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To study the frequency and severity of dry eye in patients with juvenile rheumatoid arthritis (JRA) and its relation to disease activity. Evaluation for dry eye was done in 40 patients with juvenile rheumatoid arthritis referred for ocular assessment in the Ophthalmology Clinics, Faculty of Medicine, Ain Shams University. They were 28 girls and 12 boys with age range of 7-12 years. Medical history, clinical examination, and full ophthalmologic evaluation were performed for each patient. The dry eye tests included tear film break-up time, Schirmer-1 test, and corneal fluorescein staining. Dry eye severity grading was used. Twenty healthy, age- and sex-matched children were assessed for dry eye as a control group. Thirty patients (75%) showed findings consistent with the diagnosis of dry eye. Twenty patients (50%) showed first-degree dryness, 8 (20%) showed second-degree, and 2 (5%) showed third-degree. The score of dry eye severity was significantly lower in remission compared to disease activity. Multiregression analysis showed the only factor affecting dry eye parameters was the duration of illness.

Dry eye is a common incident in children with JRA and should be screened for in all patients with this disease. Severity of eye dryness is highly correlated with the disease activity.

Rheumatoid arthritis (RA) is characterized by symmetric peripheral polyarthritis, inflammatory synovitis, and articular destruction. Statins, 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors, mediate significant vascular risk reduction in patients with coronary artery disease by promoting reduction in plasma levels of low-density-lipoprotein cholesterol. Extensive in vitro data, experimental studies and more recently few clinical trials have strongly suggested statins to possess an important role in RA mainly mediated by their anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the effect of adjunct statin therapy in comparison to standard disease modifying antirheumatic drugs (DMARD) therapy in patients with RA. In this observational study, diagnosed RA patients of age group between 40 and 60 years were selected as per the inclusion criteria from the rheumatology outdoor. From the selected patients, we identified two separate groups of patients. Group 1 included 30 patients of RA currently under DMARD therapy with adjunct statin medication. Group 2 included 30 patients of RA currently under DMARD therapy. Patients were followed up over 6 months. Standard parameters such as disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were recorded for comparing the outcome of RA in both groups. Out of a total of 60 patients who took part in the study, significant beneficial role of adjunct statin medication was found in this study when prescribed along with conventional DMARDs in active RA patients. The mean DAS28, considered by far as the most important index of clinical disease activity in RA, was found to be significantly lower (P < 0.05) in the adjunct statin-treated group (group 1) than that of the conventional DMARD treated group (group 2) after 6 months of continuous therapy. Other two important biochemical markers of RA disease activity, that is, ESR and CRP were also found to be significantly lower (P < 0.05) in RA patients who were on adjunct statin medication (group 1) than in group 2 comprising RA patients only under conventional DMARDs therapy without statin medication.

The results suggest an adjunct and potentially beneficial role of statin therapy in active cases of RA, producing significant clinical and biochemical improvement.

To examine for latent patterns of SLE disease activity trajectories that associate with specific latent patterns of health-related quality of life (HRQoL; Medical Outcomes Study Short Form-36), and to determine baseline predictors of class membership. In this retrospective longitudinal inception cohort of 222 SLE adults over 10 years, trajectories of three outcomes were studied jointly: Short Form-36 physical (PCS) and mental (MCS) component summaries and adjusted mean SLEDAI-2000 (AMS). Group-based joint trajectory modelling was used to model latent classes; univariable and multivariable analyses were used to identify predictors of class membership. Four latent classes were identified: Class 1 (C1) (24%) had moderate AMS, and persistently low PCS and MCS; C2 (26%) had low AMS, moderate PCS and improved then worsened MCS; C3 (38%) had moderate AMS, and persistently high PCS and MCS; and C4 (11%) had high AMS, moderate-low PCS and improving MCS. Baseline older age was associated with lower HRQoL trajectories. Higher AMS trajectories did not associate with a particular pattern of HRQoL trajectory. A higher prevalence of fibromyalgia (44% in C1) was associated with worse HRQoL trajectories. Disease manifestations, organ damage and cumulative glucocorticoid were not differentially distributed across the latent classes.

High disease activity did not necessarily associate with low HRQoL. More patients with worse HRQoL trajectories had fibromyalgia. Older age at diagnosis increased the probability of belonging to a class with low HRQoL trajectories. The care of SLE patients may be improved through addressing fibromyalgia in addition to disease activity.

Despite the routine use of physical therapy in the immediate and early postoperative phase for patients who undergo total knee replacement (TKR), there is a paucity of research into the optimal exercise protocols in both the acute inpatient setting and early period after discharge. Pedaling has often been recommended by clinicians after TKR for rehabilitation, but to our knowledge, there has been no investigation into its utility in the acute postoperative setting. Therefore, we performed a randomized controlled trial evaluating the efficacy of pedaling in the acute postoperative period. Sixty TKR patients were randomized to receive postoperative physical therapy involving either a 3-exercise pedaling (pedaling-based) or 10-exercise, non-pedaling (multi-exercise) protocol. Outcomes were assessed at 2 days, 2 weeks, and 4 months, and included physical tests of function, patient-reported outcomes, and other perioperative measures. With respect to the primary outcome, the 6-minute walk test (6MWT), the measured distance was significantly greater in the pedaling-based group than in the multi-exercise group at 2 days postoperatively (mean difference, 66 m; p = 0.001). Results of other functional tests, the 10-m walk test (10MWT) and the Timed Up & Go (TUG) test, were both significantly superior for the 3-exercise pedaling group at 2 days (p = 0.016 for 10MWT, and p = 0.020 for TUG), as was the patient-reported Oxford Knee Score (p = 0.034). The latter continued to be superior at 2 weeks (p = 0.007), as was the EQ-5D score (p = 0.037). The visual analogue scale (VAS) component of the EQ-5D was significantly better for the pedaling group at all time points assessed. Length of stay was also significantly shorter, by a half-day, for the pedaling-based group (median of 2.5 days compared with 3.0 days for the multi-exercise group; p = 0.024). The multi-exercise protocol was not superior for any outcome measure at any time point. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

A pedaling-based protocol in the immediate postoperative period after TKR was superior to a standard multi-exercise protocol in both functional and patient-reported outcomes, with these benefits decreasing over time.

Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis. We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications.

With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)

To examine the association between weather and pain in rheumatoid arthritis (RA). Systematic review of longitudinal observational studies (up to September 2009) with data on the association between weather variables and severity of pain in RA. The methodological quality was rated independently by the two authors according to an adapted Newcastle-Ottawa Scale. We analyzed the data on an aggregated (group) level with a meta-analysis of correlations between pain and weather, and at an individual level as the proportion of patients for whom pain was significantly affected by the weather. Nine studies were included. Many different weather variables have been studied, but only three (temperature, relative humidity and atmospheric pressure) have been studied extensively. Overall group level analyses show that associations between pain and these three variables are close to zero. Individual analyses from two studies indicate that pain reporting in a minority (<25%) of RA patients is influenced by temperature, relative humidity or atmospheric pressure. We were not able to relate the findings to methodological quality or other aspects of the studies.

The studies to date do not show any consistent group effect of weather conditions on pain in people with RA. There is, however, evidence suggesting that pain in some individuals is more affected by the weather than in others, and that patients react in different ways to the weather. Thus, the hypothesis that weather changes might significantly influence pain reporting in clinical care and research in some patients with RA cannot be rejected.

To evaluate the efficacy and safety of diclofenac etalhyaluronate (DF-HA) (ONO-5704/SI-613), a novel DF-conjugated hyaluronate, in patients with knee OA in Japan. In this randomized, double-blind, placebo-controlled phase 2 study, patients were randomly assigned (1:1) to receive either 30 mg of DF-HA or placebo intra-articularly at weeks 0, 4 and 8 and were followed up for 24 weeks. The primary outcomes were changes from baseline in the WOMAC pain subscores, 50-foot walk test pain score and daily pain score. The secondary outcomes were the WOMAC physical function subscores, patient global assessment, responder rate and safety outcome. Overall, 176 patients received the investigational drugs (87 received DF-HA and 89 received placebo). The mean changes in the WOMAC pain subscores and daily pain score from baseline over 12 weeks after the first injection were significantly higher in the DF-HA than placebo group; the mean difference was -7.0 mm [95% CI, -12.7, -1.2; P =0.018] and -0.61 (95% CI, -1.06, -0.16; P =0.008), respectively. The difference in the 50-foot walk test pain score was -5.0 mm (95% CI, -10.3, 0.3; P =0.065). Improvement of pain by DF-HA was observed at week 1 and maintained from week 12 to week 24. Significantly greater improvements in the secondary outcomes were also observed with DF-HA than with placebo. No clinically significant adverse events occurred. UMIN Clinical Trials Registry, https://www.umin.ac.jp/ctr/index.htm, UMIN000015858.

DF-HA reduced pain in patients with knee OA without major safety concerns.

To examine the conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca (SS-KCS) and non-Sjögren's keratoconjunctivitis sicca (NS-KCS) for evidence of immune-based inflammation. Conjunctival biopsy specimens were obtained from 15 patients with SS-KCS and 15 with NS-KCS. Immunohistochemistry was performed on frozen sections to characterize and quantify T-cell subtypes (CD3, CD4, and CD8) and markers of immune activation (major histocompatibility complex [MHC] class II: HLA-DR, HLA-DQ) and inflammation (intercellular adhesion molecule [ICAM]-1). The numbers of cells positive for each marker were counted by two masked observers and averaged. Conjunctival biopsy specimens from patients with SS-KCS or NS-KCS revealed lymphocytic infiltration and increased immunoreactivity for the markers of inflammation and immune activation. The extent of cellular immunoreactivity did not differ significantly between SS-KCS and NS-KCS tissue samples.

The authors' findings indicate that patients with SS-KCS or NS-KCS have conjunctival inflammation manifested by inflammatory cell infiltrates and upregulation of expression in markers of immune activation. Clinical symptoms of KCS may be more dependent on T-cell activation and resultant inflammation than previously believed. In addition to tear substitutes, anti-inflammatory therapeutics should be investigated for the treatment of KCS.

Infectious agents have long been postulated to be disease triggers for systemic sclerosis (SSc), but a definitive link has not been found. Metagenomic analyses of high-throughput data allows for the unbiased identification of potential microbiome pathogens in skin biopsies of SSc patients and allows insight into the relationship with host gene expression. We examined skin biopsies from a diverse cohort of 23 SSc patients (including lesional forearm and non-lesional back samples) by RNA-seq. Metagenomic filtering and annotation was performed using the Integrated Metagenomic Sequencing Analysis (IMSA). Associations between microbiome composition and gene expression were analyzed using single-sample gene set enrichment analysis (ssGSEA). We find the skin of SSc patients exhibits substantial changes in microbial composition relative to controls, characterized by sharp decreases in lipophilic taxa, such as Propionibacterium, combined with increases in a wide range of gram-negative taxa, including Burkholderia, Citrobacter, and Vibrio.

Microbiome dysbiosis is associated with disease duration and increased inflammatory gene expression. These data provide a comprehensive portrait of the SSc skin microbiome and its association with local gene expression, which mirrors the molecular changes in lesional skin.

To evaluate medical and work disability costs for patients with chronic inflammatory joint disease during one year before and one year after institution of infliximab treatment in routine clinical practice. Starting from 1999, clinical and laboratory variables for patients treated with biological agents for inflammatory rheumatic diseases were systematically recorded at Helsinki University Central Hospital. From this database clinical information was collected on 96 patients in whom infliximab was started during the period 1999 to 2001. Economic analyses were based on costs incurred because of outpatient and inpatient visits, orthopaedic operations, drugs used, and days on sickness or rehabilitation allowance. Medical and work disability costs were calculated separately for the one year period before (period I) and the one year period after institution of infliximab (period II). Of the study group of 96 patients (arthritis duration 16 years (range 3 to 43)), 74 completed one year of infliximab treatment. Their clinical and laboratory variables improved significantly. The mean increase in medical costs during period II was euro12 015 (95% confidence interval, 6496 to 18,076). A minimal decrease in work disability costs occurred-mean decrease euro130 (-1268 to 1072).

One year treatment with infliximab in patients with longstanding aggressive arthritis showed a good clinical effect but raised medical costs significantly. Work disability costs failed to show a substantial decrease. Starting infliximab in the earlier stages of chronic arthritis could in the long term prevent work disability and thus decrease the total cost to society.

To evaluate the efficacy of chiropractic spinal manipulation, manual flexion/distraction, and hot pack application for the treatment of low back pain from osteoarthritis (OA) compared with moist heat alone. Two hundred fifty-two patients with low back pain secondary to OA were randomly assigned to either the treatment group (moist hot pack plus chiropractic care) or the moist heat group subjects, which attended 20 treatment sessions over several weeks. At sessions 1, 5, 10, 15, and 20, they rated pain using a visual analog pain scale, activities of daily living using the Oswestry Low Back Pain Questionnaire, and a range of motion (ROM) using the J-Tech Dual Digital Inclinometer (JTECH Medical Model no. AA036). Session I ratings indicated that the two groups were equivalent on all pain and flexion scores. The treatment group reported greater and more rapid pain reduction and greater and more rapid ROM improvement than the moist heat group. The treatment group also had greater improvements than the moist heat group in daily living activities in 4 of the 9 areas measured.

Chiropractic care combined with heat is more effective than heat alone for treating OA-based lower back pain. Pain reduction occurs more rapidly and to a greater degree, and ROM increases more rapidly and to a greater degree.

CD14, the monocyte receptor for lipopolysaccharides (LPS), is an important mediator of inflammatory processes. As the T-159C exchange in the promotor of the CD14 gene was reported to lead to enhanced CD14 expression, this could be a new susceptibility gene for rheumatoid arthritis (RA). We investigated whether this single nucleotide polymorphism (SNP) serves as a risk factor for disease development or has any influence on serological activity parameters of RA or soluble CD14 (sCD14) levels. A total of 130 patients with RA, diagnosed according to the revised American College of Rheumatology (ACR) criteria, and 130 healthy subjects, all Caucasians, were genotyped using polymerase chain reaction (PCR). Genotype frequencies were compared by chi2 analysis. Forty (31%) patients vs. 39 (30%) controls were genotyped CC; 71 (55%) vs. 67 (52%) were heterozygous, and 19 (15%) vs. 24 (19%) showed the TT genotype (p = 0.7). Accordingly, the allele frequency was equally distributed (p = 0.8). There was also no significant difference in genotype distribution between subgroups of patients categorized according to serological activity parameters and sCD14 levels.

We found no association between the CD14/C-159T polymorphism and increased risk for the development of RA or serological disease activity parameters or sCD14 levels.

To investigate right ventricular diastolic function in rheumatoid arthritis (RA) and its relationship with left ventricular and pulmonary involvement. Thirty-five RA patients and 30 healthy subjects were submitted to conventional Doppler (CE) and tissue Doppler echocardiography (TDE) to assess left and right systolic and diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). To detect pulmonary involvement, pulmonary function tests and high-resolution computed tomography (HRCT) scans were performed in all RA patients. An abnormal RV filling, as expressed byan inverted tricuspid (Tr.) E/A ratio, was detected in 12 (34%) of the 35 RA patients and in 2 (7%) of the 30 controls (P<0.004). If compared to CE findings, prevalence of RV diastolic abnormalities were found higher in patients with RA by TDE (RV annulus Em/Am ratio <1 (in 31 (89%) of 35 patients) (P = 0.002). Twenty-two (63%) of 35 patients had abnormal HRCT findings. Pulmonary involvement with pulmonary hypertension (PHT) (36+/-5 mmHg) was detected in 10 (29%) of 35 RA. In this group, increase of RV annulus and basal Am wave, decrease of Tr. E/A ratio and RV annulus Em/Am ratio were statistically significant compared to RA (12 (34%) of 35) patients with pulmonary involvement who had normal PAP (19+/-5 mmHg), (P = 0.014, P = 0.006, P = 0.015, P = 0.049, respectively).

This study points out an impaired RV filling in a significant part of RA patients without overt heart failure. Impairment of RV diastolic function may be a predictor of subclinic myocardial and pulmonary involvement in patients with RA.

Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system, involved in both initiating immune responses and maintaining tolerance. Dysfunctional and via toll-like receptor (TLR) ligands activated DC have been implicated in the development of autoimmune diseases, but their role in the etiology of Sjögren's syndrome, a chronic inflammatory autoimmune disease characterized by progressive mononuclear cell infiltration in the exocrine glands, has not been revealed yet. Therefore, the aim of this study was to investigate phenotype and functional properties of immature and TLR7/8 stimulated monocyte-derived DC (moDC) of patients with primary Sjögren's syndrome (pSS) and compare them to healthy controls. The phenotype, apoptosis susceptibility and endocytic capacity of moDC were analyzed by flow cytometry. Secretion of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and multiplex Luminex analyses in moDC cell culture supernatants. The expression of TLR7 was analyzed by flow cytometry and real-time quantitative polymerase chain reaction (qPCR). Expression of Ro/Sjögren's syndrome-associated autoantigen A (Ro52/SSA), interferon regulatory factor 8 (IRF-8), Bim, signal transduction and activators of transcription (Stat) 1, p-Stat1 (Tyrosin 701), p-Stat1 (Serin 727), Stat3, pStat3 (Tyrosin 705) and glyceraldehyde 3-phosphatase dehydrogenase (GAPDH) was measured by Western blotting. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family members were quantified using the ELISA-based TransAM NF-κB family kit. We could not detect differences in expression of co-stimulatory molecules and maturation markers such as cluster of differentiation (CD) 86, CD80, CD40 or CD83 on moDC from patients compared to healthy controls. Moreover, we could not observe variations in apoptosis susceptibility, Bim and Ro52/SSA expression and the endocytic capacity of the moDC. However, we found that moDC from pSS patients expressed increased levels of the major histocompatibility complex (MHC) class II molecule human leukocyte antigen (HLA)-DR. We also found significant differences in cytokine production by moDC, where increased interleukin (IL)-12p40 secretion in mature pSS moDC correlated with increased RelB expression. Strikingly, moDC from pSS patients matured for 48 hours with TLR7/8 ligand CL097 expressed significantly less Stat1.

Our results suggest a role for moDC in the pathogenesis of Sjögren's syndrome.

Patients with rheumatoid arthritis (RA) and clinicians have different views about benefits from treatments. More knowledge is needed about how patients assess outcomes in order to update current measurements. Focus group interviews were performed at four Swedish rheumatology clinics. A total of 25 patients with RA were included, representing a wide range of ages and disease duration. Predetermined topics relating to important outcomes from and satisfaction/dissatisfaction with RA treatments were discussed. The participants' initial outcome assessments included physical and psychosocial items, which comprised overall treatment goals such as impairment in social roles, fatigue, daily activities and self-confidence. The identified themes were 'Normal life', 'Physical capacity', 'Independence' and 'Well-being'. Satisfaction with treatment was associated with the quality of communication between staff and the patient. The participants assumed this as a prerequisite for a treatment to work. Patients wanted to be accepted as experts on their own bodies, and expected all clinicians to be experts on RA. This made it possible for patients to 'take charge' of their life situation. Good resources for and access to rheumatology care were desired.

Suggesting a holistic approach to rheumatology care, the study results indicate that the illness and outcomes have to be evaluated within an individual RA patient's total life situation, described in the identified themes: 'Normal life', 'Physical capacity', 'Independence' and 'Well-being'. Development and validation of measurements covering these issues is suggested. More research is needed about communication and how patients experience their roles in the rheumatology clinic.

To evaluate the prevalence and incidence of antimalarial myopathy in patients with rheumatic diseases treated with antimalarial drugs. Over a three year period, all patients with rheumatic diseases who were taking antimalarial drugs were studied. Serum muscle enzymes were assessed at the time of inclusion and every six months thereafter. Muscle strength, electromyography (EMG), and muscle biopsy were assessed in patients with a persistent muscle enzyme disturbances. 119 patients were included (111 chloroquine, eight hydroxychloroquine). Of these, 22 (18.5%) had a persistent muscle enzyme disturbance: lactate dehydrogenase 19/22 (86%); creatine kinase 7/22 (32%), and aldolase 3/22 (14%). Findings of antimalarial myopathy were detected in 3/15 biopsied patients (20%) by light microscopy and in all 15 by electron microscopy. Eleven patients had myopathy at the time of inclusion (prevalence 9.2%) and four patients developed muscle injury during follow up (annual incidence 1.2%). Muscle weakness was observed in 8 of 15 patients with biopsy proven myopathy, giving a prevalence of clinical antimalarial myopathy of 6.7%. All these patients also had a myopathic pattern on electromyography.

The prevalence of antimalarial myopathy is higher than previously recognised when muscle enzyme determination is used as a screening method. When a persistent muscle enzyme disturbance is observed, clinical and electromyographic studies should be undertaken periodically to detect the development of clinical myopathy. In cases of clinical myopathy, an anatomical-pathological tissue study, including an ultrastructural study, is mandatory to confirm the diagnosis.

The aim of our study was to investigate the frequency of auto-immune diseases in patients suffering from autoimmune thyroid diseases. We realised a retrospective study from 1981 to 1993 including 218 patients suffering from thyroiditis who were followed in the same hospital service. There were 202 women and 16 men with a mean age 49 at the moment their thyroid pathology was discovered. Thirty patients had one or more autoimmune disease associated to their thyroid disorders, representing 13.7% of total patients. The two most frequent autoimmune diseases were lupus and Sjögren's syndrome. In 17 cases the diagnosis of the associated autoimmune disease was made simultaneously. The systemic disease preceded with an 8-year delay the thyroid disease in five cases, and the thyroid disease was annunciatory in eight cases with a delay of 5 years. The frequency of autoimmune diseases seems to be higher in patients suffering from thyroid disorders than in the general population. They are probably common physiopathological mechanisms.

The frequency of these associations suggests the need for a long-lasting survey of those patients having thyroid disorders. Initial evaluation and a regular checking in patients suffering from an autoimmune disease is recommenced.

We investigated the relations between flexion balances and functional outcomes after total knee arthroplasty (TKA). Sixty-one knees that underwent a TKA were included in this study. Clinical assessments were performed and flexion balances of the knee were assessed on varus and valgus stress radiographs at 90° of knee flexion. Total laxity was defined as the sum of medial and lateral laxities. Knees were divided into balanced (≤3°, n = 51) and unbalanced (>3°, n = 10) groups based on the only difference of mediolateral laxity regardless of total laxity. And the balanced group was divided into Grade I (<6°), Grade II (≥6° but ≤10°) or Grade III (>10°) groups based on the amount of total laxity. Although no statistically significant differences were observed between the balanced and unbalanced groups in terms of range of motion (ROM) and KS pain scores, the balanced group achieved better results in terms of KS function and WOMAC scores than the unbalanced group. Total laxity was significantly less in the balanced group. In addition, Grade II knees in the balanced group had significantly better KS pain and function scores, and WOMAC scores than Grade Ior Grade III knees.

These results suggest that total knees with good balanced flexion stability can provide good functional outcomes after TKA.

To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified. We recruited patients with at least 1 SARD clinical feature and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients, and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort. Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p < 0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count.

In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment.

Short-term, low-dose glucocorticoid (GC) treatment has anti-inflammatory and disease-modifying effects in rheumatoid arthritis (RA). However, scientific support for long-term, low-dose GC treatment, although widespread, is poor, and information on the effects on bone density is scarce. The aim of this study was to investigate how long-term GC treatment in RA affects inflammation as well as bone density, and also to investigate the feasibility of withdrawal of GC. Fifty-eight patients with RA treated with 5-7.5 mg prednisolone daily for at least 2 years were randomized either to withdraw or to continue GC treatment. The patients were followed prospectively for 2 years with respect to disease activity [using the Disease Activity Score calculated for 28 joints, (DAS28)], functional ability [using the Health Assessment Questionnaire (HAQ) score] and bone mineral density (BMD) of the lumbar spine and hip. Only 11 patients out of 26 randomized to stop GC treatment and available for outcome measures succeeded in stopping the GC medication within 1 year. Fifteen patients failed withdrawal of GC because of increased joint symptoms. A higher mean DAS28 during the study was associated with loss of bone mass in the trochanter. The group that continued with unchanged GC treatment did not deteriorate in BMD during the 2 years but in fact Z-scores improved significantly.

Our results indicate that low-dose GC treatment after several years has persisting anti-inflammatory effects in RA and no further negative impact on BMD. It thus seems to be more important to control disease activity than withdraw low-dose GC treatment in this population considering bone health.

In fibromyalgia syndrome (FMS) defined rehabilitation guidelines are yet to be validated. Our aim is to evaluate the efficacy of the Rességuier method (RM) in FMS. Forty-one patients were randomly assigned to Interventional (22 pts) and Observational (19 pts) Group (IG and OG). The study lasted 8 months. Patients were assessed at baseline (T0) after a 2-month rehabilitation (T1) and at a 6-month follow-up (T2) (only IG) with SF-36 Physical (PSI) and Mental Synthetic Index (MSI), Regional Pain Scale (RPS), Fibromyalgia Impact Questionnaire (FIQ), Number Rating Scales 0-10 to measure pain, movement quality, sleep, relax ability, analgesics number/per week. OG patients maintained their lifestyle for the duration of the study. RM aims to obtain patient awareness and control of bodily perceptions, thus reaching a modulation of responses to pain. Therapist controls patient attention and perception by verbal and manual contacts and leads them to perform bodily and respiratory active and conscious movements. In IG, at T1 all items were improved: PSI and MSI (p<0.001 and =0.001), FIQ (p<0.0001), RPS (p<0.001), pain (p<0.0001), movement quality (p=0.001), relax ability (p<0.0001), sleep (p<0.001); analgesics number/per week was reduced (p<0.001). All results obtained at T1, except FIQ, were maintained at T2. In OG at T1 versus T0, no difference in any of the assessed parameters was observed.

In FMS patients, the rehabilitation with RM improves HRQoL, FMS-related disability and perceived pain, thus reducing the assumption of analgesics.

Cervical disc herniation (CDH) is the most common cause of cervical radiculopathy and could overlap with fibromyalgia (FM). The primary aim of the present study was to investigate the prevalences of FM and widespread pain in patients with cervical radiculopathy diagnosed as CDH in a cross-sectional study. The secondary aim was to analyze the localization of tender points (TPs) and associated symptoms in these patients comparing patients with FM. Fifty-two patients with cervical radiculopathy who carried the diagnosis of CDH and 51 patients with FM included to the study. The patients were questioned for the distribution and the duration of pain and for a group of symptoms related to FM such as headache, fatigue with a two-point scale (0 "no", 1 "yes"). The diagnosis of CDH was made with patients' clinical evaluation and radiological findings with Magnetic Resonans Imaging Study. FM was diagnosed using the American College of Rheumatology criteria. Widespread pain was defined as all of the following parameters were present: pain in the left side of the body; pain in the right side of the body; pain above the waist; pain below the waist; axial skeletal pain; and duration of pain for more than 3 months. The number of TPs were counted by digital palpation. Six female patients (11.5%) with CDH fulfilled the ACR 1990 criteria for FM. Of the patients with CDH 71.8% of TPs were located around the neck and shoulder regions, while 58.7% of TPs of the patients with FM were located around these regions. There were statistically significant differences between the patients with CDH and the patients with FM in terms of the duration of widespread pain, the number of TPs and the localization of TPs (p< 0.05).

The prevalences of FM and widespread pain in patients with CDH were found as 11.5% and 78.8% respectively.

To estimate the future direct cost of OA in Canada using a population-based health microsimulation model of osteoarthritis (POHEM-OA). We used administrative health data from the province of British Columbia (BC), Canada, a survey of a random sample of BC residents diagnosed with OA (Ministry of Health of BC data), Canadian Institute of Health Information (CIHI) cost data and literature estimates to populate a microsimulation model. Cost components associated with pharmacological and non-pharmacological treatments, total joint replacement (TJR) surgery, as well as use of hospital resources and management of complications arising from the treatment of osteoarthritis (OA) were included. Future costs were then simulated using the POHEM-OA model to construct profiles for each adult Canadian. From 2010 to 2031, as the prevalence of OA is projected to increase from 13.8% to 18.6%, the total direct cost of OA is projected to increase from $2.9 billion to $7.6 billion, an almost 2.6-fold increase (in 2010 $CAD). From the highest to the lowest, the cost components that will constitute the total direct cost of OA in 2031 are hospitalization cost ($2.9 billion), outpatient services ($1.2 billion), alternative care and out-of-pocket cost categories ($1.2 billion), drugs ($1 billion), rehabilitation ($0.7 billion) and side-effect of drugs ($0.6 billion).

Projecting the future trends in the cost of OA enables policy makers to anticipate the significant shifts in its distribution of burden in the future.

To determine (i) clinicoradiological presentation and outcome of rapidly destructive knee osteoarthritis (RDKOA) after global medical treatment including knee lavage plus corticosteroid injection, (ii) predisposing factors of subsequent requirement to knee surgery. Retrolective monocenter study with tibiofemoral RDKOA, defined as a loss of at least 50% of joint space width within 1 year, with a post lavage follow-up of at least 1 year. One hundred and eleven patients were enrolled, age 64.1 years, BMI: 28.9, 70.3% female. VAS pain was 56.1mm, Lequesne index: 11.9, WOMAC function score: 51.9. Chronic mechanical effusion (216 white cells/mm3) was aspirated in 102 patients (91.9%), lasting more than 6 months in 71.4%. Medial tibiofemoral compartment was concerned in 79.3%. Joint space loss reached 52.2% in extension and 71.0% in semi-flexed position within a mean 7.3-month period. Radiological chondrocalcinosis was present in 13.5% and osteonecrosis in 12.6%. Lavage (one liter, two 14-gauge cannulae) plus corticosteroid was completed by hyaluronic acid injections in 71.2% of patients. Eighty-nine patients were reviewed with a mean follow-up period of 55.0 months. Thirty-seven (41.6%) required surgery. Mean delay between lavage and surgery was 16.1 months. Pain was acceptable in 100.0% of operated patients and 87.8% of non-operated patients. Multivariate regression analysis determined that functional impairment, assessed by the maximal walking time, and radiological severity in extension were baseline predisposing factors of subsequent requirement to surgery.

The outcome of RDKOA seems less severe than expected after global medical treatment.

The purpose of this study was to conduct a longitudinal examination of cognitive complaints and functional status in patients with chronic fatigue syndrome (CFS) alone and those who also had fibromyalgia (CFS/FM). A total of 93 patients from a tertiary care fatigue clinic were evaluated on four occasions, each 6 months apart. Each evaluation included a tender point assessment, and self-reported functional status and cognitive complaints. Patients with CFS/FM reported significantly worse physical functioning, more bodily pain, and more cognitive difficulties (visuo-perceptual ability and verbal memory) than patients with CFS alone. Over time, bodily pain decreased only for participants with CFS alone. Verbal memory problems were associated with more bodily pain for both patient groups, whereas visuo-perceptual problems were associated with worse functional status for patients with CFS alone.

This study adds to the literature on functional status, longitudinal course, and cognitive difficulties among patients with CFS and those with CFS and FM. The results suggest that patients with CFS/FM are more disabled, have more cognitive complaints, and improve more slowly over time than patients with CFS alone. Specific cognitive difficulties are related to worse functional status, which supports the addition of cognitive difficulties to the FM case criteria.

To examine daily positive affective disturbance in the context of negative affect (NA) and pain among patients with fibromyalgia (FM) to determine a) if FM patients experience a deficit in daily positive affect (PA) relative to osteoarthritis (OA) patients; b) if FM patients differ from OA patients in the day-to-day relations of PA and NA; and c) if patients diagnosed with both OA and FM differ from patients with either OA-only or FM-only with respect to major outcomes. A total of 260 women with physician-diagnosed OA (n = 106), FM (n = 53), or OA/FM (n = 101) completed a 30-day electronic diary. Participants were assessed once daily on levels of PA, NA, and pain. Multilevel models indicated that FM patients had less overall PA than OA patients and exhibited a stronger inverse PA-NA relation. Analyses further suggest that the OA/FM group may have been the most impaired of the three included in our study. This group was responsible for a lagged effect of PA on both affects, whereby high PA days resulted in low next-day PA and high next-day NA.

FM patients exhibit a PA disturbance compared with OA patients. This disturbance is reflected by an overall deficit in PA and an inability to sustain PA in the face of pain and NA. Patients with both OA and FM may represent a subgroup of FM that is at particular risk for dysregulation of PA.

To evaluate the impact of a nurse-led program of systematic screening for the management (detection/prevention) of comorbidities. Prospective, randomized, controlled, open, 12-month trial (NCT02374749). consecutive patients with axial Spondyloarthritis (axSpA) (according to the rheumatologist) THE PROGRAM: A nurse collected data on comorbidities during a specific outpatient visit. In the event of non-agreement with recommendations, the patient was informed and a specific recommendation was given to the patient (orally and in a with a detailed written report). Patients were seen after one year in a nurse-led visit. TREATMENT ALLOCATION: random allocation (i.e. either this program or an educational program not presented here and considered here as the control group). change after one year of a weighted comorbidity management score (0 to 100 where 0= optimal management). 502 patients were included (252 and 250 in the active and control groups, respectively): age: 47±12 years, male gender: 63%, disease duration: 14±11y. After one year, no differences were observed in a weighted comorbidity management score. However, the number of patients in agreement with recommendations was significantly higher in the active group for vaccinations (flu vaccination: 28.6% vs. 9.9%, p<0.01; pneumococcal vaccination:40.0% vs. 21.1%,p=0.04), for cancer screening (skin cancer screening: 36.3% vs. 17.2%, p=0.04) and for osteoporosis (bone densitometry performed: 22.6% vs. 8.7%, p<0.01; Vitamin D supplementation initiation: 51.9% vs. 9.4%, p<0.01).

This study suggests the short-term benefit of a single-visit nurse-led program for systematic screening of comorbidities for its management in agreement with recommendations, even in this young population of patients with axSpA.

To determine whether dorsolateral subluxation (DLS) scores in young dogs could be used to reliably predict which dogs would develop evidence of hip osteoarthritis and whether DLS scores measured at various ages correlated with each other. 129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds. DLS scores were measured on radiographs taken at 4, 8, and 12 months of age and at necropsy (8 to 36 months of age). At necropsy, the hip joints were examined macroscopically and a score assigned for degree of cartilage degeneration. DLS scores at 4 (n = 35, r(s) = -0.62), 8 (n = 106, r(s) = -0.54), and 12 (n = 15, r(s) = -0.87) months of age were significantly correlated with cartilage degeneration scores, and DLS scores at 8 months of age were significantly correlated with scores obtained at the time of necropsy (n = 39, r(s) = 0.87). The DLS scores at 4 months of age were significantly different from scores at 8 months of age, but scores did not differ significantly thereafter. Likelihood ratios for cartilage lesions for low (< 45%), intermediate (> or = 45 but < or = 55%), and high (> 55%) DLS scores at 8 months of age were 8.0, 2.6, and 0.2, respectively.

Results suggest that DLS score at 8 months of age was a reasonable, albeit imperfect, predictor of the condition of the hip joint cartilage at necropsy. Thus, the DLS method might be useful for early identification of dogs with hip dysplasia.

Unicondylar knee arthroplasty (UKA) has superior functional outcomes compared to total knee arthroplasty (TKA) with good mid-term and long-term survival data from high-volume institutions. We sought to quantify the risk of complications, re-operation/revision, hospital re-admission for any reason, and mortality of knee arthroplasty patients in the US patient population using 2 large databases. UKA and TKA patients who were identified in the 2002-2011, 5% sample of Medicare data and 2004-2012 (June) MarketScan Commercial and Medicare Supplemental Databases were followed to evaluate the risk of complications, hospital re-admission for any reason, and mortality within 90 days of surgery. Survival probability defined by re-operation was calculated using the Kaplan-Meier method at 0.5, 2, 5, 7, and up to 10 years post-operatively. Compared to UKA, complication rates for TKA patients were significantly higher, including wound complication, pulmonary embolism, stiffness, peri-prosthetic joint infection, myocardial infarction, re-admission, and death. Age was found to be a significant risk factor (P < .05) for all complications in the Medicare cohort, except stiffness (P = .839), and all complications in the MarketScan cohort, except re-admission (P = .418), whereas gender had a variable effect on complications based on age. Survivorship of UKA was lower than TKA at all time points. Additionally, younger age adversely affected implant survival. By 7 years post-surgery, UKA survivorship in the Medicare and MarketScan cohorts was 80.9% and 74.4%, respectively. In contrast, TKA survivorship for the same cohorts was 95.7% and 91.9% by the same time point. Level III.

Patients undergoing UKA have fewer post-operative complications and re-admissions than those undergoing TKA. However, patients undergoing UKA have a higher rate of re-operation and revision at up to 10 years of follow-up. It appears that age, as well as surgeon and hospital volume significantly impacts implant survivorship while gender does not have a relation.

The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs. Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression. Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index.

A profile consisting of high levels of MMP-8, MMP-9, hepatocyte growth factor and CXCL8 is associated with increased disease activity in AS. High MMP levels are also associated with smoking and worse function in AS.

We previously reported that interleukin-29 (IL-29) was highly expressed in the blood and synovium of rheumatoid arthritis (RA) patients and contributed to synovial inflammation by induction of proinflammatory cytokine production. Given chronic inflammation can trigger the process of bone erosion, and receptor activator of nuclear factor-κB ligand (RANKL) plays a crucial role in bone erosion of RA, we hypothesize that IL-29 mediates bone erosion in RA by regulation of RANKL expression. Here, we investigated the effect of IL-29 on RANKL expression in RA fibroblast-like synoviocytes (FLS) and the relevant signaling pathways involved in it. Primary fibroblast cells isolated from RA patients were stimulated by recombinant IL-29 in the presence or absence of anti-IL-29 antibody, and the expression levels of RANKL were assessed using real-time polymerase chain reaction and immunostaining. Furthermore, the IL-29 signaling pathway for regulation of RANKL was also examined by Western blotting assay. IL-29 upregulated RANKL expression in a dose-dependent manner, and blockade of IL-29 resulted in a significantly reduced RANKL expression in RA-FLS. Incubation RA-FLS with IL-29 (100 ng/mL) led to phosphorylation of ERK (extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase). The expression of RANKL induced by IL-29 could be completely blocked by the inhibitors of mitogen-activated protein kinase (MAPK) signal pathway, including PD98059 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor).

These findings indicate, for the first time, that IL-29 could directly induce RANKL expression in RA-FLS via MAPK signaling pathway, suggesting IL-29 might be a new target in the prevention of joint destruction in RA.

Sagittal displacement in patients with end stage ankle arthritis has been described as the tibiotalar ratio (TTR). Yet the incidence, distribution and predictive factors of talolisthesis are unknown. The radiographs of 470 cases of ankle arthritis were compared with a control group of 49 normal ankles. The TTR was measured for both groups. Additional co-variables included the anterior and lateral distal tibial angles, and talar tilt. The mean TTR in the arthritis cohort was 34.8+9.12 compared to the normal group of 34.1+2.62. Twenty-eight percent of the ankles had anterior displacement and twenty-eight percent had posterior talolisthesis, while forty-four percent had normal tibiotalar alignment. Multivariate linear regression revealed significant predictors of anterior distal tibial angle (p<0.0001) and talar tilt (p=0.0007) for abnormal TTR.

Sagittal displacement is common in end stage ankle arthritis and is affected by ligamentous laxity and joint morphology.

Radiographic progression in clinical trials is assessed by interpreting changes in total radiographic joint score, and the reliability of those scores depends on an evaluation of sum scores. It is not known how consistently changes in individual joints are identified by independent readers and in independent readings. 7255 single joints from 178 patients who participated in the Trial of Etanercept and Methothrexate with Radiographic Patient Outcomes (TEMPO) trial were evaluated. Every image was independently scored twice according to the Sharp-van der Heijde method by two independent readers, so that four scores per joint were available. Absolute agreement and consistency of negative and positive erosion change scores across readers and readings were compared on a per-joint level, as well as on a per-patient level. The number of joints showing a change for erosion was very low in this trial: 691/7255 analysed joints had at least one non-zero change score out of four readings. Absolute agreement between readings was remarkably poor: only 12 joints showed a consistently positive or negative change in all four readings. Change scores in opposite directions in the same joint across independent readings were rare (25 joints). Frequency of opposite joint scores in the same patient (mixed change patterns) was reader dependent.

Substantial intra and interreader disagreement in scoring change in individual joints is common. Opposite joint scores in the same patient, however, are rare and reader dependent. Notwithstanding these subtle inconsistencies on the individual joint level, the total Sharp score is a useful and discriminatory outcome measure.

To investigate the effects of a one year programme of running training (up to 40 km/day for 15 weeks) on the spatial orientation pattern of collagen and glycosaminoglycans in articular cartilage in different parts of the knee (stifle) and shoulder joints of young beagle dogs. Area specific measurements of the optical path difference (= retardation, gamma) and the cartilage zone thickness were performed using conventional procedures and a new computer based quantitative polarised light microscopy method. Transmission electron microscopy was used to determine the zonal volume density of collagen fibrils. The concentrations of collagen and hydroxypyridinium crosslinks were investigated biochemically. Running training decreased gamma by 24-34% (p < 0.05) in the superficial zone of the lateral femoral condyle articular cartilage and at the centre of the tibial condyles. Gamma of glycosaminoglycans decreased by 26% (p < 0.05) in the superficial zone of the lateral condyle of the femur, but at the same site the volume density of collagen fibrils was unchanged. Neither the collagen concentration nor the concentration of hydroxypyridinium crosslinks was altered as a result of running. In both control and runner dogs, the thickness and gamma values of the superficial zone were greater in the humerus and the femur than in the tibia.

Endurance type running exercise in beagles caused a reduction in the superficial zone birefringence of the articular cartilage, which indicates either a disorganisation or a reorientation of the superficial zone collagen network. Articular cartilage showed marked variability of collagen network organisation over the different knee (stifle) joint articular surfaces.

To describe the histological changes in acute enthesopathy in early spondyloarthropathies (SpA). Clinically evident acute enthesopathy was confirmed by magnetic resonance imaging and ultrasonography in four cases of plantar fasciitis and one case of patellar tendon enthesitis. Ultrasound guided biopsy of insertional points was carried out with a Jamshedi needle. Control tissue was obtained from two subjects undergoing spinal grafting surgery. Standard histochemistry and immunohistochemistry analysis using the avidin-biotin immunoperoxidase complex method employing markers against CD3, CD8, CD34, and CD68 was used to determine cellular infiltrates at the insertion point. The enthesis architecture was abnormal in the SpA group, with increased vascularity and cellular infiltration compared with normal subjects. The predominant infiltrating cell at the enthesis fibrocartilage was the macrophage, but there was a paucity of lymphocytes at the insertion point.

These preliminary findings have implications for a better understanding of the pathology in early SpA.

To determine the correlation between inflammatory cytokines and adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone sulphate (DHEAS) in normal subjects with PMR patients. In 102 patients with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis factor (TNF) were measured by immunometric assays. Serum levels of IL-6 were elevated in patients with PMR as compared with normal subjects (10.0 +/- 1.6 vs 2.1 +/- 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients, serum levels of IL-6 were positively correlated with serum levels of ASD (P < 0.001), cortisol (P < 0.001), and DHEAS (P = 0. 038) irrespective of corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were significantly lower in patients with chronic disease and long-standing corticosteroid administration as compared with patients with recent onset of the disease and without corticosteroid therapy (P < 0.01).

In PMR, as expected, there was an increase in IL-6 serum levels that was associated with elevated serum levels of ASD, DHEAS, and cortisol which was more marked in patients with recent-onset disease and without corticosteroids. However, serum levels of cortisol in patients with and without corticosteroids were lower than expected by considering the inflammatory status (increased IL-6). This may indicate a change in the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in chronic disease.

Advice to use topical or oral NSAIDs is equally effective for the treatment of knee pain in older people. The ingredient cost of topical preparations is typically more than oral preparations, but could save costs because they have fewer adverse effects. A cost-utility study is needed to decide on their comparative cost effectiveness. We recruited 585 people aged >or=50 yrs with knee pain; 282 participated in a randomized controlled trial and 303 in a patient preference study from 26 MRC General Practice Research Framework practices in the UK. They received advice to preferentially use topical or oral NSAIDs for knee pain. We calculated the comparative cost per quality-adjusted life year (QALY) from both a National Health Service (NHS) and a societal perspective over 12 and 24 months. Compared with the topical route, oral NSAIDs cost the NHS pound191 and pound72 more over 1 yr in the randomized trial and preference study, respectively. The cost per QALY, from an NHS perspective, was in the range of pound9000- pound12000 in the randomized trial. In the preference study, it was pound2564 over 1 yr, but over 2 yrs the oral route was dominant.

Our cost-effectiveness analysis supports the use of oral NSAIDs in selected patients. Nevertheless, deciding to recommend oral NSAIDs in preference to topical NSAIDs could have a substantial impact on NHS costs because of the uncertainty in the cost-effectiveness estimate.

To present a systematic review that provides updated information about proteins found in salivary fluid extracted strictly from ducts. The systematic review probing strategy was based on electronic databases word search (PubMed, EMBASE, LILACS, Web of Science, and Scopus). Risk of bias was assessed based on Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. After 2 rounds of scrutiny, 12 articles were included, totaling 231 individuals (125 were healthy, 41 were elder individuals with radicular caries, 56 had primary Sjögren's syndrome, and 9 were patients who had received radiotherapy for head and neck cancer). The selected studies had no similarities among proteins found, demonstrating the need of standard reference in experimental methodology to obtain a thorough coverage of proteins. Proteomic profile of saliva collected from ducts is essential to better understand the disease process, enabling the identification of biomarkers for specific clinical situations.

Further studies are required to better determine the relative amount of proteins described in this study. It is essential to increase the number of samples, to perform similar collection techniques, to include other analyses methods such as mass spectrometry, and to perform the validation of some proteins using immunoassay techniques such as Elisa and Western blot.

Despite recent advances in the understanding of the genetic architecture of osteoarthritis (OA), only two genetic loci have been identified for OA of the hand, in part explained by the complexity of the different hand joints and heterogeneity of OA pathology. We used data from the Rotterdam Study (RSI, RSII and RSIII) to create three hand OA phenotypes based on clustering patterns of radiographic OA severity to increase power in our modest discovery genome-wide association studies in the RS (n=8700), and sought replication in an independent cohort, the Framingham Heart Study (n=1203). We used multiple approaches that leverage different levels of information and functional data to further investigate the underlying biological mechanisms and candidate genes for replicated loci. We also attempted to replicate known OA loci at other joint sites, including the hips and knees. We found two novel genome-wide significant loci for OA in the thumb joints. We identified

We identified a robust novel genetic locus for hand OA on chromosome 1, of which

Aggrecanase activity, most notably ADAMTS-5, is implicated in pathogenic cartilage degradation. Selective monoclonal antibodies (mAbs) to both ADAMTS-5 and ADAMTS-4 were generated and in vitro, ex vivo and in vivo systems were utilized to assess target engagement, aggrecanase inhibition and modulation of disease-related endpoints with the intent of selecting a candidate for clinical development in osteoarthritis (OA). Structural mapping predicts the most potent mAbs employ a unique mode of inhibition by cross-linking the catalytic and disintegrin domains. In a surgical mouse model of OA, both ADAMTS-5 and ADAMTS-4-specific mAbs penetrate cartilage following systemic administration, demonstrating access to the anticipated site of action. Structural disease modification and associated alleviation of pain-related behavior were observed with ADAMTS-5 mAb treatment. Treatment of human OA cartilage demonstrated a preferential role for ADAMTS-5 inhibition over ADAMTS-4, as measured by ARGS neoepitope release in explant cultures. ADAMTS-5 mAb activity was most evident in a subset of patient-derived tissues and suppression of ARGS neoepitope release was sustained for weeks after a single treatment in human explants and in cynomolgus monkeys, consistent with high affinity target engagement and slow ADAMTS-5 turnover.

This data supports a hypothesis set forth from knockout mouse studies that ADAMTS-5 is the major aggrecanase involved in cartilage degradation and provides a link between a biological pathway and pharmacology which translates to human tissues, non-human primate models and points to a target OA patient population. Therefore, a humanized ADAMTS-5-selective monoclonal antibody (GSK2394002) was progressed as a potential OA disease modifying therapeutic.

To investigate histological features of deposited amyloid in the synovial tissue and its clinical significance in knee joint osteoarthritis (OA) patients. We prospectively enrolled 232 consecutive patients who underwent arthroplasty or total replacement of the knee joint for treatment of OA. Congo red staining and immunohistochemistry were performed in the synovial tissue obtained at surgery. When transthyretin (TTR)-derived amyloid was positive, we analyzed all 4 exons of the TTR gene using the direct DNA sequencing method in order to detect mutations. We analyzed 322 specimens in this study. Twenty-six specimens (8.1%) obtained from 21 patients (5 men and 16 women; mean, 79.0 ± 4.6 years) showed deposition of amyloid, which was positively stained with the anti-TTR antibody. Eighteen patients showed inhomogeneous accumulations of amyloid in the loose connective tissue under the synovial epithelia sometimes with nodule formation, while in the remaining three, small vessels in the adipose tissue were involved. Medical records of these patients revealed nothing remarkable in the clinical course, laboratory data or macroscopic intraarticular findings at surgery. No mutations were detectable in the TTR gene analysis.

Wild-type TTR-derived amyloid may affect the synovial tissue as a result of long-term mechanical stress or as a part of senile systemic amyloidosis in approximately 8% of knee joint OA patients. No obvious clinical significance was found in synovial deposition of amyloid.

The purpose of this study was to determine useful radiographic findings for differentiating psoriatic arthritis (PsA) from rheumatoid factor (RF)-positive or -negative rheumatoid arthritis (RA) in Japanese patients. We accrued 85 patients with PsA. Controls included 135 patients with RA (85 RF-positive, 50 RF-negative) matched for gender and disease duration with PsA patients. Radiographs of hands and feet were obtained, and distal interphalangeal (DIP) erosive disease, joint osteolysis, tuft osteolysis, juxta-articular bony proliferation (JBP), periosteal new bone formation and bony ankylosis, which were identified using the definitions developed by an earlier study, were compared between the PsA and RA groups. For radiographic features of hands, the frequencies of JBP, periosteal new bone, and diffuse soft tissue swelling of the fingers were significantly higher in PsA patients than in RF-positive RA patients. However, only the frequency of JBP significantly differed between PsA and RF-negative RA patients. In feet, the frequencies of DIP erosive disease, tuft osteolysis, JBP, and diffuse soft tissue swelling of the toes were significantly higher in PsA patients than in RF-positive RA patients. However, only the frequency of JBP significantly differed between PsA and RF-negative RA patients.

JBP was the most important radiographic feature for discriminating PsA from both RF-positive and -negative RA, confirming the study by the CASPAR group that showed that JBP is the only radiologic feature that can discriminate PsA from other inflammatory arthritides. This study showed the utility of plain radiographs for diagnosis of PsA.

To compare the levels of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). This study aims to clarify existing data from previously used enzyme or inhibitor activity assays performed following separation by gel filtration, by using a 1-step enzyme-linked immunosorbent assay (ELISA) for each component. Total collagenase, free TIMP, and collagenase-TIMP complex were measured using a newly developed, specific double-antibody sandwich ELISA: Levels of both collagenase and TIMP were significantly higher in RA patients (collagenase 1,560 +/- 150 ng/ml [mean +/- SEM], TIMP 1,610 +/- 130 ng/ml; n = 80) than OA patients (collagenase 420 +/- 90 ng/ml, TIMP 1,050 +/- 60 ng/ml; n = 80), with the difference being especially striking for collagenase. Sixteen RA fluids had detectable levels of collagenase-TIMP complex, compared with only 3 OA fluids.

The level of total collagenase in SF is greater in RA than OA, while levels of free TIMP show more overlap between the 2 diseases; this may simply reflect the increased inflammation seen in RA, or it may reflect a different disease mechanism.

Self-reported outcome instruments in health research have become increasingly important over the last decades. Occupational therapy interventions often focus on occupational balance. However, instruments to measure occupational balance are scarce. The aim of the study was therefore to develop a generic self-reported outcome instrument to assess occupational balance based on the experiences of patients and healthy people including an examination of its psychometric properties. We conducted a qualitative analysis of the life stories of 90 people with and without chronic autoimmune diseases to identify components of occupational balance. Based on these components, the Occupational Balance-Questionnaire (OB-Quest) was developed. Construct validity and internal consistency of the OB-Quest were examined in quantitative data. We used Rasch analyses to determine overall fit of the items to the Rasch model, person separation index and potential differential item functioning. Dimensionality testing was conducted by the use of t-tests and Cronbach's alpha. The following components emerged from the qualitative analyses: challenging and relaxing activities, activities with acknowledgement by the individual and by the sociocultural context, impact of health condition on activities, involvement in stressful activities and fewer stressing activities, rest and sleep, variety of activities, adaptation of activities according to changed living conditions and activities intended to care for oneself and for others. Based on these, the seven items of the questionnaire (OB-Quest) were developed. 251 people (132 with rheumatoid arthritis, 43 with systematic lupus erythematous and 76 healthy) filled in the OB-Quest. Dimensionality testing indicated multidimensionality of the questionnaire (t = 0.58, and 1.66 after item reduction, non-significant). The item on the component rest and sleep showed differential item functioning (health condition and age). Person separation index was 0.51. Cronbach's alpha changed from 0.38 to 0.57 after deleting two items.

This questionnaire includes new items addressing components of occupational balance meaningful to patients and healthy people which have not been measured so far. The reduction of two items of the OB-Quest showed improved internal consistency. The multidimensionality of the questionnaire indicates the need for a summary of several components into subscales.

The pro-inflammatory cytokine interleukin (IL)-6 is involved in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular events. We evaluated the correlation of prothrombotic biomarkers, in particular those of thrombin generation, with inflammatory and clinical parameters in RA patients treated with tocilizumab, an IL-6 receptor (IL-6R) inhibitor. Naïve and maintenance patients were compared. We studied 15 RA patients undergoing tocilizumab infusions at a University Outpatient Clinic. Eight received tocilizumab for the first time and were evaluated at baseline. Seven were in maintenance therapy (9 to 77 months). All 15 patients were evaluated four weeks after the last administration of tocilizumab. At each time, we assessed disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP), IL-6, soluble (s)IL-6R, tumour necrosis factor-alpha (TNF-alpha), prothrombin fragment F1+2 and fibrin fragment D-dimer. Forty healthy subjects served as basal controls. At baseline, RA patients showed a moderate-to-high disease activity and median ESR of 51 mm/1(st) hour (interquartile range 25-63). Plasma levels of CRP (p=0.0001), IL-6 (p=0.043), sIL-6R (p=0.003), TNF-alpha (p=0.0001), F1+2 (p=0.0001) and D-dimer (p=0.002) were higher than those of healthy controls. After four weeks we observed reduction of DAS28 (p=0.0001), ESR (p=0.0001), CRP (p=0.014), TNF-alpha (p=0.006), F1+2 (p=0.009) and D-dimer (p=0.04). No differences were observed between naïve and maintenance patients.

The reduction of prothrombotic biomarkers parallels the reduction of inflammatory parameters and clinical symptoms in RA patients treated with tocilizumab, both four weeks after the first administration and during maintenance therapy.

To determine the incidence, time trends, risk factors, and severity of herpes zoster in a population-based cohort of patients with newly diagnosed rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population. All residents of Olmsted County, Minnesota fulfilling for the first time the 1987 American College of Rheumatology criteria for RA between January 1, 1980 and December 31, 2007 and a cohort of similar residents without RA were assembled and followed by retrospective chart review until death, migration, or December 31, 2008. There was no difference in the presence of herpes zoster prior to the RA incidence/index date between the cohorts (P = 0.85). During followup, 84 patients with RA (rate 12.1 cases per 1,000 person-years) and 44 subjects without RA (rate 5.4 cases per 1,000 person-years) developed herpes zoster. Patients with RA were more likely to develop herpes zoster than those without RA (hazard ratio [HR] 2.4 [95% confidence interval (95% CI) 1.7-3.5]). Herpes zoster occurred more frequently in patients diagnosed with RA more recently (HR 1.06 per year [95% CI 1.02-1.10]). Erosive disease, previous joint surgery, and use of hydroxychloroquine and corticosteroids were significantly associated with the development of herpes zoster in RA. There was no apparent association of herpes zoster with the use of methotrexate or biologic agents. Complications of herpes zoster occurred at a similar rate in both cohorts.

The incidence of herpes zoster is increased in RA and has risen in recent years. There also has been an increasing incidence of herpes zoster in more recent years in the general population. RA disease severity is associated with the development of herpes zoster.

To determine the relationship between skin temperature and pressure tolerance in patients with myofascial pain. Blinded, criterion standard. Community physiatry clinic. Sixteen consecutive female patients with myofascial pain or fibromyalgia with shoulder girdle symptoms above the T4 level for at least 3 months. No patient met the exclusion criteria of recent trauma to the area or therapy within 48 hours. Skin temperature was measured by using a hand-held infrared thermometer over 36 points arranged in a grid on the upper and midtrapezius. Pressure threshold was then assessed at each point by using a pressure threshold meter. A second, blinded examiner then examined each patient to find any myofascial tender spots and noted within which square on the grid they occurred. The correlation between temperature and pressure threshold and the temperature differences between tender and nontender areas. A nonsignificant correlation of.023 (p =.57) was found between temperature and pressure threshold. The mean temperature of the tender spots was 32.1 degrees C. No significant difference existed between tender spot temperature and temperature of nontender points (32.1 degrees C, p =.653) or contralateral points (32 degrees C, p =.893).

Skin temperature, measured with a hand-held infrared thermometer, cannot be used to diagnose and follow treatment progress of myofascial tender spots, because skin temperature over tender spots does not correlate with pressure sensitivity.

The purpose of this study was to evaluate the clinical and imaging results of patients who received intra-articular injections of autologous mesenchymal stem cells for the treatment of knee osteoarthritis. The study group comprised 18 patients (6 men and 12 women), among whom the mean age was 54.6 years (range, 41 to 69 years). In each patient the adipose synovium was harvested from the inner side of the infrapatellar fat pad by skin incision extension at the arthroscopic lateral portal site after the patient underwent arthroscopic debridement. After stem cells were isolated, a mean of 1.18 × 10(6) stem cells (range, 0.3 × 10(6) to 2.7 × 10(6) stem cells) were prepared with approximately 3.0 mL of platelet-rich plasma (with a mean of 1.28 × 10(6) platelets per microliter) and injected into the selected knees of patients. Clinical outcome was evaluated with the Western Ontario and McMaster Universities Osteoarthritis Index, the Lysholm score, and the visual analog scale (VAS) for grading knee pain. We also compared magnetic resonance imaging (MRI) data collected both preoperatively and at the final follow-up. Western Ontario and McMaster Universities Osteoarthritis Index scores decreased significantly (P < .001) from 49.9 points preoperatively to 30.3 points at the final follow-up (mean follow-up, 24.3 months; range, 24 to 26 months). Lysholm scores also improved significantly (P < .001) by the last follow-up visit, increasing from a mean preoperative value of 40.1 points to 73.4 points by the end of the study. Likewise, changes in VAS scores throughout the follow-up period were also significant (P = .005); the mean VAS score decreased from 4.8 preoperatively to 2.0 at the last follow-up visit. Radiography showed that, at the final follow-up point, the whole-organ MRI score had significantly improved from 60.0 points to 48.3 points (P < .001). Particularly notable was the change in cartilage whole-organ MRI score, which improved from 28.3 points to 21.7 points (P < .001). Further analysis showed that improvements in clinical and MRI results were positively related to the number of stem cells injected. Level IV, therapeutic case series.

The results of our study are encouraging and show that intra-articular injection of infrapatellar fat pad-derived mesenchymal stem cells is effective for reducing pain and improving knee function in patients being treated for knee osteoarthritis.

To evaluate the positive predictive value (PPV) of 3 case definitions of rheumatoid arthritis (RA) based on self-reported data on RA diagnosis and use of arthritis medications, and to determine whether a validated screening survey would increase the PPVs in the 3 groups. Medical records and physician checklists were reviewed for confirmation of an RA diagnosis among a sample of Black Women's Health Study participants who reported incident RA and were categorized according to reported medications: disease-modifying antirheumatic drugs (DMARDs) (n = 102), nonsteroidal antiinflammatory drugs (NSAIDs) (n = 100), and no arthritis medications (no meds) (n = 101). PPVs for confirmed RA were calculated for each of the medication groups, both overall and according to the results of the screening survey. The PPVs of confirmed RA were 76%, 61%, and 29% in the DMARDs, NSAIDs, and no meds groups, respectively. After exclusion of women who reported other rheumatic conditions or who reported taking only prednisone, the PPV increased in the DMARDs group to 88%, but little improvement was seen in the other groups. The PPVs increased somewhat according to results of the screening survey for the DMARDs group (92% for positive screen versus 85% for negative screen; P = 1.00), and increased substantially for the NSAIDs group (89% versus 38%, respectively; P = 0.03), but only 43% of participants completed the survey.

We found that self-report of RA, along with self-reported DMARDs, is a useful case definition for identifying confirmed RA. The validated screening survey could be useful for identifying cases of confirmed RA in some, but not all, medication groups.

Kawasaki disease (KD) is an acute childhood vasculitis that may result in coronary aneurysms. Treatment of KD with a single infusion of 2 gm/kg intravenous immunoglobulin (IVIG) is well established, but acetylsalicylic acid (ASA) dose remains controversial. Our primary objective was to determine the difference in the incidence of IVIG resistance between 2 ASA doses. Our secondary objective was to compare the duration of hospital stay and the incidence of coronary artery aneurysm. We reviewed charts of patients with KD from 2 Canadian centers to assess the impact of ASA dose on IVIG resistance (operationally defined as administration of a second dose of IVIG). Both centers used standard IVIG dosing, but center 1 used low-dose ASA from diagnosis (3-5 mg/kg/day) while center 2 used initial high-dose ASA (80-100 mg/kg/day). There were no significant differences in baseline characteristics between the 2 centers. Retreatment with a second dose of IVIG was required in 28 of 122 patients (23%) treated with low-dose ASA, and in 11 of 127 patients (8.7%) treated with high-dose ASA in center 1 and center 2, respectively (P = 0.003). After adjusting for confounders, low-dose ASA was associated with higher odds of IVIG resistance (OR 3.2 [95% confidence interval 1.1, 9.1]). The mean duration of hospital stay was 4.1 and 4.7 days, respectively (P = 0.37). Coronary artery aneurysms were seen in 2 of 117 and 6 of 125 patients from centers 1 and 2, respectively (P = 0.28).

Low-dose ASA was associated with 3-times higher odds of IVIG retreatment compared to high-dose ASA, with no significant difference in duration of hospital stay or incidence of coronary artery aneurysms.

To describe and review internuclear ophthalmoplegia (INO) in systemic lupus erythematosus (SLE). A population of 268 SLE patients was retrospectively studied. INO was clinically defined as palsy of the ipsilateral rectus muscle and failure in contralateral eye adduction with dissociated nystagmus. A systematic review of the literature was made using MEDLINE (Silver-Platter) between 1966 and 1997, and for completeness, earlier references cited in identified articles. Four women with INO were identified. Their mean age at INO diagnosis was 38 years, and mean delay from diagnosis of SLE to INO was 6 years. INO was unilateral in all and coincided with disease activity in three. Cardiovascular risk factors were present in three. Magnetic brain resonance showed multiple and hyperintense (T2) lesions in white matter without correlation with clinical features. Other ancillary tests were not helpful for diagnosis. Corticosteroid therapy resulted in full resolution of INO in three cases. Review of 14 additional cases from the literature showed a similar experience.

INO is uncommon in SLE, but it should be suspected in young patients with active disease and impairment of ocular movements. Diagnosis relies largely on clinical grounds. Neuroimaging is of little help. Steroid therapy seems effective in improving eye movements.

Leg length discrepancy (LLD) following total hip arthroplasty (THA) is a leading cause of patient dissatisfaction. However, no reports have described the influence of lower limb alignment on LLD after THA. In the present study, we firstly investigated the change in lower limb alignment after THA. Secondly, we determined the influence of lower limb alignment on LLD after THA. Thirdly, we evaluated the influence of LLD in the entire lower leg on the clinical outcomes after THA. We followed up with 54 unilateral hip osteoarthritis (OA) patients 1 year after THA. For the radiological assessment of LLD and lower limb alignment, we obtained anteroposterior radiographs of the pelvis and both lower legs in entirety in a standing position before and 1 year after THA. The Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) were also obtained to assess the clinical outcome. The alignment of the affected leg, which was more valgus than the unaffected leg before THA, tended toward varus after THA, and the discrepancy between the lower limb alignments on both sides decreased. However, the alignment discrepancies that remained after THA influenced the LLD measured on the radiograph of the entire lower leg, and this LLD influenced the clinical outcome as measured by the HHS and the WOMAC score.

LLD in the entire lower leg should be corrected for a better clinical outcome after THA.

There are few clinical and epidemiological studies reporting the association between abnormal changes within the IPFP and knee osteoarthritic changes. This study aims to describe the associations between hypointense signals in the infrapatellar fat pad (IPFP) and knee structural change and symptoms in older adults. Participants (n = 874) were selected randomly from local community and followed up 2.7 years later (range 2.6-3.3 years). T1- or T2-weighted fat-suppressed magnetic resonance imaging (MRI) was assessed for IPFP hypointense signal, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic osteoarthritis was assessed using the OARSI atlas. Cross-sectionally, hypointense signals in the IPFP were significantly associated with a higher risk of knee cartilage defects at all sites, tibiofemoral BMLs and knee pain in multivariable analyses. Longitudinally, baseline signal abnormalities were significantly and positively associated with increases in knee cartilage defects (OR: 2.27, 95 % CI: 1.61-3.21), BMLs (OR: 1.91, 95 % CI: 1.39-2.62), and knee pain (OR: 1.36, 95 % CI: 1.05-1.76) in multivariable analyses. The associations with cartilage defects remained significant after adjustment for BMLs, but the associations with BMLs and knee pain decreased in magnitude or became non-significant after further adjustment for cartilage defects.

Hypointense signals in the IPFP were associated primarily with increased knee cartilage defects and also with BMLs and knee symptoms in cross-sectional and longitudinal analyses, suggesting the abnormality represented by this signal has a potentially important role in osteoarthritis progression.

To compare synovial fluid (SF) resistin concentrations in healthy dogs to dogs with osteoarthritis (OA) secondary to cranial cruciate ligament (CrCL) injury and to correlate resistin concentrations with body condition score (BCS) and evaluate resistin release from peripheral blood mononuclear cells (PBMC) and adipocytes. Controlled, prospective, clinical study ANIMALS: Thirty-nine client-owned dogs, 13 healthy and 26 with secondary OA, were enrolled. Blood was collected from six healthy purpose-bred dogs for PBMC culture. An additional six mixed-breed dogs were used for adipocyte collection and culture. Resistin concentrations were measured with a canine-specific enzyme-linked immunoabsorbent assay. Resistin was compared between healthy SF and OA SF with Student's t test. Correlation of resistin concentrations to BCS was performed. Peripheral blood mononuclear cells and adipocytes were cultured under three conditions: negative control, lipopolysaccharide, and concanavalin A (Con A). A linear mixed model was used to determine differences in resistin concentrations among treatments. Resistin concentrations in OA SF were comparable to healthy SF. Neither serum nor SF resistin was correlated with BCS. Cultured PBMC stimulated with Con A released resistin, while adipocytes did not. Resistin may not be involved in the pathogenesis of OA. However, resistin may be important in inflammation because it is released from inflammatory cells.

Neither serum nor SF resistin were altered in dogs with OA secondary to CrCL insufficiency. In addition, resistin was not correlated with canine body fat and did not appear to function as adipocytokine in the dog.

To establish if gravidity and parity associate with the development of rheumatoid arthritis (RA), and to establish if this effect is influenced by the time elapsed since pregnancy/childbirth, the number of pregnancies/childbirths, and serological status, through systematically reviewing the literature and undertaking a meta-analysis. We searched Medline/EMBASE (from 1946 to 2018) using the terms "rheumatoid arthritis.mp" or "arthritis, rheumatoid/" and "pregnancy.mp" or "pregnancy/" or "parity.mp" or "parity/" or "gravidity.mp" or "gravidity/" (observational study filter applied). Case-control/cohort studies that examined the relationship between parity/gravidity and the risk of RA in women were included. Studies reporting effect size data for RA in ever vs. never parous/gravid women as ORs/RRs with 95% confidence intervals were included in a meta-analysis. Other relationships (i.e. risk by pregnancy/childbirth numbers) were analysed descriptively. Twenty studies (from 626 articles) met our inclusion criteria, comprising 14 case-control (4799 cases; 11,941 controls) and 6 cohort studies (8575 cases; 2,368,439 individuals). No significant association was observed in the meta-analysis of studies reporting the risk of RA in ever vs. never parous women (OR 0.91; 95% CI 0.80-1.04) and ever vs. never gravid women (OR 0.86; 95% CI 0.46-1.62). No consistent evidence of a relationship between the number of pregnancies/childbirths and RA risk was seen. No significant association was observed between being pregnant, or in the immediate post-partum period, and the risk of developing RA.

Our systematic review does not support the concept that gravidity and parity are associated with the risk of RA development.

To study the value of 3 T dynamic contrast-enhanced (DCE)-MRI for assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis (EOA) for treatment response monitoring. The interphalangeal joints of fingers two to five were examined at 3 T MRI in nine patients with EOA. Two musculoskeletal radiologists recorded erosions, bone marrow oedema (BME), synovitis and osteophytes. Interobserver reliability was calculated using κ statistics. In six patients, DCE-MRI time intensity curves of synovitis in two affected joints were analysed. The maximum upslope, absolute and relative enhancement of synovitis were compared with MRI after 12 months of anti-tumour necrosis factor treatment. Intraobserver reproducibility was calculated using intra-class correlation coefficient. Interobserver reliability was 'good' for detection of erosions (κ = 0.70), BME (κ = 0.77) and synovitis (κ = 0.77), but 'poor' for osteophytes (κ = 0.12). Post-treatment DCE-MRI showed decreasing maximum upslope (p = 0.002) and absolute (p = 0.002) and relative (p = 0.01) enhancement compared to the initial scan. Intraobserver reproducibility of DCE-MRI was 'almost perfect' or 'strong' for all parameters.

3 T DCE-MRI demonstrates changes in time intensity curves of synovitis in EOA of the interphalangeal joints in a longitudinal study, indicating this technique is promising for monitoring therapy response.

We examined patient-reported outcomes (PROs) in The Study of Etanercept And Methotrexate in Patients with Psoriatic Arthritis (PsA); a 48-week, phase 3, randomised controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept monotherapy, and MTX+ etanercept in patients with PsA. Efficacy endpoints included: mean changes from baseline and proportion of patients who reported improvements≥minimal clinically important difference (MCID) at week 24 in treatment groups for Health Assessment Questionnaire-Disability Index, Patient Global Assessment (PtGA), Patient Global Assessment of Joint Pain (PtGAJP) and Medical Outcomes Study Short Form-36 Questionnaire (SF-36) Physical Component Summary (PCS), and Mental Component Summary, and eight domain scores. PROs were analysed as reported (observed), without multiplicity adjustment; therefore, p values are descriptive. At week 24, patients receiving etanercept monotherapy or MTX+ etanercept combination reported greater improvements (p≤0.05) in PtGA, PtGAJP and SF-36 PCS scores compared with those receiving MTX monotherapy. Compared with MTX monotherapy, higher proportions of patients receiving etanercept monotherapy and combination therapy reported improvements≥MCID in PtGA (etanercept vs MTX, p=0.005) and PtGAJP (MTX +etanercept vs MTX, p=0.038). Across PROs, proportions of patients reporting scores≥age and gender-matched normative values at week 24 ranged from 20.8% to 51.0% with MTX monotherapy, 30.9% to 48.8% with etanercept monotherapy, and 30.6% to 52.3% with MTX+ etanercept combination.

Patients receiving etanercept monotherapy or MTX+ etanercept reported greater improvements from baseline in several PROs compared with those receiving MTX monotherapy. PROs should be incorporated in discussions between patients and clinicians regarding their treatment choices as they can help determine which treatments are more beneficial in patients with PsA.

To investigate whether human T lymphotropic virus type I (HTLV-I) could be involved in the pathogenesis of Sjögren's syndrome (SS). Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV-I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV-I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV-I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present. Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV-I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV-I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of "flower cells," as observed in the blood of HTLV-I-infected patients.

None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV-I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA-DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland.

To describe the long term impact of football on the health related quality of life (HRQL) of former professional footballers in the United Kingdom. A cross sectional survey gathered data from 284 former professional players. Respondents reported medical treatments, osteoarthritis (OA) diagnosis, other morbidity, disability status, and work related disability since their football career. The EuroQol (EQ-5D) and global health rating scales were selected to assess HRQL. Medical treatment for football related injuries was a common feature, as was OA, with the knee being the most commonly affected joint. Respondents with OA reported poorer HRQL compared with those without OA. As with medical treatments and problems on each of the five EQ-5D dimensions (pain, mobility, usual activities, anxiety/depression, self care), frequency of disability and work related disability were higher among respondents with OA than those without.

This exploratory study suggests that playing professional football can impact on the health of United Kingdom footballers in later life. The development of OA was associated with poorer outcomes on all aspects of HRQL.

To evaluate the long-term results of distal scaphoid excision for degenerative arthritis secondary to scaphoid nonunion and compare them with our original results published in 1999. Nineteen patients who were treated by distal scaphoid resection arthroplasty from 1987 through 2010 were included. The mean follow-up was 15 years (range, 10-25 y) vs 4 years in the previous study. Clinical evaluation included measurement of the visual analog pain scale, wrist range of motion, and grip strength. Radiographs were taken at follow-up to assess for signs of arthritis and wrist collapse. The outcomes of this procedure include increased grip strength and total arc of motion, a small decrease in revised carpal height ratio, and a small increase in radiolunate angle. Two patients failed distal scaphoid resection arthroplasty necessitating proximal row carpectomy (1) and wrist arthrodesis (1) for recalcitrant pain. More than half of the remaining patients developed midcarpal arthritis on radiographs that was asymptomatic. No patients developed radiolunate arthritis. Therapeutic IV.

This study showed that distal scaphoid resection arthroplasty produced favorable, long-term clinical results and did not result in noteworthy wrist collapse. Midcarpal arthritis, which may develop after the procedure, did not cause appreciable deterioration in patient outcomes. This procedure also did not eliminate the option of using additional, more conventional reconstructive procedures if needed.

The purpose of this study is to determine whether the mean and heterogeneity of magnetic resonance (MR) knee cartilage T(2) relaxation time measurements at baseline are associated with morphologic degeneration of cartilage, meniscus, and bone marrow tissues over 3 years in subjects with risk factors for osteoarthritis (OA). Subjects with risk factors for OA (n=289) with an age range of 45-55 years were selected from the Osteoarthritis Initiative (OAI) database. 3.0 Tesla MR images were analyzed using morphological gradings of cartilage, bone marrow and menisci whole-organ magnetic resonance imaging scores (WORMS scoring). A T(2) mapping sequence was used to assess the mean and heterogeneity of cartilage T(2) (gray level co-occurrence matrix texture analysis). Regression models were used to assess the relationship between baseline T(2) parameters and changes in morphologic knee WORMS scores over 3 years. The prevalence of knee abnormalities in the cartilage (P<0.0005), meniscus (P<0.00001), and bone marrow significantly (P<0.00001) increased from baseline to 3 years in all compartments combined. The baseline mean and heterogeneity of cartilage T(2) were significantly (P<0.05) associated with morphologic joint degeneration in the cartilage, meniscus and bone marrow over 3 years.

The prevalence of knee abnormalities significantly increased over 3 years; increased cartilage T(2) at baseline predicted longitudinal morphologic degeneration in the cartilage, meniscus, and bone marrow over 3 years in subjects with risk factors for OA.

Autoinflammatory disorders are caused by a primary dysfunction of the innate immune system. Among these disorders are hereditary recurrent fevers, which are characterized by recurrent episodes of fever and inflammatory manifestations affecting multiple tissues. Hereditary recurrent fevers often lack objective diagnostic criteria, thereby hampering the identification of disease-causing genes. This study was undertaken to identify a gene responsible for hereditary recurrent fevers. Copy number variations and point mutations were sought by array-comparative genomic hybridization and polymerase chain reaction sequencing, respectively. Serum cytokine levels were measured using Luminex technology. The effect of TNFRSF11A molecular defects on NF-κB signaling in cells expressing wild-type and mutated forms of the receptor was evaluated by luciferase assay. A patient with multiple congenital anomalies and hereditary recurrent fever was found to carry a de novo heterozygous complex chromosomal rearrangement encompassing a duplication of TNFRSF11A, a gene known to regulate fever in rodents. We also identified a heterozygous frameshift mutation (p.Met416Cysfs*110) in TNFRSF11A in a mother and daughter with isolated hereditary recurrent fever. This mutation was associated with increased secretion of several inflammatory cytokines (tumor necrosis factor α [TNFα], interleukin-18 [IL-18], IL-1 receptor antagonist, interferon-γ) and altered the biologic effects of the receptor on NF-κB signaling. The disease in the patients described herein exhibits striking clinical similarities to TNF receptor-associated periodic syndrome, another hereditary recurrent fever involving a gene of the same family (TNFRSF1A).

The involvement of TNFRSF11A in hereditary recurrent fever highlights the key role of this receptor in innate immunity. The present results also suggest that TNFRSF11A screening could serve as a new diagnostic test for autoinflammatory disorders.

Non-pharmacological interventions support patients with connective tissue diseases to better cope with and self-manage their diseases. This study aimed to map existing evidence on non-pharmacological interventions in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue diseases regarding content, feasibility and potential suitability in an e-health setting. A literature search was performed in eight different databases in July 2020. The intervention's content was extracted using the 'Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide'. A Sankey diagram and descriptive statistics were used to analyse the data and illustrate the relationships between the interventions. Of 8198 identified records, 119 papers were eligible. One hundred and four of them (87.4%) were conducted between 2000 and 2020, mainly in the USA (SLE n=24 (21.2%), SSc n=16 (14.2%)), Brazil (SLE n=8 (7.1%), SSc n=5 (4.4%)) and Italy (SLE n=0 (0%), SSc n=12 (10.6%)). Fifty-two studies (SLE n=24 (21.2%), SSc n=28 (24.8%)) used multicomponent interventions. The single interventions were physical exercises (SLE n=16 (14.2%), SSc n=17 (15.0%)), coaching/counselling (SLE n=11 (18.0%), SSc n=0 (0%)) and education (SLE n=2 (1.8%), SSc n=3 (2.7%)). Primary outcomes focused on physical function (SLE n=1 (0.9%), SSc n=15 (13.3%)), mouth opening in SSc (n=4 (5.9%)) and physical capacity (SLE n=2 (1.8%), SSc n=1 (0.9%)). No interventions for mixed connective tissue disease were found.

There was a great variety in the intervention's content due to differences in body structure, activity limitations and participation restrictions in SLE and SSc. These results highlight the need for personalised, multicomponent, non-pharmacological interventions, which could be delivered as e-health interventions.

To assess the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune-mediated diseases. Health plan data were obtained from the Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases, with linkage to both vital records and medical records. Women with inflammatory arthropathies, those with systemic lupus erythematosus, and those with inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included. Major congenital malformations, fetal deaths, and life-threatening neonatal complications were identified from the electronic data and validated with medical record review. The cohort included 608 infants, including 437 with exposure to immunosuppressive drugs during the mother's pregnancy (402 during the first trimester, and 35 during the second and third trimester only) and 171 whose mothers filled prescriptions for immunosuppressive treatments before, but not during, pregnancy. There were 25 pregnancies (4.1% of the cohort) with confirmed major congenital malformations, and 10 fetal deaths (1.6% of the cohort). Among 113 preterm infants with exposures during pregnancy, 23 (20.4%) had life-threatening neonatal complications, and among 485 term infants, 10 (2.1%) had life-threatening complications. Compared to the reference group (treatment before, but not during, pregnancy), the risk ratios (RRs) for adverse fetal outcomes associated with immunosuppressive treatments (by exposure category) during pregnancy included the following: methotrexate (RR 1.39, 95% confidence interval [95% CI] 0.43-4.53), tumor necrosis factor inhibitors (RR 0.98, 95% CI 0.38-2.55), hydroxychloroquine (RR 1.33, 95% CI 0.69-2.55), and other immunosuppressive medications (RR 0.98, 95% CI 0.48-1.98).

In this study, there was no evidence of a large increase in risk of adverse fetal outcomes from first-trimester exposure to immunosuppressive medications, although the confidence intervals for the risk ratios were wide. Further studies will be needed as use of these medications increases over time.

To present the results of a Delphi consensus survey among Italian paediatric and adult rheumatologists on transitional care (TC) of young people (YP) with juvenile idiopathic arthritis (JIA). A taskforce of 27 paediatric and adult rheumatologists evaluated the applicability of the 2016 EULAR/PReS recommendations for TC to the Italian rheumatology practice and healthcare system and formulated additional country-specific statements aimed to increase their suitability. After a two-round discussion, applicability of EULAR/PReS recommendations and agreement with newly-proposed statements were voted on a 0-10 scale (where 0 = no applicability/agreement and 10 = total applicability/agreement). A mean level of agreement ≥8 was deemed acceptable. The consensus threshold was reached for only 4 of the 12 EULAR/PReS recommendations and for 25 of the 27 country-specific statements. Poor agreement with EULAR/PReS recommendations was mostly explained by paucity of centres in Italy that possess both paediatric and adult rheumatologists, disagreement about optimal time of transition start and de nition of transition coordinator, diversity between paediatric and adult clinimetric assessments, and lack of administrative and financial support.

This consensus initiative represents an important step forward toward the establishment of a nationwide TC network for YP with JIA in Italy. The main goals established for the future are the identification of adult rheumatology centres that are willing to participate in the TC process, the education of adult rheumatology teams on childhood-onset rheumatic diseases and transition issues, and the increased awareness of public healthcare authorities and other stakeholders about the importance of good-quality TC.

To investigate those characteristics of patients with rheumatoid arthritis (RA) that are associated with the development of rheumatoid vasculitis (RV). Demographic and clinical data of 69 patients who had been diagnosed as having RV were compared with those of 138 contemporaneous control patients with RA who were not suspected to have vasculitis. Vasculitis was confirmed histologically in 96% of the subjects with RV. Variables associated with the development of RV were: 1) male gender, presence of increased serum concentrations of rheumatoid factor, joint erosions, subcutaneous nodules, number of disease modifying antirheumatic drugs previously prescribed, treatment (ever) with D-penicillamine or azathioprine; 2) presence of nail fold lesions and any other extrarticular feature one year before the time of diagnosis of RV; 3) treatment with corticosteroids at the time of diagnosis of RV.

The development of RV is associated with male gender, extra-articular features, and a severe course of RA as indicated by the presence of joint destruction and need for intensive treatment with antirheumatic drugs. The strongest association was found with the presence of increased concentrations of rheumatoid factor.

To characterize and compare community-dwelling elderly with knee and/or hip osteoarthritis (OA), focusing on the frailty syndrome. Cross-sectional study of the elderly with knee and/or hip OA, using a subsample from the study of frailty in the Brazilian elderly (FIBRA), assessing the following: sociodemographic characteristics, comorbidity, medications, depression, anthropomorphic data, falls, pain, stiffness, physical function, and frailty. The subjective assessment of health was also performed. The final sample comprised 58 elderly (mean age, 74 ± 5.5 years) as follows: 17 (29.31%) non-frail, 28 (48.28%) pre-frail, and 13 (22.41%) frail. The frail elderly received more medications than the non-frail ones (7.00 ± 2.00 and 4.00 ± 2.00, respectively; P = 0.001). The mean Body Mass Index was lower in the non-frail elderly as compared with those of the pre-frail and frail ones (27.00 ± 4.50 kg/m², 30.00 ± 4.00 kg/m², and 34.00 ± 8.00 kg/m², respectively; P = 0.018). Depression was more prevalent in the frail group. Compared to the previous year, there was a difference in the health status of the groups as follows: 64.3% of the pre-frail elderly and 46.2% of the frail ones believed their health deteriorated, and 52.9% of the non-frail elderly considered that their health status remained unchanged (P = 0.016). When comparing the current physical activity levels with those of the previous year, the pre-frail and frail elderly reported a worsening (P = 0.010). Regarding physical function and fall-related self-efficacy, the frail elderly were worse than the others (P = 0.023 and 0.017, respectively). There were no significant differences between the groups for the remaining items analyzed.

The elderly with OA and frailty use more medications, are more obese and depressed, have a poorer perception of their own health and of their level of activity as compared with that of the previous year, have a worse fall-related self-efficacy, and worse physical function.

The efficacy of mizoribine (MZR) in treatment of rheumatoid arthritis (RA) was retrospectively investigated in terms of drug survival, improvement in Disease Activity Score-28 (DAS28)-C-reactive protein (CRP), and blood MZR concentration obtained 3 h after dosing (MZR-C3). To compare the efficacy of MZR administered via different regimens, the subjects were divided into 2 groups: those receiving a single dose of MZR at 100-150 mg every other day (group A) and those receiving 2 or 3 divided doses of the drug on consecutive days, which is the usual dosing method of the drug (group B). Group A had significantly higher MZR-C3 levels compared with group B, as well as significantly greater improvement in DAS28-CRP. Moreover, drug survival was significantly longer in group A. The primary regression equation suggested that the effective blood MZR concentration in RA treatment is MZR-C3 of 1.47 µg/mL or more.

The results of the present study indicate that it is possible to increase the efficacy of MZR in a blood concentration-dependent manner, and also to control RA over a prolonged period, using single administration of MZR on alternate days at an increased dose.

To measure the economic output/input ratios for the various options of prevention of rheumatic fever/rheumatic heart disease (RF/RHD) and check the viability of primary prevention vis-à-vis secondary and tertiary preventions. Cost accounting of the various prevention options was calculated for each variable as available in literature. Actual data as obtainable for the financial year ending March 2006 were computed for the Pondicherry population. Both direct and indirect costs (including community/social costs) were worked out using mostly primary data and wherever necessary, secondary data. Certain scientific assumptions were used where exact data was not available. Primary prevention is the definite viable economic option (1:1.56) compared to secondary (1: 1.07) and tertiary (1: 0.12) preventions. In fact, the current stress on only secondary and tertiary preventions is found to be economically unviable.

It is postulated that primary prevention as a practical policy in tackling RF and RHD can be recommended.

Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA), but the diagnostic accuracy of ACPA in the general population has not been thoroughly assessed. We aimed to assess the diagnostic accuracy of ACPA for RA in the general population and to further characterise the citrullinated peptide recognition pattern. Serum samples from a large population-representative twin cohort consisting of 12 590 individuals were analysed for the presence of ACPA using anti-CCP2 ELISA. All ACPA-positive samples were further tested on ELISAs for four peptide-specific ACPA. RA cases were identified by linkage to the Swedish National Patient Register at inclusion and after a median follow-up of 37 months (IQR 31-49). 350 out of 12 590 individuals had a positive anti-CCP2 test, measuring ACPA. Of these, 103 had an RA diagnosis at the time of blood donation and inclusion. During a median follow-up of 3 years, an additional 21 of the remaining 247 ACPA-positive individuals developed RA. Overall, a positive anti-CCP2 test had a positive predictive value of 29% for prevalent RA at inclusion (negative predictive value of 99.6%). High titres (>3× cut-off) of anti-CCP2 increased the positive predictive value to 48% (negative predictive value of 99.5%). ACPA-positive individuals without RA had lower anti-CCP2 titres and fewer peptide-specific ACPA than ACPA-positive patients with RA and higher C reactive protein levels than ACPA-negative individuals without RA.

Presence of ACPA and especially high titres of anti-CCP2 have a high diagnostic accuracy for an RA diagnosis in a population setting.

To compare Pneumocystis jirovecii pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population METHODS: We identified patients with ARD recorded in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model. We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16-86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82-10.35, 2.16-12.13, 2.41-6.95, and 2.06-6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk.

Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide. Key Points • Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD. • Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP. • Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP. • Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.

Pain during activities of daily living is a common presenting complaint of individuals with knee osteoarthritis and anterior cruciate ligament injury. Knee pain is also associated with a decrease in quality of life for people with osteoarthritis. The purpose of the present study was to examine the dose-response relationship between knee joint forces and painful symptoms, and whether the acute symptoms, were associated with individuals' quality of life. This was a cross-sectional cohort correlation study. Seventeen individuals with anterior cruciate ligament (ACL)-deficient knees diagnosed with ipsilateral knee osteoarthritis completed the ACL quality of life questionnaire (ACL-QOL). The subjects also rated pain associated with each of five incremental isometric knee extension tests, proportional to their body weight. Analysis of variance was used to assess the association between pain and normalized torque. Linear regression was used to assess the correlation between the ACL-QOL score and the total pain experienced during the graded test. A strong relationship was found between the level of perceived knee pain and the amount of isometric torque produced (Pearson's r = 0.98; p < 0.001). There was a statistically significant relationship between pain during the graded isometric test and the ACL-QOL (Pearson's r = -0.56; p = 0.016).

Since knee joint compression is a function of active isometric knee extension torque, increased painful symptoms were associated with increased compression forces at the knee joint for these subjects. The relationship between pain provocation and disease-specific quality of life provides evidence for the proposed joint provocation test for this subject population. Weakness caused by osteoathritis (OA) may, in part, be a negative conditioning response that would need to be overcome in rehabilitation.

Health information technology has enabled efficient measurement of patient-reported outcomes (PROs). The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) is becoming more widely adopted for research and routine care, and some PROMIS instruments might be substituted for lengthier, legacy PRO instruments. Four PROMIS computer-adaptive testing (CAT) instruments (pain interference, physical function, sleep disturbance, and fatigue) and the Routine Assessment of Patient Index Data 3 (RAPID3), along with pain intensity and patient global assessment score, were administered to participants in the ArthritisPower registry. The RAPID3 was predicted using different combinations of these variables to create a new score (CAT-PROMIS RAPID3). Kappa statistics and Bland-Altman 95% limits of agreement were used to measure agreement between the observed versus predicted RAPID3. A total of 6,154 eligible patients contributed 11,275 observations. The mean ± SD age was 52.7 ± 10.5 years, and 93% of patients were women. The median assessment times ranged from 29 seconds (PROMIS sleep disturbance) to 116 seconds (RAPID3). As single pairwise comparisons, the PROMIS CATs examined were modestly correlated (r approximately 0.4-0.7) to one other and RAPID3. Together with the pain intensity and patient global assessment, the PROMIS instruments explained a high fraction of total variance (R

There was excellent agreement between the observed RAPID3 and predicted RAPID3 scores estimated using several PROMIS instruments. The Multidimensional Health Assessment Questionnaire and patient global assessment components of RAPID3 may be unnecessary if PROMIS scores are available.

Some of the poor functional outcomes of knee arthroplasty may be due to pain in the contralateral, unreplaced knee. We investigated the relationship between the preoperative pain status of the contralateral knee and the risk of a poor postoperative functional outcome in patients who underwent knee arthroplasty. We analyzed data on 271 patients in the Multicenter Osteoarthritis Study who had undergone knee arthroplasty since the time of enrollment. Eighty-six percent of these patients were white, 72% were female, and the mean age was sixty-seven years. The severity of pain in the knee contralateral to the one that was replaced was measured before the knee arthroplasty with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale, with the scores being grouped into four categories (0, 1 to 4, 5 to 9, and 10 to 20). Poor post-arthroplasty function six months or more after surgery was determined with use of the Patient Acceptable Symptom State (PASS) outcome tool and a clinical performance measure of walking speed. We evaluated the relationship between contralateral pain severity and the functional outcomes with use of Poisson regression. Seventy-two (27%) of 264 patients demonstrated poor post-arthroplasty function by failing to attain the threshold PASS score, and seventy-six (30%) of 250 subjects had a slow walking speed. As the pre-arthroplasty pain in the contralateral knee increased, there was a steady increase in the proportion with poor post-arthroplasty function (p &lt; 0.0001 for PASS and p = 0.04 for slow walking speed). Compared with patients who had no pre-arthroplasty pain in the contralateral knee, those in the highest category of contralateral pain severity had 4.1 times the risk (95% confidence interval, 1.5 to 11.5) of having poor self-reported post-arthroplasty function. Patients in whom both knees had been replaced at the time of outcome collection were less likely to have poor self-reported function than those in whom only one knee had been replaced. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Preoperative pain in the contralateral knee is strongly associated with self-reported post-arthroplasty functional outcome and may therefore be a useful indicator of prognosis or a potential target of perioperative intervention.

To study the long-term effects of supplementation with omega-3 fatty acids (omega 3) in patients with active rheumatoid arthritis. Ninety patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementations with either 2.6 gm of omega 3, or 1.3 gm of omega 3 + 3 gm of olive oil, or 6 gm of olive oil. Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of omega 3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of omega 3.

Daily supplementation with 2.6 gm of omega 3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication.

Osteoarthritis is a serious social problem. Young people usually present with secondary degenerative changes. These patients find it particularly difficult to accept symptoms, as they are at their peak of professional activity and family life. They have high expectations regarding improvement in life comfort. The aim of this study was to analyse clinical and radiological outcomes of total hip arthroplasty for hip osteoarthritis in patients younger than 28 years old. We also assessed the correlation between aetiology of early degenerative changes and endoprosthesis survival. Thirty out of a group of 55 patients (22 women and 8 men) aged 17-28 years (mean 23.4), who underwent total hip replacement before they reached the age of 28 years, were qualified for the study. The follow-up period ranged from 16 months to 25 years (mean 6.9 years). Degenerative changes resulted most often from developmental dysplasia of the hip joint. We assessed the clinical status (HHS and MAP scores) and radiological outcomes. 6 cases of aseptic loosening (20%) out of 30 patients and one case of septic loosening of one of the endoprosthesis components occurred. The HHS and MAP scores improved markedly.

We observed a considerable improvement in hip function in patients after total hip replacement. Implant survival in the study group was slightly shorter than in the literature. Post-arthroplasty complications were more frequent in patients treated for developmental dysplasia of the hip joint and those with a history of joint infection before the age of two years.

To synthesize professional and patient expertise with available evidence to recommend best practices for post-acute rehabilitation following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) for osteoarthritis (OA). Two expert panels of clinicians, researchers, and patients from Canada and the US participated in a 3-round, online Delphi survey. Consensus was reached on 22 THA and 24 TKA best practice key statements. Recommendations common to both procedures included the need for supervised rehabilitation interventions provided by trained health professionals early after discharge from the acute care setting to optimize patient outcomes. Personal and environmental contextual factors were identified as influencing the process and outcomes of THA and TKA rehabilitation. Routine outcome assessment was recommended and several standardized outcome tools identified. Short-term followup care in the first 2 years postsurgery was recommended for both procedures. Specifics on timing, rehabilitation providers, need for long-term followup, and interventions differed for THA and TKA. Some recommendations received different levels of support based on the type of panelist (patient, physical therapist, surgeon), professional role (clinician, researcher), and/or country.

A rigorous consensus method led to key recommendations for post-acute rehabilitation after primary THA and TKA for OA, which together with available evidence and acknowledgment of contextual factors will inform the development of clinical practice guidelines. This is an important step toward reducing practice variation, closing the evidence-practice gap, and improving the quality of rehabilitation services after THA and TKA.

The aim of this study was to investigate the prevalence of temporomandibular disorders (TMD) in patients with primary Sjögren syndrome (1 degree SS), analyze the impact of the disease on mandibular function, and assess psychosocial distress. Sixty-three subjects, 60 women and 3 men, participated in the study; 21 1 degree SS patients were compared with age-matched and gender-matched groups of TMD subjects and controls. Patients were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders. Results showed that the subjective, clinical, and radiographic signs of TMD are not more common in patients with 1 degree SS than in controls. The impact of the autoimmune disease on mandibular function, e.g., speech and chewing ability, revealed limitations in oral functioning similar to those in patients with TMD pain.

Both 1 degree SS and chronic TMD may be associated with appreciable physical discomfort and psychosocial dysfunction. However, the underlying mechanisms of the oral dysfunction of 1 degree SS and TMD are quite different and essentially unrelated.

(1) To determine the test-retest reliability of monofilaments pressed against the skin as a method of assessing sensation in the feet of patients with rheumatoid arthritis (RA) and in controls using two grades of monofilaments; (2) to determine the stability of findings over 6 weeks; and (3) to calculate initial estimates of frequency of loss of sensation and to investigate its association with disease status. Clinical examination of the feet was undertaken in 51 patients with RA and 20 normal controls. Six sites on each foot were tested twice with both 10 g and 3 g research grade monofilaments and this was repeated after 6 weeks. Disease status was measured using the Disease Activity Score, the Health Assessment Questionnaire, visual analogue scales of pain, and the acute phase response using erythrocyte sedimentation rate and plasma viscosity. Reproducibility was high for 3 g (kappa=0.73) and 10 g (kappa=0.75) monofilaments. The best balance between sensitivity (58.8%) and specificity (87.5%) for distinguishing the feet of patients from the feet of controls was using the 3 g filament and defining reduced protective sensation as being sensitive to less than 11 of 12 applications. Using this definition, the prevalence of reduced protective sensation is 59% in the patient group and 12.5% in the feet of controls. There was some variation in sensation over 6 weeks in the patient group, but this was not related to measures of clinical status.

The use of monofilaments in assessing sensation levels in the RA foot is repeatable and reproducible over a six-week period and requires only a short time to perform. The frequency of reduced sensation in the feet of patients with RA was greater than previously reported. Future studies should assess relationships with disease duration and inflammatory status.

We previously implicated the lipid mediator lysophosphatidic acid (LPA) as having a role in dermal fibrosis in systemic sclerosis (SSc). The aim of this study was to identify the role of the LPA-producing enzyme autotaxin (ATX), and to connect the ATX/LPA and interleukin-6 (IL-6) pathways in SSc. We evaluated the effect of a novel ATX inhibitor, PAT-048, on fibrosis and IL-6 expression in the mouse model of bleomycin-induced dermal fibrosis. We used dermal fibroblasts from SSc patients and control subjects to evaluate LPA-induced expression of IL-6, and IL-6-induced expression of ATX. We next evaluated whether LPA-induced ATX expression is dependent on IL-6, and whether baseline IL-6 expression in fibroblasts from SSc patients is dependent on ATX. Finally, we compared ATX and IL-6 expression in the skin of patients with SSc and healthy control subjects. PAT-048 markedly attenuated bleomycin-induced dermal fibrosis when treatment was initiated before or after the development of fibrosis. LPA stimulated expression of IL-6 in human dermal fibroblasts, and IL-6 stimulated fibroblast expression of ATX, connecting the ATX/LPA and IL-6 pathways in an amplification loop. IL-6 knockdown abrogated LPA-induced ATX expression in fibroblasts, and ATX inhibition attenuated IL-6 expression in fibroblasts and the skin of bleomycin-challenged mice. Expression of both ATX and IL-6 was increased in SSc skin, and LPA-induced IL-6 levels and IL-6-induced ATX levels were increased in fibroblasts from SSc patients compared with controls.

ATX is required for the development and maintenance of dermal fibrosis in a mouse model of bleomycin-induced SSc and enables 2 major mediators of SSc fibrogenesis, LPA and IL-6, to amplify the production of each other. Our results suggest that concurrent inhibition of these 2 pathways may be an effective therapeutic strategy for dermal fibrosis in SSc.

The aim of this study was to investigate the ability of whole-body MRI (WBMRI) to visualize inflammation [synovitis, bone marrow oedema (BME) and enthesitis] and structural damage in patients with RA. The 3T WBMR images were acquired in a head-to-toe scan in 20 patients with RA and at least one swollen or tender joint. Short Tau Inversion Recovery and pre- and post-contrast T1-weighted images were evaluated for readability and the presence/absence of inflammation (synovitis, BME and enthesitis) and structural damage (erosions and fat infiltrations) in 76 peripheral joints, 30 entheseal sites and in the spine. The readability was >70% for all individual joints, except for the most peripheral joints of the hands and feet. Synovitis was most frequent in the wrist, first tarsometatarsal, first CMC joints and glenohumeral joints (67-61%); BME in the wrist, CMC, acromioclavicular and glenohumeral joints (45-35%) and erosions in the wrist, MTP and CMC joints (19-16%). Enthesitis at ≥ 1 site was registered in 16 patients. BME was frequently seen in the cervical (20%) but not the thoracic and lumbar spine, while fat infiltrations and erosions were rare. The intrareader agreement was high (85-100%) for all pathologies. The agreement between WBMRI and clinical findings was low.

Peripheral and axial inflammation and structural damage at joints and entheses was frequently identified by WBMRI, and more frequently than by clinical examination. WBMRI is a promising tool for evaluation of the total inflammatory load of inflammation (an MRI joint count) and structural damage in RA patients.

To perform a detailed deformity analysis of patients with varus alignment and to define the ideal osteotomy level (tibial vs. femoral vs. double level) to avoid an oblique joint line. A total of 303 digital full-leg standing radiographs of patients aged 18-60 years and varus alignment [mechanical tibiofemoral varus angle (mFTA) ≥ 3°] were included. All legs were analyzed regarding mFTA, mechanical medial proximal tibia angle (mMPTA), mechanical lateral distal femur angle (mLDFA), and joint line convergence angle. Based on mFTA, varus alignment was categorized as "mild" (3°-5°), "moderate" (6°-8°), or "severe" (≥ 9°). Deformity location was determined according to the malalignment test described by Paley. Two osteotomy simulations were performed with different upper limits for mMPTA: anatomic correction (mMPTA ≤ 90°, mLDFA ≥ 85°) and overcorrection (mMPTA ≤ 95°, mLDFA ≥ 85°). If a single osteotomy exceeded these limits at the intended mFTA of 2° valgus, a double-level osteotomy was simulated. If even a double-level osteotomy resulted in deviations from the defined limits, the leg was categorized as "uncorrectable". Mean mFTA was 6° ± 11° of varus (range 3°-15°). A tibial deformity was observed in 28%, a femoral deformity in 23%, a combined tibial and femoral deformity in 4%, and no bony deformity in 45%. The prevalence of a tibial deformity did not differ between varus severity groups, whereas a femoral and bifocal deformity was significantly more prevalent in knees with more distinct varus (p < 0.001). Osteotomy simulation revealed that isolated high tibial osteotomy (HTO) was appropriate in only 12% for anatomic correction, whereas a double-level osteotomy was necessary in 63%. If overcorrection of mMPTA was tolerated, the number of HTOs significantly increased to 57% (p < 0.001), whereas the number of double-level osteotomies significantly decreased to 33% (p < 0.001). Isolated DFO was considered ideal in 8% for both simulations. Significantly more knees were considered "uncorrectable" by simulating anatomic correction (18 vs. 2%; p < 0.001). A double-level osteotomy was significantly more often necessary in knees with "severe" varus (p < 0.001). III, cross-sectional study.

Less than one-third of patients (28%) with mechanical varus ≥ 3° have a tibial deformity. If anatomic correction (mMPTA ≤ 90°) is intended, only 12% of patients can be corrected via isolated HTO, whereas 63% of patients require a double-level osteotomy. If slight overcorrection is accepted (mMPTA ≤ 95°), 57% of patients can be corrected via isolated HTO, whereas 33% of patients would still require a double-level osteotomy.

To explore the possibility of integrating patient-important outcomes like pain, fatigue, and physical function into the evaluation of disease status in early rheumatoid arthritis (ERA) without compromising correct disease activity measurement. Patients from the 2-year Care in Early Rheumatoid Arthritis (CareRA) trial were included. Pain and fatigue (visual analog scales), Health Assessment Questionnaire (HAQ), standard components of disease activity [swollen/tender joint counts (SJC/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), physician (PhGH) and patient (PaGH) global health] were recorded at every visit (n = 10). Pearson correlation and exploratory factor analyses (EFA), using multiple imputation (15×) and outputation (1000×), were performed per timepoint and overall, on standard components of disease activity scores with and without pain, fatigue, and HAQ. Each of the 15,000 datasets was analyzed using EFA with principal component extraction and oblimin rotation to determine which variables belong together. We included 379 patients. EFA on standard composite score components extracted 2 factors with no substantial cross-loadings. Still, pain (0.83), fatigue (0.65), and HAQ (0.59) were strongly correlated with PaGH. When rerunning the EFA with the inclusion of pain, fatigue, and HAQ, the 2-factor model had substantial cross-loadings between factors. However, a 3-factor model was optimal, with Factor 1: patient assessment, Factor 2: clinical assessment (PhGH, SJC, and TJC), and Factor 3: laboratory assessment (ESR/CRP).

PaGH, pain, fatigue, and physical function represent a separate aspect of the disease burden of patients with ERA, which could be further explored as a target for care apart from disease activity. [ClinicalTrials.gov: NCT01172639].

Rheumatic conditions, which increase in prevalence as populations age, are a growing public health problem that disproportionately affects women. Understanding the influences of rheumatic diseases (RDs) on fatigue, stress, and perceived health status is deemed important to the improvement of physical and mental health for women with RDs. This study was designed to compare the fatigue, stress, and perceived physical and mental health status of women with RDs (RD group) with those of peers who did not have chronic illnesses (comparison group). A cross-sectional, purposive sample and comparative design was used. Four hundred forty-three women with a mean age of 46.2 years participated in this study. Those with physician-diagnosed RDs (n = 212) were enrolled in the RD group, and those without chronic disease were enrolled in the comparison group (n = 231). Measures used included a demographic datasheet, Fatigue Severity Scale, Perceived Stress Scale, and Short Form-12 Items Health Survey. Analysis of covariance was used to examine the intergroup differences for major variables based on demographic covariates. The RD group reported significantly more fatigue and stress than the comparison group. Moreover, the RD group reported significantly poorer perceived physical health status, significantly poorer physical functioning and general health, and greater bodily pain compared with the comparison group. Conversely, the RD group reported significantly better perceived mental health status, significantly lower vitality, and better role emotional status than the comparison group.

The findings support the theory that RDs have a negative impact on perceived stress and fatigue in women. Physical function, bodily pain, and general health may be the most significantly affected domains of perceived physical health in women with RDs. Of note, with the exception of the vitality subscale, RDs did not adversely affect the perceived mental health of participants with RD in this study. Healthcare professionals should cooperate with clinical rheumatologists, psychologists, and physiotherapists to provide comprehensive care that includes long-term education to help patients with RD self-manage stress, restore vitality, relieve pain, and increase physical function.

To determine the cytokine profile of the phenotypically activated T cell in rheumatoid arthritis (RA) synovium. Interleukin-2 (IL-2), IL-2 receptor (IL-2R), IL-6, IL-4, and interferon-gamma (IFN gamma) gene expression was examined in T cells from freshly isolated synovial fluids (SF) and synovial tissues (ST) from patients with RA. Estimates of baseline expression were determined using unstimulated peripheral blood (PB) T cells from healthy individuals. The corresponding positive controls were phytohemagglutinin-activated tonsil T cells. In studies of paired PB and SF T cell samples from 17 RA patients, IL-2 messenger RNA (mRNA) levels in only 1 PB and 3 SF samples were more than 2 standard deviations above the mean of levels in unstimulated PB from healthy donors. Similarly, only 5 PB and 7 SF samples exhibited elevated IL-2R mRNA levels. IFN gamma gene expression was not detected in any of the paired RA PB or SF samples. Fractionated T cells from 12 RA ST were screened with similar results: Only 1 of 12 samples exhibited IL-2 mRNA levels more than 2 standard deviations above levels in baseline controls. IL-2R mRNA levels were low or not detected, and IFN gamma mRNA was absent. Subsequent studies showed that IL-4 and IL-6 gene expression levels were also low in RA tissues compared with tonsil T cell-positive controls.

These data provide evidence for restricted cytokine expression in the T cell population in RA tissues.

The infliximab biosimilar CT-P13 has widely received regulatory approval in all indications of reference infliximab, including rheumatoid arthritis (RA) and ankylosing spondylitis (AS). This retrospective analysis investigated drug survival and long-term safety and effectiveness of CT-P13 in patients with RA or AS in the Republic of Korea. This non-interventional, retrospective, multicenter analysis collected medical record data for adult patients with RA or AS who received CT-P13 treatment at five Korean referral hospitals (2012-2017). Drug survival and long-term safety were primary outcomes. The secondary outcome was long-term effectiveness, assessed by disease activity measures. Overall, 491 patients were treated with CT-P13 (154 patients with RA [135 infliximab-naïve; 19 switched from reference infliximab]; 337 patients with AS [219 infliximab-naïve; 118 switched from reference infliximab]). Drug survival was similar in naïve and switched patients. Treatment-emergent adverse events (TEAEs) occurred in 31.8% and 29.4% of patients with RA and AS, respectively; incidence was similar in naïve and switched groups. Upper respiratory tract infection, influenza-like illness, and urticaria were the most common TEAEs. Overall, nine (1.8%) patients experienced serious adverse events (SAEs) deemed potentially drug-related; SAEs led to permanent CT-P13 discontinuation in five (1.0%) patients, including three with tuberculosis. Disease activity decreased over time.

Up to 5 years of CT-P13 treatment was safe and effective in patients with RA and AS, based on drug survival, incidence of TEAEs, and disease activity. Drug survival and safety were similar in naïve patients and switched groups, supporting switching from reference infliximab to CT-P13.

Fcγ receptor IIb (FcγRIIb) is an essential negative regulator of B cells that blocks B cell receptor (BCR) signaling and triggers c-Abl-dependent apoptosis of B cells. FcγRIIb-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIb-I232T is a hypofunctional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of the FcγRIIb-I232T polymorphism, we investigated the role of FcγRIIb in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity. We generated FcγRIIb Compared to wild-type (WT) mice, FcγRIIb

Our findings provide evidence of a critical role of FcγRIIb/c-Abl in the negative selection of GC B cells in FcγRIIb

The purpose was to evaluate the association between estimated joint stress from physical activity (PA) and hip/knee osteoarthritis (OA). A nested case-control study was performed using data from the Aerobics Center Longitudinal Study. Participants without self-reported OA at baseline who attended the clinic between 1974 and 1993 and returned a follow-up questionnaire in 1990 or 1995 were eligible. Cases were those who reported a physician diagnosis of OA of the knee and/or hip at follow-up (N = 415). A random sample of persons in the remaining cohort were classified as controls (N = 1995). PA was measured at baseline by self-report and subjects were classified as 'moderate/high' or 'low' joint stress by PA type. Those reporting no PA were classified as sedentary with 'no' joint stress (the reference group). Men and women were analyzed separately. Stratified analysis and multiple logistic regression were used to assess the relationship between hip/knee OA and joint stress as predicted by PA. After adjustment for age, body mass index, years of follow-up, and history of hip/knee joint injury, among men, there was no association between hip/knee OA and low joint stress while moderate/high joint stress was associated with reduced risk of hip/knee OA (adjusted odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.43-0.89). Among women, both levels of joint stress were associated with reduced risk of hip/knee OA (OR = 0.58, 95% CI = 0.34-0.99 for low and OR=0.24, 95% CI = 0.11-0.52 for moderate/high).

PA may reduce the risk of hip/knee OA, especially among women. Further research should assess the combined effects of frequency, intensity, duration and joint stress level of PA on incidence of hip/knee OA.

To investigate the prevalence and the predictors of silent but substantial liver fibrosis in patients with primary Sjogren's syndrome (pSS). We enrolled 101 pSS patients with normal liver function and structures, and without significant liver diseases or other conditions affecting liver fibrosis. The European league against rheumatism (EULAR) SS patients reported index (ESSPRI) and the EULAR SS disease activity index (ESSDAI) were analyzed. Liver stiffness (LS) was measured using transient elastography and 7.4 kPa was determined as the cutoff value for significant liver fibrosis. The median age of patients (91women) was 53 years and the median LS value was 4.7 kPa. The median ESSPRI and ESSDAI showed no correlation with LS values. Twelve patients (11.9%) had significant liver fibrosis. In multivariate logistic regression, white blood cells count ≤4000.0/mm(3) (Odds ratio [OR] 9.821), serum albumin ≤3.8 mg/dL (OR 16.770) and aspartate aminotransferase (AST) ≥ 27.0 IU/L (OR 20.858) independently predicted silent but substantial liver fibrosis in pSS patients.

The prevalence of silent but substantial liver fibrosis was 11.9% in pSS and its predictors were leukopenia, decreased serum albumin and increased AST levels.

To examine lipid profiles among statin-naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins. Information regarding lipid measures and statin use was gathered in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria first met between January 1, 1988 and January 1, 2008) and in a cohort of non-RA subjects from the same underlying population. Only patients with no prior history of statin use were included. The study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non-RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were lower in the RA versus the non-RA cohort (P < 0.001 and P = 0.003, respectively). The absolute and percentage change in LDL cholesterol after at least 90 days of statin use tended to be smaller in the RA versus the non-RA cohort (P = 0.03 and P = 0.09, respectively). After at least 90 days of statin use, patients with RA were less likely to achieve therapeutic goals for LDL cholesterol than the non-RA subjects (P = 0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (odds ratio 0.47, 95% confidence interval 0.26-0.85) was associated with lower likelihood of achieving therapeutic LDL goals.

Patients with RA had lower total cholesterol and LDL cholesterol levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non-RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals.

The strong genetic association between HLA-B27 and ankylosing spondylitis has been known for over 40 years. HLA-B27 positivity is possibly associated with severity of ankylosis. We studied the in vitro and in vivo impact of HLA-B27 in models of chondrogenesis and osteogenesis. Different in vitro differentiation systems were used to mimic endochondral and direct bone formation. ATDC5 cells and primary human periosteum-derived cells (hPDCs) were transduced with lentiviral vectors expressing HLA-B27 or HLA-B7. These cells and limb bud cells (from HLA-B27 transgenic and wild-type (WT) mice) were cultured in micromasses. To study direct osteogenesis in hPDCs, cells were cultured as monolayers and stimulated with osteogenic media. Chondrogenesis ( There was no difference in chondrogenesis markers or in colorimetric tests between HLA-B27

HLA-B27 seems to enhance joint inflammation in the CAIA model. We could not document a direct effect of HLA-B27 on chondrogenesis or osteogenesis.

Degeneration of articular cartilage leads to the development of osteoarthritis (OA), but the molecular pathology of the disease is poorly understood. The Disproportionate micromelia (Dmm) mouse has a deletion mutation in the C-propeptide encoding region of Col2a1, which leads to a defective cartilage matrix. The objective of this study was to determine whether heterozygous (Dmm/+) mice develop premature OA, and could therefore serve as an animal model for studying the molecular pathways leading to OA. Histological analysis was utilized to determine the state of articular cartilage degeneration in Dmm/+ mice at 3, 6, 9, 12, 15, and 22 months of age. Severity of OA was quantified with a modified Mankin scoring system. In addition, articular cartilage thickness, cell density, and the extracellular matrix (ECM) fraction of articular cartilage were quantified. Articular cartilage erosion was significantly more severe in Dmm/+ than in wild-type (+/+) mice beginning at 9 months, and modified Mankin scoring revealed Dmm/+ articular cartilage to be in a more severe osteoarthritic state as early as 3 months. In addition, Dmm/+ articular cartilage was thinner than +/+ cartilage and showed increased cell density and decreased matrix fraction compared with +/+ from the earliest time points measured.

The present study demonstrates that Dmm/+ mice develop premature OA. The observed degenerative changes of Dmm/+ articular cartilage closely resemble those of human OA patients, with or without Col2a1 mutations, suggesting that Dmm/+ mice are a useful model for investigating mechanisms involved in OA.

Impairments in work productivity and daily activities contribute to the burden of rheumatoid arthritis (RA). It is thus essential to use an instrument assessing both work and daily activity impairments when studying the full impact of RA on individuals. The Work Productivity and Activity Impairment (WPAI) questionnaire is such an instrument. This study aims to linguistically validate the RA-specific WPAI (WPAI:RA) instrument in 20 new languages and to assess its content validity for individuals with RA. The linguistic validation of the questionnaire followed a standard methodology that included comprehension test interviews (n = 5 individuals with RA per language) to assess the relevance, understanding and acceptability of the WPAI:RA. Content validity of the instrument was simultaneously investigated. Comprehension testing showed that the WPAI:RA questionnaire was well understood similarly across countries; minor changes were made to ensure fidelity to the original concepts and for ease of comprehension. The majority of interviewees (66/93) considered its content comprehensive and appropriate to measure their ability to work and perform daily activities.

The WPAI:RA questionnaire is now linguistically validated in 20 new languages [Czech (Czech Republic), Dutch (Belgium), English (Canada and UK), French (Belgium, Canada and France), German (Germany), Hungarian (Hungary), Italian (Italy), Polish (Poland), Portuguese (Brazil), Romanian (Romania), Russian (Russia and Ukraine), Spanish (Argentina, Mexico, Spain and US) and Ukrainian (Ukraine)]. The WPAI:RA questionnaire shows good content validity. It can thus be used in multi-country clinical trials to assess RA-related impact on the patients' ability to work and perform daily activities.

Gout in spine is rare and commonly mimics some infectious or tumoral lesions, the differentiation of spinal gout from other diseases is not always easy. We report a case of gout involved cervical disc and adjacent vertebral endplates whose etiology was initially not determined. Compared with the previous published 10 similar cases, this case displayed a complete and continuous image data with higher image quality and resolution than before. So we give a brief literature review for concerning cervical gout, with the emphasis on the discussion of radiological findings. A 50-year-old male with a 5-year history of neck and shoulder pain had muscle atrophy and weakness in both arms. Physical examination revealed multiple tophi were seen in left wrist, both feet and knee; bilateral superficial sensory declined below level of mastoid portion and the muscle strengths of limbs decreased. Laboratory findings showed hyperuricemia and the C-reactive protein level was very high. Imaging studies including Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) showed abnormality of the C5-6 intervertebral disc and irregular osteolytic destruction of both adjacent C5-6 endplates, narrowing of C5-6 disc space and swelling of prevertebral soft tissue. Under the circumstance of the lesions being not determined and nerve root symptoms, surgical treatment was performed and pathological examination of the specimen revealed deposited uric acid crystals surrounded by granulomatous inflammation. After surgery combined with pharmaceutical and rehabilitation treatment, the muscle strengths of limbs, the pain of neck and shoulder and the level of serum uric acid were all improved.

Cervical spinal gout involving the disc and adjacent vertebral endplates is uncommon and may misunderstand infectious spondylodiscitis. Physician and radiologist should take the gouty spondylitis into account with a combination with previous history and clinical manifestations when encountering with such this condition.

To assess hemodynamic changes related to acute gouty knee arthritis in a rabbit with CT perfusion (CTP) METHODS: Forty-two rabbits were randomly separated into two groups: the treated group of 30 and the control group of 12. The right knee was injected with monosodium urate solution and polymyxin in the treated group and saline and polymyxin in the control group. At 2, 16, 32, 48, 60, and 72 h after injection, five rabbits from the treated group and two rabbits from the control group were selected for CTP. At each time point, blood flow (BF), blood volume (BV), and clearance rate (CL) were measured, and microvessel density (MVD) was evaluated with a microscope. In the treated group, BF, BV, CL, and MVD were significantly higher than in the control group (p < 0.001). Differences within paired comparison of BV, BF, CL, and MVD were all significant (all p < 0.001). Peak time of BV, BF, and MVD was 32 h and 48 h for CL. After multivariate stepwise linear regression analysis, BV was linearly associated with MVD and vice versa, which also applied to BF with MVD and BF with CL, separately. The ascending rate of MVD was the highest among that of all parameters; so was the descending rate of CL. • Acute gouty arthritis can be evaluated with CTP in a rabbit knee model. • Following injection of MSU crystals, producing an acute gouty attack, CTP successfully assessed hemodynamic changes. • The ascending rate of MVD was the highest among that of all parameters; so was the descending rate of CL.

CTP in this rabbit knee model accurately detected hemodynamic changes during a gouty attack.

To examine the expression and regulation of chemotactic factor, macrophage inflammatory protein-1alpha (MIP-1alpha) by fibroblast-like synoviocytes (FLS), monocytes and polymorphonuclear neutrophils (PMN) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Monocytes or PMN obtained from RA SF were co-cultured with unstimulated semiconfluent RA FLS. Culture supernatants were assayed for MIP-1alpha by enzyme-linked immunosorbent assay. The expression of MIP-1alpha mRNA and protein was also determined by Northern blot analyss and immunohistochemistry respectively. Interaction of activated leucocytes with FLS synergistically increased MIP-1alpha expression and secretion via a mechanism mediated by beta2-integrin/ intercellular adhesion molecule 1.

MIP-1alpha expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.

This study assessed the health economics and outcomes of three common foot and ankle operations. Between July 2013 and October 2014 all patients undergoing ankle fusion (AF) for osteoarthritis, first metatarsophalangeal joint fusion for osteoarthritis (MF) or hallux valgus surgery (HV) were included. Patients having additional procedures were excluded. Patients completed the Manchester-Oxford Foot Questionnaire (MOX-FQ), the EuroQol EQ-5D-5L questionnaire and the EQ-VAS on presentation and at least 6 months post-operatively. 63 patients undergoing AF (n=22), MF (n=22), or HV (n=32) completed preoperative and postoperative questionnaires. 76 completed preoperative questionnaires and 63 completed the follow up questionnaires. The follow up questionnaires were completed at a median of 12 months (range 6-24 months) following surgery. The mean age at surgery was 59 years (range 26-85 years). Pre-operative MOX-FQ and EQ-5D-5L scores differed significantly between the three groups with AF and MF patients reporting worse scores compared to HV patients. MOX-FQ and EQ-5D-5L significantly improved in all groups from pre-operative levels. AF from 53.8 (CI 56.8-50.8) to 22.9 (CI 30.9-14.9), MF from 43.0 (CI 46.4-39.6) to 12.1 (CI 18.3-5.9), HV from 35.4 (CI 39.0-31.7) to 15.6 (CI 21.1-10.1). EQ-5D-5L: AF from 0.30 (CI 0.43-0.17) to 0.66 (CI 0.77-0.55), MF from 0.45(CI 0.52-0.38) to 0.83 (CI 0.90-0.76), HV from 0.71(CI 0.74-0.68) to 0.82 (CI 0.88-0.76). There was no significant difference in the EQ-VAS suggesting it may not be representative of foot and ankle health. Health economics analysis using the EQ-5D-5L data to estimate quality-adjusted life years (QALYs) suggested all three procedures were favourable compared to threshold levels of cost-effectiveness. There were differences in estimated costs between the three operations with AF at £2950 (threshold cost <£5400) and MF at £1197 (threshold cost <£5780) and HV varying from £625 to £1688 (threshold cost <£1640).

This study reveals that the joint-specific (MOX-FQ) and generic health (EQ-5D-5L) outcome scores of patients improved after AF, MF and HV. The greatest benefit from surgery was gained in the arthritic patient groups. In the future, the use of large population patient reported outcome measures data may also potentially have implications for prioritisation of healthcare provision, acting as an indicator of foot and ankle surgical procedures that produce the most benefit to patients.

The primary aim of this study was to identify independent predictors of long-term survivorship after high tibial osteotomy (HTO). The secondary aims were to describe the functional outcome of surviving HTO 10-20 years after surgery. A retrospective cohort of 223 HTO that were performed for the treatment of medial osteoarthritis was identified. Details were recorded from the patient notes. All surviving patients were contacted and asked to complete a Tegner Activity Scale, Lysholm Knee Score and rate pain using the Visual Analogue Scale (VAS). Survival analysis was performed, using conversion to arthroplasty as the definition of failure. The mean age was 54 years (24-80 years). There were 123 (55.2%) in males and 100 (44.8%) in females. The mean BMI was 27.2 (SD 3.9). Twenty (9%) patients were lost to follow-up. The mean follow-up was 12 (SD 4) years. Survival at 10 years was 75 and 55% at 15 years and less than 40% at 20 years. Cox regression analysis demonstrated age of 50 years or more, female gender and surgical technique to be significant independent predictors of failure. The median Tegner score was 3 (inter-quartile range (IQR) 1-3). The mean Lysholm score was 75.5 (SD 18.4). The median VAS was 5 (IQR 0-6).

The medium- to long-term survival and functional outcome after HTO was good to excellent at 10-20 years of follow-up. Age, gender, surgeon and surgical technique were identified as independent predictors of failure.

This study aims to investigate the risk of total knee replacement (TKR) following tibia plateau fractures. Secondary the study aims to investigate the risk of knee arthroscopy following tibial plateau fractures. The study was designed as a matched cohort study. All patients who sustained a tibial plateau fracture in Denmark between January 1, 1996, and December 31, 2000, were included and followed until December 31, 2015. For each patient with a tibial plateau fracture, 10 matched citizens without a tibial plateau fracture were included as a reference group. 7,950 patients sustained a tibial plateau fracture in Denmark during the study period. The median age of patients was 52.6 (IQR: 32.4-71.5) years. The mean observational period was 13.9 years. 5.7% were treated with a TKR (N = 452), and 2.0% of patients from the reference group were treated with a TKR (N = 1,623). Patients with a tibial plateau fracture had a 3.5 (95%CI: 3.1-3.9) times higher hazard ratio (HR) compared to patients from the reference group. 7.6% of patients with a tibial plateau fracture were treated with a secondary knee arthroscopy (N = 603) and 2.0% of patients from the reference group were treated with a knee arthroscopy (N = 1,565). Patients with a tibial plateau fracture presented with a 5.0 (95%CI: 4.5-5.6)) times higher HR compared to patients in the reference group.

Tibial plateau fractures are associated with a 3.5 times increased risk of TKR compared with an age- and gender-matched reference group with a mean follow-up of 13.9 years.

We aimed to investigate the association between Premenstrual syndrome (PMS) and fibromyalgia syndrome (FMS), to assess common symptoms and quality of life (QOL) of them. Patients with PMS formed the PMS group and age-matched healthy normal controls were included in the control group. The diagnosis of the FMS and PMS were based on new American College of Rheumatology FMS criteria and DSM-IV PMS criteria. FMS-related symptoms assessed by visual analog scale and number of tender points (TePs) were analyzed. QOL, PMS severity and FMS severity were assessed with SF-36, fibromyalgia impact questionnaire (FIQ) and premenstrual assessment form (PAF), respectively. Patients with PMS were divided into two subgroups according to coexistence of FMS or not. The frequency of FMS in PMS and control group were 20 and 0%, respectively (p = 0.002). FMS-related symptoms, number of TePs in the PMS group were higher than those in the control group. The mean mental component summary (MCS) score of SF-36 was low in the PMS group. The mean PAF score in PMS with FMS subgroup was higher than those in without FMS subgroup. The mean physical component summary of SF-36 was low in the PMS patient with FMS. There was correlation between PAF score and FIQ score (r = 0.476, p < 0.001).

FMS was common among the patients with PMS and frequently seen in the PMS patients having severe premenstrual complaints. Mental QOL was distressed in the patients with PMS but while FMS accompanied to PMS, the physical QOL was decreased.