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ID PMID Title PublicationDate abstract
33584321 The Effect of Inflammation on Bone. 2020 Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.
33209528 A Review of the Use of Biological Agents in Human Immunodeficiency Virus Positive Patients 2020 Oct 15 After approval, initial biologics etanercept, infliximab, and adalimumab became useful in the therapeutic armamentarium to treat rheumatoid arthritis (RA) patients who had an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs). However, all phase-III clinical trials submitted to the FDA, by design, excluded patients who were human immunodeficiency virus (HIV) positive. They are another subset of patients with low immunity due to their HIV-positive status. Very little information is available about the use of biologics in this new group of patients if they fail to respond to DMARDS. The available literature is limited to case reports about HIV-positive RA patients with reported side effects. These side effects range from no opportunistic infections (OIs) in some to acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulopathy (DIC) reported in others. Some HIV cases may initially present with rheumatological manifestations. With growing epidemiologic evidence of frequent joint manifestations in HIV-positive patients, HIV testing should be done more frequently in patients with RA, even those who deny risk factors for HIV. This review may help develop future guidelines on how to manage HIV-positive RA patients.
33150250 Neuroimmune Communication in the Kidney. 2020 Jul 15 Recent studies have clarified the interaction between nervous systems and immunity regarding the manner in which local inflammation is regulated and systemic homeostasis is maintained. The cholinergic anti-inflammatory pathway (CAP) is a neuroimmune pathway activated by vagus nerve stimulation. Following afferent vagus nerve stimulation, signals are transmitted to immune cells in the spleen, including β2-adrenergic receptor-positive CD4-positive T cells and α7 nicotinic acetylcholine receptor-expressing macrophages. These immune cells release the neurotransmitters norepinephrine and acetylcholine, inducing a series of reactions that reduce proinflammatory cytokines, relieving inflammation. CAP contributes to various inflammatory diseases such as endotoxemia, rheumatoid arthritis, and inflammatory bowel disease. Moreover, emerging studies have revealed that vagus nerve stimulation ameliorates kidney damage in an animal model of acute kidney injury. These studies suggest that the link between the nervous system and kidneys is associated with the pathophysiology of kidney injury. Here, we review the current knowledge of the neuroimmune circuit and kidney disease, as well as potential for therapeutic strategies based on this knowledge for treating kidney disease in clinical settings.
33102777 Refractory hemorrhagic esophageal ulcers by Candida esophagitis with advanced systemic scl 2020 Oct A 64-year-old woman diagnosed with rheumatoid arthritis (RA) and systemic sclerosis (SSc) was admitted to our hospital with chief complaints of uncontrolled bleeding from esophageal ulcers and an inability to consume meals. For RA and SSc, she was treated with prednisolone and abatacept and was taking vonoprazan as prophylaxis for steroid-induced gastric ulcers. She was diagnosed with severe Candida esophagitis, with multiple large and small ulcers with bleeding, based on esophagogastroduodenoscopy and pathological findings. We performed comprehensive treatment; abatacept was discontinued, and total parenteral nutrition was initiated along with antifungal therapy. Improvement in the esophageal ulcers was observed. Although severe Candida esophagitis is a rare condition, we should keep in mind that severe Candida esophagitis can occur in patients with an immunosuppressive compromised host and esophageal movement disorders such as SSc. Regular follow up by endoscopy and prophylactic treatment to prevent severe esophagitis may be necessary.
32522926 Methotrexate-associated Lymphoproliferative Disorder in the Liver Resembling Hepatocellula 2020 Sep 15 Methotrexate-related lymphoproliferative disorder (MTX-LPD) is known to be a side effect of MTX, but its involvement in the liver has been rarely reported. We herein report a 70-year-old woman with autoimmune hepatitis and rheumatoid arthritis who developed multiple liver tumors. We initially considered that she had developed rapid-growing hepatocellular carcinoma (HCC) in the cirrhotic liver based on imaging tests. A tumor biopsy and transcatheter arterial chemoembolization were thus performed. The tumors were then diagnosed as diffuse large B-cell lymphoma pathologically and considered to be MTX-LPD. This case indicates that MTX-LPD should be considered even in cirrhotic patients with liver tumors resembling HCC.
32308099 Costs and Health Outcomes Associated with Tofacitinib Treatment for Active Psoriatic Arthr 2020 Aug BACKGROUND: Psoriatic arthritis (PsA) is a chronic progressive inflammatory condition associated with significant direct and indirect costs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Economic evaluations, alongside clinical data, help inform papers and formulary decisions in the United States. OBJECTIVE: To evaluate outcomes and costs of including tofacitinib in treatment strategies for PsA from a third-party U.S. payer perspective, using a health economic model. METHODS: A decision tree model was developed to evaluate treatment sequences (up to 4 lines of advanced PsA therapy) with or without tofacitinib. Patients included in the model had active PsA and a previous inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor inhibitor (TNFi) therapy. The analysis time horizon was 2 years; decision points for continuing/switching treatments occurred quarterly, based on clinical response (assessed using the primary rheumatoid measure of efficacy, American College of Rheumatology [ACR]20 response only) and adverse drug reactions (ADRs). Costs included those related to ADRs and drug acquisition, monitoring, and administration. Other endpoints of PsA, such as assessment of enthesitis and dactylitis, were not integrated into the model. RESULTS: Treatment strategies including tofacitinib were associated with cost savings versus strategies without tofacitinib across all modeled scenarios, with an estimated 2-year cost saving of up to $8,454,858, based on 1 million insurants. Similarly, costs per member per month and per ACR20 responder were lower for sequences including tofacitinib versus sequences without. These savings arose because of lower ADR and drug acquisition/administration costs for sequences including tofacitinib. Deterministic sensitivity analyses showed these results to be robust. CONCLUSIONS: This analysis suggests that including tofacitinib in the treatment of active PsA in csDMARD-IR or TNFi-IR patients is a cost-saving alternative to sequences without tofacitinib, potentially reducing costs for PsA advanced therapies by up to $8.4 million over 2 years for payers insuring 1 million individuals. DISCLOSURES: This work was sponsored by Pfizer Inc. Bungey is an employee of Decision Resources Group, which received financial support from Pfizer Inc to develop the treatment-cost model used in the development of this manuscript. Chang-Douglass was an employee of Decision Resources Group at the time of the analysis. During development of this publication, Chang-Douglass started a role at the National Institute for Health and Care Excellence (NICE). The publication only reflects her views and does not reflect the views of NICE. Hsu, Cappelleri, Young, and Woolcott are employees of Pfizer Inc and own stock or stock options in Pfizer Inc. The data reported in this manuscript have been previously presented at the American College of Rheumatology Annual Scientific Meeting; October 19-24, 2018; Chicago, IL, and the AMCP Annual Meeting and Expo; March 25-28, 2019; San Diego, CA.
32764422 Incidence of Tuberculosis in Inflammatory Rheumatic Diseases: Results from a Lithuanian Re 2020 Aug 5 Background and objective: With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients' population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population. Methods: Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website. Results: Overall, 8779 patients with newly diagnosed RD were identified during the 2013-2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18-97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41-1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk. Conclusions: Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.
32719077 Glucocorticoid dose-dependent risk of type 2 diabetes in six immune-mediated inflammatory 2020 Jul INTRODUCTION: In immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose-response diabetes risk that consider changes in prescribed dose over time and disease activity. RESEARCH DESIGN AND METHODS: Population-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998-2017). We included 100 722 adult patients without diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32 593), inflammatory bowel disease (n=29 272), rheumatoid arthritis (n=28 365), vasculitis (n=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods. RESULTS: Average patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m(2). Overall, 8137 (8.1%) people developed type 2 diabetes after a median follow-up of 4.9 years. At 1 year, the cumulative risk of diabetes increased from 0.9% during periods of non-use to 5.0% when the daily prednisolone-equivalent dose was ≥25.0 mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease. CONCLUSIONS: We report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients.
32453505 Modifiable Lifestyle Factors Associated With Response to Treatment in Early Rheumatoid Art 2020 Jun OBJECTIVE: We aimed to evaluate the associations between response to algorithm-directed treat-to-target conventional synthetic disease-modifying antirheumatic drug therapy and potentially modifiable lifestyle factors, including dietary fish oil supplementation, body mass index (BMI), and smoking history in a rheumatoid arthritis (RA) inception cohort. METHODS: Patients with RA with a duration of less than 12 months were reviewed every 3 to 6 weeks to adjust therapy according to disease response. All patients received advice to take fish oil supplements, and omega-3 status was measured as plasma levels of eicosapentaenoic acid (EPA). Lifestyle factors and other variables potentially prognostic for 28-joint Disease Activity Score (DAS28) remission and DAS28 low disease activity (LDA) at the 12-month visit were included in multivariable logistic regression models. RESULTS: Of 300 participants, 57.7% reached DAS28 LDA, and 43.7% were in DAS28 remission at 1 year. Increase in plasma EPA was associated with an increase in the odds of being in LDA (adjusted odds ratio [OR] = 1.27; P < 0.0001) and remission (adjusted OR = 1.21; P < 0.001). There was some evidence that the effect of BMI on LDA might be modified by smoking history. An increase in BMI was associated with a decrease in the odds of being in LDA in current and former smokers but had no impact on LDA in patients who had never smoked. There were no meaningful associations between BMI or smoking history and remission. CONCLUSION: Omega-3 status, BMI, and smoking history are potential predictors of outcome in early RA. The possibility of an effect modification by smoking on the predictive value of BMI merits further investigation.
33269108 Circular RNAs: Promising Biomarkers for Age-related Diseases. 2020 Dec Aging is a complex biological process closely linked with the occurrence and development of age-related diseases. Despite recent advances in lifestyle management and drug therapy, the late diagnosis of these diseases causes severe complications, usually resulting in death and consequently impacting social economies. Therefore, the identification of reliable biomarkers and the creation of effective treatment alternatives for age-related diseases are needed. Circular RNAs (circRNAs) are a novel class of RNA molecules that form covalently closed loops capable of regulating gene expression at multiple levels. Several studies have reported the emerging functional roles of circRNAs in various conditions, providing new perspectives regarding cellular physiology and disease pathology. Notably, accumulating evidence demonstrates the involvement of circRNAs in the regulation of age-related pathologies, including cardio-cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis. Therefore, the association of circRNAs with these age-related pathologies highlights their potential as diagnostic biomarkers and therapeutic targets for better disease management. Here, we review the biogenesis and function of circRNAs, with a special focus on their regulatory roles in aging-related pathologies, as well as discuss their potential as biological biomarkers and therapeutic targets for these diseases.
32385880 Clinical and public health implications of periodontal and systemic diseases: An overview. 2020 Jun Severe periodontitis is defined by extensive loss of the tooth attachment apparatus. It is the sixth most common human disease and is estimated to affect 11.2% of the global adult population, hence representing a significant healthcare, social, and economic burden. Since the 1990s, multiple epidemiologic, experimental, and interventional studies have evidenced how periodontitis may also impact systemic health and it has been independently associated with the majority of chronic noncommunicable diseases. The evidence supporting these associations, mainly focusing on diabetes, pregnancy complications, and cardiovascular disease, was thoroughly reviewed in 2012 by an international consensus workshop. In the last 5 years, however, important advances have been made, not only in our understanding of the etiopathogenesis of periodontitis, or concerning the mounting evidence regarding the independent associations between periodontitis, diabetes, and cardiovascular disease, but also with many other systemic diseases including metabolic disease and obesity, rheumatoid arthritis, certain cancers, respiratory diseases, and cognitive disorders including Alzheimer's disease. This review describes these scientific advances by gathering together the existing evidence on the importance and relevance of the associations between periodontitis and many systemic diseases.
32341873 Tomographic imaging with an ultrasound and LED-based photoacoustic system. 2020 Apr 1 Pulsed lasers in photoacoustic tomography systems are expensive, which limit their use to a few clinics and small animal labs. We present a method to realize tomographic ultrasound and photoacoustic imaging using a commercial LED-based photoacoustic and ultrasound system. We present two illumination configurations using LED array units and an optimal number of angular views for tomographic reconstruction. The proposed method can be a cost-effective solution for applications demanding tomographic imaging and can be easily integrated into conventional linear array-based ultrasound systems. We present a potential application for finger joint imaging in vivo, which can be used for point-of-care rheumatoid arthritis diagnosis and monitoring.
32038645 Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity. 2019 There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characterizes Multiple Sclerosis. Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier. In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.
32600794 Ectopic Lymphoid Organs and Immune-Mediated Diseases: Molecular Basis for Pharmacological 2020 Nov Chronic inflammation is the result a persistent increase in the expression of several proinflammatory pathways with impaired inflammatory resolution. Ectopic lymphoid organs (ELOs), untypical lymphoid annexes, emerge during chronic inflammation and contribute to the physiopathology of chronic inflammatory disorders. This review discusses the pathophysiological role of ELOs in the progression of immune-mediated inflammatory diseases (IMIDs), including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), atherosclerosis, and Sjögren syndrome (SSj). The molecular pathways underlying the emergence of ELOs are of interest for the development of novel pharmacological approaches for the management of chronic inflammatory diseases.
31702066 Physicochemical characteristics of human IgG Fc fragments that expose regulatory rheumatoi 2020 Mar Previously, we showed that immunoglobulin G (IgG) Fc fragments can expose neoepitopes specific to antibodies that were named regulatory rheumatoid factor (regRF). RegRF confers resistance to experimental autoimmune diseases. Immunization of rats with rat Fc fragments exposing neoepitopes recognized by regRF reduces the symptoms of collagen-induced arthritis. Therefore, IgG Fc fragments that expose neoepitopes recognized by regRF are promising antirheumatic agents and regRF-producing lymphocytes are potential therapeutic biotargets. The purpose of this study was to elucidate the physicochemical features of human IgG Fc fragments that are associated with the presence of immunosuppressive neoepitopes recognized by regRF. It was found that the acquisition of neoepitopes recognized by regRF is associated with a reduction of the hinge disulfide bonds and conformational changes in the Fc fragment domains. Alkylation of thiol groups in the hinge leads to loss of the epitopes. Therefore, the neoepitopes recognized by regRF may form directly in the hinge when interchain disulfide bonds are reduced or in the region of the CH(2) domain as part of the conformational changes caused by the reduction of the interchain disulfide bonds in the hinge. Species-specificity studies of neoepitopes recognized by regRF revealed that human and rat neoepitopes recognized by regRF are cross-reactive.
33061689 Psychological State and Associated Factors During the 2019 Coronavirus Disease (COVID-19) 2020 BACKGROUND: Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are perceived to be more vulnerable to worse COVID-19 infection outcome. Furthermore, severe shortage in hydroxychloroquine supply was experienced. OBJECTIVE: We presented the psychological responses of Filipino SLE and RA patients to the COVID-19 pandemic and shortage of hydroxychloroquine supply. METHODS: A total of 512 completed online surveys from SLE and RA patients were gathered from May 19 to 26, 2020. The online survey collected data on socio-demographics, health status, contact history, health service utilization, use of hydroxychloroquine, COVID-19 knowledge and concerns, precautionary measures, information needs, the validated Impact of Events Scale-Revised (IES-R) and Depression, Anxiety and Stress Scales (DASS-21) ratings. RESULTS: The psychological impact of COVID-19 outbreak was at least moderate in 20%. The mean IES-R score was higher among SLE (22.34, SD=14.39) than RA (18.85, SD=13.24) patients. Stress, anxiety and depression were moderate to severe in 12.3%, 38.7%, and 27.7% of respondents. The mean stress subscale score was 10.11 (SD=7.95), mean anxiety subscale score was 6.79 (SD=6.57) and mean depression subscale score was 9.03 (SD=8.77). The risk factors for adverse mental health during the COVID-19 pandemic include the presence of comorbidity of hypertension and asthma; being a healthcare worker; and presence of specific symptoms of myalgia, cough, breathing difficulty, dizziness and sore throat. The protective factors for mental health during the pandemic include satisfaction with available health information and wearing of face masks. CONCLUSION: In the third month of the pandemic in the Philippines, 20% of the respondents with lupus and RA experienced moderate to severe psychological impact. There was moderate to severe anxiety in 38.7% and moderate to severe depression in 27%. Identification of factors that affect mental health in lupus and RA is useful in implementation of effective psychological support strategies.
32716834 Analysis of the correlation between disease activity score 28 and its ultrasonographic equ 2020 Jul OBJECTIVE: To study the differences between disease activity score 28 (DAS28) index and an ultrasound (US) approach using index echographic disease activity score (ECODAS). METHODS: This was a cross-sectional study in patients diagnosed with rheumatoid arthritis (RA). Demographic, clinical, and laboratory data were collected. We created a US index (ECODAS) evaluating the joints with synovitis using gray scale US (GSUS) and power Doppler US (PDUS) and calculated the formula of DAS28 index with both variables substituting tender joint for GSUS and swollen joint for PDUS (ECODAS1) and vice versa (ECODAS2). RESULTS: A total of 58 patients (65.5% women and 34.5% men) were included in the study. There was no significant difference between the 2 US indexes. We obtained a Pearson's correlation coefficient (Pearson's r) of 0.56 (p<0.00001) between DAS28 and ECODAS1 and of 0.57 (p<0.00001) between DAS28 and ECODAS2, respectively. However, for patients with a high disease activity [DAS28>5.1, tender joint count (TJC, high)], the correlation was poor (0.18) and ECODAS indexes were significantly lower (p=0.001). The correlation increased (0.86, p<0.001) when we excluded the tender joints and the joints with GS-positive synovitis in both the scores. CONCLUSION: US reduces the bias in the evaluation of patients with RA with a high value in DAS28 index. We found a clear difference between DAS and ECODAS when TJC was high. The results suggest that joint tenderness reported by the patient is not a good reflection of inflammation. More studies are needed to find a new combined clinical and sonographic index that would better assess the disease activity in patients with RA.
31670893 Secukinumab-induced paradoxical hidradenitis suppurativa. 2020 Jan Paradoxical reactions during treatment with biological agents may be defined as an appearance or exacerbation of a pathological condition that usually responds to this class of drug. Typical examples of paradoxical adverse effect are, among others, palmoplantar pustular and psoriasiform reactions or HS, in patients during a treatment of rheumatoid arthitis or IBD mainly. A few reports have been described an exacerbation of psoriasis1, palmoplantar pustular, or pustular psoriasis eruption with secukinumab. Marasca et al. highlights the immunological complexity that surrounds autoinflammatory diseases showing the potential double pathogenetic face of secukinumab in HS, describing a case of secukinumab-induced HS and a case of HS caused by adalimumab treatment and controlled by secukinumab therapy. Real world evidence and results from clinical trials with secukinumab for HS, will possibly show the real role that anti-IL-17 drugs play in this complex disease.
32063980 N-Butanol Extract of Gastrodia elata Suppresses Inflammatory Responses in Lipopolysacchari 2020 Gastrodia elata is a traditional herbal medicine that has been used for centuries to treat rheumatism. Previous studies have confirmed that ethanol extracts of Gastrodia elata have anti-inflammatory and antioxidant activities, and the n-butanol fraction exerts a higher inhibitory effect. However, the in vivo anti-inflammatory effects of Gastrodia elata have not been evaluated. Thus, we assessed the therapeutic effect of the n-butanol extract of Gastrodia elata (BGE) on complete Freund's adjuvant- (CFA-) induced arthritis rats which were separated into six groups (NOR; MODEL; CFA + dexamethasone (DEX); CFA + 25, 50, 100 mg/kg BGE). The paw swelling, joint radiology, and histology were used to analyze the effect of BGE on delaying the progression of rheumatoid arthritis. Furthermore, serum levels of inflammatory cytokines were analyzed via ELISA. In addition, the effect of BGE on nitric oxide (NO) production, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2), and inflammatory cytokines were detected in lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophage cells. Lastly, the impacts of BGE on the activation of the mitogen-activated protein kinases (MAPK) pathway in CFA rats and LPS-stimulated RAW264.7 macrophage were examined by western blot analysis. The results show that BGE can significantly reduce paw swelling without losing the body weight of rats. Imaging assessment confirms that BGE can protect cartilage from destruction, as well as reducing inflammatory cell infiltration and synovial proliferation. Moreover, BGE suppresses the production of inflammatory cytokines in serum and inhibits the activation of the phosphorylation of p38 and ERK in CFA rats. BGE was also demonstrated to decrease the production of NO and inflammatory cytokines in LPS-stimulated RAW264.7 cells. The effect of BGE in LPS-induced expression leads to reduced p38 and ERK phosphorylation and also downregulates the protein expression of iNOS and COX-2. Taken together, BGE exhibits a potential therapeutic effect on CFA rats, and its anti-inflammatory and antioxidant effects were possibly exerted by regulation of ERK/p38MAPK.
31791950 Tuberculosis in biologic users for rheumatic diseases: results from the South African Biol 2020 Feb OBJECTIVES: To evaluate the rate of tuberculosis (TB) in biologic users for rheumatic diseases in South Africa, the effectiveness of our latent TB infection (LTBI) programme, risk factors and outcome. METHODS: TB cases were collected from the South African Biologics Registry (SABIO), rheumatologists and pharmaceutical companies. Demographics, LTBI screening and treatment, biological and disease modifying antirheumatic drug (DMARD) therapies, TB diagnosis and outcomes were recorded. RESULTS: 96 TB cases were collected from 1999 to June 2017: rheumatoid arthritis 55, ankylosing spondylitis 27, psoriatic arthritis 4, and juvenile inflammatory arthritis 10. The TB rate was 1240/100 000 person years for biologic users (n=96) versus the biologic naive cohort of 0/100 000 years with an incidence rate difference of 0.0124 (p<0.0001). 60/96 had pulmonary and 36/96 had extra-pulmonary TB. Reactivation TB occurred in 45/96 cases. TB occurred in all biologics licenced in South Africa, the majority in monoclonal inhibitors (1683/100 000 person years) compared with etanercept (861/100 000 person years) and non-tumour necrosis factor (TNF) inhibitors (681/100 000 person years). The incidence rate ratio for monoclonal inhibitors compared with etanercept was 1.96 (p=0.005) and 2.47 (p=0.002) compared with non-TNF inhibitors with no significant difference between non-TNF inhibitors and etanercept (p=0.336). From those (12.9%) who screened LTBI positive, 14 developed TB, while the majority (77) screened LTBI negative. Black race, male sex, younger age and residence in the Western Cape were statistical risk factors. Two drug resistant TB cases and six deaths occurred. CONCLUSION: Reactivation and new onset TB is a significant risk for all biologics users in SA. Screening for LTBI is an imperative preventative strategy.