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ID PMID Title PublicationDate abstract
29183769 TPL2 kinase action and control of inflammation. 2018 Mar Tumor progression locus 2 (TPL2, also known as COT or MAP3K8) is a mitogen-activated protein kinase kinase (MAP3K) activated downstream of TNFαR, IL1R, TLR, CD40, IL17R, and some GPCRs. TPL2 regulates the MEK1/2 and ERK1/2 pathways to regulate a cascade of inflammatory responses. In parallel to this, TPL2 also activates p38α and p38δ to drive the production of various inflammatory mediators in neutrophils. We discuss the implications of this finding in the context of various inflammatory diseases.
29181586 [Indications for joint replacement : Total hip arthroplasty]. 2018 Feb Total hip arthroplasty (THA) is a very successful and effective orthopedic operation with very good immediate as well as long-term results to alleviate pain and improve health-related quality of life. A THA is indicated in end-stage hip osteoarthritis with a high degree of persistent suffering when conservative treatment has failed and in patients who wish a THA. This statement is generally valid for patients where the medical history, clinical examination and radiographic findings are conclusive, the pressure of suffering and the expectations are realistic. The timing of THA is based on the patient's discomfort. The treatment of these patients should include an interdisciplinary approach and the main goal is to improve the quality of life. Patients will learn to have reasonable expectations and should be well informed about the risks and benefits of THA. Realistic patient expectations seem to be a predictive factor for a good subjective outcome after THA.
29955387 MR signal intensity: staying on the bright side in MR image interpretation. 2018 In 2003, the Nobel Prize for Medicine was awarded for contribution to the invention of MRI, reflecting the incredible value of MRI for medicine. Since 2003, enormous technical advancements have been made in acquiring MR images. However, MRI has a complicated, accident-prone dark side; images are not calibrated and respective images are dependent on all kinds of subjective choices in the settings of the machine, acquisition technique parameters, reconstruction techniques, data transmission, filtering and postprocessing techniques. The bright side is that understanding MR techniques increases opportunities to unravel characteristics of tissue. In this viewpoint, we summarise the different subjective choices that can be made to generate MR images and stress the importance of communication between radiologists and rheumatologists to correctly interpret images.
30214164 Patient preferences for rheumatoid arthritis treatments: results from the national cross-s 2018 INTRODUCTION: To investigate the treatment preferences of patients with rheumatoid arthritis (RA) and determine whether these preferences are related to specific disease characteristics. METHOD: A national survey was designed to collect demographic, disease, treatment, and preference data on RA patients enrolled in 7 private and university hospital clinics in Lebanon. Associations between patient factors and treatment preferences for RA were analyzed by χ(2) or Mann-Whitney U test. RESULTS: A total of 693 patients (83% female; 67% aged 41-70 years) consulting 7 trained rheumatologists completed the survey. Most patients (80%) had established RA >24 months, and approximately one-third (34%) were in remission according to the disease activity score in 28 joints (DAS28). Most (87%) were receiving oral agents (60% oral only). Almost two-thirds of patients (64%) expressed a preference for oral treatments, and more than half (53%) ranked doctor's advice as the most influential factor when choosing treatment. In univariable analysis, health coverage, radiographic damage, disease duration, current therapy, and previous side effects were significantly associated with treatment preference. In multivariable analyses, only radiographic damage and current route of administration were independently associated with preference (both P<0.001), with patients with no radiographic damage and those on oral-only therapy being more likely to prefer oral agents. CONCLUSION: RA patients expressed a preference for oral rather than subcutaneous/intravenous-administered drugs. Understanding patients' preferences may help to inform policymaker decisions.
30127649 Treatment patterns, health care resource utilization and costs of rheumatoid arthritis pat 2018 OBJECTIVES: This study aimed to: 1) describe treatment patterns and drug utilization profile (in terms of therapeutic strategy used, switch, persistence and drug consumption variation) among adult patients affected by rheumatoid arthritis (RA), and 2) estimate the health care resource utilization and its associated direct cost for the management of RA patients. METHODS: A retrospective cohort analysis, using administrative databases of six Local Health Units in Italy, was performed. All adult patients with a confirmed diagnosis of RA between January 1, 2010 and December 31, 2014 were enrolled. The date of the first RA diagnosis according to the study criteria during the study period represented the index date (ID) for each patient. Patients enrolled were observed from the ID for at least 12 months (follow-up period), and their clinical characteristics were investigated for 12 months prior to the ID. RESULTS: A total of 10,401 patients with a confirmed RA diagnosis were included. Mean age was 63.0 years and 25% were male; 67% of patients were untreated at ID. During the followup period, 67.8% of patients treated with biologic agents were persistent with initial therapy, compared to 45.7% for patients on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), while 11% of patients treated with biologic agents switched during the follow-up period, compared to 17.6% of csDMARDs-treated ones. At the end of the follow-up period, 14.7% of all patients in the analysis had an increase and 12.6% of them had a decrease in their initial drug consumption. The mean cost per RA patient was €3,743. CONCLUSION: Our study showed that there is still much that needs to be learned about the prescription of csDMARDs and biologics to RA patients in Italy and to identify areas for future research. The knowledge of RA management in a real-life clinical setting could offer an opportunity to improve the management of RA in Italy.
30042603 The impacts of state and trait anxiety as moderated by perceived social support among Nige 2018 OBJECTIVES: To assess the levels of state and trait anxiety and determine their relationships with perceived social support among Nigerian patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: A cross-sectional study of 50 patients satisfying the 2010 American College of Rheumatology/European League against Rheumatism Classification Criteria for RA was conducted. Anxiety was assessed using the Spielberger State-Trait Anxiety Inventory (STAI), perceived social support by the Interpersonal Support Evaluation List (ISEL), health-related quality of life (HRQoL) by the Medical Outcome Study 36-Item Short Form Health Survey (SF-36) and disability by the Health Assessment Questionnaire-Disability Index (HAQ-DI). RESULTS: The mean state anxiety (STAI-S), trait anxiety (STAI-T) and ISEL scores among the patients were 35.2 ±10.2, 36.7 ±8.8 and 87.2 ±21.2 respectively. Pathological degrees of state and trait anxiety were found among 7 (14%) and 5 (10.4%) patients respectively. There was a negative correlation between the STAI-T score and the ISEL score (r = -0.362, p = 0.011). However, the correlation between STAI-S and ISEL was not statistically significant (r = -0.193, p = 0.179). A moderate-to-high correlation was found between each of STAI-S and STAI-T and all subscales and component summaries of the SF-36. ISEL score correlated significantly with role emotional (r = 0.377, p = 0.008), mental health (r = 0.482, p ≤ 0.001) and bodily pain (r = 0.320, p = 0.025) domains and the mental component summary (r = 0.380, p = 0.007) of SF-36. HAQ-DI correlated strongly with both STAI-S (r = 0.735, p ≤ 0.001) and STAI-T (r = 0.575, p ≤ 0.001) but not with ISEL. CONCLUSIONS: State and trait anxiety correlate negatively with all aspects of HRQoL and disability, and there is a notable relationship between perceived social support and trait anxiety as well as the mental aspect of HRQoL.
29955381 Long-term use of adalimumab as monotherapy after attainment of low disease activity with a 2018 OBJECTIVE: To evaluate long-term clinical, functional and radiographic outcomes in an open-label extension (OLE) study in patients with rheumatoid arthritis (RA) receiving adalimumab monotherapy or adalimumab+methotrexate following attainment of low disease activity (LDA) with adalimumab+methotrexate. METHODS: Methotrexate-naive patients with early RA were randomised to adalimumab, methotrexate or adalimumab +methotrexate in a double-blind, 2-year study. Patients who completed the study and achieved LDA (28-joint Disease Activity Score using C reactive protein (DAS28(CRP)<3.2) could receive adalimumab monotherapy for up to 8 additional years in the OLE; open-label methotrexate could be added per investigator's discretion. This post hoc analysis included data up to OLE year 3 (study year 5) from patients receiving adalimumab+methotrexate who achieved LDA at year 2 followed by adalimumab monotherapy or methotrexate reinitiation. Normal physical function was defined as Disability Index of the Health Assessment Questionnaire <0.5 and radiographic non-progression as change in modified total Sharp score ≤0.5. RESULTS: Of 140 patients initiating adalimumab monotherapy, 84 (60%) received adalimumab only (methotrexate non-use) and 56 (40%) reinitiated methotrexate (methotrexate use) during OLE treatment. Median (IQR) time to first methotrexate use was 5.1 (0.1-31.4) weeks. Among methotrexate users, 61% retained LDA, 48% achieved DAS28(CRP) <2.6, 45% had normal physical function and 46% had no radiographic progression at year 5; for non-users, 63%, 50%, 58% and 50%, respectively, achieved these milestones. Adverse event rates were similar between methotrexate non-use and use patients. CONCLUSIONS: Adalimumab monotherapy effectively maintained good clinical, functional and radiographic outcomes for up to 3 additional years in ≥50% of patients who attained LDA after 2 years of adalimumab+methotrexate therapy. TRIAL REGISTRATION NUMBER: NCT00195663; Post-results.
29955380 Impact of tocilizumab administered intravenously or subcutaneously on patient-reported qua 2018 OBJECTIVE: Randomised controlled trials (RCTs) have shown tocilizumab (TCZ) administered intravenously or subcutaneously with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to be superior to csDMARDs alone for improving rheumatoid arthritis (RA) disease activity. This study evaluated the effect of TCZ-intravenous and TCZ-subcutaneous on patient-reported outcomes (PROs) in three RCT populations. METHODS: OPTION (NCT00106548), BREVACTA (NCT01232569) and SUMMACTA (NCT01194414) were independent RCTs evaluating the efficacy and safety of TCZ-intravenous and/or TCZ-subcutaneous with csDMARDs in patients with RA. PROs included patient global assessment, pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and Short Form-36. Study outcomes included the proportions of patients reporting changes from baseline in PRO scores ≥ minimum clinically important differences (MCID) and scores ≥ age and gender-matched normative values. RESULTS: In OPTION, more patients who received TCZ-intravenous reported improvements in PROs ≥MCID (50%-82% vs 31%-57%) and scores ≥ normative values (16%-44% vs 5%-28%) at week 16 compared with placebo. Similarly, a greater proportion of patients in BREVACTA who received TCZ-subcutaneous reported improvements ≥ MCID (54%-73% vs 42%-55%) and scores ≥ normative values (8%-34% vs 4%-25%) at week 12 compared with placebo. In SUMMACTA, 61%-84% of patients who received TCZ-subcutaneous and 64%-84% of those who received TCZ-intravenous reported improvements ≥ MCID and 14%-41% and 15%-24%, respectively, scores ≥ normative values at week 24. CONCLUSIONS: TCZ-intravenous or TCZ-subcutaneous with csDMARDs resulted in more patients reporting clinically meaningful improvements and PRO scores ≥ normative values compared with placebo. These improvements were similar with TCZ-intravenous and TCZ-subcutaneous.
29862047 Mental health, fatigue and function are associated with increased risk of disease flare fo 2018 BACKGROUND: Tapering of anti-tumour necrosis factor (TNF) therapy appears feasible, safe and effective in selected patients with rheumatoid arthritis (RA). Depression is highly prevalent in RA and may impact on flare incidence through various mechanisms. This study aims to investigate if psychological states predict flare in patients' dose tapering their anti-TNF therapy. METHODS: This study is a post-hoc analysis of the Optimizing TNF Tapering in RA trial, a multicentre, randomised, open-label study investigating anti-TNF tapering in RA patients with sustained low disease activity. Patient-reported outcomes (Health Assessment Questionnaire, EuroQol 5-dimension scale, Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F), 36-Item Short Form Survey (SF-36)) were collected at baseline. The primary outcome was flare, defined as an increase in 28-joint count Disease Activity Score (DAS28) ≥0.6 and ≥1 swollen joint. Discrete-time survival models were used to identify patient-reported outcomes that predict flare. RESULTS: Ninety-seven patients were randomised to taper their anti-TNF dose by either 33% or 66%. Forty-one patients flared. Higher baseline DAS28 score was associated with flare (adjusted HR 1.96 (95% CI 1.18 to 3.24), p=0.01). Disability (SF-36 physical component score), fatigue (FACIT-F) and mental health (SF-36 mental health subscale (MH)) predicted flare in unadjusted models. In multivariate analyses, only SF-36 MH remained a statistically significant predictor of flare (adjusted HR per 10 units 0.74 (95% CI 0.60 to 0.93), p=0.01). CONCLUSIONS: Baseline DAS28 and mental health status are independently associated with flare in patients who taper their anti-TNF therapy. Fatigue and function also associate with flare but the effect disappears when adjusting for confounders. Given these findings, mental health and functional status should be considered in anti-TNF tapering decisions in order to optimise the likelihood of success. TRIAL REGISTRATION NUMBERS: EudraCT Number: 2010-020738-24; ISRCTN: 28955701; Post-results.
29873010 A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac. 2018 Dec Diclofenac is widely used to manage chronic inflammatory and degenerative joint diseases such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and extra-articular rheumatism. Its various mechanisms of action make it particularly effective in treating nociceptive pain, but it is also an alternative for treating spinal and chronic central pain. Osteoarthritis and rheumatoid arthritis are the most frequently encountered arthritic conditions in adults. The management of nociceptive pain requires a sequential hierarchical approach, with the initial NSAID treatment being characterized by the replacement of one drug with another, or complete discontinuation usually because of insufficient pain control. OA- and RA-related pain is complex and multifactorial, and due to physiological interactions between the signaling of the central and peripheral nervous systems. The mechanisms of action of diclofenac make it particularly effective in treating both nociceptive pain and chronic central pain. This review underlines the mechanisms of diclofenac involved in chronic and acute joint pain, the most relevant adverse events.
31276089 Primary care challenges in diagnosing and referring patients with suspected rheumatoid art 2018 OBJECTIVE: National guidelines advocate referring patients with persistent synovitis to rheumatology within 3 working days of presentation to primary care. This occurs infrequently. We aimed to identify modifiable barriers to early referral of suspected RA patients among English general practitioners (GPs). METHODS: We carried out a national cross-sectional survey of 1388 English GPs (RA Questionnaire for GPs [RA-QUEST] study). Questions addressed GPs' confidence in diagnosing RA, clinical factors influencing RA diagnosis/referral, timeliness of referrals and secondary care access. Data were captured using 10-point visual analog scales, five-point Likert scales, yes/no questions or free text, and were analysed descriptively. RESULTS: Small joint swelling and pain were most influential in diagnosing RA (91 and 84% rated the importance of these as 4 or 5 on a five-point Likert scale, respectively); investigations including RF (61% rating 4 or 5) and anti-CCP antibody (72% rating 4 or 5) were less influential. Patient history had the greatest impact on the decision to refer (92% rating this 4 or 5 on a 5-point Likert scale), with acute phase markers (74% rating 4 or 5) and serology (76% rating 4 or 5) less impactful. Despite the importance placed on history and examination, only 26% referred suspected RA immediately without investigations; 95% of GPs organizing further tests opted to test for RF. CONCLUSION: For suspected RA patients to be referred within 3 days of presentation to primary care there needs to be a paradigm shift in GPs' approaches to making referral decisions, with a focus on clinical history and examination findings, and not the use of investigations such as RF.
30647479 Pharmacoeconomic evaluation of costs of rheumatoid arthritis therapy with selected biologi 2018 OBJECTIVES: Among autoimmune diseases, rheumatoid arthritis (RA) is the most common chronic inflammatory disease of the joints. Its pathogenesis is still not fully understood, but the gained knowledge has contributed to the development of modern treatment. The introduction of biological therapy for RA has been a breakthrough in the standard approach to the treatment of this disease. MATERIAL AND METHODS: The study material was retrospectively collected in the Rheumatology and Systemic Tissue Diseases Clinic and Rheumatology Outpatient Clinic in dr. Jan Biziel University Hospital No. 2 in Bydgoszcz. Patients were divided into 3 groups: patients receiving infliximab - 43 patients, etanercept - 27 patients and adalimumab - 34 patients. In the study, the pharmacoeconomic analysis included direct and indirect medical costs. Direct medical costs analyzed in the study included costs for the purchase of medications, diagnostic and imaging costs, and medical consultations and hospitalization costs. The analysis included all direct medical costs incurred by the hospital and the patient, as well as indirect costs outside the healthcare sector - that is, the Polish Social Insurance Institution benefits (disability benefits, rehabilitation benefits, sickness absences). Direct medical costs are also presented from the perspective of the payer - The Polish National Health Fund - taking into account the cost and percentage share of medical expenses. RESULTS: The analysis concerned resources used since the beginning of treatment with a given biological medication for 24 months or earlier if disease remission occurred.A cost-benefit analysis was carried out in the study using biosimilar medications present on the market in relation to the treatment regimens. Considering the total cost, if only Inflectra were used in therapy, PLN 18 151.98 per patient could be saved, and in the case of Remsima, PLN 16 385.14. In less than 19 months, to use infliximab for 43 patients, PLN 780 475.80 more would have to be spent than in the case of the biosimilar medication Inflectra, and PLN 704 561 in the case of Remsima.The highest total cost is generated by treatment with adalimumab, followed by etanercept, and infliximab. Of the costs analyzed, a significant majority was for biological treatment. CONCLUSIONS: Given the Polish financial conditions, the best solution now is to reduce the prices of biological medications. This is possible through the introduction of biosimilar medications that, when placed on the market, reduce the price of the original medication, as is currently the case with Remicade and Enbrel. The introduction of Inflectra and Remsima, as well as Benepali and Erelzi, has reduced the price base of original medications to similar levels of treatment with biosimilar medications. The wider use of biological treatment would also reduce indirect costs.
30410636 Transcriptome analysis of peripheral blood from patients with rheumatoid arthritis: a syst 2018 In the era of precision medicine, transcriptome analysis of whole gene expression is an essential technology. While DNA microarray has a limited dynamic range and a problem of background hybridization, RNA sequencing (RNA-seq) has a broader dynamic range and a lower background signal that increase the sensitivity and reproducibility. While transcriptome analyses in rheumatoid arthritis (RA) have generally focused on whole peripheral blood mononuclear cells (PBMC), analyses of detailed cell subsets have an increased need for understanding the pathophysiology of disease because the involvement of CD4(+) T cells in the pathogenesis of RA has been established. Transcriptome analysis of detailed CD4(+) T cell subsets or neutrophils shed new light on the pathophysiology of RA. There are several analyses about the effect of biological treatment. Many studies report the association between type I interferon signature gene expression and response to therapy.
29844864 MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation a 2018 May 8 This study investigated whether microRNA-146a (miR-146a) mediating TLR4/NF-κB pathway affected proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes from 12 RA patients (RA-FLSs). FLSs in the logarithmic growth phase were assigned into the control, miR-146a mimic miR-146a inhibitor, Tak-242 (treated with TLR4/NF-κB pathway inhibitor) and mimic + lipopolysaccharide (LPS) groups. Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry. The expression of miR-146a, TLR4/NF-κB pathway-related proteins and cytokines were determined by RT-qPCR, western blotting and ELISA, and the release of NO by Greiss reaction. RA rat models were constructed and the primary cells were classified into the control, negative control (NC), miR-146a mimic, miR-146a inhibitor, Tak-242, mimic + LPS, and TLR4 groups. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen (PCNA) and intercellular adhesion molecular-1 (ICAM-1). The results showed that miR-146a levels were lower in RA-FLSs than control fibroblasts. miR-146a mimic and Tak-242 decreased RA-FLS proliferation and increased RA-FLS apoptosis, while miR-146a inhibitor had an opposite trend. miR-146a mimic and Tak-242 also decreased expression of TLR4, NF-κB, IL-1β, IL-6, IL-8, IL-17, COX-2, MMP-3, Seprase, and iNOS, as well as reduced NO level in RA-FLSs while miR-146a inhibitor and TLR4 increased them. TLR4 and NF-κB levels and the positive rates of PCNA and ICAM-1 expressions were lower in RA-FLSs from RA rats given miR-146a mimic from control or miR-146a inhibitor-treated rats. These results suggest that miR-146a inhibits the proliferation and inflammatory response of RA-FLSs by down-regulating TLR4/NF-κB pathway.
30067070 Acetazolamide protects rat articular chondrocytes from IL-1β-induced apoptosis by inhibit 2018 Nov Because the excessive apoptosis of articular chondrocytes contributes to extracellular matrix (ECM) loss and cartilage damage in rheumatoid arthritis (RA), inhibiting chondrocyte apoptosis might be a promising strategy for RA. Aquaporin1 (AQP1) is overexpressed in RA cartilage and synovial tissues, and play a vital pathogenic role in RA development. Particularly, we previously reported that acetazolamide (AZ) as an AQP1 inhibitor suppressed secondary inflammation and promoted ECM production in cartilage of adjuvant-induced arthritis rats. Here, we investigated the antiapoptotic effect of AZ on interleukin-1β (IL-1β)-induced apoptosis, a classic in vitro model of chondrocyte apoptosis. AZ treatment could inhibit IL-1β-induced apoptosis, evidenced by increasing cell viability, relieving apoptotic nuclear morphology, decreasing apoptosis rates, and restoring mitochondrial membrane potential. Additionally, AZ reversed IL-1β-induced decrease of Bcl-2 protein and reduced IL-1β-induced increases of Bax and caspase 3 protein, accompanied by inhibiting IκBα degradation and phosphorylation in cytoplasm, reducing NF-κB p65 protein level in nucleus and preventing NF-κB p65 translocation from cytoplasm to nucleus. In conclusion, our findings indicated that AZ could effectively attenuate IL-1β-induced chondrocyte apoptosis mediated by regulating the protein levels of apoptosis-related genes and inhibiting the activation of NF-κB signal pathway, suggesting that AZ might be of potential clinical interest in RA treatment.
29629295 In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera 2018 Mar BACKGROUND: The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. METHODS: Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. RESULTS: The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. CONCLUSION: Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.
30077425 A comprehensive review on adult onset Still's disease. 2018 Sep Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology usually affecting young adults; spiking fever, arthritis and evanescent rash are commonly observed during the disease. Other frequently observed clinical features include sore throat, hepatomegaly, splenomegaly, lymphadenopathy and serositis. Furthermore, AOSD patients may experience different life-threating complications. Macrophage activation syndrome (MAS) has been reported up to 15% of AOSD patients and it is considered to be the most severe complication of the disease being characterised by high mortality rate. During AOSD, laboratory tests reflect the systemic inflammatory process showing high levels of erythrocyte sedimentation rate and C-reactive protein. In addition, the ferritin levels are typically higher than those observed in other autoimmune, inflammatory, infectious, or neoplastic diseases. Analysing AOSD disease course, 3 different clinical patterns of AOSD have been identified: i. monocyclic pattern, characterised by a systemic single episode; ii. polycyclic pattern, characterised by multiple, ≤ 1 year lasting, flares, alternating with remissions; iii. chronic pattern, related to a persistently active disease with associated polyarthritis. At present, AOSD therapeutic strategy is aimed at targeting pro-inflammatory signs and symptoms, preventing organ damage and life-threating complications and minimising adverse effects of treatment. However, the treatment of AOSD remains largely empirical, lacking controlled clinical trials. High dosages of corticosteroids are usually the first line therapy when the systemic symptoms predominate. Despite this treatment, a large percentage of patients experiences several flares with an evolution toward the chronic disease course and up to 16% of patients die during the follow up, due to AOSD-related complications. On these bases, in the last years, biological agents have been successfully used in refractory cases. Finally, multiple recent lines of evidence have suggested new insights in AOSD pathogenesis unmasking further therapeutic targets. In fact, small molecules, used in experimental MAS models, might represent new therapeutic options.
32186088 Effect of methotrexate combined with Sanhuang Yilong decoction on serum and synovial fluid 2018 Aug OBJECTIVE: To study the effect of methotrexate (MTX) combined with Sanhuang Yilong decoction (SYD) on aquaporin (AQP) expression, and to explore the role of AQPs in the pathogenesis of rheumatoid arthritis (RA). METHODS: A total of 118 dampness-heat blockage type RA patients who were hospitalized in the General Chengdu Military Hospital between January 2014 and December 2016 were selected as subjects in this study (30 patient of these patients with knee joint effusion were assigned to the RA synovial fluid group). For the pre-treatment control groups, 30 healthy volunteers were recruited as the healthy control group and 30 osteoarthritis (OA) patients with knee joint effusion were included as OA synovial fluid control group. The RA dampness- heat blockage syndrome treatment groups were divided into 45 cases in the combined group and 45 cases in the MTX group. The combined group received MTX combined with SYD treatment while the MTX group received MTX alone. AQP1, AQP2 and AQP3 expressions were detected in the serum and synovial fluid. RESULTS: AQP1 had the highest expression, followed by AQP3, and AQP2. The serum levels of AQP1, AQP2 and AQP3 were all significantly lower than those in the healthy volunteers (P < 0.05), while the synovial fluid AQP1, AQP2 and AQP3 expression in the RA group were comparable to these in the OA groups (P > 0.05). After treatment for 2 weeks, serum AQP1, AQP2 , AQP3 were significantly increased and erythrocyte sedimentation rate, C-reactive protein, disease activity score of 28 joints were decreased in the combined group (P < 0.05). CONCLUSION: Abnormal expression of AQPs inhibits water metabolism in RA dampness-heat blockage syndrome, so liquid is accumulated at the joint, which may play an important role in the pathogenesis of RA. MTX combined with SYD for the treatment of RA can effectively increase AQP expression.
30400384 Epidermal Fatty Acid-Binding Protein: A Novel Marker in the Diagnosis of Dry Eye Disease i 2018 Nov 4 PURPOSE: Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease of the lacrimal and salivary glands. This study compared the concentrations of epidermal fatty-acid binding protein (E-FABP) in the saliva, serum, and tears of SS patients with dry eye and dry mouth, with those of healthy adults to investigate the usefulness of E-FABP as a diagnostic marker for SS. DESIGN: Prospective, observational case series. PARTICIPANTS: The subjects were 11 new patients with untreated Sjogren syndrome and 12 healthy control individuals. METHODS: The diagnosis of SS was in accordance with the Ministry of Health, Labour and Welfare (Japan) Diagnostic Criteria (1999). Saliva, serum, and tear specimens were collected during internal medicine, dental, and ophthalmological examinations. The ophthalmological tests included the Dry Eye-related Quality of life Score (DEQS), tear break-up time (BUT), vital staining with fluorescein (FS) and lissamine green (LG), and the Schirmer test-1. The E-FABP concentration in the tears, saliva, and serum was measured by enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOME MEASURE: The E-FABP concentrations were compared between patients and controls. RESULTS: There were significant differences between the patient and healthy control groups in all ophthalmological test results. There were no significant differences between the groups in the E-FABP concentrations in the saliva (p = 0.1513) or the serum (p = 0.4799), but the E-FABP concentration in the tears significantly differed between groups. The E-FABP concentration in tears tended to be significantly lower in patients with SS (mean, 323.5 ± 325.6 pg/mL) than healthy control subjects (mean, 4076 pg/mL; p = 0.0136). The E-FABP concentration in tears significantly correlated with the results of dry eye parameters. CONCLUSION: The E-FABP concentration in tears appears to be related to ocular surface epithelial damage and tear stability and may be a promising novel biomarker in the diagnosis of SS.
29257322 Human parvovirus B19 nonstructural protein NS1 activates NLRP3 inflammasome signaling in a 2018 Feb Dysregulation of inflammasomes serves a pathogenic role in autoinflammatory diseases (AIDs) and adult-onset Still's disease (AOSD) has been categorized as an AID. The present study investigated the expression of NLR family pyrin domain containing proteins (NLRPs) inflammasome in patients with AOSD, the effect of inflammasome inhibitors on NLRP3 signaling and whether human parvovirus B19‑associated antigens can activate NLRP3 in patients with AOSD. mRNA expression levels of NLRPs in peripheral blood mononuclear cells (PBMCs) from 34 patients with AOSD and 14 healthy individuals were determined using reverse transcription‑quantitative polymerase chain reaction. Protein expression of NLRP3 was evaluated by western blotting. Supernatant cytokine levels were measured by ELISA. Among the NLRPs investigated in the present study, NLRP3 transcripts were markedly elevated and expression of NLRP2, NLRP7 and NLRP12 was decreased in patients with AOSD compared with the controls. Treatment with NLRP3 inhibitors significantly reduced downstream NLRP3 signaling in PBMCs form patients with AOSD. B19‑nonstructural protein (NS)1 stimulation of PBMCs from patients with AOSD induced significant upregulation of transcript levels of NLRP3, caspase‑1 and interleukin (IL)‑1β compared with PBMCs from healthy controls. B19‑NS1 stimulation of PBMCs from patients with AOSD induced significant increase in supernatant levels of IL‑1β and protein expression of NLRP3, caspase‑1, IL‑1β, and IL‑18 compared with healthy controls. Elevated expression of NLRP3 and its downstream inflammasome signaling components in patients with AOSD indicated a potential pathogenic role of B19‑NS1. Thus, B19‑NS1 may induce expression of IL‑1β and IL‑18 through activation of caspase‑1‑associated NLRP3‑inflammasome in AOSD.