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ID PMID Title PublicationDate abstract
32793348 Pharmacogenetic aspects of methotrexate in a cohort of Colombian patients with rheumatoid 2020 Oct Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). However, over time, ~40% of patients may experience therapeutic failure or drug toxicity. The genetic variability of the enzymes involved in the MTX metabolic pathway seem to serve an important role in the eventual therapeutic failure or drug toxicity. Depending on the enzymes affected, the toxicity or the therapeutic response may change. The present study reports some of the polymorphisms identified in enzymes in the MTX metabolic pathway that are present in a group of Colombian patients with RA, and assesses the associations of these polymorphisms with toxicity or therapeutic response to the medication. A total of 400 patients with RA were evaluated, of which 76% were women. the average age was 60.7±13.9 years and the duration of the disease was 13.2±10.9 years. The disease activity scoring method, DAS28-CRP, was used to evaluate the therapeutic response. Toxicity was determined based on reports of adverse events during the evaluation of the patients. The single nucleotide polymorphisms (SNPs) assessed using reverse transcription-PCR in the present study were MTHFR C677T, A1298C, ATIC C347G, RFC-1-G80A, FPGS-AG and DHFR-CT. The SNPs of MTHFR C677T (P=0.05) and A1298C (P=0.048) were significantly associated with the efficacy of MTX, and DHFR-CT (P=0.01) and ATIC C347 (P=0.005) were significantly associated with documented toxicity. Haematological, hepatic or renal toxicity was not associated with any of the SNPs. The results obtained in Colombian patients with RA receiving MTX are similar to those reported in other populations; however, the SNPs associated with a lack of response previously reported in the literature were not observed in our data. The SNPs identified in the present study may be used as biomarkers to predict response to MTX in terms of efficacy and toxicity in Colombian patients with RA.
32760888 The improvement in aerobic capacity, disease activity, and function in patients with rheum 2020 Jun OBJECTIVES: This study aims to evaluate the effect of cardiac rehabilitation (CR) on disease activity, functional status, fitness, and modified cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA) with a moderate disease activity. PATIENTS AND METHODS: This single-center, controlled study included a total of 60 female RA patients (mean age 57.5 years; range, 50 to 64 years) with moderate disease activity according to the Disease Activity Score-28 (DAS28) between January 2014 and June 2015. The patients were divided into two equal groups as those receiving CR program (n=30) and those receiving home exercise program (HEP; n=30). The patients were evaluated at baseline, at Weeks 10 and 24 using exercise tolerance test (i.e., The Metabolic Equivalent of Task [MET] and maximal oxygen uptake [VO2 max]), Six-Minute Walk Test (6MWT), DAS28, Health Assessment Questionnaire (HAQ), modified Systematic Coronary Risk Evaluation (mSCORE), Short Form Health Survey-36 (SF-36), and Beck Depression Inventory (BDI). RESULTS: There was a significant improvement in the VO2 max (p<0.001), MET (p<0.001), DAS28 (p<0.001), HAQ (p<0.001), BDI (p=0.005), SF-36 physical function (p=0.039), pain (p<0.001) and vitality subscale scores (p=0.008), and 6MWT (p<0.001), after the initial and repetitive exercise programs in the CR group compared to the HEP group. At the end of Week 24, full compliance with HEP was higher in the patients with CR group, compared to the HEP group (p<0.001). There was no significant effect of supervised exercise program on the mSCORE, although systolic blood pressure (p=0.033) and resting heart rate (p=0.049) were significantly improved in the CR group versus HEP group. CONCLUSION: Based on our study results, supervised exercise program cannot reduce CVD risk as assessed by the mSCORE, although it improves physical fitness, disease activity, and functional outcomes which may reduce traditional CVD risk factors in patients with RA.
32191997 Cervical Myelopathy in Patients Suffering from Rheumatoid Arthritis-A Case Series of 9 Pat 2020 Mar 17 Cervical myelopathy occurs in approximately 2.5% of patients suffering from rheumatoid arthritis (RA) and is associated with notable morbidity and mortality. However, the surgical management of patients affected by cervical involvement in the setting of RA remains challenging and not well studied. To address this, we conducted a retrospective analysis of our clinical database between May 2007 and April 2017, and report on nine patients suffering from cervical myelopathy due to RA. We included patients treated surgically for cervical myelopathy on the basis of diagnosed RA. Clinical findings, treatment and outcome were assessed and reported. In addition, we conducted a narrative review of the literature. Four patients were male. Mean age was 64.8 ± 20.5 years. Underlying cervical pathology was anterior atlantoaxial instability (AAI) associated with retrodental pannus in four cases, anterior atlantoaxial subluxation (AAS) in two cases and basilar invagination in three cases. All patients received surgical treatment via posterior fixation, and in addition two of these cases were combined with a transnasal approach. Preoperative modified Japanese orthopaedic association scale (mJOA) improved from 12 ± 2.4 to 14.6 ± 1.89 at a mean follow-up at 18.8 ± 23.3 months (range 3-60 months) in five patients. In four patients, no follow up was available, and the mJOA of these patients at time of discharge was stable compared to the preoperative score. One patient died two days after surgery, where a pulmonary embolism was assumed to be the cause of mortality, and one patient sustained a temporary worsening of his neurological deficit postoperatively. Surgery is generally an effective treatment method in patients with inflammatory arthropathies of the cervical spine. Given the nature of the RA and potential instability, fixation in addition to cord decompression is generally required.
32152918 Risk of systemic autoimmune diseases in gastric disease patients with proton pump inhibito 2020 Sep INTRODUCTION: The risk factors for systemic autoimmune diseases (SAD) in gastric disease patients with proton pump inhibitor (PPI) use are still unclear. This study discussed this relationship in an Asian population. METHODS: Patients without a prior history of SAD were identified from Taiwan's National Health Insurance Research Database between January 1, 2000, and December 31, 2010. Cox regression models were applied to estimate the hazard ratio (HR) with 95% confidence interval [CI] of SAD. The cumulative PPI dosage was stratified by quartiles of defined daily doses and adjusted for baseline disease risk score which served as the primary variables compared against no PPI use. RESULTS: We analyzed the data of 51,291 participants aged 18 years or older and free of SAD at baseline. PPI users (n = 17,938) had a significantly increased risk of SAD over non-PPI users. There was a significantly higher risk of developing SAD in older age groups. A significant dose-dependent association was observed between cumulative PPI use and the risk of SAD. Female PPI users had significantly higher risk of developing SAD. In patients who received PPI, the autoimmune disease with significantly higher incidence was Sjögren syndrome (SjS) (adjusted HR [aHR] 1.82, 95% CI, 1.02-3.27) and rheumatoid arthritis (RA) (aHR, 2.19, 95% CI, 1.19-4.01). CONCLUSION: This study found PPI users to be associated with an increased risk of SAD. Older age or cumulative PPI use was significantly associated with SAD, and the highest incidence was SjS and RA among gastric disease patients who received PPI. Key Points • This nationwide long-term cohort study found PPI users to be associated with an increased risk of rheumatoid arthritis and Sjögren syndrome in Taiwan. • This finding may help with clinical risk evaluation and will inform further investigation of the pathogenesis between autoimmune diseases and PPI use.
32477105 Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB 2020 Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to treat RA. The present study was designed to explore the ability of Gent to combat RA and to explore the molecular basis for such anti-RA activity both in vitro using tumor necrosis factor alpha (TNF-α)-stimulated human RA fibroblast-like synoviocytes (RA-FLS) and in vivo using a rat adjuvant-induced arthritis (AIA) model. We found that Gent was able to significantly reduce the swelling of joints and arthritic index scores, with corresponding reductions in synovial inflammatory cell infiltration, synovial hyperplasia, and bone erosion in treated AIA rats. Importantly, Gent 200 mg/kg reduced thymus index in AIA rats, but had no effect on spleen index and body weight, it revealed that Gent was relatively safe at the dose we chose. We further found that Gent was able to suppress the TNF-α-induced proliferation and migration of RA-FLS cells. This suppression was attributed to the ability of Gent to block NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1, thereby disrupting the activation of the NLRP3 inflammasome. Consistent with such suppression, Gent led to a significant decrease in IL-1β secretion by treated cells. Furthermore, this reduction in NLRP3 inflammasome activation was also associated with decreases in the activation of nuclear factor (NF-κB), the production of reactive oxygen species (ROS), and the expression of inflammatory IL-6. Together these findings indicate that Gent can suppress the ROS-NF-κB-NLRP3 axis to alleviate RA symptoms. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Gentiopicroside (PubChem CID: 88708).
31644955 The gut-eye-lacrimal gland-microbiome axis in Sjögren Syndrome. 2020 Apr The bacterial communities that collectively inhabit our body are called the microbiome. Virtually all body surface harbors bacteria. Recent advances in next-generation sequencing that have provided insight into the diversity, composition of bacterial communities, and their interaction are discussed in this review, as well as the current knowledge of how the microbiome promotes ocular health. The ocular surface is a site of low bacterial load. Sjögren Syndrome is an autoimmune disease that affects the exocrine glands, causing dry mouth and dry eye. Systemic antibiotic treatment and germ-free mice have demonstrated that commensal bacteria have a protective role for the ocular surface and lacrimal gland. The existence of a gut-eye-lacrimal gland axis-microbiome is discussed.
33256735 Reprogramming of synovial macrophage metabolism by synovial fibroblasts under inflammatory 2020 Nov 30 BACKGROUND: Macrophages adapt to microenvironments, and change metabolic status and functions to regulate inflammation and/or maintain homeostasis. In joint cavities, synovial macrophages (SM) and synovial fibroblasts (SF) maintain homeostasis. However, under inflammatory conditions such as rheumatoid arthritis (RA), crosstalk between SM and SF remains largely unclear. METHODS: Immunofluorescent staining was performed to identify localization of SM and SF in synovium of collagen antibody induced arthritis (CAIA) model mice and normal mice. Murine arthritis tissue-derived SM (ADSM), arthritis tissue-derived SF (ADSF) and normal tissue-derived SF (NDSF) were isolated and the purity of isolated cells was examined by RT-qPCR and flow cytometry analysis. RNA-seq was conducted to reveal gene expression profile in ADSM, NDSF and ADSF. Cellular metabolic status and expression levels of metabolic genes and inflammatory genes were analyzed in ADSM treated with ADSM-conditioned medium (ADSM-CM), NDSF-CM and ADSF-CM. RESULTS: SM and SF were dispersed in murine hyperplastic synovium. Isolations of ADSM, NDSF and ADSF to analyze the crosstalk were successful with high purity. From gene expression profiles by RNA-seq, we focused on secretory factors in ADSF-CM, which can affect metabolism and inflammatory activity of ADSM. ADSM exposed to ADSF-CM showed significantly upregulated glycolysis and mitochondrial respiration as well as glucose and glutamine uptake relative to ADSM exposed to ADSM-CM and NDSF-CM. Furthermore, mRNA expression levels of metabolic genes, such as Slc2a1, Slc1a5, CD36, Pfkfb1, Pfkfb3 and Irg1, were significantly upregulated in ADSM treated with ADSF-CM. Inflammation marker genes, including Nos2, Tnf, Il-1b and CD86, and the anti-inflammatory marker gene, Il-10, were also substantially upregulated by ADSF-CM. On the other hand, NDSF-CM did not affect metabolism and gene expression in ADSM. CONCLUSIONS: These findings suggest that crosstalk between SM and SF under inflammatory conditions can induce metabolic reprogramming and extend SM viability that together can contribute to chronic inflammation in RA. Video Abstract.
31862360 Synergistic effect of all-trans-retinal and triptolide encapsulated in an inflammation-tar 2020 Mar 10 Targeted delivery of nano-encapsulated anti-inflammatory agent represents a promising while challenging strategy in the treatment of rheumatoid arthritis (RA). Pro-inflammatory macrophages play a major role in the pathogenesis of RA. In this study, we investigated the effect of a macrophage-targeted pH-sensitive nanoparticle on collagen-induced arthritis (CIA) in mice. To target macrophage, all-trans-retinal was conjugated into dextran backbone through pH-sensitive hydrazone bond, then grafted with galactose (GDR). This nanoparticle was used for the encapsulation of triptolide (TPT), a potent anti-inflammatory compound isolated from Chinese herb. As expected, GDR nanoparticles preferentially accumulated in the inflammatory tissues. Treatment with GDR-TPT nanoparticles resulted in a marked decrease in the infiltration of CD3(+) T cells and F4/80(+) macrophages and reduction of the expression of TNF-α, IL-6 and IL-1β in the inflamed lesions of CIA mice. Furthermore, Th1 and Th17 responses were also inhibited. Importantly, anti-arthritic effect of TPT was markedly enhanced while its toxic effect was attenuated by encapsulating with GDR. GDR by itself also had moderate effect in the inhibition of arthritis, due to its intrinsic anti-inflammatory property. Therefore, our results clearly show that GDR-TPT nanoparticle may represent a promising drug delivery system for the treatment of RA.
32896255 Direct costs in patients with chronic inflammatory arthropathies on biological therapy: a 2021 Jul OBJECTIVES: The aim of the study was to assess the direct costs for the Spanish Health System of patients with chronic inflammatory arthropathies treated with biological therapies in daily clinical practice and to establish possible factors associated with lower costs. METHODS: A descriptive, observational and retrospective study was conducted. Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who started a biological therapy between 1 January 2009 and 31 December 2016 were included. Variables related to socioeconomic status, disease and biological therapy were included. The annual cost of biological treatment and other direct medical costs were calculated for each disease. The analysis of costs was based on the National Health Service perspective. The time horizon comprised the 8-year long study period. RESULTS: A total of 422 biological therapy lines were analysed. The annual biological therapy cost per patient was €12,494±3,865 for rheumatoid arthritis, €11,248±2,763 for ankylosing spondylitis and €12,263±35,155 for psoriatic arthritis (p=0.008). The cost of biological therapies entailed about 80% of the total cost of these diseases. Hospital admission was a factor which contributed to an increasing cost in all these conditions. A longer duration of the biological therapy was associated with lower cost in all the diseases. CONCLUSIONS: The cost of ankylosing spondylitis is lower than that of rheumatoid arthritis and psoriatic arthritis. The biological therapy is the factor with the highest impact on the overall cost of these diseases. Preventing hospital admissions and a higher persistence to the biological therapy can contribute to lower costs for the system.
31957051 Interleukin-23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthro 2020 Mar The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL-23R or the interleukin-23 (IL-23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin-17 (IL-17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL-23R-expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL-23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL-23R-expressing myeloid cells and various innate and adaptive T cells that produce IL-17 family cytokines have also been described in the human enthesis. Blockade of IL-23 pathway with either anti-p40 or anti-p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL-23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.
32362840 Metabolic Checkpoints in Rheumatoid Arthritis. 2020 Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipo-cytokines and metabolic intermediates. These functions are metabolically demanding and require the most efficient use of bioenergetic pathways. The synovial membrane is the primary site of inflammation in RA and exhibits distinctive histological patterns characterized by different metabolism, prognosis and response to treatment. In the RA synovium, the high energy demand by stromal and infiltrating immune cells, causes the accumulation of metabolites, and adipo-cytokines, which carry out signaling functions, as well as activating transcription factors which act as metabolic sensors. These events drive immune and joint-resident cells to acquire pro-inflammatory effector functions which in turn perpetuate chronic inflammation. Whether metabolic changes are a consequence of the disease or one of the causes of RA pathogenesis is still under investigation. This review covers our current knowledge of cell metabolism in RA. Understanding the intricate interactions between metabolic pathways and the inflammatory and immune responses will provide more awareness of the mechanisms underlying RA pathogenesis and will identify novel therapeutic options to treat this disease.
32122171 Factors Associated With Reoperation After Silicone Metacarpophalangeal Joint Arthroplasty 2020 Nov Background: Silicone metacarpophalangeal (MCP) joint arthroplasty has a high revision rate. It has been suggested that the preoperative degree of ulnar drift and radial wrist deviation influences the durability of MCP silicone arthroplasties. The goal of this study was to evaluate what factors are associated with reoperation after silicone MCP arthroplasty. Materials and Methods: We retrospectively evaluated all adult patients who underwent MCP silicone arthroplasty between 2002 and 2016 at one institutional system for inflammatory arthritis. After manual chart review, we included 73 patients who underwent 252 arthroplasties. Fingers treated included 66 index, 67 long, 60 ring, and 59 small fingers. Results: The overall reoperation rate was 9.1% (N = 23). Indications for reoperation were implant breakage (n = 11), instability (n = 4), soft tissue complications (n = 4), infections (n = 3), and stiffness (n = 1). There was a trend that patients who underwent single-digit arthroplasty had higher rates of revision (19% vs 3.5%, P = .067). Radiographic follow-up demonstrated joint incongruency in 50% of cases, bone erosion in 58% of cases, and implant breakage in 19% of cases. There was a trend toward higher rates of revision in patients without preoperative MCP joint subluxation (19% vs 6.7%, P = .065) The 1-, 5-, and 10-year implant survival rates were 96%, 92%, and 70%, respectively. Revision surgery occurred at <14 months in 15 patients (65%) and after 5 years in 8 (35%) patients. Conclusions: Revision surgery after silicone MCP arthroplasty appears to be bimodal. Patients with greater hand function preoperatively may be at higher risk of revision surgery.
32444009 Risk of Serious Infection Associated with Agents that Target T-Cell Activation and Interle 2020 Jun Co-stimulatory T-cell inhibitors are used in the treatment of rheumatoid arthritis and to prevent rejection of renal transplants. Inhibitors of the intereukin (IL-17) cytokine are indicated for psoriasis, psoriatic arthritis and ankylosing spondylitis and anti- IL-23 drugs for psoriasis. Serious infections occur in 4.2% to 25.0% of co-stimulatory inhibitors and 1.0% to 2.0% with IL-17 or IL-23 inhibitors. Underlying disease, steroid dose greater than 7.5 to 10.0 mg, and comorbidities influence risk in individual patients. Opportunistic infections or reactivation of tuberculosis are rare.
32599145 Alternative splicing controls cell lineage-specific responses to endogenous innate immune 2020 Nov The identification of barely more than 20,000 human genes was amongst the most surprising outcomes of the human genome project. Alternative splicing provides an essential means of expanding the proteome, enabling a single gene to encode multiple, distinct isoforms by selective inclusion or exclusion of exons from mature mRNA. However, mis-regulation of this process is associated with most human diseases. Here, we examine the impact of post-transcriptional processing on extracellular matrix function, focusing on the complex alternative splicing patterns of tenascin-C, a molecule that can exist in as many as 500 different isoforms. We demonstrate that the pro-inflammatory activity of this endogenous innate immune trigger is controlled by inclusion or exclusion of a novel immunomodulatory site located within domains AD2AD1, identifying this as a mechanism that prevents unnecessary inflammation in healthy tissues but enables rapid immune cell mobilization and activation upon tissue damage, and defining how this goes awry in autoimmune disease.
33183072 Nanostructured lipid carrier-based smart gel: a delivery platform for intra-articular ther 2021 Feb The promising potential of nano-structured lipid carrier (NLC) polymeric gel of CUR as an effective treatment for rheumatoid arthritis by intra-articular route of administration was investigated. NLC composed of cetylpalmitate, Labrafac PG & Captex 200, Tween 80 and Labrasol. The hot homogenization method employed by melt ultrasonication was used. The formulated NLC dispersions were characterized and were suitably dispersed into the matrix of pluronic F-127(PLF-127) and pluronic F-68 (PLF-68). A two-factor three-level full factorial design was employed to deduce the optimal concentrations of PLF-127 and PLF-68. The optimized formulations were sterilized by gamma radiation. The formulated NLC smart gels were characterized and evaluated for various parameters. The efficacy evaluation by antigen-induced monoarthritis model and biocompatibility testing by histopathological studies was performed. Formulated NLCs exhibited an average particle size of 165.12 nm, entrapment efficiency of 72.15%, and zeta potential of -21.67 mV. The optimized CUR-NLC smart gel was demonstrated to have a sol-gel transformation at 33.21 °C and 94.32% drug release at 84 h. NLC's which were sterile and easily syringeable, continued to remain within the colloidal range. CUR-NLC smart gels were found to be biocompatible and showed a significant reduction in rat knee joint inflammation compared to free drug.
32325846 Oral-Health-Related Quality of Life in Adult Patients with Rheumatic Diseases-A Systematic 2020 Apr 19 OBJECTIVES: The aim of this systematic review was to assess the oral-health-related quality of life (OHRQoL) of adult patients with rheumatic diseases. MATERIAL AND METHODS: A systematic literature search was performed, including clinical studies on adults (aged at least 18 years) with a verified diagnosis of rheumatic disease. RESULTS: 26 out of 41 clinical studies including rheumatoid arthritis (RA, seven studies), systemic sclerosis (SSc, five), Sjögren syndrome (SS, eight), Behcet disease (BD, four), systemic lupus erythematosus (SLE, one) and ankylosing spondylitis (AS, one) were found. In 15 studies, a healthy control group was recruited. The short form of the Oral Health Impact Profile (OHIP 14) was most frequently applied. The majority of studies (14/15) reported worse OHRQoL in patients with rheumatic disease compared to healthy individuals. In particular, patients with SS (salivary flow and composition) or BD (oral ulcers) showed a relation between OHRQoL and disease-specific oral manifestations. Most studies investigating subscales of OHRQoL (5/6) found the subscale physical disability to be predominantly affected in patients with rheumatic diseases. About half of the studies reported impaired psychosocial aspects. CONCLUSION: Patients with rheumatic diseases exhibit reduced OHRQoL, especially in diseases with oral manifestations like SS and BD. Physical affections due to oral diseases and psychosocial impairments caused by disease-related parameters must be recognized within patient-centered dental care.
32215665 Interleukin 23 and autoimmune diseases: current and possible future therapies. 2020 May PURPOSE: IL-23 is a central proinflammatory cytokine with a wide range of influence over immune response. It is implicated in several autoimmune diseases due to the infinite inflammatory loops it can create through the positive feedbacks of both IL-17 and IL-22 arms. This made IL-23 a key target of autoimmune disorders therapy, which indeed was proven to inhibit inflammation and ameliorate diseases. Current autoimmune treatments targeting IL-23 are either by preventing IL-23 ligation to its receptor (IL-23R) via antibodies or inhibiting IL-23 signaling by signaling downstream mediators' inhibitors, with each approach having its own pros and cons. METHODS: Literature review was done to further understand the biology of IL-23 and current therapies. RESULTS: In this review, we discuss the biological features of IL-23 and its role in the pathogenesis of autoimmune diseases including psoriasis, rheumatoid arthritis and inflammatory bowel diseases. Advantages, limitations and side effects of each concept will be reviewed, suggesting several advanced IL-23-based bio-techniques to generate new and possible future therapies to overcome current treatments problems.
32004899 Posterior lumbar interbody fusion graft penetrated the lumbar thecal sac in a patient with 2020 INTRODUCTION: Intradural foreign bodies have been reported to be associated with disc material, tumors, and bullets following spinal gunshot injuries. In this report, we describe a case of non-union with minor trauma that caused interbody bone graft material to migrate into the intrathecal area in a patient with RA. PRESENTATION OF CASE: We present the case of a 65-year-old woman visited an outpatient clinic of our hospital after experiencing progressive lower extremity weakness, and voiding and defecation difficulty after fell down several times in the past. She had a history of two spinal decompression with fixation surgeries due to spinal stenosis with a herniated intervertebral disc. She was prescribed steroids and methotrexate for the RA. The results of MRI and CT demonstrated an intradural bone graft material migration with cauda equina syndrome after revision lumbar stenosis surgery. Calcified material protruded to the intracanal area and compressed the cauda equina fiber. After the removal of fragments operation, she recovered from cauda equina symptoms. A follow-up examination two years postoperatively revealed clinical resolution of cauda equina symptoms and a return to partial walking with a cane. DISCUSSION: The patient had a minor or major trauma, such as a fall, after the revision surgery. After that trauma, the patient presented with some dural injury, kyphotic position, or non-union state causing the dural penetration of the interbody fusion material. CONCLUSION: The first report describing displaced PLIF graft material that penetrated the dural sac and caused cauda equina symptoms in a patient with RA. Establishing strategies to minimize these complications is indicated when treating degenerative lumbar spine conditions in patients with RA.
32410564 Cardio-Rheumatology: Cardiovascular Complications in Systemic Autoimmune Rheumatic Disease 2020 In the current Thematic Issue of Current Vascular Pharmacology (CVP), entitled "Systemic Autoimmune Rheumatic Diseases and Cardiology", presented in two parts, Part 1 and Part 2, review articles are included from specialists in cardiology, rheumatology, immunology and related fields. These reviews discuss the cardiovascular complications of the main systemic Autoimmune Rheumatic Diseases (ARDs). For example, the underlying pathogenetic mechanisms, the role of cardiovascular imaging and recommendations for prevention and management. These articles place inflammation as the key process, linking cardiovascular complications with ARDs. From all these reviews, the conclusion is the need for collaboration between the disciplines of Rheumatology and Cardiology to establish the emerging field of Cardio- Rheumatology. This will aid to fine-tune risk stratification and optimize preventive strategies and pharmacological therapies for patients with ARDs.
32422132 Fluvastatin prevents the development of arthritis in env-pX rats via up-regulation of Rho 2020 Aug The pleiotropic effects of statins, including an antiarthritic potential, have been noted. This study aimed to determine the efficacy of statins on rheumatoid arthritis (RA) and clarify how statins affect its pathogenesis. Fluvastatin (500 μg/kg/day) or vehicle was given per os to env-pX rats, which carry the human T-cell leukemia virus type I env-pX gene and spontaneously develop destructive arthritis mimicking RA, for 30 days. Blood sampling and ultrasonography (US) of the ankle joints were conducted on days 0, 10, 20, and 30. On day 30, all rats were euthanized, and the ankle joints were subjected to histological analysis. To clarify how fluvastatin affects the pathogenesis of RA, comprehensive serum exosomal microRNA (miRNA) analysis was performed. Gene expression in the primary culture of synovial fibroblasts derived from arthritic rat and human and non-arthritic rat periarticular tissues was determined quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR). As a result, the development of arthritis in env-pX rats was significantly suppressed by fluvastatin, which was evident from the viewpoints of serology, US imaging, and histology. Comprehensive serum exosomal miRNA analysis suggested that the expression of Rho GTPase-activating protein 12 (Arhgap12) was decreased in arthritic env-pX rats but increased with the administration of fluvastatin. Corresponding results were obtained by quantitative RT- PCR using primary culture of synovial fibroblasts. The collective findings suggest that fluvastatin prevents the development of arthritis in env-pX rats via the up-regulation of ARHGAP12. This study suggests that ARHGAP12 can be a possible therapeutic target of RA.