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ID PMID Title PublicationDate abstract
33912249 Concomitant beta-blocker use is associated with a reduced rate of remission in patients wi 2021 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/- conventional synthetic (cs-) DMARD therapy. METHODS: Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted. RESULTS: Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57-0.87, p = 0.001] and CVD cohort [adjusted HR 0.72 (0.57-0.90, p = 0.005)]. The association was consistent between trials (interaction p = 0.44) and treatment arms (interaction p = 0.06). No significant association between remission and β1-receptor selectivity was identified (p = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed. CONCLUSION: In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.
33693010 The Relationship of Acupuncture Use to the Endometriosis Risk in Females With Rheumatoid A 2020 Objectives: Women affected by rheumatoid arthritis (RA) have a higher risk of endometriosis, an estrogen-dependent, chronic inflammatory disease. Though acupuncture has long been a safe and effective therapy for treating inflammatory conditions, it is unclear whether it could prevent the onset of endometriosis. This study aims to determine the effect of acupuncture on the subsequent risk of endometriosis in female RA patients. Methods: Between 1998 and 2010, female subjects with RA were recruited from a nationwide database (5,736 patients; age ≥20 years). Enrolled patients included 2,407 acupuncture users and 2,407 nonusers randomly selected using propensity scores. The occurrence of endometriosis was recorded through the end of 2012. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (HR) associated with acupuncture use. Results: During the follow-up period, 35 acupuncture users and 94 non-users developed endometriosis, with incidence rates of 2.36 and 4.91 per 1,000 person-years, respectively. Acupuncture use was associated with a 55% lower endometriosis risk (adjusted HR, 0.45; 95% confidence interval, 0.31-0.65). Those who received high intensity acupuncture (≥15 packages) had the greatest benefit. Conclusions: Findings suggest that adding acupuncture to conventional therapy may decrease the subsequent endometriosis risk in female RA patients. Prospective randomized trials are recommended to further clarify whether the association revealed in this study supports a causal link.
34778416 Improvements in High-Density Lipoprotein Quantity and Quality Contribute to the Cardiovasc 2021 Objective: Inflammation plays important role in atherosclerotic cardiovascular diseases (CVDs), but the interaction between the inflammation and lipid profile is largely unrevealed in humans. Patients with rheumatoid arthritis (RA) suffer from a higher risk of CVDs. Decreased total cholesterol (TC) and high-density lipoprotein (HDL) were prevalent in patients with RA. Anti-tumor necrosis factor (TNF) therapies relieve disease activity and decrease CVDs risk in RA, but their comprehensive effects on the lipid profile are unclear. This study aims to investigate the changes in blood lipid profile along time in the patients with RA accepting anti-TNF therapies by meta-analysis. Methods: The MEDLINE, the Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible literature. Data of lipids were classified into short-, mid-, and long-term according to treatment duration. Meta-analyses were performed to compare the lipid levels before and after treatments. Results: A total of 44 records and 3,935 patients were included in the meta-analyses. Anti-TNF therapies were associated with significant increase in TC [mean difference (MD): +0.14, +0.23, and +0.26 mmol/l, respectively] and HDL (MD): +0.11, +0.12, and +0.11 mmol/l, respectively) in the short-, mid-, and long-term; anti-TNF therapies were associated with increased low-density lipoprotein (LDL) (MD: +0.06 mmol/l) and apolipoprotein A1 (ApoA1) (MD: +0.07 g/l) in the short-term, but not in the mid-term and long-term; triglyceride (TG) and apolipoprotein B (ApoB) do not change significantly in all the periods; proatherosclerotic indexes (TC/HDL, ApoB/ApoA1, and LDL/HDL) tend to decrease in the short- and mid-term, but return to baseline in the long-term after TNF inhibition. Conclusion: Anti-TNF therapies were related to a long-term raised HDL level, which, together with evidence of improved HDL function, may contribute partially to the decreased CVDs risk by TNF inhibition.
34737606 Transthyretin and Receptor for Advanced Glycation End Product's Differential Levels Associ 2021 OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory joint disease. The identification of multifaceted etiological changes at the protein level in RA remains an important need. We aimed to identify differential proteins (DPs) and gene profiles to uncover inflammatory indicators and their association to RA pathogenesis. METHODS: 2-DE and SWATH-MS were used to identify DPs in RA and healthy control plasma. Fluorescence phenylboronate gel electrophoresis (Flu-PAGE) with mass spectrometry was used for protein glycation in RA plasma. Disease specificity of identified DPs was confirmed by ELISA and Western blot analysis. The gene expressions of selected DPs were evaluated by qRT-PCR in PBMCs of RA, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), and osteoarthritis (OA). The functional implication of glycated protein was determined by in- silico and validated by in vitro analysis in fibroblast-like synoviocytes. RESULTS: A total of 150 DPs (127 increased and 23 decreased) were identified by 2-DE and SWATH-MS analysis in RA plasma compared to healthy control (HC). Nine proteins were identified as glycated by Flu-PAGE LC-MS/MS. Transthyretin (TTR), serotransferrin, and apolipoprotein-A1 (Apo-A1) were found to be differential and glycated. ELISA and Western blot results revealed the disease-specific increased expression of TTR and RAGE in RA. The qRT-PCR results signify the aberrant gene expression of TTR and RAGE, found to be associated with RA when compared with SLE, SpA, and OA PBMCs. TTR-RAGE interactions were predicted by in-silico and validated by in- vitro analysis using RA-FLS. The increased levels of pro-inflammatory cytokines IL-6, IL-1β, TNF-α, and differently expressed TTR and RAGE were confirmed in fibroblast-like synoviocytes under inflammatory conditions. CONCLUSION: Our findings showed that the level of TTR was increased in RA plasma, along with an altered glycation rate. TTR and RAGE aberrant gene expression in PBMCs are the key events associated with RA, and TNF-α activates the NF-KB pathways and promote TTR and RAGE differential expressions that may have pathogenic/inflammatory significance.
34631048 Diagnostic role of lncRNA GAS5 and its genetic polymorphisms rs2067079, rs6790 and rs17359 2021 Nov The aim of the present study was to detect the serum levels of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in patients with rheumatoid arthritis (RA) and healthy controls, and determine the association between the rs2067079, rs6790, and rs17359906 single-nucleotide polymorphisms (SNPs) of lncRNA GAS5 gene with RA risk in the Egyptian population. Reverse transcription-quantitative PCR and real-time PCR were used to measure the serum levels of lncRNA GAS5 and genotype the two distinct alleles at the SNP sites of lncRNA GAS5 gene in 200 patients with RA and 150 controls. The mean serum levels of lncRNA GAS5 were significantly lower in the patients with RA compared with the controls (P<0.0001), and the serum levels of lncRNA GAS5 were significantly negatively associated with erythrocyte sedimentation rate, C-reactive protein levels and anti-cyclic citrullinated peptide levels in the patients with RA. The TT genotype of rs2067079 SNP was significantly associated with a decreased risk of RA [TT vs. CC: Odds ratio (OR)=2.358; 95% confidence interval (CI), 1.114-5.131; P=0.045) and the risk of rs2067079 SNP reduced with a recessive pattern (TT vs. TC + CC: OR=2.374; 95% CI, 1.091-5.123; P=0.037). rs6790 SNP was associated with RA risk in the recessive model (AA vs. GA + GG: OR=2.55; 95% CI=1.39-5.32; P=0.02). No significant associations were noted between the rs17359906 SNP and RA risk (P>0.05) or between the lncRNA GAS5 levels and their respective genotypes at the three SNPs in patients with RA (all P>0.05). Based on the results of the present study, lncRNA GAS5 may serve as a biomarker for the early detection of RA. The TT genotype of rs2067079 SNP was significantly associated with a decreased risk of RA, and a reduced risk of rs2067079 SNP was observed with a recessive pattern. rs6790 SNP was associated with RA risk in the recessive model.
34234419 Cross-Cultural Validation of the 5-Item Compliance Questionnaire for Rheumatology to the A 2021 PURPOSE: A simple measure to assess drug adherence in Saudi patients with rheumatoid arthritis (RA) is required. The aim of this study was to translate and validate the 5-Item Compliance Questionnaire for Rheumatology (CQR5) into Arabic. PATIENTS AND METHODS: The questionnaire was translated and culturally adapted to Arab patients in six steps: initial translation, synthesis of the translation, back translation, expert committee review, test of the pre-final version, and development of the Arabic CQR5 (ACQR-5). The resulting version was tested for validity in patients with RA. RESULTS: A total of 103 adult patients with RA were recruited from rheumatology clinics at a university hospital in Riyadh, Saudi Arabia. After extensive translation, the final tool (CQR) was piloted in 15 patients. The final validation was performed with 88 patients. Of these, 80 (90.9%) were female and 43.2% were seropositive. The mean (±SD) age and disease duration were 50 (±13) and 11.4 (±8.2) years, respectively. Cronbach's alpha reliability was 0.886, and the Kaiser-Meyer-Olkin measure of sampling adequacy for factor analysis was 0.870 (p<0.001). The mean ACQR-5 was 17.78 (2.70), with 14 (15.9%) classified as low adherents and the remaining 74 (84.1%) as high adherents. Binary logistic regression revealed that increasing age (odds ratio [OR] 1.082, 95% confidence interval [CI]: 1.025-1.142, p=0.005) and a trend toward the presence of other comorbidities (OR 3.111, 95% CI: 0.961-10.070, p=0.058) were associated with low adherence. CONCLUSION: ACQR-5 is a simple and feasible tool for identifying adherence levels in patients with RA in Saudi Arabia. A high level of adherence was observed in this study. Additional studies are required to assess ACQR-5 validity and adherence levels in a larger, more diverse population.
34079395 Influence of Age and Sex on Disease Course and Treatment in Rheumatoid Arthritis. 2021 OBJECTIVE: More than 50% of patients with rheumatoid arthritis (RA) are >65 years at diagnosis. Age of onset and sex may influence the disease course, outcome and treatment. This study follows a large cohort of patients with early RA to assess contributions of age and sex to disease outcomes. METHODS: Patients from the BARFOT cohort, n=2837 (68% women), were followed for eight years at predefined time points to assess inflammation, function, joint destruction and treatment with disease modifying anti-rheumatic drugs (DMARDs) and glucocorticoids (GC). The patients were divided by sex and age at inclusion (<40, 40-54, 55-69 and ≥70 years). RESULTS: For both sexes, disease activity, function and pain improved over time, significantly more in men than in women in all age groups. In men, those <40 years displayed significantly lower DAS28 compared with all other groups. This group was also the least represented group in the study. The Sharp van der Heijde Score (SHS) increased over time in both sexes and all age groups. Women ≥70 years showed less improvement in disability and the highest progression of SHS mainly due to increased joint space narrowing. Patients <40 years were more likely to receive biological DMARDs, while those ≥70 years more often received only GC treatment. CONCLUSION: There were significant age- and sex-dependent differences in the medical treatment and in outcome of RA 8 years after diagnosis. The differences were most pronounced in men<40 and women ≥70 years, but whether they are due to disease phenotype or treatment is unclear.
33869594 Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rhe 2021 Apr 6 BACKGROUND: The role of macrophages in rheumatoid arthritis (RA) and its mechanism have attracted much attention in RA pathogenesis. Macrophages accumulate in the synoviums of RA, and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages, leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction, which has made macrophages a potential target of RA drugs. Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity. It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio. AIM: To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA. METHODS: Elderly patients with RA and joint effusion were selected, including 10 men and 25 women, with an average age of 66.37 ± 4.42 years. Patients were treated with oral administration of 25 mg Iguratimod (Iremod, State Food and Drug Administration Approval No. H20110084) twice daily for 12 wk. Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment. Venous blood and joint effusion fluid were collected, mononuclear macrophages were extracted and expression of cell surface markers CD86, CD64, CD163, and CD206 was analyzed by flow cytometry. The concentration of inflammatory factors interleukin (IL)-6, IL-1β, transforming growth factor-β, and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay. Expression of mononuclear cells inhibitor of nuclear factor-κB (IκB) and phosphorylated IκB in peripheral blood was analyzed by western blotting. RESULTS: Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly. The percentage of cell surface markers CD86 and CD64 decreased significantly, and the percentage of CD163 and CD206 increased significantly (P < 0.05). The inflammatory factors IL-6 and IL-1β decreased significantly, and transforming growth factor-β and IL-4 increased significantly. Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment, and its phosphorylation level was significantly decreased (P < 0.05). CONCLUSION: Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway, thus improving symptoms of RA.
33815570 Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifyin 2021 OBJECTIVE: To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD). METHODS: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects. RESULTS: Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between -1.91 and -0.80) and HAQ-DI (WMDs ranging between -0.34 and -0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between -1.11 and -0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06-2.61] and rituximab (3.17, 1.11-10.80). CONCLUSIONS: Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.
33216287 Real-World 1-Year Retention Rate of Subcutaneous Tocilizumab Treatment in Patients with Mo 2021 Mar INTRODUCTION: Drug retention is particularly relevant to assess long-term treatments. This real-world study mainly aimed to describe 1-year retention rate (RR) of subcutaneously administered tocilizumab (TCZ-SC) in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: This non-interventional, prospective, multicenter study (NCT02608112) was conducted in patients with RA initiating TCZ-SC treatment, with an 18-month follow-up. RR was estimated at month 12 in the overall population and baseline subgroups (combination with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or not, age, body mass index, methotrexate dose), using the Kaplan-Meier method. Patient compliance to TCZ-SC was described using the 5-item Compliance Questionnaire for Rheumatology (CQR5). RESULTS: At inclusion 75% of the 285 analyzed patients were women, mean RA duration was 9 ± 9 years, previous RA treatments included biological agents (63%) and/or csDMARDs (94%), mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 4.8 ± 1.2. TCZ-SC RR at month 12 was estimated to be 64% (95% CI 58%-69%) with no statistical differences between subgroups. Clinical results improved with TCZ-SC; the proportion of patients treated with combined glucocorticoids decreased from 49% to 22% at month 12. At each follow-up time, at least 80% of patients were high adherers to TCZ-SC (at least 80% of theoretical injections). Among the 286 patients with at least one TCZ-SC injection, 25 patients (9%) experienced serious adverse events related to TCZ-SC with no differences according to patient age. CONCLUSIONS: This real-world study corroborates the RR at month 12 previously shown in interventional studies on TCZ-SC. Our data suggest there are no differences according to patient's profile (age, BMI), methotrexate doses, and TCZ-SC use. TRIAL REGISTRATION: NCT02608112.
34904049 Remission is not maintained over 2 years with hematopoietic stem cell transplantation for 2021 Nov 27 BACKGROUND: Hematopoietic stem cell (HSC) transplantation (HSCT) is being accepted as a standard of care in various inflammatory diseases. The treatment of rheumatoid arthritis (RA) has been closely evolving with the understanding of disease pathogenesis. With the rising resistance to the traditional disease-modifying anti-rheumatic drugs and targeted biological therapy, researchers are in pursuit of other methods for disease management. Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance, HSCT attracts much attention considering its reparative, paracrine, and anti-inflammatory effects. However, a systematic review of studies on HSCT in RA is lacking. AIM: To investigate the role of HSCT in the management of RA. METHODS: A detailed search of PubMed, Scopus, EMBASE, Cochrane, and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines. We extracted data including the number of patients, source of hematopoietic stem cells, their mobilization and conditioning regimens, results, and complications from the eligible studies. Results were dichotomized into success (ACR 50/70) and failure (ACR 20) based on the improvement from baseline characteristics. The methodological quality of the included studies was also assessed. Analysis was performed using OpenMeta[Analysis] software. RESULTS: We included 17 studies (1 randomized controlled trial, 11 prospective, and 5 retrospective studies) with 233 patients for analysis. HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria (Z = 11.309, P < 0.001). However, the remission was noted only till 24 mo and later on the significance of the result was lost (Z = 1.737, P = 0.082). A less than 1% treatment-related mortality was noted from the included studies. No major drug-related toxicities were noted in any of the included studies. All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections. It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous (Z = 9.972, P < 0.001) and allogenic (Z = 6.978, P < 0.001) sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them (I (2) = 99.4, P < 0.001). CONCLUSION: Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years, the inclusion of HSCT into the standard of care of RA needs further exploration.
34850095 Impact of age on the efficacy and safety of peficitinib (ASP015K) for the treatment of rhe 2021 Sep 3 OBJECTIVES: To evaluate peficitinib efficacy and safety in Asian patients with rheumatoid arthritis (RA), stratified by age (≥20-<50, ≥50-<65, and ≥65 years). METHODS: Efficacy data from two Phase 3 studies were analysed. Safety data from one Phase 2, two Phase 3, and one open-label extension study were pooled. Incidence rates per 100 patient-years of adverse events of special interest were calculated, and Cox proportional hazard analysis was conducted. RESULTS: 1052 patients received peficitinib for 2 years (median). Peficitinib demonstrated efficacy improvements versus placebo across all age categories. Incidence rates (95% confidence interval) per 100 patient-years for ≥20-<50, ≥50-<65, and ≥65 years were 0.8 (0.4, 1.9), 2.6 (1.8, 3.7), and 4.7 (3.1, 7.0) for serious infections and 3.7 (2.5, 5.4), 6.4 (5.0, 8.2), and 11.2 (8.5, 14.7) for herpes zoster-related disease, respectively. Twenty patients reported malignancies in pooled Phase 2/3 studies. Incidences of serious infections and herpes zoster-related disease increased significantly with age, but there was no association with baseline estimated glomerular filtration rate. CONCLUSIONS: Peficitinib was efficacious in adult Asian RA patients of all ages. Age, but not estimated glomerular filtration rate, was associated with serious infections and herpes zoster-related disease, demonstrating the importance of an appropriate RA treatment strategy in older patients.
34840926 Nucleotides modulate synoviocyte proliferation and osteoclast differentiation in macrophag 2021 Dec P2 receptors are nucleotide-activated receptors involved in inflammation, cell proliferation osteoblastogenesis, osteoclastogenesis and their function. They can be potential role players in the pathophysiology of rheumatoid arthritis (RA). Our analysis of gene expression datasets of synovial tissue biopsy from the GEO database shows changes in the expression levels of P2 receptors. HIG-82, a synovial fibroblast cell line and RAW 264.7, a macrophage cell line are good in vitro models to study RA. Nucleotide addition experiments showed UDP Glucose significantly increased the proliferation of synovial fibroblasts (HIG-82). Similarly, nucleotides such as Adenosine tri-phosphate (ATP), Adenosine di-phosphate (ADP), Uridine tri-phosphate (UTP), Uridine di-phosphate (UDP) and Uridine diphosphoglucose (UDPG) induced elevated reactive oxygen species (ROS) and tartrate Resistant Acid Phosphatase (TRAP) activity in RAW264.7 cells. The ADP-induced TRAP could be inhibited by clopidogrel a P2Y(12) inhibitor. ATP, ADP, UTP, UDP and UDPG also induced osteoclastogenesis as evident from fused multinucleate cells and expression of osteoclast markers (TRAP, Cathepsin K [CTSK]) as determined by Q-PCR. Apyrase (APY) a nucleotidase and an enzyme that is used to modulate extracellular nucleotide concentration is sufficient to induce osteoclastogenesis. Taken together our results show that nucleotides modulate synoviocyte proliferation and macrophage differentiation into osteoclast and play an important role in RA. Nucleotide receptors might be potential therapeutic targets in RA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03052-8.
34064086 Dental Implants with a Calcium Ions-Modified Surface and Platelet Concentrates for the Reh 2021 May 21 BACKGROUND: Platelet concentrates are biological, autologous products obtained from the patient's whole blood, consisting of a supraphysiological concentration of platelets and growth factors, that have proved beneficial in different applications in the medical and dental fields. They are used in several medical and dental applications to enhance tissue healing. Previous evidence shows that platelet concentrates may be beneficial in patients with compromised systemic conditions, in which the healing process is impaired. AIM: To evaluate the 5-year clinical outcome of implant treatment using acid-etched implants with calcium ions-modified surface in association with plasma rich in growth factors, in patients with systemic diseases of a different nature. METHODS: Charts of 99 medically compromised patients, who had received a total of 224 dental implants from January 2013 to June 2013, were retrospectively evaluated. Patients were divided into four groups, according to their condition: diabetes (n = 39 patients), osteoporosis (n = 36), lupus erythematosus systemic (n = 5), rheumatoid arthritis (n = 19). The main outcomes were implant survival, marginal bone level (MBL) change and complications throughout follow-up. RESULTS: Mean follow-up was 63.06 ± 1.90 months (range 60.1 to 66.4 months). In total, eight implants failed in 6 diabetic patients and 4 in 3 patients with rheumatoid arthritis. Overall 5-year implant survival was 94.6%. In total, 30 complications occurred in 24 patients, mostly transient, and no severe adverse event occurred. Overall MBL change was 0.45 ± 0.12 mm, with no significant differences among groups. CONCLUSIONS: In the present sample of medically compromised patients, rehabilitation with calcium ions-modified surface implants associated with plasma rich in growth factors proved to be a safe and effective treatment. The satisfactory results achieved after 5-year follow-up are comparable to those historically reported for healthy patients.
34781187 Matrine inhibits synovial angiogenesis in collagen-induced arthritis rats by regulating HI 2022 Jan Matrine (Mat) is an alkaloid of tetracycline quinazine, and previous studies have demonstrated its specific effect on relieving rheumatoid arthritis (RA). However, the effect of Mat on joint synovial angiogenesis in the pathogenesis of RA has not been elucidated. In this study, body weight, joint swelling, arthritis index (AI) score, histopathological changes, immunohistochemical, and western blot- were used in collagen-induced arthritis (CIA) rats to detect pro-inflammatory factors and, - expression levels of key cytokines and proteins along the hypoxia-inducible factor (HIF)-endothelial growth factor (VEGF)-angiopoietin (Ang) axis and VEGF-phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) pathway. In vitro experiments were conducted to observe the effect of Mat on the proliferation, migration and lumen formation of RA-fibroblast-like synovial cells (FLS) and human umbilical vein endothelial cells (HUVECs). Results showed that Mat reduced the degree of paw swelling and AI score in CIA rats, joint synovial tissue proliferation, inflammatory cell infiltration, and neovascularization; moreover, it down-regulated the expression levels of inflammatory factors interleukin-1β, interferon-γ, and pro-angiogenic factors VEGF, placental growth factor, HIF-α, Ang-1, Ang-2, Tie-2, and phosphorylation-Akt in the ankle joint of CIA rats. In addition, the in vitro experiments showed that Mat inhibited the proliferation and migration of RA-FLS and inhibited the proliferation and lumen formation of HUVECs. Therefore, Mat exerts an anti-angiogenesis effect by regulating the HIF-VEGF-Ang axis and inhibiting the PI3K/Akt signaling pathway. This inhibits the pathogenesis and improve the symptoms of RA, and may be offered as a candidate drug for the treatment of RA.
34055511 Pseudoseptic Arthritis: An Initial Presentation of Underlying Psoriatic Arthritis. 2021 Apr 24 Pseudoseptic arthritis is an acute inflammatory monoarthritis that clinically mimics septic arthritis. We encountered an 86-year-old male with a past medical history of hypertension, type 2 diabetes mellitus, and chronic kidney disease (CKD) stage 3 who presented in the emergency department with acute onset of severe left knee joint pain and was started on antibiotics for suspected septic arthritis. Septic arthritis was ruled out with negative synovial fluid culture. Timely initiation of steroids rapidly improved his condition, and he was discharged in stable condition on the 7th day of admission. Though pseudoseptic arthritis has been reported in a variety of settings including rheumatoid arthritis, ankylosing spondylitis, and medication such as intraarticular hyaluronic acid injection, our case report presents a case of pseudoseptic arthritis as the initial presentation of undiagnosed psoriatic arthritis.
33230683 Incidence of autoimmune diseases in people living with HIV compared to a matched populatio 2021 Jun The objective of this paper is to estimate incidence and relative risk of autoimmune conditions in patients living with HIV compared to an HIV-negative matched population. We conducted a retrospective study in the medico-administrative database of the province of Québec, Canada. All HIV-positive patients treated with antiretrovirals were matched to up to 4 HIV-negative controls for age, sex, and period of follow-up. The following autoimmune conditions were identified using medical billing codes: vasculitis, hematological (immune thrombocytopenic purpura and immune hemolytic anemia), ankylosing spondylitis, psoriasis and psoriatic arthritis, inflammatory bowel disease and associated arthritis, connectivitis, and systemic lupus erythematosus. Incidence rates and adjusted hazard ratios (aHR) were obtained using survival models. A total of 4245 HIV-positive patients were matched to 16493 HIV-negative patients. Autoimmune diseases were diagnosed in 407 (9.6%) HIV-positive and 508 (3%) HIV-negative patients. The aHR for autoimmune diseases associated to HIV was 2.40 95% CI [2.10-2.75]. The strongest associations were seen for hematological disorders (aHR 8.34 95% CI [6.13-11.36]), followed by ankylosing spondylitis (1.82 95% CI [1.03-3.21]), inflammatory bowel disease and associated arthritis (1.80 95% CI [1.37-2.35]), psoriasis and associated arthritis (1.69 95% CI [1.23-2.33]), and rheumatoid arthritis (1.51 95% CI [1.08-2.11]).We found no association between HIV and the incidence of vasculitis, connectivitis, and systemic lupus erythematosus, but the number of cases for these diseases were few. Autoimmune diseases are more frequent among people living with HIV than age and sex-matched population-based controls. Key Points • Strength: The major strength of this study is its large sample size of 4200 people treated as HIV infection, matched to 16000 HIV negative for sex and age. • Novelty: We found that people living with HIV were more than twice as likely to suffer from auto-immune diseases than their matched counterparts.
33605940 Low-dose rituximab protocol in rheumatoid arthritis-outcome and economic impact. 2021 OBJECTIVES: A significant proportion of RA patients, particularly those associated with poor prognostic factors, fail on conventional DMARDs (cDMARDs). Although rituximab (RTX) has been effective in these patients, the cost of therapy makes it unaffordable, particularly in poor and developing countries. Numerous, albeit small, studies using lower doses have shown contradictory results. We aimed to analyse the effectiveness of a low-dose RTX protocol based on clinical outcomes in RA patients. METHODS: Seropositive RA patients with moderate to high disease activity (DAS28-ESR > 3.2) despite combination cDMARDs, treated with RTX, were included in retrospective analysis. All patients were treated according to a predefined protocol, using 500 mg RTX with ongoing cDMARDs at baseline and repeat dosing at 6 weeks or beyond, on lack of moderate to good EULAR response. The B cell count was assessed at baseline, 2 and 24 weeks. RESULTS: At 12 weeks, 93% of 166 patients [mean (s.d.) age, 51.5 (11.96) years, 25 men and 141 women, with a disease duration of 10.4 (6.29) years] achieved moderate to good EULAR response. At 24 weeks, 90.8% of patients achieved moderate to good EULAR response, 19.8% achieved low disease activity and 29.5% achieved remission, with a mean change in DAS28-ESR from baseline of 2.9 (1.3). RTX failure and relapse were seen in 5.4% and 3.6%, respectively. The response was maintained for 12.3 (7.2) months with a mean RTX dose 521.1 (100.8) mg. Adverse events were seen in 9.6%. When compared with the standard dosing regimen with the originator molecule, a cost reduction of 90% was achieved. CONCLUSION: A low-dose RTX regimen achieved reasonably good clinical outcomes at the end of 6 months, with a significantly lower cost.
33816113 Treatment of collagen-induced arthritis rat model by using Notch signalling inhibitor. 2021 May BACKGROUND: The Notch signalling pathway has been reported to play a key role in rheumatoid arthritis (RA) development. Thus, inhibition of the activation of this signalling pathway may be a promising approach to the treatment of RA. In this study, the Notch signalling inhibitor LY411575, which can inhibit both Notch1 and Notch3, was used for the treatment of collagen-induced arthritis (CIA) rats. METHODS: Wistar rats were immunised with bovine type II collagen (CII) to establish rats CIA model. The inhibitory effects of LY411575 on Notch1 intracellular domain (N1ICD) and Notch3 intracellular domain (N3ICD) protein was verified by western blot (WB) in vitro. CIA rats were treated with different doses of LY411575 for 15 and 28 days, respectively. Methotrexate and sodium carboxymethyl cellulose (CMC-Na) were used as positive and negative (vehicle) control respectively. Destruction of the rat ankle joint and the bone loss on the periarticular side were evaluated by micro-computed tomography (Micro-CT). In addition, destruction of the ankle articular cartilage and the osteoclast numbers were determined by histology. Expression of N1ICD and N3ICD in the ankle joint was detected by immunohistochemistry. RESULTS: LY411575 could significantly inhibit the expression of N1ICD and N3ICD in vitro. Micro-CT test showed that the ankle joint destruction significantly improved after treatment with LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively). The bone quality in the LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively) groups were improved compared with the vehicle group. Histological analysis showed that LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively) treatment reduced the severity of ankle joint inflammation in CIA rats (including ankle joint destruction, pannus formation, and cartilage damage) and reduced the expression of N1ICD and N3ICD in CIA rats ankle joints significantly. CONCLUSION: The inhibitor of Notch signalling LY411575 is an effective treatment for CIA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study provides new evidence to support the potential clinical application of Notch signalling pathway inhibitor LY411575 as a drug candidate for the treatment of RA.
34649472 Balneotherapy for Musculoskeletal Pain Management of Hot Spring Water in Southern Ethiopia 2021 Jan Background: Balneotherapy and hydrotherapy offer interesting treatment alternatives and are commonly used as additional interventions in the management of musculoskeletal disorders and pain management. Therefore, the aim of this study was to assess the effect of balneotherapy on musculoskeletal disorder pain and its perceived improvement among users of hot spring water in Southern Ethiopia. Methods: A single-arm cohort study and convenient sampling method were used to select 1337 study participants from four hot springs in Southern Ethiopia. A structured questionnaire, a physical examination, and laboratory blood tests were used to collect data. Data were entered using Epi data and transferred to SPSS 25 for cleaning and analysis. Descriptive analysis was made. Results: A total of 1279 participants were included in the study, giving a response rate of 96%. The majority of these patients have multiple health problems. Of all, 1137 (88.9%) of the patients were visiting the hot springs for joint pain followed by muscle pain 669 (52.2). Out of all cases of joint pain, 132 (11.6%) were clinically diagnosed with rheumatoid arthritis, and 5.3% were confirmed as having the disease based on a laboratory test. Of the total number of study participants, 1064 (83.2%) reported complete relief from the complaints they had at the start of the bath. Conclusions: Hot spring baths for three and more days have significant therapeutic effects on patients with musculoskeletal disorders, including rheumatoid arthritis. Physicians who are currently working in the area of diagnosis and treatment of patients in government and public facilities of the southern region should consider hot spring bath treatment for those patients with complaints of musculoskeletal pain, nonspecific arthritis, and rheumatoid arthritis. A hot spring bath is beneficial for everyone because it is a natural treatment with few side effects and a low cost.