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ID PMID Title PublicationDate abstract
34392987 Pulmonary involvement in Sjögren's syndrome. 2022 Feb 25 Sjögren's syndrome is an autoimmune disease that involves exocrine glands. The most characteristic symptoms consist of the sicca syndrome (including xerostomia and dry eye - xerophtalmia), but can involve multiple organs. The extraglandular involvement determines the prognosis. It is typically associated with the presence of antinuclear antibodies, including Ro-60 antibodies. Pulmonary involvement appears as bronchiectasis and/or interstitial pneumonia. Considering its high prevalence, it must be ruled out in all patients with respiratory symptoms by performing pulmonary function tests and high-resolution computed tomography of the chest. Evaluation can be completed with a transbronchial biopsy if diagnostic doubts persist. Treatment includes steroid therapy, inmunosupressive or antifibrotic drugs, or biological therapy. In selected cases pulmonary transplantation must be considered.
35001319 The incidence, risk factor, and time to develop rheumatologic diseases after isolated infl 2022 Apr OBJECTIVE: The incidence, risk factors, and time to diagnosis of rheumatologic disease (RD) in patients with isolated inflammatory eye diseases (IED) were investigated. MATERIAL AND METHODS: A 12-year bidirectional cohort study was conducted in IED patients who were tested for antinuclear antibody (ANA) and rheumatoid factor (RF). Patients with prior RD were excluded. Impacts of relevant symptoms, signs, and laboratory investigations were analyzed. RESULTS: Seventy-five patients presented with IED including scleritis, anterior uveitis (AU), retinal vasculitis (RV), keratopathy, and optic neuritis (OP). AU, RV, keratopathy, and OP were associated with RD development. The incidence of RD was 36% during 12 years. RD developed most frequently in AU (55.5%) and RV (22.2%). The longest duration for RD development was 5.5 years. Prevalence of positive ANA and RF were 57.3% and 13.3%, respectively. The three most common RDs developed after IEDs were spondyloarthropathy (44.4%), systemic lupus erythematosus (SLE) (18.5%), and Sjogren's syndrome (pSS) (11.1%). The risk factors of RD from univariate analysis were age below 35 years old at onset of IED [relative risk (RR) 3.45; 95% CI (1.13-10.55), p =0.026], positive pertinent findings from history [RR 2.125; 95% CI (1.39-3.25), p<0.001], and physical examination [RR 3.23; 95% CI (1.84-5.66), p<0.001]. Multivariable logistic regression showed that bilateral eye involvement of IED was the significant risk of RD [RR 4.33; 95% CI (1.57-11.96), p=0.004]. IED patients with bilateral eye involvement had shorter time to develop RD (p=0.018). Positive ANA was the predictor for SLE and pSS in RV or OP patients [RR 2.00; 95% CI (1.14-3.52), p=0.04]. CONCLUSIONS: IED with bilateral eye involvement was the risk of RD development. Positive ANA was the predictor of RD in RV and OP patients, but not for the other IEDs. Follow-up period of at least 5 years was required to identify RD. KEY POINTS: • Bilateral involvement of isolated inflammatory eye disease was a significant risk factor of rheumatologic disease development.
34988683 Indications and risk factors for hospitalization in patients with primary Sjögren syndrom 2022 May OBJECTIVE: In this study, it was aimed to reveal the hospitalization reasons for patients diagnosed with primary Sjögren syndrome (pSS) and potentially associated factors in a tertiary health center. METHOD: One hundred and sixty-three pSS patients who regularly attended their follow-ups between January 2010 and May 2021 were included in the study. These patients' reasons for hospitalization, duration of hospitalization, and numbers of presenting to the hospital were recorded. The demographic, clinical and serological characteristics of the hospitalized and non-hospitalized patients were compared. RESULTS: Hospitalization occurred in 22.7% of the patients, and the total number of hospitalizations was 79. The hospitalization incidence density rate was 6.21 per 100 patient-years. The most frequently encountered reason for hospitalizations was pSS-related organ involvement (44.3%). Infections (17.7%), malignancy (16.5%), endocrine, and various other reasons were the other indications for hospitalization. While male sex (p = 0.005), the presence of extra-glandular involvement (p < 0.001), and interstitial lung disease (p = 0.001) were more common in the hospitalized patients, anti-nuclear antibody positivity was less frequent (p = 0.032). The usage rate of hydroxychloroquine (p = 0.022) was lower in the hospitalized patients, whereas the use of glucocorticoids (p < 0.001) and azathioprine (p = 0.005) was more frequent. The multivariable analyses revealed a relationship between extra-glandular involvement (OR: 4.57 [1.05-19.84], p = 0.043), glucocorticoid use (OR: 3.23 [1.13-9.21], p = 0.028) and hospitalization. CONCLUSION: pSS-related system involvement and infection accounted for the majority of hospitalizations of the pSS patients. The presence of extra-glandular involvement and glucocorticoid use were found to be associated with hospitalization. Key Points • pSS-related system involvement and infection accounted for the majority of hospitalizations of pSS patients. • The presence of extra-glandular involvement was found to be associated with hospitalization.
34980244 Latent class analysis of 216 patients with adult-onset Still's disease. 2022 Jan 3 BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease which encompasses patients with heterogenous presentation and a wide range of clinical courses. In this study, we aimed to identify potential subgroups of AOSD and reveal risk factors for relapse. METHODS: We included a total of 216 AOSD patients who received treatment in nine hospitals between 2000 and 2019. All patients fulfilled the Yamaguchi classification criteria. We retrospectively collected information about baseline characteristics, laboratory tests, treatment, relapse, and death. We performed latent class analysis and time-to-event analysis for relapse using the Cox proportional hazard model. RESULTS: The median age at disease onset was 51.6 years. The median follow-up period was 36.8 months. At disease onset, 22.3% of the patients had macrophage activation syndrome. The median white blood cell count was 12,600/μL, and the median serum ferritin level was 7230 ng/mL. Systemic corticosteroids were administered in all but three patients (98.6%) and the median initial dosage of prednisolone was 40mg/day. Ninety-six patients (44.4%) were treated with concomitant immunosuppressants, and 22 (10.2%) were treated with biologics. Latent class analysis revealed that AOSD patients were divided into two subgroups: the typical group (Class 1: 71.8%) and the elderly-onset group (Class 2: 28.2%). During the follow-up period, 13 of 216 patients (6.0%) died (12 infections and one senility), and 76 of 216 patients (35.1%) experienced relapses. Overall and relapse-free survival rates at 5 years were 94.9% and 57.3%, respectively, and those rates were not significantly different between Class 1 and 2 (p=0.30 and p=0.19). Time-to-event analysis suggested higher neutrophil count, lower hemoglobin, and age ≥65 years at disease onset as risk factors for death and age ≥65 years at disease onset as a risk factor for relapse. CONCLUSIONS: AOSD patients were divided into two subgroups: the typical group and the elderly-onset group. Although the survival of patients with AOSD was generally good, the patients often experienced relapses. Age ≥65 years at disease onset was the risk factor for relapse.
35282135 Total glucosides of peony induce fibroblast-like synovial apoptosis, and ameliorate cartil 2022 Jan BACKGROUND: Rheumatoid arthritis (RA) is one of the most common inflammatory arthritis worldwide. Total glucosides of peony (PG) were isolated from Paeonia lactiflora Pall, which were found to have the capacity to intervene in the progression of arthritis via an anti-inflammatory action. This study aimed to explore the protective effect of PG against RA. METHODS: In this study, we further investigated the molecular mechanisms of PG on RA. We constructed RA models by Bovine type II collagen in vitro or complete Freund's adjuvant (FCA) in vivo. The RA-MH7A cells were cultured and treated with different doses (10, 20, 50 µg/mL) of PG. Cell proliferation, apoptosis, and release of inflammatory cytokines were determined. Furthermore, the effect of PG was also explored in vivo using the collagen-induced arthritis rat model. After 30 days, the rats were sacrificed; histological changes, cytokine level, and protein expression were measured. RESULTS: It was revealed that PG dose-dependently inhibited RA-synovial cell growth and induce apoptosis by regulating relative gene level. Besides, PG downregulated the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β, and upregulated IL-10 level in vitro and in vivo. The regulation contributed to the restoration of cartilage injuries. Furthermore, PG also downregulated the expression of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. CONCLUSIONS: All these results showed that PG inhibits the excessive proliferation of synovial cells, and ameliorates cartilage injury via blocking the NF-κB/STAT3 pathway. Collectively, this study provides novel insights into the mechanism of PG, laying a foundation for the application of PG in RA.
35652495 Incidence of New Carotid Plaques in Rheumatoid Arthritis Patients: Six Years Prospective R 2022 Jun 2 OBJECTIVES: The purpose of this study was to evaluate new incidence of carotid plaques in rheumatoid arthritis (RA) patients over 6-year prospective follow-up and assess the risk factors. METHODS: This is a 10-year prospective cohort study included 208 RA patients and 205 age- and gender-matched controls. Ultrasound assessment of the bilateral carotid arteries was performed in 2011 and 2017. RESULTS: There were no differences in the incidence of new carotid atherosclerotic plaques over 6 years between the two groups (35.5% vs. 37.0%, respectively; p = 0.936). The mean Disease Activity Score 28- C-reactive protein over 6 years in RA patients was 2.73 ± 0.95. Multiple logistic regression analysis showed that RA was not a risk factor for new carotid atherosclerotic plaques (odds ratios, 0.708; 95% CI, 0.348-1.440; p = 0.340). An average glucocorticoid dose >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques (odds ratios, 8.54; 95% CI, 1.641-44.455; p =0.011). CONCLUSIONS: Incidence of new carotid atherosclerotic plaques was similar between well-controlled disease activity RA patients and control subjects. A mean glucocorticoid dose >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques.
35197789 Novel functional polymorphism on PADI-4 gene and its association with arthritis onset. 2022 Feb BACKGROUND: Citrullinated proteins formed by peptidyl arginine deiminases (PADIs) deimination of arginine residues in proteins are of particular interest in arthritis pathogenesis. Polymorphisms on the PADI-4 gene lead to the malfunctioning of PADIs leading to the onset of arthritis. OBJECTIVE: The present study was conducted to determine the polymorphisms on the PADI-4 gene and their association with rheumatoid arthritis (RA) as well as Osteoarthritis (OA). METHODOLOGY: To achieve the above-mentioned objective a case-control study was conducted. Blood samples were collected from RA, OA, and control subjects. DNA was extracted from each blood sample by modified organic method and was quantified as well as qualified by DNA gel electrophoresis and Nanodrop. Patients were tested for rs874881, rs11203366, rs11203367, rs2240336, rs2240337, rs2240339, rs1748033 and rs2240340 polymorphic sites by amplifying targeted regions through PCR with site-specific primers. Genotyping was performed by Restriction Fragment Length Polymorphism and direct sequencing method. Mutations were identified by analyzing sequences on BioEdit software. Allelic, genetic, and multiple site analysis were performed by SHEsis and PLINK software. Change in the amino acid sequence was identified by MEGA 6.0 software. RESULTS: Polymorphisms were identified on all targeted polymorphic sites except rs2240337 in both RA and OA individuals. In addition, two novel mutations were also identified in exon 4 identified i-e SCV000804840: c.218T > C and SCV000807675: c.241G > T. All the SNPs except rs11203366 were found to be significantly associated with RA at an allelic level whereas all SNP's have been significant risk factors in the onset of OA. At genotypic level rs874881, rs11203366, rs2240339, SCV000804840 and SCV000807675 were significantly associated to RA development whereas rs874881, rs11203366, rs11203367, rs2240339, SCV000804840 and SCV000807675 were genetic risk factors in OA onset. Haplotype analysis indicated that GACCACGCC and GACCACGCT were highly significant in disease development. Polymorphisms identified altered the functioning of PADIs by altering their amino acid sequence. CONCLUSION: In conclusion, it was found that PADI-4 gene polymorphism was not only involved in the onset of RA but was also found to be a significant risk factor in OA onset.
35295740 β-Sitosterol Inhibits Rheumatoid Synovial Angiogenesis Through Suppressing VEGF Signaling 2021 Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that β-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear. Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining. Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2'-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression. Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.
35069820 Transplantation of IL-1β siRNA-modified bone marrow mesenchymal stem cells ameliorates ty 2022 Feb Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosion of articular cartilage and bone and has adverse effects on both patients and livestock animals. The aim of the present study was to investigate the role of interleukin-1β (IL-1β) in the pathogenesis of RA, and to further determine whether injection of IL-1β small interfering RNA (siRNA) or transplantation of IL-1β siRNA + bone marrow mesenchymal stem cells (BMSCs) can ameliorate RA in rats. A collagen-induced arthritis (CIA) rat model was established by injecting type II collagen for 4 weeks. Next, CIA rats were randomly divided into three groups and injected or transplanted with PBS, IL-1β siRNA and IL-1β siRNA + BMSCs for another 4 weeks. The CIA rat model was successfully established, as demonstrated by the higher toe swelling value, thymus and spleen/body weight, immobility time and serum IL-1β concentration, as well as lower body weight, climbing time and mRNA expression of programmed death-1 (PD-1), transforming growth factor-β1 (TGF-β1) and forkhead box protein 3 (Foxp3) in the spleen, compared with control rats. Furthermore, histopathology results demonstrated that joint swelling and redness were observed in the knee joints of CIA rats. H&E results revealed that CIA rats presented erosive destruction of the bone and ulceration of the articular cartilage. In addition, in vitro results demonstrated that IL-1β expression was successfully silenced after IL-1β siRNA transfection in lipopolysaccharide-stimulated BMSCs. When compared with the results of PBS rats, both IL-1β siRNA injection and IL-1β siRNA + BMSC transplantation significantly increased the body weight, climbing time and mRNA expression of PD-1, TGF-β1 and Foxp3 in the spleen, while significantly reduced the immobility time and serum IL-1β concentration. In addition, when compared with that of IL-1β siRNA injection, IL-1β siRNA + BMSC transplantation exhibited markedly higher therapeutic efficacy against CIA. These results demonstrated that higher IL-1β contributed to the pathogenesis of CIA, and that IL-1β siRNA injection ameliorated CIA, while its combination with BMSCs exerted synergistic effects, which may be beneficial against RA.
35645648 Factors Associated With Increasing Length of Stay for Rheumatoid Arthritis Patients Underg 2022 May Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are cost-effective procedures that decrease pain and improve health-related quality of life for patients with advanced symptomatic arthritis, including rheumatoid arthritis (RA). Patients with RA have a longer length of stay (LOS) after THA or TKA than patients with osteoarthritis, yet the factors contributing to LOS have not been investigated. Purpose: We sought to identify the factors contributing to LOS for patients with RA undergoing THA and TKA at a single tertiary care orthopedic specialty hospital. Methods: We retrospectively reviewed data from a prospectively collected cohort of 252 RA patients undergoing either THA or TKA. Demographics, RA characteristics, medications, serologies, and disease activity were collected preoperatively. Linear regression was performed to explore the relationship between LOS (log-transformed) and possible predictors. A multivariate model was constructed through backward selection using significant predictors from a univariate analysis. Results: Of the 252 patients with RA, 83% were women; they had a median disease duration of 14 years and moderate disease activity at the time of arthroplasty. We had LOS data on 240 (95%) of the cases. The mean LOS was 3.4 ± 1.5 days. The multivariate analysis revealed a longer LOS for RA patients who underwent TKA versus THA, were women versus men, required a blood transfusion, and took preoperative opioids. Conclusion: Our retrospective study found that increased postoperative LOS in RA patients undergoing THA or TKA was associated with factors both non-modifiable (type of surgery, sex) and modifiable (postoperative blood transfusion, preoperative opioid use). These findings suggest that preoperative optimization of the patient with RA might focus on improving anemia and reducing opioid use in efforts to shorten LOS. More rigorous study is warranted.
35604524 A Decreased Absolute Number of T(reg) Cells in Patients with Active Rheumatoid Arthritis i 2022 May 23 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease characterized by synovial inflammation with unknown aetiology. Immune system dysfunction mediated by CD4(+) T lymphocytes, which is regulated by the cytokine osteopontin (OPN), plays an important role in the pathogenesis of RA. METHODS: In this study, the levels of peripheral CD4(+) T subsets and serum OPN in patients with active RA were measured and analysed to determine the possible pathogenesis of RA and to provide potential therapeutic targets. RESULTS: Serum OPN levels in both patients with active RA and patients with refractory RA were higher than those in healthy controls (HCs). Compared with HCs, the absolute numbers of Th2 cells increased in patients with active RA, while the absolute counts of Th1 and T(reg) cells decreased. There was no significant difference in CD4(+) T subset levels between new-onset and refractory patients. As the condition persisted or deteriorated, a gradual increase in the levels of OPN and gradual declines in the absolute counts of Th1 and T(reg) cells were observed in patients with active RA. The fewest Th1 and T(reg) cells and the highest OPN levels were observed in patients with high disease activity. The serum OPN level was only significantly negatively correlated with the absolute counts of T(reg) cells in the CD4(+) T lymphocyte subsets. CONCLUSIONS: Fewer T(reg) cells with the increase in disease activity may be related to the increased OPN concentration, which may provide new ideas and directions for the targeted immunoregulatory treatment of RA.
35460876 Circ_0088036 mediated progression and inflammation in fibroblast-like synoviocytes of rheu 2022 Apr 20 BACKGROUND: Rheumatoid arthritis (RA) is a common joint disease with abnormal development of human fibroblast-like synoviocytes (HFLS). Circular RNAs (circRNAs) have essential regulation in the disease progression, and this study was to explore the regulatory mechanism of circ_0088036 in RA. METHODS: RNA expression analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. Cell experiments were conducted by Cell Counting Kit-8 assay for cell viability, EdU (5-ethynyl-2'-deoxyuridine) assay for proliferation and flow cytometry for cell cycle or apoptosis. The protein detection was conducted using western blot. Enzyme-linked immunosorbent assay (ELISA) was used to examine the inflammatory cytokines. The binding identification was carried out through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. RESULTS: The level of circ_0088036 RNA was significantly upregulated in sera and in HFLS cells of RA patients. Targeted silencing of circ_0088036 restrained proliferation, cell cycle progression and inflammatory reaction through promoted the apoptosis of HFLS-RA cells via inhibiting the NF-κB pathway. The miR-1263 was identified as a target of circ_0088036. MiR-1263 was found to be down-regulated in sera and in HFLS cells of RA patients. The regulatory effects of circ_0088036 on HFLS-RA cells were attributed to inhibit the miR-1263 level. REL is a susceptibility locus for certain autoimmune diseases. MiR-1263 directly targeted REL, which was discovered to be elevated in sera and HFLS cells of RA patients, and circ_0088036 interacted with miR-1263 to affect REL expression. Functionally, overexpression of miR-1263 suppressed the development of HFLS-RA by blocking the NF-κB pathway, and this phenomenon was reversed by the upregulation of REL. CONCLUSION: These findings suggested that circ_0088036/miR-1263/REL/NF-κB pathway was involved in the functional development of HFLS-RA cells, indicating a novel molecular network in RA progression in vitro.
35364594 The declining incidence of cervical spine surgery in patients with rheumatoid arthritis: a 2022 Apr 1 OBJECTIVE: With an increasing number of disease-modifying drugs available to manage rheumatoid arthritis (RA), spine surgeons have anecdotally noted decreased rates of cervical spine surgical procedures in this population. Although these medications have been shown to mitigate RA progression and its systemic effects on joint destruction, there are currently no large-scale studies of RA patients that suggest the use of these disease-modifying drugs has truly coincided with a decline in cervical spine surgery. METHODS: Patients with RA who underwent cervical spinal fusion from 1998 to 2021 performed by the senior author were retrospectively reviewed. The cohort was stratified into 3 categories based on procedure level: 1) occipitocervical, 2) atlantoaxial, and 3) subaxial. The number of surgical procedures per year in each subgroup was evaluated to determine treatment trends over time. National (Nationwide) Inpatient Sample (NIS) data on both RA and non-RA patients who underwent cervical fusion were analyzed to assess for surgical trends over time and for differences in likelihood of surgical intervention between RA and non-RA patients over the epoch. RESULTS: From 1998 to 2021, the number of overall cervical fusions performed in RA patients significantly declined (-0.13 procedures/year, p = 0.01) in this cohort, despite an overall significant increase in cervical fusions in non-RA patients over the same period. NIS analysis of cervical fusions across all patients similarly demonstrated a significant increase in cervical fusions over the same epoch (19,278 cases/year, p < 0.0001). When normalized for changes in population size, the incidence of new surgical procedures was lower in patients with RA regardless of surgical technique. Anterior cervical fusion was the most common approach used over the epoch in both RA and non-RA patients; correspondingly, RA patients were significantly less likely to undergo anterior cervical fusion (OR 0.655, 95% CI -0.4504 to -0.3972, p < 0.0001). CONCLUSIONS: At the authors' institution, there was a clear decline in the number of cervical fusions performed to treat the 3 most common forms of cervical spine pathology in RA patients (basilar impression, atlantoaxial instability, and subaxial cervical deformity). Although national trends suggest an increase in total cervical fusions in both RA and non-RA patients, the incidence of new procedures in patients with RA was significantly lower than in patients without RA, which supports the anecdotal results of spine surgeons nationally.
35308252 Neoplasm Risk in Patients With Rheumatoid Arthritis Treated With Fostamatinib: A Systemati 2022 Objective: This study aimed to assess neoplasm risk in patients with rheumatoid arthritis (RA) treated with fostamatinib. Methods: Studies were collected from electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that reported neoplasms in patients with RA treated with fostamatinib. Study selection was repeated by two reviewers based on the study selection criteria. Data were collected and methodological quality assessment was performed. Data were pooled using the Peto odds ratio (OR) with a 95% confidence interval (CI). Subgroup analyses of the fostamatinib dose, trial duration, neoplasm nature, and neoplasm-originating systems were conducted. A funnel plot was used to estimate publication bias, and sensitivity analysis was performed to test the robustness of the results. Results: Seven trials involving 4,971 participants showing low to moderate risk of bias were included. Compared with the placebo, fostamatinib use was not associated with the risks of overall neoplasms (Peto OR = 2.62, 95%CI 0.97-7.10), malignant neoplasms (Peto OR = 3.08, 95%CI 0.96-9.91), or benign neoplasms (Peto OR = 1.71, 95%CI 0.26-11.36). Nevertheless, compared with the placebo, a longer duration of fostamatinib use had a higher risk of malignant neoplasms (Peto OR = 4.49, 95%CI 1.03-19.60) at 52 weeks. As for malignant neoplasms in the digestive system, lower doses of fostamatinib reduced the neoplasm risk (100 mg bid vs 150 mg qd: Peto OR = 0.06, 95%CI 0.01-0.59). Sensitivity analysis showed no significant differences in the effective trends, and no publication bias was found. Conclusion: Fostamatinib is not associated with the risks of overall neoplasms as compared to placebo. Nevertheless, a longer duration of fostamatinib use may be associated with a risk of malignant neoplasms and higher doses of fostamatinib may increase malignant neoplasms in the digestive system. Further well-planned cohort studies with a larger study population are needed to elucidate these outcomes. Systematic Review Registration: PROSPERO (CRD42020202121).
35248737 Management of patients with rheumatoid arthritis by telemedicine: connected monitoring. A 2022 Mar 4 OBJECTIVES: Rheumatoid arthritis (RA) is a prevalent and disabling disease that is the source of significant direct and indirect costs. The current recommended therapeutic strategy is based on the rapid introduction of therapy with conventional Disease-Modifying Anti-Rheumatic Drugs (DMARDs) combined with regular disease monitoring by the rheumatologist. The onerous nature of such intense monitoring has motivated the development of new, less demanding strategies such as telemedicine. This study aimed to estimate the cost-effectiveness of the connected monitoring of RA patients initiating a new DMARD therapy versus conventional monitoring. METHODS: An economic evaluation based on a randomized controlled trial of 89 patients was conducted. The patients in the intervention group (n=45) were monitored using a connected monitoring interface on a smartphone, while patients in the control group (n=44) were conventionally monitored. Health outcomes were measured as the gain in quality-adjusted life-years (QALYs), assessed using the EuroQol-5D questionnaire. Resource use and health outcomes were collected alongside the trial and at the six-month follow-up using application data and the related clinical case manager time, visits, hospitalisations, and transport records. These outcomes were valued using externally collected data on unit costs and QALY weights. RESULTS: Compared to conventionally monitored patients, patients receiving connected monitoring had a slightly greater but not significant gain in the average QALY of 0.07. The economic analysis found that connected monitoring resulted in a significant cost reduction of 72€ (2927€ vs. 2999€, P<0.01). The incremental cost-utility ratio of the intervention was equal to -1,029€ per QALY (95% CI: -32,033; +24,625) with a 97.8% chance of being cost-effective at a threshold of 30,000€ per QALY gained. CONCLUSION: Implementing EULAR recommendations for RA patients initiating a DMARD treatment using connected monitoring is more efficient and less expensive than conventional care. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03005925).
35631571 Dexamethasone-Loaded Radially Mesoporous Silica Nanoparticles for Sustained Anti-Inflammat 2022 May 4 Radially mesoporous silica nanoparticles (RMSNs) with protonated amine functionality are proposed to be a dexamethasone (Dex) carrier that could achieve a sustained anti-inflammatory effect in rheumatoid arthritis (RA). High-capacity loading and a sustained release of target drugs were achieved by radially oriented mesopores and surface functionality. The maximum loading efficiency was confirmed to be about 76 wt%, which is about two times greater than that of representative mesopores silica, SBA-15. In addition, Dex-loaded RMSNs allow a sustained-release profile with about 92% of the loaded Dex for 100 h in vitro, resulting in 2.3-fold better delivery efficiency of Dex than that of the SBA-15 over the same period. In vivo evaluation of the inhibitory effects on inflammation in a RA disease rat model showed that, compared with the control groups, the group treated with Dex-loaded RMSNs sustained significant anti-inflammatory effects and recovery of cartilage over a period of 8 weeks. The in vivo effects were confirmed via micro-computed tomography, bone mineral density measurements, and modified Mankin scoring. The proposed Dex-loaded RMSNs prolonged the life of the in vivo concentrations of therapeutic agents and maximized their effect, which should encourage its application.
35655798 Impact of Treat-to-Target Therapy on Bone Mineral Density Loss in Patients With Rheumatoid 2022 BACKGROUND: Osteoporosis is a common comorbidity of rheumatoid arthritis (RA). Although RA disease activity has been demonstrated to be associated with bone loss in previous studies, most of them were cross-sectional studies and not in the context of treat-to-target (T2T) strategies. OBJECTIVES: This study aimed to evaluate the association of disease activity with bone mineral density (BMD) changes in the context of T2T strategies in a prospective RA cohort. METHODS: RA patients were enrolled from a prospective CENTRA cohort of Peking University First Hospital. The follow-ups have been scheduled every 3 to 6 months. BMD was repeated at baseline, 1 year, and then every other year. Demographics, baseline clinical features, laboratory data, and medications at each visit were recorded. Time-adjusted mean disease activity scores were adopted to reflect the overall disease activity during follow-up. The influence of univariable associations between predictors and BMD was investigated using linear regression. RESULTS: A total of 268 patients were included in our analysis. Their mean age was 50 (12.9) years, and 224 (83.6%) were women. The median (IQR) disease duration was 48.7 (107.6) months. Osteoporosis in the lumbar spine was observed in 23.1% of patients and 9.3% in the femoral neck at enrollment. Older age, higher SDAI score, and lower BMI were associated with osteoporosis at baseline. The proportion of patients who achieved DAS28-ESR, CDAI, and SDAI remission or LDA at the end of the first year was 71.5%, 68.8%, and 67.4%, respectively. Reevaluations of BMD at 1 year were applied to 144 patients. Mean decreases of BMDs were 1.75% at the lumbar spine and 1.40% at the femoral neck at 1 year from baseline, respectively. Patients who achieved remission had less yearly bone loss in the lumbar spine (p = 0.036). Female gender was identified as a risk factor in the multiple linear regression analyses, and lower disease activity and bisphosphonates were protective factors of continuous bone loss. CONCLUSION: Disease activity is associated with bone loss in RA patients in the context of T2T strategies, and those who achieved remission had less yearly bone loss.
35506921 Comparison of Teleconsultations and In-Person Consultations from Outpatients with Rheumato 2022 May 3 Introduction: The objectives of this study were to compare the quality-of-care and compliance with medical record regulations between in-person consultations (QIP and CIP) and telephone consultations (QTP and CTP), from rheumatoid arthritis (RA) outpatients, during the COVID-19 pandemic, and to explore the impact of the consultation modality on the treatment. Methods: Data from 324 medical notes corresponding to rheumatic consultations between July and December 2020 were abstracted. Notes were selected considering a stratified (in-person and telephone consultations) random sampling strategy. QIP, CIP, QTP, and CTP were scored based on prespecified criteria as percentages, where higher numbers translated into better standards. Logistic regression analysis investigated the association between the consultation modality and the treatment recommendation (dependent variable). Results: There were 208 (64.2%) medical notes related to in-person consultations and 114 (35.2%) to telephone consultations. Overall, medical notes corresponded to middle-aged women with long-standing disease. QIP was superior to QTP (median, interquartile range): 60% (60-75%) versus 50% (25-60%), p ≤ 0.001, and differences were related to disease activity and prognosis documentation (81.3% vs. 34.5% and 55.8% vs. 33.6%, respectively, p ≤ 0.001) and the prolonged prescription of glucocorticoids with a documented management plan (58.5% vs. 30.4%, p = 0.045). Meanwhile, CIP and CTP were similar. Telephone consultation was a significant risk factor for no changes in the treatment recommendation (odds ratio: 2.113, 95% confidence interval: 1.284-3.479, p = 0.003), and results were consistent in the 142 medical notes with documented absence of disease activity. Conclusions: In the clinical context of RA, the quality-of-care provided by telephone consultations is below the standard of care and impacts the treatment.
35462874 RNA Editing-Associated Post-Transcriptional Gene Regulation in Rheumatoid Arthritis. 2022 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic inflammation of joints. The observed complexity of RA pathogenesis and studies that have been carried out so far indicate that RA pathogenesis is regulated at multiple levels. Given the role of RNA editing in autoimmune disease, we hypothesised that RNA editing could contribute to RA pathogenesis by regulating gene expression through post-transcriptional mechanisms. METHODS: We identified RNA editing events in synovial tissues from early and established RA compared with normal subjects from an available transcriptome data set using REDItools. To investigate the potential effect of these RNA editing events on gene expression, we carried out an analysis of differential exon usage in the vicinity of the differentially edited sites using DEXSeq. We then used STRING to identify putative interactions between differentially edited genes identified from REDItools analysis. We also investigated the possible effects of these RNA editing events on miRNA-target mRNA interactions as predicted by miRanda. RESULTS: Our analysis revealed that there is extensive RNA editing in RA, with 304 and 273 differentially edited events in early RA and established RA, respectively. Of these, 25 sites were within 11 genes in early RA, and 34 sites were within 7 genes in established RA. DEXSeq analysis revealed that RNA editing correlated with differential exon usage in 4 differentially edited genes that have previously also been associated with RA in some measure: ATM, ZEB1, ANXA4, and TIMP3. DEXSeq analysis also revealed enrichment of some non-functional isoforms of these genes, perhaps at the expense of their full-length counterparts. Network analysis using STRING showed that several edited genes were part of the p53 protein-protein interaction network. We also identified several putative miRNA binding sites in the differentially edited genes that were lost upon editing. CONCLUSIONS: Our results suggested that the expression of genes involved in DNA repair and cell cycle, including ATM and ZEB1 which are well-known functional regulators of the DNA damage response pathway, could be regulated by RNA editing in RA synovia. This may contribute to an impaired DNA damage response in synovial tissues.
35407647 Association between Androgen Deprivation Therapy and the Risk of Inflammatory Rheumatic Di 2022 Apr 5 BACKGROUND: The aim of this study was to assess the association between androgen deprivation therapy (ADT) and the risk of inflammatory rheumatic diseases in men with prostate cancer. METHODS: Patients with prostate cancer between 2012 and 2016 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database, on the basis of rheumatic diseases diagnoses and information on prescriptions for androgen deprivation therapy. Cox proportional hazard models were used to estimate hazard ratios (HR) to compare the risks of rheumatic diseases caused by androgen deprivation therapy exposure in groups of prostate cancer patients. RESULTS: A total of 12,505 prostate cancer patients were included in this study, out of whom 3070 were ADT users and 9390 were ADT non-users. We observed a higher risk of rheumatic diseases in the cohort of prostate cancer patients treated with ADT compared with ADT non-users (HR 1.55, 95% confidence interval (CI) 1.01-2.28). Detailed risk by cumulative use of ADT was performed for rheumatoid arthritis, and a statistically significant higher risk was found in the group with longest cumulative ADT exposure (>105 weeks) (HR 3.18, 95% CI 1.39-7.29). CONCLUSIONS: Our study suggests that ADT usage could be associated with increased risk of rheumatoid arthritis, adding to the many known side effects of ADT.