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ID PMID Title PublicationDate abstract
26702616 Autophagy induction contributes to the resistance to methotrexate treatment in rheumatoid 2015 Dec 23 BACKGROUND: Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) show resistance to methotrexate (MTX) treatment. To better understand the mechanisms of this resistance, RA-FLS and osteoarthritis fibroblast-like synovial cells (OA-FLS) were isolated and exposed to MTX. We analyzed the autophagy induced by MTX in vitro and its relationship to apoptosis. METHODS: Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis was detected by flow cytometry and Western blot analysis. Autophagy was determined by transmission electron microscopy as well as Western blot analysis. The expression levels of Beclin-1, LC3, Akt, p-Akt, mammalian target of rapamycin (mTOR), p-mTOR, high mobility group box chromosomal protein 1 (HMGB1), and an 85 kDa caspase cleaved fragment of poly(ADP-ribose) polymerase were measured by Western blotting. RESULTS: MTX-induced apoptosis was increased in OA-FLS compared with RA-FLS. However, MTX stimulated the autophagy response in RA-FLS by inducing autophagosome formation, but not in OA-FLS. In RA-FLS, transfection with Beclin-1 small interfering RNA inhibited autophagy and increased susceptibility to MTX, which induces cell death. MTX upregulated autophagy through its ability to enhance the expression of HMGB1 and Beclin-1 rather than through the Akt/mTOR pathway. CONCLUSIONS: Autophagy induction contributes to resistance to MTX treatment in fibroblasts from patients with rheumatoid arthritis.
27645315 Lymph node biopsy analysis reveals an altered immunoregulatory balance already during the 2016 Dec The balance between proinflammatory and regulatory CD4(+) T cells is tightly controlled in lymphoid organs. In autoimmune diseases this balance is altered in the periphery and target tissue of patients. However, not much is known about the balance initiated in lymphoid organs during the development of disease. Since systemic autoimmunity is present years before the clinical manifestations of rheumatoid arthritis (RA), it is possible to study the immunoregulatory balance during the earliest (preclinical) phases of disease. Here, we report for the first time the frequency and phenotype of proinflammatory and regulatory CD4(+) T cells in lymph node biopsies obtained from autoantibody positive individuals at risk for developing RA, patients with established disease and healthy controls. The frequency of proinflammatory LN Th1 cells was increased in RA patients compared with HCs, while the frequency of regulatory T cells was lower in LN biopsies of RA-risk individuals. Upon in vitro stimulation LN CD4(+) T cells produced lower levels of proinflammatory cytokines, IFN-γ and IL-17A, in both RA-risk individuals and early RA patients. This study shows that already during the earliest phases of systemic autoimmunity the immunoregulatory balance between proinflammatory and regulatory CD4(+) T cells is altered in LN tissue.
26119758 A visible light induced photoelectrochemical aptsensor constructed by aligned ZnO@CdTe cor 2015 Dec 15 It was reported that Proprotein convertase subtilisin/kexin type 6 (PCSK6) can promote the progression of rheumatoid arthritis to a higher aggressive status. In this work, a novel visible light induced photoelectrochemical (PEC) platform was designed to detect PCSK6 gene. ZnO@CdTe nanocable arrays/carboxylated g-C3N4 used as the PEC signal generator. Hexagonal ZnO nanorods grew on ITO electrode firstly. CdTe were then electrodeposited on the ZnO nanorods surface to enhance the photogenerated h(+)/e(-) separation efficiency. Carboxylated g-C3N4 was utilized to improve h(+)/e(-) separation efficiency and anchor the capture probes of PCSK6 gene by the covalent bonding effect. The 5' and 3' primers captured PCSK6 ssDNA by the specific recognition. The linear range was 10 pg/mL to 20.0 ng/mL with a detection limit of 2 pg/mL.
27145816 Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage 2016 May 4 BACKGROUND: Inflammation is an essential component of arthritis pain. Nerve growth factor (NGF) plays a key role in acute and chronic pain states especially those associated with inflammation. NGF acts through tropomyosin-receptor-kinase A (TrkA). NGF blockade has reduced arthritis pain in clinical trials. We explored the mechanisms within the joint which may contribute to the analgesic effects of NGF by selectively inhibiting TrkA in carrageenan-induced or collagen-induced joint pain behaviour. The goal of the current study was to elucidate whether inflammation is central to the efficacy for NGF blockade. METHODS: Rats were injected in their left knees with 2 % carrageenan or saline. Collagen-induced arthritis (CIA) was induced by intradermal injections of a mixture of bovine type II collagen (0.2 mg) and incomplete Freund's adjuvant (0.2 mg). Oral doses (30 mg/kg) of AR786 or vehicle control were given twice daily after arthritis induction. Ibuprofen-treated (35 mg/kg, orally, once daily) rats with CIA were used as positive analgesic controls. Pain behaviour was measured as hind-limb weight-bearing asymmetry and hind-paw withdrawal thresholds to von Frey hair stimulation (carrageenan synovitis), or withdrawal to joint compression using a Randall Selitto device (CIA). Inflammation was measured as increased knee joint diameter and by histopathological analysis. RESULTS: Intra-articular injections of carrageenan or induction of CIA was each associated with pain behaviour and synovial inflammation. Systemic administration of the TrkA inhibitor AR786 reduced carrageenan-induced or CIA-induced pain behaviour to control values, and inhibited joint swelling and histological evidence of synovial inflammation and joint damage. CONCLUSIONS: By using two models of varying inflammation we demonstrate for the first time that selective inhibition of TrkA may reduce carrageenan-induced or CIA-induced pain behaviour in rats, in part through potentially inhibiting synovial inflammation, although direct effects on sensory nerves are also likely. Our observations suggest that inflammatory arthritis causes pain and the presence of inflammation is fundamental to the beneficial effects (reduction in pain and pathology) of NGF blockade. Further research should determine whether TrkA inhibition may ameliorate human inflammatory arthritis.
27455991 Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases. 2016 Aug Etanercept (SB4) [Benepali(®)], a tumour necrosis factor inhibitor that is a biosimilar of reference etanercept (Enbrel(®)), is approved in the EU for use in all adult indications for which reference etanercept is approved, namely rheumatoid arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), psoriatic arthritis, and plaque psoriasis. The approval of etanercept (SB4) was based on the results of stringent comparability exercises designed to demonstrate similarity to reference etanercept in terms of quality, biological activity, efficacy, safety, and immunogenicity. In two well-designed clinical trials, etanercept (SB4) was equivalent to reference etanercept with regard to pharmacokinetic properties in healthy volunteers and in terms of efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Longer-term efficacy (up to 52 weeks) was also similar in both treatment groups. Etanercept (SB4) was generally well tolerated, with a similar safety profile to that of reference etanercept. Preliminary results of the open-label extension period (100 weeks) suggest that transitioning from reference etanercept to etanercept (SB4) was associated with sustained efficacy and no change in the adverse event profile or immunogenicity. In conclusion, etanercept (SB4) provides therapeutically equivalent alternative in adult patients with autoimmune inflammatory diseases requiring treatment with etanercept.
25873635 Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in 2015 Aug OBJECTIVES: Randomised, double-blind, placebo-controlled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR). METHODS: 1041 patients with moderate-severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks. RESULTS: There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were reported in the 90/Q2W group (2.3%, 4.3%, 2.3%). CONCLUSIONS: Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy. TRIAL REGISTRATION NUMBER: NCT01198002.
27558384 Outcome of balloon kyphoplasty for the treatment of osteoporotic vertebral compression fra 2016 Aug 24 BACKGROUND: Osteoporosis and osteoporotic fractures are widely known as complications of rheumatoid arthritis. Kyphoplasty (KP) is known as an effective treatment modality for reducing pain and correcting kyphotic deformity in osteoporotic vertebral compression fracture (OVCF). However, cutcomes of KP in rheumatoid patients are not well known. The purpose of the study was to investigate the clinical and radiological outcomes of balloon KP on OVCF in patients with rheumatoid arthritis. METHODS: A total of 23 patients (31 vertebral bodies) with rheumatoid arthritis who received KP for OVCF and could be followed up for at least 1 year were examined. For clinical outcomes, visual analogue scale (VAS) and the Korean version of the Oswestry disability index (KODI) were evaluated. For radiological outcomes, changes in anterior vertebral height and local kyphotic angle were measured, alongside cement leakage, adjacent fracture, and the recollapse of cemented vertebra. RESULTS: The anterior vertebral height was significantly restored after surgery compared with prior to surgery (p < 0.001). Cement leakage was found in 14 cases (45.1 %), and disc space leakage was prevalent (50 %), while vascular cement leakage was found in one case. Adjacent fracture was found in 3 patients (11.5 %). VAS for lumbago showed a significant decrease (p < 0.001) after surgery (VAS = 2.4) compared with that before (VAS = 8.1); it was somewhat increased after the 1-year follow-up (VAS = 2.8; p = 0.223). KODI also decreased (48.8 %) after surgery compared with before (84.6 %). However, it increased somewhat (49.9 %) after the 1-year follow-up. CONCLUSION: KP on rheumatoid arthritis patients for OVCF was effective for reducing pain in the early stage and restoring vertebral body height. Recollapse of the treated vertebral body was found relatively frequently alongside the correction loss of local kyphotic angle.
25973110 Epstein-Barr virus-positive multiple myeloma developing after immunosuppressant therapy fo 2015 A 61-year-old woman was diagnosed as having rheumatoid arthritis (RA) and began treatment with salazosulfapyridine (SASP) and methotrexate (MTX) in 2008; the administration of concomitant tacrolimus (TAC) was initiated in 2010. She subsequently developed concurrent multiple myeloma (MM), immunoglobulin G (IgG)-κ type, in 2012. A portion of the tumor cells tested positive for Epstein-Barr virus-encoded small RNA (EBER). MTX treatment was discontinued in 2014, and the exacerbation of MM ensued. The patient received two cycles of bortezomib plus dexamethasone (BD) therapy and attained a complete response (CR). She then underwent an autologous peripheral blood stem cell transplantation. The Epstein-Barr (EB) virus infection arising from the increased RA disease activity and immunosuppressant medication might have influenced the development of MM in this case. Most reported patients with EB virus-positive plasmacytoma are in a state of immunosuppression, and this condition may fall within the category of other iatrogenic immunodeficiency-associated lymphoproliferative disorders. No other reports of plasmacytoma occurring in a background of RA or after TAC or MTX therapy have been made, and the present case is the first such report.
26384029 Safety and retention of combination triple disease-modifying anti-rheumatic drugs in new-o 2015 Dec BACKGROUND: While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) ('triple therapy') has been shown in clinical trials, few studies have examined its longevity in a real-life setting. AIM: Our aim was to assess the tolerability, longevity and efficacy of a triple disease-modifying anti-rheumatic drug (DMARD) regimen initiated in new-onset rheumatoid arthritis (RA) patients. METHODS: Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response-driven step-up algorithm, which included progression to leflunomide (LEF) or a biologic agent. RESULTS: Of 181 new-onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three-DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three-drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA). CONCLUSIONS: Triple therapy in new-onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.
26784571 Trajectories of Physical Activity Over Two Years in Persons With Rheumatoid Arthritis. 2016 Aug OBJECTIVE: To identify and describe different trajectories of physical activity over 2 years and to identify baseline predictors for each trajectory within a large cohort of people with rheumatoid arthritis (RA). METHODS: The sample included 2,752 people ages 18-75 years and independent in daily living. Data on sociodemographic, disease-related, and psychosocial variables and physical activity (total weekly hours of vigorously/moderately intense activity and walking) were collected from registers and by questionnaires at baseline, and at 14 and 26 months. K-means cluster analysis was used to identify different physical activity trajectories. Multinomial logistic regression was used to identify predictors of trajectory membership. RESULTS: Three trajectories were identified: 1 stable high (n = 272; with an average of 25 hours of physical activity/week), 1 decreasing (n = 564; changing from 22 to 8 hours), and 1 stable low (n = 1,916; with an average of 3 hours). Predictors of the stable high trajectory versus the other 2 were male sex and already established physical activity at baseline. Predictors of the stable high trajectory versus decreasing trajectory were lower age and less social support for exercise, while predictors of stable high versus the stable low trajectory were less activity limitation and higher exercise self-efficacy. CONCLUSION: The results indicate that distinct trajectories of physical activity over 2 years in people with RA exist, and that stable, high physical activity is mainly predicted by male sex and already established physical activity at baseline. Additional predictors, amenable to change, include activity limitation, social support, and self-efficacy for exercise, suggesting a wide perspective on maintained physical activity in RA.
24948375 Work instability in rheumatoid arthritis patients from Argentina: prevalence and associate 2015 Jan To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.
26420546 Decreased Serotonin Levels and Serotonin-Mediated Osteoblastic Inhibitory Signaling in Pat 2016 Mar Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone-forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast-like Saos-2 cells. Serotonin levels are low in patients with AS and decrease even further during anti-TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be involved in new bone formation in AS.
27064875 Monocyte chemoattractant protein-1 promoter -2518 polymorphism and susceptibility to vascu 2016 Mar 20 The purpose of this study was to examine whether the monocyte chemoattractant protein-1 (MCP-1) promoter -2518 A/G polymorphism (rs1024611) is associated with susceptibility to vasculitis, rheumatoid arthritis (RA), or multiple sclerosis (MS). A meta-analysis was conducted on the association between the MCP-1 -2518 A/G polymorphism and vasculitis, RA, and MS. Fourteen studies from 13 articles, including six on vasculitis, five on RA, and three on MS, consisting of 3,038 patients and 3,545 controls were available for the meta-analysis. The meta-analysis revealed no association between the MCP-1 -2518 G allele and vasculitis (odds ratio [OR] = 0.990, 95% confidence interval [CI] = 0.749-1.309, p = 0.943). Stratification by ethnicity indicated no association between the G allele of the MCP-1 -2518 A/G polymorphism and vasculitis in Asians and Caucasians. Meta-analysis by vasculitis type revealed an association between the GG+GA genotype of the MCP-1 -2518 A/G polymorphism and Behçet's disease (BD; OR = 1.349, 95% CI = 1.013-1.796, p = 0.040). However, sensitivity analysis showed that the association was not statistically significant after removing a study that was conducted in China (OR = 1.030, 95% CI = 0.667-1.590, p = 0.895), which indicated that the association was not statistically robust. The meta-analysis revealed no association between the MCP-1 -2518 G allele and RA (OR = 0.986, 95% CI = 0.890-1.093, p = 0.793) or MS (OR = 1.281, 95% CI = 0.802-2.046, p = 0.301). Our meta-analysis demonstrates that the MCP-1 -2518 A/G polymorphism is not associated with susceptibility to vasculitis, RA, or MS.
27109738 High-resolution (18)F-FDG PET/CT for assessing disease activity in rheumatoid and psoriati 2016 Jul OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) commonly affect the small joints of the wrist and hand. We evaluated the performance of a new, high-resolution extremity positron emission tomography (PET)/CT scanner for characterizing and quantifying pathologies associated with the two arthritides in the wrist and hand joints. METHODS: Patients with RA or PsA underwent fluorine-18 fludeoxyglucose ((18)F-FDG) PET/CT wrist and hand imaging, respectively, on the high-resolution scanner. Calibrated CT images and co-registered PET images were reconstructed. PET/CT was derived for the radiocarpal and pisiform-triquetral compartments, joints with erosive changes, sites of synovitis or tenosynovitis and the nail bed and were correlated with clinical and MRI findings. RESULTS: Significantly elevated (18)F-FDG uptake was measured for the radiocarpal and pisiform-triquetral compartments and at sites of bone erosion, synovitis, pannus and oedema, compared with unaffected joints (p < 0.05) in patients with RA, consistent with their clinical findings. In patients with PsA, significantly elevated (18)F-FDG uptake was measured for joints with synovitis compared with unaffected joints (p < 0.05), with patterns of (18)F-FDG uptake along the tendons, at the enthesis and in the nail bed, consistent with tenosynovitis, enthesitis and nail dystrophy, respectively. CONCLUSION: High-resolution (18)F-FDG PET/CT imaging of the wrist and hand is feasible in an RA or PsA patient cohort and is capable of providing quantifiable measures of disease activity (synovitis, enthesitis, oedema and bone destruction). ADVANCES IN KNOWLEDGE: High-resolution PET/CT imaging shows promise as a tool for understanding the pathogenesis of the arthritic process and for non-invasive, objective assessment of RA or PsA severity and therapy selection.
27334658 Switching from adalimumab to tofacitinib in the treatment of patients with rheumatoid arth 2016 Jun 23 BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The aim of this study was to explore the safety and efficacy of open-label tofacitinib following blinded treatment with adalimumab or tofacitinib for moderate to severe RA. METHODS: Analyses included patients treated with adalimumab 40 mg once every 2 weeks or tofacitinib 10 mg twice daily (BID) with background methotrexate (MTX) in a 12-month randomized study (NCT00853385), who subsequently received tofacitinib 10 mg BID (with/without background MTX) in an open-label extension (NCT00413699). Patients with treatment-related serious adverse events (AEs) and serious or recurrent infections in the index study were excluded from the extension study. Exposure-adjusted incidence rates of safety-related events were assessed in 3-month and 12-month periods in the year before and in the year after switching. Efficacy was assessed 3 months before, at the time of, and 3 months after switching. RESULTS: There were 233 (107 adalimumab to tofacitinib 10 mg BID, 126 blinded to open-label tofacitinib 10 mg BID) patients included in these analyses. Patients in both treatment sequences had similar incidence rates (per 100 patient-years) of discontinuation due to AEs, serious AEs, and serious infections in the year before and in the year after switching. Incidence rates of AEs were increased in the first 3 months after switching compared with the last 3 months before switching in both treatment groups. Switching from either blinded adalimumab or tofacitinib to open-label tofacitinib resulted in numerically higher incidence of responders for signs and symptoms of disease and improved physical function. CONCLUSIONS: Treatment can be directly switched from adalimumab to tofacitinib. A similar safety and efficacy profile was seen when patients received open-label tofacitinib after receiving either blinded adalimumab or tofacitinib. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00853385 , registered 27 February 2009; NCT00413699 , registered 18 December 2006.
25449590 No difference in clinical and radiologic outcomes after total knee arthroplasty with a new 2015 Mar We retrospectively compared the clinical and radiographic results between 76 primary total knee arthroplasties (TKAs) using the e.motion Ultra-Congruent prosthesis and 155 primary TKAs using the Low Contact Stress rotating platform. All patients had a minimum 5-year follow-up. Range of motion, Hospital for Special Surgery score, Knee Society Knee Score and Knee Society Functional Score significantly increased in both groups postoperatively, but there was no significant difference between the two groups. The mechanical femorotibial angle improved in both groups postoperatively. Coronal and sagittal component angles were well maintained at the final follow-up. This study demonstrates that a new mobile-bearing prosthesis, designed to be highly congruent with a rotating bearing, could be considered with theoretical advantages and comparable outcomes of established mobile-bearing prostheses.
25387721 Operative efficiency and accuracy of patient-specific cutting guides in total knee replace 2015 Jun BACKGROUND: Total knee replacement (TKR) outcomes depend on accurate positioning of implants and restoration of the mechanical axis of the knee. Compared with standard techniques, patient-specific cutting guides are postulated to improve accuracy of bone resections, and therefore implant placement. Furthermore, patient-specific cutting guides are postulated to reduce operative time and increase efficiency by reducing the number of trays used. METHODS: This study evaluates these claims using the Visionaire (Smith & Nephew, Inc., Memphis, TN, USA) patient-specific system. The thickness of actual bone resections was compared with the predicted thickness (giving a resection 'error'). Data were also obtained on the number of trays used, skin-to-skin operating time and tourniquet time. RESULTS: Forty-one TKRs were performed on 33 females (one bilateral) and seven males. Average resection errors were 0.22 mm medially and 0.05 mm laterally for the distal femur, 0.99 mm medially and 0.74 mm laterally for posterior femoral condyles, and 0.55 mm medially and 0.71 mm laterally for the proximal tibia. There were no significant differences in tourniquet time, skin-to-skin time or the number of trays used between the patient-specific and historical comparison groups. CONCLUSION: Patient-specific cutting guides make accurate resections. Operative and tourniquet times and the number of trays used were no different to standard TKRs. Further investigation is needed to determine whether patient-specific cutting guides improve post-operative alignment and patient satisfaction.
27965984 IL-6 Promotes Islet β-Cell Dysfunction in Rat Collagen-Induced Arthritis. 2016 The aim of this study was to explore the possible mechanism of rheumatoid arthritis- (RA-) related abnormal glucose metabolism. The model of collagen-induced arthritis (CIA) was established by intradermal injection of type II collagen into Wistar rats; complete Freund's adjuvant injections were used as the control group. Fasting plasma glucose (FBG) was measured by the glucose oxidase method. Fasting insulin (FIns) and the expressions of IL-6 were detected by ELISA. Islet caspase-3 was examined by immunohistochemistry. On day 17 after immunization, FBG of the CIA group showed an elevated FBG value compared with the control group. Meanwhile, the FIns of group CIA was lower when compared with the control group. Interestingly, the inflammatory cytokine IL-6 expression was significantly increased when compared with the control group. As expected, the abnormal glucose metabolism was accompanied by the increased IL-6 expression. Furthermore, in line with the upregulated IL-6 expression, the apoptosis related enzyme caspase-3 was also markedly increased. These data showed that the elevated FBG in CIA may be associated with the reduced FIns level secondary to the overapoptosis of pancreas islet cells induced by IL-6.
26059223 Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using p 2015 Jun 10 INTRODUCTION: We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA). METHODS: The autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC® system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP)2 using the CCPlus® ELISA kit. RESULTS: Two peptides derived from the fibrinogen α chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen β chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65%, 15%, 35%, and 53% of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5% (Cit573), 6% (Cit591), 8% (Cit72), and 4% (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84% and 63% respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency. CONCLUSIONS: Here we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.
25788417 Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health. 2015 Mar 19 There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity.