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ID PMID Title PublicationDate abstract
32801432 Anti-Cyclic Citrullinated Peptide Antibody as a Predictor of Rheumathoid Arthritis Complic 2020 Jun INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, with more frequent occurrence in the female gender, it primarily affects the lining of the synovial joints, and is associated with lower quality of life, inability to work, progressive disability, and all of these patients are more likely to develop other comorbidities. AIM: To display the role of anti-cyclic citrullinated peptide antibody (anti-CCP) in evaluating RA complications during a one-year follow-up, and compare its values with values of rheumatoid factor (RF). METHODS: The study included 40 patients with RA, out of which 6 were excluded during the 1-year follow-up. All patients were treated with anti-rheumatics, methothrexate 15-25mg, occasionally corticosteroids at the same doses. RESULTS: Anti-CCP values were also significantly higher during the second examination and were 5.0 ± 1.9 (range 0.5-7.6) compared to the first examination when they were 4.2 ± 1.3 (range 0.4-6.2) indicating a higher sensitivity of Anti-CCP in detecting of disease progression (t = -2.064; p = 0.043). Anti-CCP values were statistically significant in patients with complications compared to those without during the first examination and at follow-up after one year (t = 5,382; p = 0.0001). CONCLUSION: The positivity of anti-CCP antibodies is a useful marker in terms of predicting the course and prognosis of the RA. A higher titer of anti-CCP antibodies represents a poorer prognosis for the disease. Determination of the presence of anti-CCP antibodies should be performed as a routine examination in all patients with suspected rheumatoid arthritis.
30833463 Harnessing the Inflammatory Reflex for the Treatment of Inflammation-Mediated Diseases. 2020 Jan 2 Treating diseases nonpharmacologically, using targeted neurostimulation instead of systemic drugs, is a hallmark of the burgeoning field of bioelectronic medicine. In this review, we provide a brief overview of the discovery and function of the prototypical neuroimmune reflex, the "inflammatory reflex." We discuss various biomarkers developed and used to translate early physiological discoveries into dosing parameters used in experimental settings, from the treatment of animal models of disease through a proof-of-concept clinical study in rheumatoid arthritis (RA). Finally, we relate how unique aspects of this form of therapy enabled the design of a next-generation implanted pulse generator using integrated electrodes, currently under evaluation in a U.S.-based clinical study for patients with drug refractory RA.
32552188 Disease activity affects the recurrent deformities of the lesser toes after resection arth 2021 Mar OBJECTIVES: The purpose of this study was to clarify the effect of disease activity on recurrent deformities after resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis (RA). METHODS: This study included 83 feet in 58 patients with RA who underwent resection arthroplasty of all metatarsal heads, with a minimum follow-up of 2 years. The patients' demographic characteristics, preoperative radiographic findings, and RA disease activity evaluated using the 28-joint disease activity score based on the erythrocyte sedimentation rate (determined preoperatively and at the final follow-up) were compared between feet with and without postoperative recurrent deformities of the toes. Recurrent deformities were assessed separately for the hallux and lesser toes. RESULTS: Recurrence in the hallux and lesser toes occurred in 23 feet (27.7%) and 13 feet (15.7%), respectively. With respect to recurrent hallux deformity, only the preoperative severity of hallux deformity was associated with recurrence. On the other hand, postoperative deformity of the lesser toes was positively associated with disease activity alone and not with other preoperative factors. CONCLUSION: Postoperative control of RA disease activity was associated with recurrent deformity of the lesser toes but not that of the hallux after resection arthroplasty of all metatarsals for rheumatoid forefoot deformities.
32050085 Immunomodulatory benefits of mesenchymal stem cells treated with Caffeine in adjuvant-indu 2020 Apr 1 PURPOSE: We intend to assess the effect of the conditioned medium of Caffeine pulsed MSCS in the amelioration of rheumatoid arthritis (RA)-afflicted rats. METHODS: MSCs were incubated with 0, 0.1, 0.5 or 1 mM Caffeine for 2 weeks. RA was induced by the injection of complete Freund's adjuvant (CFA) into the base of the tail of Wistar rats. According to in vitro studies, RA rats were intraperitoneally treated with MSCs, Caffeine (0.5 mM) pulsed MSCs or vehicle on day 14 when all rats had shown signs of RA. RESULTS: Our results suggest that the least effective dose concentration of Caffeine that can induce potent anti-inflammatory property in the MSC population is 0.5 mM. Without any significant impact on the vitality or MScs' marker, Caffeine at this concentration could induce lower levels of IFN-γ, IL-6, and IL-1β and a higher level of IDO, TGF-β, and IL-10 compared to other groups. Therefore, MSCs pulsed with Caffeine at 0.5 mM concentration was selected for in vitro studies. Caffeine pulsed MSCs could reduce the severity of the disease and improve weight-gaining more profoundly than treatment with MSCs alone. Furthermore, Caffeine pulsed MSCs caused a significant reduction in the serum levels C-reactive protein, Nitric oxide, Myeloperoxidase, TNF-α and conversely led a significant increase in the levels of IL-10 more prominent than the similar findings brought about by MSCs alone. CONCLUSION: In general, caffeine-treated MSCs may be a promising strategy for cell-based therapy of RA.
31521793 Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum. 2020 Mar Three Janus kinase (JAK) inhibitors, ruxolitinib, tofacitinib, and baricitinib, are currently approved by the FDA/EMA for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative rectocolitis. The inhibition of JAK/STAT signaling by these small molecules, downstream of several cytokine receptors, results in lower pro-inflammatory gene expression. Given the cytokine profiles observed in rheumatologic diseases, most of the recent therapeutic strategies target cytokines, either directly or through their receptors. Each cytokine receptor recruits a specific combination of JAKs to activate different programs in cells. The approved drugs are panJAK inhibitors, able to impede more than one pathway. These drugs are being tested in various rheumatologic disorders. At the same time, more specific molecules able to target one specific JAK are being developed. In this review, we describe the expanding spectrum of rheumatologic and autoimmune conditions for which JAK inhibition may represent new avenues in clinical practice.
32079664 Measuring ACPA in the general population or primary care: is it useful? 2020 Feb Rheumatoid arthritis (RA) is associated with a significant disease burden and high costs for society. Because the disease has identifiable preclinical stages, screening and prevention have become a possibility in RA. Anticitrullinated peptide antibodies (ACPAs) are arguably the most likely candidate biomarker to screen for RA. This paper reviews the evidence for the use of ACPAs as a screening test in the broader general population, to identify individuals at high risk of subsequent onset of RA. We will review the diagnostic properties of the test and its positive and negative predictive value in different settings. We will discuss how ACPA testing could effectively be integrated in a broader screening strategy for RA.
32056527 Cardiovascular Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). 2020 The risk of cardiovascular (CV) disease is increased among patients with systemic autoimmune rheumatic diseases and remains an underserved area of medical need. Although traditional risk factors for CV disease, such as hypertension, smoking, dyslipidemia and obesity contribute to endothelial dysfunction in rheumatoid arthritis (RA), they are not enough on their own to explain the observed excess CV risk. Rather, systemic inflammation seems to play a pivotal role in both disease states. Considering the inflammatory process in autoimmune diseases, scientific interest has focused on recently introduced biologic disease-modifying agents (bDMARDS) such as inhibitors of Tumor Necrosis Factor- α (ΤΝF-α), Interleukins -1 (IL-1) and -6 (IL-6). Despite the widespread use of bDMARDS in RA and other chronic autoimmune inflammatory diseases, their precise impact on CV disease and outcome remains to be elucidated, while prospective randomized control trials assessing their impact on hard CV endpoints are scarce. In this review, we summarize current knowledge concerning the effect of bDMARDs on CV outcome and on the risk of developing CV disease in patients with systemic autoimmune rheumatic diseases.
32366522 Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti 2020 Jul OBJECTIVES: To investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA). METHODS: Baseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400). RESULTS: BE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p<0.01). A significant correlation between BE and US synovitis in the MTP5 joints was detected (Cramer's V=0.37, p<0.01). The OR for the development of IA (ever) was highest for the following: BE in >1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1-132.8, p<0.01). CONCLUSIONS: In CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis.
31530023 Radiographic changes in TMJ in relation to serology and disease activity in RA patients. 2020 Jan OBJECTIVES: This study was undertaken as an attempt to assess radiographic temporomandibular joint (TMJ) changes in relation to rheumatoid factor (RF), anticitrullinated protein (ACCP) antibodies and disease activity score 28 (DAS28) in rheumatoid arthritis (RA) patients to find the best predictor of rheumatoid affection of the TMJ with the ultimate goal of maintaining TMJ function and preventing joint damage. METHODS: 20 Rheumatoid Arthritis patients as well as 20 volunteers were included in this study. RA group were assessed for RF, ACCP, DAS28. Both groups were assessed by CBCT for TMJ dimensions and radiographic osteoarthritic changes. All data were statistically analyzed. RESULTS: Rheumatoid Arthritis group showed significantly less condylar height and more radiographic osteoarthritic changes than the control group. RF showed no significant correlation with either TMJ measurements or TMJ radiographic osteoarthritic changes. ACCP showed significant inverse correlation with condylar height and anteroposterior (AP) dimensions, but non-significant relation with mediolateral dimension and radiographic osteoarthritic changes. DAS28 showed significant inverse correlation with condylar AP and mediolateral dimensions. It also showed significant correlation with flattening of the TMJ condylar head and flattening of the articular fossa. Patients with high and moderate disease activity showed significantly smaller AP TMJ dimension than patients with low disease activity. Disease activity showed statistically significant direct correlation with all osteoarthritic changes except for erosions of the glenoid fossa and condyle. CONCLUSION: Disease Activity Score28 score and disease activity are strong indicators of TMJ affection in RA patients when compared to RF and ACCP. ACCP is a better indicator of changes in condylar measurements than TMJ osteoarthritic changes. While RF is the least efficient indicator of TMJ involvement in RA patients.
32022855 Addition of Slowly Repeated Evoked Pain Responses to Clinical Symptoms Enhances Fibromyalg 2020 Dec 25 OBJECTIVE: Fibromyalgia is a chronic pain syndrome characterized by central sensitization. A novel protocol based on slowly repeated evoked pain (SREP) appears to be a useful marker of pain sensitization in fibromyalgia patients. Whether SREP enhances diagnostic accuracy beyond key clinical symptoms that characterize fibromyalgia has not been examined. METHODS: Fifty fibromyalgia patients, 30 rheumatoid arthritis patients, and 50 healthy individuals were evaluated to assess clinical pain, as well as fatigue, insomnia, pain catastrophizing, and negative mood. The SREP protocol consisted of a series of nine low-intensity painful pressure stimuli of five seconds' duration with 30-second interstimulus intervals. SREP sensitization was indexed by increases in pain intensity ratings across stimuli. RESULTS: SREP sensitization was observed in fibromyalgia but not in rheumatoid arthritis or healthy individuals. As expected, fibromyalgia patients exhibited a more negative psychosocial profile than did rheumatoid arthritis patients and healthy individuals. SREP was positively associated with clinical pain, fatigue, insomnia, and catastrophizing, but not with negative mood. SREP discriminated fibromyalgia cases from rheumatoid arthritis and healthy individuals even when current clinical pain was included in the analysis. Combining fatigue, insomnia, and SREP led to near perfect diagnostic accuracy (99%) in differentiating fibromyalgia from healthy individuals and 86.3% accuracy in discriminating fibromyalgia from rheumatoid arthritis. CONCLUSIONS: These results provide further evidence of SREP as a marker of pain sensitization in fibromyalgia and suggest that it captures aspects of fibromyalgia not fully captured by clinical features. Combining SREP with assessment of clinical features could potentially improve fibromyalgia diagnosis.
32238274 The basic and translational science year in review: Confucius in the era of Big Data. 2020 Jun Personalized medicine is an important goal for the treatment of rheumatic disease that seeks to improve outcomes by matching therapy more precisely with the underlying pathogenetic disturbances in the individual patient. Realization of this goal requires actionable biomarkers to identify these disturbances as well as pathways that can be targeted for novel therapy. Among advances in characterizing pathogenesis, Big Data provides an unprecedented picture of pathogenesis, with analysis of tissue lesions revealing disturbances that may not be apparent in blood. Big Data approaches include single cell RNAseq (scRNAseq) which can elucidate patterns of gene expression by individual cells. Galvanized by the Accelerating Medicines Partnership, a public-private initiative of the NIH, investigative teams have analyzed gene expression in cells in the synovium for rheumatoid arthritis and kidney for systemic lupus erythematosus. A review of basic and translational research for 2018-2019 provides the progress in these areas. Thus, the studies on rheumatoid arthritis have identified subpopulations of immune cells and fibroblasts implicated in synovitis. For lupus, transcriptomic studies have provided evidence for widespread effects of type 1 interferon. Studies in progressive sclerosis have demonstrated changes associated with stem cell therapy as well as potential new targets for anti-fibrotic agents. Other studies using molecular approaches have defined new mechanisms for vasculitis as well as the potential role of the microbiome in inflammatory arthritis and systemic lupus erythematosus. Future studies with Big Data will incorporate the spatial relationships of cells in inflammation as well as changes in gene expression over time.
31566134 Cardiovascular Risk of Synthetic, Non-Biologic Disease-Modifying Anti- Rheumatic Drugs (DM 2020 Patients with rheumatoid diseases have an increased risk of cardiovascular disease (CVD) and CVD-related death compared with the general population. Both the traditional cardiovascular risk factors and systemic inflammation are contributors to this phenomenon. This review examines the available evidence about the effects of synthetic, non-biologic disease-modifying antirheumatic drugs (DMARDs) on CVD risk. This is an important issue for clinicians when deciding on individual treatment plans in patients with rheumatic diseases. Evidence suggests that synthetic, non-biologic DMARDs such as methotrexate, sulfasalazine, hydroxychloroquine, leflunomide and tofacitinib show decreased CVD morbidity and mortality. However, the strongest data in favour of a reduction in CVD events in rheumatoid patients are shown with methotrexate, which has been the focus of most studies. Adequate proof for a favourable effect also exists for hydroxychloroquine. Larger, prospective studies and randomized clinical trials are needed to better characterize the effect of synthetic, non-biologic DMARDs on CVD outcomes in these patients. Design of future studies should include areas with lack of evidence, such as the risk for heart failure, arrhythmias and valvular heart disease. The clinically relevant question whether synthetic, non-biologic DMARDs are inferior to biologic DMARDs in terms of CVD outcomes remains not adequately addressed.
32999229 Tocilizumab-induced Leukoencephalopathy with a Reversible Clinical Course. 2020 Nov 15 Tocilizumab (TCZ; Actemra/RoActemra) is an anti-interleukin (IL)-6 receptor antibody for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases and cytokine storms. The present case is a 63-year-old female well-controlled RA patient, who presented with a progressive cognitive impairment after 34 months of TCZ administration. Brain magnetic resonance imaging (MRI) showed leukencephalopathy with a lactic acid peak in magnetic resonance spectroscopy (MRS), a decreased blood flow in single photon emission computed tomography (SPECT), and a decreased accumulation in fluorodeoxyglucose positron emission tomography (FDG-PET). The discontinuation of TCZ improved her cognitive function and brain MRI findings at 3 months after drug cessation. The present case suggests that TCZ may sometimes cause leukoencephalopathy after long-term administration, and thus the early discontinuation of TCZ is recommended to achieve a good prognosis.
32622628 Case for diagnosis. Subcutaneous nodules in the plantar region. 2020 Sep The authors report a case of mobile and painful nodules on the bilateral plantar surface of a female patient referred by the rheumatology service, where she was being followed-up for rheumatoid arthritis. A nodule excision was performed for differential diagnosis and symptom relief; the histopathological analysis was compatible with a rheumatoid nodule. Although rheumatoid nodules are a common manifestation of rheumatoid arthritis, exclusive plantar involvement is seldom described in the literature.
33074346 Google search data as a novel adjunct to patient and public involvement in rheumatology re 2021 Apr Patient and public involvement is essential in the design and implementation of research studies to ensure research remains relevant and in line with public priorities. Public views on a given area of research may be sought via platforms such as focus groups or surveys. Here, we present the use of an openly available Google search data query tool, which may be used alongside traditional forms of patient and public involvement in research to highlight public perceptions and priorities. We used an online search query tool ("AnswerThePublic.com") to explore public Google searches relating to "arthritis," and an exemplar rheumatic disease, "rheumatoid arthritis." The most common searches relating to these diseases included quality of life, treatment, prognosis, as well as impacts on life, including work. However, they also reveal concerns that may be more difficult to elicit in face-to-face focus groups, such as questions on alcohol consumption in arthritis, and impacts on mental health. Using public search engine data in research, alongside the important traditional methods of patient and public involvement, is a cost-effective and time-efficient method of gauging public views and concerns on a given topic. It may facilitate broad scoping searches of public priorities and help to guide future research questions.
31915123 The earlier, the better or the worse? Towards accurate management of patients with arthral 2020 Mar The favourable long-term results of early treatment in patients with classified rheumatoid arthritis have resulted in an increasing interest in the diseases phases preceding clinical arthritis. The hypothesis to test is that an intervention in these early phases may better prevent or reduce disease persistence than an intervention when arthritis has become clinically manifest. While several placebo-controlled trials are still ongoing, to date there is no firm evidence that this hypothesis truly holds. Therefore, it is important to reflect on the current status of arthralgia preceding clinical arthritis. Inherent to every new field of research, attitudes are conflicting, with opinions propagating innovation (based on the fear of undertreatment) on the one hand, and critical sounds pleading for more restraint (fear of overtreatment) on the other hand. In this Viewpoint, we will examine these divergent opinions, relate them to a preferred ultimate scenario and provide considerations for future studies and daily practice.
33130748 [A Case of Lung Cancer Discovered Due to Unresponsive Course of Corticosteroids for Rheuma 2020 Oct A 76-year-old female was followed up for rheumatoid arthritis-associated interstitial lung disease(RA-ILD). Consolidation and ground-glass opacities were observed in the right lung. When the corticosteroid was restarted due to a relapse of RA-ILD, most of the shadows disappeared. However, ground-glass nodules remained in the apex of the right lung. Thoracoscopic segmentectomy was performed, and lung cancer was diagnosed. Patients with rheumatoid arthritis suffer from complications such as RA-ILD, drug-induced pneumonia, pulmonary infections, and malignancies. A careful assessment of treatment response should be made in case of a differential diagnosis.
33258976 [Register and cohort studies : Overview of the most important data sources at the German R 2020 Dec Over the past 28 years the German Rheumatism Research Center in Berlin has initiated various epidemiological studies in which data on patients with inflammatory rheumatic diseases are collected nationwide and multicentric. The spectrum ranges from rheumatoid arthritis and spondylarthritis to connective tissue diseases and rheumatic diseases in childhood. Based on the respective scientific question, studies of different types were established. The German National Databases for adults and children annually collect cross-sectional data to map the care of patients. In two inception cohorts, adults with early arthritis and patients with juvenile idiopathic arthritis are investigated from disease onset. The long-term observational cohorts/registries RABBIT, RABBIT-SpA and JuMBO focus on the long-term efficacy and safety of biologic drugs and other targeted treatments. Rhekiss investigates women with inflammatory rheumatic diseases when trying to become pregnant, during pregnancy and postpartum. This article highlights each of these observational studies with its characteristics as well as national and international collaborations.
33323534 The Clinical Disease Activity Index and the Routine Assessment of Patient Index Data 3 for 2021 Dec OBJECTIVE: To compare the Clinical Disease Activity Index (CDAI) with the Routine Assessment of Patient Index Data 3 (RAPID3) from 2 large United States registries. METHODS: Using a cross section of clinic visits within 2 registries, we determined whether the outcome of each metric would place the patient in remission (REM), low (LDA), moderate (MDA), or high disease activity (HDA) using the CDAI, with the assumption that a patient in MDA or HDA would be a candidate for acceleration of treatment. RESULTS: We identified significant disparities between the 2 indices in final disease categorization using each index system. For patients identified in LDA by CDAI, RAPID3 identified 20.4% and 28.3% as LDA in Corrona and the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS), respectively. For patients identified as MDA by CDAI, RAPID3 identified 36.2% and 31.1% as MDA in Corrona and BRASS, respectively, with the greatest disparities within each system identified for LDA and MDA activity by the CDAI (20.4% and 36.2% agreement of RAPID3 with CDAI, respectively, in Corrona and 28.3% and 31.1% agreement in BRASS). Overall comparison between CDAI and RAPID3 in the 4 disease categories resulted in estimated κ = 0.285 in both. The RAPID3 scores indicated the potential for treat-to-target acceleration in 34.4% of patients in REM or LDA based on CDAI in Corrona and 27.7% in BRASS, respectively. CONCLUSION: The RAPID3, based on patient-reported outcomes, shows differences with CDAI categories of disease activity. The components of CDAI are not highly correlated with RAPID3, except for patient global assessment. These differences could significantly affect the decision to advance treatment when using a treat-to-target regimen.
33320289 Comparison of therapeutic efficacy and mechanism of paclitaxel alone or in combination wit 2022 Mar OBJECTIVE: To compare the therapeutic efficacy of paclitaxel (PTX) alone to its combination with methotrexate (MTX) on rheumatoid arthritis. METHODS: A collagen-induced arthritis (CIA) rat model was established by induction of type II collagen. Rats were divided into blank control group, CIA model group, MTX group 1 mg/kg, PTX 1.5 mg/kg, PTX 2.5 mg/kg, PTX 3.5 mg/kg, and MTX 1 mg/kg + PTX 3.5 mg/kg, with 10 rats per group. The inflammation of the ankle joint was analyzed by H&E staining and interleukin (IL)-1β and IL‑6 expression was detected by immunohistochemistry. TUNEL assay was performed to detect synovial tissue cell apoptosis after administration of PTX and MTX either alone or in combination. TLR4 and p‑NF-κBp65 protein expression in synovial tissue and the changes of serum IL‑1β, IL‑6, IL‑12, MMP‑3, and TNFα protein factors were detected by western blot and ELISA, respectively. RESULTS: PTX and MTX improved histopathological changes in CIA rats. Besides, the apoptosis rate of synovial tissue cells in the PTX 3.5 mg/kg group was more than that of the PTX + MTX group. Immunohistochemistry and western blot results indicated that PTX and MTX reduce the expression rate of IL‑6 and IL‑1β and downregulate TLR4 and p‑NF-κBp65 protein expression. Furthermore, TLR4 and p‑NF-κBp65 reduced the concentration of MMP‑3, IL‑12, IL‑6, IL1‑β, and TNFα. CONCLUSION: Both PTX and MTX exert significant suppression on rheumatoid arthritis, and the combined effect of the two drugs is weaker than that of PTX alone. Moreover, intraperitoneal injection of PTX 3.5 mg/kg every other day was the optimal dose observed in this study.