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ID PMID Title PublicationDate abstract
33788195 Sjogren's Syndrome and Pulmonary Disease. 2021 Sjogren's syndrome is an autoimmune connective tissue disease targeting the exocrine glands and frequently affecting the respiratory system. The pulmonary disease is the most important extra-glandular manifestation as it carries most of the morbidity and mortality. Typically, it affects the small airways ranging from mild to severe respiratory symptoms. The upper airways are also commonly involved, predisposing sinusitis to occur more frequently than in the normal population. Lymphocytic interstitial pneumonia was initially thought to be the prevailing parenchymal disease; however, multiple cohorts report non-interstitial pneumonia to be the most frequent subtype of interstitial lung disease. In the review of high-resolution computed tomography scans, cystic lesions are commonly found and associate with both the small airways and parenchymal disease. Under their presence, amyloidosis or lymphomas should be considered in the differential. Overall, Sjogren's syndrome has a higher risk for lymphoma, and in lungs this condition should be thought of, especially when the images reveal pulmonary nodularity, lymphocytic interstitial pneumonia and lymphadenopathy. Although, pulmonary artery hypertension was traditionally and exceptionally linked with Sjogren's syndrome, together with systemic lupus erythematosus, they are now acknowledged to be the most common pulmonary vascular disease in east Asian populations, even over patients with systemic sclerosis. Although there are no controlled prospective trials to treat pulmonary disease in Sjogren's syndrome, the mainstay treatment modality still falls on glucocorticoid therapy (systemic and inhaled), combined with immune modulators or alone. Most of the evidence sustains successful outcomes based on reported cases or case series.
35006449 Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inf 2021 Oct 25 Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibrogenic factors Lum, CIV, CXI and Tgfbi participated in the synovial inflammation, fibrosis and hyperplasia in CIA. Based on KOG function class analysis, the proteins involved in the events of the central dogma was explored. They might be hyperplasia related proteins for most of them are related to the proliferation of cancer. ETD significantly attenuated synovial inflammation, fibrosis and hyperplasia in CIA rats by downregulating these proteins. Several proteins have not been observed in RA so far, such as Tmsb4x, Pura, Nfic, Ruvbl1, Snrpd3, U2af2, Srrm2, Srsf7, Elavl1, Hnrnph1, Wars, Yars, Bzw2, Mcts1, Eif4b, Ctsh, Lamp1, Dpp7, Ptges3, Cdc37 and Septin9, they might be potentials targets for RA. Blood biochemistry tests showed the safety of 7 months use of ETD on rats. In conclusion, present study displayed a comprehensive mechanism of synovial hyperplasia in CIA rats, on this basis, the clinical value of ETD in the treatment of RA was well confirmed.
34017957 Therapeutic Effects of Gleditsia sinensis Thorn Extract Fermented by Lactobacillus casei 3 2021 May This study aimed to assess the anti-inflammatory effect of Lactobacillus casei 3260 (LC) alone and LC-fermented Gleditsia sinensis thorn (GST) extract in mouse model of type II collagen induced rheumatoid arthritis (RA). In our previous work, we confirmed the anti-inflammatory effects of LC and GST against LPS-induced inflammation in vitro. In this study, LC and GST were fermented and their effects were assessed in an animal model of RA. Both LC and fermented GST (fGST) treatment reduced mice serum nitrite and total cholesterol and triggered myeloperoxidase (MPO) activity. In addition, both LC and fGST reduced inflammation-related serum biomarkers such as tumor necrosis factor-α, interleukin (IL)-6, IL-17, and IL-1β. As per the morphological analysis, both LC and fGST protected hind paw joints against RA, and its related mRNA markers improved. Finally, arthritis scores were measured as an indicator of RA of the whole experimental period; the scores suggested that both LC and fGST protect against collagen-induced RA-related inflammation in a mouse model.
33434538 Pharmacokinetics of metformin in collagen-induced arthritis rats. 2021 Mar Due to the elevated presence of cytokines, the expressions of metabolic enzymes and drug transporters are altered in rheumatoid arthritis (RA). Given the high incidence of diabetes in patients with RA, the aim of the present study was to investigate the metformin pharmacokinetics of a single oral dose in rats with collagen-induced arthritis (CIA). Blood and urine samples were collected at different timepoints, and analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Tissue samples were also collected to investigate the expression of metabolic enzymes and drug transporters by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blot. The results indicated that the bioavailability of metformin was markedly decreased in the CIA rats. Moreover, metformin was not metabolized by enzymes of rat liver microsomes, suggesting that the decreased bioavailability of metformin was independent of the liver metabolism. In addition, the mRNA, protein expression level and activity of the renal organic cation transporter 2 (OCT2) was markedly increased, suggesting that the enhanced renal clearance of metformin in CIA rats may be due to the up-regulated activity of OCT2. In conclusion, our study suggested that the reduced bioavailability of metformin in CIA rats is possibly related to the up-regulated function of the renal protein OCT2.
34679629 Dominating Cause of Pulmonary Hypertension May Change Over Time-Diagnostic and Therapeutic 2021 Oct 19 Chronic lung diseases are one of the most frequent causes of pulmonary hypertension (PH). The diagnostic challenge is to differentiate PH due to chronic lung disease from pulmonary arterial hypertension (PAH) with coexisting chronic lung disease. Moreover, the dominating cause of PH may change over time, requiring the implementation of new diagnostic procedures and new treatment modalities. We present a 68-year-old female, initially diagnosed with PH in the course of interstitial lung disease, with restrictive impairment of lung function. Therapy with immunosuppressive drugs resulted in significant clinical, radiological and functional improvement. However, five years later, arthritis symptoms developed, with PH worsening, despite stable lung disease. The patient was diagnosed with PAH in the course of rheumatoid arthritis. The introduction of sildenafil resulted in marked clinical and hemodynamic responses. Long-term survival (eleven years from PH onset and five years from PAH confirmation) has been achieved, and the patient remains in good functional condition. As the differential diagnosis of PH in patients with lung diseases is complex, the cooperation of pulmonologists and cardiologists is mandatory to obtain therapeutic success.
34305608 PTEN Methylation Promotes Inflammation and Activation of Fibroblast-Like Synoviocytes in R 2021 Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and subsequent destruction of adjacent articular cartilage and bone. In our previous work we showed that phosphatase and tension homolog deleted on chromosome 10 (PTEN) contributes to the activation of fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA), but the underlying mechanism is not unknown. In this study, we show that PTEN is downregulated while DNA methyltransferase (DNMT)1 is upregulated in FLS from RA patients and a rat model of AIA. DNA methylation of PTEN was increased by administration of tumor necrosis factor (TNF)-α in FLS of RA patients, as determined by chromatin immunoprecipitation and methylation-specific PCR. Treatment with the methylation inhibitor 5-azacytidine suppressed cytokine and chemokine release and FLS activation in vitro and alleviated paw swelling in vivo. PTEN overexpression reduced inflammation and activation of FLS via protein kinase B (AKT) signaling in RA, and intra-articular injection of PTEN-expressing adenovirus into the knee of AIA rats markedly reduced inflammation and paw swelling. Thus, PTEN methylation promotes the inflammation and activation of FLS in the pathogenesis of RA. These findings provide insight into the molecular basis of articular cartilage destruction in RA, and indicate that therapeutic strategies that prevent PTEN methylation may an effective treatment.
34430606 Cost-effectiveness of Anbainuo plus methotrexate compared to conventional disease-modifyin 2021 Jul BACKGROUND: This study aimed to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) vs. conventional disease-modifying antirheumatic drugs (cDMARDs) in Chinese rheumatoid arthritis (RA) patients. METHODS: A total of 90 RA patients who underwent ABN + MTX [assigned as ABN + MTX group (n=47)] or cDMARDs [assigned as control group (n=43)] treatment were analyzed. Disease activity was assessed at baseline (M0), 3(rd) month (M3), 6(th) month (M6), and 12(th) month (M12) after treatment. Drug, other medical, indirect, and total costs were calculated. Then, pharmacoeconomic analyses were performed with the threshold of cost-effectiveness set as 3 times of the mean gross domestic product (GDP) per capita in China during the study period. RESULTS: Treatment response rate was similar between the 2 groups, while disease remission and low disease activity (LDA) rates were increased in the ABN + MTX group compared to control group. Drug cost, other medical costs, and total cost were higher in the ABN + MTX group than control group, while indirect cost was similar between the 2 groups. Meanwhile, the quality-adjusted life-years (QALY) in ABN + MTX group and control group were 0.72 and 0.48 years, respectively. The incremental cost-effectiveness ratios (ICER) of ABN + MTX group compared to control group among the entire participant cohort, moderate-disease-activity participants, and severe-disease-activity participants were ¥135,486.7, ¥146,450.4, and ¥124,987.2/QALY, respectively, which were all below the cost-effectiveness threshold. Further sensitivity analyses revealed that the cost-effectiveness of ABN + MTX vs. cDMARDs was relatively robust, while among all the indexes, ABN price and Health Assessment Questionnaire Disability Index (HAQ-DI) score change for the ABN + MTX group affected ICER most. CONCLUSIONS: Treatment with ABN + MTX offers acceptable cost-effectiveness compared to cDMARDs treatment in Chinese RA patients.
34675809 Disease-Modifying Anti-rheumatic Drug Prescription Baihu-Guizhi Decoction Attenuates Rheum 2021 As a traditional Chinese medicine-originated disease-modifying anti-rheumatic drug prescription, Baihu-Guizhi decoction (BHGZD) is extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic efficacy. Mechanically, our previous data indicated that BHGZD may ameliorate RA partially by restoring the balance of the "inflammation-immune" system through regulating the TLR4-c-Fos-IL2-TNF-alpha axis. Toll-like receptor 4 (TLR4) has been revealed to be involved in the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex. Thus, the aim of the current study was to determine the regulatory effects of BHGZD on the TLR4-mediated inflammasome activation during RA progression based on the modified adjuvant-induced arthritis model (AIA-M) and the lipopolysaccharide/adenosine triphosphate (LPS/ATP)-induced pyroptosis cellular models. As a result, oral administration of BHGZD exhibited prominent improvement in the disease severity of AIA-M rats, such as reducing the redness and swelling of joints, arthritis incidence, arthritic scores, and diameter of the limb and increasing pain thresholds. In line with the in vivo findings, BHGZD treatment effectively inhibited the LPS/ATP-induced pyroptosis of both Raw264.7 macrophage and MH7A cells in vitro by reducing pyroptotic cell death morphology (swollen cells) and decreasing propidium iodide-positive and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL)-positive cells. Notably, the increased expression levels of TLR4, NLRP3, interleukin 1β, and interleukin 18 proteins and the elevated activities of caspase-1 and lactic dehydrogenase in in vivo and in vitro disease models were markedly reversed by the treatment with BHGZD. In conclusion, the above findings proved the immunomodulatory and anti-inflammatory activities of BHGZD, especially in pyroptosis, which may be attributed to the activation of TLR4-mediated NLRP3 inflammasome signaling.
34388290 Fears about COVID-19 and perceived risk among people with rheumatoid arthritis or ankylosi 2021 Aug 13 BACKGROUND: The COVID-19 pandemic has disrupted all aspects of life and may raise particular fears for people with rheumatic disease. There is a need for research on fears and perceived risk of SARS-CoV-2 so as to understand the impact on wellbeing and inform service provision. OBJECTIVES: The aim of this study was to examine the correlates of COVID-19 fears and perceived risk of SARS-CoV-2 among people with rheumatoid arthritis or ankylosing spondylitis. DESIGN: A cross-sectional survey design was applied in Aotearoa New Zealand in the period after initial nationwide lockdowns. METHOD: An online survey was completed from July to September 2020 by 126 individuals with rheumatoid arthritis (n = 96) or ankylosing spondylitis (n = 30) who had previously been recruited to the Patient Opinion Real-Time Anonymous Liaison (PORTAL) study in 2015 or 2018. The survey included demographics and health information as well as measures of COVID-19 fears and experiences, functional disability and fatigue-related disability. RESULTS: Fears about COVID-19 were higher among younger participants, those who had been tested for SARS-CoV-2, and those who experienced more flares over the initial lockdown. Perceived risk of SARS-CoV-2 infection was also higher among individual who had been tested for SARS-CoV-2 and those taking biologic medications. CONCLUSION: Fears about COVID-19 and perceived risk of infection are related to age, health and medications among individuals with rheumatoid arthritis or ankylosing spondylitis. These findings inform how health professionals can help address the concerns of particular groups of people with rheumatic disease by providing relevant information about the ongoing effects of the pandemic.
33460755 Non-target metabolomic analysis reveals the therapeutic effect of Saposhnikovia divaricata 2021 May 10 ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (SD), a Chinese crude drug, has long been recognized for therapeutic effect to rheumatoid arthritis (RA). At present, the mechanisms of SD treatment in RA have not been fully understood especially on the perspective of metabolomics. AIM OF THE STUDY: To study the pharmacodynamic effects of Saposhnikovia divaricata decoction on CIA rats, and explore the therapeutic mechanism by metabolomics methods. MATERIALS AND METHODS: Wistar rats were randomly divided into normal group, CIA model group, dexamethasone group and SD decoction groups (10 g crude drug/kg, 5 g crude drug/kg and 2.5 g crude drug/kg of SDD). Body weight, arthritis scores, serum cytokine levels and histopathological parameters of rats were assessed. A metabolomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS) was established to collect the metabolic profiles of rats and explore the metabolic changes that occurred after SDD treatment. RESULTS: SDD showed its protective effect on the affected joints, especially in the middle dosage group of SDD. Eighteen and 13 potential biomarkers for the SDD treatment of CIA rats were identified in the plasma and urine, respectively. SDD could regulate the disturbed metabolic pathways including tryptophan metabolism, glycerophospholipid catabolism, primary bile acid biosynthesis and fatty acid metabolism. CONCLUSIONS: In summary, SDD treatment could effectively alleviate symptoms of RA and regulate metabolic disorders in CIA rats.
34601577 Virophages: association with human diseases and their predicted role as virus killers. 2021 Oct 23 The fascinating discovery of the first giant virus, Acanthamoeba polyphaga mimivirus (APMV), belonging to the family Mimiviridae in 2008, and its associated virophage, Sputnik, have left the world of microbiology awestruck. To date, about 18 virophages have been isolated from different environmental sources. With their unique feature of resisting host cell infection and lysis by giant viruses, analogous to bacteriophage, they have been assigned under the family Lavidaviridae. Genome of T-27, icosahedral-shaped, non-enveloped virophages, consist of dsDNA encoding four proteins, namely, major capsid protein, minor capsid protein, ATPase and cysteine protease, which are essential in the formation and assembly of new virophage particles during replication. A few virophage genomes have been observed to contain additional sequences like PolB, ZnR and S3H. Another interesting characteristic of virophage is that Mimivirus lineage A is immune to infection by the Zamilon virophage through a phenomenon termed MIMIVIRE, resembling the CRISPR-Cas mechanism in bacteria. Based on the fact that giant viruses have been found in clinical samples of hospital-acquired pneumonia and rheumatoid arthritis patients, virophages have opened a novel era in the search for cures of various diseases. This article aims to study the prospective role of virophages in the future of human therapeutics.
33968012 miRNAs Alter T Helper 17 Cell Fate in the Pathogenesis of Autoimmune Diseases. 2021 T helper 17 (Th17) cells are characterized by the secretion of the IL-17 cytokine and are essential for the immune response against bacterial and fungal infections. Despite the beneficial roles of Th17 cells, unrestrained IL-17 production can contribute to immunopathology and inflammatory autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although these diverse outcomes are directed by the activation of Th17 cells, the regulation of Th17 cells is incompletely understood. The discovery that microRNAs (miRNAs) are involved in the regulation of Th17 cell differentiation and function has greatly improved our understanding of Th17 cells in immune response and disease. Here, we provide an overview of the biogenesis and function of miRNA and summarize the role of miRNAs in Th17 cell differentiation and function. Finally, we focus on recent advances in miRNA-mediated dysregulation of Th17 cell fate in autoimmune diseases.
33927515 Atlantoaxial Stabilization by Posterior C1 and C2 Screw-Rod Fixation for Various Pathologi 2021 Apr We retrospectively analyzed atlantoaxial dislocation (AAD) of various pathologies, namely, rheumatoid arthritis (RA), os odontoideum, and trauma. Various techniques were discussed in relation to C1-C2 stabilization. The study aims to share our clinical experience in a series of six cases of C1-C2 instability that underwent posterior C1-C2 fusion, with free hand technique and limited fluoroscopy. The clinicoradiological presentation for each patient is described. We reviewed different literatures related to our case vividly and focused on the basic neuroanatomy involved in the atlantoaxial joint. All patients of AAD had evidence of severe canal compromise and chronic compressive spinal cord changes. In our study, the patients age ranged from 28 to 52 years. The study included four males and two females. Out of six patients of AAD, three had history of trauma, two had os odontoideum, and one had chronic inflammatory condition (RA). From our case series, we concluded that the Goel-Harms technique is the most versatile and surgeon friendly technique for C1-C2 fixation. Early recognition and surgical intervention of atlantoaxial joint instability is essential to prevent catastrophic neurological complications.
33604490 Extensive autoimmune keratolysis with subsequent corneal perforation managed with tectonic 2021 Mar PURPOSE: To report a case of corneal perforation secondary to an extensive rheumatologic corneal melt, that was successfully managed via systemic immunosuppression and internal tectonic endothelial keratoplasty (TEK). OBSERVATIONS: A 55-year-old male with undiagnosed rheumatoid arthritis presented with a progressively enlarging area of peripheral ulcerative keratitis with extensive keratolysis which subsequently perforated despite treatment with oral steroids. The structural integrity of the globe was restored via a combination of cyanoacrylate glue and tectonic endothelial keratoplasty (TEK). This technique provided long term structural support and improved visual acuity. CONCLUSIONS AND IMPORTANCE: TEK grafts represent a viable treatment option in a subset of patients with corneal perforation secondary to an extensive corneal melt. The familiarity and relative ease of the surgical technique along with a lack of corneal sutures represents an alternate technique when compared to full thickness or lamellar keratoplasty. Further, through the use of anterior segment spectral domain optical coherence tomography (SD-OCT) we demonstrate that the donor graft integrated within the host cornea. To our knowledge, this represents the first case in the literature of corneal perforation secondary to an inflammatory corneal melt that was successfully managed with internal tectonic endothelial keratoplasty.
34964029 Oral Hygiene Status in Rheumatoid Arthritis Patients and Related Factors. 2021 Sep OBJECTIVES: To evaluate oral hygiene status in Rheumatoid arthritis (RA) patients, to analyse possible related factors, and to investigate the role of the rheumatologist in information about importance of adequate oral hygiene status in RA patients. METHODS: A cross-sectional study that included 100 consecutive RA patients (89% female, mean age 46.7 ± 11.7 years). For each patient, we recorded oral symptoms, oral hygiene status and role of rheumatologist in information on the oral hygiene status. Factors associated with regular brushing (≥2/day) were also analysed. RESULTS: Median disease duration was 8 years (4;2). Dental pain was reported by 74% of patients and bleeding by 51% of them. Regular brushing was noted in 45% of patients. The use of a correct brushing method was noted in 14% of cases. Two patients reported visiting a dentist regularly. Information explaining that poor oral hygiene has a negative impact on RA was delivered by rheumatologist to 11 patients. Regular brushing of teeth was recommended by rheumatologist to 8 patients and 10 patients were advised by their rheumatologist to consult a dentist. Regular brushing was more important in women (48,3% vs 18,2%; p=0.05) and in the literate patients (57,6 vs 31,2%, p<0.01). No association was found between regular brushing, Disease Activity Score 28 (DAS28) and health Assessment Questionnaire (HAQ). CONCLUSION: This study illustrates bad oral hygiene status in RA patients, which seems more important in men and illiterate patients. It also highlights poor information given by the rheumatologist.
34776393 Screening of interstitial lung disease in patients with rheumatoid arthritis: A systematic 2021 Nov 11 AIMS: Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. The aim of this review was to identify the different screening methods for ILD in patients with RA. METHODS: We ran a systematic search in Pubmed, Embase and Cochrane Library up to April 2020 and did a hand search of the references of the retrieved articles. The search was limited to humans and articles published in English, Spanish or French. We selected studies with any design where: (a) the population included adult patients with RA; (b) the intervention was any screening method for ILD; and (c) validity or reliability of the screening method were evaluated, or a screening method was described. Two reviewers independently screened the articles by title and abstract and subsequently extracted the information using a specific data extraction form. RESULTS: 25 studies were included with a total of 2593 patients. The most frequently used tool for ILD screening was high resolution computed tomography (HRCT) of the lung. Electronic auscultation, biochemical markers, bronchoalveolar lavage (BAL), pulmonary function tests (PFTs) and lung ultrasonography were also evaluated. Across the different studies, electronic auscultation and lung ultrasonography achieved higher accuracy than PFTs, BAL and biochemical markers. CONCLUSIONS: HRCT resulted as the most sensitive tool for ILD screening in patients with RA. Given its harmlessness and high sensitivity, lung ultrasonography may become the first-choice tool in the future.
34675699 The Role of Clinical Activity, Loneliness, and Satisfaction with e-Health Services as Fact 2021 INTRODUCTION: During the SARS-CoV-2 pandemic, most primary and specialist care outpatient clinics have started to offer their patients teleconsultation appointments as well as electronic prescriptions and referrals. For many patients, it was the only available way to access medical care. PURPOSE: The aim of the study was to assess the quality of life in rheumatoid arthritis (RA) patients and determine whether loneliness and satisfaction with telemedicine service can affect their perceived QoL during the SARS-CoV-2 pandemic. MATERIAL AND METHODS: One hundred and forty-three RA patients (mean age 45.83±13.5 years) were included in the study. The De Jong-Gierveld Loneliness Scale (DJGLS), The Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) and the questionnaire of satisfaction with teleconsultations were used in the study. The following statistical tests were used in the study: Spearman correlation test, multivariate linear regression. A significance level of 0.05 was used in the analysis. RESULTS: The patients presented a moderate level of loneliness (DJGLS; 31.1 points). The mean ASQoL score was 11.49±4.64. The correlation analysis showed a significant positive relationship between the level of loneliness and QoL - the higher the level of loneliness, the poorer the QoL (rho=0.283; p=0.001). An analysis of the relationship between satisfaction with teleconsultations and perceived QoL showed a statistically significant negative relationship - the higher the level of satisfaction with teleconsultations, the better the QoL (b=-0.166; p=0.047). The linear multivariate regression analysis showed that the loneliness (rho=0.1; p=0.01) was significant (p<0.05) independent predictor of QoL. CONCLUSION: During the SARS-CoV-2 pandemic, RA patients experienced loneliness and their QoL was low. Teleconsultation visits proved to be unsatisfactory and negatively perceived by patients. Higher severity of RA symptoms (weakness, fatigue), being unemployed and loneliness during the blockade are independent determinants of reduced QoL in RA patients.
34632114 Effects of romosozumab or denosumab treatment on the bone mineral density and disease acti 2021 Sep OBJECTIVES: To investigate effects of romosozumab treatment on disease activity and bone mineral density (BMD) in patients with rheumatoid arthritis (RA) and severe osteoporosis in comparison with effects of denosumab treatment. METHODS: A total of 50 women were enrolled in this study. The subjects were randomized equally into 2 groups: the romosozumab group or the denosumab group. Disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and BMD at lumbar spine were evaluated. RESULTS: The percent changes (Δ) in the BMD values at 3 and 6 months for the lumbar spine were as follows: romosozumab; 4.9% and 5.2%, denosumab: 2.3% and 3.2%. The ΔBMD for the lumbar spine at 3 months was significantly higher in the romosozumab group than in the denosumab group (P = 0.044). The DAS28-ESR at baseline, 3 and 6 months in the romosozumab group were 2.88, 2.60 (P = 0.427) and 2.58 (P = 0.588), respectively. The change from baseline in DAS28-ESR did not differ significantly between these 2 groups at any time point. CONCLUSIONS: The present study revealed that romosozumab treatment is more effective than denosumab treatment in increasing BMD of the lumbar spine at 3 months. Furthermore, the present study suggested that romosozumab treatment has no effects on the disease activity of RA in patients with RA and severe osteoporosis for 6 months.
34527923 Patients with rheumatoid arthritis and osteoarthritis in terms of sex hormone receptors an 2021 Jun OBJECTIVES: This study aims to investigate the relationship between estrogen receptors (ERs) and progesterone receptors (PRs) and histopathological findings in synovial tissue in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. PATIENTS AND METHODS: Synovial tissue samples obtained from synovial surgery from 30 RA (10 males, 20 females) and 92 OA (27 males, 65 females) patients with median age of 59 (range, 50 to 67) years were analyzed retrospectively between January 2010 and January 2019. The relationship between histopathological features and hormone receptor presence was analyzed. RESULTS: There was a meaningful relationship between histopathological parameters and RA and OA (p=0.01). The sex hormone receptor's presence was significantly higher in females with RA (p=0.01). Additionally, in the RA group, there was a remarkable relationship between ER and focal aggregates of lymphocytes (p=0.01), perivascular infiltrates of lymphocytes (p=0.03), and diffuse infiltrates of lymphocytes (p=0.01). In the OA group, a significant relationship was observed between PR and subchondral inflammation (p=0.01). In multivariate analysis, it was observed that ER was an independent risk factor for focal aggregates of lymphocytes in RA group (odds ratio [OR]=1.51 [1.02-2.25], p=0.04). Besides, PR was found to be an independent risk factor for subchondral inflammation in OA group (OR=3.90 [1.28-11.80], p=0.02). CONCLUSION: The presence of the sex hormone receptor in the synovium may change histopathological features and affect the clinical course.
34442429 Inference of an Integrative, Executable Network for Rheumatoid Arthritis Combining Data-Dr 2021 Aug 12 Rheumatoid arthritis (RA) is a multifactorial, complex autoimmune disease that involves various genetic, environmental, and epigenetic factors. Systems biology approaches provide the means to study complex diseases by integrating different layers of biological information. Combining multiple data types can help compensate for missing or conflicting information and limit the possibility of false positives. In this work, we aim to unravel mechanisms governing the regulation of key transcription factors in RA and derive patient-specific models to gain more insights into the disease heterogeneity and the response to treatment. We first use publicly available transcriptomic datasets (peripheral blood) relative to RA and machine learning to create an RA-specific transcription factor (TF) co-regulatory network. The TF cooperativity network is subsequently enriched in signalling cascades and upstream regulators using a state-of-the-art, RA-specific molecular map. Then, the integrative network is used as a template to analyse patients' data regarding their response to anti-TNF treatment and identify master regulators and upstream cascades affected by the treatment. Finally, we use the Boolean formalism to simulate in silico subparts of the integrated network and identify combinations and conditions that can switch on or off the identified TFs, mimicking the effects of single and combined perturbations.