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The goal of this study was to assess the diffuse myocardial fibrosis and edema in rheumatoid arthritis (RA) using multiparametric cardiac magnetic resonance (CMR) and the association of myocardial T1 and extracellular volume (ECV) with disease activity, duration, and cardiac function. RA is a connective tissue disorder, with frequent cardiovascular disease. Myocardial inflammation and diffuse fibrosis can be detected noninvasively by using native T1 mapping and ECV quantification on CMR. Thirty-nine RA patients (28 women; mean age 50 ± 12 years) and 39 matched control subjects (28 women; mean age 49 ± 12 years) underwent CMR at 1.5-T, including cine, tagging, T2-weighted, native T1 mapping (shortened modified Look-Locker inversion recovery), late gadolinium enhancement (LGE), and ECV imaging. Focal fibrosis on LGE was found in 46% of RA patients compared with none of the control subjects. Patients with RA had larger areas of focal myocardial edema (10% vs. 0%), higher native T1 values (973 ± 27 ms vs. 961 ± 18 ms; p = 0.03), larger areas of involvement as detected by native T1 >990 ms (35% vs. 2%; p < 0.001), and expansion of ECV (30.3 ± 3.4% vs. 27.9 ± 2.0%; p < 0.001) compared with control subjects. Left ventricular volumes, mass, and ejection fraction were similar between RA patients and control subjects. Peak systolic circumferential strain (-16.9 ± 1.3 vs. -18.7 ± 1.2; p < 0.001) and peak diastolic circumferential strain rate (83 ± 21 s(-1) vs. 112 ± 20 s(-1); p < 0.001) were impaired in RA patients. Myocardial T1 and ECV were correlated with myocardial strain and RA disease activity.

Subclinical cardiovascular disease is frequent in RA, including focal and diffuse myocardial fibrosis and inflammation, which are associated with impaired strain and RA disease activity. CMR T1 mapping provides potential added value as a biomarker for disease monitoring and study of therapies aimed at reducing diffuse myocardial fibrosis in RA.

To assess the effectiveness of pulsed electromagnetic fields compared with placebo in the management of osteoarthritis of the knee. A systematic review of PubMed, EMBASE, and the Cochrane Controlled Trials Register. Randomized, controlled trials reporting on the blinded comparison of pulsed electromagnetic fields with placebo were included. Validity was tested according to the Jadad Scale. Studies were pooled using fixed-effects and random-effects models after exclusion of publication bias and assessment of heterogeneity. Sensitivity analyses and meta-regression were performed to test the stability of our findings. Nine studies, including 483 patients, were pooled. No significant difference could be shown for pain (weighted mean difference 0.2 patients; 95% confidence interval (CI): -0.4 to 0.8) or stiffness (weighted mean difference 0.3; 95% CI: -0.3 to 0.9). There was a significant effect on activities of daily living (weighted mean difference 0.8; 95% CI 0.2-1.4, p = 0.014) and scores (standardized mean difference 0.4; 95% CI: 0.05-0.8, p = 0.029). We saw only statistically insignificant differences between studies with different treatment protocols.

Pulsed electromagnetic fields improve clinical scores and function in patients with osteoarthritis of the knee and should be considered as adjuvant therapies in their management. There is still equipoise of evidence for an effect on pain in the current literature.

The intensification of infliximab (IFX) treatment, involving escalation of the dose and shortening of interval, was approved in Japan in July 2009. We consider IFX intensification therapy to be preferable for patients with treatment-resistant active rheumatoid arthritis (RA). We retrospectively compared the efficacy of IFX with that of other bDMARDs in methotrexate (MTX)-resistant patients. Patients who satisfied the following criteria were enrolled: (i) those who started bDMARDs between February 2011 and December 2016, and (ii) those who required bDMARDs after 180 d of MTX treatment. We compared 33 patients who had been treated with IFX (IFX group) and 146 who had received other bDMARDs treatment (non-IFX group). IFX was administered at a dose of 6.98 mg/kg/8-week equivalent at 52 weeks. Clinical disease activity index clinical remission (CDAI-CR) was achieved in 49 of the 179 patients at 52 weeks and 13 of these 49 patients received IFX. Logistic regression analysis showed that treatment with IFX was an important variable for the achievement of CDAI-CR at 52 weeks (odds ratio 2.69, 95% confidence interval 1.13-6.42). The severity and frequency of adverse events did not differ.

Intensification of IFX was effective and well tolerated for MTX resistant patients.

Survival curves and decimal Standardized Mortality Ratios (SMRs) were reported in 1994 for four clinical series of patients with Rheumatoid Arthritis (RA), with use of a common data processing system. It was felt to be desirable to compare the excess mortality observed in clinical patients with the excess mortality found in substandard policyholders with RA in the 1983 Medical Impairment Study. The weighted mean SMR was 2.25 for the male RA patients and 2.42 for the females. Although similar in magnitude to the percentage male and female Mortality Ratios (MRs) in the 1983 Medical Impairment Study, the derived Excess Death Rate (EDR) was higher for the clinical RA patients, despite the lower select mortality versus the population mortality, even after adjustment for difference in mean age between the clinical and insurance series.

The higher EDR in four clinical series of RA patients probably reflects a higher proportion of more severe cases, who are declined for insurance or do not accept a highly rated offer.

Although many disability questionnaires measure fact very efficiently, they do not allow for consideration of the relevance of that disability to the patient. Data suggest that professionals misinterpret the relevance of disability for the patient and thus, also, the outcome of treatment. Firstly, to examine agreement on levels of importance for the items on a validated disability scale (Health Assessment Questionnaire (HAQ) and Modified HAQ (MHAQ)), within groups of patients with rheumatoid arthritis, health professionals, and controls. Secondly, to see if functional items important to patients are included in the HAQ, and whether the HAQ items are important to patients. 25 patients with RA, 25 rheumatology health professionals, and 25 healthy controls were asked to rate the importance of the HAQ (20 items) and MHAQ (eight domains). Before seeing the HAQ, patients were asked to generate items of function important to them. Only a slight-fair agreement within each group was found for the level of importance of the HAQ and MHAQ, and also within any combination of the groups (kappa values <0.38). Most of the functional items valued by patients were contained on the HAQ (70%), and no HAQ items were consistently rated as unimportant.

Patients, professionals, and healthy controls do not agree on the importance of disabilities. These data support the need to assess the personal impact of disability, as well as disability itself. Individual importance of disability weighted by level of disability is proposed as a model for calculating the personal impact of disability. A new tool to assess the personal impact of disability is being developed.

To investigate the changes of serum BAFF and IL-21 levels in the patients with systemic lupus erythematosus (SLE) and explore their clinical significance. The serum levels of BAFF and IL-21 were detected by enzyme-linked immunosorbent assay (ELISA). The levels of serum BAFF and IL-21 in the patients with SLE were obviously higher than those in healthy control group. The BAFF level in the group of lupus nephritis (LN) with renal biopsy increased with pathologic aggravation and the IL-21 level in II, III, IV LN also increased, with the most obviously change in the type IV. The levels of BAFF and IL-21 obviously increased in SLE patients with Sjogren's syndrome (SS), but the levels of BAFF and IL-21 obviously tended to decrease in the patients after glucocorticosteroid treatment for a week, with the most significant decrease in BAFF. The changes of BAFF and IL-21 were related to major immune indexes in the patients with SLE. There was positive correlation between BAFF and IL-21 in IV LN.

The levels of serum BAFF and IL-21 level are increased in the patients with SLE. The dysfunction and synergistic effect of T and B lymphocytes play different roles in the patients with different organ damage and pathoprocess respectively.

The mechanistic target of rapamycin (mTOR) has become a therapeutic target in systemic lupus erythematosus (SLE). In T cells, mTOR plays a central role in lineage specification, including development of regulatory cells (Treg cells). This study sought to investigate whether mTOR is activated within Treg cells and whether this contributes to the depletion and dysfunction of Treg cells in patients with SLE. Activities of mTOR complexes 1 (mTORC1) and 2 (mTORC2) were examined by quantifying phosphorylation of translation initiation factor 4E-binding protein 1, S6 kinase, and Akt in SLE patients relative to age- and sex-matched female healthy control subjects. Polarization of Treg cells from naive CD4+ T cells was assessed in the presence of interleukin-6 (IL-6), IL-17, and IL-21. The suppressor function of sorted CD4+CD25+ Treg cells was measured by determining their impact on the proliferation of autologous CD4+CD25- responder T cells. Treg cell expression of FoxP3, GATA-3, and CTLA-4 was monitored by flow cytometry. Autophagy was assessed using immunoblotting of light chain 3 lipidation. The effect of mTOR blockade was evaluated by testing the impact of rapamycin treatment on Treg cell function. SLE Treg cells exhibited increased activities of mTORC1 and mTORC2, whereas autophagy, the expression of GATA-3 and CTLA-4, and the suppressor function of Treg cells were diminished. IL-21, but not IL-6 or IL-17, blocked the development of Treg cells. IL-21 stimulated mTORC1 and mTORC2, and it abrogated the autophagy, differentiation, and function of Treg cells. Moreover, IL-21 constrained the expression of GATA-3 and CTLA-4 selectively in Treg cells. In turn, blockade of mTORC1 by 3-day rapamycin treatment enhanced transforming growth factor β production, while dual blockade of mTORC1 and mTORC2 by 4-week rapamycin treatment induced autophagy, restored the expression of GATA-3 and CTLA-4, and corrected Treg cell function.

IL-21-driven mTOR activation is a pharmacologically targetable checkpoint of the deficient autophagy that underlies Treg cell dysfunction in SLE.

To describe the course of hand function in women and men during the first 3 years after diagnosis of recent-onset rheumatoid arthritis (RA), to investigate sex differences in hand function, and to study correlations between and within hand function assessments. A total of 276 patients (69% women) with RA of a maximal duration of 12 months were recruited to the study. Hand function was assessed by the Grip Ability Test (GAT) and Signals of Functional Impairment (SOFI). Peak and average grip force over 10 s in the right and left hand was measured by an electronic device. Hand function was affected at diagnosis, but had improved significantly at the 3-months' follow-up and then remained stable (but still affected) in both women and men. As assessed by SOFI, hand function was worse in men than in women, whereas women had significantly lower grip force. GAT, grip force, and SOFI correlated weakly. The average and peak values of grip force correlated strongly, as did the grip force in the right and the left hand.

Hand function was profoundly affected at diagnosis of RA, but improved significantly within 3 months and remained stable (but still affected) over 3 years. As expected, women on average had significantly lower grip force than men.

The inflammatory response following an articular fracture is thought to play a role in the development of posttraumatic arthritis (PTA) but has not been well characterized. The objective of this study was to characterize the acute inflammatory response, both locally and systemically, in joint synovium, synovial fluid (SF), and serum following articular fracture of the ankle. We hypothesized that intraarticular fracture would alter the synovial environment and lead to increased local and systemic inflammation. Synovial tissue biopsy specimens, SF samples, and serum samples were collected from patients with an acute articular ankle fracture (n = 6). Additional samples (normal, ankle osteoarthritis [OA], and knee OA [n = 6 per group]) were included for comparative analyses. Synovial tissue was assessed for synovitis and macrophage count. SF and serum were assessed for cytokines (interferon-γ [IFNγ], interleukin-1β [IL-1β], IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor α) and chemokines (eotaxin, eotaxin 3, IFNγ-inducible 10-kd protein, monocyte chemotactic protein 1 [MCP-1], MCP-4, macrophage-derived chemokine, macrophage inflammatory protein 1β, and thymus and activation-regulated chemokine). Synovitis scores were significantly higher in ankle fracture tissue compared with normal ankle tissue (P = 0.007), and there was a trend toward an increased abundance of CD68+ macrophages in ankle fracture synovium compared with normal knee synovium (P = 0.06). The concentrations of all cytokines and chemokines were elevated in the SF of patients with ankle fracture compared with those in SF from OA patients with no history of trauma. Only the concentration of IL-6 was significantly increased in the serum of patients with ankle fracture compared with normal serum (P = 0.027).

Articular fracture of the ankle increased acute local inflammation, as indicated by increased synovitis, increased macrophage infiltration into synovial tissue, and increased SF concentrations of biomarkers of inflammation. Characterizing the acute response to articular fracture provides insight into the healing process and may help to identify patients who may be at greater risk of PTA.

The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH). Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years. Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET. ClinicalTrials.gov: NCT00491309.

ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results.

Nailfold capillaroscopy (NC) is an important diagnostic tool in systemic sclerosis (SSc). Confirmation of NC as a prognostic factor could facilitate earlier intervention and slow disease progression in SSc. We undertook a systematic literature review to evaluate the prognostic value of NC in predicting SSc disease progression. Standardised searches of EMBASE and MEDLINE were undertaken to identify longitudinal studies of adult subjects with SSc reporting the prognostic value of NC for any aspect of disease progression and/or survival. Non-English, non-original research, animal studies, non-adult studies and non-full length reports were excluded from the analysis (PROSPERO 2017:CRD42017071719). Wide heterogeneity in study design, prognostic factor measurement and study outcomes necessitated a qualitative data synthesis. The "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool was used to assess study quality. Study selection, data extraction and risk-of-bias assessment were each undertaken independently by 2 reviewers and consensus reached where necessary. Of 942 retrieved articles, 18 studies fulfilled the inclusion criteria. The majority of studies (17/18, 94%) reported positive associations between baseline NC appearances (using a variety of qualitative, semi-quantitative and quantitative NC endpoints) and clinical outcomes including digital ulcer (DU) occurrence/healing, survival, disease progression (using domains of Medsger disease severity scale), calcinosis, skin progression, pulmonary arterial hypertension (PAH), and/or a composite analysis of "cardiovascular events". Application of the QUIPS tool identified a moderate-high risk of potential bias in 6/18 studies for study participation, 3/18 studies for study attrition, 10/18 for prognostic factor measurement, 5/18 for outcome measurement, 13/18 for confounders and 13/18 for statistical analyses. Study quality limited the strength of the conclusions drawn from these studies. The most important source of potential bias across the studies was insufficient adjustment for potential confounders; such as existing DU disease in studies evaluating future DU occurrence. Recent work suggests NC evolution is an important predictor of disease progression in SSc.

High levels of potential bias relating to study confounding and statistical analysis make it difficult to draw conclusions regarding the prognostic role of NC in SSc. There is strong evidence supporting an association between NC abnormalities (particularly capillary loss) and disease severity (particularly vascular manifestations such as DU, calcinosis and PAH). Evolution of NC appearances may represent a more important predictor of disease progression which could have important implications for the future use of NC in the routine longitudinal assessment and management of SSc.

Early diagnosis and treatment of Juvenile Idiopathic Arthritis (JIA) is essential to optimize outcomes. Wait times (WTs) to consultation with a pediatric rheumatologist consultation is a Canadian quality measure, with benchmarks set at 7 days for systemic JIA (sJIA) and 4 weeks for other JIA categories. In this study we assess WTs for JIA at a single academic center and describe factors associated with longer WTs. This was a retrospective cohort study of 164 patients enrolled in a pharmacogenetic study in Alberta between 2002 and 2018. Limited chart reviews were conducted to evaluate dates of referral and first rheumatology visit to calculate WTs for receipt of pediatric rheumatology care. Cox proportional hazard models identified factors associated with WTs considering variables at the first pediatric rheumatology visit including: JIA category, age, sex, distance to the pediatric rheumatology clinic, number of active joints, pain and C-reactive protein. The median age at diagnosis was 8.0 years (interquartile range, IQR 3.5, 12.0) and 46% of patients had oligoarticular JIA. Only 18 patients (11%) were from rural locations. The median WT for all patients met the national benchmark (22 days, IQR, 9, 44) with no statistically significant difference between WTs among JIA categories (p = 0.055). Importantly, the majority of sJIA cases met the 7-day benchmark (67%) with a median WT of 1.5 days. Older age was associated with longer WT (HR 0.94, 95% CI 0.89, 0.98, p = 0.005).

Median benchmarks were met, however delays in older patients highlight the need for monitoring WTs.

(1) To evaluate the effect of staged bilateral medial opening wedge high tibial osteotomy (HTO) on established biomechanical risk factors for disease progression and on validated measures of pain and function and (2) To compare outcomes in patients having the second surgery staged within or beyond 12 months of the first surgery. Thirty-seven patients with bilateral varus alignment and medial compartment osteoarthritis underwent staged bilateral medial opening wedge HTO (21 within and 16 beyond 12 months). Patients underwent full-limb standing anteroposterior radiographs to determine frontal plane alignment (mechanical axis angle) and three-dimensional gait analysis to estimate the distribution of load across the tibiofemoral compartments (external knee adduction moment). Patients also completed the Knee Injury and Osteoarthritis Outcomes Scores (KOOS), the Lower Extremity Functional Scale, the Short Form Health Survey and the six-minute walk test (6MWT). Patients (both limbs) were evaluated before and approximately 6, 12 and 24 months after each surgery. There were statistically and clinically significant changes in both limbs that were of similar magnitudes and that remained relatively stable over time postoperatively. Mean (95% CI) improvements in outcomes were as follows. Mechanical axis angle: 9.4° (8.4°, 10.4°) (i.e. average change of both limbs), peak knee adduction moment: -1.7%BW*Ht (-2.1, -1.4 %BW*Ht) (i.e. average change of both limbs), 6MWT: 36.7 m (19.4, 54.0 m), SF-12 Physical Component Summary: 12.0 (8.5, 15.5) and KOOS Pain: 25.4 (19.6, 31.2). Other than the shorter time period to reach maximum benefit of both surgeries, there were no remarkable differences at final assessment between patients having surgeries staged within or beyond 12 months. IV.

The present findings demonstrate that patients with bilateral varus gonarthrosis experience marked improvements in established biomechanical risk factors for disease progression bilaterally (mechanical axis angles and external knee adduction moments), as well as clinically important improvements in patient-important outcomes, after staged medial opening wedge HTO. Current findings suggest no difference in outcomes for patients who have the second surgery staged within or beyond 12 months of the first surgery.

S-adenosylmethionine (SAMe) is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating SAMe in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of SAMe to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee. A randomized double-blind cross-over study, comparing SAMe (1200 mg) with celecoxib (Celebrex 200 mg) for 16 weeks to reduce pain associated with OA of the knee. Sixty-one adults diagnosed with OA of the knee were enrolled and 56 completed the study. Subjects were tested for pain, functional health, mood status, isometric joint function tests, and side effects. On the first month of Phase 1, celecoxib showed significantly more reduction in pain than SAMe (p = 0.024). By the second month of Phase 1, there was no significant difference between both groups (p < 0.01). The duration of treatment and the interaction of duration with type of treatment were statistically significant (ps < or = 0.029). On most functional health measures both groups showed a notable improvement from baseline, however no significant difference between SAMe and celecoxib was observed. Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment.

SAMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. Longer studies are needed to evaluate the long-term effectiveness of SAMe and the optimal dose to be used.

Several trials to test the efficacy of a pharmacological intervention aimed at primary prevention of rheumatoid arthritis (RA) are ongoing or have recently been completed. A common issue in these trials is the severe difficulty with patient recruitment. In order to enhance recruitment, this qualitative study identified barriers and facilitators of individuals at risk of RA to participate in a prevention trial. Individuals at risk of developing RA (ie, arthralgia with anticitrullinated protein antibodies and/or rheumatoid factor without arthritis), who had previously been asked to participate in a prevention trial, participated in focus group discussions (n=18) exploring their facilitators and barriers for trial participation. Thematic analysis identified factors that were important in at-risk individuals' decision about trial participation. The prospect of personal benefit, the acknowledgement of one's symptoms and the desire to contribute to society facilitated trial participation. In contrast, misconception about what it means to be at risk, or about the aim of the prevention trial, negative views on trial medication, and a low perceived urgency to act on the possibility of developing RA versus a high perceived burden of participating in a trial discouraged participation.

To enhance inclusion in trials aimed to prevent RA, the results suggest to use strategies such as optimising education about RA, personal risk, trial aim and trial medication, explicitly addressing misconceptions and concerns, using tools to improve information provision, limiting study burden in trial design and encouraging physicians to mention trial participation.

In trapeziometacarpal osteoarthritis (or rhizarthrosis), there is great controversy over the surgical technique to choose: simple trapeziectomy, resection-interposition arthroplasty, interposition arthroplasty suspension-or arthroplasty with implant or prosthesis. These latter 2 are the most used without consensus in the literature on the technique to choose and without sufficient comparative studies. The objective is to compare the 2 techniques most used today: suspension-interposition arthroplasty and arthroplasty with prosthesis. A prospective study was conducted on 15 patients diagnosed with grade 2-3 rhizarthrosis treated with interposition arthroplasty-suspension (group 1) and 15 with prosthesis (group 2) showing clinical outcomes, advantages and disadvantages of each. The study variables were the visual analogue scale (VAS), the DASH questionnaire, the grip strength, the strength of end to end and end-lateral clamp, the joint balance adduction-abduction and preemption-retropositioning, and the opposition. The 2 groups are from 2 different hospitals operated on by a hand surgeon from the Hand Unit. The follow-up time for all patients included in the study was 12 months. The VAS, DASH and grip strength at 12 months did not show significant differences. As regards the strength of end to end and end-lateral clamp, group 2 showed the highest values in all follow-up periods with statistically significant differences.

Patient selection and surgical experience is essential, given the satisfactory results of both techniques. Arthroplasty prosthesis is reserved for grades 2 and 3, middle-aged patients, good trapezium architecture, and experienced surgeons.

Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs. A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe. Five areas of priority need were identified: increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite of 14 eRA tools included educational slides, best-practice guidance, self‑assessment questionnaires, clinical checklists, a multidisciplinary team training exercise, an interactive patient infographic, and case scenarios. By April 2020, rheumatology professionals in 17 countries had been actively engaged in the eRA programme; in 11 countries, eRA tools were selected by national leaders in rheumatology and translated for local dissemination. A web platform, with country-specific pages, was developed to support access to the translated tools (https://www.evolvingthemanagementofra.com/).

The eRA programme supports comprehensive management of RA across Europe through development and dissemination of practical educational tools. The eRA tools address priority needs and are available free of charge to the rheumatology community.

Patients with hip osteoarthritis often temporize their symptoms with multiple intra-articular steroid hip injections (IASHIs) before undergoing total hip arthroplasty (THA). Although there is recent evidence to suggest that IASHI can lead to an increased risk of future periprosthetic joint infection (PJI), the potential increase in risk of PJI after multiple IASHIs compared with single IASHI remains largely unknown. The aim of the study was to evaluate whether multiple IASHIs are associated with increased risk of PJI compared with single IASHI in THA patients. We evaluated 2 cohorts of patients consisting of 106 patients who received 2 or more IASHI in the year before THA and a matched group of 350 patients who received one IASHI in the 12 months before THA. The single and multiply-injected patient cohorts had an infection rate of 2.0% and 6.6% (7/350 and 7/106), respectively (P = .04, odds ratio 3.30) and average follow-up of 28.9 and 24.2 months. The 2 cohorts did not differ with regard to age, gender, American Society of Anesthesiologist score, presence of diabetes mellitus, or body mass index.

In comparison with patients with single IASHI, multiple IASHIs are associated with an increased risk of PJI significantly higher than the elevated risk reported with single injection before THA. The present study findings would be clinically useful in counseling patients who are considering temporizing their symptoms with multiple IASHIs before undergoing THA.

To determine whether demographic, clinical, and laboratory variables measurable at baseline predict the clinical efficacy or major toxic effects of methotrexate (MTX) therapy in children with chronic arthritis. Patient eligibility criteria: (1) monitored in our unit between 1986 and 1996 with a diagnosis of chronic arthritis and (2) treatment with MTX as the sole second-line agent and for at least 6 months. Outcomes investigated: (1) short-term (6-month) clinical response, (2) complete disease control, (3) disease relapse after MTX discontinuation after complete disease control, (4) aminotransferase elevation, (5) gastrointestinal toxicity. Independent variables that showed significant results with univariate tests or were clinically relevant for each outcome underwent multiple logistic or Poisson regression analyses. Eighty patients were available for analysis. The disease onset subtype was systemic in 37 patients, polyarticular in 20 patients, and oligoarticular in 23 patients (all with polyarticular course: extended oligoarticular subtype). The extended oligoarticular subtype was the best predictor for both the short-term clinical response (odds ratio 6.80, P =.02) and, together with a better functional ability, the complete disease control (rate ratio 3.85, P =.03 and rate ratio 3.29, P =.006, respectively). Patients with this subtype of chronic arthritis tended to have earlier, and more frequently, a disease relapse after MTX discontinuation. Thrombocytosis was the only significant risk factor for liver biochemical abnormalities (rate ratio 2.94, P =.008), whereas no variable yielded significant results for gastrointestinal toxicity.

Patients with extended oligoarticular chronic arthritis were more likely to benefit from MTX therapy and to have a relapse after treatment discontinuation, suggesting that MTX is distinctly more effective in this subset of chronic arthritis.

The CD80/CD86-CD28/CD152 costimulatory pathways transmit signals for CD4+ T cell activation and suppression and are critically involved in the pathogenesis of rheumatoid arthritis (RA). A significant number of CD4+ T cells and macrophages in the rheumatoid synovium express elevated levels of CD80, increasing the potential for costimulation in trans of naive T cells. To determine the effect of blockade of this costimulatory axis in RA, we designed novel CD80-binding peptides and evaluated their therapeutic potential in collagen-induced arthritis (CIA), an animal model of RA. The conserved MYPPPY motif of CD152 adopts a polyproline type II (PPII) helical conformation in the CD80-CD152 complex. The pairing preferences of the critical residues at the CD80-CD152 interface and their propensity to form PPII helices were integrated to design peptides with optimum PPII helical content that selectively block CD80-receptor interactions. The clinical efficacy was tested in DBA/1LacJ mice that were administered the CD80 blocking agents, called CD80-binding competitive antagonist peptides (CD80-CAPs), at the time of immunization with bovine type II collagen or 3 weeks after immunization. A single administration of select CD80-CAPs significantly reduced the clinical, radiologic, and histologic disease severity in CIA. Importantly, administration of CD80-CAPs during activated immune response significantly suppressed disease development by reducing mononuclear cell infiltration in the joints and mediating peripheral deletion of activated CD4+ T cells.

A rationally designed CD80-binding peptide both prevents and suppresses CIA, suggesting a potential application in RA. Apoptosis of activated CD4+ T cells following in vivo blockade suggests that the effects of CD80-CAPs may be long-lasting.

Regeneration of hyaline cartilage has been the focus of an increasing number of research groups around the world. One of the most important outcome measures in evaluation of its success is the histological quality of cartilaginous tissue. Currently, a variety of histological scoring systems is used to describe the quality of osteoarthritic, in vivo repaired or in vitro engineered tissue. This review aims to provide an overview of past and currently used histological scoring systems, in an effort to aid cartilage researchers in choosing adequate and validated cartilage histological scoring systems. Histological scoring systems for analysis of osteoarthritic, tissue engineered and in vivo repaired cartilage were reviewed. The chronological development as well as the validity and practical applicability of the scoring systems is evaluated. The Histological-Histochemical Grading System (HHGS) or a HHGS-related score is most often used for evaluation of osteoarthritic cartilage, however the Osteoarthritis Research Society International (OARSI) Osteoarthritis Cartilage Histopathology Assessment System seems a valid alternative. The O'Driscoll score and the International Cartilage Repair Society (ICRS) II score may be used for in vivo repaired cartilage. The 'Bern score' seems most adequate for evaluation of in vitro engineered cartilage.

A great variety of histological scoring systems exists for analysis of osteoarthritic or normal, in vivo repaired or tissue-engineered cartilage, but only few have been validated. Use of these validated scores may considerably improve exchange of information necessary for advances in the field of cartilage regeneration.

Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. Eighty two patients were included, mean age 55±10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value≥25kg/m

A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25kg/m

Aberrant posttranscriptional regulation of matrix metalloproteinases (MMPs) by microRNA has emerged as an important factor in human diseases. The aim of this study was to determine whether the expression of MMP-13 in human osteoarthritis (OA) chondrocytes is regulated by microRNA. Chondrocytes were stimulated with interleukin-1beta (IL-1beta) in vitro. Total RNA was prepared using TRIzol reagent. Polymerase chain reaction (PCR)-based arrays were used to determine the expression profile of 352 human microRNA. Gene expression was quantified using TaqMan assays, and microRNA targets were identified using bioinformatics. Transfection with reporter construct and microRNA mimic was used to verify suppression of target messenger RNA (mRNA). Gene expression of argonaute and Dicer was determined by reverse transcription-PCR, and expression of protein was determined by immunoblotting. The role of activated MAP kinases (MAPKs) and NF-kappaB was evaluated using specific inhibitors. In IL-1beta-stimulated OA chondrocytes, 42 microRNA were down-regulated, 2 microRNA were up-regulated, and the expression of 308 microRNA remained unchanged. In silico analysis identified a sequence in the 3'-untranslated region (3'-UTR) of MMP-13 mRNA complementary to the seed sequence of microRNA-27b (miR-27b). Increased expression of MMP-13 correlated with down-regulation of miR-27b. Overexpression of miR-27b suppressed the activity of a reporter construct containing the 3'-UTR of human MMP-13 mRNA and inhibited the IL-1beta-induced expression of MMP-13 protein in chondrocytes. NF-kappaB and MAPK activation down-regulated the expression of miR-27b.

Our data demonstrated the expression of miR-27b in both normal and OA chondrocytes. Furthermore, IL-1beta-induced activation of signal transduction pathways associated with the expression of MMP-13 down-regulated the expression of miR-27b. Thus, miR-27b may play a role in regulating the expression of MMP-13 in human chondrocytes.

Aiming to prevent cartilage damage during early osteoarthritis (OA), the therapeutic challenge is to restore and maintain the physiological and functional properties of such a tissue with minimally invasive therapeutic strategies. Accordingly, an in vivo model of early OA in sheep was here treated through three different cell therapies (culture expanded ADSCs, SVF, and culture expanded AECs) thus to preserve the joint surface from the progression of the pathology. Three months after the treatment injections, their performance was assessed through mechanical automated mapping (Young's modulus and cartilage thickness), gross evaluation of articular surfaces, and biochemical analysis of the synovial fluid. No severe degeneration was observed after three months from OA induction. Cartilage mechanical properties were crucial to identify early degeneration. All the treatments improved the macroscopic cartilage surface aspect and reduced pro-inflammatory cytokines in the synovial fluid. Among the three treatments, SVF highlighted the best performance while ADSCs the worst.

Despite that the evaluated experimental time is an early follow-up and, thus, longer trial is mandatory to properly assess treatments effectiveness, the proposed multidisciplinary approach allowed to obtain preliminary, but also crucial, results concerning the reduction in OA signs on cartilage properties, in osteophyte development and in all the inflammatory markers.

Studies have shown that cranberry (Vaccinium macrocarpon) has antiinflammatory and antioxidant effects; however, to our knowledge, the effects of cranberry juice consumption have not been studied in patients with rheumatoid arthritis (RA). The aim of this study was to verify the effect of cranberry juice consumption on several inflammatory biomarkers and on the disease activity of patients with RA. A prospective study was conducted with 41 women diagnosed with RA. The disease activity measured by Disease Activity Score 28 (DAS28) and anticyclic citrullinated peptide (anti-CCP) antibodies, and several inflammatory and biochemical biomarkers were analyzed. The control group (n = 18) maintained their usual diet. The cranberry group (n = 23) consumed 500 mL/d of low-calorie cranberry juice. Regarding the baseline values, the cranberry group presented a decrease in the values of DAS28 (P = 0.048) and anti-CCP (P = 0.034) after 90 d of treatment, whereas changes in inflammatory biomarkers were not found.

The present study indicated that cranberry juice decreases disease activity and therefore has beneficial effects for RA patients, although larger and long-term studies are needed to definitively probe this effect and to clarify the mechanisms involved.

Poor adherence to treatment is difficult to diagnose accurately. Hydroxychloroquine (HCQ) has a long elimination half-life and its concentration in whole blood can be measured easily. To evaluate the utility of a very low blood HCQ concentration as a marker of poor compliance in patients with systemic lupus erythematosus (SLE). HCQ concentrations were determined on a blinded basis in 203 unselected patients with SLE. At the end of the study, the patients were informed of the results and retrospectively interviewed about their adherence to treatment. 14 (7%) patients said that they had stopped taking HCQ (n = 8) or had taken it no more than once or twice a week (n = 6). Their mean (SD) HCQ concentration was 26 (46) ng/ml. range (0-129 ng/ml) By contrast, the other patients had a mean HCQ concentration of 1079 ng/ml range (205-2629 ng/ml). The principal barriers to adherence were related to HCQ treatment characteristics. Adherence subsequently improved in 10 of the 12 patients whose blood HCQ concentrations were remeasured.

Very low whole-blood HCQ concentrations are an objective marker of prolonged poor compliance in patients with SLE. Regular drug assays might help doctors in detect non-compliance and serve as a basis for counselling and supporting these patients.

To determine whether intra- and periarticular cyst-like lesions of the knee are associated with incident knee pain and incident radiographic knee osteoarthritis (OA). The Multicenter Osteoarthritis (MOST) Study is a cohort of individuals who have or are at high risk for knee OA. Using a nested case-control study design, we investigated the associations of cyst-like lesions (Baker's, meniscal and proximal tibiofibular joint (PTFJ) cysts, and prepatellar and anserine bursitides) with (1) incident pain at 15- or 30-month follow-up and (2) incident radiographic OA at 30-month follow-up. Baseline cyst-like lesions were scored semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Conditional logistic regression models were used to assess the relation between these lesions and the outcomes, adjusting for potential confounding factors (i.e., cartilage loss, meniscal damage, bone marrow lesions, synovitis and joint effusion, which were also scored using WORMS). Incident knee pain study included 157 cases and 336 controls. Prevalence of meniscal and PTFJ cysts in the case group was twice that in the control group [9 (6%) vs 9 (3%) and 9 (6%) vs 10 (3%), respectively]. Incident radiographic OA study included 149 cases and 298 controls. Prevalence of grade 2 Baker's cysts and PTFJ cysts in the case group was approximately four times that in the control group [16(11%) vs 9 (3%) and 6 (4%) vs 3 (1%), respectively]. However, none of the cyst-like lesions was associated with incident pain or radiographic OA after fully adjusted logistic regression analyses and correction of P-values for multiple comparisons.

None of the analyzed lesions was an independent predictor of incident knee pain or radiographic OA. Intra- and periarticular cyst-like lesions are likely to be a secondary phenomenon seen in painful or OA-affected knees, rather than a primary trigger for incident knee pain or radiographic OA.

To assess the role of resistin in primary Sjögren's syndrome (pSS) and its relation to local inflammation. Blood and saliva were collected from 37 patients with pSS (duration of symptoms 12.6+/-1 yrs) and 32 healthy controls. Expression of resistin in salivary glands was visualized immunohistologically, and levels of resistin were detected by ELISA. Levels of resistin were evaluated at baseline and following oral dehydroepiandrosterone (DHEA) treatment (50 mg/day). The effect of DHEA treatment on the secretion of resistin was assessed in vitro in human leukocytes after challenge with insulin and lipopolysaccharide. Levels of resistin in saliva were significantly higher in patients with pSS than in controls, while circulating levels of resistin were similar in both groups. Resistin was expressed in the epithelial cells of striated ducts and in the lymphocytic foci. Resistin levels in saliva were related to the intensity of inflammation in the minor salivary glands of pSS patients. No changes of the levels of resistin in blood or saliva were observed during DHEA treatment. Exposure of naive leukocytes to DHEA in vitro induced significant expression of resistin compared to nonstimulated peripheral blood mononuclear cells (p=0.031).

We showed that levels of resistin are upregulated locally in the salivary glands of patients with pSS; and that the levels of resistin correspond to the intensity of lymphocytic inflammation in patients with pSS. We suggest that resistin is expressed in the salivary glands of patients with pSS and may be a driving factor of local inflammation.

The aim was to describe physical and psychosocial health status in a second follow-up of a cohort of patients with chronic childhood arthritis, to compare results from the present study with the first follow-up, and to explore the course of physical and psychosocial functioning from baseline. At a median of 18.3 years after symptom onset 55 patients answered the self-administered questionnaires Health Assessment Questionnaire Disability Index (HAQ-DI), Visual Analogue Scales (VAS) of pain, fatigue and illness, and General Health Questionnaire (GHQ) 30-item version. Results from the current study were compared to first follow-up median 8.7 years after symptom onset, and the course of physical and psychosocial function from baseline was discussed. At second follow-up, 38% reported HAQ-DI above 0 indicating physical disability, 22% had a GHQ-30 score in the clinical range indicating psychiatric distress, and fatigue seemed to be an overarching aspect of the health status. Pain was an important correlate of physical disability at first and second follow-up. At second follow-up psychiatric distress was a significant correlate of pain and fatigue, indicating a relation to disease severity. The association between psychosocial functioning and chronic family difficulties observed at first follow-up is not evident at second follow-up.

The favourable physical and psychosocial outcome reported at first follow-up seems to persist. However, arthritis-related ill-health is still evident in a considerable proportion of the patients, indicating a constant impact of the disease on every-day life of the individual.

The aim of this study was to identify psychological factors that influence moderate-vigorous physical activity (MVPA) participation in patients with fibromyalgia. In this secondary data analysis, 170 patients received personalized exercise plans and completed baseline and follow-up assessments of self-reported physical activity at weeks 12, 24, and 36. Structural equation modeling was used to examine the predictive strengths of psychological factors (exercise self-efficacy, perceived barriers, and intention) on MVPA participation. Using a threshold increase in MVPA of 10 or greater metabolic equivalent hours per week (MET h/wk), 3 groups were defined based on subjects who achieved a minimum increase of 10 MET h/wk that was sustained for at least 12 weeks (SUS-PA), achieved an increase of 10 MET h/wk that was not sustained for at least 12 weeks (UNSUS-PA), and did not achieve an increase of 10 MET h/wk (LO-PA). Increases in exercise self-efficacy and intention and reductions in perceived barriers were associated with increased volume of PA, showing the greatest change in the SUS-PA, followed by UNSUS-PA. For the LO-PA group, there was no change in exercise self-efficacy, a decrease in intention, and an increase in barriers. Using path analysis, exercise self-efficacy and perceived barriers were associated with higher volumes of physical activity via greater intention to engage in MVPA.

For patients with fibromyalgia, exercise self-efficacy, perceived barriers, and intention to exercise are important constructs for increasing physical activity. Our findings provide guidance for practitioners who seek to promote physical activity in fibromyalgia and suggestions for researchers aiming to improve prediction models.

This study examines the relationship between total knee replacements (TKR), total hip replacements (THR) or replacements of either joint (total joint replacement; TJR) due to osteoarthritis and atherosclerosis in a large population-based study. The participants were 2195 men and 2975 women, mean age 76 ± 6 years. The osteoarthritis data were analysed in relation to measures of atherosclerosis, including carotid artery intima media thickness and plaque severity (ultrasound), coronary and aortic calcifications (CT), cerebral white matter lesions (MRI) and a history of previous cardiac and cerebral events. The prevalence of TKR was 223 (4.3%) and THR 316 (6.1%). The presence of TJR in women was associated with a non-significant trend towards increased carotid plaque severity, coronary calcifications and periventricular white matter hyperintensities (PVH) but not with a history of cardiac or cerebral events. No associations were seen in men. When TJR were grouped according to the presence or absence of hand osteoarthritis (HOA) there was a highly significant association in the order -TJR/-HOA < +TJR/-HOA < -TJR/+HOA < +TJR/+HOA, for carotid plaque severity, coronary calcifications and PVH.

The presence of TJR did not show a significant independent association with atherosclerosis but enhanced the strength of the positive association between HOA and subclinical atherosclerosis in women.

Cementless fixation is an alternative to cemented unicompartmental knee replacement (UKR). The aim of this study was to determine if cementless UKR fixation is as good as cemented by comparing the five-year migration measured radiostereometric analysis (RSA) in a randomised controlled trial. Thirty-nine patients were randomised to receive either a cemented or a cementless Oxford UKR and were studied at intervals up to five years to assess migration with RSA and radiolucencies with radiographs. During the first year there was a small and significant amount of migration, predominantly in an anterior direction, of both the cemented (0.24 mm, SD 0.32, p = 0.01) and cementless (0.26 mm, SD 0.31, p = 0.00) femoral components. Thereafter there was no significant migration in any direction. At no stage was there any significant difference between the migrations of the cemented or cementless femoral components. During the first year, particularly the first three months, the cementless tibial components subsided 0.28 mm (SD 0.19, p = 0.00). This was significantly (p = 0.00) greater than the subsidence of the cemented tibial component (0.09, SD 0.19, p = 0.28). Between the second and fifth years there was no significant migration of either cemented or cementless tibial components. At five years radiolucent lines occurred significantly less with cementless (one partial) compared to cemented (six partial and one complete) tibial components.

As, between two and five years, there was no significant migration of cemented or cementless components, and no significant difference between them, we conclude that cementless fixation is as reliable as cemented. It may be better as there are fewer radiolucent lines.

To describe a case of autoimmune exocrinopathy in a child at the age of 3 months who presented with the original diagnosis of recurrent parotitis. This a case report of a 9-year-old girl with recurrent parotitis who was later found to have Sjögren's syndrome. The literature relating to primary Sjögren's syndrome in the pediatric population is reviewed. The patient was seen in the rheumatology and otolaryngology clinics at a university medical center. This study did not address therapy. Diagnosis of Sjögren's syndrome. The patient had xerostomia, an abnormal result of a salivary gland biopsy, SSA and SSB antibodies, and the histocompatibility antigens HLA-B8 and HLA-DR3 that are associated with Sjögren's syndrome.

Primary Sjögren's syndrome should be considered in cases of recurrent parotitis of childhood. More studies are needed to assess the natural history of autoimmune exocrinopathy in children.

The efficacy and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) are well demonstrated. Doses of 4 and 8 mg/kg are used intravenously. The objective of our study was to report the efficacy and safety for a set of patients who had an 8 mg/kg doze of TCZ and for another set who had this treatment first at a dose of 8 followed by 4 mg/kg. All RA patients treated with TCZ in a University Hospital Centre Department of Rheumatology between January 2010 and December 2014 were included. Sixty-three patients received TCZ at a dose of 8 mg/kg and 19 patients received this treatment first receiving a dose of 8 mg/kg decreased to 4 mg/kg. The demographic characteristics, the clinical response and adverse events were reported. At the end of follow-up, 48% of patients were in clinical remission defined by disease activity score based on 28 joints with an erythrocyte sedimentation rate <2.6 in the 8 mg/kg group and 74% of patients in the 8-4 mg/kg. The rates of severe infections were 4.8 per 100 patients-years (PY) in the 8 mg/kg group and 2.9 per 100 PY in the 8 then 4 mg/kg. The infections were mainly pulmonary, ENT and skin infections.

Our study reported the efficacy and safety of the TCZ in patients with RA in 'real life' with the dose of 8 mg/kg or 8 then 4 mg/kg.

Osteoarthritis (OA) is a common disease, and early diagnosis is essential for preventing further cartilage destruction and decreasing severe complications. Ultrasound biomicroscopy (UBM) is sensitive for detecting minute lesions in tissue because of its higher resolution, but its B-mode characterization of the early stage of OA has not been widely studied. The aim of this study was to determine the usefulness of UBM for detecting the early stage of OA using a rabbit model of early OA. Eighteen adult New Zealand White female rabbits were used in this study, which included 12 rabbits that underwent transections of the left anterior cruciate ligament and six control rabbits. At 2, 4, and 6 weeks after surgery, four experimental rabbits and two control rabbits were euthanized. UBM was performed to evaluate the articular cartilage surfaces of the left knee, using a 55-MHz transducer. All the articular cartilage surfaces were independently assessed in blinded fashion by two radiologists for the severity of OA. The value of UBM, interobserver reliability, and the concordance between UBM and pathologic grades were determined. For the first radiologist, the sensitivity, specificity, positive predictive value, and negative predictive value of UBM for the diagnosis of OA were 91%, 83%, 89%, and 86%, respectively. For the second radiologist, the sensitivity, specificity, positive predictive value, and negative predictive value of UBM were 93%, 86%, 91%, and 89%, respectively. The concordance between UBM and pathologic grades for both radiologists was high (κ = 0.72 and 0.76), and the interobserver agreement was high (κ = 0.80).

UBM can be used to evaluate cartilage defects in an animal model, and further study is needed to determine whether this technique can be valuable for detecting early OA in humans.

To evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet's phenotype resistant to conventional and biologic treatment. A multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet's syndrome fulfilling the International Criteria for Behçet's Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations. At 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage.

Our study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet's syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.

The objectives of the present study were to (1) evaluate the accuracy and reliability of native acetabular offset (AO) measurements performed on conventional supine anterior-posterior (ap) pelvis radiographs with reference to computed tomography (CT) in patients with end-stage hip osteoarthritis (OA); (2) determine the minimum and maximum amount of medialization of the center of rotation (COR) simulating different reaming techniques; and (3) identify patients at increased risk of excessive medialization of the COR. A consecutive series of corresponding 131 CT scans and radiographs of patients with primary hip OA was evaluated using validated software for three-dimensional acetabular and femoral measurements. We simulated the implantation of a hemispherical press-fit cup comparing anatomic and conventional reaming techniques and assessed corresponding changes in AO. Standardized ap pelvis radiographs allowed for an accurate and reliable assessment of AO compared with CT. Cup placement in the most lateral position (anatomic reaming technique) resulted in a mean implant-related medialization of 5.9 ± 3.4 mm. Anatomic cup placement did not require reaming to the true floor in 64 hips (49%). With the conventional reaming technique, the total medialization of the COR (implant-related and reaming-related) was 6.8 ± 2.9, with 34% of cases having a medialization ≥8 mm.

The present study highlights the variability of acetabular anatomy in patients with primary OA. AO can be accurately and reliably determined on conventional radiographs and appears to be independent of femoral shape and geometry. Depending on the preferred reaming technique a substantial number of patients appear at risk for excessive cup medialization.

To study the articular cartilage surface curvature determined automatically from magnetic resonance (MR) knee scans, evaluate accuracy of the curvature estimates on digital phantoms, and an evaluation of their potential as disease markers for different stages of osteoarthritis (OA). Knee MR data were acquired using a low-field 0.18T scanner, along with posteroanterior x-rays for evaluation of radiographic signs of OA according to the Kellgren-Lawrence index (KL). Scans from a total of 114 knees from test subjects with KL 0-3, 59% females, ages 21-79 years were evaluated. The surface curvature for the medial tibial compartment was estimated automatically on a range of scales by two different methods: Euclidean shortening flow and boundary normal comparison on a cartilage shape model. The curvature estimates were normalized for joint size for intersubject comparisons. Digital phantoms were created to establish the accuracy of the curvature estimation methods. A comparison of the two curvature estimation methods to ground truth yielded absolute pairwise differences of 1.1%, and 4.8%, respectively. The interscan reproducibility for the two methods were 2.3% and 6.4% (mean coefficient of variation), respectively. The surface curvature was significantly higher in the OA population (KL > 0) compared with the healthy population (KLi = 0) for both curvature estimates, with P values of .000004 and .000006, respectively. The shape model based curvature estimate could also separate healthy from borderline OA (KL = 1) populations (P = .005).

The phantom study showed that the shape model method was more accurate for a coarse-scale analysis, whereas the shortening flow estimated fine scales better. Both the fine- and the coarse-scale curvature estimates distinguished between healthy and OA populations, and the coarse-scale curvature could even distinguish between healthy and borderline OA populations. The highly significant differences between populations demonstrate the potential of cartilage curvature as a disease marker for OA.

We investigated whether the prevalence of primary headaches was higher in patients with primary Sjøgren's syndrome (PSS) than in healthy individuals. This retrospective cohort study included 71 patients with PSS (patients) based on the American European Consensus Classification criteria, and 71 age- and gender-matched healthy subjects (controls). Headaches were classified according to the International Classification of Headache Disorders. We measured depression with the Beck Depression Inventory, and fatigue with the Fatigue Severity Scale. Fifty-one patients and 42 controls had headaches in the previous 12 months (71.8% vs. 59.2%, P = 0.10). Thirty-eight patients and 28 controls had tension type headaches (TTHs) (53.5% vs. 39.4%, P = 0.12). Eight patients (11.3%) and one control had chronic TTHs (P = 0.05). Migraines and migraines with aura were equally prevalent in patients (26.8% and 11.3%, respectively) and controls (28.2% and 15.5%, respectively; P = 0.61).

In general, patients did not have more migraines or headaches than controls. However, patients had more chronic TTHs than controls. Chronic TTHs were not associated with PSS-related autoantibodies, fatigue, depression, abnormalities on magnetic resonance imaging or abnormalities in the cerebrospinal fluid. Patients with PSS did, however, have higher depression and fatigue scores than controls.

To evaluate peripheral production and synovial expression of vascular endothelial growth factor (VEGF) in polymyalgia rheumatica (PMR). Circulating levels of VEGF in PMR (serum concentration and in vitro release by peripheral blood mononuclear cells [PBMC]) were investigated by enzyme-linked immunosorbent assay. Local expression of VEGF in shoulder synovial tissue was investigated by immunohistochemical analysis. Investigations were performed in patients with active, untreated disease and in patients treated with corticosteroids. VEGF serum concentrations were significantly higher in untreated PMR patients than in normal control subjects. During steroid treatment, VEGF serum concentrations reached their lowest level after the sixth month of treatment. PBMC isolated from untreated PMR patients spontaneously secreted a higher amount of VEGF compared with PBMC from control subjects. Corticosteroid therapy did not affect the ability of PBMC to produce VEGF. Immunohistochemical staining performed on shoulder synovial tissue showed VEGF expression in both the lining layer and the sublining area. In 3 of 4 treated patients, no VEGF staining was found in synovial tissue during corticosteroid therapy. VEGF expression correlated with vessel density, but was not associated with alphavbeta3 and alphavbeta5 integrin expression.

Peripheral and local VEGF releases have different responses to steroid treatment in PMR. The lack of response to corticosteroids by peripheral VEGF production supports the hypothesis that systemic involvement is dominant in PMR. At the synovial level, VEGF production is linked to vascular proliferation and is thus directly involved in the pathogenesis of synovitis.

To determine the prevalence and clinical significance of human parvovirus B19 (B19) infection in patients with rheumatoid arthritis (RA). One hundred patients with RA and 94 apparently healthy blood donor controls were enrolled for study. Plasma samples of patients and controls were examined for the presence of anti-B19-specific antibodies by ELISA. B19 DNA was detected in plasma and peripheral blood leukocyte (PBL) samples of all patients and controls as well as in synovial fluid cells of 38 RA patients by nested polymerase chain reaction. Disease activity and clinical manifestations were determined in RA patients with and without markers of B19 infection. IgM anti-B19-specific antibodies were detected in 24.0% of RA patients; B19 DNA was found in plasma and/or PBL, synovial fluid cells in 34.0% (34 patients); in 14.0% of the cases (14 patients) both markers were found. In blood donor controls, anti-B19 IgM antibodies were observed in 16.0% (15 donors) and B19 DNA in 6.4% (6 donors); all donors with detectable B19 genomic DNA were IgM-positive. The disease activity in patients with and without B19 infection was similar, while the frequency of clinical complications was significantly higher in the patients with anti-B19 IgM antibodies. Moreover, liver failure and sicca syndrome were observed in the viremic patients only.

Our study confirms observations regarding a high prevalence of B19 DNA in patients with RA, and a possible role of this viral infection in the pathogenesis of RA.

Bone attrition probably constitutes remodeling of the bone, resulting in flattening or depression of the articular surfaces. Defining bone attrition is challenging because it is an accentuation of the normal curvature of the tibial plateaus. We aimed to define bone attrition on magnetic resonance imaging (MRI) of the knee using information from both radiographs and MRIs, and to assess whether bone attrition is common prior to end stage disease osteoarthritis (OA) in the tibio-femoral joint. All knees of participants in the community-based sample of the Framingham OA Study were evaluated for bone attrition in radiographs and MRIs. Radiographs were scored based on templates designed to outline the normal contours of the tibio-femoral joint. MRIs were analyzed using the semi-quantitative Whole-Organ Magnetic Resonance Imaging Scoring (WORMS) method. The prevalence of bone attrition was calculated using two different thresholds for MRI scores. Inter-observer agreement for identification of bone attrition was substantial for the radiographs (kappa=0.71, 95% CI 0.67-0.81) and moderate for MRI (kappa=0.56, 95% CI 0.40-0.72). Of 964 knees, 5.7% of the radiographs showed bone attrition. Of these, 91% of MRIs were also read as showing bone attrition. We selected a conservative threshold for bone attrition on MRI scoring (> or = 2 on a 0-3 scale) based on agreement with attrition on the radiograph or when bone attrition on MRI co-occurred with cartilage loss on OA. Using this threshold for bone attrition on MRI, bone attrition was common in knees with OA. For example, in knees with mild OA but no joint space narrowing, 13 of 88 MRIs (14.8%) showed bone attrition.

Using MRI we found that many knees with mild OA without joint narrowing on radiographs had bone attrition, even using conservative definitions. The validity of our definition of bone attrition should be evaluated in further studies. Bone attrition may occur in milder OA and at earlier stages of disease than previously thought.

To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE). A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b to serum C3 concentrations. Serum C3 and C4 levels were measured by nephelometry, and blood iC3b levels were measured by a lateral flow assay. SLE disease activity was monitored with the Responder Index 50 instrument of the SLE Disease Activity Index 2000. Relative changes in the iC3b:C3 ratio, levels of anti-double-stranded DNA (anti-dsDNA) antibodies, and use of a supraphysiologic dose of prednisone (>7.5 mg/day) each independently correlated with SLE disease activity, as determined in multilevel multiple logistic regression analyses. Only the iC3b:C3 ratio was significantly associated with clinically meaningful improvements in disease activity among patients with SLE who were receiving a supraphysiologic dose of prednisone. The iC3b:C3 ratio outperformed C3 and C4 levels with regard to discriminating active SLE from inactive SLE, and major flares from no disease activity. The iC3:C3 ratio, anti-dsDNA antibody levels, erythrocyte sedimentation rate, and use of a supraphysiologic prednisone dose were each independently associated with the presence of lupus nephritis, whereas none of these measures was associated with SLE rash. The association of the iC3b:C3 ratio with lupus nephritis was independent of other observed clinical manifestations.

The ratio of blood iC3b to serum C3 concentrations correlates with the extent of SLE disease activity and with clinically meaningful changes in disease activity in patients with SLE. Furthermore, the iC3b:C3 ratio may discriminate between active and inactive SLE, and between major flares and no active disease.

Serum amyloid P component (SAP) and acute phase proteins like C-reactive protein contribute to the clearance of apoptotic cells. This response is diminished in systemic lupus erythematosus (SLE). To analyse SAP concentrations in SLE in relation to disease activity, and investigate whether SAP reacts like an acute phase protein. SAP was measured in 40 patients with SLE during active and inactive disease and compared with healthy controls and patients with rheumatoid arthritis and Wegener's granulomatosis. Normal SAP values were determined in 120 healthy controls by ELISA. C reactive protein and serum amyloid A (SAA) were measured in all subjects and their levels related to SAP. SAP was also measured serially in 11 patients with breast cancer treated with recombinant human interleukin-6, and in 16 patients with sepsis. In SLE, SAP was unaltered compared with healthy controls and was not influenced by disease activity, in contrast to C reactive protein and SAA, which increased during active disease. SAP increased in Wegener's granulomatosis but not in rheumatoid arthritis. The rise in C reactive protein and SAA was most pronounced in Wegener's granulomatosis with active disease. SAP did not change significantly during an acute phase response. No correlation was found between SAP and C reactive protein or SAA, but there was a correlation between SAA and C reactive protein (r = 0.4989, p = 0.0492).

Patients with SLE have normal circulating SAP levels. In contrast to C reactive protein or SAA, SAP does not act as an acute phase protein.

Self-monitoring the disease course is a relatively new concept in the management of patients with inflammatory rheumatic diseases (IRDs). The aims of this pilot study were to obtain patients' experiences with online self-monitoring, to assess information about the agreement between the disease course assessed with patient-reported outcome measures (PROMs) and an objectively measured Disease Activity Score 28 (DAS28) by the rheumatologist, and to assess adherence to predetermined PROM frequency intervals. Observational study using qualitative and quantitative methods. The rheumatology outpatient clinic of a teaching hospital in The Netherlands (secondary care). 47 patients with an IRD who regularly attended the outpatient clinic. Patients completed PROMs by using an online self-monitoring program. Their experiences regarding self-monitoring were qualitatively assessed through a focus group discussion and telephone interviews using a thematic analysis approach. Adherence to the predefined PROM frequency (completed PROM assessments within the predetermined frequency) and the agreement between the DAS28 course and PROM values (Rheumatoid Arthritis Disease Activity Index-5 and the Rheumatoid Arthritis Impact of Disease (RAID)) were quantitatively assessed using descriptives. Forty-seven patients participated, most of them diagnosed with rheumatoid arthritis (n=38, 80.9%). Three themes were identified: knowledge about and insight into the disease (activity), patient-professional interaction and functionality of the program. Mean adherence to the predetermined PROM frequency was 68.1%. The RAID showed the best agreement with the DAS28 course. Mean participation time was 350 days.

Patients were predominantly positive about online self-monitoring. They indicated that they gained more knowledge about their disease, felt less dependent on the healthcare professional and valued the insight into their long-term disease course. Barriers were mostly related to technical factors. Patients were able to and willing to self-monitor their disease, which could contribute to a more efficient allocation of outpatient consultations in the future.

To study if the reported association of a BamH I 2kb RFLP of the T cell receptor V beta 8 gene with DR4+ rheumatoid arthritis patients is found in non-American white populations. The frequency of this RFLP in two different populations was analysed. Eighty one northern Italians were studied for HLA-DR genotypes and V beta 8 polymorphism, and 29 DR4+ British white patients were studied for V beta 8 polymorphism. No association between the V beta 8 RFLP and DR4 was found with rheumatoid arthritis in both groups.

The reported V beta 8-DR4 association is not generally applicable. The lack of association in our populations may be due to genetic differences, or to differences in factors which shaped the T cell repertoire.

To assess the mechanisms contributing to the induction of patellofemoral arthritis (PF-OA). A computed tomography scan was taken at three levels of the lower extremity in full extension and at 30 degrees of flexion. The cuts were superimposed and 12 parameters were compared in 17 PF-OA knees and 27 normal knees to assess the rotation angle of the tibial tubercle. Although the tibial tubercle was in almost the same position in full extension in the normal and PF-OA knees, it was positioned significantly laterally at 30 degrees of flexion in PF-OA knees. Also the articular surface of the lateral femoral condyle was significantly narrower or steeper in PF-OA knees.

Anatomic variations and mechanical abnormalities were identified in the PF-OA knees.

To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic. A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by email and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus. Draft guidance statements approved by the task force have been combined to form final guidance.

These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated.

Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account. Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9).

This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.

Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sleep, psychiatric distress and pain sensitivity in RA. Fifty-nine female RA patients completed questionnaires and underwent pressure pain threshold testing to assess hyperalgesia/allodynia at joint and non-joint sites. Blood samples were taken to measure C-reactive protein (CRP). The association between disease activity, sleep problems, psychiatric distress and pain threshold was assessed using Pearson/Spearman correlations and multivariable linear regression. Disease activity levels, sleep problems and psychiatric distress were compared between RA patients with fibromyalgia and RA patients without fibromyalgia. In unadjusted analyses, CRP was not correlated with pain threshold, but tender joint count was inversely correlated with pain threshold at all sites (P < or = 0.004). Sleep problems were associated with low pain threshold at all sites (P < or = 0.0008). Psychiatric distress was associated with low pain threshold at the wrist and thumbnail (P < or = 0.006). In multivariable linear regression models, CRP was inversely associated with wrist pain threshold (P = 0.003). Sleep problems were inversely associated with pain threshold at all sites (P < or = 0.01), but psychiatric distress was not. Despite differences in pain threshold, CRP levels and sleep problems between RA patients with fibromyalgia and those without fibromyalgia, associations between these variables did not change when patients with fibromyalgia were excluded.

Multivariable models are essential in analyses of pain. Among RA patients, inflammation is associated with heightened pain sensitivity at joints. In contrast, poor sleep is associated with diffuse pain sensitivity, as noted in central pain conditions such as fibromyalgia. Future studies examining pain sensitivity at joint and non-joint sites may identify patients with different underlying pain mechanisms and suggest alternative approaches to treating RA pain.

Although the occurrence of early osteoarthritis (OA) is commonly associated with a history of anterior cruciate ligament (ACL) reconstruction, its exact prevalence in these patients remains unknown. The goal of this study was to review the current literature on long-term radiographic outcome after autologous ACL reconstruction and subsequently perform a meta-analysis to obtain evidence-based prevalences of OA at a mean of 10 years after surgery. In addition, this report aimed at identifying the relationship between meniscal status and the occurrence of radiographic OA in the ACL reconstructed knee. A systematic review of the literature was performed in PubMed MEDLINE, EMBASE and Cochrane Library databases to identify all studies concerning radiographic outcome after autologous ACL reconstruction with a follow-up of minimum 10 years. Meta-analyses were performed to obtain the average prevalence of OA and the difference between patients with and without meniscectomy. Considered study estimates were the log-transformed odds and odds ratios, the latter expressing the effect of meniscectomy on OA. A total of 16 studies could be included for meta-analysis, accounting for 1554 ACL reconstructions performed between 1978 and 1997. Of these knees, 453 (28%) showed radiological signs of osteoarthritis (IKDC grade C or D). Furthermore, 50% of the patients with meniscectomy had osteoarthritis, compared with 16% of the patients without meniscectomy. The combined odds ratio for meniscectomy equals 3.54 (95% CI 2.56-4.91). Level III.

The main finding of this meta-analysis is that the prevalence of radiographic knee OA after ACL reconstruction is lower than commonly perceived. However, associated meniscal resection dramatically increases the risk for developing OA.

Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses. Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0mg/dL. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency. Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the < 300-, 300-, and > 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA < 6.0mg/dL at month 6 was achieved by 35.9% of patients overall: 22.4%, 35.0%, and 48.3% in dosing categories < 300, 300, and > 300 mg, respectively.

This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.

To study, both qualitatively and quantitatively, morning stiffness in consecutive patients attending a rheumatology clinic. A detailed interview from 93 patients with rheumatoid arthritis (RA) and 46 patients with noninflammatory joint disease. Occurrence, duration and severity of morning stiffness were similar in both groups, as was its detailed qualitative description. Patients with RA with active disease had higher severity scores of morning stiffness than those with inactive disease.

Morning stiffness is a poor discriminator between RA and noninflammatory joint disease. Its assessment by a severity score is better than one based on duration.

To evaluate the clinical courses and outcomes of patients with monoarthritis and to investigate the predictive factors of clinical outcomes. A retrospective analysis was performed of 171 patients with chronic monoarthritis at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics, radiographic findings and the clinical course were reviewed. The most commonly involved joints were the knees (24.0%), followed by the wrists (22.8%) and ankles (18.7%). A final diagnosis was established in 74 (43.3%) patients. Thirty-one (18.1%) patients were diagnosed with rheumatoid arthritis (RA), 23 (13.5%) with peripheral spondyloarthritis (SpA), and 19 (11.1%) with Behçet's disease (BD). Among 108 patients who were initially undiagnosed, 85 (78.7%) patients remained with undiagnosed monoarthritis, with relatively shorter symptom durations and requiring less treatment. The initially involved joint was a predictive factor for the final diagnosis: the wrist joint for RA (odds ratio [OR] 11.58, P < 0.001), the ankle joint for SpA (OR 6.19, P < 0.001), and the knee joint for BD (OR 3.43, P = 0.014). Bony erosion at baseline was associated with progression to oligo- or polyarthritis (OR 2.88, P = 0.030) and with radiographic progression.

In patients presenting with monoarthritis, a final diagnosis was established in less than half of the patients, and a majority of undiagnosed patients showed benign clinical courses. The initially involved joint and the presence of erosion at baseline were predictors of the final diagnosis and of clinical outcomes.

In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment.

This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.

Patients with unilateral hip or knee replacements for end-stage osteoarthritis (OA) are at high risk for future progression of OA in other joints of the lower extremities, often requiring additional joint replacements. Although the risks of future surgery in the contralateral cognate joints (i.e., contralateral hip replacement after an initial hip replacement) have been evaluated, the evolution of end-stage hip OA to OA involving the knee joints, and vice versa (i.e., noncognate progression) has not been investigated. Because characterization of OA progression in noncognate joints may shed light on the pathogenesis of multijoint OA, we investigated the pattern of evolution of end-stage lower extremity OA in a large, clinical cohort. Total joint replacement (TJR) was selected as a marker of end-stage OA, and a database comprising all lower extremity TJRs performed at a large referral center between 1981 and 2001 was accessed. Of the 5,894 patients identified, 486 patients with idiopathic OA who underwent hip replacement and 414 who underwent initial knee replacement were analyzed to determine the relative likelihood of subsequent TJRs. Patients with the systemic inflammatory arthropathy, rheumatoid arthritis (RA), were evaluated as a control population because RA progression is not considered to be a primarily mechanically mediated process. The contralateral cognate joint was the most common second joint to undergo replacement in both the OA and the RA groups. However, in OA patients for whom the second TJR was in a noncognate joint, that joint was >2-fold more likely to be on the contralateral limb than on the ipsilateral limb (hip to knee P < 0.001; knee to hip P = 0.013). In contrast, among the RA cohort, the evolution was random and no laterality for noncognate TJR was observed at either the hip or the knee (P = 0.782).

This characterization of end-stage lower extremity OA demonstrates that the disease evolves nonrandomly; after 1 joint is replaced, the contralateral limb is significantly more likely to show progression of OA than is the ipsilateral limb. Thus, OA in 1 weight-bearing joint appears to influence the evolution of OA in other joints. The absence of such laterality in RA suggests that OA progression may be mediated by extrinsic factors such as altered joint loading.

Impaired proprioception accuracy of the knee has been proposed as a local factor in the onset and progression of knee osteoarthritis. Patients with decreased numbers of mechanoreceptors could be more likely to develop arthrosis due to a loss in proprioception of the joint. We aimed to identify and quantify the mechanoreceptors of the posterior cruciate ligament (PCL), the anterior capsule (AC) and the medial meniscocapsular junction (MCJ) in knee arthrosis. PCLs, ACs and MCJs were harvested from 30 patients with Kellgren and Lawrence grades 3 and 4 osteoarthritis (OA), and ten knees taken from five cadavers without OA were used as a control group. PCL degeneration was evaluated with haematoxylin & eosin, and the types and numbers of mechanoreceptors were evaluated using S100 immunostaining. The patient ages in the OA and control groups (n.s.) did not differ. PCL degeneration was more severe in the gonarthrosis group than in the control group (p = 0.04). The numbers of Golgi corpuscles, Ruffini corpuscles, free nerve endings, total nerve endings and small vessels of the PCL were low in the OA group, as were the numbers of Golgi corpuscles, free nerve endings and total nerve endings of the AC. No significant correlation was found regarding the mechanoreceptors of the MCJ between the two groups. Prognostic study, Level I.

The numbers of mechanoreceptors in patients with OA were low in the PCLs and ACs. A loss in proprioception could be a local risk factor in OA. The proprioceptive impact of preserving PCL while performing total knee arthroplasty may not be exaggerated as its thought.

Effect of radiosynovectomy (RS) should be evaluated both by subjective and objective parameters in patients with osteoarthritis and in patients with inflammatory joint disorders not caused by rheumatoid arthritis. A total of 98 joints in 61 patients were investigated. Patients were divided into two groups. The first group included 35 patients with therapy-resistant effusions caused by severe osteoarthritis (46 joints). The second group consisted of 26 patients (52 joints) with ankylosing spondylitis, reactive arthritis, undifferentiated spondylarthropathy, psoriatic arthritis, pigmented villo-nodular synovitis, and recurrent synovitis following surgery. Effect of RS was evaluated by a standardized questionnaire and quantified by T/B-ratios derived from blood pool images prior to and after RS. Within the first patient group suffering from osteoarthritis, 40% showed a good or excellent improvement of clinical symptoms, 51% were unchanged, and in 9% symptoms worsened. Similar results were found in the second patient group. The majority of unchanged results were small finger joints. In contrast, wrist and knee joints showed a better improvement. Good correlation between results of bone scan and patients subjective impression was found in 38% and 67% in the first and the second patient group, respectively.

Radiosynovectomy might be an effective treatment in osteoarthritis and inflammatory joint disorders not caused by rheumatoid arthritis.

To assess how serum concentrations of some cytokines, proteases and their inhibitors and cartilage oligomeric matrix protein (COMP) relate to the evolution of clinical disease and joint damage in early rheumatoid arthritis (RA). Annual assessment was performed in 24 RA patients subdivided into three groups according to disease severity as determined by the radiological progression rate. All patients were followed for 5 yr after inclusion. Functional status, Larsen's radiographic index in hands and feet (joint damage score, JDS) and C-reactive protein (CRP) were assessed annually and compared with interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1Ra), promatrix metalloproteinase 3 (proMMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1) and COMP, which were determined by specific immunological tests. The median JDS was initially between 4.5 and 7. During the study time the progression of JDS was 1 (median) for patients with slow progression, 33 for patients with intermediate progression and 62 for patients with rapid progression. Changes in CRP and proMMP-3 concentrations over time differed significantly between the groups, but no significant difference was observed for IL-1Ra, TIMP-1 or COMP. ProMMP-3 was closely related to CRP at each time point. IL-6 correlated significantly with CRP at the last four annual follow-up examinations. CRP and proMMP-3 correlated with JDS at the last two or three examinations and the combined levels of these markers over 5 yr correlated significantly with joint damage progression (Spearman rank correlation 0.73 and 0.74 respectively). IL-1Ra showed a weak negative correlation with JDS, and COMP tended to correlate with JDS only at the start. The initial proMMP-3 concentration was the only significant variable predicting rapidly developing joint damage, but the predictive value was low.

ProMMP-3 correlated closely at all time points with CRP, but gave little or no additional clinical information regarding inflammation or radiographic progression. IL-1Ra and TIMP-1 showed weaker, acute-phase-like variation, which may reflect pathogenic agonist/inhibitor imbalance in the evolution of RA. COMP, in contrast, did not reflect the inflammatory CRP-related component of the disease or the destructive aspect in this study.

To perform a longitudinal cohort study concerning the capacity of prospectively-collected erythrocyte sedimentation rates (ESR) and scores for physical function, pain, patient global estimate, and routine assessment of patient index data (RAPID3) on a multidimensional health assessment questionnaire (MDHAQ), to recognize incomplete versus adequate responses to methotrexate in rheumatoid arthritis (RA) in one usual care setting, prior to description of RAPID3. All patients were seen in one academic setting, in which MDHAQ scores were collected in all patients at all visits in the infrastructure of care. ESR was collected in all RA patients. All 93 RA patients in whom methotrexate was initiated between 1996 and 2001 with available 5-year follow-up were analyzed. "Incomplete response" was defined as initiation of subsequent biological therapy and "adequate response" as no biological therapy over 5 years. Measures were analyzed at the baseline methotrexate visit and at a subsequent visit: in 30 "incomplete responders" when biological therapy was prescribed; and in 63 "adequate responders 2.6 years after methotrexate initiation (mean interval to biological therapy in "incomplete responders"). ESR fell similarly by 33% to 36% in both groups. MDHAQ scores fell by 56% to 79% over 2.6 years in adequate responders but increased by 0% to 31% in incomplete responders. Median RAPID3 fell from 10.6 to 3.6 (low severity=3.1 to 6, remission≤3) in adequate responders and rose from 14.9 to 16.2 (high severity>12) in incomplete responders.

RAPID3, but not ESR, recognizes incomplete versus adequate methotrexate responses in usual clinical care, and may be useful in busy usual care settings.

Oxidative stress and oxidized high-density lipoprotein (HDL) are implicated as risk factors for cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Yet, how HDL is oxidized and rendered dysfunctional in SLE remains unclear. Neutrophil extracellular traps (NETs), the levels of which are elevated in lupus, possess oxidant-generating enzymes, including myeloperoxidase (MPO), NADPH oxidase (NOX), and nitric oxide synthase (NOS). We hypothesized that NETs mediate HDL oxidation, impairing cholesterol efflux capacity (CEC). Plasma MPO levels and CEC activity were examined in controls and lupus patients, and 3-chlorotyrosine (MPO specific) and 3-nitrotyrosine (derived from reactive nitrogen species) were quantified in human HDL. Multivariable linear models were used to estimate and test differences between groups. HDL was exposed to NETs from control and lupus neutrophils in the presence or absence of MPO, NOX, NOS inhibitors, and chloroquine (CQ). Murine HDL oxidation was quantified after NET inhibition in vivo. SLE patients displayed higher MPO levels and diminished CEC compared to controls. SLE HDL had higher 3-nitrotyrosine and 3-chlorotyrosine content than control HDL, with site-specific oxidation signatures on apolipoprotein A-I. Experiments with human and murine NETs confirmed that chlorination was mediated by MPO and NOX, and nitration by NOS and NOX. Mice with lupus treated with the NET inhibitor Cl-amidine displayed significantly decreased HDL oxidation. CQ inhibited NET formation in vitro.

Active NOS, NOX, and MPO within NETs significantly modify HDL, rendering the lipoprotein proatherogenic. Since NET formation is enhanced in SLE, these findings support a novel role for NET-derived lipoprotein oxidation in SLE-associated CVD and identify additional proatherogenic roles of neutrophils and putative protective roles of antimalarials in autoimmunity.

To study the functional status and health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA) after treatment with celecoxib, compared with placebo and naproxen. This was a prospective, randomized, double-blind, parallel group trial conducted at 79 sites in the United States and Canada over a 12-week treatment period. Patients were randomly assigned to 5 groups: placebo, 100 mg twice a day of celecoxib, 200 mg twice a day of celecoxib, 400 mg twice a day of celecoxib, and 500 mg twice a day of naproxen. The Health Assessment Questionnaire (HAQ) disability index was used to measure functional status. The Medical Outcomes Study Short Form 36 (SF-36) was used to measure general HRQOL. Enrollees were 1,149 patients with diagnosed and active RA. At the end of the treatment period, patients in the 4 active treatment groups had significant improvement in both functional status and overall HRQOL in comparison with the placebo group. Patients in the twice-daily 100 mg celecoxib group significantly differed from placebo at weeks 2 and 6 on HAQ scores and at week 12 on 5 domains and both summary scores of the SF-36. Patients treated with twice-daily 200 mg celecoxib had significantly better functional status than placebo at all times of testing with the HAQ, and also had significantly better function than those treated with naproxen after 2 and 12 weeks of treatment. Patients in the twice-daily 200 mg and 400 mg celecoxib groups showed similar improvement in HRQOL as determined by the 8 domain scores and 2 summary scores of the SF-36.

Celecoxib was better than placebo and comparable with naproxen in improving functional status and overall HRQOL among RA patients.

To assess rheumatologists' opinions about the feasibility of a measurement feedback system in rheumatoid arthritis (RA) and to analyse if motivational aspects play a role in assessing the value of the system and in determining the extent to which it is used. A survey sample (n=105) was randomly selected from participants of a measurement feedback system. A survey questionnaire assessed opinions on system outcome, structures and processes, motivation and overall satisfaction. Survey results are given descriptively and groups differing in motivation are compared. The overall response rate was 62%. The system was generally perceived to fulfil its aims, but the effort required to use the system was rated less positive. Rheumatologists had as their motivation either 'science/obligation' or 'individual patient evaluation'. Rheumatologists with the latter motivation were more satisfied with the measurement feedback system, perceived its feasibility as better, and made more use of it.

Motivation for participating in a measurement feedback system has a significant impact on overall satisfaction with the system and the use of the system. Influencing motivation and reduction of the amount of effort required to use the system might increase overall acceptance.

A retrospective, age- and sex-matched radiographic study. To investigate the spinopelvic alignment in patients with osteoarthosis of the hip (HOA) and those with low back pain (LBP) and to determine the characteristics and differences in both groups. Hip-spine syndrome, first described by Offierski and MacNab, is quite an important pathology when treating patients with pain in their low back and lower extremities. However, despite it being a well-known entity, few papers have adequately investigated and assessed the spinopelvic alignment in patients with hip-spine syndrome. Sagittal and coronal spinopelvic alignments were investigated in 150 patients with HOA and 150 with LBP using radiographs of the whole spine in both anteroposterior and lateral views. Parameters measured in this study were lumbar lordosis (LL), sacral slope (SS), the shift of the sagittal C7 plumb line, pelvic incidence (PI), and pelvic tilt (PT) on the lateral radiographs. On the anteroposterior (AP) films, lumbar scoliosis, pelvic obliquity, leg length discrepancy, the shift of the coronal C7 plumb line, and Sharp angle were measured. These parameters were compared between the two groups. In patients with HOA, the relationships between Sharp angle and other parameters were also analyzed to clarify the possible influence of sagittal and coronal spinopelvic alignments on HOA without acetabular dysplasia. LL, SS, PI, and PO were found to be less in patients with LBP compared with those with HOA, and there was no significant difference in LS between the two groups. PI was significantly greater in HOA patients and strongly correlated to PT, SS, and LL (i.e., as the PI increased so did the PT, SS, and LL). Sharp angles were also significantly greater in HOA patients and strongly correlated to age, LL and SS (i.e., as Sharp angles increased so did LL and SS); however, age decreased in the hip patients.

These findings suggest that higher PI in the younger individual may contribute to the development of HOA in later life without both lumbar kyphosis and acetabular dysplasia because of the anterior uncovering of the acetabulum. More investigation will be expected to analyze the spinopelvic alignment in patients with hip spine syndrome.

To explore the associations between microvascular abnormalities as assessed by nailfold capillaroscopy (NFC) and pulmonary and cardiac involvement in patients with juvenile dermatomyositis (DM) who are assessed after medium- to long-term follow-up. Fifty-eight patients with juvenile DM were examined a mean ± SD of 17.0 ± 10.6 years after symptom onset. Nailfold capillary density (NCD) and a neovascular pattern (defined as an active or late scleroderma pattern) were analyzed, with blinding to clinical data. Pulmonary involvement was assessed by pulmonary function tests including spirometry, diffusing capacity for carbon monoxide (DLco), and body plethysmography. High-resolution computed tomography (HRCT) was also performed. Cardiac involvement was assessed by electrocardiography, Holter monitoring (heart rate variability), and echocardiography. Patients with low NCD (<6 capillaries/mm) (n = 21), compared to patients with normal NCD (≥6 capillaries/mm) (n = 37) had lower forced vital capacity (89.7% versus 98.5% predicted), total lung capacity (87.8% versus 94.5% predicted), and more often had low DLco values (15 [71%] of 21 patients versus 14 [38%] of 37 controls) (all P < 0.05). Use of HRCT to assess airway disease was more frequent in the group with low NCD (6 [30%] of 20 patients versus 3 [8%] of 36 patients in the normal NCD group; P = 0.034). No associations between NCD and cardiac parameters or between neovascular pattern and pulmonary or cardiac parameters were observed.

In patients with juvenile DM, low NCD was associated with lung involvement, which was mostly subclinical. No significant associations with cardiac involvement were observed. These results shed light on possible mechanisms underlying organ involvement, but further and preferably larger studies are needed to identify NCD as a potential biomarker for lung and cardiac involvement in juvenile DM.

To provide insight into the clinical failure of the tumour necrosis factor alpha (TNFalpha) inhibitor, etanercept, in primary Sjögren syndrome (pSS), an extensive analysis of the systemic immune profile of patients with pSS was carried out and the effect of etanercept treatment on these immune parameters monitored. Peripheral blood mononuclear cells of patients with pSS and healthy controls were compared by flow cytometry to determine differences in distribution of specific cell populations (T cells, B cells, monocytes), and to determine their expression of activation markers (CD25, HLA-DR), TNF receptors and chemokine receptors (CXCR1, 2) before and after treatment. Systemic cytokine levels were measured by multiplex ELISA assay in plasma and in lipopolysaccharide-stimulated whole blood from healthy controls and from patients with pSS before and after etanercept treatment. Baseline cytokine levels were correlated with clinical markers of disease. Before treatment, salivary gland inflammatory focus scores did not correlate with circulating TNF levels. Furthermore, consistent with the lack of evidence of significant clinical benefit, enhanced markers of immune activation, frequency of cell subpopulations and aberrant cytokine profiles were not restored to normal levels by etanercept treatment. Remarkably, the levels of circulating TNFalpha were significantly increased after treatment.

Etanercept is an ineffective therapeutic agent in pSS consistent with the absence of suppression of TNFalpha and other indicators of immune activation in this patient population. These data suggest that TNFalpha may not be a pivotal cytokine in the pathogenesis of pSS, impelling continued molecular characterisation of disease parameters to define appropriate intervention targets.

To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus. Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration. Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1-null patients.

Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.

To estimate, from a public payer's perspective, the 5-year cost effectiveness of adding leflunomide (LEF) to a sequence of disease-modifying antirheumatic drugs (DMARDs) representative of a typical rheumatoid arthritis (RA) management approach adopted by Canadian rheumatologists. A DMARD sequence including LEF was compared with one excluding it, using a 5-year simulation model where patients with RA cycle through different treatment regimens. Data were obtained through a systematic literature search (drug withdrawal rates, number and type of adverse events, American College of Rheumatology 20% responder status) and separately conducted surveys (choice of DMARD sequence, management of adverse events). Costs for adverse event management were calculated using the Ontario Schedule of Benefits, and monitoring costs were calculated according to official Canadian product monograph recommendations. Wholesale prices of all drugs were adjusted by the allowable markup and prescription fees. Utilities (as measured by the standard gamble [SG] and rating scale [RS] techniques) were obtained from 482 patients who participated in a 1-year randomized controlled trial that compared LEF, methotrexate, and placebo. Costs and utilities were discounted by 3%. Probabilistic sensitivity analysis was performed. Adding LEF to a conventional strategy of DMARDs increased the 5-year management costs by $1,231 compared with the strategy without LEF, which results in a cost-effectiveness ratio of $13,096 per additional year of response to treatment, and cost-utility ratios of $54,229 (RS) and $71,988 (SG) per quality-adjusted life-year gained.

Adding LEF as a new option to a conventional sequence of DMARDs extends the time patients may benefit from DMARD therapy at a reasonable cost effectiveness and cost utility. LEF data are limited to clinical trials; data from observational studies would be needed to corroborate these findings.

The cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in osteoarthritic (OA) knees. However, to improve outcomes, an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions. To investigate the clinical and second-look arthroscopic outcomes of the implantation of MSCs loaded in fibrin glue as a scaffold in patients with OA knees and to compare these outcomes with those of MSC implantation without a scaffold. Cohort study; Level of evidence, 3. This study retrospectively evaluated 54 patients (56 knees) who were examined with second-look arthroscopy after MSC implantation for cartilage lesions in their OA knees. Patients were divided into 2 groups: 37 patients (39 knees) were treated with MSC implantation without a scaffold (group 1), and 17 patients (17 knees) underwent implantation of MSCs loaded in fibrin glue as a scaffold (group 2). Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed with the International Cartilage Repair Society (ICRS) grade. Statistical analyses were performed to identify various prognostic factors associated with the clinical and second-look arthroscopic outcomes. At final follow-up (mean, 28.6 months; range, 24-34 months), the mean IKDC score and Tegner activity scale in each group significantly improved: group 1, from 38.1±7.7 to 62.0±11.7 (IKDC) and from 2.5±0.9 to 3.5±0.8 (Tegner); group 2, from 36.1±6.2 to 64.4±11.5 (IKDC) and from 2.2±0.8 to 3.8±0.8 (Tegner) (P<.001 for all). According to the overall ICRS cartilage repair grades, 9 of the 39 lesions (23%) in group 1 and 12 of the 17 lesions (58%) in group 2 achieved a grade of I or II. There was a significant difference in ICRS grades between the groups (P=.028). Overweight (body mass index≥27.5 kg/m2) and large lesion size (≥5.7 cm2) were significant predictors of poor clinical and arthroscopic outcomes in group 1 (P<.05 for both). There was a similar trend in group 2, but the differences were not significant, possibly owing to the smaller sample size.

Clinical and arthroscopic outcomes of MSC implantation were encouraging for OA knees in both groups, although there were no significant differences in outcome scores between groups. However, at second-look arthroscopy, there were better ICRS grades in group 2.

To evaluate the prevalence and correlates of anti-pentraxin 3 (PTX3) antibodies in systemic lupus erythematosus (SLE). Serum samples from 130 patients with SLE, 130 age- and sex-matched healthy subjects and 130 patients with other autoimmune rheumatic diseases (oARD) were analysed by home-made ELISAs using as substrate human recombinant PTX3 and two peptides, PTX3_1 and PTX3_2, obtained from the complete protein, identified as potential antigenic sites using the Lasergene DNA program (DNA Star). Inhibition tests were performed to evaluate potential interferences between bovine serum albumin or C-reactive protein and anti-PTX3 or anti-PTX3 peptides, and between antigens and antibodies. Statistical analysis was performed using receiving operating characteristics curves, the Fisher exact test, two-tailed t test and Pearson correlations. Patients with SLE had higher levels and prevalence of anti-PTX3, anti-PTX3_1 and anti-PTX3_2 antibodies than patients with oARD or healthy controls (p<0.001 for all). No differences were observed between patients with oARD and healthy controls. A correlation was found between anti-PTX3 and anti-PTX3_2 antibodies (r=0.615, p<0.001). No association was observed between these antibodies and disease activity. Univariate and multivariate analyses showed that anti-PTX3 and anti-PTX3_2 antibody levels and prevalence were higher in patients without glomerulonephritis and in patients positive for antiphospholipid antibody. All inhibition tests were negative apart from PTX3 against anti-PTX3 antibody or, to a lesser extent, against anti-PTX3_2 antibody, and PTX3_2 against anti-PTX3_2 antibody, all in a dose-dependent manner.

Anti-PTX3 antibodies are significantly prevalent in patients with SLE where they might provide protection from renal involvement. The antigenic properties of PTX3_2 peptide are similar to those of PTX3, suggesting its potential use in further analyses.

There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively.

Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.

The authors relate nine cases of pure traumatic dislocation of the tibio talar joint and propose to evaluate the clinical and radiological results at a long term follow-up (mean 12 years). The series included 9 patients (7 men and 2 women) the average age was 33,2 years. The injury was a road traffic accident in 5 cases. Pure dislocation variety of the ankle joint was medial and posteromedial in 6 cases. Open skin injury was found in 7 cases. The mean follow-up was 12 years (5-19 years). 6 patients were reviewed by the same surgeon, 6 patients were examined clinically and with ankle X-rays. All patients except one were treated by reduction, immobilization with a plaster cast for 6 to 8 weeks. The joint was examined radiographically to detect the presence of tibio talar diastasis and degenerative arthritis. At term we had two very good results and 3 good results (no pain or pain occasionally). We have found in 5 cases a degenerative arthritis to the ankle joint (joint narrowing <50 per cent in 3 cases, > to 50 per cent in 2 cases). No joint instability was noted at revision. Pure traumatic dislocation of the tibio talar joint is a rare injury. Medial and posteromedial variety are not frequent. Immediate gravity is dominated by vascular and septic complications and long term result by degenerative arthritis.

The authors think that closed dislocations need orthopedic treatment (closed reduction and immobilization with a plaster cast for 6 weeks), on the other hand, open dislocation need surgical treatment (reduction, ligamentous reconstruction and immobilization in a plaster cast for 6 weeks).

Small hyaluronan (HA) oligosaccharides displace HA from the cell surface and induce cell signaling events. In articular chondrocytes this cell signaling is mediated by the HA receptor CD44 and includes stimulation of genes involved in matrix degradation such as matrix metalloproteinases (MMPs) as well as matrix repair genes including collagen type II, aggrecan and HA synthase-2 (HAS-2). The objective of this study was to determine whether stimulation of HAS-2 and MMP-3 by HA oligosaccharides is due to the activation of a single, cascading pathway or multiple signaling pathways. Bovine articular chondrocytes were pre-treated with a variety of inhibitors of major signaling pathways prior to the addition of HA oligosaccharides. Changes in HA were monitored by real time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HAS-2 mRNA, HA ELISA and HA accumulation at the cell surface. A 1900 base pair sequence containing the proximal promoter of HAS-2 was inserted into a luciferase reporter construct, transfected into human immortalized chondrocytes and assayed in a similar fashion. While our previous studies demonstrated that HA oligosaccharides stimulate MMP-13 activity via activation of p38 MAP kinase and NF-kappaB, inhibitors of these pathways did not affect the stimulation of HAS-2 mRNA expression. However, inhibiting the phosphatidylinositol-3-kinase pathway blocked HA oligosaccharide-mediated stimulation of HAS-2 yet had no effect on MMP-3. Wortmannin and LY294002 also blocked HA oligosaccharide-induced serine and threonine Akt phosphorylation. Treatment of transfected immortalized chondrocytes with HA oligosaccharides resulted in stimulation of HAS-2 mRNA, activation of Akt and enhanced luciferase activity-activity that was blocked by inhibitors of Akt phosphorylation.

Changes in chondrocyte-matrix interactions by HA oligosaccharides induce altered matrix metabolism by the activation of least two distinct signaling pathways.

The presence of bone marrow lesions (BMLs) has been linked to pain and progression of knee OA. The aim of this study was to determine the relationship between BMLs and longitudinal change in tibial cartilage volume and risk of knee joint replacement in subjects with knee OA. One hundred and nine men and women with symptomatic knee OA were recruited. The same knee was imaged using MRI at baseline and ∼2 years later. Tibial cartilage volume and BMLs were measured. Knee joint replacement over 4 years was determined. The mean age of the subjects at baseline was 63.2 (s.d. 10.3) years. BMLs were present in 66% of the subjects. Cross-sectionally, BMLs were negatively associated with both medial (regression coefficient -121.4; 95% CI -183.8, -859.1; P<0.001) and lateral (regression coefficient -142.1; 95% CI -241.8, -42.4; P=0.01) tibial cartilage volume data. Longitudinally, for every 1-score increase in baseline BML severity (range 0-4), the annual total tibial cartilage loss was increased by 1.14% (95% CI 0.29%, 1.87%; P=0.01). The risk of knee joint replacement over 4 years increased with increasing BML score (odds ratio 1.57; 95% CI 1.04, 2.35; P=0.03).

The prevalence and severity of BMLs are associated with less tibial cartilage volume and greater cartilage loss over 2 years. Moreover, severity of BMLs was positively associated with risk of knee joint replacement over 4 years. This provides further support for the importance of BMLs in identifying those with OA most likely to progress. Identifying factors that prevent or reduce the severity of BMLs may provide an important target in the prevention of disease progression and treatment of OA, and the subsequent need for arthroplasty.

To study maternal and fetal outcome of pregnancy in patients with lupus who were exposed to hydroxychloroquine (HCQ). The case records of women (n = 33) exposed to HCQ during their pregnancies (n = 36) and of 53 control patients from a single lupus pregnancy centre were reviewed to determine lupus activity, obstetric experience, and infant outcome. HCQ was not apparently teratogenic. Lupus activity and obstetric outcome in the two groups were similar.

HCQ continuation is probably safe during pregnancy in patients with lupus, but there is no obvious advantage in commencing treatment.

To quantify peptidylarginine deiminase 2 (PAD2) in SF of RA patients and OA patients, and to determine the association between PAD2 levels, disease activity and inflammatory markers in RA. Blood and SF samples were obtained from 39 RA patients and 40 patients with OA. PAD2 content and PAD activity were measured by means of in-house assays. TNF-α, IL-1β, IL-6, IL-8, IL-10 and IL-12 were measured using flow cytometry. PAD2 levels and PAD activity were higher in SF from RA than OA patients (P < 0.0001 and P = 0.03, respectively), as were all cytokine levels (P < 0.0001-0.05). SF PAD2 levels were higher among anti-CCP-positive patients than among anti-CCP-negative patients (P = 0.005). PAD2 levels in SF from RA patients correlated with disease activity, as assessed by DAS28 (P < 0.005). Moreover, SF PAD2 levels correlated with circulating CRP and anti-CCP levels (P < 0.0006), as well as with leucocyte count, IL-6, IL-8 and IL-10 levels in SF (P < 0.0001-0.02). PAD activity in SF was higher in RA patients than in OA patients, and correlated with PAD2 concentration.

Extracellular PAD2 levels in SF correlate with disease activity in RA patients. Anti-CCP-positive RA patients have higher PAD2 levels in SF than anti-CCP-negative RA patients and OA patients. Since we could demonstrate enzymatically active PADs in SF, we propose that free, extracellular PAD is of pathogenic relevance.

We aimed to determine whether the presence of depression or anxiety is associated with the achieving sustained minimal disease activity (MDA) in patients with psoriatic arthritis (PsA). Adult patients satisfying CASPAR criteria prospectively followed from 2008 to 2017 were included. A standard protocol including physician assessment and patient-reported outcomes defined whether patients achieved sustained MDA, defined when MDA criteria were met for two or more consecutive visits. The presence of depression/anxiety was determined using three definitions: 1) a score of <=38 on the Mental Component Summary score of the SF-36 questionnaire; 2) a score of <=56 on the Mental Health sub-scale score; and 3) rheumatologist's report of a diagnosis or treatment for depression/anxiety. A discrete time-to-event analyses was conducted based on a proportional odds model to identify factors associated with achieving sustained MDA. 743 patients were included in the study. The number of patients identified as having depression/anxiety at baseline was: Definition 1- 331 (44.54%), 2- 364 (48.99%), and 3- 211 (28.4%). 337 patients (45.36%) failed to achieve sustained MDA. The presence of depression/anxiety was associated with reduced probability of achieving sustained MDA with OR=0.30, p <0.0001, OR=0.34, p <0.0001, and OR=0.47, p <0.0001 for Definitions 1, 2 and 3, respectively. Other variables associated with a reduced probability of achieving sustained MDA included the Charlson comorbidity index and fibromyalgia.

Symptoms of anxiety/depression reduce the probability of achieving sustained MDA in PsA. Comprehensive management of PsA should include measures for addressing these comorbidities.

To evaluate the efficacy of intra-articular viscosupplementation therapy with hyaluronic acid for pain relief of knee osteoarthritis, we conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials. We searched systematically for randomized, double-blinded, placebo-controlled trials of hyaluronic acid (hyaluronan and hylan G-F20) for pain relief of knee osteoarthritis. Studies reporting pain visual analogue scale (VAS) differences were included in the meta-analysis. Changes in pain were measured by VAS for placebo and treatment, and summary estimates of the differences between the 2 arms were calculated at 1 week, 5 to 7 weeks, 8 to 12, and 15 to 22 weeks after the last intra-articular injection. Sources of heterogeneity were assessed using information on quality score, type of viscosupplementation, and VAS change in pain with activity or rest. Heterogeneity across the studies was significant in all analyses (P<.01); therefore a random effect model was used. Pain was measured either on activity or at rest. Eleven trials (9 hyaluronan and 2 hylan G-F 20) allowed calculation of the summary estimate of difference in change of VAS pain at 1 week, 6 of the 11 allowed the estimation between 5 to 7 weeks and 8 to 12 weeks, and only 3 at 15 to 22 weeks. The summary estimates of VAS differences between therapy and placebo injection: at 1 week, 4.4 (95% confidence interval [CI], 1.1-7.2); at 5 to 7 weeks, 17.7 (7.5-28.0); at 8 to 12 weeks, 18.1 (6.3-29.9) and at 15 to 22 weeks, 4.4 (-15.3 to 24.1).

Intra-articular viscosupplementation was moderately effective in relieving knee pain in patients with osteoarthritis at 5 to 7 and 8 to 10 weeks after the last injection but not at 15 to 22 weeks.

To assess whether the decrease in medical resource use and cost after diagnosing fibromyalgia, observed in a large primary care population in the United Kingdom can be extrapolated to France. A questionnaire was created based on medical resource use by 2,260 patients diagnosed with fibromyalgia between 01/01/1998 and 31/03/2003 in the General Practice Research Database in the UK. Sixty French experts (general practitioners, rheumatologists) assessed whether the data from that database are in line with their clinical practice and, if not, were asked to provide data reflecting their own experience. The evaluation period went from 4 years before to 4 years after diagnosis using 1-year cross-sections. Evaluated resources were drug use, diagnostics tests, general practitioners and specialist visits, and also paramedical or alternative treatments. Data regarding inpatient care and productivity loss were not collected. Medical resource use if no diagnosis had been established was estimated, so the impact of diagnosis could be evaluated. Whereas costs gradually increase before diagnosis, stagnation in costs occurs in the year after diagnosis, followed by a moderate decrease afterwards. The same trend was observed whether the panel consisted of general practitioners or rheumatologists. The savings made as a result of fibromyalgia diagnosis add up to 126 euros per patient per year for the health care payer. General practitioner visits, diagnostic tests and drug use represent respectively 57%, 23% and 12% of the savings.

Also in France, early diagnosis of fibromyalgia leads to a decrease in resource use and health care costs.

A new myositis-specific autoantibody (anti-p155) directed against transcriptional intermediary factor 1 γ (TIF1γ) has been described as a good marker of cancer-associated myositis (CAM). To analyse the feasibility of detecting this autoantibody in patient serum samples using new assays with commercially available recombinant TIF1γ. The study included 90 Spanish patients with dermatomyositis (DM), classified as clinically amyopathic DM, CAM, or DM without cancer. Anti-TIF1γ antibodies were detected by ELISA and immunoblot techniques and compared with anti-p155 antibody detection by protein immunoprecipitation assays with radiolabelled HeLa cells. The κ coefficient was used to compare the agreement between the different tests. Serum samples from 23 (25.6%) and 20 (22.2%) patients with DM recognised TIF1γ by ELISA and immunoblot, respectively. ELISA (κ=0.91) and immunoblot (κ=0.88) showed excellent agreement with immunoprecipitation analysis (anti-p155). Good concordance (κ=0.91) was also seen between ELISA and immunoblot.

Excellent agreement was found between anti-p155 detected by immunoprecipitation and anti-TIF1γ detected by ELISA or immunoblot. These data indicate that identification of this autoantibody can be reliably performed in a standard laboratory setting, with potential application in clinical practice for cancer screening in adult patients with DM.

To compare the influence of concomitant heeled footwear when wearing a lateral wedged insole for medial compartment of osteoarthritis (OA) of the knee, between everyday walking shoes for outdoor use and socks or flat footwear without a heel for indoor use. A total of 227 outpatients were prospectively randomized and treated with a neutral wedged insole inserted into shoes (placebo with shoes; n=45), a wedged insole inserted into shoes (inserted insole with shoes; n=45), a sock-type ankle supporter with a wedged insole when wearing socks or flat footwear (inserted insole without shoes; n=46), a subtalar strapped insole when wearing shoes (strapped insole with shoes; n=45), and the strapped insole with socks or flat footwear (strapped insole without shoes; n=46). The Lequesne index of knee OA at week 12 was compared with the baseline in each treatment group. Twenty patients withdrew from the study, and the 207 patients who completed the 12-week study were evaluated. At the final assessment, participants wearing the inserted insole without shoes (P=0.003), the strapped insole with shoes (P<0.0001), and the strapped insole without shoes (P<0.0001) demonstrated significantly improved Lequesne index scores in comparison with their baseline assessments. No significant differences were found in the placebo (P=0.16) or the inserted insole with shoes (P=0.2) groups.

Concomitant heeled footwear may decrease the efficacy of an inserted lateral wedged insole. The optimal usage of a lateral wedged insole for knee OA would be the combination with socks or flat footwear without heels.

Despite the growing evidence in the literature there is still a lack of consensus regarding the use of minimally invasive surgical technique (MIS) in total knee arthroplasty (TKA). A prospective, randomized, international multicentre trial including 69 patients was performed to compare computer-assisted TKA (CAS-TKA) using either mini-midvastus (MIS group) or standard medial parapatellar approach (conventional group). Patients from 3 centers (Maastricht, Zwickau, Adelaide) with end-stage osteoarthritis of the knee were randomized to either an MIS group with dedicated instrumentation or a conventional group to receive cruciate retaining CAS-TKA without patella resurfacing. The primary outcome was to compare post operative pain and range of motion (ROM). The secondary outcome was to measure the duration of surgery, blood loss, chair rise test, quadriceps strength, anterior knee pain, Knee Society Score (KSS),WOMAC scores, mechanical leg axis and component alignment. Patients in the MIS group (3.97 ± 2.16) had significant more pain at 2 weeks than patients in the conventional group (2.77 ± 1.43) p = 0.003. There was no significant difference in any of the other primary outcome parameters. Surgery time was significantly longer (p < 0.001) and there were significantly higher blood loss (p = 0.002) in the MIS group as compared to the conventional group. The difference of the mean mechanical leg alignment between the groups was not statistically significant (-0.43° (95% CI -1.50-0.64); p = 0.43). There was no significant difference of component alignment between the two surgical groups with respect to flexion/extension (p = 0.269), varus/valgus (p = 0.653) or rotational alignment (p = 0.485) of the femur component and varus valgus alignment (p = 0.778) or posterior slope (p = 0.164) of the tibial component. ClinicalTrials.gov NCT02625311 8 December 2015.

There was no advantage of the MIS approach compared to a conventional approach CAS-TKA in any of the primary outcome measurements assessed, however the MIS approach was associated with longer surgical time and greater blood loss. MIS-TKA in combination with computer navigation is safe in terms of implant positioning.

To clarify which rheumatoid arthritis (RA) patients benefit most from the anti-receptor activator of nuclear factor-κB ligand antibody denosumab to reduce the progression of joint destruction. We pooled patient data from the 12-month, double-blind, placebo-controlled DRIVE (phase II) and DESIRABLE (phase III) studies. In DRIVE, concomitant treatment was limited to methotrexate, salazosulfapyridine and bucillamine. In DESIRABLE, patients could receive any disease-modifying antirheumatic drug. RA patients were randomised to denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or placebo. Efficacy was assessed by van der Heijde-modified total Sharp score (mTSS), bone erosion score (ES) and joint space narrowing score (JSNS). Change in mTSS was assessed in subgroups stratified by risk factors for radiographic damage if the interaction factor was significant. The pooled analysis included 909 patients. Denosumab reduced worsening of mTSS (mean (SD)) at 12 months in the Q6M (0.88 (3.30), p=0.0024) and Q3M (0.66 (2.16), p=0.0002) groups versus placebo (1.50 (3.73)). This reduction in mTSS progression was due to the change in ES (Q6M, 0.44 (1.89), p=0.0006; Q3M, 0.20 (0.86), p<0.0001) versus placebo (0.98 (2.54)); no effect was observed on JSNS. Anti-cyclic citrullinated peptide (CCP) antibodies, glucocorticoid use and baseline ES showed a significant interaction. Denosumab was particularly effective in patients who were anti-CCP antibody positive (p<0.05). Changes in mTSS versus placebo were observed in all denosumab dose groups, regardless of glucocorticoid use and baseline ES.

Denosumab broadly reduced the progression of joint destruction in RA patients with risk factors for radiographic damage such as especially anti-CCP antibody positivity.

To compare objectively measured physical activity in older adults with symptomatic knee osteoarthritis (OA) with similarly aged adults without osteoarthritis (OA) or knee symptoms from the general population. We included people ages 50-85 years with symptomatic knee OA from the Osteoarthritis Initiative (OAI, n = 491), and ages 50-85 years from the general population using National Health and Nutrition Examination Survey (NHANES, n = 449) data. A uniaxial accelerometer was worn for ≥10 hours/day for ≥4 days in the NHANES group in 2003-2004 and in the OAI group in 2008-2010. We calculated time spent in moderate-to-vigorous physical activity (MVPA in minutes/day) and described differences in MVPA and demographic variables between the samples. We conducted matched-pairs sensitivity analyses to further evaluate the role of potential confounders. Both cohorts had similarly low levels of physical activity in age- and sex-specific strata. Time in MVPA ranged from a median of 1-22 minutes/day in people with symptomatic knee OA, and from 1-24 minutes/day in the general population without OA or knee pain. These results were similar in sensitivity analyses.

Time spent in MVPA was similarly low in those with symptomatic knee OA as in older adults without knee pain or OA.

To propose e-learning methods that address the fundamental problems related to sonographic training in rheumatology. The project was designed for rheumatologists with strong motivation to learn ultrasound. A modular approach was constructed, consisting of a basic 3-day residential course, followed by a 6-month period of web-based tutoring, and culminating in a final 2-day residential course with a formal assessment of competency. The website (http://www.e-sonography.com) was accessed by all 60 participants. A mean of 20 (range 10-80) log-on sessions were registered for each participant, and a mean of 250 min (range 60-600 min) of web access was recorded. A total of 163 sonographic images were submitted by 18 (30%) participants. The majority of the images focused on the following anatomical areas: shoulder 49 (30%), hand 34 (21%) and knee 20 (12%). A total time investment of approximately 14 h was made by the US tutors over the 6-month period for interaction with the participants.

The e-learning methods described in this report represent the first attempt to adopt a novel technique to circumvent several of the inherent barriers to the many facets of teaching musculoskeletal ultrasound to a wide audience.

Large-scale study of traditional Chinese medicine (TCM) usage among patients with rheumatoid arthritis (RA) is lacking. The aim of this study is to evaluate the TCM usage among RA patients in Taiwan. We examined the "registry for catastrophic illness patient dataset" of the National Health Insurance Research Database (NHIRD; n=23 million people) in Taiwan. Patients (n=25,263) newly diagnosed as RA in 2001-2009 were included and then followed-up until the end of 2011. Based on the medical utilization, they were further categorized into TCM users (n= 6891; 27.3%) and non-TCM users (n=18,372; 72.7%). The demographic data and core prescription patterns of the TCM users were analyzed. Compared to non-TCM user, TCM users were younger (mean age: 49.6 versus 54.0 years), had a higher female/male ratio (82.7%/17.3% versus 74.1%/25.9%), resided in more urbanized area. Herbal remedies were the most commonly used therapeutic approach (76.4%), followed by combining acupuncture (21.1%). The frequency of outpatient visits in TCM users was higher across all disease categories except circulatory system. The most commonly prescribed formula and herb was Shang-Jong-Shiah-Tong-Yong-Tong-Feng-Wan and Rhizoma Corydalis, respectively. The analysis of core pattern revealed that Dang-Gui-Nian-Tong-Tang, Shu-Jing-Huo-Xie-Tang, Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Myrrha and Olibanum, were among the most frequently used combinations. RA patients who had anxiety and depression, allergic rhinitis, osteoporosis, menstrual disorder, and menopausal syndrome were prone to have more TCM visits compared to non-TCM users.

Our population-based study revealed the high prevalence and specific usage patterns of TCM in the RA patients in Taiwan. The information could be used for further pharmacological investigation and clinical trials.

The aim of this study was to determine whether there is a relationship between disease experience of rheumatoid arthritis and periodontal disease. 1,412 individuals attending the University of Queensland's School of Dentistry were assessed for the prevalence of periodontal disease and rheumatoid arthritis. Analysis of data obtained from a self-reported health questionnaire and dental records was carried out and included: number of individuals referred for advanced periodontal care (test group); number of individuals attending for routine dentistry; determination of rheumatoid arthritis, cardiovascular disease and diabetes mellitus through self-reporting and assessment of prescription medications; assessment of periodontal disease through assessment of existing oral radiographs. In patients referred for periodontal treatment, the prevalence of self-reported rheumatoid arthritis was 3.95% which is significantly higher than that seen in patients not referred for periodontal treatment (0.66%) and also that reported in the general population (1%). Of those referred patients with rheumatoid arthritis, 62.5% had advanced forms of periodontal disease. These results were mirrored in the results of the self-reported prevalence of cardiovascular disease and diabetes mellitus which was consistent with the published higher prevalence in periodontal patients.

Based on data derived from self-reported health conditions, and not withstanding the limitations of such a study, we conclude that there is good evidence to suggest that individuals with moderate to severe periodontal disease are at higher risk of suffering from rheumatoid arthritis and vice versa.

It was hypothesized that the respective protein profiles of bovine cartilage from sites of localized mild to moderate (GI to GII) degeneration versus adjacent sites of intact tissue would vary in accordance with the tissue microstructural changes associated with a pre-osteoarthritic state. A total of 15 bovine patellae were obtained for this study. Paired samples of tissue were collected from the lateral region of each patella. If the patella contained a site of degeneration, a paired tissue set involved taking one sample each from the degenerated site and the intact tissue adjacent to it. Sufficient tissue was collected to facilitate 2 arms of investigation: microstructural imaging and proteome analysis. The microstructural analysis used a bespoke tissue preparation technique imaged with differential interference contrast optical microscopy to assess fibrillar scale destructuring and underlying bone spicule formation. An iTRAQ-based proteome analysis was performed using liquid chromatography-tandem mass spectrometry to identify the differential levels of proteins across the intact and degenerated cartilage and further, the results were validated with multiple reaction monitoring assay. In the healthy cartilage pairs, there was no significant variation in protein profiles between 2 adjacent sample sites. In pairs of tissue that contained a sample of GI/GII tissue, there were both significant microstructural changes as well as the difference in abundance levels of 24 proteins.

From the known functions of the 24 proteins, found to be strongly aligned with the specific microstructural changes observed, a unique "proteins ensemble" involved in the initiation and progression of early cartilage degeneration is proposed.

Femoral prosthesis design may impact the frequency of mid-thigh pain. We compared current, incidental, and persistent mid-thigh pain between the short-stem, Collum Femoris femur prosthesis, and the wedge shaped straight-stem, Zweymüller femur prosthesis and studied the associations between demographics, radiographic measurements, and mid-thigh pain. We contacted patients from a randomized controlled trial who underwent uncemented total hip arthroplasty (THA) for hip osteoarthritis at a mean follow-up of 44 months (range 24-64 months). Patients were specifically assessed for current (during assessment), incidental (any time postoperatively for >1 week) mid-thigh pain, and persistent (any time postoperatively for >2 years) mid-thigh pain. Furthermore, we used regression analysis to study associations between demographics, radiographic measurements, and mid-thigh pain. One hundred forty of 150 patients (93%) responded to our assessment. Mean age at the time of operation was 62 years (±7.0). Current mid-thigh pain occurred in 16 patients (23%) in the Collum Femoris Preserving (CFP) group compared with 10 patients (14%) in the Zweymüller group (P = .192). Incidental mid-thigh pain occurred in 24 patients (34%) in the CFP group compared with 15 patients (21%) in the Zweymüller group (P = .090). Persistent mid-thigh pain was found in 13 patients (19%) in the CFP group compared with five patients (7%) in the Zweymüller group (P = .043). Varus malalignment (odds ratio 1.819 [95% confidence interval 1.034-3.200]) and leg lengthening (odds ratio 1.107 per cm lengthening [95% confidence interval 1.026-1.195]) showed significant associations with mid-thigh pain.

We found more persistent mid-thigh pain after short-stem uncemented THA compared to wedge-shaped straight-stem uncemented THA during medium-term follow-up. Varus malalignment and leg lengthening were associated with mid-thigh pain.

This paper describes the evolutionary changes in morphology and orientation of the PFJ using species present through our ancestry over 340 million years. 37 specimens from the Devonian period to modern day were scanned using a 64-slice CT scanner. 3D geometries were created following routine segmentation and anatomical measurements taken from standardised bony landmarks. Findings are described according to gait strategy and age. The adoption of an upright bi-pedal stance caused a dramatic change in the loading of the PFJ which has subsequently led to changes in the arrangement of the PFJ. From Devonian to Miocene periods, our sprawling and climbing ancestors possessed a broad knee with a shallow, centrally located trochlea. A more rounded knee was present from the Paleolithic period onwards in erect and bipedal gait types (aspect ratio 0.93 vs 1.2 in late Devonian), with the PFJ being placed lateral to the midline compared to the medial position in quadrapeds. The depth of the trochlea groove was maximal in the Miocene period of the African ground apes with associated acute sulcus angles in Gorilla (117°) becoming more flattened towards the modern human (138°).

The evolving bipedal gait lead to anteriorisation of the patellofemoral joint, flattening of the trochlea sulcus, in a more lateral, dislocation prone arrangement. Ancestral developments might help explain the variety of presentations of anterior knee pain and patellofemoral instability.

Joint hypermobility when associated with symptoms in the absence of systemic rheumatologic disease is termed as benign joint hypermobility syndrome (BJHS). BJHS is often an under-recognised and a poorly managed entity. Indian studies on BJHS are very few and none have been carried out in any of the service rheumatology centres. Hence this retrospective study was carried out at a tertiary medical institute of the Indian Army to assess the varied clinical profile of BJHS. All patients consecutively diagnosed as BJHS at the rheumatology clinic of the Army Hospital (Research and Referral) Delhi from May 2010 to May 2011 were included in the study. Their age, sex, presenting features, clinical profile, laboratory and radiological parameters were studied. The mean age of these patients was 30 ± 5.71 years with a median duration of symptoms of 42 (06-120) months. There were 45 males and 39 females (male : female = 1.15 : 1.00). The median Beighton's score in these patients was 6/9 (range 4-9). Most of our patients were military personnel (43/84), and all had knee joint pain with evidence of degenerative changes in 19 and synovitis in two patients. Eleven patients including nine military personnel had evidence of soft tissue rheumatism with associated fibromyalgia in four and anxiety disorder in one. Out of 18 patients with a Beighton's score of ≥ 7, nine had incidental findings of lateral head tilt on frontal observation. There was evidence of carpal tunnel syndrome in a patient with wrist synovitis and one patient had associated skin laxity without features of Ehlers-Danlos syndrome.

BJHS is often under-recognized in clinical practice and is usually missed because of a lack of awareness. A high index of clinical suspicion to diagnose this entity is essential due to its associated morbidities, especially among those exposed to strenuous physical activities.

Volumes of inflamed synovial membrane determined by magnetic resonance imaging (MRI) are closely related to histopathological synovitis and may predict erosive progression in rheumatoid arthritis (RA). However, after IV injection, leakage of MRI contrast from the synovium gradually compromises the differentiation of synovium from joint fluid. To determine the time period after IV MRI contrast (gadolinium-DTPA (Gd)) injection in which synovial membrane volume determination is reliable. MRI of five RA knees with clinical synovitis was carried out, with axial, T(1) weighted, spin echo images before IV Gd injection and every 1.75 minutes for 60 minutes post-Gd. By a semiautomated "signal enhancement threshold" method, including voxels with >35% or >45% relative post-Gd enhancement, synovial membrane volumes were estimated at each time point. At 4.25 minutes post-Gd, volumes were also determined by a more accurate but time consuming "manual method". The initially observed synovium-effusion borderline remained clearly visible, and on the same location, within at least the initial 11 minutes post-Gd (that is, within the normal time frame of post-Gd imaging in RA) but started blurring and moving centripetally thereafter. Compared with volumes at all other time points, synovial membrane volumes at 0.75 and 2.50 minutes post-Gd were significantly lower (Wilcoxon-Pratt), suggesting that some synovial membrane areas had not yet exceeded the enhancement threshold. Thereafter, the measured volumes remained practically unchanged.

This study suggests that MR image acquisition in arthritic knee joints should be performed within the initial approximately 10 minutes after gadolinium contrast injection to achieve the most accurate distinction between synovium and joint fluid but that small time variations are not of major importance to the measured synovial membrane volumes.

To investigate the presence of anti-Ro/SSA and anti-La/SSB antibodies in the tear fluid and serum of patients with Sjögren's syndrome and to evaluate the association of these autoantibodies with the severity of keratoconjunctivitis sicca. Tear fluid and serum were obtained from 28 patients with Sjögren's syndrome and 17 age matched normal control subjects. Evaluation of tear fluid and sera anti-Ro/SSA and anti-La/SSB levels was done by using a quantitative enzyme linked immunosorbent assay kit designed for the quantitative measurement of IgG class autoantibodies directed against highly purified SSA and SSB antigens. Tear function and ocular surface were evaluated by Schirmer I test, tear break up time, and rose bengal staining. Dry eye symptom scores were recorded. Increased levels of anti-Ro/SSA and anti-La/SSB antibodies were detected in sera of 57.1% and 50% of SS patients, respectively. Six patients had increased levels of anti-Ro/SSA in the tear fluid, in one case anti-Ro/SSA being detected in tear fluid when it was negative in serum. Ten patients had positive anti-La/SSB titres in tear fluid and in four of these patients, anti-La/SSB titres were not elevated in serum. A positive correlation was observed between serum and tear fluid titres of anti-Ro/SSA (r = 0.43, p = 0.02), but not of anti-La/SSB. Serum anti-Ro/SSA and anti-La/SSB concentrations correlated positively with dry eye symptom scores (r = 0.42, p = 0.02 and r = 0.48, p = 0.01, respectively) and negatively correlated with Schirmer I test scores (r = -0.39, p = 0.04 and r = -0.40, p = 0.03, respectively). Significant correlations were found between tear anti-La/SSB concentrations and dry eye symptom score (r = 0.56, p = 0.02) and also rose bengal staining scores of the ocular surface (r = 0.44, p = 0.02).

This study shows that autoantibodies against Ro/SSA and La/SSB antigens are present in the tear fluid of some patients with SS and their presence in serum or tear fluid is associated with the severity of keratoconjunctivitis sicca. Additional measurement of tear fluid levels of anti-Ro/SSA and anti-La/SSB may serve as a valuable diagnostic indicator of SS.

To compare the clinical outcomes of osteoarthritis indices (WOMAC and Lequesne scores) and adverse events in the treatment of osteoarthritis (OA) of the knee with platelet-rich plasma (PRP) versus hyaluronic acid (HA) or placebo. A systematic review and meta-regression were performed to compare outcomes between PRP injections versus HA or placebo. Relevant randomized control trials were identified from Medline and Scopus from date of inception to 13 August 2015. Nine of 551 studies were eligible; 6, 5, 5, 5, 2, 2, 2 and 7 studies were included in pooling of WOMAC total, pain, stiffness and function scores, Lequesne score, IKDC score, EQ-VAS score and adverse events in OA knee patients, respectively. The PRP injections had -15.4 (95 % CI -28.6, -2.3, p = 0.021), lower mean WOMAC total scores, and 8.83 (95 % CI 5.88, 11.78, p < 0.001), 7.37 (95 % CI 4.33, 10.05, p = 0.021) higher mean IKDC and EQ-VAS scores when compared to HA injections. However, PRP injections had no significant differences in WOMAC pain, stiffness and function scores, as well as Lequesne score and adverse events when compared to HA or placebo. I.

In short-term outcomes (≤1 year), PRP injection has improved functional outcomes (WOMAC total scores, IKDC score and EQ-VAS) when compared to HA and placebo, but has no statistically significant difference in adverse events when compared to HA and placebo. This study suggests that PRP injection is more efficacious than HA injection and placebo in reducing symptoms and improving function and quality of life. It has the potential to be the treatment of choice in patients with mild-to-moderate OA of the knee who have not responded to conventional treatment.

The aim of the present study is that of characterizing, for the first time in a quantitative way, from a biochemical, physico chemical and functional point of view P2X(1) and P2X(3) purinergic receptors in bovine chondrocytes. The affinity and the potency of typical purinergic ligands were studied through competition binding experiments and their role in modulating chondrocyte actvities was investigated by analyzing nitric oxide (NO) and prostaglandin E2 (PGE(2)) release. Saturation, competition binding experiments, western blotting and immunohistochemistry assays on the P2X(1) and P2X(3) purinergic receptors in bovine chondrocytes were performed. Thermodynamic analysis of the P2X(1) and P2X(3) purinergic binding was studied to investigate the forces driving drug-receptor coupling. In the functional assays (NO and PGE(2) release) the potency of purinergic agonists and antagonists was evaluated. Bovine chondrocytes expressed P2X(1) and P2X(3) purinergic receptors and thermodynamic parameters indicated that purinergic binding is enthalpy- and entropy-driven for agonists and totally entropy-driven for antagonists. Typical purinergic agonists such as adenosine 5'-triphosphate (ATP) and alpha,beta-methyleneATP were able to increase NO and PGE(2) release. A purinergic antagonist, A317491, was able to block the stimulatory effect on functional experiments mediated by the agonists.

These data demonstrate for the first time the presence of functional P2X(1) and P2X(3) purinergic receptors in bovine chondrocytes. Agonists and antagonists are thermodynamically discriminated and are able to modulate functional responses such as NO and PGE(2) release. These results suggest the potential role of novel purinergic antagonists in the treatment of pathophysiological diseases linked to the inflammation and involved in articular cartilage resorption.

Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T Significant differences in the SIR and T

We evaluated the SIR and T

Macrovascular disease in scleroderma has recently been described in two comparative studies. The aim of this study was to map its anatomical distribution. In a retrospective cohort study of 20 scleroderma patients, the results of Doppler studies of arteries in the limbs, neck, and abdomen were compared with those from 20 cohort negative patients. The latter were matched for age, sex, and the presence/absence of hypertension, hyperlipidaemia, smoking, and diabetes status. Arteries were compared quantitatively using a body surface area adjusted measurement of intraluminal diameter, and qualitatively using descriptive characteristics of the arterial walls. The latter were binomially categorised under three non-exclusive headings--thickening, stenosis, and calcification. The ulnar arteries in scleroderma patients were significantly narrower than those of the negative cohort. The arterial walls were also characterised by smooth thickening along their entire length. The characteristics of the other arteries, including those of the lower limbs, were not significantly different from those of the negative cohort.

The ulnar artery seems to be specifically targeted in patients with scleroderma. Assessment of the ulnar artery should be considered in these patients by means of a modified Allen's test or Doppler sonography especially in the presence of digital gangrene.

Patients undergoing total knee replacements constitute a suitable population to study the natural history of traumatic joint injuries. We studied all the patients who received a TKA (Total knee arthroplasty) over the course of one year, in five different centers. The study included 474 patients who had undergone primary TKA for knee OA over a one-year period. In each patient, we analyzed age, sex, side of operation, weight, height and body mass index (BMI, kg/m2). BMI were stratified into four groups according to the WHO classification: normal (<25), overweight (>25 and <30), obese (>30 and <40), and morbidly obese (>40). In the TKA group, 74% of the patients were women, while in the THA group the percentage of men and women was similar. No differences were found in the sides operated on. Differences between both groups were found in knee alignment. Women were operated on more frequently for TKA, as there was a higher incidence of OA of the knee joints in women aged over 65.

Patients who required a total knee arthroplasty are likely to have previously undergone surgery or trauma to the knee joints.

The effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level. A total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay. Serum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate.

Patients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity.

The treatment of knee arthritis with coexistent bone or joint sepsis is challenging. Despite the condition causing considerable morbidity, there is no generally agreed-upon approach to its treatment. We used aggressive débridement of the knee and implantation of intraoperatively molded articulating antibiotic cement spacers with 4 g vancomycin and 2 g streptomycin per bag of cement for patients with unknown organisms as a first stage. When the infecting organism was known, organism-specific antibiotics were used. For fungal infections, 400 mg amphotericin B was added per bag of cement. This was followed by TKA as a second stage once soft tissues had healed 2 to 29 months later, (mean, 6 months) and return of laboratory parameters to within a normal range. One patient underwent two débridement and spacer procedures for suspected persistent infection. To determine whether this approach resulted in adequate control of infection and satisfactory scores for pain and function, we retrospectively reviewed 15 patients who presented with infected arthritic knees between 2001 and 2009; all patients with infected arthritic knees were treated with this same technique during this period. We assessed knee ROM, Knee Society scores, WOMAC scores, and VAS scores preoperatively and during followup. Followup was at a mean of 4 years (range, 2-7 years); No patient was lost to followup before 2 years. Two of the 15 patients were comfortable with the spacers and declined a more definitive reconstruction, and no patient had a recurrent infection after TKA. Before spacer placement, the mean ROM was 103.° (range, 60°-150°), with the spacers in place it decreased to a mean 87° (range, 60°-135°), and after TKA it improved to a mean of 115° (range, 75°-150°). The mean Knee Society Knee and Function scores progressed from 41 and 43 preoperatively to 85 and 83 at latest followup, respectively. The WOMAC scores improved from 51 initially to 18 after TKA. The mean VAS scores improved from 66 preoperatively to 18 after the TKA.

In this small proof-of-concept series, we found that joint débridement and use of intraoperatively molded articulating antibiotic cement spacers as part of a staged approach to treat the infected arthritic knee before TKA resulted in infection control in all patients at a minimum of 2 years' followup, reduction of knee pain, and restoration of knee function. We suggest that larger, comparative series be performed to further validate these results.