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ID PMID Title PublicationDate abstract
32742406 Estrogen downregulates TAK1 expression in human fibroblast-like synoviocytes and in a rheu 2020 Aug Transforming growth factor β-activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase family, plays a key role in the pathogenesis and progression of rheumatoid arthritis (RA). Estrogen has been previously reported to delay arthritis progression. However, the exact association between TAK1 and estrogen remains elusive. The present study demonstrated that TAK1 was upregulated in synoviocytes of patients with RA compared with patients with osteoarthritis and healthy controls. In addition, TAK1 was also expressed in cultured fibroblast-like synoviocytes (FLS), and its levels decreased significantly in 17β-estradiol (E2)-treated cells in a dose-dependent manner. Furthermore, administration of E2 significantly decreased TAK1 expression and attenuated the development of collagen-induced arthritis (CIA). Taken together, the findings of the present study suggested that E2 mediates a decrease of TAK1 in both FLS and CIA, which subsequently results in a suppression of the pathological process of CIA. Therefore, estrogen may serve as a potential therapeutic agent for the treatment of RA by targeting TAK1.
32709510 Human Papiloma Virus Screening: Evaluation Of Testing And Surveillance In Rheumatoid Arthr 2020 Jul 21 BACKGROUND AND OBJECTIVES: Immunosuppression is a known risk factor for cervical cancer. Women with rheumatic conditions are immunosuppressed due to the disease and the treatments. One of the main risk factors for this neoplasm is the lack of adherence to early detection programmes for human papillomavirus. The objectives of this study were to evaluate the adherence to the screening programme of patients in the Rheumatology Clinic, as well as to evaluate the prevalence of cervical lesions and their association with the different disease characteristics and the treatments received. MATERIAL AND METHODS: A descriptive retrospective study. The electronic medical history of patients actively being followed up in a tertiary hospital with rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus were reviewed. RESULTS: Finally, 307 patients were included. No data were found for screening programme attendance in up to 42.4% of the patients (39.6% in rheumatoid arthritis, 43.8% in psoriatic arthritis and 46% in systemic lupus erythematosus). Among the patients who attended the screening programme at least once (57.6%), the prevalence of cervical dysplasia was 5.1%. No cases of neoplasia were found. In the simple logistic regression analysis, there was no association between attending the screening programme and any variable. The study also showed no association between the variables collected and the presence of infection and dysplasia. CONCLUSION: These results are influenced by the absence of screening data in a significant percentage of patients and by the low prevalence of dysplasia found in this series of patients with rheumatic diseases.
32269439 Amyloid Goiter in a Patient with Rheumatoid Arthritis and End-Stage Renal Disease. 2020 Mar The association between amyloidosis and collagen vascular diseases, such as rheumatoid arthritis (RA) is well-documented. Amyloid goiter is an extremely rare pathologic condition caused by a massive amyloid infiltration of the thyroid tissue. Our patient had been diagnosed with RA 20 years ago and was on hemodialysis for 7 years. He was assessed for decreased appetite, dysphagia, and nausea during the hemodialysis. On physical examination, the thyroid was diffusely enlarged with multiple nodules. He was biochemically euthyroid. Ultrasound of the thyroid gland showed multinodular goiter. A total thyroidectomy was performed. Histopathological examination showed dilated follicles surrounded by abundant homogeneous substance that stained positive with Congo red. The patient was reported as amyloid goiter. Complaints of the patient improved after the surgery. In the literature, amyloid goiter with RA in a hemodialysis patient is very rare. Amyloid goiter should be considered if there is a rapid thyromegaly causing pressure symptoms in the background of any disease with chronic inflammation.
32908770 Tocilizumab Was Effective in Repairing the Large Geode in a Patient with Rheumatoid Arthri 2020 Rheumatoid arthritis is characterized by multiple chronic arthritis subsequently inducing joint destruction. Although subchondral geode is a well-known feature of high-disease activity, a large geode is rare. Moreover, the treatment effect of biologic agents in the repair of large geode has not been reported. The present report shows the significant effect of interleukin-6 receptor blocker, tocilizumab, in repairing the large geode in the left humeral lateral epicondyle. This case implies that tocilizumab might be an effective treatment in patients with rheumatoid arthritis even with large geode.
33269077 Flare-up of cytokines in rheumatoid arthritis and their role in triggering depression: Sha 2021 Jan Chronic illnesses are associated with an increased risk of depression and anxiety. Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically causes damage to the joints. RA extensively impacts patients, both physically and psychologically. Depression is a common comorbid disorder with RA, which leads to worsened health outcomes. There are several cytokines that are active in the joints of patients with RA. Inflammatory cytokines serve important roles in the key processes in the joints, which usually cause inflammation, articular damage and other comorbidities associated with RA. The key role of inflammatory cytokines could be attributed to their interactions within signaling pathways. In RA, IL-1, and the cytokines of TNF-α, IL-6 and IL-18 are primarily involved. Furthermore, depression is hypothesized to be strongly associated with systemic inflammation, particularly with dysregulation of the cytokine network. The present review summarizes the current state of knowledge on these two diseases from the perspective of inflammation and cytokines, and emphasizes the possible bridge between them by exploring the involvement of systemic cytokines in both conditions.
33227081 The importance of homocysteine in the development of cardiovascular complications in patie 2020 Rheumatoid arthritis (RA) not only leads to disability due to joint changes, but also significantly shortens the life expectancy of patients, mainly due to more frequent occurrence of heart attacks and strokes. Accelerated atherosclerosis in these patients is caused, among other factors, by high homocysteine (HCY) concentration in blood. Numerous studies have shown that treatment with vitamin B significantly reduces the concentration of HCY in blood, but does not reduce the risk of heart diseases. Recent studies have shown, however, that folic acid (FA) administration reduces the risk of stroke by 10-20%. Due to the fact that in patients with RA strokes are more frequent than in the general population and hyperhomocysteinemia (HHCY) is often found, determination of HCY concentration in blood is advisable, and in persons with HHCY it is recommended to use FA in primary and secondary stroke prevention.
31739383 PBT-6, a Novel PI3KC2γ Inhibitor in Rheumatoid Arthritis. 2020 Mar 1 Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/ AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.
30273262 Anti-DNase I Antibody: A New Serological Reactivity in Primary Sjögren Syndrome. 2020 Jan BACKGROUND AND OBJECTIVE: Primary Sjögren syndrome (pSS) is a systemic autoimmune rheumatic disease that particularly affects exocrine glands. Dry eye is one of the most important features of this syndrome, and a recent study reported reduced deoxyribonuclease I (DNase I) activity in the tear of patients with dry eye. We therefore postulated that patients with pSS might have antibodies targeting DNAse I. METHODS: We have evaluated in a cross-sectional study 85 patients with pSS (2002 American-European Consensus Group Criteria), 50 rheumatoid arthritis (RA) patients (1987 American College of Rheumatology Criteria) without sicca symptoms, and 88 healthy volunteers. IgG anti-DNase I was detected by enzyme-linked immunosorbent assay using as antigen bovine pancreas enzyme and confirmed by immunoblotting. RESULTS: Age and sex were alike in the 3 groups (p > 0.05). Anti-DNase I was detected in 43.5% of the pSS patients. In contrast, this reactivity was absent in all RA patients (p = 0.0001). Additional comparison of pSS patients with (n = 37) or without (n = 48) anti-DNase I showed that the former group had higher IgG serum levels (2293.2 ± 666.2 vs 1483.9 ± 384.6 mg/dL, p = 0.0001) and greater rate of non-drug-induced leukopenia (43% vs 19%, p = 0.02). A multivariate logistic regression analysis identified that only IgG levels were independently associated with anti-DNase I. CONCLUSIONS: We describe a high frequency of anti-DNase I antibodies in pSS patients associated with higher serum IgG levels. The lack of this reactivity in RA patients without sicca symptoms suggests that this antibody may be helpful in the differential diagnosis of these diseases.
32246670 Adult-onset still's disease, an unusual cause of severe acute liver injury: A case report. 2020 Apr Adult-onset Still's disease is a systemic inflammatory disease that often presents with spiking fever, typical rash, arthritis, and serositis. However, adult-onset-Still's-disease associated liver injury and acute liver failure are rare. Herein, we report a case of acute liver injury in a 23-year-old female patient with adult-onset Still's disease. She presented to the emergency department with a high fever and sore throat. She was then admitted to the department of infectious diseases with a preliminary diagnosis of an atypical respiratory infection. After being treated with antibiotics and antiviral agents, she was discharged. A few days later, she returned to the emergency department with jaundice and was rehospitalized. This time, she was admitted to the department of gastroenterology, where she was diagnosed with adult-onset Still's disease-associated acute liver injury. Eventually, the patient responded to immunosuppressive treatment with significant clinical improvement.
32454955 Non-surgical oral hygiene interventions on disease activity of Rheumatoid arthritis patien 2020 Winter Background. Periodontitis and rheumatoid arthritis have similar epidemiology and pathophysiology. Understanding the interaction between these two diseases is vital in our settings. We set out to assess the effect of oral hygiene interventions on disease activity of rheumatoid arthritis patients with periodontitis in Kampala, Uganda. Methods. Fifty-eight patients attending an arthritis clinic with rheumatoid arthritis and periodontitis were randomly assigned to either an intervention group or a control group. Patients diagnosed with rheumatoid arthritis at least two years before, who were on the same medication, dose, or formulation for RA treatment during the preceding three months, were included. The patients were >18 years of age, would be available for all the study visits in the next six months, had at least six natural teeth, had periodontal disease classified as Dutch Periodontal Index (DPSI) >3 and provided written informed consent. Those who had a chronic disorder requiring chronic or intermittent use of antibiotics, were pregnant, were lactating, or had intent to become pregnant were excluded. The primary outcome measure was a change in Disease Activity Score of 28 Joints (DAS28 score) in two 3-month follow-up periods after the intervention. The secondary outcome measure was a change in periodontal status. Results. There was a statistically significant improvement in the DAS-28 score in both the intervention and control arms during the follow-up period (P<0.01). The participants carrying more than one bacterial species had worse DAS-28 scores. Conclusion. Oral hygiene interventions given to RA patients could drastically improve their RA treatment outcomes, especially in resource-limited settings.
32704255 The association among 14-3-3η protein, inflammation, bone remodeling and osteoporosis in 2020 Jul OBJECTIVE: To evaluate the correlation among 14-3-3η protein, inflammation, bone remodeling and osteoporosis in patients with rheumatoid arthritis. METHODS: In this cross-sectional study, the RA patients treated in our hospital were analyzed between January 2015 and November 2019. Bone mineral density was measured using dual energy X-ray absorptiometry, and at the beginning of the study, serum samples were collected and the level of 14-3-3η, TNF-α, and IL-6 was tested using the quantitative enzyme-linked immunosorbent assay, and I-CTX and PINP were measured using automatic electrochemical luminescence immune-analyzer for all the participants. RESULTS: In the current study, 285 patients with rheumatoid arthritis were enrolled and assigned into normal, osteopenia, and osteoporotic group respectively. The level of 14-3-3η and IL-6 presented with the highest value in the osteoporosis group, but the lowest value in the normal group, and there were significant differences in the level of 14-3-3η and IL-6 among the groups (p<0.05), and there was positive correlation between 14-3-3η and IL-6 (p<0.05). There were significant differences in PINP and I-CTX among the three groups (p<0.05), and a significantly positive correlation between I-CTX and 14-3-3η (p<0.05) and a significantly negative correlation between PINP and 14-3-3η (p<0.05) were found. CONCLUSION: There was a significant correlation among 14-3-3η protein, inflammation, bone remodeling and osteoporosis in patients with rheumatoid arthritis, the influence of 14-3-3η on osteoporosis may be contributed to its adjusting inflammation and bone remodeling.
33163865 Let Food Be Thy Medicine: The Case of The Mediterranean Diet in Rheumatoid Arthritis. 2020 Sep The role of diet in rheumatoid arthritis (RA) has been the topic of extensive research. The present review aimed to present and appraise the studies assessing adherence to the Mediterranean diet (MD) and the primary/secondary prevention of rheumatoid arthritis. Based on the available studies, the evidence appears low and adherence to the MD does not appear to affect RA indices.
32977406 Homology Modeling and Optimized Expression of Truncated IK Protein, tIK, as an Anti-Inflam 2020 Sep 23 Rheumatoid arthritis, caused by abnormalities in the autoimmune system, affects about 1% of the population. Rheumatoid arthritis does not yet have a proper treatment, and current treatment has various side effects. Therefore, there is a need for a therapeutic agent that can effectively treat rheumatoid arthritis without side effects. Recently, research on pharmaceutical drugs based on peptides has been actively conducted to reduce negative effects. Because peptide drugs are bio-friendly and bio-specific, they are characterized by no side effects. Truncated-IK (tIK) protein, a fragment of IK protein, has anti-inflammatory effects, including anti-rheumatoid arthritis activity. This study focused on the fact that tIK protein phosphorylates the interleukin 10 receptor. Through homology modeling with interleukin 10, short tIK epitopes were proposed to find the essential region of the sequence for anti-inflammatory activity. T(H)17 differentiation experiments were also performed with the proposed epitope. A peptide composed of 18 amino acids with an anti-inflammatory effect was named tIK-18mer. Additionally, a tIK 9-mer and a 14-mer were also found. The procedure for the experimental expression of the proposed tIK series (9-mer, 14-mer, and 18-mer) using bacterial strain is discussed.
32707025 Surgical Management of the Lumbar Spine in Rheumatoid Arthritis. 2020 Sep STUDY DESIGN: Narrative review. OBJECTIVE: To provide an overview on the diagnosis and surgical management of rheumatoid involvement of the lumbar spine. Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints, most commonly appendicular followed by axial. Although cervical spine involvement of RA is well documented, data on lumbar spine involvement and surgical management remains limited. METHODS: Using PubMed, studies published prior to November 2018 with the keywords "RA, etiology"; "RA, spine management"; "RA, surgical management"; "RA, treatment"; "RA, DMARDs"; "RA, lumbar spine"; "RA, spine surgical outcomes"; "RA, imaging" were evaluated. RESULTS: The narrative review addresses the epidemiology, manifestations, imaging, surgical complications, and operative and nonoperative management of RA involvement of the lumbar spine. CONCLUSIONS: Rheumatoid involvement of the lumbar spine can present with lower back pain, neurogenic claudication, radiculopathy, spinal deformity, and instability. Patients with RA have significantly higher rates of vertebral fractures and complications following surgical intervention. However, in the setting of instability and spinal deformity, thoughtful surgical planning in conjunction with optimal medical management is recommended.
33299919 Granulosa cell tumor resection with subsequent onset of rheumatoid arthritis. 2020 Nov Rheumatoid arthritis (RA) is an autoimmune disorder with an estrogen correlation. The disease can worsen or present with menopause. Granulosa cell tumors (GCT) are estrogen-secreting ovarian sex-cord stromal tumors with median incidence in the early postmenopausal years. We report a 38-year-old female who presented with a 20 cm pelvic mass and elevated inhibin and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for a Stage I GCT. She developed progressive post-operative joint pain and weakness before an eventual diagnosis of seropositive RA. With tumor resection and surgical menopause, the patient experienced an abrupt decline in estrogen levels precipitating the onset of RA symptoms. Prior research identified that hormone fluctuation at menopause correlates with onset of RA. While unfortunately direct estrogen measurements were not obtained perioperatively, this case does support circumstantial evidence correlating RA with menopause and a decline in estrogen, irrespective of age.
32876781 Characteristics, evolution, and outcome of patients with non-infectious uveitis referred f 2021 Apr OBJECTIVE: To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. METHODOLOGY: Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84 (41.8%) juvenile-onset (≤ 16 years)) were retrospectively reviewed. Data were analyzed through Kruskal-Wallis and Mann-Whitney, chi-square (χ(2)) tests, and logistic regression. RESULTS: The median disease and follow-up durations were 36 (interquartile range (IQR) 24-70) and 24 (IQR 10-36) months, respectively. Fifty-eight (28.9%) patients had persistently idiopathic uveitis, and 143 (71.1%) were associated with rheumatic diseases, of whom uveitis heralded, coincided with, and succeeded the rheumatic manifestation(s) in 62/143 (43.4%), 37/143 (25.9%), and 44/143 (30.7%) patients, respectively. Established rheumatic diseases were Behçet's disease (103/201 (51.2%)), juvenile idiopathic arthritis (13/201 (6.5%)), sarcoidosis (8/201 (4%)), seronegative spondyloarthropathy (7/201 (3.5%)), and Vogt-Koyanagi-Harada (7/201 (3.5%)), and other diagnoses were present in 5/201 (2.5%) patients. Patients with idiopathic uveitis were characterized by a juvenile-onset (p < 0.001), lower male predominance (p = 0.01), prevalent granulomatous (p < 0.001), and anterior (p = 0.001) uveitis. The median visual acuity at last visit was 0.3 (IQR 0.05-0.6). Visual loss was present in 45/201 (22.3%) patients (36/201 (17.9%) unilateral and 9/201 (4.4%) bilateral). Apart from a longer disease duration (p = 0.002), lower educational level (p = 0.03), and prevalent panuveitis (p < 0.001), visual loss was not associated with any other studied ocular or extra-ocular characteristics. CONCLUSION: Behçet's disease (51.2%) and idiopathic uveitis (28.9%) were the most prevalent causes of non-infectious uveitis in our study. Visual loss (22.3%) was associated with a longer disease duration, lower education level, and prevalent panuveitis. Key Points • Most common causes of uveitis referred to rheumatologists were Behçet's disease and idiopathic uveitis. • Several rheumatic diseases initially presented only with uveitis, more commonly in adult and male patients. • Panuveitis was more frequent among patients with an established rheumatic disease, whereas granulomatous uveitis was uncommon. • Longer disease duration and presence of panuveitis were independently associated with visual loss.
33554176 Midterm clinical outcomes of reverse shoulder arthroplasty in Japanese patients with rheum 2021 Jan BACKGROUND: Reverse shoulder arthroplasty normally has adequate functional outcomes in patients with cuff tear arthropathy. The present study aimed to investigate the midterm clinical outcomes of reverse shoulder arthroplasty in Japanese patients with rheumatoid arthritis. METHODS: Between July 2014 and May 2016, reverse shoulder arthroplasty was performed in 14 rheumatic shoulders with joint destruction and rotator cuff tears. The range of motion, Constant score, and Shoulder36, which is a patient-reported outcome measure, were compared preoperatively and postoperatively. The prevalence of subscapular notching, subscapular osteophytes, postoperative fractures, and stress shielding of the humeral stem were evaluated by X-ray. RESULTS: Range of motion significantly improved from 77 to 122 degrees in flexion and from 67 to 111 degrees in abduction at four years. The Constant score significantly improved from 27 to 62, and each domain of Shoulder36 also significantly increased at four years. There was no dislocation, infection, or loosening of the prosthesis. Three shoulders presented scapular notching, and three cemented humeral stems showed stress shielding in the proximal humeral cortical bone. CONCLUSION: Reverse shoulder arthroplasty performed in Japanese patients with rheumatoid arthritis not only decreased the pain and improved the function of the shoulder joint but also significantly improved patients' health and activity of daily living in midterm results.
32982498 Tuberculosis Arthritis in the Wrist While Using Rituximab for Rheumatoid Arthritis Treatme 2020 INTRODUCTION: Data from clinical trials indicate that there are no increased risk of tuberculosis (TB) infections in rheumatoid arthritis (RA) patients while using rituximab (RTX). Herein, we report a RA patient who developed TB arthritis while using RTX. CASE REPORT: A 49-year-old patient was treated with methotrexate and prednisolone along with RTX for two years. Later, she presented with increasing pain, swelling, redness and cutaneous fistulization in her left wrist for two months. The lesion on the wrist was debritted. Histopathologic evaluation revealed the presence of acid-fast bacilli. Polymerase chain reaction test and culture confirmed mycobacterium tuberculosis. RTX, methotrexate and prednisolone were withdrawn. The patient was treated with 12-month course of antituberculous treatment and responded well. The patient, who did not have pain or swelling in her other joints, was not given any treatment for RA after antituberculous treatment. CONCLUSION: Clinicians should keep in mind that TB infections may be encountered while using RTX. Latent TB screening may be appropriate in patients using concomitant corticosteroid and living in TB endemic areas.
33149107 Refractory Urticaria with Raised Antistreptolysin O (ASO) Titer: An Intriguing Case of Adu 2020 Nov 5 BACKGROUND Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease with a myriad of clinical presentations. The diagnosis is often challenging because there is no specific confirmatory test. Uncommon presentations can delay the proper diagnosis and management. CASE REPORT A 26-year-old woman presented with a history of urticaria for 2 years that had failed to respond to many types of treatment. Cutaneous biopsy showed neutrophilic urticaria. A diagnosis of AOSD was made after infectious, drug-related, neoplastic, and rheumatic etiologies had been excluded and based on the triad of fever, evanescent rash, and joint pain. Besides leukocytosis and increased levels of inflammatory markers, the patient's laboratory results showed an extremely high D-dimer concentration and an increased antistreptolysin O (ASO) titer. Treatment with prednisolone and methotrexate resulted in resolution of the woman's symptoms. Once clinical remission had been achieved, all laboratory markers returned to normal, yet the patient's ASO titer remained elevated during 18 months of follow-up. CONCLUSIONS Urticaria is a rare cutaneous manifestation of AOSD. Histopathology typically shows predominant neutrophilic infiltrates, which is a unique entity called neutrophilic urticarial dermatosis (NUD). Identifying diseases associated with NUD will facilitate prompt diagnosis and treatment of AOSD, as therapies for it largely differ depending on the underlying cause. Known etiologies of AOS include systemic lupus erythematosus (SLE), Schnitzler syndrome, hereditary autoinflammatory periodic syndromes, and serum sickness-like drug eruption. An elevated ASO titer is unusual, and in our case, it did not seem to follow the patient's clinical course. An elevated D-dimer concentration can be an indicator of disease activity and testing might be beneficial in a subset of patients with normal ferritin levels.
32940212 One year in review 2020: comorbidities, diagnosis and treatment of primary Sjögren's synd 2020 Jul Primary Sjögren's syndrome (pSS) is a complex and heterogeneous disorder characterised by a wide spectrum of glandular and extra-glandular features. The discovery of novel biomarkers allowed to characterise the disease not only phenotypically on the basis of clinical presentation, but also on the basis of the endotype. Moreover, a better stratification of patients has important value in the evaluation of mechanisms underlying the risk of lymphoproliferative disorders in these patients. Finally, novel targeted therapies may open new possibilities for the application of personalised medicine in pSS.