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ID PMID Title PublicationDate abstract
27605245 Concentration of antibodies against Porphyromonas gingivalis is increased before the onset 2016 Sep 7 BACKGROUND: The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). We have shown that ACPA precede RA onset by years, and that anti-P. gingivalis antibody levels are elevated in RA patients. The aim of this study was to investigate whether anti-P. gingivalis antibodies pre-date symptom onset and ACPA production. METHODS: A case-control study (251 cases, 198 controls) was performed within the Biobank of Northern Sweden. Cases had donated blood samples (n = 422) before the onset of RA symptoms by 5.2 (6.2) years (median (interquartile range)). Blood was also collected from 192 RA patients following diagnosis. Antibodies against P. gingivalis virulence factor arginine gingipainB (RgpB), and a citrullinated peptide (CPP3) derived from the P. gingivalis peptidylarginine deiminase enzyme, were analysed by ELISA. RESULTS: Anti-RgpB IgG levels were significantly increased in pre-symptomatic individuals (mean ± SEM; 152.7 ± 14.8 AU/ml) and in RA patients (114.4 ± 16.9 AU/ml), compared with controls (p < 0.001). Anti-CPP3 antibodies were detected in 5 % of pre-symptomatic individuals and in 8 % of RA patients, with elevated levels in both subsets (4.33 ± 0.59 and 9.29 ± 1.81 AU/ml, respectively) compared with controls (p < 0.001). Anti-CPP3 antibodies followed the ACPA response, with increasing concentrations over time, whilst anti-RgpB antibodies were elevated and stable in the pre-symptomatic individuals with a trend towards lower levels after RA diagnosis. CONCLUSIONS: Anti-P. gingivalis antibody concentrations were significantly increased in RA patients compared with controls, and were detectable years before onset of symptoms of RA, supporting an aetiological role for P. gingivalis in the development of RA.
26467356 Protective effects of methotrexate against ischemic cardiovascular disorders in patients t 2016 Jan OBJECTIVE: The association between chronic use of methotrexate and decreased risk of ischemic cardiovascular events (CVE) among patients with psoriatic or rheumatoid arthritis (RA) was investigated using a systematic review and meta-analysis. METHODS: The studies should have recruited adults receiving methotrexate, followed up for at least one year. Moreover, studies should have reported "hard" cardiovascular endpoints, by evaluating the cardiovascular outcomes of the habitual users of the drug or of new users compared with patients with the same disease who had never used methotrexate. The outcome of interest was the overall pooled odds ratio (OR) of major adverse cardiovascular events, i.e., a composite of new- onset angina, acute coronary syndrome, need for percutaneous or surgical coronary revascularization, stroke, and cardiovascular death. The study was performed according to the PRISMA statement. RESULTS: Seven observational studies, mostly engaging patients with RA, were included in the meta-analysis. The pooled odds ratio (OR) was 0.73 (95% CI=0.70- 0.77 p<0.001). When stratified meta-analysis models were assessed, the pooled OR was 0.80 (95% CI=0.66-0.97; p=0.022) for studies adjusting for clinical severity of RA. Furthermore, the OR was even more significant after adjustment for concomitant use of other drugs specific for RA(OR=0.71, 95% CI=0.67-0.75, p<0.001). CONCLUSION: Methotrexate at low doses, such those used for maintenance therapy of RA, predicted a decreased risk of CVE. Since methotrexate doesn't interfere with blood lipids, platelet aggregation or insulin resistance, the protective association may originate from mechanisms other than those exerted by antiplatelet drugs or statins.
26268317 Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arth 2015 Aug 24 INTRODUCTION: Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA). METHODS: Platelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity. RESULTS: Platelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcγRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level. CONCLUSIONS: We show for the first time that ACPA can mediate an FcγRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset.
25889308 Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients 2015 Apr 6 INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). During the clinical development programme, increases in mean serum creatinine (SCr) of approximately 0.07 mg/dL and 0.08 mg/dL were observed which plateaued early. This study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib relative to placebo in patients with active RA. METHODS: This was a randomised, placebo-controlled, Phase 1 study (NCT01484561). Patients were aged ≥18 years with active RA. Patients were randomised 2:1 to oral tofacitinib 10 mg twice daily (BID) in Period 1 then placebo BID in Period 2 (tofacitinib → placebo); or oral placebo BID in both Periods (placebo → placebo). Change in mGFR was evaluated by iohexol serum clearance at four time points (run-in, pre-dose in Period 1, Period 1 end, and Period 2 end). The primary endpoint was the change in mGFR from baseline to Period 1 end. Secondary endpoints included: change in mGFR at other time points; change in estimated GFR (eGFR; Cockcroft-Gault equation) and SCr; efficacy; and safety. RESULTS: 148 patients were randomised to tofacitinib → placebo (N = 97) or placebo → placebo (N = 51). Baseline characteristics were similar between groups. A reduction of 8% (90% confidence interval [CI]: 2%, 14%) from baseline in adjusted geometric mean mGFR was observed during tofacitinib treatment in Period 1 vs placebo. During Period 2, mean mGFR returned towards baseline during placebo treatment, and there was no difference between the two treatment groups at the end of the study--ratio (tofacitinib → placebo/placebo → placebo) of adjusted geometric mean fold change of mGFR was 1.04 (90% CI: 0.97, 1.11). Post-hoc analyses, focussed on mGFR variability in placebo → placebo patients, were consistent with this conclusion. At study end, similar results were observed for eGFR and SCr. Clinical efficacy and safety were consistent with prior studies. CONCLUSION: Increases in mean SCr and decreases in eGFR in tofacitinib-treated patients with RA may occur in parallel with decreases in mean mGFR; mGFR returned towards baseline after tofacitinib discontinuation, with no significant difference vs placebo, even after post-hoc analyses. Safety monitoring will continue in ongoing and future clinical studies and routine pharmacovigilance. TRIAL REGISTRATION: Clinicaltrials.gov NCT01484561. Registered 30 November 2011.
27909834 Effects of maternal health anxiety on children's health complaints, emotional symptoms, an 2017 May Little is known about family risk factors and intergenerational transmission of psychological disturbance in the development of health anxiety (HA). This study investigated HA and related concepts in 8- to 17-year-old children who had been exposed to different maternal health status. Using a family case-control design, three family groups were included: (1) 50 case children of mothers with severe (HA); (2) 49 control children of mothers with rheumatoid arthritis (RA); and (3) 51 control children of healthy mothers. Children and mothers completed a battery of standardised questionnaires. Case children reported significantly higher level of HA symptoms than children of mothers with RA but not compared to children of healthy mothers. There was no significant difference between the children's self-reports in the three groups with regard to anxiety symptoms in general, physical complaints, or quality of life. In contrast, mothers with HA reported their children as having more emotional and physical symptoms than mothers in one or both control groups. Compared to mothers with RA but not healthy mothers, mothers with HA also reported more visits to the general practitioner with their children during the past year. The findings suggest that maternal HA only weakly affects children's own report of HA and thereby may not be a strong risk factor for the development of HA symptoms in childhood. However, mothers with severe HA seem to conceive their children as more ill and present them more often in the health care system which could, therefore, be an important target for intervention in adult patients.
26245941 Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Ex 2015 Dec OBJECTIVE: In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA-protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. METHODS: Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. RESULTS: Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. CONCLUSION: Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA.
26190311 Is it the time to rethink clinical decision-making strategies? From a single clinical outc 2015 Oct There are plenty of different clinical, organizational and economic parameters to consider in order having a complete assessment of the total impact of a pharmaceutical treatment. In the attempt to follow, a holistic approach aimed to provide an evaluation embracing all clinical parameters in order to choose the best treatments, it is necessary to compare and weight multiple criteria. Therefore, a change is required: we need to move from a decision-making context based on the assessment of one single criteria towards a transparent and systematic framework enabling decision makers to assess all relevant parameters simultaneously in order to choose the best treatment to use. In order to apply the MCDA methodology to clinical decision making the best pharmaceutical treatment (or medical devices) to use to treat a specific pathology, we suggest a specific application of the Multiple Criteria Decision Analysis for the purpose, like a Clinical Multi-criteria Decision Assessment CMDA. In CMDA, results from both meta-analysis and observational studies are used by a clinical consensus after attributing weights to specific domains and related parameters. The decision will result from a related comparison of all consequences (i.e., efficacy, safety, adherence, administration route) existing behind the choice to use a specific pharmacological treatment. The match will yield a score (in absolute value) that link each parameter with a specific intervention, and then a final score for each treatment. The higher is the final score; the most appropriate is the intervention to treat disease considering all criteria (domain an parameters). The results will allow the physician to evaluate the best clinical treatment for his patients considering at the same time all relevant criteria such as clinical effectiveness for all parameters and administration route. The use of CMDA model will yield a clear and complete indication of the best pharmaceutical treatment to use for patients, helping physicians to choose drugs with a complete set of information, imputed in the model.
25642720 Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Dis 2015 Human proteins are subjected to more than 200 known post-translational modifications (PTMs) (e.g., phosphorylation, glycosylation, ubiquitination, S-nitrosylation, methylation, Nacetylation, and citrullination) and these PTMs can alter protein structure and function with consequent effects on the multitude of pathways necessary for maintaining the physiological homeostasis. When dysregulated, however, the enzymes that catalyze these PTMs can impact the genesis of countless diseases. In this review, we will focus on protein citrullination, a PTM catalyzed by the Protein Arginine Deiminase (PAD) family of enzymes. Specifically, we will describe the roles of the PADs in both normal human physiology and disease. The development of PAD inhibitors and their efficacy in a variety of autoimmune disorders and cancer will also be discussed.
26669912 Safety and Efficacy of Subcutaneous Golimumab in Patients with Active Rheumatoid Arthritis 2016 Feb OBJECTIVE: To evaluate the safety and efficacy of golimumab (GOL), a human antitumor necrosis factor antibody, in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy through 5 years in the GO-FORWARD trial. METHODS: Patients with active RA despite MTX therapy were randomly assigned to receive placebo + MTX (Group 1), GOL 100 mg + placebo (Group 2), GOL 50 mg + MTX (Group 3), or GOL 100 mg + MTX (Group 4). Patients in groups 1, 2, and 3 with inadequate response could enter early escape at Week 16 to GOL 50 mg + MTX or GOL 100 mg + MTX, and all remaining Group 1 patients crossed over to GOL 50 mg + MTX at Week 24. The blind was maintained through the 52-week database lock, after which treatment adjustments were permitted. Adverse events (AE) were monitored through Week 268. Efficacy was evaluated using the American College of Rheumatology (ACR) 20/50/70 responses and a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP). Response rates at Week 256 were analyzed by an intent-to-treat analysis. RESULTS: A total of 444 patients were randomized, and 313 received GOL through Week 252; 301 patients completed the safety followup through Week 268. Infections were the most common type of AE; 172 patients (39.6%) had ≥ 1 serious AE. No unexpected safety signals were observed. At Week 256, ACR20/50/70 responses were achieved by 63.1%, 40.8%, and 24.1%, respectively, of all randomized patients. About 78% of all patients achieved a good or moderate DAS28-CRP response. CONCLUSION: Improvements in the signs and symptoms of RA were maintained through 5 years. AE through 5 years were consistent with earlier reports of the GO-FORWARD trial; no apparent increased risk was observed over time.
27593732 Patient-Reported Outcomes, Quality of Life, and Satisfaction Rates in Young Patients Aged 2017 Feb BACKGROUND: Recent studies have shown a discrepancy between traditional functional outcomes and patient satisfaction, with some reporting less than 85% satisfaction in older patients undergoing total knee arthroplasty (TKA). As native knee biomechanics are not completely replicated, the resulting functional limitations may cause dissatisfaction in higher-demand individuals. Few studies have recorded patient-reported outcomes, health-related quality of life scores, and patient satisfaction in a young population undergoing TKA. METHODS: One hundred thirty-six primary TKAs were performed in 114 patients aged 50 years or younger (mean age, 47.0 years; range, 30-50 years) at a single institution. The main diagnoses were osteoarthritis (85%) and rheumatoid arthritis (10%). RESULTS: The range of motion, Knee Society Score, Oxford Knee Score, and Physical and Mental Component Scores of Short Form-36 increased significantly (P < .001). At 2 years, 85.3% of patients had good/excellent knee scores, 71.3% had good/excellent function scores, 94.9% met the minimal clinically important difference for the Oxford Knee Score, and 84.6% met the minimal clinically important difference for the Physical Component Score. We found that 88.8% of patients were satisfied with their surgeries, whereas 86.8% had their expectations fulfilled. Survivorship using revision as an end point was 97.8% at a mean of 7 years (range, 3-16 years). CONCLUSION: Patients aged 50 years or younger undergoing TKA can experience significant improvements in their quality of life, have their expectations met, and be satisfied with their surgeries, at rates similar to those of non-age-restricted populations. Surgeons should inform them of these benefits and the potential risk of revision surgery in the future, albeit increasingly shown to be low.
27856781 Parental rheumatoid arthritis and childhood epilepsy: A nationwide cohort study. 2016 Dec 13 OBJECTIVE: To assess the influence of parental rheumatoid arthritis (RA) on risk of epilepsy. METHODS: We performed a nationwide cohort study including all singletons born in Denmark from 1977 to 2008 (n = 1,917,723) through individual linkage to nationwide Danish registries. The children were followed for an average of 16 years. Main outcome measures were adjusted hazard ratios (HRs) for epilepsy with onset in early childhood (29 days-4 years), late childhood (5-15 years), adolescence/adulthood (≥15 years), and at any age until the end of follow-up (December 31, 2010). RESULTS: Compared to unexposed children, children exposed to maternal RA had an increased risk of early and late childhood epilepsy (adjusted HRs 1.34 [95% confidence interval (CI) 1.13-1.60] and 1.26 [95% CI 1.13-1.41]), while children exposed to maternal RA had no increased risk of epilepsy in adolescence/adulthood (HR 1.15 [95% CI 0.92-1.45]). Paternal RA was not associated with an overall risk of epilepsy in the offspring (HR 0.96 [95% CI 0.81-1.15]) or at any age. Children exposed to maternal RA in utero had a more pronounced increased risk of early childhood epilepsy than children exposed to mothers who were diagnosed with RA after childbirth (HR 1.90 [95% CI 1.26-2.86] vs HR 1.26 [95% CI 1.03-1.52], respectively [p = 0.16]). CONCLUSIONS: Exposure to maternal RA was associated with an increased risk of childhood epilepsy, while exposure to paternal RA was not, which indicates that changes in the intrauterine environment may play a role.
25765685 [Osteoclast biology and osteoimmunology]. 2015 The bony skeleton enables the locomotive activity, the storage of calcium, and the harboring of the hematopoietic stem cells from which blood and immune cells are derived. The immune and skeletal systems share various molecules including cytokines, signaling molecules, transcription factors and membrane receptors. Investigation into rheumatoid arthritis (RA) as well as cloning of RANKL and various bone phenotypes found in immune-compromised gene deficient mice has highlighted the importance of the dynamic interplay between the both systems. These findings have recently led to both the emergence and subsequent rapid evolution of the field of osteoimmunology. The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions, the elucidation of which will provide a scientific basis for future therapeutic approaches to diseases related to the immune and skeletal systems.
27558249 The rapid kinetics of optimal treatment with subcutaneous methotrexate in early inflammato 2016 Aug 24 BACKGROUND: Methotrexate (MTX) is standard treatment for RA. Absorption is better in subcutaneous MTX (scMTX), which may impact speed of onset. In RA, earlier time to remission improves long-term results. Our objectives were to determine rapidity of response of subcutaneous methotrexate in early rheumatoid arthritis. METHODS: The change in several disease activity measures (including DAS28) from 0 to 6 weeks (early period) and 6 to 12 weeks (late period) was compared. The proportion achieving DAS28/CDAI/SDAI remission and/or low disease activity state was also compared. RESULTS: One hundred three patients were included from a single site between 2008 and 2014. All received MTX (98.0 % scMTX, 98 % 25 mg/week). There were no dropouts. There was a significantly greater early change in DAS28 (-1.9 vs. -0.2, p < 0.00); this effect was seen for several outcome measures. By 6 weeks, 59 % had achieved either DAS28 remission or low disease activity state, with 74 % achieving either state by 12 weeks. There were a larger proportion of patients achieving CDAI and DAS28 remission in the early versus late period (p < 0.0002 for both). There was significant improvement when using combination MTX and HCQ, however sample size was small (n = 9). The use of intra-articular steroids with MTX yielded the most disease measures that demonstrated early significant improvement. CONCLUSION: Subcutaneous MTX is rapid, as the change in many disease activity scores was significantly greater between 0-6 weeks compared to 6-12 weeks. Combination MTX + HCQ gave added value, although generalizability is limited by combination cohort sample size. Intra-articular steroid injections may contribute to the early effect.
26050104 Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety 2016 Apr The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).
25601914 A cohort incidence study of workers exposed to perfluorooctanoic acid (PFOA). 2015 May OBJECTIVES: Determine if perfluorooctanoic acid (PFOA) is associated with an incident disease in an occupational cohort. METHODS: We interviewed 3713 workers or their next of kin in 2008-2011, and sought medical records for self-reported disease. These workers were a subset of a previously studied cohort of 32,254 community residents and workers. We estimated historical PFOA serum levels via a job-exposure matrix based on over 2000 serum measurements. Non-occupational exposure from drinking water was also estimated. Lifetime serum cumulative dose (combining occupational and non-occupational exposure) was our exposure metric. We studied 17 disease outcomes with more than 20 validated cases. RESULTS: The median measured serum level was 113 ng/mL in 2005 (n=1881), compared with 4 ng/mL in the US. Ulcerative colitis (10-year lag) showed a significant trend (p≤0.05) with increasing dose (quartile rate ratios (RRs)=1.00, 3.00, 3.26, 6.57, n=28, p for trend=0.05), similar to earlier findings in the community study. Rheumatoid arthritis (no lag) showed a positive trend in a categorical trend test (RRs=1.00, 2.11, 4.08, 4.45, n=23, p for trend=0.04). Positive non-significant trends were also observed for prostate cancer, non-hepatitis liver disease and male hypothyroidism, which have been implicated in other studies. A significant negative trend was found for bladder cancer and asthma with medication. No marked trends were seen for high cholesterol, which had been seen in the community study. CONCLUSIONS: Ulcerative colitis and rheumatoid arthritis were positively linked to PFOA exposure among workers. Data were limited by small numbers, under-representation of hard-to-trace decedents and few low-exposed referents.
27692433 Moderating effects of immunosuppressive medications and risk factors for post-operative jo 2017 Feb OBJECTIVE: Inconclusive findings about infection risks, importantly the use of immunosuppressive medications in patients who have undergone large-joint total joint arthroplasty, challenge efforts to provide evidence-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a post-operative infection in patients undergoing TJA of a large joint (total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical and demographic factors, including the use of high-risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses [i.e., rheumatoid arthritis (RA), osteoarthritis (OA), gout, obesity, and diabetes mellitus] that are linked to infection status, controlling for length of follow-up. METHODS: A retrospective, case-control study (N = 2212) using de-identified patient health claims information from a commercially insured, U.S. dataset representing 15 million patients annually (from January 1, 2007 to December 31, 2009) was conducted. Descriptive statistics, t-test, chi-square test, Fisher's exact test, and multivariate logistic regression were used. RESULTS: Male gender (OR = 1.42, p < 0.001), diagnosis of RA (OR = 1.47, p = 0.031), diabetes mellitus (OR = 1.38, p = 0.001), obesity (OR = 1.66, p < 0.001) or gout (OR = 1.95, p = 0.001), and a prescription for prednisone (OR = 1.59, p < 0.001) predicted a post-operative infection following total joint arthroplasty. Persons with post-operative joint infections were significantly more likely to be prescribed allopurinol (p = 0.002) and colchicine (p = 0.006); no significant difference was found for the use of specific disease-modifying anti-rheumatic drugs and TNF-α inhibitors. CONCLUSION: High-risk, post-operative joint infection groups were identified allowing for precautionary clinical measures to be taken.
25853812 Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia synd 2015 BACKGROUND: Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA. METHODS: Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed. RESULTS: There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS. CONCLUSIONS: Combined with the currently available diagnostic procedures and criteria, analysis of MAIT cells offers a more objective standard for the diagnosis of FMS, RA, and SpA, which exhibit multifaceted and confusingly similar clinical manifestations.
26879362 Effect of Rheumatoid Arthritis on Longterm Sickness Absence in 1994-2011: A Danish Cohort 2016 Apr OBJECTIVE: By linkage of national registries, we investigated the risk of longterm sickness absence (LTSA) ≥ 3 weeks in a large cohort of Danish patients with rheumatoid arthritis (RA) and non-patients. The study aimed to (1) estimate the risk of LTSA for patients with RA compared with the general population, (2) examine whether the risk of LTSA has changed in recent years, and (3) evaluate the effect of other risk factors for LTSA (e.g., physical work demands, age, sex, education, and psychiatric and somatic comorbidities). METHODS: A total of 6677 patients with RA aged 18-59 years in the years 1994-2011 were identified in registries and compared with 56,955 controls from the general population matched by age, sex, and city size. The risk of LTSA was analyzed using Cox proportional hazards models with late entry, controlling for other risk factors and assuming separate risks in the first year after diagnosis and the following years. RESULTS: Compared with the general population, patients with RA had increased risk of LTSA in the first year after diagnosis (HR 5.4 during 1994-1999, 95% CI 4.2-6.8) and in following years (HR 2.4, 95% CI 2.1-2.8). For established RA (> 1 yr after diagnosis), the excess was 20% lower in 2006-2011 (HR 1.9, 95% CI 1.7-2.2) compared with 1994-1999 (p < 0.001). For patients with RA and controls, older age, shorter education, a physically demanding job, and somatic and/or psychiatric comorbidities increased the risk of LTSA. CONCLUSION: While improvements were observed from 1994-1999 to 2006-2011, patients with RA have significant increased risk of LTSA, in particular in the first year after diagnosis.
25900366 Clinical and radiological results of a cementless short stem shoulder prosthesis at minimu 2015 Jul PURPOSE: Uncemented short stem shoulder arthroplasty combines the advantages of a bone-saving implantation with a straightforward revision option. Uncemented humeral long stems can be associated with stress shielding and loosening. Therefore, we analysed the clinical and radiological outcome of a short stem shoulder prosthesis with metaphyseal fixation. METHODS: This two-centre study included 82 total shoulder arthroplasties in 80 patients with short stem shoulder prosthesis and a cemented polyethylene glenoid performed between 2010 and 2012. Sixty-eight shoulders had primary osteoarthritis, eight shoulders had post traumatic sequelae and six had other diagnoses. Minimum follow-up was two years. Outcome data included the Constant Score (CS), Subjective Shoulder Value (SSV), Pain Scale (0-15) and range of motion. Radiographic evaluation was done in shoulders with primary osteoarthritis in a standard view. RESULTS: The mean clinical and radiological follow-up was 31.2 ± 7.2 months (20-52). CS improved from 36.7 ± 15.2 % to 90.4 ± 16.4% and SSV improved from 39.4 ± 15.5 points to 85.5 ± 13.2 points (p < 0.0001). Pain was rated as mild or none in 76 shoulders (92.7%) with a mean value of 13.2 ± 2.6. The mean active flexion was 157.0 ± 24.7°, abduction was 152.6 ± 29.1° and the active external rotation was 38.2 ± 14.8° at recent follow-up. Radiographic assessment was done in 44 shoulders. Six shoulders (13.6%) showed features of slight stress shielding at the medial cortex and no stem with subsidence was found. Three glenoids (6.8%) had minor radiolucent lines. CONCLUSIONS: Uncemented short stem shoulder arthroplasty with a cemented polyethylene glenoid can yield a stable fixation with a good clinical outcome at minimum follow-up of two years.
26411696 Functionally active NKG2A-expressing natural killer cells are elevated in rheumatoid arthr 2015 Nov OBJECTIVES: Natural killer cell receptors (NKR) have been implicated in rheumatoid (RA) and psoriatic arthritis (PsA) pathogenesis. To gain more insight into their role, we characterised NKR (co-)expression patterns on NK and T cells and NK cell function in RA and PsA. METHODS: The frequency of NK and T cells expressing killer like immunoglobulin (KIR) and NKG2 receptors and natural cytotoxicity receptors was assessed by 10-colour flow cytometry in peripheral blood of 23 RA, 12 PsA patients and 18 healthy donors (HD). NK cell cytotoxicity and IFN-gamma production was assessed in 8 RA patients and 8 HD. RESULTS: In RA but not PsA, the frequency of NK cells (median; range) expressing NKG2A (42%; 14-81%) was elevated compared to HD (23%; 9-58%). NKG2A⁺ NK cells predominantly lack KIR, but display normal cytotoxicity and IFN-γ production. In contrast, RA patients with normal NKG2A⁺ NK cell frequency have less functional NK cells compared to HD. T cells expressing Fc-gamma receptor CD16 were elevated in RA (median 0.75%) versus HD (0.3%). Furthermore, T cells expressing the KIRs CD158ah in both RA (0.7%) and PsA (0.3%), and CD158e1e2 in RA (1.5%) were elevated compared to HD (0.2% and 0.4%, respectively). In RA, CD4⁺ T cells expressing the KIRs CD158ah, CD158b1b2j and CD158e1e2 were low (<2%) but significantly elevated compared to HD. CONCLUSIONS: This study demonstrates the presence of an elevated, functionally active NKG2A⁺ KIR- NK cell population in RA. Together with an elevated frequency of NKR-expressing T cells, these changes may reflect differential pathogenetic involvement.