Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30074417 Combined gemfibrozil (peroxisome proliferator-activated receptor alpha agonist) with reduc 2019 Jul Objectives: The study aimed to evaluate the efficacy of combined gemfibrozil with prednisolone in the management of adjuvant-induced arthritis (AIA) rat model. Methods: Seventy two adult male Wistar albino rats were divided equally into 1-control group, three diseased groups: 2- Adjuvant induced arthritis (AIA), 3- high fat diet (HF), and 4- combined AIA-HF, and treated groups: 5- gemfibrozil 30 mg/kg treated AIA group (AIA-G) and the combined AIA-HF treated groups: 6- prednisolone equivalent to human 10 mg (AIA-HF-P10), 7- prednisolone equivalent to human 5 mg (AIA-HF-P5) 8- gemfibrozil (HF-AIA-G) and 9- combined treatment (HF-AIA-G-P5) Results: HF diet represents a precipitating factor for knee arthritis. Gemfibrozil improved the inflammatory findings in both AIA and AIA-HF groups. Combined administration of gemfibrozil with reduced steroid dose gave a similar therapeutic effect to the full steroid dose. Fortunately, we reported more reduction in the nuclear factor kappa-B (NF-κB) and high mobility group box 1 (HMGB1) in the HF-AIA-G-P5 compared with the HF-AIA-P10 group. The improvement was proved by the histological findings. Conclusion: Combined reduced prednisolone dose with gemfibrozil potentiates its anti-inflammatory activity. This could be a target in the management of rheumatoid arthritis.
28950389 Design and Evaluation of Chronomodulated Drug Delivery of Tramadol Hydrochloride. 2018 Mar Rheumatoid arthritis is an auto immune disease which requires chronotherapy as it occurs during early morning. Tramadol hydrochloride (TH) is an analgesic drug, used to treat rheumatoid arthritis. The aim of the present investigation was to develop chronomodulated drug delivery system of tramadol hydrochloride such that it releases the drug early in the morning, during which the symptoms of rheumatoid arthritis worsen. To develop chronomodulated drug delivery system of TH, initially core tablets of TH were prepared using three different supradisintegrants followed by coating with pH dependent polymer of Eudragit S100. The prepared core tablets are evaluated for physical parameters and an optimal system was identified. Further, coating composition of Eudragit S100 was optimized and coating tablets of TH was prepared. The prepared coated tablets were evaluated for weight variation, hardness, drug content and in vitro release studies in 0.1N HCl, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer. Formulation with 7.5% of coating solution (ES2) had shown a significant drug release after a lag time of 3 h (in pH 6.8 medium), 6 h (in pH 6.8 medium) and 8 h (in pH 7.4 medium), respectively. DSC studies revealed that no interaction between core and coated materials with drug was observed. Thus, chronomodulated drug delivery system of TH was formulated and assuming that if a tablet is administered around 9 pm to 10 pm, the drug release starts after a lag time of 6 h i. e., around 3am to 4 am.
30619884 Targeting Inflammation to Prevent Cardiovascular Disease in Chronic Rheumatic Diseases: My 2018 Evidence for increased risk of cardiovascular morbidity and mortality in chronic inflammatory rheumatic diseases has accumulated during the last years. Traditional cardiovascular risk factors contribute in part to the excess of cardiovascular risk in these patients and several mechanisms, including precocious acceleration of subclinical atherosclerotic damage, inflammation, and immune system deregulation factors, have been demonstrated to strictly interplay in the induction and progression of atherosclerosis. In this setting, chronic inflammation is a cornerstone of rheumatic disease pathogenesis and exerts also a pivotal role in all stages of atherosclerotic damage. The strict link between inflammation and atherosclerosis suggests that cardiovascular risk may be reduced by rheumatic disease activity control. There are data to suggest that biologic therapies, in particular TNFα antagonists, may improve surrogate markers of cardiovascular disease and reduce CV adverse outcome. Thus, abrogation of inflammation is considered an important outcome for achieving not only control of rheumatic disease, but also reduction of cardiovascular risk. However, the actual effect of anti-rheumatic therapies on atherosclerosis progression and CV outcome in these patients is rather uncertain due to great literature inconsistency. In this paper, we will summarize some of the main mechanisms linking the inflammatory pathogenic background underlying rheumatic diseases and the vascular damage observed in these patients, with a particular emphasis on the pathways targeted by currently available therapies. Moreover, we will analyze current evidence on the potential atheroprotective effects of these treatments on cardiovascular outcome pointing out still unresolved questions.
30094476 The History of Psoriatic Arthritis (PsA): From Moll and Wright to Pathway-Specific Therapy 2018 Aug 9 PURPOSE OF REVIEW: Psoriatic arthritis is a distinct disorder, separate from rheumatoid arthritis, and first recognized in a thirteenth century Saxon skeleton. It was, however, the monumental work of Verna Wright in the 1950s that led to the acceptance by the American Rheumatism Association (now American College of Rheumatology) in 1964 as a distinct entity. Wright's work provided the framework for a better understanding of the pathogenic mechanisms operating on this condition, and eventually led to the development of targeted therapy that has proven to be more effective and safe than conventional therapy. RECENT FINDINGS: Pathogenesis of psoriatic arthritis has been better delineated in recent years, as well as the use of biological therapy. Recent findings are discussed in detail. Historical aspects of psoriatic arthritis, recent developments in pathogenesis, and therapy are discussed, and the contributions of Verna Wright to our understanding of the disorder are presented.
29910814 The Role of Natural Killer Group 2, Member D in Chronic Inflammation and Autoimmunity. 2018 Current medicine and medical science puts great effort into elucidating the basis of chronicity and finding appropriate treatments for inflammatory diseases; however, the mechanisms driving aberrant immune responses are mostly unknown and deserve further study. Of particular interest is the identification of checkpoints that regulate the function and differentiation of pro-inflammatory cells during pathogenesis, along with means of their modulation for therapeutic purposes. Natural killer group 2, member D (NKG2D) is a potent activator of the immune system, known as a sensor for "induced-self" ligands, i.e., cellular danger signals that, in the context of chronic inflammation and autoimmunity, can be presented by cells being exposed to an inflammatory cytokine milieu, endoplasmic reticulum stress, or cell death. Engagement by such ligands can be translated by NKG2D into activation or co-stimulation of NK cells and different subsets of T cells, respectively, thus contributing to the regulation of the inflammatory response. In this review, we discuss the current knowledge on the contribution of the NKG2D-NKG2DL signaling axis during intestinal inflammation, type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, where the role of NKG2D has been associated either by aberrant expression of the receptor and its ligands and/or by functional data in corresponding mouse models.
27550202 The Role of Autophagy in Rheumatic Disease. 2018 Autophagy is an evolutionarily conserved degradation process in triggered by metabolic stress or environmental changes. Autophagy involves formation of autophagosomes, which fuse with lysosomes and degrade encapsulated intracellular components, such as long-lived and misfolded proteins, as well as intracellular organelles. Autophagy has been implicated in a wide variety of physiological and pathological conditions, and was recently implicated in the regulation of immunity and inflammation. Rheumatic diseases are a group of disorders characterized by immune system malfunctions in which the body attacks its own tissues. These diseases can seriously threaten human health if untreated. Although the underlying pathophysiology of autoimmune diseases has not yet been fully elucidated, autophagy has been implicated in their progression. In this article, we review the basics of autophagy, and the functional role of autophagy in the pathogenesis of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Crohn's disease and ankylosing spondylitis (AS). Moreover, we reviewed the role of autophagy and autophagy-related genes (Atgs) in innate and adaptive immunity, as well as the pathogenic crosstalk between autophagy and apoptosis. Our findings should provide valuable insights into the role of autophagy in the pathogenesis of rheumatic diseases. In addition, identification of novel autophagy-associated target proteins may offer a promising target for drugs treating human rheumatic disorders.
30673921 Statins, metformin, proprotein-convertase-subtilisin-kexin type-9 (PCSK9) inhibitors and s 2018 Dec The immune system is closely intertwined with the endocrine system. Many effects of medications used for various clinical endocrine conditions such as the metabolic syndrome, hypercholesterolemia, diabetes mellitus, hypertension, Graves' disease and others also have an impact on the immune system. Some drugs including statins, metformin, angiotensin converting enzyme and proprotein-convertase-subtilisin-kexin type-9 (PCSK9) inhibitors and sex hormones are known to have immunomodulatory properties. We here review the literature on this topic and provide some clinical examples including the use of statins in Graves' orbitopathy, rheumatoid arthritis, multiple sclerosis, and adult-onset Still's disease. In that context, we introduce a special immunodiagnostics method developed at the Institute of  Diabetes "Gerhardt Katsch" in Karlsburg, Germany, to not only measure but also monitor immune disease activity.
30358982 Self-Adjusting Cytokine Neutralizer Cells as a Closed-Loop Delivery System of Anti-Inflamm 2018 Nov 16 The cytokines tumor necrosis factor α (TNFα) and interleukin 1 β (IL-1β) are both strong NF-κB activators and some of the first cytokines to be released in an inflammatory process. TNFα and IL-1β are present in many autoimmune diseases, such as rheumatoid arthritis (RA). TNFα and IL-1β-blocking therapies are quite successful and established in the treatment of RA, but may also be promising in other diseases. For the treatment of recurring autoimmune diseases, strong controlled sensor-effector cells inhibiting TNFα or IL-1β appear highly predestined. Such cells detect a disease biomarker and autonomously react with the dose-dependent production of therapeutic proteins. Hence, we aim to harness and assemble the interactions of TNFα, IL-1β, and NF-κB, which are an ideal match for synthetic biology-based circuits to rewire the transmission to approved TNFα- or IL-1β-blocking biologicals. Considering the high impact of environmental influences on the dynamics of cell-based systems, we established closed-loop controllable cytokine neutralizer cells, monitoring cytokine levels and autonomously delivering powerful biologicals. This real-time processing system may provide dose-dependent drug delivery, which may be tailored for prospective cell and gene therapies against RA, and may offer a more personalized medicine than calculated drug dosing based on body weight.
29533997 Long-Term Increase of Radiographic Damage and Disability in Patients with RA in Relation t 2018 Mar 13 OBJECTIVES: There is little information on the relation between disease duration, disability and radiographic outcome since the introduction of biologics into the therapy of rheumatoid arthritis (RA). No long -term cohort studies have been conducted on this subject so far. To analyse radiographic damage, disability, and disease activity in RA-patients dependent on disease duration in the Swiss national RA cohort (SCQM). METHODS: The primary outcome was the association between the radiographic destruction, assessed by Ratingen scores, and disease duration. All patients with at least one clinical visit were analysed with polynomial and multiple negative binomial models. RESULTS: The disease duration in the 8678 patients with available radiographs analysed ranged between less than 1 and more than 65 years (median 8.3). Disease duration and radiographic destruction were significantly associated with an average increase of Ratingen scores by 8.3% per year. Apart from disease duration, positive rheumatoid factor was the strongest predictor for radiographic destruction. While DAS28-scores remained stable in patients with a disease duration of more than 5 years (median DAS28 2.8), HAQ-DI scores increased continuously by 0.018 for each additional year. CONCLUSION: In this RA cohort, patients show a continuous increase of articular destruction and physical disability in parallel with disease duration. Even when nowadays a satisfactory control of disease activity can be achieved in most patients, RA remains a destructive disease leading to joint destruction and physical disability in many patients.
31431957 Abatacept and tocilizumab tapering in rheumatoid arthritis patients: results of SONATA-a r 2018 OBJECTIVES: As data on disease-activity-guided dose optimization of abatacept and tocilizumab are scarce, we explored the feasibility, effectiveness and safety of dose optimization of these biological DMARDs in RA patients in daily practice. METHODS: RA patients who had been treated with abatacept or tocilizumab for ≥6 months, with DAS28 <3.2, were included. Four groups were identified: abatacept dose reduction (DR) and usual care (UC), and tocilizumab DR and UC. Successful DR and discontinuation entailed being on a lower dose than at baseline or having discontinued abatacept or tocilizumab, while maintaining disease activity score with ESR using 28 joint count (DAS28) <3.2. Proportions of patients with successful DR or discontinuation at 12 months were described. Maintenance of DR was investigated using Kaplan-Meier curves. Between-group differences in mean DAS28 and Health assessment questionnaire disability index (HAQ-DI) change (Δ) over 6 and 12 months were estimated. RESULTS: One hundred and nineteen patients were included. DR was attempted in 13 of 28 (46%; 95% CI: 28, 66%) abatacept and 64 of 91 (70%; 95% CI: 60, 79%) tocilizumab patients. At 12 months, 3 of 11 (27%; 95% CI: 6, 61%) abatacept and 20 of 48 (42%; 95% CI: 28, 57%) tocilizumab patients were successfully tapered. One of 11 (9%; 95% CI: 0, 41%) abatacept and 5 of 48 (10%; 95% CI: 3, 23%) tocilizumab patients were successfully discontinued. Mean ΔDAS28 and ΔHAQ-DI at months 6 and 12 were not significantly different between DR and UC. For tocilizumab, DAS28 was significantly higher in the DR compared with the UC group at 6 months. Adverse events were comparable between groups. CONCLUSION: Abatacept and tocilizumab DR appears to be feasible and safe in clinical practice. No benefits in terms of fewer adverse events in the DR group were observed. Furthermore, DR was suboptimal, because all patients were eligible for DR, but in a substantial number of patients no DR was attempted.
29520131 The conundrum of indeterminate QuantiFERON-TB Gold results before anti-tumor necrosis fact 2018 BACKGROUND: Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI. METHODS: We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications. RESULTS: We included 107 and 89 patients with IBD and RA, respectively. We found that a higher proportion of IBD patients had indeterminate QFT-GIT result compared to RA patients. Furthermore, we found that the majority of patients with indeterminate results were tested during an acute flare of IBD (88%) and while taking corticosteroids. Of all patients receiving ≥20 mg equivalent prednisone dose (n=32), 63% resulted in indeterminate QFT-GIT, compared to only 6% indeterminate testing in patients receiving <20 mg of equivalent prednisone dose (n=164, P<0.001). There was no correlation between indeterminate results and age, gender, disease duration, or distribution, or smoking status within each population. CONCLUSION: We observed that high-dose corticosteroids may affect QFT-GIT outcomes leading to a high proportion of indeterminate results. We propose that IBD patients should be tested prior to initiation of corticosteroids to avoid equivocal results and prevent potential delays in initiation of anti-TNF medications.
29375375 Single- and Multiple-Dose Trials to Determine the Pharmacokinetics, Safety, Tolerability, 2017 Background and objectives: Ginsenoside compound K (CK) is a candidate drug for rheumatoid arthritis therapy. The objective of this study was to investigate the pharmacokinetic properties, safety and tolerability of CK. Methods: In randomized, double-blind trials, 76 healthy Chinese subjects received 1 of 7 single oral doses (25, 50, 100, 200, 400, 600, 800 mg) of CK or placebo under fasting condition, and another 36 subjects received repeated oral doses (100, 200, or 400 mg) of CK or placebo for up to 9 days a week after a corresponding single dose, after breakfast. Both sexes were equally represented in the two trials. Pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD) were calculated and statistically analyzed according to the plasma concentration data. Tolerability was evaluated by adverse events (AEs) and laboratory examinations. Results: The range of time to maximum concentration (T(max)) was 1.5-6.0 h, with a linear increase in the exposure of CK over the dose range of 100-400 mg. Steady state was reached after the 7th administration, and the accumulation index range was 2.60-2.78. Sex differences were characterized by a higher exposure in females than males with the single administration after breakfast. In addition, no severe AEs were observed. Conclusion: CK was safe and well-tolerated over the treatment period. The sex- and food-related impacts on CK pharmacokinetics need further investigations to be validated. (Registration number: ChiCTR-TRC-14004824 and ChiCTR-IPR-15006107, http://www.chictr.org.cn/index.aspx).
29298553 Conserved Citrullinating Exoenzymes in Porphyromonas Species. 2018 May Porphyromonas gingivalis is one of the major oral pathogens implicated in the widespread inflammatory disorder periodontitis. Moreover, in recent years, P. gingivalis has been associated with the autoimmune disease rheumatoid arthritis. The peptidylarginine deiminase enzyme of P. gingivalis (PPAD) is a major virulence factor that catalyzes the citrullination of both bacterial and host proteins, potentially contributing to production of anticitrullinated protein antibodies. Considering that these antibodies are very specific for rheumatoid arthritis, PPAD appears to be a link between P. gingivalis, periodontitis, and the autoimmune disorder rheumatoid arthritis. PPAD was thus far considered unique among prokaryotes, with P. gingivalis being the only bacterium known to produce and secrete it. To challenge this hypothesis, we investigated the possible secretion of PPAD by 11 previously collected Porphyromonas isolates from a dog, 2 sheep, 3 cats, 4 monkeys, and a jaguar with periodontitis. Our analyses uncovered the presence of secreted PPAD homologues in 8 isolates that were identified as Porphyromonas gulae (from a dog, monkeys, and cats) and Porphyromonas loveana (from sheep). In all 3 PPAD-producing Porphyromonas species, the dominant form of the secreted PPAD was associated with outer membrane vesicles, while a minor fraction was soluble. Our results prove for the first time that the citrullinating PPAD exoenzyme is not unique to only 1 prokaryotic species. Instead, we show that PPAD is produced by at least 2 other oral pathogens.
29225245 Oral Methotrexate-related Lymphoproliferative Disease Presenting with Severe Osteonecrosis 2018 Feb 15 Long-term methotrexate (MTX) treatment can cause MTX-related lymphoproliferative disorder (MTX-LPD). We experienced a case of MTX-LPD that was associated with severe osteonecrosis of the jaw mimicking medication-related osteonecrosis of the jaw. The patient was an 81-year-old woman with rheumatoid arthritis (RA) who was treated with MTX and bisphosphonate. After 7 years, she was referred to our department for the assessment of giant ulcer and exposure of the alveolar bone of the left maxilla. Histopathological and immunological analyses confirmed a diagnosis of MTX-LPD. At seven months after the cessation of MTX treatment, the ulcerative and necrotic lesions had markedly decreased in size. A 1-year follow-up examination showed no evidence of recurrence and good RA control.
29803792 A novel fusion protein attenuates collagen-induced arthritis by targeting interleukin 17A 2018 Aug 25 This study was undertaken to generate a novel dual targeting fusion protein (DTF), targeting tumor necrosis factor α (TNF-α) and interleukin 17A (IL-17A), and determine its anti-arthritis properties in vitro and in vivo. DTF consisted of an anti-IL-17A single chain variable fragment, a soluble TNF receptor 1, and an Fc fragment. Both clinical and histopathological evaluations suggest that DTF and etanercept can ameliorate collagen induced arthritis. However, the arthritis severity score of DTF-treated mice was lower than that of etanercept-treated mice. In addition, DTF was more potent than etanercept in decreasing the ratio of RANKL/OPG in the serum and rebalancing the population ratio of Treg/Th17 cells in the spleens. In vitro, IL-17A and TNF-α had synergistic effects in inducing the expression of inflammatory cytokines in fibroblast-like synoviocyte from RA patients (RA-FLS), human leukemia (THP-1), and rheumatoid synovial fibroblast (MH7A). IL-17A and TNF-α also had synergistic effects in inducing proliferation and migration of MH7A cells. However, we observed that DTF was more efficient than etanercept in suppressing these synergistic effects. Our results demonstrate that DTF is highly efficient in the treatment of arthritis and has the potential to overcome the limited therapeutic responses obtained with single cytokine neutralization.
29985183 Pulmonary manifestations of systemic lupus erythematosus and Sjögren's syndrome. 2018 Sep PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) and Sjögren syndrome are chronic autoimmune inflammatory disorders that can present with multiorgan involvement including the lungs. This review will focus on recent literature pertaining to the epidemiology, pathogenesis, clinical presentation and diagnosis and management of SLE and Sjögren syndrome-associated pulmonary conditions. RECENT FINDINGS: Pulmonary manifestations of both disease entities have been well characterized and lung involvement can be observed during the course of the disease in most cases. Pulmonary manifestations of SLE and Sjögren syndrome can be classified based on anatomical site of involvement; and the large and small airways, lung parenchyma, lung vasculature, pleura and respiratory muscles can be involved. The pleura is most commonly involved in SLE, whereas the airways are most commonly involved in primary Sjögren's syndrome (pSS). Sleep disturbances have also been described in both entities. SUMMARY: Although further research into treatment strategies for the pulmonary complications seen in SLE and pSS is needed, the clinician should be aware of the risk factors and clinical presentation of the various pulmonary complications in SLE and pSS in order to identify patients who should be screened and/or have modifications in treatment strategies to mitigate the morbidity and mortality associated with these complications.
29444331 Validation of the ACR-EULAR criteria for primary Sjögren's syndrome in a Dutch prospectiv 2018 May 1 OBJECTIVES: To validate the ACR-EULAR classification criteria for primary SS (pSS), and compare them to the American-European Consensus Group (AECG) and ACR criteria in a Dutch prospective diagnostic cohort. METHODS: Consecutive patients (n = 129) referred for suspicion of pSS underwent a multidisciplinary evaluation, including a labial and/or parotid gland biopsy. Patients with an incomplete work-up (n = 8) or associated systemic auto-immune disease (n = 7) were excluded. The ACR-EULAR classification was compared with expert classification, AECG and ACR classification. Additionally, the accuracy of individual ACR-EULAR items in discriminating pSS from non-pSS was evaluated. The validity of criteria sets was described separately using parotid or labial gland biopsy results for classification. RESULTS: Of the 114 evaluated patients, the expert panel classified 34 (30%) as pSS and 80 (70%) as non-pSS. Using labial gland biopsy results, ACR-EULAR classification showed 87% absolute agreement (κ = 0.73) with expert classification, with a sensitivity of 97% and specificity of 83%. Using the parotid gland biopsy results, the ACR-EULAR criteria performed excellently as well. Focus score, anti-SSA titre and ocular staining score showed good to excellent accuracy, whereas unstimulated whole saliva and Schirmer's test had poor accuracy. The ACR-EULAR and AECG criteria had equal validity. Compared with ACR classification, ACR-EULAR classification showed higher sensitivity but lower specificity. CONCLUSION: The ACR-EULAR criteria showed good agreement with expert classification, but some patients may be misclassified as pSS. Unstimulated whole saliva and Schirmer's test showed poor discriminative value. The ACR-EULAR criteria performed equally to the AECG criteria, and had higher sensitivity but lower specificity than the ACR criteria.
30154890 The role of demographic and clinical variables in assessing the quality of life of outpati 2018 Aug INTRODUCTION: The aim of this study was to assess quality of life among patients with rheumatoid arthritis (RA) treated as outpatients. The specific question was: does the quality of life of RA patients depend on demographic variables and clinical variables? MATERIAL AND METHODS: The study included 240 patients with RA recruited from outpatients. To assess quality of life, the Arthritis Impact Measurement Scales 2 was applied. Clinical tests: VAS, Morning Stiffness, Grip Strength, Richie Articular Index. RESULTS: The analysis of life quality for the total group was carried out in the particular AIMS2 of the mean scores for arthritis pain - 7.37; walking and bending - 6.62; social activity - 5.52; level of tension - 5.17; satisfaction - 5.17; hand and finger function - 4.28; mood - 4.03; physical activity - 3.27; arm function - 3.16; household tasks - 2.67; self-care - 2.18; and support from family and friends - 1.75. The arthritis impact score was 6.01. The analysis of the correlation between clinical variables and individual AIMS2 subscales showed a statistically significant relationship between the VAS Pain, Grip Strength Measurement, Morning Stiffness and quality of life subscales (p < 0.01). VAS Pain, Morning Stiffness, and Grip Strength Measurement were the most important predictors among clinical variables of physical component, affect and symptoms (p < 0.001). Among demographic variables: age over 60 years and low education were the most important predictors of physical component (p < 0.01). CONCLUSIONS: The study results may be helpful for further health-related studies on quality of life among RA studies and in making therapeutic decisions concerning quality of life improvement.
30036683 The effect of patient age and diagnosis on the 5-year outcomes of mobile-bearing total ank 2018 Sep Total Ankle Replacement is an established technique for the management of end-stage ankle arthritis. However, there are few studies focussing on patient-reported outcomes in the medium and long term related to age or arthritis type. We compared demographic data and patient-reported outcomes preoperatively and at five years postoperatively for patients who underwent total ankle replacement with the aim of establishing whether differences exist in outcome depending on patient age or diagnosis. The Foot and Ankle Score (FAOS) and 36-item Short-Form (SF-36) Health Survey were analysed by diagnosis (osteoarthritis, rheumatoid arthritis, post-traumatic arthritis) and age (under or over 60 years). At 5 years, the post-traumatic arthritis group had a significantly higher composite score than the osteoarthritis (p<0.0001) or rheumatoid arthritis groups (p<0.0001). Only the post-traumatic arthritis group experienced a significant increase in composite SF-36 score from baseline (p<0.0001). There was a significant improvement from pre-operatively to 5 years in all three domains of the FAOS and in total scores in both groups (over 60 p<0.0001; 60 and under p=0.0002). There was a significant improvement in composite SF-36 score from pre-operative to 5 years in the patients 60 years or younger at the time of surgery (p=0.0006), but not for the patients over 60. Three patients have been revised (4%), at a mean of 4.8 years following surgery with one patient awaiting revision.
30070316 The value of MiR-146a and MiR-4484 expressions in the diagnosis of anti-SSA antibody posit 2018 Aug OBJECTIVE: The aim of this study was to investigate the value of micro ribonucleic acid-146a (miR-146a) and miR-4484 expressions in the diagnosis of anti-SSA antibody positive Sjogren syndrome (SS) and their correlations with prognosis. PATIENTS AND METHODS: 70 patients with anti-SSA antibody positive SS were selected as the observation group, and the non-positive Sjogren syndrome (PSS) subjects were collected as the control group at the same time. Fluorescent quantitative polymerase chain reaction (PCR) method was used to detect serum expressions of miR-146a and miR-4484 in two groups. Expression changes of miR-146a and miR-4484 in patients before and after treatment were compared. After 3 years of follow-up, 70 patients were divided into high expression and low expression subgroups based on the average expressions of miR-146a and miR-4484. Prognosis in each subgroup was compared. RESULTS: The expressions of miR-146a and miR-4484 in the observation group were significantly up-regulated compared with those in the control group (p<0.05). After treatment, the expressions of miR-146a and miR-4484 were significantly down-regulated compared with those before treatment (p<0.05). Combined detection of miR-146a and miR-4484 was superior to single index detection in the diagnosis and prognosis of PSS (p<0.05). The 3-year follow-up showed that the incidences of renal injury and pulmonary interstitial lesion in patients with low miR-146a and miR-4484 expressions were significantly lower than those with high expressions (p<0.05). However, there were no significant differences in the survival rate between the two groups (p>0.05). CONCLUSIONS: Serum expressions of miR-146a and miR-4484 in anti-SSA antibody positive PSS patients are significantly up-regulated. Their detection can improve the diagnostic rate of SS. Expressions of miR-146a and miR-4484 are closely correlated to the prognosis of the patients, which can be used as prognostic predictors.