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ID PMID Title PublicationDate abstract
34906094 Rare case of Proteus mirabilis native mitral valve endocarditis in an immunocompromised pa 2021 Dec 14 BACKGROUND: Bacterial infective endocarditis caused by Proteus mirabilis is rare and there are few cases in the literature. The natural history and treatment of this disease is not as clear but presumed to be associated with complicated urinary tract infection (cUTI). CASE PRESENTATION: A 65-year-old female with a history of rheumatoid arthritis, factor V Leiden hypercoagulability, and prior saddle pulmonary embolism presented to the emergency department following a mechanical fall. Computed Tomography showed evidence of acute/subacute splenic emboli. Complicated UTI was likely secondary to a ureteral stone. Blood and urine cultures also grew out P. mirabilis. Transthoracic echocardiography revealed a mobile echogenic density on the anterior mitral valve (MV) leaflet consistent with a vegetation. The patient underwent MV replacement, and P. mirabilis was isolated from the surgically removed valve. CONCLUSIONS: We hypothesize that the patient's immunocompromised status following steroid and Janus Kinase inhibitor usage for rheumatoid arthritis contributed to Gram-negative bacteremia following P. mirabilis UTI, ultimately seeding the native MV. Additional studies with larger numbers of Proteus endocarditis cases are needed to investigate an association between immunosuppression and Proteus species endocarditis.
34266801 Anti-Carbamylated Protein Antibodies, Tumour Necrosis Factor Alpha and Insulin Resistance 2021 Jul 12 BACKGROUND: Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune diseases. Premature atherosclerosis and cardiovascular diseases are two of the most important complications of these diseases. Anti-carbamylated protein antibody (Anti-carP Ab) is one of the antibodies which was studied in RA and SLE. In our study, we studied the relation between anti-carP Ab, disease activity and insulin resistance in RA and SLE patients. METHODS: 90Patients with SLE and RA were enrolled and subjected to history taking, clinical examination and assessment of disease activity using SLE disease activity index 2000 (SLEDAI-2K) scoring for SLE patients and disease activity score 28 (DAS28-ESR) for RA patients. Samples were examined for complete blood count (CBC), creatinine, inflammatory markers, Tumour necrosis factor alpha (TNF alpha), fasting insulin, fasting blood sugar (FBS), lipid profile and anti-carPAb. HOMA-IR (homeostasis model assessment for insulin resistance) was calculated. RESULTS: Patients with RA and SLE showed higher levels of anti-carPAb in comparison with healthy subjects (8.25ng/ml for RA, 7ng/ml for SLE and 0.6ng/ml for healthy subjects with p value <0.001). There was a positive correlation between anti-carPAb and disease activity of RA (p value <0.001) and a positive correlation between anti-carPAb and TNF alpha in RA. In SLE, there was no correlation of anti-carP Ab with disease activity while, HOMA-IR showed a positive correlation with nephritis (p value 0.04). CONCLUSION: Anti-carP antibody is a marker of disease activity in RA patients and has high specificity for both RA and SLE detection.
34122457 Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis. 2021 Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.
33948430 Exploring the role of immunotherapeutic drugs in autoimmune diseases: A comprehensive revi 2021 Apr Autoimmune diseases are group of disorders where an immune response is mounted against the self. The prevalence and burden of this well established and recognised entity is on the rise. Irrespective of being a systemic or organ specific autoimmune disorder, the common underlying mechanism of action, is the imbalance in immune system resulting in loss of tolerance to self-antigens. The oral cavity is no alien to these disorders or to their influences. Pemphigus group of lesions, systemic lupus erythematosus, psoriasis and even Sjogren's syndrome are some of the established autoimmune disorders with prominent oral manifestations. Though these diseases are well documented and enumerated, however addressing them is where the dilemma lies. Science, research and discoveries are a crucial part of medical discipline which help in looking beyond the horizon. With the introduction of selective targeted immunotherapies for autoimmune diseases as a treatment modality either in solitary or in combination with the conventional immunosuppressive treatments, are emerging as a promising elixir for patients enduring them. However, being unique, exploration of these biologics from its inception, to its mechanism of action, recognition of its application and evaluation of its safety norms are equally vital. Therefore, this review aims to provide a comprehensive particular on the novel biologics, the immunotherapies in autoimmune disorders targeting the different cells, their receptors or cytokines of the immune system.
33269449 Quantification of Joint Space Width Difference on Radiography Via Phase-Only Correlation ( 2021 Feb Several visual scoring methods are currently used to assess progression of rheumatoid arthritis (RA) on radiography. However, they are limited by its subjectivity and insufficient sensitivity. We have developed an original measurement system which uses a technique called phase-only correlation (POC). The purpose of this study is to validate the system by using a phantom simulating the joint of RA patients.A micrometer measurement apparatus that can adjust arbitrary joint space width (JSW) in a phantom joint was developed to define true JSW. The phantom was scanned with radiography, 320 multi detector CT (MDCT), high-resolution peripheral quantitative CT (HR-pQCT), cone beam CT (CBCT), and tomosynthesis. The width was adjusted to the average size of a women's metacarpophalangeal joint, from 1.2 to 2.2 mm with increments of 0.1 mm and 0.01 mm. Radiographical images were analyzed by the POC-based system and manual method, and images from various tomographical modalities were measured via the automatic margin detection method. Correlation coefficients between true JSW difference and measured JSW difference were all strong at 0.1 mm intervals with radiography (POC-based system and manual method), CBCT, 320MDCT, HR-pQCT, and tomosynthesis. At 0.01 mm intervals, radiography (POC-based system), 320MDCT, and HR-pQCT had strong correlations, while radiography (manual method) and CBCT had low correlations, and tomosynthesis had no statistically significant correlation. The smallest detectable changes for radiography (POC-based system), radiography (manual method), 320MDCT, HR-pQCT, CBCT, and tomosynthesis were 0.020 mm, 0.041 mm, 0.076 mm, 0.077 mm, 0.057 mm, and 0.087 mm, respectively. We conclude that radiography analyzed with the POC-based system might sensitively detect minute joint space changes of the finger joint.
34300273 Effectiveness of Mind-Body Intervention for Inflammatory Conditions: Results from a 26-Wee 2021 Jul 14 Biopsychosocial intervention has been suggested as a complementary treatment strategy for patients with chronic conditions. We compared the effect of a mind-body intervention (MBI), relative to treatment-as-usual (TAU) on WHO-5 Well-being Index during an intensive period of 12 weeks and follow-up at week 26 among patients with either psoriasis (PsO) or rheumatoid arthritis (RA). The MBI was based on the 'Relaxation Response Resiliency Program' and the 'Open and Calm Program', as well as 'Mindfulness Based Stress Reduction' (MBSR). The trial was randomized, management-as-usual, and controlled. Statistical analyses were based on the intention-to-treat population using repeated measures and mixed effects models (NCT03888261). We screened 39 potential participants, 35 of which (PsO, n = 20; RA, n = 15) met the eligibility criteria and were randomized: 17 in the MBI group and 18 in the TAU group. Attrition from the intervention program was 19%, with 65% of MBI patients and 71% of TAU patients completing the outcome assessments. After 12 weeks, a statistically significant difference in WHO-5 was observed between the groups (p = 0.019). However, according to the protocol, during the entire trial period, the average (least squares mean values) WHO-5 score was higher although not statistically significant in the MBI group (65.3) compared with the TAU group (59.1), corresponding to a between-group difference over 26 weeks of 6.15 (95% CI: -0.26 to 12.56; p = 0.060). All things considered, adding biopsychosocial intervention to clinical practice to patients with conditions, such as PsO and RA, could potentially improve health-related quality of life.
34214953 Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiv 2021 Sep 15 We present the case of a young woman being treated with rituximab for rheumatoid arthritis who developed a severe enteroviral meningoencephalitis and acute flaccid myelitis (AFM). Cerebrospinal fluid (CSF) and stool reverse transcription-polymerase chain reaction (RT-PCR) testing confirmed the diagnosis and additional sequencing studies performed at the CDC further characterized the enterovirus as enterovirus A71 (EV-A71). After treatment with intravenous immunoglobulin (IVIg) and fluoxetine (based on previous reports of possible efficacy) the patient experienced a remarkable improvement over time. This case highlights the importance of considering enteroviral infection in patients treated with rituximab, depicts a possible clinical course of enteroviral meningoencephalitis and AFM, and illustrates the importance of testing multiple sites for enterovirus infection (CSF, stool, nasopharyngeal swab, blood). Here we present the case with a brief review of the literature pertaining to EV-A71.
33768402 Compounds DRG and DAG, Two Phenol Glycosides, Inhibit TNF-α-stimulated Inflammatory Respo 2021 Oct Fourteen constituents were recently isolated from the roots of Dendropanax dentiger with cyclooxygenase-2 (COX-2) inhibitory effects. However, the effect of 14 constituents on rheumatoid arthritis (RA) and their action mechanism remain unclear. The study aimed to explore the anti-RA effect and potential mechanism of these constituents in tumor necrosis factor α (TNF-α)-stimulated human RA fibroblast-like synoviocytes (MH7A cells). The cell viability, nitric oxide (NO) production, inflammatory cytokine levels, and protein expressions were measured by cell counting kit-8 (CCK-8), Griess reagent, ELISA, and Western blot assays, respectively. Results showed that 14 constituents (40 μM) have no cytotoxicity for MH7A cells. Among them, two phenols including 3,4-dimethoxyphenyl-1-O-α-L-rhamnopyranosyl-(1→6)-O-β-D-glucopyranoside (DRG) and 3,4-dimethoxyphenol-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (DAG) were shown to significantly inhibit the NO production with IC(50) values of 5.25±0.34 and 5.35±0.31 μM, respectively. They also remarkably decreased the release of interleukin (IL)-2, 6, 8, and interferon (IFN)-γ, as well as prominently reduced the phosphorylation protein levels of p65, IkBα, AKT, and JNK at a concentration of 10 μM. Taken together, DRG and DAG could inhibit TNF-α-induced inflammatory response through blocking NF-kB/AKT/JNK signaling pathways in MH7A cells, thus could be promising against RA and other inflammation-related agents.
33507149 Induction of the IL-1RII decoy receptor by NFAT/FOXP3 blocks IL-1β-dependent response of 2021 Jan 28 Derived from a common precursor cell, the balance between Th17 and Treg cells must be maintained within immune system to prevent autoimmune diseases. IL-1β-mediated IL-1 receptor (IL-1R) signaling is essential for Th17-cell biology. Fine-tuning of IL-1R signaling is controlled by two receptors, IL-1RI and IL-RII, IL-1R accessory protein, and IL-1R antagonist. We demonstrate that the decoy receptor, IL-1RII, is important for regulating IL-17 responses in TCR-stimulated CD4(+) T cells expressing functional IL-1RI via limiting IL-1β responsiveness. IL-1RII expression is regulated by NFAT via its interaction with Foxp3. The NFAT/FOXP3 complex binds to the IL-1RII promoter and is critical for its transcription. Additionally, IL-1RII expression is dysregulated in CD4(+) T cells from patients with rheumatoid arthritis. Thus, differential expression of IL-1Rs on activated CD4(+) T cells defines unique immunological features and a novel molecular mechanism underlies IL-1RII expression. These findings shed light on the modulatory effects of IL-1RII on Th17 responses.
32991221 Knowledge and attitudes about influenza vaccination in rheumatic diseases patients. 2021 May 4 Patients with rheumatic diseases (RD) have a higher risk of morbidity and mortality from vaccine-preventable infections attributed to disease activity, comorbidities, immunosuppressive therapy, and other factors. Vaccines are one of the safest and most effective public health interventions. The aim of this study was to investigate knowledge and attitudes about influenza vaccination as factors influencing vaccine uptake and hesitancy in a population with RD. A descriptive cross-sectional study was designed. A self-administered questionnaire surveyed age, RD diagnosis, ten questions about the uptake, safety and efficacy of influenza vaccine, knowledge of cost-free availability, and the relationship between influenza vaccination and RD. A total of 223 questionnaires were filled; 79.8% of patients were vaccinated for influenza at least once. Uptake by diagnosis was 80.3% in rheumatoid arthritis, 76.2% in osteoarthritis, 86.7% in lupus, 73.9% in other auto-immune diseases (AID), and 60% in other non-AID; 83.9% of patients considered influenza vaccine as safe and effective. From those who had never been vaccinated, 26.7% of patients did not consider influenza vaccine safe and effective vs. 13.5% among patients who had been vaccinated (P = .032). Only 7.6% considered that RD patients could not be vaccinated; 11.7% thought that influenza vaccine would worsen their RD symptoms. This study showed that concerns about safety, efficacy, side effects, fear of the vaccine, and knowledge of cost diminished vaccine uptake. These are factors related to confidence, complacency, and convenience as components of vaccine hesitancy that affect influenza vaccination in RD patients.
34006987 G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine 2021 May 18 G protein-coupled receptor kinase 5 (GRK5) regulates inflammatory responses via the nuclear factor-kappa B (NF-κB) pathway. This study investigated the functional involvement of GRK5 in the pathogenesis of inflammatory arthritis. Immunohistochemically, rheumatoid arthritis (RA) synovium had a significantly higher proportion of GRK5-positive cells in the synovial lining layer than healthy control synovium. Gene expression and NF-κB activation in lipopolysaccharide-stimulated human SW982 synovial cells were significantly suppressed by silencing of the GRK5 gene. Similarly, GRK5 kinase activity inhibition in human primary RA synovial cells attenuated gene expressions of inflammatory factors. In a murine model of collagen antibody-induced arthritis, arthritis scores and serum IL6 production of GRK5 knockout (GRK5(-/-)) mice were significantly lower than those of wild-type mice. Histologically, the degree of synovitis and cartilage degeneration in GRK5(-/-) mice was significantly lower than in wild-type mice. In in vitro analyses using activated murine macrophages and fibroblast-like synoviocytes, gene expression of inflammatory factors and p65 nuclear translocation were significantly lower in GRK5(-/-) mice compared to wild-type mice. In conclusion, our results suggested that GRK5 is deeply involved in the pathogenesis of inflammatory arthritis, therefore, GRK5 inhibition could be a potential therapeutic target for types of inflammatory arthritis such as RA.
33973858 A Virtual Reality-Based App to Educate Health Care Professionals and Medical Students Abou 2021 May 11 BACKGROUND: Inflammatory arthritides (IA) such as rheumatoid arthritis or psoriatic arthritis are disorders that can be difficult to comprehend for health professionals and students in terms of the heterogeneity of clinical symptoms and pathologies. New didactic approaches using innovative technologies such as virtual reality (VR) apps could be helpful to demonstrate disease manifestations as well as joint pathologies in a more comprehensive manner. However, the potential of using a VR education concept in IA has not yet been evaluated. OBJECTIVE: We evaluated the feasibility of a VR app to educate health care professionals and medical students about IA. METHODS: We developed a VR app using data from IA patients as well as 2D and 3D-visualized pathological joints from X-ray and computed tomography-generated images. This VR app (Rheumality) allows the user to interact with representative arthritic joint and bone pathologies of patients with IA. In a consensus meeting, an online questionnaire was designed to collect basic demographic data (age, sex); profession of the participants; and their feedback on the general impression, knowledge gain, and potential areas of application of the VR app. The VR app was subsequently tested and evaluated by health care professionals (physicians, researchers, and other professionals) and medical students at predefined events (two annual rheumatology conferences and academic teaching seminars at two sites in Germany). To explore associations between categorical variables, the χ(2) or Fisher test was used as appropriate. Two-sided P values ≤.05 were regarded as significant. RESULTS: A total of 125 individuals participated in this study. Among them, 56% of the participants identified as female, 43% identified as male, and 1% identified as nonbinary; 59% of the participants were 18-30 years of age, 18% were 31-40 years old, 10% were 41-50 years old, 8% were 51-60 years old, and 5% were 61-70 years old. The participants (N=125) rated the VR app as excellent, with a mean rating of 9.0 (SD 1.2) out of 10, and many participants would recommend use of the app, with a mean recommendation score of 3.2 (SD 1.1) out of 4. A large majority (120/125, 96.0%) stated that the presentation of pathological bone formation improves understanding of the disease. We did not find any association between participant characteristics and evaluation of the VR experience or recommendation scores. CONCLUSIONS: The data show that IA-targeting innovative teaching approaches based on VR technology are feasible.
33927631 Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the A 2021 Articular cartilage damage with subsequent impairment of joint function is a common feature of articular diseases, in particular, rheumatoid arthritis and osteoarthritis. While articular cartilage injury mediated by chondrocyte apoptosis is a known major pathological feature of arthritis, the specific mechanisms remain unclear at present. Transient receptor potential melastatin-like seven channel (TRPM7) is reported to play an important regulatory role in apoptosis. This study focused on the effects of TRPM7 on arthritic chondrocyte injury and its underlying mechanisms of action. Sodium nitroprusside (SNP)-induced rat primary chondrocyte apoptosis and rat adjuvant arthritis (AA) were used as in vitro and in vivo models, respectively. Blockage of TRPM7 with 2-APB or specific siRNA resulted in increased chondrocyte viability and reduced toxicity of SNP. Moreover, treatment with 2-APB enhanced the Bcl-2/Bax ratio and reduced cleaved PARP and IL-6, MMP-13 and ADAMTS-5 expression in SNP-treated chondrocytes. Activation of Indian Hedgehog with purmorphamine reversed the protective effects of 2-APB on SNP-induced chondrocyte apoptosis. Blockage of TRPM7 with 2-APB relieved the clinical signs of AA in the rat model and reduced the arthritis score and paw swelling. Similar to findings in SNP-treated chondrocytes, 2-APB treatment increased the Bcl-2/Bax ratio and suppressed cleaved PARP, IL-6, MMP-13, ADAMTS-5, TRPM7, and Indian hedgehog expression in articular cartilage of AA rats. Our collective findings suggest that blockade of TRPM7 could effectively reduce chondrocyte apoptosis and articular cartilage damage in rats with adjuvant arthritis through regulation of the Indian Hedgehog signaling pathway.
33800699 Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Oste 2021 Mar 28 Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder that primarily involves joints, further affects the life quality of patients, and has increased mortality. The pathogenesis of RA involves multiple pathways, resulting in some patients showing resistance to the existing drugs. Salubrinal is a small molecule compound that has recently been shown to exert multiple beneficial effects on bone tissue. However, the effect of Salubrinal in RA has not been clearly confirmed. Hence, we induced collagen-induced arthritis (CIA) in DBA/1J mice and found that Salubrinal treatment decreased the clinical score of CIA mice, inhibiting joint damage and bone destruction. Furthermore, Salubrinal treatment downregulated osteoclast number in knee joint of CIA in mice, and suppressed bone marrow-derived osteoclast formation and function, downregulated osteoclast-related gene expression. Moreover, Salubrinal treatment inhibited RANKL-induced NF-κB signaling pathway, and promoted P65 degradation through the ubiquitin-proteasome system, further restrained RANKL-induced osteoclastogenesis. This study explains the mechanism by which Salubrinal ameliorates arthritis of CIA in mice, indicating that Salubrinal may be a potential drug for RA, and expands the potential uses of Salubrinal in the treatment of bone destruction-related diseases.
34834283 Photodynamic Therapy Targeting Macrophages Using IRDye700DX-Liposomes Decreases Experiment 2021 Nov 5 Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system's first responders, it is inadvisable to systemically deplete these cells. By loading the liposomes with the photosensitizer IRDye700DX, we have developed and tested a novel way to perform photodynamic therapy (PDT) on macrophages in inflamed joints. PEGylated liposomes were created using the film method and post-inserted with micelles containing IRDye700DX. For radiolabeling, a chelator was also incorporated. RAW 264.7 cells were incubated with liposomes with or without IRDye700DX and exposed to 689 nm light. Viability was determined using CellTiterGlo. Subsequently, biodistribution and PDT studies were performed on mice with collagen-induced arthritis (CIA). PDT using IRDye700DX-loaded liposomes efficiently induced cell death in vitro, whilst no cell death was observed using the control liposomes. Biodistribution of the two compounds in CIA mice was comparable with excellent correlation of the uptake with macroscopic and microscopic arthritis scores. Treatment with 700DX-loaded liposomes significantly delayed arthritis development. Here we have shown the proof-of-principle of performing PDT in arthritic joints using IRDye700DX-loaded liposomes, allowing locoregional treatment of arthritis.
33355701 [Rheumatic diseases and neuropathic pain : Diagnosis and treatment]. 2021 Apr Pain is a leading symptom in inflammatory rheumatic diseases. For a long time it has been assumed that this pain is of nociceptive origin; however, in about one fifth of all patients the pain remains despite successful anti-inflammatory treatment and is not typically described as nociceptive by those affected. Recent studies indicate that some patients with rheumatoid arthritis (RA) experience pain with a neuropathic pain component. The treatment of neuropathic pain with damage to the somatosensory system differs markedly from the treatment of nociceptive pain in which the pain processing system is intact. Thus, the recognition and, above all, the more precise differentiation of the pain symptoms of affected patients make a decisive contribution to a successful treatment. With the help of a few points in the history and a physical examination, the assumption of the diagnosis neuropathic pain can often be rejected or substantiated. Pain with a neuropathic component does not adequately respond to typical analgesics. Instead, the high efficacy of co-analgesics, such as anticonvulsants and antidepressants, has been repeatedly proven.
34093764 Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthrit 2021 Aug Because damage to hyaline cartilage is irreversible, relieving progressive cartilage destruction is an important therapeutic approach for inflammatory arthritis. In the present study, human hyaline chondrocytes were isolated from total knee replacements of 15 patients with osteoarthritis (OA) and three with rheumatoid arthritis (RA). Synovial fluid of OA (n=25) and RA (n=34) were collected to measure tumor necrosis factor α (TNFα) using ELISA. Consistent with previous studies, the synovial fluid exhibited high TNFα levels and hyaline cartilage was severely destroyed in patients with RA. TNFα-treated chondrocytes were used as model for inflammatory arthritis. TNFα did not influence proliferation or extracellular matrix expression in chondrocytes, but induced matrix metalloproteinase (MMP)1, 3 and 13 expression levels in chondrocytes, which was accompanied by activation of nuclear factor-κB signaling. During chondrogenic differentiation, TNFα attenuated mRNA expression levels of anabolic factors (collagen type 2 and aggrecan) and enhanced mRNA expression of catabolic factors (MMP1, MMP3 and MMP13) in chondrocytes. Moreover, anti-TNFα agents (Golimumab) inhibited the TNFα-induced metabolic shift in chondrocytes and chondrogenic differentiation. The present study revealed a mechanism by which TNFα may induce metabolic shift in chondrocytes, leading to progressive chondrocyte destruction.
33796242 Anti-cyclic-citrullinated-protein-antibodies in psoriatic arthritis patients: how autoimmu 2021 AIM: Occasional findings of anti-cyclic-citrullinated-protein-antibodies (anti-CCP) were rarely observed in psoriatic arthritis (PsA). The aim of our study is to evaluate whether the presence of anti-CCP can determine different clinical subsets and influence methotrexate monotherapy survival, and biotechnological drug retention rate. METHODS: We conducted a retrospective study on PsA patients. All patients were required to fulfill the CASPAR criteria for PsA, and to present juxta-articular osteo-proliferative signs at X-ray. The exclusion criteria were age less than 18 years old, satisfaction of rheumatoid arthritis classification criteria, and seropositivity for rheumatoid factor. Clinical characteristics, anti-CCP titer, drug survival and comorbidities information were recorded for each patient. Statistical significance was set at p ⩽ 0.05. RESULTS: Of 407 patients with PsA screened 113 were recruited. Twelve patients were anti-CCP positive. Methotrexate monotherapy survival was shorter in patients with anti-CCP (150 ± 48.3 weeks versus 535.3 ± 65.3 weeks; p = 0.026) [discontinuation risk hazard ratio (HR) = 2.389, 95% confidence interval (CI) 1.043, 5.473; p = 0.039] than those without. Significant shorter survival of first-line biotechnological drugs (b-DMARDs) was observed in the anti-CCP positive group than in that without (102.05 ± 24.4 weeks versus 271.6 ± 41.7 weeks; p = 0.005) with higher discontinuation risk (HR = 3.230, 95% CI 1.299, 8.028; p = 0.012). A significant higher rate of multi-failure (more than second-line b-DMARDs) was found in anti-CCP positive patients than in those without (50% versus 14%, p = 0.035). CONCLUSION: Anti-CCP in PsA could be suggestive of more severe disease, with worse drug survival of both methotrexate monotherapy and first-line b-DMARDs, and higher chance to be b-DMARDs multi-failure. So, they can be considered for more intensive clinical management of these patients.
35008555 Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Deriv 2021 Dec 23 Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O(2), 5% CO(2)), hypoxically (2% O(2), 5% CO(2)) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Regulatory T cell (Treg):Th17 homeostatic balance. Normoxic EVs present the optimal strategy for broad therapeutic benefit. EVs present an effective novel technology with the potential for cell-free therapeutic translation.
33793083 Development of an Implementation Strategy for Patient Decision Aids in Rheumatoid Arthriti 2021 May OBJECTIVE: Decision aids are being developed to support guideline-based rheumatology care in Canada. The study objective was to identify barriers to decision aid use in rheumatoid arthritis (RA) within a behavior change model to inform an implementation strategy. METHODS: Perspectives from Canadian health care providers (HCPs) and patients living with RA were obtained on an early RA decision aid and on perceived facilitators and barriers to decision aid implementation. Data were collected through semistructured interviews, transcribed, and then analyzed by inductive thematic analysis. The lessons learned were then mapped to the behavior change wheel COM-B system (C = capability, O = opportunity, and M = motivation interact to influence B = behavior) to inform key elements of a national implementation strategy. RESULTS: Fifteen HCPs and fifteen patients participated. The analysis resulted in five lessons learned: 1) paternalistic decision-making is a dominant practice in early RA, 2) patients need emotional support and access to educational tools to facilitate participation in shared decision-making (SDM), 3) there are many logistical barriers to decision aid implementation in current care models, 4) flexibility is necessary for successful implementation, and 5) HCPs have limited interest in further training opportunities about decision aids. Implementation recommendations included the following: 1) making the decision aids directly available to patients (O) and providing SDM education (C/M), 2) creating an SDM rheumatology curriculum (C/O/M), 3) using "decision coaches" or patient partners as peer support (C/O/M), 4) linking decision aids to "living" rheumatology guidelines (M), and 5) designing trials of patient decision aid/SDM interventions to evaluate patient-important outcomes (O/M). CONCLUSION: A multifaceted strategy is suggested to improve uptake of decision aids.