligible patients received a paper questionnaire asking about their past and current sports activities, return time point and level of activity. Of 305 patients, 89% responded at a mean post-operative follow-up of 2.9 years (SD 1.1). The respondents had a mean age of 77.1 years (SD 7.8) and included 62% females. The overall rate of patients returning to a previous sports activity was 77%. Sixty-one percent (166/271) participated in regular sports activities before the onset of their shoulder disorders. After RSA, 47% (127/271) participated in at least one sport type with the most frequent activities including hiking (66), swimming (53), cycling (45) and callisthenics (43). Most patients carried out their main sports activity after surgery with a moderate level of intensity (83%) and between one to three times per week (69%). Forty-two percent of the respondents indicated that returning to sports was among their key demands after RSA.

Returning to previous sports activities is an important expectation of RSA patients, and the majority do. Patient expectations of post-operative sports activity need to be addressed when planning RSA.

To investigate potential predictors of response to conventional DMARDs in RA. Study design - 6-month follow-up prospective study. RA patients with active disease. INTERVENTION AND FOLLOW-UP: Introduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria). Potential predictors of response, patients' demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response. Forty-two patients (mean age = 57 ± 13 years, mean disease duration = 5.4 ± 7.2 years) were included. MTX was given to 30. The response to therapy was predicted by the baseline serum level of TNF-α (mean = 30.2 pg/ml ± 18 in non-responders vs. 11.9 pg/ml ± 11.2 in responders). The threshold, which predicted with the best accuracy the response to treatment, was 20.1 pg/ml (sensitivity, specificity, positive and negative predictive values of 75, 78.9, 83.3, and 69.2%, respectively; AUC = 80.3%, 95% CI = 62.8-97.7%). Similar results were obtained in the subgroups of patients treated with MTX and patients with early RA of less than 3 years duration.

In the present work, the serum concentration of TNF-α was related to further response to DMARDs. Other works are needed for confirmation and to assess whether such biomarker could be used to predict the response to DMARDs at the individual level.

Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake. Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment. Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant.

Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.

To report a case of aseptic meningitis related to ibuprofen ingestion. We discuss the case of a 56-year-old white man with a history of rheumatoid arthritis and hypertension who became confused, nauseated, and began to vomit within 2 hours of the ingestion of ibuprofen. A diagnosis of ibuprofen-induced aseptic meningitis was made based on the patient's physical and laboratory findings, the quick onset and resolution of symptoms, and his medical history. Ibuprofen-induced aseptic meningitis has been most frequently reported in patients with systemic lupus erythematosus. However, there have been reports of this reaction in patients with other underlying disease states. Various nonsteroidal antiinflammatory drugs have been reported to cause this reaction, but ibuprofen is the most common offending agent. A drug-related cause should be considered in any patient who presents with typical meningitis symptoms, such as fever, headache, and stiff neck, that occur within hours of ingesting a drug.

Although persons with systemic lupus erythematosus appear to have an increased risk for this type of reaction, the development of signs and symptoms in other patients warrants the consideration of nonsteroidal antiinflammatory drugs as the cause of aseptic meningitis.

This paper aims to investigate women with primary Sjögren's syndrome (pSS) and sicca syndrome (SS), focusing on the prevalence of disease-related symptoms and their impact on sexual ability, relationship, communication about sexuality with partner and health professionals (HP). Sixty-two women with pSS and 33 with SS were assessed for sexual activity, relationship with partner, communication about sex; for physical disability and body esteem, fatigue, disability, quality of life (QoL), anxiety and depression. Around 55% patients had a relationship; >79% and around 70% at least 1 gynaecological (especially dryness), and 1 muscle-skeletal symptom, respectively; around 60% sex disability for disease-related symptoms, mainly dryness (p=NS for all comparisons between pSS and SS). In both groups, disease changed sexual activity (around 50%), causing limitation (around 50%) and reduced frequency (>80%) in sexual intercourses; sex pleasure and satisfaction were around 30% and 25% (p=NS for pSS vs. SS). Around 55% patients discussed with partner disease-effects on relationship; despite in around 70% partner understood difficulties, in around 34% disease altered relationship (p=NS for pSS vs. SS). Around 16% patients were asked by HP if disease affected sexuality, around 30% never approached anyone to discuss about sex (p=NS for pSS vs. SS). Disability, QOL, mood, fatigue, similar in pSS versus SS (p=NS), were not affected by xerostomia and xeroftalmia, but by sex concerns and sex disability.

Patients with pSS and SS present, often and at the same extent, gynaecological symptoms, leading to impaired sexual intercourse, affecting pleasure, satisfaction, sexual ability.

The purpose of this study is to answer the following clinical question: Among patients with temporomandibular joint (TMJ) osteoarthritis (OA), do those undergoing arthrocentesis and corticosteroid (CS) injection, when compared with those undergoing arthrocentesis alone, have better outcomes in terms of range of motion and clinical symptoms? A randomized clinical trial in adult patients with TMJ OA referred to our clinic between May 2012 and September 2013 was implemented. The sample was composed of 24 consecutive patients with TMJ OA treated randomly with either arthrocentesis alone (control group) or arthrocentesis plus CS injection (CS group). The outcome variables were visual analog scale evaluations (ie, masticatory efficiency, joint sounds, and pain complaints), maximal interincisal opening, and mandibular motions. The outcome variables were recorded at baseline and at 12 months postoperatively. The Mann-Whitney U test was used for intergroup comparison. The paired t test and Wilcoxon signed rank test were used for intragroup comparisons. The sample was composed of 32 joints in 24 patients with TMJ OA (15 joints in 12 patients with a mean age of 35.08 ± 14.84 years comprising the control group and 17 joints in 12 adult patients with a mean age of 32.58 ± 9.58 years comprising the CS group). Pain complaints and joint sounds showed statistically significant decreases (P < .01) in both groups, whereas painless interincisal opening showed a statistically significant increase (P < .001) in only the CS group. After estimation of differences between the follow-up and baseline outcomes, the mean change in the primary outcome variables showed no statistically significant differences between the 2 groups (P > .05).

These findings suggest that arthrocentesis plus intra-articular CS injection produced no better outcomes in terms of range of motion and clinical symptoms in patients with TMJ OA, as compared with those undergoing arthrocentesis alone.

To elucidate the role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA). We evaluated their expression and that of an activation marker on CD4+ cell populations and CD4+ cell subsets in specimens of peripheral blood (PB) and synovial fluid (SF) obtained from 10 patients with RA and 7 with osteoarthritis (OA). A 2 or 3-color immunofluorescent method was used for analysis. The SF from both groups of patients showed a greater density of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells, and a higher percentage of CD4+HLA-DR+ cells compared with their PB. IN PB-CD4+ cell subsets from the arthritic and healthy subjects, the CD4+CD45RO+ cell population showed an increased expression of adhesion molecules compared with CD4+CD45RA+ cell population. The expression of adhesion molecules on circulating CD4+ cell population and CD4+ cell subsets from the patients with RA and OA was comparable to that from healthy subjects. SF from both groups of patients showed a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In SF-CD4+ cell subsets from patients with RA, the CD4+CD45RO+ cell population had an increased expression of VLA-4 alpha compared to the CD4+CD45RA+ cell population; however, there was no significant difference in other adhesion molecule expression and the percentage of HLA-DR+ cells between the 2 cell subsets. Furthermore, the expression of VLA-4 alpha on the CD4+CD45RO+ cell population in SF from patients with RA was significantly higher than that in matched PB. In CD4+CD45RA+ cell population from both groups of patients, SF showed an enhanced expression of adhesion molecules and an increased percentage of HLA-DR+ cells compared with matched PB.

Our results suggest that increased expression of adhesion molecules and increased percentage of HLA-DR+ cells on CD4+ cells in SF may be responsible for cellular interactions between these cells and synovial cells or extracellular matrix.

Improving foot orthoses (FOs) in patients with rheumatoid arthritis (RA) by using in-shoe plantar pressure measurements seems promising. The objectives of this study were to evaluate (1) the outcome on plantar pressure distribution of FOs that were adapted using in-shoe plantar pressure measurements according to a protocol and (2) the protocol feasibility. Forty-five RA patients with foot problems were included in this observational proof-of concept study. FOs were custom-made by a podiatrist according to usual care. Regions of Interest (ROIs) for plantar pressure reduction were selected. According to a protocol, usual care FOs were evaluated using in-shoe plantar pressure measurements and, if necessary, adapted. Plantar pressure-time integrals at the ROIs were compared between the following conditions: (1) no-FO versus usual care FO and (2) usual care FO versus adapted FO. Semi-structured interviews were held with patients and podiatrists to evaluate the feasibility of the protocol. Adapted FOs were developed in 70% of the patients. In these patients, usual care FOs showed a mean 9% reduction in pressure-time integral at forefoot ROIs compared to no-FOs (p=0.01). FO adaptation led to an additional mean 3% reduction in pressure-time integral (p=0.05). The protocol was considered feasible by patients. Podiatrists considered the protocol more useful to achieve individual rather than general treatment goals. A final protocol was proposed.

Using in-shoe plantar pressure measurements for adapting foot orthoses for patients with RA leads to a small additional plantar pressure reduction in the forefoot. Further research on the clinical relevance of this outcome is required.

We evaluated the incidence of medial cortical fracture and influence on the loss of the correction angle in computer-assisted closing-wedge high tibial osteotomy. Using a navigation system, 200 closing-wedge high tibial osteotomies were performed. The correction angle was defined as the difference between the pre- and postoperative medial proximal tibial angles. The change in the medial proximal tibial angle was calculated as the difference between the medial proximal tibial angles two weeks and one year postoperatively. The medial cortical fractures of the osteotomy site were evaluated. Their incidence, risk factors, and influence on the loss of correction angle were analyzed. The incidence of non-displaced cortical breakage and displaced cortical fracture was 28.0% and 6.5%, respectively. Medial cortical fracture was more frequent in younger patients and patients with severe preoperative varus deformity. The average correction angle was significantly larger in the displaced cortical fracture group (9.6° vs. 12.7°, p<0.001). The average change in the medial proximal tibial angle in the no fracture, non-displaced cortical breakage, and displaced cortical fracture groups was 0.7°, 1.8°, and 4.4°, respectively (p<0.001). IV.

Medial cortical fracture could not be prevented in all knees, even using the navigation system. The risk of medial cortical fracture and loss of the correction angle was increased, particularly when a greater correction angle is required in young patients.

Anticitrullinating autoantibodies are specific markers for rheumatoid arthritis (RA). A functional haplotype of 4 exonic single-nucleotide polymorphisms (SNPs) in a citrullinating enzyme, peptidylarginine deiminase 4 (PADI4), was shown to be associated with susceptibility to RA in a Japanese population and was shown to increase the stability of PADI4 messenger RNA. However, the association was not confirmed in 4 subsequent studies involving Caucasian RA patients living in the UK, a French Caucasian population, and a Spanish population. The aim of the current study was to investigate the association of SNPs in the PADI4 gene with RA in a Korean population. Four exonic SNPs of the PADI4 gene (padi4_89, padi4_90, padi4_92, and padi4_104) were genotyped in 545 unrelated patients with RA and 392 controls, using the MassArray SNP genotyping system. Allelic, genotypic, and haplotypic associations of the SNPs with RA susceptibility were examined using the chi-square test and multivariate logistic regression analyses. Increased RA susceptibility was significantly associated with the minor alleles of padi4_89 (P = 2.3 x 10(-5)), padi4_90 (P = 2.3 x 10(-5)), padi4_92 (P = 2.1 x 10(-5)), and padi4_104 (P = 1.1 x 10(-3)) and the haplotype carrying the 4 minor alleles (P = 1.0 x 10(-4)). Genotypes carrying the minor alleles and HLA-DRB1 shared epitope (SE) alleles (P = 9.4 x 10(-21)) were also associated with increased RA susceptibility. The genotypic associations were sustained among individuals who did not carry any SE alleles, except in the case of padi4_104. Individuals carrying the risk SNPs and/or SE alleles were more susceptible to RA than were individuals carrying neither risk SNPs nor SE alleles.

The PADI4 SNPs and haplotypes are associated with RA susceptibility in Koreans. Thus, the association of PADI4 with RA may depend on genetic heterogeneity between Asians and Europeans.

To evaluate the effect of lid debridement-scaling (LDS) on dry eye signs and symptoms in subjects with Sjögren syndrome (SS). This prospective randomized controlled study enrolled 14 female subjects with SS. Seven subjects were randomized into the treatment group where they were selected to receive LDS; the remainder did not receive LDS and served as control subjects. Lid debridement-scaling was conducted using a stainless steel golf club spud (Hilco Wilson Ophthalmics, Plainville, MA) on both the upper and lower eyelids of both eyes. Outcome variables were assessed before LDS and again 1 month later. The outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) visual analog scores, ocular staining (SICCA OSS [Sjögren's International Collaborative Clinical Alliance Ocular Staining Score]), fluorescein tear breakup time (FLBUT), meibomian gland score (MGS), meibomian gland yielding liquid secretions (MGYLS) score, and line of Marx's (LOM) position. Thirteen subjects completed the study. Data from only the right eye were analyzed. For the control group (n = 6; mean [± SD] age, 62.3 [± 11.6] years), the pre-LDS, post-LDS, and significance level (pre-LDS mean [± SD] vs. post-LDS mean [± SD]; p value) were as follows: OSDI (58.3 [± 22.1] vs. 48.3 [± 29.0]; p = 0.051), SANDE (77.4 [± 22.1] vs. 89.6 [± 32.6]; p = 0.20), SICCA OSS (7.0 [± 4.5] vs. 8.2 [± 3.5]; p = 0.25), MGS (1.3 [± 1.5] vs. 1.0 [± 0.9]; p = 0.75), MGYLS (0.3 [± 0.5] vs. 0.0 [± 0.0]; p = 0.50), FLBUT (2.99 [± 1.54] vs. 2.85 [± 1.79]; p = 0.63), and LOM (2.0 [± 0.0] vs. 2.0 [± 0.0]; p = n/a). For the treatment group (n = 7; mean [± SD] age, 58.0 [± 8.1] years), the pre-LDS, post-LDS, and significance level were as follows: OSDI (63.2 [± 13.3] vs. 46.9 [± 19.4]; p = 0.04), SANDE (72.6 [± 17.1] vs. 77.0 [± 28.0]; p = 0.54), SICCA OSS (6.6 [± 2.9] vs. 5.0 [± 3.9]; p = 0.02), MGS (1.0 [± 1.2] vs. 3.1 [± 1.7]; p = 0.01), MGYLS (0.0 [± 0.0] vs. 0.6 [± 1.0]; p = 0.50), FLBUT (3.13 [± 0.81] vs. 3.45 [± 1.03]; p = 0.53), and LOM (0.9 [± 0.9] vs. 1.0 [± 1.0]; p = 1.00).

This pilot study showed that LDS improved symptoms, ocular staining, and meibomian gland function for the group that received LDS. This indicates that LDS can aid in the management of SS dry eye.

Rheumatologists traditionally have recommended to rheumatoid arthritis (RA) patients that they avoid dynamic and weight-bearing exercises because of concerns about aggravating joint inflammation and accelerating joint damage in such patients. These restrictions may lead to inadequate levels of physical activity and deconditioning. To review the literature on tolerance and benefits of conditioning training, including dynamic and weight-bearing activities in RA patients. Medline and Cochrane databases were searched with the keywords RA, rehabilitation, physical therapy, exercise, reconditioning, and rest. Rest therapy is more deleterious than beneficial in most patients with RA and may lead to deconditioning. Dynamic and aerobic exercises do not aggravate joint inflammation and do not accelerate joint damage in such patients. The important goal of reconditioning patients with RA is the prevention of functional decline. Conditioning programs designed to prevent widespread morbidities in healthy subjects are attainable by most RA patients, but an individualized approach to exercise is required.

RA patients need to be persuaded about the effectiveness and safety of moderate and even high-intensity exercise.

To describe the qualitative process used to develop attributes and attribute levels for inclusion in a discrete choice experiments (DCE) for older adult physical activity interventions. Five focus groups (n=41) were conducted, grounded in the Health Action Process Approach framework. Discussion emphasized identification and prioritization attributes for a DCE on physical activity. Semi-structured interviews (n=6) investigated attribute levels and lay-language for the DCE. A focus group with physical activity researchers and health care providers was the final stakeholder group used to establish a comprehensive approach for the generation of attributes and levels. A DCE pilot test (n=8) was then conducted with individuals of the target patient population. All transcripts were analyzed using a constant comparative approach. General community and university-based research setting. Volunteers (N=55) aged >45 years with knee pain, aches, or stiffness for at least 1 month over the previous 12 months. Not applicable. Interview guides, attributes, attribute levels, and discrete choice experiment. The most influential identified attributes for physical activity were time, effort, cost, convenience, enjoyment, and health benefits. Each attribute had 3 levels that were understandable in the pilot test of the DCE.

The identification of 6 physical activity attributes that are most salient to adults with knee osteoarthritis resulted from a systematic qualitative process, including attribute-ranking exercises. A DCE will provide insight into the relative importance of these attributes for participating in physical activity, which can guide intervention development.

Although caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, recent evidence suggests that this enzyme maintains functions beyond its role in cell death. As cells of the innate immune system, and in particular macrophages, are now at the forefront of autoimmune disease pathogenesis, we examined the potential involvement of caspase-8 within this population. Cre (LysM) Casp8 (fl/fl) mice were bred via a cross between Casp8 (fl/fl) mice and Cre (LysM) mice, and RIPK3 (-/-) Cre (LysM) Casp8 (fl/fl) mice were generated to assess the contribution of receptor-interacting serine-threonine kinase (RIPK)3. Immunohistochemical and immunofluorescence analyses were used to examine renal damage. Flow cytometric analysis was employed to characterize splenocyte distribution and activation. Cre (LysM) Casp8 (fl/fl) mice were treated with either Toll-like receptor (TLR) agonists or oral antibiotics to assess their response to TLR activation or TLR agonist removal. Luminex-based assays and enzyme-linked immunosorbent assays were used to measure cytokine/chemokine and immunoglobulin levels in serum and cytokine levels in cell culture studies. In vitro cell culture was used to assess macrophage response to cell death stimuli, TLR activation, and M1/M2 polarization. Data were compared using the Mann-Whitney U test. Loss of caspase-8 expression in macrophages promotes onset of a mild systemic inflammatory disease, which is preventable by the deletion of RIPK3. In vitro cell culture studies reveal that caspase-8-deficient macrophages are prone to a caspase-independent death in response to death receptor ligation; yet, caspase-8-deficient macrophages are not predisposed to unchecked survival, as analysis of mixed bone marrow chimeric mice demonstrates that caspase-8 deficiency does not confer preferential expansion of myeloid populations. Loss of caspase-8 in macrophages dictates the response to TLR activation, as injection of TLR ligands upregulates expression of costimulatory CD86 on the Ly6C(high)CD11b(+)F4/80(+) splenic cells, and oral antibiotic treatment to remove microbiota prevents splenomegaly and lymphadenopathy in Cre (LysM) Casp8 (fl/fl) mice. Further, caspase-8-deficient macrophages are hyperresponsive to TLR activation and exhibit aberrant M1 macrophage polarization due to RIPK activity.

These data demonstrate that caspase-8 functions uniquely in macrophages by controlling the response to TLR activation and macrophage polarization in an RIPK-dependent manner.

Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA. Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression. FLS from patients with RA were more invasive than FLS from patients with OA (P < 0.001). The mean intraindividual variation in FLS invasion was much less than the mean interindividual variation (mean +/- SD 1,067 +/- 926 and 3,845 +/- 2,367 for intraindividual and interindividual variation, respectively; P = 0.035), which shows that the level of FLS invasion is a patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P < 0.001).

The ex vivo invasive behavior of FLS from RA patients is associated with the rate of joint destruction and is a patient characteristic, given the much smaller intraindividual than interindividual FLS variation.

To evaluate changes in healthcare utilization, costs, and disease activity from 1996 to 2011 for patients with early rheumatoid arthritis (RA). Two cohorts of patients with early RA, included in 1996-1998 (T1) and 2006-2009 (T2), were followed regularly. Healthcare utilization, costs, and disease activity were compared between cohorts during 2 years after diagnosis. Disease activity was significantly improved in T2 vs T1. Drug costs increased in T2 vs T1 (EUR 911 vs EUR 535, respectively; p = 0.017), and costs for RA-related hospitalization decreased. More than 90% in T2 were prescribed disease-modifying anti-rheumatic drugs (DMARDs) at inclusion compared to 50% in T1. At 2 year follow-up, levels were still > 90% in T2, while corresponding values in T1 were just above 70%. Comparing T2 to T1, total direct costs were slightly higher in T2 (EUR 3941 vs EUR 3364, respectively; ns), sick leave decreased (EUR 3511 vs EUR 5672; p = 0.025), while disability pension increased slightly (EUR 4889 vs EUR 4244; ns), but total indirect costs remained unchanged (EUR 8400 vs EUR 9916; ns). Total direct and indirect costs did not differ between the cohorts (EUR 12 342 in T2 vs EUR 13 280 in T1; ns), and loss of productivity still represented the largest component of total costs.

T2 patients were prescribed DMARDs earlier and more aggressively than T1 patients. Stable and better improvements in disease activity, function, and quality of life were achieved in T2 compared to T1. There was a shift within the components in direct costs and indirect costs, but total costs remained essentially unchanged.

To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double-blind, placebo-controlled trial. Participants ages 40-70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change -1.66% versus -2.17%, between-group difference 0.50% [95% confidence interval (95% CI) -0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score -36.0 versus -29.5, adjusted difference -2.7 [95% CI -27.1, 21.7]; mean change in stiffness score -14.2 versus -11.8, adjusted difference -0.2 [95% CI -12.2, 11.8]; mean change in function score -89.4 versus -87.5, adjusted difference 0.3 [95% CI -83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs).

Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA.

To compare drug continuation rates in patients with rheumatoid arthritis who start on a biological agent and in a control group of patients with a change in disease modifying antirheumatic drug (DMARD) treatment after previous DMARD failure. Patients with rheumatoid arthritis enrolled in the German biologics register between May 2001 and September 2003 were included in the study. Data were available for 511 patients treated with etanercept, 343 with infliximab, 70 with anakinra, and 599 controls. Propensity scores were used to select a subsample of patients from the control group who were likely to be treated with biological agents because of their disease severity, as well as comparable infliximab and etanercept cases. Treatment continuation after 12 months was similar for etanercept (68.6% (95% confidence interval, 62% to 75%)) and infliximab (65.4% (58% to 73%)) but lower for anakinra (59% (41% to 77%)). Treatment continuation was more likely for patients on combinations of biological agents and DMARDs than for those on infliximab or etanercept alone. Patients treated with biological agents were more severely ill than those in the control group and had more previous DMARD failures. After adjustment for baseline differences, the continuation rates were higher in patients treated with biological agents than in comparable control patients treated with leflunomide or leflunomide/methotrexate.

Treatment continuation of biological agents in clinical practice is less likely than in randomised clinical trials but more likely than in comparable controls treated with conventional DMARDs.

The Australian Canadian Osteoarthritis Hand Index (AUSCAN), Michigan Hand Outcomes Questionnaire (MHQ), and the Sequential Occupational Dexterity Assessment (SODA) are assessments of hand function. Investigation of psychometric properties, administration, acceptability, and content of an assessment add strength to the findings of research and treatment. We evaluated the validity and reliability of the AUSCAN, MHQ, and the SODA for assessing disability in patients with rheumatoid arthritis (RA). Sixty-two patients with RA completed the AUSCAN (visual analog scale version), the MHQ, and the SODA. Seventeen patients repeated the assessments within one week. The assessments recorded high variability within the sample of 62 patients with RA. The AUSCAN and MHQ provided patient and context-specific information, while the SODA provided more impairment information that could be readily compared between patients. Seventeen patients were tested twice within 5 days, showing good reliability of all assessments. Unlike the MHQ, AUSCAN and SODA do not provide information about individual hands or hand dominance. The physical function scales of the AUSCAN and the SODA were related (r = 0.81), and the AUSCAN and MHQ pain scales were related (r = 0.68).

Clinicians and researchers should decide whether impairment, ability, or handicap outcome is the goal of assessment, and whether bilateral function or the function of one hand is of interest before choosing a hand assessment. The AUSCAN and MHQ are valid and reliable for assessment of hand disability in patients with RA, and they allow the patients to answer questions about their home environment. The SODA is also valid and reliable for assessing disability in a clinical situation that cannot be generalized to the home.

To determine if patients with gout with chronic alcoholism have lower serum urate levels than nonalcoholic patients. Of 95 consecutive consults for acute gout at a VA medical center, 42 were excluded from study due to lack of crystal documentation, lack of urate value within 2 years, or treatment with allopurinol or probenecid. The remaining 53 patients were grouped by alcohol use and a retrospective chart review was done for these patients. Mean intercritical serum urate values for chronic alcoholics and nonalcoholics were similar at 9.7 +/- 2.1 for alcoholics and 9.5 +/- 2.1 for nonalcoholics. Yet, despite these similar intercritical serum urate values, and despite no difference between chronic alcoholics and nonalcoholics in frequency or severity of acute gout flares, patients with chronic alcoholism had index serum urate levels which were significantly lower than those of nonalcoholics. These mean index values, with standard deviations, were 7.7 +/- 1.3 for 15 chronic alcoholics and 10.1 +/- 1.3 for 34 nonalcoholics; p < 0.01).

Alcoholics and nonalcoholics had comparable intercritical values. However, on presentation with acute arthritis, the index serum urate values for alcoholics were lower than in nonalcoholics. Values for serum urate below 8.5 mg/dl are of less value in excluding gout in chronic alcoholics than in nonalcoholics presenting with acute gout flares.

The purpose of this study is to evaluate systemic disease activity of pediatric Sjögren's syndrome (SS) using European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). We retrospectively reviewed medical records of patients with SS who have been diagnosed according to 1999 Japanese diagnostic criteria for SS before 16 years old at KKR Sapporo Medical Center, Hokkaido University Hospital, and affiliated hospitals. We analyzed clinical and laboratory data and calculated ESSDAI at both diagnosis and peak activity. Twenty-five patients (2 boys and 23 girls) were enrolled. Only 4 patients had sicca symptoms at diagnosis. Mean ESSDAI scores at diagnosis and peak activity were 12.68 (2-31) and 15.08 (2-38), respectively. Only 3 patients were inactive (ESSDAI score <5) at diagnosis. Frequently involved domains at diagnosis were the biological (96%) followed by the constitutional (68%), glandular (44%), articular (44%), cutaneous domains (28%), renal (16%), and central nervous system (12%). At peak activity, biological domain (96%) was followed by the constitutional (72%), glandular (60%), articular (44%), cutaneous (28%), central nervous system (20%), and renal domains (16%).

Pediatric SS is suspected from active systemic manifestations. The items of ESSDAI are useful clues to the diagnosis of pediatric SS.

Exposure to inhaled mineral dust, in particular silica, is associated with increased odds of rheumatoid arthritis (RA) and other autoimmune diseases. We studied the association of RA with work-related coal and silica exposure in the Appalachian region of the US. We carried out a random-digit dialed telephone survey in selected counties in Appalachia that had elevated coal workers' pneumoconiosis mortality. Our study cohort included men ages ≥50 with any employment history, and we assessed exposure to coal mining employment, other work-related dust, and ergonomic factors. We ascertained self-reported physician diagnosis of any arthritis and of RA with glucocorticoid treatment. We used multivariable logistic regression analysis to estimate the odds ratios (ORs) and associated population attributable fraction (PAF) estimates. Among the 973 men who met study entry criteria (mean ± SD ages 66 ± 10 years; 54% ever smokers), 266 (27%) reported coal mining work and 189 (19%) reported other work-related silica exposure. There were 517 men (53%), who reported any arthritis and 112 (12%) whose disease met the study definition of RA. Adjusting for covariates, coal mining was associated with elevated odds of RA (OR 3.6 [95% confidence interval (95% CI) 2.1-6.2]), which accounted for a PAF of 33% (95% CI 26-40%) of the men studied. For any arthritis, the coal mining-associated OR was 2.3 (95% CI 1.6-3.2), with an associated PAF of 20% (95% CI 14-25%).

In this population of older males living in a coal mining region, we estimated that 20% of arthritis and 33% of RA may be attributable to coal mining work.

There are substantial differences in accessibility to biological disease modifying antirheumatic drugs (bDMARDs) across countries. The objective of this study was to analyse the impact of patient demographics, disease characteristics and gross domestic product (GDP) on abatacept (ABA) retention in patients with rheumatoid arthritis (RA) treated in clinical practice. Data from nine European observational RA cohorts of patients treated with ABA were pooled. Kaplan-Meier analysis was used to compare drug retention across registries. Specific causes of drug retention were investigated using competing risks multivariate Cox regression. A total of 3961 patients treated with ABA, with 6188 patient-years of follow-up, were included. Patients in the different national registries had similar demographic features, but varied in baseline disease characteristics. ABA drug retention differed between countries, with median drug retention rates ranging from 1.2 to more than 6 years. The differences in drug retention were marginally explained by disparities in disease characteristics, while the national GDP per capita was strongly associated with drug retention (correlation coefficient -0.74; p=0.02).

Patient characteristics at ABA initiation vary across Europe, probably reflecting differences in eligibility criteria and prescription patterns. However, the difference in ABA drug retention between countries was not primarily explained by disparities in patient characteristics. Lower ABA retention was observed in countries with a more liberal access to bDMARDs and higher GDP. National differences need to be accounted for when pooling data on treatment with bDMARDs from various countries.

Telemedicine has been proposed to improve access to care in rheumatology, but few studies of tele-rheumatology have been published. The objective of this study was to evaluate outcomes and quality of care for rheumatoid arthritis (RA) in patients seen by video telemedicine follow-up compared to in-person only. Individuals in the Alaska Tribal Health System with a diagnosis of RA were recruited when seeing a rheumatologist either in-person or by video telemedicine, both of which were offered as part of usual follow-up care. At baseline, participants completed the RAPID3 and a telemedicine perception survey and agreed to medical record review. Participants repeated surveys by telephone at 6 and 12 months, and medical record abstraction was performed at 12 months for quality measures. At the 12-month outcome assessment, 63 of 122 RA patients (52%) had ever used telemedicine for RA. In univariate analysis, functional status improved over 12 months in the telemedicine group. In multivariate analysis, RAPID3 and functional status were associated with telemedicine group (higher), with no statistically significant change over the 12-month period. The only quality measure that differed between groups at 12 months in univariate analysis was the proportion of visits in which disease activity was documented (higher in the in-person group, 40% vs. 25%, p=0.02), but this was not significant after multivariate analysis.

In short-term follow-up, there was no significant difference in most outcome and quality measures in patients with RA who incorporated telemedicine follow-up in their care compared to in-person only.

To determine how professional characteristics and practices of physicians alter the selection of medical treatments involving multiple alternatives. Situations involving multiple alternatives can increase the difficulty of making a decision, resulting in more choice deferral than when fewer alternatives are available. A survey and scenario were mailed to a random sample of 314 primary and emergency care physicians affiliated with the Indiana University Medical Center. Using a scenario involving treatment decisions for a patient with osteoarthritis, the effects of multiple treatment alternatives on decision making were explored. Other physician factors included experience, workload, fatigue, continuing education, and supervision. Physicians' treatment decisions. Physician response was 61% (n = 192). In contrast to previous studies, physicians in the present study were equally likely to prescribe a new medication, regardless of whether they were deciding about 1 medication or between 2 similar medications (54.5% v. 56.0%, P = 0.841). However, physicians who supervise medical students were far less influenced by the cognitive bias associated with multiple choices than those who did not supervise medical students. Supervising physicians were more likely to defer making a decision when there was only 1 treatment option than when there were 2 (49.3% v. 37%, P = 0.143), whereas the opposite was true for nonsupervising physicians (33.3% v. 63%, P = 0.040). The number of hours spent supervising medical students and the number of years as a physician were also important factors in the decision-making process.

Multiple treatment alternatives may result in a deferral of choice. However, this cognitive bias is attenuated by experience and supervision, thus enhancing decision making. Implicit and explicit learning gained through experience and the supervisory process appears to be a central mechanism by which the physicians are protected from this cognitive bias.

A recent trend in the field of primary knee osteoarthritis suggests that elastic tape (e.g., K-tape) relieves pressure on the joint by increasing tension on fascia. Elastic tape (ET) is expected to decrease pain and help patients to recover faster. This systematic review aims to analyze the efficacy of this method on pain in patients with knee osteoarthritis by using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for reporting systematic reviews of qualitative and quantitative evidence, we used 3 electronic databases, PubMed, Cochrane, and EBSCO, and grey literature was included. Articles were screened for duplicates, screened for inclusion and exclusion criteria, and critically appraised. People older than 45 years old with primary osteoarthritis (OA) and application of ET. 2005 Oxford standard. Amongst all the papers found, 6 Randomized Control Trials (RCT) for a total of 392 participants met the criteria and were included in our review. Three papers out of the 6 RCT had low risks of bias. When the ET was compared to sham taping, the results show no to moderate decreases of WOMAC scores in patients with primary knee osteoarthritis. We focused on a single index test (WOMAC) and could not perform meta-analyses.

Although ET does not provide strong adverse outcomes, our data do not support the use of ET as a treatment alone because of too slight reductions of the WOMAC score for reaching clinical efficiency. Thus, our systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis.

Total hip arthroplasty (THA) is a challenging option for the treatment of posttraumatic arthritis due to acetabular fractures. The study aimed to determine the short- and mid-term clinical and radiographic results of THA following acetabular fracture. The fracture pattern, the extent of injury and the initial fracture treatment were considered to evaluate the influence of these factors on the clinical-radiographic outcome. 67 patients who received THA for the treatment of posttraumatic osteoarthritis after acetabular fracture between January 2007 and December 2012 were analyzed consecutively. The group consisted of 13 female (19%) and 54 male (81%) patients with a mean age of 59 (25-87) years at the time of THA. The time between acetabular injury and arthroplasty was 107 (1-504) months on average. The all-cause 8-year survival rate was 0.87% (0.76-0.93) and there were 8 revisions, half of them were due to aseptic loosening of the cup. The Harris Hip Score achieved was 75.7 ± 21.3 (26.9-100) points. Prior to THA, heterotopic ossifications were detected in 28% and after THA implantation in 42%.

The decrease of the interval between injury and arthroplasty was associated with increasing patient age (p = 0.001) and surgical treatment of the acetabular fracture (p = 0.04). Complex fracture patterns were accompanied by acetabular bone defects more often than simple patterns (p = 0.03). Overall, arthroplasty due to posttraumatic osteoarthritis after acetabular fracture resulted in decreased overall survival rates and poorer clinical outcome as compared to primary arthroplasty.

To determine whether systemic inflammation is associated with poor proprioception; to confirm that systemic inflammation is associated with muscle weakness; and to determine whether poor proprioception mediates the association between systemic inflammation and muscle weakness in knee osteoarthritis. Cross-sectional study. A total of 689 participants with knee osteoarthritis from the Amsterdam Osteoarthritis (AMS-OA) cohort. Systemic inflammation was assessed by erythrocyte sedimentation rate, knee proprioception by determining the joint motion detection threshold, and muscle strength with an isokinetic dynamometer. Linear regression models were used to estimate direct associations between systemic inflammation, proprioception and muscle strength, and the indirect association (mediation) between systemic inflammation and muscle strength via proprioception adjusted for potential confounders. Higher erythrocyte sedimentation rates were associated with poor proprioception (p = 0.022). Poor proprioception (p < 0.001) and higher erythrocyte sedimentation rates (p < 0.001) were associated with muscle weakness. Poor proprio-ception mediated the association between systemic inflammation and muscle weakness (p = 0.035).

Results suggest that systemic inflammation is associated with poor proprioception in knee osteoarthritis. Poor proprioception may be a path-way through which systemic inflammation is associated with muscle weakness in patients with knee osteoarthritis.

To study the association between baseline vitamin D status, bone mineral density (BMD), and the development of radiographic osteoarthritis (ROA) of the knee in a large population-based cohort of men and women. A sample of 1248 subjects (728 women and 520 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. At baseline, vitamin D dietary intake was determined, and BMD and 25-hydroxy vitamin D (25(OH)D) serum levels were measured. After a mean follow-up time of 6.5 years incidence and progression of knee ROA of was assessed. The mean vitamin D intake in our study population was 64 IU/d and the mean 25(OH)D level 66 nmol/L. Vitamin D levels were associated with baseline BMD, particularly in subjects with baseline knee ROA. Progressive ROA occurred in 5.1% of the participants in the highest tertile of vitamin D intake against 12.6% in the lowest tertile, resulting in an adjusted odds ratio of 7.7 (95% CI: 1.3-43.5). Both intake and levels of 25(OH)D were not significantly related to incident ROA. However, we found a significant interaction between vitamin D intake and BMD in the association with incident knee ROA (P = 0.03): in subjects with low lumbar spine BMD at baseline we observe an increasing incidence of knee ROA with decreasing vitamin D intake and serum levels.

Low dietary vitamin D intake increases the risk of progression of knee ROA. Particularly in subjects with low baseline BMD, vitamin D status seems to influence the incidence and progression of knee ROA. Thus, improving the vitamin D status in the elderly could protect against the development and worsening of knee OA, especially in those with low BMD.

This guideline revises the 2008 Royal Dutch Society for Physical Therapy guideline for physical therapy for patients with rheumatoid arthritis (RA). This revised guideline was developed according to the Appraisal of Guidelines for Research and Evaluation tool and the Guidelines International Network standards. A multidisciplinary guideline panel formulated clinical questions based on perceived barriers in current care. For every clinical question, a narrative or systematic literature review was undertaken, where appropriate. The guideline panel formulated recommendations based on the results of the literature reviews, the values and preferences of patients and clinicians, and the acceptability, feasibility, and costs, as described in the Grading of Recommendations Assessment, Development and Evaluation evidence-to-decision framework. The eventual guideline describes a comprehensive assessment based on the International Classification of Functioning, Disability and Health Core Set for RA. It also includes a description of yellow and red flags to support direct access. Based on the assessment, 3 treatment profiles are distinguished: (1) education and exercise instructions with limited supervision, (2) education and short-term supervised exercise therapy, and (3) education and intensified supervised exercise therapy. Education includes RA-related information, advice, and self-management support. Exercises are based on recommendations concerning the desired frequency, intensity, type, and time-related characteristics of the exercises (FITT factors). Their interpretation is compliant with the individual patient's situation and with public health recommendations for health-enhancing physical activity. Recommended measurement instruments for monitoring and evaluation include the Patient-Specific Complaint instrument, Numeric Rating Scales for pain and fatigue, the Health Assessment Questionnaire Disability Index, and the 6-minute walk test. This evidence-based practice guideline guides the physical therapist in the treatment of patients with RA. The cornerstones of physical therapist treatment for patients with RA are active exercise therapy in combination with education. Passive interventions such as massage, electrotherapy, thermotherapy, low-level laser therapy, ultrasound, and medical taping play a subordinate role.

An evidence-based physical therapy guideline was delivered, providing ready-to-use recommendations on the assessment and treatment of patients with RA. An active implementation strategy to enhance its use in daily practice is advised.

To describe the first case of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy, Sjögren syndrome, and lymphocytic pneumonitis in a nonendemic area. Retroviruses are implicated in the pathogenesis of autoimmune diseases, including Sjögren syndrome. Asymptomatic lymphocytic pneumonitis is prevalent in HTLV-1-associated myelopathy. There are 7 case reports with the combination of HTLV-1-associated myelopathy, Sjögren syndrome, and lymphocytic pneumonitis, all of them in endemic areas for HTLV-1. Case report and literature review. A 40-year-old Creole woman from New Orleans, La, presented with progressive spastic paraparesis and exertional dyspnea. Review of systems revealed chronic complaints consistent with sicca syndrome. She was found to have HTLV-1-associated myelopathy by polymerase chain reaction in the cerebrospinal fluid. Increased levels of SSA, positive results on a Schirmer test, and the findings of biopsy of the minor salivary gland were consistent with Sjögren syndrome. A lung biopsy specimen showed marked lymphocytic infiltration.

The present case raises questions about the role of HTLV-1 in the development of autoimmunity. It also happens to be a unique occurrence in a nonendemic area.

To ascertain the prevalence of fibromyalgia syndrome (FMS) in systemic lupus erythematosus (SLE) and to evaluate its clinical impact and relationship to SLE disease activity. A cross-sectional analysis of 102 patients from a public hospital SLE clinic. Information was obtained on symptoms of FMS, disability, tender points, pain thresholds, and SLE disease activity. Twenty-two SLE patients (22%) met the American College of Rheumatology criteria for FMS, and another 24 (23%) had clinical FMS but did not meet the classification criteria. The patients who met the criteria for FMS had a significantly increased frequency and severity of symptoms commonly associated with FMS, and were much more likely to be unable to perform daily activities. The FMS patients also were less likely to be employed, and more likely to be divorced and to be receiving welfare or medical disability benefits. However, patients with and those without FMS did not differ in measures of SLE activity.

FMS is very common in SLE patients, and accounts for many of the symptoms and much of the disability in these patients.

Reconstructive computed tomography (CT) study of occipito-atlanto and atlantoaxial joints in RA patients. The occipitocervical region is one of the most common sites of rheumatoid arthritis (RA). Although lateral radiography has been used for the diagnosis of atlantoaxial subluxation and vertical subluxation, reconstructive CT imaging of the occipito-atlanto and atlantoaxial joints is more sensitive in detecting morphologic changes in this region. We investigated this region in RA patients, using coronal-view reconstructive CT images, and examined the relationship between the morphology and other radiographic parameters. The occipitocervical region was examined in 58 female RA patients by reconstructive CT, plain radiography, and MRI. The degree of destructive change on reconstructive CT was compared to that on other radiographic evaluations. Coronal-view reconstructive CT revealed primary destructive changes before detection by lateral radiography, using Redlund-Johnell or Ranawat values. A Redlund-Johnell value less than 34 mm was diagnostic for occipitocervical subluxation in female RA patients.

Coronal-view reconstructive CT is useful for the diagnosis of occipitocervical joint subluxation in RA.

Patient-reported outcome measures (PROMs) are increasingly in demand for outcomes evaluation by hospitals, administrators, and policymakers. However, assessing total hip arthroplasty (THA) through such instruments is challenging because most existing measures of hip health are lengthy and/or proprietary. The objective of this study was to derive a patient-relevant short-form survey based on the Hip disability and Osteoarthritis Outcome Score (HOOS), focusing specifically on outcomes after THA. We retrospectively evaluated patients with hip osteoarthritis who underwent primary unilateral THA and who had completed preoperative and 2-year postoperative PROMs using our hospital's hip replacement registry. The 2-year followup in this population was 81% (4308 of 5351 patients). Of these, 2371 completed every item on the HOOS before surgery and at 2 years, making them eligible for the formal item reduction analysis. Through semistructured interviews with 30 patients, we identified items in the HOOS deemed qualitatively most important to patients with hip osteoarthritis. The original HOOS has 40 items, the four quality-of-life items were excluded a priori, five were excluded for being redundant, and one was excluded based on patient-relevance surveys. The remaining 30 items were evaluated using Rasch modeling to yield a final six-item HOOS, Joint Replacement (HOOS, JR), representing a single construct of "hip health." We calculated HOOS, JR scores for the Hospital for Special Surgery (HSS) cohort and validated this new score for internal consistency, external validity (versus HOOS and WOMAC domains), responsiveness to THA, and floor and ceiling effects. Additional external validation was performed using calculated HOOS, JR scores in collaboration with the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) nationally representative joint replacement registry (n = 910). The resulting six-item PROM (HOOS, JR) retained items only from the pain and activities of daily living domains. It showed high internal consistency (Person Separation Index, 0.86 [HSS]; 0.87 [FORCE]), moderate to excellent external validity against other hip surveys (Spearman's correlation coefficient, 0.60-0.94), very high responsiveness (standardized response means, 2.03 [95% CI, 1.84-2.22] [FORCE]; and 2.38 [95% CI, 2.27-2.49] [HSS]), and favorable floor (0.6%-1.9%) and ceiling (37%-46%) effects. External validity was highest for the HOOS pain (Spearman's correlation coefficient, 0.87 [95% CI, 0.86-0.89] [HSS]; and 0.87 [95% CI, 0.84-0.90] [FORCE]) and HOOS activities of daily living (Spearman's correlation coefficient, 0.94 [95% CI, 0.93-0.95] [HSS]; and 0.94 [95% CI, 0.93-0.96] [FORCE]) domains in the HSS validation cohort and the FORCE-TJR cohort. Level III, diagnostic study.

The HOOS, JR provides a valid, reliable, and responsive measure of hip health for patients undergoing THA. This short-form PROM is patient relevant and efficient.

Kinematic alignment (KA) technique is an alternative technique for positioning a TKA, which aims a patient-specific implant positioning in order to reproduce the pre-arthritic knee anatomy. Because reliability in implant positioning is of interest to obtain reproducible good functional results, our study tests the hypothesis that the medial and lateral distal and posterior positions of the planned and surgically implanted kinematically aligned femoral component are similar. Preoperative knee magnetic resonance imaging (MRI) and postoperative knee computed tomography (CT) of 13 patients implanted with a KA Persona The average differences between the medial and lateral distal and posterior positions of the planned and surgically implanted kinematically-aligned femoral component were inferior to 1mm and no statistically significant. In terms of variability, 62% (8/13) of performed implants matched all four positions within 1.5mm, and the maximum difference was 3mm. Level 3.

In this small series, intraoperative kinematic positioning of the femoral component with the specific manual instrumentation closely matched the planned position, which suggests that this technique reliably aligned the flexion-extension axis of the femoral component to the cylindrical axis.

High tibial osteotomy (HTO) has been established as an effective method for the treatment of unicondylar knee osteoarthritis. This study was undertaken to quantify the potential for restoration of cartilage lesions or defects after HTO in relation to different cartilage treatment modalities. Control arthroscopy was undertaken to identify the cartilage lesions within the knee joint 1.5 years after medial opening wedge osteotomy. A total of 135 patients (72 male and 63 female) had undergone medial-opening high tibial osteotomy and arthroscopy. The mean age at operation was 48.8 (36 to 65) years. All HTO were fixed with an angle-stable, mobile spacer-containing plate (HTO-Platte, Königsee, Deutschland). All HTO were combined with a simultaneous arthroscopy. Grade III cartilage lesions had undergone either shaving or temperature-controlled chondroplasty (Paragon ArthroW Austin, TX, USA). In some case these cartilage lesions had remained untreated. Control arthroscopy and removal of the implants was performed 1.5 years after HTO. The cartilage lesions were graded accordingly to the ICRS guidelines (International Cartilage Repair Society). The KOOS at HTO was 49.9 (SD 10.6) points. We observed at follow-up a mean increase from 66.1 (SD 28.8, 95 % CI: 61.2-71.1) points. The KOOS at follow-up was 16.1 (SD 29.8) points. There was no delayed union of the HTO space. Before HTO the varus angle was 10.4° (SD 3.9 range 5 to 20°). The correction angle was 13.6° (SD 4.4, 95 % CI: 12.9-14.4°). Finally we determined a valgus angle of -3.2° (SD 1.8 minimum 0° varus, maximum -6° valgus. The clinical outcome (KOOS) significantly (p < 0.001) correlated (R = 0.605) with the extension of valgisation. Patients with a valgus angle of 3° and more had the best outcome. Of the grade III lesions 40.4 % in the medial femoral condyle and 62.3 % in the medial tibial plateau increased to grade II or I lesions. In 13.1 % of the medial femoral condyle and 8.5 % of medial tibial plateau cases we found complete (grade IV) defects at control arthroscopy. The highest rate of regenerations was detected after temperature-controlled chondroplasty. The worst results were produced after mechanical debridement. Microfracturing of complete defects produced regeneration in about ⅔ in the medial femoral condyle and about ⅓ in the medial tibial plateau. No increase was observed within the lateral or patello-femoral compartment. No correlation was seen between cartilage regeneration and outcome. The extension of valgisation did not influence the cartilage regeneration.

The main effect of the HTO is the shift of the weight-bearing line from the arthritic compartment to the opposite femorotibial healthy one. In addition, HTO also produces a partial restoration of cartilage lesions. Deep cartilage lesions (grade III) restore in about 60 % of the cases after HTO. The worst restoration is found after mechanical shaving. This method should be avoided in the future. The best restoration was found in deep lesions after thermochondroplasty. Furthermore, in about half of the patients with complete (grade IV) defects, microfracturing caused the formation of fibrocartilaginous regenerates. This procedure should always be performed if possible.

Dendritic cells (DCs) are potent antigen-presenting cells (APC) that are deeply implicated in the initiation and exacerbation of rheumatoid arthritis (RA). Active RA is associated with an activated DCs population as demonstrated by high expression of adhesion and co-stimulatory molecules. To compare the expression of adhesion and co-stimulatory molecules on DCs from synovial tissue (ST) in patients (pts) with RA and the clinical status before and after treatment with disease modifying antirheumatic drugs (DMARDs). Samples of ST were obtained from RA patients at the time of hip or knee replacement or arthroscopy. Clinical status (assessed by the American College of Rheumatology - ACR - core set and the DAS28) and co-stimulatory and adhesion molecules on DCs were evaluated before and after treatment. Immunophenotype of DCs was analyzed by two-color immunofluorescence microscopy. In patients with active RA we found a highly differentiated subpopulation of DCs that expressed an activated phenotype. After treatment, the expression of adhesion and co-stimulatory molecules on ST DCs was correlated with the ACR and DAS28 clinical response.

Clinical outcome and the immunophenotypical presentation of ST DCs after DMARDs treatment are closely correlated in pts with RA. The co-stimulatory activity in the synovium is important in determining the course of the disease and provide new therapeutic targets for immune intervention.

To ascertain the prevalence of myocardial infarction (MI) in ankylosing spondylitis (AS) relative to that in the general population. A questionnaire was sent to 593 patients with AS, aged between 50 and 75 years and registered at the Jan van Breemen Institute or VU University Medical Centre. A total of 383 (65%) patients with AS returned their questionnaire that covered the primary outcome, (non-fatal) MI. The prevalence of MI was calculated with data from the general population provided by Netherlands Information Network of General Practice databases as reference. The overall prevalence for MI was 4.4% in patients with AS versus 1.2% in the general population, resulting in an age- and gender-adjusted odds ratio of 3.1 (95% CI 1.9 to 5.1) for patients with AS. When non-responders (35%) were considered as non-MI the odds ratio decreased to 1.9 (95% CI 1.2 to 3.2).

These observations indicate that the prevalence of MI is increased in patients with AS.

Multiple surgical techniques in minimally invasive total knee arthroplasty (TKA) are associated with clinical differences. However, whether patellar eversion impairs clinical outcomes remains controversial. We conducted a systematic review of randomized controlled trials (RCTs) to provide current understanding on this topic. A literature search of the PubMed, Embase, and Cochrane library databases was performed to identify RCTs comparing patellar eversion with patellar non-eversion (PN). Two authors independently selected the studies, assessed methodological quality, and extracted data. Five RCTs involving 379 knees were included. The results revealed no significant differences in functional scores, pain, quality of life, quadriceps strength, patellar height, alignment, or complication rate between patellar eversion and PN. Power analysis showed that the power of the individual study and meta-analysis ranged from 5.0 to 70.8%, with the exception of the power of alignment and patellar height in two of the individual studies, which was 100.0 and 99.9%, respectively. Systematic review and meta-analysis, Level I.

Based on the current evidence, patellar eversion during TKA could not definitely lead to inferior postoperative outcomes. Patellar eversion and patellar non-eversion could achieve similar clinical outcomes.

Osteoarthritis (OA) is a common degenerative joint inflammation that may lead to disability. Although OA is not lethal, this disease will remarkably affect patient's mobility and their daily lives. Detecting OA at an early stage allows for early intervention and may slow down disease progression. Magnetic resonance imaging is a useful technique to visualize soft tissues within the knee joint. Cartilage delineation in magnetic resonance (MR) images helps in understanding the disease progressions. Convolutional neural networks (CNNs) have shown promising results in computer vision tasks, and various encoder-decoder-based segmentation neural networks are introduced in the last few years. However, the performances of such networks are unknown in the context of cartilage delineation. This study trained and compared 10 encoder-decoder-based CNNs in performing cartilage delineation from knee MR images. The knee MR images are obtained from the Osteoarthritis Initiative (OAI). The benchmarking process is to compare various CNNs based on physical specifications and segmentation performances. LadderNet has the least trainable parameters with the model size of 5 MB. UNetVanilla crowned the best performances by having 0.8369, 0.9108, and 0.9097 on JSC, DSC, and MCC.

UNetVanilla can be served as a benchmark for cartilage delineation in knee MR images, while LadderNet served as an alternative if there are hardware limitations during production.

Different pelvic osteotomies and various shelf procedures are used for the operative treatment of hip dysplasia. Slotted acetabular augmentation (SAA) is a well-established technique for the treatment of children and adolescents with hip dysplasia. It has not been widely accepted for treating hip dysplasia in adults although good outcomes have been reported with other augmentation techniques in adults. Since 1997, SAA has been used for the prevention of hip arthrosis in 14 dysplastic hips in 12 female patients. The median age at operation was 38.5 (17-42) years; the median follow-up period was 4 (1-8) years. The patients were evaluated on the basis of radiographic, biomechanical and clinical data prior to surgery and at follow-up. The median centre-edge angle of Wiberg increased from 9 degrees (1-26) before the operation to 43 degrees (31-55) at the latest follow-up (P < 0.001). The median peak stress on the weight-bearing area of the hip, calculated mathematically, was reduced from 14.9 (6.3-28-1) MPa prior to the operation to 4.1 (3-6.1) MPa at the latest follow-up (P < 0.001); the median Harris Hip Score increased from 60 (45-98) points preoperatively to 93 (49-100) points at the follow-up (P < 0.001). There was no difference between the preoperative and follow-up hip joint-space width (P = 0.2).

There were no postoperative complications. In our series, the procedure has proved reliable and safe. Its advantages include symptomatic pain relief, adequate acetabular roof coverage and reduced peak stress on the weight bearing area of the hip. It can be used to postpone the development of hip arthrosis in adults with acetabular dysplasia.

Blood loss following total knee arthroplasty can lead to substantial morbidity and the need for blood transfusions. Hemostatic agents have been used to minimize blood loss and to decrease transfusion rates. Floseal is a thrombin-based hemostatic agent with unknown efficacy for achieving these goals in patients undergoing total knee arthroplasty. We performed a prospective randomized controlled trial on the use of Floseal in patients undergoing total knee arthroplasty, with the primary end point being blood loss as measured through drain output. Demographic characteristics, operative side, diagnosis, intraoperative details, implant choice, hospital course, laboratory values, visual analog scale pain scores, knee range of motion, adverse events, transfusion rates, and deviations from protocol were recorded. A total of 196 patients were enrolled, with ninety-seven patients being randomized to the Floseal group and ninety-nine patients being randomized to the control group. There were no significant differences between the Floseal and control groups in terms of drain output at twenty-four hours (711 compared with 702 mL; p = 0.823). No differences were noted between the groups in terms of operative side, diagnosis, intraoperative details, implant choice, hospital course, laboratory values, visual analog scale pain scores, knee range of motion, or transfusion rates. Complications occurred infrequently. In the acute postoperative period, there were two cases of cellulitis (one in each group), two deep venous thromboses (one in each group), and one paralytic ileus (in the control group), all of which resolved with nonoperative measures. At the six-week follow-up, one patient in the Floseal group had died from a cause unrelated to surgery, two patients (one in each group) had suture abscesses with cellulitis that resolved with postoperative antibiotics, and four patients (two in each group) underwent knee manipulation under anesthesia to achieve improved knee motion. With the numbers available, there was no significant association between Floseal use and the occurrence of these adverse events.

The present study showed that Floseal had no demonstrable effect on blood loss as measured through drain output following total knee arthroplasty. There were also no notable adverse events associated with its use. The usefulness of Floseal as a hemostatic agent in total knee arthroplasty remains unclear.

To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA). Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima-media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared. 49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (-0.34, -0.37 and -0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012).

Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA.

Although no studies exist, to our knowledge, that examine the feasibility and safety of stress testing in a consecutive series of patients with severe arthritis, musculoskeletal conditions are often listed as relative contraindications to graded exercise testing. The current study was designed to examine the feasibility of maximal exercise testing in patients with end-stage arthritis prior to total joint arthroplasty. An observational and descriptive study in a consecutive series of patients with severe arthritis. This study was conducted in the outpatient clinics and cardiopulmonary exercise physiology laboratory of a rural teaching hospital. Sixty-one patients with severe osteoarthritis and rheumatoid arthritis were recruited from the orthopedic surgical service immediately before total joint arthroplasty of the hip, knee, or both. A reference group of 23 nonarthritic control patients were recruited from the general medical population of the same hospital and subjected to measures of arthritis severity. The severity of arthritis was graded by assessment of variables reflective of subjective symptoms, lifestyle impact, joint deformity, and radiographic abnormality. Arthritic subjects underwent a single graded, maximal, symptom-limited, cardiopulmonary exercise test using an electronically braked ergometer and a metabolic cart. Subjects were first asked to pedal with their legs; those apparently incapable performed the same task using their arms. Ninety-five percent of subjects who presented for an exercise test were capable of symptom-limited exercise. Of 29 patients evaluated before hip replacement, 66% completed leg tests, 31% completed arm tests, and 3% were incapable of symptom-limited exercise. Of 30 patients evaluated before knee replacement, 57% completed leg tests and 37% completed arm tests, while 7% were incapable of symptom-limited exercise. Two patients were evaluated before hip and knee surgery; one completed a leg study and one completed an arm study. Among the 37 subjects completing leg tests, a mean percentage of age-predicted maximum heart rate (APMHR) of 92 +/- 11% and a mean respiratory exchange ratio (RER) of 1.15 +/- 0.13 were noted. Among the 21 completing arm tests, a mean percentage of APMHR of 87 +/- 11% and a mean RER of 1.10 +/- 0.10 were observed. High rates of achievement of physiologic values indicative of maximal exercise (80% or more of APMHR and RER > or = 1.0) were noted in individuals in both exercise groups. Similar findings were noted regardless of the patient's subjective symptomatic limitation to exercise and the presence or absence of documented or suspected coronary heart disease.

Most patients with severe arthritis are capable of maximal, symptom-limited exercise using ergometry methods. Ergometry stress testing may be a viable, low-cost alternative to dipyramidole-thallium testing or cardiac catheterization in some patients with arthritis warranting objective assessment of known or suspected cardiac disease.

To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi-square test with 2 x 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15-1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05-2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01-2.09]).

These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.

Cartilage and bone damage in RA are associated with elevated IL-1β. The effects of IL-1β can be reduced by biological therapies that target IL-1β or TNF-α. However, the mechanisms responsible for increased IL-1β and the effect of anti-TNF-α have not been fully elucidated. Recently, sterile-α and armadillo motif containing protein (SARM) was identified as a negative regulator of toll-like receptor (TLR) induced IL-1β secretion through an interaction with the inflammasome. This study set out to investigate SARM during TLR-induced IL-1β secretion in RA peripheral blood monocytes and in patients commencing anti-TNF-α treatment. Monocytes were isolated from RA patients and healthy controls; disease activity was measured by DAS28. IL-1β secretion was measured by ELISA following TLR1/2, TLR4 and TLR7/8 stimulation. The mRNA expression of SARM1, IL-1β and the components of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome were measured by quantitative PCR. SARM protein expression was measured by western blotting. TLR1/2 activation induced elevated IL-1β in RA monocytes compared with healthy controls (P = 0.0009), which negatively correlated with SARM1 expression (P = 0.0086). Lower SARM expression also correlated with higher disease activity (P = 0.0246). Additionally, patients responding to anti-TNF-α treatment demonstrated a rapid upregulation of SARM, which was not observed in non-responders.

Together, these data highlight a potential contribution from SARM to RA pathophysiology where decreased SARM may lead to elevated IL-1β associated with RA pathogenesis. Furthermore, the data additionally present a potential mechanism by which TNF-α blockade can modify IL-1β secretion.

(a)To determine the accuracy and reliability of arthroscopic measurements of cartilage lesion diameter in an artificial right knee model; (b) to determine whether the use of a set of variable angle elongated probes improves performance; and (c) to identify other sources of variability. Ovoid "lesions" were drawn on the five cartilage surfaces of four plastic knees models. Two observers assessed these 20 lesions arthroscopically, measuring two diameters in orientations parallel and orthogonal to the probe. Observer 1 (orthopaedic surgeon) and observer 2 (arthroscopic rheumatologist) made two sets of measurements, firstly with the conventional probe and five months later with the variable angle elongated (VAE) probes. The knees were disarticulated to determine true lesion diameter. Observer 1 had negligible bias and good accuracy regardless of orientation or probe type. Observer 2 demonstrated both bias and poor accuracy using the conventional probe. Both improved using VAE probes. Poor interobserver reliability with conventional probes also improved using VAE probes. Major sources of variability could be traced to the probe type, the characteristics of the operator, and the orientation of the lesion in relation to the probe; the lesion location itself did not cause variability.

Variation in accuracy and poor interobserver reliability of measurements with conventional methods of cartilage lesion diameter measurement improved when specially designed measurement probes were used. Arthroscopic measurements performed as well as most clinical and radiographic measures. These findings have important implications for the use of arthroscopy as an outcome in multicentre trials where arthroscopists have different levels of experience.

To determine if boney morphology influences the anatomic location of hip fractures in elderly patients. All patients with hip fractures between 2008 and 2012 who had hip radiographs taken prior to the fracture were reviewed. Fractures were classified as intracapsular or extracapsular and hip morphology was measured on the pre-fracture x-rays. Hip morphology was determined by alpha angle, lateral central edge angle, acetabular index, neck-shaft angle, hip axis length, femoral neck diameter, Tönnis classification for hip osteoarthritis (OA) and the presence of a crossover sign. 148 subjects (78.4% female, age 83.5 years) with proximal femur fractures were included. 44 patients (29.7%) had intracapsular fractures and 104 (70.3%) had extracapsular fractures. 48% of patients had previous hip fractures on the contralateral side and 74.6% had the same type of fracture bilaterally. The rates of bilateral intracapsular and extracapsular fractures were similar (33.7% vs. 40.9% respectively,

Acetabular coverage and proximal femoral head-neck junction morphology, were found to partially correlate with the location of hip fractures and do not fully elucidate fracture type susceptibility.

Autophagy is a homeostatic process to recycle dispensable and damaged cell organelles. Dysregulation of autophagic pathways has recently been implicated in the pathogenesis of various diseases. Here, we investigated the role of autophagy during joint destruction in arthritis. Autophagy in osteoclasts was analysed in vitro and ex vivo by transmission electron microscopy, Western blotting and immunohistochemistry for Beclin1 and Atg7. Small molecule inhibitors, LysMCre-mediated knockout of Atg7 and lentiviral overexpression of Beclin1 were used to modulate autophagy in vitro and in vivo. Osteoclast differentiation markers were quantified by real-time PCR. The extent of bone and cartilage destruction was analysed in human tumour necrosis factor α transgenic (hTNFα tg) mice after adoptive transfer with myeloid specific Atg7-deficient bone marrow. Autophagy was activated in osteoclasts of human rheumatoid arthritis (RA) showing increased expression of Beclin1 and Atg7. TNFα potently induced the expression of autophagy-related genes and activated autophagy in vitro and in vivo. Activation of autophagy by overexpression of Beclin1-induced osteoclastogenesis and enhanced the resorptive capacity of cultured osteoclasts, whereas pharmacologic or genetic inactivation of autophagy prevented osteoclast differentiation. Arthritic hTNFα tg mice transplanted with Atg7(fl/fl)×LysMCre(+) bone marrow cells (BMC) showed reduced numbers of osteoclasts and were protected from TNFα-induced bone erosion, proteoglycan loss and chondrocyte death.

These findings demonstrate that autophagy is activated in RA in a TNFα-dependent manner and regulates osteoclast differentiation and bone resorption. We thus provide evidence for a central role of autophagy in joint destruction in RA.

The reciprocal links between comorbidities and gout are complex. We used cluster analysis to attempt to identify different phenotypes on the basis of comorbidities in a large cohort of patients with gout. This was a cross-sectional multicentre study of 2763 gout patients conducted from November 2010 to May 2011. Cluster analysis was conducted separately for variables and for observations in patients, measuring proximity between variables and identifying homogeneous subgroups of patients. Variables used in both analyses were hypertension, obesity, diabetes, dyslipidaemia, heart failure, coronary heart disease, renal failure, liver disorders and cancer. Comorbidities were common in this large cohort of patients with gout. Abdominal obesity, hypertension, metabolic syndrome and dyslipidaemia increased with gout duration, even after adjustment for age and sex. Five clusters (C1-C5) were found. Cluster C1 (n=332, 12%) consisted of patients with isolated gout and few comorbidities. In C2 (n=483, 17%), all patients were obese, with a high prevalence of hypertension. C3 (n=664, 24%) had the greatest proportion of patients with type 2 diabetes (75%). In C4 (n=782, 28%), almost all patients presented with dyslipidaemia (98%). Finally, C5 (n=502, 18%) consisted of almost all patients with a history of cardiovascular disease and renal failure, with a high rate of patients receiving diuretics.

Cluster analysis of comorbidities in gout allowed us to identify five different clinical phenotypes, which may reflect different pathophysiological processes in gout.

Transplantation of mesenchymal stem cells (MSCs) derived from synovium is a promising therapy for cartilage regeneration. For clinical application, improvement of handling operation, enhancement of chondrogenic potential, and increase of MSCs adhesion efficiency are needed to achieve a more successful cartilage regeneration with a limited number of MSCs without scaffold. The use of aggregated MSCs may be one of the solutions. Here, we investigated the handling, properties and effectiveness of aggregated MSCs for cartilage regeneration. Human and rabbit synovial MSCs were aggregated using the hanging drop technique. The gene expression changes after aggregation of synovial MSCs were analyzed by microarray and real time RT-PCR analyses. In vitro and in vivo chondrogenic potential of aggregates of synovial MSCs was examined. Aggregates of MSCs cultured for three days became visible, approximately 1 mm in diameter and solid and durable by manipulation; most of the cells were viable. Microarray analysis revealed up-regulation of chondrogenesis-related, anti-inflammatory and anti-apoptotic genes in aggregates of MSCs. In vitro studies showed higher amounts of cartilage matrix synthesis in pellets derived from aggregates of MSCs compared to pellets derived from MSCs cultured in a monolayer. In in vivo studies in rabbits, aggregates of MSCs could adhere promptly on the osteochondral defects by surface tension, and stay without any loss. Transplantation of aggregates of MSCs at relatively low density achieved successful cartilage regeneration. Contrary to our expectation, transplantation of aggregates of MSCs at high density failed to regenerate cartilage due to cell death and nutrient deprivation of aggregates of MSCs.

Aggregated synovial MSCs were a useful source for cartilage regeneration considering such factors as easy preparation, higher chondrogenic potential and efficient attachment.

The aims of the present study were to investigate the effectiveness of exercise intervention provided by a medical support team specializing in lifestyle-related diseases in the treatment of elderly lower extremity osteoarthritis and to examine the influence of bodyweight decrease on changes in the evaluation indexes. Participants were 61 patients (57 women and 4 men, aged 68.3 ± 9.6 years) with lower extremity osteoarthritis (109 total diseased joints) and either one or more of the following diseases: obesity, metabolic syndrome and type 2 diabetes. Indexes relating to metabolic diseases, orthopedic disorders, lifestyle activity level and health-related quality of life (HRQOL) were obtained before and after exercise intervention. The numbers of patients with obesity, metabolic syndrome, type 2 diabetes, gonarthrosis and coxarthrosis were 56, 49, 32, 56 and 9, respectively. The mean intervention period was 4.7 ± 1.6 months (2-10.8 months). Indexes relating to metabolic diseases and orthopedic disorders, activity level and HRQOL were all significantly improved after intervention (P < 0.05). Bodyweight decreased by 10.3% and showed a correlation with other evaluated items. Five explanatory variables were extracted through multiple regression analysis that bodyweight reduction rate was set as the criterion variable: changes of bodyweight, body mass index, percent body fat, glycated hemoglobin and total energy expenditure per bodyweight.

The exercise intervention provided by our medical support team clearly improved indexes relating to metabolic diseases and orthopedic disorders. In addition, decreased bodyweight was related to improvements in metabolic factors, motor function and HRQOL.

The Ankle Arthritis Score (AAS) is a new patient-reported outcome derived from the Ankle Osteoarthritis Scale (AOS). This study analyzed longitudinally collected data from a cohort of patients in the Canadian Orthopaedic Foot and Ankle Society (COFAS) Ankle Arthritis Study in order to evaluate whether the postoperative AAS is associated with need for revision surgery. A multicenter, prospective, ankle-reconstruction study enrolled 653 ankles undergoing total ankle replacement (TAR) or ankle arthrodesis (AA). The AAS was given at baseline and annually during postoperative follow-up. Time to revision surgery was modeled using a proportional hazards model. The final sample included 531 ankles in 509 patients. Sixty-two patients underwent metal-component revision and 8 underwent arthrodesis revision during the follow-up time period. The remaining 461 unrevised ankles (300 TAR, 161 AA) had a minimum follow-up of 2 years (average of 3.4 years). Revision surgery after TAR was found to be associated with a higher postoperative AAS and a longer follow-up. The hazard ratio for the AAS indicated that for every 1-point increase in the score, the rate of revision surgery after TAR was 1 percentage point higher. Level III, retrospective cohort study.

TAR patients who reported higher levels of postoperative functional impairment, as indicated by a higher AAS, were more likely to require metal-component revision surgery. After adjustment for other patient factors, the risk of revision surgery increased with length of follow-up after TAR. This study provides further evidence for the utility of the AAS in the clinical setting.

The objective of the study was to compare the production of metalloproteinases (MMP)-1, -3 and interleukin (IL)-6 by fibroblast-like synoviocytes (FLS) derived from synovial fluid (FD-FLS), and FLS derived from synovial tissue (TD-FLS) of patients with primary osteoarthritis (OA). The more accessible FD-FLS could facilitate the study of the role of these cells in OA pathophysiology. MMP-1, MMP-3, and IL-6 levels were measured in the supernatant culture at baseline and 22 hours after stimulation with TNF-α and IL-1 β. There was no difference at baseline between MMP-1, MMP-3 and IL-6 production by FD-FLS and TDFLS. Analogous to baseline, stimulation of FD-FLS and TD-FLS with IL-1β and TNF-α did not result in difference on MMP-3 and IL-6 production. However, TD-FLS produced more MMP-1 than FD-FLS after stimulation with IL-1β (p=0.01). Additionally, there was a positive correlation for production of MMP-1, MMP-3 and IL-6 between FD-FLS and TD-FLS (r=0.40 and p<0.0008; r=0.66 and p<0.0001; r=0.76 and p<0.0001, respectively). Supporting this statistical significant positive correlation, the Bland-Altman plotting, showed a homogeneous distribution of the values and low mean disagreement rates between all results of FD-FLS and TD-FLS (23.1%, 56.8% and 48.1%, respectively).

Our data demonstrated functional similarity between FD-FLS and TD-FLS and support the use of a more accessible source of FLS for the study of the pathogenesis of joint destruction and therapeutic targets in primary OA.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. NCT01039688; Results.

Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA.

Over the last decade, a treat-to-target (T2T) strategy has been recommended for psoriatic arthritis (PsA) and new treatment options have become available. There is a lack of data on PsA regarding any changes that may have occurred over these past years. Thus, the main aim of this study was to look for changes in clinical disease status and treatment in a PsA outpatient clinic population monitored over the period 2008 to 2017. Annual data collection included demographic data, laboratory (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and clinic measures of disease activity (e.g., 28 and 32 joint count Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and modified Disease Activity index for Psoriatic arthritis (DAPSA)), evaluator's global assessment, and patient-reported outcomes (PROs), including for example measures of physical function, pain, and patient global assessment. Disease-modifying antirheumatic drug (DMARD) use was also registered. In the PsA outpatient clinic population over the 10-year period (annual mean number of patients, 331) the mean (standard deviation) age was 58.4 (12.4) years, disease duration was 9.6 (7.9) years, 49.4% were female, and 17.6% were current smokers. From 2008 to 2017, no statistically significant increase in remission rates was seen for DAPSA (13.5% and 22.0%) or Boolean remission (6.6% and 8.9%), whereas a statistically significant increase was seen for DAS28-ESR (36.8% and 50.6%) and CDAI (20.0% and 29.6%), but not for the last 5 years (DAS28-ESR, 42.3% and 50.6%; CDAI, 27.9% and 29.6%). Furthermore, over the 10-year period no significant improvement for PROs and no significant change in the use of synthetic (annual mean 53.0%) and biologic DMARDs (annual mean 29.9%) was found.

Our data suggest that even in the biologic treatment era there is an unmet need for treating PsA patients to target remission. New treatment options and the development of more feasible and valid outcome measures for use in a T2T strategy in ordinary clinical practice may in the future to further improve clinical outcomes in PsA.

An individual patient's response to a particular drug is influenced by multiple factors, which may include genetic predisposition. Pharmacogenetic studies attempt to discover and estimate the contributions of genetic variants to the variability in response to a drug treatment. The task of identifying the genetic contribution is often complicated by response phenotypes that are based on imprecise or subjective clinical observations. Because the success of a pharmacogenetic study depends on the analysis of a heritable phenotype, it is important to identify phenotypes with a significant heritable component to ensure reliable and reproducible results in subsequent genetic association studies. We retrospectively analyzed data collected from 436 rheumatoid arthritis patients treated with golimumab during the phase III GO-FURTHER study. We investigated the reliability of several potential response outcomes after golimumab treatment. Using whole-genome sequencing of the clinical trial cohort, we estimated the heritability of each potential outcome measure. We further performed a longitudinal analysis of the clinical data to estimate variability of outcome measures over time and the degree to which each response metric could be confounded by placebo response. We determined that the high degree of within-patient variation over time makes a single follow-up visit insufficient to assess an individual patient's response to golimumab treatment. We found that different potential response outcomes had varying degrees of heritability and that averaging across multiple follow-up visits yielded higher heritability estimates than single follow-up estimates. Importantly, we found that the change in swollen and tender joint counts were the most heritable outcome metrics we tested; however, we showed that they are also more likely to be confounded by a placebo response than objective phenotypes like the change in C-reactive protein levels. Clinicaltrials.gov NCT00973479 . Registered 4 September 2009.

Our rigorous approach to finding robust and heritable response phenotypes could be beneficial to all pharmacogenetic studies and may lead to more reliable and reproducible results.

Preoperative education has been found to be responsible for patients having a realistic expectation of surgery as well as high level of satisfaction with their recovery. The Joint Academy offers preoperative educational classes for all patients undergoing elective knee and hip replacements. The purpose of this descriptive study was to determine whether the education provided by The Joint Academy has an impact on anxiety, expectation, and preparedness in patients who undergo elective total knee or hip arthroplasty. All patients who had total joint or hip arthroplasty over a 2-month period were invited to participate in this descriptive correlational study. Of the 49 study participants, 28 attended The Joint Academy. Those who attended The Joint Academy were more likely to hold surgical expectations that better correlated with actual experience (p = .425). There was no statistically significant difference between the groups for nervousness (p = .171) or feeling prepared for the surgery (p = .425).

Offering education before knee or hip arthroplasty provides patients with an understanding of the expectations related to surgery.

To investigate the involvement of candidate cytokine genes in the pathogenesis of juvenile idiopathic arthritis (JIA). Single nucleotide polymorphisms and intragenic microsatellite markers within 8 candidate cytokine genes (interleukin-1alpha [IL-1alpha], IL-2, IL-4, IL-6, IL-10, interferon-alpha1 [IFNA1], interferon-gamma [IFNG], and interferon regulatory factor 1 [IRF-1]) were investigated in 417 Caucasian patients with clinically characterized JIA and a panel of 276 unrelated, healthy Caucasian controls, all from the United Kingdom. A novel 3'-untranslated region (3'UTR) polymorphism in IRF-1 was found to be associated with susceptibility to JIA (corrected P = 0.002). No significant association with IL-1alpha, IL-2, IL-4, IL-6, IL-10, IFNA1, or IFNG was observed.

An association between JIA and a previously unreported 3'UTR polymorphism of IRF-1 was observed. This association was not found to be specific to any particular JIA subgroup. This suggests that IRF-1 may contribute to a common pathogenesis shared by all JIA patients, regardless of clinical phenotype. This is most likely to be a genetic contribution to the chronic inflammatory process that underlies JIA pathology.

To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated.

Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.

To assess the health care utilization and cost of illness for osteoarthritis (OA) patients taking pain medications. Specifically, the goals were to estimate the direct health care and indirect costs of OA. A claims database of privately insured patients was used to identify OA patients. Prescription drug pain treatments included tramadol, cyclooxygenase-II inhibitors, and nonsteroidal anti-inflammatory drugs. Mean annual per patient costs were calculated from an employer's perspective. OA patients were prescribed multiple drugs simultaneously and/or sequentially to manage pain. OA patients had a number of prevalent comorbid conditions. Average annual direct medical, drug, and indirect work loss costs were $8601, $2941, and $4603, respectively.

There was a substantial payer burden associated with OA resulting from the drug, medical, and disability costs and OA-related comorbidities and high concomitant medication utilization.

All-polyethylene (AP) tibial components in patients aged greater than 60 years have stable tibial migration patterns and favorable survival rates when compared to identical Metal-backed (MB) designs. Tibial component migration in younger patients has not been reported. The aim of this study was to examine the migration characteristics of patients aged less than 60 years compared to a previous cohort of AP and MB tibial components of identical design in older patients. A prospective consecutive study examined tibial component migration in 21 patients aged less than 60 years undergoing a cemented total knee arthroplasty with an AP tibial component by radiostereometric analysis (RSA) to 24 months. Results were compared to the authors' previous series of 21 patients aged greater than 60 years that were randomized to either an AP or MB tibial component. Both age groups of patients implanted with an AP component had stable migration patterns with no patient having greater than 0.2° rotation or 0.2 mm maximum total point motion. Five of 11 MB tibial components displayed continued migration between one and two years. Subsidence was similar in all groups, whilst maximum total point motion was greater for the MB cohort (0.34 mm, 0.33 mm, 0.61 mm; AP <60, AP >60, MB). Level II, Prospective comparative study.

Young patients implanted with an AP tibial component had stable tibial migration patterns comparable to older patients with the same AP implant. Regardless of age, AP tibial components were at least as stable as MB tibial components.

We aimed to assess whether serum cytokine/chemokine concentrations predict incident cancer in RA patients. Data from cancer-free enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked to a national VA oncology database and the National Death Index (NDI) to identify incident cancers. Seventeen serum cytokines/chemokines were measured from enrollment serum and an overall weighted cytokine/chemokine score (CK score) was calculated. Associations of cytokines/chemokines with all-site, lung, and lymphoproliferative cancers were assessed in Cox regression models accounting for relevant covariates including age, sex, RA disease activity, and smoking. In 1216 patients, 146 incident cancers (42 lung and 23 lymphoproliferative cancers) occurred over 10,072 patient-years of follow-up with a median time of 4.6 years from enrollment (cytokine/chemokine measurement) to cancer incidence. In fully adjusted models, CK score was associated with a higher risk of all-site (aHR 1.32, 95% CI 1.01-1.71, p < 0.001), lung (aHR 1.81, 1.40-2.34, p = 0.001), and lung/lymphoproliferative (aHR 1.54 [1.35-1.75], p < 0.001) cancer. The highest quartile of CK score was associated with a higher risk of all-site (aHR 1.91, 0.96-3.81, p = 0.07; p-trend = 0.005), lung (aHR 8.18, 1.63-41.23, p = 0.01; p-trend < 0.001), and lung/lymphoproliferative (aHR 4.56 [1.84-11.31], p = 0.001; p-trend < 0.001) cancer. Thirteen of 17 individual analytes were associated with incident cancer risk.

Elevated cytokine/chemokine concentrations are predictive of future cancer in RA patients, particularly lung and lymphoproliferative cancers. These results suggest that the measurement of circulating cytokines/chemokines could be informative in cancer risk stratification and could provide insight into future cancer prevention strategies in RA, and possibly individuals without RA.

This study was designed to determine the complications associated with plate and screw fixation of thumb trapeziometacarpal arthrodesis and to compare these results with a previous report from our institution using K-wire fixation. We retrospectively reviewed 26 trapeziometacarpal arthrodeses that used plate and screw fixation. The most common diagnosis was primary osteoarthritis and the average follow-up evaluation was 40 months. Nineteen patients were available for a clinical follow-up examination and radiographs. These results were compared with the previously published K-wire fixation group that consisted of 59 arthrodeses with an average follow-up period of 84 months. There were 2 (8%) painful nonunions. There were 6 (23%) hardware malpositions, most frequently associated with a screw in the trapeziotrapezoid joint. Seven (27%) arthrodeses had a second procedure, most commonly hardware removal. Twenty-one (81%) of the patients were satisfied and reported they would have arthrodesis again. In the K-wire fixation group 4 of 59 (7%) arthrodeses went on to nonunion and 2 of 59 required a secondary procedure; patient satisfaction was high (98%).

K-wire and plate and screw fixation have comparable union rates. In the plate and screw fixation group, however, the satisfaction rate was lower and a second surgery was more common. We now recommend pin fixation when performing trapeziometacarpal joint arthrodesis.

Chlamydia trachomatis and Borrelia burgdorferi infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis. Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from C trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to C trachomatis and B burgdorferi were determined. Six patients (8%) had DNA from both C trachomatis and B burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm(3), 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydia only.

DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes. PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression. Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores.

ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.

Osteoarthritis (OA) is a degenerative joint disease which causes pain and functional impairment in adults over 50 years old with consequent important disability. Unfortunately, there is no definitive cure for OA, thus the approach is characterized by multiple treatments that can manage its symptoms. Even though data from randomized controlled trials and meta-analyses indicate that intra-articular hyaluronic acid (IAHA) offers the best benefit/risk balance among the various pharmacologic treatments to improve OA-related knee pain, there is a lack of agreement among national and international guidelines about such uses of IAHA for the medical management of symptomatic knee OA. To minimize confounding factors and biases, the aim of our study was to evaluate the efficacy of the different weight and concentration of IAHA treatment in patients suffering from knee OA comparing to glucocorticoids (GC) joint injections. Furthermore, to make the procedure more accurate and assessment more objective, we use ultrasonography (US) with power Doppler (PWD) to help us differentiate between active and inactive inflammation within joints and periarticular soft tissues. We performed a retrospective evaluation of a cohort of patients with knee OA, diagnosed according to the ACR criteria, treated by US-guided joint injection of HA and GC. The patients were catalogued according to the type of treatment they underwent: group A, patients treated with HA (1.5%) >1500 kDa (three US-guided knee injections one week apart); group B, patients treated with HA (2%) 800-1200 kDa (three US-guided knee injections one week apart); group C, patients treated with glucocorticoids (three US-guided knee injections of triamcinolone acetate 40 mg one week apart). All patients were monitored for 6 months, evaluating: subjective pain using a 10-cm Visual Analogue Scale; pain, stiffness, and functionality using the Western Ontario and McMaster Universities Arthritis Index (WOMAC); the concomitant intake of anti-inflammatory and/or analgesic drugs through a questionnaire; and US results by grey scale and PWD. A total of 171 patients affected by knee OA were evaluated (women 72.3%) with a mean age of 69.3±4.1 years. All the subjects analyzed showed a pain reduction at 6 months after treatment (group A: -39.5; group B: -36.9; group C: -30.8). The difference between the three groups was statistically significant (Kruskall-Wallis P=0.001) and in particular between group A and group C (P=0.000) and between group B and group C (P=0.005), but not between A and B (P=0.258). WOMAC was statistically significantly improved from baseline in all groups examined (group A: -11.9; group B: -14.9; group C: -11.2). The PWD score showed a statistically significant improvement in group B (-0.64) even after 6 months (P=0.004). All patients in the different groups showed a statistically significant reduction of concomitant therapy compared to baseline with respect to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)/COX2 therapy, while only group B showed a statistically significant reduction for opioids.

This study demonstrated the efficacy of OA treatment with medium molecular weight HA in favor of the higher concentration of HA that may affect the reduction of pro-inflammatory mediators. Furthermore, US monitoring allowed to evaluate aspects related to synovial involvement, which cannot be appreciated with standard imaging.

To define the imaging characteristics of intra-articular tophi of the knee. Twelve patients with intra-articular tophi in the knee were studied with routine MR imaging, gadolinium (Gd)-enhanced MR imaging, and CT over a 4-year period. There were 11 men and one woman, 25-82 years of age (mean age 48 years). Four patients did not have a documented history of gout at the time of the MR examination. The diagnosis of intra-articular tophi was provided by arthroscopy and histological examination (5 patients), by microscopic study of joint fluid (5 patients), or by characteristic clinical, laboratory and imaging findings (2 patients). In 15 MR examinations the tophi were located purely intra-articularly in 10 knees. In the remaining five MR studies, periarticular soft tissues or bone, or both, were involved. All the intra-articular tophi manifested low to intermediate signal intensity on both T1- and T2-weighted images. All five Gd-enhanced MR examinations demonstrated a heterogeneous peripheral enhancement. All 10 CT scans showed varying degrees of stippled calcifications within the tophi. The nature of the calcifications was confirmed on histological examination in three patients.

Presenting clinical manifestations of gout may relate to intra-articular tophaceous deposits. Such deposits present as masses on MR images with low to intermediate signal intensity on both T1- and T2-weighted images and a characteristic enhancement pattern following intravenous Gd administration. These features relate primarily to internal calcifications, which are most evident on CT images. MR evaluation (including Gd administration) supplemented, in some cases, with CT scanning allows accurate diagnosis of intra-articular tophaceous deposits.

To evaluate a novel specific psychological intervention aimed at improving coping in patients with systemic lupus erythematosus (SLE). 34 community living SLE patients were recruited for the study. Intervention was undertaken in groups of up to eight patients and in two blocks over six months each. Eight patients were enrolled as a waiting list group. The 18 group sessions focused on information about the disease and specific problems of SLE patients, combining psychoeducative and psychotherapeutic elements. Psychological and medical evaluations were conducted at baseline and after three, six, and 12 months, using validated instruments. The 34 SLE patients (91% female, mean age 42 years) improved significantly over a six month period on most of the psychological measuring instruments applied, such as depression, anxiety, and overall mental burden. The waiting list group showed no significant changes.

Conceptualised psychoeducational support may produce a significant and sustained improvement in coping skills of SLE patients and hence in their quality of life.

Adult-onset Still disease (AOSD) has been described all over the world. Clinical presentations and prognosis have varied in different studies. The objective of this study was to determine the clinical presentation and the evolution of AOSD at a tertiary referral center in southeast Brazil. The clinical records of 16 patients were retrospectively studied to determine symptoms at diagnosis, follow up, and the medication prescribed. The mean age at onset was 30.8 years (range, 24-55 years; standard deviation [SD], 9.2 years) with a slight male prevalence (54.2%). All patients presented constitutional symptoms, fever, and skin rash. Liver involvement was observed in all cases, with hepatomegaly in 81.3%, increased liver enzymes in 50.0%, and hypergammaglobulinemia in 68.8%. Cardiac involvement was observed in 12.6%, pleuritis in 6.3%, and renal involvement in 25.0%. All patients presented leukocytosis with a predominance of neutrophils. Elevated ferritin levels were observed in 56.3%, and these levels were normalized after disease remission. Initial treatments included nonsteroidal antiinflammatory drugs and low-dosage corticosteroids in all patients; 43.8% also needed methotrexate. In 25.0% of cases, a monocyclic disease was observed; others had recurrent episodes. After a follow up of 6.9 years (SD, 1.2 years), carpal ankylosis was the main articular sequel, observed in 53.6% of the patients.

AOSD is rare in southeast Brazil. Although less severe systemic manifestations, like serositis and pneumonitis, were observed, reversible liver involvement was common; the frequency of recurrent disease and carpal ankylosis was higher than in previous studies.

Interferon-beta (IFNbeta) treatment is emerging as a potentially effective form of therapy in various immune-mediated conditions. This study evaluated the effects of IFNbeta therapy on the cell infiltrate, cytokine profile, and expression of metalloproteinase 1 (MMP-1) in synovial tissue from patients with rheumatoid arthritis (RA). To further assess the mechanism of action, in vitro experiments were conducted to determine the effects of IFNbeta on the production of MMP-1, MMP-3, tissue inhibitor of metalloproteinases 1 (TIMP-1), and prostaglandin E2 (PGE2) by human fibroblast-like synoviocytes (FLS). Eleven patients were treated for 12 weeks with purified natural fibroblast IFNbeta (Frone; Ares-Serono, Geneva, Switzerland) subcutaneously 3 times weekly with the following dosages: 6 million IU (n = 4), 12 million IU (n = 3), and 18 million IU (n = 4). Synovial biopsy specimens were obtained by needle arthroscopy at 3 time points: directly before and at 1 month and 3 months after initiation of treatment. Immunohistologic analysis was performed using monoclonal antibodies specific for the following phenotypic markers and mediators of joint inflammation and destruction: CD3, CD38, CD68, CD55, tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), IL-6, MMP-1, and TIMP-1. In addition, we measured the production of MMP-1, MMP-3, TIMP-1, and PGE2 by RA FLS and dermal fibroblasts in the presence and absence of IFNbeta. A statistically significant reduction in the mean immunohistologic scores for CD3+ T cells and the expression of MMP-1 and TIMP-1 at 1 month, CD38+ plasma cells and the expression of IL-6 at 3 months, and the expression of IL-1beta at both 1 and 3 months was observed in synovial tissue after IFNbeta treatment. The scores for CD68+ macrophages and TNFalpha expression also tended to decrease, but the differences did not reach statistical significance. The in vitro experiments revealed inhibition of MMP-1, MMP-3, and PGE2 production by RA FLS, whereas TIMP-1 production was only slightly decreased. These effects were more consistent in RA FLS than in dermal fibroblasts.

The changes in synovial tissue after IFNbeta treatment and the in vitro data support the view that IFNbeta therapy has immunomodulating effects on rheumatoid synovium and might help to diminish both joint inflammation and destruction. Larger well-controlled studies are warranted to show the efficacy of IFNbeta treatment for RA.

We determined the radiographic osteoarthritic worsening rate prior to knee arthroplasty (TKA) and whether this worsening was associated with worsening pain and function as compared to a non-surgical matched sample. We used the Osteoarthritis Initiative 5-year datasets. Extent of knee OA 2 years prior to total knee arthroplasty (TKA) was matched to knees of persons who did not undergo TKA. Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function and Knee injury and Osteoarthritis Outcome Score (KOOS) Pain scales were used to quantify functional deficit and functionally relevant pain respectively. A total of 167 persons with isolated TKA and 300 persons with matched symptomatic knee OA but no TKA were studied. During the 2 years prior to TKA, worsening by at least one Kellgren and Lawrence (KL) grade occurred in 27.4% (95% CI = 20.6-34.2) of the surgical knees compared to 6.6% (95% CI = 3.8-9.4) of matched non-surgical knees. Osteoarthritis radiographic progression was strongly associated with WOMAC Function and KOOS Pain worsening (P < 0.001) in the 2 years prior to TKA. KL worsening was strongly associated with future arthroplasty (Odds ratio = 5.0, 95% CI = 2.6-9.8) after adjustment for potential confounders.

Persons undergoing TKA 2 years later had substantial worsening pain and function over the 2-year pre-operative period as compared to a non-surgical sample matched based on KL grades. Almost 30% of persons who elect to undergo TKA undergo rapid disease progression and symptom worsening during the 2 years prior to TKA.

Little is known about the features and role of exercise discussions between rheumatologists and patients. The goals of this study were to: 1) describe rheumatologists' and patients' attitudes and beliefs regarding exercise and physical therapy for rheumatoid arthritis (RA); 2) describe frequency and length of exercise discussions; 3) determine the accuracy of recall for exercise discussions; and 4) assess the influence of attitudes regarding exercise on communication about exercise. Goals 1-3 were addressed with analysis of baseline questionnaires and audiotaped encounters. The influence of attitudes and beliefs regarding exercise on the frequency and length of exercise discussions was assessed prospectively. Patients and rheumatologists were enrolled from a large tertiary care institution. Clinical encounters were audiotaped, transcribed, coded, and analyzed to identify specific characteristics of the exercise discussions. One hundred thirty-two patients and 25 rheumatologists participated in the study. Rheumatologists and patients discussed exercise in 53% of the encounters. Rheumatologists' beliefs regarding the usefulness of exercise for RA varied, with the least positive beliefs being reported for aerobic exercise. Exercise discussions were more likely to occur if the patient was currently exercising, odds ratio (OR) = 2.4; 95% confidence interval (CI) (1.2-4.9), and when the rheumatologist believed aerobic exercises were useful in managing RA, OR = 1.4; 95% CI (1.1-1.9). Current exercise behavior was associated with patients' positive attitude toward exercise (chi 2 1 = 8.4; P = 0.004) and perceived social support for exercise (chi 2 1 = 4.5; P = 0.04). When rheumatologists initiated exercise discussions, there was nearly twice as much discussion (beta = -8.4; P = 0.001).

Exercise talk was influenced by patients' and rheumatologists' beliefs and attitudes regarding the effectiveness of exercise and physical therapy in managing RA, patient experience with exercise, and by characteristics of the rheumatologist.

Neurologic involvement occurs in approximately 25% of patients with primary Sjögren's syndrome. Manifestations are diverse and can affect the entire neuroaxis. Central nervous system dysfunction involves the brain as well as the spinal cord and may recur over time. Due to a variety of presentations, Sjögren's syndrome with neurologic involvement may be difficult to diagnose. We report 4 cases of patients with primary Sjögren's syndrome who presented with atypical neurologic manifestations. The first case describes a patient with a pseudotumoral lesion. The second patient was a 54-year-old woman suffering from a multiple mononeuropathy. The third case describes a 66-year-old man whose primary Sjögren's syndrome presented as progressive multiple sclerosis, and the fourth case reports a 57-year-old woman patient suffering from myelitis along with progressive cognitive disorders.

Neurologic impairment in Sjögren's syndrome is probably underestimated and the diagnosis is often delayed. Primary Sjögren's syndrome should be suspected in patients presenting with atypical clinical and radiologic neurologic manifestations.

Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA). Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-alpha -308G -->A, interleukin-6 (IL-6) -174G -->C and interferon-gamma +874G -->A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 -1082G -->A, -819C -->T and -592A -->C and transforming growth factor-beta1 (TGF-beta1) codon 10T -->C and codon 25G -->C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the alpha = 0.100 level in univariate analyses were entered in multivariate tests. In multivariate tests, the IL-6 genotype -174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-beta1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029].

The correlation of IL-6 genotype with pain and the possible association of the TGF-beta1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.

To investigate the clinical and laboratory characteristics of tumor like Sjögren's syndrome (TLSS) patients and non-tumor like Sjögren's syndrome (NTLSS) and the incidence of lymphoma in patients of Sjögren's syndrome (SS). A retrospective analysis was carried out in 199 primary SS (including TLSS) patients who were recruited in Peking University School and Hospital of Stomatology from 1998 to 2010. Clinical and laboratory information were collected. The patients were divided into two groups: TLSS (n = 25) and NTLSS (n = 174). Clinical and laboratory characteristics were compared between these two groups by a statistical analysis. Of the 25 TLSS patients, 23 had enlargements of parotid glands and 2 had enlargements of submandibular glands. There were significant differences of salivary scintigraphy appearance (P = 0.018), hypergammaglobulinemia (P = 0.014), rheumatoid factor positive rate (P = 0.001), formation of the ectopic germinal centers (P = 0.014), double positive rate of anti-SSA antibody and anti-SSB antibody (P < 0.001) between the TLSS and NTLSS patients. Among the 25 TLSS patients, 3 developed lymphomas, accounting for 1.5% (3/199) of the total 199 patients and 12% (3/25) of the TLSS patients. Lymphoma subtypes included one diffused large B-cell lymphoma and two mucosa-associated lymphoid tissue lymphoma. There was no lymphoma detected in NTLSS patients.

There are clinical and laboratory differences between TLSS and NTLSS patients, with a more tendency to develop lymphomas in TLSS patients.

Pain management is a cornerstone of osteoarthritis (OA) management. The aim of this review is to obtain current, literature-based estimates of the effect of common pharmacologic treatments on pain reduction in OA. A MEDLINE search (2006-2016) was conducted for randomized controlled trials studying acetaminophen, oral NSAIDs, topical NSAIDs, COX-2 inhibitors, and opioids in the treatment of OA pain. Drug effect on pain was estimated using relative change in pain, and expressed as percentage change. An overall effect for each drug category was obtained as a weighted average of study-specific effects, with weights based on each study's sample size. Twenty-nine studies were included. The effect on pain was estimated in a total of 43 treatment arms (acetaminophen n = 6, oral NSAIDs n = 9, topical NSAIDs n = 8, COX-2 inhibitors n = 9, and opioids n = 11). Relative (%) changes in pain were found to be as follows: acetaminophen = 32.5, oral NSAIDs = 34.3, topical NSAIDs = 40.9, COX-2 inhibitors = 36.9, and opioids = 35.4.

The effects of 5 major drug categories in the treatment of OA pain were reviewed with data extracted from 29 studies published from 2006 to 2016. Acetaminophen was found to have an RC value close to that of oral NSAIDs. The effects of oral NSAIDs, COX-2 inhibitors, and opioids in controlling pain were similar to what has been demonstrated in previous literature. Topical NSAIDs were found to have a greater RC than oral NSAIDs.

RA is a chronic inflammatory state, predisposing for atherosclerosis as it is an immunoinflammatory process. This study focuses on use of Carotid artery intimomedial thickness (CIMT) as a marker for subclinical atherosclerosis. To study the assessment of atherosclerosis by Carotid Intimo-Medial Thickness (CIMT) in patients with rheumatoid arthritis and Correlation of ultrasonographic findings with severity of disease (using DAS-28 score). A prospective, case-control study involving 50 cases of diagnosed RA cases, and 50 healthy control. Sonological examination of the carotid and the vertebral arteries was done using a L&T SEQUINA color Doppler scanner with a linear band probe of frequency 6.6 to 14 MHz's. This case control study was carried out in 100 subjects (50 cases and 50 controls). Cases comprised of 41 rheumatic women (Mean age 42.08+12.13 yrs) and 9 (mean age 48.4+12.8 years) rheumatic men. Mean CIMT of the study group (0.5996+0.109mm) was significantly greater (p<0.001) than that of control group (0.5290+0.006mm). We observed carotid plaques in 18% subjects of study group compared to 2% in controls (p<0.001). Mean age in the study group was 46.56+12.82 years and that of controls was 46.38+11.69 years (p>0.05). In the study group mean CIMT was significantly increased in RA factor positive patients than in RA factor negative patients. We also calculated the DAS-28 score of the study group subjects and found that 8, 27 and 15 were having Mild, Moderate & severe disease activity respectively.

CIMT has significant correlation with the age, and CIMT increases with age. Mean CIMT was found to be more with RF+(ve) patients indicating acute inflammation also has a role. When compared, the mean CIMT in each DAS sub group the result was found to be statistically insignificant.