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ID PMID Title PublicationDate abstract
29581944 Osseous changes in the temporomandibular joint in rheumatoid arthritis: A cone-beam comput 2018 Mar PURPOSE: To evaluate osseous changes of temporomandibular joint (TMJ) in patients with rheumatoid arthritis (RA) using cone-beam computed tomography (CBCT) and to correlate the imaging findings with the severity of TMJ dysfunction, clinical findings, and laboratory findings. MATERIALS AND METHODS: This study consisted of 28 subjects, including 14 RA patients and 14 controls, who were scheduled to undergo CBCT imaging for the diagnosis of a complaint not related to or affecting the TMJ. The Fonseca's questionnaire was used to assess the severity of TMJ dysfunction. Rheumatoid factor (RF) and the erythrocyte sedimentation rate (ESR) were assessed in the RA patients. CBCT was then performed in all subjects and osseous TMJ abnormalities were assessed. RESULTS: According to the Fonseca's questionnaire, 14.3% of the patients had no TMJ dysfunction, while 50%, 21.4%, and 14.3% had mild, moderate, and severe dysfunction, respectively. RF was positive in 64.3% of patients, and the ESR level was high in 100%. Imaging findings revealed a statistically significantly higher prevalence of erosion (85.7%), flattening (89.3%), osteophyte formation (32.1%), subchondral cyst (32.1%), sclerosis (64.3%), and condylar irregularities (28.6%) in the RA patients than in the controls. No correlations were found between CBCT findings and the clinical findings, the severity of TMJ dysfunction, disease duration, or laboratory results. CONCLUSION: RA patients might show extensive osseous abnormalities with no/mild clinical signs or symptoms of TMJ dysfunction that necessitate TMJ imaging for these patients. CBCT is a valuable and efficient modality that can assess osseous TMJ changes in RA patients.
30525048 Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis. 2018 Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining were altered following osteochondral injury in an experimental equine osteoarthritis (OA) model and (2) to measure galectin-1 and-3 mRNA expression and synovial fluid concentrations in naturally occurring equine carpal OA. Synovial fluid galectin-1 and-3 concentrations were quantified using custom ELISAs in two research horse cohorts undergoing experimental OA induction (n = 5 and 4) and in a cohort of horses with naturally occurring carpal OA (n = 57). Galectin mRNA expression in synovial membrane and cartilage tissue obtained from carpal joints of horses with naturally occurring OA was measured using RT-qPCR, and galectin immunostaining was assessed in synovial membrane and osteochondral tissues in the experimental model (n = 5). Synovial fluid galectin-1 and-3 concentrations increased following experimental carpal osteochondral fragmentation. Cartilage galectin-1 mRNA expression increased with OA severity in naturally occurring disease. The superficial zone of healthy articular cartilage stained intensely for galectin-3 in sham-operated joints, whereas galectin-1 staining was nearly absent. Chondrocyte galectin-1 and-3 immunoreactivity increased following cartilage injury, particularly in galectin-1 positive chondrones. Galectins-1 and-3 are present in healthy equine synovial fluid and increase following post-traumatic OA. Healthy superficial zone chondrocytes express galectin-3, whereas galectin-1 chondrocyte staining is limited predominantly to chondrones and injured cartilage. Further work is needed to clarify the functions of galectins-1 and-3 in healthy and OA joints.
29862044 Initial validation and results of the Symptoms in Persons At Risk of Rheumatoid Arthritis 2018 OBJECTIVES: To describe the development and assess the psychometric properties of the novel 'Symptoms in Persons At Risk of Rheumatoid Arthritis' (SPARRA) questionnaire in individuals at risk of rheumatoid arthritis (RA) and to quantify their symptoms. METHODS: The questionnaire items were derived from a qualitative study in patients with seropositive arthralgia. The questionnaire was administered to 219 individuals at risk of RA on the basis of symptoms or autoantibody positivity: 74% rheumatoid factor and/or anticitrullinated protein antibodies positive, 26% seronegative. Validity, reliability and responsiveness were assessed. Eighteen first degree relatives (FDR) of patients with RA were used for comparison. RESULTS: Face and content validity were high. The test-retest showed good agreement and reliability (1 week and 6 months). Overall, construct validity was low to moderate, with higher values for concurrent validity, suggesting that some questions reflect symptom content not captured with regular Visual Analogue Scale pain/well-being. Responsiveness was low (small subgroup). Finally, the burden of symptoms in both seronegative and seropositive at risk individuals was high, with pain, stiffness and fatigue being the most common ones with a major impact on daily functioning. The FDR cohort (mostly healthy individuals) showed a lower burden of symptoms; however, the distribution of symptoms was similar. CONCLUSIONS: The SPARRA questionnaire has good psychometric properties and can add information to currently available clinical measures in individuals at risk of RA. The studied group had a high burden and impact of symptoms. Future studies should evaluate whether SPARRA data can improve the prediction of RA in at risk individuals.
29410374 A novel combination of astilbin and low-dose methotrexate respectively targeting A(2A)AR a 2018 Jul Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment with frequently serious adverse effects. Therefore, combination of low-dose MTX with other drugs is often used in clinic. In this study, we investigated the improvement of astilbin and low-dose MTX combination on collagen-induced arthritis in DBA/1J mice. Results showed that the clinic score, incidence rate, paw swelling, pathological changes of joints and rheumatoid factors were more alleviated in combination therapy than MTX or astilbin alone group. Elevated antibodies (IgG, IgG1, IgG2a, IgM and anti-collagen IgG) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ and IL-17A) in serum were significantly inhibited, while anti-inflammatory cytokine, IL-10, was enhanced by combination therapy. Further studies indicated that combination therapy significantly decreased Th1 and Th17 cell differentiation and increased Treg cell differentiation. Mechanisms analysis demonstrated combination therapy greatly inhibited Con A-activated MAPK and inflammatory transcriptional signals. Moreover, MTX activated adenosine release and astilbin specifically up-regulated A(2A) adenosine receptor (A(2A)AR) expression simultaneously, which most probably contributed to the synergistic efficacy of combination therapy. ZM241385, a specific antagonist of A(2A)AR, greatly blocked the effects of combination therapy on T cell functions and downstream pathways. All these findings suggest that astilbin is a valuable candidate for low-dose MTX combined therapy in RA via increasing A(2A)AR/adenosine system and decreasing ERK/NFκB/STATs signals.
29531782 Physician global assessments for disease activity in rheumatoid arthritis are all over the 2018 INTRODUCTION: Physician global assessments of disease activity (medical doctor (MD) globals) are important outcomes. MD globals may vary based on their age, gender, practice setting and experience (number of patients seen per year and years in practice). METHODS: We determined the variability of MD globals, surveying rheumatologists from the Canadian Rheumatology Association using rheumatoid arthiritis (RA) cases rated by MD for disease activity from 0 to 10. Cases were developed to span the spectrum of disease activity. Kappa, intraclass correlation (ICC) coefficients and linear mixed models were used. RESULTS: 109 responded to the survey (approximately 30% response). The range of MD globals for the same scenario was as high as 7.6 out of 10, indicating vast discrepancies between physicians. Some scenarios outlined changes in individual patients; however, physicians surveyed were often in disagreement as to how much the patient recovered or worsened but the direction was the same (ie, if better all agreed). When physician-related factors were analysed separately, MD global scores were significantly influenced by age and experience (ranked by a physician, number of patients seen per year and years in clinical practice) in linear mixed models. Multivariate analysis revealed borderline significance for two age categories (56-65 years, P=0.049; over 65 years, P=0.058) and those who have seen 600-800 patients per year (P=0.056). CONCLUSIONS: This emphasises the need to establish evaluation criteria in RA for disease. Perhaps, a catalogue of patient scenarios that range from 0 to 10 could be developed, standardised and agreed on to decrease the wide variability of ranking by rheumatologists.
29896977 Levels of Health Theory With the Example of a Case of Juvenile Rheumatoid Arthritis. 2018 Jan OBJECTIVE: Contemporary medicine is in great need of a new patient health group classification that could be the basis for in-depth pathology assessments, disease development and prognosis, and the possibility of healing, as well as for possible complications of organism reactions to treatment processes. This classification is possible if founded on holistic approaches at the level of health assessment from the point of view of organism reactivity and resistance. Such a classification, assigning 12 levels and 4 health groups, exists in classical homeopathy. METHODS: A new method for determining the group and level of health is shown in a case of juvenile rheumatoid arthritis of a generalized form in an 11-year-old girl, treated with classical homeopathy. The follow-up of the case is 18 years. CONCLUSION: The method allows the physician to assess the organism dynamics as a whole during the pathology development.
30430560 The immunopathogenesis of fibrosis in systemic sclerosis. 2019 Mar Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease. It is characterized by a triad of hallmarks: immune dysfunction, fibrosis and vasculopathy. Immune dysfunction in SSc is characterized by the activation and recruitment of immune cells and the production of autoantibodies and cytokines. How immune abnormalities link the fibrosis and vasculopathy in SSc is poorly understood. A plethora of immune cell types are implicated in the immunopathogenesis of SSc, including T cells, B cells, dendritic cells, mast cells and macrophages. How these different cell types interact to contribute to SSc is complicated, and can involve cell-to-cell interactions and communication via cytokines, including transforming growth factor (TGF)-β, interleukin (IL)-6 and IL-4. We will attempt to review significant and recent research demonstrating the importance of immune cell regulation in the immunopathogenesis of SSc with a particular focus on fibrosis.
30488533 Gene polymorphisms and serum levels of TL1A in patients with rheumatoid arthritis. 2019 Jul Recent findings showed elevated expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) in rheumatoid arthritis (RA) patients and arthritis mice. However, whether TL1A gene polymorphisms may correlate with RA susceptibility needs to be discussed. This case-control study was performed on 350 RA patients and 556 healthy subjects to identify TL1A genetic variants (rs3810936, rs6478109, and rs7848647) and their possible association with TL1A levels, susceptibility to and severity of RA. Odds ratio and 95% confidence interval were calculated to represent the correlation between TL1A polymorphisms and RA. The TL1A serum levels were evaluated. Results showed that frequencies of TC, TT + TC genotypes of rs3810936, rs7848647 in RA patients were significantly lower in RA patients compared with controls. Patients with C allele showed more severe disease course (disease activity index: erythrocyte sedimentation rate, rheumatoid factor) than in carriers of T allele. However, the allele or genotype frequencies of rs6478109 were not associated with RA. In addition, TL1A genetic variants conferred higher TL1A levels in RA patients compared with controls. In conclusion, these findings indicated an association between TL1A rs3810936, rs7848647 variation and the susceptibility of RA in a sample of Chinese individuals, and TL1A may correlate with severity of RA.
29736147 Recombinant interferon alpha 2b in rheumatoid arthritis: good antigen for rheumatoid arthr 2018 AIM OF THE STUDY: Interferon alpha-induced arthritis and activation of the type 1 interferon pathway during rheumatoid arthritis (RA) has been well documented but the underlying mechanism remains unclear. This study addressed the binding specificity of antibodies with recombinant interferon alpha 2b (rIFN α-2b) in sera from different RA patients. Utilization of anti-hrIFN α-2b antibodies as a probe for estimation of interferon α-2b concentration in RA patients' synovial fluid (SF) was also investigated. MATERIAL AND METHODS: Binding specificities of antibodies from the sera of 60 RA patients and 35 controls subjects were studied by direct binding, inhibition ELISA, and quantitative precipitation titration. Inhibition ELISA was also used to estimate patients' SF interferon α-2b concentrations. RESULTS: RA IgG from patients' sera showed strong recognition to hrIFN α-2b in comparison to commercially available interferon (IFN α-2b) (p < 0.05) or the gene encoding this interferon (IFN α-2b gene) (p < 0.05). The affinity of RA antibodies for rIFN α-2b (1.10 × 10(-7) M) was found to be high as assessed by Langmuir plot. No significant difference in the level of interferon α in the SF of RA patients was observed as compared to the healthy controls. CONCLUSIONS: rIFN α-2b presents unique epitopes that might explain the possible antigenic role in the induction of RA antibodies and anti-rIFN α-2b antibodies represent an alternative immunological probe for the estimation of interferon α in the SF of RA patients.
30886961 Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of r 2018 Cardiovascular disease (CVD) is markedly increased in patients with rheumatoid arthritis partly due to accelerated atherosclerosis from chronic inflammation. Traditional cardiovascular risk factors such as hypertension, hyperlipidemia, smoking, diabetes mellitus and physical inactivity are also highly prevalent among patients with rheumatoid arthritis (RA) and contribute to the CVD risk. The impact of traditional risk factors on the CVD risk appears to be different in the RA and non-RA population. However, hyperlipidemia, diabetes mellitus, body mass index and family history of CVD influence the CVD risk in RA patients the same way they do for the non-RA population. Despite that, screening and treatment of these risk factors is suboptimal among patients with RA. Recent guidelines from the European League Against Rheumatism (EULAR) recommend aggressive management of traditional risk factors in addition to RA disease activity control to decrease the CVD risk. Several CVD risk calculators are available for clinical use to stratify a patients' risk of developing a CVD event. Most of these calculators do not account for RA as a risk factor; thus, a multiplication factor of 1.5 is recommended to predict the risk more accurately. In order to reduce CVD in the RA population, national guidelines for the prevention of CVD should be applied to manage traditional risk factors in addition to aggressive control of RA disease activity. While current data suggests a protective effect of non-biologic disease modifying anti-rheumatic drugs (DMARDs) and biologics on cardiovascular events among patients with RA, more data is needed to define this effect more accurately.
30874239 Tumor-Associated Antigens in Rheumatoid Arthritis Interstitial Lung Disease or Malignancy? 2018 Dec OBJECTIVES: This study aims to evaluate the serum tumor-associated antigen levels and the possible association between these markers and interstitial lung disease (ILD) or malignancy in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: The study included 83 RA patients (20 males, 63 females; mean age 59.3±12.1 years; range 25 to 83 years), 43 with ILD (13 males, 30 females; mean age 60.1±11.5 years; range 25 to 83 years) and 40 without ILD (7 males, 33 females; mean age 58.5±12.7 years; range 28 to 78 years). Clinical symptoms, pulmonary function test, chest X-ray, and high-resolution computed tomography were used for the diagnosis of ILD. Age, sex, history of smoking, acute-phase reactants, rheumatoid factor, anti-cyclic citrullinated peptide, carcinoembryonic antigen, cancer antigen (CA) 15-3, CA 125, and CA 19-9 were evaluated. The relationship between parameters in RA patients with/without ILD was assessed by t-test and Mann-Whitney U test. RESULTS: Five RA patients (11.6%) with ILD had carcinoembryonic antigen levels above the upper limit. The numbers of RA-ILD patients with above the upper limit of CA 19-9, CA 15-3, and CA 125 levels were 10 (23.2%), 13 (30.2%), and five (11.6%), respectively. Rates of RA patients without ILD with tumor-associated antigens exceeding the upper limit were 15% for carcinoembryonic antigen, 2.5% for CA 19-9, 7.5% for CA 15-3, and 7.5% for CA 125. No evidence of any malignancy was detected by medical history, physical examination, and laboratory and imaging methods in patients who had high levels of serum tumor-associated antigen. CA 15-3 (p=0.001), CA 125 (p=0.040), and CA 19-9 (p=0.018) levels were statistically significantly different in RA patients with ILD compared to those without ILD. Rheumatoid factor, anti-cyclic citrullinated peptide, and tumor-associated antigens were higher in RA patients with ILD than those without ILD. CONCLUSION: There is a relationship between ILD and tumor marker levels in connective tissue diseases. Elevated tumor markers may not be associated with hidden tumor or malignancy in RA patients. These antigens may be used as predictive biomarkers particularly in RA patients with ILD.
30886953 Perioperative medical management for patients with RA, SPA, and SLE undergoing total hip a 2018 Total hip (THA) and total knee arthroplasty (TKA) are widely used, successful procedures for symptomatic end stage arthritis of the hips or knees, but patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and spondyloarthritis (SPA) including ankylosing spondylitis (AS) and psoriatic arthritis (PSA) are at higher risk for adverse events after surgery. Utilization rates of THA and TKA remain high for patients with RA, and rates of arthroplasty have increased for patients with SLE and SPA. However, complications such as infection are increased for patients with SLE, RA, and SPA, most of whom are receiving potent immunosuppressant medications and glucocorticoids at the time of surgery. Patients with SLE and AS are also at increased risk for perioperative cardiac and venous thromboembolism (VTE), while RA patients do not have an increase in perioperative cardiac or VTE risk, despite an overall increase in VTE and cardiac disease. This narrative review will discuss the areas of heightened risk for patients with RA, SLE, and SPA, and the perioperative management strategies currently used to minimize the risks.
29415905 Anti-inflammatory Effects of a Small Molecule Gastrin-Releasing Peptide Receptor Antagonis 2018 Apr 1 The anti-inflammatory effects of (R)-2-(1H-Imidazol-1-yl) ethyl-3-(1H-indol-3-yl)-2-(2-p-tolylacetamido)propanamide (RH-1402), a previous designed small molecule Gastrin releasing peptide (GRP) antagonist were evaluated in adjuvant-induced arthritic model of rats, and the inhibitory effect on neutrophil migration induced by GRP was determined by a transwell system experiment in vitro. The arthritis was induced by injection of Complete Freund's Adjuvant (CFA) containing 10 mg/mL of heat killed mycobacterium into the left hind footpad. Experimental rats were randomly divided into 6 groups, including control, placebo, positive control group, RH-1402 of low/middle/high dose group. Disease incidence and severity was evaluated through scoring of the paw edema and histologic features of joint synovial. Blood of all experimental rats was collected for interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) cytokine levels. A transwell system was used to investigate whether RH-1402 would inhibit neutrophils migrating up a gradient of GRP in vitro. RH-1402 (5 and 10 mg/kg) significantly decreased adjuvant induced increased arthritis index during the administration period (days 14-20). Significant inhibition of joint synovial histological features can be found in the RH-1402 treated group, including alleviated Hyperplasia, Inflammatory of infiltration and activation of pannus formation. It also suppressed TNF-α and IL-1β level. Five and 10 mg/kg of RH-1402 significantly inhibited the effect of GRP on neutrophil migration with a dose dependent relationship. These findings indicate that RH-1402 have potential protective anti-inflammatory effects on experimental models of arthritis.
32185318 Secondary hemophagocytic lymphohistiocytosis in a patient with rheumatoid arthritis and va 2018 Sep Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by excessive systemic inflammation, caused by uncontrolled activation of lymphocytes and macrophages, which secrete increased amounts of cytokines. HLH may be caused by gene mutations (primary HLH) or associated with malignancy, immunodeficiency, infection or autoimmune disease (secondary HLH). A 58-year-old woman with seropositive rheumatoid arthritis (RA) presented with fever, ulcers on the left foot and in the intergluteal cleft and increased inflammation markers. Clinical and laboratory evaluation, combined with findings from intra-arterial digital subtraction angiography of the lower limbs, pointed towards the diagnosis of vasculitis. Intravenous administration of low-dose cyclophosphamide resulted in recession of fever and decrease of inflammation markers. However, the patient later developed pancytopenia, hepatomegaly, hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia, while bone marrow aspiration demonstrated hemophagocytosis. The diagnosis of HLH was established. An extensive workup excluded malignancies, systemic infections and immunodeficiencies. HLH in our patient was attributed to activation of RA and presentation of vasculitis. Treatment with corticosteroids and intravenous immunoglobulin led to resolution of fever, correction of pancytopenia and complete healing of the ulcers. Timely diagnosis and treatment of HLH is highly important for a favorable outcome for the patients. Treatment of secondary HLH associated with autoimmune diseases involves corticosteroids and/or other immunomodulatory agents, such as intravenous immunoglobulin.
29867986 Protection Against Arthritis by the Parasitic Worm Product ES-62, and Its Drug-Like Small 2018 The immunomodulatory actions of parasitic helminth excretory-secretory (ES) products that serendipitously protect against development of chronic inflammatory disorders are well established: however, knowledge of the interaction between ES products and the host musculoskeletal system in such diseases is limited. In this study, we have focused on ES-62, a glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties, and also two synthetic drug-like PC-based small molecule analogues (SMAs) that mimic ES-62's immunomodulatory activity. We have previously shown that each of these molecules prevents development of pathology in collagen-induced arthritis (CIA), a model of the musculoskeletal disease rheumatoid arthritis (RA) and reflecting this, we now report that ES-62 and its SMAs, modify bone remodeling by altering bone marrow progenitors and thus impacting on osteoclastogenesis. Consistent with this, we find that these molecules inhibit functional osteoclast differentiation in vitro. Furthermore, this appears to be achieved by induction of anti-oxidant response gene expression, thereby resulting in reduction of the reactive oxygen species production that is necessary for the increased osteoclastogenesis witnessed in musculoskeletal diseases like RA.
30828203 Bone stock reconstruction for huge bone loss using allograft-bones, bone marrow, and terip 2019 Mar Bone stock reconstruction using allograft-bones, bone marrow (BM), and teriparatide (TPTD) is reported. Huge and extensive bone losses occurred in the medullary cavity of the femur and tibia of a 55-year-old female rheumatoid arthritis patient with severe osteoporosis after debridement of her infected total knee arthroplasty. Because of the risks of unstable prosthetic fixation and intra-operation fracture, we first reconstructed the bone stock. Chipped allograft bones mixed with BM were implanted in the bone defects, and TPTD was administrated for the osteoporosis therapy. Good bone formation was found by computed tomography after 4 months. Bone turnover markers and bone mineral density (BMD) were increased at 6 months. We confirmed good bone formation at the re-implantation surgery. The newly formed bone harvested during the re-implantation surgery showed active osteoblast-like lining cells. TPTD is known to enhance allograft bone union, mesenchymal stem cell differentiation into osteoblasts, and BMD. This tissue engineering-based technique might be improved by the various effects of TPTD. This method without any laboratory cell culture might be a good option for bone stock reconstruction surgery in ordinary hospitals.
30147384 A rare case of suicidal ideation related to Adalimumab use. 2018 INTRODUCTION: Patients undergoing treatment with an anti-tumor necrosis factor-alpha (TNF-α) agent can, as an adverse event, develop anti-TNF-α-induced lupus (ATIL). Neuropsychiatric symptoms such as depression and suicidal ideations are not commonly seen in patients who develop ATIL. We describe a case of a 56-year-old female who developed ATIL and suicidal ideations while on Adalimumab. CASE PRESENTATION: A 56-year-old female with rheumatoid arthritis (RA) and no known prior history of systemic lupus erythematosus or depression presented with suicidal ideations, joint pains and a malar rash after a recent change in her Adalimumab dose. She was treated for an acute ATIL episode based on her symptoms and serologies which were positive for anti-double-stranded deoxyribonucleic acid antibody. An inpatient psychiatric consultation determined that the patient's suicidal ideations may be an associated symptom of her current ATIL episode or possibly secondary to her chronic pain and debilitation from her RA. The patient's Adalimumab was discontinued and she was treated with a course of intravenous glucocorticoid. The patient's suicidal ideations resolved and her anti-double-stranded deoxyribonucleic acid antibody serologies became negative. She was subsequently started on Abatacept and has achieved remission of her RA with no further suicidal ideations. DISCUSSION: The development of ATIL in patients undergoing treatment with an anti-TNF-α agent is a rare occurrence. The aim of reporting our case is to increase understanding of ATIL by highlighting the occurrence of neuropsychiatric symptoms in a patient who developed ATIL.
29464097 The association between hydroxychloroquine treatment and cardiovascular morbidity among rh 2018 Jan 19 OBJECTIVES: To examine the independent effect of hydroxychloroquine (HCQ) treatment on cardiovascular morbidity among RA patients. MATERIALS AND METHODS: A retrospective cohort study of RA patients treated at Meir medical center between 2003-2013 was conducted. Patients were divided into two groups, those who had been treated with HCQ during the course of their disease and those who had never received it. The two groups were compared for possible confounding factors. Study endpoints included arterial and venous thrombotic events. RESULTS: A total of 514 suitable RA patients were identified, 241 HCQ-treated and 273 non-treated patients. Of the HCQ-treated patients, 32 (13.3%) suffered from cardiovascular events compared to 104 (38.1%) of the non-treated group. HCQ treatment had a significant protective effect for all cardiovascular events examined (HR = 0.456 CI 0.287 to 0.726) as well as arterial events alone (HR = 0.461 CI 0.274 to 0.778). A dose of 400 mg HCQ per day demonstrated a protective effect for any cardiovascular event (HR = 0.432 CI 0.243 to 0.768), while the lower dose of 200 mg per day showed no significant protective effect. CONCLUSIONS: The use of HCQ is independently associated with decreased risk for cardiovascular morbidity among RA patients, particularly with a higher dose of 400 mg per day. This newly demonstrated effect of HCQ should be considered in the overall management of RA.
29900983 Relationship Between Smoking and Structural Damage, Autoimmune Antibodies, and Disability 2018 Mar OBJECTIVES: This study aims to investigate the relationship between smoking and structural damage, autoimmune antibodies, and disability in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: This cross-sectional study included 165 RA patients (36 males, 129 females; mean age 52.4±12.8 years; range 21 to 82 years). Disease duration, age at disease onset, smoking habits, rheumatoid factor (RF), and anti-cyclic citrullinated peptide levels were recorded. Morning stiffness, pain with visual analog scale, Health Assessment Questionnaire Scores And Disease Activity Score 28 were calculated. Patients' standard hand radiographs were evaluated. RESULTS: Patients were divided into three groups according to their smoking habits. Ninety-nine patients (60%) were never smokers, 45 patients (27.3%) were long-term smokers and 21 patients (12.7%) were new smokers. Three groups were compared for disease activity. Disease activity score 28 scores were 3.2±1.2, 3.2±1.3, and 3.2±1.4, respectively (p>0.05). The erosion score (2.6±5.8, 7.1±10.9, and 11.1±19.2, respectively) and joint space narrowing score (9.9±7.3, 18.6±14.9, and 17.3±12.3, respectively) according to modified Sharp method were significantly lower in never smokers group than other groups (p<0.05). RF titrations were 55.2±58.9, 60.5±63.1, and 84.9±71.5, respectively, and levels of long-term smokers group were significantly higher than the other groups (p<0.05). Joint space narrowing score was 16.2±11.9 and 6.4±10.4 in RF (+) and RF (-) patients, respectively (p<0.05). There was no significant relationship between anti-cyclic citrullinated peptide levels and others parameters. CONCLUSION: Although smoking is known as a poor prognostic factor in RA, there was no correlation between disease activity and smoking in our study. However, less radiographic damage was found in never smokers. Smoking does not appear to correlate with RA disease activity but it may be effective in the long-term joint damage.
29385909 Wu-Tou Decoction Inhibits Angiogenesis in Experimental Arthritis by Targeting VEGFR2 Signa 2018 Oct Wu-tou decoction (WTD) is a classic traditional Chinese medicine formula and has been extensively used for the treatment of rheumatoid arthritis (RA). Previous reports indicate that WTD possesses anti-inflammatory and antinociceptive activities, and inhibits the development of arthritic joints and disease severity of collagen-induced arthritis (CIA) or adjuvant-induced rats; however, its action on angiogenesis of RA has not been clarified. This study aims to determine the anti-angiogenic activity of WTD in CIA rats and in various angiogenesis models. Our data showed that WTD (0.95, 1.9, and 3.8 g/kg) markedly reduced the immature blood vessels in synovial membrane tissues of inflamed joints from CIA rats. It also inhibited in vivo angiogenesis in chick embryo and VEGF(165)-induced microvessel sprout formation ex vivo. Meanwhile, WTD suppressed VEGF(165)-/MH7A-induced migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, WTD significantly reduced the expression of angiogenic activators, including vascular endothelial growth factor (VEGF), VEGFR2, interleukin (IL)-1β, IL-17, transforming growth factor-β, platelet-derived growth factor, placenta growth factor, angiopoietin (Ang) I and Ang II in synovium of CIA rats, and/or in HUVECs. More interestingly, WTD blocked the autophosphorylation of VEGF(165)-induced VEGFR2 and consequently downregulated the signaling pathways of activated AKT, ERK1/2, JNK, and p38 in VEGF(165)-induced HUVECs. These findings suggest for the first time that WTD possesses the anti-angiogenic effect in RA in vivo, ex vivo, and in vitro by interrupting the targeting of VEGFR2 activation.