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ID PMID Title PublicationDate abstract
30772365 Bilateral epibulbar pseudorheumatoid nodulosis with a review of ocular adnexal palisading 2019 Jul We describe the clinical, histopathologic, and immunohistochemical characteristics of episcleral/conjunctival pseudorheumatoid nodulosis, a new granulomatous entity that belongs among a group of related lesions. Specifically, pseudorheumatoid nodulosis should be differentiated from solitary rheumatoid nodules, rheumatoid nodulosis, accelerated rheumatoid nodules and nodulosis, and solitary pseudorheumatoid nodules. A 53-year-old man presented with bilateral painless, large, faintly yellow-gray, partially immobile, solid, circumscribed, and occasionally confluent episcleral nodules of several months' duration. He had never had clinical rheumatoid arthritis and was rheumatoid factor negative. Biopsy revealed multiple, merging episcleral/conjunctival, nonulcerated, palisading granulomas with variably sized central zones of necrobiosis of collagen. Abundant palisading CD68/163 + histiocytes admixed with fibroblasts surrounded the necrobiotic foci, which failed to stain with Alcian blue for mucopolysaccharides. No fibrinoid deposits were detected. Numerous CD3+ T lymphocytes, fewer CD 20 + B lymphocytes, and a smaller subpopulation of CD138 + plasma cells were present. Numerous CD1a + Langerhans cells were scattered among the palisading histiocytes and overlying epithelium. Immunohistochemical stains for immunoglobulins revealed concentrations of IgG, IgM, and IgA, but not IgE, in the necrobiotic zones. Special stains did not reveal evidence of infection nor did polarization microscopy display any foreign material. An extensive systemic and serologic workup was negative. We review simulating palisading or other nonrheumatic granulomas that should be distinguished from pseudorheumatoid nodules or nodulosis and explore therapeutic options.
30311063 Prevalence of degenerative joint disease of the temporomandibular joint: a systematic revi 2019 May OBJECTIVES: The purpose of this systematic review was to evaluate evidence about the prevalence of degenerative joint disease (DJD) of the temporomandibular joints (TMJ). MATERIALS AND METHODS: We performed search on electronic databases and gray literature from their inception to January 2018. Studies reporting prevalence data of DJD on TMJ were included. DJD was assessed through clinical and imaging diagnosis. Studies risk of bias was evaluated using the Critical Appraisal Checklist for Studies Reporting Prevalence Data. RESULTS: From 1082 studies, 32 were identified, and the sample size included 3435 subjects. They were clustered into two groups: the first comprised studies that reported prevalence of DJD in TMJ secondary to rheumatic systemic diseases like juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) and the second group comprised studies that reported prevalence of DJD on temporomandibular disorder patients. The prevalence of DJD on JIA patients ranged from 40.42% (n = 47) to 93.33% (n = 15) and on RA patients from 45.00% (n = 20) to 92.85% (n = 56). Among TMD patients, the prevalence of DJD reported according to patients ranged from 18.01% (n = 1038) to 84.74% (n = 118) and reported according to joints ranged from 17.97% (n = 178) to 77.23% (n = 224). CONCLUSION: This review attempts to high prevalence of DJD in patients with systemic rheumatic disease and a less prevalent, but still high, occurrence in patients with TMD without systemic involvement. CLINICAL RELEVANCE: Specialist doctors and dentists should be alert to not underestimate and to correctly diagnose DJD of the TMJ early in patients with rheumatic disease and TMD.
31237855 Shingles: More than Meets the Eye. 2019 Mar 1 Low-dose once weekly methotrexate (MTX) is the first-line disease-modifying antirheumatic drug (DMARD) to treat rheumatoid arthritis and psoriasis. Although methotrexate is generally considered to have a good safety profile it can occasionally induce severe side effects such as pancytopenia, mucositis, disorders of kidney and liver. Oral mucositis should alert physicians to MTX toxicity. We report a 64-year-old woman with a severe drug reaction including disseminated shingles, oral mucositis and pancytopenia only three days after starting a therapeutic low-dose of MTX. Initially, mucositis and myelosuppression couldn't be accounted for by the underlying disease. In taking the patient's history, MTX intake 10 days ago was missed, the patient reporting only current medications. However, there was more to the skin rash than meets the eye. Only after further inquiry did the patient reveal the intake of 2 doses of MTX and the subsequent withdrawal of medication. Arriving at the correct diagnosis in difficult cases, as in the case presented, requires further evaluation, including repeat history taking and eliciting more details if diagnosis remains elusive.
31220991 Cost-effectiveness of five different anti-tumour necrosis factor tapering strategies in rh 2019 Nov Objective: To investigate the cost-effectiveness of five different tumour necrosis factor inhibitor tapering strategies in patients with rheumatoid arthritis (RA) and stable low disease activity, using a modelling design.Method: Using Markov models based on data from the DRESS and STRASS randomized controlled trials, and the Nijmegen RA cohort, five tapering strategies for etanercept and adalimumab were tested against continuation: 1, four-step tapering (DRESS strategy); 2, five-step tapering; 3, tapering without withdrawal; 4, use of a stricter flare criterion; and 5, use of a theoretical predictor for successful tapering. We also examined how well a biomarker should be able to predict in order for strategy 5 to become cost-effective compared to the other strategies.Results: All examined tapering strategies were cost saving (range: EUR 5128 to 7873) but yielded more short-lived flares compared to continuation. The change in utilities compared to continuation was minimal and not clinically relevant (range: -0.005 to 0.007 quality-adjusted life-years). Strategy 1 was cost-effective compared to all other strategies [highest incremental net monetary benefit (iNMB)]. However, there was a large overlap in credible intervals, especially between strategies 1 and 2. Scenario analyses showed that 50% reduction of drug prices would result in the highest iNMB for strategy 2. A biomarker only becomes cost-effective when it is inexpensive and has a sensitivity and specificity of at least 84%.Conclusion: Because our study showed a comparable iNMB for tapering in four or five steps (including discontinuation), we recommend a choice between these strategies, based on shared decision making.
31012365 Serum drug concentrations to optimize switching from adalimumab to etanercept in rheumatoi 2019 Jul Objectives: Inadequate response to adalimumab can be caused by insufficient blockade of the target tumour necrosis factor (TNF) at low serum concentrations. In such cases, patients may respond to another TNF inhibitor. We investigated whether the serum adalimumab concentration is related to the efficacy of a second TNF inhibitor, etanercept, in rheumatoid arthritis (RA). Methods: Patients with RA starting etanercept treatment were prospectively observed in the Reade Rheumatology Registry. In patients previously on adalimumab, serum concentrations were determined before treatment discontinuation. According to this concentration, three subgroups were formed: < 0.5 μg/mL, 0.5-5.0 μg/mL, and ≥ 5.0 μg/mL. The European League Against Rheumatism (EULAR) good/moderate response rate after 52 weeks of etanercept was compared between the switcher subgroups and biologic-naive patients. Results: In total, 449 consecutive patients were included, of whom 69 switched from adalimumab (15%) and 380 were biologic naive (85%). EULAR good or moderate response was achieved by 74% of the biologic-naive patients and by 72%, 50%, and 52% of switchers with adalimumab concentration < 0.5 μg/mL, 0.5-5.0 μg/mL, and ≥ 5.0 μg/mL, respectively (p = 0.15). Patients with an adalimumab concentration ≥ 0.5 μg/mL were significantly less likely to achieve EULAR good/moderate response on etanercept compared to biologic-naive patients, whereas patients with a concentration < 0.5 μg/mL did not significantly differ from patients starting etanercept without prior biologic treatment. Conclusion: RA patients with an inadequate response to adalimumab, in the presence of sufficient drug concentrations, benefit less from switching to another TNF inhibitor, etanercept.
31815649 Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and 2019 Dec 9 BACKGROUND: To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs. METHODS: Patients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests. RESULTS: Data from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients. CONCLUSIONS: Upadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.
31554310 Proportion of the CD19-Positive and CD19-Negative Lymphocytes and Monocytes within the Per 2019 Sep 24 Background and objectives: Composition of the peripheral blood (PB) cell populations and their activation state reflect the immune status of a patient. Rheumatoid arthritis (RA) is characterized by abnormal B- and T-cell functions. The objective of this study was to assess the profiles of the PB mononuclear cell (PBMC) populations in patients with rheumatoid and osteoarthritis (OA) in comparison with healthy control (HC) subjects in order to evaluate the PBMC profiles as a potential diagnostic characteristic in RA. The second aim was to assess the CCR1 and CCR2 expression on PB lymphocytes and correlate it with the plasma levels of matrix metallopeptidase 9 (MMP-9), IL-17F, TNF-α, IL-6, and IL-10. Materials and Methods: The frequency and phenotype, including CCR1 and CCR2, of the PBMC populations (monocytes, CD19(+)B cells, and T/NK lymphocytes) in RA (n = 15) and OA (n = 10) patients and HC (n = 12) were analyzed by five-color flow cytometry. DNA of the viruses, HHV-6, HHV-7, and B19, in the whole blood and cell-free plasma, were assessed by nested-polymerase chain reaction (PCR). Results: Active persistent or acute infections, caused by HHV-6, HHV-7, or B19, were not detected in patients of this study. Both CCR1 and CCR2 were determined on the PB B and T/NK lymphocytes in several RA and OA patients and HCs. However, in patients, the frequency of the CCR1-positive T/NK lymphocytes showed a weak negative correlation with the IL-10 level, while the frequency of the CCR2-positive B cells correlated positively with the level of IL-6. Statistically significant differences in the proportions of the CD19-positive and CD19-negative lymphocyte and monocyte subsets within the PBMC set were determined between RA and OA patients and HC adults. Conclusions: We have shown in our pilot study with rather small cohorts of patients that the PBMC-population profiles were very consistent, and statistically significantly differed between RA and OA patients and HC subjects.
31253945 The structure, specificity and function of anti-citrullinated protein antibodies. 2019 Aug In this Perspectives article, we outline a proposed model for understanding the specificity and function of anti-citrullinated protein antibodies (ACPAs). We suggest that ACPAs vary in specificity between two extremes: some are 'promiscuous' in that they are highly specific for the citrulline side chain, but cross-react with a range of citrullinated peptides, whereas others are 'private' in that their recognition of citrulline as well as proximal amino acid side chains enables protein-specific interactions. Promiscuous ACPAs tend to dominate in the sera both before and after the onset of rheumatoid arthritis, but their functional role has not been clarified. No firm evidence exists that these ACPAs are pathogenic. By contrast, private ACPAs encompass antibodies that specifically recognize citrullinated epitopes on joint proteins or that cross-react with joint proteins, thereby opening up the possibility that these private ACPAs are arthritogenic. These joint-reactive antibodies are more likely to target joints by binding to joint tissues and to promote the formation of local immune complexes leading to bone erosions, pain and arthritis.
31526113 Systematic review of the diagnostic accuracy, reliability, and safety of the sharp-purser 2020 May Introduction: The Sharp-Purser Test (SPT) is used to assess for atlantoaxial instability (AI) in patients with rheumatoid arthritis (RA). The test is commonly used by clinicians; however, many experts argue it lacks reliability and validity along with concerns of safety. The primary purpose of this review is to determine the diagnostic accuracy of the SPT to detect AI.Methods: A search of five databases was performed from inception to 19 December 2018 using search terms related to the SPT. Studies were eligible for inclusion if the SPT was used on a patient/participant. Methodological quality assessment of diagnostic studies was performed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) for studies that reported data to calculate sensitivity (SN), specificity (SP), positive likelihood ratio (+LR), and negative likelihood ratio (-LR).Results: The search yielded 1009 articles, and 32 studies met the inclusion criteria for analysis. Meta-analysis on diagnostic accuracy studies assessing the SPT was not possible due to statistical heterogeneity. Six diagnostic accuracy studies assessed the SN of the SPT ranging from 0.19 to 1.00. Four of the studies assessed SP of the SPT ranging from 0.71 to 0.98. The +LR was identified in 4 studies was 0.655, 1.73, 22, and 17.25. The -LR was 1.14, 0.799, 0.571, and 0.323. Seven RCTs utilized the SPT to screen for AI, and the SPT was used in 18 case reports.Conclusion: The SPT may be inappropriate to use due to inconsistent validity, poor inter-rater reliability, and potential to cause harm.Level of evidence: 1.
30696403 Association study between KIR polymorphisms and rheumatoid arthritis disease: an updated m 2019 Jan 29 BACKGROUND: Currently published studies investigating association between the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and rheumatoid arthritis (RA) reported inconsistent and contradictory results. Hence, we aim to carry out this comprehensive meta-analysis of all eligible studies meeting the inclusion criteria to achieve precise and comprehensive relationships between genetic variations in KIR gene cluster and risk of RA. METHODS: Databases of Medline/PubMed and Scopus were searched to investigate case-control studies prior to May 2018. The associations between KIR gene polymorphisms and RA susceptibility were analyzed by computing the odds ratio (OR) and 95% confidence interval (95% CI) for each study. RESULTS: A total of 11 comparative case-control studies involving 1847 RA patients and 2409 healthy individuals were included in this meta-analysis. Four significant associations of 2DL3 (OR = 0.591, 95% CI = 0.351-0.994; P = 0.047), 2DL5 (OR = 0.716, 95% CI = 0.601-0.853; P < 0.001), 2DS5 (OR = 0.623, 95% CI = 0.393-0.988; P = 0.045), and 3DL3 (OR = 0.324, 95% CI = 0.129-0.814; P = 0.016) genes with decreased RA risk were discovered in this meta-analysis. Although, other KIR receptors including 2DL1, 2DL2, 2DL4, 3DL1, 3DL2, 3DS1, 2DS1-2DS4, and two pseudo gens of 2DP1 and 3DP1 displayed no significant association with predisposition to RA. CONCLUSIONS: These findings provide reliable evidence that 2DL3, 2DL5, 3DL3, and 2DS5 might have a potential protective role for RA.
31397202 An effective and safe treatment strategy for rheumatoid arthritis based on human serum alb 2019 Aug Aim: We aimed to construct human serum albumin-Kolliphor(®) HS 15 nanoparticles (HSA-HS15 NPs) to overcome the limitations in targeted therapy for rheumatoid arthritis (RA) and enhance the safety of drug-loaded HSA NPs. Methodology: Celastrol (CLT)-loaded HSA-HS15 NPs were prepared and the properties were adequately investigated; the treatment effect were evaluated in RA rats; in vitro and in vivo studies were performed to explain the mechanism. Results: CLT-HSA-HS15 NPs had remarkable treatment ability and enhanced safety in the treatment of RA compared with free CLT and CLT-HSA NPs. Conclusion: HSA-HS15 NPs could be a safe and efficient therapeutic strategy for the treatment of RA, because of the inflammatory targeting ability of albumin, the added HS15 and ELVIS effect (extravasation through leaky vasculature followed by inflammatory cell-mediated sequestration) of nanoparticles.
31505913 Diastolic dysfunction in rheumatoid arthritis: a usual travel-mate? 2019 Sep 10 A high rate of left ventricular diastolic dysfunction (LVDD) has been described in rheumatoid arthritis (RA), compared with general population. A prospective study demonstrated that LVDD occurred in 24% in one year of follow-up in RA patients without cardiac disease. Older age, higher systolic arterial pressure and lower E/A ratio are considered predictive factors. In addition, in RA, LVDD is known to be the only risk factor for the development of cardiovascular (CV) events, also in absence of classical CV risk factors. Some occasional reports suggest that early and aggressive treatment of RA could influence the evolution of LVDD and, accordingly, modify the rate of CV events. Therefore, a correct assessment of diastolic function should be considered of pivotal importance in the routine follow-up of RA patients.
30591403 Crosstalk between tumor necrosis factor-alpha signaling and aryl hydrocarbon receptor sign 2019 Mar OBJECTIVES: To examine the influence of smoking on biologics treatment against different therapeutic targets, such as TNFα, IL-6, and T cell, in rheumatoid arthritis (RA) and elucidate the underlying molecular mechanism. METHODS: The association between drug-discontinuation due to poor therapeutic response and smoking status was analyzed individually in biologics against different therapeutic targets by a multivariable logistic regression analysis using the "NinJa" Registry, one of the largest cohorts of Japanese RA patients. In vitro enhancement of TNFα-induced NF-κB activation and subsequent proinflammatory cytokine production by cigarette chemical components was examined by RT-PCR, qPCR, ELISA, and western blotting using an immortalized rheumatoid synovial cell line, MH7A. RESULTS: The rate of drug-discontinuation due to poor therapeutic response was higher in the current smoking group than in the never- or ever-smoking groups (the odds ratio of current/never smoking: 2.189, 95%CI; 1.305-3.672,P = 0.003; current/ever: 1.580, 95%CI; 0.879-2.839,P = 0.126) in the TNF inhibitor (TNFi) treatment group. However, this tendency was not observed in either the IL-6 or T cell inhibitor treatment groups. Cigarette smoke chemical components, such as benzo[α]pyrene, known as aryl hydrocarbon receptor (AhR) ligands, themselves activated NF-κB and induced proinflammatory cytokines, IL-1β and IL-6. Furthermore, they also significantly enhanced TNFα-induced NF-κB activation and proinflammatory cytokine production. This enhancement was dominantly inhibited by Bay 11-7082, an NF-κB inhibitor. CONCLUSIONS: These results suggest a crosstalk between TNFα signaling and AhR signaling in NF-κB activation which may constitute one of the molecular mechanisms underlying the higher incidence of drug-discontinuation in RA patients undergoing TNFi treatment with smoking habits.
31148470 Radiographic Outcomes of Mobile-Bearing Total Ankle Arthroplasty for Patients With Rheumat 2019 Sep BACKGROUND: Ankle disorders in patients with rheumatoid arthritis (RA) reduce their quality of life and activities of daily living. The aim of this study was to evaluate the midterm clinical and radiographic outcomes of TAA in patients with RA. METHODS: This retrospective study included patients with a minimum follow-up of 2 years. A total of 37 RA patients (39 ankles) were enrolled in this study from August 2006 to March 2016. All the patients had undergone primary cemented mobile-bearing total ankle arthroplasty (TAA). Nine ankles received arthrodesis of the subtalar joint simultaneously. Patient-reported outcomes were measured preoperatively and at the latest follow-up by Self-Administered Foot-Evaluation Questionnaire (SAFE-Q). Radiographs of the ankle were analyzed preoperatively and at all follow-up visits to measure the periprosthetic radiolucent line, migration of the tibial component, and the subsidence of the talar component. Intraoperative and postoperative complications were recorded. The average duration of follow-up for the entire cohort was 5.0 ± 2.0 years (range 2.1-10.1 years). RESULTS: All subscales of the SAFE-Q had improved significantly at the latest follow-up. No significant difference was found between the range of motion of the ankle before and after the surgery. Radiolucent lines were observed in 28 (73.7%) ankles. Migration of the tibial component and subsidence of the talar component were found in 8 (21.1%) and 11 (28.9%) ankles, respectively. Intraoperative malleolus fractures occurred in 3 (7.7%) ankles and delayed wound healing in 10 (25.6%) ankles. Four ankles were removed because of deep infection or noninfective loosening, resulting in an implant survival rate of 88.4% (95% CI, 0.76-1.0) at 10 years. CONCLUSION: The midterm patient-reported outcomes and implant retention rate after cemented mobile-bearing TAA for RA patients were satisfactory. However, a low radiographic implant success rate was observed. LEVEL OF EVIDENCE: Level IV, retrospective case series.
30217117 Safety and effectiveness of abatacept in Japanese non-elderly and elderly patients with rh 2019 Sep Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (≥65 years: EG) rheumatoid arthritis patients. Methods: This sub-analysis of an all-cases postmarketing surveillance in Japan assessed safety in all enrolled patients and effectiveness in those with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) measurements at ≥2 time points including baseline. Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2. Results: The NEG and EG of the safety analysis set comprised 2,170 and 1,712 patients, respectively; corresponding 6-month ABA retention rates were 80.2% and 77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p = .021) and infections (4.8% vs. 7.2%, p = .002) than the EG. DAS28-CRP changed similarly between groups. The proportion of patients with low-risk/high-benefit and high-risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high-benefit patients were younger, had shorter disease duration and fewer comorbidities, and were with less use of oral glucocorticoid and prior biologics, more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients at baseline. Conclusion: ABA was well tolerated and similarly efficacious in the EG and NEG. Identification of factors related to low-risk/high-benefit may aid appropriate patient selection.
30948396 Primary malignant melanoma of the urethra in a patient with rheumatoid arthritis treated w 2019 Apr 3 We report a case of a 79-year-old woman with urinary incontinence who presented at a urogynaecology appointment. Her medical history included rheumatoid arthritis (RA) treated with methotrexate (MXT) for 22 years. A polypoidal lesion was protruding from the meatus urethrae. The histoimmunocytology confirmed a primary superficial spreading malignant melanoma. The tumour was extensively excised, but 8 months later, due to a lymphatic nodal swelling, a positron emission tomography/CT was performed showing a process suspicious of malignant melanoma and multiple distant metastasis. The subsequent treatment was palliative and 1 year later, the patient died. The aetiology of malignant melanomas in the urethra is poorly understood. There is consistent evidence that RA is associated with a number of cancers, but it remains controversial whether this risk is increased with MXT. This case emphasises the importance of gynaecological examination even in patients with only weak symptoms from the pelvic region, especially in patients undergoing immunosuppressive treatment.
31089859 Quantitative power Doppler signal assessment in the subchondral bone region of the metacar 2019 Aug Ultrasonography is useful for assessment of synovitis in the hand of rheumatoid arthritis (RA) patients. The aim of this study was to investigate the predictive value of the quantitative power Doppler (PD) signal assessment in the subchondral bone region of the metacarpophalangeal (MCP) joint in patients with RA showing radiographic progression of the hand by comparing with those of previously reported scoring systems. Twenty-two patients (20 women) with RA who underwent power Doppler ultrasonography (PDUS) of the bilateral one to five MCP joints at baseline were included in the study. Radiography of both hands was performed at baseline and at 1 year. PDUS of the synovial space was evaluated according to semi-quantitative scoring (0-3) and quantitative measurement (0-100%). The PD signal in the subchondral bone region was qualitatively (0, 1) and quantitatively (mm(2)) assessed. The performance of PDUS assessment was compared using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the risk ratio (RR). As a predictor for radiographic progression, the quantitative PD signal assessment in the subchondral bone region (AUC = 0.842, p < 0.01) was equivalent to quantitative vascularity (AUC = 0.817, p < 0.05) and semi-quantitative scoring (AUC = 0.754, p < 0.05). As for the RR of the PD signal in the subchondral bone region for radiographic progression, the quantitative PD signal assessment was 5.40 (p < 0.01), whereas the qualitative PD signal assessment was 1.60 (p = 0.204). Quantitative PD signal assessment in the subchondral bone region can predict radiographic progression in the hand of RA patients.
31747496 [Changes the cytokine profile and calcium-regulating hormones in rheumatoid arthritis.]. 2019 The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.
31223038 Plasma Leptin Does Not Reflect the Effect of High Body Mass Index on Disease Activity in R 2020 Feb Background: The effect of obesity on disease severity in rheumatoid arthritis (RA) remains controversial. Adipocytes secrete pro-inflammatory cytokines and adipokines which may contribute to RA disease activity. The goal of the present study is to address the association between body mass index (BMI) with plasma levels of leptin, pro-inflammatory cytokines, and RA disease severity.Methods: Fifty RA patients (20 newly diagnosed and 30 under treatment) as well as 30 age- and sex-matched healthy subjects were included in this survey. The plasma levels of leptin and pro-inflammatory cytokines, including TNF-α and IL-6, were measured, and the results were compared among the patients in the three different categories of BMI, including <25, ≥25-30, and ≥30.Results: In our study, a significant positive correlation was observed between disease activity score-28 (DAS-28) and BMI in overweight (OW) RA patients (p = .036 r = 0.440). The plasma levels of leptin were significantly higher in patients group, compared to healthy subjects (p < .05); moreover, leptin levels were significantly higher in OW and obese patients compared to RA patients with normal BMI (p = .011, p = .001, respectively) and also BMI had positive correlation with leptin concentrations just in the newly diagnosed patients (p < .0001, r = 0.748). There was no correlation between leptin and DAS-28. The plasma IL-6 and TNF-α did not show significant differences between RA patients and healthy subjects, and also the plasma leptin did not have any correlation with plasma levels of IL-6 and TNF-α.Conclusion: BMI contribution to RA disease severity is independent of systemic levels of leptin and pro-inflammatory cytokines.
31654331 Tocilizumab Effects on Coagulation Factor XIII in Patients with Rheumatoid Arthritis. 2019 Dec INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic auto-immune disease associated with a prothrombotic state. Tocilizumab, an interleukin-6 receptor inhibitor, is highly effective in controlling disease activity and thrombotic risk. Factor XIII (FXIII), involved in thrombotic complications, has been reported to be reduced in RA patients during maintenance treatment with tocilizumab, but no data are available before and after the drug administration. Thus, we investigated the effects of tocilizumab on FXIII, thrombin generation and inflammation in patients with RA naïve for the drug. METHODS: We studied 15 consecutive adult patients with RA at baseline and 4 weeks after the onset of parenteral administration of tocilizumab, measuring disease activity and plasma levels of C-reactive protein (CRP), FXIII, and prothrombin fragments F1+2 by immunoenzymatic methods. Fifteen healthy subjects, sex-and age-matched with patients, served as normal controls for laboratory measurements. RESULTS: At baseline, patients with established RA had a median DAS28 of 4.8 (3.2-8.3) and, compared to healthy controls, had higher plasma levels of CRP (p < 0.0001), FXIII (p = 0.017) and F1+2 (p < 0.0001). Four weeks after starting treatment with tocilizumab, based on the EULAR response criteria, eight patients were classifiable as responders and seven as non-responders. In responders, we observed a statistically significant reduction not only of the values of DAS28 and CRP (p = 0.012 for both), ut also of plasma levels of FXIII (p = 0.05) and F1+2 (p = 0.025). In non-responders, all the studied parameters were unchanged. CONCLUSION: The decrease of FXIII and F1+2 levels after tocilizumab treatment observed only in those patients who responded to the drug indicates that the effect of tocilizumab on the prothrombotic state is linked to the control of inflammation and disease activity and not to a direct effect of the drug, thus contributing to the reduction of the cardiovascular risk.