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ID PMID Title PublicationDate abstract
32591174 Anterior placement of the talar component in total ankle arthroplasty: A risk factor for t 2021 Apr BACKGROUND: Component subsidence is considered as a cause of revision surgery. The talar component subsidence may be a risk factor for revision surgery; however, there are no reports regarding talar component placement and subsidence amount following total ankle arthroplasty (TAA). We therefore investigated the relationship between talar component placement and subsidence amount. METHODS: Fifty-two ankles from 49 patients (age: 71 years [range 62-83], 13 male/ 36 female), who underwent TAA with mean follow-up of 36 months (range 12-83), were included. The subjects were divided into two groups based on talar component placement: anterior placement (n = 20, group A) and posterior placement (n = 32, group P) using weight-bearing lateral plain radiographs. The amount of the talar component subsidence and clinical outcomes, which included the Japanese Society for Surgery of the Foot (JSSF) scale, range of the motion (ROM) and the revision rate, were compared between the groups. RESULTS: Talar component subsidence was significantly higher in group A (2.1 ± 2.0 mm) than in group P (0.6 ± 1.4 mm, P = .017). There was no significant difference in the JSSF scale and ROM between group A and group P. The revision rate was 10.0% in group A and 6.3% in group P, albeit not statistically significant. CONCLUSION: Greater talar component subsidence was observed when the talar component was placed more anteriorly, suggesting that anterior placement of the talar component may need to be avoided during the surgery in order to minimize the postoperative talar component subsidence.
32843102 High frequency of methotrexate intolerance in longstanding rheumatoid arthritis: using the 2020 Aug 26 BACKGROUND: Methotrexate (MTX) intolerance is frequent, and its early identification may impact treatment, leading to timely changes in medication that may promote patient compliance and better control of rheumatoid arthritis (RA). The objective of this study was to identify the frequency of, and risk factors for, MTX intolerance using the Brazilian Portuguese version of the Methotrexate Intolerance Severity Score (MISS) questionnaire in patients with RA. METHODS: This cross-sectional study was performed between April 2018 and April 2019 and enrolled patients with RA in regular use of oral or subcutaneous MTX for at least 3 months. Patients were invited to answer the Brazilian Portuguese version of the MISS questionnaire, and MTX intolerance was defined by a score ≥ 6 points. Age, sex, disease duration, time of MTX use, dose, route of administration, concomitant medications, comorbidities, smoking, and Disease Activity Score for 28joint (DAS28) data were collected from institutional medical records. RESULTS: Among 120 patients, 103 (85.8%) were female, the mean age was 61 (±12.5) years, the mean duration of disease was 16 (±10.3) years, and the average duration of MTX use was 7 (±5.5) years. The frequency of MTX intolerance was 21.6%. The most frequent symptoms reported after the use of MTX were nausea (92.3%), abdominal pain (46.1%), and vomiting (30.7%). Behavioral symptoms occurred in 96.1% of patients with MTX intolerance, the most frequent being restlessness and irritability. Patients who used corticosteroids were more likely to develop MTX intolerance than those not using corticosteroids (odds ratio = 2.73; 95% confidence interval, 1.06 to 7.06; p = 0.038). Conversely, increasing age showed marginally significant association with decreased risk of MTX intolerance (p = 0.059). CONCLUSIONS: The use of the MISS questionnaire disclosed high frequencies of anticipatory, associative, and behavioral symptoms in MTX-intolerant patients, and the use of corticosteroid increases the risk of MTX intolerance. We suggest that the MISS questionnaire be used routinely in clinical practice.
32228568 The risk of coronary artery disease in patients with rheumatoid arthritis using Chinese he 2020 Mar 30 BACKGROUND: Few studies have evaluated the association between the risk of coronary artery disease (CAD) and the use of Chinese herbal products (CHP) in patients with rheumatoid arthritis (RA). This study investigated the risk of CAD among patients with RA using CHP in combination with conventional medicine. METHODS: A retrospective cohort study was conducted using the Taiwan National Insurance Research Database to assess 22,353 patients who had been newly diagnosed with RA between 1997 and 2010. Patients were assigned to the CHP group or non-CHP group according to their use or nonuse of CHP after being diagnosed with RA. The Cox proportional hazards model was used to estimate the hazard ratio (HR) of CAD for a 1:1 matched sample. RESULTS: Both the CHP and non-CHP groups comprised 4889 patients after 1:1 matching. The risk of CAD was significantly reduced in the CHP group [adjusted HR (aHR): 0.59, 95% confidence interval (CI): 0.50-0.71] compard with the non-CHP group. Those who used CHP for > 180 days had an even lower risk of CAD than users with CHP usage less than 30 days (aHR: 0.64, 95% CI: 0.43-0.95). Additionally, frequently prescribed formulae, such as Kuei-Chih-Shao-Yao-Chih-Mu-Tang, Tang-Kuei-Nien-Tung-Tang, and Shu-Ching-Huo-Hsieh-Tang, were associated with a reduced risk of CAD. CONCLUSION: The use of CHP was associated with a lower risk of CAD in patients with RA. Additional randomized controlled trials are required to assess any causal relationship between the effect of CHP usage and the risk of CAD.
32130577 Serum amino acid metabolic profiles of ankylosing spondylitis by targeted metabolomics ana 2020 Aug BACKGROUND: Ankylosing spondylitis (AS) is a common chronic inflammatory arthritis, causing lasting back pain with progressive loss of spinal mobility. However, the exact pathogenesis of AS remains unclear. We aim to use the metabolomics analysis to characterize the metabolic profile of AS, in order to better understand the pathogenesis of AS and monitor disease activity and progression. METHODS: The ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS) was used for investigating the serum amino acid metabolomic profiling of 30 AS patients, in comparison with 32 rheumatoid arthritis (RA) patients and 30 healthy controls, combined with multivariate statistical analysis. Metabolite association analysis with disease activity was performed using generalized linear regression. The metabolic pathway analysis for the important metabolites was performed using MetPA and the metabolic network was constructed. RESULTS: A total of 29 amino acids and biogenic amines were detected in all participants by UPLC-TQ-MS. It showed significant amino acid differences between the AS/RA patients and control subjects. Additionally, 4-hydroxy-L-proline, alanine, γ-aminobutyric acid, glutamine, and taurine were identified as candidate markers shared by AS/RA groups. Specifically, lysine, proline, serine, and alanine were found correlated with disease activity of AS. Furthermore, the most significant metabolic pathway identified were alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, aminoacyl tRNA biosynthesis and glycine, serine, and threonine metabolism. CONCLUSIONS: These preliminary results demonstrate that UPLC-TQ-MS analysis method is a powerful tool to identify metabolite profiles of AS. Research in identified disease activity-associated metabolites and biological pathways may provide assistance for clinical diagnosis and pathological mechanism of AS. Key Points • There are perturbations of serum amino acid metabolism in AS, compared with RA and healthy controls, determined by UPLC-TQ-MS. • Metabolomics pathway is used to analysis for the differential metabolites of AS. • The altered serum amino acid could monitor disease activity of AS.
33092271 Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels 2020 Oct 20 Chronic inflammatory diseases are often initiated and guided by the release of proinflammatory mediators. Rheumatoid arthritis (RA) is caused by an imbalance between the pro- and anti-inflammatory mediators in the joints, thereby favoring chronic inflammation and joint damage. Here, we investigate if short-term high-fiber dietary intervention shifts this towards anti-inflammatory mediators. Healthy controls (n = 10) and RA patients (n = 29) under routine care received daily high-fiber bars for 15 or 30 days, respectively. Stool and sera were analyzed for pro- and anti-inflammatory mediators. A high-fiber dietary intervention resulted in increased anti-inflammatory short-chain fatty acids (SCFA), decreased proarthritic cytokine concentrations, along with a durable shift in the Firmicutes-to-Bacteroidetes ratio. Together, these results further strengthen high-fiber dietary interventions as a practical approach complementing existing pharmacological therapies.
32670294 Identification of a Human SOCS1 Polymorphism That Predicts Rheumatoid Arthritis Severity. 2020 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an autoimmune response in the joints and an exacerbation of cytokine responses. A minority of patients with RA experience spontaneous remission, but most will show moderate/high disease activity, with aggressive joint damage and multiple systemic manifestations. There is thus is a great need to identify prognostic biomarkers for disease risk to improve diagnosis and prognosis, and to inform on the most appropriate therapy. Here we focused on suppressor of cytokine signaling 1 (SOCS1), a physiological negative regulator of cytokines that modulates cell activation. Using four independent cohorts of patients with arthritis, we characterized the correlation between SOCS1 mRNA levels and clinical outcome. We found a significant inverse correlation between SOCS1 mRNA expression and disease activity throughout the follow-up of patients with RA. Lower baseline SOCS1 levels were associated with poorer disease control in response to methotrexate and other conventional synthetic disease-modifying anti-rheumatic drugs in early arthritis, and to rituximab in established (active) RA. Moreover, we identified several single nucleotide polymorphisms in the SOCS1 gene that correlated with SOCS1 mRNA expression, and that might identify those patients with early arthritis that fulfill RA classification criteria. One of them, rs4780355, is in linkage disequilibrium with a microsatellite (TTTTC)(3-5), mapped 0.9 kb downstream of the SNP, and correlated with reduced SOCS1 expression in vitro. Overall, our data support the association between SOCS1 expression and disease progression, disease severity and response to treatment in RA. These observations underlie the relevance of SOCS1 mRNA levels for stratifying patients prognostically and guiding therapeutic decisions.
31837437 Generation of a robust model for inducing autoimmune arthritis in Sprague Dawley rats. 2020 Mar INTRODUCTION: The prerequisite for any experimental model in animals is similarity with the human disease, uniformity in disease severity and incidence. In antigen-induced arthritis models it is generally recognized that the major limitation is inconsistency in terms of incidence and severity. As access to strains like DBA/1 mice or Lewis rats is difficult for resource restrained laboratories, this study aimed to establish a robust and reproducible animal model of rheumatoid arthritis (RA). METHODS: Multiple approaches were undertaken for inducing arthritis in Sprague Dawley (SD) and Wistar rats using complete Freund's adjuvant (CFA), collagen type II (CII) emulsion, or different combinations of CII with low dose CFA along with lipopolysaccharide (LPS). The development of arthritis was evaluated by measuring paw edema, arthritis score, body weight, splenic index, histopathology and radiography of paw tissues. RESULTS: The combination of CII with low dose CFA and one injection of LPS resulted in 100% incidence of arthritis with disease severity ranging from moderate to severe and results were corroborated by histopathology and radiography. DISCUSSION: In a head-to-head comparison between SD and Wistar rats, the disease profile was better sustained and consistent in SD rats, and the use of CII with low dose CFA and LPS induced features akin to human RA. Taken together, a reproducible model of arthritis was established which can be replicated in any laboratory with limited resources.
32127659 Integration of single nucleotide variants and whole-genome DNA methylation profiles for cl 2020 May This study evaluated the use of multiomics data for classification accuracy of rheumatoid arthritis (RA). Three approaches were used and compared in terms of prediction accuracy: (1) whole-genome prediction (WGP) using SNP marker information only, (2) whole-methylome prediction (WMP) using methylation profiles only, and (3) whole-genome/methylome prediction (WGMP) with combining both omics layers. The number of SNP and of methylation sites varied in each scenario, with either 1, 10, or 50% of these preselected based on four approaches: randomly, evenly spaced, lowest p value (genome-wide association or epigenome-wide association study), and estimated effect size using a Bayesian ridge regression (BRR) model. To remove effects of high levels of pairwise linkage disequilibrium (LD), SNPs were also preselected with an LD-pruning method. Five Bayesian regression models were studied for classification, including BRR, Bayes-A, Bayes-B, Bayes-C, and the Bayesian LASSO. Adjusting methylation profiles for cellular heterogeneity within whole blood samples had a detrimental effect on the classification ability of the models. Overall, WGMP using Bayes-B model has the best performance. In particular, selecting SNPs based on LD-pruning with 1% of the methylation sites selected based on BRR included in the model, and fitting the most significant SNP as a fixed effect was the best method for predicting disease risk with a classification accuracy of 0.975. Our results showed that multiomics data can be used to effectively predict the risk of RA and identify cases in early stages to prevent or alter disease progression via appropriate interventions.
30241955 Efficacy and Safety of Combined Therapy With Synthetic Disease-modifying Antirheumatic Dru 2020 Sep OBJECTIVE: 1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA); 2) To design practical recommendations on their use. METHODS: A systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of 1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA; and 2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. RESULTS: Ultimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a "treat to target" strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. CONCLUSIONS: These recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA.
32002851 The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Disease 2020 Feb Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars-biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators-can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.
32646953 Trends of lymphoma incidence in US veterans with rheumatoid arthritis, 2002-2017. 2020 Jul OBJECTIVE: Past epidemiological studies have consistently demonstrated a link between rheumatoid arthritis (RA) and the incidence of lymphoma and it has been posited that high systemic inflammatory activity is a major risk determinant of lymphomagenesis. Given advances in the therapeutic armamentarium for RA management in recent years, the resulting lower level of disease activity could have led to a decline in lymphoma incidence in patients with RA. This study examined recent trends in lymphoma incidence in US veterans with RA. METHODS: Patients with RA were identified in the Veterans Affairs (VA) Corporate Data Warehouse. Lymphoma incidence was identified through the end of 2018 from the VA Central Cancer Registry and compared among patients diagnosed during 2003-2005, 2006-2008, 2009-2011 and 2012-2014. RESULTS: Among persons diagnosed with RA during 2003-2005, the incidence of lymphoma in the next 6 years was 2.0 per 1000 person-years. There was a steady decline in lymphoma incidence during the corresponding 6 years following diagnosis in the subsequent three cohorts, with a rate of 1.5 per 1000 person-years in the 2012-2014 cohort (incidence relative to that in the 2003-2005 cohort=0.79 (95% CI 0.58 to 1.1)). There was no similar decline in lymphoma incidence in VA patients diagnosed with osteoarthritis. CONCLUSION: We observed a decline in lymphoma incidence in recent years among American veterans with RA. Further studies are needed to evaluate the specific factors driving this decline.
32282749 Methotrexate-associated lymphoproliferative disorders in the central nervous system and st 2020 Apr RATIONALE: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a serious complication in patients treated using methotrexate. It occasionally develops in extra-nodal sites, but rarely in the central nervous system (CNS) or in 2 different sites at the same time. We present the rare case of a patient with rheumatoid arthritis who developed lymphoma in the CNS and stomach during MTX therapy. PATIENT CONCERNS: A 75-year-old Japanese man with rheumatoid arthritis who received methotrexate was admitted to our hospital because of gait ataxia and anorexia. DIAGNOSES: Imaging findings and biopsy led to a diagnosis of 2 different types of MTX-LPD in the central nervous system and stomach. INTERVENTIONS: The lesion in his stomach improved after methotrexate withdrawal, whereas the cerebellar mass required high-dose methotrexate and rituximab therapy. OUTCOMES: Complete remission has been maintained for the 2 years following the initiation of chemotherapy. LESSONS: In patients with RA who receive MTX and develop new neurological symptoms, CNS lymphoma as an MTX-LPD may be considered as a differential diagnosis.
31973181 Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Li 2020 Jan 21 Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent years, multifactorial diseases such as cancer, rheumatoid arthritis and neurodegenerative diseases remain major healthcare issues at present. Although pure bee venom, apitoxin, is mostly described to mediate anti-inflammatory, anti-arthritic and neuroprotective effects, its primary component melittin may represent an anticancer therapeutic. In this review, we approach the possibilities and limitations of apitoxin and its components in the treatment of these multifactorial diseases. We further discuss the observed unspecific cytotoxicity of melittin that strongly restricts its therapeutic use and review interesting possibilities of a beneficial use by selectively targeting melittin to cancer cells.
32573414 The effect of methotrexate on neutrophil reactive oxygen species and CD177 expression in r 2021 May OBJECTIVES: Neutrophils are found in abundance in the synovial fluid of patients with rheumatoid arthritis (RA), where they are activated and show high reactive oxygen species (ROS) production. However, there is limited data on circulating neutrophils in peripheral blood of patients with RA in terms of ROS production, expression of activation markers and the effect of treatment with methotrexate (MTX) on ROS. METHODS: This single-centre prospective study recruited patients of RA classified as per the 2010 ACR/EULAR criteria. In the cross-sectional arm, we included three groups, treatment-naïve RA (naïve-RA), MTX-treated RA (MTX-RA) and healthy controls, and compared ROS production and surface markers of neutrophil activation. In the longitudinal arm, we studied the change in neutrophil ROS production after 8 weeks of MTX treatment in naïve-RA patients. Neutrophil ROS production was measured by flow cytometry using dihydrorhodamine-123 (DHR) and by chemiluminescence using luminol. Surface expression of CD177, CD11b and CD64 was measured by flow cytometry. RESULTS: This study included 103 patients (50 naïve-RA, 53 MTX-RA) and 20 controls. Both naïve-RA and MTX-RA patients showed higher ROS production than healthy controls in unstimulated neutrophils in the DHR assay (p<0.001 and p=0.004). MTX-RA patients showed significantly lower ROS production than naive-RA, in both unstimulated (p=0.004) and PMA-stimulated neutrophils in the DHR assay (p=0.03). On longitudinal follow-up of 24 naïve-RA patients, there was a significant reduction of neutrophil ROS production (by 55% from baseline) (p<0.001) after 8 weeks of MTX. Neutrophil CD177 expression was higher in both naïve-RA and MTX-RA (trend) than controls (p=0.001 and p=0.09). MTX-RA neutrophils showed lower expression of CD177 than naïve-RA (p=0.01). CD11b expression was higher in MTX-RA compared to controls (p=0.01). CONCLUSIONS: Circulating neutrophils in RA showed higher ROS production and higher expression of CD177 and CD11b compared to controls. MTX treatment was associated with a reduction in ROS production and CD177 expression, which may be one of the mechanisms by which MTX works in RA.
31544222 A case of denosumab-associated membranous nephropathy in a patient with rheumatoid arthrit 2020 Feb We herein report a case of anti-RANKL monoclonal antibody-associated membranous nephropathy (MN). A 67-year-old woman with a history of rheumatoid arthritis treated with prednisolone and methotrexate for more than 30 years and osteoporosis treated with eldecalcitol and teriparatide for 4 years had achieved a stable disease condition. Her kidney function was normal and her urinalysis was negative for hematuria and proteinuria. An anti-RANKL monoclonal antibody (denosumab) was administered for the treatment of osteoporosis. Four months later, proteinuria appeared (2.3 g/g creatinine) and remained positive for about 6 months, therefore, she was admitted to our hospital. An immunofluorescence study revealed fine granular deposits of immunoglobulin G (IgG) and C3 along the capillary walls. Staining for IgG subclasses showed positive staining for IgG1 (3+), IgG2 (1+), IgG3 (1+), and IgG4 (1+); phospholipase A2 receptor was negative. Electron microscopy showed partial subepithelial and intramembranous deposits and focal thickening of the glomerular basement membrane. No evidence of malignancy or infectious disease was seen. After cessation of denosumab, the proteinuria gradually improved. Based on the renal biopsy results and clinical course (development of marked proteinuria in the presence of denosumab with subsequent amelioration in the absence of the drug), we diagnosed the patient with secondary MN due to denosumab. This is the first reported case of denosumab-associated MN.
32985955 Immunoglobulin D-kappa multiple myeloma in a patient with rheumatoid arthritis: a case rep 2021 Jan A 77-year-old Japanese woman with a 21-year history of seropositive, erosive rheumatoid arthritis (RA) and a 10-year history of methotrexate (MTX) therapy was admitted with malaise and mild consciousness disturbance. Laboratory data showed hypercalcemia, acute kidney injury, normocytic anaemia, and thrombocytopenia. As we first assumed drug-induced toxicity by MTX and eldecalcitol, both were discontinued and leucovorin rescue therapy and calcitonin were administered. However, her condition continued to worsen. Serum protein electrophoresis showed only a small M-peak, immunoelectrophoresis of both the serum and urine demonstrated Bence-Jones kappa (κ) type monoclonal protein without immunoglobulin heavy chain, and bone marrow examination revealed proliferation of plasma cells. We diagnosed her with Bence-Jones κ type multiple myeloma (MM) and transferred her to the department of haematology of a higher order medical institution. Conclusively, the diagnosis of immunoglobulin (Ig) D-κ type MM, a rare variant of this disorder, was determined in accordance with serum immunofixation. Several previous studies have suggested that pre-existing RA is a risk factor for MM. Although IgD MM is characterised by its clinical severity and poor prognosis compared to other subtypes, it is often misdiagnosed or mistaken as light chain type MM, as in the present case, because of the low level of IgD M-protein, resulting in delayed diagnosis. Physicians must take MM into consideration as a differential diagnosis when inactive RA patients present with inexplicable elevated calcium, renal failure, anaemia, and bone lesion symptoms and should be aware of IgD MM to establish the correct diagnosis promptly.
32792864 The Role of Autophagy and Mitophagy in Bone Metabolic Disorders. 2020 Bone metabolic disorders include osteolysis, osteoporosis, osteoarthritis and rheumatoid arthritis. Osteoblasts and osteoclasts are two major types of cells in bone constituting homeostasis. The imbalance between bone formation by osteoblasts and bone resorption by osteoclasts has been shown to have a direct contribution to the onset of these diseases. Recent evidence indicates that autophagy and mitophagy, the selective autophagy of mitochondria, may play a vital role in regulating the proliferation, differentiation and function of osteoblasts and osteoclasts. Several signaling pathways, including PINK1/Parkin, SIRT1, MAPK8/FOXO3, Beclin-1/BECN1, p62/SQSTM1, and mTOR pathways, have been implied in the regulation of autophagy and mitophagy in these cells. Here we review the current progress about the regulation of autophagy and mitophagy in osteoblasts and osteoclasts in these bone metabolic disorders, as well as the molecular signaling activated or deactivated during this process. Together, we hope to draw attention to the role of autophagy and mitophagy in bone metabolic disorders, and their potential as a new target for the treatment of bone metabolic diseases and the requirements of further mechanism studies.
33049484 Association between traffic-related air pollution and hospital readmissions for rheumatoid 2021 Jan 1 Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM(2.5) and PM(10)), nitrogen dioxide (NO(2)), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM(2.5) (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01-1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01-1.12). From lag2 to lag5, high-concentration NO(2) (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05-1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM(2.5) and NO(2) exposure. High-concentration PM(2.5) and NO(2) in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM(2.5) and NO(2) was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM(2.5) and NO(2) should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.
31846032 Hypoxia decreases the T helper cell-suppressive capacity of synovial fibroblasts by downre 2020 May 1 OBJECTIVE: The development of RA is linked to local infiltration of immune cells and to changes in the phenotype of synovial fibroblasts. Synovial fibroblasts possess the capacity to suppress T cell responses through indoleamine 2, 3-dioxygenase 1 (IDO1)-mediated tryptophan metabolism. However, synovial fibroblasts from RA patients are restricted in this immune-modulatory function. Moreover, hypoxic conditions are detected within synovial tissues of RA patients, with oxygen tensions of only 3.2% O2. This study aims at investigating the effects of hypoxia on the interaction between T cells and synovial fibroblasts, particularly on the T cell-suppressive capacities of synovial fibroblasts. METHODS: Synovial fibroblasts were cultured with Th cells under normoxic and hypoxic conditions (3% O2). Th cell proliferation was detected by flow cytometry. Tryptophan and kynurenine amounts were measured by HPLC. IDO1 expression and signal transducer and activator of transcription 1 (STAT1) phosphorylation were quantified by real-time PCR or western blot, and cytokine secretion by ELISA. RESULTS: Hypoxic conditions strongly diminished the Th cell-suppressive capacities of both OA synovial fibroblasts and RA synovial fibroblasts. Accordingly, IDO1 mRNA and protein expression, STAT1 phosphorylation and tryptophan metabolism were greatly reduced in OA synovial fibroblasts by hypoxia. MMP-3, IL-6, IL-10 and IFNγ secretion were significantly decreased under hypoxia in synovial fibroblast-Th cell co-cultures, while IL-17A levels were elevated. Supplementation with IFNγ, a well-known inducer of IDO1 expression, could rescue neither IDO1 expression nor Th cell suppression under hypoxic conditions. CONCLUSION: Hypoxia strongly affected the crosstalk between synovial fibroblasts and Th cells. By reducing the efficiency of synovial fibroblasts to restrict Th cell proliferation and by increasing the expression of IL-17A, hypoxia might have implications on the pathophysiology of RA.
32812344 Musculoskeletal stiffness is common in healthy adults and increases with age. 2021 Mar INTRODUCTION/OBJECTIVE: Musculoskeletal stiffness is a common feature in rheumatologic inflammatory diseases but little is known about background joint stiffness in the healthy population. The aim of this survey was to determine the variation in musculoskeletal stiffness with age in a cohort of healthy adults using a patient reported outcome instrument designed to assess stiffness in rheumatoid arthritis. METHODS: Healthy subjects ≥18 years old were enrolled at two sites. Those with a diagnosis of rheumatological disease were excluded. Each subject completed a 21-item questionnaire designed to evaluate the severity of musculoskeletal stiffness, its physical impact and psychosocial impact, and to provide an overall stiffness score, expressed as a percentage. Scores were analyzed by age group. RESULTS: Two hundred eighty-two subjects were included with a mean age of 42 years (±17, range 18-85). More than 50% of subjects reported stiffness in each age group but with a low median overall stiffness score of 5.4% (IQR 0, 12.6). Scores were markedly higher in those aged ≥60 years, median 10.0% (IQR 2.6, 21.9), and only in this age group did the majority of subjects report a physical or psychosocial impact of stiffness. Scores in males and females were similar. CONCLUSION: The prevalence of musculoskeletal stiffness in healthy subjects of all ages is not negligible, and the high frequency of stiffness and greater severity in the upper age cohort suggest that the background joint stiffness amongst older subjects should be considered when interpreting stiffness in rheumatologic patients.