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ID PMID Title PublicationDate abstract
33565301 Lower urinary tract symptoms in rheumatoid arthritis and spondyloarthritis male patients v 2021 Jun 1 Background. We aimed to evaluate the severity of lower urinary tract symptoms (LUTS) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) male patient versus control, then to determine the relation of LUTS with rheumatic diseases (RD) characteristics and with erectile dysfunction (ED).Methods. We conducted a cross-sectional case control study including 50 men with RA or SpA and 50 healthy controls. LUTS were evaluated by the International Prostate Symptom Score (IPSS). LUTS bother was evaluated by the Quality of life (QoL) score, which ranges from 0 to 6. LUTS bother was considered if QoL score exceeded 2. Moreover, erectile function was assessed by the International Index of Erectile Function-5 (IIEF5) (ED if score < 21).Results. LUTS were significantly more severe in RD patients than controls (p = 0.03). However, there was no difference between the two groups in LUTS bother (QoL) (p = 0.2). Comparing RA and SpA showed no difference as to the severity of LUTS or effect of bother on QoL (p = 0.13, p = 0.5). The prevalence of ED in RD patients was not significantly higher than controls (80% versus 70%; p = 0.2).There were also no differences either between RA and SpA groups (p = 0.74).The severity of LUTS for patients with RD (RA and SpA) was significantly associated with age (p = 0.001), age at disease onset (p = 0.002) and ED (p = 0.008).Conclusion. According to our study, men with RD seem to be exposed to more severe LUTS than controls. Also, the severity of LUTS was associated with ED, age of patients and the age of disease onset.
34836295 Ameliorating Effects of Coriander on Gastrocnemius Muscles Undergoing Precachexia in a Rat 2021 Nov 12 Coriander is a commonly used vegetable, spice, and folk medicine, possessing both nutritional and medicinal properties. Up to two-thirds of patients with rheumatoid arthritis (RA) exhibit loss of body mass, predominately skeletal muscle mass, a process called rheumatoid cachexia, and this has major effects of the quality of life of patients. Owing to a lack of effective treatments, the initial stage of cachexia has been proposed as an important period for prevention and decreasing pathogenesis. In the current study, we found that cachexia-like molecular disorders and muscle weight loss were in progress in gastrocnemius muscle after only 5 days of RA induction in rats, although rheumatoid cachexia symptoms have been reported occurring approximately 45 days after RA induction. Oral administration of coriander slightly restored muscle loss. Moreover, iTRAQ-based quantitative proteomics revealed that coriander treatment could partially restore the molecular derangements induced by RA, including impaired carbon metabolism, deteriorated mitochondrial function (tricarboxylic acid cycle and oxidative phosphorylation), and myofiber-type alterations. Therefore, coriander could be a promising functional food and/or complementary therapy for patients with RA against cachexia.
34625402 Splicing machinery is impaired in rheumatoid arthritis, associated with disease activity a 2022 Jan OBJECTIVES: To characterise splicing machinery (SM) alterations in leucocytes of patients with rheumatoid arthritis (RA), and to assess its influence on their clinical profile and therapeutic response. METHODS: Leucocyte subtypes from 129 patients with RA and 29 healthy donors (HD) were purified, and 45 selected SM elements (SME) were evaluated by quantitative PCR-array based on microfluidic technology (Fluidigm). Modulation by anti-tumour necrosis factor (TNF) therapy and underlying regulatory mechanisms were assessed. RESULTS: An altered expression of several SME was found in RA leucocytes. Eight elements (SNRNP70, SNRNP200, U2AF2, RNU4ATAC, RBM3, RBM17, KHDRBS1 and SRSF10) were equally altered in all leucocytes subtypes. Logistic regressions revealed that this signature might: discriminate RA and HD, and anti-citrullinated protein antibodies (ACPAs) positivity; classify high-disease activity (disease activity score-28 (DAS28) >5.1); recognise radiological involvement; and identify patients showing atheroma plaques. Furthermore, this signature was altered in RA synovial fluid and ankle joints of K/BxN-arthritic mice. An available RNA-seq data set enabled to validate data and identified distinctive splicing events and splicing variants among patients with RA expressing high and low SME levels. 3 and 6 months anti-TNF therapy reversed their expression in parallel to the reduction of the inflammatory profile. In vitro, ACPAs modulated SME, at least partially, by Fc Receptor (FcR)-dependent mechanisms. Key inflammatory cytokines further altered SME. Lastly, induced SNRNP70-overexpression and KHDRBS1-overexpression reversed inflammation in lymphocytes, NETosis in neutrophils and adhesion in RA monocytes and influenced activity of RA synovial fibroblasts. CONCLUSIONS: Overall, we have characterised for the first time a signature comprising eight dysregulated SME in RA leucocytes from both peripheral blood and synovial fluid, linked to disease pathophysiology, modulated by ACPAs and reversed by anti-TNF therapy.
34504248 Pentahydroxy flavonoid isolated from Madhuca indica ameliorated adjuvant-induced arthritis 2021 Sep 9 Rheumatoid arthritis (RA) is an autoimmune disease associated with advanced joint dysfunction. Madhuca indica J. F. Gmel, from the family Sapotaceae, is an Indian medicinal plant reported to have an array of pharmacological properties. The aim of present investigation was to determine the anti-arthritic potential of an isolated phytoconstituent from methanolic leaf extract of Madhuca indica (MI-ALC) against FCA-induced experimental arthritis. Polyarthritis was induced in female rats (strain: Wistar) via an intradermal injection of FCA (0.1 mL) into the tail. Polyarthritis developed after 32 days of FCA administration. Then rats were treated orally with an isolated phytoconstituent from MI-ALC at doses of 5, 10, and 20 mg/kg. Findings suggested that High-Performance Thin-Layer Chromatography, Fourier-Transform Infrared Spectroscopy, and Liquid Chromatography-Mass Spectrometry spectral analyses of the phytoconstituent isolated from MI-ALC confirmed the structure as 3,5,7,3',4'-Pentahydroxy flavone (i.e., QTN). Treatment with QTN (10 and 20 mg/kg) showed significant (p < 0.05) inhibition of increased joint diameter, paw volume, paw withdrawal threshold, and latency. The elevated synovial oxidative stress (Superoxide dismutase, reduced glutathione, and malondialdehyde) and protein levels of Tumor necrosis factor-α (TNF-α) and Interleukin (ILs) were markedly (p < 0.05) reduced by QTN. It also effectively (p < 0.05) ameliorated cyclooxygenase-2 (COX-2), Nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kβ) and its inhibitor-α (Ikβα), and ATP-activated P2 purinergic receptors (P2X7) protein expressions as determined by western blot analysis. In conclusion, QTN ameliorates FCA-induced hyperalgesia through modulation of elevated inflammatory release (NF-kβ, Ikβα, P2X7, and COX-2), oxido-nitrosative stress, and pro-inflammatory cytokines (ILs and TNF-α) in experimental rats.
34212506 Acceptance and image quality of high-resolution peripheral quantitative computed tomograph 2021 Dec OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) requires longer immobilization time than conventional radiography, which challenges patient acceptance and image quality. Therefore, the aim was to investigate the acceptance of HR-pQCT in patients with rheumatoid arthritis (RA), and secondly the effect of an inflatable hand immobilization device on motion artefacts of the metacarpophalangeal (MCP) joints. METHODS: Fifty patients with established RA and a median (interquartile range) age of 64.3 (55.0-71.2) years had their MCP joints scanned by HR-pQCT with the hand positioned with and without an inflatable immobilization device followed by a full radiographic examination and a questionnaire on the imaging experience. The comparability of the erosion measures was investigated with and without the immobilization device using Bland-Altman plot and intrareader repeatability by intraclass correlation coefficient. The motion artefacts were graded for each acquisition, and intrareader repeatability was investigated by Cohen's kappa coefficient. RESULTS: Forty percent of the patients preferred HR-pQCT imaging, only 6% preferred conventional X-ray. Seventy-four percent reported it was not difficult to keep their fingers steady during the scan. Sixty percent of the patients reported the immobilization device helped keep their fingers steady. However, as motion artefacts were sparse, no clinically relevant difference was observed concerning the effect of the immobilization device on readability. The intrareader repeatability and comparability for the erosion measures were excellent. CONCLUSION: The high patient acceptance adds to the feasibility of HR-pQCT imaging of MCP joints in RA. The inflatable immobilization device did not reduce motion-induced image degradation.
33951402 Rheumatoid Arthritis and Associated Interstitial Lung Disease: Mortality Rates and Trends. 2021 Dec Rationale: The burden of rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD) in recent years has not been well characterized. Objectives: In this study, we sought to describe RA- and RA-ILD-related mortality rates and trends in the United States from 2005 to 2018, stratified by demographics. Methods: We used the Multiple Cause of Death Database available through the Centers for Disease Control and prevention website, which contains data of all deceased U.S. residents. RA- and RA-ILD-related deaths were identified using International Classification of Diseases, 10th Revision, codes. We examined the age-adjusted mortality rates and trends stratified by demographics. Results: RA- and RA-ILD-related mortality rates were higher in women and older age groups. However, the prevalence of ILD was higher in male decedents with RA compared with female decedents with RA (13.3% vs. 8.7%). RA-related mortality rates were the highest in Native American individuals followed by White individuals. Compared with White individuals, Hispanic individuals had lower RA-related mortality rates but higher RA-ILD-related mortality rates. Overall RA-related mortality rates per 1,000,000 population members decreased from 30.6 in 2005 to 22.2 in 2018. RA-related mortality rates declined in both sexes, all races, and all age groups. However, RA-ILD-related mortality rates remained stable in both sexes, all races, and all age groups except for the group aged 65 to 84 years, in which the rates declined. Conclusions: The overall RA-related mortality rates are decreasing; however, RA-ILD-related mortality rates remain stable except in the group aged 65-84 years. This would suggest that therapies for RA and improvement in the management of other comorbidities have improved the overall outcomes in patients with RA but have had limited effect in the subgroup of patients with RA-ILD.
33323533 Impact of Comorbid Conditions on Healthcare Expenditure and Work-related Outcomes in Patie 2021 Aug OBJECTIVE: To evaluate the effect of comorbid conditions on direct healthcare expenditure and work-related outcomes in patients with rheumatoid arthritis (RA). METHODS: This is a retrospective analysis of the Medical Expenditure Panel Survey from 2006 to 2015 in 4967 adults with RA in the United States. Generalized linear models were used for healthcare expenditure and income, logistic models for employment status, and zero-inflated negative binomial models for absenteeism. Thirteen comorbid conditions were included as potential predictors of direct cost- and work-related outcomes. The models were adjusted for sociodemographic factors including sex, age, region, marital status, race/ethnicity, income, education, and smoking status. RESULTS: Patients with RA with heart failure (HF) had the highest incremental annual healthcare expenditure (US$8205, 95% CI $3683-$12,726) compared to those without the condition. Many comorbid conditions including hypertension (HTN), diabetes, depression, chronic obstructive pulmonary disease, cancer, stroke, and HF reduced the chance of patients with RA aged between 18-64 years being employed. Absenteeism of employed patients with RA was significantly affected by HTN, depression, disorders of the eye and adnexa, or stroke. On average, RA patients with HF earned US$15,833 (95% CI $4435-$27,231) per year less than RA patients without HF. CONCLUSION: Comorbid conditions in patients with RA were associated with higher annual healthcare expenditure, lower likelihood of employment, higher rates of absenteeism, and lower income. Despite its low prevalence, HF was associated with the highest incremental healthcare expenditure and the lowest likelihood of being employed compared to other common comorbid conditions.
33914984 Curcumin and rheumatoid arthritis: A systematic review of literature. 2021 Oct BACKGROUND: Curcumin is a natural polyphenol and the main compound from the rhizome of Turmeric (Curcuma longa) and other Curcuma species. It has been widely used for different medical purposes, such as improvement of pain and inflammatory conditions in various diseases. PURPOSE: This systematic review was aimed to assess all studies regarding the efficacy of the pure form of curcumin (unformulated curcumin) on rheumatoid arthritis (RA). METHODS: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Out of 2079 initial records, 51 articles (13 in vitro and 37 animal and one human) were met our inclusion criteria. RESULTS: Most studies have shown the curative effects of curcumin on clinical and inflammatory parameters of RA and reported different mechanisms; inhibition of mitogen-activated protein kinase family, extracellular signal-regulated protein kinase, activator protein-1 and nuclear factor kappa B are the main mechanisms associated with the anti-inflammatory function of curcumin in RA. The results of the only human study showed that curcumin significantly improved morning stiffness, walking time and joint swelling. CONCLUSION: In conclusion, curcumin seems to be useful, and it is recommended that more human studies be performed to approve the cellular and animal results and determine the effective and optimal doses of curcumin on RA patients.
34280485 Co-amorphous systems of sinomenine with nonsteroidal anti-inflammatory drugs: A strategy f 2021 Sep 5 Rheumatoid arthritis (RA) is a chronic autoimmune joint disorder that affects about 1% of the world population and may lead to severe disability and comorbidity. Despite breakthroughs in past decades to understand its pathogenesis and the development of transforming disease-modifying antirheumatic drugs, the symptoms of many patients are not substantially improved. Sinomenine (SIN), a natural alkaloid with poor solubility, has been used to treat RA in China for years because of its unique immunoregulative activity. However, its commercial hydrochloride form has a short half-time, which may cause huge fluctuations of blood drug concentration leading to severe adverse reactions. In this study, co-amorphous systems of SIN with three nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, naproxen, and sulindac, were prepared for the combination therapy, as well as the improvement of its aqueous solubility and controlled release. Each co-amorphous sample was characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), and Fourier transform infrared spectroscopy (FTIR). The CO(2)(-) and N(+)H stretching vibration in the three co-amorphous samples appears in FTIR spectra, suggesting the formation of salts between SIN and NSAIDs. SIN also exhibits sustained release rates in all three co-amorphous samples. These co-amorphous systems show excellent physicochemical stability because no recrystallization was observed at 25 °C and 75% relative humidity (RH) after four months. Our study suggests that SIN-NSAIDs co-amorphous systems represent an affordable and promising treatment against RA.
34859863 Venous thromboembolism risk in rheumatoid arthritis patients: a systematic review and upda 2021 Nov OBJECTIVE: Rheumatoid arthritis (RA) patients are prone to develop thromboembolic complications due to the chronic inflammatory nature of RA. Only one systematic review and meta-analysis has attempted to evaluate venous thromboembolism risk in RA patients. However, this review has become outdated due to the recent publication of several high-quality retrospective cohort studies. The aim of the study was to evaluate the risks of deep vein thrombosis, pulmonary embolism, and overall venous thromboembolism event incidence in RA patients. MATERIALS AND METHODS: Five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE) were systematically searched according to PRISMA guidelines for eligible studies. With the available literature, we conducted a random-effect meta-analysis to evaluate odds ratios of deep vein thrombosis, pulmonary embolism, and venous thromboembolism incidence in RA patients and healthy controls. RESULTS: We found 12 eligible studies detailing 272,884 RA patients and 2,280,454 age and sex-matched healthy controls. Meta-analysis revealed elevated risks for deep vein thrombosis (Odd's ratio: 2.25), pulmonary embolism (2.15), and overall venous thromboembolism incidence (2.23) in RA patients. CONCLUSIONS: This meta-analysis provides evidence concerning the elevated risks of deep vein thrombosis, pulmonary embolism, and venous thromboembolism in RA patients. The findings herein may aid in developing clinical awareness and assisting best practice guideline development for RA patients with thromboembolic complications.
33722260 Correlation of osteoarthritis or rheumatoid arthritis with bone mineral density in adults 2021 Mar 15 BACKGROUND: It is reported that osteoporosis commonly occurs among patients with rheumatoid arthritis (RA), whereas the association between osteoporosis and osteoarthritis (OA) remains controversial. Our aim in this study was to investigate the association between BMD, as a marker of osteoporosis, and OA and RA among adults 20-59 years of age, using a population-based sample from the National Health and Nutrition Examination Survey (NHANES). METHODS: Our analysis was based on the NHANES data collected between 2011 and 2018. Data regarding arthritis status and the type of arthritis (OA or RA) were obtained from questionnaires. Lumbar BMD was measured by dual-energy X-ray absorptiometry. The association between OA, RA, and lumbar BMD was evaluated using logistic regression models. Subgroup analyses, stratified by gender and race, were performed. The association between duration of arthritis and lumbar BMD was also investigated. RESULTS: A total of 11,094 adults were included in our study. Compared to the non-arthritis group, participants with OA had a higher lumbar BMD (β = 0.023, 95% CI 0.011-0.035), with no significant association between lumbar BMD and RA (β = 0.014, 95% CI - 0.003 to 0.031). On subgroup analyses stratified by gender, males with OA had a higher lumbar BMD compared to those without OA (β = 0.047, 95% CI 0.028-0.066). In females, OA was not associated with lumbar BMD (β = 0.007, 95% CI - 0.008 to 0.021). There was no association between lumbar BMD and RA in both males (β = 0.023, 95% CI - 0.003 to 0.048) and females (β = 0.008, 95% CI - 0.015 to 0.031). Duration of arthritis was not associated with lumbar BMD for both OA (β = - 0.0001, 95% CI - 0.0017 to 0.0015) and RA (β = 0.0006, 95% CI - 0.0012 to 0.0025). CONCLUSIONS: Lumbar BMD was associated with OA but not with RA. While a higher lumbar BMD was associated with OA in males, but not in females. Our findings may improve our understanding between OA, RA, and bone health.
34060972 Genetic variant in microRNA-146a gene is associated with risk of rheumatoid arthritis. 2021 Dec OBJECTIVE: To investigated the association between single nucleotide polymorphisms (SNPs) in microRNA-146a (miR-146a) gene and susceptibility of rheumatoid arthritis (RA). METHODS: We systemically extracted the genetic data of miR-146a from previous genome-wide association studies (GWASs) of RA. Subsequently, we performed a replication study in an independent Chinese cohort for selected variant. A meta-analysis combined the previous GWASs with the replication study was also conducted. The epigenetic annotation and cytokine assay were used for exploring potential variant function. RESULTS: The extracted genetic association data from three previous GWASs showed that the allele T of functional SNP rs2431697 increased RA susceptibility. The significant association for the SNP was also found in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06-1.46, p = 8.69E-03). The estimated effect size for this SNP was larger in Asian population than that in European population (Asian meta-analysis: OR = 1.15, 95% CI = 1.09-1.22, p = 4.37E-07; Tran-ethnic meta-analysis: OR = 1.07, 95% CI = 1.04-1.10, p = 1.79E-06). The cytokine assay also showed that the risk allele T of the SNP rs2431697 is inversely associated with plasma TNF-α levels in health controls (p = .016). CONCLUSIONS: In summary, this study supports that genetic variant in miR-146a gene is associated with RA risk.KEY MESSAGESThe association between SNPs in miR-146a gene and susceptibility of RA was unclear.We investigated the genetic association using GWASs data and a replication study.The SNP rs2431697 in miR-146a gene is associated with RA risk.
33502940 Risk and cost of infection-related hospitalizations in medicare beneficiaries with comorbi 2021 Jan OBJECTIVE: This study evaluated infection-related hospitalization risk and cost in tumor necrosis factor inhibitor (TNFi)-experienced and targeted DMARD (tDMARD) naïve rheumatoid arthritis (RA) patients that were treated with abatacept, TNFi, or other non-TNFi. METHODS: This retrospective study used 100% Medicare Fee-for-Service claims to identify patients ≥65 age, diagnosed with RA, and were either 1) TNFi-experienced, who switched from a TNFi to another tDMARD (subsequent tDMARD claim served as index), or 2) tDMARD naïve (first therapy claim served as index), who initiated either abatacept, TNFi, or non-TNFi as their first tDMARD, between 2010 and 2017. Follow-up ended at the date of disenrollment, death, end of study period, or end of index treatment, whichever occurred first. Infection-related hospitalizations included pneumonia, bacterial respiratory, sepsis, skin and soft tissue, joint or genitourinary infections. A Cox proportional hazard model and two part generalized linear model were developed to estimate adjusted infection-related hospitalization risk and costs. Costs were normalized to per-patient-per-month (PPPM) and inflated to 2019 US$. RESULTS: The infection-related hospitalizations rate was lower during follow-up than during baseline periods for abatacept users, but was reversed for both TNFi and other non-TNFi users in both TNFi-experience and tDMARD naïve (p value < .001 based on Breslow-Day test for homogeneity of odds ratios). Infection-related hospitalization PPPM cost was significantly lower in abatacept treated patients compared to TNFi (TNFi-experienced: by $74; tDMARD naïve: $42) and other non-TNFi (TNFi-experienced: by $68; tDMARD naïve: $60). The adjusted infection-related hospitalization risk was significantly higher for RA patients treated with TNFi (TNFi-experienced HR: 1.48; 95% CI: 1.26-1.75, p < .0001; tDMARD naïve HR:1.59; 95% CI: 1.43-1.77, p < .0001) and other non-TNFi (TNFi-experienced HR:1.46; CI:1.28-1.66; tDMARD naïve HR:1.63; 95% CI: 1.44-1.83) than with abatacept. CONCLUSION: RA Medicare Fee-For-Service beneficiaries who either switched or initiated abatacept have a lower infection-related hospitalization risk and cost compared to patients who switched to or initiated other tDMARDs.
34811544 Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation. 2021 Dec Misdirected immunity gives rise to the autoimmune tissue inflammation of rheumatoid arthritis, in which excess production of the cytokine tumor necrosis factor (TNF) is a central pathogenic event. Mechanisms underlying the breakdown of self-tolerance are unclear, but T cells in the arthritic joint have a distinctive metabolic signature of ATP(lo) acetyl-CoA(hi) proinflammatory effector cells. Here we show that a deficiency in the production of mitochondrial aspartate is an important abnormality in these autoimmune T cells. Shortage of mitochondrial aspartate disrupted the regeneration of the metabolic cofactor nicotinamide adenine dinucleotide, causing ADP deribosylation of the endoplasmic reticulum (ER) sensor GRP78/BiP. As a result, ribosome-rich ER membranes expanded, promoting co-translational translocation and enhanced biogenesis of transmembrane TNF. ER(rich) T cells were the predominant TNF producers in the arthritic joint. Transfer of intact mitochondria into T cells, as well as supplementation of exogenous aspartate, rescued the mitochondria-instructed expansion of ER membranes and suppressed TNF release and rheumatoid tissue inflammation.
32787514 C3 Gene Functional Polymorphisms and C3 Serum Levels in Patients with Rheumatoid Arthritis 2021 Nov The complement system is a key component of the innate immunity that plays a significant role in the development and clinical presentation of Rheumatoid arthritis (RA). Complement protein C3 is a central molecule in the activation of complement with a significant role in the inflammatory processes of RA. Nevertheless, the impact of C3 gene polymorphisms in the development of RA is still unknown. The current study aimed to investigate the possible influence of C3 gene polymorphisms in the susceptibility and clinical expression of RA. Three C3 polymorphisms (rs2250656:A > G, intron 2; rs2230199:C > G [p.Arg102Gly], exon 3 and rs1047286:C > T [p.Pro314Leu], exon 9) were assessed by sequence-specific PCR in a total of 156 RA patients and 270 healthy controls from Southern Brazil. In addition, C3 levels were measured in 60 patients and 60 controls by immunoturbidimetry and clinical features were collected from medical records. The frequency of rs2230199 G allele and GG genotype was significantly higher in RA patients than controls (p(adj) = 0.012 OR = 1.57 [1.11-2.31]; p(adj) = 0.008, OR = 1.60 [1.35-2.33]) as well as the rs1047286 T and TT (p(adj) = 0.010, OR = 1.67 [1.12-2.40]; p(adj) = 0.001, OR = 1.83 [1.27-2.65] and the C3 AGT haplotype (p(adj) = 0.0007 OR = 1.92 [1.32-2.80]). Moreover, C3 serum levels were higher in patients than controls (median: 169 mg/dl vs.155 mg/dl; p(adj) = 0.022), as well as in RF seronegative compared with seropositive patients (172 mg/dl vs. 165 mg/dl; p(adj) = 0.007). Our results suggest that the rs2230199 G (p.102Gly) and rs1047286 T (p.314Leu) alleles play a role in the pathophysiology of RA, possibly impacting complement activation by the alternative pathway.
34282512 IgA rheumatoid factor is associated with bone mineral density preservation in rheumatoid a 2021 Dec INTRODUCTION: Autoantibodies such as IgM rheumatoid factor (RF) and anti-citrullinated proteins/peptides antibodies (ACPA) have previously been incriminated in systemic bone loss in rheumatoid arthritis (RA). There are, however, no data describing association of IgA RF and IgG RF with systemic bone loss. OBJECTIVE: This study was aimed to investigate the association of RF isotypes with systemic bone loss among patients with RA. METHODS: RF isotypes and ACPA were measured by enzyme-linked immunosorbent assay among 153 patients with RA. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. RESULTS: Ninety-four (61.4%) patients had positive IgA RF, 89 (58.2%) had positive IgG RF, 109 (71.2%) had positive IgM RF, whereas 122 (80.3%) RA patients tested positive for ACPA. Compared to the IgA RF-negative patients, IgA RF-positive patients exhibited higher disease activity and had higher RF titers. Seven (4.6%) patients had low BMD at femoral neck, 12 (7.8%) at total femur, and 47 (30.7%) at lumbar spine. IgA RF was found to be associated with protection against low BMD at spine (OR = 0.47, 95% CI = 0.23-0.95, p = 0.034). This association was further confirmed in the multivariate regression analysis taking into account several potential confounding factors (OR = 0.21, 95% CI = 0.06-0.65, p = 0.039). No association between low BMD and the presence of IgG RF or IgM RF or ACPA was found. CONCLUSION: IgA RF for the first time ever was shown to be associated with BMD preservation at spine in RA. Key points • IgA RF was associated with protection against low spinal BMD. • No association between low BMD and the presence of IgG RF or IgM RF was found.
33857232 Influence of the shared epitope on the elicitation of experimental autoimmune arthritis bi 2021 Our previous studies have shown that inoculation of the oral cavity of "humanized" B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. We compared various immune response parameters as well as alveolar and peri-articular bone loss between humanized B6.DR1 (or B6.DR4) mice and their WT (B6) counterparts. We found that the presence of the shared epitope in the context of inoculation with P. gingivalis enhanced the percentage of Th17 cells generated, dramatically enhanced bone loss and importantly allowed for the generation of CCP2⁺ ACPAs that are not found in C57BL/6 or DBA/1 arthritic mouse serum. Due to the exceedingly complex nature of environmental factors impacting on genetic elements, it has been difficult to unravel mechanisms that drive autoimmune arthritis in susceptible individuals. The findings in this study may provide one small piece of this puzzle that can help us to better understand part of this complexity.
34785170 Carotid Artery Pathology in Inflammatory Diseases. 2022 Mar There is considerable evidence that patients with inflammatory conditions are at higher risk of developing cardiovascular (CV) disease including carotid artery stenosis. CV disease accounts for 35-50% of the excess mortality in patients with inflammatory diseases such as rheumatoid arthritis, with cerebrovascular disease being the second leading cause of death. We review current evidence regarding the association of inflammatory conditions and specifically carotid artery disease. Clinical epidemiological observations suggest that mechanisms other than classic risk factors may promote accelerated atherogenesis in rheumatoid and other inflammatory arthritis and carotid artery disease is increased in individuals with these conditions. Additional studies to better understand the underlying mechanisms and targeted strategies to mitigate such risk are indicated. For now, lifestyle modifications, aggressive treatment of risk factors and lipid lowering therapy in appropriate individuals is indicated.
33632333 Drug prices in Latin American countries: the case of rheumatoid arthritis Biosimilars. 2021 Feb 25 BACKGROUND: The objective of this paper is to analyze the prices of biological drugs in the treatment of Rheumatoid Arthritis (RA) in three Latin American countries (Brazil, Colombia and Mexico), as well as in Spain and the United States of America (US), from the point of market entry of biosimilars. METHODS: We analyzed products authorized for commercialization in the last 20 years, in Brazil, Colombia, and Mexico, comparing them to the United States of America (USA) and Spain. For this analysis, we sought the prices and registries of drugs marketed between 1999 and October 1, 2019, in the regulatory agencies' databases. The pricing between countries was based on purchasing power parity (PPP). RESULTS: The US authorized the commercialization of 13 distinct biologicals and four biosimilars in the period. Spain and Brazil marketed 14 biopharmaceuticals for RA, ten original, four biosimilars. Colombia and Mexico have authorized three biosimilars in addition to the ten biological ones. For biological drug prices, the US is the most expensive country. Spain's price behavior seems intermediate when compared to the three LA countries. Brazil has the highest LA prices, followed by Mexico and Colombia, which has the lowest prices. Spain has the lowest values in PPP, compared to LA countries, while the US has the highest prices. CONCLUSION: The economic effort that LA countries make to access these medicines is much higher than the US and Spain. The use of the PPP ensured a better understanding of the actual access to these inputs in the countries analyzed.
33774766 Synergistic effect of sarcopenia and poor balance on osteoporotic vertebral fracture in Ch 2021 Sep OBJECTIVES: This study aimed to investigate the synergistic effect of sarcopenia and poor balance on osteoporotic vertebral fracture (VOPF) in Chinese patients with rheumatoid arthritis (RA). METHODS: A total of 238 RA patients and 158 normal subjects were enrolled in the case-control study. Poor balance capability (Berg balance scale (BBS) score < 40) and sarcopenia (skeletal muscle mass index (SMI) <7.0 (male)/5.7 (female)) between RA patients and normal subjects were compared. Associations of poor balance capability or sarcopenia with disease activity, structural damage, and joint function in different groups were also investigated. RESULTS: The incidence of sarcopenia in RA was 58.4%, significantly higher than that in controls (P<0.0001). Moreover, the percentages of low balance capacity (BBS<40) in RA were 43.7%, which was higher than that in controls (P<0.0001). The prevalence of VOPF in the case group was 19.3%, which was higher than that in the controls (P<0.0001). In the RA group, compared to RA patients without VOPF, RA patients with VOPF had higher percentages of poor balance and sarcopenia (P<0.05). Compared with RA patients without sarcopenia or good balance, RA patients with sarcopenia or poor balance had a higher incidence of VOPF, higher disease activity, severer structural damage, and worse joint function (P<0.05). The incidence of VOPF in patients combined with good balance and non-sarcopenia (4.8%) was significantly lower than that in patients combined with poor balance and sarcopenia (38.2%) (P<0.0001). Logistic regression indicated that higher SMI and higher BBS scores were protective factors for VOPF in RA patients, while age was a risk factor for VOPF in RA patients (P<0.0001). CONCLUSION: Sarcopenia and poor balance are popular in Chinese patients with RA, and they are associated with disease activity and structural damage. There is a synergistic effect of sarcopenia and poor balance on VOPF in RA. Key Points • Sarcopenia and balance capability were popular (about a half) in patients with RA. • Sarcopenia and poor balance had a synergistic effect on VOPF in RA.