Objective Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first‐ever validated classification criteria for symptomatic CPPD disease. Methods Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de‐identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi‐criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. Results Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). Conclusion The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.
Abstract Objectives Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. Methods Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher’s exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. Results Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13–96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. Conclusion No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.
Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease.Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort.Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers).The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.
Abstract Background Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. Methods In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. Results A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p = 0.008) and an increase in cough (63% vs 17% p < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p = 0.004) and palpitations (12% vs 32% p < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms. Conclusion This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination.
Despite inflammation being implicated in cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in 2 independent cohorts of PWH. We identified 3 distinct inflammatory clusters present in both cohorts that were associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.
Background Patients with inflammatory arthritis die prematurely of cardiovascular disease. Inflammation activates platelets. Since treatment of inflammatory arthritis is associated with reduced mortality, and decreased platelet reactivity reduces cardiovascular events, we hypothesised that platelet reactivity as measured by dynamic platelet function (DPF) would be increased in patients with inflammatory arthritis and that reactivity could be reduced with therapeutic intervention. Objectives To characterise platelet function using a validated physiological assay in patients with inflammatory arthritis before and after disease improvement. Methods 22 patients were recruited and treated as per local protocol. DPF was measured at baseline and after clinical improvement. Video microscopy was utilised to measure dynamic platelet behaviour in microliters of blood perfused over von Willebrand factor (VWF) at arterial shear rates (1500 s-1). Motion-analysis software measured the number of platelets interacting with VWF, translocating across VWF, the speed and distance platelets travelled across VWF, and stably adhering to the surface. Platelet parameters at baseline and following improvement were compared using Wilcoxon signed rank test and paired student t-test. Changes in platelet function were correlated to inflammatory disease markers by Pearson Correlation. Results 18 patients completed the study. Platelet adhesion decreased and platelet motion increased following treatment. Tender joint count correlated with platelet adhesion (Pearson r = 0.616, p≤0.01) while CRP correlated with velocity of platelet movement (Pearson r = 0.563, p≤0.01). Conclusions Improvement in clinical markers of inflammation is associated with a corresponding change in platelet function. Given the association between reduced mortality and decreased platelet reactivity our results suggest that an appropriate assay of platelet function could guide future therapy of patients with inflammatory arthritis.
Abstract Background The immunological memory to SARS-CoV-2 (SCV-2) vaccination has multiple components, with robust antibody (Ab) and B cell responses demonstrated post vaccination. The extent and persistence of T cell responses to vaccination remains unclear. We explored SCV-2 specific Ab, B cell and T cell responses to 3rd dose vaccine and their relationship to incident COVID-19. Methods In plasma from adults enrolled in a multicentre prospective cohort, sampled before, 14 days and 10 months post 3rd dose vaccine (BNT162b2) we measured anti-SCV-2 receptor binding domain (RBD) Ab by electrochemiluminescence assays. Subjects reported incident COVID-19 that occurred post vaccination. In a subanalysis, we assessed SCV-2-specific plasma cell, memory B cell and T cell responses in peripheral blood mononuclear cells after stimulation with wild type (WT) RBD, WT full Spike antigen, Omicron RBD and Omicron S1 antigens by ELISpot (Mabtech ELISpot, Sweden, Fig 1). We compared between-group differences in immunological outcomes by incident infection by Wilcoxon signed rank or Mann–Whitney U tests. Data are median (IQR) unless specified. Results Of 132 subjects (age 43 [32-50], 81% female (Table 1), 47 (36%) reported incident SCV-2 infection at 18 (16-21) weeks post 3rd vaccine. 76 subjects contributed to the cellular immunity subanalysis [23 of whom provided additional samples 10 months post vaccine (Table 1)]. RBD titres and B cell responses increased significantly 2 weeks post 3rd vaccine (Fig 2, p< 0.001), with RBD titres and WT-specific memory B cell responses remaining significantly higher than pre-booster vaccine levels at 10 months (Fig 2, p< 0.001). In contrast, there was no significant difference in T cell responses at two weeks or 10 months post 3rd dose vaccine (Fig 2). There was no difference in 2-week post vaccine RBD or T cell responses in those with and without incident SCV-2 infection. However, those with incident infection had significantly lower WT RBD-specific plasma and memory B cell levels (Table 2, all p< 0.05). Conclusion 3rd dose vaccination induced robust antibody and B cell responses which persist at 10 months, but not T cell responses. Higher memory B cell responses post vaccination, rather than circulating antibody titres or T cells, are associated with protection from subsequent infection. Disclosures Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds
Background: There is limited data regarding the risk of hospitalisation in patients with rheumatic disease and COVID-19 in Ireland. Objectives: We used the COVID-19 Global Rheumatology Alliance (GRA) registry data to study outcomes and their predictors. Methods: We examined data on patients and their disease-related characteristics entered into the COVID-19 GRA provider registry from Ireland (24th March 2020 to 31st August 2020). Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with hospitalisation. Results: Of 105 patients, 47 (45.6%) were hospitalised and 10 (9.5%) died. Multivariable logistic regression analysis showed age (OR=1.06, 95%CI 1.01 to 1.10), number of comorbidities (OR=1.93, 95%CI 1.11 to 3.35), and glucocorticoid use (OR=15.01, 95%CI 1.77 to 127.16) were significantly associated with hospitalisation. A diagnosis of inflammatory arthritis was associated with a lower odds of hospitalisation (OR=0.09, 95%CI 0.02 to 0.32). All significant variable model Most parsimonious model Unadjusted OR (95% CI) Adjusted OR (95%CI)* Adjusted p-value* Adjusted OR (95%CI) & Adjusted p-value & Female 0.45 (0.20-1.02) 0.33 (0.05-2.23) 0.34 (0.09-1.36) 0.128 Age (years) 1.08 (1.05-1.11) 1.04 (0.97-1.10) 0.224 1.06 (1.01-1.10) 0.010 Inflammatory arthritis 0.11 (0.05-0.28) 0.14 (0.02-0.95) 0.044 0.09 (0.02-0.32) <0.001 Connective Tissue Disease and Other 1.56 (0.62 - 3.92) No comorbidities 0.11 (0.04-0.30) 0.76 (0.09-6.58) 0.802 Most common comorbidities COPD / asthma 4.77 (1.23-18.54) 3.09 (0.16-60.07) 0.456 CVD 3.40 (1.31-8.85) 0.11 (0.01-1.88) 0.129 Hypertension 3.71 (1.52-9.08) 0.56 (0.04-7.94) 0.668 Obesity 0.58 (0.10-3.30) Number of comorbidities (Median, IQR) 3.01 (1.92-4.72) 2.99 (0.59-15.02) 0.184 1.93 (1.11-3.35) 0.020 Never Smoker ref. 0.889 Ever Smoker 3.17 (1.18-8.89) 1.19 (0.10-13.68) Medication prior to COVID-19 diagnosis Glucocorticoids 9.26 (1.95-43.89) 18.14 (1.13-290.81) 0.041 15.01 (1.77-127.16) 0.013 csDMARD monotherapy 0.42 (0.17-1.00) b/tsDMARD (monotherapy or in combination with csDMARD) 0.24 (0.10-0.58) 1.36 (0.19-9.72) 0.557 Conclusion: Increasing age, comorbidity burden, and glucocorticoid use were associated with hospitalisation, while a diagnosis of inflammatory arthritis was associated with lower odds of hospitalization. Disclosure of Interests: Richard Conway Speakers bureau: Janssen, Roche, Sanofi, Abbvie, Elena Nikiphorou Speakers bureau: AbbVie, Eli-Lilly, Gilead, Celltrion, Pfizer, Sanofi, Christiana Demetriou: None declared, Candice Low: None declared, Kelly Leamy: None declared, John Ryan: None declared, Ronan Kavanagh: None declared, Alexander Fraser: None declared, John Carey: None declared, Paul O’Connell: None declared, Rachael Flood: None declared, Ronan Mullan: None declared, David Kane: None declared, Philip Robinson Speakers bureau: UCB, Roche, Pfizer, Gilead, Janssen, Novartis, Eli Lilly, Abbvie, Grant/research support from: Abbvie, UCB, Novartis, Janssen, Pfizer, Jean Liew Grant/research support from: Pfizer, Rebecca Grainger Speakers bureau: Pfizer, Cornerstones, Janssen, Novartis, Abbvie, Geraldine McCarthy: None declared.
Abstract Background Which components of the immune response to SARS-CoV-2 vaccination best protect against subsequent infection remains unclear. We explored SARS-CoV-2 specific antibody and B-cell responses post 3rd dose vaccine and their relationship to subsequent SARS-CoV-2 infection. Methods In a multicentre prospective cohort, adult subjects provided samples before and 14 days (d14) post 3rd dose vaccine with Pfizer-BioNTech 162b2. At 18-22 weeks post vaccine, subjects self-reported SARS-CoV-2 infection (confirmed by PCR or antigen test). We used electrochemiluminescence assays to quantify antibodies to SARS-CoV-2 spike subunit 1 (S1), subunit 2 (S2) and receptor-binding domain (RBD) in plasma (reported in WHO IU/mL). In a subset of subjects, we assessed SARS-CoV-2 specific differentiated B-cell (plasma cell) and memory B-cell responses from peripheral blood mononuclear cells. Unstimulated plasma cells, and memory B cells stimulated with R848 and IL2, were seeded on plates coated with RBD or full Spike antigen and antigen-specific responses measured by ELISpot (Mabtech ELISpot, Sweden). We compared between group differences by Wilcoxon signed rank or Mann–Whitney tests. Data are median [IQR] unless specified. Results Of 133 subjects (age 43 [32-50], 81.2% female (table 1), 77 subjects in the B-cell subgroup (table 2)), 47 (35.3%) reported SARS-CoV-2 infection post 3rd vaccine. Antibody titres, plasma cell and memory B-cell responses all increased significantly at d14 post 3rd vaccine (Table 1 & 2, all P< 0.001). Although d14 antibody titres did not differ in those with and without subsequent infection (table 1), those reporting subsequent infection had significantly lower d14 RBD-specific plasma cells and a lower proportion of RBD-specific memory B-cells (Figure 1a-b, both P< 0.05). Similar results were observed with full-spike-specific memory B-cell responses (Figure 1d). The differences persisted when the non-infected group was restricted only to those reporting a confirmed close contact (n=26). Conclusion Infection following 3rd dose vaccine is associated with lower d14 circulating and memory B cell responses, but not antibody titres, suggesting B-cell responses better predict protection against subsequent SARS-CoV-2 infection. Disclosures All Authors: No reported disclosures.
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