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ID PMID Title PublicationDate abstract
29146547 A gene module associated with dysregulated TCR signaling pathways in CD4(+) T cell subsets 2018 May We analyzed the transcriptome of detailed CD4(+) T cell subsets including them after abatacept treatment, and examined the difference among CD4(+) T cell subsets and identified gene sets that are closely associated disease activity and abatacept treatment. Seven CD4(+) T cell subsets (naive, Th1, Th17, Th1/17, nonTh1/17, Tfh and Treg) were sorted from PBMCs taken from 10 RA patients and 10 healthy controls, and three RA patients donated samples before and 6 months after abatacept treatment. Paired-end RNA sequencing was performed using HiSeq 2500. A total of 149 samples except for 12 outliers were analyzed. Overview of expression pattern of RA revealed that administration of abatacept exerts a large shift toward the expression pattern of HC. Most of differentially expressed gene (DEG) upregulated in RA (n = 1776) were downregulated with abatacept treatment (n = 1349). Inversely, most of DEG downregulated in RA (n = 1860) were upregulated with abatacept treatment (n = 1294). This DEG-based analysis revealed shared pathway changes in RA CD4(+) T cell subsets. Knowledge-based pathway analysis revealed the upregulation of activation-related pathways in RA that was substantially ameliorated by abatacept. Weighted gene co-expression network analysis (WGCNA) evaluated CD4(+) T cells collectively and identified a gene module that consisted of 227 genes and was correlated with DAS28-CRP (Spearman's rho = 0.46, p = 4 × 10(-9)) and abatacept administration (Spearman's rho = -0.91, p = 5 × 10(-57)). The most highly connected 30 genes of this module included ZAP70 and JAK3, and pathway analysis of this module revealed dysregulation of the TCR signaling pathway network, which was ameliorated by abatacept.
30136129 Association of CD26/dipeptidyl peptidase IV mRNA level in peripheral blood mononuclear cel 2018 Dec Dipeptidyl peptidase IV (DPP-IV, CD26) plays many roles in the pathogenesis of several autoimmune and inflammatory diseases. The current study evaluated the association of DPP-IV enzymatic activity and its gene expression with disease activity and bone erosion in rheumatoid arthritis. Blood samples were collected from 20 rheumatoid arthritis patients and 40 healthy volunteers. Patients were divided into four subgroups using DAS28 index. CD26 gene expression levels were analyzed in peripheral blood mononuclear cells by quantitative reverse transcription-polymerase chain reaction. Additionally, the enzymatic activity of this molecule in serum was determined using Gly-Pro-p-nitroanilide as substrate. Digital radiography was applied to obtain images for bone erosion assessment. No significant difference in serum DPP-IV activity level was seen between patients and controls (p = 0.140). However, patients exhibited an increase in CD26 mRNA expression (1.68 times) when compared to controls (p = 0.001). Moreover, a strong positive correlation between CD26 gene expression and DAS28 index as well as bone erosion in the hands was observed (r = 0.71, p = 0.002 and r = 0.61, p = 0.049, respectively). This study demonstrated that CD26 mRNA expression in rheumatoid arthritis patients is associated with disease activity and bone erosion, suggesting a potential role for this molecule in the immunopathology of rheumatoid arthritis and bone erosion.
29901815 Exposure-Response Modeling Analyses for Sirukumab, a Human Monoclonal Antibody Targeting I 2018 Nov To characterize the dose-exposure-response relationship of sirukumab, an anti-interleukin 6 human monoclonal antibody, in the treatment of moderately to severely active rheumatoid arthritis (RA), we conducted exposure-response (E-R) modeling analyses based on data from two pivotal phase 3 placebo-controlled trials of sirukumab in patients with RA who were inadequate responders to nonbiologic disease-modifying antirheumatic drugs or anti-tumor necrosis factor α agents. A total of 2176 patients were included for the analyses and received subcutaneous administration of either placebo or sirukumab 50 mg every 4 weeks or 100 mg every 2 weeks. The clinical endpoints were 20%, 50%, and 70% improvement in the American College of Rheumatology response criteria (ie, ACR20, ACR50, and ACR70), and 28-joint Disease Activity Index Score (DAS28) using C-reactive protein. To provide a thorough assessment of the sirukumab E-R relationship, 2 pharmacokinetic/pharmacodynamic modeling approaches were implemented, including joint longitudinal modeling (ie, indirect response modeling of the time course of the 2 clinical endpoints) and landmark analyses (ie, direct linking of selected pharmacokinetic parameters to response at week 16 or 24). Results from both modeling analyses were generally consistent, and collectively suggested that the sirukumab subcutaneous dose of 50 mg every 4 weeks would produce near-maximal efficacy. No covariates identified in the E-R modeling analyses would have a significant impact on dose-response. Despite body weight and comorbid diabetes having significant effect on sirukumab exposure, simulations suggested that their effect on efficacy was small. Our work provides a comprehensive evaluation of sirukumab E-R to support dose recommendations in patients with RA.
29625181 Hyaluronan in immune dysregulation and autoimmune diseases. 2019 May The tissue microenvironment contributes to local immunity and to the pathogenesis of autoimmune diseases - a diverse set of conditions characterized by sterile inflammation, immunity against self-antigens, and destruction of tissues. However, the specific factors within the tissue microenvironment that contribute to local immune dysregulation in autoimmunity are poorly understood. One particular tissue component implicated in multiple autoimmune diseases is hyaluronan (HA), an extracellular matrix (ECM) polymer. HA is abundant in settings of chronic inflammation and contributes to lymphocyte activation, polarization, and migration. Here, we first describe what is known about the size, amount, and distribution of HA at sites of autoimmunity and in associated lymphoid structures in type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. Next, we examine the recent literature on HA and its impact on adaptive immunity, particularly in regards to the biology of lymphocytes and Foxp3+ regulatory T-cells (Treg), a T-cell subset that maintains immune tolerance in healthy individuals. We propose that HA accumulation at sites of chronic inflammation creates a permissive environment for autoimmunity, characterized by CD44-mediated inhibition of Treg expansion. Finally, we address potential tools and strategies for targeting HA and its receptor CD44 in chronic inflammation and autoimmunity.
29388039 Molecular assembly of recombinant chicken type II collagen in the yeast Pichia pastoris. 2018 Jul Effective treatment of rheumatoid arthritis can be mediated by native chicken type II collagen (nCCII), recombinant peptide containing nCCII tolerogenic epitopes (CTEs), or a therapeutic DNA vaccine encoding the full-length CCOL2A1 cDNA. As recombinant CCII (rCCII) might avoid potential pathogenic virus contamination during nCCII preparation or chromosomal integration and oncogene activation associated with DNA vaccines, here we evaluated the importance of propeptide and telopeptide domains on rCCII triple helix molecular assembly. We constructed pC- and pN-procollagen (without N- or C-propeptides, respectively) as well as CTEs located in the triple helical domain lacking both propeptides and telopeptides, and expressed these in yeast Pichia pastoris host strain GS115 (his4, Mut(+)) simultaneously with recombinant chicken prolyl-4-hydroxylase α and β subunits. Both pC- and pN-procollagen monomers accumulated inside P. pastoris cells, whereas CTE was assembled into homotrimers with stable conformation and secreted into the supernatants, suggesting that the large molecular weight pC-or pN-procollagens were retained within the endoplasmic reticulum whereas the smaller CTEs proceeded through the secretory pathway. Furthermore, resulting recombinant chicken type II collagen pCα1(II) can induced collagen-induced arthritis (CIA) rat model, which seems to be as effective as the current standard nCCII. Notably, protease digestion assays showed that rCCII could assemble in the absence of C- and N-propeptides or telopeptides. These findings provide new insights into the minimal structural requirements for rCCII expression and folding.
28288508 Isoniazid treatment for latent tuberculosis infection is tolerable for rheumatoid arthriti 2018 Sep BACKGROUND/AIMS: To evaluate the impact of isoniazid (INH) treatment for latent tuberculosis infection (LTBI) on the development of liver function test (LFT) abnormality and the persistence of tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients. METHODS: We retrospectively enrolled patients with RA who were treated with TNF inhibitors at a university hospital between December 2000 and November 2011. After dividing the patients into two groups based on the occurrence of LFT abnormality during follow-up, we compared demographic and clinical features between the two groups. A multivariable logistic regression analysis was performed to identify the impact of INH treatment on LFT abnormality. The impact of INH treatment on the persistence of TNF inhibitors was also evaluated with the log-rank test and the Cox-proportional hazards model. RESULTS: A total of 312 RA patients including 96 patients (30.9%) who took INH for LTBI were included in this analysis. Thirty-nine patients (12.5%) experienced LFT abnormalities while using TNF inhibitors. The use of INH was associated with LFT abnormalities (odds ratio, 3.01; 95% confidence interval [CI], 1.39 to 6.48) after adjusting for covariates, including methotrexate use. However, the persistence of TNF inhibitors over 5 years did not differ between patients receiving or not receiving INH treatment (49.4 vs. 54.6%, p = 0.79). INH treatment was not a risk factor for discontinuation of TNF inhibitors (hazard ratio, 1.01; 95% CI, 0.66 to 1.57). CONCLUSION: INH treatment for LTBI in RA patients who started TNF inhibitors is associated with the occurrence of LFT abnormality; however, it does not lead to discontinuation of TNF inhibitors.
30277135 Long-lasting immunosuppressive effects of tacrolimus-loaded micelle NK61060 in preclinical 2018 Oct AIM: Tacrolimus (TAC) is an important drug for inflammatory diseases. However, TAC has several limitations, such as variable trough concentrations among individuals and a high medication frequency. In this study, we created NK61060, a novel micellar TAC formulation, to circumvent these disadvantages. MATERIALS & METHODS: Immunosuppressive activity of NK61060 was determined in the collagen-induced arthritis rat model, mannan-induced arthritis mouse model and dextran sodium sulfate-induced colitis mouse model. The pharmacokinetics and toxicology of NK61060 were evaluated in those models. RESULTS: In arthritis and colitis models, NK61060 exhibited superior immunosuppressive activity compared with that of TAC. Pharmacokinetic and toxicological analyses indicated that NK61060 had a wider safety margin and could be administered at a reduced medication frequency. CONCLUSION: NK61060 mitigates the trough concentration variability and the medication frequency and it may be a safer and more effective option for use in clinical settings. Further studies are needed to determine its clinical usefulness.
29594389 Follistatin-like 1 in development and human diseases. 2018 Jul Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression changes during development and disease, among which cardiovascular disease, cancer, and arthritis. The cardioprotective role of FSTL1 has been intensively studied over the last years, though its mechanism of action remains elusive. FSTL1 is involved in multiple signaling pathways and biological processes, including vascularization and regulation of the immune response, a feature that complicates its study. Binding to the DIP2A, TLR4 and BMP receptors have been shown, but other molecular partners probably exist. During cancer progression and rheumatoid arthritis, controversial data have been reported with respect to the proliferative, apoptotic, migratory, and inflammatory effects of FSTL1. This controversy might reside in the extensive post-transcriptional regulation of FSTL1. The FSTL1 primary transcript also encodes for a microRNA (miR-198) in primates and multiple microRNA-binding sites are present in the 3'UTR. The switch between expression of the FSTL1 protein and miR-198 is an important regulator of tumour metastasis and wound healing. The glycosylation state of FSTL1 is a determinant of biological activity, in cardiomyocytes the glycosylated form promoting proliferation and the non-glycosylated working anti-apoptotic. Moreover, the glycosylation state shows differences between species and tissues which might underlie the differences observed in in vitro studies. Finally, regulation at the level of protein secretion has been described.
29353098 The anti-inflammatory effects of statins on patients with rheumatoid arthritis: A systemic 2018 Mar BACKGROUND: Over the past several years, numerous studies investigated the anti-inflammatory effects of statin on patients with RA. However, the findings of the individual studies were often inconsistent or conflicting. MATERIALS AND METHODS: The Pubmed, Web of Science, Embase, Cochrane Library and CNKI literature databases were searched in order to identify randomized controlled clinical trials where the association between the anti-inflammatory effect of statin and RA was investigated. Two researchers performed data extraction from eligible independently. Quality parameters and risk of bias in the included studies were assessed according to Cochrane's guidelines. The pooled Standardized Mean Difference (SMD) with a 95%CI was used to assess the anti-inflammatory effect of statin in patients with RA. RESULTS: Fifteen randomized controlled clinical, classified as "high quality" and with a relatively low risk of selection bias, were included in the meta-analysis. Of these, eight reported that there was no difference in the level of serum total lipids between the atorvastatin-treated and the conventional treatment group. However, the pooled analysis showed that atorvastatin could increase the level of serum amount of high-density lipoprotein (HDL) in RA patients by approximately x ± SD95% [HDL: SMD = 0.807, 95%CI = (0.187, 1.426), p = .011]. Meanwhile atorvastatin could reduce the level of serum low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride (TG) in RA patient by x ± SD95% [LDL: SMD = -4.015, 95%CI = (-5.848, -2.183), p = .000; TC: SMD = -4.497, 95%CI = (-6.457, -2.537), p = .000; TG: SMD = -1.475, 95%CI = (-2.352, -0.599), p = .001]. Nine studies reported a change in C-Reactive Protein (CRP) after atorvastatin treatment, and the pooled analysis showed that atorvastatin decreased CRP in RA patients by x ± SD95% [SMD = -3.033, 95%CI = (-4.460, -1.606), p = .000]. Seven studies investigated the change of Erythrocyte Sedimentation Rate (ESR), and the pooled analysis showed that atorvastatin decreased ESR by x ± SD95% [SMD = -2.097, 95%CI = (-3.408, -0.786), p = .002]. Nine studies reported the improvement of disease activity score in RA patients after taking atorvastatin for 12 weeks, and the pooled analysis showed atorvastatin could decrease the DAS28 score in RA patients by x ± SD95% [SMD = -2.001, 95%CI = (-3.191, -0.811), p = .001]. CONCLUSIONS: Statins have a significant anti-inflammatory effect in RA patients. However, atorvastatin was superior to simvastatin both in terms of its anti-inflammatory and lipid-lowering activities.
29552838 [Aconitum in treatment of rheumatoid arthritis: benefit-risk assessment]. 2018 Jan Rheumatoid arthritis (RA) has the characteristics of long course of disease and difficulty in treatment. The conventional therapy may easily induce adverse drug reactions or events (ADR/ADE) due to the long-time medication. Thus, it should be given special attentions to treatment benefit and medication risk of RA patients. Aconitum, a kind of toxic traditional Chinese herbs, is an important complement therapy for RA, with some controversy in clinical application. Coming straight to the practical problem of combined use of traditional Chinese medicines (TCM) and Western medicines (WM), this study conducted quantitative assessment on the benefits and risks of Aconitum using combined with WM or not, which was carried out by the method of multi-criteria decision analysis model. RevMan 5.2 software was used to separately analyze the results of every index of 21 random clinical trials (RCTs) of Aconitum exclusive use in the treatment of RA, and 49 RCTs of Aconitum combined use with WM. The merged results indicated that as compared with the conventional therapy of WM, no matter the exclusive use or the combined use of Aconitum could improve the efficacy and decrease the incidence of ADR/ADEs. Based on the benefit-risk assessment decision tree of RA treatment, Hiview 3 software and Crystal Ball Monte Carlo simulation were used to calculate the benefit value, risk value and benefit-risk value of Aconitum exclusive use and the combined use of Aconitum with WM. The results showed that the combination therapy had significantly better benefits than Aconitum exclusive using, difference value was 15, (95%CI[9.72, 20.25]), but the risk of combined use was higher difference value=23, （95%CI[15.57, 30.55]）. In comprehensive consideration of the benefit and risk, the total benefit-risk value of using Aconitum alone was 58, while that of the combination therapy was 55, and the probability of the former superior to the latter was 81.07%. The study showed that Aconitum was the important therapy to supply RA treatment. In clinical application, the patient's acceptability of benefit and risk need to be considered; if patients cannot bear the risk, the combination use of Aconitum and WM is not recommended.
29589504 Long-term results of the lateral resurfacing elbow arthroplasty. 2018 Mar 1 AIMS: The aim of this study was to report the long-term outcome and implant survival of the lateral resurfacing elbow (LRE) arthroplasty in the treatment of elbow arthritis. PATIENTS AND METHODS: We reviewed a consecutive series of 27 patients (30 elbows) who underwent LRE arthroplasty between December 2005 and January 2008. There were 15 women and 12 men, with a mean age of 61 years (25 to 82). The diagnosis was primary hypotrophic osteoarthritis (OA) in 12 patients (14 elbows), post-traumatic osteoarthritis (PTOA) in five (five elbows) and rheumatoid arthritis (RA) in ten patients (11 elbows). The mean clinical outcome scores including the Mayo Elbow Performance Score (MEPS), the American Shoulder and Elbow Surgeons elbow score (ASES-e), the mean range of movement and the radiological outcome were recorded at three, six and 12 months and at a mean final follow-up of 8.3 years (7.3 to 9.4). A one sample t-test comparing pre and postoperative values, and survival analysis using the Kaplan-Meier method were undertaken. RESULTS: A statistically significantly increased outcome score was noted for the whole group at each time interval. This was also significantly increased at each time in each of the subgroups (OA, RA, and PTOA). Implant survivorship was 100%. CONCLUSION: We found that the LRE arthroplasty, which was initially developed for younger patients with osteoarthritis, is an effective form of surgical treatment for a wider range of patients with more severe degenerative changes, irrespective of their cause. It is therefore a satisfactory alternative to total elbow arthroplasty (TEA) and has lower rates of complications in the subgroups of patients we have studied. It does not require activities to be restricted to the same extent as following TEA. Based on this experience, we now recommend LRE arthroplasty rather than TEA as the primary form of implant for the treatment of patients with OA of the elbow. Cite this article: Bone Joint J 2018;100-B:338-45.
29951696 Analysis of Polymorphisms in the Mediator Complex Subunit 13-like (Med13L) Gene in the Con 2018 Oct The Mediator complex subunit 13-like (MED13L) protein is part of the multi-protein mediator complex and plays an important role in gene transcription. Polymorphisms in the MED13L gene have been linked to congenital heart anomalies and intellectual disabilities. Despite recent evidence of indirect links of MED13L to cytokine release and inflammation, impact of genetic variations in MED13L on immune cells remains unexplored. The B10.RIII and RIIIS/J mouse strains vary in susceptibility to induced experimental autoimmune disease models. From sequencing data of the two mouse strains, we identified six polymorphisms in the coding regions of Med13L. Using congenic mice, we studied the effect of these polymorphisms on immune cell development and function along with susceptibility to collagen-induced arthritis, an animal model for rheumatoid arthritis. Combining in vivo disease data, in vitro functional data, and computational analysis of the reported non-synonymous polymorphisms, we report that genetic polymorphisms in Med13L do not affect the immune phenotype in these mice and are predicted to be non-disease associated.
28963724 The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumato 2018 Feb Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.
28967035 Comparative efficacy and tolerability of monotherapy with leflunomide or tacrolimus for th 2018 Feb We aimed to assess the relative efficacy and tolerability of monotherapy with leflunomide or tacrolimus at recommended dosages in rheumatoid arthritis (RA) patients. Randomized controlled trials (RCTs) examining the efficacy and tolerability of leflunomide 20 mg, leflunomide 10 mg, tacrolimus 3 mg, tacrolimus 1.5-2 mg, and placebo, based on the number of withdrawals of RA patients, were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. Six RCTs including 1510 patients met the inclusion criteria. The proportion of patient withdrawals owing to lack of efficacy was significantly lower in the leflunomide 20 mg (OR 0.17, 95% credible interval (CrI) 0.08-0.34); leflunomide 10 mg (OR 0.16, 95% CrI 0.02-0.75); and tacrolimus 3 mg (OR 0.41, 95% CrI 0.21-0.74) groups than in the placebo group. Rank probability based on the surface under the cumulative ranking curve (SUCRA) values indicated that leflunomide 20 mg had the highest probability of being the best treatment based on the number of withdrawals owing to lack of efficacy (SUCRA = 0.8530), followed by leflunomide 10 mg (SUCRA = 0.8321), tacrolimus 3 mg (SUCRA = 0.4965), tacrolimus 1.5-2 mg (SUCRA = 0.3035), and placebo (SUCRA = 0.0150). Patient withdrawals owing to adverse events did not differ significantly among the groups; however, withdrawals in the placebo group were fewer than those in the leflunomide 20 mg group (OR 0.22, 95% CrI 0.07-0.74). Placebo had the highest probability of being the most tolerable treatment (SUCRA = 0.8161) followed by tacrolimus 3 mg (SUCRA = 0.6490), tacrolimus 1.5-2 mg (SUCRA = 0.4857), leflunomide 10 mg (SUCRA = 0.4651), and leflunomide 20 mg (SUCRA = 0.0841). Leflunomide 20 mg, leflunomide 10 mg, and tacrolimus 3 mg were more efficacious than placebo, while leflunomide 20 mg was less tolerable than placebo. Leflunomide is likely to be more efficacious but less tolerable than tacrolimus for RA treatment.
29490980 Are MRI-detected erosions specific for RA? A large explorative cross-sectional study. 2018 Jun OBJECTIVES: MRI is recommended in the diagnostic process of rheumatoid arthritis (RA) to detect joint damage early. MRI-detected erosions are also present in symptom-free controls, especially at older age. It is unclear if RA-specific MRI-detected erosions can be distinguished from 'physiological' erosions in symptom-free individuals. This study compared MRI-detected erosions of patients with RA with healthy controls and with other arthritides. METHODS: 589 newly presenting patients with early arthritis (238 RA, 351 other arthritides) and 193 symptom-free controls underwent contrast-enhanced 1.5T MRI of unilateral metacarpophalangeal and metatarsophalangeal (MTP) joints. Total erosion score (according to the Rheumatoid Arthritis MRI Scoring System), number, severity, location of erosions and simultaneous presence of MRI-detected inflammation (synovitis and/or bone marrow oedema) were compared; participants were categorised in three age groups (<40, 40-59, ≥60). RESULTS: Patients with RA had statistically significant higher total erosion scores than controls but scores of individual persons largely overlapped. Grade ≥2 erosions and MTP5 erosions were specific for RA (specificity 98%-100% and 90%-98% for different age groups). MTP1 erosions were only specific if aged <40 (specificity 98%) and erosions with inflammation if aged <60 (specificity 91%-100%). ≥1 of the mentioned erosion characteristics were present in 29% of patients with RA. Comparing patients with RA with other arthritides revealed that grade ≥2 erosions and MTP5 erosions remained specific for RA (specificity ≥89%) as well as MTP1 erosions if aged <40 (specificity 93%), in contrast to erosions combined with inflammation (specificity 49%-85%). CONCLUSIONS: Total erosion scores of individual persons were largely overlapping. Erosion characteristics specific for RA were identified, but were infrequently present. Caution is needed not to overestimate the value of MRI erosions in the diagnostic process.
30514640 Rheumatoid Arthritis Patients Achieve Better Satisfaction but Lower Functional Activities 2019 Mar BACKGROUND: Recently, poor patient satisfaction after total knee arthroplasty (TKA) has gained attention mainly in osteoarthritis (OA) patients; however, satisfaction after TKA remains to be understood in rheumatoid arthritis (RA) patients. This study aimed to examine satisfaction and function after RA TKA using patient-reported outcome measures and to compare the results with those of OA-TKA. METHODS: This study enrolled 534 TKAs of 501 patients consisting of 75 TKAs of 70 RA patients and 459 TKAs of 431 OA patients. Data of patient-reported outcome measures such as new Knee Society Score 2011, Pain Catastrophizing Scale, and Pain DETECT Score were collected at 2 years. Multiple regression analysis was performed with Knee Society Score satisfaction score set as a dependent variable in order to clarify factors affecting patient satisfaction. Principle component analysis was performed, and satisfaction and function components were compared between RA and OA. RESULTS: All activity scores were significantly lower in RA TKA than in OA TKA, whereas the range of motion and patient satisfaction scores were significantly better in RA TKA than in OA TKA. Scores for symptom, expectation, basic activity, and discretional activity positively affected patient satisfaction (P < .001), while Pain Catastrophizing Scale negatively did (P = .021). Importantly, diagnosis of RA itself pushed up the patient satisfaction score by 1.5 points. Principle component analysis revealed that RA TKA achieved significantly higher satisfaction component (P = .001), but lower function component (P < .0001) compared to OA TKA. CONCLUSION: Patient satisfaction was better but functional activity was lower in RA than in OA. As poor functional activity was evident preoperatively in RA patients, to improve functional outcome should be future challenge for RA TKA.
29846726 The anti-carbamylated protein antibody response is of overall low avidity despite extensiv 2018 Sep 1 OBJECTIVE: To better understand the contribution of autoantibodies in RA and the biology of their responses, we evaluated the avidity of the anti-carbamylated protein (anti-CarP) antibody response. METHODS: The avidity of anti-CarP antibody, ACPA and anti-tetanus toxoid IgG were determined using elution assays. Anti-CarP IgG avidity was measured in sera of 107 RA patients, 15 paired SF and serum samples and 8 serially sampled sera before and after disease onset. RESULTS: The avidity of anti-CarP IgG is low compared with the avidity of anti-tetanus toxoid IgG present in the same sera. Likewise, although less pronounced, anti-CarP also displayed a lower avidity as compared with the avidity of ACPA IgG. No difference in anti-CarP IgG avidity is observed between ACPA positive or ACPA negative patients. Anti-CarP IgG avidity is higher in anti-CarP IgM-negative compared with IgM-positive individuals. Furthermore, the anti-CarP avidity in serum is higher than in SF. Using samples of individuals that over time developed RA we observed no anti-CarP avidity maturation in the years before disease onset. In contrast to ACPA avidity, the anti-CarP avidity is not associated with severity of joint destruction. CONCLUSION: The anti-CarP response is of overall low avidity, even lower than the ACPA IgG avidity, and does not show apparent avidity maturation before or around disease onset. Overall, isotype switch and avidity maturation seem to be uncoupled as isotype switch occurs without avidity maturation, pointing towards a commonality in the regulation of both autoantibody responses as opposed to the pathways governing recall responses.
28849709 Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in 2018 May OBJECTIVES: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. METHODS: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 - erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. RESULTS: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. CONCLUSION: A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.
29843290 Novel techniques for a wireless motion capture system for the monitoring and rehabilitatio 2018 BACKGROUND: Due to the problem of aging societies, there is a need for smart buildings to monitor and support people with various disabilities, including rheumatoid arthritis. OBJECTIVE: The aim of this paper is to elaborate on novel techniques for wireless motion capture systems for the monitoring and rehabilitation of disabled people for application in smart buildings. METHODS: The proposed techniques are based on cross-verification of distance measurements between markers and transponders in an environment with highly variable parameters. To their verification, algorithms that enable comprehensive investigation of a system with different numbers of transponders and varying ambient parameters (temperature and noise) were developed. In the estimation of the real positions of markers, various linear and nonlinear filters were used. Several thousand tests were carried out for various system parameters and different marker locations. RESULTS: The results show that localization error may be reduced by as much as 90%. It was observed that repetition of measurements reduces localization error by as much as one order of magnitude. CONCLUSIONS: The proposed system, based on wireless techniques, offers a high commercial potential. However, it requires extensive cooperation between teams, including hardware and software design, system modelling, and architectural design.
29967925 The best cardiovascular risk calculator to predict carotid plaques in rheumatoid arthritis 2018 Sep Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Chronic inflammation and traditional risk factors increase cardiovascular risk (CVR) in these patients. Several CVR calculators are used in general population and in RA patients to predict cardiovascular outcomes and tailor therapy but the precision of these calculators in RA patients has yet to be determined. The aim of this study is to determine which risk calculator correlates best with carotid ultrasound (US) findings, specifically carotid plaque (CP) and carotid intima-media thickness (CIMT) in RA patients without clinical manifestations. This was a cross-sectional observational study relating CVR scores in RA patients with the presence of carotid US findings. A total of 97 patients 40 to 75 years old who fulfilled the 2010 ACR/EULAR and/or the 1987 ACR classification criteria for RA were selected. Clinical assessment of cardiovascular risk was performed using seven calculators and carotid US measurement of intima-media thickness and plaque. The tests with the highest sensitivity for CIMT were the Framingham BMI, Framingham lipids, ACC/AHA 2013, and QRISK2. In CP, the highest sensitivity was in QRISK2, SCORE, and ACC/AHA 2013. RA patients should be comprehensively evaluated to detect cardiovascular risk. Carotid US may be routinely recommended to detect subclinical atherosclerosis in RA patients. A lower cutoff point in CVR scales may be necessary to identify patients with a low and intermediate CVR to detect subclinical atherosclerosis earlier and personalize therapy.