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To examine the effects of agonists of peroxisome proliferator-activated receptor (PPAR) gamma on proteoglycan degradation induced by interleukin (IL)-1beta or tumor necrosis factor (TNF)alpha in cartilage in vitro. Proteoglycan degradation was measured as release of radioactivity from rat cartilage explants previously labeled with (35)SO2-4. Western blots were used to examine tissue levels of aggrecan neoepitopes NITEGE and VDIPEN, generated by aggrecanases and matrix metalloproteinases (MMP), respectively. Production of MMP-2, -3 and -9 by cultured rat chondrocytes was measured by zymography and by fluorimetric assay. IL-1beta-induced proteoglycan degradation was likely due to aggrecanase, since it was associated with a strong increase of NITEGE signal. MMP-dependent VDIPEN signal increased only after further incubation with pro-MMP activator APMA. PPAR agonists 15d-PGJ(2) and GI262570 (10 microM) inhibited IL-1beta- and TNFalpha-induced proteoglycan degradation measured both before and after addition of APMA. The agonists also inhibited cytokine-induced MMP production by isolated chondrocytes.

This study shows that PPARgamma agonists inhibit cytokine-induced proteoglycan degradation mediated by both aggrecanase and MMP. This effect is associated with inhibition of production of MMP-3 and -9. These results support the interest for PPARgamma agonists as candidate inhibitors of pathological cartilage degradation.

To examine the effect of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in psoriatic arthritis (PsA) patients with and without prior tumor necrosis factor (TNF) inhibitor exposure. The ongoing phase III RAPID-PsA trial was double blind and placebo controlled to week 24. Patients were randomized 1:1:1 to placebo every 2 weeks or CZP 400 mg at weeks 0, 2, and 4, followed by either CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks. PRO measures evaluated were the Health Assessment Questionnaire (HAQ) disability index (DI), health status (measured by the Short Form 36 [SF-36] health survey), Psoriatic Arthritis Quality of Life (PsAQOL), Fatigue Assessment Scale, patient assessment of pain (visual analog scale), and Dermatology Life Quality Index (DLQI). Post hoc analyses of PROs in patients with and without prior TNF inhibitor exposure were conducted. Change from baseline for all PROs was analyzed for the randomized population using analysis of covariance with last observation carried forward imputation. A total of 409 patients were randomized. Twenty percent had received a prior TNF inhibitor. Baseline demographics were similar between the treatment groups. At week 24, clinically meaningful differences in HAQ DI, SF-36, PsAQOL, fatigue, pain, and DLQI were observed in both CZP arms versus placebo (P < 0.001), irrespective of prior TNF inhibitor exposure. More CZP-treated patients reached SF-36 general population norms than placebo-treated patients.

Both CZP dosing schedules provided rapid improvements in PROs across multiple disease aspects in patients with PsA. The benefits of CZP treatment for health-related quality of life were seen across generic, PsA-specific, and dermatology-specific measures and were observed in patients regardless of prior TNF inhibitor exposure.

Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. To analyse the effect of the 6q23 region on the rate of joint destruction. Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment.

These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.

Hepatitis C virus infection (HCV) is associated with various extrahepatic manifestations. Antibodies against alpha-fodrin are associated with sicca symptoms and may valuable diagnostic markers in patients with primary Sjögren syndrome (SS) lacking Ro antibodies. The frequency and role of alpha-fodrin antibodies in patients with chronic HCV infection are unknown. The aim of this study was to investigate the prevalence of alpha-fodrin antibodies in HCV-infected patients with SS. Alpha-fodrin antibodies were detected more often in hepatitis C patients (25%; n=142) than in HBV-infected individuals (8%; n=49) and healthy controls (6%; n=174) (p<0.01). Based on these findings, we investigated the frequency of sicca symptoms in a second cohort and studied other antibodies associated with SS. HCV-infected individuals showed sicca symptoms in 53% of cases as determined by the Saxon and Schirmer tests, which was more frequent than in healthy controls (1%, p<0.01) but not in patients with autoimmune liver disease (51%). Antibodies specific for Ro (SS-A) were significantly more common in patients with autoimmune liver disease than in HCV-infected patients and healthy controls (16% versus 1% and 0%, p<0.003). SS was found in 18% of patients with HCV, in 15% of patients with autoimmune liver disease and in 1% of healthy controls. However, we found no correlation between sicca symptoms and the presence of antibodies against alpha-fodrin, Ro and La.

Patients with chronic HCV infection show a high prevalence of sicca symptoms and antibodies against alpha-fodrin. However, neither the frequency nor the severity of symptoms correlated with the presence of alpha-fodrin antibodies.

To evaluate whether cervical spine changes are associated with the destruction of shoulder or peripheral joints and with bone mineral density (BMD) in patients with long-term RA. An inception cohort of 67 patients with seropositive and erosive RA were followed up for 20 years. Cervical spine, shoulder, hand and foot radiographs, and the BMD of the lumbar spine and femoral neck were evaluated. A positive relationship was detected between the occurrence of atlantoaxial disorders and the destruction of both shoulder (p < 0.001) and peripheral (p = 0.001) joints. In addition, the severity of anterior atlantoaxial subluxation and atlantoaxial impaction positively correlated with the grade of destruction in the evaluated joints. Furthermore, patients with atlantoaxial disorders presented decreased BMD of the femoral neck (p = 0.019). The occurrences of subaxial subluxations (SAS) and subaxial disc space narrowings only associated with higher onset age of RA.

Patients with severe RA and osteoporosis have an increased risk for atlantoaxial disorders. The co-existence of shoulder destruction and cervical spine disorders makes the differential diagnosis of shoulder and neck pain challenging.

The aim of this article is to describe the technique used to perform ultrasound guided steroid joint injections in children in a group of joints that can be injected using ultrasound as the only image guidance modality. The technique is described and didactic figures are provided to illustrate key technical concepts.

It is very important to be familiar with the sonographic appearance of the pediatric joints and the developing bone when performing ultrasound-guided joint injections in children.

To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA). A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non-loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)-naive patients. Safety analyses included all patients who received ≥1 dose of study treatment. Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported.

Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.

To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. Randomised controlled trials (RCTs) comparing PE vs. non-PE in AAV patients (microscopic polyangiitis [MPA], granulomatosis with polyangiitis [GPA], or eosinophilic granulomatosis with polyangiitis [EGPA]) were included. The combined risk ratio (RR) was calculated by the random-effects model using the Mantel-Haenszel method. Heterogeneity was measured using the I Four RCTs comparing PE vs. no PE (N = 827) and 1 RCT comparing PE vs. pulse steroid treatment (N = 137) were included. All participants were MPA or GPA patients (no EGPA patients). PE was not associated with main primary outcomes compared with no PE (mortality RR 0.93 [95% confidence interval {CI} 0.70-1.24], I UMIN R000045239 , PROSPERO CRD42020182566 .

We carried out a systematic review and meta-analysis targeting all AAV patients, including MPA, GPA, and EGPA. In AAV patients, performing PE was not associated with the risk of mortality, CR, and AE. No RCT exists evaluating the efficacy of PE for EGPA; hence, this is required in the future. The results may affect the development of guidelines for AAV and may indicate the direction of future clinical research on AAV.

Reports regarding the association between body composition and inflammatory activity in rheumatoid arthritis (RA) have consistently yielded contradictory results. To perform a systematic review on the association between overweight/obesity and inflammatory activity in RA. FAST approach: Article search (Medline, EBSCO, Cochrane Library), followed by abstract retrieval, full text review and blinded assessment of methodological quality for final inclusion. Because of marked heterogeneity in statistical approach and RA activity assessment method, a meta-analysis could not be done. Results are presented as qualitative synthesis. One hundred and nineteen reports were found, 16 of them qualified for full text review. Eleven studies (8,147 patients; n range: 37-5,161) approved the methodological quality filter and were finally included. Interobserver agreement for methodological quality score (ICC: 0.93; 95% CI: 0.82-0.98; P<.001) and inclusion/rejection decision (k 1.00, P>.001) was excellent. In all reports body composition was assessed by BMI; however a marked heterogeneity was found in the method used for RA activity assessment. A significant association between BMI and RA activity was found in 6 reports having larger mean sample size: 1,274 (range: 140-5,161). On the other hand, this association was not found in 5 studies having lower mean sample size: 100 (range: 7-150).

The modulation of RA clinical status by body fat mass is suggested because a significant association was found between BMI and inflammatory activity in those reports with a trend toward higher statistical power. The relationship between body composition and clinical activity in RA requires be approached with further studies with higher methodological quality.

To enhance guideline-based nonsurgical management of osteoarthritis (OA), a multidisciplinary stepped-care strategy has been implemented in clinical practice. This study aimed to describe health care use after implementation of this strategy and to identify factors related to such use at multiple levels. For this 2-year observational prospective cohort, patients with symptomatic hip or knee OA were included by their general practitioner. Activities aligned with patients and health care providers were executed to implement the strategy. Health care use was described as the cumulative percentage of "users" for each modality recommended in the strategy. Determinants were identified at the level of the patient, general practitioner, and practice using backward stepwise logistic multilevel regression models. Three hundred thirteen patients were included by 70 general practitioners of 38 practices. Their mean ± SD age was 64 ± 10 years and 120 (38%) were men. The most frequently used modalities were education, acetaminophen, lifestyle advice, and exercise therapy, which were used by 242 (82%), 250 (83%), 214 (73%), and 187 (63%) patients, respectively. Fourteen percent of the overweight patients reported being treated by a dietician. Being female, having an active coping style, using the booklet "Care for Osteoarthritis," and having limitations in functioning were recurrently identified as determinants of health care use.

After implementation of the stepped-care strategy, most recommended nonsurgical modalities seem to be well used. Health care could be further improved by providing dietary therapy in overweight patients and making more efforts to encourage patients with a passive coping style to use nonsurgical modalities.

To investigate the potential interaction of naproxen and methotrexate (MTX) in children with juvenile rheumatoid arthritis (JRA). Nine children with JRA served as their own control taking their usual doses of MTX (0.22-1.02 mg/kg/week) and naproxen (14.6-18.8 mg/kg/day) separately and in combination. MTX affected a > or = 30% change in naproxen kinetics in 6/8 patients, while naproxen altered MTX kinetics by > or = 30% in 4/9 patients.

MTX can alter nonsteroidal antiinflammatory drug (NSAID) kinetics in children with JRA and NSAID can alter MTX kinetics. NSAID toxicity should be considered when assessing adverse reactions in patients receiving the combination treatment of MTX and NSAID:

To describe the use of generalist and rheumatologist services in a population-based cohort of patients with polymyalgia rheumatica (PMR) and to identify predictors of rheumatology care. We identified all incident cases of PMR among residents of Olmsted County, Minnesota between 1970 and 1999. Patients were followed for a maximum of 5 years after their incidence date. Logistic regression and zero-inflated Poisson regression models were used to assess the association between rheumatology care and age, sex, giant cell arteritis (GCA), PMR relapses, corticosteroid complications, comorbidity, and various laboratory findings, adjusting for the total number of visits. Of the 364 incident cases of PMR eligible for this analysis, 67% were women and the mean age at incidence was 73 years. Over a mean followup of 4.1 years, individuals in this cohort utilized a total of 5,108 physician office visits and 2,015 telephone calls. The mean number of generalist and rheumatologist visits per person-years of follow-up during the first year of PMR was 7.02 and 2.15, respectively. Thereafter, there was a steady decline in both generalist and rheumatologist visits. One hundred forty-four (40%) patients had no rheumatologist visits and 102 (28%) had only 1 rheumatologist visit, mostly for diagnostic confirmation. Men and patients with several comorbid conditions were significantly more likely to be seen by rheumatologists (P < 0.001). However, once referred, women, older patients, and those with GCA, PMR relapses, and corticosteroid complications had significantly more rheumatologist visits (P < 0.001).

The use of physician services in PMR is considerable. Generalists provide the large majority of care. Rheumatologist involvement is generally limited to diagnostic confirmation and management of complications. The relative paucity of rheumatology care following the period of diagnosis may represent an opportunity for improving the care of patients with PMR.

To determine if a polymorphism in the immunoproteasome subunit LMP7 was associated with juvenile rheumatoid arthritis (JRA) and had functional significance. The frequency of LMP7QQ+ vs QQ- (QK and KK genotypes) among 207 patients with JRA and 50 controls was determined. JRA subtypes were pauciarticular (53%), polyarticular (33%), and systemic (14%). Onset was before age 6 (early onset) in 60% of patients. The functional significance of the LMP7 polymorphism was determined by comparing incorporation of LMP7Q vs LMP7K into proteasomes. There was an increased frequency of LMP7QQ in patients vs controls (73 vs 56%; p = 0.016), mainly due to the pauciarticular and systemic JRA subtypes (p = 0.037), and more pronounced in early onset disease (77 vs 56%; p = 0.006). The association persisted with stratification for HLA-DR5(11) and -DPB 1 *0201 (p = 0.002 and 0.013). We found no difference in the relative incorporation of LMP7Q and LMP7K into proteasomes.

These results support an association between LMP7QQ homozygosity and JRA, particularly early onset disease. The difference persists with stratification, at least for DR5(11) and DPB1*0201, suggesting that this effect is unlikely to be due to linkage disequilibrium with HLA alleles known to be associated with early onset pauciarticular JRA. Importantly, as there does not appear to be functional significance associated with the LMP7 polymorphism, this may be a marker for another as yet unidentified susceptibility locus.

Due to increasing concerns about post-chikungunya (pCHIK) rheumatic disorders in Latin America we aimed to evaluate its occurrence in travelers returning to NYC from the Caribbean. Patients diagnosed with chikungunya (CHIK) during 2014 at the Bronx-Lebanon Hospital Center (Bronx, NewYork) were identified by reviewing laboratory and electronic medical records. Patients and caregivers of pediatric patients were interviewed by phone ≥9 months after the CHIK diagnosis to survey for chronic symptomatology and current health care needs. Reported chronic musculoskeletal complaints were categorized according to validated criteria. A total of 28 patients (54% females, median age [range] of 51.5 [0, 88] years) diagnosed with CHIK at our center were identified. Most (82%) had returned from the Dominican Republic. Nineteen (68%) patients were successfully contacted at a median (range) of 13 (9, 16) months since the acute diagnosis. A third (37%) reported ongoing complaints related to CHIK including joint pain (32%), muscle pain (32%), and joint swelling (26%). A presumptive diagnosis of pCHIK chronic inflammatory arthritis (n = 4) and pCHIK musculoskeletal disorder (n = 3) was established.

A third of travelers with CHIK acquired in the Caribbean may be at risk for developing persistent symptoms suggestive of pCHIK rheumatic disorder.

We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36).

Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.

Valvular heart disease constitutes the majority of all causes of cardiac disease in pregnancy. The significant physiological haemodynamic changes of pregnancy may cause serious cardiac problems leading to severe maternal and foetal morbidity and mortality. In this study, we evaluate the effect of maternal rheumatic valvular disease requiring definitive operation concurrent with caesarian delivery on maternal and foetal outcome. Between 2003 and 2010, a total of nine pregnant women and nine live births were examined. Immediately after caesarean section, the newborns were examined by the neonatologist and transferred to the neonatal intensive care unit. All the mothers were followed routinely with clinical and echocardiographic examinations. The age at the time of delivery ranged between 21 and 36 years (median 31 years). Postoperative period of mothers was uneventful and mean hospital stay was 7.56±3.97 days. Birth weight for the newborns was ranged between 1370 and 2900g. Six of the newborns were premature (≤37 weeks). Four newborns were small for gestational age (SGA). There was no mortality in newborns. Hospital stay for the newborns ranged between four and 54 days.

Careful follow-up of pregnancies with valvular heart diseases and determining the optimal time of cardiac intervention are the essential issues. We suggest that careful follow-up of both mother and foetus until at least the 28th gestational week, following which combined caesarian section and cardiac surgery can be performed.

Rheumatoid arthritis (RA) has been associated with inhaled pollutants in several studies, and it is a disease of chronic inflammation. The association between air pollution and the risk of RA remains unclear. Therefore, we conducted this nationwide, retrospective, sex-stratification study to evaluate this association. We collected data from the Longitudinal Health Insurance Database (LHID), maintained by the Taiwan Bureau of National Health Insurance, and the Taiwan Air Quality-Monitoring Database (TAQMD), released by the Taiwan Environmental Protection Agency. The TAQMD provides the daily concentrations of particulate matter with the aerodynamic diameter <2.5μm (PM2.5) and nitrogen dioxide (NO2) from 74 ambient air quality-monitoring stations distributed all over Taiwan during 1998-2010. The LHID and TAQMD were linked according to the residential areas of insurants and the areas where the air quality-monitoring stations were located. A residential area was defined according to the location of the clinic and hospital that treated acute upper respiratory tract infections. The yearly average air pollutant concentrations were categorized into 4 levels based on quartiles. We evaluated the risk of RA in residents exposed to 4 levels of PM2.5 and NO2 concentrations. We detected an increased risk of RA in participants exposed to PM2.5 and NO2. Among four quartiles of NO2 concentration, namely Q1, Q2, Q3, and Q4, the adjusted hazard ratios (aHRs) in Q2, Q3, and Q4 compared with that in Q1 were 1.07 (95% confidence interval [CI]=0.76-1.50), 1.63 (95% CI=1.16-2.31),and 1.49 (95% CI=1.05-2.12), respectively. Regarding the PM2.5 concentrations, the aHRs after exposure to the Q2, Q3, and Q4 levels were 1.22 (95% CI=0.85-1.74), 1.15 (95% CI=0.82-1.62), and 0.79 (95% CI=0.53-1.16), respectively.

The results of this nationwide study suggest an increased risk of RA in residents exposed to NO2.

Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA. Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter. Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF-alpha in up-regulating OPG production.

Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA.

Our hypothesis is that increased apoptosis in synovium might contribute to temporomandibular joint (TMJ) degeneration. To investigate this, we measured soluble Fas (sFas) and nuclear matrix protein (NMP) levels in TMJ synovial fluid from patients with disc displacement without reduction as indicators of apoptosis in the synovium. Synovial fluid was obtained from 17 joints in 17 patients (11 female, 6 male; mean age, 31.5 +/- 11.9 years; range, 19 to 55). Patients were referred to our clinic because of limited mouth opening, joint sounds, or TMJ pain. Synovial fluid obtained by arthrocentesis for therapeutic reasons was analyzed by enzyme-linked immunosorbent assays for APO-1/Fas and cell death detection (NMP). We studied 12 left (71%) and 5 right (29%) joints with disc displacement without reduction. The chief complaint was pain on the affected side and limited mouth opening. Only 2 patients had a click in the affected joint, whereas 14 reported pain and 17 had the limited mouth opening. All patients experienced a significant (P < .01) increase in maximal mouth opening immediately after arthrocentesis. Mean sFas and NMP levels were 484.9 +/- 466.7 pg/mL (range, 17 to 1501) and 29.2 +/- 13.7 U/mL (range, 8 to 52.8) respectively.

Considering reports that increased sFas blocks apoptosis by inhibiting binding of FasL to Fas on the cell membrane, low level of sFas in our patients' synovial fluid (compared with amounts reported in joint inflammation or degeneration) suggests vulnerability to apoptosis in patients with internal derangement.

To estimate the incidence of childhood uveitis not associated with juvenile idiopathic arthritis (JIA) in the United Kingdom. Children under 16 years who presented with a new diagnosis of uveitis from November 2014 to October 2015 were identified prospectively through the British and Scottish Ophthalmological Surveillance Unit reporting card system. Incident questionnaires were sent to reporting ophthalmologists at presentation and 12 months. From 1st November 2014 to 31st October 2015, 119 cases were reported. Thirty-nine cases were excluded. The estimated minimum annual incidence of non-JIA uveitis in children younger than 16 years is 0.66 per 100,000 (95% CI 0.52-0.82). Median age at presentation was 10 years. 73% had bilateral uveitis. Median (IQR) BCVA in the worse eye was 0.3 (IQR 0.1-0.66) logMAR. The location of uveitis was: anterior 36%, intermediate 24%, posterior 6.8% and panuveitis 30%. 70% of cases were idiopathic. Most children were started on topical corticosteroids at presentation (86%, n = 51). At presentation, 31% (n = 19) were on started on systemic corticosteroids. At 1 year only 13% (n = 7) remained on corticosteroids, with the majority transitioned to steroid-sparing agents: methotrexate (30.8%, n = 16), mycophenolate (5.8%) and anti-TNF agents 5 (9.6%). At 1 year, 46% had ongoing intraocular inflammation despite treatment. The most common ocular adverse event was raised intraocular pressure (13.5%, n = 7).

Our study provides the first national population-based data of non-JIA childhood uveitis. Most children remain on treatment at 1 year, but visual acuity improves and none were eligible for sight-impairment registration.

To investigate the potential role of interleukin (IL) 27 in rheumatoid arthritis (RA) by examining the expression of IL27 in the articular joints of patients with RA and the effect of recombinant IL27 in vivo in a murine model of collagen-induced arthritis (CIA). Synovial membranes from patients with RA were examined for the presence of IL27 by immunohistochemistry and by western blot. Mice developing CIA were treated with IL27 and the ensuing disease progression and immunological profile determined. The effect of IL27 on T-cell response in vitro was also ascertained. IL27 was clearly detected in the RA synovial membranes. Short-term administration of IL27 at the onset of the disease significantly attenuated disease severity compared with untreated controls. Histological examination showed that while untreated mice developed severe cellular infiltration in the joints, synovial hyperplasia and joint erosion, this pathology was profoundly reduced in IL27-treated animals. Treatment of mice with IL27 also decreased the amounts of serum IL6 and collagen-specific IgG2a. Spleen and lymph node cells from the IL27-treated mice produced significantly less interferon gamma and IL17 than cells from the control mice when cultured with collagen in vitro.

These results demonstrate that IL27 may be a potential therapeutic agent against RA at the onset of the disease.

To study the time trends in sociodemographic and clinical characteristics of patients undergoing primary total knee arthroplasty (TKA). We used the Mayo Clinic Total Joint Registry to examine the time trends in patient demographics (body mass index [BMI] and age), underlying diagnosis, medical (Deyo-Charlson Index) and psychological comorbidity (anxiety and depression), and examination findings of primary TKA patients from 1993-2005. We used the chi-square test and analysis of variance. In total, 7,229 patients constituted the primary TKA cohort; 55% were women. The mean age decreased by 1.3 years (69.3 to 68.0 years), mean BMI increased by 1.7 kg/m(2) (30.1 to 31.8 kg/m(2) ), and mean Deyo-Charlson Index increased by 36% (1.1 to 1.5) over the 13-year study period (P ≤ 0.001 for all). Compared with 1993-1995, significantly more patients (by 2-3 times) in 2002-2005 had a BMI ≥40 kg/m(2) (4.8% versus 10.6%), age <50 years (2.9% versus 5.2%), Deyo-Charlson Index of ≥3 (12% versus 22.3%), depression (4.1% versus 14.8%), and anxiety (4.1% versus 8.9%), and significantly fewer patients had an underlying diagnosis of rheumatoid/inflammatory arthritis (6.4% versus 1.5%; P < 0.001 for all). Compared with 1993-1995, significant reductions were noted in 2002-2005 for the physical examination findings of anteroposterior knee instability, mediolateral knee instability, moderate to severe knee synovitis, severe limp, fair or poor muscle strength, and absent peripheral pulses (P ≤ 0.001 for all).

In this large US total joint registry study, we found significant time trends in patient characteristics, diagnosis, comorbidity, and knee/extremity examination findings in primary TKA patients over 13 years. These secular trends should be taken into account when comparing outcomes over time and in policy-making decisions.

Articular cartilage is well studied in osteoarthritis (OA). However, the role of supporting structures, such as the acetabular labrum, a sealing structure surrounding the hip joint, has been investigated much less. We recently showed that fibrochondrocytic labrum cells are metabolically active. This study was undertaken to investigate hip OA–associated changes in human acetabular labrum cells. Microarray analysis was performed to compare OA labrum cells to healthy labrum cells cultured in a 3-dimensional alginate bead system. Data were analyzed by cluster analysis using gene set enrichment analysis software and by gene list analysis using PANTHER gene family tools. Selected candidates were validated by quantitative polymerase chain reaction analysis on labrum and cartilage samples and by immunohistochemistry. The functional impacts of the genes identified were investigated by in vitro stimulation experiments in labrum cells. Pathway analysis revealed increased cytokine and chemokine signaling in OA labrum cells, whereas reduced extracellular matrix interactions and transforming growth factor β signaling were observed. Several genes were significantly differentially expressed in OA compared to healthy labrum. We specifically focused on 3 small leucine-rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage. SLRPs were strongly down-regulated in OA labrum but up-regulated in OA articular chondrocytes. Moreover, in vitro stimulation with osteomodulin increased aggrecan expression in OA labrum cells.

OA labrum fibrochondrocytes have several features similar to OA chondrocytes. However, SLRP expression seems to be differentially influenced by degeneration in OA labrum compared to cartilage, suggesting a specific role for this supporting structure in OA. The functional impact of SLRPs on labrum cells makes them interesting targets for further studies in hip OA.

The RAMRIS [Outcome Measures in Rheumatology rheumatoid arthritis (RA) magnetic resonance imaging (MRI) Scoring system] is used in clinical RA trials. We have investigated methods to combine the RAMRIS features into valid and responsive scores for inflammation and joint damage. We used data from 3 large randomized early RA trials to assess 5 methods to develop a combined score for inflammation based on RAMRIS bone marrow edema, synovitis, and tenosynovitis scores, and a combined joint damage score based on erosions and joint space narrowing. Methods included unweighted summation, normalized summation, and 3 different variants of weighted summation of the RAMRIS features. We used a derivation cohort to calculate summation weights to maximize the responsiveness of the combined score. Construct validity of the combined scores was examined by assessing correlations to imaging, clinical, and biochemical measures. Responsiveness was tested by calculating the standardized response mean (SRM) and the relative efficiency of each score in a validation cohort. Patient characteristics, as well as baseline and followup RAMRIS scores, were comparable between cohorts. All combined scores were significantly correlated to other imaging, clinical, and biochemical measures. Inflammation scores combined by normalized and weighted summation had significantly higher responsiveness in comparison to unweighted summation, with SRM (95% CI) for unweighted summation 0.62 (0.51-0.73), normalized summation 0.73 (0.63-0.83), and weighted summation 0.74 (0.64-0.84). For the damage score, there was a trend toward higher responsiveness for weighted summation.

Combined MRI scores calculated by normalized or weighted summation of individual MRI pathologies were valid and responsive.

To compare the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) with topical capsaicin for pain relief in osteoarthritis (OA). A systematic literature search was conducted for randomised controlled trials (RCTs) examining any topical NSAID or capsaicin in OA. Pain relief at or nearest to 4 weeks was pooled using a random-effects network meta-analysis (NMA) in a Frequentist and Bayesian setting. Analysis was conducted for all trials and for trials using drugs listed as licensed for OA in the British National Formulary (BNF). The trial network comprised 28 RCTs (7372 participants), of which 17 RCTs (3174 participants) were included in the as licensed analyses. No RCTs directly compared topical NSAIDs with capsaicin. Placebo was the only common comparator for topical NSAIDs and capsaicin. Frequentist and Bayesian effect size (ES) estimates were in agreement. Topical NSAIDs were statistically superior to placebo overall (ES 0.30, 95% confidence interval [CI] 0.19 to 0.41) and as licensed (ES 0.32, 95% CI 0.24 to 0.39). However, capsaicin was only statistically superior to placebo when used at licensed doses (ES 0.41, 95% CI 0.17 to 0.64). No significant differences were observed in pain relief between topical NSAIDs and capsaicin (overall: ES 0.04, 95% CI -0.26 to 0.33; as licensed: ES-0.09, 95% CI -0.34 to 0.16).

Current evidence indicates that topical NSAIDs and capsaicin in licensed doses may be equally effective for pain relief in OA. Whether the equivalence varies between individuals remains unknown.

To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA). Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20). Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1).

Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.

To test the hypothesis that the interaction between low back pain (LBP) and knee pain intensity contributes to the disability level of individuals with knee osteoarthritis (OA). Community-dwelling participants with knee OA (Kellgren/Lawrence [K/L] grade ≥1) were enrolled. LBP and its severity were identified using questionnaires. Knee pain severity and disability level were evaluated using the Japanese Knee Osteoarthritis Measure (JKOM) subscale. Multiple linear regression analyses were performed to examine the effect of the LBP-knee pain interaction, an independent variable, on disability, a dependent variable. A total of 260 participants (age, 48-88 years; 77.7% women) were included. Of them, 151 (58.1%) had LBP. The LBP-knee pain interaction was significantly associated with disability after the adjustment for covariates. A post-hoc subgroup analysis revealed that the relationship between knee pain intensity and disability level was higher in individuals with LBP (beta: 0.621 points; 95% confidence interval [CI]: 0.511 to 0.731 points) than in those without LBP (beta: 0.402 points; 95% CI: 0.316 to 0.487 points).

LBP interacts with knee pain intensity and contributes to disability level in individuals with knee OA. Coexisting LBP and knee pain had a stronger impact on disability level than LBP or knee pain alone. These findings highlight the potential deteriorative effects of the LBP-knee interaction on disability. Maximal treatment effects for disability might be achieved when LBP and knee pain are targeted simultaneously, rather than separately.

Electrocardiogram (ECG) abnormalities are predictive of subsequent cardiovascular events. Cardiac involvement is common in systemic lupus erythematosus (SLE). We aimed to determine the prevalence of ECG abnormalities in SLE patients and to examine the factors associated with ECG abnormalities with machine learning approaches. Consecutive SLE patients' records were retrieved from the database of the hospital for the cross-sectional study. Abnormal ECGs with clinical significance were grouped into tachyarrhythmias, atrioventricular block, non-specific ST-segment changes, T-wave abnormalities, ventricular hypertrophy, axis deviation, bundle branch block, and QT interval prolongation. Associated factors of the most common ECG abnormalities were assessed by comparing logistic regression and four other machine learning approaches. Two hundred ninety-nine patients were enrolled. One hundred twenty-eight out of them were clinically significant abnormalities. T-wave changes (52.3%), non-specific ST-T changes (26.6%), and prolonged QT interval (8.6%) were the most prevalent abnormalities among patients with abnormal ECG. Random forest models had the best performance in the discovery of associated factors. Age, disease duration, ANA titer, disease activity (SLEDAI-2K) were associated with non-specific ST-T changes, prolonged QT interval, and T-wave changes. Hypertension, positive anti-SSA, and secondary Sjögren syndrome were influential factors for non-specific ST-T changes, prolonged QT interval, and T-wave changes specifically.

ST-T changes/T-wave changes were the most common abnormalities seen in ECGs of SLE patients. Our finding suggests that age, longer disease duration, higher disease activity, hypertension, anti-SSA antibody positive, and secondary Sjögren syndrome are important, influential factors for these ECG abnormalities.

To examine cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis registry for the association between socioeconomic status (SES) with clinical and self-report health outcomes. We analyzed data on 937 African Americans who provided comprehensive sociodemographic data in addition to self-reported health outcomes. SES measures included educational attainment, homeownership, household income, and occupation. Outcomes included measures of disease activity, joint damage, autoantibody status, and self-reported measures. Multivariable linear, logistic, and zero-inflated Poisson regression models were used to estimate associations of each SES measure with rheumatoid arthritis (RA) outcomes, controlling for sex, age, disease duration, comorbid conditions, body mass index, smoking, methotrexate/leflunomide use, and biologic agent use. The mean age was 54 years, 86% were women, and the mean RA disease duration was 7.8 years. Approximately 24% had less than a high school degree, 56% had a nonprofessional occupation, 75% had a household income ≤$30,000, and 55% were nonhomeowners. In multivariable regression models, significantly increased associations of disease activity measures and self-reported health outcomes were observed with low household income (≤$30,000/year) and nonhomeownership. Education less than high school was primarily associated with self-reported health outcomes. Among participants with disease duration <2 years, associations of SES were confined to self-reported measures.

Our results indicate significant socioeconomic disparities in self-reported physical and mental health, clinical disease activity measures, and autoantibody status among African Americans with RA not explained by differences in demographics, medication use, and health behaviors.

To examine medication adherence and healthcare costs for combination prescription initiators (duloxetine/milnacipran/venlafaxine with pregabalin) vs. monotherapy initiators (duloxetine, milnacipran, venlafaxine, and pregabalin) among patients with fibromyalgia syndrome (FMS). Our retrospective cohort study used claims data for the South Carolina Blue Cross Blue Shield State Health Plan (SHP). Patients with FMS ≥ 18 years of age, with prescription initiation from July 1, 2007, through June 30, 2010, and SHP enrollment for 12 months pre- and post-index periods were included (combination: n = 100; pregabalin: n = 665; duloxetine: n = 713; milnacipran: n = 131; venlafaxine: n = 272). Medication adherence measures included high adherence (medication possession ratio ≥ 80%) and total supply days. Healthcare costs comprised direct medical expenditures. Propensity score methods of inverse probability of treatment weights were used to control for selection bias due to differing pre-index characteristics. Odds ratios for high adherence were significantly increased (P < 0.05) among the combination cohort vs. the venlafaxine (2.15), duloxetine (1.39), and pregabalin (2.20) cohorts. Rate ratios for total supply days were significantly higher (P < 0.05) for combination vs. venlafaxine (1.23), duloxetine (1.08), and pregabalin (1.32) cohorts. Expenditures for total health care were significantly higher (P < 0.05) for combination vs. duloxetine ($26,291 vs. $17,190), milnacipran ($33,638 vs. $22,886), and venlafaxine ($26,586 vs. $16,857) cohorts.

Medication adherence was considerably better for combination prescription initiators; however, expenditures for total health care were higher. Still, our findings suggest important clinical benefits with the use of combination prescription therapy, and prospective studies of medication adherence are warranted to examine causal relationships with outcomes not captured by healthcare claims databases.

To compare the outcome of 145 women who underwent conventional total knee arthroplasty (TKA) with 77 women who underwent gender-specific TKA. Records of 222 women who underwent primary TKA using a conventional (n=145) or gender-specific (n=77) size E or F prosthesis for end-stage osteoarthritis were reviewed. The gender-specific prosthesis has a narrower mediolateral dimension. Patients were assessed for flexion, Oxford Knee Score, Knee Society function and knee scores, and Short Form-36 Health Survey preoperatively and postoperatively (at 6 months and 2 years). The 2 groups were comparable in terms of age (67.8 vs. 68.1 years, p=0.789), body mass index (28.6 vs. 27.8 kg/m(2), p=0.189), and preoperative scores. 12 women with conventional TKA and 4 women with gender-specific TKA were lost to followup. Compared with women with conventional TKA, women with gender-specific TKA had better flexion at 6 months (116° vs. 121.9°, p=0.007) and 2 years (118.7° vs. 124.6°, p=0.006), better bodily pain score at 2 years (65.1 vs. 72.4, p=0.049), and greater improvement in bodily pain score from baseline to 2 years (30 vs. 38.5, p=0.034).

Gender-specific TKA enables better knee flexion and less bodily pain in women who have a high propensity to develop mediolateral overhang of the femoral component.

To characterize laser evoked potentials (LEP), pain psychophysics and local tissue response in fibromyalgia patients. LEP were recorded in 14 women with fibromyalgia in response to bilateral stimulation of tender and control points in upper limbs by 4 blocks of 20 stimuli at each point. Subsequently, heat pain thresholds were measured and supra-threshold magnitude estimations of heat pain stimuli were obtained on a visual analogue scale. Finally, the extent of the local tissue response induced by the previous stimuli was evaluated. Laser stimuli elicited two long latency waves: A late wave (mean latency 368.9+/-66.9 ms) in most patients (13/14) from stimuli at all points, and an ultra-late wave (mean latency 917.3+/-91.8 ms) in 78.5% of the patients at the control points and in 71.4% at the tender points. Amplitude of ultra-late waves was higher at the tender points (20.67+/-11.1 microV) than at the control points (10.47+/-4.1 microV) (P=0.016). Pain thresholds were lower in the tender (41.2+/-2.7 degrees C) than the control points (43.9+/-3.2 degrees C) (P=0.008). Local tissue response was significantly more intense at tender than control points (P=0.004).

Ultra-late laser evoked potentials can be recorded simultaneously with late potentials. Our findings are compatible with presence of peripheral C-fiber sensitization, mostly at tender points, probably combined with generalized central sensitization of pain pathways in fibromyalgia.

To determine whether a home-based pedometer-driven walking program with arthritis self-management education (Walk +) would increase physical activity, muscle strength, and functional performance in older adults with osteoarthritis (OA) of the knee as opposed to arthritis self-management education alone (EDU). A randomized two-by-three (group-by-time) design with participants assigned to Walk + (n = 17, mean age +/- standard deviation = 69.6 +/- 6.7) or EDU (n = 17, age = 70.8 +/- 4.7). Community located in the Baltimore-Washington area. Thirty-four community-dwelling adults, aged 60 and older with symptomatic knee OA and self-reported functional impairment. Both groups received 12 hours of the Arthritis Self-Management program over 12 weeks and were followed for an additional 12 weeks. In addition, the Walk + group received individualized instruction in the use of a pedometer, with the goal of increasing their step count by 30% of their baseline step count. The outcome measures were physical activity (daily step counts and total activity vector magnitude as measured by a pedometer and Tritrac-R3D accelerometer), quadriceps femoris strength (isometric peak torque), and functional performance tasks (100-foot walk-turn-walk, timed stair climb, timed chair rise, and pain status). Daily steps walked showed a significant group-by-time interaction (P =.04) after controlling for age. From baseline to completion of training, a 23% increase in daily steps occurred in the Walk + group and a 15% decrease in the EDU group. Although steps increased in the Walk + group, total activity vector magnitude was maintained, suggesting a more efficient gait. The Walk + group became quicker than the EDU group in the normal-pace walk-turn-walk (P =.04). An isometric strength gain of 21% postintervention was seen in the Walk + group, compared with a loss of 3.5% in the EDU group.

In older adults with symptomatic knee OA, Walk + appears to increase walking, with improvements in muscle strength and walking performance. The use of a home-based pedometer-driven program to increase physical activity, strength, and function in this population warrants further research.

The different radiographic procedures and methods for reading films and assessing the status and progression of hand osteoarthritis (OA) were reviewed. The methods that relate to each of the above procedures were assigned to categories upon which there was or was not general agreement. It was agreed that the radiographic method should use published standardized radiographic protocols; that X-ray features should be graded separately for determining the extent of the disease and that changes in osteophyte size was the most sensitive indicator of progression. For epidemiological studies films should be read blind and randomly, but for assessing progression films should be read in pairs and in sequence. No agreement was obtained on the value of the lateral radiographic view of the hand nor on which radiographic atlas would be best for long-term longitudinal studies.

Further work was required to evaluate the role of MRI and scintigraphy in hand OA; radiographic atlases could be improved by incorporating diagrams to illustrate the change in grade for each feature; validation was required for methods of assessment in long-term trials.

To assess the prevalence and distribution patterns of multimorbidity among urban older adults in Burkina Faso. Cross-sectional study among community-dwelling elderly people aged ≥60 in Bobo-Dioulasso. We performed interviews, clinical examination and medical record review. Multimorbidity was defined as co-occurrence of at least two chronic diseases in one person whether as a coincidence or not. The overall prevalence of multimorbidity among older adults was 65%. Age ≥70 was associated with multimorbidity in multivariate analysis: adjusted OR = 1.65, 95% CI (1.01-2.68, P = 0.04). The most common chronic diseases were hypertension (82%) 95% CI (78; 86), malnutrition (39%) 95% CI (34; 44), visual impairments (28%) 95% CI (24; 33) and diabetes mellitus (27%) 95% CI (22; 31). Those aged ≥70 had significantly more malnutrition (50% vs. 31%, P = 0.0003) and osteoarthritis (8% vs. 3%, P = 0.01) than those aged 60-69.

The high prevalence of multimorbidity requires a reorganization of healthcare systems in sub-Saharan Africa, especially in Burkina Faso. Interventions and care guidelines usually focused on individual diseases should be improved to better reflect this reality.

The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to adalimumab were assessed in rheumatoid arthritis (RA) patients with inadequate responses to methotrexate (MTX). We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients with inadequate responses to MTX. Four RCTs comprising 5451 patients met the inclusion criteria. Baricitinib 4 mg + MTX and upadacitinib 15 mg + MTX showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than adalimumab 40 mg + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4 mg + MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15 mg + MTX, tofacitinib 5 mg + MTX, filgotinib 200 mg + MTX, filgotinib 100 mg + MTX, adalimumab 40 mg + MTX, and placebo + MTX. Upadacitinib 15 mg + MTX and baricitinib 4 mg + MTX showed significantly higher ACR50 and ACR70 response rates than adalimumab 40 mg + MTX. For herpes zoster infection, the ranking probability based on SUCRA indicated that placebo + MTX was likely to be the safest treatment, followed by filgotinib 200 mg + MTX, filgotinib 100 mg + MTX, adalimumab 40 mg + MTX, tofacitinib 5 mg + MTX, upadacitinib 15 mg + MTX, and baricitinib 4 mg + MTX. No statistically significant differences were found between the intervention groups in terms of safety. ZIEL DER ARBEIT: Bei Patienten mit rheumatoider Arthritis (RA) und inadäquatem Ansprechen auf Methotrexat (Mtx) wurde die relative Wirksamkeit und Verträglichkeit von Tofacitinib, Baricitinib, Upadacitinib und Filgotinib im Vergleich zu Adalimumab untersucht. Die Autoren führten eine Bayes-Netzwerk-Metaanalyse durch, um direkte und indirekte Evidenz aus randomisierten kontrollierten Studien (RCT) zu kombinieren und so die Wirksamkeit und Sicherheit von Tofacitinib, Baricitinib, Upadacitinib, Filgotinib und Adalimumab bei RA-Patienten mit inadäquatem Ansprechen auf MTX zu untersuchen. Die Einschlusskriterien wurden von 4 RCT mit 5451 Patienten erfüllt. Unter Baricitinib 4 mg + MTX und Upadacitinib 15 mg + MTX zeigte sich eine signifikant höhere ACR20-Ansprechrate (gemäß American College of Rheumatology) als unter Adalimumab 40 mg + MTX. Wie die Rangfolgewahrscheinlichkeit, basierend auf der Oberfläche unter der kumulativen Rangfolgenkurve (SUCRA, „surface under the cumulative ranking curve“), ergab, stellte Baricitinib 4 mg + MTX mit größter Wahrscheinlichkeit die beste Behandlung zur Erzielung der ACR20-Ansprechrate dar, es folgten Upadacitinib 15 mg + MTX, Tofacitinib 5 mg + MTX, Filgotinib 200 mg + MTX, Filgotinib 100 mg + MTX, Adalimumab 40 mg + MTX und Placebo + MTX. Upadacitinib 15 mg + MTX und Baricitinib 4 mg + MTX wiesen signifikant höhere ACR50- und ACR70-Ansprechraten auf als Adalimumab 40 mg + MTX. In Bezug auf eine Herpes-zoster-Infektion ergab die auf SUCRA basierende Rangfolgewahrscheinlichkeit, dass Placebo + MTX am ehesten die sicherste Therapie darstellte, dem folgten Filgotinib 200 mg + MTX, Filgotinib 100 mg + MTX, Adalimumab 40 mg + MTX, Tofacitinib 5 mg + MTX, Upadacitinib 15 mg + MTX und Baricitinib 4 mg + MTX. Es wurden keine statistisch signifikanten Unterschiede zwischen den Interventionsgruppen hinsichtlich der Sicherheit festgestellt. Bei RA-Patienten mit inadäquatem Ansprechen auf MTX ergaben Baricitinib 4 mg + MTX und Upadacitinib 15 mg + MTX die höchsten ACR-Ansprechraten, was ein Hinweis auf einen Unterschied in der Wirksamkeit der verschiedenen JAK-Inhibitoren sein könnte.

In RA patients with an inadequate response to MTX, baricitinib 4 mg + MTX and upadacitinib 15 mg + MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.

There is a paucity of community-based data regarding the prevalence and impact of gout flares as these may often be self-managed. The aim of this study was to determine the prevalence of self-reported gout and gout flares, the use of urate-lowering therapy (ULT), and the association of gout flares with health-related quality of life (HRQoL) in a large community sample. Covariate associations with flare frequency and allopurinol use were also examined. The South Australian Health Omnibus Survey is an annual, face-to-face population-based survey. Data collected in the 2017 survey included self-reported medically diagnosed gout, allopurinol use (first-line ULT in Australia), and gout attacks (flares) in the last 12 months, in addition to sociodemographic variables and health-related quality of life (HRQoL, SF-12). Data were weighted to the Australian Bureau of Statistics 2016 census data to reflect the South Australian population. Participants 25 years and over (n = 2778) were included in the analysis. The prevalence of gout was 6.5% (95%CI 5.5, 7.5). Amongst participants with gout, 37.1% (95%CI 29.6, 45.3) reported currently using allopurinol, while 23.2% (95%CI 16.9, 21.0) reported prior use (38% discontinuation rate). Frequent flares (≥ 2 in the last year) were reported by 25% of participants with gout and were more likely with younger age, higher body mass index, and current allopurinol use (p < 0.05). The frequency of gout flares was associated with a lower physical HRQoL (p = 0.012). Current allopurinol use was reported by 51% of participants with frequent gout flares.

Flares were frequently reported by people with gout in the community. Gout flares were associated with reduced physical HRQoL. Almost one half of people with frequent gout flares were not receiving allopurinol, and current allopurinol use was associated with frequent gout flares, suggesting undertreated disease and suboptimal use of ULT. Determining covariate associations with flares and ineffective allopurinol use may identify means of improving treatment and reducing flares.

To evaluate coping strategies of Asian RA patients and their associations with health-related quality of life (HRQoL). A cross-sectional sample of patients with established RA was evaluated using measures of coping (Coping in Rheumatoid Arthritis Questionnaire [C-RAQ]; appraisal of coping effectiveness and helplessness), HRQoL (Mental and Physical Components [MCS/PCS] of the Short Form 12v2; Rheumatoid Arthritis Impact of Disease score [RAID]) and clinical/laboratory assessments. Principal component analysis was conducted to identify coping strategies. Multiple linear regression analyses were performed to evaluate the associations between coping strategies and HRQoL outcomes. The study sample comprised 101 patients, 81% female, 72.3% Chinese, mean age 54.2 ± 12.6 years. Five coping strategies were identified: Active problem solving (E = 5.36), Distancing (E = 2.30), Concealment (E = 1.89), Cognitive reframing (E = 1.55) and Emotional expression (E = 1.26). Concealment was consistently associated with PCS (r

Concealment and Emotional expression are associated with lower disease-specific HRQoL and physical HRQoL respectively, with the former coping strategy likely to be culture-specific. Interventions should tailor psychosocial support needs to address not only coping strategies, but patients' perception of their coping.

To determine the influence of low-dose prednisolone on atherosclerosis, endothelial function, and risk factors for atherosclerosis in patients with early rheumatoid arthritis (RA). At start of the first disease modifying antirheumatic drug, 67 patients with early, active RA were randomized to either 7.5 mg prednisolone daily (n = 34) or no prednisolone (n = 33). In the prednisolone group, 21 were treated for 2 years and 13 continuously. After a mean of 5 years intima-media thickness (IMT) and calculated intima-media area (cIMa) of the carotid arteries were determined by B-mode ultrasound. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery. IMT [median (interquartile range) 0.675 mm (0.58-0.82) vs 0.673 mm (0.0.62-0.80)], cIMa [13.7 mm2 (11.45-20.37) vs 14.1 mm2 (12.34-17.38)], prevalence of atherosclerotic plaques (82.3% vs 81.9%), and endothelial function [FMD% (mean +/- SD) 3.88% +/- 2.8 vs 3.74% +/- 2.9] did not differ between patients treated with and those not treated with prednisolone. There were no differences in lumen diameter of carotid arteries, or levels of lipoproteins, glucose, and blood pressure. Patients treated for at least 4 years (and currently treated) with prednisolone had a trend to higher systolic blood pressure (157 +/- 29 mm Hg) compared with untreated patients (141 +/- 28 mm Hg; p = 0.06) and had higher cholesterol levels (5.6 mmol/L +/- 1.39 vs 4.9 +/- 28; p = 0.03). In the whole cohort, age and HDL were independently associated with IMT; age, HDL, and blood pressure with cIMa; and age and serum creatinine with presence of atherosclerotic plaques.

Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA. However, total cholesterol was higher in patients treated with prednisolone.

Despite an increasing awareness of the importance of fidelity of delivery within complex behaviour change interventions, it is often poorly assessed. This mixed methods study aimed to establish the fidelity of delivery of a complex self-management intervention and explore the reasons for these findings using a convergent/triangulation design. Feasibility trial of the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention (ISRCTN49875385), delivered in primary care physiotherapy. 60 SOLAS sessions were delivered across seven sites by nine physiotherapists. Fidelity of delivery of prespecified intervention components was evaluated using (1) audio-recordings (n=60), direct observations (n=24) and self-report checklists (n=60) and (2) individual interviews with physiotherapists (n=9). Quantitatively, fidelity scores were calculated using percentage means and SD of components delivered. Associations between fidelity scores and physiotherapist variables were analysed using Spearman's correlations. Interviews were analysed using thematic analysis to explore potential reasons for fidelity scores. Integration of quantitative and qualitative data occurred at an interpretation level using triangulation. Quantitatively, fidelity scores were high for all assessment methods; with self-report (92.7%) consistently higher than direct observations (82.7%) or audio-recordings (81.7%). There was significant variation between physiotherapists' individual scores (69.8% - 100%). Both qualitative and quantitative data (from physiotherapist variables) found that physiotherapists' knowledge (Spearman's association at p=0.003) and previous experience (p=0.008) were factors that influenced their fidelity. The qualitative data also postulated participant-level (eg, individual needs) and programme-level factors (eg, resources) as additional elements that influenced fidelity. ISRCTN49875385; Pre-results.

The intervention was delivered with high fidelity. This study contributes to the limited evidence regarding fidelity assessment methods within complex behaviour change interventions. The findings suggest a combination of quantitative methods is suitable for the assessment of fidelity of delivery. A mixed methods approach provided a more insightful understanding of fidelity and its influencing factors.

To report a case of retroperitoneal fibrosis (RPF) in a patient with ankylosing spondylitis (AS) and to review the medical literature for similar cases to detect possible links between the 2 diseases. The presentation, clinical course, diagnostic work-up, and treatment of our patient are described, and the English and French medical literature from 1960 to 2000 is reviewed using a MEDLINE search for cases with coexisting RPF and spondyloarthritis. Our patient with AS had RPF, which mimicked rectal cancer with retroperitoneal and vertebral metastases. Special attention is paid to the unusual clinical presentation, the multistep diagnostic process, and the therapeutic strategy which was both radiologically and histologically successful. Literature review revealed 18 cases of concomitant RPF and spondyloarthritis, mainly AS. Patients were more frequently male (M/F, 3/1) and developed spondyloarthritis several years before RPF.

RPF may result from a local immune response to products of aortic atheromatous plaques, with subsequent periaortic deposition of fibrous tissue. However, the clinical features and the frequent association with other fibrosing disorders suggest that RPF is a systemic inflammatory condition. The role of AS-associated aortitis in the development of RPF warrants consideration.

Background/Study Context: Theory of Mind (ToM) reflects the ability to reason about mental states in order to understand and predict behavior. Research has identified links between increased pulse pressure, a measure of vascular health, and reduced cognitive ToM in older adults. However, the relationships between other vascular and nonvascular conditions and reduced ToM are unknown. We examined (1) illnesses as predictors of cognitive and affective ToM and (2) neurocognitive mediators of illness burden and ToM. We used hierarchical regression and mediation to investigate the effects of vascular illness burden (hypertension, Type 2 diabetes, high cholesterol, and high pulse pressure) and nonvascular illness burden (osteoporosis, osteoarthritis, rheumatoid arthritis, and thyroid dysfunction) on cognitive and affective ToM in N = 86 community-dwelling older adults (59 females; 27 males, M age = 71.74 years). Vascular illness burden emerged as a significant predictor of older adults' cognitive ToM (R

Our findings highlight the specific importance of considering vascular health as a risk factor for declines in ToM in later life. Further elucidation of the associations between health, neurocognition, and ToM will be valuable in developing effective interventions for older adults given the high prevalence of vascular illness in later life.

To identify an immunologic basis for the male sex bias in ankylosing spondylitis (AS). Cohorts of male and female patients with AS and age- and sex-matched healthy control subjects were selected, and the levels of serum cytokines (interferon-γ [IFNγ], tumor necrosis factor α, interleukin-17A [IL-17A], and IL-6) were examined by enzyme-linked immunosorbent assay, the frequencies of Th1 and Th17 cells were assessed by flow cytometry, and whole blood gene expression was analyzed using both microarray and NanoString approaches. The frequency of IL-17A and Th17 cells, both of which are key factors in the inflammatory Th17 axis, was elevated in male patients with AS but not in female patients with AS. In contrast, AS-associated alterations in the Th1 axis, such as the frequency of IFNγ and Th1 cells in serum, were independent of a patient's sex. Results of microarray analysis supported an altered Th17 axis in male patients, with a specific increase in IL17RA. In addition, male and female patients with AS displayed shared gene expression patterns, while male patients with AS had additional alterations in gene expression that were not seen in female patients with AS. The differential sex-related immune profiles were independent of HLA-B27 status, clinical disease activity (as measured by the Bath Ankylosing Spondylitis Disease Activity Index), or treatment (with nonsteroidal antiinflammatory drugs or biologic agents), implicating intrinsic sexual dimorphism in AS.

The results of this study demonstrate distinct sexual dimorphism in the activation status of the immune system in patients with AS, particularly in the Th17 axis. This dimorphism could underlie sex-related differences in the clinical features of AS and could provide a rationale for sex-specific treatment of AS.

To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD). Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated. Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive.

Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.

To study efficiency in rheumatoid arthritis (RA) of local radiotherapy methods: radionuclide synovectomy (RS), x-ray therapy (XRT) and local gamma-therapy (LGT) proposed by the authors. 175 patients with RA received local radiotherapy on the knee joints. The patients were divided into three groups comparable by age, sex and disease characteristics receiving RS, XRT and LGT. The patients were for the most part women over 45 years with RA (duration 5 years and longer), polyarthritis, the disease x-ray stage II, moderate activity. RS was most effective of the above methods, especially in long-term period. It produces antiinflammatory and immunosuppressive action. The new method, LGT, was effective in more than half the patients. It is antiinflammatory and immunosuppressive. XRT was the less effective of the three methods as it has only nonspecific antiinflammatory action.

Local radiotherapy enhances efficacy of RA treatment. RS and LGT produce immunosuppressive and antiinflammatory actions while XRT has only antiinflammatory action.

To report on the process and criteria for selecting acquisition protocols to include in the osteoarthritis initiative (OAI) magnetic resonance imaging (MRI) study protocol for the knee. Candidate knee MR acquisition protocols identified from the literature were first optimized at 3Tesla (T). Twelve knees from 10 subjects were scanned one time with each of 16 acquisitions considered most likely to achieve the study goals and having the best optimization results. The resultant images and multi-planar reformats were evaluated for artifacts and structural discrimination of articular cartilage at the cartilage-fluid, cartilage-fat, cartilage-capsule, cartilage-meniscus and cartilage-cartilage interfaces. The five acquisitions comprising the final OAI MRI protocol were assembled based on the study goals for the imaging protocol, the image evaluation results and the need to image both knees within a 75 min time slot, including positioning. For quantitative cartilage morphometry, fat-suppressed, 3D dual-echo in steady state (DESS) acquisitions appear to provide the best universal cartilage discrimination.

The OAI knee MRI protocol provides imaging data on multiple articular structures and features relevant to knee OA that will support a broad range of existing and anticipated measurement methods while balancing requirements for high image quality and consistency against the practical considerations of a large multi-center cohort study. Strengths of the final knee MRI protocol include cartilage quantification capabilities in three planes due to multi-planar reconstruction of a thin slice, high spatial resolution 3D DESS acquisition and the multiple, non-fat-suppressed image contrasts measured during the T2 relaxation time mapping acquisition.

The hyaluronan receptor CD44 provides chondrocytes with a mechanism for sensing and responding to changes in the extracellular matrix. The purpose of this study was to document the fragmentation and loss of CD44 and to determine the likely mechanisms involved. A polyclonal anti-CD44 cytotail antibody was generated to detect CD44 fragmentation by Western blot analysis. Chondrocytes were isolated from human or bovine articular cartilage. Primary articular chondrocytes were treated with interleukin-1beta (IL-1beta), hyaluronan oligosaccharides, or phorbol myristate acetate or were passaged and subcultured in monolayer to induce dedifferentiation. Conditions that altered the capacity of CD44 to transit into lipid rafts, or pharmacologic inhibitors of metalloproteinase or gamma-secretase activity were used to define the mechanism of fragmentation of CD44. Chondrocytes from osteoarthritic cartilage exhibited CD44 fragmentation as low molecular mass bands, corresponding to the CD44-EXT and CD44-ICD bands. Following dedifferentiation of chondrocytes or treatment of primary chondrocytes with hyaluronan oligosaccharides, IL-1beta, or phorbol myristate acetate, CD44 fragmentation was enhanced. Subsequent culture of the dedifferentiated chondrocytes in 3-dimensional alginate beads rescued the chondrocyte phenotype and diminished the fragmentation of CD44. Fragmentation of CD44 in chondrocytes was blocked in the presence of the metalloproteinase inhibitor GM6001 and the gamma-secretase inhibitor DAPT.

CD44 fragmentation, consistent with a signature pattern reported for sequential metalloproteinase/gamma-secretase cleavage of CD44, is a common metabolic feature of chondrocytes that have undergone dedifferentiation in vitro and osteoarthritic chondrocytes. Transit of CD44 into lipid rafts may be required for its fragmentation.

Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain. To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy. Retrospective cohort study. Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015. Adults with RA receiving a stable DMARD regimen for more than 6 months. Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models. 247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all Potential for residual confounding and misclassification of glucocorticoid dose. National Institute of Arthritis and Musculoskeletal and Skin Diseases.

In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk.

Juvenile idiopathic arthritis (JIA) may affect natural growth. The aim of the study has been to assess auxological parameters of JIA patients, receiving different anti-rheumatic treatments. This is a retrospective study; JIA patients were recruited from the Rheumatology Unit of Anna Meyer Children's University Hospital of Florence, Italy from March 1996 to June 2016. Two hundred and thirty-two patients were included in the current study. The best result in terms of catch-up growth occurred in systemic JIA patients. All JIA categories showed standard deviation score (SDS) gain for height except those belonging to enthesitis related arthritis category. Patients treated with disease-modifying anti-rheumatic drugs (DMARDs) only maintained constant growth during study follow-up. Patients who needed biologic therapy showed an impaired growth during pre-DMARDs treatment and an increased growth velocity mostly during biologic therapy. Body mass index (BMI) decreased in almost all JIA categories. The best BMI reduction was observed among patient receiving biologic drugs.

Patients with JIA followed in our centre had a gain of height SDS and lost BMI SDS in 5 years of follow-up. We observed a stable and good pattern of growth in patients treated with DMARDs and an increased growth velocity during biologic treatment.

Bone loss, osteoarthritis (OA) and age-related changes in reproduction are some of the most apparent and troubling results of advancing age in the human population. The significance of these changes underscores the need for developing appropriate animal models to study aging of bone and the reproductive system. This review surveys the literature regarding the current state of nonhuman primates (NHP) as models for skeletal and reproductive aging in humans. Several species of NHP exhibit age-related bone loss as well as changes in the mineral content and architecture of bone that are similar to those reported in humans. In addition, since aged females of some species of NHP exhibit cessation of menses and serum hormone profiles consistent with those described in peri- and premenopausal women, they provide useful models of postmenopausal bone loss. Sensitivity to surgical estrogen depletion and hormone replacement has also been demonstrated in female NHP. Spontaneous development of degenerative arthritis, analogous to humans in age at onset, joint involvement and histologic changes, suggest that NHP are suitable for the study of human OA. Many similarities exist between female NHPs and women in age-related changes in reproductive function including hormone concentrations, menstrual cycling, fertility and the development of endometriosis. Changes in male sexual behavior and fertility with age are also comparable in men and male NHP.

Genetic similarity, long lives and similar reproductive endocrinology suggest that NHPs are likely candidates as models of skeletal and reproductive aging in humans. Current data confirm that several species of NHP exhibit changes in bone and reproduction that are comparable to those known to occur in humans.

Quality of life (QoL) improvement is important to demonstrate in RA clinical trials, but can be abstract. More meaningful measures of QoL include medical expenditure and job loss, aspects that have marked importance for RA patients, physicians and society. We re-examined previous positive QoL findings for abatacept over placebo by converting existing QoL measures into estimated medical expenditure and estimated likelihood of job loss. Two double-blind, placebo-controlled, multicentre randomized clinical trials were undertaken: one for MTX failure (n = 652) and one for more severe anti-TNF failure patients (n = 391). Based on derived scores using previously published formulae, measures of monthly medical expenditure, current inability to work and job loss at 6 months, 1 yr and 2 yrs were analysed. Abatacept led to greater reduction in medical expenditure over time in MTX failure ($152 lower) and anti-TNF failure patients ($122 lower) compared with placebo at end-point. Likewise, significantly more reduction in likelihood for current and future job loss was achieved with abatacept compared with placebo, which has 25-64% greater likelihood.

QoL changes provided greater reduction in medical expenditure and likelihood of an inability to work. The strong effect sizes obtained for all significant analyses suggest that the results are clinically meaningful. Moreover, given the nature of the variables, results should also be meaningful for patients, physicians, employers and health care insurance entities. Limitations are discussed regarding using estimated outcomes rather than analysis of actual outcomes.

There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients.

Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.

Knee osteoarthritis (OA) is the most common cause of chronic disability amongst community-dwelling older adults. Yet, little is understood about the daily experience of knee OA. As clinicians we fail to understand a large group of individuals that we aim to help. We conducted an exploratory study that aimed to understand the experience of living with knee OA in older adults. We used a descriptive phenomenology, grounded in the phenomenology in practice tradition. We conducted nine interviews with participants with physician-diagnosed knee OA, of different ages, sexes, cultural backgrounds and self-perceptions. Ninety-minute interviews with each participant were audio-taped and transcribed verbatim. We used the vanKaam method of phenomenological analysis, modified by Moustakas, as the framework for data analysis. The following five themes on living with knee OA emerged: experiencing knee pain is central to daily living, experiencing mobility limitations devalues self-worth, sharing the experience, assessing our own health and managing chronic pain.

The implications of these findings highlight the profound impact knee OA has on daily living, which have been poorly documented in the past. Clinicians should consider that the consequences of living with knee OA are significant enough to influence a person's sense of self-worth.

To address the question of whether the human T cell leukemia virus type I (HTLV-I) gene is associated with the etiology of Sjögren's syndrome (SS). RNA expression of HTLV-I gag, pol, env, and tax genes in labial salivary glands (LSGs) from SS patients who were seronegative for antibodies to HTLV-I was examined using reverse transcription and polymerase chain reaction techniques. The HTLV-I tax gene, but not the HTLV-I gag, pol, or env genes, was detected in LSG samples from 4 of 14 patients (29%). The nucleotide sequences of the HTLV-I pXIV region in these 4 patients' LSGs showed 100% homology to the HTLV-I pXIV gene from the MT-2 cell line.

These findings suggest that products encoding sequences homologous to the HTLV-I pXIV gene in SS patients' LSGs might be candidates for self-antigen and/or lead to activation of autoreactive T lymphocytes through trans-acting transcriptional activation.

We compared the effectiveness of mechanical debridement (MD) and bipolar radiofrequency chondroplasty (RF) with regard to clinical outcome, rate of revision, and progression of knee osteoarthritis. Sixty patients with MRI-detected grade III cartilage lesions on the medial femoral condyle were considered for the study. For MD (group 1; n = 30), each lesion was debrided using a mechanical shaver. For RF (group 2; n = 30), each lesion was smoothed using a temperature-controlled RF probe set at 50 °C. The 10-year follow-up was available for 47 patients (78.3 %). Sixty per cent of group 1 (n = 18) underwent revision during the follow-up period. In contrast, the revision rate in group 2 was 23.3 % (n = 7; p = 0.061). The mean survival was 94.1 months (95 % CI 77.1-111.3) and 62.5 months (95 % CI 45.9-79.2) for group 2 and group 1, respectively. Patients who did not require revision (group 1, n = 9; group 2, n = 13) were assessed before surgery and 1, 4, and 10 years after surgery using the knee injury and osteoarthritis outcome score (KOOS). At follow-up, the KOOS was higher for group 2 than group 1. At the time of surgery, no patient showed any radiological signs of osteoarthritis. The width of the medial joint was 5.4 mm (95 % CI 4.3-6.5) and 5.6 mm (95 % CI 4.9-6.3) in the MD and RF groups, respectively (n.s.). During the follow-up period, the joint space width narrowed continuously in both groups (p < 0.001), but more rapidly in the group 1 (n.s). I.

Compared to conventional MD, 50° RF treatment appears to be a superior method based on short- and medium-term clinical outcomes and the progression of knee osteoarthritis. Clear predictors for the indications of different cartilage treatments and more randomized clinical trials are needed.

To evaluate a vasculitis centre based management strategy for eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA). A retrospective cohort study at a vasculitis referral centre was performed. All EGPA patients admitted from 1990 to 2009 were included. A structured interdisciplinary work-up for proof of diagnosis, Disease Extent Index and Birmingham Vasculitis Activity Score was performed. Immunosuppressive therapy was initiated and regularly adapted. Treatment targets were induction and maintenance of remission according to definitions given by the European League Against Rheumatism and the European Vasculitis Study Group. Outcomes were mortality, rate of remission, relapses, adverse events and prednisolone-dose. Out of 269 patients with suspected EGPA 150 fulfilled the inclusion criteria. Of those, 104 had more than one follow-up visit resulting in a mean follow up of 53±4.9 months. By using additional data sources the follow-up concerning survival was extended to 92±5 month. Severe organ manifestations occurred at heart (46%), kidney (18%) and lungs (10%). Cyclophosphamide was used in 107 patients (71%). The prednisolone-doses of all patients were within the targeted range (i.e. ≤7.5 mg) in 69% of the total follow-up time; the median dose at end of follow-up was 5mg/d. The 10-year survival rate was 89% resulting in mortality comparable to the general population (SMR 1.29). Only patients with cardiac failure associated with EGPA had an increased mortality (SMR 3.06).

Regular re-evaluation and target-orientated adaption of therapy may lead to normalization of life expectancy and attenuation of disease progression. Continued centre based interdisciplinary treatment should be standard of care.

The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc). In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema. Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10

The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management.

MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity. Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays. Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a.

Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis.

The study was undertaken to determine the value of standard radiographs in the early stages of osteoarthritis. Standard radiographs and arthro-MRI's from thirty hips operated on for early arthrosis (age 25-57 years) were independently analyzed by two orthopaedic surgeons and one radiologist blinded from the intra-operative findings. The radiographs were read on two occasions two months apart. The radiographic findings were then compared to the intra-operative findings. Intra-operatively, all cases had a labral lesion and, in all but three of the cases, there was a major acetabular cartilage lesion. Each investigator diagnosed all of the labral and/or cartilage lesions on the arthro-MRI. However, on average, the investigators judged 20% (10-35%) of the hips to be normal on the standard radiographs. The probability of detecting an abnormal hip joint was statistically significantly better with arthro-MRI in four of six readings (p < 0.05) and there was a trend in favor of the arthro-MRI in the other two readings (p < 0.1). Intra-observer agreement when using the Tönnis classification of arthrosis on standard radiographs was 0.26 (-0.1-0.62), 0.69 (0.42-0.96) and 0.83 (0.53-1) [kappa-statistic, (95% confidence interval)]. The interobserver agreement was 0.24 (-0.07-0.55).

Plain radiographs in the early stages of osteoarthrosis of the hip are neither reliable nor valid to diagnose the onset of disease. Therefore, in the case of a normal radiograph and clinical suspicion of arthrosis, a "normal" radiograph does not exclude the diagnosis and an artho-MRI should be obtained for further evaluation.

To validate the objective monitoring of ambulatory activity as an outcome measure for rheumatoid arthritis (RA). We have compared ambulatory activity to a range of currently favoured outcome measures, ranging from subjective opinions to X-ray damage, in a population of 93 RA sufferers. Correlations were stronger with measures of joint damage and disability, and less strong with measures of disease activity. Sensitivity to change was good. Three different interventions were compared for the quantity of the response, and the results agree with clinical experience, with steroid injection of the knee and use of non-steroidal anti-inflammatory drugs (NSAIDs) having a similar response and the provision of surgical shoes producing a more modest increase in ambulation.

The measurement of ambulatory activity has validity for RA assessment. It provides different but related data to the currently used measures. It is objective, relevant, quantifiable and of unlimited scale. It could be used to quantify interventions aimed at increasing ambulation, in carefully constructed studies.

To investigate whether patients with acute septic arthritis (SA) diagnosed by positive synovial fluid (SF) culture (Newman grade A) have different clinical and serological features from those with sterile SF in whom there is nonetheless a high suspicion of SA (Newman grades B and C). A prospective 12 month multicentre hospital based study of adult patients with SA recruited 47 patients with culture positive SA and 35 patients with clinically suspected SA but sterile SF. Patient demography, clinical and laboratory features at presentation were similar irrespective of the underlying diagnosis, SF culture, and the presence of prosthetic joints. Medical and surgical treatment and outcome were comparable in the two patient groups. Patients with both suspected and proven SA were more likely to be from the more socially deprived areas of our community (p<0.0001).

Patients in whom there is a high clinical suspicion of SA are comparable to those patients with SA with a positive SF culture and have similar morbidity and mortality on follow up. Therefore, if clinical suspicion of SA is high then it is correct to treat as SA in the absence of bacterial proof.

It has been suggested that anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. Mouse models of RA have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study was undertaken to investigate whether human anti-cyclic citrullinated peptide (anti-CCP) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used. We set up novel assays to analyze complement activation by anti-CCP antibodies, using cyclic citrullinated peptide-coated plates, specific buffers, and normal and complement-deficient sera as a source of complement. Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. The lectin pathway was not activated by anti-CCP antibodies. Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of C5a, took place.

Our findings indicate that anti-CCP antibodies activate the complement system in vitro via the classical and alternative pathways but not via the lectin pathway. These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in RA.

To compare the efficacy, safety, and tolerability of AZD3582 with that of rofecoxib, naproxen, and placebo in patients with osteoarthritis (OA) of the knee, and to define the dosage of AZD3582 (125 mg, 375 mg, and 750 mg twice a day) that is noninferior in efficacy to rofecoxib. A double-blind study of 672 patients with OA of the knee was conducted. Patients who experienced increased pain on withdrawal of analgesia were randomized to receive AZD3582 125 mg, 375 mg, or 750 mg twice a day; rofecoxib 25 mg once a day; naproxen 500 mg twice a day; or placebo for 6 weeks. Efficacy, tolerability, and safety were monitored throughout the study. The primary variable was the change in Western Ontario and McMaster Universities Osteoarthritis Index pain subscale from baseline to the mean of weeks 4 and 6, comparing AZD3582 with placebo for superiority and with rofecoxib for noninferiority using a predefined margin of 10 mm. For the primary variable, AZD3582 375 mg and 750 mg were superior to placebo (least squares mean difference [95% confidence interval] -12 mm [-18, -6], P < 0.001 and -13 mm [-19, -7], P < 0.001, respectively) and were noninferior to rofecoxib (-2 mm [-8, 4], P < 0.001 and -3 mm [-9, 3], P < 0.001, respectively). AZD3582 125 mg was not significantly different from placebo for the primary variable.

AZD3582 375 mg and 750 mg twice a day were superior to placebo and as effective as rofecoxib 25 mg/day in treating the signs and symptoms of OA of the knee. AZD3582 125 mg twice a day was not statistically different from placebo.

Assess the effects of belimumab treatment plus standard systemic lupus erythematosus (SLE) therapy on health-related quality of life (HRQOL) in patients with active, autoantibody-positive SLE. Patients received standard therapy plus placebo or belimumab 1 or 10 mg/kg in two multicentre, randomised controlled trials of 52 (BLISS-52; N=865) and 76 (BLISS-76; N=819) weeks' duration. Responders were evaluated by SLE Responder Index at week 52. Patient-reported outcome assessments included SF-36, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, and EQ-5D. Mean SF-36 Physical Component Summary (PCS) scores at week 24 was a major secondary endpoint. Baseline SF-36 scores were 1.5 SDs below age-/sex-matched US norms with similar improvement at week 24 across treatment groups. Mean changes from baseline in PCS scores were significantly (p<0.05) greater with belimumab 1 mg/kg (4.20) and 10 mg/kg (4.18) versus placebo (2.96) in BLISS-52, week 52. In BLISS-76, significantly (p<0.05) greater improvements were seen with belimumab 1 mg/kg in PCS (belimumab 1 mg/kg=4.37, 10 mg/kg=3.41 vs placebo=2.85) and Mental Component Summary (MCS) scores (belimumab 1 mg/kg=3.14, 10 mg/kg=2.70 vs placebo=1.40) at week 52, and in MCS score at week 76 (belimumab 1 mg/kg=3.05, 10 mg/kg=2.28 vs placebo=1.36). In pooled analysis, significantly greater improvements in PCS, SF-36 vitality domain, and FACIT-Fatigue scores at week 52 were evident with both belimumab doses. NCT00424476, NCT00410384.

The clinically meaningful improvements in HRQOL in autoantibody-positive patients with active SLE treated with belimumab and standard therapy are consistent with the reductions in disease activity observed in these trials.

The objective of this study was to evaluate whether musculoskeletal (MS) ultrasound (US) can be useful in helping medical students to detect joint inflammation through physical examination. The study was performed by two groups of four 6th year medical students. None had received any previous training in the clinical examination of joints or the use of ultrasound. Students were put through a 5-session training programme on the clinical detection of either knee [group 1] or metacarpophalangeal (MCP) [group 2] inflammation. After an initial training session on physical examination of normal and inflamed joints, the students examined 170 joints from 41 patients attending the hospital outpatient clinic in 4 separate sessions. The same joints were assessed for synovitis with US with the ensuing data compared to that of the students and analyzed for concordance with Cohen's unweighted kappa. In total 60 knees [group 1] and 110 MCP [group 2] were evaluated. The agreement between the presence of arthritis detected by the students in the four sessions and the presence of synovitis detected by US improved from the session I to sessions III with a marked improvement in the last session.

MSUS may be an effective technique for helping students to acquire the ability to detect joint inflammation.

To study the effects of neglecting intra-articular glucocorticoid injections (IAGCIs) into swollen joints in early rheumatoid arthritis (RA). Ninety-nine patients with early, DMARD naive RA were treated, aiming at remission, with methotrexate, sulfasalazine, hydroxychloroquine, low-dose oral prednisolone and, when needed, IAGCIs for 2 years, and randomised to receive infliximab or placebo from weeks 4 to 26. During each of the 15 study visits, patients were scored retrospectively 0.2-0.4 points (depending on the number of non-injected joints) if IAGCIs to all swollen joints were not given. Patients were divided into tertiles by their cumulative scores for neglected injections (CSNI) over 24 months. 28-joint disease activity score (DAS28) area under the curve (AUC) between 0-24 months, remission rates, changes in quality of life, and radiological changes during the follow-up were assessed. Trends across tertiles of CSNI were tested with generalised linear models. Higher CSNI was associated with lower strict remission rates (p=0.005), and lower quality of life (p=0.004) at 24 months, and higher DAS28 AUC (p<0.001) during the follow-up. At 24 months, DAS28 remission rates were 90%, 93% and 76% (p=0.081), and strict remission rates were 74%, 77% and 39% by tertiles of CSNI. No significant differences were observed in radiological progression (p=0.089). IAGCIs were well tolerated.

Neglecting IAGCIs into swollen joints is associated with lower remission rates, higher disease activity, and lower quality of life. Hence, IAGCIs should be used as an integral part of the targeted treatment of early RA.

Systemic lupus erythematosus has a wide spectrum of immunological and clinical manifestations. Its course is characterised by exacerbations which may result in mortality or morbidity to vital organs/systems. To determine clear and early prognostic markers to avoid further complications. 245 adult patients diagnosed between January 1978 and March 2001 were studied. Clinical manifestations and laboratory findings both at onset and during the clinical course were collected. The number, type, and severity of the flares were also noted. Statistical analyses between disease features at onset, subsequent flares, and mortality were performed. 239 patients entered the study. Their mean age at onset was 30 years. The mean time between onset and diagnosis was 36 months and the mean evolution time was 114 months. 205 patients developed 915 flares; 205 (22.4%) of these flares were major flares, and affected 110 patients. Cardiac, neurological, or renal affection at onset were associated with a higher probability of developing cardiac (p=0.022), neurological (p<0.001), and renal (p<0.001) exacerbations, respectively, during the evolution. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) were predictors of stroke (aCL, p=0.000; LA, p=0.001). Age at diagnosis (p=0.003) and valvular disease at onset (p=0.008) were independent predictors of low survival.

Renal, cardiac, or neurological involvement and the presence of LA or aCL positivity at onset were predictors of renal, cardiac, or neurological flares, respectively. Age and valvular involvement at onset were found to be independent adverse outcome predictors for low survival.

We report a case of pyoderma gangrenosum (PG) associated with a complication comprising ascending aortic dissection (neutrophilic aortitis) in a setting of rheumatoid arthritis (RA). A 79-year-old female patient was hospitalized in late 2009 for vegetating PG. Treatment with general steroids followed by colchicine and topical steroids resulted in complete healing of skin lesions. During hospitalization, the patient presented dissection of the ascending part of the aorta, for which emergency surgery proved effective. Histological examination of the excised tissue revealed diffuse neutrophilic aortitis. Diagnoses of Takayashu's disease and of lupus were ruled out. A chest CT scan showed interstitial lung disease with mild lymphocytosis in the bronchoalveolar fluid, but with no isolated pathogenic organisms. Relapse of skin lesions occurred 3 and 4 years later, associated with the development of RA, and worsening of the interstitial lung disease was noted in a scan carried out it in 2013, following which stabilization was observed in April 2014. There was no recurrence of the PG lesions.

To our knowledge, no other cases involving association of neutrophilic aortitis with PG and RA has been published to date. The literature describes the emergence of the concept of systemic neutrophilic dermatoses, and this notion is reinforced by the presence of a cutaneous and aortic site of the neutrophilic disease in a single patient.

Schnitzler's syndrome is an inflammatory disorder characterised by chronic urticarial rash and monoclonal gammopathy, accompanied by periodic fever, arthralgia or arthritis, and bone pain. The cause and treatment are still unknown. To assess treatment with thalidomide and an interleukin 1 receptor antagonist, anakinra, in Schnitzler's syndrome. Three patients with Schnitzler's syndrome are described, one with IgM gammopathy, two with IgG type. In one patient, thalidomide induced complete remission, but was stopped because of polyneuropathy. Anakinra 100 mg daily in all three patients led to disappearance of fever and skin lesions within 24 hours. After a follow up of 6-18 months, all patients are free of symptoms.

Anakinra proved to be effective in three patients with Schnitzler's syndrome. This treatment is preferable to thalidomide, which induced a complete remission in one of our patients, as it has fewer side effects.

In a retrospective comparative analysis in patients undergoing primary guided-motion total knee arthroplasty (TKA), the authors have evaluated whether different TKA implant design would influence the clinical and functional outcomes. Between 2007 and 2009, 227 computer-assisted primary TKAs were performed in 219 consecutive patients. Patients received one of the two different fixed-bearing guided-motion TKA designs assisted by navigation surgery: the Scorpio Non-Restrictive Geometry (NRG) knee system and the Journey Bi-Cruciate Stabilized (BCS) knee systems. Data were available for 180 patients (187 knees). No significant differences were observed between the two groups with respect to preoperative demographic characteristics, range of motion (ROM) and radiographic knee alignment. At a mean follow-up of 29 months, the Journey BCS group had higher mean Knee Injury and Osteoarthritis Outcome Score (KOOS) in all subscales and a greater ROM than the Scorpio NRG group. This difference was statistically significant for the KOOS subscales of pain (p = 0.007) and knee-related quality of life (p = 0.045), as well as for postoperative ROM (p = 0.018). Considering the overall complications, 1 patient of Scorpio NRG group (0.5%) and 5 in Journey BCS (2.7%) had stiffness. Anterior knee pain was reported in 4 cases of Scorpio NRG group (2.1%). In the Journey BCS group were observed 2 cases (1.1%) of frontal plane instability and 1 case (0.5%) of synovitis pain. Clinical study, Level III.

The bearing geometry and kinematic pattern of different guided-motion prosthetic designs can affect the clinical-functional outcome and complications type in primary TKA.

To clarify the effects of transforming growth factor beta 1 (TGF beta 1), TGF beta 2, and basic fibroblast growth factor (bFGF) on cell proliferation and proteoglycan (PG) synthesis in articular chondrocytes obtained from immobilised rabbit knees. The right knees of rabbits were immobilised in full extension for up to 42 days using fiberglass casts. Specimens for histology were stained with safranin O. Chondrocytes were isolated from the weight bearing regions of the femur and tibia of the immobilised knees and cultured with combinations of growth factors. Cell proliferation and PG synthesis were determined by 3H-thymidine and 35S-sulphate incorporations. Histological study revealed loss of metachromasia in the articular cartilage at seven days, fissuring and cell clusters at 28 days, and loss of cartilage layers 42 days after immobilisation. Radioisotope assay of the chondrocytes revealed no remarkable change in DNA synthesis in the presence of either TGF beta 1 or TGF beta 2 alone. bFGF markedly stimulated cell proliferation in specimens obtained 0 to seven days after immobilisation. The combination of either TGF beta 1 or TGF beta 2 with bFGF had a synergistic effect, inducing significant increases in DNA synthesis four, seven, and 14 days after immobilisation. PG synthesis by chondrocytes from immobilised joints was not significantly altered by these agents.

TGF beta 1 or TGF beta 2 in combination with bFGF exert synergistic effects on cell proliferation in articular chondrocytes obtained from the rabbit knee during the early days after immobilisation by a cast. These results suggest a critical role of cytokine combinations in the development of articular cartilage degeneration after immobilisation.

Cataract secondary to juvenile rheumatoid arthritis is a severe, vision-threatening complication in early childhood. Intraocular lens implantation is controversial. The follow-up of four pseudophakic eyes of three patients and their perioperative therapeutic regimen were retrospectively analyzed. Early and late postoperative complications are reported. Both girls had lens aspiration and posterior lens implantation at the ages of 6 and 12 years, the boy at the age of 10 and 14 years. All patients had relapsing anterior uveitis. The follow-up time was 3 years (1-6 years). One girl was diagnosed with sarcoidosis, causing juvenile arthritis. Both girls had perioperative methothrexate and prednisolone therapy. The boy had azathioprine therapy at the time of his first cataract surgery; later he had no systemic therapy. Both girls' intraocular lenses were implanted at different eye hospitals. Both girls had severe inflammatory reactions after surgery. At the hospitals both eyes had surgical revision for iris capture. In one case this was combined with exchanging the intraocular lens. Iris capture persisted for this eye and later vitrectomy with silicone oil filling was necessary to delay phthisis, resulting in amaurosis. For two pseudophakic eyes vitrectomy was necessary later because of severe vitreous opacities, but visual acuity was severely diminished by chronic cystoid macular edema and epiretinal membranes. The boy developed in his second eye intermittent iris bombata and persistent secondary glaucoma, visual acuity was stabilized at 0.5.

Secondary cataract due to juvenile rheumatoid arthritis or sarcoidosis is a difficult situation for phacoemulsification with intraocular lens implantation in children. For severe inflammatory complications intense local and systemic anti-inflammatory therapy is mandatory. Visual prognosis is reduced for the uveitic posterior segment and glaucoma complications. IOL implantation can be recommended for only a very few patients.

The purpose of this study was to examine the effect of salivary flow rate on the levels of antimicrobial salivary proteins in 24 patients with Sjögren's syndrome and 22 age- and race-matched healthy control subjects. Parameters examined included stimulated salivary flow rate, total salivary protein, lactoferrin, lysozyme, amylase, and secretory immunoglobulin A. The mean total salivary protein and the mean salivary amylase were significantly greater in patients than in controls. However, no significant difference was observed in the mean stimulated salivary flow rates or the levels of lactoferrin, lysozyme, or secretory immunoglobulin A of patients and controls. To examine the effect of salivary flow rate on the levels of salivary antimicrobial protein, the levels of these proteins in patients with salivary flow rate of < or = 0.3 mL/min per gland were compared to those in healthy controls with salivary flow rate > or = 0.4 mL/min per gland. Analyses showed the levels of lactoferrin to be significantly higher among patients than among controls.

The levels of salivary amylase and lactoferrin may be influenced by the levels of salivary output in patients with Sjögren's syndrome. The relationship between salivary flow rate and the levels of amylase and lactoferrin is not clear at the present time.

Substantial effort has been devoted for devising effective and safe interventions to reduce preventable hospital admissions in chronic disease patients. In rheumatoid arthritis (RA), identifying risk factors for admission has important health policy implications, but knowledge of which factors cause or prevent hospital admissions is currently lacking. We hypothesised that disease activity/severity and physical activity are major predictors for the need of hospitalisation in patients with RA. A total of 244 RA patients were assessed for: physical activity (International Physical Activity Questionnaire), RA activity (C-reactive protein: CRP; disease activity score: DAS28) and disability (Health Assessment Questionnaire: HAQ). The number of hospital admissions and length of hospitalisation within a year from baseline assessment were collected prospectively. Disease activity and disability as well as levels of overall and vigorous physical activity levels correlated significantly with both the number of admissions and length of hospitalisation (P < 0.05); regression analyses revealed that only disease activity (DAS28) and physical activity were significant independent predictors of numbers of hospital admissions (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046)) and length of hospitalisation (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046). Sub-analysis of the data demonstrated that only 19% (n = 49) of patients engaged in recommended levels of physical activity.

This study provides evidence that physical activity along with disease activity are important predictors of the number of hospital admissions and length of hospitalisation in RA. The combination of lifestyle changes, particularly increased physical activity along with effective pharmacological therapy may improve multiple health outcomes as well as cost of care for RA patients.

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA.

The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.

Arthroscopic and open debridement arthroplasty for elbow arthrosis produce excellent results. Resection of the tip of the olecranon and coronoid, as well as debridement of the associated fossae, is frequently described as sufficient for restoring range of motion and reducing pain. The purpose of this study was to demonstrate that medial and lateral osteophytes of the olecranon and the coronoid usually mark the first bony contact and may, therefore, restrict range of motion. 11 fresh-frozen elbows were dissected. The fossae were coated with Optosil P Plus (C-silicone), and maximal flexion and extension was simulated. The distribution of C‑silicone impressions was documented. 6/7 donors were male. The mean age at the time of death was 82 . Out of 11 elbows, 4 exhibited arthritic changes. All arthritic elbows showed marginal osteophytes of the olecranon without characteristic dipping of the olecranon into its fossa. In 1/4 cases, additional osteophytes at the side of the coronoid were detected (in comparison to 1/7 in healthy elbows).

The distribution of osteophytes in elbow arthrosis may be underestimated. Many clinicians describe a resection of the tip of the olecranon and the coronoid and debridement of the related fossa as sufficient. Our study supports the theory that marginal osteophytes, especially of the olecranon, should be resected during debridement arthroplasty, since the distribution of bony contact differs in arthritic and healthy elbows.

Cardiovascular (CV) involvement in patients with systemic lupus erythematosus (SLE) is presumably subclinical for the major part of its evolution. We evaluated the associations between high-sensitive troponin T (hs-TropT), a sensitive marker of myocardial injury, and CV involvement using cardiac magnetic resonance (CMR). This is a two-centre (London and Frankfurt) CMR imaging study at 3.0 Tesla of consecutive 92 patients with SLE free of cardiac symptoms, undergoing screening for cardiac involvement. Venous samples were drawn and analysed post-hoc for cardiac biomarkers, including hs-TropT, high-sensitive C reactive protein and N-terminal pro brain natriuretic peptide. Compared with age-matched/gender-matched non-SLE controls (n=78), patients had significantly raised cardiac biomarker levels, native T1 and T2, aortic and ventricular stiffness, and reduced global longitudinal strain (p<0.01). In SLE, hs-TropT was significantly and independently associated with native T2, followed by the models including native T1 and aortic stiffness (Χ NCT02407197; Results.

Patients with SLE have a high prevalence of subclinical myocardial injury as demonstrated by raised high-sensitive troponin levels. CMR with T2 mapping reveals myocardial oedema as the strongest predictor of hs-TropT release, underscoring the inflammatory interstitial remodelling as the main mechanism of injury. Patients without active myocardial inflammation demonstrate diffuse interstitial remodelling and increased vascular stiffness. These findings substantiate the role of CMR in screening of subclinical cardiac involvement.

Staphylococcus aureus is a common cause of bacterial arthritis, which is associated with progressive bone loss in affected joints. We recently showed that S. aureus infection also induces a significant systemic bone loss in mice. This study was performed to assess the effect of estradiol treatment on the clinical course and outcome of S. aureus arthritis and on infection-induced bone loss in experimental S. aureus infection. Mice were ovariectomized, treated with estradiol or placebo, and S. aureus infection was established by intravenous inoculation of bacteria. Estradiol treatment was found to decrease significantly the frequency and clinical severity of S. aureus arthritis, a finding that was accompanied with significantly higher serum levels of interleukin-10 in estradiol-treated mice. Estradiol was also highly protective against S. aureus-induced systemic trabecular, and cortical bone loss. Lack of endogenous estrogens and S. aureus infection had additive effects on trabecular bone loss. The S. aureus-infected, ovariectomized mice lost as much as 76% of their trabecular bone mass.

Treatment with estradiol ameliorates S. aureus arthritis and is protective against infection-induced systemic bone loss in experimental S. aureus infection.

Persistent postoperative pain has a significant relationship with patient health and satisfaction. To investigate the prevalence and association of neglect-like symptoms (NLS) and other psychological factors on postoperative pain in patients following total knee arthroplasty (TKA). NLS are defined as the loss of perception of the limb with pain and excessive effort required to move the limb. The authors hypothesized that NLS were an important contributor to postoperative pain. The factors influencing pain were investigated using a longitudinal study with assessments at three and six weeks postsurgery. The relationships among demographic factors (age, body weight, body mass index), psychological factors (State-Trait Anxiety Inventory and Pain Catastrophizing Scale [PCS]) and NLS with postoperative pain were investigated in 90 patients after TKA. The associations among motor functions (muscle strength of knee extension, range of motion), sensory functions (joint position sense and two-point discrimination in the thigh) and NLS were also investigated. At three and six weeks after surgery, 36% and 19% of patients, respectively, experienced NLS. In hierarchical multiple regression analysis, NLS and PCS scores were significantly associated with postoperative pain, while joint position sense and range of motion were significantly associated with NLS.

These results suggest that facilitation of sensory integration is important in rehabilitation after TKA because NLS appears to result from impaired sensory integration. The association of PCS scores with postoperative pain and NLS suggests the need to provide appropriate postoperative education to reduce persistent negative thoughts regarding future pain.

To observe and evaluate the clinical effect of intra-articular injection of parecoxib in patients with early knee osteoarthritis. From September 2016 to August 2017, 107 patients with early knee osteoarthritis were treated, including 50 males and 57 females, aged 45 to 64 (51.9±4.2) years. They were divided into basic therapy+oral glucosamine group(group A) 36 cases, oral celecoxib+basic therapy+oral glucosamine group(group B) 36 cases, intra-articular injection of parecoxib+basic therapy+oral glucosamine group(group C) 35 cases. There was no significant difference in gender, age, BMI and clinical stage(Kellgren-Lawrence classification) between the three groups before treatment. VAS score, HSS score and patient satisfaction were compared before and after treatment in the three groups. The levels of inflammatory cytokines in synovial fluid were measured before and after treatment in the three groups. All cases were followed up for(15.2±2.6) months on average. The VAS score and HSS score of each group were improved after treatment(

For patients with early knee osteoarthritis, intra-articular injection of parecoxib can significantly improve clinical symptoms and avoid adverse reactions of long-term oral NSAIDs, which is an effective treatment.

Lateral unicompartmental arthroplasty (UKA) constitutes only 5-10% of all unicompartmental replacements performed. Whilst the short and medium term benefits are well documented, there remains concern regarding the higher revision rate when compared with total knee replacement. We report the long term clinical outcome and survivorship of a large series of lateral UKA. Between 1974 and 1994, 71 patients (82 knees) underwent a lateral fixed-bearing St Georg Sled UKA. Prospective data was collected pre-operatively and at regular intervals post-operatively using the Bristol Knee Score (BKS), with later introduction of the Oxford Knee (OKS) and Western Ontario MacMaster (WOMAC) scores. Kaplan Meier survival analysis was used, with revision, or need for revision, as end point. 85% of the patients were female. No patients were lost to follow-up. Functional knee scores improved post-operatively up to 10 years, at which point they demonstrated a steady decline. Survivorship was 72% at 15 years, and 68% at 20 and 25 years. Nineteen knees were revised, with progression of disease in another compartment the commonest reason. There were two revisions due to implant fracture. In patients aged over 70 years at time of index procedure, 81% died with a functioning prosthesis in situ.

This represents the longest follow-up of a large series of lateral UKA. Results of this early design of fixed bearing UKA demonstrate satisfactory long term survivorship. In elderly patients, further intervention is rarely required. More contemporary designs or techniques may show improved long term survivorship in time.

Crowned dens syndrome (CDS) is defined as acute cervical or occipital pain due to a local inflammatory reaction related to calcifications in the ligaments surrounding the odontoid process. Virtually, all previous descriptions of CDS have related to calcium pyrophosphate dehydrate (CPPD) arthropathy. We prospectively identified a total of twenty-four consecutive inpatients with Crowned dens syndrome from January 2016 to December 2017 in our institution. All patients (age range 54 to 87 years, 67% females) presented with acute onset pain in the upper neck and/or occiput accompanied with extreme neck stiffness. Most patients (79%) had elevated inflammatory markers. Four patients underwent temporal artery biopsy, which was negative for arteritis in all cases, and one was subjected to lumbar puncture, which was non-contributory. Seventeen patients (71%) had known rheumatic disease on presentation: 10 patients had the diagnosis of calcium pyrophosphate dehydrate arthropathy, 3 patients had ankylosing spondylitis, 2 patients had rheumatoid arthritis, 1 patient had Behcet's disease, and 1 suffered from Familial Mediterranean Fever. In 4 more patients, crowned dens syndrome was the presenting symptom of calcium pyrophosphate dehydrate disease. All patients were treated with glucocorticoids as 0.5 mg/kg prednisone plus colchicine 0.5 mg bid resulting in dramatic improvement in both clinical (head/neck pain alleviated and cervical spinal mobility regained) and laboratory measures.

Crowned dens syndrome should be considered, and craniocervical junction imaged in the context of acute cervical or occipital pain with stiffness and elevated inflammation markers not only in patients previously diagnosed with calcium pyrophosphate dehydrate arthropathy but also in diverse clinical settings.Key Points• This report highlights that crowned dens syndrome should be considered in various clinical setting besides calcium pyrophosphate dehydrate (CPPD) arthropathy.• Vigilance to this syndrome allows rapid treatment and may spare the patient unnecessary invasive procedures (i.e., temporal artery biopsy or lumbar puncture).

To investigate an 8-year change in waist circumference (WC) with the risk of incident low physical function over 1 year in adults with, or at risk of, knee osteoarthritis (OA). Data from the Osteoarthritis Initiative were used. Change in WC was measured from study enrollment (0 month) to the 96-month visit and classified as Increase (≥ 5cm gain) or Maintain (< 5cm gain). We identified World Health Organization (WHO) risk category based on WC at study enrollment as Large WC (males ≥ 102 cm, females ≥ 88 cm) or Small WC (males < 102 cm, females < 88 cm). The outcome was incident low physical function (≥ 28 Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale) at the 108-month visit. To investigate the association of the 8-year change in WC with the risk of low physical function, we calculated risk ratios (95% CI) and adjusted for potential confounders. We repeated the analyses stratified by the WHO disease risk category. The Increase WC group had 1.43 (95% CI 1.04-1.96) times the risk of incident low physical function compared to adults in the Maintain WC group. Adults with a Large WC at baseline who increased WC had 1.55 (95% CI 1.00-2.37) times the risk of incident low physical function compared to those who maintained WC. Adults with a Small WC at baseline who increased WC had 1.97 (95% CI 0.84-4.63) times the risk compared to those who maintained WC.

Increasing WC increases the risk of incident low physical function in the following year. Maintaining WC may mitigate developing low physical function.

To clarify the effects of tourniquet use on pain, early rehabilitation, blood loss, incidence rate of thrombosis in primary total knee arthroplasty (TKA) through a randomized controlled trial. Between Janurary 2014 and August 2015, 168 patients with knee osteoarthritis undergoing primary TKA were randomly allocated to tourniquet group (n = 84) or non-tourniquet group (n = 82). There was no significant difference in gender, age, body mass index, affected side, osteoarthritis grading, disease duration, preoperative range of motion (ROM), visual analogue scale (VAS), Hospital for Special Surgery (HSS) score, and hemoglobin (Hb) between 2 groups (P > 0.05). The operation time, hospitalization time, 90° knee flexion time, straight leg lifting time, and ambulation time were compared between 2 groups. Intraoperative blood loss, Hb decrease, postoperative VAS score, HSS score, ROM, and postoperative complications were recorded and compared. There was no significant difference in operation time (t = -1.353, P = 0.178). The patients were followed up 3-20 months (mean, 12 months) in tourniquet group, and 3-22 months (mean, 13 months) in non-tourniquet group. No significant difference was found in Hb decrease (t = -1.855, P = 0.066) and transfusion rate (23.81% of tourniquest group vs. 25.61% of non-tourniquest group) (χ² = 0.072, P = 0.788) between 2 groups. Significant difference was found in the incidence rate of thrombosis between tourniquet and non-tourniquet groups (10.71% vs. 2.44%) (χ² = 4.592, P = 0.032), and the intraoperative blood loss of tourniquet group was significantly less than that of non-tourniquet group (t = -16.066, P = 0.000). The 90° knee flexion time, straight leg lifting time, ambulation time, and hospitalization time of tourniquet group were significantly later than those of non-tourniquet group (P < 0.05). The tourniquet group had significantly higher VAS score at 3, 5, 7, and 14 days after operation (P < 0.05) and lower HSS score at 28 days after operation (t = -4.192, P = 0.000) than non-tourniquet group, but there was no significant difference in the ROM between 2 groups (t = 0.676, P = 0.500).

The use of a tourniquet during TKA will increase knee pain and thrombotic events, but can not decrease total blood loss and transfusion rate. A tourniquet use during TKA is unfavorable for early rehabilitation progress.

The aim of this study was to understand the health care needs and related factors for patients with knee osteoarthritis during the early recovery period after total knee-replacement surgery. Knee-replacement surgery effectively relieves pain and improves mobility for patients with knee osteoarthritis. With shorter hospital stays, postoperative knee-replacement patients need guidance from medical personnel about self-care, but little is known about these patients' health care needs. This descriptive, correlational study used a longitudinal design. A convenience sample of 85 patients undergoing total knee-replacement surgery in northern Taiwan was interviewed before and 1-2 weeks after hospital discharge. Data were collected on participants' demographic characteristics, disease characteristics, symptom distress and health care needs. Participants' health care needs diminished significantly after hospital discharge. Before hospital discharge, the most important need was medical personnel to help relieve postoperative pain, and health care needs were predicted by symptom distress and age. After hospital discharge, the most important need was medical personnel to help understand the conditions requiring a return visit to hospital, and health care needs were predicted by symptom distress, health care needs before discharge, age and gender. Given today's shorter hospital stays, clinicians need to prioritise health care needs indicated by predictive variables. This strategy would help optimise assessment and care management by focusing on patients' greater health care needs and by tailoring care information and skills to patients' individual needs.

The results of this study provide a comprehensive understanding of health care needs before and after discharge, as well as predictive factors for patients undergoing total knee-replacement surgery.

We sought to study the long-term outcome of juvenile chronic arthritis (JCA) in the temporomandibular joint (TMJ). Temporomandibular disorders, including TMJ involvement, were assessed in 42 women with pauciarticular or polyarticular JCA--on average 25.8 years from disease onset--and compared with those found in matched control subjects. Disease-related parameters associated with temporomandibular disorders were identified. The TMJ was involved in 66.7% of the patients, most severely in extended pauciarticular JCA. Temporomandibular disorders were more frequent in the patients than in the control subjects, especially in those with persistent disease. The TMJ involvement was positively correlated with disease duration and negatively correlated with jaw opening and occlusal support. Duration of active JCA and history of functional pain were identified as predictors of present TMJ involvement.

In a long-term follow-up, TMJ involvement proved frequent in the studied patients and was associated with long disease duration and previous pain on jaw opening. The findings suggest that patients with JCA should undergo orofacial evaluation on a regular basis.

It has been proposed that bone mineral density has an influence on cement penetration in hip and knee arthroplasty. The hypotheses of this study were that: 1) there is a negative correlation between bone mineral density (BMD) and cement penetration in cemented glenoid components; and 2) that implant design has an influence on cement penetration into the glenoid bone. BMD of 10 pairs of fresh frozen scapulas was measured. Micro-computed tomography (micro-CT) scans in 3 different sections were analyzed after implantation of keeled and pegged glenoid components using a 3(rd)-generation cementing technique with a vacuum mixing system. Cement penetration was analyzed and correlated with BMD. Pull-out strength testing was performed to analyze primary stability. The overall peak BMD was 0.6 [g/cm(2)] (range, 0.33-0.98). A strong negative correlation between BMD and mean cement penetration was found for the peg (R(2) = -.83; P < .003) and for the keel group (R(2) = -.81; P < .005). Mean cement penetration was 78.4 mm(2) (range, 60.6-94.2) in the keel and 113.9 mm(2) (range, 78.2-143.4) in the peg group (P < .0001). In all cases, the components were pulled out of the cement mantle, whereas the bone-cement interfaces remained intact. The mean pull-out strength was 1093N (764-1343N) for keeled and 884N (650-1264N) for pegged components (P < .05).

A modern cementing technique, leading to a deep bonding between bone and cement, is crucial to prevent loosening of glenoid components. The findings of this study might help us to better understand the results of follow-up studies of cemented glenoid implants. Our results could be helpful for the choice of implants in patients with poor bone quality like osteoporosis or rheumatoid arthritis.

To determine the spectrum and prevalence of the varied manifestations, associated conditions and laboratory abnormalities of patients with primary Sjögren's syndrome in Israel and compare them between individuals of Sephardic and Ashkenazi descent and with data from the literature. A retrospective study of a cohort of 201 consecutive patients diagnosed and followed at a single academic medical center. All cases were diagnosed using stringent criteria according to the American European Concensus Group including a labial minor salivary gland biopsy in all cases. Patients' mean age was 57 years and 84% were women. Overall, more than 98% of patients had sicca symptoms of dry eyes and mouth. About 35% of the cohort had hematological manifestations--primarily immune cytopenias, protein immunoelectrophoresis abnormalities and lymphoma. About 20% had associated neurological conditions (not only peripheral but often central nervous system) and 15% had pulmonary involvement. In addition, thyroid disease, liver disease, vascular or cutaneous manifestations, synovitis, ocular and renal disease could be found. In fact, the presenting manifestation was extraglandular or an abnormal test result in 39% of the patients.

No significant differences were found in glandular or extraglandular manifestations or laboratory test results between Ashkenazi and Sephardic patients, despite their genetic differences. A negative history of sicca symptoms effectively rules out primary Sjögren's syndrome in this cohort. These symptoms may not be volunteered by patients and the large variety of extraglandular involvement patterns and associated conditions observed may dominate the patient's presentation, and mandate physicians' awareness and a high index of suspicion for a timely diagnosis.

To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria. Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint. Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score.

Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of "deeper remission" of RA.

To evaluate the cardiovascular risk profile of spondylarthropathy patients, particularly ankylosing spondylitis and psoriatic arthritis. A Pubmed literature search was performed to collect English-language articles for this clinically orientated review. Studies were selected if they included (cardiovascular) mortality and morbidity and/or data about cardiovascular risk factors in spondylarthropathies. Ankylosing spondylitis as well as psoriatic arthritis appear to be associated with an increased cardiovascular mortality and morbidity. Several factors, ie, smoking, altered lipid profile, hypertension, increased fibrinogen level, enhanced number of platelets, and hypercoagulability might explain the enhanced cardiovascular risk. Moreover, a decline in physical activity, the presence of HLA-B27, and inflammation may play a role. Finally, undertreatment of cardiovascular morbidity also may contribute to the higher cardiovascular risk. Rheumatologists should be aware of the enhanced cardiovascular risk in patients with ankylosing spondylitis and psoriatic arthritis. If modifiable cardiovascular risk factors are identified, treatment could ultimately result in a lower cardiovascular morbidity and mortality.

The available data indicate an increased cardiovascular risk in spondylarthropathy patients, particularly those with ankylosing spondylitis and psoriatic arthritis.

(1) To assess the responsiveness of the Short Form 36 Health Survey (SF-36) and Patient Generated Index (PGI) in people with knee pain who were given oral analgesics; and (2) to perform content analysis of the SF-36 and PGI aiming to identify differences between the instruments and causes of different responsiveness. An observational study nested within a randomised controlled trial comparing oral paracetamol, ibuprofen or a combination of the two in 884 community-derived people with chronic knee pain. Each participant was given the SF-36 and PGI questionnaires to fill out at baseline, day 10, week 7 and week 13 after commencement on analgesia. Responsiveness was measured as a standardised response mean from baseline, and contents of the instruments were analysed. The PGI showed the greater responsiveness to analgesics than the SF-36 throughout the study period. Only the Bodily Pain Score of the SF-36 showed comparable responsiveness to the PGI. The standardised response mean of the PGI at 13 weeks was 0.61 (95% CI 0.51-0.72), and that of the Bodily Pain Score of the SF-36 was 0.49 (95% CI 0.39-0.58). Content analysis of the PGI identified multiple areas which are not represented in the SF-36 which may help explain its performance.

Overall the PGI is more responsive than the SF-36 to commonly used oral analgesics taken for knee pain. The PGI is able to elicit areas of individualised health-related quality of life which are not captured by the SF-36.

The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS). We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study.

This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.

To optimize treatment for rheumatoid arthritis (RA) and to define indications for D-penicillamine and methotrexate therapies on an individual basis by taking into account the levels of rheumatoid factor (RF) isotopes circulating in blood. A total of 105 patients (mean age 46.39 +/- 1.35 years) with varying RA were observed. Indirect solid-phase enzyme immunoassay was used to analyze RF isotopes; the pattern of the disease and the efficiency of therapy for RA were compared with the patients' immunity. With elevated RF IgG levels, the cardiovascular system, thyroid, mucous membranes were found to be more frequently impaired and vasculitis was diagnosed.

The use of cuprenil and methotrexate in RA substantially improves patients' immunity.

To evaluate attitudes and behaviors of patients with rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. An online survey delivered by text message to 4695 patients on follow-up at a tertiary rheumatology center. Latent class analysis was performed on the survey variables. There were 2239 (47.7%) who responded to the survey and 3 clusters were identified. Cluster 3 (C3) was defined by patients who were most worried about COVID-19, more likely to wear face masks, and more likely to alter or stop their medications. Patients in C3 were more likely to be female, Malay, and unemployed.

We identified 3 clusters with different healthcare beliefs and distinct sociodemographics.

Although cartilage loss occurs with advancing age and is a hallmark of OA, the factors that affect cartilage change are not well established. The aim of this study was to explore the determinants of change in patella cartilage volume over 2 yrs among healthy middle-aged women with no clinical knee OA. One hundred and forty-eight women with no clinical knee OA were recruited from a previous population-based cross-sectional study of healthy women aged 40-67 yrs. MRI was performed at baseline and at 2 yrs, to assess patella cartilage and bone volume. Self-reported exercise was assessed by questionnaire. Annual loss of patella cartilage volume was 1.6% (95% CI 1.2, 1.9). Age was positively associated with patella cartilage volume loss after adjustment for confounders (P = 0.05). For every 1 mm(3) increase in patella bone volume at baseline, annual cartilage loss was reduced by 8.05 mm(3) (95% CI 12.91, 3.19; P < 0.001). Fortnightly participation in exercise promoting an increased heart and respiratory rate for at least 20 min also tended to be associated with a reduced rate of patella cartilage volume loss (P = 0.09).

Among middle-aged women with no clinical knee OA, advancing age expedites the rate of patella cartilage volume loss, while increased patella bone volume and exercise participation tends to be associated with a reduction in the rate of patella cartilage volume loss. Interventions targeting modifiable factors, such as physical activity, warrant further investigation as they may help to prevent patellofemoral OA.

Cysteine proteinases B and L have been shown to be involved in matrix degradation of joints in patients with rheumatoid arthritis (RA). Since the cysteine proteinase cathepsin K is assumed to play a pivotal role in osteoclast mediated bone resorption, we investigated the expression of cathepsin K in RA joints. We studied 10 RA and 4 normal synovial specimens and 5 articular heads with RA lesions by in situ hybridization, applying specific riboprobes for cathepsin K, human collagen type I, and cathepsin B. Antibodies against monocyte/macrophage associated CD68 antigen were applied in immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were performed on 4 RA, 1 normal, and 1 immortalized normal fibroblast cultures. Cathepsin K mRNA expression was upregulated in RA synovium compared to normal synovium. Cathepsin K mRNA was expressed mainly by synovial fibroblasts. These data were confirmed by RT-PCR and RPA. In RA articular heads, cathepsin K mRNA was detected at sites where synovium attached and invaded underlying bone. The cells at these sites represented collagen type I and cathepsin B mRNA expressing fibroblasts as well as CD68+ macrophages and giant cells. In addition, a distinct expression of cathepsin K mRNA was also detected around lymphocytic infiltrates in RA synovium.

The data indicate that cathepsin K is not only expressed by osteoclasts but also by synovial fibroblasts, and suggest that cathepsin K contributes to bone destruction mediated by RA synovial cells. The expression of cathepsin K around lymphocytic infiltrates suggests further to facilitate the movement of mononuclear cells through the perivascular interstitial matrix and thereby contribute to interstitial matrix turnover.

To determine the relationship between aerobic and anaerobic physical fitness and functional ability in children with juvenile idiopathic arthritis (JIA). Eighteen children with JIA (age 7 to 14 yr., 3 male/15 female) performed a maximal aerobic exercise test and a Wingate anaerobic exercise test. Functional ability was concurrently assessed using the Childhood Health Assessment Questionnaire (CHAQ). A low relationship between aerobic fitness and functional ability was found (r = 0.0 to 0.4, p > 0.05, except for eating r = 0.46, p < 0.05). The correlations between anaerobic physical fitness and functional ability in JIA patients were strong (r = 0.5 to 0.75, p < 0.05). This indicated a good relationship between anaerobic fitness and functional ability.

The strong association between anaerobic physical fitness and functional ability showed the importance of anaerobic physical fitness for children with JIA.

To quantify the changes in synovial expression of mediators of macrophage chemotaxis, matrix degradation, and macrophage infiltration in the synovial membrane of patients with rheumatoid arthritis (RA) achieving American College of Rheumatology (ACR) defined remission and radiological arrest. Knee synovial biopsies were taken from a selected group of 18 patients with RA before and after treatment and immunostained with antibodies specific for CD68; the chemokines macrophage inflammatory protein (MIP)-1a and monocyte chemoattractant protein (MCP)-1; matrix metalloproteinases (MMP-1 and 3) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMP-1 and 2); as well as isotype-specific negative controls. Immunostaining was quantified using a computer assisted color video image analysis system. Radiographs were performed before and after treatment and the Larsen score determined. Patients were arbitrarily divided into 2 groups: the radiological arrest group (defined as change in Larsen score pound 5 from baseline) and radiological progressors (defined as change in Larsen score > 5). Patients were classified according to ACR response criteria. In the 8 patients who achieved ACR defined remission, there were tendencies toward reductions in the synovial lining layer (LL) expression of MIP-1a by 36% (p = 0.1) and MCP-1 by 48% (p = 0.1). Significant reductions occurred in the expression of MMP-1, by 53% in the LL (p = 0.008) and 59% in synovial sublining layer (SL) (p = 0.02) and MMP-3, by 76% in LL (p = 0.02), and 72% in SL (p = 0.008), but not in TIMP expression. In this group of patients there were reductions in MMP:TIMP ratios, in particular the MMP-1:TIMP-1 ratio in the LL (p = 0.05), MMP-3:TIMP-1 ratio in the LL (p = 0.05) and SL (p = 0.008), and MMP-3:TIMP-2 ratio in the LL (p = 0.04) and SL (p = 0.08). In this group of patients CD68+ macrophage infiltration was significantly reduced in the LL by 59% (p = 0.008) and in the SL by 52% (p = 0.008), which corresponded with the reductions in chemokine expression. In the remaining 10 patients who did not achieve full remission there were no significant changes in the variables studied. In the group achieving ACR 50% or 70% response there was a reduction in CD68 expression that approached significance (p = 0.06 in LL and SL), but there was no significant change in the other variables. There were no significant changes in the patients with an ACR 20% response. In the radiological arrest group (12 patients) there was a 41% reduction in LL expression of MIP-1a (p = 0.05) and MMP-1 (p = 0.06). Reductions in MMP:TIMP expression were also noted, in particular in MMP-1:TIMP-1 expression in the LL (p = 0.04) and MMP-3:TIMP-1 in the SL (p = 0.01). There were corresponding reductions in CD68 expression by 49% (p = 0.009) in LL and by 42% (p = 0.0005) in SL. In the radiological progressors (6 patients) there were no significant reductions in mediator expression.

In RA, ACR defined remission is associated with reductions in MMP-1 and 3 expression, with a corresponding reduction in macrophage infiltration and a tendency to reduction in MIP-1a expression. Radiological arrest is associated with reductions in MMP-1 expression, and significant reductions in macrophage infiltration, MIP-1 expression, and MMP:TIMP ratio.

To investigate long-term radiographic and patient-relevant outcome of isolated limited meniscectomy with regard to type of meniscal tear and extent of surgical resection. We studied 155 patients with intact cruciate ligaments (mean +/- SD age 54 +/- 12 years) who had undergone meniscectomy an average of 16 +/- 1 years earlier. The patients were examined using standardized radiography and validated self-administered questionnaires. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to quantify knee-related symptoms, and the definition of a symptomatic knee was determined. We used 68 control subjects matched for age, sex, and body mass index to calculate the relative risks (RRs). Radiographic tibiofemoral osteoarthritis (OA) (Kellgren/Lawrence grade > or =2) was present in 66 index knees (43%), of which 39 (59%) were considered to be symptomatic according to the KOOS. In total, 77 patients (50%) had a symptomatic index knee. In a multivariate model, degenerative meniscal tears were associated with both radiographic OA (P = 0.030) and combined radiographic and symptomatic OA (P < or = 0.015). The RRs for combined radiographic and symptomatic OA after degenerative and traumatic types of meniscal tear were 7.0 (95% confidence interval [95% CI] 2.1-23.5) and 2.7 (95% CI 0.9-7.7), respectively, compared with matched controls.

An isolated meniscal tear treated by limited meniscectomy is associated with a high risk of radiographic and symptomatic tibiofemoral OA at 16-year followup. Factors associated with worse outcome were degenerative meniscal lesions and extensive resections. We suggest that degenerative meniscal tears may be associated with incipient OA, and that the meniscal tear signals the first symptom of the disease.

Low-density granulocytes (LDGs) can form neutrophil extracellular traps (NETs) spontaneously and excessively. When peripheral blood mononuclear cells (PBMCs) are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs. The percentages of LDGs in PBMCs from 55 patients with dermatomyositis (DM), 15 with polymyositis (PM), 42 with rheumatoid arthritis (RA), 25 with systemic lupus erythematosus (SLE), and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions. Significantly higher LDG percentages were found in PBMCs from patients with DM ((8.41±10.87)%, P<0.0001), PM ((8.41±10.39)%, P<0.0001), RA ((4.05±6.97)%, P=0.0249), and SLE ((7.53±11.52)%, P=0.0006), compared with the controls ((1.28±0.73)%). The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force (RCF) within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs.

The LDG percentage in PBMCs is significantly increased in patients with SLE, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.