Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
35599718 Functional outcomes and complications following convertible primary total elbow arthroplas 2022 Jun BACKGROUND: The data on convertible total elbow arthroplasty are limited and primarily based on multiple centre/multiple surgeon series. The aim of this study was to report the mid-term functional outcomes, radiological findings, complications and survivorship of the Latitude total elbow arthroplasty performed by a single surgeon. STUDY DESIGN & METHODS: The study included 13 patients (10 females, mean age of 72 years and varying indications) over eight years. The Oxford Elbow Score (OES), Mayo Elbow Performance Score (MEPS), range of movements (ROM), Subjective Elbow Value (SEV), satisfaction score (SS) and the revision rate of the implant per 100 observed component years (OCY) were assessed. RESULTS: The mean follow-up was 5.9 years (3-10 years). The Oxford Elbow Score/Mayo Elbow Performance Score improved from 15 to 42 (p value < 0.005)/26% to 93% (p value < 0.005) respectively. The arc of extension-flexion/supination-pronation improved from 63° to 106° (p = 0.00002)/123° to 142° (p = 0.32) respectively. The Subjective Elbow Value/Satisfaction Score was 83/98 respectively. There was one re-operation for a deep infection. There were no radiologic signs of loosening and the revision rate was 0.15 per 100 observed component years. CONCLUSIONS: With careful patient selection, convertible total elbow arthroplasty provides patients with good to excellent outcomes and substantial improvements in the range of movements.
35349660 Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporos 2022 Mar 29 INTRODUCTION: Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes whilst additionally considering an inflammatory component, C-reactive protein (CRP). MATERIAL AND METHODS: Genome-wide association study summary (GWAS) statistics were acquired from the GEFOS consortium, CHARGE consortium, and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits due to shared causal SNPs was performed using pleiotropic analysis under composite null hypothesis (PLACO). RESULTS: MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95%CI = 0.016 to 0.038). There was no evidence of CRP → OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis were all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. DISCUSSION: We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation; (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.
35488383 Association of CD90 Expression by CD14(+) Dendritic-Shaped Cells in Rheumatoid Arthritis S 2022 Apr 29 OBJECTIVE: CD14(+) dendritic-shaped cells show a dendritic morphology under the electron microscopy and engage in a pseudoemperipolesis phenomenon with lymphocytes. CD90 has been used as a marker of a major subset of fibroblast-like synoviocytes in rheumatoid arthritis (RA). In this study, we investigated the significance of CD90 expression in CD14(+) dendritic-shaped cells and its correlation with RA chronic inflammation. METHODS: Double immunofluorescence staining for CD14 and CD90 was performed in the collected tissues, including 12 active RA synovial tissues. The localization of CD14(+) CD90(+) cells, the percentages of CD14(+) CD90(+) cells and vascular areas, the degree of synovitis, and clinical data were investigated. Furthermore, CD14(+) CD90(+) cells analyzed by flow cytometry (CD14(high) CD90(intermediate (int)) cells) were sorted from RA synovial cells, and we examined their potential to differentiate into dendritic cells. RESULTS: Double immunofluorescence staining showed that CD14(+) CD90(+) cells were abundant in RA synovial tissues. The percentages of CD14(+) CD90(+) cells and vascular areas correlated with some of the Krenn synovitis scores, but neither showed a strong correlation with RA disease activity parameters. Flow cytometry analysis indicated that CD14(high) CD90(int) cells were more abundant in both peripheral blood samples and synovial tissues in patients with active RA. CD14(high) CD90(int) cells were more likely to differentiate into dendritic cells in vitro. CONCLUSION: CD14(+) dendritic-shaped cells expressed CD90 in the perivascular areas of RA synovial tissues. These findings suggest that CD14(+) CD90(+) dendritic-shaped cells migrate from the peripheral blood to the synovial tissue, the site of inflammation, and may contribute to the chronic inflammation of RA as dendritic progenitor cells.
35089655 Efficacy and Acceptability of Intermittent Aerobic Exercise on Polysomnography-Measured Sl 2022 May OBJECTIVE: This study's objective was to investigate the efficacy and acceptability of intermittent aerobic exercise training on sleep parameters, fatigue, pain, depressive symptoms, physical function, and cardiorespiratory fitness in people with rheumatoid arthritis (RA). METHODS: Thirty-eight people with RA were assigned to intermittent aerobic exercise training (three sessions/week for 6 weeks; intervention group, n = 17) or usual care (control group, n = 21). The primary outcome was a change in polysomnography-assessed sleep efficiency from baseline to the end of the intervention. Secondary outcomes were sleep quality (Pittsburgh Sleep Quality Index), fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire), depression (Center for Epidemiological Studies-Depression), and cardiorespiratory fitness (watt max test). RESULTS: No between-group differences were found in changes in polysomnography-assessed sleep efficiency (0.04; 95% confidence interval [CI]: -0.02 to 0.09, P = 0.17). In the intervention group, sleep efficiency was improved significantly from baseline (0.84; 95% CI: 0.80-0.88) compared with the end of the intervention (6 weeks) (0.88; 95% CI: 0.85-0.92); however, there was no significant difference in the control group. Fatigue and depression measures were significantly lower in the intervention group than in the control group. Between-group differences were overall fatigue (-16.1; 95% CI: -25.1 to -7.0, P = 0.001), physical fatigue (-5.0; 95% CI: -7.3 to -2.7, P = 0.0001), cognitive fatigue (-2.4; 95% CI: -4.2 to 0.6, P = 0.009), living with fatigue (-2.5; 95% CI: -4.5 to -0.5, P = 0.01), and depressive symptoms (-6.8; 95% CI: -12.4 to -1.1, P = 0.02). CONCLUSION: The intervention yielded no significantly better sleep efficiency compared with usual care. However, aspects of fatigue, including physical and cognitive fatigue, and depressive symptoms were significantly improved in the intervention group.
34998078 The effects of autoimmune rheumatic-related diseases on male reproductive health: A system 2022 Mar Autoimmune rheumatic-related diseases (ARRDs) have physical and psychological impact on patients, including their sexual life. While many studies have investigated fertility problems in females, data on males-related fertility are scarce, which explains the lack of guidance. The main objective of this systematic review was to evaluate the reproductive health in males with ARRDs. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until September 16, 2021, and tackling the effects of ARRDs and/or ARRDs treatments on male fertility and/or pregnancy outcomes, were included. A total of twenty-five studies met the inclusion criteria. They were published between 1981 and 2018. The studied ARRDs were spondyloarthritis (n = 9), systematic lupus erythematosus (SLE, n = 6), Behcet disease (BD, n = 5), rheumatoid arthritis (RA, n = 5), antiphospholipid syndrome (n = 1), and dermatomyositis (n = 1). The most reported effects of ARRDs on fertility are i) high levels of reproductive hormones, mainly in RA and SLE; ii) impaired semen quality in SLE, spondyloarthritis, and BD; and iii) higher rate of varicocele in BD and spondyloarthritis. Regarding the treatments effects, i) conventional synthetic disease-modifying anti-rheumatic drugs (e.g.; methotrexate and salazopyrine) increase testosterone level, ii) cyclophosphamide impairs fertility, iii) anti-tumor necrosis factor agents are associated with improvement in semen quality, and iv) no increased number of miscarriages or congenital abnormalities in children fathered by BD was reported. To conclude, both ARRDs and their treatments alter fertility in males with ARRDs. In practice, in addition to the conventional semen analysis, screening for infertility seems legitimate in males with ARRDs.
35395090 The development of inflammatory arthritis following SARS-CoV-2 infection: a systematic rev 2022 Apr 8 BACKGROUND: Given the widespread impact of COVID-19, it is important to explore any atypical presentations and long-term sequelae associated with this viral infection, including the precipitation of inflammatory arthritis. OBJECTIVE: To identify and summarize clinical reports of acute inflammatory arthritis associated with COVID-19. METHODS: A systematic review of the PubMed (MEDLINE), Google Scholar, and Cochrane Central databases through January 31, 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The inclusion criteria were: human subjects and English language. Data extraction and qualitative synthesis of the demographics, clinical presentations, treatments, and outcomes were performed. Quality assessment was performed using the Joanna-Briggs Institute critical appraisal tools. RESULTS: A total of 37 articles collectively describing the cases of 54 patients were included. The mean age was 48.2 years (6-78 years). 53.7% of patients were male and 46.3% were female. The onset of articular symptoms varied considerably, and the majority of cases were described as polyarticular (29). The classification of inflammatory arthritis in the included studies was as follows: reactive (19), post-viral (13), new-onset rheumatoid arthritis (RA) (8), crystal-proven arthropathy flare (4), acute viral (2), new-onset psoriatic arthritis (2), flare of preexisting RA (2), and other (4). Arthritis treatment regimens varied but consisted largely of NSAIDs and corticosteroids with most patients experiencing improvement or resolution of their joint symptoms. CONCLUSION: There is limited low-level evidence suggesting that patients may develop acute arthritis during or after SARS-CoV-2 infection. This review highlights the need for further research to elucidate the relationship between COVID-19 and the development of inflammatory arthritis.
34405886 Interleukin-6 and Serum/Fecal Calprotectin as Useful Specific Markers for Monitoring Rheum 2022 Mar 7 OBJECTIVE: Some conventional laboratory tests are routinely used for the prediction of systemic autoimmune disease activity, such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); however, they can give false-negative results, pointing out the need to identify more specific markers. METHODS: We evaluated biomarkers in 21 Italian patients naïve to treatment with a diagnosis of autoimmune rheumatic disease according to the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis during 6 months of therapeutic treatments. RESULTS: We found a significant difference in interleukin-6 (IL-6), CRP, ESR, platelet count, and fecal calprotectin in diagnosed patients compared with healthy participants and a significant decrease in these values during follow-up, except for IL-6 and platelet count. CONCLUSION: We found that CRP, ESR, and fecal calprotectin seemed to be related to autoimmune rheumatic disorders and to be associated with therapy, whereas serum calprotectin and IL-6 did not seem to be associated with disease improvement after the start of treatment, along with leukocyte count and platelet count.
35449643 H Syndrome: Report of The First Case in African Ethnicity. 2022 Mar H syndrome is an autosomal recessive multisystemic disease with a very low prevalence rate, characterized by indurated cutaneous hyperpigmentation, hypertrichosis, and various systemic manifestations. The syndrome is caused by mutations in SLC29A3 gene on chromosome 10q23, encoding for human equilibrative transporter 3 (hENT3). So far, only 100-120 patients with H syndrome have been described in the literature, with predominance among Indian, North-American, and Arab ethnicities. This case report describes the first one of H-syndrome rarities in African ethnicity, a 30-year-old Sudanese male misdiagnosed with rheumatoid arthritis. The patient exhibited more than 90% of the clinical characteristics of H syndrome including obesity, short stature, characteristic hyperpigmented, sclerotic cutaneous plaques with induration and hypertrichosis, inflammatory arthropathy, hallux valgus, flexion deformity of toes, exophthalmos, cardiac anomaly, hypogonadism, and splenomegaly and characteristic histologic findings of dermal fibrosis, histiocytosis, lymphoid aggregation, and vascular proliferation. H syndrome is an extremely rare autoinflammatory condition that has a complex constellation of pleiotropic manifestations with multisystemic involvement. And while further identification and better pathophysiological understanding of H syndrome are needed, physicians worldwide should be vigilant about the overlapping features of H syndrome with many other rheumatological, cutaneous, and genetic diseases.
35360728 Deep Learning-Based Classification of Inflammatory Arthritis by Identification of Joint Sh 2022 OBJECTIVE: We investigated whether a neural network based on the shape of joints can differentiate between rheumatoid arthritis (RA), psoriatic arthritis (PsA), and healthy controls (HC), which class patients with undifferentiated arthritis (UA) are assigned to, and whether this neural network is able to identify disease-specific regions in joints. METHODS: We trained a novel neural network on 3D articular bone shapes of hand joints of RA and PsA patients as well as HC. Bone shapes were created from high-resolution peripheral-computed-tomography (HR-pQCT) data of the second metacarpal bone head. Heat maps of critical spots were generated using GradCAM. After training, we fed shape patterns of UA into the neural network to classify them into RA, PsA, or HC. RESULTS: Hand bone shapes from 932 HR-pQCT scans of 617 patients were available. The network could differentiate the classes with an area-under-receiver-operator-curve of 82% for HC, 75% for RA, and 68% for PsA. Heat maps identified anatomical regions such as bare area or ligament attachments prone to erosions and bony spurs. When feeding UA data into the neural network, 86% were classified as "RA," 11% as "PsA," and 3% as "HC" based on the joint shape. CONCLUSION: We investigated neural networks to differentiate the shape of joints of RA, PsA, and HC and extracted disease-specific characteristics as heat maps on 3D joint shapes that can be utilized in clinical routine examination using ultrasound. Finally, unspecific diseases such as UA could be grouped using the trained network based on joint shape.
35416958 An ultrasound negative for subclinical synovitis in arthralgia patients: is it helpful in 2022 Apr 13 OBJECTIVE: To investigate the negative predictive value (NPV) of musculoskeletal-ultrasound (MSUS) in arthralgia-patients at risk for developing inflammatory arthritis (IA). METHODS: An MSUS examination of hands and feet was performed in arthralgia-patients at risk for IA in four independent cohorts. Patients were followed for one-year on the development of IA. Subclinical synovitis was defined as greyscale ≥ 2 and/or power Doppler ≥ 1. NPVs were determined and compared with the prior risks of not developing IA. Outcomes were pooled using meta-analyses and meta-regression analyses. In sensitivity analyses, MSUS-imaging of tender joints only (rather than the full US-protocol) was analyzed and ACPA-stratification applied. RESULTS: After one-year 78%, 82%, 77% and 72% of patients in the four cohorts did not develop IA. The NPV of a negative US was 86%, 85%, 82% and 90%, respectively. The meta-analysis showed a pooled non-IA prevalence of 79% (95%CI: 75%-83%) and a pooled NPV of 86% (95%CI : 81-89%). Imaging tender joints only (as generally done in clinical practice) and ACPA-stratification showed similar results. CONCLUSION: A negative US result in arthralgia has a high NPV for not developing IA, which is mainly due to the high a-priori risk of not developing IA. The added value of a negative US (<10% increase) was limited.
35110573 Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rhe 2022 Feb 2 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints affecting ~7.5 million people worldwide. Disease pathology is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of macrophage phenotype, specifically an M1 to M2, pro- to anti-inflammatory transition, can be induced by biologic scaffold materials composed of extracellular matrix (ECM). The ECM-based immunomodulatory effect is thought to be mediated in part through recently identified matrix-bound nanovesicles (MBV) embedded within ECM. Isolated MBV was delivered via intravenous (i.v.) or peri-articular (p.a.) injection to rats with pristane-induced arthritis (PIA). The results of MBV administration were compared to intraperitoneal (i.p.) administration of methotrexate (MTX), the clinical standard of care. Relative to the diseased animals, i.p. MTX, i.v. MBV, and p.a. MBV reduced arthritis scores in both acute and chronic pristane-induced arthritis, decreased synovial inflammation, decreased adverse joint remodeling, and reduced the ratio of synovial and splenic M1 to M2 macrophages (p < 0.05). Both p.a. and i.v. MBV reduced the serum concentration of RA and PIA biomarkers CXCL10 and MCP-3 in the acute and chronic phases of disease (p < 0.05). Flow-cytometry revealed the presence of a systemic CD43hi/His48lo/CD206+, immunoregulatory monocyte population unique to p.a. and i.v. MBV treatment associated with disease resolution. The results show that the therapeutic efficacy of MBV is equal to that of MTX for the management of acute and chronic pristane-induced arthritis and, further, this effect is associated with modulation of local synovial macrophages and systemic myeloid populations.
35169059 Basic Science Session 2. Recent Advances in Our Understanding of Psoriatic Arthritis Patho 2022 Jun The second basic science session at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting focused on 2 recent publications that have increased our understanding of the pathogenesis of psoriatic arthritis (PsA). Data from the first publication, presented by Prof. Erik Lubberts, showed that interleukin (IL)-17A is produced by CD4+ and not CD8+ T cells in PsA synovial fluid following T cell receptor activation. These findings contrast with previously published data, which had suggested that CD8+ T cells are a prominent source of IL-17A. In further experiments, they showed that when CD8+ T cells were stimulated with paramethoxyamphetamine/ionomycin, relatively high levels of IL-17A were detected. Prof. Jose Scher presented work on the role of the microbiome in PsA and more specifically, on pharmacomicrobiomics. He demonstrated the baseline collection of genomes and genes from the microbiota community (the metagenome) can be used as predictor for future treatment response in early rheumatoid arthritis and also likely in PsA.
35046940 Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/Bx 2021 Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.
35018685 Primary Sjögren's syndrome: Longitudinal real-world, observational data on health-related 2022 Jun INTRODUCTION: Primary Sjögren's syndrome (pSS) is a chronic inflammatory condition, which presents with symptoms of dryness, pain, fatigue and often symptoms of anxiety and depression. Health-related quality of life (HRQoL) is significantly reduced in pSS and the direct and indirect health costs of pSS are substantial. This study aims to determine how symptom burden, disease activity and demographics associate with HRQoL longitudinally over a median of 24-month follow-up period in pSS. METHODS: Longitudinal EuroQoL-5 dimension (EQ-5D)-3L data from the Newcastle pSS cohort (n = 377) were evaluated using a survival analysis strategy. Kaplan-Meier and Cox proportional hazards analysis were performed using baseline Newcastle Sjogren's Stratification Tool (NSST) subgroup, EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), disease duration, age and sex as covariates including polypharmacy and comorbidity score, where data were available (n = 191). RESULTS: Of the 377 pSS participants analysed in this study, 16% experienced a decline in HRQoL to a health state comparable to or worse than death. NSST subgroup and ESSPRI score had a significant relationship with time to 'EQ-5D event', whereas baseline ESSDAI, age, disease duration and sex did not. CONCLUSION: In pSS, symptom burden and to a great extent NSST subgroup, rather than systemic disease activity, has a significant relationship with HRQoL longitudinally. Improvements in symptom burden have the potential to produce significant impacts on long-term HRQoL in pSS.
34212822 Increased salivary syndecan-1 level is associated with salivary gland function and inflamm 2022 May OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.
35289149 Comparative Study between ZOOMit and Conventional Intravoxel Incoherent Motion MRI for Ass 2022 Apr OBJECTIVE: To compare the reproducibility and performance of quantitative metrics between ZOOMit and conventional intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the diagnosis of early- and mid-stage Sjögren's syndrome (SS). MATERIALS AND METHODS: Twenty-two patients (mean age ± standard deviation, 52.0 ± 10.8 years; male:female, 2:20) with early- or mid-stage SS and 20 healthy controls (46.9 ± 14.6 years; male:female, 7:13) were prospectively enrolled in our study. ZOOMit IVIM and conventional IVIM MRI were performed simultaneously in all individuals using a 3T scanner. Quantitative IVIM parameters - including tissue diffusivity (D), pseudodiffusion coefficient (D(*)), and perfusion fraction (f) - inter- and intra-observer reproducibility in measuring these parameters, and their ability to distinguish patients with SS from healthy individuals were assessed and compared between ZOOMit IVIM and conventional IVIM methods, appropriately. MR gland nodular grade (MRG) was also examined. RESULTS: Inter- and intra-observer reproducibility was better with ZOOMit imaging than with conventional IVIM imaging (ZOOMit vs. conventional, intraclass correlation coefficient of 0.897-0.941 vs. 0.667-0.782 for inter-observer reproducibility and 0.891-0.968 vs. 0.814-0.853 for intra-observer reproducibility). Significant differences in ZOOMit f, ZOOMit D(*), conventional D(*), and MRG between patients with SS and healthy individuals (all p < 0.05) were observed. ZOOMit D(*) outperformed conventional D(*) in diagnosing early- and mid-stage SS (area under receiver operating curve, 0.867 and 0.658, respectively; p = 0.002). The combination of ZOOMit D(*), MRG, and ZOOMit f as a new diagnostic index for SS, increased diagnostic area under the curve to 0.961, which was higher than that of any single parameter (all p < 0.01). CONCLUSION: Considering its better reproducibility and performance, ZOOMit IVIM may be preferred over conventional IVIM MRI, and may subsequently improve the ability to diagnose early- and mid-stage SS.
34999918 Use of the Behavioral Regulation in Exercise Questionnaire-2 to assess motivation for phys 2022 Jan 9 Arthritis patients may show little motivation for physical activity (PA), resulting in a sedentary lifestyle. The primary objective of the study was to investigate whether motivation for PA and fulfillment of PA recommendations were associated with cardiorespiratory fitness in patients with RA. The exploratory objective was to study whether university students could be used as controls for RA patients in future studies of PA motivation. Peak oxygen uptake (VO(2peak)) was measured in 93 RA patients. The patients and 354 students filled in the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Data were analyzed using structural equation modeling with adjustment for age and sex. The BREQ-2 scores were also compiled to an overall motivational style "Relative Autonomy Index" as previously published. Mean VO(2peak) for the RA patients was 32.2 (SD: 9.6) mL × min(-1) × kg(-1). Only 29 patients (31%) fulfilled the current recommendations for PA. BREQ-2 scores were associated with measured VO(2peak) (standardized coefficient 0.33, p < 0.001). Whether a person fulfilled the current recommendations for PA was a significant mediator of this effect (standardized coefficients: mediated effect; 0.22, p = 0.001, remaining direct effect; 0.11, p = 0.18). The Relative Autonomy Index also significantly predicted measured VO(2peak) (standardized coefficient 0.30, p < 0.001). The underlying BREQ-2 factor structure was significantly different between RA patients and university students, and comparison of scores would not be adequate. Motivation for PA was significantly associated with measured VO(2peak) in RA patients. The effect was mediated by whether the patient fulfilled the current recommendations for PA. Addressing and stimulating motivation is important when intervening to increase PA and cardiovascular fitness in RA patients.
35091325 Long-term abatacept treatment for 48 weeks in patients with primary Sjögren's syndrome: T 2022 Apr OBJECTIVE: To investigate treatment efficacy of long-term abatacept treatment in pSS patients. METHODS: The single-centre ASAP-III trial consisted of two phases: the randomised, double-blind, placebo-controlled phase (1:1 randomisation) from baseline to week 24, of which results have been published previously, and the open-label extension phase from week 24 to 48, in which all patients received abatacept. Main inclusion criteria were fulfilment of the AECG criteria, positive gland biopsy, disease duration ≤ 7 years and ESSDAI ≥ 5. Long-term treatment effects of abatacept on clinical, patient-reported, glandular and laboratory outcome measures were assessed in patients treated with abatacept from baseline to week 48. Furthermore, Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS) response (response on ≥3 of 5 items) was analysed. RESULTS: In patients on abatacept treatment for 48 weeks (n = 40), median ESSDAI improved from baseline 14.0 (IQR 9.0-16.8) to 4.0 (2.0-8.0) at week 48 (p < 0.001), with 50% of patients reaching low disease activity (ESSDAI < 5) at week 48. Median ESSPRI improved from 7.0 (IQR 5.4-7.7) to 5.0 (3.7-6.7) (p < 0.001). Significant improvement was also seen in dry eye and laboratory tests. Combining response at multiple clinically relevant items, 73% of patients were CRESS responders at week 48. Additional improvement was seen between week 24 and week 48 of abatacept treatment. CONCLUSION: In the open-label extension phase of the ASAP-III trial, improvement was seen up to 48 weeks of abatacept treatment in clinical, patient-reported, dry eye and laboratory outcomes. The majority of patients were CRESS responders at week 48.
35330475 Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to A 2022 Mar 16 Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms. This paper examines the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), CFS-like (Fibro-fatigue Scale) symptoms and immune-inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylcer-amide (CD17) in RA. The serum biomarkers were assayed in 118 RA and 50 healthy controls. Results were analyzed using the new precision nomothetic psychiatry approach. We found significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tender and swollen joints, and patient and evaluator global assessment scores. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning psychopathology and RA symptoms was explained by immune-inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. We constructed a new endophenotype class comprising patients with very high immune-inflammatory markers, CD17, RA, affective and CF-like symptoms, and tobacco use disorder. We extracted a reliable and replicable latent vector (pathway phenotype) from immune data, psychopathology, and RA-severity scales. Depression, anxiety, and CFS-like symptoms due to RA are manifestations of the phenome of RA and are mediated by the effects of the same immune-inflammatory, autoimmune, and other pathways that underpin the pathophysiology of RA.
35214136 Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of 2022 Feb 12 Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1β protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1β protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.