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Children with juvenile idiopathic arthritis (JIA) often have impaired growth and short stature. There is evidence that the therapeutic use of growth hormone (GH) is useful and safe in these patients. To analyze the effects of GH use in patients with JIA. A systematic review of the literature over the last 18 years in Medline and Embase databases. The criteria were analyzed independently by the researchers. We used the following keywords: "growth hormone", "arthritis, juvenile", "arthritis, rheumatoid", "child" and "adolescent". Among the 192 identified articles, 20 corresponded to the inclusion criteria. Seventeen longitudinal studies and 3 case reports were found. Most studies analyzed observed increased growth, muscle mass and bone mass using GH. Adverse effects observed were glucose intolerance, diabetes, bone deformities, osteonecrosis, reactivation of the disease and low final height.

The majority of studies reported positive effects after the therapeutic use of GH, but some variability in response to treatment was observed. The combination of growth hormone with other drugs seems to be a good option.

Necroscopic and surgical studies have suggested that giant cell arteritis (GCA) may target the aorta and its main branches. Imaging techniques are able to detect large vessel vasculitis (LVV) non-invasively in patients, but the prevalence of LVV in GCA has not been clearly established. To assess prospectively the prevalence, characteristics and topography of LVV in patients with newly diagnosed GCA and to determine the associated clinical and laboratory features. CT angiography (CTA) was performed in 40 consecutive patients with newly diagnosed biopsy-proven GCA. Patients were treatment-naïve or had been treated with corticosteroids for <3 days. Vessel wall thickness and vessel diameter (dilation or stenoses) at four aortic segments (ascending aorta, aortic arch, descending thoracic and abdominal aorta) and at the main aortic branches were evaluated. LVV was detected in 27 patients (67.5%). The vessels involved were as follows: aorta (26 patients, 65%), brachiocephalic trunk (19 patients, 47.5%), carotid arteries (14 patients, 35%), subclavian arteries (17 patients, 42.5%), axillary arteries (7 patients, 17.5%), splanchnic arteries (9 patients, 22.5%), renal arteries (3 patients, 7.5%), iliac arteries (6 patients, 15%) and femoral arteries (11 patients, 30%). Dilation of the thoracic aorta was already present in 6 patients (15%). Cranial ischaemic events were significantly less frequent in patients with LVV (p=0.029). Treatment-naïve patients had a higher frequency of LVV (77% vs 29%, p=0.005).

CTA-defined LVV occurs in two-thirds of patients with GCA at the time of diagnosis and aortic dilation is already present in 15%. Previous corticosteroid treatment may decrease CTA-detected LVV.

To evaluate the contributions of shared but unmeasured genetic and environmental factors to hallux valgus (HV). Between 2011 and 2012, 74 monozygotic (MZ) and 56 dizygotic (DZ) female twin pairs self-reported HV and putative risk factors, including footwear use across their lifespan. Estimates of casewise concordance (P A total of 70 participants (27%) reported HV, with 12 MZ and 7 DZ pairs being concordant. After adjusting for age, twins were correlated (ρ = 0.27 [95% confidence interval (95% CI) 0.08, 0.46]) and concordant (P

Twins are correlated for HV, but we found no evidence that correlation was due to shared genetic factors. We identified an environmental risk factor, footwear with a constrictive toe-box, that is not shared to the same extent by MZ and DZ pairs, contrary to the assumption of the classic twin model. Footwear, and possibly genetic factors and unknown shared environmental factors, could contribute to developing HV.

To examine the effect of IL-1 beta-induced *NO and PGE(2)release by stimulated superficial and deep chondrocyte/agarose constructs subjected to mechanical compression. Chondrocyte sub-populations were seeded separately in agarose constructs and cultured unstrained, within a 24-well tissue culture plate, for 48 h in medium supplemented with IL-1 beta and/or L-N-(1-iminoethyl)-ornithine (L-NIO). In a separate experiment, superficial and deep cell containing constructs were subjected to 15% dynamic compressive strain at 1 Hz, for 48 h, in the presence or absence of IL-1 beta and/or L-NIO. Nitrite was measured using the Griess assay, PGE(2)release was determined using an EIA kit and [3H]-thymidine and 35SO(4)incorporation were assessed by TCA and alcian blue precipitation, respectively. The current data reveal that IL-1 beta significantly enhanced *NO and PGE(2)release for superficial chondrocytes, an effect reversed with L-NIO. *NO and PGE(2)levels did not significantly change by deep cells in the presence of IL-1 beta and/or L-NIO. For both cell sub-populations, IL-1 beta inhibited cell proliferation whereas proteoglycan synthesis was not affected. Dynamic compression inhibited the release of *NO and PGE(2)in the presence and absence of IL-1 beta, for cells from both sub-populations. L-NIO reduced *NO and enhanced PGE(2)release for superficial zone chondrocytes, an effect not observed for deep cells in response to dynamic compression. The magnitude of stimulation of [3H]-thymidine incorporation was similar for both cell sub-populations and was not influenced by L-NIO, indicating an z.rad;NO-independent pathway. The dynamic compression-induced stimulation of 35SO(4)incorporation was enhanced with L-NIO for IL-1 beta-stimulated deep cells, indicating an *NO-dependent pathway.

The present findings suggest that dynamic compression inhibits *NO and PGE(2)release in IL-1 beta-stimulated superficial cells via distinct pathways, a significant finding that may contribute to the development of intervention strategies for the treatment of inflammatory joint disorders.

Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population. Peripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K. For Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77-2.74, p=8.99×10⁻¹³). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49-5.68, p=1.57×10⁻³). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43-0.71, p=2.55×10⁻⁶). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR=2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases.

The ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.

Findings from a study examining how women with fibromyalgia remain employed are used to explicate a conceptualization that adds to literature on workplace disclosure of stigmatized illnesses and impairments: disclosure dances that employees improvise in response to workplace-relationships needs and disclosure risks. Critical-discourse-analysis (CDA) methodology framed the study. Data were collected through 26 semi-structured, individual interviews with participant triads or dyads comprising women with fibromyalgia, family members and supervisors or co-workers. Interviews with managers who supervised disabled employees other than the women supplemented these data. Following coding, data were compared within and across triads/dyads through code-dimension summaries, narrative summaries and relational diagrams. Women with fibromyalgia and other stigmatized illnesses improvised everyday disclosures when they needed to explain fluctuating work ability, when others needed reminding about invisible impairments, and when workplace relationships changed. These impromptu disclosures comprised three dimensions: exposing oneself to scrutiny by disclosing both illness and impairments, divulging stigmatized illness, and revealing invisible impairments selectively.

Through impromptu disclosure dances, women tailored disclosure to changing immediate circumstances. While assumptions from psychological theories of risk underlie current conceptualizations of disclosure as planned in advance, this article examines disclosure through a different lens: social theories of everyday risk. Implications for rehabilitation For women with fibromyalgia, disclosing illness and impairments at work may entail risks to their jobs and workplace relationships. Rehabilitation professionals need to consider these risks when advising women with fibromyalgia about disclosing their illness and impairments at work. Professionals may first want to learn from clients about their workplace cultures and relationships, and their perceptions of disclosure risk. Professionals can then suggest a range of disclosure responses, depending on the relationship and risk.

Rheumatoid arthritis (RA) is a chronic, deforming arthritis that can lead to disabilities and poor quality of life. Cytokines are protein mediators of inflammation and are produced as a result of the activation of various cellular reactions. They are the final mediators and/or regulators of the inflammatory process. The sera from 64 RA patients were assayed for both Th-1 and Th-2 related cytokines and soluble TNF-alpha receptors (IFN-gamma, TGF-beta, TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, sTNF-R1 and sTNFR2) using ELISA. The pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-18 and TNF- alpha) were significantly elevated in RA patients, while TGF-beta, an immunomodulatory cytokine, was elevated in control individuals. When the RA patients were categorised as active or inactive based on DAS scores, similar cytokines profiles were observed in both RA sub-groups. However, assays of sTNF-R1 and sTNFR-2 were noted to be significantly elevated in inactive RA patients when compared to active patients.

Our findings indicate that local production of cytokine inhibitors is capable of diminishing disease activity and cytokine activity.

Despite looming rheumatologist shortages and a growing number of patients with arthritis and other rheumatic conditions, nationwide estimates of access to rheumatology care have never been reported. We aimed to measure travel times as a proxy to access to care and to determine the individual and area-level factors associated with long travel times to rheumatologists in the U.S. We used Medicare Part B claims for the 2009 Medicare Chronic Condition Warehouse 5% rheumatoid arthritis/osteoarthritis cohort. Using Google Maps we estimated driving time from the center of a beneficiary's home ZIP code to the center of their rheumatologist's office ZIP code. We examined predictors of travel time ≥90 min in a series of generalized linear mixed models adjusting for rheumatologist supply, rurality, and individual patient characteristics including age, race, gender, and income. We included 41,693 Medicare beneficiaries with 1 or more visits to a rheumatologist in 2009. The median estimated beneficiary travel time to a rheumatologist was 22 min [interquartile range (IQR): 12-40 min]. Overall, 7% of beneficiaries traveled 90 min or longer to visit a rheumatologist. Even after adjusting for covariates, independent predictors of long travel times included living in areas with no or low supply of rheumatologists and living in the Mountain region of the U.S.

A small but significant proportion of patients in the U.S. traveled very long distances to visit a rheumatologist, and most of these individuals resided in areas with no or low supplies of rheumatologists. These data suggest that addressing shortages in rheumatology care for patients in low-supply areas is a key target for improving access to rheumatologists.

To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care. Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering. IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduced the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN-K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable. NCT02665364.

IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering.

Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001).

NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.

To compare obesity among individuals with PsA, psoriasis (PsO), RA and the general population (n), and identify correlates of obesity among individuals with PsO and PsA. We compared the BMI of patients with PsA (n = 644), PsO (n = 448), RA (n = 350) and the general population using age- and sex-adjusted linear and logistic regression analyses. We conducted multivariate analyses limited to PsO and PsA to determine correlates of BMI and obesity. The mean BMI (kilogram per square metre) for individuals with PsA, PsO, RA and the general population were 29.6, 27.9, 27.3 and 26.1, respectively. The proportion with obesity was 37, 29, 27 and 18% for individuals with PsA, PsO, RA and the general population, respectively. The differences in BMI were significant between all categories (P < 0.05) except between PsO and RA. Age- and sex-adjusted linear and logistic regression confirmed that these differences were significant. In multivariate logistic regression analyses adjusted for age, sex, smoking, PsO duration, psoriasis area severity index score, use of DMARDs, glucocorticoids and biologics, the odds of obesity were 61% higher for PsA patients than PsO patients (95% CI 1.10, 2.37). When we additionally adjusted for the physical component summary of the short form-36, the association was attenuated and became insignificant.

Individuals with PsA have a higher mean BMI than those with PsO, RA or the general population. The BMI difference between PsA and PsO correlates with physical health.

Chronic fatigue syndrome (CFS) and fibromyalgia frequently are associated with symptoms of major depression. For this reason, antidepressants have been used in treatment of these disorders; however, little direction has been provided into this application in psychopharmacology. First, nine studies were reviewed regarding the relationship of the symptoms of fatigue and depression. Next, 23 reports (12 double-blind studies, 7 open studies, and 4 case reports) were reviewed for the effectiveness of therapy as assessed by global response and improvement of both depression and pain. Studies were differentiated by type of controls, as well as by alleged mechanism of action of the pharmacologic agent. Disturbances in brain neurochemistry shared by CFS and major depression may serve as a basis for the effectiveness of some antidepressants in CFS. Response to some antidepressants in patients with CFS or fibromyalgia may occur at doses lower than those used in major depression, e.g., amitriptyline 25-75 mg/day. We further found that the more serotonergic treatments (e.g., clomipramine) were more successful in alleviating pain than depression, whereas catecholaminergic agents (e.g., maprotiline, bupropion) seemed particularly effective for symptoms of associated depression.

To maximize response of the physiologic and psychological consequences of the disorder, more investigation is needed to replicate the apparent findings that relate the neurochemical impairment underlying CFS and fibromyalgia to the type of antidepressant mechanism.

Chronic arthritis of familial Mediterranean fever (FMF) involves weight-bearing joints and can occur in patients without a history of acute attack. Our aim was to investigate a possible causal relationship between FMF and osteoarthritis in a population in which FMF is quite common. Patients with late stage primary osteoarthritis were enrolled, and five MEFV gene mutations were investigated. The frequency of MEFV gene mutations was compared among patients with osteoarthritis and a previous healthy group from our center. One hundred patients with primary osteoarthritis and 100 healthy controls were studied. The frequency of MEFV gene mutations was significantly lower in the osteoarthritis group (9% vs. 19%). M694V was the most frequent mutation (5%) in the osteoarthritis group, whereas in the control group, E148Q was the most common (16%). In subgroup analyses, the mutation frequency of patients with hip osteoarthritis was not different from that of patients with knee osteoarthritis and controls (7.1%, 9.7%, and 19%, respectively). There were no differences among the three groups with respect to MEFV gene mutations other than E148Q (8.1% vs. 3.6%). E148Q was significantly lower in the osteoarthritis group than in the controls (16% vs. 1%), although the mutations did not differ between patients with knee osteoarthritis and controls.

In a population with a high prevalence of MEFV gene mutations, we did not find an increased mutation rate in patients with primary osteoarthritis. Furthermore, we found that some mutations were significantly less frequent in patients with osteoarthritis. Although the number of patients studied was insufficient to claim that E148Q gene mutation protects against osteoarthritis, the potential of this gene merits further investigation.

Systemic lupus erythematosus (SLE) is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus; however, early T cell events triggering disease flares are incompletely understood. This study was undertaken to examine DNA methylation in naive CD4+ T cells from lupus patients to determine if epigenetic remodeling in CD4+ T cells is an early event in lupus flares. A total of 74 lupus patients with an SLE Disease Activity Index score of 0-18 were included. Naive CD4+ T cells were isolated from peripheral blood samples, and DNA was extracted for genome-wide methylation assessment. RNA was also extracted from a subset of patients to determine the relationship between epigenetic changes and transcription activity using RNA sequencing and microRNA arrays. We demonstrated that naive CD4+ T cells in lupus undergo an epigenetic proinflammatory shift, implicating effector T cell responses in lupus flare. This epigenetic landscape change occurs without changes in expression of the corresponding genes, poises naive CD4+ T cells for Th2, Th17, and follicular helper T cell immune responses, and opposes inhibitory transforming growth factor β signaling. Bioinformatics analyses indicate that the epigenetic modulator EZH2 might play an important role in shifting the epigenetic landscape, with increased disease activity in lupus naive CD4+ T cells. Further, the expression of microRNA-26a, which is sensitive to glucose availability and targets EZH2, was negatively correlated with disease activity in lupus patients.

An epigenetic landscape shift in naive CD4+ T cells that favors T cell activation and non-Th1 immune responses predates transcription activity and correlates with lupus activity. A role for EZH2 dysregulation in triggering lupus flares warrants further investigation.

The damage to cartilage collagen is a central event in the pathogenesis of cartilage aging and osteoarthritis (OA). We have previously developed an in vitro model of cartilage degradation which shows that chondrocyte-dependent lipid peroxidation mediates cartilage collagen degradation. The goal of our study was to investigate the role of vitamin C in this degradation model and to investigate effect of chondrocyte-dependent lipid peroxidation in the oxidation of cartilage collagen. We studied primary articular chondrocytes. Effect of vitamin C was investigated in the previously described model. Serum-free stimulated and unstimulated chondrocyte-matrix extracts were subjected to SDS-PAGE and immunoblot analysis. Malondialdehyde (MDA)-protein oxidation of cartilage proteins was demonstrated by the reactivity of chondrocyte extracts to a monoclonal antibody, MDA2, which detects MDA-lysine adducts. Vitamin C treatment of chondrocyte cultures resulted in significant enhanced incorporation of 3H-proline label in cell-matrix. Cells treated with vitamin C, as compared to control untreated cells showed decreased spontaneous release of labeled matrix. Vitamin C treated or not treated chondrocytes responded comparably to stimulation with the agonist calcium ionophore A23187. The serum-free in vitro culture of chondrocytes resulted in MDA-protein oxidation. The treatment of chondrocytes with A23187 resulted in the enhancement of MDA-protein oxidation. The immunoblot reactivity pattern of extracts to MDA2 antibody and to polyclonal anti-type II collagen antibody was somewhat similar, which suggests that these two different types of antisera exhibit a crossreaction to chondrocyte proteins. Chondrocyte extracts were pretreated both with and without pure collagenase, and then subjected to immunoblot analysis. Only collagenase treated extracts showed a disappearance, or significant reduction, of larger than 60 kDa size MDA2 immunoreactive proteins. This suggests that the proteins that disappeared after the enzyme treatment were collagen proteins and which had also been modified by MDA oxidation.

These observations suggest that collagen hydroxylation of matrix by vitamin C does not play a role in this model of chondrocyte-dependent collagen degradation. Also, this study demonstrates that chondrocyte-derived lipid peroxidation product MDA mediates oxidation of cartilage collagens. Oxidative modification of cartilage collagen in vivo could result in alteration of biochemical and biophysical properties of cartilage collagen fibrils, making them prone to degradation, thus initiating the changes observed in aging and OA.

OPAL (Optimising Patient outcomes in Australian rheumatoLogy) Rheumatology is an independent not for profit Australian clinical research organisation which is the custodian of one of the largest datasets of patients with rheumatic diseases in the world, containing real-world clinical data from more than >175,000 unique patients collected over more than 900,000 clinical consultations. We describe the evolution and outcomes of the OPAL dataset, with particular reference to the use of big data derived from real-world clinical encounters to enhance clinical care and research. De-identified data are regularly extracted and aggregated from the electronic medical records (EMR) of consenting patients treated by approximately 100 rheumatologists around Australia. The EMR shared by OPAL clinicians was specifically customised for rheumatology and collects comprehensive information on demographics, disease history, activity and severity, co-morbidities, pathology, and medication use. In addition, OPAL captures multifaceted outcomes data from the patient perspective through a novel electronic patient-reported outcome (ePRO) delivery system which allows for health-related quality of life measures to be matched with clinical indices. Since inception in 2009, OPAL has produced 35 publications and abstracts. OPAL also provides real-world data to determine drug utilisation, efficacy and safety, elucidate the natural history of disease, highlight areas of unmet need, guide medical affairs and commercial strategy, and to support regulatory and reimbursement submissions.

The extensive, evolving and organic OPAL dataset reflects the complexities of clinical rheumatological practice. It provides unique opportunities to enhance clinical care and research.

To determine rheumatoid arthritis related out of pocket expenditure (OOPE) in Germany and to disaggregate the total OOPE into contributing cost domains. Data for the cost analysis were drawn from a multicentre randomised controlled prospective trial to assess the effectiveness of clinical quality management in patients with rheumatoid arthritis. Both payer sources and patient cost questionnaires were used to generate health care utilisation data. All cost domains of a recently published matrix were reviewed and potential sources of OOPE were determined. Health care utilisation data were developed throughout 2001. Co-payment regulations as per January 2004 were applied in order to indicate the most recent level of OOPE in Germany. Data were analysed in both physical and monetary units using descriptive statistics. In all, 136 patients with rheumatoid arthritis were included. Mean total OOPE per patient and year was 417.20 Euro (SEM 38.8, median 271.2). OOPE accounted for 15.3% of the total direct costs of rheumatoid arthritis. Total OOPE were further subdivided into cost domains: "non-physician service utilisation"' (194.40 Euro per patient and year; SEM 24.2), "medication" (99.00 Euro; 6.1), "transportation" (56.20 Euro; 17.4), "visits to physicians" (38.40 Euro; 0.6), "hospital facilities" (24.00 Euro; 5.6), and "devices and aids" (5.10 Euro; 0.8).

Rheumatoid arthritis is associated with substantial OOPE, imposing a considerable economic burden for patients. OOPE contribute significantly to the total health care expenditure in rheumatoid arthritis. The patient perspective has to be taken into account when calculating the overall direct costs of rheumatoid arthritis from a societal point of view.

To analyze the prevalence and location of tooth loss in Sjögren's syndrome (SS) patients and compare them with an age- and gender-matched control group. Dental charts and x-rays of 108 (SS) patients were retrieved from an academic dental center and special care dentistry department. For each SS patient, an age- and gender-matched non-SS patient was randomly selected. Medication, number of extractions and date and location of extractions were assessed. Differences between SS and non-SS patients were analyzed using Mann-Whitney U tests, Chi-square tests and Fisher's exact tests. Significantly more SS patients were edentulous compared to the non-SS group (14.8% versus 1.9%, p = 0.001). SS patients had a 61% higher risk to have experienced one or more extractions than control patients. In the SS group, there was a non-significant tendency for more maxillary teeth to have been extracted than mandibular teeth (42:34). In the control group, the number of extractions in the maxilla and mandible were comparable (21:20). When divided into sextants, the number of SS patients with one or more extractions was significantly higher than for non-SS patients for each sextant (p = 0.001 to p = 0.032). The largest difference in the proportion of patients with one or more extractions between the SS and non-SS patients occurred in the upper anterior sextant (3.4 times more frequent).

SS patients are more prone to experience dental extractions compared to patients without SS. It could be speculated that this is related to a decreased salivary secretion.

To examine the prevalence of immune activation in gastrointestinal (GI) mucosa in children with juvenile idiopathic arthritis (JIA) or connective tissue disease (CTD). We studied 27 children (15 girls, mean age 9.8+/-4.8 years) with JIA/CTD and GI symptoms, including nine with oligoarthritis, nine with polyarthritis, two with systemic arthritis, three with enthesitis-related arthritis, and four with various CTDs. The control group consists of 54 children (31 girls, mean age 11.3+/-6.3 years) with GI symptoms but shown to have no significant GI or rheumatoid disorder. The subjects were examined by gastroduodenoscopy (22 patients, 50 controls) and colonoscopy (23 patients, 16 controls). Intraepithelial CD3+, alpha/beta+, and gamma/delta+ lymphocytes were counted from duodenal and ileal biopsies. Five patients with JIA/CTD (19%) had ulcerative colitis. Lymphoid nodular hyperplasia (LNH) was more common in the patients [74% (20/27)] than in the controls [16% (8/50), p = 0.001], as well in the duodenal bulb [29% (7/24) vs. 10% (5/50)], terminal ileum [74% (14/19) vs. 38% (5/13)], and the colon [50% (11/22) vs. 14% (2/14)]. In the duodenum, CD3, alpha/beta+, and gamma/delta+ lymphocytes counts were higher in JIA/CTD (p<0.05). In the ileum, gamma/delta+ cell numbers had increased in JIA/CTD (p<0.05). Either LNH, increased gamma/delta+ count, or both were more common in JIA/CTD [89% (24/27)] than in the controls [13% (7/54), p<0.0001].

The majority of children suffering from JIA or CTD with GI symptoms show abnormalities consistent with activation of the intestinal immune system. The aetiology of this reaction remains unknown, but similar features are seen in delayed-type food allergy.

To assess rates of early remission and investigate the concordance across different remission definitions, and to identify predictors of early remission in Chinese patients with rheumatoid arthritis (RA). For this study, clinical records were retrospectively reviewed for RA patients at rheumatologic clinic in Peking University First Hospital from 2009 to 2018. Disease activity and remission were determined according to DAS28-ESR, CDAI, SDAI, and Boolean criteria. Early remission was defined as time to remission ≤ 6 months. A secondary definition evaluated early remission as ≤ 3 months. Logistic-regression analyses were performed to identify determinants of early remission. A total of 869 consecutive patients contributing 8640 clinic visits were studied. Early remission rates were respectively 42.0% (DAS28-ESR), 25.0% (CDAI), 29.4% (SDAI), and 26.1% (Boolean). Notably, patients achieving remission within 6 months more frequently attained sustained remission in contrast to those not achieving early remission (68.7-75.1% vs. 31.2-33.1%, p < 0.0001). Further logistic-regression analyses revealed male, early RA, as well as initial hydroxycloroquine treatment were independently associated higher probability of early remission, as demonstrated by nearly all definitions, while a higher baseline disease activity (DAS28-ESR, CDAI, and SDAI) lowered the possibility of early remission in corresponding remission indices. The significant associations of treatment-naïve, serological features with early remission were not confirmed.

Early remission was strongly associated with sustained remission, however. infrequently achievable in real-life practice. Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were stable independent predictors of early remission.Key Points• Early remission was infrequently achievable in real-life practice, especially measured by stringent indices.DAS28-based early remission appears to be the loosest criterion and the remaining three broadly agreed with each other.• Early remission was significantly associated with sustained remission.• Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were positively correlated with early remission.

The Sauvé-Kapandji procedure has become popular for the treatment of disorders of the distal radioulnar joint in patients with rheumatoid arthritis, but this procedure is impossible to perform in patients with poor bone quality in the distal part of the ulna. We have modified the procedure for patients with poor bone quality in the distal part of the ulna. The modified procedure involves resecting the distal part of the ulna, making a drill-hole in the ulnar cortex of the distal part of the radius, rotating the resected portion of the ulna 90 degrees , inserting it into the distal part of the radius, and fixing it at that site with use of an AO cancellous-bone screw. In the present report, we describe the new operative technique and report the results after a minimum duration of follow-up of three years. This operation was performed in fifty-six patients (sixty-six wrists) with rheumatoid arthritis. The mean age at the time of the operation was 59.3 years. The mean duration of follow-up was forty-eight months. Patients were evaluated in terms of wrist pain, grip strength, and range of motion. Radiographic evaluation included calculation of the carpal translation index to assess the extent of ulnar translation of the carpus. Osseous union was achieved in all cases. Wrist pain resolved or decreased in all patients. The mean total range of forearm rotation increased from 144 degrees preoperatively to 167 degrees at the time of the most recent follow-up (p < 0.01). The mean carpal translation index did not change after the operation.

The modified Sauvé-Kapandji procedure results in rigid fixation of the grafted bone. The technique provides sufficient osseous support of the carpus even in patients with rheumatoid arthritis and poor bone quality in the distal part of the ulna.

To analyze if exercise interventions for patients with knee osteoarthritis (OA) following the American College of Sports Medicine (ACSM) definition of muscle strength training differs from other types of exercise, and to analyze associations between changes in muscle strength, pain, and disability. A systematic search in 5 electronic databases was performed to identify randomized controlled trials comparing exercise interventions with no intervention in knee OA, and reporting changes in muscle strength and in pain or disability assessed as standardized mean differences (SMD) with 95% confidence intervals (95% CI). Interventions were categorized as ACSM interventions or not-ACSM interventions and compared using stratified random effects meta-analysis models. Associations between knee extensor strength gain and changes in pain/disability were assessed using meta-regression analyses. The 45 eligible trials with 4699 participants and 56 comparisons (22 ACSM interventions) were included in this analysis. A statistically significant difference favoring the ACSM interventions with respect to knee extensor strength was found [SMD difference: 0.448 (95% CI: 0.091-0.805)]. No differences were observed regarding effects on pain and disability. The meta-regressions indicated that increases in knee extensor strength of 30-40% would be necessary for a likely concomitant beneficial effect on pain and disability, respectively.

Exercise interventions following the ACSM criteria for strength training provide superior outcomes in knee extensor strength but not in pain or disability. An increase of less than 30% in knee extensor strength is not likely to be clinically beneficial in terms of changes in pain and disability (PROSPERO: CRD42014015344).

Thoughtful use of assessment tools to monitor disease requires an understanding of clinimetric properties. These properties are often under-reported and, thus, potentially overlooked in the clinic. This study aimed to determine the minimal detectable change (MDC) and coefficient of variation per cent (CV%) for tools commonly used to assess the symptomatic and functional severity of knee and hip osteoarthritis. We performed a test-retest study on 136 people awaiting knee or hip arthroplasty at one of two hospitals. The MDC95 (the range over which the difference [change] for 95% of patients is expected to lie) and the coefficient of variation per cent (CV%) for the visual analogue scale (VAS) for joint pain, the six-minute walk test (6MWT), the timed up-and-go (TUG) test, the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS) subscales were calculated. Knee cohort (n = 75) - The MDC95 and CV% values were as follows: VAS 2.8 cm, 15%; 6MWT 79 m, 8%; TUG +/-36.7%, 13%; KOOS pain 20.2, 19%; KOOS symptoms 24.1, 22%; KOOS activities of daily living 20.8, 17%; KOOS quality of life 26.6, 44. Hip cohort (n = 61) - The MDC95 and CV% values were as follows: VAS 3.3 cm, 17%; 6MWT 81.5 m, 9%; TUG +/-44.6%, 16%; HOOS pain 21.6, 22%; HOOS symptoms 22.7, 19%; HOOS activities of daily living 17.7, 17%; HOOS quality of life 24.4, 43%.

Distinguishing real change from error is difficult in people with severe osteoarthritis. The 6MWT demonstrates the smallest measurement error amongst a range of tools commonly used to assess disease severity, thus, has the capacity to detect the smallest real change above measurement error in everyday clinical practice.

Previous studies have demonstrated that the lower renal excretion of urates in patients with hyperuricaemia is inversely related to plasma very low-density lipoprotein (VLDL) levels, and the different genotypes of the apolipoprotein E gene are related to the plasma levels of lipids. The aim of this study was to determine the prevalence of apolipoprotein E in hyperuricaemic patients and to investigate whether the renal excretion of urates is conditioned by the apoliprotein E genotype. The plasma levels of lipoproteins, cholesterol, triglycerides and uric acid, and the renal excretion of uric acid were studied in 68 patients with gout and in another control group of 50 healthy subjects. Both groups were genotyped for apolipoprotein E by means of an amplification technique and inverse hybridization. The prevalence of the E2 allele was greater in the patients than in the control group. The levels of cholesterol, triglycerides and uric acid were greater in the patients, whereas the levels of high-density lipoprotein were lower. The patients with the E2 allele had higher levels of triglycerides in VLDL and intermediate-density lipoproteins and a lower renal excretion of urates.

These results show that the reduced renal excretion of uric acid in patients with gout is mediated by high levels of VLDL and by the high prevalence of the E2 allele of apolipoprotein E.

To determine the impact that upper respiratory tract infections have on patients' physical, social, and emotional functioning, we measured the health-related quality of life (HRQL) of adults with upper respiratory tract infections. Acute care clinic from November 2001 to February 2002. Prospectively administered survey. To measure HRQL, we used the Acute Form of the Short Form-36, version 2 (SF-36). For all 8 SF-36 subscales, we used norm-based scoring, in which the general U.S. population has a mean of 50. Adults who had symptoms for fewer than 30 days completed the SF-36; and were diagnosed with nonspecific upper respiratory infection, viral syndrome, otitis media, sinusitis, nonstreptococcal pharyngitis, streptococcal pharyngitis, or acute bronchitis. The sample of 318 patients was 63% female, 81% white, and had a mean age of 35 years. The primary diagnoses were nonspecific upper respiratory infection (42%), acute bronchitis (16%), sinusitis (12%), viral syndrome (9%), nonstreptococcal pharyngitis (8%), otitis media (7%), and streptococcal pharyngitis (6%). Patients had a mean general health subscale score of 50.9, which is not significantly different from the mean population value of 50 (P =.09). However, there were significant decrements in the remaining 7 subscales of the SF-36: physical functioning (45.5), role-physical (38.5), bodily pain (42.6), vitality (40.8), social functioning (37.8), role-emotional (46.8), and mental health (46.8; P <.0001 for all 7 subscales compared with normative values). Results were similar for the subset of patients with no comorbid illnesses (P <.001 for the same 7 subscales) and patients diagnosed with nonspecific upper respiratory infection (P <.001 for the same 7 subscales). These decrements were similar in magnitude, but somewhat different in subscale pattern, to those of adults with chronic lung disease, osteoarthritis, and depression.

Physicians should remember that adults who seek care for upper respiratory tract infections have measurable, significant decrements in HRQL. For researchers, HRQL is an attractive, potential measure of outcome in future trials of established and novel therapies for upper respiratory tract infections.

To investigate moderators and biomechanical mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis (OA). Exploratory analysis from 164 participants in a clinical trial comparing unloading (ASICS GEL-Melbourne OA) to conventional walking shoes. The primary outcome was 6-month change in knee pain (11-point numerical rating scale (NRS)). Moderators included baseline peak knee adduction moment (KAM), radiographic severity (Kellgren & Lawrence (KL) scale), body mass, foot posture, neuropathic pain and diffuse knee pain. Mediators included change in peak KAM and KAM impulse. Radiographic severity was the only moderator to interact with footwear group (P = 0.02). Participants with KL = 2 experienced greater pain reductions with conventional compared to unloading shoes (mean difference in change in pain -1.64 units, 95% CI -3.07, -0.21), while unloading shoes tended to result in greater pain reductions than conventional shoes in KL = 3 (0.98, 95% CI -0.44, 2.39) and KL = 4 (0.64, 95% CI -0.64, 1.93). No variable showed any significant mediating effect in the entire cohort. However, there was some evidence that unloading shoes may reduce pain through reductions in peak KAM (indirect effect -0.31, 95% CIs -0.65, 0.03; P = 0.07) in people with KL ≥ 3, compared to conventional shoes.

Unloading shoes conferred additional symptomatic benefits over conventional shoes in people with moderate to severe knee OA. There was some evidence effects may be mediated by a reduction in peak KAM. However, we were underpowered for subgroup analyses. These patients may represent a subgroup to which biomechanical interventions designed to reduce the KAM may be more effectively targeted.

To review the fundamental concepts of pharmacogenetics and analyse how the broad principles of this rapidly emerging field may influence the treatment of rheumatic disease in future. The names of common rheumatic drugs and the terms 'pharmacogenetics', 'pharmacogenomics' and 'genetic polymorphism' were used as keywords to search the Medline and Current Contents databases. General review articles on pharmacogenetics were also examined. Pharmacogenetics is the study of how genetic differences influence the variability in drug toxicity and efficacy. Although the principles of pharmacogenetics have been known for several decades, recent technological advances have hastened the possibility of direct clinical applications. Most studies so far have been phenotypic analyses, but genotyping is now readily available for many polymorphisms. There are several examples pertinent to rheumatology that illustrate the important principles and foretell the usefulness of pharmacogenetics in individualizing therapy. However, further studies are needed.

Because traditional pharmacotherapy in rheumatology has been empirical and because of the slow acting nature of many anti-rheumatic medications, the risk of significant side-effects and the increasing armamentarium of drugs available, pharmacogenetics is particularly relevant to rheumatology. There are many scientific and non-scientific concerns that should be addressed in future studies.

To explore the main barriers to and facilitators of physical activity in young adults with childhood-onset physical disabilities. Qualitative study using focus groups. Sixteen persons (12 men and 4 women) aged 22.4 (standard deviation 3.4) years, of whom 50% were wheelchair-dependent, participated in the study. Eight were diagnosed with myelomeningocele, 4 with cerebral palsy, 2 with acquired brain injury and 2 with rheumatoid arthritis. Three focus group sessions of 1.5 h were conducted using a semi-structured question route to assess perceived barriers to and facilitators of physical activity. Tape recordings were transcribed verbatim and content analysed. According to the Physical Activity for People with a Physical Disability model, barriers and facilitators were subdivided into personal factors and environmental factors. Participants reported several barriers related to attitude and motivation. In addition, lack of energy, existing injury or fear of developing injuries or complications, limited physical activity facilities, and lack of information and knowledge, appeared to be barriers to physical activity. Fun and social contacts were mentioned as facilitators of engaging in physical activity, as well as improved health and fitness.

Young adults with childhood-onset physical disabilities perceived various personal and environmental factors as barriers to or facilitators of physical activity. These should be taken into account when developing interventions to promote physical activity in this population.

Systemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype. A high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined. Using this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon.

These data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and transcriptomic analysis.

To conduct a systematic review to assess the effectiveness of patient education interventions delivered or directed by health professionals for people with musculoskeletal conditions who also have lower levels of literacy. Electronic databases were searched from 1946 to May 2012. Randomized controlled trials with primary interventions designed specifically for individuals with musculoskeletal conditions and lower levels of literacy were eligible for inclusion. The quality of the study was determined by assessing method of randomization, allocation concealment, creation and maintenance of comparable groups, blinding of patients and providers, control of confounding, and the validity and reliability of outcome measures. Of the 2,440 studies located using the search strategy, 6 studies met the inclusion criteria. Three public health community studies and 3 rheumatology clinic-based studies delivered educational programs to people with musculoskeletal conditions who also had lower levels of literacy. Three moderate quality studies suggest that musculoskeletal educational interventions had a small short-term effect on knowledge and 2 moderate quality studies suggest musculoskeletal interventions had a small effect on self-efficacy (although results on self-efficacy were conflicting in 1 of these studies). Only 1 moderate quality study showed a small effect on anxiety and 1 on self-perceived health and well-being in people with lower literacy.

High quality evidence is lacking on the effectiveness of musculoskeletal education interventions for people with lower literacy levels. Research programs that test the effectiveness of patient education interventions for arthritis must recruit and engage people with lower levels of literacy.

The aim of our study was to conduct a systematic review with meta-analysis of the current case-control studies about the valvular and pericardial involvement in patients with Rheumatoid Arthritis (RA), asymptomatic for cardiovascular diseases. Case-control studies were identified by searching PubMed (1975-2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (1975-2010). Participants were adult patients with RA asymptomatic for cardiovascular diseases, and the outcome measure was the presence of cardiac involvement. Quantitative synthesis included 10 relevant studies out of 2326 bibliographic citations that had been found. RA resulted significantly associated to pericardial effusion (OR 10.7; 95% CI 5.0-23.0), valvular nodules (OR 12.5; 95% CI 2.8-55.4), tricuspidal valve insufficiency (OR 5.3; 95% CI 2.4-11.6), aortic valve stenosis (OR 5.2; 95% CI 1.1-24.1), mitral valve insufficiency (OR 3.4; 95% CI 1.7-6.7), aortic valve insufficiency (OR 1.7; 95% CI 1.0-2.7), combined valvular alterations (OR 4.3; 95% CI 2.3-8.0), mitral valve thickening and/or calcification (OR 5.0; 95% CI 2.0-12.7), aortic valve thickening and/or calcification (OR 4.4; 95% CI 1.1-17.4), valvular thickening and/or calcification (OR 4.8; 95% CI 2.2-10.5), and mitral valve prolapse (OR 2.2; 95% CI 1.2-4.0).

Our systematic review pointed out the strength and the grade of both pericardial and cardiac valvular involvement in RA patients. Our findings underscore the importance of an echocardiographic assessment at least in clinical research when RA patients are involved. Moreover, further research is needed to understand the possible relationship of our findings and the increased cardiovascular mortality.

Evaluate relationships between MRI and clinical/laboratory/radiographic findings in rheumatoid arthritis (RA). 637 methotrexate-naive patients (GO-BEFORE) and 444 patients with active RA despite methotrexate (GO-FORWARD) were randomly assigned to subcutaneous placebo + methotrexate, golimumab 100mg + placebo, golimumab 50mg + methotrexate, or golimumab 100mg + methotrexate every-4-weeks. In GO-BEFORE(n=318) and GO-FORWARD(n=240) substudies, MRI of dominant wrist/metacarpophalangeal joints were scored for synovitis, bone oedema and bone erosion (RA MRI scoring (RAMRIS) system). Relationships between RAMRIS scores and serum C-reactive protein (CRP), 28-joint count disease activity score (DAS28-CRP) and van der Heijde modified Sharp (vdH-S) scores were assessed. Baseline and weeks 24/28 DAS28-CRP, CRP, and vdH-S generally correlated well with baseline and week 24 RAMRIS synovitis, oedema and erosion scores. Early (week 4) CRP changes correlated with later (week 12) RAMRIS synovitis/oedema change scores; earlier (week 12) changes in some RAMRIS scores correlated with later (weeks 24/28) changes in vdH-S. Significant correlations between RAMRIS change scores and clinical/radiographic change scores were weak.

MRI and clinical/laboratory/radiographic measures generally correlated well. Associations between earlier changes in CRP and later changes in RAMRIS synovitis/osteitis were observed. Changes in MRI and clinical/radiographic measures did not correlate well, probably because MRI is more sensitive than radiographs and more objective than DAS28-CRP.

The aim of the study was to analyze the results of the hip joint torques within the patients with osteoarthritis (OA). A total of 119 women were divided into 3 groups performing 3 dimensional strength tests. For the measurements a new apparatus was invented and used. Specially designed position was safety and comfortable during testing OA and elderly women. Significant differences (p≤0.05) in strength tests were found both between body side and muscle groups in most of the performed tests. The biggest unilateral deficit in OA group was found in muscles most important for gait and weight bearing − 0.55 for both flexors and extensors. Surprisingly no lateral difference was found for the hip joint adductors. Analysis of the correlation coefficient between the hip joint muscles proved that complex movements needed well-developed coordination between the muscle groups. The most important agonist muscle coordination occurs between hip extensors and abductors − 0.68 to 0.80.

Unilateral hip OA affecting older women is directly responsible for significantly lower muscle strength when compared with both control groups. Lost of balance and coordination needed for dynamic actions like gait is caused by strength asymmetry of crucial hip muscles as well as near zero correlation between important agonist muscles.

This study investigated preoperative interventions and their costs in the 2-year period before a patient undergoing a unicompartmental knee arthroplasty (UKA). A retrospective cohort analysis of patients undergoing UKA between 2009 and 2011 was conducted using the PearlDiver Patient Record Database to track inpatient and outpatient billing records. One thousand eight hundred forty-one patients from Medicare and 4704 patients from United Healthcare underwent UKA between 2009 and 2011. In the 2 years before UKA, the per patient average charge was $3919.96 for Medicare patients and $5219.14 for United Healthcare patients, with 21.7% of Medicare-associated charges and 28.2% of United Healthcare-associated charges occurring within 3 months of surgery. In the 2-year period before surgery, 65.5% of Medicare patients and 53.6% of United Healthcare patients received an intra-articular injection, with 29.1% (Medicare) and 46.0% (United Healthcare) of these injections occurring within 3 months of surgery. In addition, 15.1% of Medicare patients and 20.7% of United Healthcare patients underwent an arthroscopy, with between 32.4% and 43.8% of these occurring in the final 6 months before UKA.

Preoperative interventions (ie, imaging, procedures, physical therapy, and injections) occur at a high frequency in close proximity to UKA resulting in substantial costs. The development of algorithms to guide management of these patients is critical in reducing costs before UKA.

To compare concentrations of joint biomarkers in synovial fluid (SF) between idiopathic osteonecrosis of the femoral head (ION) and osteoarthritis (OA) of the hip joint. Levels of the joint biomarkers cartilage oligomeric matrix protein (COMP), antigenic keratan sulfate (AgKS), and hyaluronan (HA) in SF samples from 21 cases of ION and their relationship to disease stage and history of steroid use were assessed and compared to the result of 29 cases of hip OA. In both the ION and hip OA groups, levels of COMP and AgKS in SF showed a significant positive correlation. The ION group had significantly higher levels of AgKS in SF than the hip OA group. In the ION group, stage II patients had significantly higher SF levels of both COMP and AgKS than those in stage III patients. No difference in level of HA in hip joint SF was found between steroid and non-steroid treated ION patients or between the stage II and III subgroups.

SF levels of COMP and AgKS may serve as useful joint biomarkers that reflect cartilage metabolism not only in hip OA but also in ION.

Although once thought to be a benign condition, retinal vascular occlusive disease and proliferative retinopathy can occur with sickle cell trait (hemoglobin AS) when additional systemic diseases or trauma are present. The authors discuss the ophthalmologic evaluation and clinical course of a 49-year-old woman with sickle cell trait and rheumatoid arthritis who presented with a cilioretinal artery occlusion. The patient's laboratory evaluation showed both a high rheumatoid factor titer and a mild hypergammaglobulinemia, causing increased serum viscosity. The high level of sickle hemoglobin-42.3% (range in trait, 22%-46%)-increased serum viscosity, and lower cilioretinal artery perfusion pressure relative to the central retinal artery resulted in cilioretinal artery occlusion.

Isolated cilioretinal artery occlusions carry a good prognosis, and this patient recovered 20/20 visual acuity in the affected eye. The association between sickle cell trait and rheumatoid arthritis resulting in retinal vascular occlusive disease has not been reported previously. The presence of retinal vascular occlusion in sickle cell trait necessitates a medical evaluation for additional systemic diseases.

Horizontal, degenerative tears of the medial meniscus and subsequent meniscectomy can compromise the biomechanical function of the meniscus in load transmission and weightbearing, leading to the development of radiographic and symptomatic tibiofemoral arthritis. Resection of both leaflets of a horizontal medial meniscal tear will increase peak contact pressures and decrease contact areas in comparison with resection of only the inferior leaflet. Controlled laboratory study. Twelve fresh-frozen human cadaveric knees had tibiofemoral peak contact pressures and contact areas under an 1800-N axial load measured by Tekscan in the control state. A horizontal tear was created in the posterior horn of the medial meniscus, and the knees were retested. The knees were tested a third time after resection of the inferior leaflet (single leaflet) and a final time after resection of the superior leaflet (both leaflets). The Friedman test was used to test for group differences in peak pressure (psi) and contact area (mm(2)) between test conditions (native, tear, inferior leaflet resection, and resection of both leaflets). For the medial compartment, there was a statistically significant difference in peak pressure (P = .03) but not in contact area (P = .70) between testing conditions. Median peak pressure in the medial compartment was significantly greater for resection of both leaflets compared with the tear (406.5 vs 294.7 psi, respectively; P = .002). Median contact area in the medial compartment was greatest for resection of both leaflets (602.7 mm(2)), but there were no statistically significant differences between test conditions (P = .70). For the lateral compartment, there were no statistically significant differences in peak pressure (P = .99) or contact area (P = .77) between test conditions. Arthroscopic inferior leaflet resection is a viable option for providing symptomatic relief of horizontal medial meniscal tears and preserves the ability of the meniscus to absorb axial loading on the knee joint, theoretically decreasing the risk of subsequent osteoarthritis.

Resection of a single inferior leaflet after a horizontal medial meniscal tear preserves much of the original biomechanical function of the meniscus. Resection of both leaflets leads to a significant increase in contact pressure dispersed over the same contact area, which results in an undesirable biomechanical environment.

In the synovial membrane of patients with rheumatoid arthritis (RA), a strong expression of laminins and matrix degrading proteases was reported. To investigate the regulation of matrix metalloproteinases (MMPs) in synovial fibroblasts (SFs) of patients with osteoarthritis (OA) and RA by attachment to laminin-1 (LM-111) and in the presence or absence of costimulatory signals provided by transforming growth factor beta (TGFbeta). SFs were seeded in laminin-coated flasks and activated by addition of TGFbeta. The expression of genes was investigated by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunocytochemistry and ELISA, and intracellular signalling pathways by immunoblotting, and by poisoning p38MAPK by SB203580, MEK-ERK by PD98059 and SMAD2 by A-83-01. Attachment of SF to LM-111 did not activate the expression of MMPs, but addition of TGFbeta induced a fivefold higher expression of MMP-3. Incubation of SF on LM-111 in the presence of TGFbeta induced a significant 12-fold higher expression of MMP-3 mRNA, and secretion of MMP-3 was elevated 20-fold above controls. Functional blocking of LM-111-integrin interaction reduced the laminin-activated MMP-3 expression significantly. Stimulation of SF by LM-111 and TGFbeta activated the p38MAPK, ERK and SMAD2 pathways, and inhibition of these pathways by using SB203580, PD98059 or A-83-01 confirmed the involvement of these pathways in the regulation of MMP-3.

Attachment of SF to LM-111 by itself has only minor effects on the expression of MMP-1 or MMP-3, but it facilitates the TGFbeta-induced expression of MMP-3 significantly. This mode of MMP-3 induction may therefore contribute to inflammatory joint destruction in RA independent of the proinflammatory cytokines interleukin (IL)1beta or tumour necrosis factor (TNF)alpha.

Osteoarthritis (OA) is a disease with a significant inflammatory component. The aim of this analysis was to determine the relationship between synovial fluid (SF) white blood cell (WBC) count and 2 parameters: disease severity and the reduction in knee pain after intraarticular (IA) steroid injection. Subjects with painful knee OA were recruited for participation in an open-label study of IA steroid therapy. Information was obtained about knee pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, and a proportion of subjects underwent magnetic resonance imaging (MRI). Prior to injection with 80 mg methylprednisolone acetate, the index knee joint was aspirated and the fluid obtained was forwarded for assessment of SF WBC count. Information on SF WBC count was available for 55 subjects. An increase in WBC count category (≤100, 101-250, and 251-1,000 cells/mm

Although all participants in the analysis had SF WBC counts within the "normal" range, total SF WBC count appears to be a biomarker for synovitis on MRI and may also predict response to antiinflammatory treatment.

To investigate the treatment practice in myofascial pain syndrome among physical therapists in an urban setting. The cross-sectional study was conducted from June to December, 2016, at the Institute of Physical Medicine and Rehabilitation, Dow University of Health Science, Karachi Pakistan, and comprised qualified physical therapists of either gender working at various health centres in the city. Data was collected using a self-administered questionnaire, and was analysed using SPSS 16. Of the 93 respondents, 37(39.8%) were males and 56(60.2%) were females; 39(41.9%) had Masters level professional education; and 29(31.2%) had 5-8 years of experience. Myofascial Pain Syndrome was diagnosed through physical examination by 78(83.9%) subjects, on the basis of history by 70(75.3%) and palpable band by 75(80%). Preferred treatment strategy was ischaemic compression for 63(67.7%) and postural re-education for 64(68.8%), while dry needling was used by 29(31.2%) subjects. Also, 75(80%) therapists preferred manual therapy superior combined with other treatments.

Physical examination was found to be the most common diagnostic method used for myofascial pain syndrome by the therapists.

To test the hypothesis that an association exists between the characteristics of the knee adduction moment and foot progression angle (FPA) in asymptomatic individuals and those with mild to moderate and severe knee osteoarthritis (OA). Fifty asymptomatic individuals, 46 patients with mild to moderate and 44 patients with severe knee OA were recruited. Maximum knee adduction moment during late stance and principal component analysis (PCA) were used to describe the knee adduction moment captured during gait. Multiple regression models were used for each of the three group assignments to analyze the association between the independent variables and the knee adduction moment. FPA explained a significant amount of the variability associated with the shape of the knee adduction moment waveform for the asymptomatic and mild to moderate groups (P<0.05), but not for the severe group (P>0.05). Walking velocity alone explained significant variance associated with the shape of the knee adduction moment in the severe OA group (P<0.05).

A toe out FPA was associated with altered knee adduction moment waveform characteristics, extracted using PCA, in asymptomatic individuals and those with mild to moderate knee OA only. These findings are directly implicated in medial knee compartment loading. This relationship was not evident in those with severe knee OA.

Gnaphalium affine D. Don is a folk medicine of China believed to be efficacious in the treatment of many ailments, including hyperuricemia and gout. Based on a previous study, we isolated two flavones, luteolin and luteolin-4'-O-glucoside, from G. affine. Our aim was to assess the potential beneficial effects of treatment and mechanisms of these two flavones on hyperuricemia and acute gouty arthritis. The model of potassium oxonate (PO)-induced hyperuricemia and monosodium urate (MSU) crystal-induced inflammation in mice has been established. We evaluated serum uric acid (Sur), xanthine oxidase (XO) activity, protein expression of urate transporter 1 (mURAT1) and glucose transporter 9 (mGLUT9) in renal and kidney protection in a hyperuricemia model. In addition, paw swelling and levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum were assessed in MSU crystal-induced mice. Luteolin and luteolin-4'-O-glucoside showed a potent clinical effect in treating hyperuricemia and gout. We observed that the two flavones possess potent effect in hyperuricemia mice by decreasing the level of mURAT1 and inhibiting XO activity, which contribute to enhancing uric acid (UA) excretion and improving hyperuricemia-induced renal dysfunction. In addition, luteolin and luteolin-4'-O-glucoside also alleviated paw swelling and inflammation induced by MSU crystals. Further investigation implied that luteolin and luteolin-4'-O-glucoside improved the symptoms of inflammation by decreasing the levels of IL-1β and TNF-α.

The present study suggests that luteolin and luteolin-4'-O-glucoside could be developed as therapeutics for treating hyperuricemia and gouty arthritis.

To develop recommendations, based on best evidence and experience, on pain management in patients undertaking total knee or hip replacement. Nominal group methodology was followed. A group of experts was selected (5 orthopedics, 1 anesthesiologist), who defined the scope, users, topics, preliminary recommendations, and 3 systematic reviews: efficacy and safety of pre-surgical analgesia regarding to post-surgical pain, efficacy and safety of pre-emptive analgesia and pre-operative factors of post-operative pain. The level of evidence and grade of recommendation was established using the Oxford Centre for Evidence Based Medicine, and the level of agreement with the Delphi technique (2 rounds). The Delphi was extended to 39 orthopedics and anesthesiologists. The whole document was reviewed by all the experts. A total of 21 recommendations were produced. They include specific pharmacological treatment, as well as the evaluation and monitoring of patients on this treatment, and post-operative pre-emptive treatment. Agreement above 70% was reached in 19 recommendations.

In patients undergoing total knee or hip replacement, a proper evaluation, follow-up, pharmacological and non-pharmacological treatment of predictors of poor surgical outcomes should be performed, especially those related to pre-operative pain. This can improve post-operative pain and surgery outcomes.

To investigate the pharmacokinetics (PK) and dynamics of tocilizumab (TCZ) in daily practice. An observational study of 66 consecutive RA patients treated with TCZ 8 mg/kg once every 4 weeks intravenously, monitored for 24 weeks. Spearman's rank test was used to investigate the correlation between TCZ concentration and C-reactive protein (CRP). Clinical improvement was assessed at week 24 using the Disease Activity Score in 28 joints (DAS28) compared to baseline, and its relationship with TCZ concentration was investigated using linear regression analyses. TCZ trough concentrations and anti-drug antibodies were measured using an enzyme-linked immunosorbent assay (ELISA) and antigen binding test, respectively. At baseline, 26 patients (39.4%) had a CRP level above 10 mg/L with a median (interquartile range, IQR) of 37.7 (21.9-49.7) mg/L. A TCZ concentration above 1 mg/L was sufficient to normalize CRP levels. Spearman's rank test showed a correlation coefficient of -0.460 (p < 0.0001). The TCZ concentration varied widely, with concentrations < 1 mg/L in 17-31% of patients, depending on the time point of measurement. Anti-TCZ antibodies were detected in one sample. Linear regression analyses showed a coefficient of 0.080 with a 95% confidence interval (CI) of 0.039-0.113 (p < 0.001) for the association between TCZ concentration and ΔDAS28. No confounders were identified.

The TCZ standard regimen results in a wide variety of serum TCZ trough concentrations; this is mostly due to target binding and to a lesser extent to immunogenicity. The majority of patients obtained TCZ concentrations > 1 mg/L, which is sufficient for CRP normalization. Therefore, dose taper strategies might be possible in a substantial proportion of patients.

A nonapoptotic role of Fas signaling has been implicated in the regulation of inflammation and innate immunity. This study was undertaken to elucidate the contribution of Fas signaling in macrophages to the development of arthritis. K/BxN serum-transfer arthritis was induced in a mouse line in which Fas was conditionally deleted in the myeloid lineage (Cre(LysM) Fas(flox/flox) mice). The arthritis was assessed clinically and histologically. Expression of interleukin-1β (IL-1β), CXCL5, IL-10, IL-6, and gp96 was determined by enzyme-linked immunosorbent assay. Bone marrow-derived macrophages were activated with IL-1β and gp96. Cell phenotype and apoptosis were analyzed by flow cytometry. Arthritis onset in Cre(LysM) Fas(flox/flox) mice was comparable with that observed in control mice; however, resolution was accelerated during the chronic phase. The attenuated arthritis was associated with reduced articular expression of the endogenous Toll-like receptor 2 (TLR-2) ligand gp96 and the neutrophil chemotactic chemokine CXCL5, and enhanced expression of IL-10. Activation with IL-1β or gp96 induced increased IL-10 expression in Fas-deficient murine macrophages compared with control macrophages. IL-10 suppressed IL-6 and CXCL5 expression induced by IL-1β plus gp96. IL-1β-mediated activation of ERK, which regulates IL-10 expression, was increased in Fas-deficient mouse macrophages.

Taken together, our findings indicate that impaired Fas signaling results in enhanced expression of antiinflammatory IL-10 and reduced expression of gp96, and these effects are associated with accelerated resolution of inflammation during the chronic phase of arthritis. These observations suggest that strategies to reduce endogenous TLR ligands and increase IL-10 may be beneficial in the treatment of rheumatoid arthritis.

The treatment of periprosthetic shoulder infections and proximal humerus osteomyelitis is challenging. The outcomes of antibiotic cement spacer retention are poorly defined in the literature. The purpose of this study was to review long-term functional and patient-reported outcomes data of patients with retained antibiotic cement spacers. We predict reasonable functional outcomes and minimal pain. We identified 22 patients of the senior author who have been treated with definitive antibiotic spacer placement. All patients were originally offered a 2-stage revision and declined. Twelve patients had a minimum follow-up of 2 years and were included in our cohort. Mean age was 70.7 (range 59-81), 8/12 patients were female, and the average body mass index was 27.8 (range = 17-45). Functional outcome assessments included the Standardized Shoulder Assessment Form, the Quick Disabilities of the Arm, Shoulder, and Hand Score (QuickDASH), and visual analog scale (VAS) along with clinical range of motion examination. The patients were followed up for a mean of 5.6 years. Eight patients had spacer placement for chronic shoulder arthroplasty infections, whereas 4 patients had spacer placement for chronic osteomyelitis of the proximal humerus. No patients were currently being treated with suppressive antibiotics. One patient had negative cultures at the time of antibiotic spacer placement. The most common organisms were Cutibacterium acnes (6), Staphylococcus epidermidis (6), and methicillin-resistant Staphylococcus aureus (4), with 4 patients growing more than 1 species. The average ASES score was 54 (range = 27-73), QuickDASH was 45 (range = 14-89), and VAS score 2.8 (range = 0-8). Average active range of motion was 68° of forward elevation and 35° of external rotation.

Retention of antibiotic cement spacer is a viable option in the treatment algorithm for chronic shoulder infections. Long-term antibiotic cement spacer may be considered for those patients who are unwilling or unable to undergo a 2-stage revision. Patients can expect a reasonable amount of function and little to no pain with an antibiotic cement spacer.

Observational studies examining the association between oral health and juvenile idiopathic arthritis (JIA) among children and adolescents have reported inconsistent findings. The aims of this systematic review and meta-analysis were to ascertain a potential difference in oral health and oral health-related quality of life (OHRQoL) among children and adolescents with JIA and healthy peers, and to assess the association of prevalence of oral diseases/conditions, temporomandibular disorders (TMD), including temporomandibular joint (TMJ) diseases, in relation to activity and severity of JIA. Medline Ovid, Embase, CINAHL, SweMed+ and Cochrane Library were searched up to 25 November 2018. All articles published in English, German and Scandinavian languages focusing on children and adolescents with JIA and without JIA in relation to oral health measures, were considered. Two authors independently evaluated observational studies for inclusion. The study quality was assessed using modified Newcastle Ottawa Scale. Meta-analysis was performed for studies focusing on dental caries as an outcome. Nineteen articles met the inclusion criteria, covering a range of oral diseases/conditions and OHRQoL. Eighteen studies had cross-sectional design. No mean difference of dmft/DMFT indices (decayed/missed/filled teeth) was observed between the JIA - and healthy group. None of the oral health measures including dental erosive wear, enamel defects, dental maturation and OHRQoL, indicated better oral health among children and adolescents with JIA compared to healthy group. However, periodontal conditions and TMD were more predominant among children and adolescents with JIA compared to healthy peers.

Based on the cross-sectional studies, periodontal diseases and TMD were found to be more frequent in children and adolescents with JIA compared to healthy peers. Furthermore, more high-quality studies with large sample size are needed before we infer any concrete conclusion regarding the association between the prevalence of oral and TMJ diseases or oral conditions in relation to activity and severity of JIA.

Bone marrow lesions (BML) are associated with painful and progressive osteoarthritis (OA). Quantitative MRI has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium enhanced MRI of cartilage (dGEMRIC) relaxation values (T Study participants (n=128) were recruited from a cross-sectional population-based study of people aged 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of one hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T 32 of the 128 participants (25%) had at least one BML. Subjects with at least one BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T

Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.

To investigate various manifestations and treatment of subclinical Sjögren's syndrome (SS). A long term clinical, laboratory and sialographic observations were performed in 24 patients with subclinical SS. Injectin of thymosin intramusularly was used to treat the patients and clinical effect of this treatment was evaluated. All of 24 cases had experienced recurrent parotid swellings (RPS) for 2-17 years (mean 7 years) before dry mouth and dry eyes occurred and all of them were misdiagnosed as chronic suppurative parotitis or sialadenitis. Follow-up showed that all of these patients developed SS. Vasculitis was found in 8 cases, purpura in 2 cases. The vascular involvement was relatively common in subclinical SS. Main sialographic findings was sialectasis of terminal ducts with irregular dilation of main duct. Frequency of RPS was markedly decreased in the patients treated with thymosin.

The proposal of subclinical SS has theoretical value for understanding the entity and reclassification of chronic suppurative parotitis, and has guide value for diagnosis and treatment of SS in the early stage. Injection of thymosin is considered an effective therapy to reduce RPS in subclinical SS.

Chromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA). Plasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1-76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling. Levels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension.

The plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available.

Recurrent episodes of acute rheumatic fever may contribute to the development or worsening of rheumatic heart disease. Secondary penicillin prophylaxis (SPP) has been found to significantly reduce the incidence of rheumatic heart disease. This study sought to evaluate adherence to oral and intramuscular SPP in pediatric patients with rheumatic fever using real-world data spanning 10 years. The study population included patients <18 years old insured by a 2.1-million-member health maintenance organization in Israel who were diagnosed with acute rheumatic fever between 1/1996 and 5/2015 and had purchased at least one monthly dose of oral or intramuscular penicillin by prescription. The mean proportion of days covered by SPP was calculated. The endpoint of the retrospective follow-up for therapy discontinuation was leaving the health maintenance organization, death, age 18 years, or end of follow-up. The cohort included 842 children: 734 treated with oral penicillin and 108 with intramuscular penicillin. The respective mean (SD) ages of the two groups at diagnosis were 8.6 (3.7) years and 10.9 (3.2) years, and the median (interquartile range) proportions of days covered by SPP were 8% (2%-33%) and 10% (3%-28%). Overall, the number of days covered decreased exponentially from 103 days in the first year of therapy to 20 days in the tenth year of follow-up.

Adherence to SPP for rheumatic fever is poor. This renders this mode of long term prophylaxis futile. Although the IM route has been previously shown to be more effective, the oral route was more extensively used.

To evaluate the contribution of assessing forefoot joints to the measurement range and measurement precision of joint counts in early rheumatoid arthritis (RA) using item response theory. Baseline measures of tender and swollen joint counts were analyzed in 459 early RA patients from the Dutch Rheumatoid Arthritis Monitoring remission induction cohort. The contribution of forefoot joints was studied by evaluating their effect on the measurement range and measurement precision of measures based on 28-joint counts. In addition, the alignment between the patient and joint distributions was investigated to determine whether the forefoot joints were informative for measuring joint tenderness or swelling of an early RA patient. In total, 233 patients (50.76%) experienced tenderness and 200 patients (43.57%) experienced swelling in ≥1 forefoot joint. Forefoot joints were more informative for measuring joint tenderness than joint swelling, but did not significantly improve the measurement range and measurement precision of the 28-joint counts. Furthermore, including forefoot joints did not remove the existing discrepancy between the joint and patient distributions in both joint counts.

Forefoot joints were frequently affected on an individual level, but did not significantly improve the measurement range or precision of 28-joint counts in patients with early RA. From a measurement perspective, reduced joint counts are appropriate for use on a population level. The contribution of assessing forefoot joints on an individual level requires further investigation. Additionally, the results should be cross-validated in patients with longer disease durations to determine whether the pattern of joint involvement is similar in later stages of RA.

To demonstrate that a fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg has comparable efficacy to celecoxib for knee osteoarthritis. Two randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III studies (PN400-307 and PN400-309) enrolled patients aged ≥50 years with symptomatic knee osteoarthritis. Following an osteoarthritis flare, patients received naproxen/esomeprazole magnesium twice daily, celecoxib 200 mg once daily, or placebo for 12 weeks. NCT00664560 and NCT00665431. Three co-primary efficacy endpoints were mean change from baseline to week 12 in Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain and function subscales, and Patient Global Assessment of osteoarthritis using a visual analog scale (PGA-VAS). In Study 307, 619 patients were randomized and 614 treated. In Study 309, 615 patients were randomized and 610 treated. Both naproxen/esomeprazole magnesium and celecoxib were associated with improvements (least squares mean change from baseline to week 12) in WOMAC pain (Study 307: -42.0 and -41.8, respectively; Study 309: -44.2 and -42.9, respectively), WOMAC function (Study 307: -36.4 and -36.3, respectively; Study 309: -38.9 and -36.8, respectively), and PGA-VAS (Study 307: 21.2 and 21.6, respectively; Study 309: 29.0 and 25.6, respectively). A prespecified non-inferiority margin of 10 mm between naproxen/esomeprazole magnesium and celecoxib was satisfied for each co-primary endpoint at week 12 in both studies. Significant improvements were observed with naproxen/esomeprazole magnesium versus placebo in both studies (p < 0.05). Celecoxib was significantly different from placebo in Study 307 (p < 0.05); however, the improvements were not significant in Study 309. Acetaminophen use and patient expectation of receiving active treatment (80% probability) may have contributed to a high placebo response observed.

Naproxen/esomeprazole magnesium has comparable efficacy to celecoxib for the management of pain associated with osteoarthritis of the knee over 12 weeks.

To assess medical students' clinical competence in addressing musculoskeletal problems. Nineteen junior medical students completed 2 standardized patient-based tests structured to capture their clinical decisions from undiagnosed chief complaint to management. No student approached the highest possible score on either test, and the students as a group received less than half the possible points on 5 important aspects of diagnostic reasoning.

Standardized patient-based tests can be structured to provide enlightening information about medical students' clinical competence with regard to musculoskeletal problems.

While few studies with various types of outcomes and methodology have investigated the seasonality of gout, no internet data has been used in any study. This novel methodology may complement and extend the previous traditional data sources and has increasingly been used in investigating the seasonality of health conditions. Therefore, the objective of this study was to utilize the Google Trends data to test whether there is a seasonal variation in the internet searches for gout on a population basis. In this observational ecological study, the Google Trends was searched for the [gout] within the USA, the UK, Canada, Ireland, Australia, and New Zealand from January 01, 2004, to December 31, 2017, utilizing the "health" category. The cosinor analyses revealed a statistically significant seasonal variation in relative search volume of the [gout] in the USA, the UK (p < 0.001), Canada (p < 0.001), Ireland (p < 0.001), Australia (p < 0.001), and New Zealand (p < 0.001), with a peak in the late spring/early summer months and trough in the late fall/early winter months. The peaks in late spring/early summer and troughs in late fall/early winter were out of phase by 6 months in the northern compared to the southern hemisphere countries.

Another line of evidence from internet search query data showed a seasonal variation in gout, with a peak in the late spring/early summer months. Further studies aimed at elucidating the possible mechanisms behind seasonality in gout are needed.

The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes. A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease. Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.

The relationship between functional disability and MRI-inflammation has been studied for the hands, but has not been well established for the feet, even though walking-difficulties are common. Therefore we studied whether walking-difficulties were associated with MRI-inflammation at metatarsophalangeal(MTP)-joints in early arthritis patients, at diagnosis and during 24-months follow-up. 532 consecutive patients presenting with early arthritis reported on presence and severity of walking-difficulties (HAQ-question 4a, scale 0-3), and underwent unilateral contrast-enhanced MRI of MTP(1-5)-joints at baseline. 107 patients had clinical and MRI-data at follow-up (4-, 12- and 24-months). MRI-inflammation (synovitis, tenosynovitis and osteitis) was scored in line with RAMRIS. At baseline the association of walking-disability with MRI-inflammation was assessed using regression. Longitudinally the association between a change in walking-disability with a change in MRI-inflammation was studied with linear mixed models. At baseline, 81% patients with walking-disabilities had MRI-inflammation at MTP-joints, versus 68% without walking-disabilities (P<0.001). Total MRI-inflammation (i.e. the sum of tenosynovitis, synovitis and osteitis) was associated with severity of walking disability (β=0.023, P<0.001). Studying the MRI-features separately, tenosynovitis, synovitis and osteitis were all univariable associated with severity of walking-disability (P<0.001, P<0.001 and P=0.014 respectively). Multivariable, the association was strongest for tenosynovitis. During follow-up a decrease in MTP-inflammation was associated with a decrease in walking-disability (β=0.029, P=0.001): in multivariable analyses only tenosynovitis was independently associated (β=0.073, P=0.049).

Of the different inflamed tissues in MTP-joints, predominantly MRI-detected tenosynovitis was associated with walking-disabilities. Likewise a reduction in tenosynovitis related to a decrease in walking-disabilities. This increases our understanding of the involvement of tenosynovitis in walking-disabilities in early arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints. Our aim is to explore the change of gene expression profile in patients with RA, and investigate the underlying mechanism of the pathogenesis and progression of RA. We downloaded the dataset GSE2053 from Gene Expression Omnibus database and screened the differentially expressed genes by analyzing the profiles between RA and normal cells with bioinformatics methods. Furthermore, Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to screen GO and the significantly changed signaling pathways in RA cells with the Database for Annotation, Visualization and Integrated Discovery (DAVID). By bioinformatics methods, we obtained the metabolic pathway changed in the cells of patients with RA, and explored small molecule drugs that can restore these changes.

These results may provide a new approach for explore the pathogenesis of RA and a new breakthrough in the medical treatment of patients with RA.

We investigated alterations of levels of plasma tetranectin, a new regulator of plasminogen activation, in patients with rheumatoid arthritis (RA) in relation to disease activity and other fibrinolytic variables. Tetranectin (TN), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) were quantitatively assessed (ELISA) in plasma of 41 patients with RA and 30 healthy subjects, alpha 2-Antiplasmin activity was assessed by the amidolytic method. Disease activity was determined as a composite Stoke Index, which measures inflammatory processes in RA. Patients were divided into 3 groups according to Stoke Index score of disease activity: A, minimal-mild, 1-7: B. moderate. 8-11: C. severe. 12-17. Plasma TN in patients was significantly lower compared to that of healthy subjects [9.11 (4.97-13.49) mg/l, 12.05 (9.50-13.60) mg/l, median (range), respectively; p = 0.0001]. TN decreases with the increase of disease activity from group to group. A significant negative correlation between TN and Stoke Index. C-reactive protein and erythrocyte sedimentation rate was found (rs = -0.49, p = 0.0012; rs = -0.44, p = 0.0044; rs = -0.37, p = 0.016, respectively). alpha 2-Antiplasmin activity was elevated in patients compared to healthy subjects [105.0% (53.0-146.0), 70.6% (48.2-124.0), median (range), respectively; p = 0.0001], showing a negative correlation with Stoke Index (rs = -0.38, p = 0.0139). The close positive correlation of TN with alpha 2-antiplasmin (rs = 0.66, p = 0.0001) and the absence of correlation with t-PA and PAI-1 were explained by the involvement of TN and alpha 2-antiplasmin in localized rather than in systemic fibrinolysis.

Our findings suggest TN plays a role in the pathophysiology of RA and point to the usefulness of TN assessment as a specific fibrinolytic marker in the evaluation of disease activity in patients with RA. The role of TN in the intraarticular regulation of fibrinolysis, important for the expansion of pannus, tissue remodeling and angiogenesis, is discussed.

Clinical audits are critical and systematic quality analysis of medical care. Total hip arthroplasty (THA) is a routine practice and cost-effective, although there is little information on the quality of care of it. To evaluate the impact of a clinical audit cycle in the quality of care in the primary THA procedures for non-traumatic cause. A series of two audits (first audit in 2005 and second one in 2007) were performed. Patients of both sexes with non-traumatic primary THA and with a follow-up of 6 months were included. Time (days) in hospital stay and the rate (percentage) of readmissions were used as indicators of management; and as indicators of clinical practice: the index (percentage) of dislocation and the rate (percentage) of infection. Both audits were compared with respect to these indicators. A total of 160 patients (79 and 81, first and second audit respectively) were analysed. Management indicators: median (range) of hospital stay was 8 (7-78) and 7 (6-16), p<0.001, and the percentage of readmissions 5% (4/79) and 0 (0/81), p=0.057. Indicators of clinical practice: the rate of dislocation was 8% (6/79) and 0 (0/81), p=0.013, and the rate of infection 1% (1/79) and 1% (1/81), p=1. A multivariate analysis did not find other factors related to these indicators.

The implementation of a clinical audit cycle has improved the quality of care of primary THA procedures for non-traumatic cause.

Little is known about the characteristics of patients seeking help from dedicated centers for undiagnosed and rare diseases. However, information about their demographics, symptoms, prior diagnoses and medical specialty is crucial to optimize these centers' processes and infrastructure. Using a questionnaire, structured information from 522 adult patients contacting a center for undiagnosed and rare diseases was obtained. The information included basic sociodemographic data (age, gender, insurance status), previous hospital admissions, primary symptoms of complaint and previously determined diagnosis. The majority of patients completing the questionnaire were female, 300 (57 %) vs. 222 men (43 %). The median age was 52 years (range 18-92). More than half, 309 (59 %), of our patients had never been admitted to a university hospital. Common diagnoses included other soft tissue disorders, not classified elsewhere (ICD M79, n = 63, 15.3 %), somatoform disorders (ICD F45, n = 51, 12.3 %) and other polyneuropathies (ICD G62, n=36, 8.7 %). The most frequent symptoms were general weakness (n = 180, 36.6 %) followed by arthralgia (n = 124, 25.2 %) and abdominal discomfort (n = 113, 23.0 %). The majority of patients had either internal medicine (81.3 %) and/or neurologic (37.6 %) health problems.

Pain-associated diagnoses and the typical "unexplained" medical conditions (chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome) are frequent among people contacting a center dedicated to undiagnosed diseases. The chief symptoms are mostly unspecific. An interdisciplinary organizational approach involving mainly internal medicine, neurology and psychiatry/psychosomatic care is needed.

To examine gait in children with juvenile chronic arthritis (JCA) with reference to velocity, ground reaction forces and temporal parameters. Fifteen children with JCA were assigned into two groups (uni- and bilateral involvement and classified as pauci- or polyarticular arthritis). Fourteen healthy children participated in the control group. Light-beams were used to determine walking velocity and the children with JCA rated their pain on a visual analogue scale. Two force plates registered the ground reaction forces and foot-switches were used to obtain temporal parameters. The mean velocity for the children with JCA was significantly less than for the healthy controls. Velocity normalized to height showed a tendency for the children with JCA to walk slower than controls. Differences between JCA children and healthy controls were observed for peak vertical forces during heel contact and push-off. No temporal differences were observed between the groups.

Such kinetic and temporal information may provide the clinician with a sensitive tool for pre- and post assessment of intra-articular steroid injections and/or physical therapy.

Activated Wnt signalling with decreased expression of endogenous inhibitors has recently been characterised as a central pathomechanism in systemic sclerosis (SSc). Aberrant epigenetic modifications also contribute to the persistent activation of SSc fibroblasts. We investigated whether increased Wnt signalling and epigenetic changes in SSc are causally linked via promoter hypermethylation-induced silencing of Wnt antagonists. The methylation status of endogenous Wnt antagonists in leucocytes and fibroblasts was evaluated by methylation-specific PCR. 5-aza-2'-deoxycytidine was used to inhibit DNA methyltransferases (Dnmts) in cultured fibroblasts and in the mouse model of bleomycin-induced skin fibrosis. Activation of Wnt signalling was assessed by analysing Axin2 mRNA levels and by staining for β-catenin. The promoters of DKK1 and SFRP1 were hypermethylated in fibroblasts and peripheral blood mononuclear cells of patients with SSc. Promoter hypermethylation resulted in impaired transcription and decreased expression of DKK1 and SFRP1 in SSc. Treatment of SSc fibroblasts or bleomycin-challenged mice with 5-aza prevented promoter methylation-induced silencing and increased the expression of both genes to normal levels. Reactivation of DKK1 and SFRP1 transcription by 5-aza inhibited canonical Wnt signalling in vitro and in vivo and effectively ameliorated experimental fibrosis.

We demonstrate that hypermethylation of the promoters of DKK1 and SFRP1 contributes to aberrant Wnt signalling in SSc and that Dnmt inhibition effectively reduces Wnt signalling. These data provide a novel link between epigenetic alterations and increased Wnt signalling in SSc and also have translational implications because Dnmt inhibitors are already approved for clinical use.

Liver X receptors are established sensors of lipid and cholesterol homeostasis. Recent studies have reported that these receptors are involved in the regulation of inflammation and immune responses. We attempted to identify single nucleotide polymorphisms (SNPs) of the NR1H3 gene associated with the susceptibility to systemic lupus erythematosus (SLE). SNPs were genotyped using SNaPSHOT assay in 300 Korean patients with SLE and 217 normal controls (NC), and in replication samples (160 SLE patients and 143 NC). Also, the functional effects of NR1H3 gene promoter polymorphisms were analyzed using a luciferase assay, real-time polymerase chain reaction, B cell proliferation assay and an electrophoretic mobility shift assay. We identified five polymorphisms: -1851 T > C (rs3758673), -1830 T > C (rs3758674), -1003 G > A (new), -840 C > A (rs61896015) and -115 G > A (rs12221497). There was a significant and reproducible difference in the -1830 T > C, -1003 G > A and -115 G > A polymorphisms between the SLE and the NC. Luciferase activity of the structure containing -1830 C was less enhanced compared to the structure containing -1830 T in basal, GW3965 and T0901317 treated Hep3B cells (P = 0.009, P = 0.034 and P <0.001, respectively). Proliferation of the -1830 TC type was increased compared to the -1830 TT type in basal, GW3965 and T0901317 treated B cells from SLE patients (P = 0.011, P = 0.040 and P = 0.017, respectively). Transcription factor GATA-3 preferentially bound the -1830 T allele in the promoter.

NR1H3 genetic polymorphisms may be associated with disease susceptibility and clinical manifestations of SLE. Specifically, -1830 T > C polymorphism within NR1H3 promoter region may be involved in regulation of NR1H3 expression.

Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results.

The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.

To compare the care of patients with suspected early inflammatory arthritis (EIA) in the Wellington region with the quality standards from the British Society of Rheumatology (BSR) 2013/14 best practice tariffs. The case notes for patients first seen in clinic from the beginning of 2015 were reviewed until at least 100 cases of suspected inflammatory arthritis were identified. Data gathered included the length of time from referral to first specialist rheumatology clinic, the length of time from referral to the commencement of disease modifying therapy for cases of inflammatory arthritis and the number of specialist-led clinics within the first 12 months of the first appointment. 117 cases of suspected inflammatory arthritis were reviewed. The median time from referral to the first appointment was 11.4 weeks (IQR 6.6-13.3). 61 of the 117 cases had clinically confirmed EIA. The median time from referral to the commencement of disease-modifying therapy was 10.5 weeks (IQR 5-15). For confirmed EIA, the median number of clinics in the first year was four (IQR 3-4).

Patients with suspected inflammatory arthritis in the Wellington region wait much longer to be seen than is recommended by the BSR guidelines.

To measure hyaluronic acid (HA) levels, which are raised in active rheumatoid arthritis (RA), in patients with early RA, and to assess the correlation with clinical and laboratory indices of disease activity and with subsequent radiographic erosive status. Patients fulfilling ACR criteria were recruited into a prospective cohort within 6 months of disease onset and reviewed every 6 months. An HA binding protein based sandwich ELISA was used to measure HA in 240 sera from 82 patients at regular intervals. Patients had higher HA levels than age matched healthy blood donor controls (median 37.4 v 29.1 ng/ml, respectively, p<0.02), which increased with more prolonged disease. Baseline HA level correlated with measures of disease activity, including swollen and tender joint counts, HAQ, global assessments, ESR, and CRP; was higher in men; and increased with age. There was no relationship with HLA-DRB1 shared epitope or rheumatoid factor status. At 6 and 12 month follow up visits, HA levels were higher in patients who later developed erosions. However, a raised HA level was not a good predictor of erosions.

Serum HA level correlates with clinical and laboratory measures of disease activity in early RA, but is unlikely to be of practical use in clinical practice.

Our objective was to determine if there are ethnic differences in the use of over-the-counter (OTC) and prescription oral nonsteroidal anti-inflammatory drugs (NSAIDs) and if observed ethnic differences persist after adjustment for sociodemographic and clinical factors. Knee and hip osteoarthritis study participants were identified. Surveys were administered to collect sociodemographics, clinical information, and oral treatment methods for arthritis. Multivariable logistic regression models were created using a fully conditional method. Hispanics (n = 130), compared to non-Hispanic whites (n = 204), were less likely to have a high school education (26.9% vs 63.2%, P <0.001), less likely to have private medical insurance (P <0.001), and more likely to have worse health (P = 0.004). OTC oral NSAID use was less common (52.9% vs 66.3%, P = 0.019), whereas prescription oral NSAID use was more common (43.4% vs 31.7%, P = 0.042) among Hispanics than non-Hispanic whites in the last 6 months. The ethnic difference in using an OTC NSAID instead of not using any oral NSAID was attenuated and no longer significant when adjusted for age, sex, education, and medical insurance (odds ratio [OR] 0.54 [95% confidence interval [CI]: 0.28-1.02]). The odds of using a prescription instead of an OTC NSAID remained significantly higher among Hispanics than non-Hispanic whites when adjusted for the same variables (odds ratio 2.17 [95% confidence interval: 1.16-4.05]).

Among patients with osteoarthritis, OTC NSAIDs were less commonly used but prescription NSAIDs were more commonly used by Hispanics than non-Hispanic whites. Sociodemographic factors partially mediate ethnic differences in the use of oral NSAIDs.

To examine the impact of 5-Aza-2'-deoxycytidine (5-AzadC) on methylation status of miR-124a genes in rheumatoid arthritis (RA) associated fibroblast-like synoviocytes (FLS) and its effect on RA-FLS proliferation and TNF-α expression. FLS were isolated from seven RA-derived synovial tissues and cultured in vitro. The expression of miR-124a was measured by real time quantitative polymerase chain reaction (PCR) in FLS with or without 5-AzadC treatment. MiR-124a gene methylation was detected by methylation-specific PCR. FLS were divided into three groups as control, IL-1β and IL-1β/5-AzadC, respectively. The cells in the IL-1β group were treated with 5 μg/L of IL-1β for 24 hours, whereas the cells in the IL-1β/5-AzadC group were first treated with IL-1β exactly as those in the IL-1β group for 24 h but further treated with 1μM 5-AzadC for additional 3 days. The cell growth was estimated based on absorbance at UV450nm. Secreted TNF-α from the cells was evaluated by enzyme-linked immunosorbent assay. After that, RA-FLS treated with IL-1β plus 5-AzadC were further transfected with miR-124a inhibitor or scrambled control. After culturing for 3 days, cell growth and TNF-α concentrations were measured. After 5-AzadC treatment, the expression of miR-124a was significantly increased compared with the control group (1.545 ± 0.189 vs 0.836 ± 0.166, p = 0.001). On the other hand, 5-AzadC significantly reduced IL-1β-mediated cell proliferation by nearly 2.5 fold (p = 0.006). Also, the level of TNF-α secreted from the cells treated with IL-1β plus 5-AzadC was considerably less than that from the cells treated with IL-1β alone (324.99 ± 22.73 ng/L vs 387.91 ± 58.51 ng/L, p = 0.022). After transfection with miR-124a inhibitor in RA-FLS treated with IL-1β plus 5-AzadC, the cell proliferation was increased by 18.2% and the TNF-α expression was increased by 19.0% (p = 0.001 and 0.011, respectively).

Methylation of miR-124a genes contributed to IL-1β-mediated RA-FLS proliferation and TNF-α expression.

To compile a simple questionnaire, named 'Foot Health Questionnaire-1' (FHQ1), which would evaluate the state of the foot in rheumatic diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Sixty-three consecutive subjects entered the study: 25 with RA; 14 with OA; 10 with CTD and 14 healthy control subjects. It was possible to establish that the highest mean value of FHQ1 refers to RA patients (median FHQ1 value, 41) and OA patients (median FHQ1 value, 37) whereas for CTD patients the mean value was 14 and for healthy subjects was = 0, as expected. It results that 72% of RA patients and 65% of OA patients enter classes III and IV of FHQ1, whereas 70% of CTD patients were in class I.

An evaluation questionnaire regarding the algo-functioning of the foot could be a useful tool in routine rheumatologic clinical practice.

To evaluate the performance of the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in clinical practice in a Chinese patient cohort, and to compare outcomes with the 1980 ACR criteria. Patients clinically diagnosed with SSc between September 2013 and May 2015 were prospectively recruited from the EUSTAR database of the Peking Union Medical College Hospital. Diagnosis of SSc was based on the evaluation of three experienced rheumatologists. Patients diagnosed with other connective tissue diseases were recruited as disease controls. The 1980 ACR and 2013 ACR/EULAR criteria were applied to the cohort, and patients who fulfilled the criteria were classified as definite SSc patients. Sensitivity and specificity were analyzed for the 2013 and 1980 criteria. A total of 143 SSc patients and 87 patients with other connective diseases were recruited. 41 (28.7%) and 102 (71.3%) cases were diffuse cutaneous SSc and limited cutaneous SSc, respectively. Although the sensitivity of the 2013 criteria (94.4%) exceeded the 1980 criteria (72.7%) (P<0.001), the 1980 and 2013 criteria sets showed no significant difference in specificity (97.7% and 93.1%, respectively, P = 0.278). The sensitivity of the 2013 criteria was significantly higher than the 1980 criteria in some SSc subgroups (e.g., lcSSc, abnormal pattern of nailfold videocapillaroscopy [NVC] and presence of Raynaud's phenomenon [RP]) compared to others.

Relative to the 1980 ACR criteria, in Chinese SSc patients the new 2013 ACR/EULAR criteria had similar specificity and higher sensitivity, especially for patients with mild skin thickening or prominent microvascular diseases.

Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper T cells (Tfh). There are three subpopulations of circulating Tfh (cTfh): CXCR5 + CXCR3 + CCR6- (Tfh-Th1), CXCR5 + CXCR3-CCR6- (Tfh-Th2) and CXCR5 + CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity of cTfh subsets, and examine their frequency in Rheumatoid Arthritis (RA) patients, together with the frequency of circulating plasmablasts (CD19 + CD20-CD38high). Peripheral blood was drawn from RA patients with active disease (RA-a, DAS28 >2.6) (n = 17), RA in remission (RA-r, DAS28 <2.6) (n = 17) and healthy controls (HC) (n = 34). cTfh and plasmablast frequencies were determined by flow cytometry. Cocultures of sorted CD4 + CXCR5+ T cell subpopulations were established with autologous CD19 + CD27- naïve B cells of HC, and concentrations of IgG, A and M were measured in supernatants. Isolated Tfh-Th2 and Tfh-Th17 but not Tfh-Th1 cells, induced naïve B cells to secrete IgG and IgA. The frequency of CXCR5+ cells gated for CD4+ T cells was not different among HC, RA-a and RA-r. In contrast, both RA-a and RA-r patients demonstrated an increased frequency of CD4 + CXCR5 + ICOS+ T cells and augmented (%Tfh-Th2 + %Tfh-Th17)/%Tfh-Th1 ratio as compared with HC. In addition, RA-a but not RA-r patients, showed an increased frequency of circulating plasmablasts.

Both RA-a and RA-r patients demonstrate an increased frequency of cTfh and overrepresentation of cTfh subsets bearing a B cell helper phenotype, suggesting that altered germinal center dynamics play a role in RA pathogenesis. In contrast, only RA-a patients show an increased proportion of circulating plasmablasts.

To measure the marginal costs of providing complementary medicine services (mostly homoeopathy) in outpatient clinics for patients with rheumatoid arthritis (RA) and to illustrate how parameters to which the cost of complementary medicine may be sensitive can be identified. Retrospective, observational costing study. The outpatient clinic of the Royal London Homoeopathic Hospital. Random sample of 89 patients from the 427 (RA) patients attending outpatient clinics from April 1995 to March 1996. The marginal costs incurred by the hospital of treating 89 patients attending outpatient clinics and the relative contribution of the different resources to the total costs. The total costs of treating 89 patients were 7,124 Pounds of which 543 Pounds was assumed to be fixed and the remainder variable. The marginal costs of treating additional patients, starting from zero patients treated, are presented. Consultation time (doctors and dietician) contributed to 29% of the total costs, non-conventional drugs contributed to 22% of the total costs.

Understanding the marginal costs of providing complementary care to RA patients will inform the debate over whether these therapies are likely to be cost-effective. In addition, those who would like to explore the practicalities of establishing a service involving complementary medicine will gain an understanding of the likely provider costs. The cost of complementary medicine appears to be most sensitive to the time spent with the patient by the doctor.

Outpatient clinical studies of magnet therapy, a complementary therapy commonly used to treat osteoarthritis (OA), have been limited by the absence of a credible placebo control. Our objective was to assess the feasibility and promise of studying static magnetic therapy for knee OA and determine the ability of a new placebo-magnet device to provide concealment of group assignment. Randomized, double-blind, placebo-controlled clinical trial. Academic teaching hospital in Boston. We enrolled 29 subjects with idiopathic or post-traumatic OA of the knee. Subjects received either high-strength magnetic (active) or placebo-magnetic (placebo) knee sleeve treatment for 4 hours in a monitored setting and self-treatment 6 hours daily for 6 weeks. Primary outcomes were change in knee pain as measured by the WOMAC Osteoarthritis Index Pain Subscale at 6 weeks and extent of group concealment at study end. At 4 hours, VAS pain scores (+/- SE) on a 5-item scale (0-500, 500 worst) decreased 79 +/- 18 mm in the active group and 10 +/- 21 mm in the placebo group (P < 0.05). There were no significant differences in any primary or secondary measure of efficacy between the treatment groups at 6 weeks. Despite widespread testing for magnetic properties, at study end, 69% of the active group and 77% of the placebo group (P > 0.2) believed that they had been assigned to the active treatment group.

Despite our small sample size, magnets showed statistically significant efficacy compared to placebo after 4 hours under rigorously controlled conditions. The sustained efficacy of magnetic therapy for knee osteoarthritis could be assessed in an adequately powered trial utilizing an appropriate control such our new placebo-magnet device.

To assess the effectiveness and efficiency of the two alternatives mainly used in our area, etanercept (ETN) and adalimumab (ADA), for the treatment of rheumatoid arthritis (RA) patients under real clinical practice. We performed a retrospective observational study, where the time horizon was 12 months referred to the year 2012. We analyzed the characteristics of patients, and the effectiveness and efficiency of ETN and ADA in our study population. patients over 18 years, diagnosed with RA treated at the outpatient clinic of the Rheumatology Health Sector of Teruel. We determined the mean decrease in DAS28 value (DAS28r) of each drug and we defined as a unit of effectiveness in pharmacoeconomic study, a DAS28 value at baseline (DAS28a) less than 3.2 points and DAS28r greater than 1.2 points. As parameter to determine the cost-effectiveness of both alternatives we used net health benefits (NHB). The average value of DAS28a was 2,25 and 2,72 points for ETN and ADA respectively, with a value of DAS28r 1,01 points higher for ETN, although not statistically significant (p> 0.05). NHB obtained a value of -0.121, 95% CI (-0.951 to 0.709). Objetivo: Valorar el grado de efectividad y eficiencia de las dos alternativas principalmente utilizadas en nuestro ámbito, etanercept (ETN) y adalimumab (ADA), para el tratamiento de pacientes diagnosticados de artritis reumatoide (AR) en condiciones reales de la práctica clínica diaria. Material y método: Se realizó un estudio observacional retrospectivo, cuyo horizonte temporal fue de 12 meses referidos al año 2012, en el que se analizaron las características de los pacientes, así como la efectividad y eficiencia de ETN y ADA en la población de estudio. Se estudiaron todos los pacientes de ambos sexos mayores de 18 años, diagnosticados de AR, atendidos en las consultas externas del Servicio de Reumatología del Sector Sanitario de Teruel. Se determinó el descenso medio del valor de DAS28 (DAS28r) de cada fármaco y se definió como unidad de efectividad en el estudio farmacoeconómico un valor DAS28 al inicio (DAS28a) inferior a 3,2 puntos y DAS28r mayor a 1,2 puntos. Como parámetro del estudio para determinar el coste-efectividad de ambas alternativas se utilizó el beneficio neto sanitario (BNS). Resultados: El valor medio de DAS28a fue 2,25 y 2,72 puntos para ETN y ADA respectivamente, con un valor DAS28r de 1,01 puntos superior para ETN, aunque sin ser estadísticamente significativo (p > 0,05). El cálculo del parámetro BNS obtuvo un valor igual a -0,121; IC95% (-0,951 a 0,709), sin embargo la inclusión del valor 0 en el intervalo de confianza hizo que no se observaran diferencias de coste-efectividad. Conclusiones: Ambas alternativas son efectivas en el tratamiento de la AR, aunque parece existir una tendencia a favor de ETN en el grado coste-efectividad sin ser significativa.

Both alternatives are effective in the treatment of RA, although it seems to be a trend in favor of ETN in cost-effectiveness degree.

Calcanei are the most common sites for bony spurs. Although calcaneal enthesophytes have been extensively researched, many unknowns remain. Whether biological factors, such as age, weight and genetics, play a greater role in calcaneal spur etiology than activity is still unknown. The current study examines 121 adults from a prehistoric hunter-gatherer population to aid in understanding bony spur etiology. Calcaneal spurs are scored as present or absent on the dorsal or plantar side; they are analyzed in regards to their relationships with age, sex, osteoarthritis, cortical index, femoral head breadth and muscle markers. Dorsal and plantar spurs frequencies increase with age (chi-squares=16.90, 7.268, Ps<0.05, respectively). Dorsal spurs were more frequent than plantar spurs (chi-square=38.000; P<0.0001). There is a positive relationship with calcaneal spurs and upper limb and lower limb osteoarthritis (chi-squares=5.587, 7.640, Ps<0.05, respectively).

The data presented support that dorsal spurs are in part the result of activities, but plantar spurs may be a more modern phenomena resulting from long periods of standing and excess weight.

We have shown that patients with osteoarthritis are at increased risk of fracture after total knee replacement (TKR). We conducted a population-based cohort study to assess the effect of bisphosphonate use on their post-surgery fracture risk. Cox regression adjusted by propensity score suggested a 50-55% reduction in risk of fracture post-surgery. Patients with osteoarthritis have a higher bone mass but similar or higher risk of fracture. We recently demonstrated that patients have an elevated fracture risk after TKR, but it is unknown if bisphosphonate therapy in this patient group would reduce fracture risk. We aimed to assess the effect of bisphosphonate prescription to patients undergoing a TKR, on their risk of fracture after surgery. From the General Practice Research Database, all patients ≥ 40 years old, who received a TKR from 1986 to 2006 for knee osteoarthritis were eligible. We identified bisphosphonate use (BPU) as the main exposure. Propensity scores (equivalent to the estimated conditional probability of being treated given the individual's covariates) were calculated using logistic regression and used to reduce observed confounding. We fitted Cox models to study the effect of BPU on post-surgery fracture occurrence. Analyses were stratified by history of previous fracture: no fracture, osteoporotic fracture (hip, wrist, humerus, spine), and other fractures. The hazard ratio (HR) associated with BPU in non-previously fractured patients was 0.50 (95% confidence interval, 0.37-0.68; propensity-adjusted model), and 0.48 (0.35-0.65; matched analysis). In subjects with osteoporotic and with other previous fracture, BPU was associated with a propensity-adjusted HR of 0.46 (0.30 to 0.71) and 0.47 (0.26-0.85), respectively, and with a propensity-matched HR of 0.45 (0.29 to 0.70) and 0.45 (0.25-0.82).

Our results suggest that BPU in primary prevention could reduce post-operative risk of fracture by 50% and by 55% in secondary prevention.

It is unclear why medial unicompartmental knee arthroplasty (UKA) with postoperative valgus alignment causes adjacent compartment osteoarthritis more often than high tibial osteotomy (HTO) for moderate medial osteoarthritis of the knee with varus deformity. This study used a computer simulation to evaluate differences in knee conditions between UKA and HTO with identical valgus alignment. Dynamic musculoskeletal computer analyses of gait were performed. The hip-knee-ankle angle in fixed-bearing UKA was changed from neutral to 7° valgus by changing the tibial insert thickness. The hip-knee-ankle angle in open-wedge HTO was also changed from neutral to 7° valgus by opening the osteotomy gap. The lateral tibiofemoral contact forces in HTO were larger than those in UKA until moderate valgus alignments. However, the impact of valgus alignment on increasing lateral forces was more pronounced in UKA, which ultimately demonstrated a larger lateral force than HTO. Valgus alignment in UKA caused progressive ligamentous tightness, including that of the anterior cruciate ligament, resulting in compression of the lateral tibiofemoral compartment. Simultaneously, patellofemoral shear forces were slightly increased and excessive external femoral rotation against the tibia occurred due to the flat medial tibial insert surface and decreased lateral compartment congruency. By contrast, only lateral femoral slide against the tibia occurred in excessively valgus-aligned HTO.

In contrast to extra-articular correction in HTO, which results from opening the osteotomy gap, intra-articular valgus correction in UKA with thicker tibial inserts caused progressive ligamentous tightness and kinematic abnormalities, resulting in early osteoarthritis progression into adjacent compartments.

Systemic sclerosis (SSc) has been suggested to cause exocrine pancreatic dysfunction. However, a case-control-based autopsy study failed to associate systemic sclerosis with any pancreatic histopathology. The primary objective of this study was to examine the exocrine pancreatic function in consecutive SSc patients in relation to an age- and sex-matched control group. A secondary objective was to relate exocrine pancreatic function to radiological, laboratory, and clinical SSc characteristics. One hundred twelve consecutive patients fulfilling the 2013 American Congress of Rheumatology/European League Against Rheumatism criteria for SSc and 52 control subjects were matched for sex and age. Exocrine pancreatic function was assessed by ELISA-based measurement of fecal elastase, and levels ≤ 200 μg/g were considered pathological, i.e., representing exocrine pancreatic insufficiency. Patients were characterized regarding SSc manifestations including gastrointestinal and hepatobiliary function, by use of laboratory and clinical examinations. Pancreas parenchyma characteristics were evaluated by high-resolution computer tomography (HRCT). A similar proportion of subjects exhibited pathological levels of fecal elastase among SSc patients (6/112; 5.4%) and control subjects (3/52; 5.8%). Patients with fecal elastase ≤ 200 μg/g did not differ from other SSc patients with respect to laboratory and clinical characteristics, including malnutrition. SSc subjects with low levels of fecal elastase displayed significantly lower pancreas attenuation on HRCT examinations compared to the control subjects.

In this study encompassing 112 consecutive SSc patients and 52 matched control subjects, we were unable to associate systemic sclerosis with clinically significant exocrine pancreatic dysfunction.

At least 50% of pediatric patients with Juvenile Idiopathic Arthritis (JIA) will require continued fo llow-up in adult rheumatology. The present International League of Associations for Rheumatology (ILAR) classification, currently under revision, differs from its classification of inflammatory arthritis in adults. Category changes have been reported in 10.8% of patients during follow-up. To analyze JIA patients in follow-up for at least 7 years to detect diagnosis changes during transition to adult care, identifying factors of poor functional prognosis. Retrospective study based on medical records of JIA patients seen at the pediatric polyclinic of the Puerto Montt Hospital between 2005 and 2017, who were monitored for at least 7 years. Descriptive analysis was performed according to clinical variables: diagnostic category, evolution before diagnosis, clinical and serological activity, and evolution before starting drug therapy. We evaluated 18 pa tients, corresponding to 3 patients with persistent oligoarticular arthritis (OA), 1 with extended OA, 4 with polyarticular arthritis (PA) rheumatoid factor (RF) negative, 4 with PA RF positive, 5 with syste mic JIA, and 1 with psoriatic arthritis, all have had follow-up more than 7 years. 11 out of 18 patients transitioned to adult care. Three out of 11 patients changed diagnosis to Rheumatoid Arthritis (RA) plus another autoimmune disease such as Sjögren's Syndrome + Systemic Lupus Erythematosus, Immune thrombocytopenia, or unclassified autoimmune disease, and 5 out of 11 children changed ILAR category from OA to Juvenile Rheumatoid Arthritis, extended OA to PA RF negative, and 3 from Systemic arthritis to PA RF negative. Age of onset, polyarticular forms, delay in diagnosis, and the start of therapy were associated with sequelae and persistent inflammation.

Eight of the eleven JIA patients who transitioned to adult care changed their diagnosis or presented other autoimmune diseases. Some factors of poor prognosis must improve.

Recent studies have indicated that cardiac autonomic dysfunction is an early sign of cardiovascular impairment in rheumatoid arthritis (RA). Previous studies have mainly focused on resting assessments; however, analysis of heart rate (HR) responses to exercise might provide additional information on cardiac autonomic dysfunction in this disease. Thus, we aimed to assess the HR responses during and after a maximal graded exercise test in patients with RA and healthy controls (CONs). This was a cross-sectional study in which 27 female RA patients and 14 female CONs frequency matched by physical activity, age, and body mass index were compared for HR responses during and after a maximal graded exercise test. Rheumatoid arthritis patients showed reduced chronotropic response (94.3% ± 16.3% vs. 106.1% ± 10.3%, p = 0.02) and lower HR recovery (HRR) at 30 seconds (8.6 ± 6.7 vs. 13.4 ± 5.2 beats/min [bpm], p = 0.02), 60 seconds (16.5 ± 7.8 vs. 24.0 ± 9.9 bpm, p = 0.01), 120 seconds (32.6 ± 9.9 vs. 40.7 ± 12.3 bpm, p = 0.03), and 180 seconds (46.5 ± 12.6 vs. 55.5 ± 13.4 bpm, p = 0.05) post-maximal exercise test when compared with CONs. Moreover, the prevalence of chronotropic incompetence (i.e., failure to reach 80% of the HR-predicted response) and abnormal HRR (i.e., HRR ≤12 bpm) were, respectively, 22.2% and 37.1% in RA patients.

Patients with RA showed reduced chronotropic response to exercise and slower postexercise HRR. These abnormal autonomic responses to exercise indicate the presence of cardiac autonomic dysfunction and increased cardiovascular risk in this population.

Osteoarthritis (OA) is a type of progressive rheumatoid disease, which leads to the degeneration of the articular cartilage, synovium, subchondral bone, tendons, and the surrounding ligaments.There are various treatments for knee OA, including pharmaceutical, nonpharmaceutical, and surgical treatments. Considering the chronic nature of the disease as well as the necessity for the long-term use of chemical medications, various side effects could occur that include gastrointestinal bleeding, hypertension, congestive heart failure, hyperkalemia, and kidney failure. Therefore, suitable treatments with fewer side effects should be recommended. Recent investigations suggest increased tendency in people to use Complementary and Alternative Medicine (CAM) for knee OA treatment. This systematic review aimed to assess the effectiveness and safety of herbal preparations for the treatment of OA. The searched databases were Cochrane, Scopus, and PubMed. All the selected papers pertained to randomized controlled trials until August 8, 2017 in English in which one or several specific herbs had been used in knee OA treatment. We included 24 randomized trials (involving 2399 women and men). There were several different herbal medicines used within the included trials.

The results show that the methods used in these trials may reduce symptoms and the extent of NSAID consumption and enhance the quality of life. Additional trials are suggested to investigate the safety and efficacy of herbs for the treatment of patients with OA.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA.

To study the demographic and clinical characteristics of patients with antiphospholipid syndrome (APS) with serious haemorrhagic complications of anticoagulant treatment in an attempt to establish risk factors for bleeding. Patients with APS who were attending our lupus unit and who presented with severe bleeding while receiving oral anticoagulation were studied retrospectively. Severe bleeding was defined by the need for admission to hospital. Demographic data, clinical features, concomitant diseases and drugs, warfarin doses, duration of anticoagulation, and International Normalised Ratios (INR) at the time of bleeding were collected. Fifteen patients were included in the study (12 with systemic lupus erythematosus (SLE) plus APS and 3 with primary APS). The median age was 41.7 (range 27-66) and the median duration of the disease was 12.9 years (range 3-22). Duration of anticoagulation was between 10 days and 17 years. The INR at the time of bleeding was under 3 in 4 patients, between 3 and 4 in 5 patients and above 4 in 6 patients. There were 4 episodes of subdural haematoma, 4 episodes of renal haematoma (two after renal biopsy), 2 episodes of ovarian haemorrhage, 2 episodes of rectal haemorrhage, 1 episode of menorrhagia, 1 episode of haemarthrosis, and 1 episode of spinal haematoma. Concomitant drugs were aspirin in 9 patients, antibiotics in 2 patients, and azathioprine in 3 patients. In 6 patients hypertension was present as a concomitant disease. There were no deaths due to bleeding. Anticoagulant treatment was restarted in all patients and 3 of them had a new episode of bleeding.

No relation was established between age, duration of oral anticoagulant treatment, and bleeding. Concomitant drugs, mainly aspirin, and high blood pressure were present at the time of bleeding in a large number of patients.

To study the functional brain activation signals before and after sufficient disease control in patients with systemic lupus erythematosus (SLE) without clinical neuropsychiatric symptoms. Blood-oxygen-level-dependent signals during event-related functional magnetic resonance imaging brain were recorded, while 14 new-onset SLE patients and 14 demographically and intelligence quotient matched healthy controls performed the computer-based Wisconsin card sorting test for assessing executive function, which probes strategic planning and goal-directed task performance during feedback evaluation (FE) and response selection (RS), respectively. Composite beta maps were constructed by a general linear model to identify regions of cortical activation. Blood-oxygen-level-dependent functional magnetic resonance imaging signals were compared between (1) new-onset SLE patients and healthy controls and (2) SLE patients before and after sufficient control of their disease activity. During RS, SLE patients demonstrated significantly higher activation than healthy controls in both caudate bodies and Brodmann area (BA) 9 to enhance event anticipation, attention, and working memory, respectively, to compensate for the reduced activation during FE in BA6, 13, 24, and 32, which serve complex motor planning and decision-making, sensory integration, error detection, and conflict processing, respectively. Despite significant reduction of SLE activity, BA32 was activated during RS to compensate for reduced activation during FE in BA6, 9, 37, and 23/32, which serve motor planning, response inhibition and attention, color processing and word recognition, error detection, and conflict evaluation, respectively.

Even without clinically overt neuropsychiatric symptoms, SLE patients recruited additional pathways to execute goal-directed tasks to compensate for their reduced strategic planning skill despite clinically sufficient disease control.

We report the incidence and treatment of infusion reactions to infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor alpha, in a large cohort of patients with rheumatoid arthritis. One hundred eighty six patients with rheumatoid arthritis treated with infliximab for a total of 216.6 patient years were retrospectively evaluated. Patients received 2160 infliximab infusions at the Division of Rheumatology at the University Hospital of Padua from May, 2000 to April, 2004. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. The overall incidence of infusion reactions to infliximab was 0.8% (19 out of 2160 of infusions), affecting 10.2% of patients (19 out of 186). Mild, moderate, or severe acute reactions occurred in 0.1% (3 of 2160), 0.6% (13 of 2160), and 0.04% (1 of 2160) of infliximab infusions, respectively. Delayed infusion reactions occurred in 0.09% (2 of 2160) of infusions. Use of specific treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With a prophylaxis protocol, all patients who experienced an initial mild acute reaction were able to receive additional infusions.

Using appropriate treatment protocols, infliximab infusion reactions were effectively treated and prevented in patients with mild acute reactions upon retreatment. In the case of moderate to severe infusion reactions, the risks and the benefits of the continuation of infliximab therapy need to be carefully considered.

Curcuma longa Linn, "the golden spice" is a common spice used in Southern Asia and Middle East countries. It has a history of ethnopharmacological use for its various activities like anti-septic, anti-inflammatory, anti-oxidant, anti-microbial, anti-cancer and so on. To investigate the effects of polar extract of C. longa (PCL) against monosodium iodoacetate (MIA) induced osteoarthritis in rat and to compare with curcuminoids, which are contemporarily believed to be the only active phytochemicals of C. longa for relieving pain in osteoarthritis. Osteoarthritis in rats was induced by intra-articular injection of monosodium iodoacetate (MIA) in right knee. PCL or curcuminoids or tramadol was administered orally as single dose on the 5th day post MIA injection to rats. Weight bearing capacity and percentage inhibition of nociception of PCL treated groups were determined and compared with curcuminoids and tramadol (reference drug). In addition, gene expression levels of type II collagen and matrix metalloproteinases (MMP) in joint cartilage was measured by Reverse transcription polymerase chain reaction. PCL significantly decreased the difference in weight distribution between left and right limb in a dose dependent manner. Anti-arthritic activity of PCL is evident from significant up regulation of type II collagen gene (COL2A1) and down regulation of MMP-3 and MMP-7.

Polar extract of C. longa showed beneficial effects on joints by exhibiting antiosteoarthritic effects via maintaining equilibrium between anabolic and catabolic factors of joint cartilage.

Large, long-term databases are needed in order to provide information on the safety and efficacy of new agents used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). These databases can provide data which is well beyond what is available from industry-sponsored investigations. The structure, governance, content, context and developmental plan of the CORRONA database are described. The CORRONA database has grown from start up in 2002 to the largest independent database in North America which collects data from both rheumatologists and patients at the time of a clinical encounter. Data are collected as often as every 3 months in RA and every 6 months in PsA. As of the time of this writing, the CORRONA database consists of approximately 9000 patients with RA and 1000 with PsA. Data can be used to elucidate toxicities found in frequencies which would be considerably less common than can be uncovered in industry-sponsored investigations. In addition, actual prescribing patterns and responses in clinical practice can be investigated and described.

After 3 years of data collection, the CORRONA database is now appropriately able to make significant contributions to our understanding of the safety, efficacy of drugs, as well as demographic, and socioeconomic profiles of patients with RA and PsA. It has evolved from a nascent database to a mature one poised to make significant contributions.

Extra corporeal shock waves (ESW) have been proposed as additional therapy in bone fracture repair and osteoarthrtitis (OA). However, little is known on the effects of ESW on osteoblast metabolism. The aim of this study was to evaluate phenotype changes of healthy and OA human osteoblasts following ESW treatment. Osteoblasts were isolated from subchondral bone of 13 OA patients and 7 healthy donors. Osteoblasts were treated or not with ESW at different levels of energy and impulses. IL-10, TNF-alpha, CD29/Beta1 integrin, and CD105/endoglin expression was evaluated by flowcytometry. Intracellular IL-10 significantly increased using 1000 impulses at 0.055 mJ/mm2 in both healthy and OA osteoblasts in comparison with untreated osteoblasts (p<0.01). Only in the OA osteoblasts CD29 and CD105 expression significantly increased at 500 impulses and 0.17 mJ/mm2 ESW treatment (p<0.05).

ESW are capable of modifying IL-10 expression in osteoblasts. There is evidence that IL-10 can play a role in bone remodelling by inhibiting osteoclast differentiation and this suggests that ESW may favour bone growth and healing. This further supports the use of ESW in treating bone fracture to promote callus formation. However, the possible use of ESW in OA therapy needs further studies since in OA, osteoblast metabolism is already enhanced with bone sclerosis and ESW application may further increase bone deposition and osteophyte formation, leading to a subsequent worsening of the disease.

Fatty acid oxidation (FAO) and glycolysis have been implicated in immune regulation and activation of macrophages. However, investigation of human monocyte intracellular metabolism in the context of the hypoxic and inflammatory rheumatoid arthritis (RA) synovium is lacking. We hypothesized that exposure of monocytes to the hypoxic and inflammatory RA environment would have a profound impact on their metabolic state, and potential to contribute to disease pathology. Human monocytes were isolated from buffy coats and exposed to hypoxia. Metabolic profiling of monocytes was carried out by LC-MS metabolomics. Inflammatory mediator release after LPS or RA-synovial fluid (RA-SF) stimulation was analysed by ELISA. FAO was inhibited by etomoxir or enhanced with exogenous carnitine supplementation. Transcriptomics of RA blood monocytes and RA-SF macrophages was carried out by microarray. Hypoxia exacerbated monocyte-derived CCL20 and IL-1β release in response to LPS, and increased glycolytic intermediates at the expense of carnitines. Modulation of carnitine identified a novel role for FAO in the production of CCL20 in response to LPS. Transcriptional analysis of RA blood monocytes and RA-SF macrophages revealed that fatty acid metabolism was altered and CCL20 increased when monocytes enter the synovial environment. In vitro analysis of monocytes showed that RA-SF increases carnitine abundance and CCL20 production in hypoxia, which was exacerbated by exogenous carnitine.

This work has revealed a novel inflammatory mechanism in RA that links FAO to CCL20 production in human monocytes, which could subsequently contribute to RA disease pathogenesis by promoting the recruitment of Th17 cells and osteoclastogenesis.

To compare the clinical effect of proximal fibular osteotomy (PFO) and single condyle replacement (UKA) in the treatment of knee osteoarthritis of different severity. From June 2015 to September 2017, 53 patients with knee osteoarthritis were analyzed retrospectively. According to the operation mode, they were divided into PFO group (26 cases) and UKA group (27 cases) . According to Kellygren-Lawrence imaging classification standard：PFO group, 5 cases of gradeⅡ, 11 cases of grade Ⅲ, 10 cases of grade Ⅳ; UKA group, 7 cases of gradeⅡ, 9 cases of grade Ⅲ, 11 cases of grade Ⅳ. The amount of intraoperative bleeding, operation time and postoperative hospital stay were compared between the two groups. The patients were followed up regularly in the outpatient clinic before operation, 3 months after operation and 1 year after operation. The WOMAC score and the angle of tibiofemoral angle at each time point in the same group were compared, and the OMAC score and the angle of tibiofemoral angle at each time between the two groups were compared. Fifty-three patients were followed up for 12 to 24 (16.6±4.8) months. Compared with UKA group, PFO group had less intraoperative bleeding, shorter operative time and shorter postoperative hospital stay (

Compared with UKA, PFO has the advantages of small trauma, fast recovery and low cost. The curative effect of PFO is equal to or more than UKA in the patients with gradeⅡand Ⅲ knee osteoarthritis. It is an alternative surgical method for the treatment of knee osteoarthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, and the damage of cartilage as well as bone. Resolvin D1 (RvD1) can promote inflammation resolution in acute inflammatory diseases, and recently, effects of RvD1 on chronic inflammatory diseases also attracted attention. This study aimed to examine the effect of RvD1 on pannus formation in RA and the underlying mechanism. Serum levels of RvD1 and CTGF were determined in RA patients and healthy persons by UPLC-MS/MS and ELISA respectively. The levels of CTGF and inflammatory factors were assessed by qRT-PCR and ELISA. MicroRNA expression profile was determined by miRNA microarray. The effects of CTGF, RvD1, and miR-146a-5p on angiogenesis were evaluated with tube formation and chick chorioallantoic membrane (CAM) assays. Collagen-induced arthritis (CIA) mice were constructed to detect the effects of RvD1 and miR146a-5p on RA. STAT3 activation was determined by Western blotting. RvD1 levels decreased while CTGF levels increased in RA patients' serum, and an inverse correlation of the concentrations of RvD1 and CTGF in the serum of RA patients was synchronously observed. In CIA mice, RvD1 suppressed angiopoiesis and decreased the expression of CTGF. Simultaneously, RvD1 significantly decreased CTGF and pro-inflammation cytokines levels in RA FLS. Furthermore, CTGF suppressed angiopoiesis and RvD1 inhibited the proliferation and migration of RA FLS and angiopoiesis. MiRNA microarray and qRT-PCR results showed that RvD1 upregulated miRNA-146a-5p. The transfection experiments demonstrated that miRNA-146a-5p could decrease inflammatory factors and CTGF levels. Moreover, miRNA-146a-5p decreased the proliferation of FLS and angiogenesis in vivo. MiRNA-146a-5p also suppressed angiogenesis and downregulated the expression of CTGF in CIA mice. Finally, Western blot results revealed that miRNA-146a-5p inhibited the activation of STAT3.

RvD1 is prone to alleviate RA progression through the upregulation of miRNA-146a-5p to suppress the expression of CTGF and inflammatory mediators, thereby decreasing pannus formation and cartilage damage.

Navigation has been introduced to achieve more accurate positioning of the implants after TKA. The scientific attention was mainly paid on limb alignment rather than restoration of the natural joint line. The aim of our study was to compare the accuracy of the joint line restoration in primary TKA with and without navigation. We hypothesized that joint line reconstruction in navigated TKA is more accurate. A total of 493 primary TKAs operated in a single medical centre were consecutively selected and divided into two groups. 206 cases were performed computer assisted (BrainLab CI-System), whereas 287 knees were implanted conventionally. For both groups, the joint line position of the knee was determined on standardized calibrated standing pre- and postoperative digital radiographs in ap view by a modified method of Kawamura et al. A joint line shift of more than 8 mm was defined as outlier. In the conventional group, the joint line shift averaged 0.7 mm (±4.4 mm), whereas the findings in the computer-assisted cases were in average 0.6 mm (±4.5 mm). The joint line was located above 8 mm in 6 % of non-navigated versus 6.8 % of navigated primary TKAs. There were no statistically significant differences of joint line shift between the different component types. A statistically significant relation was not found between joint line shift and leg alignment changes. Diagnostic study, Level III.

Conventional surgical technique allows a precise joint line reconstruction in primary TKA. Navigation did not improve the joint line reconstruction.

To determine the relationship between surgeon experience with, and complications following, total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA). Using administrative data, we assembled a cohort of patients with RA who had undergone at least 1 elective primary hip or knee replacement procedure between 2002 and 2009. Cox proportional hazards, censored on death and accounting for clustering of patients within surgeons, were used to determine the relationship between overall and "RA-specific" surgeon TJA volume and the occurrence of a composite "complication" outcome (revision, infection, dislocation, or periprosthetic fracture within 2 years of the initial TJA), controlling for potential confounders (patient age, sex, comorbidity, and disease severity). We identified 4,762 patients with RA who were eligible for TJAs (1,515 total hip arthroplasties and 3,247 total knee arthroplasties). Among these patients, 152 (3.2%) experienced a surgical complication within 2 years of the procedure. After controlling for patient and hospital factors, greater surgeon TJA volume in patients with RA (RA TJA), but not overall TJA volume (all TJA), was associated with a reduced risk of complications (for surgeon RA TJA volume per 10 cases, adjusted hazard ratio [HR] 0.81, 95% confidence interval [95% CI] 0.71-0.93, P = 0.002; for surgeon all TJA volume, adjusted HR 0.98, 95% CI 0.97-1.00, P = 0.09).

In a cohort of patients with RA who underwent hip or knee TJA, increased surgeon experience performing TJA in patients with RA, irrespective of their overall TJA experience and hospital factors, was associated with a decreased risk of surgical complications. These findings have potential implications for surgeon training and the referral practices of rheumatologists.

To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28-based response to each second-line treatment was analyzed at randomization with the Breslow-Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30-44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]). Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab.

In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post-MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.

Personality traits have been associated with primary depression. However, it is not known whether this association takes place in the case of depression comorbid with fibromyalgia. The authors investigated the association between a current major depressive episode and temperament traits (e.g., harm avoidance). A sample of 69 adult female patients with fibromyalgia was assessed with the Temperament and Character Inventory. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview severity of depressive symptomatology with the Beck Depression Inventory, and anxiety symptomatology with the IDATE-state and pain intensity with a visual analog scale. A current major depressive episode was diagnosed in 28 (40.5%) of the patients. They presented higher levels of harm avoidance and lower levels of cooperativeness and self-directedness compared with non-depressed patients, which is consistent with the Temperament and Character Inventory profile of subjects with primary depression. However, in contrast to previous results in primary depression, no association between a major depressive episode and self-transcendence was found.

The results highlight specific features of depression in fibromyalgia subjects and may prove important for enhancing the diagnosis and prognosis of depression in fibromyalgia patients.

A major complication of allogenic bone marrow transplantation (BMT) is graft-versus-host disease (GVHD), characterized principally by involvement of the eyes, producing a Sjögren-like syndrome (SLS). This study assessed the predictive role of the eye involvement in the onset of GVHD. Thirty-five patients transplanted for hematological malignancies were routinely examined for ocular manifestation of dry eye. Examination includes the Schirmer I test, break-up time, Lissamine Green staining, fluorescein test, lactoferrin test and impression cytology. A threshold was established for quantitative analysis of SLS. Fifteen of 35 patients (40%) developed SLS during long-term follow-up. Ten of these (77%) developed acute or chronic GVHD.

The possible etiology of SLS includes three factors: total body irradiation, ocular toxicity of chemotherapy and GVHD. A correlation was found between poor-prognosis GVHD and the occurrence of SLS.

Although multiple studies have reported the prevalence of primary hip osteoarthritis (OA), little has been reported on incidence rates of hip OA. We sought to determine the incidence rate and demographic risk factors of hip OA in an ethnically diverse and physically active population of US military servicemembers. A query was performed using the US Defense Medical Epidemiology Database for the International Classification of Diseases, Ninth Revision, Clinical Modification code for hip OA (715.95). Multivariate Poisson regression analysis was used to estimate the rate of hip OA per 100,000 person-years, controlling for sex, race, age, rank, and service. The overall unadjusted incidence rate of hip OA was 35 per 100,000 person-years. Women, compared with men, had a significantly increased adjusted incidence rate ratio for hip OA of 1.87 (95% confidence interval [95% CI] 1.73-2.01). The adjusted incidence rate ratio for black servicemembers when compared with white servicemembers was 1.32 (95% CI 1.23-1.41). The adjusted incidence rate ratio for the > or =40-year-old age group compared with the 20-year-old group was 22.21 (95% CI 17.54-28.14). With junior officers as the referent category, junior enlisted, senior enlisted, and senior officers rank groups had a significantly increased adjusted incidence rate ratio for hip OA. With the Air Force as the referent category, each service had a significantly increased adjusted incidence rate ratio for hip OA.

Female sex; black race; age > or =40 years; junior enlisted, senior enlisted, and senior officer rank groups; and military service in the Navy, Army, or Marines were all risk factors for hip OA.

To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).

The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

We hypothesize that thumb basilar joint osteoarthritis (TBJA) radiographic stage does not correlate with patient-reported measures of symptom severity. Patients with unilateral TBJA who completed the 11-item QuickDASH (Disabilities of the Arm, Shoulder, and Hand), Short-Form 12 Health Survey (SF-12) Mental Component and SF-12 Physical Component surveys were prospectively enrolled in the study. The Eaton-Littler radiographic stage was assigned for each patient. The correlation between the radiographic score and disease stage was calculated. Sixty-two patients (15 men, 47 women; average age, 62.3 years) formed the basis of this study. The average QuickDASH score (and standard deviation) for patients with stage 1 TBJA was 31.5 (11.4); for those with stage 2, it was 37.9 (17.4); with stage 3, it was 30.1 (13.0), and with stage 4, it was 39.4 (12.5). Eaton-Littler stage did not correlate significantly with QuickDASH scores (rho = -0.014, P = 0.91). Neither SF-12 Mental Component scores (MCS-12: rho = 0.019, P = 0.89) nor the SF-12 Physical Component scores (PCS-12: rho = 0.145, P = 0.26) correlated with TBJA stage. Prognostic, level II.

Radiographic severity in TBJA does not correlate with validated patient-reported symptom scores. Metrics that link radiographic and subjective components of TBJA may improve surgical decision making and monitoring of treatment response.