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ID PMID Title PublicationDate abstract
33159950 Changes in serum citrullinated fibrinogen concentration associated with the phase of bacte 2021 Jan BACKGROUND: Citrullinated fibrinogen (C-Fbg) has been detected in rheumatoid arthritis; however, few studies have reported the role of C-Fbg in other inflammatory diseases. This study aimed to clarify the changes in serum C-Fbg associated with the bacteremia phase. METHODS: We measured serum C-Fbg concentration in bacteremia patients. C-Fbg levels at each phase of bacteremia, classified by white blood cell (WBC) count and neutrophil left shift change, were compared with those of healthy control (HC). The correlation between C-Fbg concentration and certain inflammatory markers, or citrullinated histone H3 concentration was assessed. Multiple linear regression (MLR) analysis was used to examine the association of log C-Fbg with certain inflammatory markers. RESULT: Serum C-Fbg levels were significantly higher in bacteremia patients than in HC (p < 0.001) and positively correlated with WBC and neutrophil count. Further, C-Fbg levels were significantly higher in phases III and IV of bacteremia than in HC (p < 0.001). MLR analysis indicated that log C-Fbg had a stronger relationship with log neutrophil counts than other certain inflammatory markers (p < 0.01). CONCLUSION: Serum C-Fbg levels increased in bacteremia patients, and this was consistent with an influx of neutrophils into the blood stream in accordance with the bacteremia phase.
34390826 Synthesis, activity and mechanism for double-ring conjugated enones. 2021 Oct 1 The relationship between TLR4 and inflammation-related diseases has been paid more and more attention. The studies have shown that TLR4/NF-κB signaling pathway plays an important role in the transmission of inflammatory signals. A large number of pro-inflammatory factors, chemokines, adhesion factors, TLR4 and its ligands interact with each other, and jointly promote the development of diseases. In this work, 8 target compounds were synthesized to screen the inhibitory activity of TLR4 in vitro. The results of TLR4 inhibition test in vitro showed that the double-ring conjugated enones had a good inhibitory activity, and the IC(50) value of compound 4f was 0.56 ± 0.10 μM, and it was superior to the positive control methotrexate. To further study the anti-inflammatory effect and mechanism of double-ring conjugated enones by using LPS induced rat synovial cell inflammation model. The results of the mechanism test showed that compound 4f could effectively promote the apoptosis of rat synovial cells, and the mechanism might be related to the up-regulation of the expression of apoptosis-related protein Caspase-3. In addition, compound 4f could significantly inhibit the increase of inflammatory factors TNF-α, IL-1β and IL-6 in rat synovial cells induced by LPS, showing a good anti-inflammatory activity. In the TLR4/NF-κB signaling pathway test of rat synovial cells, compound 4f can effectively regulate the expression levels of TLR4, MyD88, NF-κB and IκB related proteins in TLR4/NF-κB signaling pathway, which may be due to its inhibition of LPS-induced inflammation in rat synovial cells. At the same time, it inhibits the abnormal proliferation of cells and its important mechanism promoted of apoptosis.
34106665 Determinants of first-line biological treatment in patients with rheumatoid arthritis: Res 2021 May 14 Guidelines for the treatment of rheumatoid arthritis (RA) recommend the use of conventional synthetic disease modifying anti-rheumatic drugs (cs-DMARDs) at the onset of the disease and only in the case of therapeutic failure, the addition of a biological drug (b-DMARD) is suggested.The study aimed to evaluate determinants for first-line biological treatment in patients with RA in clinical practice.A cohort of patients with RA, resident in Lazio, a central Italian Region, where Rome is located, and with at least one disease modifying anti-rheumatic drugs (DMARD) prescription between 2010 and 2016 was selected using health information systems linkable with each other by an individual unique anonymous identifier. In particular RA cohort was defined retrieving all patients with at least a RA disease code in regional data claims (hospital discharge, exemption code, emergency department access, or therapeutic plan). Only new users were included and the first-line treatment was identified: cs-DMARD or b-DMARD.Descriptive analysis according to type of DMARD treatment was performed. Through multivariate logistic regression models (odds ratio [OR]; confidence interval [CI95%]) determinants of therapy such as age, comorbidity, and comedication were investigated.Finally, switching during the first year of treatment from cs-DAMARDs to b-DMARDs was analyzed.DMARD-new users with RA were 5641; 7.1% of them with b-DMARD as first-line treatment. Considering the year of dispensing, this percentage ranged from 4.9% (2011) to 8.2% (2015). Among cs-DMARD the most prescribed active agent was methotrexate (59.3%), while among b-DMARD it was etarnecept (37.0%), followed by adalimumab (21.2%). The average age of the cohort was 54 years with 77% of women. Determinants of first-line b-DMARD use were: age (OR<30vs>65 = 3.7; 2.6-5.2, OR[30-45)vs>65 = 1.7; 1.2-2.4, OR[45-55)vs>65 = 1.6; 1.1-2.4, OR[55-65)vs>65 = 1.2; 0.8-1.7), cancers (OR = 2.3; 1.3-4.2), cardio-cerebrovascular disease (OR = 1.4; 1.0-1.9), use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR = 0.6; 0.4-0.7) and corticosteroids (OR = 0.6; 0.5-0.7) in the 6 months preceding diagnosis.In the first year of treatment, we observed a percentage of switch from cs-DMARDs to b-DMARDs of 7.9%.In clinical practice, about 7% of patients with RA are prescribed with a b-DMARD as first-line treatment. This therapeutic option, even if not supported by guide lines, is mostly link to younger age and clinical profile of the patients.
33497394 Potential applicability of cytokines as biomarkers of disease activity in rheumatoid arthr 2021 Biomarkers play a pivotal role in the management of rheumatoid arthritis (RA) by facilitating early diagnosis and 'treat to the target.' However, no gold standard biomarker has been identified for monitoring the disease activity in RA. Cytokines, a diverse group of small protein molecules secreted by peripheral blood mononuclear cells (PBMCs), play a pivotal role in pathogenesis and disease progression in RA. Research is currently underway to find out the applicability of cytokines as biomarkers in RA. This study aimed to quantify the PBMCs that secrete four types of cytokines; TNF-α, IL-1β, IL-10 and IL-17A in two cohorts of active RA patients (early RA patients and established RA patients), compared to healthy controls (HC), using the enzyme-linked immunosorbent spot (ELISPOT) assay, and to assess their association with measures of disease activity of RA. Patients were recruited from outpatient rheumatology clinics, and the disease activity was assessed using single and composite measures of disease activity. The cytokine expression was evaluated using freshly separated PBMCs from whole blood of RA patients using the ELISPOT assay. The number of PBMCs (counted as spot-forming cells (SFCs) per 105 PBMCs) that secreted the cytokine of interest were statistically significantly higher in early RA patients, compared to HC, for IL-17A (P<0.05). Such an increased number of SFCs was not observed in the established RA group, compared to controls, for any of the cytokines tested. The correlation analysis showed that IL-17A is having a moderate correlation (Spearman`s ρ, p <0.05) with five clinical measures of disease activity, including disease activity score 28 (DAS28). According to the multivariable linear regression models, IL17A was a good predictor of both the disease activity score 28 (DAS28) and clinical disease activity index (CDAI). In conclusion, IL-17A has potential applicability as a biomarker of disease activity of RA.
34321218 Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, tar 2022 Jan OBJECTIVE: To compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication. RESULTS: Data of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs. CONCLUSION: Our results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.
33515115 Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arth 2021 Jul OBJECTIVES: The aim of this multicenter, retrospective study was to clarify the retention rates of sarilumab (SAR), baricitinib (BAR), and tofacitinib (TOF) in patients with rheumatoid arthritis (RA). METHODS: Patients treated with either SAR (n = 62), BAR (n = 166), or TOF (n = 185) (females, 80.9%; age, 61.0 years; disease duration, 11.1 years; rheumatoid factor positivity, 84.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone dose, 5.3 mg/day [47.0%] and methotrexate dose, 8.8 mg/week [58.4%]; biologics- or Janus kinase inhibitors-switched cases 78.4%) were included. The reasons for drug discontinuation were classified into 4 major categories (lack of effectiveness, toxic adverse events, non-toxic reasons, and remission) by each attending physician. The drug retention rate was estimated at 18 months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling. RESULTS: The discontinuation rates of SAR, BAR, and TOF for the corresponding reasons were as follows, respectively: lack of effectiveness (15.7%, 15.6%, and 21.5%; P = 0.84), toxic adverse events (15.8%, 12.1%, and 12.3%; P = 0.35), non-toxic reasons (10.9%, 7.7%, and 6.8%; P = 0.35), and remission (0.0%, 2.8%, and 0.0%; P = 1.0). The overall retention rates excluding non-toxic reasons and remission were as follows: 68.8% for SAR, 72.5% for BAR, and 66.7% for TOF (P = 0.54). CONCLUSIONS: After adjustment by potent confounders, SAR, BAR, and TOF showed similar discontinuation rates due to lack of effectiveness and toxic adverse events. Key Points • This is the first retrospective multicenter study that aimed to clarify the retention rates and reasons for discontinuation of SAR, BAR, and TOF in patients with RA.
33547777 Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort s 2021 Oct 2 OBJECTIVE: To assess the relationships between female hormonal exposures and risk of RA in a prospective cohort of French women. METHODS: E3N (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l'Education Nationale) is an on-going French prospective cohort that included 98 995 women aged 40-65 years in 1990. Every 2-3 years, women completed mailed questionnaires on their lifestyles, reproductive factors and health conditions. Cox proportional hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% CIs were estimated. Effect modification by smoking history was investigated. RESULTS: A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (<22 vs ≥27 years; HR = 1.34; 95% CI 1.0, 1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95% CI 1.0, 1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95% CI 1.0, 2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95% CI 0.2, 0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (>24 vs 0 months; multi-adjusted HR = 0.77; 95% CI 0.6, 0.9). CONCLUSIONS: These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.
34766540 Targeted therapy of rheumatoid arthritis via macrophage repolarization. 2021 Dec The polarization of macrophages plays a critical role in the physiological and pathological progression of rheumatoid arthritis (RA). Activated M1 macrophages overexpress folate receptors in arthritic joints. Hence, we developed folic acid (FA)-modified liposomes (FA-Lips) to encapsulate triptolide (TP) (FA-Lips/TP) for the targeted therapy of RA. FA-Lips exhibited significantly higher internalization efficiency in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than liposomes (Lips) in the absence of folate. Next, an adjuvant-induced arthritis (AIA) rat model was established to explore the biodistribution profiles of FA-Lips which showed markedly selective accumulation in inflammatory paws. Moreover, FA-Lips/TP exhibited greatly improved therapeutic efficacy and low toxicity in AIA rats by targeting M1 macrophages and repolarizing macrophages from M1 to M2 subtypes. Overall, a safe FA-modified liposomal delivery system encapsulating TP was shown to achieve inflammation-targeted therapy against RA via macrophage repolarization.
34290503 Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Rena 2021 BACKGROUND: Tacrolimus (TAC) is a powerful immunosuppressive agent whose therapeutic applicability is confined owing to its systemic side effects. OBJECTIVE: Herein, we harnessed a natural polymer based bioconjugate composed of maltodextrin and α-tocopherol (MD-α-TOC) to encapsulate TAC as an attempt to overcome its biological limitations while enhancing its therapeutic anti-rheumatic efficacy. METHODS: The designed TAC loaded maltodextrin-α-tocopherol nano-micelles (TAC@MD-α-TOC) were assessed for their physical properties, safety, toxicological behavior, their ability to combat arthritis and assist bone/cartilage formation. RESULTS: In vitro cell viability assay revealed enhanced safety profile of optimized TAC@MD-α-TOC with 1.6- to 2-fold increase in Vero cells viability compared with free TAC. Subacute toxicity study demonstrated a diminished nephro- and hepato-toxicity accompanied with optimized TAC@MD-α-TOC. TAC@MD-α-TOC also showed significantly enhanced anti-arthritic activity compared with free TAC, as reflected by improved clinical scores and decreased IL-6 and TNF-α levels in serum and synovial fluids. Unique bone formation criteria were proved with TAC@MD-α-TOC by elevated serum and synovial fluid levels of osteocalcin and osteopontin mRNA and proteins expression. Chondrogenic differentiation abilities of TAC@MD-α-TOC were proved by increased serum and synovial fluid levels of SOX9 mRNA and protein expression. CONCLUSION: Overall, our designed bioconjugate micelles offered an excellent approach for improved TAC safety profile with enhanced anti-arthritic activity and unique bone formation characteristics.
34030721 Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD). 2021 May 24 BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4(+) plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements. METHODS: Serum samples were collected from untreated 59 patients with IgG4-RD, 13 patients with rheumatoid arthritis, and 37 healthy controls (HCs). HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within 7 days. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical phenotypes of IgG4-RD. RESULTS: In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between the serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements, although both Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy. CONCLUSION: Serum levels of Gal-9 and sTIM-3 were significantly elevated in untreated patients with IgG4-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.
32719038 Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour 2021 Jan OBJECTIVES: This study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice. METHODS: Data were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding. RESULTS: There were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant. CONCLUSIONS: The findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.
34567013 Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs 2021 Artemisinin and its derivatives (ARTs) are known as conventional antimalarial drugs with clinical safety and efficacy. Youyou Tu was awarded a Nobel Prize in Physiology and Medicine due to her discovery of artemisinin and its therapeutic effects on malaria. Apart from antimalarial effects, mounting evidence has demonstrated that ARTs exert therapeutic effects on inflammation and autoimmune disorders because of their anti-inflammatory and immunoregulatory properties. In this aspect, tremendous progress has been made during the past five to seven years. Therefore, the present review summarizes recent studies that have explored the anti-inflammatory and immunomodulatory effects of ARTs on autoimmune diseases and transplant rejection. In this review, we also discuss the cellular and molecular mechanisms underlying the immunomodulatory effects of ARTs. Recent preclinical studies will help lay the groundwork for clinical trials using ARTs to treat various immune-based disorders, especially autoimmune diseases.
33667301 Patients with rheumatoid arthritis have impaired long-term outcomes after myocardial infar 2021 Nov 3 OBJECTIVE: To investigate the long-term outcomes of patients with RA after myocardial infarction (MI). METHODS: All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients' outcomes were also studied. The median follow-up was 7.3 years. RESULTS: RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P <0.0001]. Patients with RA were at higher risk of new MI (HR 1.22; CI: 1.09, 1.36; P =0.0001) and revascularization (HR 1.28; CI: 1.10, 1.49; P =0.002) after discharge from index MI. Cumulative stroke rate after MI did not differ between RA and non-RA patients (P =0.322). RA duration and corticosteroid usage before MI, but not use of methotrexate or biologic antirheumatic drugs, were independently associated with higher mortality (P <0.001) and new MI (P =0.009). A higher dosage of corticosteroids prior to MI was independently associated with higher long-term mortality (P =0.002) and methotrexate usage with lower stroke rate (P =0.034). Serological status of RA was not associated with outcomes. CONCLUSION: RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.
33535700 Factor XIII-A in Diseases: Role Beyond Blood Coagulation. 2021 Feb 1 Multidisciplinary research from the last few decades has revealed that Factor XIII subunit A (FXIII-A) is not only involved in blood coagulation, but may have roles in various diseases. Here, we aim to summarize data from studies involving patients with mutations in the F13A1 gene, performed in FXIII-A knock-out mice models, clinical and histological studies assessing correlations between diseases severity and FXIII-A levels, as well as from in vitro experiments. By providing a complex overview on its possible role in wound healing, chronic inflammatory bowel diseases, athe-rosclerosis, rheumatoid arthritis, chronic inflammatory lung diseases, chronic rhinosinusitis, solid tumors, hematological malignancies, and obesity, we also demonstrate how the field evolved from using FXIII-A as a marker to accept and understand its active role in inflammatory and malignant diseases.
33945907 Efficacy of home-based physical activity interventions in patients with autoimmune rheumat 2021 Jun INTRODUCTION: Physical activity (PA) has been receiving increasing interest in recent years as an adjuvant therapy for autoimmune rheumatic disease (ARDs), but there is scarce information about the efficacy of home-based PA for patients with ARDs. OBJECTIVE: To perform a systematic review and meta-analysis on the efficacy of home-based physical activity (PA) interventions in improving health-related quality of life, functional capacity, pain, and disease activity in patients with ARDs. METHODS: Searches were performed in PubMed, Web of Science, Scopus, Cochrane, CINAHL database and Sport Discus. Trials were considered eligible if they included a home-based physical activity intervention. The population included adults with autoimmune rheumatic diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis and ankylosing spondylitis), comparisons included non-physical activity control or centre-based interventions (i.e., interventions performed on a specialized exercise centre) and the outcomes were quality of life, pain, functional capacity, disease activity and inflammation. RESULTS: Home-based physical activity improved quality of life (p<0.01; g = 0.69; IC95%, 0.61 to 1.07) and functional capacity (p = 0.04; g = - 0.51; IC95%, -0.86; -0.16), and reduced disease activity (p = 0.03; g = - 0.60; IC95%, -1.16; -0.04) and pain (p = 0.01; g = -1.62; IC95%, -2.94 to -0.31) compared to the non-physical activity control condition. Additionally, home-based physical activity interventions were as effective as centre-based interventions for all investigated outcomes. CONCLUSION: Home-based PA is an efficacious strategy to improve disease control and aleviate symptoms in ARD.
34521672 Evaluating associations of joint swelling, joint stiffness and joint pain with physical ac 2021 Sep 14 OBJECTIVE: Physical activity (PA) in preclinical rheumatoid arthritis (RA) is associated with lower RA risk and disease severity. As joint signs and symptoms of inflammatory arthritis serve as a barrier to PA in RA, it is important to consider whether they affect PA in the time prior to RA. Therefore, we investigated whether joint swelling, stiffness or pain were associated with PA in first-degree relatives (FDRs) of patients with RA, a population at higher risk for future RA. DESIGN: Prospective study design. SETTING: We recruited FDRs of patients with RA from academic centres, Veterans' hospitals and rheumatology clinics or through responses to advertising from six sites across the USA. PARTICIPANTS: We evaluated associations of joint stiffness, joint swelling and joint pain with PA time in 268 FDRs with ≥2 visits over an average 1.2 years. Clinicians confirmed joint swelling. Participants self-reported joint stiffness and/or pain. PRIMARY OUTCOME MEASURES: PA during a typical 24-hour day was quantified via questionnaire, weighted to reflect metabolic expenditure, where 24 hours was the minimum PA time. Linear mixed models evaluated associations between symptoms and change in PA over time, adjusting for age, sex, race, body mass index, smoking and RA-related autoantibodies. RESULTS: Average weighted PA time was 37±7 hours. In the cross-sectional analysis, PA time was 1.3±0.9 hours higher in FDRs reporting joint pain (p=0.15); and 0.8±1.6 and 0.4±1 hours lower in FDRs with joint swelling (p=0.60) and stiffness (p=0.69), respectively. Longitudinally, adjusting for baseline PA time, baseline symptoms were not significantly associated with changes in PA time. However, on average over time, joint stiffness and pain were associated with lower PA time (p(interaction)=0.0002, p(interaction)=0.002), and joint swelling was associated with higher PA time (p(interaction) <0.0001). CONCLUSION: Baseline symptoms did not predict future PA time, but on average over time, joint symptoms influenced PA time.
33934647 Two-year RSA migration results of symmetrical and asymmetrical tibial components in total 2021 May AIMS: The objective of this study was to compare the two-year migration pattern and clinical outcomes of a total knee arthroplasty (TKA) with an asymmetrical tibial design (Persona PS) and a well-proven TKA with a symmetrical tibial design (NexGen LPS). METHODS: A randomized controlled radiostereometric analysis (RSA) trial was conducted including 75 cemented posterior-stabilized TKAs. Implant migration was measured with RSA. Maximum total point motion (MTPM), translations, rotations, clinical outcomes, and patient-reported outcome measures (PROMs) were assessed at one week postoperatively and at three, six, 12, and 24 months postoperatively. RESULTS: A linear mixed-effect model using RSA data of 31 asymmetrical and 38 symmetrical TKAs did not show a difference in mean MTPM migration pattern of the tibial or femoral components. Mean tibial component MTPM at two years postoperative of the asymmetrical TKA design was 0.93 mm and 1.00 mm for the symmetrical design. For the femoral component these values were 1.04 mm and 1.14 mm, respectively. No significant differences were observed in other migration parameters or in clinical and PROM measurements. CONCLUSION: The TKA design with an asymmetrical tibial component has comparable component migration with the proven TKA with a symmetrical tibial component. This suggests the risk of long-term aseptic loosening of the two designs is comparable. Cite this article: Bone Joint J 2021;103-B(5):855-863.
33844448 Notch-1 and Notch-3 Mediate Hypoxia-Induced Activation of Synovial Fibroblasts in Rheumato 2021 Oct OBJECTIVE: To investigate the molecular mechanism of hypoxia-induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch-1 and Notch-3 signaling, and to evaluate its potential as a therapeutic target. METHODS: Expression of Notch-1 intracellular domain (N1ICD), N3ICD, and hypoxia-inducible factor 1α (HIF-1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen-induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. RESULTS: N1ICD, N3ICD, and HIF-1α were expressed abundantly in the synovial tissue of RA patients. HIF-1α was shown to directly regulate the expression of Notch-1 and Notch-3 genes under hypoxic conditions. Moreover, hypoxia-induced N1ICD and N3ICD expression in RASFs was blocked by HIF-1α siRNA. Notch-1 siRNA and Notch-3 siRNA inhibited hypoxia-induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch-1 was shown to regulate RASF migration and epithelial-mesenchymal transition under hypoxic conditions, whereas Notch-3 was shown to regulate the processes of anti-apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. CONCLUSION: This study identified a functional link between HIF-1α, Notch-1, and Notch-3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.
34653827 Investigation of the relationship between periodontal and systemic inflammation in childre 2022 Jan Periodontal diseases are chronic inflammatory diseases and tissue destruction increases with oxidative stress in periodontal tissues. Periodontal diseases are associated with systemic diseases such as diabetes, cardio-vascular diseases and rheumatoid arthritis by means of systemic inflammation. Sickle cell disease (SCD) is a chronic inflammatory disease in which vaso-occlusive crisis and endothelial dysfunction are present. It is not known whether the chronic systemic inflammation seen in SCD affect periodontal tissues. The aim of this study was to investigate the relationship between periodontal and systemic inflammation in children with SCD. Forty-three children with SCD and 43 healthy children were included in the study. Physical, dental and periodontal statuses were examined, blood and saliva samples were taken. Levels of pro-inflammatory and oxidative stress mediators in serum and saliva were evaluated. The periodontal findings of the groups were similar. The majority of the subjects in both groups had gingival inflammation. In SCD group, significantly higher serum high sensitive C-reactive protein (Hs-CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, total oxidant status (TOS), nitric oxide (NO) and salivary IL-6 were observed (p < 0.05). There were positive correlations between salivary IL-6 levels and serum Hs-CRP levels (r = 0.303, p < 0.05). In addition; it was determined that salivary IL-6, TNF-α and NO levels were increased 3-6 times in children with a history of painful crisis or acute chest syndrome compared to children who had never had a painful crisis or acute chest syndrome. Although, observed oral health status was similar in both groups, salivary cytokine levels were increased in children with SCD. The higher salivary cytokine levels may be associated with chronic systemic inflammation and vaso-occlusion observed in children with SCD.
34381453 Autonomic Nervous System Dysfunction in Primary Sjögren's Syndrome. 2021 Primary Sjögren's syndrome (pSS) is an autoimmune disease which primarily affects the exocrine glands, but can also affect other organs, including the nervous system. Many studies have reported evidence of autonomic nervous system (ANS) dysfunction in pSS which may contribute to a wide range of symptoms and functional burden. Symptoms of ANS dysfunction are common and widespread among patients with pSS and are associated with other features of the disease, particularly fatigue. Accumulating data on the inter-relationship between the ANS and the immune system via the vagus nerve have been reported. Vagus nerve stimulation (VNS) has also been associated with improvement in fatigue in patients with pSS. Taken together, these data suggest that the ANS may be a potential treatment target for pSS, in particularly those with fatigue being a predominant symptom. Future research to dissect the link between the ANS, immune dysregulation and clinical manifestations in pSS and to evaluate the potential of VNS as a therapy for pSS is warranted.