Datasets:

austin

/

rheum_abstracts

like 0

Follow

Austin Health 2

This study examined whether daily weather conditions, 3-day average weather conditions, and changes in weather conditions influence joint pain in older people with osteoarthritis (OA) in 6 European countries. Data from the population-based European Project on OSteoArthritis were used. The American College of Rheumatology classification criteria were used to diagnose OA in older people (65-85 yrs). After the baseline interview, at 6 months, and after the 12-18 months followup interview, joint pain was assessed using 2-week pain calendars. Daily values for temperature, precipitation, atmospheric pressure, relative humidity, and wind speed were obtained from local weather stations. Multilevel regression modelling was used to examine the pain-weather associations, adjusted for several confounders. The study included 810 participants with OA in the knee, hand, and/or hip. After adjustment, there were significant associations of joint pain with daily average humidity (B = 0.004, p < 0.01) and 3-day average humidity (B = 0.004, p = 0.01). A significant interaction effect was found between daily average humidity and temperature on joint pain. The effect of humidity on pain was stronger in relatively cold weather conditions. Changes in weather variables between 2 consecutive days were not significantly associated with reported joint pain.

The associations between pain and daily average weather conditions suggest that a causal relationship exist between joint pain and weather variables, but the associations between day-to-day weather changes and pain do not confirm causation. Knowledge about the relationship between joint pain in OA and weather may help individuals with OA, physicians, and therapists to better understand and manage fluctuations in pain.

To assess the association of bone mineral density (BMD) of the femoral and tibial condyles with knee pain and disease severity in women with symptomatic medial knee osteoarthritis (OA). We enrolled 192 women (ages 41-90 years) between April 2007 and March 2011. The subjects were divided into 2 groups according to joint space narrowing (JSN) on weight-bearing radiographs. BMD of the lumbar spine, proximal femur, and knee condyles was measured. Medial and lateral condyle BMDs of the femur and tibia as well as the medial versus lateral condyle BMD ratios were measured. Mean medial condyle BMDs, medial versus lateral condyle BMD ratios, and visual analog scale (VAS) pain in both the femur and the tibia were higher in the obliteration group compared with the narrowing group (P < 0.001 for all). A significant positive correlation was observed between the femoral and tibial condyles in the following parameters: medial condyle BMDs, lateral condyle BMDs, and medial versus lateral condyle BMD ratios (r = 0.791-0.844). In both the femur and the tibia, medial versus lateral condyle BMD ratios had significant positive correlations with femorotibial angle, medial osteophytes, lateral osteophytes, medial JSN, and VAS pain, and had significant negative correlations with the Knee Society pain and function scores.

Although this study was a cross-sectional study, the femoral and tibial medial versus lateral condyle BMD ratios increased with more severe knee pain and might be a potential marker for monitoring disease severity in women with symptomatic medial knee OA.

Rheumatoid arthritis (RA) is known to be associated with multiple comorbidities and, therefore, overall management is critical for those patients undergoing elective major orthopaedic surgeries, such as total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to compare in-hospital outcomes of elective THA and TKA between patients with and without RA in the US during the last decade. We hypothesised that patients with RA would have similar perioperative outcomes after elective THA and TKA. Clinical data were derived from the US Nationwide Inpatient Sample (NIS) between 2000 and 2009. Patients who underwent elective THA and TKA were identified. Data regarding patient- and healthcare system-related characteristics, comorbidities, in-hospital complications, and mortality were retrieved. In-hospital outcomes of the procedures were compared between patients with and without RA. Comparison between patients with and without RA showed that patients with RA had significantly lower overall in-hospital complication rates following THA and TKA, and lower in-hospital mortality rate following THA. Patients with RA undergoing THA and TKA had decreased risk of overall in-hospital complications compared to those without RA.

Contrary to our hypothesis, perioperative outcomes of elective THA and TKA in patients with RA were better than those in patients without RA. These results may indicate that patient selection and pre- and perioperative management of patients with RA undergoing elective THA and TKA were well conducted in the US during the last decade.

Rheumatoid arthritis (RA) increases the mortality and morbidity of cardiovascular disease (CVD). However, the relationship between RA and the risk of CVD in the Japanese population remains unclear. This study comprised 571 RA patients who were admitted to Juntendo University Hospital from January 1990 to December 2000. Cardiovascular events (CVEs) were defined as cardiac death, acute coronary syndrome (ACS), symptomatic stroke, and congestive heart failure. During follow-up (mean 11.7 ± 5.8 years), 7.5% of the patients died from all causes and 11.0% experienced CVEs. The morbidity of stroke and ACS was 3.6 and 2.5 per 1000 person-years, respectively. The mean RA disease duration at enrolment was significantly longer in patients who experienced CVEs than in those who did not experience CVEs (15.0 ± 12.7 years vs. 10. 8 ± 9.7 years; p = 0.01). Physical disabilities due to RA were more severe in patients who experienced CVEs than in those who did not experience CVEs. Patients with a long RA disease duration showed significantly higher event rates (p = 0.033). Cox proportional hazards analysis identified a longer RA duration as an independent risk factor for CVD (hazard ratio 1.57, 95% CI 1.09-2.30, p = 0.02).

Japanese RA patients showed a relatively high incidence of CVD, despite the fact that they had few coronary risk factors. The RA disease duration was an independent risk factor for CVEs.

Studies comparing the outcome of spine surgery with that of large-joint replacement report equivocal findings. The patient-reported outcome measures (PROMs) used in such studies are typically generic and may not be sufficiently sensitive to the successes/failures of treatment. This study compared different indices of "success" in patients undergoing surgery for degenerative disorders of the lumbar spine, hip, or knee, using a validated, multidimensional, and joint-specific PROM. Preoperatively and 12 months postoperatively, 4594 patients (3937 lumbar spine, 368 hip, 269 knee) undergoing first-time surgery completed a PROM that included the Core Outcome Measures Index (COMI) for the affected joint. The latter comprises a set of single items on pain, function, symptom-specific well-being, quality of life, and disability-all in relation to the specified joint problem. Other single-item ratings of treatment success were made 12 months postoperatively. In multiple regression analyses, controlling for confounders, the mean improvement in COMI at 12 months was greatest for the hip patients and lowest for those with degenerative spinal deformity (= the statistical reference group) (p < 0.05). Compared with spinal deformity, the odds of achieving "success" were: higher for hip (OR 4.6; 95% CI 2.5-8.5) and knee (OR 4.0; 95% CI 2.1-7.7) (no difference between spine subgroups) for "satisfaction with care"; higher for hip (OR 16.9; 95% CI 7.3-39.6), knee (OR 6.3; 95% CI 3.4-11.6), degenerative spondylolisthesis (OR 1.6; 95% CI 1.2-2.2), and herniated disc (OR 1.7; 95% CI 1.2-2.4) for "global treatment outcome"; and higher for hip (OR 13.8; 95% CI 8.8-21.6), knee (OR 5.3; 95% CI 3.6-7.8), degenerative spondylolisthesis (OR 1.6; 95% CI 1.3-2.1), and herniated disc (1.5; 95% CI 1.1-2.0) for "patient-acceptable symptom state". Patient-rated complications were the greatest in degenerative spinal deformity (29%) and the lowest in hip (18%).

The current study is the largest of its kind and the first to use a common, but joint-specific instrument to report patient-reported outcomes after surgery for degenerative disorders of the spine, hip, or knee. The findings provide a sobering account of the significantly poorer outcomes after spine surgery compared with large-joint replacement. Further work is required to hone the indications and patient selection criteria for spine surgery. The data should be used to lobby research funding-bodies, governmental agencies, industry, and charitable foundations to invest more in spine research/registries, in the hope of ultimately improving spine outcomes. These slides can be retrieved under Electronic Supplementary Material.

To determine whether fibromyalgia (FM) is more common in patients with primary Sjögren's syndrome (pSS) who complain of fatigue. The association and prevalence of fatigue and FM was recorded in a group of patients with pSS and a control group of lupus patients, a subset of whom had secondary Sjögren's syndrome (sSS). 74 patients with pSS and 216 patients with lupus were assessed with a questionnaire to identify the presence of fatigue and generalised pain. From the lupus group, in a subset of 117 lupus patients (from the Bloomsbury unit) those with sSS were identified. All patients were studied for the presence of FM. 50 of 74 patients with pSS (68%) reported fatigue-a prevalence significantly higher than in the lupus group (108/216 (50%); p<0.0087). Fatigue was present in 7/13 (54%) patients with SLE/sSS. FM was present in 9/74 patients with pSS (12%), compared with 11/216 lupus patients (5%), and in none of the patients with SLE/sSS. None of these values corresponds with previously reported figures of the incidence of FM in pSS.

The results show that fatigue in patients with pSS and sSS is not due to the coexistence of FM in most cases. A lower incidence in the United Kingdom of FM in patients with pSS was found than has been previously reported.

The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the function of RANKL in the matrix metabolism of the rat IVD. Sprague-Dawley, 12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected thoracolumbar discs were monolayer-cultured. RANK/RANKL/OPG expression in rat IVDs was examined using real-time polymerase chain reaction (PCR) and immunohistochemical analysis (cultured cells and IVD tissues). To examine the effect of interleukin-1β (IL-1β) stimulation on the mRNA levels of RANK, RANKL and OPG, the cells were cultured with or without recombinant human IL-1β (rhIL-1β). To evaluate the effect of RANKL on the mRNA expression of catabolic factors (IL-1β, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were cultured with RANKL in the presence or absence of rhIL-1β. The immunohistochemical expression of this system was also evaluated using human IVD tissues with different grades of degeneration. mRNA expression levels of RANK, RANKL, and OPG were clearly identified in AF, NP and CEP cells. Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes and/or cytoplasm of the three types of cells. The mRNA level of RANKL was significantly upregulated by treatment with rhIL-1β of the three types of cells. Treatment with RANKL without rhIL-1β did not induce significant effects on the mRNA expression of catabolic factors by AF, NP and CEP cells. However, the expression was significantly upregulated by stimulation with RANKL in the presence of rhIL-1β. There was a general trend for more RANK/RANKL/OPG-positive cells in human IVD tissues in an advanced stage of degeneration compared to an early stage.

Our study showed the possibility that the RANK/RANKL/OPG system may play a part in the process of intervertebral disc degeneration.

Bone pathologies as detected on MRI are associated with the presence of pain in knee osteoarthritis (OA). The authors examined whether bone attrition assessed on x-rays was associated with pain, stiffness and disability. The authors analysed x-rays of 1326 knees with OA from 783 individuals participating in the cross-sectional population-based Somerset and Avon Survey of Health. The diagnosis of OA was defined by the presence of osteophytes in anteroposterior (AP) or lateral views. Bone attrition was graded from 0 (no attrition) to 3 (severe attrition >10 mm) and Kellgren and Lawrence (K/L) scores were assigned on AP views. Logistic regression models adjusted for gender, age, body mass index, effusion and K/L scores were used to determine whether bone attrition was associated with pain, stiffness and disability. Pain was reported in 84 knees (74%) with radiographic bone attrition compared with 505 (42%) without bone attrition (adjusted OR 2.22, 95% CI 1.29 to 3.80). The adjusted OR was increased for day pain but not for night pain (p for interaction <0.001). Stiffness was reported for 85 knees with bone attrition (75%) and 437 knees without (36%) (adjusted OR 3.23, 95% CI 1.85 to 5.64). Disability was reported by 40 individuals with bone attrition (50%) and 140 individuals without (24%) (adjusted OR 2.09, 95% CI 1.19 to 3.68).

Bone attrition detected on conventional x-rays using a simple cheap technique is strongly associated with the presence of day pain, stiffness and disability in knee OA.

Our primary objective was to summarise the known effects of locally administered glucocorticoid on tendon tissue and tendon cells. We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines of the Medline database using specific search criteria. The search yielded 50 articles, which consisted of 13 human studies, 36 animal studies and one combined human/animal study. Histologically, there was a loss of collagen organisation (6 studies) and an increase in collagen necrosis (3 studies). The proliferation (8 studies) and viability (9 studies) of fibroblasts was reduced. Collagen synthesis was decreased in 17 studies. An increased inflammatory cell infiltrate was shown in 4 studies. Increased cellular toxicity was demonstrated by 3 studies. The mechanical properties of tendon were investigated by 18 studies. Descriptively, 6 of these studies showed a decrease in mechanical properties, 3 showed an increase, while the remaining 9 showed no significant change. A meta-analysis of the mechanical data revealed a significant deterioration in mechanical properties, with an overall effect size of -0.67 (95% CI = 0.01 to -1.33) (data from 9 studies).

Overall it is clear that the local administration of glucocorticoid has significant negative effects on tendon cells in vitro, including reduced cell viability, cell proliferation and collagen synthesis. There is increased collagen disorganisation and necrosis as shown by in vivo studies. The mechanical properties of tendon are also significantly reduced. This review supports the emerging clinical evidence that shows significant long-term harms to tendon tissue and cells associated with glucocorticoid injections.

To determine whether parvovirus B19 (B19) infection is associated with rheumatoid arthritis (RA). The polymerase chain reaction was applied to serum, cells isolated from synovial fluid, and synovial fluid. Enzyme immunoassay technique was used to detect antibodies against B19. Of 142 patients with early RA (onset of disease under one year) and 67 control patients, serological evidence of recent parvoviral infection was found in 4/135 and 2/62, respectively. However, no evidence for the presence of parvoviral DNA was observed in 18 synovial fluids, 21 samples of synovial fluid granulocytes or 40 sera, all obtained from 65 patients diagnosed with early RA.

Although there is published evidence of chronic rheumatoid-like arthropathy following acute parvovirus infection, our findings do not support the involvement of B19 in the aetiopathogenesis of RA.

To evaluate the long-term results of intertrochanteric osteotomies for posttraumatic arthritis after acetabular fractures. Retrospective study of eight patients who underwent a total of ten intertrochanteric osteotomies. Two patients underwent two osteotomies of the same hip. Academic Level I trauma center. Patients who developed posttraumatic hip arthritis after nonoperatively or operatively treated acetabulum fractures. The average age of patients was twenty-nine years (range 16 to 47 years). Patients underwent an intertrochanteric osteotomy to decrease contact pressures on damaged cartilage and to lessen contractures. All intertrochanteric osteotomies at our institution were performed by the senior author (R.K.M.). The Merle d'Aubigné score and the Thompson and Epstein score were determined based on each patient's last follow-up. At an average long-term follow-up of 10.2 years (range 2.5 to 22 years), all eight patients had a significant improvement based on the Merle d'Aubigné score (average increase 5.3 points). Less improvement was observed according to the Thompson and Epstein score, which is consistent with the fact that radiographic appearance is weighted disproportionally in that score.

Because most acetabular fracture patients are relatively young, the option of joint replacement for posttraumatic hip arthritis is less than ideal. However, we have observed significant improvement in hip function with a decrease in pain and disability when such patients are treated with an intertochanteric osteotomy.

Biologics are an important therapeutic option for treating patients with rheumatoid arthritis (RA). However, they are associated with rare but severe adverse events such as serious infections, lymphoma, or chronic heart failure. In addition, dosing regimens and routes of administration differ substantially among biologics. In a systematic review, we assessed the comparative efficacy and safety of biologic agents for RA. We searched electronic databases up to May 2006. We limited evidence to controlled trials for efficacy but included observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, and quality of life. Given the paucity of head-to-head evidence, we conducted adjusted, indirect comparisons of placebo-controlled trials. Twenty-six controlled trials provided efficacy data; 18 additional studies assessed safety. The only evidence directly comparing 2 biologic agents was a nonrandomized, open-label trial that found no differences in effectiveness and safety between etanercept and infliximab. Adjusted indirect comparisons indicate no significant differences in efficacy between anti-tumor necrosis factor (TNF) drugs. However, anti-TNF drugs appear to be more efficacious than anakinra, although not all comparisons reached statistical significance. Because of the lack of sound longterm safety data, evidence is insufficient to draw firm conclusions about the comparative safety of biologics.

Anti-TNF drugs appear to be more efficacious than anakinra but do not differ significantly among each other. Clinical considerations such as comorbidities, route of administration, dosing regimens, and specific side effect profiles may guide the choice of an anti-TNF drug.

SIRT1 is known to inhibit apoptosis and to promote survival of various types of cells. However, the roles of SIRT1 in apoptosis of human chondrocytes have never been reported. We undertook this study to investigate the relationship of SIRT1 to apoptosis of human chondrocytes, which is a characteristic feature of osteoarthritis (OA). The expression of SIRT1 in human chondrocytes was examined by reverse transcription-polymerase chain reaction, immunoblotting, and immunohistology of human cartilage samples. The expression of SIRT1 under catabolic, mechanical, and nutritional stresses was investigated by immunoblotting. To examine the effect of SIRT1 on apoptosis, SIRT1 was inhibited by small interfering RNA (siRNA) and activated by resveratrol during nitric oxide (NO)-induced apoptosis. TUNEL staining and immunoblotting of cleaved poly(ADP-ribose) polymerase (PARP) were performed to detect apoptosis. To examine the mechanisms of apoptosis, we used immunoblotting to determine the levels of cleaved caspases and mitochondria-related apoptotic signaling proteins, Bax and Bcl-2, in the mitochondrial fraction. SIRT1 expression was confirmed in human chondrocytes and human cartilage samples. All catabolic, mechanical, and nutritional stresses inhibited SIRT1 expression. SIRT1 inhibition by siRNA for SIRT1 increased the percentage of TUNEL-positive cells and increased the amounts of cleaved PARP and cleaved caspases 3 and 9 induced by NO. In contrast, treatment with resveratrol decreased the percentage of TUNEL-positive cells and decreased the amounts of cleaved PARP and cleaved caspases 3 and 9 induced by NO. Furthermore, in the mitochondrial fraction, SIRT1 inhibition by siRNA for SIRT1 increased the amount of Bax but reduced the amount of Bcl-2, while resveratrol reduced the amount of Bax but increased the amount of Bcl-2.

These results indicate that SIRT1 regulates apoptosis in human chondrocytes through the modulation of mitochondria-related apoptotic signals. Further research on SIRT1 might contribute to resolving the pathogenesis of OA.

Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges. Together with the transverse metatarsal ligament they prevent splaying of the forefoot and subluxation of the MTP joints. Damage to the plantar plates is a plausible mechanism therefore, through which the forefoot presentation, commonly described as 'walking on pebbles', may develop in patients with RA. The aims of this study were to investigate the relationship between plantar plate pathology and clinical, biomechanical and plain radiography findings in the painful forefoot of patients with RA. Secondly, to compare plantar plate pathology at the symptomatic lesser (2nd-5th) MTP joints in patients with RA, with a group of healthy age and gender matched control subjects without foot pain. In 41 patients with RA and ten control subjects the forefoot was imaged using 3T MRI. Intermediate weighted fat-suppressed sagittal and short axis sequences were acquired through the lesser MTP joints. Images were read prospectively by two radiologists and consensus reached. Plantar plate pathology in patients with RA was compared with control subjects. Multivariable multilevel modelling was used to assess the association between plantar plate pathology and the clinical, biomechanical and plain radiography findings. There were significant differences between control subjects and patients with RA in the presence of plantar plate pathology at the lesser MTP joints. No substantive or statistically significant associations were found between plantar plate pathology and clinical and biomechanical findings. The presence of plantar plate pathology was independently associated with an increase in the odds of erosion (OR = 52.50 [8.38-326.97], p < 0.001).

The distribution of plantar plate pathology at the lesser MTP joints in healthy control subjects differs to that seen in patients with RA who have the consequence of inflammatory disease in the forefoot. Longitudinal follow-up is required to determine the mechanism and presentation of plantar plate pathology in the painful forefoot of patients with RA.

To describe the clinical and epidemiological characteristics of patients with posterior scleritis, and to analyze the response to treatment and time to relapse. Retrospective study of 114 cases of posterior scleritis from two tertiary care, university-affiliated, referral centers in the United Kingdom and India between 2004 and 2013. Data included sociodemographic factors, medical history, clinical, laboratory and ultrasound findings, therapies, and outcomes. LogMAR visual acuity at presentation and final visit and time to relapse were the main outcome measures. The mean age was 45.9 ± 16.8 years, 71.1% were women, and 18 (15.8%) patients had bilateral disease; 71 (62.3%) cases were idiopathic. Rheumatoid polyarthritis (12.28%), systemic lupus erythematous (4.38%) and pANCA(+) systemic vasculitis (5.26%) were the most frequent systemic associations. VA improved by 0.24 ± 0.36 LogMAR between presentation and last follow up (p < 0.001). The median time to remission was 210 days (95% CI: 184-256 days). Recurrences after remission were observed in 36.63%. The observed incidence rate of posterior scleritis relapse after remission was 15.81% per person-year (95% CI: 11.78-20.77%). Systemic disease was present significantly in patients more than 50 years of age (OR = 2.29; 95% CI: 1.01-5.17; p = 0.044).

Posterior scleritis is an uncommon disease causing pain and visual loss. In around 40% of the cases, it can be associated with other systemic diseases. Median time to relapse was 210 days. Relapses may occur in around 1 in 3 patients, with an incidence rate of 15.81% per person/year.

Clinically evident tenosynovitis can be seen in established rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA, contributes to typical RA symptoms (including joint swelling) and is infrequent in healthy controls. Imaging-detectable tenosynovitis is often not recognisable at joint examination, hence its prevalence can therefore be underestimated. We hypothesised that if MRI-detectable tenosynovitis is a true RA feature, the sensitivity for RA is high, in both anti-citrullinated protein antibodies (ACPA)-positive and ACPA-negative RA, and lower in other diseases that are associated with enthesitis (such as spondyloarthritis (SpA) and psoriatic arthritis (PsA)). So far, no large MRI study addressed these questions. Consecutive patients with early arthritis (n=1211) from one healthcare region underwent contrast-enhanced 1.5T MRI of hand and foot at diagnosis. MRIs were scored for synovitis and tenosynovitis by two readers blinded for clinical data. All included patients with ACPA-positive RA (n=250), ACPA-negative RA (n=282), PsA (n=88), peripheral SpA (n=24), reactive arthritis (n=30) and self-limiting undifferentiated arthritis (UA; n=76) were studied. Sensitivity was calculated. The sensitivity of tenosynovitis in RA was 85%; 88% for ACPA-positive RA and 82% for and ACPA-negative RA (p=0.19). The sensitivity for RA was significantly higher than for PsA (65%; p=0.001), SpA (53%; p<0.001), reactive arthritis (36%; p<0.001) and self-limiting UA (42%; p<0.001). The observed sensitivity of MRI synovitis was 91% in RA and ranged from 83% to 54% in other groups.

MRI-detected tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA. This supports that both juxta-articular (tenosynovitis) and intra-articular synovial involvement is characteristic of RA.

Genetic factors are thought to be crucial in the pathogenesis of ankylosing spondylitis. Transforming growth factor beta 1 (TGF beta 1) is a multifunctional cytokine that plays a key role in inflammation. Two functional single nucleotide polymorphisms (SNPs) in the TGFB1 gene have been described: TGFB1 T869C and TGFB1 G915C. To determine whether these SNPs contribute to ankylosing spondylitis susceptibility or its disease characteristics. Genomic DNA was isolated from the peripheral blood of 134 patients with ankylosing spondylitis and 194 healthy blood donors. All subjects were unrelated and of white Dutch ethnicity. The diagnosis of ankylosing spondylitis was made according to the modified New York criteria. The TGFB1 T869C and TGFB1 G915C SNPs were genotyped by a polymerase chain reaction-single strand conformation polymorphism haplotyping method. No significant differences were found between patients and controls in genotype, allele, and haplotype frequencies or in the carrier rate of the rare alleles of the TGFB1 T869C and TGFB1 G915C SNPs.

TGFB1 T869C and TGFB1 G915C SNPs are not major factors in the susceptibility to ankylosing spondylitis or its disease characteristics.

The use of nonsteroidal antiinflammatory drug (NSAID) therapy in osteoarthritis (OA) is controversial because of suggestions that pure analgesics can be as effective as NSAID for pain relief. In addition, there is incomplete information whether antiinflammatory effects have any longterm benefit in OA. NSAID have been known to affect synovial fluid (SF) prostaglandins in rheumatoid arthritis. We describe the first examination of the effect of an NSAID, etodolac, on SF prostaglandins, cytokines, and cells in OA. Joint fluids were studied before and 2 weeks after initiation of therapy with etodolac 400 mg tid. Leukocyte counts, prostaglandin, interleukin 6, and tumor necrosis factor were measured. Pretreatment features of SF did not predict clinical response. We found no change in the relatively low leukocyte counts. However, SF prostaglandin levels and interleukin 6 levels were significantly decreased and tumor necrosis factor alpha levels were increased after therapy with NSAID.

This NSAID had potentially important local effects that could be either beneficial or deleterious. Further studies on effects of this and other NSAID on a broader variety of SF and synovial cytokines may help predict longterm effects of NSAID on progression of OA.

To determine the long-term effectiveness (>/=6 months after treatment) of exercise therapy on pain, physical function, and patient global assessment of effectiveness in patients with osteoarthritis (OA) of the hip and/or knee. We conducted an extensive literature search in PubMed, EMBase, CINAHL, SciSearch, PEDro, and the Cochrane Central Register of Controlled Trials. Both randomized clinical trials and controlled clinical trials on the long-term effectiveness of exercise therapy were included. The followup assessments were at least 6 months after treatment ended. Methodologic quality was independently assessed by 2 reviewers. Effect estimates were calculated and a best evidence synthesis was performed based on design, methodologic quality, and statistical significance of findings. Five high-quality and 6 low-quality randomized clinical trials were included. Strong evidence was found for no long-term effectiveness on pain and self-reported physical function, moderate evidence for long-term effectiveness on patient global assessment of effectiveness, and conflicting evidence for observed physical function. For exercise programs with additional booster sessions, moderate evidence was found for long-term effectiveness on pain, self-reported physical function, and observed physical function.

The positive posttreatment effects of exercise therapy on pain and physical function in patients with OA of the hip and/or knee are not sustained in the long term. Long-term effectiveness was only found for patient global assessment of effectiveness. However, additional booster sessions after the treatment period positively influenced maintenance of beneficial posttreatment effects on pain and physical function in the long term.

To determine the prevalence and clinical significance of hepatitis C virus (HCV) infection in a large cohort of patients with "primary' Sjögren's syndrome (SS). 90 consecutive patients (83 female and seven male) were included, with a mean age of 62 years (range 31-80) who prospectively visited our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Serum from all patients was tested for antibodies to HCV by third generation enzyme linked immunoassay and positivity was confirmed by polymerase chain reaction. Antibodies to HCV were present in 13 (14%) patients with 'primary' SS. When compared with patients without HCV infection, patients with HCV infection presented a higher prevalence of hepatic involvement, (100% v 8%, p < 0.05). Transcutaneous liver biopsy was performed in five patients with HCV infection, and specimens obtained showed in all cases a chronic active hepatitis with varying degrees of portal inflammation.

HCV infection is frequent in patients with "primary' SS and liver involvement is presented in all these patients. The possible pathogenic role of HCV infection in these patients is still unclear.

To examine seasonality and long-term trends in the incidence and prevalence of gout. A retrospective study (1994-2007) using routinely collected surveillance data from the Royal College of General Practitioners Weekly Returns Service sentinel general practice network in England and Wales. New cases and acute attacks of gout per 10,000 population were calculated for age groups 0-44, 45-64, 65-74 and > or =75 years. Long-term trends of annual incidence were assessed by regression analysis. Seasonality indices were calculated using 4-weekly data, and the relative risk of gout incidence during the summer was estimated. Annual prevalence was estimated from the consulting patient population (2001-7) and from prescribing data on defined daily doses (DDD) of allopurinol (2003-7). The annual incidence rate of new gout cases was stable over the period 1998-2007; acute attacks decreased on average 4% per annum. New gout cases and acute attacks combined into 4-weekly incidence rates peaked during the "summer" period of each year. There was an increased risk of gout diagnosis during summer months (late April to mid-September; odds ratio 1.22, 95% CI 1.18 to 1.26). The annual prevalence of gout in 2001-7 was 0.46%, with highest rates in men > or =75 years (2.57%). Estimated prevalence based on a DDD of 400 mg allopurinol was 0.37%.

The incidence of gout is seasonal. This has implications for the management of patients who currently have gout, and for those who are at risk of future attacks. The decreasing trend in the incidence of acute attacks suggests that patient management is improving.

Progesterone receptor (PR) affects immunomodulation, and lack of PR in osteoprogenitor cells primarily affects pathways associated with immunomodulation, especially in males. In this study, we selectively deleted PR from osteoprogenitor cells using Prx1-Cre to evaluate the tissue-specific effects of PR on the pathegenesis of inflammatary arthritis (IA). Collagen-induced arthritis (CIA) was used as an IA animal model. Both male and female PR Bone erosions developed in both paw joints in 37.5% and 41.7% of the WT and PR

The presence of PR in osteoprogenitor cells decreased the development of collagen-induced arthritis and might help to explain the sex differences observed in human inflammatory arthritis.

Many symptoms of primary immunodeficiency (PI) disease can be successfully managed with intravenous immunoglobulin infusion. Although survival rates and prognosis have greatly improved, children with PI disease are still at risk for physical, social, and psychological problems owing to their chronic health condition. However, to our knowledge, there are no empirical data concerning health-related quality of life (HRQOL) in children with PI disease receiving intravenous immunoglobulin infusion. To compare parental reports of HRQOL of children with PI disease receiving intravenous immunoglobulin infusion with children with juvenile idiopathic arthritis (JIA) and a healthy sample. Demographic, illness, and HRQOL data were collected from parents of 4- to 18-year-old children with PI disease (n = 36), children with JIA (n = 36), and healthy children (n = 36). The HRQOL was evaluated using the Child Health Questionnaire-Parent Report version. Compared with children with JIA, children with PI disease were similar in many aspects of their HRQOL. However, parents of children with PI disease reported greater limitations in their personal time, poorer general health of their children, greater limitations in their children's physical functioning and family activities, and less bodily pain than children with JIA. In contrast, children with PI disease scored lower on most HRQOL domains compared with healthy children.

Children with PI disease experience similar HRQOL to children with JIA and poorer HRQOL than healthy children, indicating potential areas to be addressed by future medical and psychosocial interventions.

Osteoarthritis (OA) is the leading cause of musculoskeletal pain and functional disability worldwide, affecting a growing number of individuals in the western society. Despite various conservative and interventional treatment approaches, the overall management of the condition is problematic, and pain-the major clinical problem of the disease-remains sub-optimally controlled. The objectives of this review are to present the pathophysiologic mechanisms underlying the complexity of pain in OA and to discuss the challenges for new treatment strategies aiming to translate experimental findings into daily clinical practice. A narrative literature review of studies investigating the existence of a neuropathic component in OA pain was conducted. We searched PubMed, Embase and Scopus for English language publications. A hand-search of reference lists of relevant studies was also performed. Recent advances have shed additional light on the pathophysiology of osteoarthritic pain, highlighting the contribution of central pain pathways together with the sensitisation of peripheral joint receptors and changes of the nociceptive process induced by local joint inflammation and structural bone tissue changes. Thus, a neuropathic pain component may be predominant in individuals with minor joint changes but with high levels of pain refractory to analgesic treatment, providing an alternative explanation for osteoarthritic pain perception.

A growing amount of evidence suggests that the pain in OA has a neuropathic component in some patients. The deeper understanding of multiple mechanisms of OA pain has led to the use of centrally acting medicines that may have a benefit on alleviating osteoarthritic pain. The ineffective pain management and the increasing rates of disability associated with OA mandate for change in our treatment paradigm.

To analyse the short-term effects of kinesio taping (KT) with tension (KTT) or without tension (KTNT) in older women with knee osteoarthritis (KOA), and compare them to controls who did not receive KT. Randomised controlled trial. University physiotherapy school clinic. Forty-five older women (fifteen participants per group) with 66.8 (±5.6) years and clinical diagnosis of KOA were assessed pre, post and 3 days after intervention. Participants were randomly allocated to KTT, who received two simultaneous applications of KT with tension on the knee and rectus femoris; KTNT, who received the same application as the KTT group, but without tension and a control group that attended a class on KOA. Primary outcome was pain intensity and secondary outcomes were knee-related health status, functional capacity, muscle strength and global rating of change. No between-group differences were observed in pain after the first intervention (KTT vs KTNT: mean difference (MD), -1.8 points; 95% CI -4.2 to 0.5; KTT vs control: MD, -1.2 points; 95% CI -3.6 to 1.2; KTNT vs control: MD, 0.66 points; 95% CI -1.7 to 3.0) or 3 days later (KTT vs KTNT: MD, -1.3 points; 95% CI -3.7 to 1.0; KTT vs control: MD, 0.13 points; 95% CI -2.2 to 2.5; KTNT vs control: MD, 1.4 points; 95% CI -0.9 to 3.8). The lack of between-group differences was also found for secondary outcomes. NCT03624075.

The short

Gout is the most prevalent inflammatory arthritis in developed countries. A gout flare is mediated by phagocytosis of monosodium urate crystals by macrophages and neutrophils leading to subsequent activation of neutrophils contributing to synovitis, local joint destruction, and systemic inflammation. We hypothesize that biomarkers from activated neutrophils reflect gout disease activity. The objective of this study therefore was to investigate the clinical utility of neutrophil-derived biomarkers in gout disease activity. Plasma samples from 75 gout patients participating in the "Reade gout cohort Amsterdam" were compared with 30 healthy controls (HC). Levels of neutrophil extracellular traps (NETs) and neutrophil activation markers (calprotectin and peroxidase activity) were analyzed by ELISA and fluorimetry, compared to healthy controls, and related to markers of inflammation and disease activity. Levels of NETs, as well as neutrophil activation markers, were increased in gout patients compared to HC (p < 0.01). No associations were found between markers of cell death (cell-free DNA and NETs) and disease activity. Cell-free levels of genomic DNA were elevated among gout patients compared to HC (p < 0.05) and related to the number of gout attacks in the last year (β = 0.35, p < 0.01). Peroxidase activity correlated with disease activity (RAPID score: β = 0.49, p < 0.01, MHAQ: β = 0.66, p < 0.01) and inflammation markers (CRP: β = 0.25, p = 0.04, and ESR: β = 0.57, p < 0.001). Involvement of ankle or wrist resulted in significant higher peroxidase levels compared to mono-articular disease (β = 0.34, p < 0.01), indicating that peroxidase activity is a marker of poly-articular gout. Calprotectin (S100A8/A9) correlated with the inflammation marker CRP (β = 0.23, p = 0.05) and morning stiffness, especially in patients with chronic poly-articular gout (β = 0.71, p < 0.01).

Neutrophil activation markers are associated with characteristics of active, polyarticular gout. Furthermore, NETs are present in the peripheral blood of gout patients. However, NETs do not associate with markers of disease activity or inflammation. Future research should point out if peroxidase and calprotectin could be used in clinical practice as biomarkers for monitoring gout disease activity.

The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the experimental dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action. Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred dogs. There were two experimental groups (n=6-7 dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of dogs was performed. Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p<0.02) of osteoarthritis cartilage lesions. BCD treatment also significantly reduced the osteoarthritis chondrocyte level of key inflammatory and catabolic factors (iNOS, p=0.009 and MMP-13, p=0.003) as well as the level of PAR-2 (p=0.03). Dogs treated with BCD showed a significant improvement in peak vertical force measured at 8 weeks (p<0.05).

Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.

To investigate perceived exertion at work in women with fibromyalgia. A controlled cross-sectional multi-centre study. Seventy-three women with fibromyalgia and 73 healthy women matched by occupation and physical workload were compared in terms of perceived exertion at work (0-14), muscle strength, 6-min walk test, symptoms rated by Fibromyalgia Impact Questionnaire (FIQ), work status (25-100%), fear avoidance work beliefs (0-42), physical activity at work (7-21) and physical workload (1-5). Spearman's correlation coefficient and linear regression analysis were conducted. Perceived exertion at work was significantly higher in the fibromyalgia group than in the reference group (p = 0.002), while physical activity at work did not differ between the groups. Physical capacity was lower and symptom severity higher in fibromyalgia compared with references (p < 0.05). In fibromyalgia, perceived exertion at work showed moderate correlation with physical activity at work, physical workload and fear avoidance work beliefs (rs = 0.53-0.65, p < 0.001) and a fair correlation with anxiety (rs = 0.26, p = 0.027). Regression analysis indicated that the physical activity at work and fear avoidance work beliefs explained 50% of the perceived exertion at work.

Women with fibromyalgia perceive an elevated exertion at work, which is associated with physical work-related factors and factors related to fear and anxiety.

The role of increased femoral antetorsion (femAT) as a contributor to patellofemoral (PF) osteoarthritis (OA) is unknown. The purpose of this study was to investigate whether increased femAT was associated with advanced cartilage degeneration in the lateral PF joint. Patients who underwent complete radiographic workup for surgical intervention due to OA in any knee joint compartment were included. Cartilage morphology according to the International Cartilage Repair Society (ICRS) cartilage lesion classification system in the PF joint, femoral and tibial torsion, frontal leg axis, and tibial tuberosity-trochlear groove (TT-TG) distance were assessed. Increased femAT was defined as  > 20° according to previous reports. A total of 144 patients were included. Ninety-seven patients had a femAT of  < 20° and 45 of  > 20°. A significant odds ratio (OR) was found for lateral retropatellar (OR 3.5; p = 0.02) ICRS grade 3 and 4 cartilage degeneration and increased femAT  ≥ 20°. In the medial PF compartment, increased femAT had an inverse effect (OR 0.16; p = 0.01). No significant ORs were found for TT-TG distance, tibial torsion, or leg axis. The lateral retropatellar ICRS grade showed a linear correlation to increased femAT values. In valgus knees, isolated lateral PF OA had an even more pronounced correlation to increased femAT (p = 0.004). Cohort study: Level III.

Increased femAT showed higher grades of lateral retropatellar cartilage degeneration, which was even more pronounced in valgus knees.

To determine the proportion of responders in two identical osteoarthritis (OA) trials using Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria and to assess the comparability and correlation of individual component measurements. Data were pooled from two identical 26-week, double-blind, randomized, parallel, multicenter trials comparing once daily etoricoxib 30 mg (N=475), celecoxib 200 mg (N=488), and placebo (N=244) in patients with OA of the knee or hip. OMERACT-OARSI criteria were (1) improvement in pain or physical function > or =50% and an absolute change > or =20 mm on a 100-mm visual analog scale (VAS); or (2) improvement of > or =20% and with an absolute change > or =10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment. Correlations were assessed between endpoints measured as time-weighted average change from baseline over 12 weeks using Pearson's correlation coefficient (r). There were significantly greater proportions of responders in the etoricoxib (66.2%) and celecoxib (63.5%) groups compared with the placebo group (43.0%; P<0.001). There was no difference between the two active treatment groups. There was high correlation between pain and physical function (r=0.903), pain and global assessment (r=0.778), and physical function and global assessment (r=0.820). There was high sensitivity (75-87%) and specificity (80-96%) for changes in individual component measurements to predict OMERACT-OARSI responders.

Significantly more patients receiving etoricoxib or celecoxib than placebo were OMERACT-OARSI responders. The high correlation between individual scales composing this composite response measurement suggests some redundancies between individual components, particularly between pain and physical function.

The aim of our study was to evaluate the association between patellar alignment (using standard MRI images of extended knees) and MRI indices of patellofemoral (PF) osteoarthritis (OA) features. In this cross-sectional observational study, subjects were recruited to participate in the Boston Osteoarthritis of the Knee Study (BOKS). The association of patellar alignment [patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA) and bisect offset (BO)] with measures of PF OA [cartilage morphology and bone marrow lesion (BML) in the medial and lateral PF compartment] were examined using a logistic regression model while adjusting for age, sex and BMI. Study sample comprised 126 males (mean age 68.0, BMI 31.2) and 87 females (mean age 64.7, BMI 31.6). All measurements of patellar alignment were statistically significantly associated with cartilage morphology and BML in the lateral compartment of PF joint. PLR and SA were significantly associated with medial cartilage loss. With increasing PLR there was an increased prevalence of lateral and medial cartilage loss as well as of lateral BML. Increasing SA was positively associated with increased lateral and medial cartilage loss and lateral BML. LPTA range was negatively associated with lateral cartilage loss and BML. More laterally displaced patella (higher BO) was associated with increased lateral cartilage loss and BML.

The results of our study clearly indicated that patellar alignment is associated with manifestations of PF OA such as cartilage thickness loss and BML.

Hip osteoarthritis (OA) is a frequent cause of pain and disability in Western countries, but the disorder is less common in Japan. A case-control study in Britain found obesity, hip injury, and occupational lifting to be associated with hip OA among men and women. However, there are few epidemiological studies concerning factors associated with hip OA in Japan. We performed a comparable case-control study of the disorder in Japan, and contrasted the findings with those from Britain. The study was carried out in 2 health districts in Wakayama Prefecture, Japan. Cases were men and women aged > or = 45 years listed for total hip arthroplasty due to OA over one year, and who did not have an established cause of secondary OA (e.g., rheumatoid arthritis, ankylosing spondylitis). For each case, a control was selected randomly from the general population and was individually matched to the case for age, sex, and district of residence. Cases and controls were interviewed with a structured questionnaire about medical history, physical activity, socioeconomic factors, and occupation. Measurements were made of height and weight. One hundred fourteen cases (103 women, 11 men) were compared with 114 controls. We found no relationship between obesity and hip OA (OR = 1.0, 95% CI 0.5-1.9; highest vs lowest thirds of distribution of body mass index). There was, however, a statistically significant association between occupational lifting and hip OA, such that regular lifting of 25 kg in the individual's first job (OR = 3.6, 95% CI 1.3-9.7) or of 50 kg in their main job (OR = 4.0, 95% CI 1.1-14.2) was associated with increased risk of hip OA. These associations remained after adjustment for potential confounding variables. In contrast, those subjects who spent > 2 h each day sitting during their first job were significantly less likely to have the disorder (crude OR = 0.5, 95% CI 0.3-0.9). This association also remained statistically significant after adjustment for potential risk factors.

Our findings support the hypothesis that occupational physical activity, particularly the lifting of very heavy loads in the workplace at regular intervals, predisposes to hip OA in both Britain and Japan. The lack of association between obesity or hand involvement and hip OA in Japan suggests that the contribution of constitutional and mechanical risk factors to this disorder might differ in different populations. However, attention to manual handling in the workplace would appear an important aspect of preventive strategies against hip OA in Western and Oriental populations.

To compare median nerve conduction velocity measured using a new, portable electroneurometer with measurements made using conventional hospital nerve conduction apparatus. Twenty five patients were studied who were consecutively referred to a hospital neurophysiology department with a clinical diagnosis of carpal tunnel syndrome. Sensory and motor latencies for the median nerve at the wrist were measured bilaterally using the portable electroneurometer and a Medilec MS 92 hospital apparatus operated by a trained technician. There was strong agreement between motor latency values obtained by the two techniques (r = 0.89, p < 0.001; mean difference -0.03 ms, limits of agreement -0.33 to 0.27 ms). Sensory latencies were less easy to detect with the electroneurometer, and correlated less well with the hospital apparatus (r = 0.78, p < 0.001; mean difference -0.16 ms, limits of agreement -0.50 to 0.18 ms).

The portable electroneurometer provides a convenient, rapid, and inexpensive means of assessing median nerve conduction velocity at the wrist. Measurements of motor latency obtained with this new instrument agree more strongly with those made by conventional apparatus than do measurements of sensory latency. Although the utility of the instrument in clinical practice will be limited, it provides a helpful tool in epidemiological studies of carpal tunnel syndrome.

To compare health-related quality of life (HR-QOL), employment and disability of primary and secondary SS (pSS and sSS, respectively) patients with the general Dutch population. HR-QOL, employment and disability were assessed in SS patients regularly attending the University Medical Center Groningen (n = 235). HR-QOL, employment and disability were evaluated with the Short Form-36 questionnaire (SF-36) and an employment and disability questionnaire. Results were compared with Dutch population data (matched for sex and age). Demographical and clinical data associated with HR-QOL, employment and disability were assessed. Response rate was 83%. SS patients scored lower on HR-QOL than the general Dutch population. sSS patients scored lower on physical functioning, bodily pain and general health than pSS patients. Predictors for reduced HR-QOL were fatigue, tendomyalgia, articular involvement, use of artificial saliva, use of anti-depressants, comorbidity, male sex and eligibility for disability compensation (DC). Employment was lower and DC rates were higher in SS patients compared with the Dutch population.

SS has a large impact on HR-QOL, employment and disability.

To describe the frequency, duration, and management of flares as reported by patients with rheumatoid arthritis (RA). Data were collected in a prospective observational study of patients with RA recruited from a single academic center and treated according to the rheumatologists' discretion. Every 6 months, patients reported the number and duration of RA flares and described how these were managed in terms of adding or changing medication and use of nonpharmacologic strategies. Of patients who reported flares at least once during the study, 74% reported having flares 6 months prior to study entry and 59% reported flares prior to the first 6-month visit. At subsequent visits, 54-57% reported having > 1 flare. Thirty percent of patients in remission reported flares. Flare duration lasted ≥ 2 weeks in 30%, 1-2 weeks in 13%, and < 1 week in 57%. Forty percent reported medication changes at the time of their flare; 16% changed medication and used nonpharmacologic strategies and 26% of patients reported no changes in treatment as a result of flares. Longer duration of flare was associated with changes in disease-modifying therapy.

Patients with RA experienced flares more often when noted to be in higher disease activity states than when in remission and reported changes in disease-modifying antirheumatic drugs or biologics more frequently when flares were of longer duration. There is a need to prospectively study symptom intensity and duration of flare in relation to disease activity and consider self-management strategies in the development of a measure of flare.

Patients with rheumatoid arthritis are at increased risk of death from cardiovascular disease (CVD). This risk is influenced by the inflammatory activity of the rheumatoid arthritis as well as by traditional risk factors for CVD. However, little is known about whether or to what extent hereditary factors for CVD contribute additional risk in patients with rheumatoid arthritis. To assess the clinical impact of a parental history of CVD in patients with rheumatoid arthritis. Population based cohort study of 10,805 Swedish patients with rheumatoid arthritis aged 16-67 years during follow up (1990-2000). Parents, and cardiovascular deaths among patients and parents, were identified through register linkages. Relative risk of death v the general population was assessed using standardised mortality ratios (SMR), which were compared by Poisson regression. Rheumatoid patients with a parental history of fatal CVD had an SMR of death from CVD of 2.9 (95% confidence interval, 2.5 to 3.4). By contrast, rheumatoid patients without a parental history of fatal CVD had an SMR of 1.7 (1.2 to 2.3). A parental death from CVD was associated with a 70% increase in the risk of fatal CVD in rheumatoid arthritis (SMR ratio = 1.7 (1.2 to 2.4), and an increase in the 10 year mortality from CVD from 5% to 10% in men and from 2% to 4% in women aged 50 to 67 years.

Parental history of death from CVD is an important (and easily assessable) risk factor for fatal CVD in rheumatoid arthritis.

Fatigue is a major symptom of rheumatoid arthritis (RA), the most common chronic inflammatory joint disease. The present study explored patients' experiences of RA fatigue to elucidate unique elements and management strategies. This single site study recruited tumour necrosis factor-α inhibitor (TNFi)-treated RA patients with a moderate/good response in disease activity and persistent moderate/greater fatigue on a five-point verbal rating scale. This qualitative descriptive design used semi-structured questions, individual interviews and content analysis of narrative data. Ten patients were interviewed (six women), with age and disease duration ranges of 44-75 and 6-36 years, respectively. Perceptions of the RA fatigue experience generated four categories (experiencing a distinct, yet seldom discussed RA symptom; seeking an explanation for fatigue; being in an incapacitating state; and trying to manage) and eight subcategories. Fatigue was newly identified as a distinct part of the entity of RA. While patients proposed many plausible root causes, the only rational explanation for the nature of this fatigue was that it was integral to their RA. Singularly, fatigue contributed considerably to RA-imposed lifestyle restrictions. Patients had learnt to accommodate and self-manage fatigue in the absence of professional input. Novel management strategies proposed included patients talking about the nature of RA fatigue with others and the need for staff to alert patients to this distinct symptom of RA.

Fatigue, branded as a distinct symptom of RA, exerted an identifiable impact on patients. Fatigue is potentially amenable to modification; talking about fatigue was proposed as a novel management strategy. Copyright © 2016 John Wiley & Sons, Ltd.

To compare the hemodynamic and ventilatory responses to autonomic challenge evoked by upright tilt table testing in patients with chronic fatigue syndrome (CFS) to healthy individuals. Thirty-two consecutive patients with CFS and 32 healthy volunteers were evaluated with the aid of the recently introduced capnography head-up tilt test (CHUTT). The main outcome measures were values of blood pressure (BP), heart rate (HR), respiratory rate (RR), and end-tidal pressure of co2 (ETPco2) recorded during recumbence and tilt. In addition, the end points of vasodepressor and cardioinhibitory reactions, hyperventilation (defined by ETPco2 <25 mm Hg) and the postural tachycardia syndrome, were recorded. The BP, HR, RR, and ETPco2 recorded during recumbence were similar in both groups. During tilt, patients with CFS developed significantly lower systolic BP, diastolic BP, and ETPco2, and a significant rise in HR and RR (P<.01). In CFS patients, the postural tachycardia syndrome occurred in 44%, vasodepressor reaction in 41%, cardioinhibitory reaction in 13%, and hyperventilation in 31% of cases. One or more end points of the CHUTT were reached in 78% of patients with CFS but in none of the controls (P<.0001).

In most patients with CFS, a spectrum of abnormal homeostatic reactions is diagnosed with the aid of the CHUTT. Data provided by the CHUTT may reinforce the clinical diagnosis by adding objective and unbiased criteria to the subjective assessment of CFS.

The pathogenesis of giant cell arteritis (GCA) remains unclear. T IL-12 and IL-23 expression were quantified by immunohistochemistry in temporal artery biopsies (TABs). Temporal artery (TA) explant, peripheral blood mononuclear cell (PBMC) and myofibroblast outgrowth culture models were established. PBMCs and TA explants were cultured for 24 hours in the presence or absence of IL-12 (50 ng/mL) or IL-23 (10 ng/mL). Gene expression in TA was quantified by real-time PCR and cytokine secretion by ELISA. Myofibroblast outgrowths were quantified following 28-day culture. Immunohistochemistry demonstrated increased expression of interleukin 12p35 (IL-12p35) and interleukin 23p19 (IL-23p19) in biopsy-positive TAs, localised to inflammatory cells. IL-12p35 TA expression was significantly increased in those with cranial ischaemic complications (p=0.026) and large vessel vasculitis (p=0.006). IL-23p19 TA expression was increased in those with two or more relapses (p=0.007). In PBMC cultures, exogenous IL-12 significantly increased interleukin 6 (IL-6) (p=0.009), interleukin 22 (IL-22) (p=0.003) and interferon γ (IFN-γ) (p=0.0001) and decreased interleukin 8 (IL-8) (p=0.0006) secretion, while exogenous IL-23 significantly increased IL-6 (p=0.029), IL-22 (p=0.001), interleukin 17A (IL-17A) (p=0.0003) and interleukin 17F (IL-17F) (p=0.012) secretion. In ex vivo TA explants, IL-23 significantly increased gene expression of IL-8 (p=0.0001) and CCL-20 (p=0.027) and protein expression of IL-6 (p=0.002) and IL-8 (p=0.004). IL-12 (p=0.0005) and IL-23 (p<0.0001) stimulation increased the quantity of myofibroblast outgrowths from TABs.

IL-12 and IL-23 play central and distinct roles in stimulating inflammatory and proliferative pathways relevant to GCA pathogenesis.

To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. This is a prospective, double-blind, placebo-controlled and intention-to-treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. Of 84 patients screened, 74 patients formed the intent-to-treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry-over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05).

Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.

The role of CD3-CD56+ natural killer (NK) cells in granulomatosis with polyangiitis (GPA) is poorly understood. Recently, it has been shown that peripheral blood NK cells can kill renal microvascular endothelial cells, suggesting a pathogenic role of NK cells in this disease. So far, subset distribution, phenotype, and function of peripheral blood NK cells in relation to GPA disease activity have not been elucidated. Moreover, it is not known whether NK cells infiltrate GPA tissue lesions. Paraffin sections of GPA granulomas and controls were stained with anti-CD56 and anti-CD3 antibodies. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. NK cell degranulation was analyzed using cocultures of patient PBMCs with target cells and surface expression of CD107a. Clinical data were extracted from medical records. Statistical analysis was performed in an exploratory way. CD56+ cells were not detectable in active granulomatous GPA lesions but were found frequently in granulomas from tuberculosis and sarcoidosis patients. In GPA, the proportion of NK cells among peripheral blood lymphocytes correlated negatively with the Birmingham Vasculitis Activity Score (BVAS) (n = 28). Accordingly, NK cell percentages correlated positively with the duration of remission (n = 28) and were significantly higher in inactive GPA (BVAS = 0, n = 17) than in active GPA, healthy controls (n = 29), and inactive control diseases (n = 12). The highest NK cell percentages were found in patients with long-term remission and tapered immunosuppressive therapy. NK cell percentages >18.5% of peripheral blood lymphocytes (n = 12/28) determined GPA inactivity with a specificity of 100%. The differentiation into CD56(dim) and CD56(bright) NK cell subsets was unchanged in GPA (n = 28), irrespective of disease activity. Similar surface expression of the activating NK cell-receptors (NKp30, NKp46, and NKG2D) was determined. Like in healthy controls, GPA NK cells degranulated in the presence of NK cell receptor ligand bearing epithelial and lymphatic target cells.

NK cells were not detectable in GPA granulomas. Peripheral blood NK cell percentages positively correlate with the suppression of GPA activity and could serve as a biomarker for GPA activity. Peripheral blood NK cells in GPA patients are mature NK cells with preserved immune recognition.

To use statistical methods to establish a threshold for individual response in patient-reported outcomes (PROs) in patients with rheumatoid arthritis. We used an analysis of variance model in patients on stable therapy (discovery cohort) to establish critical differences (d In the discovery cohort (n = 700), PROs showed excellent long-term retest reliability. The minimum change that exceeded random fluctuation was conservatively determined to be 3 points for pain, 4 points for fatigue, and 16 points for function. In the treatment cohort (n = 2,788), 1,483 patients (53.2%) achieved a significant individual therapeutic response as assessed by Disease Activity Score in 28 joints (DAS28)-d

The establishment of critical differences in PROs distinguishes true responses from random variation and provides insights into appropriate patient management.

Dysfunction of central nervous pain processing is assumed to play a key role in primary fibromyalgia (FM) syndrome. This pilot study examined differences of pain processing associated with adopting different interpersonal perspectives. Eleven FM patients and 11 healthy controls (HC) were scanned with functional magnetic resonance imaging. Participants were trained to take either a self-perspective or another person's perspective when viewing the visual stimuli. Stimuli showed body parts in painful situations of varying intensity (low, medium, and high) and visually similar but neutral situations. Patients with FM showed a higher increase in blood oxygen level dependent (BOLD) response, particularly in the supplementary motor area (SMA). All pain-related regions of interest (anterior insula, somatosensory cortices, anterior cingulate cortex, and SMA) showed stronger modulation of BOLD responses in FM patients in the self-perspective. In contrast to pain processing regions, perspective-related regions (e.g. temporoparietal junction) did not differ between FM and HC.

The stronger response of all four pain processing cerebral regions during self-perspective is discussed in the light of disturbed bottom-up processing. Furthermore, the results confirm earlier reports of augmented pain processing in FM, and provide evidence for sensitization of central nervous pain processing.

To determine patient motivations for surgery and satisfaction with outcomes for metacarpophalangeal (MCP) joint arthroplasty in 3 domains (appearance, function, and pain) and whether patient-reported satisfaction correlates with standard outcome measures. In a randomized controlled trial of MCP joint implants, 33 patients with rheumatoid arthritis had primary MCP joint arthroplasty: 15 hands received Swanson implants, and 18 received NeuFlex implants. Range of motion, ulnar drift, grip strength, Sollerman hand function test, and the Michigan Hand Questionnaire were collected before surgery and 1 year after surgery. Preoperative patient motivations for and expectations of MCP joint arthroplasty were assessed for function, pain, and appearance. Patient-perceived improvement and satisfaction within the 3 domains and global satisfaction were assessed after surgery. Function was rated the most important motivator for surgery by 31 patients, pain by 22, and appearance by 15. Twenty-six patients rated 2 or more motivators equally high. Michigan Hand Questionnaire subscores were moderately correlated or weakly correlated with patient-reported satisfaction. The Sollerman score was weakly correlated with patient-reported satisfaction. Range of motion, ulnar drift, and grip strength were not correlated with patient-reported satisfaction. More patients stated that a much better improvement was obtained for appearance than for function or pain relief. Therapeutic I.

Patient expectations of MCP joint arthroplasty were uniformly high. The greatest motivation for surgery was functional improvement. Pain was highly ranked, and 25 patients rated hand appearance as the first or second motivator. Patient satisfaction correlated poorly with traditional outcome measures and moderately with patient-reported outcomes. We conclude that appearance should be considered an important motivator for surgery and determinant of satisfaction.

Articular erosions correlate with disability in rheumatoid arthritis (RA). Biologic agents reduce erosion progression in RA, but erosion healing occurs infrequently. This study was undertaken to assess the effects of the anabolic agent teriparatide on joint erosion volume in RA patients treated with a tumor necrosis factor inhibitor (TNFi). We conducted a randomized controlled trial in 24 patients with erosive RA, osteopenia, and disease activity controlled by TNFi treatment for at least 3 months. Half were randomized to receive teriparatide for 1 year and the others constituted a wait-list control group. Subjects and primary rheumatologists were not blinded with regard to treatment assignment, but all outcomes were assessed in a blinded manner. The primary outcome measure was change in erosion volume determined by computed tomography at 6 anatomic sites. Significance within each hand and anatomic site was based on a 2-tailed test, with P values less than 0.05 considered significant. Baseline characteristics of the treatment groups were well balanced. After 52 weeks, the median change in erosion volume in the teriparatide group was -0.4 mm

Our findings indicate that teriparatide treatment for 1 year does not significantly reduce erosion volume in the hands or wrists of patients with established RA with disease activity controlled by TNFi treatment.

Hereditary multiple osteochondromas (hereditary multiple exostoses, HME) is a rare genetic disease characterized by the development of benign osteocartilaginous tumors that may cause severe limb deformities and early onset osteoarthritis. Total knee arthroplasty (TKA) is the method of choice for the treatment of advanced gonarthrosis, however the surgical management with coexisting severe axial limb deformity remains unclear. 65-year-old man with HME and extra-articular multi-axial limb deformity was admitted to the orthopedic department due to chronic knee pain and limited range of motion caused by secondary osteoarthritis. Regarding to the clinical and radiological examinations, after preoperative planning he was qualified to a one-stage TKA combined with tibial shaft osteotomy (TSO). In a one year follow-up full bone union was confirmed with no signs of implant loosening or prosthesis displacement. Patient was very satisfied, did not report any joint pain and has sufficient range of motion without knee instability.

The improvement of mechanical axis during TKA is a crucial factor for achieve operative success and long implant survival. Despite the higher risk of complication rate in comparison to two-stage treatment, one-stage TKA with simultaneous TSO should be a considerable method for patients with osteoarthritis and multiaxial limb deformities. This method can give a good clinical and functional outcomes, however should be performed subsequently to careful preoperative planning and proper patient qualification.

Although outcome studies generally demonstrate the superiority of a total shoulder arthroplasty (TSA) over a hemiarthroplasty (HA), comparative cost-effectiveness has not been well studied. From a publicly funded health-care system's perspective, this study compared the costs and quality-adjusted life-years (QALYs) in patients who underwent TSA with those in patients who underwent HA. We conducted a cost-utility analysis using a Markov model to simulate the costs and QALYs for patients undergoing either TSA or HA over a lifetime horizon to account for costs and medically important events over the patient lifetime. Subgroup analyses by age groups (≤50 or >50 years) were performed. A series of sensitivity analyses were performed to assess robustness of study findings. The results were presented in 2019 U.S. dollars. TSA was dominant as it was less costly ($115,785 compared with $118,501) and more effective (10.21 compared with 8.47 QALYs) than HA over a lifetime horizon. Changes to health utility values after TSA and HA had the largest impact on the cost-effectiveness findings. At a willingness-to-pay (WTP) threshold of $50,000 per QALY gained, HA was not found to be cost-effective. The probability that TSA was cost-effective was 100%. Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.

Based on a WTP of $50,000 per QALY gained, from the perspective of Canada's publicly funded health-care system, TSA was found to be cost-effective in all patients, including those ≤50 years of age, compared with HA.

To investigate serum protein expression in participants with psoriatic arthritis (PsA) and changes after guselkumab treatment. Participants with PsA were treated with guselkumab or placebo in the DISCOVER-1 and DISCOVER-2 studies. Serum levels of acute phase reactants C reactive protein (CRP) and serum amyloid A (SAA) and inflammatory cytokines/chemokines were measured at weeks 0, 4 and 24 in 300 study participants and 34 healthy controls (HCs). The PSUMMIT studies measured serum interleukin (IL)-17A, IL-17F and CRP after ustekinumab treatment and levels with ustekinumab versus guselkumab treatment were compared. Baseline serum levels of CRP, SAA, IL-6, IL-17A and IL-17F were elevated in participants with active PsA vs HCs (p<0.05, geometric mean (GM) ≥40% higher). Baseline T-helper cell 17 (Th17) effector cytokines were significantly associated with baseline psoriasis but not joint disease activity. Compared with placebo, guselkumab treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F and IL-22 as early as week 4 and continued to decrease through week 24 (p<0.05, GM decrease from baseline ≥33%). At week 24, IL-17A and IL-17F levels were not significantly different from HCs, suggesting normalisation of peripheral IL-23/Th17 axis effector cytokines postguselkumab treatment. Reductions in IL-17A/IL-17F levels were greater in guselkumab-treated versus ustekinumab-treated participants, whereas effects on CRP levels were similar.

Guselkumab treatment reduced serum protein levels of acute phase and Th17 effector cytokines and achieved comparable levels to those in HCs. In participants with PsA, reductions of IL-17A and IL-17F were of greater magnitude after treatment with guselkumab than with ustekinumab.

Data on the effect of gender in rheumatoid arthritis (RA) in non-Caucasian populations is scarce. Latin America and the Caribbean (LAC) is a large population with unique characteristics, including high admixture. Our aim was to examine the effect of gender in patients with RA in LAC. This was a 2-phase study. First we conducted a cross-sectional and analytical study in which 1128 consecutive Colombian patients with RA were assessed. Second, a systematic review of the literature was done to evaluate the effect of gender in LAC patients with RA. Our results show a high prevalence of RA in LAC women with a ratio of 5.2 women per man. Colombian women with RA are more at risk of having an early age at onset and developing polyautoimmunity and abdominal obesity, and they perform more household duties than their male counterparts. However, male gender was associated with the presence of extra-articular manifestations. Of a total of 641 potentially relevant articles, 38 were considered for final analysis, in which several factors and outcomes related to gender were identified.

RA in LAC women is not only more common but presents with some clinical characteristics that differ from RA presentation in men. Some of those characteristics could explain the high rates of disability and worse prognosis observed in women with RA in LAC.

Risk predicting models have been applied in idiopathic pulmonary fibrosis (IPF), but still not validated in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The purpose of this study was to test the suitability of three prediction models as well as individual lung function and demographic factors for evaluating the prognosis of RA-ILD patients. Clinical and radiological data of 59 RA-ILD patients was re-assessed. GAP (gender, age, physiologic variables) and the modified interstitial lung disease (ILD)-GAP as well as the composite physiologic indexes (CPI) were tested for predicting mortality using the goodness-of-fit test and Cox model. Potential predictors of mortality were also sought from single lung function parameters and clinical characteristics. The median survival was 152 and 61 months in GAP / ILD-GAP stages I and II (p = 0.017). Both GAP and ILD-GAP models accurately estimated 1-year, 2-year and 3-year mortality. CPI (p = 0.025), GAP (p = 0.008) and ILD-GAP (p = 0.028) scores, age (p = 0.002), baseline diffusion capacity to carbon monoxide (DLCO) (p = 0.014) and hospitalization due to respiratory reasons (p = 0.039), were significant predictors of mortality in the univariate analysis, whereas forced vital capacity (FVC) was not predictive. CPI score (HR 1.03, p = 0.018) and baseline DLCO (HR 0.97, p = 0.011) remained significant predictors of mortality after adjusting for age.

GAP and ILD-GAP are applicable for evaluating the risk of death of patients with RA-ILD in a similar manner as in those with IPF. Baseline DLCO and CPI score also predicted survival.

Meniscectomy (MX) of sheep induces a well-established animal model of human osteoarthritis (OA). This study compared the clinical (lameness) and pathological outcomes of unilateral, complete medial MX vs two less traumatic and more easily performed meniscal destabilisation procedures. Four-year old wethers (n = 6/group) underwent sham operation, cranial pole release (CPR), mid-body transection (MBT) or total MX of the medial meniscus. Joints were assessed for gross pathology (cartilage erosion and osteophytes), histomorphometry, two histopathology scoring methods (modified Mankin-type and Pritzker score), and immunohistology for ADAMTS- and MMP-cleaved neoepitopes, at 12 weeks post-op. Ground reaction forces (GRFs) were determined by force plate in a subset (n = 4/group) at baseline, 2.5, 8, and 12 weeks post-op. Gross pathology scores of operated groups differed significantly from sham animals (P < 0.05) but not from each other, though qualitative differences were noted: CPR sheep developed more cranial and focal lesions, while MBT and MX joints showed more widespread lesions and osteophyte formation. Similarly, histopathology scores were significantly elevated vs sham but did not differ between operated groups at P < 0.05, except for a trend for lower tibial cartilage histopathology in MBT consistent with the immunohistologic pattern of reduced aggrecanase-cleavage neoepitope in that model. CPR sheep developed less femoral subchondral sclerosis, suggesting some residual biomechanical effect from the destabilised but intact meniscus. Few significant differences were noted between operated groups in force plate analyses, though gait abnormalities appeared to be least in CPR sheep, and most persistent (>12 weeks) in MBT animals.

The well-validated ovine MX model and the simpler meniscal destabilisation procedures resulted in broadly similar joint pathology and lameness. Meniscal CPR or MBT, as easier and more clinically relevant procedures, may represent preferred models for the induction of OA and evaluation of potential disease-modifying therapies.

To determine effects of allogeneic human chondrocytes expressing TGF-β1 (TG-C) on structural progression of MRI features of knee osteoarthritis over a 1 year period. This phase II randomized controlled trial of TG-C included patients with moderate to advanced osteoarthritis. Patients were randomized to receive an intraarticular 3:1 mixture of non-transduced allogeneic human chondrocytes and TG-C or placebo. 3 T MRI was acquired for all patients at baseline and follow-up (3, 6 and 12 months). MRIs were assessed using the WORMS system including cartilage damage, bone marrow lesions (BMLs), meniscal damage/extrusion, Hoffa-, effusion-synovitis, and osteophytes. Analyses were performed on a whole knee level, compartmental level, and subregional level. Binary logistic regression with Generalized Estimating Equation was used to compare risks of progression, adjusting for baseline age and gender. Mann - Whitney - Wilcoxon tests were used to assess differences for continuous variables. Fifty-seven Patients were included in the TG-C group and 29 in the placebo group. At 12 months, knees in the TG-C group showed less progression of cartilage damage compared to placebo on a whole knee level (34.6% vs. 47.9%; adjusted RR 0.7, 95%CI [0.5-1.1], p = 0.077). Less progression of Hoffa-synovitis and effusion-synovitis was observed in the TG-C group compared to placebo (9.6% vs. 21.1%, adjusted RR 0.5, 95%CI [0.2,1.2], p = 0.115). No statistically significant differences were seen for BMLs, meniscal damage and osteophytes. NCT01221441 .Registered 13th October, 2010.

Intraarticular treatment with TG-C showed fewer patients in the treated group with progression in structural OA features and other MRI-defined inflammatory markers such as Hoffa-synovitis and effusion-synovitis. However, no differences were observed in regard to progression of BMLs and meniscal damage, or hypertrophic osteophyte formation.

To examine the therapeutic effect of the interleukin 1 (IL1) receptor antagonist anakinra in ankylosing spondylitis in an open label trial. Anakinra (100 mg) was given subcutaneously daily over 24 weeks to 20 NSAID refractory patients with ankylosing spondylitis. Thirteen completed the study. Clinical outcome assessments included disease activity, function, metrology, patients' and physicians' global assessment, peripheral joint assessment, quality of life, and C reactive protein. Dynamic magnetic resonance imaging (MRI) of sacroiliac joints or spine, using gadolinium DTPA as contrast agent, was done before treatment in 15/20 patients, and in 10 patients at study end. The primary end point was the Bath ankylosing spondylitis disease activity index (BASDAI) and ASAS (assessments in ankylosing spondylitis) short term response after six months. Using an intention to treat analysis, an ASAS 20% response (ASAS 20) was achieved in five patients, ASAS 40 in four, and ASAS 70 in two after 24 weeks. There was no change in mean C reactive protein (22.3 v 33.1 mg/l) or in MRI score. The drug was well tolerated. Injection site reaction was the commonest adverse event.

In this open study, anakinra improved spinal symptoms in only a small subgroup of patients with active ankylosing spondylitis.

Ocular involvement is a common manifestation of rheumatic disease. Recognition of associated systemic findings strengthens our diagnostic armamentarium. The previous ophthalmic and medical literature was reviewed and synthesized into a focused review of rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa; the seronegative spondyloarthropathies, including ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis, ulcerative colitis and Crohn's disease. New and improved diagnostic and therapeutic measures have added a great deal to our understanding of the ocular manifestations of rheumatologic disease and the systemic management of rheumatologic disease.

Optometry can fill an important role in the health care of patients with rheumatologic disease. Regular optometric care and coordination with the patient's rheumatologist can significantly benefit the patient's care.

To determine whether the nonsteroidal anti-inflammatory drug carprofen directly influences canine chondrocyte metabolism. Cartilage from the femoral heads of 13 dogs undergoing total hip replacement. Rates of glycosaminoglycan (GAG) synthesis and degradation, protein synthesis, cell viability, and prostaglandin release were determined in canine explant cartilage or monolayer canine chondrocyte cultures in the presence of 0 to 100 micrograms of carprofen/ml. Rate of GAG synthesis was assessed as incorporation of [35S]sulfate into cartilage matrix during a 3-hour pulse label. Degradation of cartilage GAG was assessed as rate of release of [35S]sulfate from prelabeled explant cultures. Rates of total protein synthesis were assessed as incorporation of [35S]methionine into trichloracetic acid precipitable material during a 3-hour pulse label. Radiolabeled chondrocyte proteins were separated by polyacrylamide gel electrophoresis and visualized by fluorography. Rates of prostaglandin E2 release were assessed by radioimmunoassay. Carprofen stimulated a significant increase in the rate of GAG synthesis at concentrations of 1 and 10 micrograms/ml, with no change in total protein synthesis, pattern of new protein synthesis, or cell viability. At concentration > or = 20 micrograms/ml, inhibition of GAG synthesis and total protein synthesis was observed. There was no significant change in rate of release of GAG from cartilage explants, but potent inhibition of prostaglandin release was observed. In determining the optimal therapeutic dose of carprofen for arthritic conditions in dogs, it is important to consider potential influences on cartilage, as well as anti-inflammatory actions.

Carprofen has a direct influence on chondrocyte activity, resulting in changes in rate of production of cartilage matrix.

This was a retrospective review. Provide a validated method of radiographic evaluation of cervical disk replacement (CDR) patients linked to outcomes. Preoperative radiographic criteria for CDRs and the impact of intraoperative positioning remain without formalized guidelines. The association between preexisting degenerative changes, optimal implant positioning, and patient-reported outcome measures (PROMs) are not well understood. Our study establishes a systematic radiographic evaluation of preoperative spondylosis, implant placement, and associated clinical outcomes. Preoperative radiographs for CDR patients were evaluated for disk height, facet arthrosis, and uncovertebral joint degeneration. Postoperative radiographs were scored based on the position of the CDR implant on anterior-posterior (AP) and lateral radiographs. PROMs including Visual Analogue Scale (VAS) arm pain, VAS neck pain, Neck Disability Index (NDI), Short Form 12 physical health (SF12-PCS) and mental health (SF12-M) were collected preoperatively, at early follow, and at late follow-up. A total of 115 patients were included. Preoperative disk height had the highest reliability, intraclass correlation coefficient of 0.798). Facet arthrosis had the lowest intraclass correlation coefficient at 0.563. Preoperative disk height scores showed a significant correlation with AP radiographs and implant positioning score. Patients with more advanced uncovertebral degenerative changes showed less improvement 6 months postoperatively, based on SF-12 PCS scores (R=0.446, P=0.025). Postoperative implant position on lateral radiograph showed a significant correlation with SF-12 MCS scores at follow-up beyond 6 months (R=0.385, P=0.011). Overall postoperative implant position scores demonstrated significant correlation with SF-12 PCS (R=0.350, P=0.046) scores.

This study provides a systematic method of evaluation of preoperative and intraoperative radiographs that can optimize outcomes. On the basis of our study, spine surgeons performing cervical disk replacement surgery should consider: (a) the presence of preexisting uncovertebral joint degeneration can negatively impact outcomes, (b) achieving optimal implant positioning can be increasingly difficult with more severe loss of disk height, and (c) overall implant position as judged on AP and lateral fluoroscopy can impact outcomes.

Our study analyzes the association between chemokine-ligand-2 (CCL2) serum concentrations at baseline and knee radiographic osteoarthritis (OA) (knee-rOA), knee-rOA progression, individual radiographic features and knee symptomatic OA at 5-year follow-up. OA outcomes were analyzed in a community-based cohort including a baseline enrollment and a 5-year follow-up. Baseline CCL2 serum concentrations were assessed by multiplex assay and associated with presence or progression of individual radiographic features at 5-year follow-up. Separate multiple logistic regression models were used to examine adjusted associations between baseline CCL2 and each of the knee OA variables at follow-up. CCL2 at baseline was modeled as an explanatory variable, whereas each of the knee OA variables at follow-up served as the response variables. Models were adjusted for age, BMI, race, and sex. Trend tests were conducted to assess any linear effect on outcomes across CCL2 tertiles. Participants (n = 168) had a median age of 57-years and median BMI of 29 kg/m2. About 63% of all participants were women, and 58% Caucasian (42% African American). In adjusted logistic models, continuous log-CCL2 was significantly associated with knee-rOA. For each unit increase in log CCL2, the odds of having knee-rOA at follow-up was increased by 72%. CCL2 tertiles showed significant linear associations with presence and progression of knee-rOA and medial joint space narrowing (JSN), but not with presence or progression of osteophytes, bone sclerosis, knee symptoms, or symptomatic knee-rOA.

Serum CCL2 may help to elucidate some mechanisms of joint destruction and identify individuals with higher odds of structural knee changes.

Our aim was to clarify the distribution of hip pain in patients with osteoarthritis of the hip secondary to developmental dysplasia of the hip (DDH). We retrospectively studied 443 hips in 369 patients with osteoarthritis secondary to DDH; mean age was 61 years, and follow-up rate was 84 %. Hip pain was defined as preoperative pain that was relieved 3 months after total hip arthroplasty. Distribution of pain originating in the hip was 89 % (393 hips) to the groin, 38 % (170 hips) to the buttock, 33 % (144 hips) to the anterior thigh, 29 % (130 hips) to the knee, 27 % (118 hips) to the greater trochanter, 17 % (76 hips) to the low back, and 8 % (34 hips) to the lower leg. When the groin, buttock, and greater trochanter were combined as the hip region, 95 % (421 hips) of pain was located in the hip region. On the other hand, when the anterior thigh, knee, lower leg, and low back were combined as the referral region, 55 % (242 hips) showed referred pain.

We suggest that rheumatologists be aware of hip disease masquerading as knee pain or low back pain.

To measure inorganic phosphate (Pi), phosphocreatine (PCr), ATP and phosphodiesters (PDE) in fibromyalgic muscle tissue by (31)P magnetic resonance spectroscopy. A 1.5 Tesla scanner with a P 100 surface coil was used to examine 15 patients (mean age 49.9+/-14.3 yr) with fibromyalgia, according to the American College of Rheumatology criteria, and 17 healthy controls (mean age 30.2+/-5.8 yr). Compared with the controls, there were increases in the levels of PDE (+22%, P = 0.032) and Pi (+19%, P = 0.019) in the spectra of fibromyalgia patients, but there was no difference in pH.

The metabolic differences we found may have been related to weakness and fatigue in the fibromyalgia patients, but they do not fully explain the fibromyalgia symptoms.

To investigate whether weight change during the early rheumatoid arthritis (RA) period is associated with subsequent mortality and to evaluate whether there is an RA-specific effect. We identified patients with incident RA during the Nurses' Health Study (NHS; 1976-2016) and created a comparison cohort by matching each RA patient with up to 10 non-RA comparators by age and calendar year of the RA diagnosis (index date). To capture weight change around the early RA period ("peri-RA/index"), we used weight measurements collected 2-4 years before and 2-4 years after the index date. We used Cox regression analysis to estimate hazard ratios (HRs) for mortality according to peri-RA/index weight change categories, separately in each cohort and in the combined cohorts, evaluating for an RA-specific effect. Among 121,701 women in the NHS, 902 patients with incident RA were identified and matched to 7,884 non-RA comparators. In the RA cohort, 371 deaths (41.1%) occurred during a mean follow-up of 17.0 years after the early RA period, and 2,303 deaths (29.2%) occurred in the comparison cohort during a mean follow-up of 18.4 years. Weight loss of >30 pounds during the peri-RA period had a hazard ratio (HR) for mortality of 2.78 (95% confidence interval [95% CI] 1.58-4.89) compared to stable weight; results in the comparison cohort were similar (HR 2.16, 95% CI 1.61-2.88). A weight gain of >30 pounds had no association with mortality in patients with RA (HR 1.45, 95% CI 0.69-3.07) or comparators (HR 1.19, 95% CI 0.89-1.59). For mortality, there was no statistically significant interaction between RA/comparator status and weight change category (P = 0.68).

Severe weight loss during the early RA period was associated with an increased subsequent mortality risk for women with and those without RA. These results extend prior observations by including non-RA comparators and finding no protective association between weight gain and mortality, providing evidence against an RA-specific obesity paradox for mortality.

We previously showed that type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification), is constitutively expressed by mesenchymal stem cells (MSCs) from osteoarthritis patients and this may be related to Naproxen (Npx), a nonsteroidal anti-inflammatory drug used for therapy. Hedgehog (HH) signaling plays an important role during the development of bone. We tested the hypothesis that Npx affected osteogenic differentiation of human MSCs through the expression of Indian hedgehog (IHH), Patched-1 (PTC1) and GLI family members GLI1, GLI2, GLI3 in vitro. MSCs were cultured in osteogenic differentiation medium without (control) or with 0.5 μM Npx. The expression of collagen type X, alpha 1 (COL10A1), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OC), collagen type I, alpha 1 (COL1A1) was analyzed with real-time reverse transcription (RT) PCR, and the ALP activity was measured. The osteogenesis of MSCs was monitored by mineral staining and quantification with alizarin red S. To examine whether Npx affects osteogenic differentiation through HH signaling, the effect of Npx on the expression of IHH, GLI1, GLI2, GLI3 and PTC1 was analyzed with real-time RT PCR. The effect of cyclopamine (Cpn), a HH signaling inhibitor, on the expression of COL10A1, ALP, OC and COL1A1 was also determined. When MSCs were cultured in osteogenic differentiation medium, Npx supplementation led to a significant decrease in ALP gene expression as well as its activity, and had a tendency to decrease mineral deposition. It also decreased the expression of COL1A1 significantly. In contrast, the gene expression of COL10A1 and OPN were upregulated significantly by Npx. No significant effect was found on OC expression. The expression of IHH, PTC1, GLI1, and GLI2 was increased by Npx, while no significant difference was observed on GLI3 expression. Cpn reversed the effect of Npx on the expression of COL10A1, ALP, OPN and COL1A1.

These results indicate that Npx can affect gene expression during osteogenic differentiation of MSCs, and downregulate mineral deposition in the extracellular matrix through IHH signaling. Therefore, Npx could affect MSC-mediated repair of subchondral bone in OA patients.

Prokinetics are used to treat enteric dismotility symptoms in systemic sclerosis (SSc) patients, but they often lack adequate efficacy. The most effective prokinetics belonging to the serotonin (5-HT Forty patients with self-reported mild to moderately severe enteric symptoms were enrolled in a cross-over 2 × 2 study. Subjects were randomized 1:1 to prucalopride 2 mg/day or no treatment for one month and vice versa after a 2-week washout period. Before and after each sequence the patients compiled the University of California Los Angeles gastrointestinal tract (UCLA GIT) 2.0 questionnaire and the numbers of complete intestinal movements were recorded. Oro-cecal transit time (OCTT) was evaluated by lactulose breath test in a subgroup of patients. Data were evaluated by mixed linear models corrected for the number of laxatives used during the study periods. There were 29 subjects who completed the study; 7 subjects withdrew due to side-effects and 4 subjects were not compliant with the study procedures. As compared to dummy treatment, prucalopride was associated with more intestinal evacuations (p < 0.001), improvement of UCLA GIT constipation (-0.672 ± 0.112 vs 0.086 ± 0.115; p < 0.001), reflux (-0.409 ± 0.094 vs 0.01 ± 0.096; p < 0.005) and bloating (-0.418 ± 0.088 vs -0.084 ± 0.09; p = 0.01) scores. Treatment was ranked moderately to more than moderately effective by 22 patients (72.4%). OCTT was significantly reduced during prucalopruide consumption (prucalopride: -20.1 ± 20.1 vs no treatment: 45.8 ± 21.3 minutes; treatment effect = -65.9 minutes; p = 0.035). EU Clinical Trial Registry, EudraCT2012-005348-92 . Registered on 19 February 2013.

The safety profile of prucalopride in SSc is similar to what is known from the literature. In patients with mild to severe gastrointestinal problems, prucalopride may be effective in treating dismotility symptoms, increasing the number of complete bowel movements and improving bowel transit, reducing reflux disease and bloating.

Tumor necrosis factor is a pleiotropic cytokine with potent immune regulatory functions. Although tumor necrosis factor inhibitors have demonstrated great utility in treating other autoimmune diseases, such as rheumatoid arthritis, there are conflicting results in Sjögren's syndrome. The aim of this study was to assess the effect of a locally expressed tumor necrosis factor inhibitor on the salivary gland function and histopathology in an animal model of Sjögren's syndrome. Using in vivo adeno associated viral gene transfer, we have stably expressed soluble tumor necrosis factor-receptor 1-Fc fusion protein locally in the salivary glands in the Non Obese Diabetic model of Sjögren's syndrome. Pilocarpine stimulated saliva flow was measured to address the salivary gland function and salivary glands were analyzed for focus score and cytokine profiles. Additionally, cytokines and autoantibody levels were measured in plasma. Local expression of tumor necrosis factor-receptor 1:immunoglobulin G fusion protein resulted in decreased saliva flow over time. While no change in lymphocytic infiltrates or autoantibody levels was detected, statistically significant increased levels of tumor growth factor-beta1 and decreased levels of interleukin-5, interleukin-12p70 and interleukin -17 were detected in the salivary glands. In contrast, plasma levels showed significantly decreased levels of tumor growth factor-beta1 and increased levels of interleukin-4, interferon-gamma, interleukin-10 and interleukin-12p70.

Our findings suggest that expression of tumor necrosis factor inhibitors in the salivary gland can have a negative effect on salivary gland function and that other cytokines should be explored as points for therapeutic intervention in Sjögren's syndrome.

In patients with juvenile idiopathic arthritis (JIA) temporomandibular joint (TMJ) involvement is a common cause of severe growth disturbances. Extent of growth deviation depends on age of onset and duration of arthritis in the TMJ. TMJ arthritis is difficult to diagnose at an early stage since relatively few symptoms and clinical findings are related to this joint. The pathologic process can affect growth long before radiographic changes are seen. We investigated the relationship between TMJ arthritis and symptoms and clinical findings to suggest a clinical routine for diagnosing TMJ arthritis. We also describe the course of TMJ arthritis in relation to a commonly used radiographic method versus MRI. Fifteen children with JIA were examined 4 times at 6 month intervals for TMJ involvement by clinical examination, MRI-scanning, and orthopantomograms (OPG). At baseline, 10 healthy children served as a control group. Patients reported more inability to chew and open their mouth than the control group. Translation of the condyle and range of mandibular movements were diminished in the arthritis group. Decreased translation was correlated to condylar changes seen on both OPG and MRI. MRI was superior to OPG in following changes of the condyle over time, and inflammation was detected in nearly all joints.

OPG cannot be recommended for diagnosis or to follow the course of changes in the TMJ. We advocate recording condylar translation and mandibular range of motion as a current clinical routine to find early TMJ arthritis in contrast to the often used OPG performed in our study, which was an uncertain method.

To test the role of fatigue and its subtypes (general, physical, emotional, mental, and vigor) in mediating the relationship between psychological distress and pain interference. Retrospective, de-identified records were examined for 431 patients seeking treatment for persistent orofacial pain. Primary diagnoses of participants were muscle pain (29.8%), joint pain (26.0%), neuropathic pain (19.5%), and other (ie, fibromyalgia, centrally mediated myalgia, tendonitis, dental pain, cervical spine displacement, and no diagnosis; 24.7%). Mediation models were tested with distress as the independent variable, interference as the dependent variable, and fatigue or its subtypes as the mediators. After controlling for pain duration and average levels of pain, total fatigue mediated the relationship between distress and interference. Fatigue subtypes partially mediated the relationship between distress and interference, but mediation was strongest with the composite fatigue variable. The results, however, should be interpreted cautiously, as data were collected at a single time point and do not imply causality.

These results suggest that interventions targeted specifically at fatigue symptoms may be helpful for reducing interference and improving quality of life in patients with persistent orofacial pain.

To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized controlled trials (RCTs). Treatment-naïve patients with early RA (< 6 months' duration) and active disease, participating in two investigator-initiated RCTs, were treated according to a predefined treat-to-target algorithm aiming at inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX + placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus MTX + placebo (OPERA study, n = 180, 2 year follow-up). The 28-joint Disease Activity Score (DAS28) and conventional radiography [bilateral hands and feet at baseline, 2 years and 5 years (only CIMESTRA)] were obtained at baseline and during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in baseline blood samples and during follow-up. Hypotheses regarding the biomarkers' relation with DAS28 and ability to predict clinical remission (DAS28 < 2.6) and radiographic progression (change in total Sharp van der Heijde score ≥ 2) were generated in CIMESTRA and validated in OPERA, by Spearman's correlation and logistic regression analyses. Baseline IL-6, YKL-40, and VEGF correlated significantly with DAS28 in CIMESTRA (r = 0.50, r = 0.36, r = 0.36, respectively, all p < 0.01) and these results were confirmed in OPERA patients (r = 0.52, p < 0.01; r = 0.18, p = 0.01; r = 0.23, p = 0.002, respectively). None of the biomarkers (absolute values or change) was predictive of clinical remission or radiographic progression at 2 or 5 years in either study.

Serum IL-6, serum YKL-40, and plasma VEGF were significantly correlated with DAS28 at baseline, but did not have consistent predictive value for clinical remission or radiographic progression in two early RA RCTs.

To prospectively determine the comparability of 1.0-T extremity magnetic resonance (MR) imaging and 1.5-T conventional MR for the evaluation of the hand and wrist in assessment of patients with rheumatoid arthritis (RA). Institutional ethics approval and written informed consent were obtained. Thirty-two patients (30 women, two men; mean age, 52 years) with RA twice underwent MR of either the most symptomatic hand (n = 21) or wrist (n = 11), once performed with a 1.0-T extremity MR system and once with a 1.5-T conventional MR system. The MR examinations were independently assessed by two radiologists blinded to imaging platform and patient clinical information for erosions, synovitis, and bone marrow edema (BME), according to the Rheumatoid Arthritis MR Imaging Score (RAMRIS). One radiologist reevaluated all cases a second time to determine the intraobserver variability for each system. Patient comfort was assessed with a questionnaire. Intraclass correlation coefficients (ICCs) and smallest detectable differences (SDDs) were measured. ICCs for intermachine agreement were 0.97-0.99 for erosions, 0.88-0.97 for synovitis, and 0.98-0.99 for BME for both readers. The SDDs between the two systems, expressed as a percentage of the maximum score, ranged from 3.3% to 12.2% for erosions, from 7.4% to 14.8% for synovitis, and from 5% to 9.9% for BME for both readers. ICCs for interreader agreement ranged from 0.69 to 0.99 and for intrareader agreement, from 0.88 to 0.99. There were substantial differences in the subjective patient assessment of confinement, system noise, and difficulty with immobilization, and 95.8% of patients preferred examinations performed with extremity MR.

The 1.0-T extremity MR system demonstrates synovial and osseous changes in RA equally as well as a 1.5-T conventional MR system and is preferred by patients.

To determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA). 104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in 70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively.

An association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.

Detection of antinuclear antibodies (ANA) by indirect immunofluorescence assay (IIFA) is increasingly substituted by fully automated solid phase immunoassays. This study evaluated the performance of an automated chemiluminescence immunoassay (CIA) and fluorescence enzyme immunoassay (FEIA) and compared their performance to that of IIFA. The study included an unselected prospective study population suspected of systemic autoimmune rheumatic disease. ANA were measured by IIFA, while in parallel sera were tested by CIA QUANTA Flash CTD Screen Plus on the BIO-FLASH® and FEIA EliA CTD Screen on the Phadia® 250 system. As validation, retrospective cohorts of patients with ANA-associated rheumatic disease (AARD) and healthy controls were tested. Prospectively, sensitivity of IIFA, CIA and FEIA was 90%, 99% and 92%, respectively. Specificity was 76%, 76% and 84%, respectively. Total percent agreements between the three methods were 75.2% (IIFA vs. CIA), 79.2% (IIFA vs. FEIA) and 85.4% (FEIA vs. CIA). The AUC values were 0.95 for CIA and 0.93 for FEIA and did not significantly differ. Retrospectively in individual AARD cohorts, similar results were obtained comparing both CTD screens.

Both FEIA and CIA CTD screen significantly outperformed IIFA, with a higher specificity for FEIA and higher sensitivity for CIA. Based on ROC analysis, major contributor to the difference between the two solid phase immunoassays was the cut-off.

Major salivary gland ultrasonography (SGUS) is a suitable diagnostic tool in Sjögren's syndrome (SS). We aimed to determine the more representative gland, projection and format most applicable for reproducible image analysis. One investigator performed SGUS in patients with SS. Parotid and submandibular glands were examined in longitudinal and transverse planes and evaluated bedside using a simplified scoring system (0-3). Longitudinal and transverse images and videos of all glands were stored and later evaluated/graded by three investigators, at two time-points. Agreement was calculated using intraclass correlation coefficient (ICC). The ICC for static image and video scoring compared to bedside evaluation ranged from 0.131 to 0.882. Average ICC for longitudinal/transverse image was 0.667/0.662, and 0.683/0.510 for longitudinal/transverse video. Interobserver reliability was good to excellent (0.81-0.94). Intraobserver reliability scores ranged from fair to excellent (0.46-0.96). The correlation between image and video evaluations of all modalities and examiners was good to excellent (0.614-0.904). The best mean ICC was found for the longitudinal projection of the left parotid gland (0.861) and the lowest mean ICC was for the transverse projection of the left submandibular gland (0.66).

Our study indicates a trend favouring longitudinal video of the parotid gland as preferred projection, gland and storage format.

Rapid cartilage degradation in the joints is observed in rheumatoid arthritis (RA). ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) degrades aggrecan, the primary component of cartilage, therefore contributing to joint erosion in RA. The proteolytic activity of ADAMTS4 is inhibited by fibronectin (FN). FN is abundantly expressed in the synovia in RA and is modified by citrullination, the conversion of peptidylarginine to citrulline. This study aims to investigate the binding ability of citrullinated FN (cFN) to ADAMTS4 and the effect of cFN on aggrecanase activity. The full-length recombinant ADAMTS4 was purified from HEK293 cells that were transiently transfected with a full-length cDNA coding for human ADAMTS4. A 40-kDa FN fragment exhibiting heparin binding was citrullinised with rabbit peptidylarginine deaminase. The binding activity of the full-length recombinant ADAMTS4 to cFN was investigated in an in vitro binding assay. The proteolytic activity of ADAMTS4 after incubation with cFN was determined using an aggrecanase activity kit, in which the ARGSVIL peptide is produced by digestion with aggrecanase. cFN displayed significantly decreased binding activity with ADAMTS4 compared with FN. The full-length ADAMTS4 produced large amounts of the ARGSVIL peptide, but the amount was markedly decreased in the presence of FN. The production of this peptide approached the normal level when the full-length ADAMTS4 was incubated with cFN.

FN following citrullination is less effective in inhibiting the proteolytic activity of ADAMTS4. It is known that PADI4, an enzyme active in citrullination, is highly expressed in the synovial tissue in RA. Our results suggest that PADI4 in the RA synovium may contribute to cartilage destruction via the citrullination of FN.

To determine how well self-report functional ability reflects the impairment due to the arthritic process in rheumatoid arthritis (RA) and how much it is affected by other factors of health status. We examined the relationships between self-report measures such as the Health Assessment Questionnaire (HAQ) and Arthritis Impact Measurement Scales (AIMS) and measures of impairment such as the Keitel function test (KFT), which is intended to reflect the degree of functional limitation of the joints, grip strength and radiological destruction as well as anxiety and depression in a population-based series of RA. First, the HAQ and AIMS had a high correlation coefficient (r = 0.89, p < 0.0001). Second, the above measures of impairment were more significant predictors of self-report functional measures than, for example, mental health perceptions. The AIMS scales also correlated well with the corresponding physical function of the KFT.

Patients' self-report functional ability in RA reflects their physical impairment due to the arthritic joint disease and is less influenced by other factors such as emotional adjustment.

To evaluate the psychometric properties of Patient's Knee Implant Performance Questionnaire (PKIP), a new patient-reported measure of knee implant functional performance assessing patient experiences before and after primary total knee arthroplasty (TKA). The psychometric analysis sample (n = 761) was based on an ongoing, multisite, prospective, noncomparative, longitudinal study of patients undergoing TKA. The PKIP was completed at three study visits: presurgery (visit 1), less than 1 year (visit 3, days 1-303), and minimum 1 year (visit 4, days 304-668). Visit 2 was an operative visit. Supporting outcome measures were collected at each study visit. The PKIP structure and its psychometric properties were assessed as part of a secondary data analysis using an interim data cut before the end of the clinical trial. The PKIP includes four subscales (confidence, stability, activity modification, and satisfaction) and an overall PKIP score. The overall PKIP score met internal consistency (visit 4 = 0.79) and test-retest reliability (intraclass correlation coefficient = 0.77) standards. Correlations between the PKIP and other measures (e.g., the American Knee Society score and the Knee Injury and Osteoarthritis Outcome Score) provided evidence of construct validity. The PKIP was capable of discriminating between groups of patients with better or worse knee function. The effect size for the overall PKIP score was 2.96 from baseline to visit 4, indicating that the PKIP was highly responsive.

The reliability, validity, and responsiveness of the PKIP support its use among patients undergoing TKA.

Published small case series suggest that inflammatory bowel disease [IBD; Crohn's disease (CD) or ulcerative colitis (UC)] and vasculitis co-occur more frequently than would be expected by chance. To describe this association by an analysis of a large cohort of carefully studied patients and through a systematic literature review. Patients with both IBD and vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Studies, followed in Canadian Vasculitis research network (CanVasc) centers and/or in the University of Toronto's IBD clinic were included in this case series. A systematic literature review of patients with IBD and vasculitis involved a PubMed search through February 2014. The main characteristics of patients with Takayasu arteritis (TAK) and IBD were compared to those in patients with TAK without IBD followed in the VCRC. The study identified 32 patients with IBD and vasculitis: 13 with large-vessel vasculitis [LVV; 12 with TAK, 1 with giant cell arteritis (GCA); 8 with CD, 5 with UC]; 8 with ANCA-associated vasculitis [AAV; 6 granulomatosis with polyangiitis (GPA), 2 with eosinophilic granulomatosis with polyangiitis (EGPA)]; 5 with isolated cutaneous vasculitis; and 6 with other vasculitides. Patients with LVV and AAV were mostly female (18/21). The diagnosis of IBD preceded that of vasculitis in 12/13 patients with LVV and 8/8 patients with AAV. The review of the literature identified 306 patients with IBD and vasculitis: 144 with LVV (133 TAK; 87 with IBD preceding LVV), 19 with AAV [14 GPA, 1 EGPA, 4 microscopic polyangiitis (MPA)], 66 with isolated cutaneous vasculitis, and 77 with other vasculitides. Patients with IBD and TAK were younger and had more frequent headaches, constitutional symptoms, or gastrointestinal symptoms compared to those patients in the VCRC who had TAK without IBD.

These findings highlight the risk of vasculitis, especially TAK, in patients with IBD (both CD and UC).

Methotrexate is a mainstay of treatment for autoimmune conditions such as rheumatoid arthritis and psoriasis. Methotrexate has numerous potential side effects and, in rare circumstances, can lead to cutaneous ulceration. Methotrexate can cause skin ulceration, and stopping this medication can lead to complete healing of the ulcerated lesion. A 67-year-old man with rheumatoid arthritis on long-term methotrexate therapy presented to hospital with ulcers on his hands, elbows, and lower extremities. He had no history of psoriasis. Shortly after admission, the patient was noted to have pancytopenia. A bone marrow biopsy showed a hypocellular marrow. Both the cutaneous ulcers and the hypocellular marrow were thought to be induced by methotrexate. The ulcerated areas were biopsied, and histopathology showed no evidence of vasculitis. After 1 month of rehabilitative skin care, the patient's ulcers healed almost completely and his bone marrow suppression recovered.

We report the fifth case of methotrexate-induced cutaneous ulceration in a nonpsoriatic patient and review the literature on this unusual drug reaction. Methotrexate can induce cutaneous ulceration in nonpsoriatic patients and should be considered a potential cause of ulceration in patients treated with this antimitotic agent.

Depression and anxiety are common in medical patients and are associated with diminished health status and increased health care utilization. This article presents a quantitative review and synthesis of studies correlating medical patients' treatment noncompliance with their anxiety and depression. Research on patient adherence catalogued on MEDLINE and PsychLit from January 1, 1968, through March 31, 1998, was examined, and studies were included in this review if they measured patient compliance and depression or anxiety (with n>10); involved a medical regimen recommended by a nonpsychiatrist physician to a patient not being treated for anxiety, depression, or a psychiatric illness; and measured the relationship between patient compliance and patient anxiety and/or depression (or provided data to calculate it). Twelve articles about depression and 13 about anxiety met the inclusion criteria. The associations between anxiety and noncompliance were variable, and their averages were small and nonsignificant. The relationship between depression and noncompliance, however, was substantial and significant, with an odds ratio of 3.03 (95% confidence interval, 1.96-4.89).

Compared with nondepressed patients, the odds are 3 times greater that depressed patients will be noncompliant with medical treatment recommendations. Recommendations for future research include attention to causal inferences and exploration of mechanisms to explain the effects. Evidence of strong covariation of depression and medical noncompliance suggests the importance of recognizing depression as a risk factor for poor outcomes among patients who might not be adhering to medical advice.

To determine the effect of weight loss and exercise interventions on serum leptin and to investigate the relationship of physical function and osteoarthritis (OA) severity with serum leptin in older overweight and obese adults with knee OA. In addition, the study examined if serum leptin predicts weight loss. Longitudinal, controlled clinical trial of weight loss and exercise interventions. Community dwelling, older, overweight and obese adults (n=316; >60 years of age; body mass index >/=28.0 kg m(-2)) with symptomatic knee OA and self-reported difficulty in performing selected physical activities were recruited. Participants were randomized into one of four groups for the 18-month study duration: Healthy Lifestyle Controls, Dietary Weight Loss (Diet), Exercise Training (Exercise), and a combination of Dietary Weight Loss and Exercise Training (Diet+Exercise). The weight loss goal for the two Diet groups was 5% from baseline at 18 months. Participants in the Exercise groups were trained for 3 days week(-1), 60 min day(-1). Body weight, body mass index, serum leptin, physical function, and OA severity were measured at baseline, 6 months, and 18 months. Diet and Diet+Exercise groups lost 5.3 and 6.1% of their weight, respectively, at 18 months with the Exercise group losing 2.9%. There was a significant main effect of weight loss on serum leptin with a decrease in serum leptin averaged across the 6- and 18-month time points for the Diet and Diet+Exercise groups compared to the other two groups (beta=0.245; P<0.01). No main effect for exercise training was observed. Serum leptin was related to self-reported physical function. In all participants, a mixed model analysis demonstrated that lower levels of baseline serum leptin predict larger weight loss (beta=-2.779; P=0.048).

Decreases in serum leptin may be one mechanism by which weight loss improves physical function and symptoms in OA patients.

It is known that anti-citrullinated protein (a-CCP) antibodies and rheumatoid factor (RF) can be present in systemic sclerosis (SSc) patients, particularly with joint involvement. The aim of the study was to assess the prevalence of a-CCP antibodies and immunoglobulin M class (IgM) RF, and the relationships between their presence and joint manifestations in patients with SSc. The study included 100 European Caucasian SSc patients hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases (Lublin, Poland). Anti-citrullinated protein antibodies and IgM RF were determined using a commercial enzyme-linked immunosorbent assay (ELISA) test. Anti-citrullinated protein antibodies were found in 10 out of 100 (10%) SSc patients and IgM RF in 71 out of 100 (71%) SSc patients. In the study, 90/100 (90%) SSc patients had joint manifestations (arthralgia or arthritis), 34/100 (34%) had arthritis and 6/100 (6%) had a systemic sclerosis-rheumatoid arthritis (SSc-RA) overlap syndrome. Significantly higher a-CCP antibody levels (p = 0.012), erythrocyte sedimentation rate (ESR) (p = 0.029) and C-reactive protein (CRP) levels (p = 0.020) were observed in the SSc group with arthritis. A significant correlation was found between the group with arthritis and the presence of a-CCP antibodies, and between the arthralgia group and the presence of IgM RF.

The prevalence of RF and a-CCP antibodies is relatively high in SSc, and joint involvement occurs frequently. There was a significantly higher prevalence of IgM RF in the group with joint manifestations. About 1/3 of SSc patients had symptoms of arthritis. Arthritis is connected with the presence of a-CCP antibodies, while arthralgia is connected with the presence of IgM RF.

The dual mobility acetabular cup (DMC) was designed to reduce prosthetic instability and has gained popularity for both primary and revision total hip arthroplasty (THA). We compared the risk of revision of primary THA for primary osteoarthritis between patients treated with a DMC and those who received a metal-on-polyethylene (MoP) or ceramic-on-polyethylene (CoP) bearing. A search of the Nordic Arthroplasty Register Association (NARA) database identified THAs performed with a DMC during 1995 to 2013. With use of propensity score matching, 2,277 of these patients were matched (1:1), with regard to sex, age, component fixation, and year of surgery, with patients with an MoP or CoP bearing. We estimated the cumulative incidence of revision taking death as a competing risk into consideration and performed competing risk regression with revision or death as end points. There was no difference in the overall risk of revision between the DMC group and the propensity-score-matched MoP/CoP group (adjusted hazard ratio [HR] = 1.18; 95% confidence interval [95% CI] = 0.87 to 1.62). Patients with a DMC bearing had a lower risk of revision due to dislocation (adjusted HR = 0.09; 95% CI = 0.03 to 0.29) but a higher risk of revision caused by infection (adjusted HR = 3.20; 95% CI = 1.49 to 6.85). Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

There was no difference in overall risk of revision between the DMC and MoP/CoP groups. The DMCs protected against revision due to dislocation but THAs performed with this bearing were more commonly revised because of infection. There may have been a selection bias toward placing DMC implants in patients with greater frailty as the mortality rates were higher in the DMC group than in the age and sex-matched MoP/CoP group.

Patient-reported health-related quality-of-life (HRQoL) measures such as the EuroQol 5 dimension (EQ-5D) index are commonplace when assessing healthcare providers or efficiency of medical techniques. HRQoL measures are generally bounded, and the magnitude of possible improvement depends on the pre-treatment HRQoL value. This paper aimed to assess and illustrated the possibility of modelling the relationship between pre- and post-treatment HRQoL measures with piecewise linear splines. The method was illustrated using a longitudinal dataset of 36,625 patients with one EQ-5D index before and one a year after total hip arthroplasty. We considered four models: intercept only model, single line regression, and segmented regression with 1 and 2 change points. The post-operative EQ-5D index served as the outcome, while the preoperative EQ-5D index was the predictor. We found that a two-line regression best described the data with the lines meeting at 0.159 on the preoperative EQ-5D index scale. In the low preoperative group (with an initial preoperative index from -0.594 to 0.159), the predicted post-operative scores ranged from 0.368 to 0.765, with post-operative scores increasing 0.528 points for each unit in the preoperative score. In the high preoperative group (initial range from 0.159 to 1), the predicted post-operative scores ranged from 0.765 to 0.855, increasing 0.106 points for each unit in the preoperative score.

Piecewise linear regression is a straightforward approach to analyse baseline and follow-up HRQoL measures such as the EQ-5D index. It can provide a reasonable approximation of the shape of the underlying relationship where the threshold and slopes prove informative and meaningful.

To determine the effect of avian chondroitin sulfate (CS) on interleukin-1beta (IL-1beta)-induced expression of genes related to catabolic, anabolic and inflammatory aspects in chondrocytes cultured in hypoxic alginate beads. Articular chondrocytes from bovine metacarpal joint were isolated and cultured in alginate beads, using low oxygen atmosphere (5% O2). After 1-week exposure to CS (1, 10 and 100microg/ml), they were treated by recIL-1beta (10ng/ml) for 24 or 48h, in the presence of CS. RNA was extracted and used to determine, by quantitative reverse transcription-polymerase chain reaction, the steady-state levels of mRNAs encoding several genes related to anabolic, catabolic and inflammatory aspects. Glycosaminoglycan (GAG) synthesis was also assayed by 35S-sulfate incorporation. CS decreased IL-1beta-induced expression of matrix metalloproteases-1, -3 and -13 and aggrecanases-1 and -2. It slightly enhanced the aggrecan core protein mRNA and the GAG synthesis. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA levels were found to be reduced by CS treatment. However, no CS-induced decrease of NO was observed in IL-1beta-treated chondrocytes, whereas prostaglandin E2 production was diminished in correlation with the COX-2 mRNA amounts. Furthermore, CS was capable of counteracting IL-1beta-depressed expression of transforming growth factor-beta (TGF-beta) receptors.

CS can repress expression of genes encoding proteolytic enzymes involved in cartilage degradation. It also inhibits IL-1beta-induced expression of the pro-inflammatory genes iNOS and COX-2 and restores TGF-beta receptors I and II (TGF-betaRI and RII) mRNA levels. These data suggest that CS may exert both chondroprotective and anti-inflammatory limited effects on articular cartilage that could have long-term beneficial action on the osteoarthritic process.

Recent genome-wide association studies have identified TRAF1/C5 as a rheumatoid arthritis (RA) susceptibility locus. Tumor necrosis factor receptor-associated factor 1 (TRAF1) has been implicated in the regulation of antiapoptotic pathways, whereas C5 has a well-established role in defense against infection. The purpose of this study was to examine the association of the TRAF1/C5 locus with death in patients with RA. Genomic DNA samples were collected from a prospective cohort of 400 RA patients. TRAF1/C5 rs3761847 was identified using real-time polymerase chain reaction and melting curve analyses. The association of TRAF1/C5 rs3761847 alleles with the risk of death was assessed using Cox proportional hazards regression analyses. TRAF1/C5 rs3761847 GG homozygote status was associated with an increased risk of death (hazard ratio 3.96 [95% confidence interval 1.24-12.6], P=0.020) as compared with AA homozygote status. The excess mortality was attributed to deaths due to malignancies and sepsis but not cardiovascular disease (CVD). This polymorphism was one of the strongest predictors of death in RA (for TRAF1/C5 GG versus AA, hazard ratio 3.85 [95% confidence interval 1.18-12.59], P=0.026) alongside the erythrocyte sedimentation rate, triglyceride level, prednisolone use, and age.

The risk of death in RA is increased in TRAF1/C5 rs3761847 GG homozygotes and appears to be independent of RA activity and severity as well as comorbidities relevant to CVD. If this finding is replicated in future studies, TRAF1/C5 genotyping could identify patients at increased risk of death, particularly death due to malignancy or sepsis.

Autologous chondrocyte implantation is a necessary procedure for the repair of articular cartilage defects; however, isolated chondrocyte implantation requires a 2-step procedure (for harvesting and implantation) and is limited by cytotoxicity due to enzymatic digestion. Therefore, in this Cartilage fragments were obtained from 7 female patients with knee osteoarthritis (OA) and embedded in atelocollagen gels. As a control, chondrocytes were isolated and embedded in gels in the same manner. These composites were cultured for 3 weeks, and cell proliferation and matrix production were evaluated using histology and immunochemistry. Histologically, minced cartilage showed cell migration from the cartilage fragments into the gel, with the Bern score and cell count in the minced cartilage group being significantly higher than those in the control group. Immunohistochemistry revealed that the number of Ki67-positive cells, the expression of LECT-1 and TGF-β, and the glycosaminoglycan content were significantly higher in the minced cartilage than in the control group. Minced cartilage exhibited superior cell migration, proliferation, and glycosaminoglycan content than isolated chondrocytes.

Our findings support that minced cartilage has a favorable potential for cell proliferation and matrix production compared with the isolated chondrocytes after enzymatic treatment.

The tibial tubercle-trochlear groove distance (TT-TG) is an established measurement to assist diagnosis and treatment of patellofemoral instability. However, little is known about the distribution of TT-TG in osteoarthritic knees. The purpose of the current study is to investigate the TT-TG in a large cohort of osteoarthritic knees and to analyse, in particular, the association of knee alignment and TT-TG. Data from 962 consecutive patients [455 male, 507 female; mean age ± SD 70.8 ± 9.3 (37-96)] who had undergone 3D-CT and preoperative knee planning with validated commercial 3D planning software before total knee arthroplasty (TKA) were collected prospectively. The TT-TG, coronal hip knee ankle angle (HKA), femoral anteversion (AVF), external tibial torsion (ETT), and femorotibial rotation (Rot FT) were analysed. Pearson correlations were performed to assess correlations between TT-TG, mechanical axis, and rotational parameters (p < 0.05). HKA showed a strong correlation with TT-TG (r = 0.488; p < 0.001) with 98 (67.1%) and 45 (30.8%) of valgus knees having respective abnormal and pathological TT-TG values. There were no significant correlations between parameters of rotational alignment (AVF, ETT, Rot FT) and TT-TG. Mean TT-TG was 12.9 ± 5.6 mm, ranging from 0.0 to 33.7 mm. 325 (33.8%) of all patients had abnormal (> 15 mm) and 101 (10.5%) had pathological (> 20 mm) values. A varus alignment was present in 716 (74.4%) of the cases (HKA < - 1.5°), a neutral alignment in 100 (10.4%), and a valgus alignment in 146 (15.2%) (HKA > 1.5°). III. Retrospective cohort study.

A wide variation of TT-TG values in osteoarthritic knees was shown by our results. There was a relevant influence of coronal limb alignment on the TT-TG-the more valgus the higher and more pathological the TT-TG. With the aim of having a more personalised TKA, the individual TT-TG should be taken into account to improve the outcome.

Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin-D may play a role in the pathogenic process and disease expression. Thus, we aimed to evaluate levels of vitamin-D and their association with manifestations of SS. Vitamin-D levels were determined in 176 primary SS patients and 163 matched healthy volunteers utilizing the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). A correlation between vitamin-D levels and clinical and serological manifestations of SS was performed. Mean vitamin-D levels were comparable between SS patients and control 21.2 ± 9.4 ng/ml and 22.4 ± 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of SS patients and associated with lower vitamin-D levels (18.6 ± 5.5 ng/ml vs. 22.6±8 ng/ml (p = 0.04)). Lymphoma was diagnosed in 4.3% of SS patients, who had lower levels of vitamin-D (13.2 ± 6.25 ng/ml), compared to SS patients without lymphoma (22 ± 8 ng/ml), (p = 0.03). Other clinical and serological manifestations did not correlate with vitamin-D status.

In this study, low levels of vitamin-D correlated with the presence of peripheral neuropathy and lymphoma among SS patients. The link between vitamin-D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin-D in the pathogenesis of these processes. Plausible beneficial effect for vitamin-D supplementation may thus be suggested.

To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway. Participants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids). Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use.

Participants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

Variable definitions of outcome (Constant score, Simple Shoulder Test [SST]) have been used to assess outcome after shoulder treatment, although none has been accepted as the universal standard. Physicians lack an objective method to reliably assess the activity of their patients in dynamic conditions. Our purpose was to clinically validate the shoulder kinematic scores given by a portable movement analysis device, using the activities of daily living described in the SST as a reference. The secondary objective was to determine whether this device could be used to document the effectiveness of shoulder treatments (for glenohumeral osteoarthritis and rotator cuff disease) and detect early failures. A clinical trial including 34 patients and a control group of 31 subjects over an observation period of 1 year was set up. Evaluations were made at baseline and 3, 6, and 12 months after surgery by 2 independent observers. Miniature sensors (3-dimensional gyroscopes and accelerometers) allowed kinematic scores to be computed. They were compared with the regular outcome scores: SST; Disabilities of the Arm, Shoulder and Hand; American Shoulder and Elbow Surgeons; and Constant. Good to excellent correlations (0.61-0.80) were found between kinematics and clinical scores. Significant differences were found at each follow-up in comparison with the baseline status for all the kinematic scores (P < .015). The kinematic scores were able to point out abnormal patient outcomes at the first postoperative follow-up.

Kinematic scores add information to the regular outcome tools. They offer an effective way to measure the functional performance of patients with shoulder pathology and have the potential to detect early treatment failures.

The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.

The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

Treatment options for rheumatoid arthritis (RA) include conventional synthetic disease-modifying antirheumatic drugs (sDMARDs) and newer biologic DMARDs (biologics). This study describes treatment patterns, adherence to guidance and outcomes at hospital/regional level in the UK. This was a retrospective cohort study of RA patients selected from six health regions and from four hospitals in each region, including at least one major teaching hospital and two to three district/general hospitals. Treatment with sDMARDs/biologics was examined between November 2009 and June 2010 in comparison with National Institute for Health and Clinical Excellence (NICE) guidance and in relation to disease activity. NICE guidance focuses on initiation of therapy and recommends combination sDMARD/biologic therapy. Analysis of 588 patient records indicates that overall 23% of patients were receiving biologic monotherapy. NICE guidance recommends initiation of biologics in patients with active RA (DAS28 >5.1): average DAS28 score on initiation of biologic therapy was above six in all regions. Range of DAS28 improvement post-biologic therapy was similar across all regions. DAS28 scores were well recorded within patient records at baseline and 6 months but not at other time points.

Our data highlight that nearly a quarter of patients receiving biologic treatments are not receiving concomitant sDMARD therapy and that DAS28 is poorly documented in patient medical records other than when initiating biologics and at the 6-month review. Limitations of this study include the limited sample size, the retrospective rather than prospective nature of the audit and the use of medical records only rather than other records such as nursing and pharmacy data. Nevertheless, the reasons for our findings merit further investigation to ensure that optimum treatment regimes and long term outcomes are being achieved for patients.

To evaluate perioperative changes in rheumatoid arthritis (RA) patients treated with tocilizumab. We collected RA cases with tocilizumab and orthopaedic surgery from 1999 to 2010. Incidences of postoperative infections, delayed wound healing, and RA symptom flare-ups were extracted from the data for comparison with patients without these postoperative events. We also evaluated the changes in C-reactive protein (CRP) and body temperature in patients without postoperative complications with normal CRP before surgery, i.e., patients without postoperative events in whom the tocilizumab level was maintained, for each duration to discontinuation before surgery. A total of 161 cases (n = 122) were collected. The patients had mean age of 56.9 years, and mean disease duration of 12.8 years at operation. Joint replacement surgery was performed in 89 cases. Three patients had postoperative infections (two superficial and one organ/space surgical-site infection), 20 had delayed wound healing, and 36 had RA symptom flare-ups. Delayed wound healing occurred most commonly in patients who underwent spinal surgery (P = 0.0061, versus patients without delayed wound healing). CRP levels were high when tocilizumab was restarted in patients with RA symptom flare-ups (P = 0.0010, versus patients without RA symptom flare-ups). Increased postoperative CRP was observed in patients without postoperative events when the duration from final tocilizumab infusion to surgery was long. The changes in body temperature showed a similar trend to CRP.

Although it has been demonstrated that infection rates in patients treated with tocilizumab are by no means high, incidence of delayed wound healing was significantly higher in cases with surgical interventions such as foot and spinal surgeries. Many patients treated with tocilizumab remained in a normal range of CRP even during the perioperative period. For prevention of perioperative complications, observation of postoperative conditions and surgical wounds, and subjective symptoms of patients are considered important.

The aim of this report is to describe a fatal disseminated thrombotic micoangiopathy with renal, pancreatic, and cerebral involvement in a patient with recently diagnosed adult's Still disease (ASD). A previously healthy 15 year old girl was admitted to our hospital. According to the clinical and laboratory data the diagnosis of adult's still Disease was established. The treatment was begun and few days after an initial improvement a sudden neurologic deterioration with coma and seizures has occurred. Hours later the patient died. Clinical, laboratorial, and pathologic data will be presented.

To our knowledge this is the second description of a fatal disseminated cerebral thrombotic microangiopathy in a patient with adult's Still disease, but with a much more fulminating evolution than previously reported. Some etiopathogenic mechanisms could be shared in these two disorders explaining this coexistence.

Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment. Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5 mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30 μg or 100 μg or placebo every 6 (q6mo) or 12 months. 1.5- or 3 T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening. 549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100 μg q6mo vs placebo; mean DSM (95% confidence interval [CI]) -0.6 (-1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100 μg q6mo vs placebo; mean DSM (95% CI) -0.2 (-0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis.

Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined.

To investigate the involvement of arteries other than the temporal arteries in active giant cell arteritis using color Doppler sonography. The occipital, facial, vertebral, carotid, subclavian, axillary, brachial, ulnar radial, femoral, popliteal, posterior tibial, and dorsal pedal arteries, and the abdominal aorta of 33 consecutive patients with acute giant cell arteritis and 33 age- and sex-matched controls were investigated. In 10 patients (30%), but in none of the controls, a characteristic inflammatory mural thickening (halo) could be demonstrated in these arteries. The subclavian, external carotid, and/or facial arteries were involved in 4 patients, the occipital and/or axillary arteries in 3 patients, the brachial and/or ulnar arteries in 2 patients, and the common carotid, vertebral, popliteal, and/or radial arteries in 1 patient each. Two patients had symptomatic large vessel giant cell arteritis with arm claudication. The other patients were asymptomatic concerning the involved arteries. Furthermore the ulnar artery was occluded in 3 cases, the posterior tibial artery in 2 cases, and the dorsal pedal and the vertebral artery in 1 case each. No occlusions were found in the controls. Occlusion of the temporal arteries occurred more frequently in patients with peripheral artery involvement than in those without peripheral involvement (60% versus 26%). In most of the non-stenotic, small arteries the halo disappeared within 9 to 21 days. Mural thickening remained in large, stenotic arteries.

Peripheral artery involvement occurs more frequently in acute temporal arteritis than has been assumed up to now. Color Doppler sonography offers a new method to evaluate this peripheral involvement.

Despite the popularity of minimally invasive approaches in total hip arthroplasty, studies regarding their impact on soft tissues and long-term benefits are lacking. This study aims to compare the 10-year functional outcome of the piriformis-sparing minimally invasive approach to the standard posterior approach for total hip arthroplasty surgery. Hundred patients were randomized, 48 patients to the piriformis-sparing approach and 52 to the standard approach. Primary outcomes were hip function and piriformis muscle volume and grade on magnetic resonance imaging. Secondary outcomes were pain, satisfaction score, and complications. Evaluators were blinded to allocation. Participants were followed up to 10 years. Ten years following surgery, both groups reported excellent pain relief, improved hip function, and high satisfaction. The significant differences were improvement in piriformis muscle volume (P = .001) and muscle grade (P = .007) in the piriformis-sparing group compared to the standard group. There were no significant differences in all other outcomes.

Aside from being less injurious to the piriformis muscle, the piriformis-sparing approach offered the same long-term functional benefits as the standard posterior approach at 10 years.

To evaluate the association between circulating leptin and bone mineral density (BMD) in patients with rheumatoid arthritis (RA). One-hundred thirty postmenopausal women with RA were assessed for body mass index (BMI), disease characteristics, history of drug use, rheumatoid factor, and erythrocyte sedimentation rate (ESR). BMD (g/cm(2)) was determined in the hip and spine by DEXA. Serum leptin concentrations were measured by ELISA. Spearman's correlation coefficients (rho) were determined between BMD and leptin and other variables. A multiple regression analysis was used to adjust for confounders. Patients' serum leptin levels varied widely (range 2-128 ng/ml). Thirty-three patients (25%) had osteoporosis. Higher levels of leptin correlated significantly with BMD in the lumbar spine (rho = 0.17, p = 0.04) and total hip (rho = 0.21, p = 0.01). The variables that were negatively correlated with BMD were age, duration of menopause, and ESR. After adjustment for confounders, leptin was no longer associated with BMD. In the multivariate model, factors that remained associated with BMD in the total hip were age (p = 0.021) and BMI (p = 0.003); and the factors that remained associated with BMD in the lumbar spine were BMI (p = 0.03) and ESR (p = 0.01).

No relevant association was found between circulating leptin levels and BMD in patients with RA in this cross-sectional study. Followup studies are needed to evaluate whether abnormal leptin levels confer a risk for fractures due to osteoporosis.

Rheumatoid arthritis (RA) is biologically marked by a positive serum rate of rheumatoid factor (RA) and/or anti-citrullinated protein antibodies (ACPA). Nevertheless, 20% of RA cases remain seronegative. The main purpose of this study, is to bring out the clinical, biological, imaging, therapeutic, and evolutionary distinctions between seropositive RA and seronegative one. This is an observational cross-sectional study that involves patients with RA admitted in the rheumatology department, from the period between January 2012 and January 2018. RA seronegativity is described as the absence of both RF and ACPA, while seropositivity is recognized by the presence of at least one of the two antibodies. 294 patients were included, of which 90% were seropositive and 10% seronegative. Therefore, RA in this study is seropositive most often. The bivariate analysis underscored plenty of differences, statistically notable, according to the RA immune status. In fact, patients with seropositive RA had more synovitis (p=0.049), more deformities (p=0.01), and more bone destruction on radiographs (p=0.04). Furthermore, RA in this Moroccan study was quite severe (p=0.006) and got more complicated by systemic manifestations (p=0.02). Whereas, no distinction was brought up between the two groups, concerning the use of biotherapy. As for the multivariate study, seropositive RA in these patients, had greater severity (p=0.009, OR=4.53) and was more deforming (p=0.03 OR=2.45).

RA in our Moroccan context is dominated by the seropositive form. This seropositivity is often coupled with clinical severity and joint destruction, resulting in more deformities.

Osteoarthritis (OA) has become by far the most common joint disorder. A number of studies using OA animal models have explored the effects of agents that can modulate bone metabolism. In the present study, we investigated the effect of acetylated derivative of plant alkaloid glaucine (ADG) on experimental OA in mice. Arthritis was induced by two intraarticular (i.a.) injections of collaganase. Histopathological changes were observed through hematoxylin and eosine (H&E), safranin O and toluidine blue staining. Differentiation of bone marrow (BM) cells was evaluated by tartarate-resistant acid phosphatase (TRAP) assay. The expression of phospho-Janus kinase 2 (pJAK2) and phospho signal transducer and activator of transcription3 (pSTAT3) expression in the joints was determined by immunohistochemistry. We established that ADG significantly decreased cell infiltration (2.32 ± 0.14 versus 1.62 ± 0.13), cartilage loss (2.42 ± 0.12 versus 1.12 ± 0.10) and bone erosion (1.76 ± 0.13 versus 1.04 ± 0.14) in arthritic mice. It appeared that the substance inhibited in a dose-dependent manner osteoclast differentiation in vitro. ADG suppressed the expression of pJAK2 in the joint and partially affected the expression of pSTAT3.

Present results suggest that ADG is a suitable candidate for further development as an anti-arthritic agent.

To quantify adherence to oral therapies in ethnically diverse and economically disadvantaged patients with rheumatoid arthritis (RA), using electronic medication monitoring, and to evaluate the clinical consequences of low adherence. A total of 107 patients with RA enrolled in a 2-year prospective cohort study agreed to have their oral RA drug therapy intake electronically monitored using the Medication Event Monitoring System. Adherence to disease-modifying antirheumatic drugs (DMARDs) and prednisone was determined as the percentage of days (or weeks for methotrexate) on which the patient took the correct dose as prescribed by the physician. Patient outcomes were assessed, including function measured by the modified Health Assessment Questionnaire, disease activity measured by the Disease Activity Score in 28 joints (DAS28), health-related quality of life, and radiographic damage measured using the modified Sharp/van der Heijde scoring method. Adherence to the treatment regimen as determined by the percentage of correct doses was 64% for DMARDs and 70% for prednisone. Patients who had better mental health were statistically more likely to be adherent. Only 23 of the patients (21%) had an average adherence to DMARDs ≥80%. These patients showed significantly better mean DAS28 values across 2 years of followup than those who were less adherent (3.28 versus 4.09; P = 0.02). Radiographic scores were also worse in nonadherent patients at baseline and at 12 months.

Only one-fifth of RA patients had an overall adherence to DMARDs of at least 80%. Less than two-thirds of the prescribed DMARD doses were correctly taken. Adherent patients had lower disease activity across the 2 years of followup.

Although current advances in surgical techniques have improved outcomes of the medial opening-wedge high tibial osteotomy (MOWHTO), the factors associated with patient dissatisfaction remain unclear. Thus, the purpose of this study is to identify risk factors for patient dissatisfaction following contemporary MOWHTO. We retrospectively reviewed prospectively collected data on 140 consecutive MOWHTO patients using an anatomical locking plate with a minimum follow-up of 2 years. Patient demographics, pain Visual Analogue Scale, Western Ontario and McMaster Universities Osteoarthritis Index, Kellgren-Lawrence (K-L) grade, activity level, articular cartilage and meniscal status, hip-knee-ankle angle, change in alignment, and postoperative weight-bearing line ratio were recorded. Patients were categorized using the New Knee Society Score into satisfied (satisfaction score ≥20) or dissatisfied (satisfaction score <20) groups. Patient and surgical factors were compared between the groups by the identified predictors. Multiple logistic regression analysis was used to analyze risk factors, including K-L grade IV medial osteoarthritis (OA), preoperative pain Visual Analogue Scale, total Western Ontario and McMaster Universities Osteoarthritis Index score, postoperative hip-knee-ankle angle, change in alignment, and partial meniscectomy. Of the 140 patients, 24 (17.1%) were dissatisfied with their results. Multiple logistic regression analysis showed that only K-L grade IV medial OA was statistically associated with patient dissatisfaction following MOWHTO (odds ratio 4.911, 95% confidence interval 1.820-13.256, P < .01). Level III.

Severe medial OA was an independent risk factor for dissatisfaction following contemporary MOWHTO using a rigid locking plate. Surgeons should take this into consideration when counseling and choosing surgical options in MOWHTO candidates with severe medial OA.

Many theories have been proposed as to the relationship between fibromyalgia (FM) and temporomandibular disorders (TMD). The aim of this study was to investigate the clinical features of the involvement of the stomatognathic system in patients with fibromyalgia, and to compare signs and symptoms of masticatory dysfunction between TMD and FM patients. The study sample consisted of 30 subjects with fibromyalgia recruited at the Rheumatology Disease Department, University of Pisa, Italy, and of 30 with temporomandibular disorders at the Section of Prosthetic Dentistry, Department of Neurosciences, University of Pisa, Italy. Masticatory dysfunction has been compared between the 2 groups by means of a clinical assessment conducted according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Patients of the TMD group underwent a rheumatologic examination to investigate for the presence of previously undiagnosed fibromyalgia. As regards specific clinical variables and RDC/TMD diagnoses, differences between the 2 groups appear to be not relevant, with the exception of the values of mouth opening, both voluntary and passive, and the presence of trigger points. FM patients showed a decrease in both maximum voluntary and passive mouth opening which was about 2 mm worse than that recorded in TMD patients. FM patients also showed a significantly higher number of trigger points, even though muscle palpation evoked tenderness in the same number of sites in the 2 groups.

This study showed that most patients with fibromyalgia (86.7%) report signs and symptoms localized at the stomatognathic system; by contrast, only a minority of patients with temporomandibular disorders (10%) are actually affected by fibromyalgia.