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ID PMID Title PublicationDate abstract
35389771 Multiple dissecting intracranial and extracranial aneurysms in rheumatoid arthritis: a rar 2022 Apr 7 A 52 year old female with a history of rheumatoid arthritis (RA) and persistently raised levels of serum rheumatoid factor and cyclic citrunillated peptide, presented with dissecting aneurysms at the right internal carotid artery, and intact aneurysms at the supraclinoid segment and opening of the right opthalmic artery. Coil embolization was performed. The patient developed an ischaemic stroke two days later.Intra and extra-cranial large vessel aneurysms in RA have rarely been reported in the literature. RA patients with persistent systemic inflammation are at increased risk of developing vascular complications and ischaemic stroke. Here, high levels of tissue-deposited immune complexes may have resulted in cerebral artery vasculopathy. Risk stratification for the development of vascular complications, including cranial aneurysms and ischaemic stroke, in RA patients with poorly controlled systemic inflammation, is important; especially when we consider the neurological sequelae associated with dissecting cerebral aneurysms, cerebral infarction and surgical intervention.
28723028 Rheumatoid Arthritis. 2022 Jan Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. It is a chronic inflammatory disorder of unknown etiology that primarily involves synovial joints. It typically starts in small peripheral joints, is often symmetric, and progresses to involve proximal joints if left untreated. Joint inflammation over time leads to the destruction of the joint with cartilage and bone erosion. RA with a symptom duration of fewer than six months is defined as early RA, and when the symptoms have been present for more than six months, it is defined as established RA.  There is no pathognomonic laboratory test for rheumatoid arthritis, which makes the diagnosis of this disease challenging. An astute and comprehensive clinical approach is required to make the diagnosis and prevent debilitating joint damage. The treatment of patients with rheumatoid arthritis requires both pharmacological and non-pharmacological therapy. Today, the standard of care is early treatment with disease-modifying anti-rheumatic drugs. Despite treatment, many patients progress to disability and suffer significant morbidity over time. A comprehensive pharmacological and non-pharmacological support (physical therapy, counseling, and patient education) is required to improve clinical outcomes.
35355255 Systems model identifies baseline cytokine concentrations as potential predictors of rheum 2022 Mar 30 BACKGROUND AND PURPOSE: Circulating cytokines are central pathological mediators of inflammatory autoimmune diseases like rheumatoid arthritis. Immunological diversity in patients might contribute to inadequate responses to biological drugs. To address this therapeutic challenge, we developed a mathematical model that simultaneously describes temporal patterns of drug disposition for several biologics and their corresponding targeted cytokines, which were linked to triggering inflammatory responses. EXPERIMENTAL APPROACH: A modelling framework was applied to rheumatoid arthritis-relevant cytokines regulating C-reactive protein (CRP) as an inflammatory marker. Clinical data were extracted from the literature for anakinra, canakinumab, infliximab, secukinumab and tocilizumab, along with their corresponding cytokines, interleukin-1 receptor antagonist, IL-1β, tumour necrosis factor α (TNFα), IL-17A and IL-6 receptor (IL-6R). Based on prior knowledge of regulatory mechanisms, cytokines were integrated with CRP profiles. KEY RESULTS: The model well captured all serum concentration-time profiles of cytokines and CRP ratios to respective baselines following drug treatment with good precision. On external validation, reasonable model performance on CRP dynamics, including rebound effects, was confirmed with clinical data not used in model development. Model-based simulations demonstrated that serum infliximab concentrations were accurately recapitulated in both a dose- and baseline TNFα-dependent manner. Furthermore, high baseline profiles of both IL-1β and/or targeted cytokines could be predictors of poor responses to biologics targeting TNFα and IL-6R, although the impact of IL-1β must be carefully interpreted. CONCLUSIONS AND IMPLICATION: Our model provides a quantitative platform to guide targeting and dosing strategies, including combination and/or sequential therapy, according to distinct baseline cytokine patterns in rheumatoid arthritis patients.
35623305 Tectoridin ameliorates proliferation and inflammation in TNF-α-induced HFLS-RA cells via 2022 May 19 Tectoridin, isolated from the dry rhizome of iris, is a compound with multiple biological activities. However, its biological roles in rheumatoid arthritis (RA) have still not been clearly elucidated. The aim of this study was to focus on the effects of tectoridin on tumor necrosis factor (TNF)-α-induced human fibroblast‑like synoviocyte rheumatoid arthritis (HFLS‑RA) cells, and its associated mechanisms. After TNF-α stimulation, CCK8 and MTT assays, TUNEL assay and flow cytometry, Western blotting and immunohistochemistry analysis were performed to check the cell proliferation, cell apoptosis and cycle analysis, and the expression of related proteins, respectively. Our results showed that tectoridin significantly hindered cell proliferation, S-to-G2/M phase transition and down-regulated Cyclind 1 and PCNA protein levels. Additionally, tectoridin markedly promoted apoptosis rates of HFSL-RA cells and elevated the expression levels of Cleaved Caspase-3 and Bax, while reduced the expression level of Bcl-2. Moreover, tectoridin reversed TNF-α-induced overexpression of MMPs and factors associated with the TLR4/NLRP3/NF-κB pathway. We conclude that tectoridin ameliorated TNF-α-induced proliferation and inflammation by inhibiting TLR4/NLRP3/NF-κB pathway. It might provide a new insight for the clinical application of RA.
35645589 The relationship between hydroxychloroquine plasma concentration and COVID-19 outcomes in 2022 May 23 BACKGROUND: The drug hydroxychloroquine (HCQ) is widely used to treat rheumatoid arthritis (RA) and has been repurposed for the treatment of COVID-19. This study aims to determine whether HCQ concentration levels in individuals with RA alter the incidence of COVID-19 or its complications. METHODS: We collected plasma samples from 13 individuals with confirmed rheumatoid arthritis (RA) to measure HCQ concentration levels. The study included individuals at least 18 years old who had been taking HCQ for at least six months at daily doses ranging from 200 to 400 mg. RESULTS: The study enrolled a total of 13 RA patients. All patients were chronic HCQ users. Among the 13 patients, 7 patients were receiving HCQ at a dose of 200 mg per day, and 6 patients were receiving HCQ at a dose of 400 mg per day. COVID-19 confirmed cases accounted for approximately 46% of all patients. Half of the infected patients (n=3) were taking a daily dose of 200 mg daily, while the other half were taking 400 mg daily. COVID-19 symptoms ranged from mild to moderate, and the intensity of the symptoms was not severe enough to necessitate hospitalization. COVID-19 symptoms in RA patients included headache, fever, fatigue, dry cough, and loss of taste or smell. CONCLUSIONS: Our findings indicated that there was no correlation between HCQ concentrations in rheumatoid arthritis patients and the occurrence of COVID-19 or its complications.
35453032 Treatment of early rheumatoid arthritis: Methotrexate and beyond. 2022 Jun For the last several decades, the standard of care for the initial management of rheumatoid arthritis (RA) has been methotrexate. Methotrexate is effective as monotherapy and in combination with conventional, biologic, and targeted-synthetic therapies. Methotrexate is generally well-tolerated, but has important, albeit uncommon, potential side-effects including a risk of liver toxicity and cytopenias. Some studies suggest that more active monitoring in patients with fatty liver disease may be appropriate. With reassuring safety data, more rapid dose escalation and use of subcutaneous therapy may provide even greater success. Some off-target benefits such as a reduction in cardiovascular disease risk have also been demonstrated, though these studies may suffer from confounding. Recent published guidelines continue to endorse methotrexate as first-line therapy. Methotrexate is a low-cost, safe, and effective therapy for RA that should not be overlooked nor too quickly abandoned.
35611100 Anti-Rheumatic Drugs May Ameliorate the Clinical Course and Outcome of COVID-19 In Rheumat 2022 Mar Current data demonstrated that in patients with coronavirus disease-19 (COVID-19), there is a dysregulation of the immune system during the severe form of the disease. This dysregulation is expressed with an uncontrolled release of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-17, tumour necrosis factor alpha (TNFa) and chemokines, associated with increased serum ferritin levels and other acute phase reactants. On the other side, these cytokines play a pivotal role in autoimmune rheumatic diseases (ARD), mostly in rheumatoid arthritis (RA) and the spondyloarthropathies. Patients affected with ARD represent a particular vulnerable group, considering that they may be in an immunocompromised status due to their ailment and its treatment on one side, but on the other side, they may be protected from their immunosuppressive therapy. To this end, we present five patients with RA treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and biologic (b) DMARDs who were affected from COVID-19 and we will try to give answers to the above hypothesis.
35636363 An acid-enhanced OFF-ON fluorescent probe for the detection of hypochlorous acid in rheuma 2022 May 25 Excessive production of hypochlorite acid (HClO) and lactic acid are general hallmarks in the microenvironment of rheumatoid arthritis (RA). Here, we, for the first time, report an acid-enhanced "OFF-ON" fluorescent probe PPS for the detection of HClO in vivo. The probe PPS showed good water solubility, large Stokes shift (143 nm), and fast response toward HClO within 100 s. In the presence of HClO, the sulfur atom in the core of phenothiazine would be oxidized into sulfoxide, triggering intense fluorescence at 580 nm, whose fluorescence intensity could be further enhanced under acidic conditions. Moreover, the exogenous and endogenous HClO in living cells could be sensitively and selectively detected by PPS with a low LOD of 24 nM. Notably, PPS was able to rapidly visualize endogenous HClO generation in a RA mouse model, exhibiting a 2.3-fold higher fluorescence intensity than it in normal joint and 4.1-fold enhanced fluorescence intensity at acidic pH.
35608340 MiR-361-5p promotes proliferation and inhibits apoptosis of fibroblast-like synoviocytes v 2022 May 24 OBJECTIVES: This study is aimed to explore the key role of miR-361-5p in fibroblast-like synovial (FLS) cells of rheumatoid arthritis (RA) and explore the underlying mechanism. METHODS: First, we performed RT-qPCR to evaluate the expression of miR-361-5p in both synovial tissues of RA patients and cultured RA-FLS cells. Then CCK-8 assay, EdU staining, Western blot, flow cytometry, and ELISA were conducted to estimate the influence of inhibiting miR-361-5p on RA-FLS cells. Moreover, we used bioinformatics analysis to predict the potential targets of miR-361-5p and perform a dual luciferase report assay for verification. Finally, rescue experiments were performed to prove the role of miR-361-5p/Zinc Finger And BTB Domain Containing 10 (ZBTB10) in the proliferation, cell cycle, and apoptosis of RA-FLS. RESULTS: We find that the expression of miR-361-5p is increased in both RA tissues and cultured RA-FLS cells. The inhibition of miR-361-5p can not only inhibit proliferation, arrest the cell cycle in G1/G0 phase, and increase apoptosis, but also reduce the inflammatory factors secreted by RA-FLS cells. In addition, ZBTB10 is a direct target for miR-361-5p, over-expression of ZBTB10 reverses the effect of miR-361-5p in RA-FLS. CONCLUSIONS: MiR-361-5p promotes the progression of rheumatoid arthritis by targeting ZBTB10. Key pointsThe influences of miR-361-5p on RA-FLS cells.
35156474 Self-reported sleep disturbance is significantly associated with depression, anxiety, self 2022 Feb 13 The objective of this article is to assess self-reported sleep disturbance and identify psychological, clinical, and sociodemographic factors that might influence sleep disturbance in patients with rheumatoid arthritis (RA). The study included 141 patients with confirmed RA (84.4% women, mean age 56.87 years). The Pittsburgh Sleep Quality Index, the Chinese version of rheumatoid arthritis self-efficacy scale, the Chinese version of Anxiety Depression Distress Inventory-27, the Chinese version of Stigma Scale for Chronic Illness, Visual Analogue Scale-Pain, disease activity index were used. Sleep disturbance was positively correlated with age, pain, disease activity, depression and anxiety, and stigma, while self-efficacy was correlated negatively with sleep disturbance. Multiple linear regression analysis revealed that depression, anxiety, self-efficacy, and stigma explained 77.4% of sleep quality variance. The data has demonstrated a suggestive relationship between low sleep quality and anxiety, depression, self-efficacy, and stigma. Patients reporting poor sleep, fatigue, and pain might have particular psychological intervention needs focusing on distress or anxiety symptoms, low self-efficacy, and high stigma.
34283430 Baricitinib. 2022 Jan Baricitinib is a medication used in the management and treatment of severe rheumatoid arthritis. This activity reviews the indications, action, and contraindication for Baricitinib as a valuable agent in managing rheumatoid arthritis in a clinical setting.
34550626 Fever and flagellate dermatosis in an otherwise healthy woman. 2022 Jan We report a rare presentation of adult-onset Still disease (AoSD) with flagellate dermatosis and unknown trigger. Atypical skin findings have been increasingly reported for AoSD and may be associated with worse prognosis and systemic complications. Increased awareness of nonclassic skin findings in AoSD may lead to earlier diagnosis and treatment.
35634625 Effect of glucocorticoids combined with disease modifying anti-rheumatic drugs on the impr 2022 Mar OBJECTIVES: To explore the effect of glucocorticoids combined with disease modifying anti-rheumatic drugs in the treatment of symptoms in patients with rheumatoid arthritis. METHODS: Medical records of patients with rheumatoid arthritis treated in the Rheumatology and Immunology Department of Yiwu Central Hospital from March 2020 to March 2021 were selected. A total of 38 patients were treated with disease modifying anti-rheumatic drugs Group-I and 44 patients were treated with disease modifying anti-rheumatic drugs and glucocorticoids Group-II. The symptom improvement of the two groups were compared and analyzed Serological indexes and adverse reactions. RESULTS: Swollen joint counts (SJC), tender joint counts (TJC), rheumatoid arthritis disease activity evaluation form (DAS28) score, erythrocyte sedimentation rate, levels of ESR, C-reaction protein (CRP) and rheumatoid factor (RF) of Group-II patients were lower than those in Group-I (P<0.05). The adverse reaction rate in Group-II patients was 12.20%, which was similar to that of Group-I patients. There was no significant difference in 9.76% of the patients (P>0.05). CONCLUSION: The combination of glucocorticoids and disease modifying anti-rheumatic drugs in the treatment of patients with rheumatoid arthritis is safe can further improve their symptoms and serological indexes, and will not lead to increased adverse reactions.
35391896 A Case of Rapidly Progressing Hepatocellular Carcinoma after Administration of JAK Inhibit 2022 We report a case of rapidly progressing hepatocellular carcinoma after administration of Janus kinase (JAK) inhibitors to treat rheumatoid arthritis. A 76-year-old man was referred to our Department for pain in multiple joints and was diagnosed with rheumatoid arthritis. Blood tests revealed elevated hepatobiliary enzymes, but various tests revealed no signs suggestive of malignancy. He took baricitinib for 2 months followed by tofacitinib for 4 months. After that, he was diagnosed with hepatocellular carcinoma based on imaging findings and elevated tumor markers. This case showed the possibility of a causal relationship between JAK inhibitors and malignancy.
35650123 A Case of Endothelial Damage-dominant Nephritis Related to IgA Vasculitis after 11 Years' 2022 May 31 A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.
35611452 Engineering approaches to investigate the roles of lymphatics vessels in rheumatoid arthri 2022 May 24 Rheumatoid arthritis (RA) is one of the most common chronic inflammatory joint disorders. While our understanding of the autoimmune processes that lead to synovial degradation has improved, a majority of patients are still resistant to current treatments and require new therapeutics. An understudied and promising area for therapy involves the roles of lymphatic vessels (LVs) in RA progression, which has been observed to have a significant effect on mediating chronic inflammation. RA disease progression has been shown to correlate with dramatic changes in LV structure and interstitial fluid drainage, manifesting in the retention of distinct immune cell phenotypes within the synovium. Advances in dynamic imaging technologies have demonstrated that LVs in RA undergo an initial expansion phase of increased LVs and abnormal contractions followed by a collapsed phase of reduced lymphatic function and immune cell clearance in vivo. However, current animal models of RA fail to decouple biological and biophysical factors that might be responsible for this lymphatic dysfunction in RA, and a few attempted in vitro models of the synovium in RA have not yet included the contributions from the LVs. Various methods of replicating LVs in vitro have been developed to study lymphatic biology, but these have yet not been integrated into the RA context. This review discusses the roles of LVs in RA and the current engineering approaches to improve our understanding of lymphatic pathophysiology in RA.
34283514 Tofacitinib. 2022 Jan Tofacitinib is FDA approved for the treatment of moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PA), ulcerative colitis (UC), and polyarticular course juvenile idiopathic arthritis (pcJIA). It is a second-generation selective Janus kinase (JAK) inhibitor targeting the JAK1 enzyme. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to interprofessional team members in the management of patients with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PA), ulcerative colitis (UC), and polyarticular course juvenile idiopathic arthritis (pcJIA) that is unresponsive to first-line therapy.
35504517 Roles of osteoclast-associated receptor in rheumatoid arthritis and osteoarthritis. 2022 Apr 30 Osteoclast-associated receptor (OSCAR) is a member of the leukocyte receptor complex (LRC)-encoded protein family, which is characterized by the presence of immunoglobulin (Ig)-like domains. OSCAR recognizes collagen and was first identified as a co-stimulatory receptor that is needed for complete osteoclast differentiation. However, it is now clear that OSCAR is also expressed by multiple immune cells that participate in many innate and adaptive immune cell activities. We also showed recently that chondrocytes express OSCAR. Our and other studies suggest that OSCAR participates in the pathogenesis of two common joint diseases, namely, rheumatoid arthritis (RA) and osteoarthritis (OA). Specifically, OSCAR promotes osteoclast formation and therefore bone erosion in RA while in OA, it triggers chondrocyte death, thereby inducing cartilage fragility. Significantly, blocking the interaction of OSCAR with its collagen ligand can markedly reduce these activities in vitro and in vivo. Thus, this novel approach may have therapeutic potential for joint diseases.
35595049 Caffeine and rheumatoid arthritis: A complicated relationship. 2022 May 17 The current ideal goal of rheumatoid arthritis (RA) management is to resolve joint and systemic inflammation by using pharmacological interventions, assuming this will correspondingly lead to overall well-being. Nonetheless, it has emerged that a substantial number of RA patients do not reach optimal disease control, thus suggesting the holistic management of subjective symptoms might be overlooked. This poses significant medical challenges; hence the proposal of incorporating lifestyle interventions as part of a multidimensional approach. Among these aspects, both patients and physicians perceive the important role of nutrition. This review shall examine how caffeine, one of the most studied bioactive components of the most widely consumed beverages, may potentially interfere with RA management. In particular, the mechanism by which caffeine affects RA pathogenesis, as a trigger for RA onset or flare, including its influence on rheumatic drug metabolism and the most common RA comorbidities and constitutional symptoms are outlined, highlighting important knowledge gaps and unmet research needs.
34979563 Clinical Observations of Osteoporosis in Japanese Patients with Rheumatoid Arthritis. 2022 Jan 4 Osteoporosis is the one of the major adverse outcomes in patients with rheumatoid arthritis (RA). Recently, we and others have been reported many clinical observations related to osteoporosis in Japanese RA patients. In this article, I reviewed these findings. Japanese patients with RA have a two-fold risk of fractures compared with those without RA. Among the fractures in Japanese RA patients, three quarters of the fractures were non-vertebral fractures. The incidence of non-vertebral fractures did not change, despite an improvement in RA disease activity. Older age, female gender, history of fractures, history of total knee replacements, disease activity scores in 28 joints (DAS28), health assessment questionnaire disability index (HAQ-DI), low bone mineral density, glucocorticoid dose, and vitamin D deficiency were significantly associated with fractures. Older age, high body mass index (BMI), HAQ-DI, and polypharmacy were significantly associated with falls. BMI (both overweight and underweight), DAS28, and HAQ-DI were significantly associated with frailty. Half and three quarters of Japanese men and women with RA had vitamin D deficiency, respectively. The incidence of osteonecrosis of the jaw may be higher in Japanese RA patients than those without RA. Undertreatment of osteoporosis appears to exist in Japanese patients with RA.