Evolution Of Rheumatoid Arthritis Research Articles

The predictive value of self-efficacy in the evolution of rheumatoid arthritis and its relationship with pain and function

Background and objectivesRheumatoid arthritis (RA) primarily affects the upper limbs and can cause disturbances in the performance of daily activities. The main objective of this study was to establish the relationship between self-efficacy, pain intensity, and duration of symptoms in patients with RA and analyse how each influences functional disability, and to determine the predictive value of self-efficacy over the other variables. MethodsCross-sectional study with a sample of 117 women diagnosed with RA. The endpoints were the visual analogue scale (VAS), Quick-DASH questionnaire and the Spanish scale of self-efficacy in rheumatic diseases. ResultsThe most significant model for function (R2 = 0.35) includes function and pain, therefore, there is a relationship between self-efficacy, pain intensity, and upper limb functionality. Discussion and conclusionsOur results agree with previous studies where a relationship between self-efficacy and functional disability is established, as well as self-efficacy and its relationship with physical functions, demonstrating that a low level of self-efficacy implies a decrease in functionality; however, no variable is more predictive than another.

Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis

Macrophage polarization determines the production of cytokines that fuel the initiation and evolution of rheumatoid arthritis (RA). Thus, modulation of macrophage polarization might represent a potential therapeutic strategy for RA. However, coordinated modulation of macrophages in the synovium and synovial fluid has not been achieved thus far. Herein, we develop a biomimetic ApoA-I mimetic peptide-modified neutrophil membrane-wrapped F127 polymer (R4F-NM@F127) for targeted drug delivery during RA treatment. Due to the high expression of adhesion molecules and chemokine receptors on neutrophils, the neutrophil membrane coating can endow the nanocarrier with synovitis-targeting ability, with subsequent recruitment to the synovial fluid under the chemotactic effects of IL-8. Moreover, R4F peptide modification further endows the nanocarrier with the ability to target the SR-B1 receptor, which is highly expressed on macrophages in the synovium and synovial fluid. Long-term in vivo imaging shows that R4F-NM@F127 preferentially accumulates in inflamed joints and is engulfed by macrophages. After loading of the anti-inflammatory drug celastrol (Cel), R4F-NM@F127-Cel shows a significant reduction in hepatotoxicity, and effectively inhibits synovial inflammation and alleviates joint damage by reprogramming macrophage polarization. Thus, our results highlight the potential of the coordinated targeted modulation of macrophages as a promising therapeutic option for the treatment of RA.

Factors associated with long-term persistence of rituximab in rheumatoid arthritis in clinical practice: RITAR Study

Background and objectiveTreatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice. MethodsRituximab in rheumatoid arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan–Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment. Results454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. ConclusionsThe persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence.

Factores asociados a la persistencia a largo plazo de rituximab en artritis reumatoide en la práctica clínica: Estudio RITAR

Background and objectiveTreatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice. MethodsRituximab in Rheumatoid Arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan-Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment. Results454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100 patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. ConclusionsThe persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence.

Complement in the Initiation and Evolution of Rheumatoid Arthritis.

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA.

Local up-sampling and morphological analysis of low-resolution magnetic resonance images

Limitations in the resolution of acquired images, which are due to sensor manufacturing and acquisition conditions, are reduced with the help of algorithms that enhance the spatial resolution by assigning pixel values that are interpolated or approximated from known pixels. We propose a variant of the moving least-squares approximation for image up-sampling, with a specific focus on biomedical MR images. For each evaluation point, we locally compute the best approximation by minimizing a weighted least-squares error between the input data and their approximation with an implicit function. The proposed approach provides a continuous approximation, an accuracy and extrapolation capabilities higher than previous work, and a lower computational cost. As main application, we consider the up-sampling of low field MR images, where the volumetric and meshless properties of the approximation allow us to easily process images with anisotropic voxel size by rescaling the image and inter-slices resolution. Finally, we include the resolution rescaling into a pipeline that performs a morphological characterization of 3D anatomical districts, which has been developed with a focus on rheumatoid arthritis evolution and provides a more accurate segmentation as an input to quantitative analysis.

Poliartrita reumatoidă – un subiect mereu în actualitate

Aim. The main objective of this study is represented by a clinical and epidemiological evaluation of the impact that biologic therapy exerts on patients suffering from rheumatoid arthritis. Material and methods. We have performed a study on a lot made up of 92 patients with rheumatoid arthritis, treated and accounted for inside the Rheumatology Clinic of Cantacuzino Hospital Bucharest, where they underwent biologic therapy, and we have analyzed the epidemiological, clinical and paraclinical data, establishing correlations with the received therapy. Results. Results show that the lot was predominantly made up of patients from urban areas, with an average education level. Men have presented higher percentages of highly seropositive forms, whereas women had higher DAS 28 and increased ESR levels, as well as more frequently associated cardiovascular pathology, dyslipidemia and diabetes mellitus. A connection between the evolution of the disease and the number of births could not be confirmed. Smokers have recorded different responses to biologic therapy. Dyslipidemia was present in 69.6% of the patients, but cholesterol levels did not positively correlate with inflammation markers and were not influenced by treatment in order to establish a statistical significance, although patients treated with etanercept presented decreased levels of cholesterol. 89.1% of patients with dyslipidemia already had statins included in their therapy. The evolution of DAS 28 and ESR in the studied lot was in favor of patients treated with adalimumab and rituximab. Conclusions. An urban lifestyle, the level of education (an average level), gender, menopause, and smoking as well as intensely positive serology have all represented factors which determined the onset and evolution of rheumatoid arthritis. Smokers exhibited decreased responses to biologic therapy.

Basic trends and variability of rheumatoid arthritis evolution: long-term follow-up results

Objective. To evaluate basic trends and variability of the course of rheumatoid arthritis, to reveal parameters of long-term prognosis. Material and Methods. 238 pts with RA (30 male, 208 female) were followed for (M±o) I5,5±6,4 years. They were investigated with standard clinical and laboratory methods. X-ray evaluation was done by Larsen method. Functional disability was investigated by Stanford Health Assessment Questionnaire. Results. At 2002 162 (68,1%) pts continue following up, 47 (19,7%) pts died, 29 (12,2%) patients were lost to follow-up. The activity of disease had a tendency to decrease, but X-ray changes and functional lesions developed. According to the dynamics of disease, 4 subgroups of pts were defined: 1st subgroup (16,3% of pts) with stable low activity and slow X-ray progression; 2nd subgroup (27,3%) with high initial activity and slow progression, 3rd subgroup (34%) with low or moderate activity and fast progression; 4th subgroup (22,5%) with persistent high activity of disease and fast X-ray progression. The subgroups differed significantly by severity of functional lesions, by frequency of secondary amyloidosis and by frequency of lethal outcomes. The main clinical signs of unfavorable course of disease were large joint involvement during first 2 years, the development of extraarticular changes during first 5 years and the development of joint erosions during first 2 years. Conclusion. Some simple clinical signs in the first years of disease (large joint involvement, the development of joint erosion and extraarticular lesions) allow to predict the course and long-term outcomes in the pts wit rheumatoid arthritis.

Abnormal sonographic findings in the asymptomatic arthritic shoulder

Objective: To assess the diagnostic value of ultrasonography (US) in the evaluation of arthritic shoulder joints, especially in painless shoulders. Methods: US examinations were performed in 57 consecutive patients with rheumatoid arthritis (114 shoulders) and in 32 controls (32 shoulders), using a 7.5 MHz linear probe and a standardized study protocol. US findings were compared with clinical, laboratory, and radiological data to find any relationship. Results: Abnormal sonographic findings were found in 80 shoulders (70%); the most common were lesions in the supraspinatus tendon (38%), subacromial-subdeltoid bursitis (29%), bone erosions of the humeral head (20%), glenohumeral joint effusion (19%), and biceps tendinitis (13%). Although US abnormalities were most frequent in patients with painful shoulders or abnormal findings on physical examination or radiography, a high rate of alterations was found in asymptomatic shoulders (51%), in normal shoulders on physical examination (44%) and in normal shoulders on radiographic assessment (61%). Differences of US findings in relation to time of evolution of rheumatoid arthritis, patient's age, and radiographic stage in hand and/or wrist joints were not found. Conclusion: US abnormalities in the shoulder joint are frequent in rheumatoid arthritis, both in patients with and without shoulder complaints as well as in patients with normal findings on physical examination.

Bone abnormalities in the surgical treatment of patients with rheumatoid arthritis.

Profound abnormalities of bone are an important component of the morbidity of rheumatoid arthritis and partly determine the orthopaedic treatment of patients. The principal bone abnormality, which is osteoporosis associated with rapid remodeling, degrades the mechanical properties of the skeleton in juxtaarticular bone, in the diaphyses of long bones, in the pelvis, and in the base of skull. Abnormalities of bone affect clinical decision making in the surgical treatment of patients with rheumatoid arthritis and must be considered for the optimal treatment of these patients. Increased fracture risk and compromised bony fixation complicate fracture treatment. Techniques of surgery must be modified to protect bone from intraoperative fracture. Methods of fixation of implants and other devices must be appropriate to the biomechanics of the bone. Bone healing usually is rapid if not compromised by mechanical instability. Specific patterns of bone deformation and failure can be identified in the evolution of rheumatoid arthritis. Bone graft used in reconstruction of the protruded acetabulum is incorporated rapidly. Bone resorption with joint instability is a common feature of rheumatoid arthritis; however, the opposite pattern of bony ankylosis with stiffness is observed in a smaller percentage of patients. Recognition of the tissue type is necessary for the individualization of surgical procedures to achieve optimal joint stability and mobility. Based on growing understanding of the pathophysiology of bone in patients with rheumatoid arthritis, new pharmacologic therapies may become available for the prevention and treatment of bone abnormalities in patients with rheumatoid arthritis.

Modulation of monocyte chemotactic function in inflammatory lesions. Role of inflammatory mediators.

Monocyte recruitment and accumulation in the synovial tissue is pivotal in the evolution of rheumatoid arthritis (RA). In the present study we examined the chemotactic potential of monocytes obtained from synovial fluid (SF) of patients with RA. Functionally, SF monocytes exhibited greatly diminished chemotactic activity to C5a compared with monocytes from the peripheral blood. In contrast, their chemotactic responsiveness to the synthetic peptide, FMLP, was nearly normal. To define a mechanism for this differential chemotactic dysfunction, cell-surface receptors for C5a (C5aR) and FMLP (FMLP-R) were evaluated. Whereas FMLP-R expression was similar on both blood and inflammatory monocytes, C5aR expression was markedly reduced on SF cells. Because decreased C5a binding in certain RA SF samples could not be attributed to free C5a, known or suspected components of inflammatory SF were evaluated for their ability to modulate chemotactic ligand receptors. Bacterial products including LPS and streptococcal cell walls, which are potent monocyte activators, down-regulated C5aR without affecting FMLP-R. Moreover, the cytokines IFN-gamma and granulocyte-macrophage-CSF selectively decreased C5aR in parallel with decreased in vitro chemotactic activity to C5a. Thus, these data indicate that 1) synovial effusions may contain C5a and/or inflammatory mediators that modulate phenotypic and functional changes in monocytes, 2) chemotactic ligand receptors are independently regulated in inflammatory lesions, and 3) decreased C5aR expression and chemotactic potential likely provide a mechanism whereby monocyte-macrophages persist within the inflamed synovium.

An assessment of the physiological significance of cimetidine interactions with copper and zinc in biofluids as based on the computer-simulated distribution of the involved complexes at therapeutic levels of the drug.

The hypothesis was formerly put forward that the main therapeutic action of cimetidine (the histamine H2-receptor antagonist marketed as Tagamet) as well as some of its side effects might be mediated by its interactions with essential metal ions. The present paper reports the potentiometric study of the coordination of the drug with copper(II) and zinc(II) in NaCl 0.15 mol dm-3 at 37 degrees C. Special attention was paid to copper complexes, due to (i) the involvement of cimetidine in rheumatoid arthritis evolution which could be related to the well-established role of copper against this disease, (ii) the anti-ulcer and anti-inflammatory properties of copper. In particular, the copper-cimetidine-histamine and copper-cimetidine-histidine ternary systems were investigated. Computer simulations of the distribution of cimetidine, zinc and copper in blood plasma were performed at therapeutic levels of the drug. No influence can be expected from cimetidine on the bioavailability of these metal ions, the opposite being also true. The mediation of copper in the action of cimetidine on rheumatoid arthritis should thus be ruled out, the influence of the drug being rather interpretable in terms of reduction of histamine release. Similarly, the sexual dysfunctions due to cimetidine administration are unlikely to arise from the interactions of drug with zinc in blood plasma. The possible involvement of copper and zinc in cimetidine gastrointestinal absorption is also discussed.