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Pro-inflammatory cytokines such as TNF-α are important in the pathogenesis of fatigue in conditions such as RA. This study aimed to determine whether fatigue improved in a cohort of RA patients with clinically relevant fatigue commencing anti-TNF-α therapy and, if so, to identify predictors of improvement. Participants recruited to a long-term observational cohort study (the British Society for Rheumatology Biologics Register for RA) provided information on fatigue using the 36-item Short Form Health Survey (SF-36) vitality subscale. The prevalence of severe baseline fatigue (SF-36 vitality ≤12.5) was calculated and improvements, considered as (i) absolute values and (ii) improvement from severe to non-severe fatigue (SF-36 vitality >12.5), were examined 6 months subsequently. A comprehensive set of putative predictors of fatigue improvement were evaluated using multivariable logistic regression. In 6835 participants the prevalence of severe baseline fatigue was 38.8%. Of those with severe fatigue, 70% reported clinically relevant improvement and 66% moved to the non-severe fatigue category (i.e. improvers). The mean change for improvers was three times the minimum clinically important difference for improvement (33.0 U). Independent baseline predictors of improvement were female sex [odds ratio (OR) 1.3 (95% CI 1.1, 1.7)], not being unemployed due to ill health [OR 1.5 (95% CI 1.2, 1.7)], low disability [OR 1.2 (95% CI 1.001, 1.5)], seropositivity [OR 1.2 (95% CI 0.98, 1.4)], not using steroids [OR 1.2 (95% CI 1.03, 1.5)], no history of hypertension [OR 1.4 (95% CI 1.1, 1.6)] or depression [OR 1.3 (95% CI 1.1, 1.5)] and good mental health [SF-36 mental health subscale >35; OR 1.4 (95% CI 1.2, 1.7)].

Fatigued RA patients reported substantial improvement in their fatigue after commencing anti-TNF-α therapy. Further, a number of clinical and psychosocial baseline factors identified those most likely to improve, supporting future stratified approaches to RA fatigue management.

To assess CD23 status in rheumatoid arthritis (RA) patients, as defined by the levels of CD23 expression on peripheral blood mononuclear cells (PBMC), the levels of soluble CD23 (sCD23) in sera, and the production of sCD23 by PBMC cultures and its regulation by interleukin-4 (IL-4). CD23 expression as determined by double fluorescence-activated cell sorter analysis and sCD23 production as determined by immunoradiometric assay were investigated in 24 RA patients and 21 controls. Soluble CD23 was measured in sera and supernatants of PBMC, activated with polyclonal activators (pokeweed mitogen [PWM] or Staphylococcus aureus Cowan strain 1, [SAC]) used either alone or in combination with IL-2 or IL-4. The percentage of B cells expressing CD23 and serum levels of sCD23 were increased in patients with RA. IL-4 was a potent inducer of sCD23 production in supernatants, whereas IL-2 was inactive. Costimulation with SAC or PWM did not increase the effect obtained with IL-4 alone. When sCD23 levels in RA and control supernatants were compared, spontaneous production was found to be increased in RA PBMC: This difference from control values was even more pronounced when sCD23 levels in PBMC and purified B cells in response to IL-4, either alone or in combination with SAC or PWM, were tested. In the same supernatants, the increased secretion of sCD23 induced by IL-4 was associated with an inhibitory effect of IL-4 on Ig production, a phenomenon that was more pronounced in RA PBMC than in controls.

CD23 status in RA is characterized by increased expression of CD23 on B cells, increased production of sCD23 in sera and supernatants, and increased sensitivity of RA PBMC and B cells to IL-4.

Disability from chronic illness is a major problem for society, yet the study of its determinants lacks an overall theoretical paradigm. Johnston (1996) has proposed conceptualizing disability as behavior and integrating biomedical and behavioral predictors. Dixon, Johnston, Rowley, and Pollard (2008) tested a model including constructs from the International Classification of Functioning, Disability and Health (ICF) and the theory of planned behavior (TPB) using structural equation modeling; it fitted better and explained more variance than the ICF or TPB alone. We replicated their study with a new sample from the same population (orthopedic patients awaiting joint replacement) and also tested the model after the patients had surgery. Two weeks before surgery, 342 orthopedic patients who had joint pain (most with arthritis) completed a questionnaire, with 228 completing it again 1 year after surgery. The authors tested Dixon et al.'s best-fit models cross-sectionally (before and after surgery) and assessed the goodness of fit of these imposed models to our data using structural equation modeling. Findings strongly supported those of Dixon et al. Before surgery, results were very similar to Dixon et al. with all models accounting for significant variance and fitting well, but the integrated model fitted better and accounted for more variance. One year after surgery, Dixon et al.'s models showed even stronger fit to the data.

Although behavioral and biomedical (ICF) models were supported, the integrated model provided a better explanation of disability in this population than either of these models alone and suggests biopsychosocial interventions to reduce disability.

It remains unclear whether Tai Chi is effective for walking function and posture control improvements in aged populations with knee osteoarthritis. The aim of this study was to systematically evaluate the effects of Tai Chi on improving walking function and posture control in elderly patients with knee osteoarthritis by updating the latest trial evidence. Web of Science, PubMed/Medline, Embase, Scopus, PEDro, and Cochrane library were searched up to October 1, 2020 to identify RCTs evaluating Tai Chi for improving walking function and posture control in older adults with knee osteoarthritis. The primary outcomes were walking function and posture control. Meta-analysis was performed with RevMan Version 5.3 software. A total of 603 participants with knee osteoarthritis in the 11 trials were included. The results of meta-analysis showed that: The Tai Chi group was associated with better performance in 6-minute walk test (6 MWT), time up and go test (TUG) and "Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index" Physical Function Score than the control group ([MD: 46.67, 95% CI 36.91-56.43, P < .001]), ([MD: -0.89, 95% CI -1.16 to -0.61, P < .001]), ([MD: -11.28, 95% CI -13.33 to -9.24, P < .001]).

This meta-analysis provided evidence from 11 RCTs that Tai Chi could be an excellent physical training strategy for improving walking function and posture control in older adults with knee osteoarthritis. Assuming that Tai Chi is at least effective and safe in most areas, it can be used as an adjuvant and reliable physical training strategy for walking function upgrading and balance control improvements for older patients with knee osteoarthritis.

Some studies indicate that the mitochondrion is implicated in osteoarthritis (OA). To test the hypothesis that mitochondrial DNA (mtDNA) haplogroups contribute to the prevalence and severity of knee OA, we analyzed the European mtDNA haplogroups in a Spanish population of patients with knee OA and healthy control subjects. We combined the single-base extension assay with the polymerase chain reaction-restriction fragment length polymorphism technique to obtain the different single-nucleotide polymorphisms that characterize the European haplogroups in 457 patients with knee OA and 262 radiologic controls. Knee OA radiographs had previously been classified as grades 1-4 according to Kellgren/Lawrence (K/L) scoring system. Individuals carrying haplogroup J showed a significantly decreased risk of knee OA (odds ratio [OR] 0.460 [95% confidence interval (95% CI) 0.282-0.748], P = 0.002). In terms of K/L scores, patients carrying haplogroup J had a less severe progression of knee OA (OR 0.351 [95% CI 0.156-0.787], P = 0.012), while those carrying haplogroup U had a more severe progression (OR 1.788 [95% CI 1.094-2.922], P = 0.025).

People carrying haplogroup J may be at a lower risk of developing knee OA, and those carrying this haplogroup in whom knee OA does not develop may have a less severe progression of the disease. Patients with knee OA carrying haplogroup U may have a more severe progression of the disease. These results indicate that mtDNA haplogroups contribute to the pathogenesis of OA.

Although previous studies report associations between increased body mass index (BMI) and fibromyalgia symptoms, there is uncertainty as to whether this relationship is driven by physical factors, psychological factors, or both. To assess these relationships in a clinical sample of patients with fibromyalgia. Cross-sectional study. Tertiary care facility. A total of 686 patients from an existing national fibromyalgia registry. Patients completed a demographic form and self-report questionnaires including the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), the Medical Outcomes Study Short Form-36 (SF-36), the Brief Pain Inventory (BPI), and the 30-item Profile of Mood States (30-item POMS). FIQ-R overall impact subscale. BMI was significantly correlated with fibromyalgia impact (P < .001). The relationship between BMI and fibromyalgia impact was almost fully accounted for by physical factors and not by psychological factors.

Despite patient report that pain hinders physical activity, clinicians who encounter patients with fibromyalgia, particularly patients with increased BMI, should be cognizant of the need to invest time and resources to counsel patients on physical factors (ie, physical activity) that could improve the patients' symptom experience.

The present study was undertaken to determine which factors differentiate patients with a good outcome after treatment for Thoracic Outlet Syndrome (TOS) from patients with a poor outcome. A total of 85 patients, who were examined during one year, had at least 6 months of follow up after treatment for TOS with either surgery or botulinum chemodenervation. Socioeconomic factors of work disability or workers' compensation claims did not differentiate treatment-responsive TOS from treatment-resistant cases. There was no difference between the 2 groups regarding the presence of anomalous anatomy detected by ultrasonography or regarding the presence of subclavian artery flow acceleration or occlusion detected by duplex sonography. Several factors were noted more frequently in treatment-resistant patients: sensory complaints extending beyond lower trunk dermatomes (42% vs. 10%), weakness extending beyond lower trunk myotomes (19% vs. 2%), histories of previous non-TOS surgery of the neck or upper limbs (50% vs.17%), comorbidities of fibromyalgia or complex regional pain syndrome (81% vs. 12%), and depression (35% vs. 10%). Treatment-resistant patients complained about more widespread functional impairments on a validated Cervical Brachial Symptom Questionnaire (CBSQ) than treatment-responsive patients. Resistant cases responded less often to a scalene test block (38% vs. 100%), which is designed to simulate the effects of targeted treatment.

In summary, compared to patients with a good outcome after targeted treatment, patients with a poor outcome had more diffuse complaints and responded less often to a scalene test block.

Recently, an association of a single nucleotide polymorphism, 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for nuclear factor kappaB, has been reported in type 1 diabetes. To establish whether SUMO4 locus contributes to the genetic susceptibility to other autoimmune disorders, a case-control analysis was carried out using genomic DNA from type 1 diabetes, autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), and primary Sjögren's syndrome. A total of 1480 samples, including 929 cases (411 patients with type 1 diabetes, 292 AITD, 172 RA, and 54 primary Sjögren's syndrome) and 551 healthy control subjects of Japanese origin participated in the study. The 163A>G (rs237025, M55V) polymorphism of SUMO4 was genotyped. SUMO4 M55V variant was associated not only with type 1 diabetes [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.09-1.84; P = 0.0072], but also with increased risk of other autoimmune diseases, AITD (OR, 1.52; 95% CI, 1.14-2.03; P = 0.0041) and RA without amyloidosis (OR, 1.53; 95% CI, 1.65-2.24; P = 0.027), but not primary Sjögren's syndrome. Furthermore, the association of SUMO4 M55V variant was stronger in type 1 diabetic patients complicated with AITD (OR, 1.62; 95% CI, 1.06-2.47; P = 0.023) and in patients who have neither type 1 diabetes-susceptible class II HLA, DRB1*0405 nor DRB1*0901 (OR, 2.28; 95% CI, 1.34-3.87; P = 0.0018).

These results indicate that the SUMO4 is a more common autoimmune disease gene and a supplementary risk factor to type 1 diabetes in conjunction with class II HLA.

Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels.

Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology.

Calprotectin (S100A8/S100A9 protein) is known as a damage-associated molecular pattern (DAMP) protein and reflects mainly neutrophil activation. Serum calprotectin levels might be a good alternative to acute-phase protein as a biomarker in inflammatory rheumatic diseases. The aim of this study is to investigate the association of serum calprotectin with disease activity and severity in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). Serum calprotectin was measured in patients with RA, axSpA, and PsA from the prospective Swiss Clinical Quality Management (SCQM) registry. Asymptomatic first-degree relatives of RA patients were used as healthy controls (HC). Outcomes included swollen joint count (SJC), Disease Activity Score (DAS), Health Assessment questionnaire (HAQ), joint radiographs, and ultrasound power Doppler (USPD) score for RA; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and coxitis for axSpA; and SJC and Disease Activity Index for PSoriatic Arthritis (DAPSA) for PsA. Comparison of outcomes by calprotectin quartile levels was performed using Kruskal-Wallis tests for continuous outcomes or trend tests for categorical outcomes. A total of 1729 subjects [RA = 969, axSpA = 451, PsA = 237, and HC = 72] were included. Median levels of serum calprotectin were higher in each disease group compared to HC (p < 0.01). In RA patients, all clinical outcomes were statistically different between quartiles of serum calprotectin, indicating an association between calprotectin levels and higher disease activity (SJC, DAS, and USPD scores) and severity (joint radiographs and HAQ). In axSpA, an association between calprotectin levels and ASDAS score (p < 0.01) and prevalence of coxitis (p = 0.02) was observed. For PsA patients, SJC and DAPSA did not differ across calprotectin quartiles.

This large study supports the association of serum calprotectin levels with disease activity in both RA and axSpA, but not in PsA.

To compare the short-term efficacy of the Artelon trapeziometacarpal (TMC) implant with that of total trapeziectomy and abductor pollicis longus (APL) tendon suspension interposition arthroplasty in TMC osteoarthritis. A single-center matched cohort study was designed. The Artelon cohort comprised 13 consecutive patients (10 women, 3 men; mean age, 54 years) operated on with Artelon implant arthroplasty. The APL cohort comprised 40 patients (33 women, 7 men; mean age, 58 years) randomly selected among 88 consecutive age-matched patients operated on with APL arthroplasty during the same period. The mean follow-up time was 13 (SD, 4) months for the Artelon group and 12 (SD, 3) months for the APL group. All patients completed the short-form Disabilities of the Arm, Shoulder, and Hand (QuickDASH) survey and a scale measuring thumb pain and related activity limitation, both scored 0 (best) to 100 (worst). Patient satisfaction was recorded. Physical examination was performed by a blinded therapist. The median QuickDASH score was 25 for the Artelon group and 20 for the APL group; the median pain scores were 38 and 28, respectively; the differences were not statistically significant. In the Artelon group, 8 patients were satisfied, compared with 32 in the APL group; the adjusted odds ratio of not being satisfied following Artelon implant compared to APL arthroplasty was 4. The median grip strength as a percentage of the contralateral hand was 82% in the Artelon group and 95% in the APL group; the median pinch strength was 61% and 86%, respectively. No statistically significant differences were found in thumb palmar or radial abduction. Two Artelon patients had revision to APL arthroplasty. Therapeutic III.

The short-term outcomes of the Artelon TMC implant were not superior to those of tendon suspension interposition arthroplasty, a factor to be considered when comparing treatment cost effectiveness.

Serum levels of IgA, IgG and IgM were measured in 46 patients (34 women, 12 men) with rheumatoid arthritis. The duration of the disease ranged from 6 months to 30 years; the patients follow-up ranged from 6 months to 12 years. Serum IgA levels higher than the normal (> 450 mg/dl) were found in 20 patients (43.4%). These patients had mean levels of IgG, C3c and erythrocyte sedimentation rate significantly higher than the patients with normal IgA levels.

A significant relationship between the IgA levels and the activity of the disease or its clinical and radiological features was not observed. On the other hand, a relationship was observed between IgA levels and the mean duration of the disease which was significantly more prolonged in patients with high IgA serum levels.

Patients with inflammatory rheumatic diseases (IRDs) have a higher morbidity and mortality from accelerated atherosclerosis than the general population. We hypothesized that patients with the combination of IRD and coronary artery disease (CAD) would have a certain inflammatory phenotype compared with CAD patients without this comorbidity. Four groups of patients were included: patients with IRD, referred to coronary artery bypass grafting (CABG) (CAD-IRD, n = 67), patients without IRD, referred to CABG (CAD, n = 52), patients with IRD without CAD (IRD, n = 32) and healthy controls (n = 30). Plasma levels of several inflammatory markers were analysed by enzyme immunoassays. (i) Plasma levels of markers of endothelial cell activation [i.e. vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor] and osteoprotegerin (OPG) were significantly increased and plasma levels of CCL21 significantly decreased in CAD-IRD patients as compared with CAD patients without IRD. (ii) Within the CAD-IRD group, acute coronary syndrome was a significant predictor of OPG, suggesting an enhanced inflammatory response during plaque destabilization in CAD-IRD patients. (iii) Plasma levels of VCAM-1, OPG and CCL21, but not lipid parameters, IRD characteristics and several other inflammatory markers (e.g. CRP), were significant predictors of CAD-IRD as opposed to CAD in two logistic regression models.

Our findings further support a role for inflammation in the accelerated form of atherosclerosis in IRD patients, and suggest that certain inflammatory pathways, such as the enhanced endothelial cell activation and the RANK ligand/RANK/OPG system, may be of particular importance.

Insomnia is increasingly recognized to be comorbid with one or more medical conditions. This study used an online research platform to characterize insomnia across different mental and physical conditions. A custom cross-sectional survey was fielded online to 31,208 users of the patient community PatientsLikeMe. The survey queried members on National Sleep Foundation-defined insomnia risk (waking up feeling unrefreshed, difficulty falling asleep, waking in the middle of the night, or waking too early). Complete results were obtained from 5256 patients with 11 comorbid conditions. Seventy-six percent of US-based respondents were at risk for insomnia. Patients who reported difficulty falling asleep were found to have nearly twice the odds of self-reporting insomnia (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.5-2.1) when compared to those who do not have difficulty falling asleep, whereas those who reported waking during the night or waking up unrefreshed were no more likely (OR: 1.025 and 1.032, respectively) to report that they suffered from insomnia than those who did not experience these issues. Although insomnia was self-reported as severe or very severe across most conditions, few respondents had actually been diagnosed with insomnia by a physician. After adjustment for age and gender, there was an independent and strong effect of primary condition severity on insomnia risk, and those with severe epilepsy (0.93), depressive disorders (0.92), and fibromyalgia (0.92) occupied the highest risk probabilities.

The high rate of severity and frequency of insomnia across a multitude of mental and physical conditions reveals an opportunity for better disease management through enhanced insomnia awareness.

Fourier transform infrared (FT-IR) spectroscopic imaging is a promising method that enables the analysis of spatial distribution of biochemical components within histological sections. However, analysis of FT-IR spectroscopic data is complicated since absorption peaks often overlap with each other. Second derivative spectroscopy is a technique which enhances the separation of overlapping peaks. The objective of this study was to evaluate the specificity of the second derivative peaks for the main tissue components of articular cartilage (AC), i.e., collagen and proteoglycans (PGs). Histological bovine AC sections were measured before and after enzymatic removal of PGs. Both formalin-fixed sections (n = 10) and cryosections (n = 6) were investigated. Relative changes in the second derivative peak heights caused by the removal of PGs were calculated for both sample groups. The results showed that numerous peaks, e.g., peaks located at 1202 cm(-1) and 1336 cm(-1), altered less than 5% in the experiment. These peaks were assumed to be specific for collagen. In contrast, two peaks located at 1064 cm(-1) and 1376 cm(-1) were seen to alter notably, approximately 50% or more. These peaks were regarded to be specific for PGs. The changes were greater in cryosections than formalin-fixed sections.

The results of this study suggest that the second derivative spectroscopy offers a practical and more specific method than routinely used absorption spectrum analysis methods to obtain compositional information on AC with FT-IR spectroscopic imaging.

Osteoarthritis (OA) is the most prevalent chronic disease in the elderly, and it is generally diagnosed at an advanced state when treatment is difficult if not impossible. The early form of OA is characterized by an elevated water content in the cartilage tissue. The purpose of this study was to verify in vivo if changes in the water content of patellar cartilage typically occurring in early OA can be detected using T(2) mapping MRI methods. Twenty healthy volunteers performed 60 knee bends in order to compress their patellar cartilage thereby reducing its water content. MR images of the patellar cartilage were acquired immediately following exercise and after 45 min of rest. Patellar cartilage thickness and T(2) maps were determined and their difference between the time points evaluated. Cartilage thickness increased by 5.4+/-1.5% from 2.94+/-0.15 mm to 3.10+/-0.15 mm (P< 0.001) following 45 min of rest, while T(2) increased by 2.6+/-1.0% from 23.1+/-0.5 ms to 23.7+/-0.6 ms (P< 0.05).

Small, physiologic changes in the water content of patellar cartilage and the concomitant change in proteoglycan and collagen density following exercise can be detected using MRI. The proposed T(2)-mapping method, together with other non-invasive MR cartilage imaging techniques, could aid in the early diagnosis of OA.

We previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy. The relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study). In the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA 6 months after the initiation of remission-induction therapy than in patients in remission. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months.

We herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.

Fibromyalgia (FM) patients have been regarded as great utilizers of health resources, with important related costs. The aim of this study is to describe health care resource utilisation and related costs of FM from the perspective of the National Health System in Spain. A cross-sectional multicenter study was conducted on FM patients based on a patient interview. Data about demographic and clinical variables, physical examination, self-perceived health, psychosocial variables and health resource utilisation, were collected. Direct and indirect costs were calculated, and a correlational study between costs and clinical variables was performed. Three-hundred and one patients were studied. During the year 2006 the mean total cost per patient per year was 9,982 Euros, of which 3,245.8 (32.5%) corresponded to health care costs and 6,736.2 (67.5%) to indirect costs attributable to productivity losses. Non-drug therapies accounted for the largest proportion of the health care costs, three times greater than the drug treatment. Patients with higher total costs showed the greatest disease involvement. The variables associated to the total health care costs were functional capacity, depression, comorbidities and age. Patients with permanent working disability were the greatest resource utilizers.

FM patients with higher costs show the greatest disease involvement. Direct and indirect costs are well correlated to disease severity. The indirect costs account for most of the economic burden of FM and approximately double the health care costs. Patients with permanent working disability present more severe disease and generate greater health care costs.

Immune complexes (IC) are frequently detected in patients with rheumatoid vasculitis (RV). To explore the pathogenic role of IC in the development of vasculitis among patients with rheumatoid arthritis (RA), we examined the effect of IC on the expression of cell adhesion molecules (CAM) on polymorphonuclear cells (PMN). PMN from healthy volunteers were incubated with the sera from 26 patients with RA including 9 patients with RV, and the expression of CAM on the PMN was assessed by flow cytometry. We found that 67% (6/9) of the serum samples from RV patients and 18% (3/17) of the samples from RA patients without RV revealed up-regulated CD11b expression. On the other hand, 89% (8/9) of the samples from RV patients and 12% (2/17) of the samples from RA patients without RV revealed up-regulated CD18 expression. However, the expression of CD11a was not affected. Up-regulation of CD11b and CD18 on PMN was also induced by the immunoglobulin G (IgG) fraction of the sera of RV patients. Moreover, L-selectin expression on PMN was down-regulated by the sera or IgG of some patients with RV. These changes in CAM expression on PMN induced by IgG of RV patients were not observed when PMN were incubated with the IgG of RV patients from which the IC formed by IgG had been removed.

These results suggest that IC formed by IgG in patients with RA are involved in the development of vasculitis by affecting the expression of CAM on PMN.

Measuring health-related quality of life (HRQOL) is important in arthritis and the SF-36v2 is the current state-of-the-art. It is only emerging how well the Centers for Disease Control and Prevention (CDC) HRQOL measures HRQOL for people with arthritis. This study's purpose is to assess the psychometric properties of the 9-item CDC HRQOL (4-item Healthy Days Core Module and 5-item Healthy Days Symptoms Module) in an arthritis sample using the SF-36v2 as a comparison. In Fall 2002, a cross-sectional study acquired survey data including the CDC HRQOL and SF-36v2 from 2 North Carolina populations of adult patients reporting osteoarthritis, rheumatoid arthritis, and fibromyalgia; 2182 (52%) responded. The first item of both the CDC HRQOL and the SF-36v2 was general health (GEN). All 8 other CDC HRQOL items ask for the number of days in the past 30 days that respondents experienced various aspects of HRQOL. Exploratory principal components analyses (PCA) were conducted on each sample and the combined samples of the CDC HRQOL. The multitrait-multimethod matrix (MTMM) was used to compute correlations between each trait (physical health and mental health) and between each method of measurement (CDC HRQOL and SF36v2). The relative contribution of the CDC HRQOL in predicting the physical component summary (PCS) and the mental component summary (MCS) was determined by regressing the CDC HRQOL items on the PCS and MCS scales. All 9 CDC HRQOL items loaded primarily onto 1 factor (explaining 57% of the item variance) representing a reasonable solution for capturing overall HRQOL. After rotation a 2 factor interpretation for the 9 items was clear, with 4 items capturing physical health (physical, activity, pain, and energy days) and 3 items capturing mental health (mental, depression, and anxiety days). All of the loadings for these two factors were greater than 0.70. The CDC HRQOL physical health factor correlated with PCS (r = -.78, p < 0.0001) and the mental health factor correlated with MCS (r = -.71, p < 0.0001). The relative contribution of the CDC HRQOL in predicting PCS was 73% (R2 = .73) when GEN was included in the CDC HRQOL score and 65% (R2 = .65) when GEN was removed. The relative contribution of the CDC HRQOL in predicting MCS was 56% (R2 = .56) when GEN was included and removed.

The CDC HRQOL appears to have strong psychometric properties in individuals with arthritis in both community-based and subspecialty clinical settings. The 9 item CDC HRQOL is a reasonable measure for overall HRQOL and the two subscales, representing physical and mental health, are reasonable when the goal is to examine those aspects.

To evaluate if contrast-enhanced ultrasound (CEUS) can improve the detection and quantification of the vascularization of mild enthesitis in spondyloarthritis (SpA) and to evaluate the influence of nonsteroidal antiinflammatory drugs (NSAIDs) on such detection. Fourteen patients with mildly active SpA were evaluated at 3 consecutive visits: at baseline while undergoing NSAID treatment (V1), after 1 week of stopping NSAIDs (V2), and after 1 week of resuming NSAIDs (V3). At each visit, enthesitis was evaluated clinically and by power Doppler US (PDUS). A selected enthesis with a doubtful PDUS vascularization signal was studied by CEUS in 2 steps: (1) using a dedicated technology that preserves microbubbles (Contrast Tuned Imaging technology [CEUS-CnTI]) and (2) using high PD (CEUS-PD) to destroy microbubbles. A linear mixed model statistical analysis, taking visits and contrast agent as fixed factors and the patient as a random factor, was used. Disease activity and PDUS findings increased between V1 and V2 and then decreased between V2 and V3. As compared with PDUS alone, CEUS-PD and CEUS-CnTI each detected 1 supplementary vascularized enthesis at V1, CEUS-PD detected 1 vascularized enthesis and CEUS-CnTI detected 3 vascularized entheses at V2, and CEUS-PD and CEUS-CnTI each detected 2 vascularized entheses at V3. The mean inflammation score was increased by the use of CEUS (P = 0.04). This score increased between V1 and V2 (P = 0.03 by CEUS-PD and P = 0.01 by CEUS-CnTI) and decreased between V2 and V3.

CEUS improved the detection of enthesitis in SpA patients by confirming all doubtful enthesitis signals and confirming the absence of enthesis vascularization. The use of NSAIDs influenced the detection of vascularization.

This study investigates the prevalence of different types of childhood adversities (CA) and posttraumatic stress disorder (PTSD) in female patients with Fibromyalgia or Chronic Widespread Pain (FM/CWP) compared to patients with Functional Dyspepsia (FD) and achalasia. In FM/CWP, we also investigated the association between CA and PTSD on the one hand and pain severity on the other. Patient samples consisted of 154 female FM/CWP, 83 female FD and 53 female achalasia patients consecutively recruited from a tertiary care hospital. Well-validated self-report questionnaires were used to investigate CA and PTSD. Forty-nine per cent of FM/CWP patients reported at least 1 type of CA, compared to 39.7% of FD patients and 23.4% of achalasia patients (p < 0.01). The prevalence of CA did not differ significantly between FM/CWP and FD, but both groups had a higher prevalence of CA compared to both achalasia and healthy controls (p < 0.01). FM/CWP patients were six times more likely to report PTSD than both FD (p < 0.001) and achalasia (p < 0.001) patients. As expected and has been shown in other functional disorders, we found elevated levels of childhood adversity in FM/CWP patients. Results of this study however suggest that the impact of childhood adversity (i.e. whether such events have led to the development of PTSD symptoms), rather than the mere presence of such adversity, is of crucial importance in FM/CWP patients. Screening for PTSD symptoms should be an essential part of the assessment process in patients suffering from FM/CWP, and both prevention and intervention efforts should take into account PTSD symptoms and their impact on pain severity and general functioning.

In FM/CWP, PTSD comorbidity, but not CA, was associated with self-reported pain severity and PTSD severity mediated the relationship between CA and pain severity. In summary, the prevalence of CA is higher in FM/CWP compared to achalasia, but similar to FD. However, PTSD is more prevalent in FM/CWP compared to FD and associated with higher pain intensity in FM/CWP.

Many previous researches showed clinical benefits, effects on inflammatory mediators and pain, immune system, hormones and on the diencephalic-pituitary-adrenal axis. Our study evalues the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy's Chianciano Spa in patients with osteoarthritis of the knee. In study we compared: physical examination of the knee joint, visual analogue scale (VAS) assessment of pain, and Lequesne Algo-functional Index. Tests were performed in 61 patients divided into 2 groups. The group A underwent three full cycles of mud-bath therapy over 1 year's time, the group B did not. An observational longitudinal study was also conducted on the patients of group A, before and after completion of the treatment protocol. Statistical analyses were based on use of Pearson's chi² test, Student's t tests for paired and unpaired data. The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B (differences were highly significant); the mean value of VAS and the overall Lequesne indexes mean score reported in group A was significantly lower than that reported in group B. The same we observed comparing the clinical conditions of group A patients before and after mud-bath therapy. No adverse effects were observed in any of the patients in group A.

The mud-bath therapy at Chianciano Spa significantly improves the clinical conditions of patients with knee osteoarthritis and significantly reduces the frequency and severity of symptoms and the disability they cause.

This study aims to provide a comprehensive analysis of the age-dependent risk of psoriatic arthritis (PsA). For this purpose, it focuses on the varying incidences within the different age groups. The data were collected as part of the morbidity-based risk adjustment of the statutory health insurance companies in Germany. This survey recorded the International Statistical Classification of Diseases and Related Health Problems (ICD)-coded diagnoses of 65 million German citizens. Our population-based study used these raw data to calculate the prevalence of PsA in the first step. Subsequently, we employed a new approach for the estimation of the age-specific and sex-specific incidence of PsA. The age-specific and sex-specific incidence of PsA showed a continuous increase with rising age until it peaked slightly before the age of 60 and declined thereafter. The maximum value was higher in women (40 per 100 000 py) than in men (30 per 100 000 py). Furthermore, the incidence rate tends to climb over the survey period.

The data sets identified an unexpected high incidence. A meta-analysis by Scotti

Systemic sclerosis (SSc) is accompanied by abnormalities in humoral and cellular immune systems. To determine the genes specifically expressed in the immune system in SSc by analysis of the gene expression profile of peripheral blood mononuclear cells (PBMC) from patients with SSc, including those treated with haematopoietic stem cell transplantation (HSCT). Additionally, to investigate the clinical significance of the up regulation of tumour necrosis factor alpha (TNFalpha) converting enzyme (TACE). PBMC from patients with SSc (n = 23) and other autoimmune diseases (systemic lupus erythematosus (SLE, n = 16), rheumatoid arthritis (RA, n = 29)), and from disease-free controls (n = 36) were examined. Complementary DNA arrays were used to evaluate gene expression of PBMC, in combination with real time quantitative polymerase chain reactions. TACE protein expression in PBMC was examined by fluorescence activated cell sorter (FACS). In patients with SSc 118 genes were down regulated after HSCT. Subsequent comparative analysis of SSc without HSCT and healthy controls indicated SSc-specific up regulation for three genes: monocyte chemoattractant protein-3 (p = 0.0015), macrophage inflammatory protein 3alpha (p = 0.0339), and TACE (p = 0.0251). In the FACS analysis, TACE protein was mainly expressed on CD14(+) monocytes both in patients with SSc and controls. TACE expression on CD14(+) cells was significantly increased in patients with early SSc (p = 0.0096), but not in those with chronic SSc, SLE, or RA. TACE protein levels in SSc monocytes correlated with the intracellular CD68 levels (p = 0.0016).

Up regulation of TACE expression was a unique profile in early SSc, and may affect the function of TNFalpha and other immunoregulatory molecules.

Trochleoplasty aims to restore patellar stability. Various techniques have been described and almost all authors report successful results. However, the procedure has a significant risk of complications. Purpose of this study was to perform a systematic review and meta-analysis of the available literature to assess the rate of complications after the various techniques used for trochleoplasty procedures. MEDLINE, EMBASE, Web of Science and Cochrane Library databases were searched. Studies on patients with recurrent patellar instability treated with a trochleoplasty with or without additional procedure, and reported complications were included. The primary outcome was the rate of complications per technique. A meta-analysis was performed whenever three or more studies per surgical technique could be included. The selection process resulted in 20 studies included for analysis. A lateral facet elevating trochlear osteotomy was reported by two studies, ten studies reported on a Bereiter trochleoplasty, five on a Dejour trochleoplasty, one on an arthroscopic technique, one on a 'modified' technique and one on a recession wedge trochleoplasty. Meta-analysis showed that proportion of recurrent dislocation was 0.04 (95% CI 0.02-0.07) for Bereiter trochleoplasty and 0.02 (95% CI 0-0.08) for Dejour trochleoplasty. These proportions were 0.06 (95% CI 0.02-0.13) and 0.09 (95% CI 0.03-0.27) for recurrent instability, 0.07 (95% CI 0.02-0.19) and 0.12 (95% CI 0.00-0.91) for patellofemoral osteoarthritis and 0.08 (95% CI 0.04-0.14) and 0.20 (95% CI 0.11-0.32) for further surgery respectively. Level IV.

This study demonstrates that the complications after a Bereiter and Dejour trochleoplasty including additional procedures are in the range of those of other patellar stabilizing procedures. For four other techniques, no meta-analysis could be performed. The clinical relevance of this study is that it provides clinicians with the best currently available evidence on the rate of complications after trochleoplasty procedures. This can be helpful in the process of deciding whether or not to perform such a procedure, and can be used to better inform patients about the advantages and disadvantages of different trochleoplasty procedures.

To demonstrate the involvement of 4-hydroxynonenal (HNE), a very reactive aldehyde derived from lipid peroxidation, in the pathogenesis of osteoarthritis (OA) in vivo. In the first experimental protocol, OA was induced by anterior cruciate ligament transection (ACLT) of the right knees of crossbred dogs (n = 6 per group). The animals were treated with placebo or HNE-trapping carnosine (5 or 20 mg/kg/day) orally for 8 weeks. Another group of dogs was treated for 4 weeks with 20 mg/kg/day of carnosine starting 4 weeks after surgery. Sham-operated dogs served as controls. In the second experimental protocol, a pathophysiologic dose of HNE (80 nmoles/ml) or vehicle was injected weekly into the right knee joints of crossbred dogs (n = 6 per group) for 8 weeks. Articular cartilage was subjected to macroscopic, histomorphologic, and immunohistochemical analyses. Cartilage-degrading enzymes and oxidative stress-related products were assessed in synovial fluid and cartilage explants. Markers of inflammation were evaluated in synovium and synovial fluid. In dogs that had undergone ACLT, carnosine treatment reduced the severity and histopathology score of OA cartilage lesions and also decreased HNE-protein adducts, pentosidine, nitrosylated proteins, cartilage-degrading enzymes, and markers of inflammation. Intraarticular injection of HNE induced cartilage lesions, as assessed by macroscopic and microscopic criteria. Cartilage-degrading enzymes and markers of inflammation increased in HNE-treated dogs.

This is the first in vivo study to demonstrate the pathophysiologic role of HNE in OA. That carnosine abolishes HNE production and a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.

Main objective: Describe the effectiveness and safety of baricitinib and tofacitinib in patients diagnosed with rheumatoid arthritis in our hospital. Analyse whether there are  differences between the two drugs in routine clinical practice. Two-year retrospective study of patients diagnosed with  rheumatoid arthritis treated in our hospital with baricitinib and tofacitinib  for at least 6 months. Databases: Electronic medical record and outpatient medication dispensing software. Variables collected:  Demographic variables, poor prognosis factors, previous treatment,  duration of treatment, concomitant treatment, DAS28, number of swollen  and painful joints, pain visual analogy scale, treatment discontinuation,  and adverse reactions. Effectiveness evaluation: Decreases in the DAS28  scale, the number of swollen and painful joints, and the pain Visual  Analogy Scale at 6 months and 12 months after starting treatment. Safety evaluation: Detection of adverse reactions. Student t- test. A total of 44 patients were evaluated. Of these, 20 (70%  women) received treatment with baricitinib and 24 (95.8% women)  received tofacitinib. Baricitinib reduced the DAS28 by 2.3 and 1.7 at 6  months and 12 months, respectively, and tofacitinib reduced the scale by 2 and 1.9 at 6 months and 12 months, respectively. Baricitinib reduced the  number of swollen and painful joints by 7 at both 6 months and 12  months, and tofacitinib reduced the number of swollen and painful joints  by 4 and 6 at 6 months and 12 months, respectively. Baricitinib reduced  the Visual Analogy Scale score by 7.8 and 6.8 at 6 months and 12 months, respectively, and tofacitinib reduced the score by 5 and 6 at 6 months and 12 months, respectively. Corticosteroid treatment was needed in 40% of patients treated with baricitinib and 62.5% of patients treated with  rofacitinib. Treatment was discontinued due to loss of effectiveness in 10% of patients receiving baricitinib and 25% of patients treated with  tofacitinib. Adverse reactions were experienced by 10% of patients treated with baricitinib and 12.5% of patients treated with tofacitinib. Adverse  reactions led to treatment discontinuation in only 1 patient in each group.  No statistically significant differences were observed between the two  drugs. Objetivo: Objetivo principal: describir la efectividad y seguridad de baricitinib y tofacitinib en pacientes diagnosticados de artritis  reumatoide en nuestro centro. Objetivo secundario: analizar si existen  diferencias entre ambos fármacos en práctica clínica real.Método: Estudio observacional retrospectivo de 2 años de duración que  incluyó pacientes diagnosticados de artritis reumatoide en tratamiento con  baricitinib o tofacitinib en nuestro centro durante al menos 6 meses. Bases de datos: historia clínica electrónica, aplicativo informático de dispensación a pacientes externos. Variables recogidas: demográficas, factores de mal  pronóstico, tratamiento previo, duración de tratamiento, tratamiento  concomitante, escala DAS28, número de articulaciones inflamadas y  dolorosas, escala visual analógica del dolor, suspensión del tratamiento y  reacciones adversas. Evaluación de la efectividad: disminución en la escala DAS28, articulaciones inflamadas y dolorosas y escala visual analógica del  dolor a los 6 y 12 meses de iniciado el tratamiento. Evaluación de la  seguridad: detección de reacciones adversas.Análisis estadístico: prueba t-student.Resultados: Se evaluaron 44 pacientes, 20 (70% mujeres) recibieron tratamiento con baricitinib, 24 (95,8% mujeres) con tofacitinib.  Baricitinib redujo la puntuación en la escala DAS28 en 2,3 y 1,7 a los 6 y  12 meses. Tofacitinib en 2 y 1,9 respectivamente. Baricitinib redujo el  número de articulaciones inflamadas y dolorosas en 7 a los 6 y 12 meses,  tofacitinib en 4 las inflamadas y 6 las dolorosas. Baricitinib redujo la  puntuación en la escala visual analógica del dolor en 7,8 y 6,8; tofacitinib  en 5 y 6 a los 6 y 12 meses. El 40% de los pacientes con baricitinib y el 62,5% con tofacitinib precisaron tratamiento con corticoides. El 10% de los pacientes con baricitinib y el 25% de los pacientes con tofacitinib suspendieron el tratamiento por ineficacia. El 10% de los pacientes de baricitinib y el 12,5% de tofacitinib experimentaron reacciones adversas. Sólo un paciente de cada grupo suspendió el tratamiento por reacciones adversas. No se observaron diferencias estadísticamente significativas entre ambos fármacos.Conclusiones: Según nuestros resultados, baricitinib y tofacitinib han demostrado ser efectivos y seguros en todas las variables analizadas. Además, ambos fármacos resultaron similares en efectividad y  seguridad en la práctica clínica habitual del tratamiento de la artritis  reumatoide.

The results show that baricitinib and tofacitinib were  effective and safe in relation to all the variables analysed. Moreover, both drugs were similar in terms of effectiveness and safety for the  treatment of rheumatoid arthritis in real-world clinical practice.

To examine the association between hand and knee osteoarthritis (OA) in a community based population. Radiographs of 695 participants aged > or = 40 years in the Baltimore Longitudinal Study of Aging were read for changes of OA, using Kellgren-Lawrence grade > or = 2 as the case definition. Logistic regression analyses, adjusting for age, gender and body mass index, revealed a significant association between OA in the knee and the following joint groups: distal and proximal interphalangeal (DIP, PIP) and Hand2 (OA in two or more hand joint groups) for grade 2-4 and grade 3-4 disease, and the first carpometacarpal (CMC1) joint for grade 3-4 disease.

There is an association between OA in hand sites and the knee. The strength of the associations increases with increasing disease severity. For the PIP site, there is a trend toward increasing strength of association for increasing numbers of affected joints and bilateral disease.

Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been reported to reduce platelet aggregation. Our aim was to prospectively assess the potential influence of different supplementation omega-3 PUFA on the antiplatelet effects in rheumatoid arthritis (RA) patients. The study included 60 patients with RA at the Department of Rheumatology, Clinical Center Kragujevac. Patients were divided into three groups depending on who used concentrated fish oil only or concentrated fish oil in combination with evening primrose oil or control group without supplementation in a period of 3 months. Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test, aranchidonic acid-induced aggregation (ASPI) test, thrombin receptor-activating peptide (TRAP) test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP representing the degree of inhibition of platelet aggregation compared to the basal value. The platelet function analysis in whole blood was performed 18-24 h before starting supplementation and after 90 days. Considerations were taken in the representation of demographic, clinical characteristics, and laboratory parameters between the groups. Patients who used concentrated fish oil only had a significantly lower value of the ratio of ADP/TRAP (0.68 ± 0.20) compared to patients without supplementation (0.83 ± 0.12; p = 0.008), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. • Omega-3 PUFAs are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases.. • In this paper, we report on anti-aggregation effects n-3 PUFAs and ɤ-linolenic acid in RA. • The risk of cardiovascular morbidity and mortality is increased in RA, and dietary supplementation of n-3 PUFA may have preventive potential for the cardiovascular management in rheumatoid arthritis.

Co-administration of supplementation-concentrated fish oil may reduce platelet aggregation in adults with RA.

We used real time, three-dimensional transthoracic echocardiography (3DTTE) to evaluate left atrial (LA) volume and mechanical function in patients with primary Sjögren's syndrome (SS). We prospectively included 42 consecutive patients with primary SS and 42 controls who were similar in terms of basal characteristics. 3DTTE was used to assess LA function. Maximum LA volume, minimum LA volume, pre-atrial contraction LA volume, LA Active Stroke Volume (ASV), LA Total Stroke Volume (TSV), maximal left atrial volume index (LAVImax), Left atrial pre-contraction volume index, and Left atrial minimum volume index, ASV index, and TSV index were significantly higher in the SS group, and the LA Total Emptying Fraction, LA Expansion Index, and LA Passive Emptying Fraction were significantly lower. Although the active emptying fraction was higher in the SS group, the difference was not statistically significant. LAVImax was positive correlated with disease duration (r = .753).

Left atrial function is impaired in SS patients and serves as an early marker of subclinical cardiac involvement.

United Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA. The study included biologic-naïve patients receiving csDMARDs only with MDA (3.2 <DAS28≤ 5.1) when recruited to the control cohort of the British Society for Rheumatology Biologics Register-RA (BSRBR-RA). Disability scores, measured using the Health Assessment Questionnaire (HAQ), were recorded every six months for three years. Trajectories of HAQ scores over follow-up were assessed using latent class growth models (LCGMs). Baseline age, gender, DAS28, symptom duration, rheumatoid factor status, number of prior csDMARDs and co-morbidities were assessed as potential predictors of group membership. In total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group.

There is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy.

This study sought to investigate the associations between personality traits and medication adherence and to identify predictors of good medication adherence in rheumatoid arthritis (RA) patients. A total of 207 RA patients using disease-modifying anti-rheumatic drugs were invited for an interview and questionnaire study. Medication adherence was measured using the Compliance Questionnaire for Rheumatology (CQR). Personality traits were analyzed with the five-factor model of the Korean version of the Big Five Inventory 10. Psychological factors were assessed with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and British Columbia Cognitive Inventory. Health-related Quality of Life (HRQoL) and functional disability were evaluated with the EuroQoL-5 dimension questionnaire and Health Assessment Questionnaire. Multivariate logistic regression analyses were performed to investigate predictors of good medication adherence. Nonadherence to medication was reported by 66.7%. The number of daily prescribed pills was higher in the medication adherence group than in the nonadherence group. Concomitant oral glucocorticoid doses were associated with medication adherence. A high level of conscientiousness and diabetes mellitus comorbidity were associated with better medication adherence [odds ratio (OR), 2.11; 95% confidence interval (CI), 1.01-4.38 and OR, 3.00; 95% CI, 1.12-8.07, respectively]. There were no significant differences in psychological factors or HRQoL between medication adherence and nonadherence groups.

The personality trait of conscientiousness was associated with medication adherence among the five personality traits evaluated. Patients with diabetes mellitus also showed higher medication adherence than those without this comorbidity.

Joint-line restitution is one objective of unicompartmental knee arthroplasty (UKA). However, the joint line is often lowered when resurfacing femoral implants are used. The aim of this study was to compare the joint-line height in UKA performed by robotic-assisted and conventional techniques. This retrospective case-control study compared two matched groups of patients receiving a resurfacing UKA between 2013 and 2016 by either a robotic-assisted (n = 40) or conventional (n = 40) technique. Each group comprised 27 women and 13 menm wuth a mean age of 69 and 68 years, respectively. Indications for surgery were osteoarthritis (n = 35) and condylar osteonecrosis (n = 5). Two validated radiologic measurement methods were used to assess joint-line height. Forty UKA (23 medial and 17 lateral) were analysed in each group. Restitution of joint-line height was significantly improved in the robotic-assisted group compared than the control group: +1.4 mm ±2.6 vs +4.7 mm ± 2.4 (p < 0.05) as assessed using method 1, and +1.5 mm ±2.3 vs +4.6 mm ±2.5 (p < 0.05) as assessed using method 2.

Restitution of joint-line height in resurfacing UKA can be improved with robotic-assisted surgery. Improvement in clinical outcome measures must be demonstrated with long-term studies.

To investigate predictors of long term prognosis in patients treated for shoulder pain in primary care. Data were taken from two pragmatic randomised clinical trials investigating the effectiveness of conservative treatments for shoulder pain presenting to primary care. Shoulder pain severity, disability, and perceived recovery measured in the long term (UK, 18 months; Netherlands, 12 months) were considered as outcome measures. Prognostic indicators measured before randomisation were determined by linear regression (pain severity and disability) and logistic regression (perceived recovery). 316 adults with a new episode of shoulder pain were recruited (UK, n = 207; Netherlands, n = 109). In multivariate analysis, greater shoulder disability at follow up was associated with higher baseline disability score, concomitant neck pain, and a gradual onset and longer duration of shoulder symptoms. Pain scores at follow up were higher in women and in those with longer baseline duration of symptoms and higher baseline pain or disability scores. Being female, reporting gradual onset of symptoms, and a higher baseline disability score each independently reduced the likelihood of perceived recovery.

The results suggest that there is no long term difference in outcome between patients with shoulder pain treated with different clinical interventions in different clinical settings, or having different clinical diagnoses. Baseline clinical characteristics of this consulting population, rather than the randomised treatments which they received, were the most powerful predictors of outcome. Whether this highlights the need for earlier intervention or reflects different natural histories of shoulder pain is a topic for further research.

Interleukin-18 (IL-18) is a proinflammatory regulator of immune responses. Its similarities to IL-1beta and ability to induce tumour necrosis factor-alpha (TNF-alpha) make it potentially important in the pathogenesis of rheumatoid arthritis (RA). The level of IL-18 was assessed in matched pairs of blood and synovial fluid samples from 90 RA patients (47 erosive, 43 non-erosive) by an enzyme-linked immunosorbent assay (ELISA), and the results compared to 40 healthy controls. In RA patients with erosive joint disease, the IL-18 level was higher than that in non-erosive RA [(median+/-QR) blood: 385+/-200 vs. 235+/-183 pg/mL, p = 0.02; synovial fluid: 392+/-392 vs. 224+/-324 pg/mL, p = 0.05]. IL-18 levels in blood of RA patients were similar and closely related to the local, intra-articular level (r = 0.96). The IL-18 level was not related to other markers of inflammation, to the duration of RA, or to the treatment modality. The IL-18 level in RA patients was similar to that of the controls (278+/-234 vs. 344+/-179 pg/mL, not significant).

An increased IL-18 level is associated with erosive joint disease, but the measurement of IL-18 does not help to distinguish between RA patients and healthy controls.

There is ongoing debate in the literature as to whether or not patellofemoral joint overstuffing has a clinically significant effect on postoperative outcomes following total knee arthroplasty (TKA). This study investigates the effect of patellofemoral joint overstuffing on patient-reported outcomes using novel methods of radiographic measurement. The study population consisted of a prospective cohort of 266 patients receiving a Triathlon® (Stryker, Kalamazoo, MI, USA) TKA between 2006 and 2009. Participants completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire preoperatively and at 12 months postoperatively. Pre- and postoperative radiographic measurements were taken according to a defined protocol to assess for patellofemoral overstuffing. Measurement reproducibility was assessed using inter-observer intraclass correlation coefficients. Associations between radiographic measurements and patient-reported outcomes were analysed using linear regression analysis. A total of 107 patients had adequate images and were included in the analysis for this study. Three different radiographic measurements were used to identify patellofemoral overstuffing all with good intra- and inter-observer reliability. There was no association identified between combined (patella and trochlea) patellofemoral overstuffing measurements and WOMAC scores. However, a statistically significant association was identified between an increase in anterior trochlear offset and worse knee pain and function scores (P < 0.05).

There is no identifiable association between true patellofemoral overstuffing and clinical outcome; however, there is a small association with the anterior trochlear offset though further studies are warranted to confirm the clinical significance of this finding.

To investigate the effects of AOD9604 intra-articular injections with or without hyaluronic acid (HA) in a collagenase-induced knee osteoarthritis (OA) rabbit model. Mature New Zealand white rabbits (n=32) were randomly administered 2 mg collagenase type II twice in each knee joint. Weekly injections of 0.6 mL saline (Group 1), 6 mg HA (Group 2), 0.25 mg AOD9604 (Group 3), and 0.25 mg AOD9604 with 6 mg HA (Group 4) were administered for 4-7 weeks after the first intra-articular collagenase injection. The degree of cartilage degeneration was assessed using morphological and histopathological findings, and the degree of lameness was observed at 8 weeks after the first collagenase injection. Mean gross morphological and histopathological scores were significantly higher in Group 1 than in Groups 2, 3, and 4, and the scores were significantly lower in Group 4 than in Groups 2 and 3. The lameness period in Group 4 was significantly shorter than those in Groups 1, 2, and 3. The lameness period in Group 1 was significantly longer than those in Groups 2 and 3.

Intra-articular AOD9604 injections using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA injections were more effective than HA or AOD9604 injections alone in the collagenase-induced knee OA rabbit model.

To characterize the clinical features of patients with autoantibodies against dymple, a dynamin-related protein. Serum samples from 281 patients with rheumatic diseases were examined. The characteristics of antidymple and antibody-reactive determinants were investigated by immunoblotting with the recombinant dymple antigen, including its deletion mutants, and by immunofluorescence studies with affinity-purified serum. Five serum samples (2%) were found to have antidymple. All of these patients were male, and 4 of them had interstitial pneumonitis. Their sera were considered to mainly recognize the N-terminus of dymple, which contains GTP-binding motifs.

Dymple, which joins the cytoplasmic autoantigens, could be a marker for a newly recognized subset of connective tissue diseases.

Clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are useful tools for the evaluation of disease activity in patients with rheumatoid arthritis (RA), but have not been comparatively validated in Moroccan population. Therefore, this study was designed to assess validity and reliability of CDAI and SDAI in comparison to disease activity score-28 joints (DAS-28) in Moroccan patients with RA. Patients with RA were included in a cross-sectional study. Patient characteristics and RA were collected. The disease activity was assessed by DAS-28, CDAI and SDAI. Patients were splitted into groups of remission, low, moderate and high activity on the basis of predefined cut-offs for DAS-28, CDAI, and SDAI. A Spearman correlation between composite indexes and inter-group comparison of the indexes were performed. Using DAS-28 as a gold standard, the Receiver operator characteristic (ROC) curve was used to assess the performance of a screening test at different levels. The study was conducted with 103 patients of female predominance (87.4%). Mean age was 49.7 ± 11.4 years. Median disease duration was in the order of 8 years [3-14]. There was an excellent correlation between DAS-28 and CDAI (r = 0.95, p <0.001), CDAI and SDAI (r = 0.90, p <0.001), and DAS-28 and SDAI (r = 0.92, p <0.001). There was a good inter-rater alignment between the DAS-28 and CDAI (Weighted kappa =0.743) and there was a moderate inter-rater alignment between the DAS-28 and SDAI (Weighted kappa =0.60), and also between the SDAI and CDAI (Weighted kappa = 0.589). There was no statistically significant difference between AUROC of CDAI and SDAI as both were performed equally well. This study is the first Moroccan case study to compare the performance of both CDAI and SDAI in evaluation of disease activity in patients with RA. Our study showed that there was a direct and excellent correlation between DAS-28 and CDAI, and SDAI and DAS-28.

Our study shows a strong positive correlation between DAS-28, CDAI and SDAI. The cut-off values for CDAI and SDAI used in western literature can be used with minor modifications in Moroccan scenario.

We investigated access to biologic and synthetic disease modifying drugs (bDMARDs and sDMARDs) in patients with rheumatoid arthritis (RA) across Europe. A cross-sectional study at national level was performed in 49 European countries. A questionnaire was sent to one expert, addressing the number of approved and reimbursed bDMARDs and sDMARDs, prices and co-payments, as well as acceptability of bDMARDs (barriers). Data on socio-economic welfare (gross domestic product per capita (GDP), health expenditure, income) were retrieved from web-based sources. Data on health status of RA patients were retrieved from an observational study. Dimensions of access (availability, affordability and acceptability) were correlated with the country's welfare and RA health status. In total, 46 countries (94%) participated. Six countries did not reimburse any of the five sDMARDs surveyed, and in ten countries no bDMARDs were reimbursed. While the price of annual treatment with an average sDMARD was never higher than GPD, the price of one year treatment with a bDMARD exceeded GPD in 26 countries. Perceived barriers for access to bDMARDs were mainly found among financial and administrative restrictions. All dimensions of access were positively correlated with the country's economic welfare (coefficients 0.69 to 0.86 for overall access scores).

Patients with RA in lower income European countries have less access to bDMARDs and sDMARDs, with particularly striking unaffordability of bDMARDs in some of these countries. When accepting that sDMARDs and bDMARDs are equally needed across countries to treat RA, our data point to inequities in access to pharmacological treatment for RA in Europe.

The therapeutic value of proprioceptive-based exercises in knee osteoarthritis (KOA) management warrants investigation of proprioceptive testing methods easily accessible in clinical practice. To estimate inter- and intrarater reliability of the knee joint position sense (KJPS) test and knee force sense (KFS) test in subjects with and without KOA. Cross-sectional test-retest design. Two blinded raters performed independently repeated measures of the KJPS and KFS test, using an analogue inclinometer and handheld dynamometer, respectively, in eight KOA patients (12 symptomatic knees) and 26 healthy controls (52 asymptomatic knees). Intraclass correlation coefficients (ICCs; model 2,1), standard error of measurement (SEM) and minimal detectable change with 95% confidence bounds (MDC For KJPS, results showed good to excellent test-retest agreement (ICCs 0.70-0.95 in KOA patients; ICCs 0.65-0.85 in healthy controls). A 2° measurement error (SEM 1°) was reported when measuring KJPS in multiple test positions and calculating mean repositioning error. Testing KOA patients pre and post therapy a repositioning error larger than 4° (MDC

Measuring KJPS in multiple test positions using an analogue inclinometer and calculating mean repositioning error is reliable and can be used in clinical practice. We do not recommend the use of the KFS test to clinicians. Further research is required to establish diagnostic accuracy and validity of our KJPS test in larger knee pain populations.

Lower leg torsion was measured by computerized tomography (CT-scan) in the knees with osteoarthritis. Experimental studies; Using the Toshiba CT/TCT-60A, the degree of torsion in five dried tibias were measured in three positions of varus, 0 degrees, 10 degrees and 20 degrees; and in two positions of flexion 0 degrees and 20 degrees. Clinical studies; The degree of tibial torsion was measured by CT-scan in 68 adult patients (85 knees) and compared with the torsion in 13 controls (24 tibias). The correlation between tibial torsion and osteoporosity was investigated by measuring CT-density of the third lumbar vertebra. No statistically significant difference was found among the results of measurement obtained in five dried tibias placed in three positions of varus and in two positions of flexion. These results indicate that measurement of torsion using CT-scan is not influenced by the position when varus and flexion deformity are less than 20 degrees. Osteoarthritic knees were divided into five radiographic stages. There were significant differences between the lateral tibial torsions for each stage. The lateral tibial torsion was 23.5 degrees in normal adults, 14.1 degrees in stage II, 11.9 degrees in stage III, 7.5 degrees in stage IV and V, for an average of 11.3 degrees. The rate of decrease in lateral tibial torsion was 59.6% in the proximal tibia, 4.2% in the tibial shaft and 36.2% in the distal tibia. The decreases of lateral tibial torsion were correlated with decrease of CT-density of the third lumbar vertebra.

It is apparent from this study that there is a correlation between decreasing lateral tibial torsion with the radiographic stage of osteoarthritis of the knee and general osteoporosity.

SB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4. In the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100. Of 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer. NCT01895309; 2012-005026-30.

SB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4.

To investigate the efficacy and safety of Isoniazid prophylaxis (INHP) for tuberculosis in Chinese patients with rheumatoid arthritis (RA) who receive long-term Methotrexate (MTX) therapy. Two hundred and one (201) patients with RA were randomized to initial treatment with either MTX/Isoniazid (INH) [MTX, 0.1-0.3 mg/(kg x week), maximal 20 mg/week; INH, 5 mg/(kg x d), max 300 mg/d] or MTX alone [0.1-0.3 mg/(kg x week), maximal 20 mg/week]. The doses of MTX remained the same after 6-month INH treatment. All patients were followed up for 36 months, the incidence of pulmonary tuberculosis (TB) was investigated, while the toxicity of INH and MTX were assessed. There were 77 patients completed INHP. Two withdrew due to unwilling to participate. Treatment was discontinued in 4 cases (4.9%) owing to toxicity: increasing ALT/AST in two (2.5%), decrease of white blood cell (WBC) in one (1.2%) and anaphylaxis in one (1.2%). In control group, 5 patients withdrew for personal reasons. The incidence of adverse effect due to MTX in this group was 6.2%: Hepatotoxicity appeared in 4 patients (3.5%) and decrease of WBC was seen in 3 (2.7%). Nine patients (8.5%) developed TB in control group, and 1 patient (1.3%) developed TB 14 months after INH treatment. The risk of TB infection in control group was 6 times more than that in INHP group (chi2 = 4.47, P < 0.05).

INHP is safe and effective to prevent TB in RA patients treated with MTX.

We evaluated the results of Fulkerson osteotomy in patients with chronic patellofemoral malalignment. Fulkerson osteotomy (anteromedial tibial tubercle transfer) was performed in 21 knees of 18 patients (10 females, 8 males; mean age 28.6 years; range 21 to 42 years). The patellofemoral congruence angle, lateral patellofemoral angle, and patellofemoral index were measured pre- and postoperatively on tangential radiograms obtained at 45 degrees knee flexion. Malalignment patterns were determined by computed tomography as lateral tilt (n=12), lateral patellar subluxation (n=4), and both (n=5). All the patients underwent arthroscopic examination preoperatively and all had severe osteoarthrosis in the patellar articular surfaces (Outerbridge type III-IV). The mean anteriorization was 10.5 mm (range 7 to 15 mm). The vastus medialis oblique muscle was advanced in seven knees. The patients were assessed according to the criteria of Fulkerson et al. pre- and postoperatively. The mean follow-up was 28 months (range 20 to 60 months). According to the criteria of Fulkerson et al., the results were excellent, very good, or good in 18 knees (85.7%), fair in two knees (9.5%), and poor in one knee (4.8%). Pain and instability scores showed significant improvement (p<0.05). On final radiographic assessment, the mean patellofemoral congruence angle and patellofemoral index were -6.8 degrees (range -26 degrees to 10 degrees ) and 1.4 (range 0.8 to 1.6), respectively (p<0.05). The lateral patellofemoral angle had a lateral orientation in all the knees. Complications included tibial tubercle avulsion (n=1), deep vein thrombosis (n=1), and slight knee flexion contractures (n=4). Wound-related problems, compartment syndrome, peroneal nerve palsy, or proximal tibial fracture were not encountered.

Successful results are obtained by Fulkerson osteotomy in the treatment of chronic patellofemoral malalignment with severe articular degeneration (Outerbridge type III-IV) particularly in the lateral and distal regions of the patella.

Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3.

The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings.

To observe the effect of Yangfei Ziyin Decoction (YZD) on symptoms, serum levels of TNF-alpha, IL-6, and aquaporin-5 (AQP-5), and pathology of Sj6gren's syndrome (SS) model mice. Totally 60 mice were divided into 6 groups according to random digit table, i.e., the model group, the normal control group, the high, medium, low dose YZD groups (administered with YZD at 36.7, 18.4, 9.2 g/kg, 0.2 mL/10 g), the Chinese patent medicine group [CPM, administered with total glucosides of paeony at 0.6 g/kg], 10 mice in each group. All intervention was performed for six successive days in a week, with an interval of one day, a total of 50 days. Body weight, salivary secretion, food and water intake were measured at day10, 20, 30, 40, and 50, respectively. At day 50 blood was collected. Submandibular gland, thymus, and spleen were weighed. Serum levels of TNF-alpha, IL-6, and AQP-5 were detected by ELISA. Pathological changes of submandibular gland were observed. Results Compared with the normal control group, there was no change in water intake of mice in the model group, but with reduced salivary secretion (P < 0.01, P < 0.05). Thymus/spleen/submandibular gland weight and index increased in the model group (P < 0.01, P < 0.05). Compared with the model group at the same time point, salivary secretion increased in the CPM group and 3 YZD groups (P < 0.01 , P < 0.05). Compared with the model group, thymus/spleen/submandibular gland weight and index decreased in the CPM group (P < 0.01, P < 0.05). Thymus/submandibular gland weight and index decreased in the low dose YZD group (P < 0.01, P < 0.05). Thymus/submandibular gland weight and index, and spleen index decreased in high and medium dose YZD groups (P < 0.01 , P < 0.05). Levels of TNF-alpha and IL-6 decreased, but AQP-5 level increased in the CPM group (P < 0.05). AQP-5 level increased in high and medium dose YZD groups (P < 0.01 , P < 0.05). In the model group alveoli and duct of salivary gland were destroyed, alveoli and duct were irregular, epithelial cells were degenerated, necrotic, and desquamated. Mild-to-moderate lymphocytic infiltration occurred around submandibular gland. Pathological changes were alleviated in the CPM group and 3 YZD groups.

YZD could improve clinical symptoms, serum levels of TNF-alpha, IL-6, AQP-5, and pathological changes of SS model mice.

To assess the sensitivity of the phagocyte-specific molecules myeloid-related protein (MRP) 8 and MRP14 (calprotectin) for monitoring disease activity during anti-interleukin (IL)-1 therapies in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular (CINCA) syndrome. A total of 39 patients with CAPS, including 5 FCAS, 16 MWS and 18 CINCA syndrome, received anti-IL-1 therapy. All patients with CINCA and 12 with MWS were treated with IL-1Ra (anakinra), 14 patients with MWS with a monoclonal anti-IL-1β antibody (canakinumab) and patients with FCAS received IL-1 Trap (rilonacept). During serial clinical visits serum amyloid A, C-reactive protein, erythrocyte sedimentation rate and MRP8/14 serum levels were analysed. Untreated patients with CAPS had significantly elevated MRP8/14 values. In response to treatment there was a significant reduction of MRP8/14 levels in CINCA (2,830 (range 690 - 8,480) ng/ml to 670 ng/ml, p < 0.001) and MWS patients (anakinra-treated: 4,390 (1790 - 9780) ng/ml to 1,315 ng/ml (p = 0.003); canakinumab-treated: 3,000 (500 - 13060) ng/ml to 630 ng/ml (p=0.001)). However, in many patients with CAPS, MRP8/14 levels were still elevated compared with healthy individuals, reflecting residual disease activity. However, canakinumab-treated patients with CAPS showed normalised MRP8/14 levels, suggesting control of phagocyte activation.

Monitoring of cellular systems involved in inflammatory cascades of the innate immunity was successfully applied to the IL-1-driven CAPS diseases. This is the first study illustrating different states of subclinical disease activity in all types of CAPS depending on the type of anti-IL-1 therapy. MRP8/14 is a sensitive biomarker for monitoring disease activity, status of inflammation and response to IL-1 blockade in patients with CAPS.

In cementless total hip arthroplasty, femoral stems should preferably not migrate at all postoperatively. This goal is difficult to achieve in postmenopausal women with impaired bone quality. Here, we explored the clinical importance of initial stem migration, measured by radiostereometric analysis (RSA), in women who underwent quantitative computed tomography (CT) of the involved hip preoperatively. A prospective cohort of 65 postmenopausal women (mean age, 69 years) with hip osteoarthritis and Dorr type-A or B femoral anatomy underwent total hip arthroplasty with implantation of a tapered, single-wedge femoral stem. Volumetric bone mineral density (BMD) was measured using quantitative CT. Femoral stem translation and rotation were measured using model-based RSA within 3 days after the surgical procedure and were repeated at 3, 5, and 11 months. Postoperative recovery parameters included walking speed, walking activity, and patient-reported outcome measures. Subjects were categorized into 2 groups according to the magnitude of initial 5-month stem subsidence (<2 mm or ≥2 mm); RSA outliers (n = 7) were analyzed separately. Subjects with stem subsidence of ≥2 mm (mean, 3.09 mm [95% confidence interval (CI), 2.70 to 3.47 mm]) had lower intertrochanteric volumetric BMD (p = 0.008). Subjects with subsidence of <2 mm (mean, 0.80 mm [95% CI, 0.51 to 1.09 mm]) had faster improvement of patient-reported outcome measures and exhibited faster walking speed (p = 0.007) and greater walking activity (p = 0.010) at 11 months as well as better Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p = 0.002) and RAND 36-Item Health Survey mental component scores (p = 0.006) at 2 years. All cohort stems were osseointegrated at 2 years. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Femoral stem stability and resistance to subsidence were sensitive to adequate intertrochanteric volumetric BMD. Low intertrochanteric volumetric BMD was associated with greater stem migration. With initial migration, clinical recovery was slower and patient-reported outcome measures were less satisfactory.

In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS). A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central Register of Controlled Trials, EMBASE, and CAMBASE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Meta-analysis showed moderate-to-strong evidence for a small reduction in pain (SMD -0.42; 95% CI [-0.61, -0.24]; P < 0.00001; I2 = 0%) with regard to HT (8 studies, 462 participants; 3 low-risk studies, 223 participants), and moderate-to-strong evidence for a small improvement in health-related quality of life (HRQOL; 7 studies, 398 participants; 3 low-risk studies, 223 participants) at the end of treatment (SMD -0.40; 95% CI [-0.62, -0.18]; P = 0.0004; I2 = 15%). No effect was seen at the end of treatment for depressive symptoms and tender point count (TPC).

High-quality studies with larger sample sizes are needed to confirm the therapeutic benefit of BT and HT, with focus on long-term results and maintenance of the beneficial effects.

The purpose of this study was to compare the clinical and radiographic outcomes of total ankle arthroplasty (TAA) in patients with pre-operatively moderate and severe arthritic varus ankles to those achieved for patients with neutral ankles. A total of 105 patients (105 ankles), matched for age, gender, body mass index, and follow-up duration, were divided into three groups by pre-operative coronal plane tibiotalar angle; neutral (< 5°), moderate (5° to 15°) and severe (> 15°) varus deformity. American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, a visual analogue scale (VAS), and Short Form (SF)-36 score were used to compare the clinical outcomes after a mean follow-up period of 51 months (24 to 147). The post-operative AOFAS, VAS scores, range of movement and complication rates did not significantly differ among three groups. However, there was less improvement in the SF-36 score of the severe varus group (p = 0.008). The mean post-operative tibiotalar alignment was 2.6° (0.1° to 8.9°), 3.1° (0.1° to 6.5°) and 4.6° (1.0° to 10.6°) in the neutral, moderate and severe groups respectively. Although the severe varus group showed less corrected alignment than the neutral group, the mean tibiotalar angles of the three groups were within neutral alignment.

TAA for moderate and severe varus arthritic deformity showed similar satisfactory clinical and radiographic outcomes as those obtained by patients in the neutral group when post-operative neutral alignment was achieved. Cite this article:

The primary goal of this study was to assess the difference in active flexion between patients with a mobile versus a fixed bearing, cruciate retaining, and total knee arthroplasty. The study was designed as a randomised controlled multi-centre trial. Participants were assigned to interventions by using block-stratified, random allocation. Outcome parameters were active flexion, passive flexion, and Knee Society Score (KSS). Outcome parameters were assessed preoperatively and at 3, 6, and 12 months postoperatively by an independent nurse. Ninety-two patients from one centre were included, 46 in each group. Active flexion was comparable for the two groups, 99.9° for the mobile bearing group and 101° for the fixed bearing group with a baseline controlled difference of 1.0 (95% CI -3.9 to 5.8, n.s.). The Clinical KSS was comparable between the two bearing groups (Mobile 90.0 vs. fixed 92.4, n.s.). The functional KSS showed a difference that was attributable to the stair climbing subscore, which showed a difference in favour of the fixed bearing design between preoperative and 3 months (7.3 point difference; 95% CI 2.3-12.5; P = 0.005) as well as 12 months (4.8 point difference; 95% CI 0.1-9.6; P = 0.045). I.

There were no short-term differences in active flexion between fixed bearing and mobile bearing total knee arthroplasty.

The purposes of this study are to examine the associations between pain coping strategies and daily diary-based pain measures and to determine whether these associations differed by race (African American and Caucasian). Primary care patients from the Durham Veterans Affairs and Duke University Medical Centers (N = 153) with hand, hip, or knee osteoarthritis (OA) completed electronic pain diaries on a one-weekend day and one weekday. The maximum, range (maximum minus minimum pain), and area under the curve (AUC) of joint pain ratings were calculated. Pain coping (Coping Strategies Questionnaire (CSQ) coping attempts, catastrophizing, and praying/hoping subscale scores) was assessed prior to diary entries and at the end of each diary day (total, problem-focused, and emotion-focused scores from Stone and Neale's Daily Coping Inventory). Pearson correlations between pain variables and coping measures were examined. Linear mixed models were fit including age, race, weekend/weekday, study enrollment site, education level, pain medication use, self-rated health, Arthritis Impact Measurement Scales affect and function subscales, and interactions of coping measures with race and weekend day/weekday status. Correlations between coping and pain measures were 0.12-0.45. In adjusted models, maximum pain and pain range were associated with all three diary-based coping measures; maximum pain was associated with CSQ coping attempts; and AUC was associated with CSQ praying/hoping. Interactions were not significant.

Among participants with OA, pain coping strategies were related to important aspects of the pain experience, particularly pain range and maximum pain. However, race did not modify associations of pain coping strategy use and the pain experience.

To describe the incidence and progression of radiographic and symptomatic hand osteoarthritis (rHOA and sxHOA) in a large community-based cohort. Data were from the Johnston County OA Project (1999-2015, 12 ± 1.2 years follow-up, age 45+). Participants had bilateral hand radiographs each visit, read for Kellgren-Lawrence grade (KLG) at 30 joints. We defined rHOA as KLG ≥2 in ≥1 joint. SxHOA was defined in a hand/joint with rHOA and self-reported symptoms or tenderness on exam. Incidence was assessed in those without, while progression was assessed in those with, baseline rHOA. Proportions or medians are reported; differences by sex and race were assessed using models appropriate for dichotomous or continuous definitions, additionally adjusted for age, education, body mass index (BMI), and weight change. Of 800 participants (68% women, 32% African American, mean age 60 years), 327 had baseline rHOA and were older, more often white and female, than those without rHOA (n = 473). The incidence of HOA was high, for rHOA (60%) and for sxHOA (13%). Women were more likely than men to have incident HOA, particularly for distal interphalangeal joint radiographic osteoarthritis (DIP rOA) (adjusted odds ratios (aOR) 1.60 95% confidence intervals (95% CI) [1.03, 2.49]) and sxHOA (aOR 2.98 [1.50, 5.91]). Progressive HOA was more similar by sex, although thumb base rOA progressed more frequently in women than in men (aOR 2.56 [1.44, 4.55]). Particularly HOA incidence, but also progression, was more frequent among whites compared with African Americans.

This study provides much needed information about the natural history of HOA, a common and frequently debilitating condition, in the general population.

The aim of the study was to describe school attendance and participation in physical education in school among children with juvenile idiopathic arthritis (JIA). Consecutive cases of JIA from defined geographical areas of Finland, Sweden and Norway with disease onset in 1997 to 2000 were followed for 8 years in a multi-center cohort study, aimed to be as close to population-based as possible. Clinical characteristics and information on school attendance and participation in physical education (PE) were registered. Participation in school and in PE was lowest initially and increased during the disease course. Eight years after disease onset 228/274 (83.2%) of the children reported no school absence due to JIA, while 16.8% reported absence during the last 2 months due to JIA. Full participation in PE was reported by 194/242 (80.2%), partly by 16.9%, and none by 2.9%. Lowest participation in PE was found among children with ERA and the undifferentiated categories. Absence in school and PE was associated with higher disease activity measures at the 8-year visit. School absence > 1 day at baseline predicted use of disease-modifying anti-rheumatic drugs, including biologics (DMARDs) (OR 1.2 (1.1-1.5)), and non-remission off medication (OR 1.4 (1.1-1.7) 8 years after disease onset.

School absence at baseline predicted adverse long-term outcome. In children and adolescents with JIA participation in school activities is mostly high after 8 years of disease. For the minority with low participation, special attention is warranted to promote their full potential of social interaction and improve long-term outcome.

Modern clinicians are often frustrated by their inability to understand fibromyalgia and similar maladies since these illnesses cannot be explained by the prevailing linear-reductionist medical paradigm. This article proposes that new concepts derived from the Complexity Theory may help understand the pathogenesis of fibromyalgia, chronic fatigue syndrome, and Gulf War syndrome. This hypothesis is based on the recent recognition of chaos fractals and complex systems in human physiology. These nonlinear dynamics concepts offer a different perspective to the notion of homeostasis and disease. They propose that the essence of disease is dysfunction and not structural damage. Studies using novel nonlinear instruments have shown that fibromyalgia and similar maladies may be caused by the degraded performance of our main complex adaptive system. This dysfunction explains the multifaceted manifestations of these entities.

To understand and alleviate the suffering associated with these complex illnesses, a paradigm shift from reductionism to holism based on the Complexity Theory is suggested. This shift perceives health as resilient adaptation and some chronic illnesses as rigid dysfunction.

Polymorphonuclear leukocyte (PMN) elastase is able to degrade the extra-cellular matrix components of cartilage. However, in vitro several proteinases can degrade elastin. The purpose of this study was to evaluate the role of the serine proteinases and metalloproteinases in the elastase activity measured in cartilage extracts from patients with osteoarthritis (OA), as well as in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and OA. Elastase activity was determined using synthetic low molecular weight substrates and radiolabelled insoluble elastin. Aminophenyl mercuric acetate was used to activate the prometalloproteinases. Elastase activity, measured using synthetic substrates, was higher in BA SF (0.76 + 0.03 microU/ml, n = 12) than in OA SF (0.14 + 0.04 microU/ml, n = 12) (p < 0.001). This activity was inhibited by metal chelating agents: 86% inhibition in OA and 75% inhibition in RA. However, in RA SF the inhibitor of serine proteinase (PMSF) also induced a 40% inhibition. Elastase activity, measured using radiolabelled elastin, in OA SF and RA SF samples and in OA cartilage extract was very low, but increased following activation by mercurial agents. Again this activity was inhibited by metal chelating agents.

Taken together these results indicate that elastase activity (measured by standard methods) in OA and RA SF is mainly due to metalloenzymes.

Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior. A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study. Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression.

Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as "common mental disorders" does not seem fully appropriate.

Glenohumeral arthritis with a massive rotator cuff tear is a devastating condition that seriously compromises the comfort and function of the shoulder. Cuff tear arthropathy presents a unique surgical challenge and many arthroplasty options were used for its treatment. The purpose of this study was to evaluate the clinical and radiological results of Copeland cementless surface replacement arthroplasty (CSRA) applied in patients with cuff tear arthropathy and intact subscapularis function. The study was conducted on twenty-five shoulders in twenty-five patients with cuff tear arthropathy with the subscapularis tendon still intact. The patients were prospectively followed-up clinically and radiologically for a mean of 26 months (range: 15 - 38 months). There were 16 female and 9 male patients. The mean age was 69.04 years (range: 53 - 83 years). The mean operative time was 38 minutes (range: 28 - 56 minutes). The clinical assessment was performed with the Constant score. The Constant score significantly improved from a mean of 14.04 points preoperatively to 53.17 points postoperatively. Of the patients, 88 % considered the shoulder to be much better or better as a result of the operation. Radiologically, the humeral offset, the lateral glenohumeral offset (coracoid base to the greater tuberosity), height of centre of instant rotation and the acromiohumeral distance were significantly increased. No intra- or postoperative complications were encountered.

Our early results with the use of Copeland surface replacement in selected cases with cuff tear arthropathy are encouraging. The patients showed significant clinical (pain and range of motion) and radiological improvements. Moreover, if the surface replacement were to fail for any reason, it can be revised to a reverse prosthesis type as there is no lack of bone stock.

Articular chondrocytes undergo an obvious phenotypic change when cultured in monolayers. During this change, or dedifferentiation, the expression of type I and type III procollagen is induced where normal chondrocytes express little type I and type III procollagen. In this study, we attempted to determine the mechanism(s) for the induction of such procollagen expression in dedifferentiating chondrocytes. All experiments were performed using primary-cultured human articular chondrocytes under approval of institutional review boards. Integrin(s) responsible for the induction of type I and type III procollagen expression were specified by RNAi experiments. The signal pathway(s) involved in the induction were determined by specific inhibitors and RNAi experiments. Adenovirus-mediated experiments were performed to identify a small GTPase regulating the activity of integrins in dedifferentiating chondrocytes. The effect of inhibition of integrins on dedifferentiation was investigated by experiments using echistatin, a potent disintegrin. The effect of echistatin was investigated first with monolayer-cultured chondrocytes, and then with pellet-cultured chondrocytes. In dedifferentiating chondrocytes, α5β1 integrin was found to be involved in the induction of type I and type III procollagen expression. The induction was known to be mediated by v-akt murine thymoma viral oncogene homolog (AKT) signaling. Among the three AKT isoforms, AKT1 seemed to be most involved in the signaling. Elated RAS viral (r-ras) oncogene homolog (RRAS) was considered to regulate the progression of dedifferentiation by modulating the affinity and avidity of α5β1 integrin to ligands. Echistatin inhibited dedifferentiation of monolayer-cultured chondrocytes. Furthermore, the matrix formed by pellet-cultured chondrocytes more closely resembled that of normal cartilage compared with the controls.

The result of this study has shown, for the first time, that α5β1 integrin may be responsible for the induction of non-cartilaginous collagen expression in chondrocytes undergoing dedifferentiation. Again, this study has shown that the inhibition of ligand ligation to integrins may be an effective strategy to inhibit phenotypic change of cultured chondrocytes, and to improve the quality of matrix synthesized by primary cultured chondrocytes.

The prospective investigation of the therapeutic effect of CT-guided intra-articular corticosteroid injection into inflammatory sacroiliac (SI) joints compared to conventional treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) in children with juvenile spondyloarthropathy (jSpA) and the determination of the role of dynamic magnetic resonance imaging (MRI) in establishing the indication and monitoring the therapy. The study comprises 89 children with known jSpA who were diagnosed by MRI to have a unilateral or bilateral sacroiliitis. Therapy with NSAIDS was initiated or continued in all 89 patients. Four weeks after the diagnostic MRI, two groups were distinguished according to the clinical response to NSAIDS, with group 1 consisting of 33 responders and group 2 of 56 non-responders. The patients of group 2 were treated with CT-guided intra-articular corticosteroid injection (low-dose injection) while the therapy with NSAIDS was continued. A total of 83 SI joints were punctured without complications, 27 bilaterally and 29 unilaterally. The indication for the intervention was based on inflammatory activity as determined by MRI. The therapy was monitored by clinical follow-up every 8 to 12 weeks over a period of 20 months. Follow-up by dynamic MRI was performed in all 56 children of group 2 and in 15 of the 33 children of group 1 within 8 +/- 4 months of the initial examination. A total of 87.5% of the children in group 2 showed a statistically significant decrease in their subjective complaints from 6.9 +/- 3.4 to 1.8 +/- 1.7 (p < 0.05) as measured on a visual analog scale (VAS from 0 to 10). Improvement was seen as early as 1.5 +/- 1.0 weeks after the intervention and lasted for a mean of 12 +/- 6 months. The children in group 1 already showed similar improvement of the VAS from 6.8 +/- 3.2 to 1.5 +/- 1.4 (p < 0.05) during the initial four weeks of NSAIDS therapy, with the improvement lasting for the 20-month observation period. The follow-up dynamic MRI (0.1 mmol/kg body weight) during therapy showed a statistically significant lower contrast-enhancement in both groups (group 1: 117 +/- 43 % versus 38 +/- 24 %, p < 0.05; group 2: 127 +/- 59 % versus 38 +/- 22 %, p < 0.05). One third of the patients of group 2 showed progression of joint destruction despite absence of subjective complaints.

CT-guided intra-articular corticosteroid injection has proven an effective, symptomatic, and uncomplicated therapy of acute sacroiliitis in patients with jSpA. Dynamic MRI has a role in establishing the indication for intervention but its role for any follow-up is restricted to cases with inconclusive clinical response.

Contralateral responses to unilateral stimuli have been well described in animal models. These range from central sensitization to peripheral inflammatory responses. Our aim was to test for contralateral responses following unilateral intradermal capsaicin injection in man. Three groups were investigated. A healthy volunteer group (1) was injected with capsaicin into the volar aspect of one forearm. A group of patients with RA (2) was also injected with capsaicin. A control group of healthy volunteers (3) was not injected with capsaicin. All groups were tested for hyperalgesia and allodynia every 10 min for 1 h following the injection using quantitative sensory testing. A total of 9/14 healthy volunteers (Group 1) and 10/14 patients with RA (Group 2) demonstrated contralateral sensitization that subsided within 1 h following intradermal capsaicin injection. A total of 2/23 control subjects (Group 3) demonstrated positive responses with the monofilaments. The frequency of the contralateral responses in the experimental groups compared with the control group is significant (P < 0.05). The peak hyperalgesia was relatively delayed contralaterally compared with the ipsilateral side (35 min vs 15 min). The area of sensitization, where present, was reduced compared with the ipsilateral side (5-50%).

This is the first demonstration of a contralateral response following a unilateral stimulus in man. Bilateral neural pathways mediating contralateral responses may have a role in the pathophysiology of chronically painful or inflammatory diseases and a confounding influence on using the contralateral limb as a control experimentally. We did not find that a systemic inflammatory disease sensitized for this phenomenon.

Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in 75 % of subjects. Four serious AEs were described during the study. None of them was related to the investigational product, and all serious AEs could be resolved during hospitalization.

This prospective, open-label study of abatacept shows for the first time that switching from weekly SC to IV abatacept and back after 4 weeks is an effective and safe way to bridge vacations in RA patients in LDA or remission. (NCT1846975, registered April 19, 2013.).

Systemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-β) and endothelin-1 (ET-1) play a major role. In this paper we show that TGF-β and ET-1 receptors co-operate in myofibroblast activation, and macitentan, an ET-1 receptor antagonist binding ET-1 receptors, might interfere with both TGF-β and ET-1 pathways, preventing myofibroblast differentiation. Fibroblasts isolated from healthy controls and SSc patients were treated with TGF-β and ET-1 and successively analyzed for alpha smooth muscle actin (α-SMA) and collagen (Col1A1) expression and for the Sma and Mad Related (SMAD) phosphorylation. We further tested the ability of macitentan to interfere with these process. Furthermore, we silenced ET-1 and endothelin-1 receptor A expression and evaluated the formation of an ET-1/TGF-β receptor complex by immunoprecitation assay. We showed myofibroblast activation in SSc fibroblasts assessing the expression of α-SMA and Col1A1, after stimulation with TGF-β and ET-1. Macitentan interfered with both ET-1- and TGF-β-induced fibroblast activation. To explain this unexpected inhibitory effect of macitentan on TGF-β activity, we silenced ET-1 expression on SSc fibroblasts and co-immunoprecipitated these two receptors, showing the formation of an ET-1/TGF-β receptor complex.

During SSc, ET-1 produced by activated endothelia contributes to myofibroblast activation using TGF-β machinery via an ET-1/TGF-β receptor complex. Macitentan interferes with the profibrotic action of TGF-β, blocking the ET-1 receptor portion of the ET-1/TGF-β receptor complex.

Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)-stimulated conditions. Cytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4 Prg4

PRG4 plays an important anti-inflammatory role in regulating OA synoviocyte proliferation and reduces basal and IL-1β-stimulated expression of catabolic mediators. Exogenous rhPRG4 autoregulates native PRG4 expression in OA synoviocytes.

Disorders of the cervical spine are often observed in patients with rheumatoid arthritis (RA). However, the best head position for RA patients with atlantoaxial subluxation in the perioperative period is unknown. This study investigated head position during general anesthesia for the patients with RA and proven atlantoaxial subluxation. During anesthesia of patients with RA and proven atlantoaxial subluxation, the authors used fluoroscopy to obtain a lateral view of the upper cervical spine in four different positions: the mask position, the intubation position, the flat pillow position, and the protrusion position. Copies of the still fluoroscopic images were used to determine the anterior atlantodental interval, the posterior atlantodental interval, and the angle of atlas and axis (C1-C2 angle). The anterior atlantodental interval was significantly smaller in the protrusion position (2.3 mm) than in the flat pillow position (5.1 mm) (P < 0.05). The posterior atlantodental interval was significantly greater in the protrusion position (18.9 mm) than in the flat pillow position (16.2 mm) (P < 0.05). The C1-C2 angle was, on average, 9.3 degrees greater in the protrusion position than in the flat pillow position (P < 0.05).

This study showed that the protrusion position using a flat pillow and a donut-shaped pillow during general anesthesia reduced the anterior atlantodental interval and increased the posterior atlantodental interval in RA patients with atlantoaxial subluxation. This suggests that the protrusion position, which involves support of the upper cervical spine and extension at the craniocervical junction, might be advantageous for these patients.

The study aims to elucidate the roles of 1,25(OH)2D3 and vitamin D receptor (VDR) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by regulating the activation of CD4+ T cells and the PKCδ/ERK signaling pathway. From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH)2D3 and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR). Density gradient centrifugation was performed to separate peripheral blood mononuclear cells (PBMCs). CD4+ T cells were separated using magnetic activated cell sorting (MACS). CD4+T cells in logarithmic growth phase were collected and assigned into 9 groups: the normal control group, the normal negative control (NC) group, the VDR siRNA group, the RA control group, the RA NC group, the VDR over-expressed RA group, the SLE control group, the SLE NC group, and the VDR over-expressed SLE group. The mRNA and protein expressions of VDR, PKCδ, ERK1/2, CD11a, CD70 and CD40L were detected by RT-qPCR and Western blotting. Bisulfite genomic sequencing was conducted to monitor the methylation status of CD11a, CD70 and CD40L. Compared with healthy controls, serum 1,25(OH)2D3 level and VDR mRNA expression in peripheral blood were decreased in SLE patients and RA patients. With the increase of concentrations of 1,25(OH)2D3 treatment, the VDR mRNA expression and DNA methylation levels of CD11a, CD70 and CD40L were declined, while the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L were elevated in SLE, RA and normal CD4+T cells. Compared with the SLE contro, RA control, SLE NC and RA NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L decreased but DNA methylation levels of CD11a, CD70 and CD40L increased in the VDR over-expressed SLE group and VDR over-expressed RA group. However, compared with the normal control and normal NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the VDR siRNA group. Compared with the normal control group, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the SLE control and RA control groups.

Our study provide evidence that 1,25(OH)2D3 and VDR could inhibit the activation of CD4+ T cells and suppress the immune response of SLE and RA through inhibiting PKCδ/ERK pathway and promoting DNA methylation of CD11a, CD70 and CD40L.

To study the role of conventional and new factors of cardiovascular risk in development of atherosclerosis in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PA). Sixty patients with psoriatic arthritis, 414 RA patients and 79 healthy controls entered the trial. All of them had no manifestations of cardiovascular diseases. Screening was made of the leading risk factors of cardiovascular diseases and cardiovascular complications, thickness of the complex intima-media (TIM) of the carotid arteries, vascular wall stiffness were measured, vasoregulatory function of the endothelium, markers of endothelial damage were examined. Patients with psoriatic and rheumatoid arthritis were found to have increased TIM of the carotid arteries, high incidence of atherosclerotic plaques, increased stiffness, damage of the vascular wall, affected endothelial vasoregulation. These alterations were associated with high arthritis activity, systemic manifestations, seropositivity by rheumatoid factor (in RA), presence of entesitis, uveitis and dactilitis (in psoriatic arthritis), dislipidemia, arterial hypertension (AH).

To determine cardiovascular risk in patients with arthritis, it is necessary to consider not only standard risk factors (dislipidemia and AH), but also severity of systemic inflammation, arterial stiffness, endothelial damage and ability of the vascular wall to relax reflecting endothelial dysfunction.

Systemic sclerosis (SSc) is an autoimmune disease associated with immune abnormalities and widespread vascular lesions, including increased intimal and medial thickness. These changes may be reflected in early atherosclerosis and cardiovascular risks. We aimed in this study to examine the carotid artery intima-media thickness and MRI brain findings in SSc patients and compared them to a group of normal controls. A relationship between these parameters and clinical measures in SSc was also sought. Seventy-two SSc patients with no central nervous system (CNS) symptoms and 42 healthy controls were included. Clinical and laboratory measures, Medsger's severity scale, and Doppler ultrasound common carotid artery intima-media thickness (CCA-IMT) were measured. Brain fluid-attenuated inversion recovery (FLAIR)-MRI and diffusion-weighted MRI (DWI) were also done. SSc patients had more CCA-IMT, higher CRP, and more brain MRI hyperintense lesions than controls (P < 0.05). Significant positive correlations existed between CCA-IMT and Medsger vascular (r = 0.7, P = 0.02). The FLAIR-MRI showed multiple hyperintense lesions in 24 patients (33%), ranging 0-36 lesions. SSc patients with more lesions (positive MRI) had longer disease duration (P = 0.001) and left and right carotid artery atheromata (P = 0.001, and 0.013, respectively) than SSc patients with negative MRIs; Medsger vascular score did not separate the SSc groups (P = 0.08).

In systemic sclerosis patients without central nervous system symptoms, MRI lesion numbers correlated with CCA-IMT. MRI abnormalities were found more frequently if CRP was elevated, if the Medsger SSc Severity Scale was increased, or if there was thickened carotid IMT.

Joints are often affected in Lyme disease and in some instances this may be due to immune autoreactivity. To characterise further the immune response in this disease investigations were carried out to determine the expression of three public idiotypes on serum immunoglobulins in patients with Lyme disease during the development of varying degrees of arthritis. The expression of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on monoclonal antibodies to DNA, was determined by an enzyme linked immunosorbent assay (ELISA) in serial blood samples from 12 patients with Lyme disease over a mean period of six years during the development of a variety of arthritic symptoms, and in serum samples from healthy control subjects and control subjects with systemic lupus erythematosus. Expression of serum IgM or IgG public Ids 16/6 and BEG2 was significantly increased in patients with Lyme disease. IgA Id 16/6 expression, in contrast, was significantly increased only during episodes of arthritis and was also related to its severity. IgM and IgG Id 16/6 expression was related to their respective total immunoglobulin concentration and, in the case of IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas similar findings were not apparent with IgA antibodies. This may indicate that the IgA response is related to the pathogenesis of arthritis, especially as total IgA and IgA Id 16/6 levels were found to increase over the duration of disease. Sequential analysis of antibodies also showed restriction in the expression of Id 16/6 as it was never found on all immunoglobulin isotypes at the same time, and Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however, may be associated as seven patients expressed these idiotypes simultaneously.

These data indicate the use of public idiotypes in the immune response against B burgdorferi, which may be restricted in terms of idiotype class and isotype expression, and a possible association between IgA antibodies bearing Id 16/6 with arthritis.

The present study was undertaken to validate whether TNF-α and calreticulin (CRT) serve as dual signaling to activate nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and HUVECs. The effect of human antigen R (HuR) in NLRP3 inflammasome activation was also explored in RA FLS. Immunofluorescence was used to determine the expression of NLRP3 and adaptor protein apoptosis associated speck-like protein containing a CARD (ASC) in RA synovial tissue and HuR location in RA FLS. Western blot and quantitative real-time PCR were employed to measure the priming effect of NLRP3 inflammasome in cells and HuR expression in synovial tissue. The concentrations of IL-1β and IL-18 were detected by enzyme linked immunosorbent assay. Immunohistochemistry was used to visualize the expression of HuR in synovial tissue. HuR knockdown in RA FLS was achieved by siRNA-mediated gene silencing. Higher expression of NLRP3 and ASC in RA synovial tissue than those in osteoarthritis was detected. The staining of NLRP3, ASC and cleaved IL-1β were observed in FLS and vascular endothelial cells in RA synovium. Expression of NLRP3 and pro-IL-1β in RA FLS and HUVECs treated with TNF-α was increased. The pro-IL-18 expression was also enhanced in HUVECs, but not in RA FLS. TNF-α/CRT dual stimulation of cells gave rise to caspase-1 p20 expression and the secretion of IL-1β. The secreted IL-18 was also elevated in HUVECs but not in RA FLS. HuR expression was significantly elevated in RA synovial tissue. TNF-α initiated the nucleocytoplasmic shuttling of HuR in both FLS and HUVECs. The knockdown of HuR in FLS incubated with TNF-α led to reduced caspase-1 p20 protein expression and further resulted in decreased secretion of IL-1β in the presence of CRT.

TNF-α/CRT dual signaling induced NLRP3 inflammasome activation, which could be suppressed by HuR knockdown presumably due to the block of HuR translocating from nucleus to cytoplasma.

To investigate whether patients with improved clinical markers during their anti-TNFα treatment experience improvements in their functional and psychological ability to undertake activities. Patients receiving anti-TNFα treatment for rheumatoid arthritis (RA) or ankylosing spondylitis (AS) were recruited from outpatient clinics in East Anglia and North West England. Purposive sampling recruited variety in demographic and treatment experiences. Data were collected through in-depth qualitative interviews and analysed using an interpretive phenomenological framework. Twenty-seven patients were recruited; 19 with RA, eight with AS, and aged from 21 to 73 years. While people generally experienced an improvement in their functional ability, known as occupational gain, they continued to experience difficulties through previous biomechanical damage, continuing symptoms of inflammatory arthritis, or concerns about anti-TNFα treatment. These disruptions affected how participants retained or regained employment. Lack of healthcare support, including an absence of occupational therapy intervention, resulted in people testing new boundaries through a process of unsupported trial and error.

Occupational gain was not maximised for people on anti-TNFα treatment. Improved referral pathways to occupational therapy could facilitate the management of continuing functional difficulties, thereby maximising the benefit of treatment to people with inflammatory arthritis.

To determine patient-specific factors that can be used to predict the presence of severe articular cartilage damage in the hip in patients without osteoarthritis. The prevalence of severe (Outerbridge grade III or IV) cartilage damage to the acetabulum and femoral head was prospectively recorded at hip arthroscopy. Patients who underwent primary hip arthroscopic surgery between 2006 and 2016 performed by a single surgeon were included. Patients were excluded if they underwent previous hip surgery, had poor-quality radiographs, were younger than 16 years at the time of surgery, or had a minimal joint space of 2 mm or less. The relation between severe cartilage damage and preoperative patient characteristics was examined using multivariable logistic regression analysis with restricted cubic splines. Of the 2,396 hips presenting for hip arthroscopy, 995 (41%) had severe cartilage damage to the acetabulum and 257 (11%) had severe cartilage damage to the femoral head. Older age was a significant risk factor for severe cartilage damage both to the acetabulum (χ Level III, cross-sectional study.

The primary risk factors for severe hip cartilage damage were older age for both the femoral head and acetabulum; a lower center-edge angle and larger Tönnis angle for the femoral head; and male sex, body mass index, alpha angle, and joint space for the acetabulum. The likelihood of cartilage damage to the hip can be estimated clinically using a prediction nomogram.

To measure serum interleukin 18 (IL18) and IL18 binding protein (IL18BP) levels in patients with inflammatory arthropathies, and to identify associations with disease status and the response to treatment. Serum samples were obtained before and after methotrexate treatment from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) attending an early arthritis clinic. IL18 and IL18BP were measured by enzyme linked immunosorbent assay (ELISA). Sixty patients with RA and 13 with PsA were evaluated. Serum IL18 levels were significantly higher in RA than in PsA (p<0.001). After six months' treatment with methotrexate, IL18 levels were reduced, but the differences were not significant (p=0.052). In cross sectional analyses, no correlations between IL18 levels and measures of disease activity or structural damage in RA were found. In longitudinal analyses, no correlations between IL18 levels and the response to treatment or the degree of progressive joint damage were found. Similarly, IL18BP levels were raised in RA, and were not associated with measures of the clinical status or the response to treatment.

Raised serum levels of IL18 are consistent with a pathophysiological role in RA. However, in this study measurement of circulating IL18 and IL18BP did not correlate significantly with clinical measures of disease activity or the response to treatment in patients with early RA.

To determine the pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in the Australian community, 1990-1994. Data from the national drug utilisation database were expressed in defined daily doses per 1000 population per day (DDDs/1000 population per day). Temporal trends were assessed and comparisons were made with NSAID use in other countries. Epidemiological data were used to estimate the likely impact of changing NSAID use on peptic ulcer hospitalisation rates. Australian community (excluding hospitals). Estimated consumption of prescription NSAIDs, expressed in DDDs/1000 population per day. NSAID use in the Australian community fell from 50.1 DDDs/1000 population per day in 1990 to 34.6 DDDs/1000 population per day in 1994 (down 31%). From this reduced exposure we estimated that the number of admissions for NSAID-related upper gastrointestinal complications will have fallen by about 400 per year. Market research data for this period show a lower percentage use of NSAIDs for osteoarthritis and a decrease in the proportion of use in age groups over 50 years.

The level of use of non-steroidal anti-inflammatory drugs in Australia has been high in comparison with other countries, but in recent years has fallen markedly. This fall occurred in conjunction with regulatory interventions, educational campaigns and increased concern in the medical and lay press regarding the risks associated with the use of NSAIDs.

Relatively little is known about the prevalence of knee and hip osteoarthritis in the general population. To estimate the prevalence of knee and hip osteoarthritis and the appropriateness of joint replacement in a general population of older individuals, the validated Knee and Hip OsteoArthritis Screening Questionnaire (KHOA-SQ) was sent to a random sample of individuals aged 60 to 90 years, stratified by age and sex, living in a single province in Spain. Respondents positive for knee or hip osteoarthritis on the KHOA-SQ were invited to be examined by an orthopedic surgeon. Diagnosis of knee or hip osteoarthritis was based on clinical and radiographic data. For respondents judged as having osteoarthritis, the appropriateness of knee or hip replacement was evaluated using published explicit criteria. Of 11 002 individuals contacted, 7577 completed the KHOA-SQ. The derived prevalence of hip osteoarthritis was approximately 7.4%. It was slightly higher in women (8.0%) than in men (6.7%) and tended to increase with age. The estimated appropriateness rate for hip replacement was 37.7% in men and 52.7% in women with osteoarthritis. The derived prevalence of knee osteoarthritis was 12.2%; it was significantly higher in women (14.9%) than in men (8.7%) and tended to increase with age. The estimated appropriateness rate for knee replacement was 11.8% in men and 17.9% in women with osteoarthritis.

Knee and hip osteoarthritis are highly prevalent diseases in the older population. The estimation of appropriateness for hip replacement seems to be significantly higher than that for knee replacement.

Physical performance measures play an important role in the measurement of outcome in patients undergoing hip and knee arthroplasty. However, many of the commonly used measures lack information on their psychometric properties in this population. The purposes of this study were to examine the reliability and sensitivity to change of the six minute walk test (6MWT), timed up and go test (TUG), stair measure (ST), and a fast self-paced walk test (SPWT) in patients with hip or knee osteoarthritis (OA) who subsequently underwent total joint arthroplasty. A sample of convenience of 150 eligible patients, part of an ongoing, larger observational study, was selected. This included 69 subjects who had a diagnosis of hip OA and 81 diagnosed with knee OA with an overall mean age of 63.7 +/- 10.7 years. Test-retest reliability, using Shrout and Fleiss Type 2,1 intraclass correlations (ICCs), was assessed preoperatively in a sub-sample of 21 patients at 3 time points during the waiting period prior to surgery. Error associated with the measures' scores and the minimal detectable change at the 90% confidence level was determined. A construct validation process was applied to evaluate the measures' abilities to detect deterioration and improvement at two different time points post-operatively. The standardized response mean (SRM) was used to quantify change for all measures for the two change intervals. Bootstrapping was used to estimate the 95% confidence intervals (CI) for the SRMs. The ICCs (95% CI) were as follows: 6MWT 0.94 (0.88,0.98), TUG 0.75 (0.51, 0.89), ST 0.90 (0.79, 0.96), and the SPWT 0.91 (0.81, 0.97). Standardized response means varied from .79 to 1.98, being greatest for the ST and 6MWT over the studied time intervals.

The test-retest estimates of the 6MWT, ST, and the SPWT met the requisite standards for making decisions at the individual patient level. All measures were responsive to detecting deterioration and improvement in the early postoperative period.

The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification. We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention and satisfaction with study website. Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65-88 for all; higher = better). The amount of time spent for the study was acceptable. Participant satisfaction with website interaction and content was very high; 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate, and saturated fat intake were noted at 6 months in the diet modification versus cherry extract group; differences were insignificant at 9 months. Six of the 8 Health Assessment Questionnaire sections/domains improved significantly from baseline to 9 months in cherry extract versus 2 Health Assessment Questionnaire sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient reporting of classification criteria, and centralized laboratory-assisted serum urate testing.

High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicate that hypothesis-testing internet gout trials of cherry extract and/or diet modification can be conducted in the future.

To date, no specific serum marker for giant cell arteritis and polymyalgia rheumatica has been established in routine practice. Therefore, the aim of this study was to examine whether immunoglobulin G4 serum concentrations could be a potential biomarker for the differentiation of both diseases. Serum immunoglobulin G4 (IgG4) concentrations were measured in patients with giant cell arteritis (n=41) and polymyalgia rheumatica (n=27) by an in-house enzyme-linked immunosorbent assay. In the subgroup of untreated patients with disease activity (polymyalgia rheumatica n=27, giant cell arteritis n=19) additional parameters of T-helper 2 cell inflammatory responses were analysed. IgG4-values above the prior determined cut-off value of 1400 μg/ml in giant cell arteritis were rare and also significantly less frequent in giant cell arteritis than in polymyalgia rheumatica patients (7.3% vs. 44.4%; p<0.001). The relative risk that patients with clinical features of PMR, presenting without elevated IgG4 levels, have simultaneously GCA was 5.8 compared to those patients with elevated IgG4 levels. In untreated patients absolute counts of eosinophilic leukocytes were lower in giant cell arteritis than in polymyalgia rheumatica (p=0.002) and the cytokines interleukin-4 (p=0.013) and interleukin-10 (p=0.033) were less frequently detectable in giant cell arteritis than in polymyalgia rheumatica.

In giant cell arteritis serum levels of IgG4 usually are within the normal range. In polymyalgia rheumatica however, increased IgG4 serum levels are frequently found. Normal IgG4 serum levels in polymyalgia rheumatica may have predictive value in identifying patients with additional, clinically non-apparent giant cell arteritis.

Postoperative exercise rehabilitation helps patients recover normal joint functions after total hip arthroplasty (total hip replacement surgery or THR) by strengthening the muscles that surround the replaced hip joint. However, the high cost of professionally supervised exercise rehabilitation programs limits access to program participation and, thus, to optimal recovery of normal joint functions. Therefore, the development of an effective home-based, self-monitored exercise rehabilitation program is critical to promote the optimal recovery of THR patients. This study tests the efficacy of a home-based resistance-band exercise program on mobility, functional exercise capacity, and health-related quality of life in THR patients. This study uses a preexperimental repeated measures design. A convenience sample of 30 patients who underwent total hip replacement for osteoarthritis was recruited. All patients participated in a 12-week home-based resistance training program. Data were collected at baseline and at 2, 6, and 12 weeks postoperation on the following dimensions: up-and-go time, timed walking distance, and quality of life. In addition, intervention-related adverse events and the exercise adherence rate were monitored. Generalized estimation equations were used to analyze changes in the outcome variables across time. The study included 21 women and nine men. The mean age of the participants was 67.9 years (SD = 8.1 years, range = 55-86 years). Results of the generalized estimation equations showed a statistically significant time effect for up-and-go time, 6-minute walking distance, and health-related quality of life. After 12 weeks of training, the participants' up-and-go time decreased 40.33% from the baseline measurements, with a mean change of 6.38 seconds (p < .001). The 6-minute walking distance increased 41.34%, with a mean change of 117.12 meters (p < .001). The score for health-related quality of life decreased 78.94%, with a mean change of 39.10 (p < .001). The average exercise adherence rate was 72.63%. The average score for the feasibility of the intervention was 8.8 (range = 6-10).

The results of this study support the hypothesis that a home-based resistance training program is safe, feasible, and effective for improving the mobility, functional exercise capacity, and health-related quality of life of THR patients. Considering the low cost and convenience of a home-based resistance training program, health professionals should consider this and similar exercise programs when providing guidance to THR patients.

There is a re-occurring question in medical practice: do positive attitude and communication of the medical staff make any difference? Our aim is to present a comprehensive image of the medically relevant effects of positive suggestions by reviewing the recent literature. We review the studies measuring the effects of suggestive communication of the past 20 years. In cases of studies presented in more details we quote from the suggestion scripts used in the study, too. Most of the reviewed papers affirm that positive suggestions lead to decreased pain and use of pain medication. But physiological factors like bowel motility, blood pressure and bleeding during surgery can be positively affected, too.

Suggestive communication - a yet poorly utilized tool - used appropriately can significantly affect healing and recovery of a patient. Thus we emphasize further, more detailed study of this technique and its integration into the education of medical professionals.

Only few studies have addressed the prognostic impact of chronic obstructive pulmonary disease (COPD) among patients with rheumatoid arthritis (RA), although both diseases are frequent and smoking is a shared risk factor. The objectives of the present study were to investigate the burden of COPD among RA patients and the subsequent mortality. We included patients who had a first-time diagnosis of RA in the Danish National Patient Registry between 2004 and 2016. RA patients with COPD were identified and matched with RA patients without COPD for year of birth, gender, and age at RA diagnosis. Mortality risks were assessed using Kaplan-Meier mortality curves. Adjusted hazard rate ratios (aHRRs) for death were estimated using Cox regression models. The study population included 31,333 individuals with RA. 3254 of those (10.4%) had a diagnosis of COPD and were matched to 9706 RA patients without COPD. The mortality risks in RA patients with COPD and RA patients without COPD were 4.5% and 1.5% within 2-6 months (aHRR = 3.0, CI 2.3-3.9), and 59.3% and 39.8% within 0.5-10 years (aHRR = 2.1, CI 1.9-2.1).

Mortality was significantly increased among RA patients with COPD. The relative mortality risk remained significantly increased throughout the course of follow up.

Variants in the growth differentiation factor 5 (GDF5) and in the double von Willebrand factor A (DVWA) have recently been reported to be associated with osteoarthritis (OA) in Asian populations. To assess the role of such variants in OA susceptibility in two independent UK samples of Caucasian origin. Polymorphisms rs11718863 and rs7639618 (DVWA) and rs143383 (GDF5) were genotyped in 999 patients with knee OA, 843 patients with hip OA and 1166 controls from two UK studies from Nottingham and Chingford. In agreement with previous reports, the major allele at rs143383 (GDF5) was associated with a higher risk of knee OA in our samples (OR(MH) = 1.29, 95% CI 1.14 to 1.47 p = 8 x 10(-5)). Conversely, the major allele at the DVWA SNP rs7639618, which increased risk in Asians, was not associated with a risk of knee OA, (OR(MH) = 0.88, 95% CI 0.74 to 1.04; p = 0.12). A meta-analysis of Asian and UK knee OA data indicated highly significant heterogeneity (I(2) = 92%, Q = 48.5, p = 7 x 10(-10)) and no significant association with knee OA using a random effects meta-analysis (OR(DL) = 1.18, 95% CI 0.86 to 1.63; p = 0.309).

These data confirm that the GDF5 variant is consistently associated with the risk of knee OA. Considerable ethnic variation in allele frequencies at the DVWA gene was found and no significant association was found in UK samples or by combining UK and Asian samples. The results suggest that the effect of DVWA amino acid changes on tubulin binding is unlikely to influence the risk of OA in Caucasians.

To assess how the level of the deformity, the stage of the osteoarthritic process, and the role of additional surgeries impact radiographic and clinical outcomes following an extra-articular medial closing supramalleolar osteotomy for treatment of post-traumatic valgus ankle osteoarthritis. About 56 consecutive patients who underwent an extra-articular medial closing wedge osteotomy for post-traumatic valgus ankle osteoarthritis were retrospectively analyzed. Subgroups were formed according to the pre-operative level of deformity and preoperative stage of ankle osteoarthritis. Additional surgical steps required to achieve a properly balanced hindfoot were also noted. Radiographic and clinical outcomes of each subgroup were compared with each other, and the role of additional surgical steps required to achieve a balanced hindfoot was investigated. Radiographic and clinical outcomes improved significantly between pre-operative assessment and the last follow-up. Patients with a pre-operative supramalleolar deformity showed superior radiographic outcomes compared to patients with an intra-articular deformity. Clinical outcomes did not differ significantly between these two subgroups. The pre-operative stage of ankle osteoarthritis significantly impacted radiographic outcomes but did not influence clinical outcome measures. An additional fibula or calcaneus osteotomy was necessary for 55% and 23% of all patients, respectively.

Extra-articular medial closing supramalleolar osteotomies show satisfactory mid- to long-term radiographic and clinical outcomes in patients with post-traumatic valgus ankle osteoarthritis.

To investigate the impact of infliximab treatment on anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in patients with rheumatoid arthritis (RA). Sera from 33 RA patients receiving infliximab and disease modifying antirheumatic drugs were tested for anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available semiquantitative ELISA at baseline, 30 and 54 weeks after treatment. The serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30 weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54 (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and 54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at 30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = < 0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05) and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks.

Treatment with infliximab results in decreased anti-CCP antibody and IgA-RF early in the course of therapy that is not sustained. IgM-RF declines and remains decreased for at least 54 weeks. Investigations in larger cohorts of RA patients (especially early RA) with longer follow-up are needed to assess the impact of specific therapeutic interventions on anti-CCP antibody and RF levels and the relationship of their levels to disease activity.

To evaluate the genetic influence of PvuII and XbaI polymorphisms of oestrogen receptor alpha (ORalpha) in patients with systemic lupus erythematosus (SLE) in Korea. Genomic DNA from 268 female controls and 137 female SLE patients (41 childhood onset and 96 adult onset) were analysed using PvuII and XbaI restriction fragment length polymorphism. Comparison of the frequencies of alleles and genotypes was made in control and patient groups and in childhood onset and adult onset SLE subgroups. Although the Pp genotype occurred more often in SLE patients than in controls (p(c) = 0.017), ORalpha genotype distributions of adult onset SLE did not differ significantly from controls. The PP, Pp, and xx genotypes occurred less often in childhood onset SLE (p(c) = 0.0045, 0.0498, and 0.0255, respectively) than in controls. Additionally, the PP genotype was less common in childhood onset than in adult onset SLE (p(c) = 0.016). SLE patients with the PP genotypes were older at disease onset than those with the other genotypes (p = 0.001). Patients with the Xx genotype had an earlier onset of SLE than those with the xx genotype (p = 0.025). The frequency of the combined ppXx genotype was greater in childhood onset SLE than in controls (p(c) = 0.0009) or adult onset SLE (p(c) = 0.027). The same trend was supported by subgroup analyses according to age at menarche and logistic multivariate analyses.

ORalpha polymorphisms are significantly associated with the age at disease onset in Koreans with SLE.

Tenosynovial giant cell tumour (TGCT) is locally aggressive entity affecting young people (around 4 We conducted a retrospective study of 35 patients with an anatomopathological diagnosis of TGCT in our Institution from 1991 to 2017. The mean follow-up was 8.2 years. Demographic variables, characteristics of the primary tumor and its evolution were collected to assess the risk factors for local recurrence and early osteoarthritis. The diffuse type was identified as a risk factor for the development of osteoarthritis (p=0.01) and for local recurrence (p=0.015). Osteoarthritis was more frequent in the hip and ankle than in the knee (p=0.03). A difference of 16 months in the duration of symptoms prior to diagnosis between those who developed osteoarthritis and those who did not was observed (p=0.05).

The diffuse type is more aggressive than the nodular type; it is associated with a higher risk of osteoarthritis and local recurrence. The hip and ankle present a higher risk of osteoarthritis than other joints. The time of evolution of the symptoms before diagnosis and adequate treatment, negatively influences the development of osteoarthritis.

To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid antibodies (aPL). Sera and clinical data were obtained from the Hospital for Special Surgery Autoimmune Disease Registry for 78 aPL-positive and 91 aPL-negative SLE patients without heparin-induced thrombocytopenia (HIT). Controls were 90 blood donors of comparable age and sex. Sera were assayed for anti-HPF4, IgG/IgM antiphospholipid antibodies (APhL), and IgG/IgM anti-beta2-glycoprotein 1 antibodies (anti-beta 2GP1). Serotonin release assays (SRAs) were performed for subjects with positive anti-HPF4. Positive anti-HPF4 was seen in 9% of aPL-positive SLE patients, 4% of aPL-negative SLE patients and 1% of controls (p = 0.026, aPL-positive SLE vs controls). Two of 12 subjects with positive anti-HPF4 had reactive SRAs. In SLE patients, anti-HPF4 significantly correlated with IgM APhL, IgM anti-beta2GP1, and inversely with complement C4. In immunoabsorption experiments, there was partial cross-reactivity of IgM anti-HPF4 with IgM APhL, but not with IgM anti-beta 2GP1. SLE patients with positive anti-HPF4 had increased odds of the antiphospholipid syndrome (APS; odds ratio (OR) 4.5, p = 0.019), and APS with arterial thrombosis (OR 6.1, p = 0.007). In multivariate linear regression analyses, APS and IgM APhL were independently associated with anti-HPF4.

Anti-HPF4 is detectable in SLE patients with and without aPL in the absence of HIT, and is most prevalent in aPL-positive SLE patients. In this SLE cohort, anti-HPF4 correlates with IgM APhL, IgM anti-beta 2GP1 and inversely with C4, and is associated with manifestations of APS.

To compare direct evaluation of cartilage with high resolution MRI (hrMRI) to indirect cartilage evaluation using MRI inter-bone distance in hand OA patients and healthy controls. 41 hand OA patients and 18 healthy controls underwent hrMRI of the 2 The intra- and inter-reader reliability of both scores was comparable, with exact agreement in 73-83% and close agreement in 95-100%. In hand OA patients 27% of 161 joints had both cartilage damage and loss of inter-bone distance, cartilage damage by hrMRI only was present in 20% of joints and reduced inter-bone distance only in 4% of joints. In the healthy controls, 1 of 71 joints were scored as abnormal by both hrMRI and inter bone distance scoring, 1 joint was scored as abnormal using the hrMRI cartilage score only, whereas 15% of joints had only reduced inter bone distance.

Direct cartilage evaluation of MCP and PIP joints using hrMRI has a good reliability, and the higher prevalence of hrMRI cartilage damage in hand OA patients and the lower prevalence in healthy controls in comparison to evaluation of inter-bone distance suggests a better validity.

We present a software designed to improve hip joint osteoarthritis (OA) understanding using 3D anatomical models, magnetic resonance imaging (MRI) and motion capture. In addition to a standard static clinical evaluation (anamnesis, medical images examination), the software provides a dynamic assessment of the hip joint. The operator can compute automatically and in real-time the hip joint kinematics from optical motion capture data. From the estimated motion, the software allows for the calculation of the active range of motion, the congruency and the center of rotation of the hip joint and the detection and localization of the femoroacetabular impingement region. All these measurements cannot be performed clinically. Moreover, to improve the subjective reading of medical images, the software provides a set of 3D measurement tools based on MRI and 3D anatomical models to assist and improve the analysis of hip morphological abnormalities. Finally, the software is driven by a medical ontology to support data storage, processing and analysis. We performed an in vivo assessment of the software in a clinical study conducted with 30 professional ballet dancers, a population who are at high risk of developing OA. We studied the causes of OA in this selected population. Our results show that extreme motion exposes the morphologically "normal" dancer's hip to recurrent superior or posterosuperior FAI and to joint subluxation.

Our new hip software includes all the required materials and knowledge (images data, 3D models, motion, morphological measurements, etc.) to improve orthopedists' performances in hip joint OA analysis.

It is estimated that 50-70% of patients with rheumatoid arthritis (RA) are non-adherent to their recommended treatment. Non-adherent patients have a higher risk of not reaching an optimal clinical outcome. We explored factors associated with nonadherence from the patient's perspective. Four hundred and fifty-nine RA patients (346 (75.4%) females; mean age 63.0 ± 14.8 years) who failed to attend follow-up visits in two rheumatology centres were eligible to participate in a qualitative interview study. We used this strategy to identify patients who were potentially non-adherent to medicines and/or non-pharmacological interventions. By means of meaning condensation analysis, we identified new and some already well known insights to factors associated with non-adherence. We used the capability, opportunity, and motivation model of behaviour (COM-B) model as a frame of reference to classify the factors. Forty-three of 131 patients (32.8%) who agreed to participate in the qualitative interviews were found to be non-adherent. New insights on factors associated with non-adherence included strong opinions of patients, such as pain being considered as an indicator of hard work and something to be proud of, or inflammation being a natural process that should not be suppressed; feeling not to be in expert's hands when being treated by a physician/health professional; the experience of excessive self-control over the treatment; and rheumatologists addressing only drugs and omitting non-pharmacological aspects. The COM-B model comprehensively covered the range of our findings.

The new insights on factors associated with non-adherence allow a better understanding of this phenomenon and can substantially enhance patient care by helping to develop targeted interventions.

The high-affinity receptor for IgG Fcgamma/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was to determine whether expression of Fc receptor (FcgammaR) I on circulating monocytes is associated with systemic inflammation and renal disease in SLE patients. We studied 205 SLE patients (132 with LN and 73 without LN) along with 74 healthy control individuals. Surface expression of CD14 (monocytes), FcgammaRI/CD64, FcgammaRII/CD32, and FcgammaRIII/CD16 was evaluated by flow cytometry. Monocyte function was assessed by determining the migratory capacity and the ability to produce CCL2 (monocyte chemotractic protein 1). High-sensitivity C-reactive protein, C3 and C4 were measured by nephelometry. There was little difference in the expression of FcgammaRIII/CD16 or FcgammaRIII/CD32 on circulating monocytes between patients with SLE and control individuals. In contrast, FcgammaRI/CD64 expression was significantly higher in SLE patients and even higher in patients with LN. FcgammaRI/CD64 expression was positively associated with serum creatinine and indicators of systemic inflammation. Monocytes from patients with high FcgammaRI/CD64 expression also exhibited increased chemotaxis and capacity to produce monocyte chemotractic protein 1.

Increased FcgammaRI/CD64 expression on circulating monocytes parallels systemic inflammation and renal disease in SLE patients. We propose that circulating monocytes activated by immune complexes and/or proinflammatory mediators upregulate surface expression of FcgammaRI/CD64 in SLE. The enhanced chemotactic and inflammatory potential of the activated monocytes may participate in a vicious cycle of immune cell recruitment and renal injury in SLE.

To determine the extent to which different entheses form part of a "synovio-entheseal complex" (SEC) and whether such SECs are commonly associated with the presence of inflammatory cells and evidence of enthesis microdamage. Specimens from 49 cadaveric entheses were processed for histologic study, and all soft tissue components of the entheses or enthesis organs were examined. To exclude articular cartilage degeneration as a triggering factor for synovitis, the selected entheses included 17 that were not immediately adjacent to such cartilage. An SEC was present at 82% of entheses. These included 47% of the attachments not adjacent to articular cartilage, where the synovium was that of bursae or tendon sheaths. One or more of a wide variety of degenerative changes were noted on the soft tissue side of every enthesis; the most common changes were cell clustering and/or fissuring (in 76% of entheses). Synovial villus formation or inflammatory cell infiltration was seen in 85% of entheses, and in 73% of attachments there were also inflammatory cells in the enthesis organ itself. The changes included synovial invasion (pannus formation) of the enthesis.

Entheses are frequently juxtaposed to synovium, thus forming SECs. They are also often associated with both degenerative and inflammatory changes, and the latter may involve the immediately adjacent synovium. These findings suggest a novel mechanism by which synovitis could develop in both degenerative joint disease and spondylarthritis.

Little published evidence exists on the incidence of continuing acromioclavicular joint pain with no published outcomes for revision surgery. This study aimed to establish the incidence and outcomes of revision acromioclavicular joint excision surgery. A consecutive retrospective cohort of patients undergoing revision arthroscopic or open acromioclavicular joint excision was identified. Patients were identified from a prospectively collected database. Inclusion criteria were revision acromioclavicular joint excisions over a 14-year period between 2001 and 2015. Exclusion criteria were previous surgery for acromioclavicular joint instability or shoulder arthroplasty. Outcome measures were Oxford Shoulder scores and a satisfaction survey. Forty-three consecutive cases of revision acromioclavicular joint excision over 14 years (37 after arthroscopic excision with subacromial decompression, 5 after arthroscopic excision with rotator cuff repair, 1 after open excision). Continuing acromioclavicular joint pain was associated with incomplete resection from arthroscopic surgery, which was the primary indication for revision surgery. Revision occurred a mean 14.2 months after primary surgery (standard deviation 7.6 months). Mean Oxford Shoulder score was preoperatively 18 (standard deviation 8.1) and 23.4 (standard deviation 11.1) after primary surgery, which did not reach significance until after revision surgery with a mean 31.7 (standard deviation 13.6;

Functional outcomes after revision surgery showed improvement from scores taken before primary surgery; however, long-term satisfaction rates were relatively low.

The Health Assessment Questionnaire - Disability Index (HAQ), used as a disability and outcome measurement in rheumatoid arthritis (RA), has been validated in several languages, but not in Chinese. Our aim was to validate the Chinese version of HAQ (Chinese-HAQ) to suit the needs of Chinese speaking patients with RA in an Asian setting. The original HAQ was modified in the context of Chinese culture and translated into Chinese by 2 translators aware of the objective of the questionnaire. The Chinese HAQ was self-administered by 42 patients with RA during their routine followup visit and one week later. The test-retest reliability assessed using Spearman's correlation coefficient was 0.84. Between dimensions measured in the HAQ, the highest test-retest reliability was observed for walking (Spearman correlation coefficient rs=0.80) and the lowest was for eating (rs=0.54). The internal consistency of the scale using Cronbach's alpha was high at 0.86. In terms of criterion validity, the Chinese-HAQ score was found to correlate well with American College of Rheumatology functional status (rs=0.501, p=0.01). The Chinese-HAQ scores also correlated well with markers of disease activity such as patient's perception of pain measured on a visual analog scale (rs=0.55, p < 0.001), grip strength in mm Hg (rs=-0.55. p < 0.001 ), and physician's assessment of disease activity (rs=0.59, p < 0.001).

The Chinese HAQ is a reliable and valid instrument for studies measuring disability of patients with RA in Singapore.

Construction of a simple nailfold videocapillaroscopic (NVC) scoring modality as a prognostic index for digital trophic lesions for day-to-day clinical use. An association with a single simple (semi)-quantitatively scored NVC parameter, mean score of capillary loss, was explored in 71 consecutive patients with systemic sclerosis (SSc), and reliable reduction in the number of investigated fields (F32-F16-F8-F4). The cut-off value of the prognostic index (mean score of capillary loss calculated over a reduced number of fields) for present/future digital trophic lesions was selected by receiver operating curve (ROC) analysis. Reduction in the number of fields for mean score of capillary loss was reliable from F32 to F8 (intraclass correlation coefficient of F16/F32: 0.97; F8/F32: 0.90). Based on ROC analysis, a prognostic index (mean score of capillary loss as calculated over F8) with a cut-off value of 1.67 is proposed. This value has a sensitivity of 72.22/70.00, specificity of 70.59/69.77, positive likelihood ratio of 2.46/2.32 and a negative likelihood ratio of 0.39/0.43 for present/future digital trophic lesions.

A simple prognostic index for digital trophic lesions for daily use in SSc clinics is proposed, limited to the mean score of capillary loss as calculated over eight fields (8 fingers, 1 field per finger).

Self-management is a key recommendation for people with rheumatoid arthritis (RA). Educational materials may support self-management, and increasingly patients are becoming involved with the development of these materials. The TITRATE trial compares the effectiveness of intensive management to standard care in patients with moderate RA across England. As part of the intensive management intervention, participants are given a handbook. The aim of this study was to develop a handbook to support the intensive management. The objectives were to: (i) involve patients in the identification of relevant information for inclusion in the TITRATE handbook; (ii) ensure the content of the handbook is acceptable and accessible. We held an audio-taped workshop with RA patients. The transcript of the workshop was analysed using thematic content analysis. Five main themes were identified as follows: 'rheumatoid arthritis treatment, perceptions of rheumatoid arthritis, the importance of individualized goals, benefits of self-management and the patient handbook'. Feedback from the workshop was incorporated into the handbook, and patients' anonymous testimonies were added.

This study demonstrates that patient contribution to the development of educational material to support intensive management of RA is both feasible and valuable. A qualitative evaluation of the use and impact of the handbook with patients and practitioners is planned on completion of the TITRATE trial.

To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial. A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted.

Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.

Enhanced B cell activity, particularly memory B cells have gained interest in evaluating response during therapies with biologics. CD27-IgD- double-negative (DN) B cells lacking the conventional memory marker CD27 are reported to be part of the memory compartment, however, only scarce data is available for rheumatoid arthritis (RA). We therefore focused on DN B cells in RA, studied their isotypes and modulation during interleukin-6 receptor (IL-6R) inhibition by tocilizumab (TCZ). DN B cells were phenotypically analyzed from 40 RA patients during TCZ at baseline week 12, week 24 and 1 year. A single B cell polymerase chain reaction (PCR) approach was used to study Ig receptors, VH gene rearrangements and specific isotypes. Phenotypic analysis showed a significantly expanded population of DN B cells in RA which contain a heterogeneous mixture of IgG-, IgA- and IgM-expressing cells with a clear dominance of IgG+ cells. DN B cells carry rearranged heavy chain gene sequences with a diversified mutational pattern consistent with memory B cells. In contrast to tumor necrosis factor alpha (TNF-α) inhibition, a significant reduction in mutational frequency of BCR gene rearrangements at week 12, 24 and 1 year (P <0.0001) was observed by in vivo IL-6R inhibition. These changes were observed for all BCR isotypes IgG, IgA and IgM at week 12, 24 and 1 year (P <0.0001). IgA-RF, IgA serum level and IgA+ DN B cells decreased significantly (P <0.05) at week 12 and week 24 during TCZ. Patients with a good European League Against Rheumatism (EULAR) response to TCZ had less DN B cells at baseline as compared to moderate responders (P = 0.006). Univariate logistic regression analysis revealed that the frequency of DN B cells at baseline is inversely correlated to a subsequent good EULAR response (P = 0.024) with an odds ratio of 1.48 (95% confidence interval as 1.05 to 2.06).

In RA, the heterogeneous DN B cell compartment is expanded and dominated by IgG isotype. TCZ can modulate the mutational status of DN Ig isotype receptors over 1 year. Interestingly, the frequency of DN B cells in RA may serve as a baseline predictor of subsequent EULAR response to TCZ.