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ID PMID Title PublicationDate abstract
30097330 Temporomandibular and Odontological Abnormalities in Patients with Rheumatoid Arthritis. 2020 Jul OBJECTIVE: To characterize the orofacial abnormalities in patients with rheumatoid arthritis (RA) and compare them with those in a reference population. METHODS: The study included 30 RA patients and 30 consecutive patients in an odontology clinic in whom RA was ruled out. Patients underwent a clinical dental examination which included: 1) clinical and radiographic abnormalities of the temporomandibular joint; 2) biomechanical craniocervical analysis; 3) state of dentition and treatment needs; 4) periodontal status; 5) oral hygiene status; and 6) facial pain, which was compared among study groups. In addition, the association between the variables studied was determined through correlation tests. RESULTS: Patients with RA showed a higher prevalence of temporomandibular abnormalities, both clinical (100.0% vs. 60.0%, P<.001) and radiographic, including erosions (50.0% vs. 16.0%, P=.010), compared with individuals in the control group. Likewise, patients with RA had a greater number of missing teeth (6.9±5.7 vs. 3.0±2.0, P=.001), more caries (13.4±5.4 vs. 4.9±6.5, P=.001), periodontitis (1.3±0.9 vs. 0.8±0.8, P=.015), poorer oral hygiene (43.3% vs. 13.3%, P=.005) and greater facial pain (66.7% vs. 20.0%, P <.001). The cephalometric analysis of Rocabado showed differences in the craniocervical angle and hyoid triangle between RA and controls. Significant correlations were obtained between oral and temporomandibular abnormalities. CONCLUSIONS: Patients with RA showed a greater orofacial deterioration, which reflects the importance of multidisciplinary care, including periodic dental examination.
29195011 Experiences With Telehealth Followup in Patients With Rheumatoid Arthritis: A Qualitative 2018 Sep OBJECTIVE: To explore the experiences of a patient-reported outcome (PRO)-based telehealth followup from the perspective of patients with rheumatoid arthritis (RA) and their experiences of increasing their active role, and responsibility for disease control in particular. METHODS: Adopting a strategy of interpretive description, we conducted individual, semistructured interviews with 15 RA patients participating in a telehealth followup. Participants were selected purposively and consecutively from both sexes and with various ages, disease durations, and disease severity. The analysis was inductive, with a constant comparative approach. First, we identified the main themes conveying the participants' experiences. Then we constructed patient typologies to explain different perspectives on the telehealth followup. RESULTS: Five themes covered the participants' experiences: a flexible solution, responsibility, knowledge of RA, communication and involvement, and continuity. Two typologies, the keen patient and the reluctant patient, represented opposite perspectives and preferences regarding the core value of and approach to the telehealth followup. CONCLUSION: The participants had positive perceptions of the PRO-based telehealth followup and saw it as a flexible and resource-saving solution. They reported disadvantages related to missing face-to-face contact with health professionals. The 2 typologies, the keen and the reluctant patient, help us understand the patients' different needs, wishes, and abilities to take part in telehealth followup. Our findings reveal a need for more insight into how telehealth followup could be integrated in routine clinical practice, paying special attention to how reluctant patients may be supported.
29707921 Obesity, Weight Loss, and Progression of Disability in Rheumatoid Arthritis. 2018 Dec OBJECTIVE: Cross-sectional studies have demonstrated that obese patients with rheumatoid arthritis (RA) often report greater disability. The longitudinal effects of obesity, however, are not well-characterized. We evaluated associations between obesity, weight loss, and worsening of disability in patients of 2 large registry studies, which included patients who were followed for longer periods of time. METHODS: This study included patients with RA from the National Data Bank for Rheumatic Diseases (FORWARD) (n = 23,323) and the Veterans Affairs RA (VARA) registry study (n = 1,697). Results of the Health Assessment Questionnaire (HAQ) or Multidimensional HAQ (MD-HAQ) were recorded through follow-up. Significant worsening of disability was defined as an increase of >0.2 in HAQ or MD-HAQ scores. The Cox proportional hazards model was used to evaluate the risk of worsening of disability from baseline and to adjust for demographics, baseline disability, comorbidity, disease duration, and other disease features. RESULTS: At enrollment, disability scores were higher among severely obese patients compared to those who were overweight both in FORWARD (β = 0.17 [95% confidence interval (95% CI) 0.14, 0.20]; P < 0.001) and in the VARA registry (β = 0.17 [95% CI 0.074, 0.27]; P = 0.001). In multivariable models, patients who were severely obese at enrollment had a greater risk of progressive disability compared to overweight patients in FORWARD (HR 1.25 [95% CI 1.18, 1.33] P < 0.001) and in the VARA registry (HR 1.33 [95% CI 1.07, 1.66]; P = 0.01). Weight loss following enrollment was also associated with a greater risk in both cohorts. In the VARA registry, associations were independent of other clinical factors, including time-varying C-reactive protein and swollen joint count. CONCLUSION: Severe obesity is associated with a more rapid progression of disability in RA. Weight loss is also associated with worsening disability, possibly due to it being an indication of chronic illness and the development of age-related or disease-related frailty.
29696564 A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and saf 2018 Jun BACKGROUND: Following the potent efficacy of β-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. METHOD: The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. RESULTS: There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. CONCLUSION: Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.
29545454 A Systematic Review and Metaanalysis of Antirheumatic Drugs and Vaccine Immunogenicity in 2018 Jun OBJECTIVE: Vaccination is a key strategy to reduce infection risk in patients with rheumatoid arthritis (RA) and is advocated in internationally recognized rheumatology society guidelines. The aim was to evaluate to the effect of antirheumatic drugs on influenza and pneumococcal vaccine immunogenicity. METHODS: We conducted a systematic literature review and metaanalysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit vaccines) and pneumococcal (23-valent pneumococcal polysaccharide vaccine, 7- and 13-valent pneumococcal conjugated vaccines) vaccination in adult patients with RA treated with antirheumatic drugs. Vaccine immunogenicity was assessed by seroprotection rates measured 3 to 6 weeks postimmunization. Risk ratios (RR) and 95% CI were pooled. RESULTS: Nine studies were included in the metaanalysis (7 studies investigating antirheumatic drug exposures and influenza humoral response, 2 studies investigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) drug exposure. MTX but not TNFi drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (RR 0.42, 95% CI 0.28-0.63 vs RR 0.98, 95% CI 0.58-1.67); however, limited data were available to draw any firm conclusions. Combination of MTX with tocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses. CONCLUSION: Antirheumatic drugs may limit humoral responses to vaccination as evidenced by pneumococcal responses with MTX exposure; however, they are safe and should not preclude immunization against vaccine-preventable disease. Vaccination should be considered in all patients with RA and encouraged as part of routine care. (Systematic review registration number: PROSPERO 2016: CRD42016048093.).
29973208 A novel gene-expression-signature-based model for prediction of response to Tripterysium g 2018 Jul 4 BACKGROUND: Approximately 30% of rheumatoid arthritis (RA) patients treated with Tripterysium glycosides (TG) tablets fail to achieve clinical improvement, implying the essentiality of predictive biomarkers and tools. Herein, we aimed to identify possible biomarkers predictive of therapeutic effects of TG tablets in RA. METHODS: Gene expression profile in peripheral blood mononuclear cells obtained from a discovery cohort treated with TG tablets was detected by Affymetrix EG1.0 arrays. Then, a list of candidate gene biomarkers of response to TG tablets were identified by integrating differential expression data analysis and gene signal transduction network analysis. After that, a partial-least-squares (PLS) model based on the expression levels of the candidate gene biomarkers in RA patients was constructed and evaluated using a validation cohort. RESULTS: Six candidate gene biomarkers (MX1, OASL, SPINK1, CRK, GRAPL and RNF2) were identified to be predictors of TG therapy. Following the construction of a PLS-based model using their expression levels in peripheral blood, both the 5-fold cross-validation and independent dataset validations showed the high predictive efficiency of this model, and demonstrated a distinguished improvement of the PLS-model based on six candidate gene biomarkers' expression in combination over the commonly used clinical and inflammatory parameters, as well as the gene biomarkers alone, in predicting RA patients' response to TG tablets. CONCLUSIONS: This hypothesis-generating study identified MX1, OASL, SPINK1, CRK, GRAPL and RNF2 as novel targets for RA therapeutic intervention, and the PLS model based on the expression levels of these candidate biomarkers may have a potential prognostic value in RA patients treated with TG tablets.
29665496 The serum level of Dickkopf-1 in patients with rheumatoid arthritis: A systematic review a 2018 Jun OBJECTIVE: Dickkopf-1 (DKK-1) is an endogenous inhibitor of canonical Wnt pathway that was implicated in the pathogenesis of rheumatoid arthritis (RA), but the serum levels of DKK-1 in RA were inconsistent among studies. Therefore, we conducted a meta-analysis to systematically evaluate the relationship between serum DKK-1 levels and RA. METHODS: PubMed, Web of Science and Cochrane Library were comprehensively retrieved till 1 January 2018 for pertinent studies. The pooled standard mean differences (SMDs) of serum DKK-1 levels were calculated according to the random effects model. RESULTS: Nine original studies containing 1305 RA patients and 504 healthy controls were included in the meta-analysis. The pooled SMD of serum DKK-1 between RA patients and healthy controls was 0.79 (95% CI = 0.11 to 1.48, Z = 2.28 and P = 0.023), indicating a significantly higher serum level of DKK-1 in RA patients. CONCLUSION: Serum level of DKK-1 is elevated in patients with RA compared to healthy controls, suggesting an important role of DKK-1 in the pathogenesis and treatment of RA.
28324149 [Outpatient care and disease burden of rheumatoid arthritis : Results of a linkage of cla 2018 Mar BACKGROUND: Healthcare of patients with rheumatoid arthritis (RA) in Germany has mainly been evaluated in the past in RA cohorts from specialized arthritis centers. This study investigated rheumatological care on a population basis, using claims data from a nationwide statutory health insurance fund (BARMER GEK) in combination with patient-reported outcomes from a questionnaire survey of insured persons with RA. METHODS: Data from insurants aged 18-79 years with M05 (seropositive RA) or M06 (other RA, ICD-10) diagnoses were analyzed concerning diagnostics, medication and prescribing physician. A 31-item questionnaire covering patient reported diagnosis, healthcare utilization and burden of illness was sent to a stratified random sample of 6193 insured persons. Data from the respondents regarding rheumatological care and disease status were evaluated. RESULTS: In 2013 and 2014, a total of 96,921 adults with M05 or M06 diagnosis were insured. The questionnaire was answered by 51% of the sample and of these 81% confirmed the RA diagnosis. RA had been diagnosed by a rheumatologist in 59% of the cases, 70% reported moderate to severe pain and 46% had functional disability. Between at least 40% (claims data) and up to 68% (respondents) were in specialized rheumatological care. Treatment with disease-modifying antirheumatic drugs (DMARDs) was 61% (claims data) and 63% (respondents) in persons in rheumatological care but only 18% outside rheumatological care. CONCLUSION: The results indicate that specialized rheumatological care is required to provide adequate treatment for patients with RA in Germany. Patients with higher age and patients with M06 diagnosis had less drug prescriptions and were less frequently treated by rheumatologists.
28463029 High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts re 2018 Jan OBJECTIVE: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA). METHODS: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis. RESULTS: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively. CONCLUSION: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.
28765254 Risk of Obstructive Sleep Apnea and Its Association with Cardiovascular and Noncardiac Vas 2018 Jan OBJECTIVE: To define the incidence of obstructive sleep apnea (OSA) in patients with rheumatoid arthritis (RA) and determine whether OSA diagnosis predicts future cardiovascular disease (CVD) and noncardiac vascular events. METHODS: Medical information pertaining to RA, OSA, CVD, and vascular diagnoses was extracted from a comprehensive medical record system for a geographically defined population of 813 patients previously diagnosed with RA and 813 age- and sex-matched comparator subjects. RESULTS: The risk for OSA in persons with RA versus comparators was elevated, although not reaching statistical significance (HR 1.32, 95% CI 0.98-1.77; p = 0.07). Patients with RA were more likely to be diagnosed with OSA if they had traditional risk factors for OSA, including male sex, current smoking status, hypertension, diabetes, dyslipidemia, and increased body mass index. Features of RA disease associated with OSA included large joint swelling and joint surgery. Patients with RA with decreased renal function were also at higher risk of OSA. The increased risk of overall CVD among patients with RA who have OSA was similar to the increased CVD risk associated with OSA in the comparator cohort (interaction p = 0.86). OSA diagnosis was associated with an increased risk of both CVD (HR 1.9, 95% CI 1.08-3.27), and cerebrovascular disease (HR 2.4, 95% CI 1.14-5.26) in patients with RA. CONCLUSION: Patients with RA may be at increased risk of OSA secondary to both traditional and RA-related risk factors. Diagnosis with OSA predicts future CVD in RA and may provide an opportunity for CVD intervention.
29155458 Localization of surfactant protein-D in the rheumatoid synovial membrane. 2018 Jan Surfactant protein-D (SP-D) is a collectin, which plays an important role in airway protection and inflammation. The molecule has both pro- and anti-inflammatory capacities depending on its molecular size. Its involvement in joint diseases is largely unknown and the aim of this investigation was to study SP-D occurrence and distribution in the synovial membrane of patients with long-standing rheumatoid arthritis (RA) and osteoarthritis (OA). Six RA patients and six OA patients, who underwent total hip arthroplasty, were included in the study. Synovial tissue biopsies were obtained during surgery and subsequently prepared for immunohistochemistry. In this first, small-scale comparative study on the occurrence of SP-D in the synovial membrane of RA and OA, we report that SP-D was only present in the microvascular endothelium in subsynovial and pannus tissue and that the immunostaining was much stronger than in OA. This distribution pattern suggests that SP-D modulates RA inflammatory activities.
29936570 Rheumatoid factor isotype and Ro epitope distribution in primary Sjögren syndrome and rhe 2018 Aug Primary Sjögren syndrome (pS) is associated with autoantibodies such as rheumatoid factor (RF) and anti-nuclear antibodies such as anti-Ro (SS-A) and/or La (SS-B). Recent developments within autoimmune diagnostics allow quantitation of RF subclasses and anti-Ro epitopes. Will this refinement by autoimmune diagnostics help predicting development of extraglandular manifestations (EGM) in pS patients? A cohort of pS and rheumatoid arthritis (RA) patients with keratoconjunctivitis sicca (n = 35 and 16, resp) was included. Of the pS patients, 54% developed one or more EGM. Antibodies quantitated were IgM-RF, IgA-RF, IgG-RF, anti-Ro52, and anti-Ro60. Upon analysis of RF isotypes, pS patients generally displayed higher IgA-RF concentrations than RA patients (126 versus 49 U/ml, p = 0.015), while the dominant RF isotype in RA patients was IgM-RF (82.5 versus 38 U/ml, p = 0.012). No differences were observed regarding IgG-RF concentrations. In pS without/with EGM, the median RF IgM concentrations were similar, while RF IgA and IgG concentrations tended to be lower in pS patients with EGM > 1. Both Ro epitopes were strongly recognized by almost all pS patients, independent from EGM, while these antibodies were absent in RA patients. Primary Sjögren syndrome and RA patients have distinct serological profiles when analysing RF and Ro-specific antibodies. A longitudinal study of switched RF isotypes in pS patients is worthwhile from an immunological point of view, but its value is limited regarding identification of pS patients prone to developing EGM or RA patients prone to developing secondary sicca symptoms.
29706963 Protective Role of the MER Tyrosine Kinase via Efferocytosis in Rheumatoid Arthritis Model 2018 OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and progressive joint disease. It appears that anti-inflammatory feedback mechanisms that could restrain joint inflammation and restore homeostasis are insufficient to perform this control. In this study, we investigated the contribution of the MER tyrosine kinase-mediated anti-inflammatory response on arthritis and whether targeting MER could be a valid approach to treat RA. METHODS: KRN serum transfer arthritis (KRN STA) was induced in either Mertk-deficient mice or in mice that adenovirally overexpressed Pros1. Human synovial micromasses were treated with MER-specific antibodies or PROS1. Collagen-induced arthritis (CIA) mice were treated with MER-specific agonistic antibodies or by viral overexpression of Pros1. RESULTS: Mertk(-/-) mice showed exacerbated arthritis pathology, whereas Pros1 overexpression diminished joint pathology in KRN STA. Human synovial micromasses challenged with MER-specific antibodies enhanced the secretion of inflammatory cytokines, whereas stimulating MER with PROS1 reduced the secretion of these cytokines, confirming the protective role of MER. Next, we treated CIA mice with MER-specific agonistic antibodies, and this unexpectedly resulted in exacerbated arthritis pathology. This was associated with increased numbers of apoptotic cells in their knee joints and higher serum levels of interleukin (IL)-16C, a cytokine released by secondary necrotic neutrophils. Apoptotic cell numbers and IL-16C levels were enhanced during arthritis in Mertk(-/-) mice and reduced in Pros1-overexpressing mice. CONCLUSION: MER plays a protective role during joint inflammation and activating MER by its ligand PROS1 ameliorates disease. Treatment of mice with MER receptor agonistic antibodies is deleterious due to its counterproductive effect of blocking efferocytosis in the arthritic joint.
29514802 Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus 2018 Jul OBJECTIVES: Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA. METHODS: Patients with SLE (n=1045) were genotyped using the 200K Immunochip SNP array (Illumina). The allele frequency was compared between patients with and without different manifestations of CVD. Results were replicated in a second SLE cohort (n=1043) and in an RA cohort (n=824). We analysed publicly available genetic data from general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of antiphospholipid antibodies (aPLs). RESULTS: We identified two new putative risk loci associated with increased risk for CVD in two SLE populations, which remained after adjustment for traditional CVD risk factors. An IL19 risk allele, rs17581834(T) was associated with stroke/myocardial infarction (MI) in SLE (OR 2.3 (1.5 to 3.4), P=8.5×10(-5)) and RA (OR 2.8 (1.4 to 5.6), P=3.8×10(-3)), meta-analysis (OR 2.5 (2.0 to 2.9), P=3.5×10(-7)), but not in population controls. The IL19 risk allele affected protein binding, and SLE patients with the risk allele had increased levels of plasma-IL10 (P=0.004) and aPL (P=0.01). An SRP54-AS1 risk allele, rs799454(G) was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3 to 2.2), P=2.5×10(-5)) but not in RA. The SRP54-AS1 risk allele is an expression quantitative trait locus for four genes. CONCLUSIONS: The IL19 risk allele was associated with stroke/MI in SLE and RA, but not in the general population, indicating that shared immune pathways may be involved in the CVD pathogenesis in inflammatory rheumatic diseases.
29780094 [The treatment of patients with elderly-onset rheumatoid arthritis at Niigata Rheumatic Ce 2018 AIM: To investigate the clinical course of patients with elderly-onset rheumatoid arthritis (RA). METHODS: We compared the characteristics, and clinical course of 55 patients who developed RA at over 80 years of age (elderly-onset [EO] group) with 119 patients who developed RA at 40-59 years of age (non-elderly onset [non-EO] group). We also investigated the characteristics and clinical course of 19 patients who developed RA at over 80 and who received biological disease-modifying anti-rheumatic drugs (bDMARDs). RESULTS: The mean DAS28-ESR (DAS) and HAQ-DI (HAQ) of the EO were significantly higher in comparison to the non-EO group (4.91±1.31 vs 4.41±1.47, p=0.043, 1.2±0.9 vs 0.5±0.6, p<0.01). For the first treatment, 87.3% in the EO group received conventional synthetic DMARDs (csDMARDs), none received MTX. The rate of prednisolone (PSL) administration in the EO group was significantly higher than the non-EO group (56.4% vs 30.3%, p<0.01). The DAS and HAQ were significantly decreased in both groups, while the HAQ of the EO group was higher than the non-EO group. The decrease in DAS and HAQ of the PSL users was significantly greater than the non-PSL users (ΔDAS: 2.55±1.83 vs 1.83±1.23, p<0.01, ΔHAQ: 0.9±1.0 vs 0.3±0.6, p=0.027). Among the 19 patients with bDMARDs, the mean DAS and HAQ at baseline were significantly decreased 6 months later. CONCLUSION: Early use of csDMARDs and PSL was effective for functional disability of elderly-onset RA; however, some of them required bDMARDs. Further study should be performed to investigate the effectiveness of the early induction of MTX and bDMARDs.
28914370 Thioredoxin 1 is associated with the proliferation and apoptosis of rheumatoid arthritis f 2018 Jan We aimed to investigate the possible effects of thioredoxin 1 (Trx1) on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and elucidate the possible mechanisms involved. We investigated the distribution and expression of Trx1 in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analyses. RA-FLSs were isolated and cultured under normoxic (21% oxygen) or hypoxic (3% oxygen) concentrations. Transfection of Trx1-siRNAs and a Trx1 overexpression construct was conducted to manipulate the expression of Trx1. Protein expression was detected by Western blot. Doxorubicin (Adriamycin, ADR) was used to induce apoptosis. LY-294002 was used for the inhibition of PI3K-Akt. Cell proliferation and apoptosis were determined by MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay and flow cytometry, respectively. The mRNA and protein expression of Trx1 in RA tissues was higher than that in OA tissues. The expression levels of Trx1 and cell proliferation in RA-FLSs were increased under hypoxia in comparison to those under normoxia. In hypoxia, downregulation of Trx1 significantly suppressed FLS proliferation, and the expression of PI3Kp85, phospho-Akt, and Bcl-2, while notably increased FLS apoptosis and the expression of active Caspase3 and Bax. In normoxia, Trx1 overexpression promoted the FLS proliferation and the expression of PI3Kp85, phospho-Akt, and Bcl-2, but inhibited FLS apoptosis and the expression of active Caspase3 and Bax in FLSs. Such effects were partially repressed by LY-294002 treatment. Trx1 may play an important role in regulating the proliferation and apoptosis of RA-FLSs by modulating PI3K-Akt activation.
30865952 Weighted Transmission Disequilibrium Test for Family Trio Association Design. 2018 BACKGROUND: Family-based design is one of the most popular designs in genetic studies. Transmission disequilibrium test (TDT) for family trio design is optimal only under the additive trait model and may lose power under the other trait models. The TDT-type tests are powerful only when the underlying trait model is correctly specified. Usually, the true trait model is unknown, and the selection of the TDT-type test is problematic. Several methods, which are robust against the mis-specification of the trait model, have been proposed. In this paper, we propose a new efficiency robust procedure for family trio design, namely, the weighted TDT (WTDT) test. METHODS: We combine information of the largest two TDT-type tests by using weights related to the three TDT-type tests and take the weighted sum as the test statistic. RESULTS: Simulation results demonstrate that WTDT has power close to, but much more robust than, the optimal TDT-type test based on a single trait model. WTDT also outperforms other efficiency robust methods in terms of power. Applications to real and simulated data from Genetic Analysis Workshop (GAW15) illustrate the practical application of the WTDT method. CONCLUSION: WTDT is not only efficiency robust to model mis-specifications but also efficiency robust against mis-specifications of risk allele.
27143214 Hallux valgus deformity after total ankle arthroplasty for rheumatoid arthritis: A case re 2018 Sep Hallux valgus (HV) deformity is associated with hindfoot valgus deformity. We experienced a case that suggests the possibility that valgus correction for varus hindfoot with bony ankylosis of the subtalar joint by total ankle arthroplasty may have caused a forefoot HV deformity, despite adequate valgus correction.
29231984 Evidence for increased chylomicron remnants in rheumatoid arthritis. 2018 Feb BACKGROUND: Levels of apolipoprotein (apo) B48 may be increased in conditions associated with systemic inflammation and increased cardiovascular disease (CVD) risk such as rheumatoid arthritis (RA). We aimed to evaluate apo B48 levels in patients with RA in relation to subclinical atherosclerosis. METHODS: Patients with RA (without CVD) and controls without RA but with high CVD risk (based on the presence of diabetes mellitus or a history of CVD) and healthy controls were included in this cross-sectional study. Carotid intima-media thickness (cIMT) was measured as a surrogate for vascular damage. RESULTS: In total, 312 patients with RA, 65 controls with high CVD risk and 36 healthy controls were included. Patients with RA had the highest mean apo B48 (10.00 ± 6.65 mg/L) compared to controls with high CVD risk and healthy controls (8.37 ± 5.16 and 5.22 ± 2.46, P < .001). Triglycerides levels were comparable with controls. In RA, apo B48 correlated positively with triglycerides (r = .645; P < .001) but not with cIMT. However, in RA subjects not using lipid or blood pressure lowering medication, a weak correlation was found with cIMT (r = .157; P = .014). RA patients in the highest apo B48 tertile were more often rheumatoid factor positive and anti-CCP positive compared to the lowest tertile. CONCLUSION: Rheumatoid arthritis patients have higher levels of apo B48 compared to controls with high CVD risk and healthy controls, with normal levels of triglycerides. This accumulation of atherogenic chylomicron remnants may contribute to the elevated CVD risk in RA patients.
30701887 Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in 2018 May 11 AIM: To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. MATERIALS AND METHODS: The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of *04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10 alleles were categorized as SE+ (Shared Epitope) alleles. RESULTS: As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (р<0,005, and р<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (∆) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1*(SE) genotypes: the carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (р<0,028, р<0,019, р<0,035 respectively). CONCLUSION: Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.