Datasets:

austin

/

rheum_abstracts

like 0

Follow

Austin Health 2

Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes. In a longitudinal study, BMD in Swedish AS patients, 50 ± 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes. Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, β = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (β = 3.15, p = 0.012).

The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.

Fibromyalgia (FM), characterized by wide-spread diffuse pain and sensory abnormalities, is associated with elevated indices of distress and pain-related catastrophizing compared to both pain-free samples and those with chronic pain conditions. Catastrophizing is a pervasive negative mental set, and is a strong predictor of negative pain-related outcomes such as clinical pain intensity, and physical disability. Situational catastrophizing, measured in the context of experimentally-induced pain, is strongly related to enhanced pain sensitivity, a core aspect of the pathophysiology of fibromyalgia. However, little is known regarding the temporal course of the association between catastrophizing and pain-related "outcomes". Most studies involve only static assessments of pain and catastrophizing at a single time point, which provides little insight into the direction of the observed associations. We sought to investigate the temporal relationships between catastrophizing and indices of both clinical pain (substudy 1) and experimentally-induced pain (substudy 2) in a larger randomized controlled longitudinal trial. Fifty-seven patients with FM completed catastrophizing, depression, and pain questionnaires as well as laboratory cold pressor pain testing at baseline, post-intervention and three month follow-up during a lifestyle physical activity study. Cross-lagged panel analyses were used to address these temporal relationships. In substudy 1, analyses revealed that pre-to-post changes in dispositional catastrophizing ratings prospectively accounted for unique variance in subsequent post-to-follow-up changes in clinical pain ratings (p = 0.005), while pre-to-post changes in pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. An identical pattern was observed experimentally in substudy 2, with pre-to-post changes in situational catastrophizing ratings prospectively accounting for unique variance in subsequent post-to-follow-up changes in experimental pain ratings (p = 0.014), while pre-to-post changes in pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. Specifically, initial alterations in catastrophizing were associated with subsequent alterations in clinical and experimentally induced pain. Controlling for levels of depression did not affect the results. clinicaltrials.gov: NCT00383084.

These findings provide empirical evidence that catastrophizing processes might precede and contribute to subsequent alterations in the pain experience for FM patients.

While cross-sectional and retrospective case-control studies suggest that gout is associated with knee osteoarthritis (KOA), no prospective study has evaluated the risk of total knee replacement (TKR) for KOA in association with gout. We prospectively evaluated the association between gout and the risk of TKR due to severe KOA. We used data from the Singapore Chinese Health Study (SCHS), a prospective cohort with 63,257 Chinese adults aged 45-74 years at recruitment (1993-1998). Self-report of physician-diagnosed gout was enquired at follow-up I interview (1999-2004) from 52,322 subjects. TKR cases for KOA after follow-up I were identified via linkage with nationwide hospital discharge database through 31 December 2011. Multivariable Cox proportional hazards regression model was applied with adjustment for potential risk factors of KOA. Among 51,858 subjects (22,180 men and 29,678 women) included in this analysis, after average 9.7 follow-up years, there were 1,435 cases of TKR. Gout was associated with 39% higher risk of TKR in women [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.08-1.79] but not in men (HR 0.78; 95% CI 0.49-1.23). The positive gout-TKR association in women remained after excluding participants with self-reported history of arthritis (HR 1.57; 95% CI 1.04-2.37). This association was stronger in women who were lean (body mass index [BMI] < 23 kg/m

Gout is associated with risk of severe KOA, especially in lean women, suggesting the crystal arthritis may play a role in the pathogenesis or progression of OA.

To assess, using both qualitative/inductive and quantitative data, whether people with rheumatoid arthritis (RA) have schemas related to arthritis. Themes identified from interview and focus group transcripts were used to develop 1) questionnaire items, and 2) statements participants were asked to recall during home interviews. Two hundred one people with RA completed questionnaires and recall tasks of the type used in cognitive research, followed 10 days later by another recall assessment by telephone. Qualitative methods, item-level questionnaire data, and category-level recall data yielded convergent results supporting 4 final categories: mastery, support, loss of independence, and depression. Regression analyses indicated that category of earlier recollections predicted subsequent recollections assessed via phone.

Results from widely different methods offer at least partial support for arthritis schemas and suggest that the concepts identified are meaningful to patients as well as to researchers.

Atherosclerosis is emerging as one of the most important causes of morbidity and mortality among patients with different rheumatologic disease. Endothelial dysfunction may be an early sign of atherosclerosis. To evaluate the occurrence of endothelial dysfunction in children with autoimmune diseases, including juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and dermatomyositis, using a novel noninvasive technique. The study group consisted of 24 children with autoimmune diseases, and was compared to a control group of 17 healthy, age- and BMI-matched controls. Endothelial function was assessed by a noninvasive technology that captures a beat-to-beat plethysmographic recording of the finger arterial pulse-wave amplitude with pneumatic probes, utilizing a Peripheral Arterial Tonometry (PAT) device. In the study group, 7 out of the 24 (29%) patients had evidence of impaired endothelial function, compared to 1 out of 17 (6%) children in the control group (p <0.05). Thirty-three per cent of our patients with SLE and 23% of patients with JIA had impaired endothelial function. There were no differences between the two groups of patients with and without endothelial dysfunction as to age, body mass index, fasting glucose level, triglycerides, cholesterol, and dose and duration of steroid treatment. The patients with normal endothelial function had higher systolic blood pressure compared with the group with impaired endothelial function (112.82 ± 7.65 vs13.88 ± 104.85 respectively, p=0.04).

Children with autoimmune diseases may have a high tendency to develop endothelial dysfunction. Larger studies are needed to confirm our findings and to explore the influence of endothelial dysfunction on the development of atherosclerosis in young children.

Rheumatoid arthritis (RA) represents a challenge for therapeutic interventions due to complex inflammatory signalling pathways underlying its pathogenesis. The MAPK signalling network, a major effector limb of the inflammatory lesion, is an attractive therapeutic target. MAPK phosphatases (MKPs), endogenous negative regulators of MAPK signalling, have received increasing recognition as modulators of inflammatory and immune responses, and hence as a potential therapeutic avenue for RA. To present the rationale for therapeutically targeting MAPK signalling and explore the case for addressing MKP1 as a novel therapeutic strategy for RA. We summarise literature describing the importance of MAPK signalling in RA and review reports describing the roles of MKPs in modulating innate and adaptive immune responses. Finally we expand on the role of MKP1 in RA pathogenesis and explore data defining MKP1 as a mediator of glucocorticoid action.

MKP1 constitutes an exciting, novel potential therapeutic target for RA.

Some autoantibodies are associated with peculiar clinical findings. Patients with rheumatoid arthritis (RA) may have anti-Ro antibodies. To study prevalence and clinical associations of anti-Ro antibodies in RA patients. We studied 385 patients with RA for anti-Ro by Elisa testing and for clinical profile, functional assessment, DAS-28 4v. (ESR), extra-articular manifestations, thyroid function, autoantibodies and treatment. The prevalence of anti-Ro was 8.31%. There was no significant difference in sex distribution, HAQ, DAS-28 or functional classification in patients with positive anti-Ro (p=ns). Patients with anti-Ro were younger at diagnosis (p=0.02). Analyzing extra-articular disorders we found a greater prevalence of cardiac valvular lesions (p<0.001) in patients with anti-Ro antibodies. No differences were found in other extra-articular manifestations, associated hypothyroidism, amyloidosis, treatment requirements, presence of rheumatoid factor (RF) or anti citrullinated protein antibodies (ACPA).

We conclude that in RA patients with anti-Ro have disease onset at an earlier age. Anti-Ro may be a risk factor for the development of cardiac valvular lesions. There was no association between this antibody and thyroid disease, amyloidosis and treatment needs.

Mannan-binding lectin (MBL) is present in serum and synovial fluid; its levels vary widely, and the variations are strongly associated with polymorphisms in the MBL2 gene. Studies have compared MBL in patients with rheumatoid arthritis (RA) and in unrelated controls, but the findings have been contradictory. In the first family-based study, we compared MBL levels in patients with RA to population controls and also to their nonaffected first-degree relatives, who may be regarded as optimal controls because of less genetic variation. Serum levels of MBL and rheumatoid factor were analyzed in 210 patients with RA and 406 of their first-degree relatives from 74 extended families. Population controls for MBL levels were 330 randomly selected adult Icelanders. Patients with RA had higher MBL levels in serum (median 1553 microg/l) than their first-degree relatives (1073 microg/l; p = 0.003) and the unrelated controls (938 microg/l; p < 0.0001). No association was found between MBL and rheumatoid factor.

Patients with RA had markedly higher MBL levels than their close relatives and controls, indicating that high MBL may predispose to RA. As MBL has been shown to bind potential arthritogenic agents including modified immunoglobulins, cellular debris, and microorganisms, our findings suggest that high MBL could trigger complement mediated inflammation within joints.

In a clinical retrospective study, the authors review long-term results of occipitocervical fusion using a wide diameter, contoured, threaded Steinmann pin. To evaluate the clinical and radiographic results of occipitocervical fusion using this technique in a variety of abnormalities including rheumatoid arthritis. SUMMARY OF BACKGROUND DATA. The various surgical techniques and hardware developed for occipitocervical fusion have been associated with mixed results, particularly in patients with rheumatoid arthritis or basilar invagination. Thirty-nine patients with occipitocervical instability were internally fixed with a wide diameter, contoured, threaded Steinmann pin wired to the occiput and cervical laminae or facets. Fusion was facilitated using autologous iliac crest bone graft and a cervical orthosis. Instability resulted from rheumatoid arthritis (n = 12), congenital anomalies (n = 12), trauma (n = 10), tumor (n = 4), or osteogenesis imperfecta (n = 1). Fifteen patients had radiographic evidence of basilar invagination. Long-term outcome (mean follow-up period, 38.9 months; range, 12-78 months) was based on clinical and radiographic review. Thirty-seven patients (97%) had a stable postoperative occipitocervical construct: there were 35 osseous unions, two fibrous unions, and one nonunion. There was on postoperative death from pulmonary complications. No patient developed evidence of new, recurrent, or progressive basilar invagination.

The authors concluded that rigid segmental fixation of the craniovertebral junction using a wide diameter, contoured, threaded Steinmann pin and supplemental autograft creates excellent fusion with minimal complications. This technique is appropriate for a variety of abnormalities including rheumatoid arthritis.

To investigate the reliability of ultrasonographic assessment of osteophytes and explore the concordance of osteophytes detected by ultrasound, MRI, conventional radiography (CR) and clinical joint examination in patients with hand osteoarthritis (HOA). The study included 127 HOA patients (116 women, mean age 68.6 years (SD 5.8)) with ultrasound, CR and clinical examination of both hands and MRI of dominant hand. Osteophytes were assessed by all imaging modalities on 0-3 scales, whereas clinical bony enlargement was assessed as absent/present. An ultrasound atlas of ostephytes was developed, and the intra and inter-reader reliability of scoring ultrasound osteophytes on still images using the atlas as reference was examined. The reliability for ultrasound readings was examined with κ and percentage exact agreement (PEA) and percentage close agreement (PCA), and the sensitivity, specificity and PEA/PCA of ultrasound was calculated in comparison with MRI, CR and clinical examination. Ultrasound had high sensitivity (0.83) and specificity (0.75) in detecting osteophytes compared with MRI, with excellent PCA (96.1%). Moderate/large osteophytes (grade 2-3) were demonstrated more often by ultrasound (n=401) than by MRI (n=288) in 851 interphalangeal joints. Ultrasound detected more osteophytes (53.2%) than CR (30.0%) and clinical examination (36.9%). Intra and inter-reader reliability of ultrasound was excellent (PEA >88%, PCA 100% and weighted kappa >0.91).

Ultrasound can reliably assess osteophytes in patients with HOA. Good agreement was found between osteophytes detected by ultrasound and MRI, while ultrasound was more sensitive than CR and clinical examination, which could be due to a multiplanar joint demonstration by ultrasound.

The aim of this study was to examine whether circulating levels of the pro-inflammatory glycoprotein tenascin-C (TNC) are elevated in musculoskeletal disorders including rheumatoid arthritis (RA) and to assess in RA whether levels are related to clinical disease status and/or patient response to treatment. TNC in serum or plasma was quantified by ELISA. Samples from 4 cohorts of RA patients were examined and compared to normal human subjects and to patients with other inflammatory diseases. Circulating TNC levels were significantly raised in patients with RA, as well as patients with systemic lupus erythematosus, idiopathic inflammatory myositis, psoriatic arthritis and ankylosing spondylitis, whilst patients with Sjogren's syndrome displayed levels similar to healthy controls. The highest levels of TNC were observed in RA patients with late stage disease. In early disease TNC levels correlated positively with ultrasound determined erosion scores. Treatment of early RA patients with infliximab plus methotrexate (MTX) resulted in a transient decrease in circulating TNC over the first year of therapy. In contrast, TNC levels increased over time in RA patients receiving MTX alone. In patients treated with infliximab plus MTX, baseline TNC levels significantly correlated with tender joint counts (TJC) at 18 and 54 weeks after initiation of infliximab therapy.

Raised circulating TNC levels are detected in specific inflammatory diseases. Levels are especially high in RA where they may act as a biomarker of bone erosion and a predictor of the effect of infliximab on RA patient joint pain.

It is often that patients with rheumatoid arthritis (RA) who require ankle surgeries already have the degeneration of talocalcaneal joints. When talocalcaneal joint was fused, whether operatively or spontaneously, ankle kinematics would be affected. The purpose of this paper was to study in vivo kinematics of mobile-bearing total ankle replacement (TAR) in rheumatoid ankle with concomitant talocalcaneal arthrodesis or with preexisting spontaneous talocalcaneal fusion. Thirteen TARs in ten patients with RA, in whom talocalcaneal joints had already been fused spontaneously or surgically, were studied. Fluoroscopic images were obtained while each patient was walking with full weightbearing on the implanted ankle. Thereafter tibio-talar motion was analyzed by 2D/3D registration technique. Average tibio-talar motion was 4.0 ± 5.3° for plantarflexion and 6.6 ± 0.3° for dorsiflexion. Average range of internal/external rotation, inversion/eversion and AP translation was 3.8 ± 1.3°, 2.7 ± 1.0° and 1.6 ± 0.6 mm, respectively.

Mobility of mobile-bearing TAR with talocalcaneal fusion was small during the stance phase of gait, but clinically measured ROM was mostly preserved. The movements of internal/external rotation and AP translation were allowed to a certain degree, but not of inversion/eversion. Even though the movement of inversion/eversion is limited, talocalcaneal arthrodesis could be accompanied with mobile-bearing TAR in rheumatoid ankles.

The Time Trade-Off (TTO) is an instrument used for valuing health-related quality of life. This study evaluated the test-retest reliability of a computer TTO in rheumatoid arthritis (RA), and compared the computer with the interview TTO regarding feasibility and agreement. In study 1 using a cross-over design, thirty patients completed both TTOs. In study 2, twenty-nine other patients completed the computer TTO twice to examine test-retest reliability. Feasibility was measured by assessing actual and perceived time duration and general experience of the patient. Agreement between utility scores of both TTOs was measured by Bland-Altman analysis. Both TTOs were feasible. The computer TTO showed high test-retest reliability (ICC = 0.88). Bland-Altman analysis showed a small mean difference (0.06, SD = 0.14, effect size=0.30) between both TTOs. Limits of agreement were wide (-0.22 to 0.34). Differences between interview and computer TTO utilities did not vary over the range of scores.

The computer TTO was feasible and reliable, but did not provide similar results as the interview TTO. However, no systematic biases in the differences were found over the range of scores.

Cutibacterium are the most common cause of periprosthetic shoulder infections, as defined by ≥2 deep cultures. Established Cutibacterium periprosthetic infections cannot be resolved without prosthesis removal. However, the decision for implant removal must be made from an assessment of infection risk before the results of intraoperative cultures are finalized. We hypothesized that the risk for a Cutibacterium infection is associated with characteristics that are available at the time of revision arthroplasty. In a retrospective review of 342 patients having prosthetic revisions between 2006 and 2018 for whom definitive deep culture results were available, we used univariate and multivariate analyses to compare the preoperative and intraoperative characteristics of 101 revisions with Cutibacterium periprosthetic infections to the characteristics of 241 concurrent revisions not meeting the definition of infection. Patients with definite Cutibacterium periprosthetic infections were younger (59 ± 10 vs. 64 ± 12, P < .001), were more likely to be male (91% vs. 44%, P < .001), were more likely to have had their index procedure performed for primary osteoarthritis (54% vs. 39%, P = .007), were more likely to be taking testosterone supplements (8% vs. 2%, P = .02), had lower American Society of Anesthesiologists scores (1.9 ± 0.7 vs. 2.3 ± 0.7, P < .001), and had lower body mass indices (29 ± 5 vs. 31 ± 7, P = .005). Patients with definite Cutibacterium periprosthetic infections also had significantly higher preoperative loads of Cutibacterium on their unprepared skin surface (1.7 ± 0.9 vs. 0.4 ± 0.8, P < .001) and were more likely to have the surgical finding of synovitis (41% vs. 16%, P < .001).

The risk of definite Cutibacterium periprosthetic infections is associated with observations that can be made before or at the time of revision arthroplasty.

To study the analgesia mechanism of needle-knife lysis in spinal cord and other parts of central nervous system by comparing the changes of Leu-Enkephalin (L-ENK) content in different parts of centrium of rats undergone needle-knife lysis and electro-acupuncture respectively. Sixty healthy SD rats were randomly devided into normal control group, model group, needle-knife lysis (NKL) group and electro-acupuncture (EA) group. 4% papain solution mixed with 0.3 mol/L cysteine solutin in the ratio of 1:1, paused for 0.5 h,injected the mixture, 20 microl each time,into the left knee joint cavities of rats in model, NKL, EA groups at the 1st, 4th, 7th day. After 4 weeks in NKL group and EA group were treated with needle-knife lysis and electro-acupuncture, respectively. Three weeks after treatment, samples of spinal cord of the swollen part of rat waists and rat brains were taken from and the content of L-ENK of medulla oblongata, midbrain, pituitary gland, and hippocampus were measured. L-ENK content of model group increased higher than that of normal control group in spinal cord, hippocampus and midbrain (P < 0.01); there were no significant difference between normal control group and modle group on L-ENK in medulla oblongata and thalamus (P > 0.05). After intervening of NKL or EA, L-ENK content of NKL group increased higher in hippocampus than that of model group and EC group (P < 0.05); but L-ENK content of NKL group in midbrain was lower than that of model group (P < 0.05).

Needle-knife lysis has characteristic of regulation for the L-ENK content in different parts of central nervous system of rats with knee osteoarthritis, and analgesic effect of needle-knife was possibly related with regulation of center L-ENK.

MiR-146a acts as a negative inflammatory mediator in different diseases and has been implicated in osteoarthritis (OA) pathogenesis. In our study, we investigated the association between miR-SNP rs2910164 and OA susceptibility and its role on the expression of miR-146a, inflammatory and catabolic mediators in osteoarthritic chondrocytes. Genetic association analysis was performed in 1688 knee OA patients and healthy individuals of Greek origin. Genomic DNA was extracted from blood and genotyped for rs2910164 (G > C) using Restriction-Fragment Length Polymorphism (RFLP). Total RNA was extracted from chondrocytes of 18 OA patients and miR-146a, IL-1 Receptor-Associated Kinase 1 (IRAK-1), TNF Receptor-Associated Factor 6 (TRAF-6), A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS-5), Matrix Metalloproteinase-13 (MMP-13), Interleukin-6 (IL-6), Interleukin-1 Beta (IL-1β) and Tumor Necrosis Factor-Alpha (TNF-α) expression was evaluated using quantitative Real-Time PCR (qRT-PCR). OA patients carrying rs2910164-GC and CC genotypes did not have an increased risk for OA development compared to GG genotype carriers. MiR-146a expression in OA chondrocytes was significantly lower in patients with rs2910164-GC genotype than in the GG carriers. OA patients carrying the rs2910164-GC genotype in their chondrocytes exhibited increased IRAK-1, TRAF-6, MMP-13, IL-1β and IL-6 expression levels compared with rs2910164-GG carriers.

We demonstrate, for the first time, that miR-SNP rs2910164 in miR-146a gene is associated with reduced miR-146a and increased inflammatory and catabolic mediators' expression in OA chondrocytes. Our data imply that genetic variations in miRNAs linked to OA pathogenesis may regulate their expression levels, suggesting new therapeutic strategies for patients with cartilage diseases.

Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts. The purpose of this study was to position GILZ in OA through its involvement in the anti-inflammatory activities of glucocorticoids and/or in the metabolic pathway of leptin induction. The influences of mineralocorticoids on GILZ and leptin expression were also investigated. Human synovial fibroblasts were isolated from OA patients during knee replacement surgery. Then, the cells were treated with a glucocorticoid (prednisolone), a mineralocorticoid (aldosterone), a glucocorticoid receptor (GR) antagonist (mifepristone), a selective glucocorticoid receptor agonist (Compound A), mineralocorticoid receptor (MR) antagonists (eplerenone and spironolactone), TNF-α or transforming growth factor (TGF)-β. Cells were transfected with shRNA lentiviruses for the silencing of GILZ and GR. The leptin, IL-6, IL-8 and matrix metalloproteinase (MMP)-1 levels were measured by ELISA. Leptin, the leptin receptor (Ob-R), GR and GILZ expression levels were analyzed by western blotting and/or RT-qPCR. (1) The glucocorticoid prednisolone and the mineralocorticoid aldosterone induced GILZ expression dose-dependently in OA synovial fibroblasts, through GR but not MR. Similar effects on leptin and Ob-R were observed: leptin secretion and Ob-R expression were also induced by prednisolone and aldosterone through GR; (2) GILZ silencing experiments demonstrated that GILZ was involved in the glucocorticoid-induced and mineralocorticoid-induced leptin secretion and Ob-R expression in OA synovial fibroblasts; and (3) GILZ inhibition did not alter the production of pro-inflammatory cytokines by OA synovial fibroblast or the anti-inflammatory properties of glucocorticoids.

The absence of GILZ prevents corticoid-induced leptin and Ob-R expression without affecting the anti-inflammatory properties of glucocorticoids in OA synovial fibroblasts. Mineralocorticoids also induce leptin and Ob-R expression through GILZ.

To investigate chronic arthritis and rheumatoid factor (RF) for their prediction of premature total and cardiovascular mortality. In 1978-80, a representative population sample of 8000 Finns aged 30 or more was invited to participate in a comprehensive health examination; 90% complied. Arthritis was diagnosed on the basis of medical history, symptoms, and physical examination. Serum RF was determined by the sensitised sheep cell agglutination test. By the end of 1992 1597 of the subjects had died from all causes, including 876 deaths from cardiovascular diseases. When adjusted for age, gender and smoking, the relative risk of persons with RF positive arthritis dying from any cause was 1.61 (95% confidence interval (CI) 1.03 to 2.51); RF negative non-erosive arthritis was not associated with mortality (relative risk 1.03; 95% CI 0.72 to 1.49). In the absence of arthritis, 'false positive' RF titres > or = 128 predicted cardiovascular deaths with a relative risk of 1.74 (95% CI 1.06 to 2.86).

Both RF positive arthritis and false positive RF reactions predict mortality, but through different disease patterns.

Understanding the pattern of recovery and expected rate of change after shoulder arthroplasty is helpful to clinicians and patients for setting realistic expectations and goals. The purpose of this study was to describe the pattern of recovery over a 2-year period for patients receiving either a Total Shoulder Arthroplasty (TSA) or Humeral Head Replacement (HHR). This was a secondary analysis of prospectively collected data of patients who had undergone TSA or HHR and were followed for up to 2 years. Patients were seen prior to surgery and at 6 months, one year and two years after surgery and completed the American Shoulder and Elbow Surgeon's (ASES) questionnaire, Relative Constant Murley score (RCMS) and underwent range of motion and strength assessment. Data of 134 patients who had surgery from April 2001 to July 2011 were used for analysis. One hundred and eight patients underwent TSA (81%) and 26 (19%) had HHR. Both surgeries were associated with a statistically significant improvement in physical symptoms, ASES, RCMS, range of motion and strength (p <0.0001). The greatest change for all outcomes occurred within the first 6-months of surgery. Improvement in ASES, RCMS continued up to 12-months and then plateaued. Improvement in physical symptoms leveled off at 6-months in the HHR group but continued up to 12-months in the TSR group. Strength showed improvement in both groups up to 24-months post-surgery.

Both TSA and HHR groups showed a statistically significant improvement in perceived disability, range of motion and strength over two years with the greatest improvement made by 6 months. The recovery profiles for the surgeries showed different patterns.

To investigate the expression of Gremlin 1 (GREM1), an antagonist of bone morphogenetic protein, in rheumatoid arthritis (RA) synovia and its involvement in the hyperplasia and invasiveness of fibroblast-like synoviocytes of RA (RA-FLS). Computational analysis was introduced to identify FLS-predominant regulators. GREM1 expression was examined by immunohistochemistry, real-time PCR, and ELISA. FLS proliferation and apoptosis were determined using tetrazolium-based colorimetric assay and APOPercentage assay, respectively. FLS migration and invasion were evaluated by wound migration and Matrigel invasion assay, respectively. Expressions of Bax, Bcl2, pErk1/2, and pAkt were detected by Western blot analysis. Through global transcriptome profiling, we identified a GREM1 gene predominantly expressed in RA-FLS. Indeed, the GREM1 expression was higher in synovia, synovial fluids, and FLS of patients with RA than in those of patients with osteoarthritis, and its levels correlated well with proinflammatory cytokine concentrations. Knockdown of GREM1 transcripts using short interfering RNA (siRNA) reduced the proliferation and survival of RA-FLS along with downregulation of pErk1/2, pAkt, and Bcl2 expressions, whereas it induced Bax expression. Conversely, the addition of recombinant GREM1 to RA-FLS showed the opposite results. Moreover, GREM1 siRNA decreased the migratory and invasive capacity of RA-FLS, whereas exogenous GREM1 increased it. The GREM1-induced FLS survival, migration, and invasion were completely blocked by neutralizing antibodies to ανβ3 integrin on RA-FLS, suggesting that ανβ3 integrin mediates the antiapoptotic and promigratory effects of GREM1.

GREM1 is highly expressed in RA joints, and functions as a regulator of survival, proliferation, migration, and invasion of RA-FLS.

Emerging evidence indicates that low-grade inflammation is part of the clinical picture of OA and that there is a need to identify soluble biomarkers of ongoing inflammation in the joint from a translational aspect. The aim of this study was to compare levels of pro-inflammatory biomarkers in SF, serum and/or EDTA plasma. SF and blood from rats subjected to Freund's complete adjuvant (FCA; n = 48) or monoiodoacetate (MIA; n = 88) monoarthritis and from control rats were collected over time. SF, EDTA plasma and serum were obtained from six individuals with OA of the knee and healthy controls. Levels of IL-6, KC/GRO, IL-8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 3α (MIP-3α), IL-1β, TNF and l(+)-lactate were assessed either by immune assay or by a colorimetric method. Elevated levels of biomarkers were shown in monoarthritic animals in SF compared with the control groups, although with considerably lower magnitude in the MIA groups, which also indicated a biphasic pattern. Levels of KC/GRO and MIP-3α in serum from the FCA model and IL-6 in the MIA model followed the pattern of SF. In serum samples from OA individuals, MIP-3α correlated significantly with levels in SF.

While we found increased levels of markers in joint fluid and blood, no single systemic biochemical biomarkers that were a common denominator between the animal models and the patient material could be identified. Our data indicate that it is critical to delineate the temporal profile of multiple local and systemic factors in order to pinpoint soluble biomarkers for OA.

To evaluate the feasibility and efficacy of tilt whole-body vibration (WBV) for improving dynamic balance in women with fibromyalgia (FM). Forty-one women (ages 41-65 years) were randomly assigned to either a vibration (n = 21) or control (n = 20) group. The vibration intervention consisted of a 30-minute session of instruction plus 3 sessions of WBV per week over a period of 12 weeks. Each vibration session consisted of 6 repetitions of a 45-60-second 12.5-Hz vibration. The posture of the patient was lateral. Dynamic balance was assessed with a balance platform, and the level of stability could be controlled. We performed intent-to-treat (ITT) analysis and efficacy analysis in participants who completed the study (vibration, n = 18; control, n = 18). Based on ITT analysis, the dynamic balance of the vibration group improved by 36% as compared with baseline, whereas that of the control group was unchanged. Differences in the dynamic balance index were predicted (61%; P < 0.001) by the following linear model: (0.027 x body weight) - (0.800 x dynamic balance at baseline) - (0.632 x group).

The vibration program was useful and feasible for improving dynamic balance in women with FM. These novel results support further research aimed at the development of physical therapy programs that utilize controlled vibration.

To analyse the potential contribution of low-density granulocytes (LDGs) and NETosis, as well as the differential protein cargo of neutrophil extracellular traps (NETs), as physiopathogenic mechanisms of adult-onset Still's disease (AOSD). We recruited 30 patients with AOSD according to the Yamaguchi diagnostic criteria. LDGs were addressed by multiparametric flow cytometry as those CD14-, CD15+, CD10+ cells in the peripheral blood mononuclear cells fraction. NETs were quantified by ELISA, immunofluorescence and fluorescence spectrometry. The expression of LL-37 and high mobility group box 1 (HMGB-1) in NETs was measured by immunofluorescence and confocal microscopy. Additionally, normal density neutrophils from healthy controls were stimulated with serum from patients with AOSD and NET induction was assessed by immunofluorescence. Patients with active disease as well as those with arthritis, cutaneous manifestations and fever had a higher amount of NETs and LDGs. Serum NETs from AOSD patients correlated with the number of swollen joints (r=0.41, p=0.032), absolute number of monocytes (r=0.529, p=0.005). The spontaneous NETs from patients with cutaneous manifestations and fever had higher cargo of HMGB-1 compared with patients in remission.

LDGs and NETs are increased in patients with active AOSD and correlate with particular clinical features. Patients with cutaneous lesions and fever present a higher cargo of HMGB1 in their spontaneous NETs.

To investigate the development of osteoarthritis (OA) after transection of the medial collateral ligament and partial medial meniscectomy in mice in which genes encoding either interleukin-1beta (IL-1beta), IL-1beta-converting enzyme (ICE), stromelysin 1, or inducible nitric oxide synthase (iNOS) were deleted. Sectioning of the medial collateral ligament and partial medial meniscectomy were performed on right knee joints of wild-type and knockout mice. Left joints served as unoperated controls. Serial histologic sections were obtained from throughout the whole joint of both knees 4 days or 1, 2, 3, or 4 weeks after surgery. Sections were graded for OA lesions on a scale of 0-6 and were assessed for breakdown of tibial cartilage matrix proteoglycan (aggrecan) and type II collagen by matrix metalloproteinases (MMPs) and aggrecanases with immunohistochemistry studies using anti-VDIPEN, anti-NITEGE, and Col2-3/4C(short) neoepitope antibodies. Proteoglycan depletion was assessed by Alcian blue staining and chondrocyte cell death, with the TUNEL technique. All knockout mice showed accelerated development of OA lesions in the medial tibial cartilage after surgery, compared with wild-type mice. ICE-, iNOS-, and particularly IL-1beta-knockout mice developed OA lesions in the lateral cartilage of unoperated limbs. Development of focal histopathologic lesions was accompanied by increased levels of MMP-, aggrecanase-, and collagenase-generated cleavage neoepitopes in areas around lesions, while nonlesional areas showed no change in immunostaining. Extensive cell death was also detected by TUNEL staining in focal areas around lesions.

We postulate that deletion of each of these genes, which encode molecules capable of producing degenerative changes in cartilage, leads to changes in the homeostatic controls regulating the balance between anabolism and catabolism, favoring accelerated cartilage degeneration. These observations suggest that these genes may play important regulatory roles in maintaining normal homeostasis in articular cartilage matrix turnover.

Pneumatosis cystoides intestinalis (PCI) is a rare life-threatening gastrointestinal complication in the course of connective tissue disease (CTD). PCI is characterised by the appearance of intramural clusters of gas in the small and large bowel wall on X-ray or computed tomography and often is accompanied by free air in the peritoneal cavity. We present three cases of PCI in patients with scleroderma-related conditions. A review of the English language literature published on MEDLINE from 1973 to 2008 was conducted using the terms: 'systemic sclerosis', 'connective tissue disease' and 'pneumatosis cystoides intestinalis'. This review focused on clinical features, diagnostic and treatment strategies of PCI in the context of CTD. Symptoms of PCI are non-specific: abdominal pain, vomiting, constipation, bloating and weight loss. Coexistence of PCI with other manifestations of CTD, such as intestinal pseudo-obstruction and/or bacterial overgrowth, complicates the clinical diagnosis. Treatment approach to PCI is mostly conservative: intestinal 'rest', parenteral nutrition, antibiotics, fluids and electrolyte supplementation, and inhaled oxygen. Surgical intervention should be performed only in cases of bowel perforation, ischaemia or necrosis. Patients with PCI have high mortality rates due to PCI itself but also to the severity and variety of basic CTD complications.

Recognition of PCI, particularly in the context of underlying CTD, is necessary for proper therapeutic application. In patients with underlying CTD and symptoms of abdominal emergency, recruitment of multidisciplinary teams, including rheumatologist, gastroenterologist, imaging specialist and surgeons familiar with intestinal complications of CTD-related conditions, is warranted.

To examine a learned helplessness conceptualization of psychological sequela in children and adolescents with juvenile rheumatic diseases (JRD) via an experimental procedure utilizing behavior-outcome contingent and noncontingent feedback. Thirty-eight children and adolescents with JRD completed measures of transient affect, self-efficacy for functional ability, and causal attributions prior to and immediately following a computerized learned helplessness induction procedure. Children across contingent and noncontingent feedback conditions experienced decreased positive affect with a slightly more pronounced decline in the noncontingent condition. Noncontingent feedback resulted in poorer internalization of success for problem solving, while contingent feedback resulted in greater internalization of success for problem solving. Additionally, posttreatment control self-efficacy was significantly greater for children in the contingent condition that initially endorsed higher levels of internal task attributions.

Children with JRD who experience behavior-outcome contingency in their environment may develop increased perceptions of control over functional ability. Furthermore, environmental noncontingency may result in poorer internalization of success, whereas contingent reinforcement may enhance cognitive appraisal mechanisms (i.e., causal attributions) associated with favorable disease outcome. Despite a modest decline in positive affect for children in the noncontingent condition, mood dysfunction is not entirely explicable within the context of noncontingent reinforcement.

The purpose of this study was to conduct a prospective outcome analysis of proximal tibial opening wedge osteotomies performed in young and middle-aged patients (aged <55 years) for the treatment of symptomatic medial compartment osteoarthritis of the knee. A consecutive series of young and middle-aged adults who underwent proximal tibial opening wedge osteotomies for symptomatic medial compartment osteoarthritis and genu varus alignment were prospectively followed up. Patients were evaluated with preoperative and postoperative modified Cincinnati Knee Scores and International Knee Documentation Committee objective knee subscores for knee effusions and the single-leg hop. Calculations were made of the preoperative and postoperative long-leg radiographic mechanical weight-bearing axis, patellar height (Insall-Salvati index), and tibial slope. A separate cohort of asymptomatic patients was used to quantify tibial plateau anatomy to provide an objective description of the lower extremity mechanical axis. There were 47 patients, with a mean age of 40.5 years, with a minimum of 2 years' follow-up, who formed this patient cohort. Modified Cincinnati Knee Scores improved significantly from 42.9 preoperatively to 65.1 at a mean of 3.6 years of follow-up. Radiographic analysis of a separate cohort showed the medial tibial eminence to be located at the 41% point along the tibial plateau from medial (0%) to lateral (100%). There was a significant improvement in malalignment: the mean mechanical axis passed through the tibial plateau at 23% of the distance along the proximal tibia preoperatively versus 54% postoperatively. The Insall-Salvati index decreased from 1.03 to 0.95 (P < .05), and posterior tibial slope increased from 9.4° to 11.7° (P < .05). Of the osteotomies, 3 (6%) were considered failures, defined by revision of the osteotomy or conversion to total knee arthroplasty. Level IV, therapeutic case series.

Performing proximal tibial opening wedge osteotomies to treat symptomatic medial compartment osteoarthritis in carefully selected patients leads to a significant improvement in subjective and objective clinical outcome scores with correction of malalignment at a mean of 3.6 years postoperatively.

In osteoarthritis (OA), subchondral bone changes alter the joint's mechanical environment and potentially influence progression of cartilage degeneration. Joint distraction as a treatment for OA has been shown to provide pain relief and functional improvement through mechanisms that are not well understood. This study evaluated whether subchondral bone remodeling was associated with clinical improvement in OA patients treated with joint distraction. Twenty-six patients with advanced post-traumatic ankle OA were treated with joint distraction for 3 months using an Ilizarov frame in a referral center. Primary outcome measure was bone density change analyzed on computed tomography (CT) scans. Longitudinal, manually segmented CT datasets for a given patient were brought into a common spatial alignment. Changes in bone density (Hounsfield Units (HU), relative to baseline) were calculated at the weight-bearing region, extending subchondrally to a depth of 8mm. Clinical outcome was assessed using the ankle OA scale. Baseline scans demonstrated subchondral sclerosis with local cysts. At 1 and 2 years of follow-up, an overall decrease in bone density (-23% and -21%, respectively) was observed. Interestingly, density in originally low-density (cystic) areas increased. Joint distraction resulted in a decrease in pain (from 60 to 35, scale of 100) and functional deficit (from 67 to 36). Improvements in clinical outcomes were best correlated with disappearance of low-density (cystic) areas (r=0.69).

Treatment of advanced post-traumatic ankle OA with 3 months of joint distraction resulted in bone density normalization that was associated with clinical improvement.

To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs -7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs -7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases.

The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.

Idiopathic multicentric osteolysis (IMO) is an uncommon disease presenting during childhood with resorption of the carpus and tarsus with nephropathy. The few case reports and literature reviews do not focus on the upper extremity disease manifestations or surgical treatment options. We review our experience with the upper extremity in IMO. We evaluated 8 affected children, specifically assessing early disease manifestations, misdiagnoses, radiographic progression, and surgical treatments rendered. Wrist pain and swelling are typically the first manifestations of IMO. Characteristic upper extremity findings, once the disease has progressed, include metacarpophalangeal joint hyperextension, wrist ulnar deviation and flexion, and loss of elbow extension. Radiographically, there is osteolysis of the carpus and proximal metacarpals with resorption of the elbow joint in some patients. Surgical treatments, including soft tissue release with pinning or joint arthrodesis, may offer pain relief and improve alignment, but outcomes are inconsistent. Prognostic IV.

Children with IMO are almost always misdiagnosed initially, and the correct diagnosis may be delayed by years. The hand surgeon is ideally suited to provide an accurate diagnosis of IMO, because wrist pain and swelling and thumb interphalangeal joint contracture are common early manifestations.

To test a multisegment foot model for kinematic analysis during barefoot walking in patients with well established rheumatoid arthritis (RA) and foot impairments. Five healthy adult subjects and 11 RA patients with advanced disease were studied. Foot impairments were assessed using standardized outcomes and clinical examination techniques. A 6-camera 60 Hz video-based motion analysis system was used to measure motion of the shank, rearfoot, forefoot, and hallux segments and the vertical displacement of the navicular. Face validity and estimates of repeatability were determined. Motion patterns were calculated and comparisons were made between healthy subjects and patients with RA. Relationships between clinical impairment and abnormal motion were determined through inspection of individual RA cases. Across the motion variables, the within-day and between-day coefficient of multiple correlation values ranged from 0.677 to 0.982 for the healthy subjects and 0.830 to 0.981 for RA patients. Based on previous studies, motion parameters for the healthy subjects showed excellent face validity. In RA patients, there was reduced range of motion across all segments and all planes of motion, which was consistent with joint stiffness. In the RA patients, rearfoot motion was shifted towards eversion and external rotation and peak values for these variables were increased, on average, by 7 degrees and 11 degrees, respectively. Forefoot range of motion was reduced in all 3 planes (between 31% and 53%), but the maximum and minimum angles were comparable to normal. The navicular height, during full foot contact, was on average 3 mm lower in the RA patients in comparison to normal. The hallux was less extended in the RA subjects in comparison to normal (21 degrees vs 33 degrees) during the terminal stance phase. Individual cases showed abnormal patterns of motion consistent with their clinical impairments, especially those with predominant forefoot pain or pes planovalgus.

In RA, multisegment foot models may provide a more complete description of foot motion abnormalities where pathology presents at multiple joints, leading to complex and varied patterns of impairment. This technique may be useful to evaluate functional changes in the foot and to help plan and assess logical, structurally based corrective interventions.

Gene therapy is a growing concept in many fields of medicine, and its potential applications are numerous. With a growing understanding of the molecular and cellular biology of intervertebral disc degeneration, alternatives to current treatment options are under investigation. Gene therapy offers an exciting new direction in the treatment of intervertebral disc degeneration, and potential targets of genetic alteration are being explored. To describe and update the recent advances in research on gene therapy for the treatment of intervertebral disc degeneration. Review of current research for the application of gene therapy as potential treatment for intervertebral disc degeneration. Literature review. There is a growing body of research pertaining to the use of gene therapy as an adjunct or alternative to the current treatment options for intervertebral disc degeneration. In vitro studies have demonstrated that transfer of cDNA encoding growth factors to intervertebral disc cells can favorably modify their metabolic and biological functions. Additionally, initial in vivo studies have demonstrated successful transduction of growth factors to the intervertebral disc with confirmed upregulation of extracellular matrix synthesis. Investigators continue to explore the potential of gene therapy with several factors for the treatment of intervertebral disc degeneration.

The potential of gene therapy to alter the course of intervertebral disc degeneration holds much clinical promise and continues to stimulate further investigations.

Increasing evidence points to a strong genetic component to osteoarthritis (OA) and that certain changes that occur in osteoarthritic cartilage recapitulate the developmental process of endochondral ossification. As zebrafish are a well validated model for genetic studies and developmental biology, our objective was to establish the spatiotemporal expression pattern of a number of OA susceptibility genes in the larval zebrafish providing a platform for functional studies into the role of these genes in OA. We identified the zebrafish homologues for Mcf2l, Gdf5, PthrP/Pthlh, Col9a2, and Col10a1 from the Ensembl genome browser. Labelled probes were generated for these genes and in situ hybridisations were performed on wild type zebrafish larvae. In addition, we generated transgenic reporter lines by modification of bacterial artificial chromosomes (BACs) containing full length promoters for col2a1 and col10a1. For the first time, we show the spatiotemporal expression pattern of Mcf2l. Furthermore, we show that all six putative OA genes are dynamically expressed during zebrafish larval development, and that all are expressed in the developing skeletal system. Furthermore, we demonstrate that the transgenic reporters we have generated for col2a1 and col10a1 can be used to visualise chondrocyte hypertrophy in vivo.

In this study we describe the expression pattern of six OA susceptibility genes in zebrafish larvae and the generation of two new transgenic lines marking chondrocytes at different stages of maturation. Moreover, the tools used demonstrate the utility of the zebrafish model for functional studies on genes identified as playing a role in OA.

To determine the frequency of antibodies to cyclic citrullinated peptides (CCP) in a group of patients with a diversity of rheumatic diseases. 249 consecutive sera from an arthritis clinic sent for rheumatology testing were selected for testing with the anti-CCP2 assays and for the presence of rheumatoid factor (RF). Patient charts were reviewed for demographic information, clinical diagnosis, radiographic information, and other laboratory data. The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis (RA) were 66.0% and 90.4%, respectively. This compared with the sensitivity and specificity of RF for RA at 71.6% and 80.3%. Furthermore, 10/29 (34%) RF- patients with RA demonstrated reactivity to CCP. The presence of either anti-CCP or RF increased testing sensitivity for diagnosis of RA to 81.4%; the presence of both RF and anti-CCP demonstrated a testing specificity similar to that of anti-CCP reactivity alone for the diagnosis of RA (91.1%).

The detection of anti-CCP is useful for the diagnosis of RA, in fact even more so than RF, because of its higher specificity.

Intraoperative periprosthetic femoral fractures (PFF) during the implantation of primary non-cemented total hip arthroplasties (THA) are an increasing problem. Thus, the goal of this study was to analyse the postoperative performance of primary non-cemented THA in patients with intraoperative PFFs, with respect to the patient's subjective health-related satisfaction. 42 PFFs in 1216 primary THAs using the non-cemented BiCONTACT stem were monitored. Patients were compared to a control group of 42 non-cemented THA patients without intraoperative fracture complications, using the matched-pair analysis. Preoperative and after 2.2 years (0.8-3.2 years), patients were followed-up clinically and radiographically. Clinical parameters were Harris hip score, SF-36 health score, function and pain score and postoperative complications. Radiographic parameters were bone union, stem and trochanter migration. Fractures were graded using the Vancouver classification. Results showed a significant increase in both Harris hip score and motion score and a significant decrease in pain score in both groups (p<0.001). The SF-36 health score increased significantly in nearly every dimension in both groups. Except for 2 patients with trochanter migrations of 25 and 20 mm, all fractures showed bony union. In 3 patients the stems subsided by 4.7 +/- 2.9 mm. The stems showed no further migration at final follow-up. 2 patients without intraoperative fractures underwent stem revision. Overall increases and postoperative complication rates were not significantly different between the groups.

Mid-term THA performance and patient satisfaction are not influenced by intraoperative Vancouver A and B1 fractures during implantation of the non-cemented BiCONTACT stem compared to a collective without intraoperative fractures during implantation.

The investigation of copy number variations (CNVs) analysis of candidate genes is currently an important research area in modulating human diseases. We aimed to quantify CNVs in glutathione S-transferase M1 (GSTM1) gene and determine its genetic contribution in Tunisian rheumatoid arthritis (RA) and its subsets through an innovative technique for quantification. A total of 165 RA cases and 102 healthy controls were included in the study. Using a recently powerful approach of digital droplet PCR (ddPCR), we quantified GSTM1 gene to determine the presence of no, one, or multiple copy number (CN) at high levels of sensitivity and specificity. Odds ratio and Fisher exact test were performed to estimate the association risk for GSTM1CNVs in RA. Copy number identified by ddPCR was 0, 1, and 2 copies per diploid genome. A high frequency of '0' copy was revealed with 54% in RA patients. The deletion ('0' copy) of GSTM1 was found to be a significant risk factor for anti-cyclic citrullinated peptide (anti-CCP) positive RA (OR=4.16, CI

This study highlights the powerful accuracy of ddPCR for the quantification of CNVs and suggests that the variation in the CN of GSTM1 is associated with anti-CCP positivity in RA. However, it does not indicate a specific role in the susceptibility to the disease in our Tunisian sample.

To describe actual cardiovascular events over a decade in patients with diffuse idiopathic skeletal hyperostosis (DISH), without previously known CV diseases. The medical records of patients with DISH and controls, beginning in 2006 (without known CV disease), were reviewed. Demographic, constitutional, and laboratory data were collected. Comparison of CV events following 2006 was performed according to the outcome definitions set by the Framingham score 2: coronary event demonstrated by a coronary imaging modality, acute myocardial infarction (MI), coronary death, congestive heart failure with a reduced ejection fraction, and angina pectoris. Data were available for 45 patients with DISH and 47 controls without DISH from the original cohort (91.8% and 97.9% respectively). By the Framingham score, 28.6% (± 20.33) of the DISH patients were expected to be affected with CVD at 10 years of follow-up. We observed that nearly 39% of them developed CVD during that period (95% CI 23.8-53.5%). The incidence of MI over the 10-year period was significantly higher in the DISH group (P = 0.005). The DISH group had higher morbidity with a higher composite outcome of 38.8% vs 25.5% in the control cohort, and the number of non-elective hospital admissions per patient, despite neither reaching statistical significance.

Our study showed that the Framingham score underestimates the real risk for developing CVD in patients with DISH, specifically the risk for MI. We propose more scrutiny is warranted in evaluating CV risk in these patients, more demanding treatment target goals should be established, and earlier and more aggressive medical interventions should be undertaken, particularly primary prevention. Larger prospective studies are needed to corroborate these findings.

Rheumatoid Arthritis (RA) has been associated with insulin resistance (IR), a well-established pathophysiological feature of Type 2 Diabetes (T2DM). Inconsistent literature evidence suggests that IR could be ameliorated by biological medications targeting TNFα. The aim of this systematic review was to evaluate the effect of TNFα inhibitors (TNFi) on IR in RA patients. We performed a systematic review in order to identify the available data on the effect of anti- TNFα medications on IR in RA patients. For this purpose, MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and SCOPUS were searched up to December 2016. The search strategy retrieved 209 individual records. Of these, only 12 articles were included in the systematic review. The pooled analysis under a random-effects model demonstrated a significant improvement of IR after treatment with TNFi quantified with the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR), with a standardized difference in means (SDM) of -0.847 (95%CI: -1.278 - 0.417, p < 0.0001). Heterogeneity across studies was high (Q = 65.00 with df = 9, p < 0.001, I2 = 89.15%).

Our meta-analysis suggests that TNFα blockade might improve IR in RA patients.

Risk of knee osteoarthritis (OA) is much higher in women than in men. Previous studies have shown that bone shape is a risk factor for knee OA. However, few studies have examined whether knee bone shape differs between men and women. The purpose of the present study was to determine whether there are differences between men and women in knee bone shape. We used information from the NIH-funded Osteoarthritis Initiative (OAI), a cohort of persons aged 45-79 at baseline who either had symptomatic knee OA or were at high risk of it. Among participants aged between 45 and 60 years, we randomly sampled 340 knees without radiographic OA (i.e., Kellgren/Lawrence grade of 0 in central readings on baseline radiograph). We characterized distal femur and proximal tibia shape of these selected radiographs using statistical shape modeling (SSM). We performed linear regression analysis to examine the association between sex and each knee shape mode (proximal tibia and distal femur), adjusting for age, race, body mass index (BMI), and clinic site. The mean age was 52.7 years (±4.3 SD) for both men and women. There were 192 female and 147 male knees for the distal femur analysis. Thirteen modes were derived for femoral shape, accounting for 95.5% of the total variance. Distal femur mode 1 had the greatest difference in standardized score of knee shape between females and males (1.04, p < 0.01); modes 3, 5, 6, 8, and 12 were also significantly associated with sex. For tibial shape, 191 female knees and 149 male knees were used for the analysis. Overall, 10 modes explained 95.5% of shape variance. Of the significantly associated modes in the proximal tibia, mode 2 had the greatest difference in standardized score of bone shape between males and females (-0.30, p = 0.01); modes 3 and 4 were also significantly associated.

The shapes of the distal femur and proximal tibia that form the knee joint differ by sex. Additional analyses are warranted to assess whether the difference in risk of OA between the sexes arises from bone shape differences.

Chondroitin sulfate (CS) and glucosamine sulfate (GS) are symptomatic slow-acting drugs for osteoarthritis (OA) widely used in clinic. Despite their widespread use, knowledge of the specific molecular mechanisms of their action is limited. The aim of this work is to explore the utility of a pharmacoproteomic approach for the identification of specific molecules involved in the pharmacological effect of GS and CS. Chondrocytes obtained from three healthy donors were treated with GS 10 mM and/or CS 200 μg/mL, and then stimulated with interleukin-1β (IL-1β) 10 ng/mL. Whole cell proteins were isolated 24 hours later and resolved by two-dimensional electrophoresis. The gels were stained with SYPRORuby. Modulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/TOF) mass spectrometry. Real-time PCR and Western blot analyses were performed to validate our results. A total of 31 different proteins were altered by GS or/and CS treatment when compared to control. Regarding their predicted biological function, 35% of the proteins modulated by GS are involved in signal transduction pathways, 15% in redox and stress response, and 25% in protein synthesis and folding processes. Interestingly, CS affects mainly energy production (31%) and metabolic pathways (13%), decreasing the expression levels of ten proteins. The chaperone GRP78 was found to be remarkably increased by GS alone and in combination with CS, a fact that unveils a putative mechanism for the reported anti-inflammatory effect of GS in OA. On the other hand, the antioxidant enzyme superoxide dismutase 2 (SOD2) was significantly decreased by both drugs and synergistically by their combination, thus suggesting a drug-induced decrease of the oxidative stress caused by IL-1β in chondrocytes.

CS and GS differentially modulate the proteomic profile of human chondrocytes. This pharmacoproteomic approach unravels the complex intracellular mechanisms that are modulated by these drugs on IL1β-stimulated human articular chondrocytes.

To determine if children with juvenile rheumatoid arthritis (JRA) are less likely to have been breast fed than controls. Case-control study of data obtained from a survey of mothers 54 children with JRA and 79 playmates regarding breast feeding. Duration of breast feeding was tabulated and odds ratios (OR) with 95% confidence intervals (CI) were determined. OR for breast feeding in children with JRA was 0.40 (0.20-0.81, 95% CI) compared to playmates. For pauciarticular JRA (N = 28) OR was 0.31 (0.10-0.93); in polyarticular JRA (N = 24) OR was 0.60 (0.21-1.70). Lower OR for increased durations of breast feeding were noted in children with JRA.

Children who have had JRA, especially pauciarticular JRA, are less likely to have been breast fed than controls, suggesting that breast feeding may have a protective effect on the development of JRA.

While the efficacy of pulsed radiofrequency (PRF) for shoulder pain has been demonstrated, its efficacy on the saphenous nerves for knee osteoarthritis (OA)-associated pain has only been reported in observational studies. The aim of this study was to compare saphenous nerve PRF to placebo for knee OA-associated pain. Patients, practitioners, and outcome assessor-blinded randomized placebo-controlled trial. Pain management clinics at 2 hospitals in Japan. Patients were randomly allocated to the PRF (n = 37) or placebo group (n = 33). Patients aged 40-85 years with refractory anteromedial knee pain. PRF in the saphenous nerve under ultrasound guidance. The placebo group underwent the same procedure, but with motor stimulation. The primary endpoint was the average pain intensity measured using the visual analog scale (VAS) at the 12-week post-treatment visit; secondary outcomes included the average VAS at 1 and 4 weeks, and pain intensities at rest, in flexion, at standing, and at walking. Other secondary outcomes were knee pain, symptoms, activities of daily living, knee-related quality of life, mobility, range of motion, and adverse events. In the PRF group, the mean VAS score was 52.41 ± 26.17 at 12 weeks, while in the sham group, the mean VAS score was 63.06 ± 27.12 (P < 0.05). There were no significant differences between the groups in any of the secondary outcomes. Patients with comorbidities were excluded from this study. The follow-up time was limited to 12 weeks.

Ultrasound-guided saphenous nerve PRF proved to be effective for at least 12 weeks in patients with knee OA and showed no adverse events.

This study was set up to identify the native trochlear geometry and define its relationship with the rotational landmarks of the distal femur. The rotational landmarks of the distal femur were analysed on CT-scans of 281 patients with end-stage knee osteoarthritis. The anterior trochlear line (ATL) was on average 4.3° (SD 3.3°) internally rotated relative to the surgical transepicondylar axis (sTEA). The ATL was on average 2.1° (SD 3.0°) internally rotated relative to the posterior condylar line (PCL). The relationship between the ATL and the sTEA was statistically different in the different coronal alignment groups (p = 0.004): 3.9° (SD 3.0°) in varus knees, 4.0° (SD 2.9°) in neutral knees and 5.4° (SD 3.8°) in valgus knees. The lateralisation of the trochlea, represented by the distance between the perpendicular to PCL and the perpendicular to the posterior parallel line to the sTEA, was on average 2.2 mm (SD 1.8 mm). III.

The ATL was on average 4.3° (SD 3.3°) internally rotated relative to the sTEA and 2.1° (SD 3.0°) internally rotated relative to the PCL. The ATL is more externally orientated in varus knees and more internally rotated in valgus knees. The trochlear groove is lateralised by only 2.2 mm when the femoral component is externally rotated.

Disease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA. RA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged  28 joint disease activity score (DAS28) for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were used for the analyses. During follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders.

Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.

The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA). Flow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.

Elevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.

A new classification for osteoarthritis of the knee associated with varus deformity is presented. This classification is derived from the combination of conventional radiographs, stress radiographs (when needed), and clinical examination. This study included the analysis of coronal alignment on full-leg standing radiographs of 526 patients awaiting knee arthroplasty for varus deformity in a single institution. Various mechanical and anatomic angles were measured, and these findings were combined with a basic clinical examination of patients. The radiographs were measured on 2 separate occasions to determine the intraobserver reliability. Cross-sectional studies such as computed tomography or magnetic resonance imaging were used to further refine observations about different wear patterns. Varus deformity can either be intra-articular or extra-articular. Intra-articular deformities can be correctable or fixed. In fixed deformities, the status of the lateral ligament is taken into account. Extra-articular deformity can be metaphyseal or diaphyseal, and the possibility for intra-articular correction will depend on the degree of deformity and its distance from the joint.

This new classification allows for better definition of varus deformity, which can help surgeons during preoperative planning, particularly with their choice of implant and potentially the degree of constraint. The classification can also be a tool for further prospective studies about varus deformity.

To compare concentrations of tear cytokines in 3 groups composed of Sjögren syndrome (SS) dry eye, non-Sjögren syndrome (non-SS) dry eye, and normal subjects. Correlations between ocular surface parameters and tear cytokines were also investigated. Prospective cross-sectional study. SS dry eye patients (n = 24; 40 eyes) were diagnosed with primary SS according to the criteria set by the American-European Consensus Group. Non-SS dry eye patients (n = 25; 40 eyes) and normal subjects (n = 21; 35 eyes) were also enrolled. Tear concentrations of interleukin (IL)-17, IL-6, IL-10, IL-4, IL-2, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) were measured by a multiplex immunobead assay. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), Schirmer I test, and fluorescein staining scores were obtained from dry eye patients. All cytokine levels except for IL-2 were highest in the SS group, followed by non-SS dry eye group and control subjects. Concentrations of IL-17, TNF-α, and IL-6 were significantly different among the 3 groups (IL-17: SS > control P < .001, non-SS > control P = .042, SS > non-SS P < .001; TNF-α: SS > control P = .006, non-SS > control P = .034, SS > non-SS P = .029; IL-6: SS > control P = .002, non-SS > control P = .032, SS > non-SS P = .002). IL-17 was significantly correlated with TBUT (R = -0.22, P = .012) and Schirmer I test (R = -0.36, P = .027) scores in the SS group. IL-6 was significantly correlated only with TBUT (R = -0.38, P = .02) in the non-SS group.

Differences in tear cytokine levels and correlation patterns between SS dry eye and non-SS dry eye patients suggest the involvement of different inflammatory processes as causes of dry eye syndrome.

Bone marrow edema (BME) is a condition detectable with magnetic resonance imaging (MRI) and is present in different stages of osteoarthritis (OA). Its pathogenesis is still not completely known. To evaluate the longitudinal occurrence and persistence of BME in early OA of the knee. Twenty-three patients (eight females, 15 males; mean age 55.5+/-10.3 years) were scanned with a 1.5T MR imaging unit (sagittal fat-suppressed intermediate-weighted fast spin echo; 4-mm section thickness, 1-mm intersection gap, 256 x 192 matrix, 120-mm field of view). Images were obtained in all 23 patients at two time points (TPs) and in 12 patients at three TPs. Images were evaluated by two readers independently; discrepancies in image grading were reviewed and evaluated in consensus. A four-point image-grading scale was used (absence of BME to severe BME). Four main anatomical regions were evaluated (medial femur, lateral femur, medial tibia, lateral tibia), which were subcategorized into anterior, central, and posterior regions. One hundred five areas of BME in the 23 patients were found at all three TPs. In 16 areas, the BME was consistent at the same location over time, in seven locations the BME became larger, in six areas the BME became smaller, and in 16 locations it could not be detected in follow-up MRIs. In one case, the BME was smaller at TP2 but increased at TP3. In eight cases, only at the last time point could a BME be detected.

BME is not a static phenomenon but changes over time. Correlation to physical activity and local inflammatory reaction should be evaluated.

Herein, we describe and evaluate a curved periacetabular osteotomy (CPO) via an intermuscular approach (IM-CPO) between the sartorius and iliac muscles. Between January 2009 and January 2016, IM-CPO was performed in 17 joints (16 patients), and a traditional CPO was performed in 17 joints. The length of incision at wound closure, operative time, intraoperative blood loss, serum creatinine kinase (CK) level the day after surgery, correctional angle, walking ability assessed using the gait items of the Harris Hip Score (at 3 and 6 months after surgery), and perioperative complications were evaluated. Group differences were assessed using t-tests. The IM-CPO and CPO groups did not differ in the mean operative time (130 minutes and 124 minutes, respectively), mean serum CK the day after surgery (349 IU/L and 425 IU/L, respectively), or mean correctional angle (24.9° and 24.6°, respectively). The mean incision length was significantly shorter in the IM-CPO group (8.3 cm) compared to that in the CPO group (9.5 cm). The mean walking ability was significantly higher in the IM-CPO group (24.2 points) compared to that in the CPO group (20.9 points) at 3 months after surgery, but not at 6 months after surgery (26.4 points and 24.9 points, respectively). No serious complications were observed in either group.

In addition to demonstrating a similarly satisfactory correctional angle, IM-CPO is anticipated to enable early weight-bearing and recovery of walking ability. Thus, IM-CPO is considered a superior surgical technique.

In adults, osteoarthritis (OA) is associated with obesity and knee alignment. Whether knee alignment differences develop during childhood and are associated with obesity is unknown. We assessed the distribution of knee alignment in children and adolescents, and determined how knee alignment differs between obese and nonobese children. This cross-sectional study examined knee alignment in 155 healthy weight and 165 obese subjects. Knee alignment [metaphyseal-diaphyseal angle (MDA) and anterior tibiofemoral angle (ATFA)] and fat mass were measured using whole body dual-energy X-ray absorptiometry (DEXA). National reference data were used to generate age- and sex-specific body mass index (BMI, kg/m(2)) Z-scores. Multivariable linear regression was used to identify independent factors associated with ATFA and MDA. The mean MDA and ATFA were similar between obese and nonobese subjects. In stratified analyses, females had greater variability in MDA and ATFA values (p < 0.001 and p = 0.04, respectively) at higher BMI Z-scores. Compared with healthy weight controls, obese subjects had less valgus of the MDA prior to the onset of puberty (+ 2.0°, p = 0.001), but had greater valgus at later pubertal stages (-1.9°, p = 0.01).

We found significantly greater variability in knee alignment among females at higher BMI Z-scores, and greater valgus alignment in obese adolescents in late puberty. The major limitation is the use of DEXA for assessment of alignment, which needs validation against longstanding radiographs. Longitudinal studies are needed to determine whether childhood obesity is a risk factor for progressive malalignment that may predispose to pain and risk of early osteoarthritis.

Despite major progress in the imaging of gout, it is unclear which domains these techniques can evaluate and whether imaging modalities have the potential to provide valid outcome measures. The aim of this study was to assess the use of imaging instruments in gout according to the Outcomes in Rheumatology Clinical Trials (OMERACT) filter to inform the development of imaging as an outcome measure. A systematic literature search of imaging modalities for gout was undertaken. Articles were assessed by two reviewers to identify imaging domains and summarize information according to the OMERACT filter. The search identified 78 articles (one abstract). Modalities included were conventional radiography (CR) (16 articles), ultrasound (US) (29), conventional computed tomography (CT) (11), dual energy computed tomography (DECT) (20), and magnetic resonance imaging (MRI) (16). Three domains were identified as follows: urate deposition, joint damage, and inflammation. Although sufficient data were available to assess feasibility, validity, and reliability, comprehensive assessment of discrimination was not possible due to the paucity of prospective imaging studies. CR is widely accessible, inexpensive with a validated damage scoring system. US and MRI offer radiation-free methods of evaluating urate deposition, damage and inflammation, but may be limited by accessibility. DECT provides excellent definition of urate deposition and bone damage, but has restricted availability and requires radiation.

Imaging methods can detect urate deposition, damage, and inflammation in gout. More than one modality may be required depending on the domains and therapeutic agent of interest. No single imaging method currently fulfils all aspects of the OMERACT filter for any domain.

Granulomatosis with polyangiitis-a primary systemic vasculitis-most frequent manifestations are respiratory. Airway disease can present with stenosis, and although subglottic stenosis (SGS) is well described, narrowing distal to the glottis has been more recently the focus of reporting. Our objectives, therefore, are to describe the frequency, characteristics, and treatment of tracheobronchial stenoses (TBS) in granulomatosis with polyangiitis (GPA) at our institution, a national referral center for respiratory diseases. Also, to identify factors associated with TBS development in GPA. We undertook a retrospective study of all identified TBS cases (n-29) in whom their demographics, clinical and paraclinical features, and treatment were analyzed with descriptive statistics. Comparisons between those who developed and did not develop TBS (n-79) were established with the χ Females were predominantly affected by TBS (76%). Most patients had limited GPA (n-20, 69%). TBS appeared at a mean of 29 months after diagnosis of GPA. Main symptoms were dysphonia, stridor, and dyspnea. All TBS patients had tracheal involvement and 12 (41%) additional bronchial stenoses. Other accompanying manifestations by organ/system were rhinosinusal (n-26, 87%), musculoskeletal (n-16, 55%), ocular (n-13, 45%), pulmonary (n-12, 41%), renal (n-8, 27%), mucocutaneous (n-5, 17%), neurological (n-4, 13%). At TBS diagnosis, 17 patients were PR3-ANCA and/or C-ANCA positive, while 9 were MPO-ANCA and/or P-ANCA positive; results on the remaining were either negative or ANCA were not performed at that time. Seventeen patients had simultaneous medical (8 with glucocorticoid therapy, 9 with immunosuppressants) and surgical therapy, while the rest only the latter at the time of TBS diagnosis. Relapses were frequent (one in 18 patients; two in 11, three in 9 and 2 individuals had ≥4 relapses). Factors positively associated with TBS were the presence of general and musculoskeletal symptoms and rhinosinusal disease, while those negatively associated were prednisone oral daily dose >10mgqd and azathioprine intake. The extent of disease, either generalized or limited was not associated with TBS development, nor were ANCA levels.

TBS are serious complications of GPA which can arise at any stage of the disease. Timely diagnosis plus optimal treatment and follow-up remain unmet needs.

The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjögren's syndrome (pSS) patients treated with abatacept. In all 15 pSS patients included in the open-label Active Sjögren Abatacept Pilot (ASAP, 8 abatacept infusions) study parotid gland biopsies were taken before treatment and at 24 weeks of follow up. Biopsies were analysed for pSS-related histopathological features and placed in context of clini- cal responsiveness as assessed with EULAR Sjögren's syndrome disease activity index (ESSDAI). Abatacept treatment resulted in a decrease of germinal centres (GCs)/ mm2 (p=0.173). Number of GCs/mm2 at baseline was associated with response in the glandular domain of ESSDAI (Spearman ρ=0.644, p=0.009). Abatacept treatment did not reduce focus score, lymphoepithelial lesions, area of lymphocytic infiltrate, amount of CD21+ networks of follicular dendritic cells, and numbers of CD3+ T-cells or CD20+ B- cells. Number of IgM plasma cells/mm2 increased (p=0.041), while numbers of IgA and IgG plasma cells/mm2 were unaffected during abatacept treatment.

Abatacept affects formation of GCs of pSS patients in parotid glands, which is dependent on co-stimulation of activated follicular-helper-T-cells. Herewith, local formation of (autoreactive) memory B-cells is inhibited. Presence of GCs at baseline predicts responsiveness to abatacept in the ESSDAI glandular domain.

To explore the method for establishing animal models of gouty nephropathy complicated with chronic renal failure. Six-eight weeks old male Wistar rats were fed with 10% fodder yeast. The adenine at the daily dose of 100, 150, 200, 250, and 300 mg/kg was administrated to them by gastrogavage. The serum levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) were dynamically monitored. Meanwhile, the pathological changes of rat kidney were observed. Compared with the normal control group, serum BUN, Cr, and UA obviously increased in rats administered with 100 mg/kg for 7 days (P<0.05). Meanwhile, pathological changes as gouty nephropathy occurred. Along with the prolongation of the modeling time, the aforesaid biochemical indices and pathohistological changes of the kidney were more obvious. The blood Cr level just reached the chronic renal failure level on the 26th day of the administration (about the 4th week), and obviously exceeded the renal failure level on the 41st day (about the 6th week). The blood UA level increased to a higher level on the 7th day of modeling, and maintained at a higher level for a long time. It decreased rapidly from the 41st day to the 48th day. The renal pathological examination showed aggravated infiltration of lymphocytes and stromal fibrous proliferation. On the 48th day of modeling, the proliferation of the fibrous tissue and the interstitial fibrosis were obvious on the bases of the aforesaid changes. The serum BUN, Cr, and blood UA obviously increased in the rats administered with 150, 200, 250, and 300 mg/kg when compared with the normal control group, reaching the level of chronic renal failure (P<0.05). These levels obviously decreased 17 days after restoring to normal fodder feeding, and approached the normal levels till the 35th day.

Ideal experimental animal models of gouty nephropathy complicated with chronic renal failure could be established in male Wistar rats by feeding with 10% fodder yeast and 100 mg/kg adenine by gastrogavage for 5 weeks.

To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05).

Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico. Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were characterized by immunoprecipitation using 35S-methionine labeled K562 cell extract. Clinical information was obtained from medical records. DM represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%), followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody profile in adult-onset DM in Mexico City versus Guadalajara showed striking differences: anti-Mi-2 was 59% versus 12% (P = 0.0012) whereas anti-p155/140 was 9% versus 35% (P = 0.02), respectively. A strong association of anti-Mi-2 with DM was confirmed and when clinical features of anti-Mi-2 (+) DM (n = 30) versus anti-Mi-2 (-) DM (n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was more common in the anti-Mi-2 (+) group (P = 0.0001). Levels of creatine phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they responded well to therapy.

Anti-Mi-2 has a high prevalence in Mexican DM and is associated with the shawl sign and high CPK. The prevalence of anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus Guadalajara, which have a similar UV index. This suggests roles of factors other than UV in anti-Mi-2 antibody production.

Osteoarthritis (OA) pain is a health care highly demanding and costing condition. To estimate disease burden on health care in OA in Spain, determining whether burden differs by pain severity and usual analgesic treatment. A cross-sectional design using the 2017-Spanish-National-Health-Survey was used to abstract data of 5,234 adult patients (women 70.8%; 69.9 years) with a self-reported physician OA diagnosis. Patients were assembled according to pain severity (no/mild, moderate, severe) and use of usual analgesia (treated [66.5%]/untreated). Healthcare resource utilization (HRU) and corresponding costs were expressed Per-Patient-Per-Year (PPPY) and adjusted for covariates. Average (SD) healthcare cost was €2,274 (5,461) PPPY, with costs linked to outpatient medical visits being the major driver; ~43%. Adjusted PPPY medical visits, days of hospitalization, other healthcare visits, and corresponding costs were significantly higher in severe pain OA patients, compared to moderate or mild/no pain regardless of being currently treated with usual analgesics or not (p < 0.001). Treated OA patients showed higher HRU and costs than untreated patients.

Severity of pain was the main driver of HRU and costs in OA patients from a nationwide representative survey in Spain. These findings seem to be more consistent in treated versus not treated patients with usual analgesics.

The aim of this study was to characterise the use and costs of subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits schemes. Dispensing and expenditure data on conventional and biologic DMARDs were extracted from Medicare Australia and temporal trends were analysed. Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000 population per day (DDD/1,000 population/day). Conventional and biologic DMARD use increased 74% over the study period (4.86 to 8.46 DDD/1,000 population/day; average annual increase 6.7%). Conventional DMARDs accounted for the vast majority of total use and increased 55% (4.81 to 7.43 DDD/1,000 population/day), while biologic DMARD use increased 1,784% (0.055 to 1.030 DDD/1,000 population/day). The most frequently used conventional DMARD was methotrexate (56% total conventional DMARD use) and use increased 95%. Hydroxychloroquine and leflunomide use increased marginally while sulfasalazine use declined 4.2%. Etanercept was the most commonly used biologic DMARD in 2004 and adalimumab in 2014. Conventional DMARD expenditure decreased 4.2% to AUD$33.3 million but biologic DMARD expenditure increased 2,089% to AUD$585.4 million.

The use of conventional and biologic DMARDs increased substantially over a decade in Australia. Patterns of use of conventional DMARDs have changed, and costs have decreased. In contrast a significant escalation in both the use and cost of biologic DMARDs has occurred. Further research is required to address cost-effectiveness, regulation and quality use of these medicines in clinical practice.

The objectives of the present study were, with multidetector computed tomography (CT) as the reference method, to determine the performance of magnetic resonance imaging (MRI) and radiography for the detection of bone erosions in rheumatoid arthritis wrist bones, and to test whether measuring volumes of erosions on CT and MRI is reproducible and correlated to semiquantitative assessments (scores) of erosions on CT, MRI and radiography. Seventeen patients with rheumatoid arthritis and four healthy control individuals underwent CT, MRI and radiography of one wrist, performed on the same day. CT was performed on a Philips Mx8000IDT unit (voxel size 0.4 mm x 0.4 mm x 1 mm) and MRI was performed on a Philips Panorama 0.6T unit (voxel size 0.4 mm x 0.4 mm x 0.4 mm). Images were evaluated separately for erosions in all wrist bones and were scored according to the principles of the Outcome Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (CT and MRI) and the Sharp/van der Heijde (radiographs) scoring methods. Measurements of erosion volumes of all erosions were performed twice with a 1-week interval. With CT as the reference method, the overall sensitivity, specificity and accuracy (concordance) of MRI for detecting erosions were 61%, 93% and 77%, respectively, while the respective values were 24%, 99% and 63% for radiography. The intramodality agreements when measuring erosion volumes were high for both CT and MRI (Spearman correlation coefficients 0.92 and 0.90 (both P < 0.01), respectively). Correlations between volumes and scores of individual erosions were 0.96 for CT and 0.99 for MRI, while they were 0.83 (CT) and 0.80 (MRI) for persons' total erosion volume and total score (all P < 0.01).

With CT as the reference method, MRI showed moderate sensitivity and good specificity and accuracy for detection of erosions in rheumatoid arthritis and healthy wrist bones, while radiography showed very low sensitivity. The tested volumetric method was highly reproducible and correlated to scores of erosions.

To assess the efficacy of interferon beta (IFN beta) in combination with methotrexate in treatment of patients with rheumatoid arthritis. 209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study. Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFN beta treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups.

At the doses tested, treatment with IFN beta three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.

To develop and assess the effectiveness of a drug information leaflet (DIL) for D-penicillamine (DPA) and determine whether additional verbal information provides enhanced benefit. Three preliminary studies were undertaken: a reading age study; the development of a DIL for DPA; and a DPA knowledge questionnaire. The primary study assessed the effect of the DIL on the knowledge of 30 patients at weeks 0 and 24 after commencing DPA. A follow-up study of 100 patients randomly assigned to receive the DIL alone (control group) or with additional verbal backup (experimental group) determined the effects of additional verbal information by comparison of DPA knowledge questionnaire scores at weeks 0 and 24. The reading study showed that 12% of the sample had difficulty reading and so the DPA DIL was designed to be easy to read using the Flesch Reading Index. An assessment of knowledge of DPA prior to reading the DIL resulted in scores ranging from 0 to 13 with a median of 2 (maximum possible 14). By week 24 the median score was 10 (range 6-14), which was significant at P < 0.0001. The assessment of additional verbal backup showed that both the control group and the experimental group knew little about DPA on study entry, with a median score 2 in each group. On study exit, both groups knew significantly more (P < 0.001) about the drug; the control group scored 9 and the experimental group 11 (not significantly different; P=0.109).

A large minority of patients have poor reading skills, but when a DIL is designed to be easy to read patients gain significant amounts of knowledge from it. Providing additional verbal explanations did bring about increases in knowledge but these were not significant.

To use meta-analysis techniques to evaluate the efficacy and safety of platelet-rich plasma (PRP) injections for the treatment knee of osteoarthritis (OA). We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane database through April 2016 to identify Level I randomized controlled trials that evaluated the clinical efficacy of PRP versus control treatments for knee OA. The primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores. The primary outcomes were compared with their minimum clinically important differences (MCID)-defined as the smallest difference perceived as important by the average patient. We included 10 randomized controlled trials with a total of 1069 patients. Our analysis showed that at 6 months postinjection, PRP and hyaluronic acid (HA) had similar effects with respect to pain relief (WOMAC pain score) and functional improvement (WOMAC function score, WOMAC total score, International Knee Documentation Committee score, Lequesne score). At 12 months postinjection, however, PRP was associated with significantly better pain relief (WOMAC pain score, mean difference -2.83, 95% confidence interval [CI] -4.26 to -1.39, P = .0001) and functional improvement (WOMAC function score, mean difference -12.53, 95% CI -14.58 to -10.47, P  < .00001; WOMAC total score, International Knee Documentation Committee score, Lequesne score, standardized mean difference 1.05, 95% CI 0.21-1.89, P = .01) than HA, and the effect sizes of WOMAC pain and function scores at 12 months exceeded the MCID (-0.79 for WOMAC pain and -2.85 for WOMAC function score). Compared with saline, PRP was more effective for pain relief (WOMAC pain score) and functional improvement (WOMAC function score) at 6 months and 12 months postinjection, and the effect sizes of WOMAC pain and function scores at 6 months and 12 months exceeded the MCID. We also found that PRP did not increase the risk of adverse events compared with HA and saline. Level I, meta-analysis of Level I studies.

Current evidence indicates that, compared with HA and saline, intra-articular PRP injection may have more benefit in pain relief and functional improvement in patients with symptomatic knee OA at 1 year postinjection.

To assess in-hospital gout flares in patients with gout. Hospitalizations were evaluated for gout flares in a cohort of Olmsted County, Minnesota, residents with incident gout in 1989-1992 or 2009-2010. There were 429 patients followed up to 5 years. Of these, 169 patients experienced 454 hospitalizations. Hospitalization rates increased without reaching statistical significance from 1989-1992 to 2009-2010 [rate ratio (RR) 1.19, 95% CI 0.98-1.45]. The gout flare rate increased significantly during hospitalization (RR 10.2, 95% CI 6.8-14.5). In-hospital gout flare increased the average hospital stay by 1.8 days (p < 0.001).

Hospitalization increased the risk of gout flares 10-fold. In-hospital gout flares were associated with longer hospitalization.

In SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1. Patients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised. Consistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups.

Efficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

To determine onset subtypes and HLA associations of juvenile rheumatoid arthritis (JRA) in a First Nations (aboriginal) population; to determine whether population frequencies of HLA antigens may explain the distribution of subtypes of JRA in this population. All patients were children from Manitoba and Northwestern Ontario seen in a single pediatric rheumatology clinic between 1975 and 1996. Patients were identified from a clinic registry. Controls were adults of Algonkian Cree and Ojibway heritage. Class I and II major histocompatibility (HLA) typing was performed for First Nations patients and controls. There were a total of 74 First Nations patients with JRA. The relative frequency of rheumatoid factor (RF) positive polyarticular JRA was higher and that of pauciarticular JRA was lower in First Nations compared with Caucasian patients (42 versus 3% and 22 versus 58%, respectively; p = 0.00000). HLA-DRB1*04 (63%), 08 (43%), and 1402 (25%) were the most common DRB1 antigens among controls. The main subtypes of DRB1*04 were 0404 (33% of controls) and 0407 (23%). HLA typing was performed for 39 First Nations patients; 27 were Cree or Ojibway, 4 were from other tribes, and 8 were part First Nations. Among Cree and Ojibway, 59% of controls and 63% of patients with RF positive polyarticular JRA (n = 16) had HLA-DRB1 antigens bearing the rheumatoid arthritis (RA) shared epitope (OR 1.16, 95% CI: 0.38, 3.48). The OR for polyarticular RF positive JRA in those with DRB1*0802 and 0901 were 0.15, 95% CI: 0.02; and 1.24 and 5.83, 95% CI: 1.58, 28.38, respectively.

There was a high frequency of the RA shared epitope represented by both HLA-DRB1*0404 and 1402 in this Algonkian population. This high frequency may explain the high frequency of RF positive polyarticular JRA. DRB1*0802 may be protective, whereas DRB1*0901 may increase the risk for this subtype of JRA.

Premature cardiovascular events complicate chronic inflammatory conditions. Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug for rheumatoid arthritis (RA), reduces disease-associated cardiovascular mortality. MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). We hypothesised that MTX specifically protects the vascular endothelium against inflammatory injury via induction of AMPK-regulated protective genes. In the (NZW×BXSB)F1 murine model of inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial vasculopathy and attenuated end-organ damage. Studies of human umbilical vein endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that therapeutically relevant concentrations of MTX phosphorylate AMPKα(Thr172), and induce cytoprotective genes including manganese superoxide dismutase (MnSOD) and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were pretreated with tumour necrosis factor-α to mimic dysfunctional endothelium. Furthermore, MTX protected against glucose deprivation-induced endothelial apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element-binding protein (CREB)(Ser133) phosphorylation, while AMPK depletion attenuated this response and the induction of MnSOD and HO-1. CREB siRNA inhibited upregulation of both cytoprotective genes by MTX, while chromatin immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX-treated EC. Likewise, treatment of (NZW×BXSB)F1 mice with MTX enhanced AMPKα(Thr172) phosphorylation and MnSOD, and reduced aortic intercellular adhesion molecule-1 expression.

These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX.

Nearly all secreted proteins are glycosylated, and serum glycoproteins that exhibit disease-associated glycosylation changes have potential to be biomarkers. In rheumatoid arthritis (RA), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) are widely used as serologic biomarkers, but they lack sufficient specificity or precision. We performed comparative glycosylation profiling of MMP-3 using a recently developed antibody-overlay lectin microarray technology that allows semicomprehensive and quantitative analysis of specific protein glycosylation to develop an RA-specific disease activity biomarker. Serum was taken from patients with RA (n = 24) whose disease activity was scored using composite measures, and MMP-3 was immunoprecipitated and subjected to lectin microarray analysis. A disease activity index (DAI) based on lectin signal was developed and validated using another cohort (n = 60). Synovial fluid MMP-3 in patients with RA and patients with osteoarthritis (OA) was also analyzed. Intense signals were observed on a sialic acid-binding lectin (Agrocybe cylindracea galectin [ACG]) and O-glycan-binding lectins (Jacalin, Agaricus bisporus agglutinin [ABA], and Amaranthus caudatus agglutinin [ACA]) by applying subnanogram levels of serum MMP-3. ACG, ABA, and ACA revealed differences in MMP-3 quantity, and Jacalin revealed differences in MMP-3 quality. The resultant index, ACG/Jacalin, correlated well with disease activity. Further validation using another cohort confirmed that this index correlated well with several DAIs and their components, and reflected DAI changes following RA treatment, with correlations greater than those for MMP-3 and CRP. Furthermore, MMP-3, which generated a high ACG/Jacalin score, accumulated in synovial fluid of patients with RA but not in that of patients with OA. Sialidase digestion revealed that the difference in quality was derived from O-glycan α-2,6-sialylation.

This is the first report of a glycoprotein biomarker using glycan change at a local lesion to assess disease activity in autoimmune diseases. Differences in the degree of serum MMP-3 α-2,6-sialylation may be a useful index for estimating disease activity.

Galectin-9 (Gal-9) is involved in the regulatory process of immune responses or inflammation. The aim of the present study is to characterize circulating Gal-9 in patients with rheumatoid arthritis (RA) and its relationship with RA disease activity and phenotype. A total of 116 RA patients and 31 age-matched healthy controls were included in this study. Disease activity of RA patients was determined by Disease Activity Score of 28 joint scoring system (DAS28-ESR). Levels of Gal-9 in serum were determined by enzyme-linked immunosorbent assay (ELISA). Serum levels of Gal-9 were significantly higher in patients with RA compared to those in controls (median 7577 pg/ml [interquartile range (IQR) 5570-10,201] versus 4738 pg/ml [IQR 4267-5630], p = 0.001). There were significant differences in serum Gal-9 between RA patients with and without RA-ILD (9606 pg/ml [IQR 8522-12,167] versus 7078 pg/ml [IQR 5225-9447], p < 0.001) or those with and without advanced joint damage (stage II-IV, 9606 pg/ml [IQR 8522-12,167] versus 7078 pg/ml [IQR 5225-9447], p < 0.001). Although serum levels of Gal-9 correlated with the titers of ACPA (r = 0.275, p = 0.002), levels of ACPA titers conferred the different relationship, between serum Gal-9 and inflammatory mediators or RA disease activity. Although Gal-9 was correlated with ACPA titers (r = 0.508, p = 0.002), there was no correlation between Gal-9 levels and erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3 (MMP-3), or DAS28-ESR in RA patients with high titers of ACPA (> 200 U/ml). Conversely, Gal-9 was correlated with MMP-3 (r = 0.300, p = 0.007) or DAS28-ESR (r = 0.331, p = 0.004) but not with ACPA titer in RA patients with low titers of ACPA titers (< 200 U/ml).

Serum levels of Gal-9 were increased in RA patients and associated with RA disease activity in RA patients without high titers of ACPA. The levels of ACPA titers may influence the values of circulating Gal-9 in RA patients with various clinical phenotypes. These data suggest that Gal-9 possessed the properties of pro-inflammatory or arthropathic biomarker under the status of ACPA titers.

We have shown in vitro and in vivo that osteoclast maturation requires calcium-release activated calcium (CRAC) channels. In inflammatory arthritis, osteoclasts mediate severe and debilitating bone erosion. In the current study, we assess the value of CRAC channels as a therapeutic target to suppress bone erosion in acute inflammatory arthritis. Collagen-induced arthritis (CIA) was induced in mice. The CRAC channel inhibitor 3,4-dichloropropionaniline (DCPA) and a placebo was administered 1 day prior to collagen II booster to induce arthritis. Effects on swelling, inflammatory cell invasion in joints, serum cytokines and bone erosion were measured. Assays, by blinded observers, of arthritis severity showed that DCPA, 21 mg/kg/day, suppressed arthritis development over 3 weeks. Bone and cartilage damage in sections of animal feet was reduced approximately 50%; overall swelling of joints was reduced by a similar amount. Effects on bone density by µCT showed clear separation in DCPA-treated CIA animals from CIA without treatment, while differences between controls without CIA and CIA treated with DCPA differed by small amounts and in most cases were not statistically different. Response was not related to anticollagen titres. There were no adverse effects in the treated group on animal weight or activity, consistent with low toxicity. The effect was maximal 12-17 days after collagen booster, during the rapid appearance of arthritis in untreated CIA. At 20 days after treatment (day 40), differences in arthritis score were reduced and tumour necrosis factor α, interleukin (IL)-1, or IL-6 in the serum of the animals were similar in treated and untreated animals.

DCPA, a novel inhibitor of CRAC channels, suppresses bone erosion associated with acute arthritis in mice and might represent a new treatment modality for acute arthrits.

To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001 for mild-moderate).

The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.

To determine whether ethnicity was associated with baseline and 18-month health status within a merged sample of older adults with knee osteoarthritis (OA) from the Fitness Arthritis in Seniors Trial and the Arthritis, Diet, and Activity Promotion Trial. Cross-sectional and prospective study. Center-based exercise therapy at two universities. A total of 584 African-American (n=143) and Caucasian-American (n=441) adults aged 60 and older with knee OA were examined for baseline and 18-month health status. Six-minute-walk distance, 36-item Short Form General Health Scale (SF-36 GHS), and Physical Functioning Questionnaire index score. Ethnicity was obtained via self-report. Analyses of covariance testing the effect of ethnicity, adjusted for demographic and health status covariates, revealed significant effects for ethnicity upon baseline 6-minute-walk distance and SF-36 GHS, with Caucasian Americans reporting better scores (P=.001), although these differences were not significant after 18 months of exercise therapy.

Ethnicity and baseline function are important factors that should not be overlooked in knee OA research involving exercise interventions. Moreover, not only should physical activity be recommended to improve functional outcomes, it may also be a useful strategy in reducing health disparities.

To estimate the prevalence of rheumatic diseases in residents of Montes Claros, Brazil, of both sexes, aged above 16 years, using the COPCORD questionnaire. This was a cross-sectional study of 3038 people; the sample was probabilistic, by conglomerates, multiple stages, within homogeneous strata, the sampling unit being the domicile. The COPCORD questionnaire was used for all subjects, and a rheumatologist evaluated those patients who presented pain and/or functional disability. Laboratory tests and radiographs of small and large joints were done in some patients to confirm the diagnosis. Subjects were identified by socioeconomic level in quintiles A, B, C, D, and E, A being the highest. Two hundred nineteen patients were identified with rheumatic diseases, mean age 37 (SD 27) years, with female predominance. Seventy-seven (35.2%) were unemployed and socioeconomic level D was the most prevalent. Of all patients with rheumatic disease, osteoarthritis (OA) was observed in 126 (57.5%) patients, fibromyalgia (FM) in 76 (34.7%), rheumatoid arthritis (RA) in 14 (6.4%), and lupus in 3 (1.4%). Women were predominant in all diseases except OA. The mean (SD) age was 56 (12.7) years for OA, 43.2 (9.1) for FM, 53.4 (13.9) for RA, and 40 (14) for lupus.

The prevalence of rheumatic diseases evaluated by the COPCORD questionnaire was 4.14% for OA, 2.5% for FM, 0.46% for RA, and 0.098% for lupus.

To compare educational and vocational outcomes among adults with childhood-onset systemic lupus erythematosus (SLE) and adult-onset SLE. We used data derived from the 2002–2010 cycles of the Lupus Outcomes Study, a longitudinal cohort of 1,204 adult subjects with SLE. Subjects ages 18–60 years living in the US (n = 929) were included in the analysis and were classified as childhood-onset SLE if age at diagnosis was <18 years (n = 115). Logistic regression was used to assess the unadjusted and adjusted effect of childhood-onset SLE, sex, race/ethnicity, baseline age, urban or rural location, and US region on the likelihood of completing a bachelor's degree. Generalized estimating equations were used to assess the effect of childhood-onset SLE, demographics, education, and disease-related factors on the odds of employment, accounting for multiple observations over the study period. Subjects with childhood-onset SLE were on average younger (mean ± SD 29 ± 10 years versus 44 ± 9 years), with longer disease duration (mean ± SD 15 ± 10 years versus 11 ± 8 years). Subjects with adult-onset SLE and childhood-onset SLE subjects were equally likely to complete a bachelor's degree. However, subjects with childhood-onset SLE were significantly less likely to be employed, independent of demographic and disease characteristics (odds ratio 0.62, 95% confidence interval 0.42–0.91).

While subjects with SLE are just as likely as those with adult-onset SLE to complete college education, childhood-onset SLE significantly increases the risk of not working in adulthood, even when controlling for disease and demographic factors. Exploring reasons for low rates of employment and providing vocational support may be important to maximize long-term functional outcomes in patients with childhood-onset SLE.

Enrichment strategies which select subjects who appear to respond to the drug have been used in drug studies to demonstrate clinical efficacy. We have used clinical trial simulation techniques to examine factors that are relevant in clinical trial design based on enrichment where poor responders are excluded from the double-blind phase of the study. Simulations were performed for an analgesic trial design involving an open-dose titration phase (enrichment phase) followed by a double-blind, randomized, placebo-controlled maintenance phase. Enrichment was examined by excluding subjects above a predefined pain score (cutoff) from analysis of efficacy for the maintenance phase. Cutoff pain scores ranging from 4 to 7 on a 0 to 10 categorical scale were examined. A database consisting of chronic pain patients who participated in studies with a new formulation of buprenorphine was used to build the simulation model. Since no data were available for the key model variable "correlation between treatment and placebo response", values of 0.25, 0.5, and 0.75 were used for the simulations. A correlation between treatment and placebo effect ranging from 0.75 to 0.25 will cause the likelihood of trial success to vary from 50% to 95%. This model also shows that recruitment efficiency will decrease with the use of lower cutoff pain scores.

Prior to using enrichment techniques, investigators must consider the correlation between treatment effect and placebo response to optimize clinical trial design.

The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway. The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study. Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P<0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P<0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P<0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P<0.05).

Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients.

To assess the prevalence and factors related to rheumatic musculoskeletal disorders (RMSD) in a rural population of south India. The cross-sectional study included all individuals, 15 years and above, in a rural unit of Calicut District in North Kerala. Data were collected using the validated World Health Organization - International League of Associations for Rheumatology - Community Oriented Program for the Control of Rheumatic Diseases - Bhigwan model questionnaire by trained volunteers. In Phase 1 details of demographic characteristics, major co-morbidities and perceived musculoskeletal aches and pains were elicited. Phases 2 and 3 further evaluated and diagnosed the subjects. Predictors for RMSD were assessed using binary logistic regression analysis. There were 4999 individuals in the study. The prevalence of RMSD was 24.9% (95% CI 23.73; 26.12%). Females constituted 50.7% of the population; 5.1% of the respondents were illiterate; 80.9% belonged to low-income groups. Diabetes mellitus and hypertension affected 4.1% and 5.4% of the subjects respectively. The predictors for RMSD in the population were female sex, age, illiteracy, married status, low-income group, vegetarian diet, current alcohol consumption, current tobacco use, history of injury or accidents, diabetes and hypertension. Symptom-related ill-defined rheumatism (10.39%) followed by osteoarthritis (3.85%) were the most prevalent in the Phase 3 rheumatological evaluation.

There is an urgent need to introduce lifestyle modifications in high-risk groups and start rehabilitation for those affected. Community rheumatology in primary health care settings in rural areas needs to be strengthened by introducing national programs addressing RMSD at the grassroots level.

Behçet's disease (BD) susceptibility had been associated with single-nucleotide polymorphisms (SNPs) in IL23R-IL12RB2, IL10, STAT4, or ERAP1 locus in Japanese, Turkish, Chinese, and other populations, but not in a Korean genome-wide association study (GWAS). We aimed to fine-map BD risk association of these four loci using extensive imputation and additional genotyping for replication. In the discovery phase, 369 patients with BD enrolled in the previous Korean GWAS and 2000 controls retrieved from a population-based cohort of healthy Koreans were imputed for their genotypes of all SNPs in the four loci using the Asian data of the 1000 Genomes Project as reference. For genotype imputation of ERAP1 SNPs, the adjacent ERAP2 SNPs were also covered. For the 10 most significantly associated SNPs (8 imputed and 2 GWAS-genotyped), an additional 84 patients with BD and 283 healthy controls were genotyped for replication. The results from the discovery and replication phases were pooled for meta-analysis using the Mantel-Haenszel test to estimate the odds ratio (OR) and 95% confidence interval (CI). An IL23R-IL12RB2 intergenic SNP rs1495965 was significantly associated with BD risk (OR (95% CI) = 1.5 (1.3, 1.7), P = 2.5 × 10

BD susceptibility association was fine-mapped on the intergenic region between IL23R and IL12RB2 as marked by three correlated SNPs, rs1495965, rs1495966, and rs4655535.

To evaluate the therapeutic and economic consequences of various disease activity indices (DAIs) in RA according to 1987 and 2010 criteria. Data on disease activity states from all sustained visits were assessed from all patients who participate in the treatment in the Rotterdam Early Arthritis Cohort (tREACH) study, a stratified randomized trial to evaluate different treatment strategies in patients with a symptom duration of <1 year. Frequencies of treatment adaptations, based upon exclusive thresholds of various DAIs, were visualized in reclassification tables. The Stuart-Maxwell test was applied to analyse any significant differences between treatment decisions according to the different DAIs. Simulated annual median medication costs were estimated using the tREACH medication protocol with standard national costs. DAIs perform similar in RA according to 1987 and 2010 criteria. A total of 1104 DASs per DAI were available from 296 patients. DAIs differ significantly, compared with DASs, in classifying a patient's disease state. Consequently, treatment intensifications occur more frequently with SDAI, CDAI and DAS-28 usage, compared with DAS. Tapering treatment occurs less frequently with SDAI and CDAI and more frequently with DAS-28 usage. Simulated annual median medication costs are significantly higher if DAS-28, SDAI and CDAI are used compared with DAS usage.

Usage of various DAIs in a single patient leads to inconsistent disease state categorizations. Consequently, these inconsistencies significantly influence therapeutic decisions and accompanying costs. As DAI usage is imperative to uphold current European League Against Rheumatology (EULAR) treatment recommendations, physicians should consider these therapeutic and economic consequences before choosing a particular DAI.

Despite improved treatments and reduced disability, people with rheumatoid arthritis (RA) experience difficulties in daily life, which may negatively affect their balance of everyday life activities (occupational balance). The aim of this study was to describe occupational balance and its association with self-rated life satisfaction in men and women with RA. A survey, including demographic and health-related questions, was sent to 1,277 people who met the following criteria: with RA >4 years, aged 18-80 years, included in the Swedish Rheumatology Quality Register (SRQ), and had at least one registered visit to the participating rheumatology units in the year before inclusion. The 682 who answered all items in the Occupational Balance Questionnaire (OBQ) were included in the study. Their answers were analysed with descriptive statistics, and logistic regression analyses were conducted on men and women separately. Significantly higher occupational balance was identified in those participants who were >65 years, had no children at home, had a lower disease activity score, were not continuously stressed and reported low pain intensity. The results of the logistic regression analyses of both genders showed that higher occupational balance was significantly associated with a higher probability for rating themselves as being satisfied with life as a whole.

Occupational balance was identified as related to satisfaction with life as a whole, which is valuable information for health professionals. Enhanced occupational balance may be achieved in people with RA by working towards reducing their stress and pain.

To examine differences by sex in correlates of work status in rheumatoid arthritis (RA) patients seen in rheumatology clinical settings. Associations of demographic factors, occupation, duration of RA, and scores for disease and psychological scales with work status according to sex were examined in a cross-sectional study of 960 RA patients, aged 18-64 years, of whom 451 were working and 254 were work-disabled. Comparisons of characteristics were conducted by logistic regression between working and work-disabled, and between working and not working subjects. For both men and women, the odds of work disability increased with age, duration of RA, nonwhite race, and scores indicating high levels of functional disability, pain, and helplessness. Work-disabled women were more likely than working women to have less than a high school education or a nonprofessional occupation, compared with little association of these variables with work disability in men. Unmarried men were more likely to be work-disabled than working, while marital status was not associated with work disability in women. Differences by sex in the associations of pain and helplessness scores with work disability were also observed. Similar results were observed in associations of these characteristics when the outcome was coded as working versus not working.

These findings indicate some differences between men and women with RA in correlates of work disability that may help to more effectively target interventions. A patient's sex should be an important consideration in studies of work disability due to arthritis.

To evaluate the applicability of the ILAR criteria for classification of childhood arthritis in an outpatient pediatric rheumatology clinic population, and to determine the proportion of children who met standard classification criteria, but failed to meet ILAR criteria for specific arthritides, and therefore became unclassifiable. We reviewed the charts of 70 consecutive patients who had arthritis for at least 6 months, and attended the clinic between September and November 1997. Sixty-nine patients were categorized according to one of the traditional classifications [ACR for juvenile rheumatoid arthritis (JRA), European Spondylarthropathy Study Group (ESSG) for spondyloarthropathy, Vancouver Criteria for juvenile psoriatic arthritis (JPsA)], and the ILAR classification system. Sixty-one patients (88.4%) were classifiable by the ILAR system; 8 others failed to fulfill ILAR criteria for any specific category, and were assigned to the "other arthritis" category. Of the 29 patients with oligoarticular onset JRA, 6 were unclassified, 5 because of exclusions, and one because he fulfilled criteria for 2 categories. Presence of a family history of psoriasis accounted for most of the exclusions in the oligoarthritis and enthesitis related arthritis categories. All patients with polyarticular onset or systemic onset JRA were classified in the corresponding category in the ILAR system. One 9-year-old patient with spondyloarthropathy was reclassified as "other arthritis" because of exclusions. All 6 children with definite JPsA met ILAR criteria for PsA. Of 4 patients with probable JPsA, only 2 met ILAR criteria for PsA, a third was classified as rheumatoid factor negative polyarthritis, and the fourth was classified as "other arthritis" because of exclusions.

The ILAR classification criteria applied to a group of children with chronic arthritis classified by traditional criteria results in reassignment of 11.6% of the patients, predominantly in the oligoarticular group. It will be important to determine the role of the presence of a family history of psoriasis in classifying these patients.

The accumulation of advanced glycation endproducts in articular cartilage has been suggested as an etiologic factor in the development and progression of knee osteoarthritis (KOA). We conducted a prospective cohort study of skin advanced glycation endproducts (sAGEs) measured non-invasively by skin intrinsic fluorescence and the relationship between sAGE KOA progression in 160 men and 287 women in a sub-cohort of the Osteoarthritis Initiative at a single site. KOA progression was measured by yearly changes in Osteoarthritis Research Society International (OARSI)-defined joint space narrowing (JSN) and by yearly changes in joint space width (JSW) from baseline to 48 months. Sex-stratified repeated measures, mixed models to account for correlation between the knees within persons and adjusted for age, body mass index (BMI), Kellgren-Lawrence (KL) grade, beam angle and rim-to-rim distance were utilized. Increasing tertiles of sAGE measured at 36 months were associated with greater JSN over 4 years in men but not in women. The percentage of knees with JSN at 48 months, by tertiles of sAGE, were 7.0%, 16.0% and 17.7% in men (p for linear trend = 0.03) and 11.4%, 14.4% and 8.4% in women (p for linear trend = 0.33). Using change in JSW as the outcome, a similar trend was found in men but it was not statistically significant in fully adjusted models and no association was found in women.

This study provides preliminary evidence that sAGEs independent of age and BMI, are associated with knee JSN in men but not in women.

Cartilage destruction in osteoarthritis (OA) is generally accepted as a failed repair process. Cell adhesion is implicated in tissue repair. Therefore, adhesion of OA chondrocytes to extracellular matrix proteins was investigated. Using chondrocytes from human OA femoral head cartilage, adhesion to fibronectin and type II collagen of cells from distinct areas showing an intact cartilage surface or a fibrillated cartilage surface was studied. Modulation of chondrocyte adhesion by both protein kinase C (PKC) inhibitors and glucosamine sulfate (GS) was also investigated. A significant (P < 0.05) decrease in adhesion to fibronectin of chondrocytes from fibrillated cartilage, relative to those from grossly normal OA cartilage, was demonstrated. Adhesion to type II collagen was not modified by the chondrocyte origins (either from normal or fibrillated OA cartilage). Adhesion to fibronectin of cells from grossly intact cartilage was decreased by the addition of PKC and calmodulin-dependent kinase inhibitors, W7 and sphingosine, to the cell culture. Adhesion to fibronectin of chondrocytes from fibrillated cartilage was significantly (P < 0.05) increased after glucosamine sulfate treatment.

Fibrillation of cartilage from OA femoral head is associated with a defective adhesion of chondrocytes to fibronectin. The process is suggested to be dependent of PKC and/or calmodulin-dependent kinases and potentially reversible. Conceivably, it could play a role in OA cartilage destruction.

Failure rates are higher in medial unicompartmental knee arthroplasty (UKA) than total knee arthroplasty. To improve these failure rates, it is important to understand why medial UKA fail. Because individual studies lack power to show failure modes, a systematic review was performed to assess medial UKA failure modes. Furthermore, we compared cohort studies with registry-based studies, early with midterm and late failures and fixed-bearing with mobile-bearing implants. Databases of PubMed, EMBASE, and Cochrane and annual registries were searched for medial UKA failures. Studies were included when they reported >25 failures or when they reported early (<5 years), midterm (5-10 years), or late failures (>10 years). Thirty-seven cohort studies (4 level II studies and 33 level III studies) and 2 registry-based studies were included. A total of 3967 overall failures, 388 time-dependent failures, and 1305 implant design failures were identified. Aseptic loosening (36%) and osteoarthritis (OA) progression (20%) were the most common failure modes. Aseptic loosening (26%) was most common early failure mode, whereas OA progression was more commonly seen in midterm and late failures (38% and 40%, respectively). Polyethylene wear (12%) and instability (12%) were more common in fixed-bearing implants, whereas pain (14%) and bearing dislocation (11%) were more common in mobile-bearing implants.

This level III systematic review identified aseptic loosening and OA progression as the major failure modes. Aseptic loosening was the main failure mode in early years and mobile-bearing implants, whereas OA progression caused most failures in late years and fixed-bearing implants.

Hip resurfacing arthroplasty (HRA) typically uses a hybrid design (cemented femoral component and cementless acetabular shell) but has recently been performed with fully cementless components. There is a paucity of information on the clinical performance of these cementless designs. The UCLA clinical scores, SF-12 quality of life scores, complication rates, survivorship and radiographic signs of loosening or gross stress shielding of 39 hips (39 male patients) implanted with cementless HRA were compared with those of 40 hips (37 male patients) implanted with hybrid HRA during the same time frame. There were no significant differences in postoperative clinical and quality of life scores, complication rates, or radiographic signs of loosening between the 2 groups. The 5-year Kaplan-Meier survivorship was 97.2% for the cementless group and 100% for the hybrid group. This difference was not significant (

At a mean follow-up of 6 years, there is no tangible difference between the performance of cementless HRA compared to hybrid HRA. The absence of learning curve associated with this device and the potential for better preservation of femoral neck bone mineral density suggest that this technology is well suited for young patients with good bone quality seeking to resume an active lifestyle including high-impact activities.

To examine clinical effectiveness, treatment complications, and healthcare costs for indigenous and non-indigenous Albertans with rheumatoid arthritis (RA) participating in the Alberta Biologics Pharmacosurveillance program. Patients initiating biologic therapy in Alberta (2004-2012) were characterized for disease severity and treatment response. Provincial hospitalization separations, physician claims, outpatient department data, and emergency department data were used to estimate treatment complication event rates and healthcare costs. Indigenous patients (n = 90) presented with higher disease activity [mean 28-joint count Disease Activity Score (DAS28) 6.11] than non-indigenous patients (n = 1400, mean DAS28 5.19, p < 0.0001). Improvements in DAS28, function, swollen joint count, CRP, and patient and physician global evaluation scores were comparable to non-indigenous patients, but indigenous patients did not have a significant improvement in erythrocyte sedimentation rate (-0.31 per month, 95% CI -0.79 to 0.16, p = 0.199). At the end of study followup, 13% (12/90) of indigenous and 33% (455/1400) of non-indigenous patients were in DAS28 remission (p < 0.001). Indigenous patients had a 40% increased risk of all-cause hospitalization [adjusted incidence rate ratio (IRR) 1.4, 95% CI 1.1-1.8, p = 0.01] and a 4-fold increase in serious infection rate (adjusted IRR 4.0, 95% CI 2.3-7.0, p < 0.001). Non-indigenous patients incurred higher costs for RA-related hospitalizations (difference $896, 95% CI 520-1273, p < 0.001), and outpatient department visits (difference $128, 95% CI 2-255, p = 0.047).

We identified disparities in treatment outcomes, safety profiles, and patient-experienced effects of RA for the indigenous population in Alberta. These disparities are critical to address to facilitate and achieve desired RA outcomes from individual and population perspectives.

National estimates of arthritis prevalence rely on a single survey question about doctor-diagnosed arthritis without using survey information on joint symptoms, even though some subjects with only the latter have been shown to have arthritis. The sensitivity of the current surveillance definition is only 53% and 69% in subjects ages 45-64 years and ages ≥65 years, respectively, resulting in misclassification of nearly one-half and one-third of subjects in those age groups. This study was undertaken to estimate arthritis prevalence based on an expansive surveillance definition that is adjusted for the measurement errors in the current definition. Using the 2015 National Health Interview Survey, we developed a Bayesian multinomial latent class model for arthritis surveillance based on doctor-diagnosed arthritis, joint symptoms, and whether symptom duration exceeded 3 months. Of 33,672 participants, 19.3% of men and 16.7% of women ages 18-64 years and 15.7% of men and 13.5% of women ages ≥65 years affirmed joint symptoms without doctor-diagnosed arthritis. The measurement error-adjusted prevalence of arthritis was 29.9% (95% Bayesian probability interval [95% PI] 23.4-42.3) in men ages 18-64 years, 31.2% (95% PI 25.8-44.1) in women ages 18-64 years, 55.8% (95% PI 49.9-70.4) in men ages ≥65 years, and 68.7% (95% PI 62.1-79.9) in women ages ≥65 years. Arthritis affected 91.2 million adults (of 247.7 million; 36.8%) in the US in 2015, which included 61.1 million persons between 18 and 64 years of age (of 199.9 million; 30.6%). Our arthritis prevalence estimate was 68% higher than the previously reported national estimate.

Arthritis prevalence in the US population has been substantially underestimated, especially among adults younger than 65 years of age.

First peak internal knee abduction moment (KAM) has been associated with knee osteoarthritis. Gait modification including trunk lean, medial knee thrust, and toe-in gait have shown to reduce KAM. Due to heterogeneity between study designs, it remains unclear which strategy is most effective. We compared the effects of these modifications in healthy individuals to determine their effectiveness to reduce KAM, internal knee extension moment (KEM), and medial contact force (MCF). Twenty healthy individuals volunteered for this study (26.7 ± 4.7 years, 1.75 ± 0.1 m, 73.4 ± 12.4 kg). Using real-time biofeedback, we collected 10 trials for each modification using individualized gait parameters based on participants' baseline mean and standard deviation (SD). Two sizes of each modification were tested: 1-3 SD greater (toe-in and trunk lean) or lesser (knee adduction) than baseline for the first five trials and 3-5 SD greater or lesser than baseline for the last five trials. A significant main effect was found for KAM and KEM (p < .001). All modifications reduced KAM from baseline by at least five percent; however, only medial knee thrust and small trunk lean resulted in significant KAM reductions. Only medial knee thrust reduced KEM from baseline. MCF was unchanged.

Medial knee thrust was superior to trunk lean and toe-in modifications in reducing KAM. Subsequent increases in KEM and variation in individual responses to modification suggests that future interventions should be individualized by type and magnitude to optimize KAM reductions and avoid detrimental effects.

Older adults who experience pain are more likely to reduce their community and life-space mobility (ie, the usual range of places in an environment in which a person engages). However, there is significant day-to-day variability in pain experiences that offer unique insights into the consequences on life-space mobility, which are not well understood. This variability is complex and cannot be captured with traditional recall-based pain surveys. As a solution, ecological momentary assessments record repeated pain experiences throughout the day in the natural environment. The aim of this study was to examine the temporal association between ecological momentary assessments of pain and GPS metrics in older adults with symptomatic knee osteoarthritis by using a smartwatch platform called Real-time Online Assessment and Mobility Monitor. Participants (n=19, mean 73.1 years, SD 4.8; female: 13/19, 68%; male: 6/19, 32%) wore a smartwatch for a mean period of 13.16 days (SD 2.94). Participants were prompted in their natural environment about their pain intensity (range 0-10) at random time windows in the morning, afternoon, and evening. GPS coordinates were collected at 15-minute intervals and aggregated each day into excursion, ellipsoid, clustering, and trip frequency features. Pain intensity ratings were averaged across time windows for each day. A random effects model was used to investigate the within and between-person effects. The daily mean pain intensities reported by participants ranged between 0 and 8 with 40% reporting intensities ≥2. The within-person associations between pain intensity and GPS features were more likely to be statistically significant than those observed between persons. Within-person pain intensity was significantly associated with excursion size, and others (excursion span, total distance, and ellipse major axis) showed a statistical trend (excursion span: P=.08; total distance: P=.07; ellipse major axis: P=.07). Each point increase in the mean pain intensity was associated with a 3.06 km decrease in excursion size, 2.89 km decrease in excursion span, 5.71 km decrease total distance travelled per day, 31.4 km

In this demonstration study, higher intensity knee pain in older adults was associated with lower life-space mobility. Results demonstrate that a custom-designed smartwatch platform is effective at simultaneously collecting rich information about ecological pain and life-space mobility. Such smart tools are expected to be important for remote health interventions that harness the variability in pain symptoms while understanding their impact on life-space mobility.

Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in monocytes and macrophages and, since this family of molecules plays an important role in the regulation of cell activity, CD148 is a potential target for the manipulation of macrophage activation. For any molecule to be considered a therapeutic target, it is important for it to be increased in activity or expression during disease. We have investigated the expression of CD148 in two murine models of arthritis and in joints from rheumatoid arthritis (RA) patients using real-time PCR, immunohistochemistry, and studied the effects of proinflammatory stimuli on CD148 activity using biochemical assays. We report that CD148 mRNA is upregulated in diseased joints of mice with collagen-induced arthritis. Furthermore, we report that in mice CD148 protein is highly expressed in infiltrating monocytes of diseased joints, with a small fraction of T cells also expressing CD148. In human arthritic joints both T cells and monocytes expressed high levels of CD148, however, we show differential expression of CD148 in T cells and monocytes from normal human peripheral blood compared to peripheral blood from RA and both normal and RA synovial fluid. Finally, we show that synovial fluid from rheumatoid arthritis patients suppresses CD148 phosphatase activity.

CD148 is upregulated in macrophages and T cells in human RA samples, and its activity is enhanced by treatment with tumour necrosis factor alpha (TNFα), and reduced by synovial fluid or oxidising conditions. A greater understanding of the role of CD148 in chronic inflammation may lead to alternative therapeutic approaches to these diseases.

Osteoarthritis at the base of the thumb is a common problem, especially in women. Among the many surgical procedures aimed at restoring the function of the trapeziometacarpal joint, total trapeziectomy has been shown to provide good long-term results in most patients. But in some patients continued pain may lead the surgeon to consider a revision procedure. We report the use of costochondral autograft as an interposition material in revision of trapeziectomy in trapeziometacarpal osteoarthritis and to study its usefulness. The study design was retrospective. All of the patients had a costochondral autograft as a revision procedure after a failed trapeziectomy with ligament reconstruction. Patients were clinically assessed before and after surgery. The follow-up period was 24 months. Results were assessed as follows: good, complete relief of pain; fair, persistent mild pain and stiffness; poor, no relief of pain or any improvement with revision surgery. Four patients were included; there were 2 good results, 2 fair results, and no poor result. Pain relief was obtained in all patients. Thumb opposition showed a slight improvement in 1 patient and no change in the other 3 patients. Pinch strength showed no change. One case of iatrogenic injury of the sensory branch of the radial nerve was noted.

Costochondral autograft as a revision procedure after failed trapeziectomy is a reliable procedure. These preliminary outcomes showed that the result did not compare favorably with soft-tissue interposition. Nevertheless, in case of an iterative procedure, the lack of available soft-tissue material to interpose may lead the surgeon to consider a costochondral autograft. This procedure should be considered a salvage procedure.

The interaction between CXCL12 and its receptor, CXCR4, in the synovium of patients with rheumatoid arthritis (RA) is important for local inflammatory cell recruitment, angiogenesis, and cytokine production. CXCR7 was recently identified as an alternative receptor for CXCL12. We undertook this study to analyze the expression of CXCR7 in RA synovium and the pathogenic role of the CXCL12/CXCR7 pathway in RA. CXCR7 expression in RA synovial tissue was analyzed using immunohistochemistry, while expression of CXCR4 and CXCR7 on human umbilical vein endothelial cells (HUVECs) was examined using quantitative reverse transcription-polymerase chain reaction, and CXCR7 expression was also analyzed by flow cytometry. Tube formation and rat aortic ring angiogenesis assays were used to assess the effects of CCX733 (a CXCR7 antagonist) and AMD3100 (a CXCR4 antagonist) on CXCL12-induced angiogenesis. The effect of anti-CXCR4 monoclonal antibody (mAb) was also analyzed using a tube formation assay. The effects of CCX733 in a murine model of collagen-induced arthritis (CIA) were also evaluated. CXCR7 was expressed on endothelial cells in RA synovium and also on unstimulated HUVECs. The expression of CXCR7 on HUVECs was markedly up-regulated by interleukin-1β (IL-1β) stimulation, and this overexpression was further enhanced by CXCL12 treatment. Incubation with CXCL12 also promoted angiogenic activity, with addition of IL-1β again augmenting the effect. CXCL12-induced angiogenesis was inhibited by both CXCR4 and CXCR7 antagonists and by anti-CXCR4 mAb. Furthermore, treatment with CCX733 significantly reduced the clinical arthritis scores and the numbers of vessels in the inflamed synovial tissue in mice with CIA.

CXCR7 and CXCR4 are both important for angiogenesis in RA synovium, making CXCR7 another potential target molecule for novel RA angiogenesis-blocking therapies.

In recent years ankle distraction arthroplasty has gained popularity in the treatment of ankle arthritis as a means of both maintaining range of motion and avoiding fusion. We present a retrospective review of 25 patients who have undergone ankle distraction from 1999 to 2006. The mean age was 43 years; 16 were male, and 7 were female. Followup was 30 months after frame removal (range, 12 to 60 months). We were able to obtain followup on 23 of 25 patients. Adjuvant procedures were performed in some cases including Achilles tendon lengthening (5), ankle arthroscopy (4), open arthrotomy (1), and supramalleolar tibial and distal fibular osteotomy to correct distal tibial deformity (6). Twenty-one patients (91%) reported improved pain with those furthest post-op experiencing the best results. The average preoperative AOFAS score was 55 (range, 29 to 82), and the average postoperative score was 74 (range, 47 to 96). The difference between pre- and postoperative scores was significant (p = 0.005). SF-36 scores showed modest improvement in all components. Only two of the patients in the study underwent fusion after ankle distraction. Total ankle motion was maintained in all patients with improvement in the functional arc of motion in five patients who started with mild equinus contractures.

We feel that ankle distraction offers a promising solution for many people with ankle arthritis.

Obesity is associated with an increased risk of developing osteoarthritis (OA), which is postulated to be secondary to adipose tissue-dependent inflammation. Periarticular adipose tissue depots are present in synovial joints, but the association of this tissue with OA has not been extensively explored. The aim of this study was to investigate differences in local adipose tissue depots in knees with OA and characterize the changes related to class II and class III obesity in patients with end-stage knee OA. Synovium and the infrapatellar fat pad (IPFP) were collected during total knee replacement from 69 patients with end-stage OA. Histologic changes, changes in gene and protein expression of adiponectin, peroxisome proliferator-activated receptor γ (PPARγ), and Toll-like receptor 4 (TLR-4), and immune cell infiltration into the adipose tissue were investigated. IPFP and synovium adipose tissue depots differed significantly and were influenced by the patient's body mass index. Compared to adipocytes from the IPFP and synovium of lean patients, adipocytes from the IPFP of obese patients were significantly larger and the synovium of obese patients displayed marked fibrosis, increased macrophage infiltration, and higher levels of TLR4 gene expression. The adipose-related markers PPARγ in the IPFP and adiponectin and PPARγ in the synovium were expressed at lower levels in obese patients compared to lean patients. Furthermore, there were increased numbers of CD45+ hematopoietic cells, CD45+CD14+ total macrophages, and CD14+CD206+ M2-type macrophages in both the IPFP and synovial tissue of obese patients.

These differences suggest that IPFP and synovium may contain 2 different white adipose tissue depots and support the theory of inflammation-induced OA in patients with class II or III obesity. These findings warrant further investigation as a potentially reversible, or at least suppressible, cause of OA in obese patients.

To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment. A consensus meeting was held in Chicago on April 23-24, 2010, involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans that represented typical management of moderate juvenile DM. A preconference survey of CARRA, completed by 151 (56%) of 272 members, was used to provide additional guidance to the discussion. Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, or experiencing medication side effects or disease complications. Of particular importance, a single consensus steroid taper was developed.

We were able to develop consensus treatment plans that describe therapy for moderate juvenile DM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate juvenile DM.

The outcomes of total hip arthroplasty (THA) for the treatment of posttraumatic arthritis after acetabular fractures were inferior to those after primary non-traumatic THA. This study was performed in academic level I trauma center. From January 2011 to December 2014, a consecutive series of 21 patients (9 females), with average age of 56.7 years (range 29-75 years) who had posttraumatic hip joint arthritis after acetabular fractures, were included in our study. All patients underwent cementless THA. The average duration of follow-up was 26 months (range 24-36 months). At the latest follow-up, all patients could walk independently, thirteen (62%) patients had excellent Harris hip score, five (24%) had good HHS, and 3 (14%) had fair score. WOMAC scale decreased from 63 (range 42-92) to 4 (range 0-19). Two patients (9.5%) had heterotopic bone formation which did not affect the activity of the patients. There were no signs of loosening of the acetabular cups or around the femoral stem.

Cementless THA is an ideal treatment for posttraumatic hip arthritis with anatomic restoration of the hip center to improve the functional results and decrease the incidence of complications and revision rate.

The aim of this study was to radiographically analyze the long-term glenoid migration patterns following total shoulder arthroplasty to better understand the factors responsible for loosening. Complete radiographic follow-up of more than five years was available for 518 total shoulder arthroplasties performed for primary glenohumeral osteoarthritis with use of an anatomically designed prosthesis with a cemented, all-polyethylene, keeled glenoid component. Radiographs were assessed for humeral head subluxation, periprosthetic radiolucent lines, and shifting of the position of the glenoid component. The type of migration of the glenoid was defined according to the direction of tilt, or as subsidence in the case of medial migration. Definite radiographic evidence of glenoid loosening was observed in 166 shoulders (32%) and was characterized by radiolucency of ≥2 mm over the entire bone-cement interface in thirty shoulders and by a migration of the glenoid component (shift or subsidence) in 136 shoulders. Three predominant patterns of migration of the glenoid component were observed: superior tilting in fifty-two shoulders (10%), subsidence in forty-one shoulders (7.9%), and posterior tilting in thirty-three shoulders (6.4%). Superior tilting of the glenoid was associated with three risk factors: low positioning of the glenoid component, superior tilt of the glenoid component on the immediate postoperative coronal plane radiographs, and superior subluxation of the humeral head (p < 0.05 for all). Subsidence of the glenoid component was associated with the use of reaming to optimize the seating and positioning of the glenoid component (p < 0.001). Posterior tilting of the glenoid component was associated with preoperative posterior subluxation (i.e., a Walch type-B glenoid) and with excessive reaming (p < 0.01 for both).

The three patterns of migration observed in this study underscore the potential importance of the supporting bone beneath the glenoid component. In some shoulders, use of a keel or pegs to provide fixation of a polyethylene component in the absence of good support from subchondral bone may not be sufficient to resist compressive and eccentric forces, resulting in loosening. Preserving subchondral bone may be important for long-term longevity of the glenoid component.

From an initial group of 206 hips in 190 patients we carried out a retrospective clinical and radiological control of 74 hips in 72 patients covering a period of 20 years. Indications in 74 operated hips evidenced 48x(64.9%) primary and 26x(35.1%) secondary coxarthrosis. The average age at the time of operation was 53 years (37 years-68 years). All 72 patients with 74 hips received cement-free self- cutting Alloclassic screw cups of pure Titanium together with a cement-free square Alloclassic stem consisting of Titan- Aluminium-Niob alloy according to Zweymüller. Regarding the technique of operation we used the approach after Watson-Jones in the supine position. As prophylaxis against thrombosis 40% of the patients received derivates of heparine and 60% had anticoagulant therapy with cumarine. Prophylaxis against heterotopic ossifications were not carried out at this juncture in our department. After an average post-operational examination lapse of 20 years we were able to examine 72 patients (37.9%) with 74 hips (35.9%) clinically and radiologically. Further classification of the 72 patients records 47 females and 25 males. The average age at the time of operation was 53 years and at the time of post-operational check-up to 74 years. For the clinical post-operational check-up (n=74) we used the Harris Hip Score. Further evaluation shows 12x(16.2%) excellent results, 26x(35.1%) good and 29x(39.2%) fair results. In 7 patients (9.5%) we had to observe poor results because of multimorbidity, although also in these cases stability of TEP had been achieved. The radiological post-operational check-up of the 74 stable hips (35.9%) shows an average excentric position of the head of 1.4 mm (0 mm up until 4 mm) compared with 1 mm after 10 years. Over an average of about 20 years we carried out an exchange of the inlay and the head because of excentric position of the head, which correlates to a rate of reoperation of 6.8%. In 2000 and 2001 we published our 10 year results with cement-free Alloclassic screw cup and cement-free stem in 133 hips in 123 patients and compared our findings with those of other authors. After 10 years we saw only 3 % complications with cups and an overall re-operation rate of 6.7%. The 20-year-results show in all cases stable components of both cups and stems. 5 patients (6.8%) had to undergo re-operation with an exchange of inlay and head, whereby the components of the prosthesis themselves turned out to be stable. An average polyethylene abrasion of 1 mm after 10 years compares with a value of abrasion of 1,4 mm after 20 years. The 6.8% rate of re-operation after 20 years indicates the excellent results of the use of cement-free Alloclassic total endoprosthesis system of the hip according to Zweymüller.

The biocompatible qualities of modern prosthesis material lead to a quicker and optimal bony incorporation of the pros- thesis components. The excellent 20-year-results show a broad indicative spectrum, component stability of the prosthesis in all patients and therefore encourage the further use of cement-free hip implants in the future.

To evaluate tocilizumab (TLZ) effects on blood lipids composition and severity of carotid arteries (CA) atherosclerosis in rheumatoid arthritis (RA) patients after 24 week TLZ treatment. Before and 24 weeks after TLZ treatment 43 RA patients (33 women and 10 men) were examined by DAS 28 index, for blood serum concentration of cholesterol, triglycerides (TG), LPHD and LPLD cholesterol. The drug was injected intravenously in drops in a dose 8 mg/kg each 4 weeks. A 24 week TLZ treatment produced satisfactory and good anti-inflammatory effects in RA patients. Hypoalphalipoproteinemia incidence and atherogenicity index (AI) reduced 3 and 5 times, respectively (p < 0.05). Elevated levels of cholesterol, TG, LDPL cholesterol occurred with the same frequency before and after TLZ treatment. Cholesterol rose by 11.6%, LPHD cholesterol--by 48.9%, TG lowered by 7%, Al--by 31.9% (p < 0.05). LDLP cholesterol decreased Blood lipids composition shifts were associated with marked reduction in the disease activity: decreased concentration of C-reactive protein, IgM rheumatoid factor, DAS28 index, improvement of the patient functional status. Maximal thickness of the intima-media complex of CA increased by 8.2%. Atherosclerotic plaques were revealed before and after treatment in 17 (41.4%) patients from 41, in 5 (12.2%) patients the plaques arose after 6 months and in 5 (12.2%) patients the number of plaques increased.

Because of both positive and negative effects of IL-6 receptor inhibitors on blood lipids, combined treatment of RA must include statins for correction of dyslipidemia.

To answer the question, are the Jones Criteria being used appropriately in the diagnosis of acute rheumatic fever (ARF) by non-specialist medical staff in a remote Australian setting? The medical records of all patients discharged from Katherine Hospital (Northern Territory) with a diagnosis of ARF between January 2000 and April 2004 were retrospectively reviewed for adherence to the Jones Criteria. Data were also collected on specialist follow-up and need for transfer to a tertiary hospital. Twenty-five patients had a diagnosis of ARF and all were Aboriginal or Torres Strait Islander. Thirty-two per cent did not fulfil the Jones Criteria and of these 63% were recurrent cases. Eighty-eight per cent received specialist follow-up and of those who did not fulfil the Jones Criteria, all were diagnosed as ARF by the specialist. Only 20% required transfer to a tertiary hospital for higher-level care. The diagnosis of ARF results in long-term penicillin prophylaxis. This is a major public health undertaking that requires correct diagnosis. This study demonstrates that the Jones Criteria are being used appropriately to diagnose ARF in a remote setting. The ability to diagnose and treat Indigenous patients within their local region reduces social isolation and creates a more positive health care experience.

The Jones Criteria are being used appropriately to diagnose initial episodes of ARF but less successfully in recurrent episodes. Specialist follow-up is essential but acute episodes can be managed in remote settings, reducing the need to transfer patients to tertiary care with resultant patient dislocation and social isolation.