Datasets:

austin

/

rheum_abstracts

like 0

Follow

Austin Health 2

Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA. Patients with RA (n = 185 (46 with incident and 139 with prevalent disease) were followed for 30.9 ± 9.1 months. Baseline and annual assessments comprised the disease activity score in 28 joints (DAS28), HAQ and US7S. The US7S includes semiquantitative measurements of synovitis assessed by greyscale (GS) and power Doppler (PD) in seven joints of the clinically dominant hand and foot, which are then aggregated in PD and GS synovitis sum-scores (PDsynSS and GSsynSS). A linear mixed-effect model was used to assess the longitudinal relationship between GSsynSS, PDsynSS and HAQ. We used standard and time-lag models to explore the association between HAQ, and GSsynSS, PDsynSS and DAS28 measured at the same time or at the previous visit 12 months ago, respectively. When the standard model was applied, in univariate analyses HAQ score was positively associated with GSsynSS and PDsynSS with β coefficients significantly higher in incident than in prevalent disease. In multivariate analysis both synSSs were individually no longer significant predictors of HAQ score. When using the time-lag model, after adjustment for the previous DAS28 or HAQ score, both PDsynSS and GSsynSS were significantly and negatively associated with the current HAQ.

US7 PD and GS synovitis sum-scores alone were positively associated with current functional status reflected by the HAQ in patients with RA, and this relationship was stronger in patients with early disease. When combined with the DAS28 or HAQ, US7 PD and GS synovitis sum-scores were predictive of the change in HAQ score over one year.

The disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity. We conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34 Enhanced numbers of EMPs, CFU-ECs and non-haematopoietic CD34

This study identifies the mobilisation of CD34

To develop an accurate method for quantifying differences in the trabecular structure in the tibial bone between subjects with and without knee osteoarthritis (OA). Standard knee radiographs were taken from 26 subjects (seven women) with meniscectomy and radiographic OA Kellgren & Lawrence grade 2 or worse in the medial compartment. Each case knee was individually matched by sex, age, body mass index and medial or lateral compartment with a control knee. A newly developed augmented Hurst orientation transform (HOT) method was used to calculate texture parameters for regions selected in X-ray images of non-OA and OA tibial bones. This method produces a mean value of fractal dimensions (FD MEAN), FDs in the vertical (FDV) and horizontal (FDH) directions and along a direction of the roughest part of the tibial bone (FDSta), fractal signatures and a texture aspect ratio (Str). The ratio determines a degree of the bone texture anisotropy. Reproducibility was calculated using an intraclass correlation coefficient (ICC). Comparisons between cases and controls were made with paired t tests. The performance of the HOT method was evaluated against a benchmark fractal signature analysis (FSA) method. Compared with controls, trabecular bone in OA knees showed significantly lower FD MEAN, FDV, FDH and FDSta and higher Str at trabecular image sizes 0.2-1.1mm (P<0.05, HOT). The reproducibility of all parameters was very good (ICC>0.8). In the medial compartment, fractal signatures calculated for OA horizontal and vertical trabeculae were significantly lower at sizes 0.3-0.55 mm (P<0.05, HOT) and 0.3-0.65 mm (P<0.001, FSA). In the lateral compartment, FDs calculated for OA trabeculae were lower than controls (horizontal: 0.3-0.55 mm (P<0.05, HOT) and 0.3-0.65 mm (P<0.001, FSA); vertical: 0.3-0.4mm (P<0.05, HOT) and 0.3-0.35 mm (P<0.001, FSA).

The augmented HOT method produces fractal signatures that are comparable to those obtained from the benchmark FSA method. The HOT method provides a more detailed description of OA changes in bone anisotropy than the FSA method. This includes a degree of bone anisotropy measured using data from all possible directions and a texture roughness calculated for the roughest part of the bone. It appears that the augmented HOT method is well suited to quantify OA changes in the tibial bone structure.

To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA). A multicenter, randomized, parallel-group, placebo-controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment. Eighty-five patients were randomized to the HA group (n = 42) or placebo group (n = 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis (mean +/- SD decrease 7.8 +/- 24.9 mm with HA versus 9.1 +/- 27.4 mm with placebo; P = 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P = 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events.

Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA.

High levels of rheumatoid factors (RF) are detectable in serum of the majority of patients with rheumatoid arthritis (RA), but 5-10% of patients remain seronegative (SN). Despite clinical and genetic similarities between these two subsets of RA, it has been proposed that they may be regarded as distinct clinical entities. In the present study a panel of monoclonal antibodies (mAb) recognizing RF-associated cross-reactive idiotypes (CRI) linked to the VH1 (G8), VH4 (LC1), VK3b (17-109) and a mAb recognizing the VK3 subgroup (C7) of immunoglobulin variable region (IgV) gene products were used to quantitate the level of expression of these gene products in serum and synovial fluid of 35 seropositive (SP) and 8 SN RA patients by capture ELISA. While the concentration and relative proportion of the IgV are recognized by the mAb G8, 17-109 and C7 were significantly higher in serum and synovial fluid of the SP RA, compared to the SN-RA patients (G8, p = 0.009; 17-109, p = 0.0001; C7, p = 0.001). The CRI recognized by the mAb LC1 was highly represented in serum and synovial fluid of the SN-RA patients. There have been no significant differences in the level of expression of these IgV gene products (other than the product recognized by C7 mAb in SP patients) between serum and synovial fluid of either group of patients.

Our results suggest that the expressed repertoire of Ig VH and VK genes in these two subsets of RA is differentially regulated and may be influenced by selective mechanisms leading to positive or negative selection of certain genes.

There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA) are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score < or =3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. Patients had higher intima-media thickness than controls of all the sites evaluated at carotid artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found.

Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.

The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints.

We provide evidence that environmental cold exposure enhances pain and increases blood flow in a mono-arthritis model. These changes are dependent on TRPA1. Thus, TRPA1 may act locally within the joint to influence blood flow via sensory nerves, in addition to its established nociceptive actions.

Knee osteoarthritis (OA) is a leading joint disease. In most of the early stages it does not involve the whole knee joint. Often, symptoms only or mainly concern the medial compartment combined with a slight varus malalignment. Do valgus braces or laterally wedged insoles influence biomechanics and thus improve pain and function in patients with medial OA? Does the OA grade, severity of malalignment or patient's body weight predict the efficacy of the above-mentioned conservative treatment options? The current literature was reviewed in regard to biomechanical changes to joint loading and their correlation to clinical results. Valgus braces and laterally wedged insoles reduce knee adduction moment, varus malalignment and analgesic consumption. Some authors suggest that mainly an alteration in muscle activity (diminished muscle co-contractions) is responsible for pain relief. Body weight and severity of varus malalignment did not influence treatment results; a significant correlation with OA severity was shown only for laterally wedged insoles. For both devices, compliance problems - especially long-term - should be considered, and conclusive evidence of positive clinical effects cannot be stated.

Despite positive evidence in the current literature, a recommendation for or against valgus (unloader) braces in medial OA is not possible due to inconclusive results. Laterally wedged insoles are not recommended. Especially the long-term results are doubtful, and are possibly related to lacking compliance.

Disorders that affect glucose metabolism, namely diabetes mellitus (DM), may favor the development and/or progression of osteoarthritis (OA). Thus far, little is known regarding the ability of chondrocytes to adjust to variations in the extracellular glucose concentration, resulting from hypoglycemia and hyperglycemia episodes, and so, to avoid deleterious effects resulting from deprivation or intracellular accumulation of glucose. The aim of this study was to compare the ability of normal and OA chondrocytes to regulate their glucose transport capacity in conditions of insufficient or excessive extracellular glucose and to identify the mechanisms involved and eventual deleterious consequences, namely the production of reactive oxygen species (ROS). Chondrocytes, isolated from normal and OA human cartilage, were maintained in high-density monolayer cultures, in media without or with 10 or 30 mM glucose. Glucose transport was measured as the uptake of 2-deoxy-D-glucose (2-DG). Glucose transporter-1 (GLUT-1) mRNA and protein content were evaluated by real-time RT-PCR and western blot, respectively. ROS production was measured with 2',7'-dichlorodihydrofluorescein diacetate. Basal and IL-1beta-induced 2-DG uptake, including the affinity (1.066 +/- 0.284 and 1.49 +/- 0.59 mM) and maximal velocity (0.27 +/- 0.08 and 0.33 +/- 0.08 nmol/microg protein/hour), and GLUT-1 content were identical in normal and OA chondrocytes. Glucose deprivation increased 2-DG uptake and GLUT-1 protein both in normal and OA chondrocytes. Exposure to high glucose (30 mM) for 18 or 48 hours decreased those parameters in normal but not in OA chondrocytes. GLUT-1 mRNA levels were unaffected by high glucose, either in normal or OA chondrocytes. The high glucose-induced reduction in GLUT-1 protein in normal chondrocytes was reversed by treatment with a lysosome inhibitor. High glucose induced ROS production, which lasted significantly longer in OA than in normal chondrocytes.

Normal human chondrocytes adjust to variations in the extracellular glucose concentration by modulating GLUT-1 synthesis and degradation which involves the lysosome pathway. Although capable of adjusting to glucose deprivation, OA chondrocytes exposed to high glucose were unable downregulate GLUT-1, accumulating more glucose and producing more ROS. Impaired GLUT-1 downregulation may constitute an important pathogenic mechanism by which conditions characterized by hyperglycemia, like DM, can promote degenerative changes in chondrocytes that can facilitate the progression of OA.

To determine whether altered IL8 methylation status is associated with increased expression of IL8 in human osteoarthritic (OA) chondrocytes. IL8 expression levels and the percentage CpG methylation in human chondrocytes were quantified by qRT-PCR and pyrosequencing in OA patients and in non-OA osteoporotic controls. The effect of CpG methylation on IL8 promoter activity was determined using a CpG-free vector; co-transfections with expression vectors encoding nuclear factor-kappa B (NF-κB), AP-1 and C/EBP were subsequently undertaken to analyse for IL8 promoter activity in response to changes in methylation status. IL8 expression in OA patients was 37-fold higher than in osteoporotic controls. Three CpG sites in the IL8 promoter were significantly demethylated in OA patients. Multiple regression analysis revealed that the degree of methylation of the CpG site located at -116-bp was the strongest predictor of IL8 expression. In vitro DNA methylation was noted to decrease IL8 promoter basal activity. Furthermore, NF-κB, AP-1 and C/EBP strongly enhanced IL8 promoter activity whilst DNA methylation inhibited the effects of these three transcription factors.

The present study demonstrates the key role of DNA methylation status on the expression of IL8 in human chondrocytes. We demonstrate a quantitative relationship between percentage methylation and gene expression within clinical samples. These studies provide direct evidence linking the activation of IL8, DNA demethylation and the induction of the OA process with important therapeutic implications therein for patients with this debilitating disease.

In a recent study we demonstrated that the postpartum period, particularly after the first pregnancy, is a time of increased risk for the development of rheumatoid arthritis (RA). The present study was undertaken to investigate whether this risk might be explained by breast-feeding. Through a nationwide media campaign, we identified 187 women who had developed RA within 12 months of a pregnancy, and we compared their breast-feeding histories with those of 149 similarly aged women chosen from the patient registers of a nationwide group of general practitioners. In all, 88 of the women with RA developed the disease after their first pregnancy. Eighty-one percent of these 88 women had breast-fed. This was higher than the breast-feeding prevalence of 50% in the 129 controls whose first pregnancy had resulted in a live birth (adjusted odds ratio [OR] 5.4, 95% confidence interval 2.5-11.4). There was a smaller increased risk of breast-feeding after a second pregnancy in the RA cases (OR 2.0) and no increase after a third pregnancy (OR 0.6). The increase in risk was greatest in those cases whose disease was erosive and who were rheumatoid factor positive.

In a small group of susceptible women, exposure to breast-feeding after the first pregnancy is associated with a significant increase in risk for RA development. We postulate that this may reflect hormonal influences, specifically the high level of the proinflammatory hormone prolactin.

To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2-b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between-group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo-treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008).

The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow-acting drug for use in rheumatoid arthritis.

Multidisciplinary rehabilitation has beneficial effects on health-related quality of life (HRQoL) in patients with chronic rheumatic diseases. However, whether this intervention benefits different age groups in women or men is largely unknown. To investigate HRQoL in patients with chronic rheumatic disease after completion of a 3-week multidisciplinary treatment, with special focus on differences in effect between age and gender groups. HRQoL was measured with SF-36. Mean scores for all SF-36 domains were compared before and after the 3-week regimen and again at 3-, 6-, and 12-month follow-ups. Multivariable linear regression models using generalized estimating equations to account for repeated measurement were employed. A weighting procedure to account for differential dropouts was applied. Three hundred fifty-six women and 74 men with chronic rheumatic disease were included. There were short-term improvements in all SF-36 domains irrespective of age or gender. These effects persisted for up to 1 year in the psychological, social, and energy domains for women under 50. We found no lasting effects for men; however, young men showed similar trends.

Inpatient multidisciplinary rehabilitation improves short-term HRQoL in all patients. Younger women maintain these beneficial effects for up to 1 year. Additional intervention should be considered for elderly women and for men in order to sustain rehabilitation effects.

The objective of this report is to investigate the feasibility of collecting patient-reported outcomes (PROs) via e-questionnaires delivered to patients with chronic inflammatory diseases (CIDs). Consecutive outpatients with a confirmed diagnosis of systemic lupus erythematosus, primary Sjögren's syndrome or inflammatory bowel disease were followed at two medical departments. Patients received monthly e-mails containing the SF36, Hospital Anxiety and Depression scale and an analogue symptom scale over a six-month period. Participation rate, socio-demographic characteristics and patients' satisfaction were analysed. A total of 128 patients were included (79% female; mean age: 42 ± 12 years). Eighty-two per cent of questionnaires were returned. The monthly participation rate ranged from 89% to 77%, with a six-month attrition rate of 13%. The mean completion rate of questionnaires was 98%. Factors significantly associated with increased answer rate were: married/couple status, greater number of children at home and previous participation in online surveys. The main reasons for non-response were: 'too busy to participate' (35%) and 'away from home Internet access' (31%). Overall, 68% of the participants found the study convenient and 96% agreed to continue at a monthly or bimonthly frequency.

Online home self-assessment of PROs was feasible in the setting of CIDs. Patients were satisfied and willing to continue the survey. The Internet allows immediate and sophisticated presentation of PROs to clinicians. Future studies are warranted to determine how PRO monitoring may contribute to routine care in CIDs and other diseases.

Little is known about the effect of fibromyalgia on absence due to sickness in working populations. To examine the risk of absence due to sickness among employees with fibromyalgia. A prospective cohort study with 1-year follow-up of recorded and certified absence due to sickness after a survey of chronic diseases among 34 100 Finnish public sector employees (27 360 women and 6740 men) aged 17-65 years at baseline in 2000-2. 20 224 days of absence due to sickness for the 644 employees with fibromyalgia and 454 816 days for others were documented. Of those with fibromyalgia, 67% had co-occurring chronic conditions such as osteoarthritis, rheumatoid arthritis, depression or other psychiatric disorders. Compared with employees with none of these chronic conditions, the hazard ratio (HR) adjusted for age, sex and occupational status was 1.85-fold (95% confidence interval (CI) 1.53 to 2.18) for people with fibromyalgia alone and 2.63-fold (95% CI 2.34 to 2.96) for employees with fibromyalgia with coexisting conditions. The excess rate of absence due to sickness was 61 episodes/100 person-years among people with fibromyalgia alone. Among employees with musculoskeletal and psychiatric disorders, secondary fibromyalgia was associated with a 1.4-1.5-fold increase in risk of absence.

Fibromyalgia is associated with a substantially increased risk of medically certified absence due to sickness that is not accounted for by coexisting osteoarthritis, rheumatoid arthritis or psychiatric disorders.

Assess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg + methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD + methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate. Microsimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care. Lifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold. Sanofi and Regeneron Pharmaceuticals, Inc.

In patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks + methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+ methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab + methotrexate or csDMARD active treatment.

To evaluate the surgical outcomes and clinical experience of the treatment of degenerative osteoarthritis of the temporomandibular joint with metal fossa-eminence hemijoint replacement. A retrospective chart review showed 99 patients (94 females and 5 males) who underwent treatment of degenerative joint disease with hemijoint replacement surgery, including data on 141 operated joints (57 unilateral, and 42 bilateral). A visual analog scale (VAS) patient-response questionnaire with directives was mailed to the 99 patients. The questionnaire investigated the patient's experience before and after the treatment procedure in 5 areas: 1) pain intensity, 2) pain experience, 3) chewing ability, 4) mouth opening, and 5) joint noise. In addition, patients were requested to score on a VAS of 1 to 10 their overall satisfaction with the treatment outcome. Treatment outcomes were also compared between patients who received an autogenous abdominal fat graft placement before wound closure, and those who did not receive this adjunctive treatment. Forty-two of 99 patients responded to the questionnaires, with an average follow-up time of 5.1 years. In these 42 patients, pain experience was reduced by 68.6% (4.5 +/- 1.3 [mean +/- SD], presurgery, vs 1.4 +/- 1.7, current, on a 6-point scale). In addition, pain intensity was reduced by 58.7% (7.5 +/- 2.2, presurgery, vs 3.1 +/- 3.0, current, on a 10-point scale). Thirty-three of 42 patients (78.6%) stated in the questionnaire that they were highly satisfied with the results of surgical treatment (average, 9.0 +/- 1.2 on a 0-to-10-point VAS scale). Fifty-one patients (71 joints) did not receive an adjunctive abdominal fat graft, whereas 48 patients (70 joints) received this adjunctive treatment. In the nonfat group, 17 (21.5%) joints required revision surgery, and in the fat group, 4 joints (6.5%) required revision surgery.

Temporomandibular hemiarthroplasty with metal fossa-eminence prosthesis provides predictable and satisfactory results in patients operated upon for advanced osteoarthritis. The incidence of revision surgery was found to be reduced with the application of fat graft adjunctive treatment.

To investigate an immunopathogenesis of central and paracentral corneal ulceration associated with rheumatoid arthritis. Sparse infiltrating cells in the ulcer area were identified by immunohistochemistry applied to archived formalin fixed, paraffin embedded tissues that had been recovered from patients undergoing penetrating keratoplasty necessitated by rheumatoid-associated central or paracentral corneal ulceration. Clinically, the ulcers presented as non-infiltrated lesions with a modicum of other ocular inflammation. Sparse T-lymphocytes were consistently identified in the subepithelial areas adjacent to the ulcer, with some neutrophils and macrophages in the stroma. B-lymphocytes were not detected. MHC Class II antigens reactivity was noted on some infiltrating cells and on corneal endothelium of two specimens.

Immunohistochemistry of archival tissue facilitated detection and identification of sparse infiltrate in this infrequent corneal melting. Selective, consistent finding of T-lymphocyte infiltration in the ulcer area supports an immunopathogenesis of this clinical entity.

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by muscle weakness, which limit activities of daily living. Patient Reported Outcomes Measurement Information System (PROMIS) is a set of outcome measures developed using NIH funding, but has not yet been studied in adult IIM. Currently, the most commonly used PROs in IIM are Health Assessment Questionnaire (HAQ-DI) and SF-36 physical function-10 (PF10), both of which have several limitations. In this study, we investigated psychometric properties of PROMIS physical function-20 (PF-20) and compared to HAQ-DI and SF-36 PF10. Patients with IIM completed PROMIS PF-20 and six myositis core set measures [manual muscle testing (MMT), physician (MD-GDA), patient (PT-GDA) and extra-muscular global disease activity, HAQ-DI and creatine kinase], SF-36 PF10 and functional tests [six-minute walk, timed up-and-go and sit-to-stand tests] at monthly visits over 6-months. Total improvement score (TIS) using 2016 ACR/EULAR myositis response criteria was obtained as measures of change. Fifty patients [mean age, 51.6; 60% females] were enrolled; 6 PM, 24 DM, 9 NM and 11 with AS. PROMIS PF-20 showed strong test-retest reliability when repeated in 1-month. PROMIS PF-20 had moderate-strong correlations with MD-GDA, PT-GDA, MMT, HAQ-DI, SF-36 PF10, and functional tests indicating good convergent validity. Change in PROMIS PF-20 strongly correlated with TIS demonstrating good responsiveness. HAQ-DI and SF-36 PF10 exhibited similar validity and responsiveness; HAQ-DI was found to have a ceiling effect.

PROMIS PF-20 demonstrates favorable psychometric properties in a large cohort of myositis patients and offers distinct advantages.

Fibromyalgia is a pathological entity characterized by chronic widespread musculoskeletal pain and the presence of "tender points". It constitutes a significant health problem because of its prevalence and economic impact. The aim of the present study was to determine the therapeutic benefits of low impact aerobic exercise alone or in combination with music therapy in patients with fibromyalgia. A single-blind randomized controlled pilot trial was performed. Thirty-five individuals with fibromyalgia were divided into three groups: (G1) therapeutic aerobic exercise with music therapy (n=13); (G2) therapeutic aerobic exercise at any rhythm (n=13) and (CG) control (n=9). The intervention period lasted eight weeks. Depression, quality of life, general discomfort and balance were assessed before and after intervention. At post-intervention, group G1 improved in all variables (depression (p=0.002), quality of life (p=0.017), general discomfort (p=0.001), and balance (p=0.000)), while group G2 improved in general discomfort (p=0.002). The change observed in balance was statistically different between groups (p=0.01).

Therapeutic aerobic exercise is effective in improving depression and general discomfort in individuals with fibromyalgia. However, effectiveness is higher when combined with music therapy, which brings about further improvements in quality of life and balance.

To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients. Periodontitis, healthy periodontal and RA-affected synovial tissue samples were collected in addition to buccal swabs. These samples were stained for the presence of citrullinated proteins using polyclonal (Ab5612) and monoclonal (F95) antibodies. Furthermore, Western blotting with F95 was performed on lysates prepared from periodontal and synovial tissues. In periodontitis stroma, increased citrullinated protein presence (80%) was observed compared with control stroma (33%), the latter was associated with inflammation of non-periodontitis origin. Periodontal epithelium always stained positive for Ab5612. Noteworthy, only periodontitis-affected epithelium stained positive for F95. All buccal mucosal swabs and 3 of 4 synovial tissue samples stained positive for both Ab5612 and F95. Western blotting with F95 showed presence of similar citrullinated proteins in both periodontitis and RA-affected synovial tissue.

Within the periodontal stroma, citrullination is an inflammation-depended process. In periodontal epithelium, citrullination is a physiological process. Additional citrullinated proteins are formed in periodontitis, apparently similar to those formed in RA-affected synovial tissue. Periodontitis induced citrullination may play a role in the aetiology of rheumatoid arthritis.

The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease. The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide. Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively.

Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function.

To compare the efficacy and tolerability of paroxetine (a selective serotonin reuptake inhibitor) with that of amitriptyline (a tricyclic antidepressant) in the treatment of depression in 191 patients with rheumatoid arthritis (RA). A randomized, double blind, double dummy, parallel group study. A placebo washout period of 3-7 days was followed by an 8 week active treatment phase during which patients received either paroxetine (20-40 mg daily) or amitriptyline (75-150 mg daily). The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint. Paroxetine was as effective as amitriptyline for the treatment of depression, with similar improvements in RA associated pain and disability also seen in both groups. However, paroxetine was better tolerated than amitriptyline, with an overall frequency of adverse experiences of 56.4% and 67.7% in the 2 groups, respectively. The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group (18.1% vs 43.8% taking amitriptyline) and paroxetine treated patients also experienced fewer severe (16.0% vs 21.9%), serious nonfatal (0% vs 4.2%), and drug related adverse experiences (12.8% vs 29.2%).

Tolerability is an important consideration in this patient population, which is largely composed of elderly patients who are taking additional medications for RA. Paroxetine shows a number of advantages in the management of depression comorbid with RA.

G protein-coupled receptors (GPCRs) are transmembrane receptor proteins, which allow the transfer of signals across the membrane. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. GPCRs signaling pathways play a significant role in inflammatory and immune response processes including RA. In this review, we have focused on the advances in GPCRs signaling pathway implicating the inflammatory and immune response of RA. The signaling pathways of GPCRs-adenylyl cyclase (AC)-cyclic adenosine 3', 5'-monophosphate (cAMP) include β

GPCRs-AC-cAMP signal pathways involve in the inflammatory and immune response of RA. Different signaling pathways are mediated by different receptors, such as β

Osteoarthritis (OA) is an age-related disease characterized by articular cartilage degeneration. It is largely heritable, and genetic screening has identified single-nucleotide polymorphisms (SNPs) marking genomic risk loci. One such locus is marked by the G>A SNP rs75621460, downstream of TGFB1. This gene encodes transforming growth factor β1, the correct expression of which is essential for cartilage maintenance. This study investigated the regulatory activity of rs75621460 to characterize its impact on TGFB1 expression in disease-relevant patient samples (n = 319) and in Tc28a2 immortalized chondrocytes. Articular cartilage samples from human patients were genotyped, and DNA methylation levels were quantified using pyrosequencing. Gene reporter and electrophoretic mobility shift assays were used to determine differential nuclear protein binding to the region. The functional impact of DNA methylation on TGFB1 expression was tested using targeted epigenome editing. The analyses showed that SNP rs75621460 was located within a TGFB1 enhancer region, and the OA risk allele A altered transcription factor binding, with decreased enhancer activity. Protein complexes binding to A (but not G) induced DNA methylation at flanking CG dinucleotides. Strong correlations between patient DNA methylation levels and TGFB1 expression were observed, with directly opposing effects in the cartilage and the synovium at this locus. This demonstrated biologic pleiotropy in the impact of the SNP within different tissues of the articulating joint.

The OA risk SNP rs75621460 impacts TGFB1 expression by modulating the function of a gene enhancer. We propose a mechanism by which the SNP impacts enhancer function, providing novel biologic insight into one mechanism of OA genetic risk, which may facilitate the development of future pharmacologic therapies.

To investigate the effects of intraarticular glucocorticoid treatment on macrophage infiltration, the expression of the chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha), and the expression of matrix metalloproteinases 1 and 3 (MMPs 1 and 3) and their inhibitors, the tissue inhibitors of metalloproteinases 1 and 2 (TIMPs 1 and 2), in osteoarthritis (OA) synovial membranes. Forty patients underwent arthroscopic biopsy before and 1 month after intraarticular injection of glucocorticoids. Twenty-one patients received 120 mg of methylprednisolone acetate (Depo-Medrol; Upjohn, Kalamazoo, MI), and 20 patients received placebo (1 patient received placebo in 1 knee and methylprednisolone acetate in the other). Immunoperoxidase staining for the expression of CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 was performed, and the immunostaining was quantified by color video image analysis. CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining was observed in all synovial membranes. Intraarticular glucocorticoid treatment was associated with a small (30%) but statistically significant (P = 0.048) reduction in CD68+ macrophage staining in the synovial lining layer, but there was no change in the CD68 expression in the synovial sublining layer. No significant differences were observed for MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining in the synovial lining or sublining layers.

Intraarticular glucocorticoids may reduce CD68+ macrophage infiltration into the synovial lining layer, but not the expression of MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 in the synovial membrane, in patients with OA.

To study the anisotropic characteristics of individual histological zones in articular cartilage using Fourier-transform infrared imaging (FTIRI) at 6.25microm pixel resolution. A canine humeral cartilage-bone block was paraffin-embedded and microtomed into 6microm sections. Each of the five sections was infrared (IR)-imaged 26 times with identical acquisition parameters, for a 5-10 degrees increment of a wire grid polarizer introduced before the detector in 0-180 degrees angular space. Following the IR imaging experiments, the same tissue sections were also imaged by polarized light microscopy (PLM). The IR absorption components of cartilage (amide I, amide II, amide III, and sugar) exhibit distinctly different anisotropies, which vary differently as a function of the tissue depth. A new type of image, "the absorbance anisotropy map", was constructed for each major component, which shows that (1) the absorbance of the amide components in most parts of the tissue is anisotropic, (2) the anisotropic behavior in the radial and the superficial zones of the tissue is opposite, (3) the absorption profile of amide I is inverse to those of amide II and amide III, and (4) the IR absorption of the sugar component is almost isotropic. The anisotropic variations of the amide components were fitted to an empirical equation.

The IR anisotropy map is a powerful tool to monitor the individual chemical components in articular cartilage. The ability to examine the same tissue section using both FTIRI and PLM offers the possibility of correlating the tissue's morphology with chemical distribution.

To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized, and the correlation of FLIP expression with the degree of synovial inflammation, as well as the activity of caspase 8 was then analyzed. RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples, but not in 3 normal synovial tissues. In JIA, FLIP expression could be found in both the lining and sublining layers, mainly in the macrophage-like cells. Moreover, the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r = 0.563, P < 0.05).

The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.

The duration of treatment with glucocorticoids (GC) in polymyalgia rheumatica (PMR) is often longterm. Amino bisphosphonates (N-BP) are used in PMR for the prevention of GC-induced osteoporosis, but they coulsd also have immunomodulatory properties. Whether they can be effective as an adjuvant treatment in PMR is unknown. We aimed to establish whether the use of N-BP in our PMR cohort may be associated with GC discontinuation. We conducted a retrospective review of all patients diagnosed with PMR recorded in our electronic medical notes. Cox regression analyses were used to examine the association between the use of N-BP and discontinuation of GC. Data were retrieved for 385 patients (mean age 71 ± 10 yrs, 64% females, mean initial prednisone dose 19 ± 9 mg/day). The median followup time was 38 months (range 9-57); more than 60% of patients were exposed to N-BP. GC were discontinued in 47% of patients after a median time of 20 months (range 14-27), but subsequently restarted in 39%. Overall, 276/385 patients (72%) were actively treated at their last available evaluation (mean prednisone dose 4.9 ± 5.5 mg/day), while 123/205 (60%) were still receiving GC after 24 months of followup. The use of N-BP was associated with the discontinuation of GC (adjusted HR 0.66, 95% CI 0.50-0.88), independent of age, initial GC dose, and osteoporosis.

Unlike current guidelines, longterm treatment with GC is often necessary. These preliminary data suggest that N-BP may be involved in the management of PMR.

The non-neuronal cholinergic system represents non-neuronal cells that have the biochemical machinery to synthetize de novo and/or respond to acetylcholine (ACh). We undertook this study to investigate this biochemical machinery in chondrocytes and its involvement in osteoarthritis (OA). Expression of the biochemical machinery for ACh metabolism and nicotinic ACh receptors (nAChR), particularly α7-nAChR, in human OA and murine chondrocytes was determined by polymerase chain reaction and ligand-binding. We investigated the messenger RNA expression of the human duplicate α7-nACh subunit, called CHRFAM7A, which is responsible for truncated α7-nAChR. We assessed the effect of nAChR on chondrocytes activated by interleukin-1β (IL-1β) and the involvement of α7-nAChR using chondrocytes from wild-type (WT) and α7-deficient Chrna7 Human and murine chondrocytes express the biochemical partners of the non-neuronal cholinergic system and a functional α7-nAChR at their cell surface (n = 5 experiments with 5 samples each). The expression of CHRFAM7A in human OA chondrocytes (n = 23 samples) correlated positively with matrix metalloproteinase 3 (MMP-3) (r = 0.38, P < 0.05) and MMP-13 (r = 0.48, P < 0.05) expression. Nicotine decreased the IL-1β-induced IL-6 and MMP expression, in a dose-dependent manner, in WT chondrocytes but not in Chrna7

The non-neuronal cholinergic system is functionally expressed in chondrocytes. Stimulation of nAChR induces antiinflammatory and anticatabolic activity through α7-nAChR, but the anticatabolic activity may be mitigated by truncated α7-nAChR in human chondrocytes. In vivo experiments strongly suggest that α7-nAChR has a protective role in OA.

B regulatory cells and their regulatory products/markers, such us semaphorin 3A (sema3A) and its receptor NP-1, FcγIIB, IL-10, and others, act at the very base of self-tolerance, maintenance, and prevention of autoimmune disease development. The aim of the present study was to assess the involvement of CD72, a regulatory receptor on B cells, in systemic lupus erythematosus (SLE). In addition, the potential of soluble sema3A in enhancing the expression of CD72 on B cells of SLE patients was investigated. CD72 expression on activated B cells of SLE patients was significantly lower than that of normal controls. This lower expression of CD72 in SLE patients correlated inversely with SLE disease activity and was associated with lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. Co-culture of purified B cells from healthy controls with condition-media containing recombinant sema3A resulted in significant enhancement of CD72. Similar enhancement of CD72 on activated B cells from SLE patients, though significant, was still lower than in normal individuals.

The lower expression of CD72 on activated B cells from SLE patients correlates with SLE disease activity, lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. The improvement of CD72 expression following the addition of soluble semaphorin 3A suggests that CD72 may be useful as a biomarker to be followed during the treatment of SLE.

BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS). BUILDER-1 was a two part, phase II-III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP). 102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found.

BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.

Case-series study. To assess range of cervical rotation possible after atlantoaxial fixation in rheumatoid arthritis (RA) patients using axial CT. The atlantoaxial complex is primarily responsible for rotation, and the percentage of global cervical rotation dependent on C1-C2 is 60%. Fusion of C1-C2 was expected to cause a loss of almost half the normal cervical rotation. However, some authors had reported that cervical rotation in RA patients increased after atlantoaxial fixation because of pain relief. Nineteen consecutive patients with atlantoaxial instability secondary to RA who had undergone transarticular fixation were included in our study. Visual analog scale was used for assessment of neck pain. We recorded functional CTs to assess C1 to T1 rotation angles before surgery and 6 months after surgery. The patient actively rotated his neck toward right as far as possible, taking care that the shoulders remained in the horizontal plane. The average visual analog scale for neck pain decreased significantly from 7 (range, 4-9) before surgery to 3 (range, 0-5) at 6 months after surgery. The average preoperative C1-T1 rotation angles that were measured using axial CT were 80 degrees in total. C1-T1 rotation angle significantly decreased (55% decrease) after surgery, but there was no difference between right and left motion. Average subaxial rotation (C2-T1) was 31 degrees before surgery and did not increase after surgery.

All 19 patients with RA and atlantoaxial instability in our study had relief of pain and a significant decrease in the C1-T1 rotation angle after atlantoaxial fixation. Subaxial rotation did not change from before to after the operation.

Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. The goal of our meta-analysis was to summarize the contribution of TAP2 polymorphisms to the risk of RA. Meta-analyses were performed between RA and 3 TAP2 coding polymorphisms that comprised TAP2-379Ile > Val (rs1800454), TAP2-565Ala > Thr (rs2228396) and TAP2-665Thr > Ala (rs241447). The meta-analyses were involved with 9 studies (24 individual studies) among 973 cases and 965 controls. Meta-analyses showed that TAP2-379Ile allele was significantly associated with an increased risk of RA (p = 0.0002, odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.18-1.74). This association was further shown only in the dominant model (p = 0.006, OR = 1.59, 95% CI = 1.14-2.22). Subgroup analyses by ethnicity revealed that the association of TAP2-379Ile was significant in Asians (p = 0.03, OR = 1.38, 95% CI = 1.04-1.83). In addition, another significant association of TAP2-565Thr allele with RA was observed in Europeans (p = 0.002, OR = 1.62, 95% CI = 1.20-2.20). The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2097080313124700.

Our meta-analyses suggested that TAP2-379Ile allele was significantly associated with a 59% increased risk in the dominant effect model. Subgroup analyses by ethnicity showed that TAP2-379-Ile increased the risk of RA by 38% in Asians and TAP2-565Thr increased the risk of RA by 38% in Europeans.

Disability has been identified as a core outcome measure in rheumatoid arthritis (RA). The aim of this study was to test the Recent-Onset Arthritis Disability (ROAD) questionnaire for validity, reliability and responsiveness in Italian patients with early RA. The psychometric properties of ROAD were tested in 159 patients with early RA, mean age 54.7 (+/- 8.8), 74.3% women, mean disease duration 14.5 months (+/- 1.9 months). All completed the ROAD, the Medical Outcomes Study SF-36 Health Survey (SF-36), the Health Assessment Questionnaire (HAQ) and the patient global assessment (PGA) of functional disability twice, in order to test for validity and responsiveness. Of the 159 patients who completed the health status instruments on two occasions, 121 were included in the responsiveness analyses. The test-retest reliability of the ROAD questionnaire was calculated using intraclass correlation coefficients (ICCs) and the Bland and Altman method on 77 patients who completed the questionnaire twice over an interval of one week. Construct validity was assessed using Spearman's correlations, while responsiveness was evaluated by 3 different methods: (1) effect size (the mean difference between the baseline scores and thefollow-up scores divided by the standard deviation of the baseline scores); (2) standardized response mean (the mean change in scores divided by the standard deviation of the change in scores); (3) receiver operating characteristics (ROC) curve analysis. ROAD fulfilled the established criteria for validity, reliability and responsiveness. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, thus supporting the convergent construct validity. Significant correlations were seen between ROAD scores and HAQ scores (rho = 0.372), SF-36 physical component summary (PCS) (rho = -0.413), PGA functional disability (rho = 0.417), pain (rho = 0.639), Ritchie index (rho = 0.357), number of swollen joints (rho = 0.387), patient and physician assessment of disease activity (rho = 0.467 and 0.323, respectively), and Disease Activity Score (rho = 0.476). Test-retest reliability was satisfactory, with ICCs of 0.927 (upper extremity function), 0.892 (lower extremity function), and 0.851 (activity of daily living/work). Bland-Altman plots confirmed this finding. The results of responsiveness analysis indicate that the ROAD subscales were slightly more sensitive to perceived change in functional disability than those of HAQ, SF-36 PCS, and PGA offunctional disability.

Our data suggest that the ROAD index is a reliable, valid and responsive tool for measuring physical functioning in patients with early RA, and is suitable for use in clinical trials and daily clinical practice. Its generalizability and utility for assessing aggressive treatment and functional outcomes must now be evaluated in broader settings.

To study daily pain trajectories (DPT) in patients with knee (KOA) and hip osteoarthritis (HOA) over a one-month period and identify relationships with patients characteristics and acceptability. This prospective, multicenter cohort study was conducted in France by 602 GPs, on outpatients, with painful KOA or HOA. Patients were asked to fill-in a 28-days daily pain diary. DPT were determined by the difference between daily pain and mean pain over 28 days. Pain peaks were defined as an increase of more than 1 point above the mean for up to three consecutive days. The number of pain peaks over the 28 day period allowed classifying the patient's pain trajectory as either "stable" or "unstable". A logistic regression model was used to identify predicting factors associated with stable pain profile. Overall, 1645 patients were included and 886 were analyzed, (56% women, 67.8 years, BMI 27.6 kg/m

In lower limb OA, pain is mostly stable over a 28-days period. Pain is better accepted when stable, with different determining factors according location. DPT should be considered when establishing HOA and KOA management.

To investigate the presence of subclinical synovitis by ultrasound (US) and the clinical phenotype in patients with palindromic rheumatism (PR) according to anticitrullinated protein antibody (ACPA) status. Fifty-four patients with PR were studied. Clinical, demographic, serological, and therapeutic characteristics were compared in ACPA-positive and ACPA-negative patients. US searching for synovial hypertrophy (SH) and power Doppler signal (PDUS) in 22 joints of the hands was performed in the intercritical period. The results were compared according to ACPA status and with a healthy control group (n = 30). In 10 patients, US was performed during the joint attack. Most patients were female (63%) with a mean disease duration of 11.6 ± 10.7 years. Thirty-six patients (66.7%) were ACPA-positive. ACPA-positive patients had a shorter duration of attacks, a younger age, and less knee involvement at disease onset. US examination showed SH grade ≥ 1 in 79.6% of patients with PR and 50% of controls. Significant US results (SH ≥ 2 or PDUS) were observed in 2.7% and 1.4% of joints assessed and in 33% and 25.9% of patients with PR, respectively. Only 4 patients (7.4%) had US active synovitis (SH ≥ 2 plus PDUS) in at least 1 joint. US assessment showed no significant differences between ACPA-positive and ACPA-negative patients. PDUS was observed in 7 out of 10 patients during attacks.

Some differences emerged in the clinical phenotype of PR according to ACPA status. Most patients with PR do not have US subclinical synovitis in the intercritical period, even those who are ACPA-positive.

There is abundant evidence that patients with rheumatoid arthritis (RA) are at elevated cardiovascular (CV) risk. The contribution of lipids in general is well recognised, but is as yet unclear in inflammatory diseases such as RA in part because inflammation appears inversely associated with lipid levels in RA. The CARRE study is a cohort study of 353 randomly selected RA outpatients followed since their enrollment in 2001-2002. We used data from this cohort to (i) evaluate the relationship at baseline between lipid levels [total cholesterol (TC), high-density lipoprotein (HDL)-cholesterol and the TC:HDLc ratio] and inflammation [by means of C-reactive protein (CRP)]; and (ii) determine the association of baseline TC and TC:HDLc ratio with incident (fatal and non-fatal) CV events. C-reactive protein correlated negatively with TC (r = -0.184, p = 0.002), more so with HDLc (r = -0.327, p = 0.001) and therefore positively with TC:HDLc ratio (r = 0.204, p = 0.001). These associations were most evident when CRP exceeded 10 mg/l. Furthermore, the TC:HDLc ratio, but not TC, was positively related to event risk, again most marked in those with elevated CRP.

Our observations support use of TC:HDLc ratio rather than TC alone in assessing cardiovascular risk in RA patients, especially in those with high inflammatory activity.

Scottish fold cats, named for their unique ear shape, have a dominantly inherited osteochondrodysplasia involving malformation in the distal forelimbs, distal hindlimbs and tail, and progressive joint destruction. This study aimed to identify the gene and the underlying variant responsible for the osteochondrodysplasia. DNA samples from 44 Scottish fold and 54 control cats were genotyped using a feline DNA array and a case-control genome-wide association analysis conducted. The gene encoding a calcium permeable ion channel, transient receptor potential cation channel, subfamily V, member 4 (TRPV4) was identified as a candidate within the associated region and sequenced. Stably transfected HEK293 cells were used to compare wild-type and mutant TRPV4 expression, cell surface localisation and responses to activation with a synthetic agonist GSK1016709A, hypo-osmolarity, and protease-activated receptor 2 stimulation. The dominantly inherited folded ear and osteochondrodysplasia in Scottish fold cats is associated with a p.V342F substitution (c.1024G>T) in TRPV4. The change was not found in 648 unaffected cats. Functional analysis in HEK293 cells showed V342F mutant TRPV4 was poorly expressed at the cell surface compared to wild-type TRPV4 and as a consequence the maximum response to a synthetic agonist was reduced. Mutant TRPV4 channels had a higher basal activity and an increased response to hypotonic conditions.

Access to a naturally-occurring TRPV4 mutation in the Scottish fold cat will allow further functional studies to identify how and why the mutations affect cartilage and bone development.

To determine the frequency of a precipitating event occurring prior to the onset of fibromyalgia syndrome, in a consecutive series of patients. Outcome in patients in whom there was a causative factor was compared with that in patients with primary fibromyalgia. Records of patients presenting over a 4-year period who fulfilled criteria for fibromyalgia were reviewed, and patients were classified as having reactive fibromyalgia if a specific event prior to the onset of illness could be identified. Outcome features, including employment status and disability compensation, were compared in patients with reactive fibromyalgia versus those with primary fibromyalgia. Twenty-nine of 127 patients (23%) with a primary rheumatologic diagnosis of fibromyalgia reported having trauma, surgery, or a medical illness before the onset of fibromyalgia, and were classified as having reactive fibromyalgia. Patients in this group were more disabled than those with primary fibromyalgia, resulting in loss of employment in 70%, disability compensation in 34%, and reduced physical activity in 45%.

The development of fibromyalgia after a precipitating event may represent the onset of a prolonged and disabling pain syndrome with considerable social and economic implications.

To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity. From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed. One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients.

Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.

This study was developed to compare the incidence of endoscopically diagnosed ulcers in elderly patients taking nabumetone, ibuprofen, or concomitant ibuprofen/misoprostol. Further research is indicated to better establish the clinical relevance of these endoscopy findings. We conducted a prospective, multicenter, randomized, endoscopist-blinded, 12-week study involving 171 patients with osteoarthritis aged 60 years and older. Patients were randomized to receive nabumetone, 1000 mg (n = 58); ibuprofen, 600 mg four times daily (n = 53); or ibuprofen, 600 mg four times daily, administered concomitantly with misoprostol, 200 micrograms four times daily (n = 60). Endoscopy was performed at baseline and at weeks 2, 6, and 12. Endoscopy results were scored on a scale of 1 to 9. Significant ulcers were defined as breaks in the mucosa greater than 5 mm with appreciable depth. Of the 171 randomized patients, 148 completed the study. There was no significant difference in the incidence of significant ulcers between the nabumetone group and the ibuprofen/misoprostol group (one vs zero). There were significantly fewer significant ulcers in the nabumetone and ibuprofen/misoprostol groups than in the ibuprofen monotherapy group (one and zero vs eight; P < .01). There also was a significant difference in the time to ulcer development, with a greater risk of developing an ulcer sooner with ibuprofen treatment (P < .01) than either nabumetone or ibuprofen/misoprostol treatment. The severity of osteoarthritis, based on physicians' assessments, improved in 64% of patients in the nabumetone group, 55% of those in the ibuprofen group, and 63% of those in the ibuprofen/misoprostol group.

Nabumetone is equivalent in ulcerogenicity to concomitant ibuprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH). To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls. Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants k(off) for each interaction were calculated. Several significant interactions were observed: i) high stability (lower k(off) values) between P₅₅₋₇₀ and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher k(off) values) between P₁₁₈₋₁₃₃ and P₂₆₂₋₂₇₇ and SLE sera, P₁₄₅₋₁₆₀ and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and k(off) values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P₅₅₋₇₀ and also between controls and the peptides studied.

These results indicate that P₅₅₋₇₀ of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformity and disability, as well as muscle involvement. Sarcopenia is characterized by a progressive age-related loss of muscle mass and strength. The aim of this study was to evaluate the prevalence of sarcopenia and possible contributing factors associated with sarcopenia in RA patients. Adult RA patients (n = 105) of both sexes and 100 subjects as control group (CG) matched by age, sex, and body mass index were included in this cross-sectional study. Whole-body composition was measured by dual-energy x-ray absorptiometry. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass [ASM] index by dual-energy x-ray absorptiometry). The association between sarcopenia and associated factors was evaluated using logistic regression analyses. Significantly lower percentage of lean mass and ASM were found in the whole RA group compared with controls. However, lower lean parameters (total lean mass, percentage of lean mass, and ASM) were observed only in female subjects. The ASM index was significantly lower in female subjects with RA (RA 31.0% vs CG 11.9%) without differences in male subjects. On the other hand, fat mass and most adipose indices were significantly higher in both female and male subjects with RA. Female RA patients had higher prevalence of sarcopenia and sarcopenic obesity. Through univariate logistic regression analysis, the time of corticosteroids use, cumulative corticosteroid dose, previous fragility fractures, total lean mass, and ASM were associated with sarcopenia.

Higher prevalence of sarcopenia and sarcopenic obesity were found in female RA patients. Sarcopenia was found in younger female subjects with RA compared with healthy control subjects. Sarcopenia was associated with previous fragility fractures in female patients with RA.

To describe the prevalence, associated characteristics, and course of enthesitis in a juvenile idiopathic arthritis (JIA) inception cohort. Canadian children newly diagnosed with JIA between 2005 and 2010 were categorized using International League of Associations for Rheumatology criteria at the 6-month visit and followed in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) cohort for up to 5 years. The presence of entheseal tenderness on examination at 33 sites shown on a homunculus was recorded at 0, 6, 12, 18, 24, 36, 48, and 60 months after enrollment. Enthesitis was defined as entheseal tenderness at more than 1 site or on more than 1 occasion. Analyses consisted of descriptive statistics and linear mixed models for longitudinal data. Of 1,406 patients, 219 (16%) had enthesitis and, of those with enthesitis, 141 (64%) were classified as having enthesitis-related arthritis (ERA). Children with enthesitis were more often older (10.7 versus 7.5 years), male (57% versus 31%), and with polyarthritis (57% versus 41%) and sacroiliac involvement (30% versus 4%). Entheseal tenderness was most frequent at the calcaneal plantar fascial insertion (39%), Achilles tendon insertion (31%), and tibial tuberosity (30%). The mean number of tender entheseal sites decreased in parallel with active joint counts. There was no difference in active joint counts over time in children with or without enthesitis (P = 0.73).

Enthesitis was observed in 16% of patients with JIA, but only two thirds were categorized as having ERA. Contrary to expectations, most children with enthesitis had polyarticular involvement. The course of enthesitis paralleled the course of active joint counts.

To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs). Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed before and 1 year after bDMARDs initiation. At baseline, mean age was 57.1 years and mean disease duration was 3.0 years. Median disease activity score in 28 joints improved from 5.1 to 2.1. Treatment with bDMARDs improved mean whole-body synovitis score from 31.2 to 23.2 and median whole-body bone-edema score from 11 to 3. Whole-body bone-erosion score improved in seven patients and deteriorated in 17 patients. Logistic regression analysis identified whole-body synovitis score as a poor prognostic factor for whole-body bone-erosion progression. Bone-edema score in individual bones was identified as a poor prognostic factor for the progression of bone-erosion. Changes in hand synovitis score correlated with those of other joints, but neither changes in bone-edema nor erosion score of hands correlated with those of other joints in WBMRI.

WBMRI scoring may be a novel useful tool to evaluate the efficacy of anti-rheumatic drugs, as well as a potential predictor of joint prognosis, in patients with RA.

Rheumatoid arthritis (RA) has a wide range of clinical expressions which probably reflects different genetic backgrounds. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory synovial activity in RA. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with RA and its severity. Seventy-eight seropositive Italian RA patients with erosive disease entered the study. Radiographs of hands and feet 5 years after the diagnosis were available for 68 patients and were evaluated for the number of eroded joints. We obtained an erosive score for each patient by counting the number of joints with at least one erosion. Patients in the upper part of the distribution over the median were considered as fast eroders (FE) and the others as slow eroders (SE). Patients' records were also evaluated for the presence of extra-articular features. 228 healthy subjects of the same ethnic origin were selected as a control group. All of the RA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 (exon 4) and E/K at codon 469 (exon 6). The carriage rate of allele R241 was significantly higher in RA patients than in healthy controls (12.8% versus 5.7%, p = 0.039; odds ratio: 2.4 [95% CI 1.02 to 5.79]). The allele frequencies and carriage rate of the E 469 gene did not differ significantly between RA patients and the control group. When we compared the control group with the patients with more or less severe disease (presence or absence of extra-articular features, SE and FE) we found that only the group of patients with the more favourable course maintained a significant difference in the carriage rate of R241 (16.7 vs 5.7%, p = 0.009 for patients without extra-articular features and 18.9 vs 5.7%, p = 0.004 for SE patients).

Our preliminary findings show that G/R 241 polymorphism of ICAM-1 is associated with RA, and that this confers a reduced risk of extra-articular manifestations and is associated with a slow rate of joint destruction.

Previous studies have shown that lower-extremity malalignment increases the risk and rate of progression of knee osteoarthritis. The authors of such studies have used full-length lower-extremity radiographs to quantify alignment. However, a radiograph that includes only the knee is commonly ordered for a patient with early symptoms of knee osteoarthritis. The purpose of this study was to investigate whether local malalignment, as determined with use of a standing short knee radiograph, is associated with an increased risk of having osteoarthritis and having more severe compartmental disease. Short fluoroscopically guided standing anteroposterior knee radiographs of 306 patients (608 knees) with radiographic evidence of knee osteoarthritis were used to determine the compartment-specific Kellgren-Lawrence grade of osteoarthritis and the local (distal femoral to proximal tibial) knee alignment. The relationship between local alignment and compartmental patterns of osteoarthritis was assessed. Each degree of increase in the local varus angle was associated with a significantly increased risk of having predominantly medial compartment osteoarthritis, even when we adjusted for age, sex, and body mass index (odds ratio, 1.39; 95% confidence interval, 1.29 to 1.49; p < 0.001). A similar association was found between valgus angulation and lateral compartment osteoarthritis (odds ratio, 1.55; 95% confidence interval, 1.36 to 1.75; p < 0.001). Analysis of the 362 knees with predominantly medial compartment osteoarthritis showed that each degree of increase in the varus angle was associated with a significantly increased adjusted risk of having severe medial disease (odds ratio, 1.52, p < 0.001). In the forty-seven knees with predominantly lateral compartment osteoarthritis, a similar trend was found between an increase in the valgus angle and the severity of the lateral disease, with the results approaching but not reaching significance.

In patients with early symptomatic knee osteoarthritis, there is a clear relationship between local knee alignment, as determined from short standing knee radiographs, and the compartmental pattern and severity of the knee osteoarthritis. This study provides data with which physicians can assess how knee alignment contributes to the observed patterns and severity of osteoarthritis in an individual patient.

We hypothesize that chondrocytes from the deepest articular cartilage layer are pivotal in maintaining cartilage integrity and that the modification of their prehypertrophic phenotype to a hypertrophic phenotype will drive cartilage degradation in osteoarthritis. Murine immature articular chondrocytes (iMACs) were successively cultured into three different culture media to induce a progressive hypertrophic differentiation. Chondrocyte were phenotypically characterized by whole-genome microarray analysis. The expression of IL-34 and its receptors PTPRZ1 and CSF1R in chondrocytes and in human osteoarthritis tissues was assessed by RT-qPCR, ELISA and immunohistochemistry. The expression of bone remodeling and angiogenesis factors and the cell response to IL-1β and IL-34 were investigated by RT-qPCR and ELISA. Whole-genome microarray analysis showed that iMACs, prehypertrophic and hypertrophic chondrocytes each displayed a specific phenotype. IL-1β induced a stronger catabolic effect in prehypertrophic chondrocytes than in iMACs. Hypertrophic differentiation of prehypertrophic chondrocytes increased Bmp-2 (95%CI [0.78; 1.98]), Bmp-4 (95%CI [0.89; 1.59]), Cxcl12 (95%CI [2.19; 5.41]), CCL2 (95%CI [3.59; 11.86]), Mmp 3 (95%CI [10.29; 32.14]) and Vegf mRNA expression (95%CI [0.20; 1.74]). Microarray analysis identified IL-34, PTPRZ1 and CSFR1 as being strongly overexpressed in hypertrophic chondrocytes. IL-34 was released by human osteoarthritis cartilage; its receptors were expressed in human osteoarthritis tissues. IL-34 stimulated CCL2 and MMP13 in osteoblasts and hypertrophic chondrocytes but not in iMACs or prehypertrophic chondrocytes.

Our results identify prehypertrophic chondrocytes as being potentially pivotal in the control of cartilage and subchondral bone integrity. Their differentiation into hypertrophic chondrocytes initiates a remodeling program in which IL-34 may be involved.

To assess the incidence of Reiter's syndrome aboard The Golden Venture, a ship carrying illegal immigrants from China to the United States. After identification of an index case, we conducted telephone interviews with medical staff at immigrant detention centers in Pennsylvania, New York, and Virginia. When a potential case was identified at one facility, we performed a site inspection, reviewing the medical records of all detainees and performing histories and physicals on all those with joint and/or ocular complaints. We identified two patients, both HLA B27 positive, with Reiter's syndrome. The observed incidence (0.87%) approximated the predicted incidence but may have underestimated the actual incidence. We review the history of shipboard Reiter's syndrome, and discuss the pathogenic roles of HLA B27 and particular infectious agents.

Continued transportation of illegal immigrants from China and other parts of the world is likely to result in occasional clusters of Reiter's syndrome. Physicians treating immigrant populations should remain aware of the possibility of reactive arthritis.

Many people suffer with Osteoarthritis (OA) and subsequent morbidity. Therefore, measuring outcome associated with OA is important. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been a widely used patient reported outcome in OA. However, there is relatively little evidence to support the use of the Visual Analogue Scale (VAS) version of the scale. We aimed to explore the internal validity and responsiveness of this VAS version of the WOMAC. Patients with chronic hip or knee pain of mechanical origin, waiting for a hip or knee joint replacement completed the WOMAC as part of a study to investigate the effects of acupuncture and placebo controls. Validity was tested using factor analysis and Rasch analysis, and responsiveness using standardised response means. Two hundred and twenty one patients (mean age 66.8, SD 8.29, 58% female) were recruited. Factor and Rasch analysis confirmed unidimensional Pain and Physical Functioning scales, capable of transformation to interval scaling and invariant over time. Some Differential Item Functioning (DIF) was observed, but this cancelled out at the test level. The Stiffness scale fitted the Rasch model but adjustments for DIF could not be made due to the shortness of the scale. Using the interval transformed data, Standardised Response Means were smaller than when using the raw, ordinal data. UKCRN study ID: 4881 ISRCTN78434638.

The WOMAC Pain and Physical Functioning subscales satisfied unidimensionality and ordinal scaling tests, and the ability to transform to an interval scale. Some Differential Item Functioning was observed, but this cancelled out at the test level and, by doing so, at the same time removed the disturbance of unidimensionality. The scaling characteristics of sets of items which use VAS require further analysis, as it would appear that they can lead to spurious levels of responsiveness and scale compression because they exaggerate the distortion of the ordinal scale.

To assess ex vivo CD4(+) T-cell cytokine expression from patients with primary Sjögren's syndrome (SS) following in vitro stimulation to induce proliferation, as proliferation is closely related to differentiation of cytokine-producing cells. Peripheral blood mononuclear cells (PBMCs) separated from primary SS patients (n = 28) and controls (n = 25) were analysed. PBMCs were stimulated with concanavalin A followed by phorbol 12-myristate 13-acetate and ionomycin. Intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL)-4 in proliferating CD4(+) T cells were assessed by flow cytometry. The proportion of cytokine-producing cells and proliferating cells in each division cycle was assessed using [5(and 6)-carboxyfluorescein diacetate, succinimidyl ester]-labelled CD4(+/-) T cells. The proportion of IFN-gamma+ proliferating CD4(+) T cells in each cell division cycle from extraglandular SS was increased in glandular SS patients compared glandular SS patients with controls (P<0.05 approximately 0.01). The percentage of IFN-gamma single positive proliferating CD4(+) T cells was greater in extraglandular SS patients (26.7+/-14.1%) compared with glandular SS (9.9 +/- 9.1%) (P<0.01) and controls (9.4 +/- 5.8%) (P<0.001). There was no significant difference in the percentages of IL-4(+) proliferating CD4(+) T cells among the groups. However, the proliferating response of CD4(+) T cells was significantly decreased in extraglandular SS patients (percentage of proliferating cells 38.4 +/- 18.6%) compared with that in glandular SS patients (64.2 +/- 17.2%) (P<0.05) and controls (63.1+/-10.6%) (P<0.01).

CD4(+) T cells from extraglandular SS patients may have a predisposition for entry into the IFN-gamma-producing effector pathway as a result of the stimulations. These results are helpful for understanding the immunological difference between glandular and extraglandular SS and the mechanisms of disease progression.

Th17 cells and interleukin-17 (IL-17) cytokine family members are implicated in the pathogenesis of many rheumatic diseases. Most studies in mouse models of inflammatory arthritis have demonstrated a key role for the proinflammatory cytokine IL-17A and its receptor, the IL-17 receptor (IL-17R) A/C heterodimer. The aim of this study was to use a rigorous genetic approach to evaluate the contribution of Th17 cells and IL-17 in the autoantibody-dependent KRN T cell receptor-transgenic mouse model of arthritis. We bred KRN mice expressing the major histocompatibility complex class II molecule A(g7) (referred to as K/B/g7 mice) and genetically lacking the related cytokines IL-17A and IL-17F or their critical receptor subunit, IL-17RA. Using bone marrow transplantation, we generated mice in which hematopoietic cells from K/B/g7 donor mice lacked the key Th17-differentiating transcription factor, retinoic acid receptor-related orphan nuclear receptor γt (Rorγt). K/B/g7 mice lacking both IL-17A and IL-17F produced normal titers of pathogenic autoantibodies, and arthritis developed in a typical manner. Similarly, neither IL-17RA nor Rorγt expression by hematopoietic cells was required for disease development in this model.

Despite prior reports suggesting that Th17 cells and IL-17A are crucially involved in the pathogenesis of arthritis in K/BxN mice, the results presented here provide genetic evidence that IL-17A and IL-17F, IL-17RA, and Rorγt expression by hematopoietic cells are dispensable for normal arthritis progression in the K/B/g7 mouse model system. We discuss potential explanations for the discrepancies between these 2 highly similar model systems. These findings plus those in other mouse models of arthritis provide insight regarding why therapeutic biologic agents targeting the Th17/IL-17 axis are beneficial in some human rheumatic diseases but not others.

To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation. Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and <6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit. Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression.

Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

(1) To determine 6-month follow-up adherence and persistence with disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis with disease under control. (2) To compare disease flares across adherent, nonadherent, persistent and nonpersistent patients. (3) To identify differences in adherent and persistent rates among therapeutic regimens. (4) To identify baseline prognosticators of poor compliance. Ninety-three patients (86% female) had 4 consecutive 2-month apart evaluations during which the 28-joint disease activity score and the Health Assessment Questionnaire were scored, comorbidities and treatment recorded and a compliance questionnaire and a drug record registry applied. Descriptive statistics, Student t and χ tests and logistic regression analysis were used. At the study entry, patients had mean ± standard deviation age of 40.8 ± 13.9 years, the 28-joint disease activity score of 2.1 ± 1.1, the Health Assessment Questionnaire of 0.09 ± 0.2, and 68 of them (73.1%) had remission. During follow-up, 47 patients (50.5%) were adherent and 51 (54.8%) persistent; 14 of 68 patients (20.6%) who achieved remission had a disease flare. Incidence rate and individual risk of a disease flare were significantly greater in nonadherent and nonpersistent patients. Compared with methotrexate monotherapy, therapeutic regimens with >3 disease-modifying antirheumatic drugs had increased risk of nonadherence and nonpersistence (P ≤ 0.02). Higher previous serial erythrocyte sedimentation rate was associated to nonadherence (as was a shorter follow-up at the Clinic) and to nonpersistence (odds ratio: 1.03; 95% confidence interval: 1.01-1.05 for both, P = 0.05 and P = 0.001, respectively).

Therapy behavior of patients with rheumatoid arthritis with mild/no disease activity and disability was poor and translated into disease flares. Higher serologic activity was associated to poor compliance with therapy.

To quantify early stage microstructural changes of periarticular cancellous bone in a canine anterior cruciate ligament transection model for experimental osteoarthritis. Unilateral transection of the anterior cruciate ligament was performed in 10 animals. Bone structure changes were quantified in five animals at 3-week post-transection and five animals at 12-week post-transection. An additional two non-operated animals were used as controls. Changes in trabecular architecture of the periarticular cancellous bone in early stage post-traumatic osteoarthritis is not well understood. Previous studies have found alterations in bone mineral density in experimental osteoarthritis suggesting adaptation of the trabecular structure. Early change of the periarticular bone following a ligament injury may contribute to the long-term development of osteoarthritis. ++. Bone cores from the medial condyles of the femoral and tibial pairs were scanned with a three-dimensional microtomographic system. Structural indices were quantified including bone volume ratio, bone surface ratio, trabecular thickness, trabecular separation, trabecular number, as well as structural anisotropy determined by the mean-intercept-length method.Results. Significant structural changes were observed at 3-week post-transection, and were more prominent at 12-week post-transection. These changes were accompanied by decreasing anisotropy. The pathogenesis of post-traumatic osteoarthritis is poorly understood, but it is clear that this disease involves the entire organ system of the joint, including the cartilages, synovium, ligaments, and bones. This study focuses on the changes that occur in the bones during the early stages following a joint injury, and contributes to a better overall understanding of the disease aetiology.

Periarticular cancellous bone microstructure is significantly altered in experimental osteoarthritis. These changes occurred as early as 3-week post-transection, and were large at 12-week post-transection.

The aim of this review was to identify a reliable sequential medial release protocol for restoration of soft tissue balance in total knee arthroplasty of the varus osteoarthritic knee and to allow for improved intraoperative decision-making. Current medial release sequences and applicability based upon pre-operative deformity have been reviewed. Furthermore, risks associated with over release, and the necessity of medial release, are discussed. The different medial release sequences are discussed in relation to pre-operative deformity, along with potential complications associated with medial release. It was found that release sequences may include the deep and superficial components of the medial collateral ligament, the posteromedial capsule, the posterior oblique ligament, the pes anserinus (pes A), and tendons of the semimembranosus and medial gastrocnemius muscle. The sequences described were found to vary substantially between studies, and very few studies had systematically quantified the effect of each release on balance. V (expert opinion).

While medial release is the standard intraoperative mode of balancing, there is a lack of evidence to support current methods. The correct method for defining intraoperatively the sequence, extent and magnitude of releases required remains ill-defined. It could be argued that the classic extensive medial release may be unnecessary and may be associated with iatrogenic injury to the pes A and saphenous nerve, instability and abnormal knee kinematics. Minimal medial release may allow for improved soft tissue balancing leading ultimately to improved functional outcome.

To investigate in situ the expression of the integrin receptor subunits alpha 6 and beta 1 and the distribution of the ligand laminin in the synovia from osteoarthritis (OA) and rheumatoid arthritis (RA) patients and to study the effect of cytokines and antirheumatic drugs on the expression of the alpha 6 and beta 1 integrin subunits on long term cultures of fibroblast-like synoviocytes (FBS) derived from OA and RA. The expression of the alpha 6 and beta 1 integrin subunits and the distribution of laminin were examined immunohistochemically in normal synovia and in synovia from patients with OA and RA. The effect of proinflammatory cytokines (IL1 beta and TNF alpha), and of antirheumatic drugs (salicylic acid, dexamethasone, and methotrexate) on the alpha 6 and beta 1 expression of cultured normal FBS and FBS from patients with OA and RA was determined by flow cytometry. In normal synovia and in OA synovia samples with a low grade of inflammation, synovial lining cells (SLC) showed a parallel expression and distribution of alpha 6 and laminin. In synovia samples of OA with a higher grade of inflammation and in the majority of RA synovia samples laminin was pericellularly distributed in a low number of SLC, whereas alpha 6 was expressed on the surface of a high number of SLC. In RA synovia samples with severe inflammatory changes the gradual loss of laminin generally corresponded to a decrease of the alpha 6 integrin subunit. beta 1 was always strongly expressed in all synovia samples detected. Proinflammatory cytokines up regulated the expression of alpha 6 and beta 1 on OA-FBS, whereas these effectors decreases alpha 6 and beta 1 on RA-FBS. In contrast, antirheumatic drugs, in particular methotrexate and dexamethasone, reduced the expression of alpha 6 and beta 1 on OA-FBS, whereas the same treatment on RA-FBS stimulated the expression of these integrin subunits.

The gradual loss of laminin in chronic synovitis may contribute to the altered expression of alpha 6 in SLC. IL1 beta and TNF alpha down regulated the expression of the alpha 6 and beta 1 integrin subunits on long term cultures of FBS derived from RA. Therefore, these cytokines may be among the effectors regulating the expression of the alpha 6 integrin subunit in SLC in vivo. As antirheumatic drugs increase the expression of alpha 6 on RA-FBS, the presence of the laminin receptor may confer a protective effect on the synovia in vivo.

The Knee injury and Osteoarthritis Outcome Score (KOOS) is an extension of the Western Ontario and McMaster Universities Osteoarthrtis Index (WOMAC), the most commonly used outcome instrument for assessment of patient-relevant treatment effects in osteoarthritis. KOOS was developed for younger and/or more active patients with knee injury and knee osteoarthritis and has in previous studies on these groups been the more responsive instrument compared to the WOMAC. Some patients eligible for total knee replacement have expectations of more demanding physical functions than required for daily living. This encouraged us to study the use of the Knee injury and Osteoarthritis Outcome Score (KOOS) to assess the outcome of total knee replacement. We studied the test-retest reliability, validity and responsiveness of the Swedish version LK 1.0 of the KOOS when used to prospectively evaluate the outcome of 105 patients (mean age 71.3, 66 women) after total knee replacement. The follow-up rates at 6 and 12 months were 92% and 86%, respectively. The intraclass correlation coefficients were over 0.75 for all subscales indicating sufficient test-retest reliability. Bland-Altman plots confirmed this finding. Over 90% of the patients regarded improvement in the subscales Pain, Symptoms, Activities of Daily Living, and knee-related Quality of Life to be extremely or very important when deciding to have their knee operated on indicating good content validity. The correlations found in comparison to the SF-36 indicated the KOOS measured expected constructs. The most responsive subscale was knee-related Quality of Life. The effect sizes of the five KOOS subscales at 12 months ranged from 1.08 to 3.54 and for the WOMAC from 1.65 to 2.56.

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a valid, reliable, and responsive outcome measure in total joint replacement. In comparison to the WOMAC, the KOOS improved validity and may be at least as responsive as the WOMAC.

Health-related quality of life (HRQoL) data generated by generic, preference-based instruments (i.e., EQ-5D) are highly demanded in health policy decision making, because they allow for direct comparisons of HRQoL outcomes between disease areas. We aimed to quantify HRQoL outcomes in breast cancer (BC), rheumatoid arthritis (RA), multiple sclerosis (MS), rare cancers (RC), and rare disease (RD) patients and understand the patterns that differentiate HRQoL outcomes between these disease areas, and more specifically between rare and more common disease population groups. An international, Web survey of patients measured HRQoL (EQ-5D-5L), self-perceived health (EQ-5D-5L Visual Analogue Scale), and additional QoL dimensions, such as patient disability level. We received 675 completed responses. Average utility loss was 53.5 percent, 32.5 percent, and 33.3 percent for RD, RA, and MS patients, respectively, in contrast to 18.6 percent for BC and RC patients. Statistically significant differences (p < .05) were observed between disease groups in all EQ-5D-5L domain outcomes, apart from that of "Anxiety/Depression." Severe and/or extreme problems were reported in performing usual activities for RD and RC (34 percent and 13 percent of overall problems reported respectively), mobility for MS (18 percent), pain/discomfort for RA (13 percent), and anxiety/depression for BC (7 percent) patients.

We demonstrated significant differences in the dimensions that drive HRQoL outcomes between rare and more common diseases and showcased that the same EQ-5D utility may reflect very different severities depending on the patient population under investigation. Future research should examine whether outcomes in other, critical HRQoL domains not included in generic measures also highlight significant differences across disease areas.

Juvenile-onset fibromyalgia (JFM) is a chronic debilitating pain condition that negatively impacts physical, social and academic functioning. Cognitive-behavioral therapy (CBT) is beneficial in reducing functional disability among adolescents with JFM but has only a modest impact on pain reduction and does not improve physical exercise participation. This randomized controlled trial (RCT) aims to test whether a novel intervention that combines CBT with specialized neuromuscular exercise training (the Fibromyalgia Integrative Training program for Teens "FIT Teens") is superior to CBT alone or a graded aerobic exercise (GAE) program. This 3-arm multi-site RCT will examine the efficacy of the FIT Teens intervention in reducing functional disability (primary outcome) and pain intensity (secondary outcome), relative to CBT or GAE. All interventions are 8-weeks (16 sessions) in duration and are delivered in small groups of 4-6 adolescents with JFM. A total of 420 participants are anticipated to be enrolled across seven sites with approximately equal allocation to each treatment arm. Functional disability and average pain intensity in the past week will be assessed at baseline, post-treatment and at 3-, 6-, 9- and 12-month follow-up. The 3-month follow-up is the primary endpoint to evaluate treatment efficacy; longitudinal assessments will determine maintenance of treatment gains. Changes in coping, fear of movement, biomechanical changes and physical fitness will also be evaluated.

This multi-site RCT is designed to evaluate whether the combined FIT Teens intervention will have significantly greater effects on disability and pain reduction than CBT or GAE alone for youth with JFM. Clinical trials.gov registration: NCT03268421.

To compare synovial tissue cytokine mRNA expression between patients with juvenile rheumatoid arthritis (JRA) and a heterogeneous group of non-autoimmune arthropathies (controls) with respect to type 1/type 2 balance. Thirty-five JRA (average 9.1 years' disease duration) and 13 control synovial tissues were studied. As a measure of the type 1/type 2 cytokine balance in a subset of the JRA and control tissues, interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) mRNA levels were measured by competitive fragment reverse transcription-polymerase chain reaction. To quantitate additional cytokines relevant to this balance, multiprobe ribonuclease protection assays were employed measuring IL-5, IL-10, IL-13, IL-15, IL-18, and IL-12 (p35 and p40 subunits). Immunohistochemistry was performed on JRA tissues using antibodies specific for IL-15 and IL-18. A higher IFN-gamma:IL-4 ratio (p = 0.034) was found in JRA tissues compared to controls. JRA tissues also displayed higher mRNA levels of IL-12p35 (p = 0.021), IL-15 (p = 0.002), and IL-18 (p = 0.017), but not IL-4 and IL-10. IFN-gamma expression in JRA, but not controls, correlated strongly with IL-12p35 (r = 0.63) and IL-12p40 (r = 0.73) levels. A subset of IL-15+ and IL-18+ cells was detected in JRA synovial tissues, largely within perivascular aggregates.

JRA synovial tissue cytokine expression patterns indicate a type 1 bias, even in the later stages of disease. The strong correlation between IFN-gamma and IL-12 in JRA suggests a prominent role for IL-12 in promoting the type I bias, while IL-15 and IL-18 may also indirectly increase IFN-gamma expression and further bias the immune response.

The objective of this study was to elicit and assess important symptom domains and the impact of fibromyalgia on patients' quality of life and functioning from a patient's perspective. The intention was to collect this information as part of an overall effort to overcome shortcomings of existing outcome measures in fibromyalgia. This was a qualitative study in which six focus group sessions with 48 women diagnosed with fibromyalgia were conducted to elicit concepts and ideas to assess the impact of fibromyalgia on their lives. The focus groups conducted with fibromyalgia patients identified symptom domains that had the greatest impact on their quality of life including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive impairment. Fibromyalgia had a substantial negative impact on social and occupational function. Patients reported disrupted relationships with family and friends, social isolation, reduced activities of daily living and leisure activities, avoidance of physical activity, and loss of career or inability to advance in careers or education. A comprehensive assessment of the multiple symptoms domains associated with fibromyalgia and the impact of fibromyalgia on multidimensional aspects of function should be a routine part of the care of fibromyalgia patients.

The findings from the focus groups revealed that fibromyalgia has a substantial negative impact on patients' lives.

The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg/ml), an anti-TLR2 antibody (OPN301, 1 μg/ml) or an immunoglobulin G (IgG) (1 μg/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab.

These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.

Knee periarticular bone mineral density (BMD) is influenced by limb malalignment. The purpose of this study is to determine if the nature and magnitude of alignment correction (ΔAlign°) performed during primary total knee arthroplasty (TKA) had an impact on BMD at the metaphysis of the distal femur (DFmr) and proximal tibia (PTb). Seventy-one patients (male = 37 |female = 34; age: 65 ± 2 years) underwent full-length standing X-rays and knee-specific BMD measurements using dual-energy X-ray absorptiometry before and 3 and 6 months following TKA. A t-test was used to compare baseline demographics and knee-specific BMD measures (medial/lateral DFmr/PTb) between patients with preoperative valgus (VAL, N = 18) and varus (VAR, N = 53) malalignment. Pearson correlation analysis was used to determine if ΔAlign° correlated with site-specific knee BMD changes. A 2 (varus/valgus) by 3 (time) analysis of variance was used to compare site-specific BMD (%ΔBMD) changes following TKA. Type I error was set at α = 0.05 for all analyses. VAR patients had higher preoperative BMD for medial measurement at both the DFmr (VAR: 1.17 ± 0.06 g/cm Level II, prospective cohort study.

Valgus patients exhibited reduced medial BMD at DFmr and PTb and showed sustained improvements 6 months postsurgery. Mechanical axis correction may be clinically impactful to bone remodeling when correcting valgus malalignment.

Total knee arthroplasty (TKA) for valgus knee osteoarthritis is challenging. Although overcorrection in TKA for valgus knee osteoarthritis is recommended, supportive data based on biomechanics have rarely been reported. The purpose of this study was to elucidate whether coronal rotation of the femoral compartment causes abnormal kinematics with or without medial looseness. Multi- and single-radius posterior-stabilised TKA implants were utilised in a computer simulation. A total of 4 mm of slack were provided in the medial collateral ligament (MCL) with varus or valgus position of the femoral component to simulate the context of valgus knee osteoarthritis. Kinematics during gait and squatting activities were evaluated in each condition. During squatting, medial looseness and valgus replacement caused anterior translation of the medial femoral component in mid-flexion in the multi-radius implant. In the worst condition (7° valgus replacement with MCL looseness), there was rapid anterior translation in the multi-radius implant, and moderate anterior translation in the single-radius implant. Although medial looseness alone did not cause abnormal kinematics during gait, the worst condition exhibited an anterior translation to 4.9 mm in the multi-radius implant. This worst condition also exhibited a marked lift-off of 8.0 and 2.9 mm in the multi- and single-radius implants, respectively. Varus position caused little abnormal kinematics even with MCL looseness.

Valgus, not varus position of the femoral component caused abnormal kinematics with MCL looseness. To avoid valgus position, the safety target angle of femoral component would be slight varus rather than neutral in valgus knee OA.

To investigate the hip inflammatory lesions and to evaluate the accuracy of clinical examination compared to magnetic resonance imaging (MRI) in patients with polymyalgia rheumatica (PMR) with pelvic girdle symptoms. Secondary end-point was to evaluate the sensitivity and specificity of ultrasonography (US) compared to MRI in the assessment of hip lesions. Case-control study of 20 consecutive PMR patients and 40 controls with different rheumatic conditions. Both groups were clinically assessed for the presence of hip synovitis, trochanteric, iliopsoas and ischiogluteal bursitis. Hip MRI was performed in all case-patients and in 10 controls. Both groups were examined by US. An additional group of 10 healthy controls was examined by hip US. Both MRI and US detected trochanteric bursitis in 100% of PMR patients, bilateral in 18/20 (90%), and in 12/40 (30%) controls (p < 0.001). Hip synovitis was detected in 17/20 (85%) by MRI and in 9/20 (45%) by US (p < 0.02) in case-patients and in 18/40 (45%) controls. In PMR, MRI and US showed iliopsoas bursitis in 10/20 (50%) and 6/20 (30%) and ischiogluteal bursitis in 5/20 (25%) and 4/20 (20%) with no differences compared to controls. Clinical examination showed a good accuracy for hip synovitis, trochanteric and ischiogluteal bursitis, while it overestimated the presence of iliopsoas bursitis. US was less sensitive than MRI for the detection of hip synovitis and iliopsoas bursitis (53% and 60%).

Trochanteric bursitis represents the most frequent hip lesion in PMR. A careful physical examination allows to detect all inflammatory lesions excluding iliopsoas bursitis. US is less sensitive than MRI in the assessment of hip synovitis and iliopsoas bursitis.

Interleukin-6 is a pro-inflammatory cytokine involved in the pathogenesis of osteoarthritis (OA). We investigated the role of two single nucleotide polymorphisms (SNPs) mapping to the promoter of the IL-6 gene on genetic susceptibility to hip and knee OA. The -174G/C (rs1800795) and -597G/A (rs1800797) SNPs, implicated in the literature in risk of hip and hand OA, were genotyped in 2511 controls, 1101 hip OA cases and 1904 knee OA cases from four cohorts from the UK and Estonia. Data were analysed in conjuntion with published data on rs1800797 from the Genetics of OA and Lifestyle study (UK) on 791 controls, 1034 knee and 997 hip OA cases and rs1800795 data on 75 hip OA cases and 96 controls from Italy. Cases included both radiographic OA only and radiographic and symptomatic OA. Fixed and random-effects meta-analysis models were tested. No significant association was found with hip OA or knee OA with either SNP nor with the haplotypes formed by them. For individual SNPs the smallest P-value for hip OA was observed using a random-effects model for rs1800795 OR(Gallele)=1.066 (95% CI 0.89-1.28) P<0.49, and significant heterogeneity between cohorts (I(2)=65%, P<0.034) was detected. For knee OA the smallest P-value was seen for rs1800797 OR(Aallele)=1.055 (95%CI 0.98-1.12) P<0.18, no significant heterogeneity was observed (I(2)=0%, P<0.68).

Our data do not support a role for the -174 and -597 IL-6 promoter polymorphisms in genetic susceptibility to knee or hip OA in Caucasian populations.

To evaluate salivary hyaluronic acid (HA) concentration in patients with primary Sjögren's syndrome (SS). Salivary and serum HA concentrations were evaluated using a radiometric assay. Thirty nine patients with SS served as the study group and their results were compared with 19 patients having clinical symptoms and signs of dry mouth and with 10 normal controls. Salivary HA concentrations were significantly increased (p < 0.05) in the 39 patients with SS compared with the 19 patients with dry mouth and the 10 normal controls (240.7 (38.5) v 99.8 (14.6) and 91.3 (7.9) ng/ml, respectively) (mean (SEM)). No significant differences were noted in the serum HA concentrations between the three groups (42 (3.9) v 36.3 (4.1) and 32 (4.3) ng/ml, respectively) (mean (SEM)). No correlation could be found between salivary HA concentrations and the focus score of lip biopsies, nor between salivary HA concentrations and erythrocyte sedimentation rate or other serological tests.

Increased salivary HA concentrations can serve as a marker of local inflammation and may be of value in the diagnosis of SS.

Pancytopenia is an unusual complication of low-dose methotrexate therapy in rheumatoid arthritis. We report a near fatal case that followed an accidental overdose. An 80-year-old Caucasian woman with rheumatoid arthritis presented with pancytopenia and severe mucositis. She had taken her weekly methotrexate dose on four sequential days, due to an error in filling a "Dosette" box. Following treatment with piperacillin, gentamicin and folinic acid, she recovered completely.

Low-dose methotrexate therapy is uncommonly associated with haematological toxicity. This generally occurs in patients with known risk factors for such reactions. Patient reliability should be considered if methotrexate therapy is contemplated.

To examine the relations of the family environment to adjustment to juvenile rheumatoid arthritis (JRA), and to examine how those relations are influenced by child sex and age. Ninety-four children with JRA completed a questionnaire on family environment and adjustment. Family cohesion was related to good adjustment, whereas family conflict was related to poor adjustment. Some relations of family cohesion to adjustment were stronger for younger than for older children. The relations of child autonomy to adjustment depended on child sex and age.

The relations of the family environment to adjustment to JRA are dependent on child sex and age.

To assess sociodemographic, clinical, and psychological characteristics of patients with internal diseases who use relaxation techniques as a coping strategy. Cross-sectional analysis among patients with internal diseases. Department of Internal and Integrative Medicine at an academic teaching hospital in Germany. Prior use of relaxation techniques (e.g. meditation, autogenic training), perceived benefit, and perceived harm. Potential predictors of relaxation techniques use (sociodemographic characteristics, health behavior, internal medicine diagnosis, general health status, mental health, satisfaction, and health locus of control) were tested using multiple logistic regression analysis. Of 2486 participants, 1075 (43.2%) reported to have used relaxation techniques, 648 (60.3%) reported benefits, and 11 (1.0%) reported harms. Use of relaxation techniques was independently associated with female gender (Odds ratio [OR]=1.43; 95% confidence interval [CI]=1.08-1.89), higher education (OR=1.32; 95%CI=1.03-1.71), fibromyalgia (OR=1.78; 95%CI=1.22-2.61), and internal health locus of control (OR=1.27; 95%CI=1.01-1.60). Use of relaxation techniques was negatively associated with age below 30 (OR=0.32; 95%CI=0.20-0.52) or above 64 (OR=0.65; 95%CI=0.49-0.88), full-time employment (OR=0.75; 95%CI=0.57-0.98), current smoking (OR=0.72; 95%CI=0.54-0.95), osteoarthritis (OR=0.51; 95%CI=0.34-0.77), rheumatic arthritis (OR=0.59; 95%CI=0.37-0.93), good to excellent health status (OR=0.70; 95%CI=0.52-0.96), and high life satisfaction (OR=0.78; 95%CI=0.62-0.98).

In a German sample of patients with internal diseases, relaxation techniques were used as a coping strategy by about 43%. Users were more likely to be middle-aged, female, well-educated, diagnosed with fibromyalgia, not smoking, not full-time employed, and not to have a good health status or high life satisfaction. A high internal health locus of control predicted relaxation techniques use. Considering health locus of control might improve adherence to relaxation techniques in internal medicine patients.

To estimate efficacy, safety and adherence to therapy of ankylosing spondlitis (AS) patients included in the Czech National Registry ATTRA, and to look for predictive factors for therapy discontinuation. Patients were included according to the guidelines of the Czech Society for Rheumatology, which involve failure of previous therapy, BASDAI >4, and CRP >10 mg/l. Only patients with anti-TNF administered for the first time were analysed. Adherence to therapy was evaluated using Kaplan-Meier analysis and results were presented as cumulative survival. Comparison with data on patients with rheumatoid arthritis (RA) followed in the same registry was made. 310 of AS patients who had reached at least 1 year as well as those who discontinued the treatment before this time point were analysed. Drug survival was longer in patients with AS than in those with RA: 84% vs. 78% and 72% vs. 49% after 1 and 3 years of treatment. Significant risk factors for treatment discontinuation were female gender (RR 2.22, p=0.001) and CRP (RR 1.33, p=0.025). The proportion of patients with BASDAI <4 during the treatment period was higher in the etanercept group than in the infliximab group (p<0.001). The number of patients fully employed increased in the whole group from 48% to 63% after 1 year of treatment.

Follow-up of patients with AS in the national registry shows that it is an effective and safe way of treatment with longer adherence to anti-TNF therapy in comparison with RA patients.

There is approximately a 17 % dissatisfaction rate with knee replacements. Calls for tools that can pre-operatively identify patients at risk of being dissatisfied have been widespread. However, it is not known how to present such information to patients, how it would affect their decision making process, and at what part of the pathway such a tool should be used. Using focus groups involving 12 participants and in-depth interviews with 10 participants, we examined how individual predictions of outcome could affect patients' decision making by providing fictitious predictions to patients at different stages of treatment. A thematic analysis was used to analyse the data. Our results demonstrate several interesting findings. Firstly, patients who have received information from friends and family are unwilling to adjust their expectation of outcome down (i.e. to a worse outcome), but highly willing to adjust it up (to a better outcome). This is an example of the optimism bias, and suggests that the effect on expectation of a poor outcome prediction would be blunted. Secondly, patients generally wanted a "bottom line" outcome, rather than lots of detail. Thirdly, patients who were earlier in their treatment for osteoarthritis were more likely to find the information useful, and it was more likely to affect their decision, than patients later in their treatment pathway.

This research suggest that an outcome prediction tool would have most effect targeted towards people at the start of their treatment pathway, with a "bottom line" prediction of outcome. However, any effect on expectation and decision making of a poor outcome prediction is likely to be blunted by the optimism bias. These findings merit replication in a larger sample size.

Loosening of the glenoid component continues to be the main cause of medium and long-term failure of shoulder replacements. The purpose of this study was to evaluate the early clinical and radiographic results following use of an all-polyethylene pegged glenoid component designed for hybrid (biological and cement) fixation. Eighty-three shoulders in 77 patients (mean age, 68.6 years) underwent total shoulder arthroplasty with a pegged hybrid-fixation component (bone-ingrowth glenoid and cemented peg). Outcomes were determined with the American Shoulder and Elbow Surgeons (ASES) score and the Oxford shoulder score. A detailed analysis of radiographs and fine-slice computed tomography (CT) images was performed to determine the extent of bone ingrowth between the flanges and the extent of radiolucent lines at the prosthesis-bone interface. The mean duration of follow-up was 46.7 months (range, 24 to 99 months). At the time of final follow-up, the median ASES score was 97 points (range, 43 to 100 points) and the median Oxford score was 48 points (range, 24 to 48 points). The median active forward elevation was 130° (range, 65° to 170°), median external rotation was 45° (range, 5° to 80°), and median internal rotation was to T11 (range, buttock to T4). Seventy-eight shoulders demonstrated a perfect Lazarus score for radiolucency (0, indicating no radiolucency). Sixty-eight shoulders demonstrated complete osseointegration, with bone ingrowth between all of the flanges seen on coronal CT; 5 demonstrated partial osseointegration; and 10 demonstrated osteolysis around the central peg. Most radiolucent lines were in the inferior Yian zones. There were no correlations between the Yian CT scores and either the ASES or Oxford score (rho = 0.13 and 0.07, respectively). Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Total shoulder arthroplasty with an all-polyethylene pegged glenoid component, utilizing hybrid fixation, demonstrated excellent clinical and radiographic results at the time of early follow-up. Radiolucent lines were seen most commonly around the inferior pegs of the prosthesis, and this may represent an incipient mode of failure.

Degenerative osteoarthritis (OA) often leads to pain and stiffness of the affected joints, which may affect the physical performance and decrease the quality of life of people with degenerative knee OA. Compared to traditional exercise, tai chi is a safe exercise with slow movements which can facilitate physical functioning and psychological well being, and might be suitable for improving the physical activities of older adults with knee OA. Therefore, this study investigated the impacts of tai chi exercise on the functional fitness of community-dwelling older adults with degenerative knee OA. Sixty-eight community-dwelling older adults with knee OA were recruited from the local community to participate in this randomized controlled clinical trial. All subjects were randomly assigned to either an TCE group that practiced tai chi exercise (TCE) (n = 36) or a control group (CON) (n = 32) that received regular health education programs twice per week for 12 weeks. Outcome measurements were determined using functional fitness tests before and after the intervention, including a 30-s chair stand (number of repeats), 30-s arm-curl (number of repeats), 2-min step (number of steps), chair sit-and-reach (reaching distance, cm), back-scratch flexibility (distance between hands, cm), single-leg stand (time, s), functional reach (reaching distance, cm), 8-foot up-and-go (time, s), and 10-m walk tests (time, s). Pre-post comparisons of functional fitness were analyzed using the ANCOVA test with SPSS software version 18.0. Results revealed that participants' functional fitness in the TCE group had significantly higher adjusted mean post-tests scores than that in the CON group after the intervention, including the 8-foot up-and-go (s) (mean difference [MD]=-2.92 [-3.93, -1.91], p = 2.39*10

Community-dwelling older adults with knee OA in the TCE group had better functional fitness performances after the 12-week tai chi intervention than those receiving only health education.

Biomechanical studies in vitro suggested that patellofemoral (PF) stuffing would cause knee flexion restriction after total knee arthroplasty (TKA). We investigated the effect of anterior PF stuffing on the postoperative knee flexion after cemented TKA of posterior cruciate-substituting (PS) design. A retrospective review of 140 primary TKAs for osteoarthritis with an average age of 68.5 was conducted. The patella was resurfaced. The height of PF joint and the patella thickness were evaluated radiographically, preoperatively and 2-year postoperatively. The maximum flexion angle was 129.7° (standard deviation: SD 16.9) pre-operatively and 129.3° (SD 11.9) 2-year postoperatively. The increase in height was associated with the differences in maximum flexion angle between preoperatively and postoperatively (R = 0.254 P < 0.01). The patella thickness change did not show any significant influences.

The increase in patellofemoral volume has decreased range of motion after total knee arthroplasty of posterior cruciate-substituting prosthesis.

Examine caregiver demand and general parent distress as mediators in the parent illness uncertainty-child depressive symptom association in youth with juvenile rheumatic diseases. Children and adolescents completed the Child Depression Inventory; caregivers completed the Parent Perceptions of Uncertainty Scale, the Care for My Child with Rheumatic Disease Scale, and the Brief Symptom Inventory. The pediatric rheumatologist provided ratings of clinical disease status. Analyses revealed significant direct associations between illness uncertainty and caregiver demand, and between caregiver demand and both parent distress and child depressive symptoms. Results also revealed significant parent uncertainty → caregiver demand → parent distress and parent uncertainty → caregiver demand → child depressive symptom indirect paths.

Results highlight the role of illness appraisals in adjustment to juvenile rheumatic diseases, and provide preliminary evidence that parent appraisals of illness uncertainty impact parent distress and child depressive symptoms indirectly through increased perceptions of caregiver demand.

We sought to determine whether symptomatic medial knee osteoarthritis is associated with aberrant loading across the foot during gait. Twenty-five individuals with medial knee osteoarthritis were compared with 25 controls. Knee radiographs and Western Ontario and McMaster Universities Arthritis Index questionnaires were obtained. Participants walked barefoot over pressure sensors, and the center-of-pressure trace was plotted against the axis of the foot, and a center-of-pressure index was calculated. The center-of-pressure indices in the medial knee osteoarthritis group demonstrated high lateral loading compared with the central center-of-pressure pattern in controls (P < .001). There was a correlation between the severity of pain and the center-of-pressure index in patients with medial knee osteoarthritis but no correlation between center of pressure and radiographic severity.

The plantar pressure patterns of patients with medial knee osteoarthritis demonstrated greater loading of the lateral aspect of the foot during the contact and midstance phases of gait but not during propulsion compared with those of controls, suggesting that loading patterns in the feet are related to osteoarthritis in the knee.

Pulmonary disease represents an important extraarticular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess the incidence, risk factors, and mortality of OLD in patients with RA. We examined a population-based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox proportional hazards models were used to compare OLD incidence between the RA and comparator cohorts to investigate risk factors and to explore the impact of OLD on patient survival. A total of 594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA (hazard ratio [HR] 1.54, 95% confidence interval [95% CI] 1.01-2.34). The risk of developing OLD was higher among male patients, among current or former smokers, and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47-2.97).

Patients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survival in these patients.

To automate the grading of histological images of engineered cartilage tissues using deep learning. Cartilaginous tissues were engineered from various cell sources. Safranin O and fast green stained histological images of the tissues were graded for chondrogenic quality according to the Modified Bern Score, which ranks images on a scale from zero to six according to the intensity of staining and cell morphology. The whole images were tiled, and the tiles were graded by two experts and grouped into four categories with the following grades: 0, 1-2, 3-4, and 5-6. Deep learning was used to train models to classify images into these histological score groups. Finally, the tile grades per donor were averaged. The root mean square errors (RMSEs) were calculated between each user and the model. Transfer learning using a pretrained DenseNet model was selected. The RMSEs of the model predictions and 95% confidence intervals were 0.49 (0.37, 0.61) and 0.78 (0.57, 0.99) for each user, which was in the same range as the inter-user RMSE of 0.71 (0.51, 0.93).

Using supervised deep learning, we could automate the scoring of histological images of engineered cartilage and achieve results with errors comparable to inter-user error. Thus, the model could enable the automation and standardization of assessments currently used for experimental studies as well as release criteria that ensure the quality of manufactured clinical grafts and compliance with regulatory requirements.

To describe the prevalence and longitudinal course of radiographic, erosive and symptomatic hand osteoarthritis (HOA) in the general population. Framingham osteoarthritis (OA) study participants obtained bilateral hand radiographs at baseline and 9-year follow-up. The authors defined radiographic HOA at joint level as Kellgren-Lawrence grade (KLG)≥2, erosive HOA as KLG≥2 plus erosion and symptomatic HOA as KLG≥2 plus pain/aching/stiffness. Presence of HOA at individual level was defined as ≥1 affected joint. The prevalence was age-standardised (US 2000 Population 40-84 years). Mean (SD) baseline age was 58.9 (9.9) years (56.5% women). The age-standardised prevalence of HOA was only modestly higher in women (44.2%) than men (37.7%), whereas the age-standardised prevalence of erosive and symptomatic OA was much higher in women (9.9% vs 3.3%, and 15.9% vs 8.2%). The crude incidence of HOA over 9-year follow-up was similar in women (34.6%) and men (33.7%), whereas the majority of those women (96.4%) and men (91.4%) with HOA at baseline showed progression during follow-up. Incident metacarpophalangeal and wrist OA were rare, but occurred more frequently and from an earlier age in men than women. Development of erosive disease occurred mainly in those with non-erosive HOA at baseline (as opposed to those without HOA), and was more frequent in women (17.3%) than men (9.6%).

The usual female predominance of prevalent and incident HOA was less clear for radiographic HOA than for symptomatic and erosive HOA. With an ageing population, the impact of HOA will further increase.

Polymyalgia rheumatica is uncommon in young women and remains a diagnostic challenge for pregnant women. A 28-year-old pregnant woman developed polymyalgia rheumatica in the third trimester. Laboratory investigations revealed elevated erythrocyte sedimentation rate and C-reactive protein levels with normal muscle enzyme levels and seronegativity for rheumatoid factor. Although her symptoms deteriorated as pregnancy progressed, she drastically improved by treatment with prednisone. She underwent cesarean delivery at 39 weeks. She was relapse-free of polymyalgia rheumatica after discontinuation of prednisone on the 50th postoperative day.

The diagnosis of polymyalgia rheumatica is important to properly manage pregnancy.

To define the germline counterparts of potentially highly mutated autoantibodies in disease states. We developed a systematic approach by first characterizing a rearranged Ig gene and its upstream flank, and then designing suitable primers to amplify specifically the putative germline counterpart. We identified and characterized the germline counterpart of a rheumatoid factor heavy chain variable region.

We showed unequivocally that the heavy chain of a rheumatoid factor, derived from synovial tissue, has 4 replacement mutations from the corresponding germline gene. The technique allows quick assessment of the degree of somatic mutation in many autoantibodies, and thus can help to elucidate the underlying mechanisms for the induction and sustained production of such antibodies in patients.

We have reported that a single intra-articular injection of diclofenac etalhyaluronate (SI-613) exerted a potent and long-lasting analgesic effect in experimental arthritis models. In the present study, we investigated the effect of SI-613 on the production of high molecular weight hyaluronic acid (HMW-HA) in synoviocytes from osteoarthritis (OA) patients and compared its efficacy with that of hyaluronic acid (HA). We compared the effect of SI-613, HA, and diclofenac sodium (DF-Na) on high molecular weight HA production by human synoviocytes. SI-613 and exogenous HA induced the production of high molecular weight HA in synoviocytes from OA patients, whereas DF-Na had no effect. The molecular weight of newly produced HA was about 1000 kDa in the HA-treated synoviocytes and much higher than 2400 kDa in the SI-613-treated cells. The effect of the mixture of HA and DF-Na was similar to that of HA alone in that the molecular weight of newly produced HA was around 1000 kDa. SI-613 significantly suppressed hyaluronidase 2 (HYAL2) mRNA expression and significantly enhanced hyaluronan synthase 2 (HAS2) mRNA expression. HA had no effect on the expression levels of HYAL and HAS.

The present results clearly demonstrate that SI-613 induces the production of high molecular weight HA in synoviocytes from OA patients, suggesting the long-lasting analgesic and disease modifying effect of SI-613 for OA. Taken together with the anti-inflammatory and analgesic effects we recently reported for the intra-articular administration of SI-613 to experimental animal models, SI-613 holds great promise for the treatment of knee osteoarthritis.

There is increasing evidence that kinematic changes after anterior cruciate ligament (ACL) injury can influence the risk for premature osteoarthritis. However, kinematics can change over time, and the factors influencing those changes remain unknown but potentially important. The purpose of this study was to perform gait analysis on a population of ACL-deficient (ACLD) subjects without knee osteoarthritis after considerable time had elapsed since their injuries. The following hypotheses were tested: (1) ACLD knees will have greater anterior femoral translation, external femoral rotation, and flexion moment as compared with healthy contralateral knees with increased time since injury; (2) side-to-side differences in anterior femoral translation and external femoral rotation are positively associated with side-to-side differences in knee flexion moment. Cross-sectional study; Level of evidence, 3. Nineteen subjects with unilateral ACLD (time since injury, 1-384 months) underwent gait testing. Linear regression testing was performed for significant relationships between side-to-side differences in tibial translation and rotation during stance and the amount of time since injury, as well as the relationship between differences in peak flexion moment and differences in translation and rotation. There was a time dependency in side-to-side differences. Subjects with shorter times since injury had the femur of the ACLD knee more posteriorly translated and internally rotated than the femur of the contralateral knee, and subjects with longer times since injury had the femur of the ACLD knee more anteriorly translated (R2=0.33) and externally rotated (R2=0.53) than the femur of the contralateral knee. Additionally, when the population was stratified into 2 subgroups based on time after injury (short-term: 1.4-18.7 months; long-term: 58-383.5 months), a relationship between side-to-side differences in knee flexion moment and side-to-side differences in knee translation and rotation was found for the long-term subgroup.

The results of this study provide an understanding of the relationship between kinematics and kinetics of the ACLD knee and the amount of time since injury. They suggest that elapsed time since injury might be an important factor when the function of ACL-injured knees is interpreted as it relates to osteoarthritis.

We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. Current Controlled Trials, ID: ISRCTN46017566 . Registered on 4 July 2014.

There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.

Disturbed sleep is commonly reported in fibromyalgia (FM). Both the Sleep Quality Numeric Rating Scale (NRS) and the Medical Outcomes Study Sleep Scale (MOS-Sleep) have demonstrated positive psychometric properties in patients with FM. However, these assessments were developed prior to the current recommendation to include patient input during the concept elicitation or item generation phases. Therefore, the objective of this study was to evaluate the impact of FM on participants, including their sleep, and to test the content validity of these two sleep measures in FM patients. Qualitative interviews were conducted in Raleigh, North Carolina and Detroit, Michigan with 20 adults who reported a physician diagnosis of FM. Sixteen participants were female, 13 were white, and the average age was 50 years. Two researchers conducted all interviews using a structured guide. Participants consistently reported that FM had a debilitating impact on their lives and their sleep, particularly getting to sleep and staying asleep. Participants responded positively to the Sleep Quality NRS as an assessment of their sleep. The majority of participants stated that they would not change the response numbering or wording of the item's anchors. Participants also responded positively to the 24-hour recall period of the Sleep Quality NRS. Participants found the 12-item MOS-Sleep to be appropriate and relevant; 19 participants indicated the measure captured all of their sleep-related symptoms. However, areas for potential modification were identified, such as the need to separate the item regarding awakening short of breath and awakening with a headache into two separate questions. Participants also questioned the relevance of the snoring and awakening short of breath items to FM. Half of participants expressed a preference for a daily rather than a weekly recall period.

This study demonstrates the significant impact that FM has on patients' lives, particularly sleep. While patients with FM were not part of the development of the generic sleep assessments that were evaluated, this study provides evidence of their content validity, supporting their use in FM studies. Modifications to the MOS-Sleep may improve the psychometric properties and relevance to patients with FM.

To determine clinicians' accuracy and reliability for the clinical diagnosis of unstable meniscus tears in patients with symptomatic osteoarthritis of the knee. A prospective cohort study. A single tertiary care centre. One hundred and fifty-two patients with symptomatic osteoarthritis of the knee refractory to conservative medical treatment were selected for prospective evaluation of arthroscopic debridement. Arthroscopic debridement of the knee, including meniscal tear and chondral flap resection, without abrasion arthroplasty. A standardized assessment protocol was administered to each patient by 2 independent observers. Arthroscopic determination of unstable meniscal tears was recorded by 1 observer who reviewed a video recording and was blinded to preoperative data. Those variables that had the highest interobserver agreement and the strongest association with meniscal tear by univariate methods were entered into logistic regression to model the best prediction of resectable tears. There were 92 meniscal tears (77 medial, 15 lateral). Interobserver agreement between clinical fellows and treating surgeons was poor to fair (kappa < 0.4) for all clinical variables except radiographic measures, which were good. Fellows and surgeons predicted unstable meniscal tear preoperatively with equivalent accuracy of 60%. Logistic regression modelling revealed that a history of swelling and a ballottable effusion were negative predictors. A positive McMurray test was the only positive predictor of unstable meniscal tear. "Mechanical" symptoms were not reliable predictors in this prospective study. The model was 69% accurate for all patients and 76% for those with advanced medial compartment osteoarthritis defined by a joint space height of 2 mm or less.

This study underscored the difficulty in using clinical variables to predict unstable medial meniscal tears in patients with pre-existing osteoarthritis of the knee. The lack of interobserver agreement must be overcome to ensure that the findings can be generalized to other physician observers.

Repeated hemarthrosis in hemophilia causes arthropathy with pain and dysfunction. The Hemophilia Joint Health Score (HJHS) was developed to be more sensitive for detecting arthropathy than the World Federation of Hemophilia (WFH) physical examination scale, especially for children and those using factor prophylaxis. The HJHS has been shown to be highly reliable. We compared its validity and sensitivity to the WFH scale. We studied 226 boys with mild, moderate, and severe hemophilia at 5 centers. The HJHS was scored by trained physiotherapists. Study physicians at each site blindly determined individual and total joint scores using a series of visual analog scales. The mean age was 10.8 years. Sixty-eight percent were severe (93% of whom were treated with prophylaxis), 15% were moderate (24% treated with prophylaxis), and 17% were mild (3% treated with prophylaxis). The HJHS correlated moderately with the physician total joint score (rs=0.42, P<0.0001) and with overall arthropathy impact (rs=0.42, P<0.0001). The HJHS was 97% more efficient than the WFH at differentiating severe from mild and moderate hemophilia. The HJHS was 74% more efficient than the WFH at differentiating subjects treated with prophylaxis from those treated on demand. We identified items on the HJHS that may be redundant or rarely endorsed and could be removed from future versions.

Both the HJHS and WFH showed evidence of strong construct validity. The HJHS is somewhat more sensitive for mild arthropathy; its use should be considered for studies of children receiving prophylaxis.

Distal tibial tuberosity high tibial osteotomy (DTT-HTO) can prevent distalization of the tibial tuberosity and thus patellar infera. However, no studies on the clinical and radiological effects of DTT-HTO on the patellofemoral joint have been conducted. The purpose of the study was to evaluate the effect of DTT-HTO on patella height and patellofemoral joint congruity based on the severity of patellofemoral joint OA. Twenty-nine patients (33 knees) who underwent DTT-HTO and second-look arthroscopy when implant was removed between January 2018 and May 2020 were eligible for the study. Among them, 6 were males, and 23 were females, with ages from 51 to 78 years old. The Caton-Deschamps index (CDI), congruence angle (CA), and lateral patellar tilt (LPT) were measured to evaluate the effect of surgery on patellar height and patellofemoral joint congruity. The weight-bearing line ratio (WBLR) was measured to assess lower limb alignment. The cartilage lesion in the patellofemoral joint was assessed arthroscopically during surgery and implant removal by the International Cartilage Repair Society (ICRS) grading system at 18-24 months after surgery. The Hospital for Special Surgery (HSS) scale was used to evaluate knee joint function. Twenty-nine patients were followed up for 18-28 months. The preoperative CDI, CA, and LPT changed from 0.92 ± 0.16 to 0.89 ± 0.14, from 5.52 ± 2.19 to 5.44 ± 2.27, and from 6.95 ± 2.88 to 6.54 ± 2.42, respectively, and the differences were not statistically significant (p > 0.05). The preoperative WBLR significantly increased from 16.72 ± 6.77 to 58.77 ± 7.69% (p < 0.001). The cartilage lesions in the patella and femoral trochlea did not progress significantly from the first- to the second-look arthroscopy, according to the ICRS grades (p > 0.05). The HSS score significantly improved from 50.64 ± 19.18 preoperatively to 67.33 ± 14.72, 81.63 ± 11.92, and 82.73 ± 8.05 at the 3-month, 12-month, and last follow-up after surgery (p < 0.001).

DTT-HTO can effectively prevent patellar infera, and its effects on postoperative patellofemoral joint congruity and patellofemoral joint OA progression are inconspicuous. It can be recommended as a treatment of varus knee combined with patellar infera or patellofemoral joint OA.

Rheumatoid arthritis (RA) may affect the postural control through abnormal sensory inputs and impaired motor responses. Sensory Organization Test (SOT) objectively evaluates contribution of different sensorial afferences in postural control. The aim of the study is to assess mechanisms of postural instability and their relations with disability and disease characteristics in an early RA(ERA) cohort. The equilibrium scores were assessed in 30 ERA patients and 30 age- and sex-matched controls. The somatosensory (SOM), visual (VIS) and vestibular (VEST) ratios were computed to assess the use of different sensory and the composite equilibrium score (CES) as a measure of global balance performance. ERA patients had lower CES (78.4±6.0% vs. 83.4±5.0%, p=0.002), SOM ratio (98.5±1.8% vs. 99.6±2.1%, p=0.035), VIS ratio (85.2±7.6% vs. 91.5±6.0%, p=0.001) and VEST ratio (70.8±10.0% vs. 80.3±7.8%, p<0.001) compared to controls. The presence of ankle arthritis correlated negatively to both SOM (r=-0.369, p=0.045) and VIS ratio (r=0.470, p=0.009), pain severity to CES (r=-0.389, p=0.045) and VIS ratio (r=-0.385, p=0.048) and HAQ-DI to CES (r=-0.591, p=0.001), SOM (r=-0.510, p=0.004) and VIS ratio (r=-0.390, p=0.033.). Patients-reported postural instability was associated with lower CES (75.4±5.4% vs. 80.7±5.5%, p=0.016) and VEST ratios (66.5±10.1% vs. 74.1±8.8%, p=0.036). SOT outcomes did not differ according to acute phase reactants, disease activity or autoantibody positivity.

RA patients showed an early impairment of postural control related to the degree of disability and subjective postural instability. Our data suggest that the lack of balance could result from both impaired motor response and abnormal sensory organisation.

Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population. The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis. Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p=0.000, OR: 0.20, 95% CI: 0.10-0.41, OR: 0.22, 95% CI: 0.12-0.42, respectively).

Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA.

Open-wedge high tibial osteotomy (OWHTO) is a well-established surgical option for medial compartment osteoarthritis of the varus knee. The initial strength of the fixation plate is critical for successful correction maintenance and healing of the osteotomy site. This study was conducted to verify if a newly designed anatomical plate (LCfit) improves the stability of both the medial implant and lateral hinge area, as well as to evaluate how the metal block contributes to both medial and lateral stability. A finite element (FE) tibial model was combined with TomoFix plate, a LCfit plate with and without a metal block. Data analysis was conducted to evaluate the balanced stability, which refers to the enforced lateral stability resulting from redistribution of overall stress. We assessed the balanced stability of the medial implant and lateral hinge area in three cases using the same Sawbones and loads using the tibia FE model. The LCfit plate reduced stress by 23.1% at the lateral hinge compared to the TomoFix plate (TomoFix vs. LCfit: 34.2 ± 23.3 MPa vs. 26.3 ± 17.5 MPa). The LCfit plate with a metal block reduced stress by 40.1% at the medial plate (210.1 ± 64.2 MPa vs. 125.8 ± 65.7 MPa) and by 31.2% (26.3 ± 17.5 MPa vs. 18.1 ± 12.1 MPa) at the lateral hinge area compared to the reduction using the LCfit plate without a metal block.

The newly designed fixation system for OWHTO balanced the overall stress distribution and reduced stress at the lateral hinge area compared to that using a conventional fixation system. The addition of the metal block showed additional benefits for balanced stability between the medial implant and lateral hinge area. However, this conclusion could only be drawn using the FE model in this study. Therefore, further clinical studies are necessary to reveal the clinical effect of reduced lateral stress on the occurrence of the lateral hinge fracture and the biologic effect of the metal block on the healing of the medial cortex.

To evaluate the clinical and radiological results of no bone graft (NBG) after opening wedge high tibial osteotomy (OWHTO) with a locking plate and to compare the bone union rate between the synthetic bone graft (SBG) group and the NBG group after OWHTO using serial radiographs. From 2012 to 2015, OWHTOs were performed with SBG or without bone graft using long locking plates. Inclusion criteria were: (1) OWHTO for disease of the medial compartment with varus deformity, and (2) minimum 2-year follow-up and radiographs taken serially to 2 years. Exclusion criteria were: (1) follow-up period <2 years (n = 8) or (2) absence of at least 1 radiograph taken at each follow-up point (n = 14). We retrospectively reviewed radiographs taken preoperatively and at 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Groups comprised those filled with a synthetic bone [hydroxyapatite (HA) and β-tricalciumphosphate (TCP), n=33, SBG group] or without a bone graft (n = 38, NBG group). We compared bone union rate between the 2 groups by measuring the union zone from zone 1 to zone 5 in serial radiographs using Fisher's exact test. OWHTO was performed in a total of 93 knees and 71 knees were included in this study. Both groups showed good clinical and radiological results without correction loss at 2 years. The entire NBG group and 93.9% of the SBG group showed union over zone 3 at 2 years. However, the NBG group showed significantly more incorporation than the SBG group at 6 months (P = .006), 1 year (P = .0003), and 2 years (P = .0003). Level IV, case series.

Union without correction loss was obtained after OWHTO without bone graft. The NBG group showed significantly more incorporation than the SBG group (HA and β-TCP) within 2 years.

Cystic lung disease (CLD) in Sjögren syndrome (SS) is a condition with unclear prognostic implications. Our objectives in this study are to determine its frequency, progression over time, and associated risk factors and complications. Eighty-four patients with primary or secondary SS and chest imaging, chest radiograph, or CT scan were retrospectively evaluated for CLD. Thirteen patients with cysts were found. Baseline characteristics of all patients were collected. A multivariate logistic regression model was used to look for predictors of CLD in patients with CT scan. Additional imaging, SS activity, and complications from CLD and SS were collected for the patients with cysts. CLD had a frequency of 15.4% for all patients with chest imaging. Not all cysts were evident on radiography, and CLD frequency was 30.9% for the patients with chest CT scan. Six patients had cysts without other radiographic findings. CLD was associated with older age (OR, 1.1; 95% CI, 1.0-1.16), a diagnosis of secondary SS (OR, 12.1; 95% CI, 1.12-130.4), and seropositivity for anti-SS-related antigen A/Ro autoantibodies (OR, 26.9; 95% CI, 1.44-93.61). There was no radiologic progression of CLD for 12 patients after a 4-year median follow-up. Lung function did not exhibit temporal worsening. CLD did not correlate with a specific pattern in pulmonary function testing. Two patients had secondary infectious complications of the cysts.

CLD is a relatively common condition in SS that does not progress on serial radiologic and lung function follow-up. CLD, without other radiographic findings, may represent a direct manifestation of SS.

This study evaluated the clinical efficacy of continuous passive motion (CPM) following knee arthroplasty and determined the predictors of effect sizes of range of motion (ROM) and functional outcomes in patients with knee arthritis. A comprehensive electronic database search was performed for randomized controlled trials (RCTs), without publication year or language restrictions. The included RCTs were analyzed through meta-analysis and risk of bias assessment. Study methodological quality (MQ) was assessed using the Physiotherapy Evidence Database (PEDro) scale. Inverse-variance weighted univariate and multivariate metaregression analyses were performed to determine the predictors of treatment outcomes. A total of 77 RCTs with PEDro scores ranging from 6/10 to 8/10 were included. Meta-analyses revealed an overall significant favorable effect of CPM on treatment success rates [odds ratio: 3.64, 95% confidence interval (CI) 2.21-6.00]. Significant immediate [postoperative day 14; standard mean difference (SMD): 1.06; 95% CI 0.61-1.51] and short-term (3-month follow-up; SMD: 0.80; 95% CI 0.45-1.15) effects on knee ROM and a long-term effect on function (12-month follow-up; SMD: 1.08; 95% CI 0.28-1.89) were observed. The preoperative ROM, postoperative day of CPM initiation, daily ROM increment, and total application days were significant independent predictors of CPM efficacy. II.

Early CPM initiation with rapid progress over a long duration of CPM application predicts higher treatment effect on knee ROM and function. The results were based on a moderate level of evidence, with good MQ and potential blinding biases in the included RCTs. An aggressive protocol of CPM has clinically relevant beneficial short-term and long-term effects on postoperative outcomes.

Serologically active clinically quiescent (SACQ) systemic lupus erythematosus (SLE) patients' discordance presents a clinical dilemma. Does active serology alone warrant treatment? We explore outcomes in patients with and without a prolonged SACQ period, comparing the rate of damage accrual by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and incidences of renal damage and coronary artery disease (CAD) over a decade. SACQ was defined as a ≥2-year sustained period without clinical activity, with persistent serologic activity (increased anti-double-stranded DNA and/or hypocomplementemia). Antimalarials were permissible and corticosteroids/immunosuppressives were not. The SACQ patients were matched for relevant variables with SLE controls. Change in the SDI and incidences of CAD and renal damage were compared. Descriptive statistics were used; comparisons were made using t-tests and McNemar's tests. Fifty-five SACQ patients and 110 controls were identified. The mean ± SD SDI score at 3 years from the start of the SACQ period was 0.70 ± 1.27 in the SACQ patients versus 1.13 ± 1.54 in controls (P < 0.0001), and by 10 years was 1.26 ± 1.68 versus 2.26 ± 2.23 (P = 0.001); the intergroup difference in damage significantly increased over 10 years. Initially, 2 (3.6%) of the SACQ patients had CAD versus 7 (6.4%) of the controls (P = 0.32), with 1 (1.8%) new case in SACQ patients versus 8 (7.3%) new cases in controls over 10 years (P = 0.06). Baseline serum creatinine level did not differ between the groups. By definition, the SACQ patients had no baseline proteinuria versus 13 (12.3%) of the controls (P < 0.0001). By year 10, 2 (3.6%) SACQ patients versus 26 (23.6%) controls had renal damage (P < 0.0001).

Patients with a prolonged SACQ period accrued less damage over a decade compared to matched controls, supporting management with active surveillance without treatment during an SACQ period.

To adapt culturally and validate Persian-version of the Knee injury and Osteoarthritis Outcome Score (KOOS) in a sample of Iranians with knee injuries. Cultural adaptation included providing of forward and backward translations, quality rating and pilot testing. A sample of 147 patients with anterior cruciate ligament (ACL), meniscus and combined (ACL and meniscus) injuries was asked to complete two questionnaires including the KOOS and Short-Form 36 Health Survey (SF-36). The KOOS was readministered to 54 patients 6-8 days after the first visit. Test-retest reliability and internal consistency were assessed, using Intraclass Correlation Coefficient (ICC) and Cronbach's alpha, respectively. Dimensionality was assessed, using item-scale correlation after correction for overlap and construct validity, using a priori hypothesized correlations with the SF-36. All patients found the Persian-version of the KOOS to be clear and unambiguous in pilot testing. Minimum ICC level of 0.70 was exceeded by all subscales with the exception of Sport and Recreation (Sport/Rec) subscale. Minimum Cronbach's alpha level of 0.70 was exceeded by all subscales with the exception of Symptoms and Knee-related Quality of Life (QoL). Minimum Spearman correlation coefficient of 0.40 for each item-scale was exceeded by 34 items. All priori hypotheses were supported by the presence of higher correlations between similar constructs than between dissimilar constructs of the KOOS and SF-36.

The Persian-version of the KOOS is a culturally-adapted, reliable and valid outcome measure to be used in Iranian patients with knee injuries, with its psychometric properties in agreement with the original versions.

One out of three adults over the age of 65 years and one out of two over the age of 80 falls annually. Fall risk increases for older adults with severe knee osteoarthritis, a matter that should be further researched. The main purpose of this study was to investigate the history of falls including frequency, mechanism and location of falls, activity during falling and injuries sustained from falls examining at the same time their physical status. The secondary purpose was to determine the effect of age, gender, chronic diseases, social environment, pain elsewhere in the body and components of health related quality of life such as pain, stiffness, physical function, and dynamic stability on falls frequency in older adults aged 65 years and older with severe knee osteoarthritis. An observational longitudinal study was conducted on 68 patients (11 males and 57 females) scheduled for total knee replacement due to severe knee osteoarthritis (grade 3 or 4) and knee pain lasting at least one year or more. Patients were personally interviewed for fall history and asked to complete self-administered questionnaires, such as the 36-item Short Form Health Survey (SF-36) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and physical performance test was performed. The frequency of falls was 63.2% for the past year. The majority of falls took place during walking (89.23%). The main cause of falling was stumbling (41.54%). There was a high rate of injurious falling (29.3%). The time patients needed to complete the physical performance test implied the presence of disability and frailty. The high rates of fall risk, the high disability levels, and the low quality of life were confirmed by questionnaires and the mobility test.

Patients with severe knee osteoarthritis were at greater risk of falling, as compared to healthy older adults. Pain, stiffness, limited physical ability, reduced muscle strength, all consequences of severe knee osteoarthritis, restricted patient's quality of life and increased the fall risk. Therefore, patients with severe knee osteoarthritis should not postpone having total knee replacement, since it was clear that they would face more complicated matters when combining with fractures other serious injuries and disability.