Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35229925 | The role of plant-derived natural antioxidants in reduction of oxidative stress. | 2022 Mar 1 | Free radicals are a group of damaging molecules produced during the normal metabolism of cells in the human body. Exposure to ultraviolet radiation, cigarette smoking, and other environmental pollutants enhances free radicals in the human body. The destructive effects of free radicals may also cause harm to membranes, enzymes, and DNA, leading to several human diseases such as cancer, atherosclerosis, malaria, coronavirus disease (COVID-19), rheumatoid arthritis, and neurodegenerative illnesses. This process occurs when there is an imbalance between free radicals and antioxidant defenses. Since antioxidants scavenge free radicals and repair damaged cells, increasing the consumption of fruits and vegetables containing high antioxidant values is recommended to slow down oxidative stress in the body. Additionally, natural products demonstrated a wide range of biological impacts such as anti-inflammatory, anti-aging, anti-atherosclerosis, and anti-cancer properties. Hence, in this review article, our goal is to explore the role of natural therapeutic antioxidant effects to reduce oxidative stress in the diseases. | |
| 35277889 | Synthesis of [(2) H(5) ]baricitinib via [(2) H(5) ]ethanesulfonyl chloride. | 2022 May 30 | Baricitinib, typically applied as a treatment for rheumatoid arthritis, has recently attracted the attention of clinicians and researchers as a potential treatment for COVID-19. Naturally, there has been a need for the preparation of the isotope-labelled analogue of baricitinib to probe the pharmacokinetics of baricitinib in this new role. As such, we have developed a simple synthetic route to deuterated [(2) H(5) ]baricitinib, facilitating its formation over four steps and in a 29% overall yield based on starting [(2) H(5) ]ethanethiol (19% if we start with [(2) H(5) ]bromoethane instead). A critical component of the overall process involves the synthesis of [(2) H(5) ]ethanesulfonyl chloride, and we describe in detail the two routes that were explored to optimize this step. | |
| 35463070 | Tripterygium wilfordii Hook. f. Preparations for Rheumatoid Arthritis: An Overview of Syst | 2022 | OBJECTIVES: To summarize the quantity and quality of evidence for using Tripterygium wilfordii Hook. f. (TwHF) preparations in patients with rheumatoid arthritis (RA) and to find the reasons of the disparity by comprehensively appraising the related systematic reviews (SRs). METHODS: We performed an overview of evidence for the effectiveness and safety of TwHF preparations for patients with RA. We searched seven literature databases from inception to July 15, 2021. We included SRs of TwHF preparations in the treatment of RA. Four tools were used to evaluate the reporting quality, methodological quality, risk of bias, and the certainty of evidence for the included SRs, which are the PRISMA, the AMSTAR-2, the ROBIS, and the GRADE approach. RESULTS: We included 27 SRs (with 385 studies and 33,888 participants) for this overview. The AMSTAR-2 showed that 19 SRs had critically low methodological quality and the remaining 8 had low methodological quality. The rate of overlaps was 68.31% (263/385), and the CCA (corrected covered area) was 0.53, which indicated the degree of overlap is slight. Based on the assessment of ROBIS, all 27 SRs were rated as low risk in phase 1; one SR was rated as low risk in domain 1, 9 SRs were in low risk in domain 2, 16 SRs were in low risk in domain 3, and 16 SRs were in low risk in domain 4 in phase 2; 7 SRs were rated as low risk in phase 3. Among 27 items of PRISMA, 15 items were reported over 70% of compliance, the reporting quality of 16 SRs was rated as "fair," and 11 were "good." Using GRADE assessment, moderate quality of evidence was found in 5 outcomes, and 5 outcomes were low quality. CONCLUSION: The use of TwHF preparations for the treatment of RA may be clinically effective according to the moderate-quality evidence. There are methodological issues, risk of bias, and reporting deficiencies still needed to be improved. SRs with good quality and further randomized clinical trials that focus on clinical important outcomes are needed. | |
| 35644970 | [The characteristics of non-alcoholic fatty liver disease and its associated factors in pa | 2022 May 6 | Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized. | |
| 35247807 | Rheumatoid arthritis drug sinomenine induces apoptosis of cervical tumor cells by targetin | 2022 May | Overexpression of thioredoxin reductase (TrxR) has been linked to tumorigenesis and phenotypic maintenance of malignant tumors. Thus, targeting TrxR with natural molecules is a promising strategy for developing anticancer drugs. Sinomenine is a naturally occurring alkaloid isolated from Sinomenium acutum. The drug, Zhengqing Fengtongning made from sinomenine, has been universally applied in rheumatoid arthritis treatment in China as well as other Asian countries for decades. Recently, increasing evidence indicates that sinomenine appears to be a promising therapeutic agent against various cancer cells. However, the exact mechanism underlying the anticancer activity of sinomenine remains unclear. In this study, we identified sinomenine as a kind of new inhibitor for TrxR. Pharmacological inhibition of TrxR by sinomenine results in the decrease of thiols content, increases the levels of reactive oxygen species, and finally facilitates oxidative stress-mediated cancer cell apoptosis. It is vital that knockdown in TrxR1 by shRNA can increase cell sensitivity to sinomenine. Treatment with sinomenine in vivo leads to a decrease in TrxR activity and tumor growth, and an increase in apoptosis. Our findings provide a novel action mechanism related to sinomenine and presents an insight on how to develop sinomenine as a chemotherapeutic agent for cancer therapy. | |
| 35274588 | NT-proBNP and sRAGE levels in early rheumatoid arthritis. | 2022 Mar 11 | OBJECTIVE: Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD: Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS: After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION: Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated. | |
| 35652240 | Clinical relevance of rheumatoid factor and anti-citrullinated peptides in fibrotic inters | 2022 Jun 2 | BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti-citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non-CTD ILD. METHODS: A total of 1570 non-CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA-ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant-free survival and incidence of progressive fibrosing-ILD (PF-ILD) were compared between seronegative non-CTD ILD (reference group), seropositive non-CTD ILD and RA-ILD using linear mixed-effect and Cox proportional hazards models adjusted for age, sex, smoking pack-years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow-up before and after the treatment. RESULTS: Two hundred and seventeen (13.8%) patients with seropositive non-CTD ILD had similar rates of FVC decline and transplant-free survival compared to seronegative non-CTD ILD, but more frequently met the criteria for PF-ILD (hazard ratio [HR] = 1.35, p = 0.004). RA-ILD had slower FVC decline (p = 0.03), less PF-ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non-CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non-CTD ILD. CONCLUSION: Seropositivity in non-CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression. | |
| 35340587 | Ebosin Attenuates the Inflammatory Responses Induced by TNF-α through Inhibiting NF-κB a | 2022 | Tumor necrosis factor-α (TNF-α) lies at the apex of signal transduction cascades that results in induced destruction of joints in rheumatoid arthritis. It is therefore of great medicinal interest to modulate the cellular responses to TNF-α. Ebosin, a novel exopolysaccharide derived from Streptomyces sp, has been demonstrated to have remarkable therapeutic actions on collagen-induced arthritis in rats, while it also suppressed the production of IL-1β, TNF-α, and IL-6 at both mRNA and protein levels in cultured fibroblast-like synoviocytes. In order to further understand the potential mechanisms involved in the anti-inflammatory effects of ebosin at molecular level, we investigated the impact of it on the activation of MAPK and NF-κB pathways following TNF-α induced in fibroblast-like synoviocytes (FLS). The results showed that the phosphorylation levels of TNF-α-induced p38, JNK1, JNK2, IKKα, IKKβ, and IκB, as well as NF-κB nuclear translocation, were reduced significantly in FLS cells in response to ebosin. Furthermore, we proved that ebosin decreased the level of NF-κB in the nucleus and blocked the DNA-binding ability of NF-κB using electrophoresis mobility gel shift assay. Besides, low levels of matrix metalloproteinases (MMP-1 and MMP-3) and chemokines (interleukin-8 and RANTES) were found in TNF-α-stimulated fibroblast-like synoviocytes treated with ebosin. These results indicate that ebosin can suppress a range of activities in both MAPK and NF-κB pathways induced by TNF-α in rat fibroblast-like synoviocytes, which provides a rationale for examining the use of ebosin as a potential therapeutic candidate for rheumatic arthritis. | |
| 35474846 | Sarcococca saligna Hydroalcoholic Extract Ameliorates Arthritis in Complete Freund's Adjuv | 2022 Apr 19 | Traditionally, Sarcococca saligna has been used for the treatment of arthritis and many other inflammatory disorders. The current study was planned to give scientific evidence to this traditional use of S. saligna. Phytochemical profiling of SSME was carried out by using electrospray ionization mass spectrometry (ESI-MS/MS). Complete Freund's adjuvant (CFA), 150 μL was injected in the subplantar region of the left hind paw to induce arthritis in rats. Aqueous methanolic extract of S. saligna (SSME) was administered orally at 250, 500, or 1000 mg/kg dose from the 7th day to the 28th day of the study to explore its anti-arthritic potential. Histopathological and radiographic assessment of joints and enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) analyses were performed. Determination of oxidative stress biomarkers in the serum was also carried out. ESI-MS/MS identified ten such phytoconstituents which have reported strong anti-inflammatory and anti-arthritic activity. The SSME extract considerably reduced paw inflammation and arthritic index, subdued cachexia, and significantly improved biochemical and hematological changes. Oxidative stress decreased in SSME administered rats dose-dependently. Histopathological and radiographic evaluations also showed the anti-arthritic activity of SSME, which was associated with the downregulation of tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, COX-2, interleukin (IL)-6, and IL-1β and upregulation of I-kB, IL-4, and IL-10, in contrast to disease group rats. The outcomes of the study proposed that S. saligna have anti-arthritic potential, supporting its traditional use for rheumatoid arthritis treatment. | |
| 33878180 | Patients with early-onset primary Sjögren's syndrome have distinctive clinical manifestat | 2022 Feb 2 | OBJECTIVES: To further investigate the clinical characteristics and circulating lymphocyte profiles of patients with early-onset primary Sjögren's syndrome (pSS). METHOD: Data of 333 patients with pSS were analysed retrospectively. Early onset was defined as a pSS diagnosis at an age of 35 years or younger. The clinical, laboratory and immunophenotypic profiles of peripheral blood lymphocyte subsets were compared between early- and later-onset pSS. RESULTS: Thirty-six (10.81%) patients matched the definition of early-onset pSS, with age at disease onset being 28.97  (5.53) years. Elevated serum IgG level (77.14% vs 31.16%, P <0.001), low C3 (41.67% vs 20.20%, P =0.004) and C4 levels (27.78% vs 6.40%, P <0.001), anti-SSA positivity (91.67% vs 51.85%, P <0.001) and anti-SSB positivity (50% vs 20.54%, P <0.001) were more frequent in early-onset patients. The frequencies of hematological (80.56% vs 52.53%, P =0.001), renal (19.44% vs 5.05%, P =0.005) and mucocutaneous involvement (50% vs 22.56%, P <0.001) were significantly higher in the early-onset pSS group, which showed a higher 2010 EULAR SS Disease Activity Index (ESSDAI) [11(6.25-17) vs 7(3-12); P =0.003], compared with the later-onset group. In addition, profound CD4+ T-cell lymphopenia was found in patients with early-onset. CONCLUSIONS: Patients with early-onset pSS have distinctive clinical manifestations and greater activation of the cellular immune system, present with more severe clinical symptoms and immunological features, have increased activation of circulating T cells and have an unfavourable prognosis. Thus, they require more positive treatment with glucocorticoids and/or immunosuppressants and merit closer follow-up and regular monitoring. | |
| 35098838 | Comparison of the deep immune profiling of B cell subsets between healthy adults and Sjög | 2022 Dec | OBJECTIVES: Detailed analysis targeting B cell subgroups was considered crucial in monitoring autoimmune diseases and treatment responses. Thus, precisely describing the phenotypes of B cell differentiation and their variation in primary Sjögren's syndrome (pSS) is particularly needed. METHODS: To characterize the proportions and absolute counts of B cell subsets, peripheral blood from 114 healthy adults of China (age range: 19-73 years) and 55 patients with pSS were performed by flow cytometry and CD19, CD20, CD24, CD27, CD38 and IgD were used as surface markers to identify B cell mature process. Age- and gender-stratified analyses were then carried out to improve the interpretation of B cell subsets. RESULTS: The assessments from healthy adults showed that the proportion of naive B cells presented a significant increase with age. A reversal trend was noted that the percentage of B10 decreased markedly with age. In addition, analysis based on gender showed that the relative percentage and number of naive B cells were higher in females than in males whereas the proportions of switched memory B cells and B10 cells were decreased in female. Patients with pSS exhibited a significant expansion in naïve B cells and unswitched memory B cells, accompanied with decreased switched memory B cells and B10 cells, which were identified to be associated with autoantibody production. CONCLUSIONS: Our study presented a reliable analysis by flow cytometry to cover the principal B cell subtypes. These different stages of B lymphocytes may have implications for evaluating the activation of pSS and other autoimmune diseases and treatment efficacy.KEY MESSAGESB cell subsets play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS) and other autoimmune diseases. A practical and accurate flow cytometry method to profile B cell phenotypes in peripheral blood of healthy adults is especially essential.Additionally, we presented reliable reference ranges for B cell subsets in regards to the local population. Age- and gender-related analyses are available to better understand their influence in immune status and treatment outcome.The distribution of B-cell subsets is found substantially altered in patients with pSS, bringing novel avenues for pSS research in the future. | |
| 35409074 | Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compa | 2022 Mar 28 | Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers. | |
| 35168946 | Ageing and interferon gamma response drive the phenotype of neutrophils in the inflamed jo | 2022 Jun | OBJECTIVE: Neutrophils are typically the most abundant leucocyte in arthritic synovial fluid. We sought to understand changes that occur in neutrophils as they migrate from blood to joint. METHODS: We performed RNA sequencing of neutrophils from healthy human blood, arthritic blood and arthritic synovial fluid, comparing transcriptional signatures with those from murine K/BxN serum transfer arthritis. We employed mass cytometry to quantify protein expression and sought to reproduce the synovial fluid phenotype ex vivo in cultured healthy blood neutrophils. RESULTS: Blood neutrophils from healthy donors and patients with active arthritis showed largely similar transcriptional signatures. By contrast, synovial fluid neutrophils exhibited more than 1600 differentially expressed genes. Gene signatures identified a prominent response to interferon gamma (IFN-γ), as well as to tumour necrosis factor, interleukin-6 and hypoxia, in both humans and mice. Mass cytometry confirmed that healthy and arthritic donor blood neutrophils are largely indistinguishable but revealed a range of neutrophil phenotypes in synovial fluid defined by downregulation of CXCR1 and upregulation of FcγRI, HLA-DR, PD-L1, ICAM-1 and CXCR4. Reproduction of key elements of this signature in cultured blood neutrophils required both IFN-γ and prolonged culture. CONCLUSIONS: Circulating neutrophils from patients with arthritis resemble those from healthy controls, but joint fluid cells exhibit a network of changes, conserved across species, that implicate IFN-γ response and ageing as complementary drivers of the synovial fluid neutrophil phenotype. | |
| 35234840 | Cardiorenal Risk of Celecoxib compared to Naproxen, or Ibuprofen in Arthritis Patients: In | 2022 Mar 2 | INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs both prescribed and over the counter. The long-term cardiovascular safety of NSAIDs in patients with arthritis has engendered controversy. Concerns remain regarding the relative incidence and severity of adverse cardiorenal effects, particularly in arthritis patients with established CV disease, or risk factors for disease as illustrated by the PRECISION trial participants (NCT00346216). HYPOTHESIS: The selective COX-2 Inhibitor celecoxib has a superior cardiorenal safety profile when compared to ibuprofen or naproxen in the PRECISION population. METHODS: 24,081 patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and had increased CV risk randomly received celecoxib, ibuprofen or naproxen. The current prespecified secondary analysis assessed the incidence, severity and NSAID-related risk of the pre-specified composite cardiorenal outcome [adjudicated renal event, hospitalization for congestive heart failure (CHF), or hospitalization for hypertension (HTN)] in the intention-to-treat (ITT) population. An on-treatment analysis assessed safety in those taking the study medication. RESULTS: Following a mean treatment duration of 20.3±16.0 months and a mean follow-up of 34.1±13.4 months, the primary cardiorenal composite outcome occurred in 423 patients (1.76%) in the ITT population. Of these 423 patients, 118 (28%) were in the celecoxib, 166 (39%) in the ibuprofen and 139 (33%) in the naproxen group. In a multivariable Cox regression model adjusted for independent clinical variables, celecoxib showed a significantly lower risk compared with ibuprofen (hazard ratio [HR] 0.67, confidence interval [CI] 0.53 - 0.85, p = 0.001) and a trend to lower risk compared to naproxen (HR 0.79, CI 0.61 - 1.00, p = 0.058).In the intention-to-treat analysis, clinically significant renal events occurred in 220 patients with events rates of 0.71%, 1.14% and 0.89% for celecoxib, ibuprofen and naproxen respectively (p = 0.052), while in the on -treatment analysis the rates were 0.52%, 0.91% and 0.78% (p<0.001). CONCLUSION: In the current era, long-term NSAID use was associated with few cardiorenal events in arthritis patients. At the doses studied, celecoxib displayed fewer renal events and hence more favorable cardiovascular safety compared to ibuprofen or naproxen. These results have considerable clinical implications for practitioners managing individuals with chronic arthritis pain and high risk of impaired renal function and/or heart failure. (Funded by Pfizer) Clinical Trial Registration: NCT00346216. | |
| 35442139 | Risk of Staphylococcus aureus bacteraemia in patients with rheumatoid arthritis and the ef | 2022 Apr 20 | OBJECTIVE: It remains disputed how much the risk of Staphylococcus aureus bacteraemia (SAB) is increased in patients with rheumatoid arthritis (RA), and the extent to which orthopaedic implants explain the risk. We assessed SAB incidence rates (IRs) and incidence rate ratios (IRRs), comparing RA patients with a general population cohort (GPC) and individuals with versus without orthopaedic implants. METHOD: Danish residents aged ≥ 18 years without prior RA or SAB (=GPC) were followed up for RA and microbiologically verified SAB events (1996-2017). IRRs were calculated by age- and sex-stratified Poisson regression adjusted for age, comorbidities, calendar year, and socioeconomic status. RESULTS: The GPC comprised 5 398 690 individuals. We identified 33 567 incident RA patients (=RA cohort) (median follow-up 7.3 years, IQR 3.6-12.3). We observed 25 023 SAB events (n = 224 in the RA cohort). IRs per 100 000 person-years were 81.0 (RA cohort) and 29.9 (GPC). IRs increased with age. Adjusted IRRs in 18-59-year-old RA patients were 2.6 (95% confidence interval 1.8-3.7) for women and 1.8 (1.1-3.1) for men, compared with same sex and age group GPC. IRRs declined with age. Compared with the GPC without implants, IRRs for RA patients with implants ranged from 1.9 (1.3-2.8) (women ≥ 70 years) to 5.3 (2.2-12.8) (18-59-year-old men). CONCLUSION: In this nationwide registry-based cohort study RA was a risk factor for SAB, and orthopaedic implants further increased the risk. Clinicians should be aware of potential SAB in patients with RA and orthopaedic implants. | |
| 35484889 | Clinical usefulness of anti-cell membrane DNA autoantibodies in serology negative systemic | 2022 Apr | INTRODUCTION: Systemic lupus erythematosus (SLE) diagnosis is dependent on the detection of serum autoantibodies. To date, there is no autoantibody highly sensitive and specific enough to be considered as a gold standard. This study aimed to determine the diagnostic usefulness of anti-cmDNA antibodies which found to be associated with SLE. MATERIALS AND METHODS: Serum samples from 83 SLE, 86 other connective tissue diseases (OCTD) and 61 healthy subjects were randomly selected for the study. The OCTD cases included 56 rheumatoid arthritis, 12 scleroderma, 10 Sjogren's syndrome and 8 mixed connected tissue diseases. All samples were assayed for anti-cmDNA by indirect immunofluorescence assay (IFA) using Raji cells as substrate. SLE samples were also tested for antidsDNA and anti-Sm antibodies using enzyme-immunoassays. RESULTS: Anti-cmDNA positivity was highest in SLE (55.4%) compared to OCTD (9.3%) and healthy subjects (0%). It was 100% specific at differentiating SLE from healthy subjects and 90.7% specific at differentiating SLE from OCTD. There were no significant differences in the sensitivity (55.4%) of anti-cmDNA at differentiating SLE from OCTD and healthy groups. Anti-cmDNA was present in 52.9% of SLE samples negative for standard SLE-specific autoantibodies. It was detected in 7 (36.8%) of anti-dsDNA, 25 (52.1%) of anti-Sm and 5 (31.3%) of both anti-Sm and anti-dsDNA negative samples. Anti-cmDNA positive SLE was significantly associated with arthritis (p=0.019). CONCLUSION: The high specificity of anticmDNA detection by IFA makes it an excellent diagnostic test for SLE. Anti-cmDNA is also useful for identifying SLE with negative anti-dsDNA or/and anti-Sm antibodies. | |
| 35383651 | AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonart | 2022 May 1 | Management of Osteoarthritis of the Knee (nonarthroplasty) Evidence-Based Clinical Practice Guideline is based on a systematic review of published studies for the nonarthroplasty treatment of osteoarthritis of the knee in adults (ages 17 years and older). The purpose of this clinical practice guideline is to evaluate current best evidence associated with treatment. The scope of this guideline contains nonpharmacologic and pharmacologic interventions for symptomatic osteoarthritis of the knee, including surgical procedures less invasive than knee arthroplasty. It does not provide recommendations for patients with rheumatoid arthritis, arthritis of other joints, or other imflammatory athropathies. This guideline contains 29 recommendations to assist all qualified and appropriately trained healthcare professionals involved in the nonarthroplasty management of osteoarthritis of the knee and provide information for patients. In addition, the work group highlighted the need for better research into intra-articular corticosteroid, hyaluronic acid, and platelet-rich plasma detailing osteoarthritis characterization, including subgroup analyses and osteoarthrosis severity stratification, and clinically relevant outcomes with control subjects for bias and cost-effectiveness analysis. Studies comparing outcomes in patients with mild-to-moderate knee osteoarthritis and an MRI confirmed meniscal tear who have undergone partial meniscectomy after failing to improve with a course of conservative treatment (nonsteroidal anti-inflammatory drugs, steroid injection, and physical therapy) versus those who have undergone partial meniscectomy without a dedicated course of conservative treatment. Prospective randomized trials or prospective cohort studies are still needed to establish efficacy of individual oral nonsteroidal anti-inflammatory drugs within specific subgroups and populations to tailor systemic medications to help increase efficacy and decrease the risk of adverse effects. | |
| 35484086 | Multifunctional Nanoparticles Co-Loaded with Perfluoropropane, Indocyanine Green, and Meth | 2022 Apr 28 | Rheumatoid arthritis (RA), a common chronic inflammatory joint disease with features of synovitis and pannus formation, may lead to irreparable joint damage and disability. Methotrexate (MTX) is known as the cornerstone of therapy for RA. However, the therapeutic effects of MTX are unsatisfactory due to its low retention in the inflammatory joints as well as systemic toxic effects. Fortunately, the use of multifunctional nanoparticles for diagnostics and in treatment shows potential for application as a strategy for traceable and targeted RA therapy. This research aims to develop novel nanoparticles that carry with perfluoropropane (PFP), indocyanine green (ICG), and MTX and investigate the corresponding enhancement in multimodal imaging both in vitro and in vivo. A modified double emulsion method was applied for the construction of encapsulated PFP-O(2), ICG, and MTX (OIM@NPs), and the essential properties of the developed NPs were determined. The fluorescence and ultrasonic and photoacoustic imaging characteristics were experimentally evaluated both in in vitro and in vivo models. The OIM@NPs are stable and efficient nanoagents. They enable more targeted distribution in the inflammatory joints in RA rats. Moreover, the NPs play an important role as contrast agents for prominent ultrasound and photoacoustic imaging after laser and low-intensity focused ultrasound excitation, providing precision guidance and monitoring for subsequent treatment. This research may provide a novel and efficient strategy to better enable monitoring in inflammatory joints of RA patients and the developed NPs may be a promising nanoplatform for integrating multimodal image monitoring. | |
| 35084321 | Changes of immunosuppressive medication because of COVID-19 by patients with chronic infla | 2022 Jan 5 | OBJECTIVES: To study treatment decisions of patients with chronic inflammatory rheumatic diseases (CIRD) at the beginning of the SARS- CoV-2 pandemic in relation to disease characteristics with focus on anxiety. METHODS: A total of 970 CIRD patients diagnosed with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriasis arthritis (PsA) and connective tissue diseases (CTD), selected from our records who had presented to our hospital at least twice during last year, were contacted by telephone to be asked about medication changes, health status and therapy satisfaction. Standardised tools were used to assess disease activity, anxiety and depression, the latter by Hospital Anxiety and Depression Score (HADS) with a score ≥8 denoting definite anxiety and/or depression. The cut-off for RADAI was set at ≥3.2 and for BASDAI ≥4. Compliance with prevention rules and vaccination status were assessed. RESULTS: Complete interviews of 557 patients (57.4%) made between April and July 2020 were available for analysis. The median age was 55 (47-63), disease duration 9.0 (4.5-17.0) years, 61.9% females. A recent change in medication was reported by 197 patients (35.4%), 51.2% of which admitted that this decision was mainly made due to the pandemic with more changes occurring with bDMARDs (21.8%) than cDMARDs (6.6%) and corticosteroids (5.4%). There was no major difference between patients who changed because of the pandemic or self-reported inactive disease versus patients who did not change therapy regarding disease activity, depression and anxiety (41%, 17.2%, 31.3% vs. 47.5%, 22.5%, 35.0% vs. 48.9%, 27.7%, 34.1%). More than 90% of patients reported that they rigorously followed Corona prevention rules. The majority of patients were vaccinated against influenza (55.3%) and pneumococci (61.3%), respectively. CONCLUSIONS: Anxiety, depression and disease activity did not play an important role in decisions favouring change of therapy, even though many patients changed medication due to the pandemic. Patients probably protected themselves by strictly adhering to hygiene recommendations. Vaccination rates against influenza and pneumococci were better than previously reported, but still too low. | |
| 34423733 | Extracellular vesicles in obesity and its associated inflammation. | 2022 | Obesity is characterized by low-grade, chronic inflammation, which promotes insulin resistance and diabetes. Obesity can lead to the development and progression of many autoimmune diseases, including inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, thyroid autoimmunity, and type 1 diabetes mellitus (T1DM). These diseases result from an alteration of self-tolerance by promoting pro-inflammatory immune response by lowering numbers of regulatory T cells (T(regs)), increasing Th1 and Th17 immune responses, and inflammatory cytokine production. Therefore, understanding the immunological changes that lead to this low-grade inflammatory milieu becomes crucial for the development of therapies that suppress the risk of autoimmune diseases and other immunological conditions. Cells generate extracellular vesicles (EVs) to eliminate cellular waste as well as communicating the adjacent and distant cells through exchanging the components (genetic material [DNA or RNA], lipids, and proteins) between them. Immune cells and adipocytes from individuals with obesity and a high basal metabolic index (BMI) produce also release exosomes (EXOs) and microvesicles (MVs), which are collectively called EVs. These EVs play a crucial role in the development of autoimmune diseases. The current review discusses the immunological dysregulation that leads to inflammation, inflammatory diseases associated with obesity, and the role played by EXOs and MVs in the induction and progression of this devastating conditi8on. |