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The study aims to determine from the physician's perspective, the conditions and symptoms most relevant to the diagnosis of fibromyalgia (FM) for identifying International Classification of Diseases-diagnosis codes and prescription medications to evaluate FM-related healthcare resource utilization. A questionnaire was administered using an online physician network (SERMO™) from which responses of 102 physicians were evaluated: anesthesiologists (n = 6), neurologists (n = 18), primary care physicians (n = 16), pain specialists (n = 16), psychiatrists (n = 15), and rheumatologists (n = 31). Physicians scored the relative importance to a diagnosis of FM (0 = least relevant/important, 10 = most relevant/important) of 24 conditions and symptoms derived from a list provided by the National Data Bank for Rheumatic Diseases. Conditions and symptoms with mean scores ≥ 5 were considered the most relevant. Other survey questions included treatment goals, assessment of disease severity, medication use, and characterization of the physicians' experience and clinical practice. Ten conditions and symptoms (mean score) were reported as most relevant: Muscle pain (8.7), Fatigue/tiredness (8.5), Insomnia (8.0), Depression (7.8), Thinking/remembering (6.7), Nervousness (6.0), Muscle weakness (5.9), Headache (5.7), Irritable bowel syndrome (5.5), and Pain/cramps in abdomen (5.1). Treatment goals, severity assessment, and use of medications were generally similar across physician specialties.

This survey identified 10 conditions and symptoms that physician respondents considered most relevant to a diagnosis of FM. Further evaluation to determine how these conditions and symptoms contribute to FM-associated healthcare resource utilization is warranted.

International registries with large, heterogeneous patient populations provide excellent research opportunities for studying factors that influence treatment outcomes after total hip arthroplasty. In the present study, we used a European multinational database to investigate whether there is an association between three functional variables (preoperative pain, mobility, and motion) and functional outcome. We performed a retrospective cohort study on preoperative and follow-up clinical data that were prospectively entered into the International Documentation and Evaluation System European hip registry between 1967 and 2002. The inclusion criteria for this study were an age of more than twenty years, an underlying diagnosis of osteoarthritis, and a Charnley class-A functional designation at the time of surgery. A total of 12,925 patients (13,766 total hip arthroplasties) who met these criteria were entered into the analysis. Three functional variables (pain, mobility, and motion) that were assessed preoperatively were evaluated postoperatively at various follow-up examinations for a maximum of ten years. Six thousand four hundred and one patients could walk longer than ten minutes preoperatively; of these, 57.1% had a walking capacity of more than sixty minutes at the time of the most recent follow-up. In comparison, 6896 patients had a preoperative walking capacity of less than ten minutes and only 38.9% of these patients could walk more than sixty minutes at the time of the most recent follow-up. The difference was significant (p < 0.01). Similarly, 10,375 patients had a preoperative hip flexion range of >70 degrees ; of these, 74.7% had a flexion range of >90 degrees at the time of the most recent follow-up. In comparison, 2793 patients had a preoperative hip flexion range of <70 degrees and only 62.6% of these patients had a flexion range of >90 degrees at the time of the most recent follow-up. The difference was also significant (p < 0.01). Lasting, complete, or almost complete pain relief was achieved by >80% of the patients following total hip arthroplasty regardless of their preoperative categorization of pain.

Patients with poor preoperative walking capacity and hip flexion are less likely to achieve an optimal outcome with regard to walking and motion. In contrast, there is no correlation between the preoperative pain level and pain alleviation, which is generally good and long-lasting after total hip arthroplasty.

Computer-assisted navigation (CAS) was developed to improve the surgical accuracy and precision. Many studies demonstrated better alignment in the coronal plane in CAS TKA compared to conventional technique. The influence on the functional outcome is still unclear. Only few studies report long-term results of CAS TKA. This study was initiated to investigate 10-year patient-reported outcome of CAS and conventional TKA. From initially 80 patients of a randomized study of CAS and conventional TKA a total of 50 patients could be evaluated at the 10-year follow-up. The Knee Society Score and EuroQuol Questionnaire were assessed. For all patients a competing risk analysis for revision was performed. The patient-reported outcome measures demonstrated similar values for both groups. The 10-year risk for revision was 2.5% for conventional TKA and 7.5% for CAS TKA (p=0.237). This study was registered at clinicaltrials.gov on 11/30/2009, ID: NCT01022099 .

There was no difference between CAS and conventional TKA with regard to patient-reported outcome and revision risk ten years after surgery.

To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings. Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings. Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means -0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41-0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57-0.84) and physicians (r = 0.37-0.63), but demonstrated less responsiveness (standardized response means -0.21 and -0.12, respectively, over 8 months).

Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.

To explore the influence of chemokine, CXCL16, on the expression of the receptor activator nuclear factor κB ligand (RANKL) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS). The expression of CXCL16/CXCR6 and RANKL in RA or osteoarthritis (OA) patient synovia was examined by Western blot and immunohistochemistry. The serum concentration of CXCL16 and RANKL was measured by enzyme-linked immunosorbent assay (ELISA). RA-FLS were treated with recombinant CXCL16, and RANKL mRNA and protein were measured using PCR, Western blot and ELISA. The synovial expression of CXCL16, CXCR6, and RANKL was higher in RA patients than in patients with OA. The serum CXCL16 and RANKL levels were higher in RA patients compared with OA patients and healthy controls. CXCL16 correlated with erythrocyte sedimentation rate, C reactive protein, disease activity, serum rheumatoid factor, and RANKL. RA-FLS treated with CXCL16 showed markedly increased expression of RANKL. When STAT3 or p38 activation was blocked by an inhibitor, CXCL16 failed to upregulate RANKL expression. In contrast, inhibiting the Akt or Erk pathway did not achieve the same effect.

CXCL16 upregulates RANKL expression in RA-FLS and these effects are mainly mediated by the JAK2/STAT3 and p38/MAPK signaling pathways.

To observe the effect of resveratrol (Res) on in vitro proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further to investigate the PI3 K/Akt/BAD signal mechanism. The inhibition rate of RA FLS was examined by MTT assay. Cell cycle and the amount of apoptotic cells was measured by flow cytometry. PI3K/Akt/BAD signal transduction proteins expression was measured by western blot. The living cells measured by MTT dose and time-dependently reduced in Res groups. In Res groups, the fraction of living cells in the S-phase and G2/M-phase decreased respectively, while that in G1-phase increased, the difference was statistically significant compared with the TNF-alpha group (P < 0.05). Flow cytometry demonstrated that the apoptosis rate increased with increased Res concentration. Res inhibited TNF-alpha induced phosphorylation of Akt and BAD in RA FLS.

Res can inhibit RA FLS proliferation and induce apoptosis through inhibition of PI3K/Akt/BAD signalling pathway. Res may provide a new therapeutic approach in treatment of RA.

Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients. A prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group. Seventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547-8.380) was associated with an increased risk of pneumonia in RA patients. UMIN-CTR UMIN000009566 . Registered 17 December 2012.

PPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA.

To evaluate the duration of rheumatoid arthritis (RA) remission with respect to different drug treatments. Remission duration observed at 20-year follow-up of 442 RA patients living in the south of Estonia has been reviewed. Also, the data are provided on the disease onset, articular status, systemic lesions, RA activity and progression, the latest exacerbation and previous remission, standard laboratory indices, humoral immunity, examination of the biopsy of the articular tissues and subcutaneous fat for amyloid. According to the retrospective analysis, slow-progressive RA course occurs primarily in remissions longer than 5 years and less frequently in remissions lasting from 1 to 5 years. No matter what the drug was used, 14% of the patients have failed the treatment. 3% of the patients were in remission longer than 5 years. Short-term remissions (1-3 months) were induced in 13%, stable ones (3 months-1 year) in 39% of the cases. These remissions were observed in early RA, more frequently in patients with initial arthritis of the small joints. Remissions from 1 to 5 years were registered in 31% of the patients.

RA remissions up to 1 year represent temporary clinical improvement and do not inhibit progression of the rheumatoid process. Consideration of association between RA clinical course and remission duration helps to recognize groups of RA risk and to timely change treatment policy.

Realignment osteotomies of valgus knee deformities are usually performed at the distal femur, as valgus alignment is considered to be a femoral-based deformity. This dogma, however, has not been proven in a large patient population. Valgus malalignment may also be caused by a tibial deformity or a combined tibial and femoral deformity. The purposes of this study were (1) to analyze the coronal geometry of patients with valgus malalignment and identify the location of the underlying deformity and (2) to investigate the proportion of cases that require realignment osteotomy at the tibia, the femur, or both locations to avoid an oblique joint line. Cross-sectional study; Level of evidence, 3. The analysis included 420 standing full-leg radiographs of patients with valgus malalignment (mechanical femorotibial angle [mFTA], ≥4°). A systematic analysis of the coronal leg geometry was performed including the mFTA, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and joint-line convergence angle (JLCA). The localization of the deformity was determined according to the malalignment test described by Paley, and patients were assigned to 1 of 4 groups: femoral-based valgus deformity, tibial-based valgus deformity, femoral- and tibial-based valgus deformity, or intra-articular/ligamentary-based valgus deformity. Subsequently, the ideal osteotomy site was identified with the goal of a postoperative change of the joint line of two different maximum values, ±2° and ±4°, from its physiological varus position of 3°. Measurements of the coronal alignment revealed a mean (±SD) mFTA of 7.4° ± 4.3° (range, 4°-28.2°). The mean mLDFA and mean mMPTA were 84.8° ± 2.4° and 90.9° ± 2.6°, respectively. The mean JLCA was 1.2° ± 3.1°. The majority (41.0%) of valgus deformities were tibial based, 23.6% were femoral based, 26.9% were femoral and tibial based, and 8.6% were intra-articular/ligamentary based. To achieve a straight-leg axis and an anatomic postoperative joint line with a tolerance of ±4°, the ideal site of a corrective osteotomy was tibial in 55.2% of cases and femoral in 19.5% of cases. A double-level osteotomy would be necessary in 25.2% of cases. With a tolerance of ±2°, the ideal osteotomy site was the proximal tibia in 41.0% of cases and the distal femur in 13.6% of cases; a double-level osteotomy would be necessary in 45.5% of cases.

In contrast to the widespread belief that valgus malalignment is usually caused by a femoral deformity, this study found that valgus malalignment was attributable to tibial deformity in the majority of patients. In addition, a combined femoral- and tibial-based deformity was more common than an isolated femoral-based deformity. As a clinical consequence, varus osteotomies to treat lateral compartment osteoarthritis must be performed at the tibial site or as a double-level osteotomy in a relevant number of patients to avoid an oblique joint line.

To ultrasonographically quantify experimentally induced effusion of the distal interphalangeal (DIP) joint of horses and compare results with those obtained with palpation. 8 forelimbs from equine cadavers and forelimbs of 5 mares. Preliminary ex vivo experiments were performed to validate the methods. Then, the DIP joints of the forelimbs of standing horses were serially distended with saline (0.9% NaCl) solution (1, 4, and 10 mL) by injection through an intra-articular catheter. Two ultrasonographers measured distension of the dorsal recess of the DIP joint, and 2 surgeons, who were not aware of the volume injected, graded joint effusion by palpation. Intraobserver and interobserver repeatability was excellent for ultrasonographic measurements. Interobserver agreement for use of palpation to detect joint distension was moderate (κ = 0.45). There was an overall increase in the palpation distension grade with an increase in injected volume. Sensitivity for detection with palpation of larger volumes (4 and 10 mL) was high (92% and 100%, respectively). However, sensitivity was lower (57%) for detection with palpation of minimal distension (1 mL).

Although palpation provided a reliable clinical assessment of DIP joint effusion for volumes of 4 to 10 mL, ultrasonographic measurements were easy to obtain, more accurate, and able to detect smaller amounts of distension. This may be clinically relevant for the assessment of effusion of the DIP joint that can arise in horses with early osteoarthritis or infectious arthritis with concomitant soft tissue swelling that precludes accurate assessment with palpation.

The aim of the study was to assess the safety, tolerability and efficacy of palmitoylethanolamide (PEA) when dosed at 300 mg and 600 mg per day on symptoms of knee osteoarthritis. This was a single site, comparative, double-blind placebo controlled study in adults with mild to moderate knee osteoarthritis with 111 participants randomized to receive 300 mg PEA, 600 mg PEA or placebo each day, in divided doses b.i.d, for 8 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The secondary outcomes were the Numerical Rating Scales (NRS) for pain, the Depression Anxiety Stress Scale (DASS), the Perceived Stress Scale (PSS), the Pittsburg Sleep Quality Index (PSQI), the Short Form Health Survey (SF-36), the use of rescue pain medication and clinical safety assessment. There was a significant reduction in the total WOMAC score in the 300 mg PEA (p = 0.0372) and the 600 mg PEA (p = 0.0012) groups, the WOMAC pain score (300 mg PEA, p = 0.0074; 600 mg PEA, p =  < 0.001), the WOMAC stiffness score (PEA 300 mg, p < 0.0490; 600 mg PEA, p = 0.001) and in the WOMAC function score in the 600 mg PEA group (p = 0.033) compared to placebo. The NRS pain evaluations for "worst pain" and "least pain" were significantly reduced in the 300 mg PEA group (p < 0.001, p = 0.005) and the 600 mg PEA group (p < 0.001, p < 0.001) compared to placebo. There was a significant reduction in anxiety (DASS) in both active treatment groups (300 mg PEA, p = 0.042; 600 mg PEA group (p = 0.043) compared to placebo. There were no changes in the clinical markers and the product was well tolerated.

The study demonstrated that palmitoylethanolamide may be a novel treatment for attenuating pain and reducing other associated symptoms of knee osteoarthritis. Further studies on the pharmacological basis of this anti-inflammatory effect are now required.

Poor intake of vitamin K is common. Insufficient vitamin K can result in abnormal cartilage and bone mineralization. Furthermore, osteophyte growth, seen in osteoarthritis (OA), may be a vitamin K-dependent process. We undertook this study to determine whether vitamin K deficiency is associated with radiographic features of OA. We conducted an analysis among 672 participants (mean age 65.6 years, 358 women) in the Framingham Offspring Study, a population-based prospective observational cohort. Levels of plasma phylloquinone (the primary form of vitamin K) had previously been measured in these participants, for whom we also had bilateral hand and knee radiographs. The main outcomes were 1) prevalence ratios (PRs) of OA, osteophytes, and joint space narrowing (JSN) per quartile of plasma phylloquinone level for each joint, adjusting for correlated joints using generalized estimating equations, and 2) adjusted mean number of joints with each feature per quartile of plasma phylloquinone level. Analyses were conducted in hands and knees separately and adjusted for age, sex, body mass index, total energy intake, plasma vitamin D, and femoral neck bone mineral density. The PRs for OA, osteophytes, and JSN and adjusted mean number of joints with all 3 features in the hand decreased significantly with increasing plasma phylloquinone levels (P<or=0.03 for all). For example, as plasma phylloquinone levels rose, the PR for hand OA decreased from 1.0 to 0.7 (P=0.005). For the knee, only the PR for osteophytes and the adjusted mean number of knee joints with osteophytes decreased significantly with increasing plasma phylloquinone levels (PR decreased from 1.0 to 0.6, P=0.01).

These observational data support the hypothesis of an association between low plasma levels of vitamin K and increased prevalence of OA manifestations in the hand and knee.

To estimate and analyse the long-term outcome of arthroscopy for the treatment of the temporomandibular joint (TMJ) internal derangements. Twenty-nine patients (35 joints) who underwent TMJ arthroscopy under general anaesthesia due to osteoarthritis between years 2000 and 2007 (Wilkes stages IV and V) were included in this study. The age range at the time of surgery was from 18 to 69 years. The scores for preoperative maximal interincisal opening (MIO), and visual analogue scale (VAS) score for pain before arthroscopy, 6 months and 5 years after arthroscopy were compared. Fibrous adherences were found in all cases, fibrillations in 76% of cases. The most frequent radiographic sign was erosion (69%). There was a significant increase in the MIO postoperatively after 6 months (r(s)=0.56; n=29, p>0.01) that held during the longer-term follow-up (5 years) period (r(s)=0.58; p<0.001). VAS after 6 months was positively correlated to VAS after 5 years (r(s)=0.38; p=0.040). There were no significant differences between the results of follow-up when comparing the shorter (6 months) and longer (5 years) results.

Arthroscopic lysis and lavage for the treatment of TMJ disorders offers favourable long-term stable results with regard to increasing MIO and reduced pain and dysfunction.

Duloxetine has been studied in four distinct chronic pain conditions - osteoarthritis (OA), fibromyalgia, chronic low back pain (CLBP) and diabetic peripheral neuropathic pain (DPNP). These trials have involved large numbers of patients with at least moderate pain, and have used similar methods for recording pain intensity, over about 12 weeks. Data from the trials were pooled according to painful condition, and reanalysed at the level of the individual patient and using increasing levels of pain intensity reduction (<15%, 15-29%, 30-49%, ≥ 50%), with different imputation methods on withdrawal. The proportion of patients recording at least 50% pain intensity reduction plateaued after 2-6 weeks in fibromyalgia, and 8-12 weeks in other conditions. The duloxetine-specific benefit [number needed to treat (NNT) for at least 50% pain intensity reduction] was fairly constant after about 2 weeks for DPNP and fibromyalgia and after about 4 or 5 weeks for OA and CLBP. In all conditions, responses were bimodal, with patients generally experiencing either very good or very poor pain relief. Last-observation-carried-forward imputation produced numerically and occasionally statistically better (lower) NNTs than use of baseline-observation-carried-forward (true response).

Baseline-observation-carried-forward (true response), which combines the success of high levels of pain relief with the failure to experience pain relief on withdrawal of the drug is conservative and probably reflective of clinical practice experience. The distribution of effect was not normal; few patients had the average response and averages are not an appropriate descriptor for these data.

This study investigates differences in femoral head penetration between highly cross-linked polyethylene (HXLPE) cemented sockets both with and without radiolucent lines (RLLs) in the early postoperative phase and at 5 years follow-up. There were 35 patients (37 hips), mean age of 66.8 years, who underwent total hip arthroplasty (THA) using highly HXLPE cemented sockets. They were divided into 2 groups based on postoperative the early appearance of RLLs. Femoral head penetrations on both anteroposterior- and Lauenstein-view radiographs were evaluated, and the mean polyethylene (PE) wear rate was calculated based on femoral head penetrations between 2 and 5 years. Femoral head penetrations in the proximal direction were 0.075 mm and 0.150 mm in the RLL and non-RLL groups at 1 year postoperatively ( p = 0.019). At 5 years measured penetration was 0.107 mm and 0.125 mm in the RLL and non-RLL groups, respectively ( p = 0.320). The mean PE wear rates in anteroposterior-view were 0.008 mm/year and 0.003 mm/year in the RLL and non-RLL groups ( p = 0.390) and those in Lauenstein-view were 0.010 mm/year and 0.005 mm/year, respectively ( p = 0.239).

In the RLL group, the PE bedding-in was less compared with those in the non-RLL group. Additionally, the mean PE wear rate in the RLL group tended to be higher than that in the non-RLL group. The distribution of stress loading through the cement may differ according to whether early RLLs appear.

Rheumatic heart disease is still the commonest valvular heart disease in India. There is no population based study regarding the prevalence of rheumatic fever/rheumatic heart disease (RF/RHD) from Himachal and hence the purpose of study. A community based survey for prevalence of RF/RHD was done in four villages of different districts of Himachal. The subjects suspected to have RF/RHD on clinical ground were subjected to echocardiography to confirm the diagnosis. Total 1882 subjects were screened. 909 were male and 973 were female. 11 of these were found to have RF/RHD (5.8/1000). Mean age of these patients was 30.35 +/- 14.17 years. 10 of these were female and one was male. Mitral valve was the commonest to be involved. Seven were known to have RF/ RHD and five were on penicillin prophylaxis.

RF/RHD is still common in rural population of Himachal. Mitral valve is commonest to be involved and prevalence is much more in female than in male.

Mesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA. Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and CNKI (National Knowledge Infrastructure, China) databases were systematically reviewed. The pain level and function improvements were evaluated using visual analog scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC). The pooled estimate was calculated with weighted mean difference (WMD) with 95% confidence intervals (95%CIs). Nine RCTs involving 476 patients were included in this meta-analysis. The pooled estimate showed that the treatment of MSCs significantly reduced VAS, WOMAC pain, WOMAC stiffness, and WOMAC function scores at a long-term follow-up (12 or 24 months). However, for the IKDC and WOMAC total scores, MSCs also showed significant improvement in these outcomes, although this was not statistically significant when compared to the control.

Based on the current studies, our results suggested that MSCs were a promising option for the treatment of patients with knee OA. However, considering the potential limitations, more well-performed, large-scale RCTs are needed to verify our findings.

Although it is common for rheumatologists to initiate biologic agents after failure of methotrexate monotherapy in rheumatoid arthritis (RA), ample data support the initial use of combinations of conventional therapies in this clinical scenario. Our study explores the durability of triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) versus methotrexate-etanercept in RA. RA patients with suboptimal response to methotrexate (n = 353) were randomized to either triple therapy or methotrexate-etanercept therapy in a 48-week, double-blinded, noninferiority trial. Patients without clinical improvement at 24 weeks were switched to the alternative treatment. Of the total, 289 participated in followup. We report treatment durability, Disease Activity Score in 28 joints (DAS28), and other measures during an open-label extension for an additional period up to 72 weeks. Mean ± SD duration of open-label followup was 11 ± 6 months. The likelihood of continuing conventional therapy at 1 year was 78% for triple therapy versus 63% for methotrexate-etanercept, with most treatment changes occurring at the start of followup. More patients changed from methotrexate-etanercept to triple therapy than from triple therapy to methotrexate-etanercept (P = 0.005). DAS28 scores and other disease activity measures were not different for the 2 treatments and were stable during followup.

In RA patients with suboptimal methotrexate response randomized to receive triple therapy or methotrexate-etanercept, the former was found to be significantly more durable. Given cost differences and similar outcomes, the variable durability demonstrated provides additional evidence supporting conventional combinations over biologic agent combinations as the first choice after methotrexate inadequate response.

Anti-cyclic citrullinated peptide (CCP) antibodies have emerged as sensitive and specific serological markers of rheumatoid arthritis (RA). However, antibodies to several other citrulline-containing proteins, including citrullinated fibrin and vimentin, have been detected in patients with RA, suggesting that citrulline is an essential constituent of autoantigens for RA-specific autoantibodies. We examined the diagnostic performance of the newly developed anti-mutated citrullinated vimentin (MCV) antibody assay. Concentrations of anti-MCV, anti-CCP2, and rheumatoid factors (RF) were determined in the sera of 237 individuals: 119 patients with RA and 118 controls, including patients with other rheumatic diseases and healthy subjects. Diagnostic properties were compared by receiver-operating characteristic curve analysis. Using manufacturer's recommended cutoff values, sensitivity and specificity of anti-MCV antibodies were 75.6% and 91.5% in RA, compared to 66.4% and 98.3% for anti-CCP2. Introducing cutoff values to obtain the same 95% specificity resulted in decreased sensitivity of the anti-MCV test (69.7%) and increased sensitivity of the anti-CCP2 test (74.8%). At optimal cutoff levels, 29.4% of IgM RF-negative cases as well as 13.3% of anti-CCP2-negative cases in the RA group were anti-MCV-positive. Double-positivity for anti-MCV and anti-CCP2 provided 98.3% specificity with 97.5% positive predictive value in RA.

Overall, the performance of the novel anti-MCV ELISA for the diagnosis of RA is similar to that of the anti-CCP2 test [area under the curve 0.853 (95% CI 0.801-0.905) vs 0.910 (95% CI 0.873-0.946); p not significant]. As the diagnostic spectrum of the anti-MCV assay is somewhat different from that of anti-CCP2, the combined application of the 2 assays can improve the laboratory diagnostics of RA.

In our previous proteomic surveillance, we found that at least 11 proteins in neutrophils were increased more than 2.5-fold by the stimulation of GM-CSF. In this paper, focusing on one of the 11 proteins, S100 calcium binding protein A8 (S100A8), we tried to elucidate the effect of S100A8 and the cooperative effect of S100A8 and GM-CSF on production and secretion of cytokines of neutrophils. S100A8 in neutrophil was detected by western blotting, and concentrations of S100A8 in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were measured by ELISA. Cytokine levels in the culture medium of neutrophils incubated with and without S100A8 were measured by an antibody array. IL-8 and IL-16 levels in the culture medium of neutrophils stimulated with S100A8, GM-CSF, and the combination of S100A8 and GM-CSF were measured by ELISA. The mRNA levels of IL-8 and IL-16 in the stimulated neutrophils were analysed by real-time PCR. The western blotting analysis confirmed that S100A8 is up-regulated in neutrophil by the stimulation of GM-CSF. Furthermore, the ELISA analysis confirmed that S100A8 was significantly elevated in SF of patients with RA compared to SF of patients with OA. S100A8 induced mRNA expression and secretion of IL-8 and IL-16. S100A8 further enhanced production of IL-8 by GM-CSF but not that of IL-16.

These data suggest that S100A8 may be involved in the exacerbation of RA, and that S100A8 may be a therapeutic target of RA.

To establish an expert consensus on which criteria are the most appropriate in clinical practice to refer patients with systemic sclerosis (SSc) for right heart catheterisation (RHC) when pulmonary hypertension (PH) is suspected. A three stage internet based Delphi consensus exercise involving worldwide PH experts was designed. In the first stage, a comprehensive list of domains and items combining evidence based indications and expert opinions were obtained. In the second and third stages, experts were asked to rate each item selected in the list. After each of stages 2 and 3, the number of items and criteria were reduced according to a cluster analysis. A literature search and the opinions of 47 experts participating in Delphi stage 1 provided a list of seven domains containing 142 criteria. After stages 2 and 3, these domains and tools were reduced to three domains containing eight tools: clinical (progressive dyspnoea over the past 3 months, unexplained dyspnoea, worsening of WHO dyspnoea functional class, any finding on physical examination suggestive of elevated right heart pressures and any sign of right heart failure), echocardiography (systolic pulmonary artery pressure >45 mm Hg and right ventricle dilation) and pulmonary function tests (diffusion lung capacity for carbon monoxide <50% without pulmonary fibrosis).

Among experts in pulmonary arterial hypertension-SSc, a core set of criteria for clinical practice to refer SSc patients for RHC has been defined by Delphi consensus methods. Although these indications are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present tools in further studies.

The aim of this study is to point out the recent characteristics and developments of therapeutic patient education (TPE) in rheumatoid arthritis through an analysis of the international articles published from 2003 to 2008. Studies were selected from major databases, using the following keywords: rheumatoid arthritis, patient education, self-management, programs. Three authors independently reviewed each study and selected the data using the patient education research categories (PERC). Articles consistently related to patient education in rheumatoid arthritis (37 among 109) were included. The selected articles have been published in 23 scientific journals. The majority of them concern TPE for adult patients with rheumatoid arthritis. TPE is delivered in several structures and group education represents the most widespread educational strategy mainly provided by a multiprofessional team. There are two types of programs: educational, aiming to make the patient competent in the daily management of his disease and psycho-educational ones, aiming to improve coping and to decrease stress, anxiety and depression. Twenty-eight studies show the effectiveness of TPE on the basis of bio-clinical, educational, psychosocial, economical criteria, but the majority of these positive results are observed in short-term. Barriers to TPE are linked to cultural and socio-economic factors.

A large number of studies still assess the positive effects of TPE. Nowadays, the problems of short-term efficacy of TPE and the cultural and social barriers to this practice have become a major issue for research.

To evaluate effects of meloxicam on severity of lameness and other clinical signs in dogs with osteoarthritis (OA). Randomized, controlled, multicenter clinical trial. 217 client-owned dogs with clinical and radiographic signs of OA. Dogs were randomly assigned to be treated with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1 mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general clinical score was assigned by investigators on days 1 (ie, prior to initiation of treatment), 8, and 15 on the basis of severity of lameness, extent of weight bearing, and severity of signs during palpation of the affected joint. Owners and investigators provided overall evaluations on days 8 and 15. Dogs treated with meloxicam had significantly greater improvements in general clinical scores, compared with baseline scores, on days 8 and 15 than did dogs treated with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in which owners and investigators considered treatment to be successful were significantly higher than percentages of control dogs in which treatment was considered to be successful. No abnormalities in hematologic and serum biochemical test results were detected.

Results suggest that compared with administration of a placebo, administration of meloxicam for 14 days significantly improved the clinical condition of dogs with OA without causing adverse effects.

Although rates of arthroplasty have increased dramatically, rates among patients with rheumatoid arthritis (RA) are reported to be decreasing. It is not known if this is also the case among patients with other inflammatory arthritides. This study was undertaken to evaluate rates of arthroplasty due to RA, juvenile idiopathic arthritis (JIA), spondyloarthritis (SpA), and a composite group of patients with inflammatory arthritides (IA), compared to arthroplasty rates among patients without inflammatory or autoimmune conditions. Administrative discharge databases (State Inpatient Databases of the Healthcare Cost and Utilization Project, New York Department of Health Statewide Planning and Research Cooperative System, California Statewide Health Planning and Development) were used to compare rates of knee, hip, and shoulder arthroplasty occurring from 1991 to 2005. Of 2,839,325 arthroplasties in 1991-2005, 2.7% were performed in patients with IA. The rate of arthroplasty for noninflammatory conditions doubled (124.5 per 100,000 persons in 1991 versus 247.5 per 100,000 persons in 2005), while the rate for IA remained stable at 5.1 per 100,000. Rates of arthroplasty for RA decreased slightly (4.6 per 100,000 versus 4.5 per 100,000) and those for JIA decreased by nearly 50% (0.22 per 100,000 versus 0.13 per 100,000), but the rate of arthroplasty for SpA increased by nearly 50% (0.22 per 100,000 versus 0.31 per 100,000). Age at the time of arthroplasty increased for patients with RA (mean ± SD 63.4 ± 12.7 years versus 64.9 ± 12.8 years), JIA (30.9 ± 12.2 years versus 36.7 ± 14.9 years), and SpA (54.3 ± 16.1 years versus 60.4 ± 13.9 years). However, the mean age at the time of arthroplasty among non-IA cases decreased (71.5 ± 11.8 years versus 69.0 ± 12.0 years).

This population-based study is the first to show that arthroplasty rates have decreased significantly among patients with JIA and minimally among patients with RA, and have increased among patients with SpA. The increased age at the time of arthroplasty among patients with JIA and SpA suggests that these patients are increasingly able to defer surgical interventions. Further research is needed to assess the ongoing effect of biologic agents on the need for arthroplasties in patients with IA.

Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA. Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee OA in rats was used. A novel automated 3-dimensional indentation tester (Mach-1) was used to quantify the thickness and stiffness properties of the articular cartilage. Inhibition of HH signaling through KOR activation was achieved with a selective peptide agonist, JT09, which reduced HH signaling via the cAMP/CREB pathway in OA human articular chondrocytes (P = 0.002 for treated versus untreated OA chondrocytes). Moreover, JT09 markedly decreased matrix degeneration induced by an HH agonist, SAG, in pig articular chondrocytes and cartilage explants (P = 0.026 versus untreated controls). In vivo application of JT09 via intraarticular injection into the rat knee joint after PMM surgery significantly attenuated articular cartilage degeneration (60% improvement in the tibial plateau; P = 0.021 versus vehicle-treated controls). In JT09-treated rats, cartilage content, structure, and functional properties were largely maintained, and osteophyte formation was reduced by 70% (P = 0.005 versus vehicle-treated controls).

The results of this study define a novel mechanism for the role of KOR in articular cartilage homeostasis and disease, providing a potential unifying mechanistic basis for the overlap in disease processes and features involving opioid and HH signaling. Moreover, this study identifies a potential novel therapeutic strategy in which KOR modulation can improve outcomes in patients with OA.

Balancing the relative advantages and disadvantages of unicompartmental knee arthroplasties (UKAs) against those for TKAs can be challenging. Survivorship is one important end point; arthroplasty registers repeatedly report inferior midterm survival rates, but longer-term data are sparse. Comparing survival directly by using arthroplasty register survival reports also may be inadequate because of differences in indications, implant designs, and patient demographics in patients having UKAs and TKAs. The aims of this study were to assess the survivorship of UKA in the context of one large, northern European registry, and to compare the rates of survivorship with those of cemented TKAs performed for primary knee osteoarthritis during the same 27-year period. From the Finnish Arthroplasty Register, we obtained the data for 4713 patients undergoing UKAs for primary osteoarthritis (mean age, 63.5 years; minimum followup, 0 years; mean, 6.0 years; range, 0-24 years) who had surgical revision between 1985 and 2011. From this cohort, we calculated the Kaplan-Meier survivorship for revision performed for any reason and compared it with the survivorship of 83,511 patients (mean age, 69.5 years; minimum followup 0 years; mean, 6.4 years; range, 0-27 years) with TKAs treated for primary osteoarthritis during the same period. Data were adjusted for age and sex in a comparative analysis. Kaplan-Meier survivorship of UKAs was 89.4% at 5 years, 80.6% at 10 years, and 69.6% at 15 years; the corresponding rates for TKAs were 96.3%, 93.3%, and 88.7%, respectively. UKAs had inferior long-term survivorship compared with cemented TKAs, even after adjusting for the age and sex of the patients (hazard ratio 2.2, p < 0.001). Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

A UKA offers tempting advantages compared with a TKA; however, the revision frequency for UKAs in widespread use, as measured in a large, national registry, was poorer than that of TKAs. When choosing between a UKA and a TKA, patients should be informed of advantages of both procedures, but they also should be advised about the generally higher revision risk after UKA.

Patients with autoimmune rheumatic disease (AIRD) are at an increased risk of coronary artery disease. The present study sought to examine the prevalence and outcomes of AIRD patients undergoing percutaneous coronary intervention (PCI) from a national perspective. All PCI-related hospitalizations recorded in the US National Inpatient Sample (2004-2014) were included, stratified into four groups: no AIRD, RA, SLE and SSc. We examined the prevalence of AIRD subtypes and assessed their association with in-hospital adverse events using multivariable logistic regression [odds ratios (OR) (95% CI)]. Patients with AIRD represented 1.4% (n = 90 469) of PCI hospitalizations. The prevalence of RA increased from 0.8% in 2004 to 1.4% in 2014, but other AIRD subtypes remained stable. In multivariable analysis, the adjusted odds ratio (aOR) of in-hospital complications [aOR any complication 1.13 (95% CI 1.01, 1.26), all-cause mortality 1.32 (1.03, 1.71), bleeding 1.50 (1.30, 1.74), stroke 1.36 (1.14, 1.62)] were significantly higher in patients with SSc compared with those without AIRD. There was no difference in complications between the SLE and RA groups and those without AIRD, except higher odds of bleeding in SLE patients [aOR 1.19 (95% CI 1.09, 1.29)] and reduced odds of all-cause mortality in RA patients [aOR 0.79 (95% CI 0.70, 0.88)].

In a nationwide cohort of US hospitalizations, we demonstrate increased rates of all adverse clinical outcomes following PCI in people with SSc and increased bleeding in SLE. Management of such patients should involve a multiteam approach with rheumatologists.

To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity.

The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM.

The aim of this study was to investigate the ability of clinical and magnetic resonance imaging (MRI) diagnoses to predict pain in the temporomandibular joint (TMJ). One hundred forty-nine patients were examined by 2 calibrated examiners in strict accordance with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All patients who presented with a defined clinical RDC/TMD diagnosis were included and underwent bilateral coronal and sagittal MRI of the TMJ. Two raters blinded to the clinical diagnosis interpreted the MRI scans for TMJ pathology. The results were tested against the clinical diagnosis according to the RDC/TMD, including pain-related disability and psychosocial status, for associations to TMJ arthralgia using logistic regression analysis (GENMOD procedure, P < .05). MRI-depicted anatomic changes, such as joint effusions, disc displacement, and osteoarthrosis, were not significantly correlated with the presence of pain in the TMJ. However, a significant relationship between pain on palpation of the masseter muscle origin (P = .0050) and psychosocial factors (P = .0452) and pain in the TMJ was demonstrated.

Pain in the TMJ caused by the anatomic proximity of the muscle masseter origin and the lateral TMJ pole and the possible existence of trigger points in the musculature may lead to a false-positive or a false-negative diagnosis of arthralgia. Additionally, clinicians must consider the psychosocial aspects of pain in ideal treatment planning.

Many patients with rheumatoid arthritis develop superior migration of the humeral head because of massive cuff tears, causing loss of active motion. Reverse shoulder arthroplasty could potentially restore biomechanical balance but a high incidence of glenoid failure has been reported. These studies do not, however, typically include many patients with rheumatoid arthritis (RA) and it is unclear whether the failure rates are similar. We therefore (1) evaluated pain relief and shoulder function after reverse arthroplasty in RA; (2) compared results between primary and revision procedures; (3) determined the incidence of scapular notching; and (4) determined the complication rate. We identified 29 patients with RA who had 33 reverse arthroplasties from among 412 patients having the surgery. Six patients were lost to followup. Twenty three patients (27 shoulders) were evaluated after a minimum followup of 18 months (mean, 56 months; range, 18-143 months), including 18 primary and nine revision arthroplasties. All patients were evaluated preoperatively and 23 shoulders postoperatively by an independent physiotherapist and four were assessed postoperatively by phone. Level of pain, range of motion, and Constant-Murley score were recorded and new radiographs taken. Visual Analog Scale score for pain decreased from 8.0 to 1.0. Constant-Murley score increased from 13 to 52. Primary procedures had higher scores compared with revisions. Three patients had revision surgery. Notching occurred in 52% of shoulders but no loosening was seen. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Reverse arthroplasty in rheumatoid arthritis improved shoulder function with a low incidence of complications. We believe it should be considered in elderly patients with rheumatoid arthritis with pain and poor active range of motion resulting from massive cuff tears.

A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characterised by cartilage degeneration and debilitating pain, is that the severity of joint pain does not strictly correlate with radiographic and histological defects in joint tissues. Here, we determined whether protein kinase Cδ (PKCδ), a key mediator of cartilage degeneration, is critical to the mechanism by which OA develops from an asymptomatic joint-degenerative condition to a painful disease. OA was induced in 10-week-old PKCδ null (PKCδ In the DMM model, the loss of PKCδ expression prevented cartilage degeneration but exacerbated OA-associated hyperalgesia. Cartilage preservation corresponded with reduced levels of inflammatory cytokines and of cartilage-degrading enzymes in the joints of PKCδ-deficient DMM mice. Hyperalgesia was associated with stimulation of nerve growth factor (NGF) by fibroblast-like synovial cells and with increased synovial angiogenesis. Results from tissue specimens of patients with symptomatic OA strikingly resembled our findings from the OA animal model. In PKCδ null mice, increases in sensory neuron distribution in knee OA synovium and activation of the NGF-tropomyosin receptor kinase (TrkA) axis in innervating dorsal root ganglia were highly correlated with knee OA hyperalgesia.

Increased distribution of synovial sensory neurons in the joints, and augmentation of NGF/TrkA signalling, causes OA hyperalgesia independently of cartilage preservation.

Osteoarthritis (OA) is the most common disease of joints in adults around the world. Current available drugs to treat osteoarthritis are predominantly directed towards the symptomatic relief of pain and inflammation but they do little to reduce joint destruction. Effective prevention of the structural damage must be a key objective of new therapeutic approaches. Therefore, it is worthwhile to search for important molecular markers that hold great promise for further treatment of patients with osteoarthritis. In this study, we used a graph-clustering approach to identify gene expression profiles that distinguish OA patients from normal samples. We performed a comprehensive gene level assessment of osteoarthritis using five osteoarthritis samples and five normal samples graph-clustering approach. The results showed that TNFAIP3, ATF3, PPARG, etc, have related with osteoarthritis. Besides, we further mined the underlying molecular mechanism within these differently genes.

The results indicated tyrosine metabolism pathway and cell cycle pathway were two significant pathways, and there was evident to demonstrate them based on previous reports. We hope to provide insights into the development of novel therapeutic targets and pathways.

To evaluate the effect of disease-modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA). The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age-, sex-, and practice-matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined. A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1-16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29-4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04-2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93-4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect.

Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.

As the first approved oral kinase inhibitor, tofacitinib is effective and well-tolerated, but more expensive than conventional treatments for uncontrolled rheumatoid arthritis. Public formulary listing typically exerts a positive impact on the uptake of new drugs. We aimed to assess the budgetary impact of introducing tofacitinib into the Hospital Authority Drug Formulary as a fully subsidised drug in Hong Kong. We applied a population-based budget impact model to trace the number of eligible patients receiving biologics or tofacitinib treatment, then estimated the 5-year healthcare expenditure on rheumatoid arthritis treatments, with or without tofacitinib (2017-2021). We used linear regression to estimate the number of target patients and compound annual growth rate to estimate market share. Competing treatments included abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and tofacitinib. Retail price was used for drug costs, valued in Hong Kong dollars (HK$) in 2017 and discounted at 4% per year. The annual treatment cost of tofacitinib was HK$74 214 per patient, and the costs of biologics ranged from HK$64 350 to HK$115 700. Without tofacitinib, the annual government health expenditures for rheumatoid arthritis treatment were estimated to increase from HK$147.9 million (2017) to HK$190.6 million (2021). The introduction of tofacitinib to the formulary would reduce healthcare expenditures by 17.3% to 20.3% per year, with cumulative savings of HK$192.8 million; this change was estimated to provide consistent savings (HK$66.4 million to HK$196.8 million) in all tested scenarios.

Introduction of tofacitinib to the formulary will provide 5-year savings, given the current drug price and patient volume.

To investigate the association between specimen length and number of sections evaluated and the diagnostic yield of temporal artery biopsy (TAB) for giant cell arteritis (GCA). A pathologist reviewed all TABs performed for suspected GCA between January 1991 and December 2012. The blocks of all the inadequate and negative biopsy specimens were recut, and further slides at deeper levels were stained with hematoxylin and eosin in order to avoid missing inflammatory changes. In total, findings from 662 TABs were included in the study (71% female; mean age 73.2 years). A total of 427 TAB specimens (65%) were classified as negative, and 235 (35%) were classified as positive for GCA. Compared to those with negative TAB results, patients with positive TAB results were older and more frequently female. There was no difference in postfixation TAB specimen length between TAB specimens negative and positive for GCA (mean 6.5 mm versus 6.9 mm; P = 0.068). Cuts of additional biopsy sections revealed inflammation at deeper levels in 26 of 408 TAB specimens (6.4%) originally reported as uninflamed. The inflamed section was the second in 14 TAB specimens, the third in 9 specimens, and the fourth in 3 specimens. Piecewise logistic regression identified 5 mm as the TAB specimen length change point for diagnostic sensitivity. Compared to a TAB specimen length of <5 mm, the age- and sex-adjusted odds ratio for positive TAB results in samples ≥5 mm long was 1.5 (95% confidence interval 1.0-2.0), P = 0.032.

A postfixation TAB specimen length of at least 5 mm should be sufficient to make a histologic diagnosis of GCA. In order not to miss inflammatory changes, at least 3 further sections at deeper levels should be evaluated in all negative TAB specimens.

The present study established characteristics of tissue regrowth in patients suffering knee lesions treated with grafts of autologous chondrocytes grown on three-dimensional hyaluronic acid biomaterials. This multicentred study involved a second-look arthroscopy/biopsy, 5 to 33 months post implant (n = 63). Seven patients allowed a third-look biopsy, three of which were performed 18 months post implant. Characteristics of tissues were histologically and histochemically evaluated. The remaining bone stubs were evaluated for cartilage/bone integration. For data analysis, biopsies were further divided into those obtained from postoperative symptomatic patients (n = 41) or from asymptomatic patients (n = 22). The percentage of hyaline regenerated tissues was significantly greater in biopsies obtained after, versus within, 18 months of implantation. Differences were also observed between symptomatic and asymptomatic patients: reparative tissues taken from symptomatic patients 18 months after grafting were mainly fibrocartilage or mixed (hyaline-fibrocartilage) tissue, while tissues taken from asymptomatic patients were hyaline cartilage in 83% of biopsies. In a small group of asymptomatic patients (n = 3), second-look and third-look biopsies taken 18 months after surgery confirmed maturation of the newly formed tissue over time. Cartilage maturation occurred from the inner regions of the graft, in contact with subchondral bone, towards the periphery of the implant.

The study indicates that, in asymptomatic patients after chondrocyte implantation, regenerated tissue undergoes a process of maturation that in the majority of cases takes longer than 18 months for completion and leads to hyaline tissue and not fibrous cartilage. Persistence of symptoms might reflect the presence of a nonhyaline cartilage repair tissue.

Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective. We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments. The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.

Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.

Independent reports on the longitudinal performance of non-fluoroscopic fixed-flexion knee radiography have not been published. Therefore, we evaluated the sensitivity of fixed-flexion radiography to detect knee joint space narrowing (JSN) over 2 years in patients with osteoarthritis (OA) and compared the effect of reproducibility and quality of medial tibial plateau (MTP) alignment on sensitivity to JSN. Fixed-flexion radiographs of both knees of 193 OA patients were obtained at baseline and after 24 months. Minimum joint space width (JSW) of the medial tibiofemoral joint spaces was measured manually in paired digitised radiographs without knowledge of the chronology. The degree of MTP alignment was assessed by measuring the distance between the anterior and posterior margins of the MTP (intermargin distance [IMD]). Accurate repositioning was achieved if, in the 24-month radiograph, the IMD was reproduced to within 1mm. The quality of MTP alignment was satisfactory if the IMD was <or=1mm. The mean (standard deviation [SD]) JSN between baseline and 24 months was 0.18 (0.49)mm and the standardised response mean (SRM) was 0.37. The SRM was 0.36 in the knee film pairs (86%) in which the IMD was accurately reproduced after 24 months and 0.52 in the film pairs (42%) with satisfactory MTP alignment on both the baseline and 24-month radiographs.

The sensitivity to radiographic JSN on fixed-flexion knee radiographs over 2 years was higher in satisfactorily aligned than accurately reproduced serial pairs of radiographs. These findings have implications for longitudinal knee OA studies using fixed-flexion radiographs.

Intra-articular pain catheters effectively reduce postoperative pain in total knee arthroplasty (TKA) by delivering analgesia to the surgical site. However, concerns exist regarding the potential for increasing deep infections. This study tested the hypothesis that intra-articular pain catheters in TKA increase the rate of deep surgical site infections. A retrospective analysis of 1915 patients undergoing primary TKA between January 2008 and December 2013 was undertaken, comparing infection rates between patients with intra-articular catheters inserted and those without. Deep infection rate was 0.53% with intra-articular pain catheters, compared with 0.77% when the catheters were not inserted. There was no statistically significant difference between the groups (P = 0.56).

Intra-articular pain catheters in TKA did not increase the rate of deep infection.

To describe the clinical manifestations of rheumatic disorders with isolated head and neck (H&N) affection and to introduce a novel diagnostic pathway. From 2004 to 2010, 90 patients presented with isolated H&N symptoms of a rheumatic disorder were included in the study. Rheumatic disorders were classified according to the ACR criteria. In 2008, we introduced a novel diagnostic pathway to reduce under-diagnosis of primary rheumatic disorders in the H&N. Disease-related data were assessed retrospectively and set into clinical context. The majority of patients suffered from SS (n = 42), granulomatosis with polyangiitis (Wegener's) (n = 13) and sarcoidosis (n = 18) with predominance for female patients (n = 65). Enlargement of the major salivary glands (n = 47), sicca symptoms (n = 41) and cervical lymphadenopathy (n = 25) represented the most frequent symptoms. Interestingly, 3% of all enlargements of salivary glands and 4% of all cervical lymphadenopathy could be contributed to rheumatic disorders. The mean time to diagnosis was 20.71 months for SS, 8.4 months for granulomatosis with polyangiitis and 57.5 months for sarcoidosis. After implementation of the newly developed diagnostic pathway in 2008, the annually diagnosed rheumatic disorders increased 5-fold.

The majority of rheumatic diseases of the H&N can be related to SS, granulomatosis with polyangiitis and sarcoidosis. However, the lack of specific symptoms and the clinical variability of H&N manifestation may contribute to a prolonged time to diagnosis. Our retrospective study points out the variability of symptoms and suggests a diagnostic pathway to reduce the cases of undetected H&N affection in rheumatic disorders.

To study the effect of tumour necrosis factor (TNF)-α, responsible for the inflammation and circadian rhythm of rheumatoid arthritis (RA), on the expression of circadian clock genes in primary cultured human rheumatoid synovial cells. The expression of circadian clock genes, including circadian locomotor output cycles kaput (Clock), brain and muscle Arnt-like protein-1 (Bmal1), period (Per)1/2, and cryptochrome (Cry)1/2, and the proline and acidic amino acid-rich basic leucine zipper (PAR bZip) genes, a transcriptional activator of Per2, including D site of albumin promoter binding protein (Dbp), hepatic leukaemia factor (Hlf), and thyrotroph embryonic factor (Tef), and a transcriptional repressor of Per2, E4-binding protein 4 (E4bp4), in TNF-α-stimulated synovial cells was determined by real-time polymerase chain reaction (PCR). The D-box motifs in the Per2 promoter were mutated by site-directed mutagenesis, and the promoter activity of the Per2 gene was examined using the luciferase assay. TNF-α enhanced the mRNA expression of Bmal1 and Cry1 but did not affect that of Clock, Per1, or Cry2. However, TNF-α inhibited the mRNA expression of the Per2 gene, as well as Dbp, Hlf, and Tef, but enhanced the mRNA expression of E4bp4. Furthermore, TNF-α inhibited the transcriptional activity of the wild-type Per2 gene in a manner dependent on the D-box 1 and D-box 2 motifs in the Per2 promoter.

TNF-α modulates the expression of the Per2 gene through the D-box binding proteins DBP, HLF, TEF, and E4BP4, in rheumatoid synovial cells, and thereby may contribute to the pathogenesis of RA.

CD4-positive T cells are the main target of human T-cell leukemia virus type 1 (HTLV-1). Interferon-γ release assays rely on the fact that T-lymphocytes release this cytokine when exposed to tuberculosis-specific antigens and are useful in testing for latent tuberculosis infection before initiating biologic therapy, such as anti-tumor necrosis factor agents. However, the reliability of interferon-γ release assays in detecting tuberculosis infection among HTLV-1-positive patients with rheumatoid arthritis (RA) remains unclear. The present study aimed to evaluate the use of the T-SPOT.TB assay in HTLV-1-positive RA patients. Overall, 29 HTLV-1-positive RA patients and 87 age- and sex-matched HTLV-1-negative RA patients (controls) were included from the HTLV-1 RA Miyazaki Cohort Study. Results of the T-SPOT.TB assay for latent tuberculosis infection screening were collected from medical records of patients. Approximately 55% of the HTLV-1-positive RA patients showed invalid T-SPOT.TB assay results (odds ratio: 108, 95% confidence interval: 13.1-890, p < 0.0001) owing to a spot count of >10 in the negative controls. HTLV-1 proviral load values were significantly higher in patients with invalid results compared with those without invalid results (p = 0.003).

HTLV-1 infection affects T-SPOT.TB assay results in RA patients. Assay results in HTLV-1 endemic regions should be interpreted with caution when screening for latent tuberculosis infection before initiation of biologic therapy.

Atrial fibrillation (AF) after rheumatic valve replacement is the most common arrhythmic complication. Previous studies reported angiotensin-II receptor blocker can prevent AF. This study aimed to assess the effect of a combination of irbesartan and amiodarone on the maintenance of sinus rhythm after cardioversion of AF in patients with post-rheumatic valve replacement in a randomized, controlled trial. Eighty-five consecutive patients undergoing rheumatic valve surgery were enrolled and randomly assigned to an irbesartan plus amiodarone (irbesartan 150 mg/d, n=43) or an amiodarone group (n=42) starting 10 days before scheduled electrical cardioversion. The primary end-point was recurrence of AF. Pharmacological conversion was documented in 7 patients, and electrical conversion in 68 patients (87.2%). A higher rate of maintenance of sinus rhythm (69.8% vs 40.5%, P=0.01) and a better AF-free survival (chi(2)=7.466, P=0.006) were observed in the irbesartan plus amiodarone group compared to the amiodarone group during the 1-year follow-up period. Cox regression showed that use of irbesartan was an independent factor associated with the maintenance of sinus rhythm after cardioversion (OR=0.43, P=0.018), whereas increased left atrium diameter was associated with increased risk (OR=1.54, P=0.005).

In patients with post-rheumatic valve replacement, the combination of amiodarone and irbesartan demonstrated a lower rate of AF recurrence after cardioversion than amiodarone alone, which might be due to preventing the atrial remodeling.

Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA. We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003-2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted. Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97-1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients.

No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40-60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.

Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients. This study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits. The mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P <0.05 for both). High sCD163 levels and a high sCD163/sTWEAK ratio (defined as > mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P <0.01 for both) and HC (P <0.05 for both). A high sCD163/sTWEAK ratio, but not high sCD163 levels, was associated with greater skin involvement.

The results of our study indicate that CD163-TWEAK interactions might play a role in the pathogenesis of SSc and that CD163 may protect against the development of digital ulcers in SSc. Further studies are required to reveal whether targeting of the CD163-TWEAK pathway might be a potential strategy for treating vascular disease and/or skin fibrosis in SSc.

The older person is more likely to have pain since degenerative diseases and the effects of cancer are more common after 65 years of age. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used due to perceived safety, relatively low cost and over-the-counter availability. This brief review describes the necessity for, but risks of, NSAIDs in the older patient. A literature search was undertaken using PubMed and search terms including pain, aging, treatment, nonsteroidal anti-inflammatory drugs, arthritis, older patient, and guidelines.

Pain complaints are common in the older population. Low back pain and osteoarthritis affects over two thirds of this group. Patients and clinicians are increasingly wary about treatment since no medication appears to be safe. Older patients opting for no treatment may have worsening function including decreased sleep, mobility, socialization, and increased depression. Ninety percent of all prescription NSAIDs are taken by patients over 65. Guidelines for safe use are available but frequently not followed by the practitioner including the FDA recommended "lowest dose possible for your treatment … for the shortest time needed." NSAIDs can be an effective treatment option for many older persons but caution should be exercised in this often fragile population.

To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008).

The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.

Accurately assessing treatment outcomes has become increasingly important for maintaining hospital privileges. When these assessments are based on the judgment of the treating doctor, there is often an inherent positive bias. As a result, there has been increased interest in using patient-based assessments. The purpose of this study was to compare doctor's and patient's assessments of the outcomes of treatment in a series of patients with various temporomandibular disorders (TMDs). Fifty-two consecutive TMD patients were initially given a questionnaire designed to evaluate their pain, problems eating and sleeping, the occurrence of headache and earache, the presence of temporomandibular joint pain and/or jaw stiffness in the morning, and interference with daily activity. The patients then filled out the same questionnaire at each post-treatment visit, and the findings were compared with the baseline information. At each visit, the treating doctor also recorded a global evaluation of the patient's progress as excellent, good, fair, or poor. Comparison of the doctor's global evaluation with the patient's evaluation based on the questionnaire showed a discrepancy in 44% of the cases. When there was a discrepancy, the doctor scored the improvement better than the patient 54.5% of the time and worse than the patient 45.5% of the time.

The results of this study confirm the unreliability of using a global opinion by the treating doctor for outcome assessment in patients with various TMDs.

To study the expression of adhesion molecules in patients with systemic sclerosis (SSc) with and without pulmonary arterial hypertension (PAH) and the effects of therapy with the endothelin-1 (ET-1) receptor antagonist, bosentan. In all, 35 patients with SSc and 25 healthy donors (HD) were selected for this study. Of 35 patients, 10 had isolated PAH assessed by Doppler echocardiography and treated with bosentan. Peripheral blood (PB) lymphocytes were isolated by density gradient centrifugation, and the expression of lymphocyte function-associated antigen-1 (LFA-1), very late antigen-4 (VLA-4) and L-selectin on CD3 T cells was assessed by double immunofluorescence and flow-cytometry. As endothelial activation markers, serum soluble P-selectin, platelet/endothelial cell adhesion molecule (PECAM)-1, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1 and von Willebrand factor (vWF) antigen were assessed by ELISA. In patients with SSc-PAH, T cell subsets and soluble endothelial markers were assessed at baseline and after 6 and 12 months of bosentan therapy. In patients with SSc-PAH, serum soluble ICAM-1, VCAM-1, P-selectin and PECAM-1 levels were higher than in HD at baseline and fell to normal values after 12 months of bosentan therapy. CD3-LFA1 T cells were significantly higher in PAH-SSc at baseline than in HD or SSc and significantly decreased after therapy. CD3-L-selectin T cells were significantly lower in SSc-PAH at baseline than in HD or SSc and rose to normal levels after bosentan therapy.

This study confirms that endothelial activation occurs in SSc, and suggests that changes in the T cell/endothelium interplay take place in SSc-associated PAH. Bosentan seems to be able to hamper these changes and restore T cell functions in these patients.

The Weilby procedure is one of several accepted methods to treat primary thumb carpometacarpal osteoarthritis. We found no previous studies that included preoperative and postoperative subjective outcomes using validated questionnaires or preoperative and postoperative objective outcomes such as specific strength and range-of-motion measurements. Therefore, we performed a prospective cohort study in which we analyzed preoperative and postoperative objective and subjective outcomes after Weilby interposition tendoplasty. Nineteen patients (20 thumbs) with primary thumb carpometacarpal osteoarthritis were treated with Weilby interposition tendoplasty. For subjective assessment, the Disabilities of the Arm, Shoulder, and Hand (DASH) outcome data collection instrument was used to evaluate preoperative and postoperative outcomes at 0, 3, 6, and 12 months. Furthermore, patients completed a specific personal questionnaire at 12 months of follow-up. Objective assessments included interphalangeal joint flexion/extension; metacarpophalangeal joint flexion/extension; and carpometacarpal joint palmar abduction, opposition, and extension. Tip pinch, key pinch, 3-point pinch, and overall grip strengths were also measured. The measurements were performed preoperatively and at 3, 6, and 12 months after surgery. All complications were registered. The DASH score was significantly improved, and 17 of 19 patients were satisfied with the procedure. The interphalangeal joint flexion/extension, metacarpophalangeal joint flexion/extension, and carpometacarpal joint extension did not significantly change. Carpometacarpal joint palmar abduction and opposition were significantly improved at 12 months. The tip pinch and key pinch strengths were increased but not significantly. The 3-point pinch and overall grip strengths were significantly improved at 12 months. Therapeutic IV.

The Weilby procedure is a reliable alternative to treat primary thumb carpometacarpal osteoarthritis without requiring bone tunnel creation. It achieves pain relief, stability, mobility, and strength. The objective and subjective outcomes of this study compare favorably with those of earlier reports of the Weilby procedure and are similar to the published results of the more commonly performed Burton-Pellegrini technique.

Research is needed to assess the validity of clinical decision criteria for the diagnoses of temporomandibular disorders. The objective of this study was to assess the reliability of clinical diagnoses in predicting magnetic resonance imaging diagnoses of temporomandibular joint internal derangement and osteoarthrosis in a patient pain group with temporomandibular disorders. One clinician used the Clinical Diagnostic Criteria for Temporomandibular Disorders to classify 163 consecutive patients with temporomandibular disorders on physical diagnosis. The radiologist subsequently performed magnetic resonance imaging on 326 temporomandibular joints. Diagnostic agreement was determined for the diagnostic categories of absence of internal derangement, disk displacement with reduction, disk displacement without reduction, and osteoarthrosis. Use of the Kappa statistic test indicated a poor diagnostic agreement between the clinician and the radiologist.

The classification system of the Clinical Diagnostic Criteria for Temporomandibular Disorders provides insufficient reliability for determination of the presence of temporomandibular joint internal derangement and osteoarthrosis. It should be supplemented by evidence from cross-sectional and longitudinal investigations to assess decisive differences in the areas of pathogenesis, treatment, and prognosis.

Vascular health is of concern in patients with Juvenile Idiopathic Arthritis (JIA) since Rheumatoid Arthritis (RA) epidemiologically has a well-described association with premature development of atherosclerosis. Chronic inflammation with persisting systemic circulating inflammatory proteins may be a cause of vascular damage, but general physical inactivity could be an important contributor. Pain and fatigue are common complaints in patients with JIA and may well lead to an inactive sedentary lifestyle. For this reason we assessed the physical activity (PA) objectively in patients with moderate to severe Juvenile Idiopathic Arthritis (JIA) in comparison with gender and age matched healthy schoolchildren, and looked for associations between PA and features of JIA. One hundred thirty-three patients, 7-20 years of age, participated. Disease activity, disability, functional ability, and pain were assessed and PA was measured by accelerometry through 7 days and compared to PA in age- and gender-matched healthy schoolchildren. We found a significantly lower level of PA in patients compared to gender- and age-matched healthy schoolchildren both in average activity (counts per minute, cpm) (475.6 vs. 522.7, p = 0.0000018) and in minutes per day spent with cpm >1500 (67.9 vs. 76.4, p = 0.0000014), with cpm >2000 (moderate physical activity) (48.4 vs. 52.8, p = 0.0001, and with cpm >3000 (high physical activity) (24.7 vs. 26.5, p = 0.00015). A negative association (β = -0.213, p = 0.014) between active disease in weight bearing joints and high physical activity remained the only significant association between disease related factors and PA. Of the girls 19% and of the boys 45% (vs. 39% and 61% in the reference group) met standards set by Danish Health Authorities for daily PA in childhood.

Children and adolescents with JIA are less physically active than their healthy peers and less active than recommended for general health by the Danish Health Authorities. This is not explained by pain or objective signs of inflammation. When inflammation has been curbed, restoration of an active healthy lifestyle should be highly prioritized.

To determine the clinical significance of human parvovirus B19 infection in patients with primary Sjögren's syndrome (SS) and to investigate the immunologic and hematologic features related to B19 infection. We included 80 consecutive patients with primary SS (74 women and 6 men), with a mean age of 62 years (range, 24 to 87 years) that were seen in our Unit. All patients fulfilled the European Community criteria for SS. As controls, we included 140 consecutive sera samples analyzed for B19 antibodies in our Microbiology Department and obtained from adult inpatients and outpatients of our Hospital. Serum from all patients and controls was tested for antibodies to B19 by enzyme-linked immunosorbent assay (ELISA). Additionally, the presence of B19 DNA in serum and in circulating leukocytes was investigated by nested polymerase chain reaction (PCR). Serological evidence of past B19 infection (positive IgG antibodies without IgM antibodies) was present in 28 (35%) patients with primary SS. None of these patients showed evidence for B19 viremia, and B19 virus DNA was not detected in the circulating leukocytes of IgG-B19(+) patients. Positivity for IgM antibodies to B19 was not detected in any patient. When compared with patients without evidence of past B19 infection, those with primary SS and past B19 infection showed a higher prevalence of cytopenia (57% v 15%; P < .001), and, specifically, of leukopenia (36% v 4%; P < .001). Additionally, when compared with controls positive for IgG-B19, SS patients with these antibodies had a higher prevalence of cytopenia (57% v 13%; P < .001), leukopenia (36% v 3%; P < .001) and thrombocytopenia (21% v 0%; P = .003).

Serological evidence of past B19 infection is associated with the presence of cytopenia in our patients with primary SS. A possible relationship between B19 infection and the presence of cytopenia in primary SS may occur in some patients immunologically or genetically predisposed.

To determine the type and frequency of physical therapy (PT) prescribed by physicians for patients in the registry of the German Network for Systemic Sclerosis. The data for 4,252 patients were analyzed using descriptive statistics, chi-square tests, and odds ratios (ORs). Overall, 37.4% of patients (1,590 of 4,252) received PT at the end of a yearly follow-up. The most frequently used type of PT was lymphatic drainage (n = 1,061, 36.8%), followed by exercise therapy (n = 1,047, 36.3%) and heat therapy (n = 689, 23.9%). More than three-fourths of treated patients (82%) received 1 or 2 different forms of PT simultaneously. The prescription of PT was associated with the extent of skin fibrosis as measured by the modified Rodnan skin thickness score (<10 [41.8% of patients], 11-20 [55.8% of patients], and >21 [63.9% of patients]; P < 0.001). Patients with musculoskeletal involvement (e.g., arthritis, muscle weakness, joint contractures, tendon friction rubs) had a higher chance of receiving PT than patients without these symptoms, with corresponding ORs ranging from 1.96 (95% confidence interval [95% CI] 1.69-2.28) for joint contractures to 3.83 (95% CI 2.89-5.08) for arthritis. When comparing the type of PT prescription across the initial and all follow-up visits from 2003 to 2017, significant alterations with a decreasing frequency of patients receiving PT could be observed (P = 0.001).

To our knowledge, this is the first study reporting the use of PT in patients with systemic sclerosis (SSc) in a large cohort. Although SSc is characterized by considerable disability and restriction of motion, <40% of patients received PT.

To evaluate the influence of Fcgamma receptor IIIA (FcgammaRIIIA) 158V/F polymorphism on susceptibility and disease severity in early rheumatoid arthritis (RA). In 181 Swedish patients (128 women, 53 men) with RA of recent onset, disease and disability variables such as erythrocyte sedimentation rate, 28-joint disease activity score (DAS28) and health assessment questionnaire (HAQ) scores were monitored regularly during 3 yr. Three hundred and sixty-two controls were recruited from the same geographical area as the patients. FcgammaRIIIA genotyping was performed using denaturing high-performance liquid chromatography. In all RA patients, FcgammaRIIIA-158VV was significantly over-represented compared with controls [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.01-3.5, P<0.05]. After stratifying for sex, the difference remained in the male population (OR 3.2, 95%CI 1.03-11, P<0.05) but disappeared among women (OR 1.4, 95%CI 0.7-3.1, P=0.4). In addition, 158VV patients were more likely to exhibit early joint erosions (OR 6.1, 95%CI 1.4-28, P<0.01). At baseline, patients with different FcgammaRIIIA genotypes did not differ with respect to measures of disease activity or functional ability. Thereafter, in male patients with at least one V allele the mean DAS28 and HAQ scores were higher compared with 158FF. In contrast, female patients with at least one 158V allele displayed lower mean DAS28 and HAQ scores compared with those with 158FF.

In a male population, the FcgammaRIIIA-158VV genotype is associated with an increased risk of developing RA, and the 158V allele with more severe disease in early RA.

To determine the prevalence of knee pain, radiographic knee osteoarthritis (RKOA), total knee replacement (TKR) and associated risk factors in male ex-professional footballers compared with men in the general population (comparison group). 1207 male ex-footballers and 4085 men in the general population in the UK were assessed by postal questionnaire. Current knee pain was defined as pain in or around the knees on most days of the previous month. Presence and severity of RKOA were assessed on standardised radiographs using the Nottingham Line Drawing Atlas (NLDA) in a subsample of 470 ex-footballers and 491 men in the comparison group. The adjusted risk ratio (aRR) and adjusted risk difference (aRD) with 95% CI in ex-footballers compared with the general population were calculated using the marginal model in Stata. Ex-footballers were more likely than the comparison group to have current knee pain (aRR 1.91, 95% CI 1.77 to 2.06), RKOA (aRR 2.21, 95% CI 1.92 to 2.54) and TKR (aRR 3.61, 95% CI 2.90 to 4.50). Ex-footballers were also more likely to present with chondrocalcinosis (aRR 3.41, 95% CI 2.44 to 4.77). Prevalence of knee pain and RKOA were higher in ex-footballers at all ages. However, even after adjustment for significant knee injury and other risk factors, there was more than a doubling of risk of these outcomes in footballers.

The prevalence of all knee osteoarthritis outcomes (knee pain, RKOA and TKR) were two to three times higher in male ex-footballers compared with men in the general population group. Knee injury is the main attributable risk factor. Even after adjustment for recognised risk factors, knee osteoarthritis appear to be an occupational hazard of professional football.

To examine the correlation between hip-knee-ankle and femur-tibia radiograph angles, calculate the offset of the femur-tibia angle with respect to the hip-knee-ankle angle, calculate the sensitivity and specificity and area under the receiver operating characteristic (ROC) curve of the femur-tibia angle, and examine the relationship of malalignment by each approach with osteoarthritis (OA) tissue pathology in the mechanically stressed compartment using magnetic resonance imaging (MRI). Individuals with knee OA underwent full-limb and knee radiographs and knee MRI. Linear regression was used to determine if the 2 angles differed systematically and to identify the cutoff. Alignment means for MRI grades were compared using Dunnett's t-test. In the 146 participants (109 women, mean age 70 years, body mass index 30.6 kg/m(2)), femur-tibia and hip-knee-ankle angles correlated (r = 0.86; 95% confidence interval [95% CI] 0.81, 0.90). On average, the femur-tibia angle was 3.4 degrees more valgus (3.0 degrees in women and 4.7 degrees in men); after correction, its sensitivity and specificity (to predict the hip-knee-ankle angle) were 0.84 and 0.84 for identifying varus and 0.98 and 0.73 for valgus, respectively. The area under the ROC curve (95% CI) was 0.91 (0.86, 0.96) for varus and 0.94 (0.89, 0.99) for valgus. Varus severity worsened comparably with each alignment measure as medial lesion score on MRI worsened. Laterally, as lesion score worsened, comparably worse valgus was seen with either assessment approach.

In knee OA, the knee radiograph femur-tibia and full-limb radiograph hip-knee-ankle angles were correlated. The femur-tibia angle, corrected for mean offset, was sensitive, specific, and had excellent discriminative ability for identifying varus and valgus alignment evidenced by area under the ROC curve. The relationship between alignment and specific OA MRI features was comparable with the 2 approaches. Use of the femur-tibia angle, corrected for offset, should be considered in research and clinical settings.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting joints. Elevated plasma levels of microRNA-223-3p (miR-223-3p) in patients with RA are implicated in the pathogenesis of the disease. This study aimed to analyze the functional role of miR-223-3p in the pathogenesis of RA by overexpressing miR-223-3p in synovial cell lines. Arthritis was induced in the RA model of SKG mice by injection of ß-glucan. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Plasma levels of miRNA were determined by panel real-time PCR analysis. Target genes of the differentially expressed miRNAs in SKG mice were analyzed using miRNA target prediction algorithms. The dual-luciferase reporter system was used to evaluate the relationship between miR-223-3p and IL-17 receptor D (IL-17RD). The activity of miR-223-3p was analyzed by transfection of plasmid vectors overexpressing miR-223-3p into IL-17RD-expressing NIH3T3 and MH7A cell lines. Il6 and Il17rd mRNA expression was analyzed by quantitative real-time PCR. IL-17RD protein expression was analyzed by western blot analysis. We identified 17 upregulated miRNAs (fold change > 2.0) in plasma of SKG mice injected with ß-glucan relative to untreated SKG mice. Il17rd was identified as the candidate target gene of miR-223-3p using five miRNA target prediction algorithms. The transfection of plasmid vectors overexpressing miR-223-3p into NIH3T3 and MH7A cells resulted in the downregulation of Il17rd expression and upregulation of Il6 expression. Expression of miR-223-3p and Il6 mRNA in MH7A cells was upregulated; however, that of Il17rd mRNA was downregulated following TNF-α stimulation. IL-17RD expression in synovial tissues from SKG mice and RA patients was inversely correlated with the severity of arthritis.

This study is the first to demonstrate that miR-223-3p downregulates IL-17RD in both mouse and human cells; miR-223-3p may contribute to the pathogenesis of RA by downregulating the expression of IL-17RD and upregulating that of IL-6 in synovial cells.

To investigate the primary culture and adipogenic process of pre-adipocytes from infrapatellar fat pad of osteoarthritic patients. The pre-adipocytes were isolated by enzymatic digestion. The morphological changes of cultured cells were observed and the growth curve was drawn by CCK-8 method. During the adipogenic process, the intracytoplasmic lipid of differentiated cells was determined by oil red O staining. And the adiponectin levels in the culture supernatants were measured by ELISA (enzyme-linked immunosorbent assay). The primary cultured fibroblast-like cells were spindle-shaped. In the process of adipogenesis, the intracytoplasmic lipid droplets were observed at Day 3 and over 80% of the cells differentiated into adipocytes at Day 21. With the increasing number of adipocytes, the adiponectin levels in the culture supernatant elevated and peaked at Week 3. The differentiated cells were proven to be adipocytes functioning actively.

The primary culture and adipogenic process of pre-adipocytes in infrapatellar fat pad of osteoarthritic patients has been successfully established. Thus it may provide an ideal model for the study of endocrine function of infrapatellar fat pad and understanding its role in the pathogenesis of osteoarthritis.

To investigate relationship between serum hyaluronan (HA) level and the presence and severity of radiographic knee osteoarthritis (OA) as well as degree of knee pain in Japanese population. A total of 616 volunteers participated in this study. Based on the Kellgren-Lawrence (K-L) grade, participants were radiographically classified into three groups: Normal (K-L grade 0 or 1), Moderate (grade 2) and Severe (grade 3 or 4). The degree of knee pain was quantified by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) Pain. Serum HA levels were compared among the Normal, Moderate and Severe groups, and the relationship between serum HA level and the severity of knee OA was analyzed after age, sex and body mass index (BMI) were adjusted. In addition, the correlation between serum HA level and the degree of knee pain was analyzed in each group. Regarding relationship between serum HA level and the severity of radiographic knee OA, serum HA levels of the Moderate and Severe groups were significantly higher than in the Normal group (P<0.001). Furthermore, serum HA level correlated with the severity of radiographic knee OA (r=0.289, P<0.001) after adjusting for age, sex and BMI. Serum HA level correlated with VAS of knee pain and/or KOOS Pain in the Normal and Moderate groups.

Serum HA level has the potential to be useful for the diagnosis of the presence and severity of knee OA.

To characterize treatment patterns, healthcare resource utilization (HRU), and disease activity among patients with early rapidly progressive rheumatoid arthritis (eRPRA) in the United States when treated with a first-line biologic disease-modifying antirheumatic drug (bDMARD) tumor necrosis factor-α (TNF) inhibitor or first-line abatacept. Observational, multicenter, retrospective, longitudinal, medical records-based, cohort study. Patients with eRPRA were identified by anti-citrullinated protein antibody positivity, 28-joint Disease Activity Score-C-reactive protein of 3.2 or greater, symptomatic synovitis in 2 or more joints for at least 8 weeks prior to the index date, and onset of symptoms within 2 years or less of the index date. Patients received abatacept or a TNF inhibitor as first-line treatment. Patient characteristics, treatment patterns, HRU, and disease activity following bDMARD initiation were compared across the 2 groups. Odds ratios (ORs) of HRU in the first 6 months of bDMARD treatment were estimated using multivariable logistic regression to adjust for patient mix. There were 60 patients treated with abatacept and 192 treated with a TNF inhibitor in the first line. Those treated with first-line abatacept had lower adjusted odds of hospitalization (OR, 0.42; 95% CI, 0.18-0.95), emergency department (ED) visits (OR, 0.39; 95% CI, 0.16-0.93), and magnetic resonance imaging (MRI) (OR, 0.45; 95% CI, 0.21-0.97) than those treated with a first-line TNF inhibitor (all P <.05). Adjusted odds of achieving low disease activity as measured by clinical disease activity index within 100 days of bDMARD initiation favored first-line abatacept versus a first-line TNF inhibitor (OR, 4.37; 95% CI, 1.34-13.94; P = .01).

Adjusting for disease severity, patients with eRPRA who were treated with first-line abatacept were less likely to have hospitalizations, ED visits, and MRI use during the first 6 months of bDMARD treatment and more likely to achieve low disease activity within 100 days of bDMARD start compared with those who received a first-line TNF inhibitor.

There is significant variability in the trajectory of structural progression across people with knee osteoarthritis (OA). We aimed to identify distinct trajectories of femorotibial cartilage thickness over 2 years and develop a prediction model to identify individuals experiencing progressive cartilage loss. We analysed data from the Osteoarthritis Initiative (OAI) (n = 1,014). Latent class growth analysis (LCGA) was used to identify trajectories of medial femorotibial cartilage thickness assessed on magnetic resonance imaging (MRI) at baseline, 1 and 2 years. Baseline characteristics were compared between trajectory-based subgroups and a prediction model was developed including those with frequent knee symptoms at baseline (n = 686). To examine clinical relevance of the trajectories, we assessed their association with concurrent changes in knee pain and incidence of total knee replacement (TKR) over 4 years. The optimal model identified three distinct trajectories: (1) stable (87.7% of the population, mean change -0.08 mm, SD 0.19); (2) moderate cartilage loss (10.0%, -0.75 mm, SD 0.16) and (3) substantial cartilage loss (2.2%, -1.38 mm, SD 0.23). Higher Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) pain scores, family history of TKR, obesity, radiographic medial joint space narrowing (JSN) ≥1 and pain duration ≤1 year were predictive of belonging to either the moderate or substantial cartilage loss trajectory [area under the curve (AUC) 0.79, 95% confidence interval (CI) 0.74, 0.84]. The two progression trajectories combined were associated with pain progression (OR 1.99, 95% CI 1.34, 2.97) and incidence of TKR (OR 4.34, 1.62, 11.62).

A minority of individuals follow a progressive cartilage loss trajectory which was strongly associated with poorer clinical outcomes. If externally validated, the prediction model may help to select individuals who may benefit from cartilage-targeted therapies.

To compare the dorsal and palmar ultrasound (US) examination of finger joints in early rheumatoid arthritis (RA) with regard to the concurrence of greyscale (GSUS) and power Doppler (PDUS) positivity, and to correlate both approaches with clinical variables. Patients with newly diagnosed RA were assessed by clinical examination and US. GSUS and PDUS of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were performed using the dorsal and palmar approach. Findings of synovitis in GSUS and PDUS were graded semiquantitatively from 0 to 3. Clinical and sonographic reevaluation was performed after 6 months. With 44.6% versus 32.2% positive findings, palmar GSUS identified significantly more joints with synovitis than did dorsal GSUS. With 22.1% versus 8.9%, PDUS abnormalities were detected significantly more often from the dorsal side. With 71.2% versus 21.8% for the MCP and 57.5% versus 17.4% for the PIP joints, significantly more GSUS and PDUS double-positive joints were found with the dorsal as opposed to the palmar approach. These differences remained significant at Month 6. Both palmar and dorsal GSUS and PDUS correlated with comparable strength with clinical variables such as the Disease Activity Score 28, Clinical Disease Activity Index, and Simple Disease Activity Index.

Although the dorsal approach detected fewer GSUS findings than the palmar approach, PDUS signals were significantly more frequently detected by dorsal US. In addition, the prevalence of double-positive joints with concurrent GSUS and PDUS findings was significantly higher with the dorsal approach. These data argue in favor of the dorsal US approach to finger joints in RA.

With improvements in biomaterials and design, implant arthroplasty is becoming a useful option for treatment of disorders of the hallux. Forty-eight patients (53 implants) who had Bio-Action great toe implants (Osteomed, Addison, TX) for symptomatic advanced degenerative changes in the first metatarsophalangeal (MTP) joint have been followed prospectively since August of 1998. We reviewed the functional results of 32 patients (36 implants) at a minimum followup of 36 (range 36 to 69, mean 47) months. The scoring system designed by Kitaoka etal. was used to assess the functional results. Patient satisfaction, length of hospital stay, time to return to routine activities, footwear problems, radiographic appearances, and complications also were studied. With the numbers available, there was significant improvement in the range of motion achieved and hallux MTP scale after the operation. There was a positive correlation (r = 0.87) between patient satisfaction and the hallux MTP scale. However, there was no correlation between patient age and patient satisfaction or hallux MTP scale. Seventy-seven percent of patients considered the result of the operation to be good or excellent.

Overall, the 5-year functional results of this total joint system appeared to be satisfactory.

The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (sJIA) occasionally overlap. Therefore, serum levels of cytokine and ferritin are used as markers to distinguish between KD and sJIA. KD patients have a high level of interleukin (IL)-6, low level of IL-18, and no elevation of the level of serum ferritin. Conversely, sJIA patients have a low level of IL-6 and high levels of IL-18 and ferritin in the serum. However, to the best of our knowledge, no case report of KD with a low serum level of IL-6 and extremely high levels of IL-18 and ferritin is found. A 6-year-old boy presented with a history of fever for 9 days and a rash that appeared 7 days from the onset. He was diagnosed with incomplete KD because of fever, skin rash, oral cavity erythematous changes, and erythema and edema of the hands with laboratory findings of serum albumin level < 3.0 g/dL, elevated alanine aminotransferase level and leukocyturia. Intravenous immunoglobulin and prednisolone and oral aspirin were introduced on the 10th day. Fever subsided 1 day after initiating the treatment, but arthritis of both knees appeared in addition to hepatosplenomegaly. We suspected sJIA, as the serum level of ferritin was 19,740 ng/mL, IL-6 was < 3 pg/mL, and IL-18 was 132,000 pg/mL. Skin desquamation of the fingertips was observed 18 days from the onset; thus, he was finally diagnosed with incomplete KD with arthritis. At 32 days from the onset, we stopped the prednisolone therapy and no symptoms of relapse were observed afterwards. In the follow-up at 16 months from the onset, he had neither signs of active joint or skin involvement, nor cardiac involvement.

Although patients with sJIA generally have high serum levels of IL-18 and ferritin, this was a case of incomplete KD with extremely high serum levels of IL-18 and ferritin. Serum cytokine and ferritin are often used for the differential diagnosis of KD and sJIA. We need to recognize the existence of KD with high serum levels of IL-18 and ferritin.

Arthroplasty remains prevalent for patients with rheumatoid arthritis (RA), but outcomes are not equivalent to patients with osteoarthritis, and complications including infection are increased. The objective of this article is to review the current evidence supporting perioperative medication management. Challenges are discussed such as continuing potent disease-modifying therapy (DMARDs) and biologics, which may increase infection risk, versus withholding these medications, which may result in disease flares. Published literature regarding arthroplasty in RA has been reviewed and discussed. Some DMARDs such as methotrexate and hydroxychloroquine appear safe in the perioperative period. Anti-TNFα biologics should be withheld due to increase in infection risk, while the impact of rituximab and abatacept on infection risk has not been as clearly defined.

This article provides an overview of arthroplasty in RA, summarizes the evidence supporting perioperative medication management including corticosteroids, and identifies areas where further study is needed.

To identify potentially modifiable risk factors for the development of gout. Longitudinal cohort study (The Johns Hopkins Precursors Study). Of 1337 eligible medical students, 1271 (95%) received a standardized medical examination and questionnaire during medical school. The participants were predominantly male (91%), white (97%), and young (median age, 22 years) at cohort entry. The development of gout. Sixty cases of gout (47 primary and 13 secondary) were identified among 1216 men; none occurred among 121 women (P = .01). The cumulative incidence of all gout was 8.6% among men (95% confidence interval, 5.9% to 11.3%). Body mass index at age 35 years (P = .01), excessive weight gain (greater than 1.88 kg/m2) between cohort entry and age 35 years (P = .007), and development of hypertension (P = .004) were significant risk factors for all gout in univariate analysis. Multivariate Cox proportional hazards models confirmed the association of body mass index at age 35 years (relative risk [RR] = 1.12; P = .02), excessive weight gain (RR = 2.07; P = .02), and hypertension (RR = 3.26; P = .002) as risk factors for all gout. Hypertension, however, was not a significant risk factor for primary gout.

Obesity, excessive weight gain in young adulthood, and hypertension are risk factors for the development of gout. Prevention of obesity and hypertension may decrease the incidence of and morbidity from gout; studies of weight reduction in the primary and secondary prevention of gout are indicated.

The purpose of the current study was to investigate the roles of combined selenium and iodine deficiency in bone development as a possible experimental model of Kashin-Beck osteoarthropathy. Sprague-Dawley rats (n=48) were randomly divided into selenium deficiency (-Se+I), iodine deficiency (+Se-I), combined selenium and iodine deficiency (-Se-I), and selenium and iodine sufficient (+Se+I) groups. Growth of bone and cartilage, and the expression of type X collagen (ColX) and parathyroid hormone-related peptide (PTHrP) were measured in two generations of rats (F(0) and F(1)). The tibial length in -Se-I rats was significantly shorter in F(1) generation. In +Se-I of F(1) rats, the thickness of the growth plate cartilage, and the proliferative zone was smaller, while in -Se-I rats the growth plate, and the proliferative and hypertrophic zones were also thinner in F(1) generation. In articular cartilage, ColX expression was increased in the deep zone in -Se-I rats of F(0) generation, and in -Se+I, +Se-I and -Se-I rats of F(1) generation. PTHrP expression was increased in the middle zone of -Se+I, +Se-I and -Se-I rats of both F(0) and F(1) generations. In the growth plate cartilage, ColX and PTHrP were expressed in the hypertrophic zone. ColX expression was significantly weaker in -Se+I and -Se-I rats in both F(0) and F(1) generations, while PTHrP expression was stronger in -Se+I, +Se-I and -Se-I rats in both F(0) and F(1) animals.

Combined selenium and iodine deficiency impaired the growth of bone and cartilage. The changes in the expression of ColX and PTHrP induced by combined selenium and iodine deficiency were compatible to measurements of ColX and PTHrP in Kashin-Beck osteoarthropathy.

Enhancing rheumatology fellows' teaching skills in the setting of inpatient consultation may have a broad positive impact. Such efforts may improve fellows' clinical skills and overall patient care. Most importantly, effective resident-fellow teaching interactions may not only increase residents' knowledge of rheumatology but may influence their career choice. However, a number of barriers to the resident-fellow teaching interaction have been identified, including fellows' teaching skills. We developed the Fellow As Clinical Teacher (FACT) curriculum in order to enhance fellows' teaching skills during inpatient consultation. The FACT curriculum was delivered in two 45-minute workshops during the 3-day Winter Symposium of the Carolinas Fellows Collaborative. We evaluated its effect with self-assessment surveys and fellow performance on the objective structured teaching exercise (OSTE) before and after participation in the curriculum. Nineteen fellows from 4 rheumatology training programs participated in the pre- and post-curriculum OSTEs and 18 fellows completed pre- and post-curriculum surveys. OSTE scores improved on 5 of the 8 items assessed, and the total OSTE score improved as well (34.7 versus 29.5; P < 0.01) after the FACT curriculum. Fellows' self-assessment of their teaching skills and intent to teach during consultation also increased after participation in the curriculum.

The FACT curriculum, focused on teaching during consultation, improved fellows' teaching skills and attitudes toward teaching. Improving and increasing fellow teaching, particularly in the consultation setting, may impact patient care, resident and fellow learning, and teaching skills of future faculty, and could potentially influence residents' career choice.

RA associates with significantly increased morbidity and mortality from cardiovascular disease (CVD). This may be due to complex interactions between traditional CVD risk factors, systemic rheumatoid inflammation and the vasculature. We reviewed the current literature to answer: (i) whether there is sufficient evidence that patients with RA have altered vascular function and morphology compared with normal controls; (ii) whether there is sufficient evidence to determine if such changes relate predominantly to systemic inflammation; and (iii) whether any changes of vascular function and morphology in RA can be modified with therapy. The MEDLINE database was searched to identify publications from 1974 to 1 November 2010 pertaining to vascular function and morphology in RA. The total number of articles included in the present review was 93. This included 57 cross-sectional studies, 27 longitudinal studies without randomization and 9 longitudinal studies with randomization. Vascular function and morphology was impaired in RA relative to healthy controls. The majority of studies reported no associations between systemic inflammation and vascular function. Treatment with anti-inflammatory medication resulted in both transient and long-term improvements in the vasculature, but only a few studies reported associations between change in inflammation and change in vascular function and morphology.

The link between systemic inflammation and vascular function and morphology is not wholly supported by the available literature. Long-term studies examining specific predictors (including CVD risk factors) on the vasculature in RA are needed.

Based upon evidence in animal and in vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and the inflammatory marker C-reactive protein (CRP) would be inversely associated with bone mineral density (BMD) in a community-based cohort of men and women, with the strongest associations among postmenopausal women not receiving menopause hormonal therapy (MHT). We ascertained fasting serum concentrations of IL-6, TNFα, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual x-ray absorptiometry in 2,915 members of the Framingham Offspring Study (1996-2001). We used multivariable linear regression to estimate the difference (β) in BMD at each bone site associated with a 1-unit increase in log-transformed serum concentrations of IL-6, TNFα, and CRP separately for men (n = 1,293), premenopausal women (n = 231), postmenopausal women receiving MHT (n = 498), and postmenopausal women not receiving MHT (n = 893). Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (β = -0.030, P < 0.01) and between CRP and femoral neck (β = -0.015, P = 0.05) and trochanter BMD (β = -0.014, P = 0.04). TNFα was positively associated with spine BMD (β = 0.043, P = 0.01). In postmenopausal women receiving MHT, CRP was positively associated with femoral neck BMD (β = 0.011, P = 0.04). There were no associations among postmenopausal women not receiving MHT.

The lack of consistency in our results suggests that elevated circulating concentrations of inflammatory biomarkers may not be a risk factor for low BMD.

To compare the Rome and New York criteria for gout. The Rome and New York criteria were compared in 59 patients with gout and in 761 with non-gout by calculating statistical indices such as sensitivity, specificity, relative value (sensitivity + specificity) and the log-likelihood ratio. The best individual criterion was one or more attacks of podagra (New York version) which had a relative value of 194. In contrast, the presence of a tophus was the least valuable criterion with a discriminatory value which was less than three times the most valuable (podagra). The rarity with which either response to Colchicine therapy or measurement for urate crystals were sought makes them poor criteria. Serum uric acid (SUA) followed an approximate Normal Distribution in both sexes, although there were some interesting differences across age strata. In males, SUA showed a progressive rise with age interrupted by a hiccup in the mid-40s. In females, SUA fell slowly as menstruation started, followed by a gradual postmenopausal rise. The mean SUA in males was 294 mumol/l (95% CI = 278-330 mumol/l) and in females 230 mumol/l (95% CI = 224-236 mumol/l).

Despite higher levels of SUA in gouty patients, there was no lower level of SUA from which gout was not diagnosed, which vindicates its removal from the New York criteria set.

To investigate the short-term effects of recreational running on the deformation of knee articular cartilage and to examine the relationship between changes in knee cartilage volume and biomechanical modulators of knee joint load. Twenty healthy volunteers participated in a two phase cross-sectional study. Session 1 involved Magnetic Resonance Imaging (MRI) of femoral and tibial cartilage volumes prior to and following a 30 min period of relaxed sitting, which was directly followed by a recreational run of 5000 steps. Subsequently, all participants undertook a laboratory study of their running gait to compare biomechanical derived measures of knee joint loading with changes in cartilage volume. Estimates of knee joint load were determined using a rigid-link segment, dynamic biomechanical model of the lower limbs and a simplified muscle model. Running resulted in significant deformation of the medial (5.3%, P<0.01) and lateral femoral cartilage (4.0%, P<0.05) and lateral aspect of the tibial cartilage (5.7%, P<0.01), with no significant differences between genders. Maximum compression stress was significantly correlated with percentage changes in lateral femoral cartilage volume (r(2)=0.456, P<0.05). No other biomechanical variables correlated with volume changes.

Limited evidence was found linking biomechanical measures of knee joint loading and observed short-term deformation of knee articular cartilage volume following running. Further enhancement of knee muscle modelling and analysis of stress distribution across cartilage are needed if we are to fully understand the contribution of biomechanical factors to knee joint loading and the pathogenesis of knee osteoarthritis (OA).

A large number of nerve fibres containing different neuropeptides/transmitters are also found in the salivary glands. The number and the distribution of nerve fibres is altered in many diseases, including in Sjögren's syndrome. Therefore in the present study the distribution and precise localisation of the nerve fibres containing the frequently observed neuropeptides were studied in the minor salivary glands. Vasoactive intestinal polypeptide, neuropeptide Y, substance P, calcitonin gene-related peptide, somatostatin, nitric oxide synthase and tyrosine beta-hydroxylase antibodies were used as primary antisera, and then by the aid of avidin-biotin-peroxidase complex method the immunoreactive fibers in human labial glands (control and with Sjögren's syndrome) and in minor glands of the root of the rat's tongue were detected. Large number of vasoactive intestinal polypeptide and nitric oxide synthase immunoreactive nerve fibres were seen around the acini. The neuropeptide Y and tyrosine beta-hydroxylase positive nerve fibres were mainly found around the blood vessels. Some of the IR fibers were also found around the excretory ducts. In the biopsy of patients with Sjögren's syndrome, the acini were destroyed and only few excretory ducts were seen. The number of the nerve fibres was significantly decreased and many degenerated fibres were also observed among the acini. The electron-microscopic examinations showed that the immunoreactive nerve fibres were in close association to the secretory cells, to the smooth muscle cells of blood vessels and to the immunocells. The synaptic gap between the nerve fibres and the target cells were 40-200 nm.

On the bases of the distribution of the different transmitters containing nerve fibres and their relationship to effector cells, the authors suppose that these transmitters control the function of the gland and regulate the blood flow. The close association to immunocells and decreasing the nerve fibres in Sjögren's syndrome imply that they may have also a role in the neuroimmunologic processes.

To evaluate the reliability of a crosswalk, developed in The Netherlands, between the Health Assessment Questionnaire (HAQ) disability index (DI) and the Short Form 36 physical functioning scale (PF-10) in a sample of patients with various rheumatic diseases in the US. Baseline data from patients with rheumatoid arthritis (RA; n = 29,020), fibromyalgia (FM; n = 3,776), and systemic lupus erythematosus (SLE; n = 1,609) participating in the National Data Bank for Rheumatic Diseases were analyzed. Reliability of the crosswalk was evaluated by calculating intraclass correlation coefficients (ICCs), and agreement between observed and predicted scores was evaluated using the Bland-Altman approach. RESULTS. The crosswalk produced reliable conversions for both the HAQ DI (ICC range 0.70-0.77) and PF-10 (ICC range 0.73-0.78) in all 3 disease groups. The mean difference between observed and expected scores was close to zero in US patients with RA. For all 3 disease groups, the limits of agreement were fairly wide and conversion at the level of individual patients is not recommended.

The crosswalk produced reliable conversions at the group level in a crosscultural setting and can be used to convert HAQ DI to PF-10 scores and vice versa in US patients with RA, FM, or SLE.

Treatment of patients with knee osteoarthritis is challenging. Unloader braces have been developed with various success. Unloader One® Knee Brace is light, easily-fitted and shown to be effective by the unloading of the affected compartment. The aim of the study was to assess the clinical outcome of the brace vs. a placebo on patients with knee osteoarthritis. Initially 150 patients were randomized to receive either the Unloader brace or a control placebo group look-alike brace where the active strips had been removed. The patients were followed up at 6,12,26 and 52 weeks with Knee Society Score (KSS) and Knee injury and Osteoarthritis Outcome Score (KOOS). The reason for dropout was recorded. A total of 149 patients were included, 74 in the study and 75 in the control group. The mean age was 59.6 vs. 60.2, BMI was 27.5 vs. 26.9, 37% vs. 44% were women in the study vs. control group. Both groups showed improvement in KSS over 52 weeks, with the study group showing higher improvement in mean scores. KSS increased from 64.3 to 84.0 for the study group and from 64.0 to 74.6 for the control group (p = 0.009). The study group improved in KSS function from 67.0 to 78.6 (p < 0.001) and KOOS for knee related symptoms increased/improved from 64.3 to 72.4 (p < 0.001). Activity of daily living increased/improved from 65.3 to 75.2 and Sports/Recreation from 24.6 to 40.2 (p > 0.001) whereas the control group did not show significant improvements in any of the scores. The dropout was higher in the control group, 40 vs. 25. The trial was retrospectively registered with ClinicalTrials.gov ( NCT03454776 ) on March 6th 2018.

The brace seems to be more effective and better tolerated than the placebo.

Bone erosion is a major problem worsening quality of rheumatoid arthritis (RA) patients' lives. However, causal factors responsible for bone erosion in RA have remained unclear. We aimed to examine genetic variants conferring bone erosion in RA using a Korean genome-wide association study (GWAS) and to search for possible biological mechanisms underlying the development of bone erosion. We obtained genome-wide single nucleotide polymorphism (SNP) data for 711 Korean RA patients using Illumina HapMap 550v3/660W arrays. Associations between SNPs and bone erosion status based on the Steinbrocker staging system were examined using multivariate logistic regression. Cell-type-specific enrichment of the epigenomic chromatin annotation H3K4me3 at the bone erosion associated variants was further investigated using National Institute of Health Roadmap Epigenomics data. As we tested the associations between 439 289 SNPs and bone erosion in 385 patients with erosive RA and 326 with non-erosive RA, none of the tested SNPs reached the genome-wide significance threshold, although many loci showed modest genetic effect on bone erosion status with suggestive association (e.g., rs2741200 [P = 3.75 × 10

Although, there was no large-effect variants associated with bone erosion in our GWAS, we have shown that CD8

This retrospective study evaluates lung abnormalities on high-resolution CT (HRCT) and clarifies which abnormality can predict the progressive fibrosis of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). We identified 1096 RA patients, and enrolled 213 patients with a diagnosis of RA-ILD who underwent serial chest HRCT. Clinical data of the patients were obtained. The presence, extent, and distribution of lung abnormalities were assessed on CT scans. Logistic regression analysis was used to determine positive indicators with predictive value for progressive fibrosis, and 2 × 2 contingency tables were constructed to assess their diagnostic efficiency. Of 213 RA-ILD patients, 106 (49.8%) were diagnosed as progressive fibrosis. The rates of advanced age, male, smoking history, shortness of breath, and anti-CCP antibody high titer positive were higher, and RA duration was shorter in progressive fibrosis patients. Reticular pattern (RP), peribronchovascular interstitium (PBVI) thickening, interlobular septal thickening, and traction bronchiolectasis were more common in the progressive fibrosis group (84.9% vs 42.1%, P < 0.001; 79.3% vs 45.8%, P < 0.001; 74.5% vs 43.9%, P < 0.001; 67.0% vs 40.2%, P < 0.001; respectively). Lung abnormalities demonstrated subpleural predominance, and the subpleural RP and/or interlobular septal thickening had a wide distribution in the progressive fibrosis group (71.7% vs 14.0%, P < 0.001). The overall extent of lung abnormalities was more extensive in the progressive fibrosis group (18.4% vs 14.2%, P < 0.05). Logistic regression analysis showed that a wide distribution of subpleural RP and/or interlobular septal thickening (OR, 18.15) and PBVI thickening (OR, 4.98) were independent risk factors predictive of progressive fibrosis. For the combination of these two CT abnormalities, sensitivity was 63.2%, specificity was 92.5%, positive likelihood ratio was 8.5, and negative likelihood ratio was 0.4 in predicting progressive fibrosis.

A wide distribution of subpleural RP and/or interlobular septal thickening and PBVI thickening on HRCT appear predictive of progressive fibrosis in RA-ILD. The combined evaluation of these two CT abnormalities has a good judgment value. Key Points • We designed this study to investigate the risk factors for progressive fibrosis in patients with RA-ILD. Factors including clinical, physiological, radiological and therapeutic variables were all included in the data analysis. • Our results showed HRCT abnormalities, rather than other parameters, appeared predictive of progressive fibrosis in RA-ILD. • The methods and results of image evaluation in this article would provide reference to rheumatologists in identifying early stage of progressive fibrosis which helps to improve poor prognosis of RA-ILD.

Homeostatic B Cell-Attracting chemokine 1 (BCA-1) otherwise known as CXCL13 is constitutively expressed in secondary lymphoid organs by follicular dendritic cells (FDC) and macrophages. It is the only known ligand for the CXCR5 receptor, which is expressed on mature B cells, follicular helper T cells (Tfh), Th17 cells and regulatory T (Treg) cells. Aberrant expression of CXCL13 within ectopic germinal centers has been linked to the development of autoimmune disorders (e.g. Rheumatoid Arthritis, Multiple Sclerosis, Systemic Lupus Erythematosis). We, therefore, hypothesized that antibody-mediated disruption of the CXCL13 signaling pathway would interfere with the formation of ectopic lymphoid follicles in the target organs and inhibit autoimmune disease progression. This work describes pre-clinical development of human anti-CXCL13 antibody MAb 5261 and includes therapeutic efficacy data of its mouse counterpart in murine models of autoimmunity. We developed a human IgG1 monoclonal antibody, MAb 5261 that specifically binds to human, rodent and primate CXCL13 with an affinity of approximately 5 nM and is capable of neutralizing the activity of CXCL13 from these various species in in vitro functional assays. For in vivo studies we have engineered a chimeric antibody to contain the same human heavy and light chain variable genes along with mouse constant regions. Treatment with this antibody led to a reduction in the number of germinal centers in mice immunized with 4-Hydroxy-3-nitrophenylacetyl hapten conjugated to Keyhole Limpet Hemocyanin (NP-KLH) and, in adoptive transfer studies, interfered with the trafficking of B cells to the B cell areas of mouse spleen. Furthermore, this mouse anti-CXCL13 antibody demonstrated efficacy in a mouse model of Rheumatoid arthritis (Collagen-Induced Arthritis (CIA)) and Th17-mediated murine model of Multiple Sclerosis (passively-induced Experimental Autoimmune Encephalomyelitis (EAE)).

We developed a novel therapeutic antibody targeting CXCL13-mediated signaling pathway for the treatment of autoimmune disorders.

Methotrexate (MTX) has become the most commonly prescribed disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). In the Western countries, the MTX dosage is safely increased to a maximum of 25 mg/wk until a significant response is observed. On the contrary, in Japan, MTX has been approved only as a second-line agent, and the approved maximum MTX dosage is only 8 mg/wk. This suboptimal dosage may affect MTX survival in Japanese RA patients. To study risk factors associated with the cumulative survival of MTX in Japanese RA patients. Data on 273 patients (male 44, female 229) with RA treated with MTX between January 1, 2000 and September 30, 2004 in our center were studied. Two hundred seventy-three patients were followed for 437 person-years of MTX exposure. Mean MTX dosage was 5.5 +/- 1.9 mg/wk. The cumulative MTX survival probability after 5 years was 61.9%. Univariate Cox regression analysis showed a significant correlation between MTX survival probability and use of fewer previous DMARDs, higher dose of MTX, inclusion of folate supplementation, and shorter disease duration. In the multivariate Cox regression model, use of fewer previous DMARDs remained significantly related to MTX survival. Reasons for discontinuation included adverse effects in 34 patients (12.5%) and inefficacy in 6 patients (2.2%).

Cumulative survival was the same or slightly better than those in reports from Western countries, with less withdrawals reported due to adverse events or inefficacy. Whether these results are due to different MTX needs in Japanese or to acceptance of less clinical efficacy will require further studies. The use of fewer previous DMARDs was associated with longer MTX survival.

The Gout Impact Scale (GIS) is a gout-specific quality of life instrument that assesses impact of gout during an attack and impact of overall gout. The GIS has five scales and each is scored from 0 to 100 (worse health). Our objective was to assess minimally important differences (MIDs) for the GIS administered in a randomized controlled trial (RCT) assessing rilonacept vs placebo for prevention of gout flares during initiation of allopurinol therapy. Trial subjects (n = 83) included those with two or more gout flares (self-reported) in the past year. Of these, 73 had data for Weeks 8 vs 4 and formed the MID analysis group and were analysed irrespective of the treatment assignment. Subjects completed the GIS and seven patient-reported anchors. Subjects with a one-step change (e.g. from very poor to poor) were considered as the MID group for each anchor. The mean change in GIS scores and effect size (ES) was calculated for each anchor's MID group. The average of these created the overall summary MID statistics for each GIS. An ES of 0.2-0.5 was considered to represent MID estimates. Results. Trial subjects (n = 73) were males (96.0%), White (90.4%), with mean age of 50.5 years and serum uric acid of 9.0 mg/dl. The mean change score for the MID improvement group for scales ranged from -5.24 to -7.61 (0-100 scale). The ES for the MID improvement group for the four scales ranged from 0.22 to 0.38.

The MID estimates for GIS scales are between 5 and 8 points (0-100 scale). This information can aid in interpreting the GIS results in future gout RCTs. Trial Registration. Clinicaltrials.gov, www.clinicaltrials.gov, NCT00610363.

Tophaceous gout is the nonarticular deposition of monosodium urate resulting from a disorder in purine metabolism that causes an elevation of serum uric acid. Cutaneous variants of tophaceous gout include papular, nodular, ulcerative, and pustular forms. We present a case of a 67-year-old man who presented with multiple cutaneous creamy white papules and nodules. A biopsy was taken, and a diagnosis of cutaneous tophaceous gout was made. The treatment and pathophysiology are discussed.

Miliarial gout is a rare form of cutaneous tophaceous gout that is treated using xanthine oxidase inhibitors such as allopurinol and febuxostat or uricosurics such as probenecid.

To assess the intra- and inter-observer reliability of three commonly referenced radiographic classification systems for knee osteoarthritis in a cohort of arthroplasty candidates. Pre-operative radiographs of 112 patients who subsequently underwent primary total knee arthroplasty were evaluated by four independent observers of varying experience. Each x-ray was de-identified, randomised, and classified according to the International Knee Documentation Committee, Kellgren-Lawrence, and Ahlbäck classifications. After a 2-week interval period, each x-ray was again randomised and re-classified. Regarding inter-observer reliability, the Ahlbäck and Kellgren-Lawrence classifications were shown to have 'substantial agreement' (AC 0.79 and 0.85 respectively), and the IKDC was shown to have 'almost perfect agreement' (AC 0.97). Regarding intra-observer reliability, the two more experienced observers demonstrated 'good' or 'excellent' reliability for all classification systems, and the two less experienced observers demonstrated 'moderate' intra-observer reliability for all classification systems.

The International Knee Documentation Committee, Kellgren-Lawrence, and Ahlbäck radiographic classifications demonstrated adequate intra- and inter-observer reliability, supporting their potential implementation in surgical practice, or in epidemiological and clinical studies of knee osteoarthritis in a comparable cohort of patients. Clinical experience was positively correlated with intra-observer reliability. Whilst the International Knee Documentation Committee classification demonstrated the greatest reliability, this is likely due to its conservative definitions, and the Ahlbäck and Kellgren-Lawrence classifications are likely more reflective of the spectrum of disease severity encountered in an older patient cohort.

To determine the prevalence of coeliac disease in rheumatoid arthritis. One hundred and sixty patients with seropositive rheumatoid arthritis were tested for the endomysial antibody. Those found positive were studied further with endoscopic small bowel biopsy. Only one patient was found to have coeliac disease, and that had already been diagnosed. Thus the prevalence of previously undiagnosed coeliac disease in rheumatoid arthritis is 0 (95% CI 0-0.24%) and the overall prevalence of coeliac disease is 0.63% (95% CI 0.1-3.5%). These prevalences are not significantly different from the reported prevalences of coeliac disease in the general population.

This study does not support an association between coeliac disease and seropositive rheumatoid arthritis or the screening of such patients for coeliac disease.

The presence or relative proportion of progesterone nuclear receptors (PR) in different tissues may contribute to sexual dimorphism in these tissues. PR is expressed in chondrocytes, but its function is mostly unknown. We hypothesized that the PR may regulate chondrocyte metabolism and affect subchondral bone structure. We utilized genetic fate mapping and immunohistochemistry to elucidate PR expression in and effect on cartilage. To define sex-dependent and chondrocyte-specific effects of the PR on subchondral bone, we selectively deleted PR in osteochondrogenic progenitor cells marked by Prx1 (Prx1; PRcKO) and Collagen 2 (Col2; PRcKO), or in matured chondrocytes marked by aggrecan (Acan; PRcKO) and evaluated subchondral bone structure at 4 months of age. Chondrocyte aging was monitored by anti-senescence marker p16INK4a, and MMP13, one of the Senescence-Associated Secretary Phenotype (SASP) components. Compared to wild-type (WT) mice, the female Prx1; PRcKO and the Col2; PRcKO mice had greater total subchondral bone volume and greater subchondral cortical bone thickness, with increased estimated subchondral bone stiffness and failure load in both female and male Col2; PRcKO mice. Moreover, Col2; PRcKO mice from both sexes had greater bone formation and bone strength at the femurs. In contrast, we did not observe any subchondral bone changes in Acan; PRcKO mice other than higher work-to-failure observed in the male Acan; PRcKO mice. Despite no detected difference in articular cartilage between the WT and the PR; chondrocyte conditional deletion mice, there were greater numbers of senescent chondrocytes and increased MMP13 expression, especially in the male mutant mice.

These findings suggest that selective inhibition of PR in osteoprogenitor cells, but not in terminally differentiated chondrocytes, induced an increased subchondral bone phenotype and high estimated subchondral bone strength, which might be associated with the development of osteoarthritis in older age.

Utilising fluorescence optical imaging (FOI), the distribution of an intravenously applied colouring agent indocyanine green (ICG) can be analysed with the potential to identify malperfusion by little to no tissue enhancement. Systemic sclerosis (SSc) is characterised by the presence of digital ulcers reflecting progressive vasculopathy. The objective was to investigate the potential of FOI in the detection of disturbed microcirculation in the hands and fingers of patients with SSc and to link FOI findings to clinical signs of ischemia such as digital ulcers and pitting scars. In this cross-sectional study, 63 patients with SSc and 26 healthy subjects were examined. FOI was performed in all 89 individuals and compared to clinical data and capillaroscopic findings assembled for the SSc cohort. Healthy subjects showed initial ICG signals in their fingertips in 93.6%, SSc patients in 78.5% (limited SSc) and 43.2% (diffuse SSc). Moreover, in SSc patients, FOI findings were significantly associated with a late capillaroscopic pattern, disseminated SSc features, a diffuse SSc subtype, and the presence of digital ulcers or pitting scars. Intra- and inter-reader reliability for FOI amounted to κ = 0.786 and κ = 0.834, respectively.

FOI is able to detect areas of reduced microcirculation in patients with SSc with high association to capillaroscopic findings. The results pave the way for future FOI investigations into its role in the prediction of complications due to an impaired acral perfusion.

Although intra-operative local infiltration analgesia has gained increasing popularity in joint replacement surgery, it is not clear whether postoperative local infusion analgesia using an indwelling catheter provides clinically important additional effects. We, therefore, conducted a randomized controlled trial to clarify the efficacy of the originally developed local infusion analgesia technique in total knee arthroplasty. Forty patients were randomly allocated to the local infusion analgesia or control group. Patients in the local infusion analgesia group received intermittent bolus intra-articular injection of analgesics consisting of ropivacaine, dexamethasone, and isepamicin until postoperative 48 h. Primary outcome was pain severity at rest using 100-mm visual analogue scale. Pain severity in patients of the local infusion analgesia group was lower than control group, and there were significant differences between groups at POD1 (p = 0.025) and POD3 (p = 0.007). Reduction of postoperative pain was associated with a decrease in C-reactive protein level and earlier achievement of straight leg raise. In addition, postoperative drain volume was reduced in the local infusion analgesia group.

Although larger studies are needed to examine its safety, the local infusion analgesia alone provided clinically significant analgesic effects and rapid recovery in total knee arthroplasty.

Neer modified the Bankart procedure by combining a superoinferior capsular shift with the labral reattachment. The theoretical advantages of the modification were that such a procedure would restore the patient's anatomy and also treat the repeated capsular stretching encountered in anteroinferior instability without limiting external rotation and, thereby reducing the risk of arthritis. We therefore determined: (1) the rate of recurrent instability after this modification, (2) patient function, and (3) the incidence and stage of glenohumeral osteoarthritis at greater than 2 years followup in patients with traumatic anteroinferior instability. We retrospectively reviewed all 64 patients (average age, 27 years) who had the modified Bankart procedure for recurrent dislocations (n = 39) or subluxation (n = 25) from 1991 to 1997. The labrum was reattached with suture anchors and a superoinferior capsular shift was added. We determined the rate of recurrent instability, Rowe and Walch-Duplay scores and shoulder ROM, and the presence of glenohumeral osteoarthritis (modified Samilson and Prieto classification). The minimum followup was 24 months (median, 40 months; range, 24-120 months). Recurrent instability occurred in seven of the 64 patients (11%) at an average of 25 months postoperatively (range, 7 days to 6 years); in six patients the recurrence was associated with trauma; five of the six patients underwent reoperation with a Latarjet procedure. Eight additional patients (13%) presented with persistent shoulder apprehension or discomfort. The average Rowe score was 83% (range, 20-100%) and average Walch-Duplay score 83% (range, 15-100%). However, only 36 of 64 (56%) patients could return to the same sport at the same level. The loss of external rotation was 13° compared with the contralateral side. Glenohumeral osteoarthritis incidence increased from 4% preoperatively to 17% postoperatively.

The open Bankart procedure modified by Neer provided high function scores but a relatively low rate of return to sport and high rate of recurrent instability. Our rate of recurrent instability, similar to that obtained with arthroscopic Bankart procedures, has prompted us to abandon the open procedure.

Macrophage activation syndrome (MAS) is a rare and potentially lethal complication of chronic rheumatic diseases of childhood, in particular of systemic-onset juvenile idiopathic arthritis (s-JIA), resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. The onset, acute and dramatic, may mimic a flare of the underlying disease or a severe sepsis. Diagnosis is difficult and, until now, no specific criteria have been developed. Laboratory data show pancytopenia, coagulopathy, low ESR and low concentrations of serum albumin, and high levels of ferritin, liver enzymes and triglycerides. Activated macrophages are found in various organs, particularly in bone marrow. Most hypotheses on the mechanism underlying MAS are based on the data obtained in primary haemophagocytic lymphohistiocytosis (HLH), a genetic disease very similar to MAS. Prompt diagnosis is essential because prognosis is highly related to early treatment. The first approach was to use intravenous methylprednisolone pulse therapy; cyclosporin A was proposed in patients resistant to steroids. We describe nine patients affected by haemophagocytosis: seven patients developed MAS and two patients developed HLH. A child with s-JIA developed three episodes of MAS. After the third episode, as there was no improvement with pulses of methylprednisolone and cyclosporine, he was successfully given etanercept.

Our data, together with a similar, published observation, suggest that the TNF inhibitor etanercept is potentially useful for obtaining remission in children not responding to steroids and cyclosporin A.

To report the clinical outcome of the treatment of dry eyes using 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) (Ophthalmos, Sao Paulo, Brazil). Sixteen eyes of 8 patients with Sjögren syndrome dry eyes (age, 51.13 ± 9.45 years) were enrolled in this study (prospective noncontrolled interventional case series). Patients were instructed to use topical 0.03% tacrolimus eye drops twice a day (every 12 hours) in the lower conjunctival sac. Schirmer I test, break-up time, corneal fluorescein, and rose bengal staining score were performed in all patients 1 day before, and 14, 28, and 90 days after treatment with 0.03% tacrolimus eye drops. The average fluorescein staining and rose bengal staining scores improved statistically significantly after 14 days of treatment and improved even more after 28 and 90 days. The average Schirmer I test did not improve statistically significantly after 28 days of treatment, although we did observe a significant improvement after 90 days of treatment with 0.03% tacrolimus eye drops. The average break-up time did not improve statistically after 14 days of treatment, although we observed a significant improvement after 28 and 90 days of treatment with 0.03% tacrolimus eye drops.

Topical 0.03% tacrolimus eye drops successfully improved tear stability and ocular surface status in patients with dry eyes.

We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-beta)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARgamma), for which RXR is an obligate dimerization partner. The goals of this study were to evaluate the inhibition of IL-1-beta-induced expression of MMP-1 and MMP-13 by combinatorial treatment with RXR and PPARgamma ligands and to investigate the molecular mechanisms of this inhibition. We used real-time reverse transcription-polymerase chain reaction to measure LG268- and rosiglitazone-mediated inhibition of MMP gene transcription in IL-1-beta-treated SW-1353 chondrosarcoma cells. An in vitro collagen destruction assay was a functional readout of MMP collagenolytic activity. Luciferase reporter assays tested the function of a putative regulatory element in the promoters of MMP-1 and MMP-13, and chromatin immunoprecipitation (ChIP) assays detected PPARgamma and changes in histone acetylation at this site. Post-translational modification of RXR and PPARgamma by small ubiquitin-like modifier (SUMO) was assayed with immunoprecipitation and Western blot. Rosiglitazone inhibited MMP-1 and MMP-13 expression in IL-1-beta-treated SW-1353 cells at the mRNA and heterogeneous nuclear RNA levels and blunted IL-1-beta-induced collagen destruction in vitro. Combining LG268 and rosiglitazone had an additive inhibitory effect on MMP-1 and MMP-13 transcription and collagenolysis. IL-1-beta inhibited luciferase expression in the MMP reporter assay, but rosiglitazone and LG268 had no effect. ChIP indicated that treatment with IL-1-beta, but not LG268 and rosiglitazone, increased PPARgamma at the proximal promoters of both MMPs. Finally, rosiglitazone or LG268 induced 'cross-SUMOylation' of both the target receptor and its binding partner, and IL-1-beta-alone had no effect on SUMOylation of RXR and PPARgamma but antagonized the ligand-induced SUMOylation of both receptors.

The PPARgamma and RXR ligands rosiglitazone and LG268 may act through similar mechanisms, inhibiting MMP-1 and MMP-13 transcription. Combinatorial treatment activates each partner of the RXR:PPARgamma heterodimer and inhibits IL-1-beta-induced expression of MMP-1 and MMP-13 more effectively than either compound alone. We conclude that the efficacy of combined treatment with lower doses of each drug may minimize potential side effects of treatment with these compounds.

Osteoarthritis (OA) is the most common form of arthritis with multiple risk factors implicated including female sex and obesity. Metabolic dysregulation associated with obesity leading to metabolic syndrome is a proposed component of that association. Polycystic ovary syndrome (PCOS) commonly affects women of reproductive age and these women are at higher risk of developing metabolic syndrome and thus likely to represent a high-risk group for early OA development. There are no published studies exploring the epidemiology of knee, hip and hand OA in women diagnosed with PCOS. To assess the prevalence and incidence of knee, hip and hand osteoarthritis (OA) in women with polycystic ovary syndrome (PCOS) when compared with age-matched controls. Prospective Danish national registry-based cohort study. The prevalence of OA in 2015 and incidence rates of OA over 11.1 years were calculated and compared in more than 75,000 Danish women with either a documented diagnosis of PCOS ± hirsutism (during the period of 1995 to 2012) or age-matched females without those diagnoses randomly drawn from the same population register. In 2015, the prevalence of hospital treated knee, hip and hand OA was 5.2% in women with PCOS diagnosis. It was 73% higher than that seen in age-matched controls. Significantly higher incidence rates were observed in the PCOS cohort compared with the age-matched controls during the follow-up period (up to 20 years), with the following hazard ratios (HR): 1.9 (95% CI 1.7 to 2.1) for knee, 1.8 (95% CI 1.3-2.4) for hand and 1.3 (95% CI 1.1 to 1.6) for hip OA. After excluding women with obesity, similar associations were observed for knee and hand OA. However, risk of developing hip OA was no longer significant.

In this large prospective study, women with PCOS diagnosis had higher prevalence and accelerated onset of OA of both weight and non-weight bearing joints, when compared with age-matched controls. Further studies are needed to understand the relative effect of metabolic and hormonal changes linked with PCOS and their role in promoting development of OA.

To determine whether there are differences in matrix turnover within early cartilage lesions of the ankle (talocrural) joint compared with the knee (tibiofemoral) joint that may help explain differences in the prevalence of osteoarthritis in these 2 joints. Cartilage removed from lesions of the tali and femoral condyles was analyzed for type IIB collagen messenger RNA, C-terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2-3/4C(short)), and the denaturation epitope (Col2-3/4m). The content of collagen, glycosaminoglycan, and epitope 846 of aggrecan was quantitated. In ankle lesions, there was an up-regulation of markers of synthesis (CPII [P = 0.07]; epitope 846 [P < or = 0.0001]), but these were down-regulated in the knee (CPII [P = 0.1]; epitope 846 [P = 0.004]). In lesions of the knee, but not the ankle, there was an up-regulation of collagen degradation markers (P = 0.008). On a molar basis, there was 24 times more cleavage epitope than denaturation epitope in knee lesions compared with ankle lesions.

The up-regulation of matrix turnover that is seen in early cartilage lesions of the ankle would appear to represent an attempt to repair the damaged matrix. The increase in collagen synthesis and aggrecan turnover seen in ankle lesions is absent from knee lesions. Instead, there is an increase in type II collagen cleavage. Together with the differences in collagen denaturation, these changes point to an emphasis on matrix assembly during early lesion development in the ankle and to degradation in the knee, resulting in fundamental differences in matrix turnover in these lesions.

Disease-specific beliefs may impact patients' perceptions of the efficacy of various treatment options, thus, it is important to understand these beliefs. We examined the relationship between patients' demographic characteristics and arthritis-specific beliefs related to aging. We performed a cross-sectional survey of 591 elderly primary care patients, who had symptomatic osteoarthritis (OA) of the knee and/or hip, at the Louis Stokes VA Medical Center in Cleveland, Ohio. Data were collected on age, race, educational level, income, and whether patients agreed or disagreed with four statements regarding aging and arthritis. We also assessed OA symptom severity using the Western Ontario McMaster Universities Index (WOMAC) and depressive symptoms using the Geriatric Depression Scale. We used logistic regression analyses to examine relationships between patients' age, race, and educational level and arthritis-specific health beliefs, while adjusting for OA symptom severity, radiographic confirmation of OA, OA joint burden, depressive symptoms, and income. Patients 70 years old or older, as compared to patients 50-59 years old, were more likely to believe that: arthritis is a natural part of growing old; people should expect that when they get older, they won't be able to walk as well, and people should expect to live with pain as they grow older.

Among older, male veterans, health beliefs regarding the relationship between aging and arthritis vary by age. Clinicians should consider these differences when discussing treatment strategies with their patients with knee and/or hip OA.

Osteoarthitis (OA) leads to progressive loss of articular cartilage, pain and joint disability. An acute injury constitutes an important risk factor for early OA, determining an inflammatory process responsible of cartilage degeneration and muscle atrophy, due to the joint pain and immobility. The study aims to assess the effects of conjugation of physical activity and diet enriched by olive tree compounds [extra virgin olive oil (EVOO) and olive leaf extract (OLE)], on the musculoskeletal system in OA rat model. OA was induced by anterior cruciate ligament transection and confirmed by Mankin and OARSI scores. Rats were subjected to physical activity on treadmill 5 days a week for 10 min daily and fed with experimental diets (standard diet enriched with Sicilian EVOO, Tunisian EVOO and Tunisian EVOO-OLE) for 12 weeks. Immunohistochemistry was used to evaluate IL-6 and lubricin expression in cartilage tissue and ELISA was used to quantify these proteins in serum at different time points. Histology and histomorphometry analysis were done to valuate liver steatosis, muscle atrophy and cartilage pathological changes. Compared to the OA group, the experimental groups showed general increased lubricin and decreased IL-6 expression, significant muscle hypertrophy and no signs of liver steatosis, suggesting the beneficial effects of physical activity coupled with EVOO-enriched diets on rat articular cartilage. Interestingly, the best result was shown for Sicilian EVOO-enriched diet.

In conclusion, the conjugation of physical activity and EVOO-enriched diet determines a significant articular cartilage recovery process in early OA.

The effects of estrogen may be exerted via the nuclear estrogen receptors (ERs) ERalpha or ERbeta or via the recently proposed transmembrane estrogen receptor G protein-coupled receptor 30 (GPR-30). The purpose of this study was to elucidate the ER specificity for the ameliorating effects of estrogen on arthritis and bone loss in a model of postmenopausal rheumatoid arthritis (RA). Female DBA/1 mice underwent ovariectomy or sham operation, and type II collagen-induced arthritis was induced. Mice were treated subcutaneously 5 days/week with the specific agonists propylpyrazoletriol (PPT; for ERalpha), diarylpropionitrile (DPN; for ERbeta), G1 (for GPR-30), or with a physiologic dose of estradiol. Clinical arthritis scores were determined continuously. At termination of the study, bone mineral density (BMD) was analyzed, paws were collected for histologic assessment, serum was analyzed for cytokines and markers of bone and cartilage turnover, and bone marrow was subjected to fluorescence-activated cell sorting. Treatment with PPT as well as estradiol dramatically decreased the frequency and severity of arthritis. Furthermore, estradiol and PPT treatment resulted in preservation of bone and cartilage, as demonstrated by increased BMD and decreased serum levels of bone resorption markers and cartilage degradation markers, whereas no effect was seen after DPN or G1 treatment.

In a well-established model of postmenopausal RA, ERalpha, but not ERbeta or GPR-30 signaling, was shown to ameliorate the disease and the associated development of osteoporosis. Since long-term treatment with estrogen has been associated with significant side effects, increased knowledge about the mechanisms behind the beneficial effects of estrogen is useful in the search for novel treatments of postmenopausal RA.

The incidence of lung cancer (LC) is reported to be higher in patients with rheumatoid arthritis (RA). The present study investigated whether or not RA altered the clinical manifestation of LC. In this retrospective, cohort study, a total of 23 patients with both RA and LC (RA + LC group), and 6,570 patients with primary LC alone (LCA group), were identified from records at Taipei Veterans General Hospital between 1993 and 2002. Data about clinical characteristics, smoking habit, tumor location, LC histology, staging, and survival, were compared between the 2 groups. There was no significant difference in mean age at LC diagnosis between the RA + LC and LCA groups (70.2 vs 67.6 years; p = 0.154). Adenocarcinoma was the major histologic type in both groups, especially among women. There was no significant difference in histology, location, or staging of LC between the RA + LC and LCA groups. In the RA + LC group, all patients had RA before LC was diagnosed; pulmonary fibrosis was noted in 3 patients, 1 of whom had secondary Sjogren's syndrome. Median survival in the LCA group was not significantly different from that in the RA + LC group (10 [95% confidence interval, CI, 9.6, 10.4] vs 11 [95% CI, 3.7, 18.3] months; p = 0.69); the relative risk of LCA compared with RA + LC for survival was 0.938 (95% CI, 0.555, 1.585). The incidence of LC in RA patients in our hospital was 1.32% (23 of 1,740 patients).

RA has no influence on LC stage and does not shorten the survival of LC patients.

Protein deimination, a process to modify arginine residues to citrulline by the addition of a neutral oxygen group, is associated with apoptosis. The presence of autoantibodies recognizing citrullinated peptides is highly specific to rheumatoid arthritis (RA) and is therefore a useful marker for the early diagnosis of RA. In this study, we explored whether anti-cyclic citrullinated peptide (anti-CCP) autoantibodies are produced in several experimental models of autoimmune diseases in mice. The levels of anti-CCP autoantibodies were analyzed by enzyme-linked immunosorbent assay in several lupus-prone strains of mice, in animals with type II collagen (CII)-induced arthritis, and after induction of neonatal tolerance to alloantigens. We observed the production of these autoantibodies in 2 different lupus-prone mice, MRL-lpr/lpr and (NZW x B6)F(1)-hbcl-2 transgenic mice, characterized by the presence of abnormalities in the regulation of B cell apoptosis. Other genetic defects, determining autoimmune susceptibility, present in MRL and NZW mice were additionally required for anti-CCP autoantibody production. The induction of autoantibodies in normal BALB/c mice injected at birth with semiallogeneic spleen cells from (BALB/c x B6)F(1)-hbcl-2 transgenic mice suggested that these additional autoimmune defects may be related, at least in part, to the establishment of abnormal interactions between T cells and B cells. In addition, anti-CCP autoantibodies were not produced in the course of CII-induced arthritis, an experimental model of RA in mice.

Our study provides evidence for the association between defects in the regulatory cell death machinery of B lymphocytes and the production of certain autoantibody specificities.

To gain insight into patient experience of the disease course and health related quality of life during and after pregnancy in women with rheumatoid arthritis and ankylosing spondylitis. 10 patients with rheumatoid arthritis, 10 patients with ankylosing spondylitis, and 29 age matched healthy pregnant controls were evaluated by the medical outcomes study short form 36 (SF-36) health survey once at each trimester and at 6, 12, and 24 weeks postpartum. A group of non-pregnant age matched female patients (40 rheumatoid arthritis, 16 ankylosing spondylitis) was studied for comparison. Impaired physical dimensions as well as increased bodily pain was observed in healthy women in late pregnancy. Patients with rheumatoid arthritis showed improved physical functioning scores in the second trimester and reduced pain in the third trimester. Among pregnant patients, those with ankylosing spondylitis suffered the greatest impairment of health related quality of life during pregnancy. In all patient groups the physical impairment in the third trimester was less pronounced than in healthy controls. Mental health scores remained stable even with persisting active disease during pregnancy, or with a postpartum flare.

Pregnancy reduced physical functioning in healthy women and patients, but had no impact on mental and emotional health, even at times of disease aggravation. The pregnancy experience documented in our patients may be helpful when counselling patients contemplating pregnancy.

Subsidence has been noted with both cemented and uncemented stems in hip arthroplasty. On most occasions, it's minimal (i.e. less than 2 mm) and stabilises at 1 year. However, when its progressive and significant, it causes loss of length and horizontal offset, and when symptomatic warrants a revision. A retrospective radiological review of the patient database was carried out to identify all patients with age ≥ 70 years who underwent elective hip arthroplasty using uncemented HA coated collared stem and had radiographs at 1 year follow up. A total of 176 patients were identified from January 2009 to June 2010. 2 independent investigators classified the proximal femur based on Dorr type and calculated the subsidence based on Engh and Massin method of calculating the distance between the tip of greater trochanter and shoulder of the prosthesis. 7 patients (4 Bs, 2 As, 1 C) had a subsidence of ≥ 2 mm (2-3.2 mm) at 1 year. None of them was symptomatic. 1 of them was secondary to a missed calcar crack and continued to subside for 9 mm before it stabilised on the lesser trochanter at 4 years follow up. There were Dorr 22 (12.5%) type A, 147(83.5%) type B and 7(4%) type C. The mean age was 77.4 years (70-91 years) and male: female ratio was 7:15. 3 patients had an intraoperative calcar crack requiring cabling. All were mobilised full weight-bearing postoperatively, and none had a subsidence of >2 mm at 1 year follow-up. Our subgroup analysis identified that subsidence can happen when the collar is "non-functional" and the initial press fit of the stem wasn't achieved. It can also occur in an event of calcar crack, which is missed intraoperatively. In cases of calcar crack which went on to have to cable during the primary procedure, it neither changed the post-operative rehabilitation nor did it show an increased risk of subsidence.

A fully hydroxyapatite (HA) coated collared stem, when used in elderly age group for elective THR, has only 2% risk of intraoperative periprosthetic fracture. There's a 4% risk of radiologically significant subsidence (i.e. ≥2 mm), however, it has not proven to be clinically significant in our study. Dorr canal type had no bearing on either risk of periprosthetic fracture or subsidence. Collared stems did not have a statistically significant difference in risk of subsidence and peri-prosthetic fracture in comparison to un-collared stem, although there was a non-significant trend in favour of collar use.