Currently, it is not possible to predict whether patients with hyperuricemia (HUA) will develop gout and how this progression may be affected by urate-lowering treatment (ULT). Our study aimed to ...evaluate differences in plasma lipidome between patients with asymptomatic HUA detected ≤ 40 years (HUA ≤ 40) and > 40 years, gout patients with disease onset ≤ 40 years (Gout ≤ 40) and > 40 years, and normouricemic healthy controls (HC).
Plasma samples were collected from 94 asymptomatic HUA (77% HUA ≤ 40) subjects, 196 gout patients (59% Gout ≤ 40), and 53 HC. A comprehensive targeted lipidomic analysis was performed to semi-quantify 608 lipids in plasma. Univariate and multivariate statistics and advanced visualizations were applied.
Both HUA and gout patients showed alterations in lipid profiles with the most significant upregulation of phosphatidylethanolamines and downregulation of lysophosphatidylcholine plasmalogens/plasmanyls. More profound changes were observed in HUA ≤ 40 and Gout ≤ 40 without ULT. Multivariate statistics differentiated HUA ≤ 40 and Gout ≤ 40 groups from HC with an overall accuracy of > 95%.
Alterations in the lipidome of HUA and Gout patients show a significant impact on lipid metabolism. The most significant glycerophospholipid dysregulation was found in HUA ≤ 40 and Gout ≤ 40 patients, together with a correction of this imbalance with ULT.
Abstract
Background
In European axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) clinical registries, we aimed to investigate commonalities and differences in (1) set-up, clinical data ...collection; (2) data availability and completeness; and (3) wording, recall period, and scale used for selected patient-reported outcome measures (PROMs).
Methods
Data was obtained as part of the EuroSpA Research Collaboration Network and consisted of (1) an online survey and follow-up interview, (2) upload of real-world data, and (3) selected PROMs included in the online survey.
Results
Fifteen registries participated, contributing 33,948 patients (axSpA: 21,330 (63%), PsA: 12,618 (37%)). The reported coverage of eligible patients ranged from 0.5 to 100%. Information on age, sex, biological/targeted synthetic disease-modifying anti-rheumatic drug treatment, disease duration, and C-reactive protein was available in all registries with data completeness between 85% and 100%. All PROMs (Bath Ankylosing Spondylitis Disease Activity and Functional Indices, Health Assessment Questionnaire, and patient global, pain and fatigue assessments) were more complete after 2015 (68–86%) compared to prior (50–79%). Patient global, pain and fatigue assessments showed heterogeneity between registries in terms of wording, recall periods, and scale.
Conclusion
Important heterogeneity in registry design and data collection across fifteen European axSpA and PsA registries was observed. Several core measures were widely available, and an increase in data completeness of PROMs in recent years was identified. This study might serve as a basis for examining how differences in data collection across registries may impact the results of collaborative research in the future.
Interleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated ...the function of IL-40 in rheumatoid arthritis (RA).
IL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined.
IL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p<0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p<0.0001 for all) and decreased after 16 and 24 weeks (p<0.01 and p<0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p<0.0001 and p<0.01), as well as in the synovial fluid (p<0.0001 and p<0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), neutrophil attractants IL-8 (p<0.01), MIP-1α (p<0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p<0.0001) and neutrophil elastase (p<0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p<0.01), MCP-1 (p<0.05), and MMP-13 (p<0.01) compared to the unstimulated cells.
We show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.
Abstract
Objective
Achieving targeted disease activity (DA) is the primary therapeutic strategy in RA. Point measurements of DA are done at out-patient visits, however true DA between visits remains ...unobserved. This study sought to describe and validate a new outcome measure, i.e. time in remission (TIR).
Methods
Patients were enrolled in the Czech ATTRA-RA registry. TIR was calculated using linear interpolation of the DAS28-ESR determined at outpatient visits. Correlation coefficients were computed between TIR and DAS28-CRP, HAQ, Simple Disease Activity Index (SDAI), patient global assessment (PGA) and physician global assessment (PhGA). Using logistic regression, TIR was used as a predictor of remission (SDAI ≤3.3) and non-disability (HAQ <0.5). The predictive value of TIR was compared with point and sustained remission using the cross-validated area under receiver-operating curves.
Results
Since 2010, 2618 RA patients started anti-TNF therapy and were followed until 2020 or until treatment discontinuation. During the first 6 months of therapy, 56% of patients had no remission (TIR = 0), and 22% of patients reached sustained remission (TIR = 1), while 22% of patients had point remissions with 0 < TIR < 1. EULAR good responders and moderate/non-responders spent 64 ± 42% and 6 ± 18% of time in remission, respectively. The mean TIR grew during the follow-up and was correlated with DAS28-CRP, SDAI, HAQ, PGA, and PhGA (P < 0.0001). TIR at 3 and 6 months predicted remission (SDAI ≤3.3) and non-disability (HAQ <0.5) at 13 and 19 months better than point or sustained remission.
Conclusions
TIR is an intuitive way of estimating unobserved DA between scheduled visits; its calculation only requires two consecutive DA values (https://www.medevio.cz/tir-calculator/). TIR is a valid predictor of RA outcomes.
A pre-morbid 'baseline' creatinine is required in order to diagnose and stage acute kidney injury (AKI) using the RIFLE classification. Estimation of baseline creatinine by solving the Modification ...of Diet in Renal Disease (MDRD) equation assuming a glomerular filtration rate of 75 ml/min/1.73 m(2) has been widely used but never validated.
We analysed four cohorts of intensive care unit (ICU) patients from three centres (two from Pittsburgh and one from Mayo and Austin). Three cohorts consisted of preselected patients without AKI (Pittsburgh 1 n = 1048, Mayo n = 737, Austin n = 333), and measured creatinine values in these cohorts were taken to represent baseline creatinine values. The last cohort (Pittsburgh 2 n = 468) consisted of unselected ICU patients with baseline creatinine values recorded within 1 year before ICU admission. Using the Pittsburgh 1 cohort, we derived an equation using the same anthropometric variables as the MDRD equation: baseline creatinine = 0.74 - 0.2 (if female) + 0.08 (if black) + 0.003 × age (in years). We then compared measured creatinine in the Mayo and Austin cohorts and recorded creatinine in the Pittsburgh 2 cohort to the estimated creatinine from: (i) the MDRD equation; (ii) our new equation; (iii) a gender-fixed creatinine of 0.8 mg/dl for females and 1.0 mg/dl for males.
Using any of the three methods, the median absolute error of the estimates was of the order of 0.1-0.2 mg/dl, and overall accuracy was similar. When the definition of AKI was limited to the severity grades of Injury and Failure, all three methods were able to generate 78-90% reliable results for preselected normal range cohorts, and 63-70% for the unselected cohort of ICU patients.
Estimates of incidence of AKI in the critically ill using RIFLE classification can be affected by the bias and limited accuracy of methods to estimate baseline creatinine. Whenever possible, recorded creatinine values should be used as a reference of baseline. The use of the MDRD equation to estimate baseline creatinine when it is unknown may over- or underestimate some mild (Risk) AKI cases but is unlikely to misclassify patients in Injury and Failure.
Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by ...musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA.
Patients with RA (n = 185 (46 with incident and 139 with prevalent disease) were followed for 30.9 ± 9.1 months. Baseline and annual assessments comprised the disease activity score in 28 joints (DAS28), HAQ and US7S. The US7S includes semiquantitative measurements of synovitis assessed by greyscale (GS) and power Doppler (PD) in seven joints of the clinically dominant hand and foot, which are then aggregated in PD and GS synovitis sum-scores (PDsynSS and GSsynSS). A linear mixed-effect model was used to assess the longitudinal relationship between GSsynSS, PDsynSS and HAQ. We used standard and time-lag models to explore the association between HAQ, and GSsynSS, PDsynSS and DAS28 measured at the same time or at the previous visit 12 months ago, respectively.
When the standard model was applied, in univariate analyses HAQ score was positively associated with GSsynSS and PDsynSS with β coefficients significantly higher in incident than in prevalent disease. In multivariate analysis both synSSs were individually no longer significant predictors of HAQ score. When using the time-lag model, after adjustment for the previous DAS28 or HAQ score, both PDsynSS and GSsynSS were significantly and negatively associated with the current HAQ.
US7 PD and GS synovitis sum-scores alone were positively associated with current functional status reflected by the HAQ in patients with RA, and this relationship was stronger in patients with early disease. When combined with the DAS28 or HAQ, US7 PD and GS synovitis sum-scores were predictive of the change in HAQ score over one year.
Abstract Objective To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with (i) treatment line ...(second and third TNFi-series) and (ii) reason for withdrawal from the preceding TNFi lack of efficacy (LOE) vs adverse events (AE). Methods Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID) were assessed in second and third TNFi-series and stratified by withdrawal reason. Results We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE vs LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE <26 vs ≥26 weeks) (58% vs 71%, P < 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) vs LOE (17%), P < 0.001, while similar for the third TNFi (19% vs 13%, P = 0.20). Conclusion A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE vs LOE.
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