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ID PMID Title PublicationDate abstract
33106501 Preclinical validation of therapeutic targets predicted by tensor factorization on heterog 2020 Oct 26 Incorrect drug target identification is a major obstacle in drug discovery. Only 15% of drugs advance from Phase II to approval, with ineffective targets accounting for over 50% of these failures(1-3). Advances in data fusion and computational modeling have independently progressed towards addressing this issue. Here, we capitalize on both these approaches with Rosalind, a comprehensive gene prioritization method that combines heterogeneous knowledge graph construction with relational inference via tensor factorization to accurately predict disease-gene links. Rosalind demonstrates an increase in performance of 18%-50% over five comparable state-of-the-art algorithms. On historical data, Rosalind prospectively identifies 1 in 4 therapeutic relationships eventually proven true. Beyond efficacy, Rosalind is able to accurately predict clinical trial successes (75% recall at rank 200) and distinguish likely failures (74% recall at rank 200). Lastly, Rosalind predictions were experimentally tested in a patient-derived in-vitro assay for Rheumatoid arthritis (RA), which yielded 5 promising genes, one of which is unexplored in RA.
32008154 Experience of musculoskeletal ultrasound scanning improves physicians' physical examinatio 2020 Apr OBJECTIVE: Musculoskeletal ultrasound (US) is more sensitive than physical examination in detecting synovitis and helps physicians to understand its pathophysiology. In this study, we aimed to determine if the experience in musculoskeletal US scanning is independently associated with improved physical examination skills to detect synovitis. METHOD: Seventy patients with rheumatoid arthritis and twenty-three physicians were enrolled. Patients were first assessed by multiple physicians with a range of clinical/sonographic experience for the swelling of the wrist, metacarpophalangeal and proximal interphalangeal (PIP) joints and next underwent US assessment performed by another physician experienced in musculoskeletal US. We then calculated the positive/negative predictive values (PPV/NPV) of joint swelling to identify US-detected synovial hypertrophy. Finally, the factors independently associated with the accuracy of clinical assessment were identified by using multivariate analyses. RESULTS: One thousand five hundred forty joints were assessed 6116 times in total for swelling. Overall, PPV and NPV of joint swelling were 51.7% and 88.3%, respectively. Multivariate analyses identified wrist joint, tenderness, male and greater patients' age as the factors significantly associated with higher PPV. In addition, there was a trend that longer experience in rheumatology clinical practice was associated with higher PPV (p = 0.058). On the other hand, longer experience in musculoskeletal US, PIP joint and positive rheumatoid factor were identified as the significant factors for higher NPV, while wrist joint, tenderness, presence of osteophyte and obesity as those for lower NPV. CONCLUSION: Our data suggest that the experience in musculoskeletal US improves physical examination skills particularly to avoid overestimation.Key Points• Physicians with longer US experience are less likely to overestimate synovitis by physical examination.• Musculoskeletal US is a useful tool for rheumatologists to improve their physical examination skill.• Presence of osteophytes, joint tenderness and obesity influence the accuracy of physical examination of joints.
31557525 Discordances between clinical and ultrasound measurements of disease activity among RA pat 2020 Jan OBJECTIVE: Measurements of disease activity, such as the clinical disease activity score (DAS28) or ultrasound (US) scores, often yield discordant results. This study's objectives were to determine the proportion of disagreements between the two assessment methods in patients with rheumatoid arthritis (RA) and to describe factors associated with discrepancy in assessment. METHODS: All RA patients in the Swiss registry for inflammatory arthritides (SCQM) with at least one concomitant DAS28 and US score, were included. Disease activity was categorized as remission, low-to-moderate, and high, based on previously established cut-offs, for both the DAS28 and the US score. A longitudinal analysis was performed among patients who underwent at least two assessments. RESULTS: Of 2369 assessments included (1091 patients), 1196 (50.4%) were discordant. The US score both over- and under-estimated disease activity compared to the DAS28 score (23.5% and 26.8% respectively). Clinical and demographic factors significantly associated with discordant results were the individual components of the DAS28 score when US was used as the reference and age, disease duration, and the swollen joint count when the DAS28 was used as the reference. The main US-related factor associated with discordance was the presence of US tenosynovitis. In the longitudinal analysis of 1081 patients, the proportion of disagreements remained essentially unchanged. CONCLUSION: Rates of disagreement between clinical and US assessments of disease activity among RA patients are high and remain high during follow-up, even when the US assessors were aware of the clinical examination findings. Both clinical- and ultrasound- related factors were associated with discordances.
32314524 Educational needs of patients with rheumatic and musculoskeletal diseases attending a larg 2020 Sep INTRODUCTION: Patient education is an important part of the management of rheumatic and musculoskeletal diseases. Given that patients with diverse diseases do not have the same needs, it is crucial to assess the educational requirements of targeted groups to provide tailored educational interventions. The aim of our study was to assess educational needs of a large cohort of patients with different rheumatic and musculoskeletal diseases attending a health facility in Austria. METHODS: We assessed educational needs, via an online survey of patients with fibromyalgia (FMS), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) recruited from an Austrian health-care facility, using the Austrian version of the Educational Needs Assessment Tool (OENAT). RESULTS: For our sample of 603 patients, AS (62%), RA (15%), and FMS (24%), there were no educational need differences for the domains of movements, disease process, and self-help measures. Patients with FMS had less need for pain management education and greater need for education about feelings, than other disease groups. Patients with RA had a greater need for education related to treatments than other groups, and patients with AS had a greater need for treatment education than patients with FMS. Patients with AS reported greater need for support system education than other patient groups. CONCLUSION: Educational needs vary by disease groups, suggesting that health-care professionals should assess disease-specific needs for education to provide optimal assistance in disease management for patients.
31819995 Disease activity measures at baseline predict structural damage progression: data from the 2020 Aug 1 OBJECTIVE: Data from two double-blind, randomized, Phase III studies were analysed to investigate the ability of Routine Assessment of Patient Index Data 3, DAS28 (CRP), modified (M)-DAS28 (CRP) and Simplified or Clinical Disease Activity Indices to predict structural damage progression in RA. METHODS: This post hoc analysis included data from the 2-year Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX (AMPLE) trial in biologic-naïve patients with active RA (<5 years) and an inadequate response to MTX, and the 12-month treatment period of the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial in MTX-naïve patients with early RA (⩽2 years) and poor prognostic indicators. Adjusted logistic regression analysis assessed the relationship between baseline disease activity and structural damage progression (defined as change from baseline greater than the smallest detectable change) at 12 and 24 months in AMPLE and 6 and 12 months in AVERT. Areas under the receiver operating characteristic curves for the impact of baseline disease activity on structural damage progression were calculated. RESULTS: Adjusted logistic regression analyses included all randomized and treated patients in AMPLE (N = 646) and those who received abatacept plus MTX or MTX monotherapy in AVERT (N = 235). Baseline Routine Assessment of Patient Index Data 3, DAS28 (CRP) and M-DAS28 (CRP) scores significantly predicted structural progression at months 12 and 24 in AMPLE (P < 0.05) and months 6 and 12 in AVERT (P < 0.01), and were stronger predictors than Simplified or Clinical Disease Activity Indices. CONCLUSION: In this post hoc analysis of two patient populations with RA, Routine Assessment of Patient Index Data 3, DAS28 (CRP) and M-DAS28 (CRP) were good at predicting structural damage. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov: NCT00929864 (AMPLE); NCT01142726 (AVERT).
33090049 It Is Just a Rash They Said! Acute Skin Manifestation in a Patient With Vasculitis in Rura 2020 Jan A 76-year-old Caucasian male with a history of rheumatoid arthritis, Raynaud's phenomenon, pulmonary embolism on warfarin, and a previous amputation of his left partial ring and fifth finger presented with acute onset of rash in bilateral lower extremities. He was recently started on trimethoprim-sulfamethoxazole due to concern for cellulitis. Differential diagnosis for acute-onset rash with the patient's history presented as a challenge to the internist, as the differential is broad. Our case goes through the differential diagnosis to contrast the different presentations of rash in a patient with vasculitis. Ultimately skin biopsy in conjunction with a past positive cryoglobulinemic level helped confirm the diagnosis of cutaneous vasculitis, following which he was started on appropriate treatment and recovered.
31651077 Metabolomic Profiling to Identify Molecular Biomarkers of Cellular Response to Methotrexat 2020 Jan Variation in methotrexate (MTX) efficacy represents a significant barrier to early and effective disease control in the treatment of autoimmune arthritis. We hypothesize that the utilization of metabolomic techniques will allow for an improved understanding of the biochemical basis for the pharmacological activity of MTX, and can promote the identification and evaluation of novel molecular biomarkers of MTX response. In this work, erythroblastoid cells were exposed to MTX at the physiologic concentration of 1,000 nM and analyzed using three metabolomic platforms to give a broad spectrum of cellular metabolites. MTX pharmacological activity, defined as cellular growth inhibition, was associated with an altered cellular metabolomic profile based on the analysis of 724 identified metabolites. By discriminant analysis, MTX treatment was associated with increases in ketoisovaleric acid, fructose, galactose, and 2-deoxycytidine, and corresponding reductions in 2-deoxyuridine, phosphatidylinositol 32:0, orotic acid, and inosine monophosphate. Inclusion of data from analysis of folate metabolism in combination with chemometric and metabolic network analysis demonstrated that MTX treatment is associated with dysregulated folate metabolism and nucleotide biosynthesis, which is in line with its known mechanism of action. However, MTX treatment was also associated with alterations in a diversity of metabolites, including intermediates of amino acid, carbohydrate, and lipid metabolism. Collectively, these findings support a robust metabolic response following exposure to physiologic concentrations of MTX. They also identify various metabolic intermediates that are associated with the pharmacological activity of MTX, and are, therefore, potential molecular biomarker candidates in future preclinical and clinical studies of MTX efficacy in autoimmune arthritis.
32423845 Three-dimensional printed assistive devices for addressing occupational performance issues 2020 Apr STUDY DESIGN: This is a case report. INTRODUCTION: Persons with rheumatoid arthritis frequently use assistive devices as a compensatory strategy to enhance occupational performance when client factors such as hand weakness, pain, and/or limited range of motion interfere with activity performance. Computer-aided design software and 3D printers are increasingly being used to design and make assistive devices. PURPOSE OF THE STUDY: This case report describes a client-centered approach in the selection, three-dimensional (3D) printing, and evaluation of outcomes for three assistive devices to enhance occupational performance in a subject with rheumatoid arthritis. METHODS: Outcome measures used in this study included the Patient-Specific Functional Scale, Numeric Pain Rating Scale, and Quebec User Evaluation of Satisfaction with Assistive Technology V2.0. Activity analysis along with the subject input informed a client-centered approach in the selection, color, and design modifications of 3D printed assistive devices made for the study. RESULTS: The subject reported decreased pain, improved occupational performance, and satisfaction with use of 3D printed assistive devices to open plastic beverage bottles, unlock/lock doors, and write. DISCUSSION: 3D printing offers therapists a means to design and make assistive devices that can be cost-effective, customizable, and client-centered. CONCLUSION: Assistive devices made with 3D printing resulted in positive outcomes in a subject with rheumatoid arthritis.
32983133 LncRNA NEAT1 Targets Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via the miR-410- 2020 LncRNA NEAT1 functions as an oncogene in multiple human cancers. However, its expression and role in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) remain unclear. Thus, we investigated the expression of NEAT1 in synovial tissues and FLSs in RA, to determine its role in the development of RA. Quantitative real-time polymerase chain reaction was used to measure the expression of NEAT1. FLS proliferation was evaluated using cell proliferation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis in FLSs. Binding between NEAT1 and miR-410-3p was demonstrated by dual-luciferase assays. We found that NEAT1 was upregulated in synovial tissues and FLSs in RA. Upregulation of NEAT1 promoted cell proliferation, induced S-to G2/M phase transition, and suppressed apoptosis in RA FLSs. NEAT1 directly bound to and negatively modulated miR-410-3p expression, while positively regulating YinYang 1(YY1; a miR-410-3p target). Inhibiting miR-410-3p and upregulating YY1 partially restored the inhibitory role in cell viability induced by the depletion of NEAT1 in RA FLSs. Besides pro-proliferative and anti-apoptotic roles, upregulation of NEAT1 promoted migration, invasion, and inflammatory cytokines secretion in RA FLSs. Taken together, our results suggest that the NEAT1 may serve as a novel diagnostic and therapeutic target for patients with RA.
32679549 Quercetin alleviates rheumatoid arthritis by inhibiting neutrophil inflammatory activities 2020 Oct Rheumatoid arthritis (RA) is a prototypical autoimmune disorder mainly characterized by joint inflammation and cartilage destruction. Neutrophils actively take part in the initiation and progression of RA. Neutrophils express inflammatory mediators, including cytokines and chemokines. Aberrant formation of neutrophil extracellular traps (NETs) has been demonstrated in the pathogenesis of RA. Thus, neutrophils are regarded as important therapeutic targets in RA treatment. Quercetin is one of the major flavonoids found in fruits and vegetables. Previous studies have demonstrated that quercetin is a potential agent for the treatment of RA. However, the underlying antiarthritic mechanism of quercetin has not been investigated clearly. In this study, we analyzed the therapeutic mechanism of quercetin for RA. Our results showed that quercetin ameliorates inflammation in RA mice by inhibiting neutrophil activities. Quercetin inhibited neutrophil infiltration and reduced the plasma levels of inflammatory cytokines. Quercetin promoted the apoptosis of activated neutrophils. In addition, quercetin inhibited NET formation by suppressing autophagy. These findings suggest that quercetin may be an alternative agent for the treatment of RA by inhibiting neutrophil activities.
31504982 Role of good oral hygiene on clinical evolution of rheumatoid arthritis: a randomized stud 2020 May 1 OBJECTIVE: There is a relationship between RA and periodontal disease. We aimed to investigate if a good oral hygiene could improve activity of RA. METHODS: The patients with RA according to ACR/EULAR 2010 criteria and included in the French early arthritis ESPOIR cohort were included in a randomized nested study into: (i) intervention group: general recommendations of good oral hygiene including teeth brushing, daily antiseptic mouthwash and twice a year scaling; and (ii) control group: no intervention. The primary end point was the delta DAS28-ESR. RESULTS: Four hundred and seventy-two patients were randomized (238 in intervention and 234 in control). 92/238 from the intervention group accepted the procedure and 81 had a first visit to the dentist. 56% of patients had periodontal disease at baseline. Duration of RA was 9.0±0.7 years. Baseline DAS28-ESR was 2.7±1.3. After a median duration of 24 months, delta DAS28-ESR was -0.17±1.29 and -0.09±1.28 in intervention and control groups, respectively (mean difference (complier average causal effect): -0.37 (95% CI -1.12, 0.37), P = 0.33). In the intervention group, there was a significant decrease of the bacteria involved in the red complex: Porphyromonas gingivalis (P = 0.002), Tannerella forsythia (P = 0.002) and Treponema denticola (P = 0.019). The patients with baseline periodontal disease and those who became negative for one red complex bacterium had a slightly more important decrease of DAS28-ESR. CONCLUSION: Oral hygiene instruction together with regular scaling and polishing of the teeth significantly decreased the load of periodontal pathogens but did not decrease RA activity. This intervention should be tested in patients with earlier RA and more active disease. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01831648.
31333130 The Utility of Radiographic Focal Erosions of Hands or Feet in Predicting DXA-defined Oste 2020 INTRODUCTION: Osteoporosis is a common comorbidity in Rheumatoid Arthritis (RA) patients and can result in estimated double risk of pathological fractures. Bone Mineral Density (BMD) is known to decrease with RA because of mechanisms incorporating traditional as well as disease-specific causes. With the advent of newer disease-modifying antirheumatic agents and bone protection medications, it is becoming important to identify those individuals who are at increased risk of developing osteoporosis among RA patients. AIM: In the current study, we aim to evaluate a multitude of factors including focal erosions on radiographs of hands or feet that can predict osteoporosis in RA patients. METHODS: After obtaining IRB approval, 26 patients (20 females & 6 males) with a median age of 62 years (95% CI: 57.4 - 66.0) were retrospectively identified from a Rheumatology clinic database with an established diagnosis of RA but not taking osteoporosis medications. A detailed assessment was accomplished including evaluating a number of disease-specific variables, hands/feet radiographs and Dual-energy X-ray Absorptiometry (DXA). RESULTS: The total hip BMD was lower in RA patients with radiographic erosions (0.862 g/cm2 ± 0.17) compared to those patients without erosions (1.011 g/cm2 ± 0.13). On univariate logistic regression, the presence of radiographic erosions predicted osteoporosis of the hip (p = 0.04). ROC curve demonstrated satisfactory performance of erosions in predicting WHO-defined osteoporosis or osteopenia at the hip (AUC = 0.732). CONCLUSION: RA patients who show radiographic erosions are more likely to develop hip osteoporosis that may require further intervention.
33089617 Neopterin serum level does not reflect the disease activity in rheumatoid arthritis: A sys 2020 Dec Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by established chronic inflammation. Neopterin levels have extensively been considered as a marker of immune activation during inflammation. In this study, we performed a systematic evaluation and meta-analysis to elucidate the overall relationship between neopterin concentration and RA disease activity. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using PubMed, Google Scholar, Web of Science, and Scopus from 2000 to August 2020. The Newcastle-Ottawa scale was used to assess the quality of eligible studies. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to evaluate this association. A total of 15 studies out of 98 met our inclusion criteria. The pooled analysis found that patients with RA had high level of neopterin; however, no statistically significant association was found between neopterin levels with high, intermediate, and low diseases activity score (DAS)-28 (ES =11.18, 95% CI: 6.02 to 16.34, and I(2) = 91.8%; and ES = 8.57, 95% CI: 6.41 to 10.37, and I(2) = 99.5%; and ES =12.45, 95% CI: -1.68 to 26.58, and I(2) = 99.0%, respectively). Our results indicated that the neopterin concentration does not seem to have any substantial impact on the RA disease activity.
31493148 The American English version of the validated French Flare Assessment in RA Questionnaire 2020 Jan OBJECTIVE: To evaluate use of a British English version of the validated French FLARE-RA questionnaire among American English speaking patients. In addition, to create a culturally adapted American English (AmE) FLARE-RA questionnaire and to examine its attributes of patient-reported RA flare status. METHODS: Using standardized cultural adaptation guidelines, we cognitively debriefed 25 American English speaking rheumatoid arthritis (RA) outpatients and created AmE-FLARE-RA with their input. One hundred three additional RA patients were recruited. Patients completed the Routine Assessment of Patient Index Data 3 (RAPID3), patient global visual analogue scale (VAS), AmE-FLARE-RA, and self-reports of flare. Physician global VAS, physician-assessed flare, swollen and tender joint count (TJC), and clinical disease activity index (CDAI) were documented. AmE-FLARE-RA and disease activity measures were compared between patient-reported and physician-reported flare categories. RESULTS: Patients were female (89%), with mean (SD) age 51.1 (± 15.3) years and mean disease duration (SD) 11.9 (± 10.1) years, with 26% in remission/low disease activity. Total AmE-FLARE-RA scores, RAPID3, CDAI, and patient global VAS were significantly higher for both patient-reported flares and physician-reported flares compared with non-flaring patients by self- or physician report (p < 0.05). Total AmE-FLARE-RA scores correlated significantly with RAPID3 (corr = 0.50, p < 0.0001) and with CDAI (corr = 0.45, p < 0.0001). Across "no flares," "one flare," and "several flare" groups, there was a non-significant increase in AmE-FLARE-RA scores (p = 0.07). CONCLUSION: The British English FLARE-RA was successfully adapted for AmE-speaking RA patients. AmE-FLARE-RA significantly correlated with RAPID3 and CDAI and distinguished between patient-reported and physician-reported flares, making it useful to detect flares in American RA patients.Key Points• The American English FLARE-RA (AmE-FLARE-RA) questionnaire is the result of cognitive debriefing with American RA patients using the British English version of the validated French FLARE-RA and incorporates patient-recommended language modifications..• Patients self-reporting flares had significantly higher AmE-FLARE-RA scores, compared with those without flares at the time of visit. AmE-FLARE-RA scores correlate with RAPID3 and CDAI.• There was a non-statistically significant trend using the AmE-FLARE-RA scores when examining patients with no flare, one flare, or several flares.• AmE-FLARE-RA total scores are uniformly elevated (~ 6.0 on a 0-10 scale), regardless of discordance between patient and MD assessment of flare at time of visit (~ 30%).
31376255 Revealed heterogeneity in rheumatoid arthritis based on multivariate innate signature anal 2020 Mar OBJECTIVES: A growing body of evidence highlights the persistent activation of the innate immune system and type I interferon (IFN) signature in the pathogenesis of rheumatoid arthritis (RA) and its association with disease activity. Since the recent study revealed heterogeneity in the IFN signature in RA, we investigated for the first time the heterogeneity in innate signature in RA. METHODS: The innate gene expression signature (10 TLRs, 7 IL1/IL1R family members, and CXCL8/IL8) was assessed in peripheral blood mononuclear cells from RA patients (n=67), both with active (DAS28≥3.2, n=32) and inactive disease (DAS28<3.2, n=35), and in healthy control subjects (n=55). RESULTS: Of the 13 deregulated innate genes (TLR2, TLR3, TLR4, TLR5, TLR8, TLR10, IL1B, IL1RN, IL18, IL18R1, IL1RAP, and SIGIRR/IL1R8) associated with RA, TLR10 and IL1RAP are being reported for the first time. Multivariate analysis based on utilising patient similarity networks revealed the existence of four patient's subsets (clusters) based on different TLR8 and IL1RN expression profiles, two in active and two in inactive RA. Moreover, neural network analysis identified two main gene sets describing active RA within an activity-related innate signature (TLR1, TLR2, TLR3, TLR7, TLR8, CXCL8/IL8, IL1RN, IL18R1). When comparing active and inactive RA, upregulated TLR2, TLR4, TLR6, and TLR8 and downregulated TLR10 (P<0.04) expression was associated with the disease activity. CONCLUSIONS: Our study on the comprehensive innate gene profiling together with multivariate analysis revealed a certain heterogeneity in innate signature within RA patients. Whether the heterogeneity of RA elucidated from diversity in innate signatures may impact the disease course and treatment response deserves future investigations.
30942638 Expressions of circadian clock genes represent disease activities of RA patients treated w 2020 Mar Objectives: Rheumatoid Arthritis (RA) is the autoimmune disease representing the circadian variations of symptoms such as morning stiffness of joints or increased production of cytokines around midnight. Clock genes have been reported to affect on the pathogenesis of RA, however, the detailed relation between clock genes and disease activities of RA has remained unclear.Methods: In this study, 15 RA patients treated with biological disease modifying anti-rheumatic drugs (bDMARDs) were enrolled (TNF inhibitor, 5; IL-6 inhibitor, 5; CTLA4-IgG, 5). Blood samples were collected from RA patients before treatment and at the study end-point fulfilling DAS28-ESR < 3.2. Total RNA was extracted from leukocytes to examine the expressions of the clock genes. We then evaluated the correlation of the clock gene expression with disease activity and the diagnostic values of the clock genes.Results: The expressions of the clock genes were significantly modulated by bDMARDs treatments. Disease activities were significantly correlated with the clock genes expressions, and disease remission/low disease activity could be distinguished from moderate/high disease activity due to the sensitivities, the specificities and the areas under the curves of that.Conclusion: The expressions of the clock genes in leukocytes could be useful as novel biomarkers predicting disease activities and therapeutic efficacies for bDMARDs in RA treatments.
31992083 IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid a 2020 Mar Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1β, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T IL1β (rs1143634), -137 G/C IL18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92; p = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p = .021) and rs2430561 with DAS28 (p = .029) and CDAI (p = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p < .001) and ESR (p = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F = 5.497; p < .001) and ESR (F = 2.727; p = .032)). Our analysis indicated that in the studied population +3953 C/T IL-1β (rs1143634), -137 G/C IL-18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.
33329548 Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis 2020 Rheumatoid arthritis (RA) is a complex autoimmune disease targeting synovial joints. Traditionally, RA is divided into seropositive (SP) and seronegative (SN) disease forms, the latter consisting of an array of unrelated diseases with joint involvement. Recently, we described a severe form of SN-RA that associates with characteristic joint destruction. Here, we sought biological characteristics to differentiate this rare but aggressive anti-citrullinated peptide antibody-negative destructive RA (CND-RA) from early seropositive (SP-RA) and seronegative rheumatoid arthritis (SN-RA). We also aimed to study cytotoxic CD8+ lymphocytes in autoimmune arthritis. CND-RA, SP-RA and SN-RA were compared to healthy controls to reveal differences in T-cell receptor beta (TCRβ) repertoire, cytokine levels and autoantibody repertoires. Whole-exome sequencing (WES) followed by single-cell RNA-sequencing (sc-RNA-seq) was performed to study somatic mutations in a clonally expanded CD8+ lymphocyte population in an index patient. A unique TCRβ signature was detected in CND-RA patients. In addition, CND-RA patients expressed higher levels of the bone destruction-associated TNFSF14 cytokine. Blood IgG repertoire from CND-RA patients recognized fewer endogenous proteins than SP-RA patients' repertoires. Using WES, we detected a stable mutation profile in the clonally expanded CD8+ T-cell population characterized by cytotoxic gene expression signature discovered by sc-RNA-sequencing. Our results identify CND-RA as an independent RA subset and reveal a CND-RA specific TCR signature in the CD8+ lymphocytes. Improved classification of seronegative RA patients underlines the heterogeneity of RA and also, facilitates development of improved therapeutic options for the treatment resistant patients.
32259851 Cementless Fixation for Total Knee Arthroplasty in Various Patient Populations: A Literatu 2020 Sep The number of total knee arthroplasties (TKAs) performed in the United States has increased considerably in recent years, with a major contribution from younger patients. Maximizing survivorship of these implants has always been a point of emphasis. Early TKA designs with cementless fixation were associated with high rates of complications and implant failures. However, recent advances in cementless designs have shown excellent results. The decision to use cemented or cementless fixation for patients undergoing TKA is typically based on the surgeon's experience and preference. However, several patient characteristics must also be taken into account. The purpose of this review was to describe the clinical outcomes of studies in which a cementless TKA system was utilized for patients who (1) were less than 60 years of age, (2) were greater than 75 years of age, (3) were obese, (4) had rheumatoid arthritis, and (5) had osteonecrosis of the knee. Based on the studies included in this review, it appears that cementless fixation is a viable option for patients who have all of the above demographics.
33191869 Arthroscopic triple arthrodesis for the patient with rheumatoid arthritis; a case report. 2021 Jan We treated a 60 - year - old man with pes planovalgus due to rheumatoid arthritis. He had been suffering from left foot pain with swelling. Despite drug therapy, his foot pain and deformity had got worsen. Taking into consideration his skin and bone quality, arthroscopic triple arthrodesis was performed. To access the subtalar joint, 2 portals were applied at the sinus tarsi, and decortication was performed. For calcaneocuboid joint, 1.5 cm portal was applied along with joint line at calcaneocuboid joint. Calcaneocuboid joint was fully decorticated, then, 1.5 cm portal was applied at the joint line of talonavicular joint in parallel. Synovectomy and decortication under arthroscopy were performed. Once each joint was sufficiently prepared, it was fixed using screws via a percutaneous stab incision with an autologous bone graft from the iliac crest to the calcaneocuboid and talonavicular joint. At 12 weeks postoperatively, bone union was confirmed. The Japan Society for Surgery of the Foot (JSSF) RA foot and ankle scale had improved from the postoperative value of 38 points to a postoperative score of 86 points at one year. Plain radiographs showed that good alignment of the patient's hindfoot was maintained. We found that arthroscopic approach was able to achieve satisfactory outcome and minimise soft tissue trauma in a compromised patient.