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The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation. We thus postulated that CLEC12A expression on circulating myeloid cells of rheumatoid arthritis patients is associated with disease manifestations. Cell-surface, CLEC12A receptor expression was determined on circulating neutrophils and monocytes of eRA patients and of healthy donors. Generalized estimating equations model, Student’s t -test and Spearman’s correlations were performed to compare CLEC12A expression between groups and test its association with disease activity and clinical parameters. Plasma cytokines were measured by multiplex immunoassay. Patients with reduced neutrophil or monocyte CLEC12A expression at baseline and at 3 months have an increased simple disease activity index. Low baseline CLEC12A expression also correlates with a higher SDAI at 6 months. In contrast, positive correlations were observed between baseline CLEC12A expression and several cytokines. Moreover, neutrophil and monocyte CLEC12A expression is significantly higher in early rheumatoid arthritis patients at baseline than healthy controls. Circulating neutrophil and monocyte CLEC12A expression correlates with disease activity at baseline and is predictive of SDAI at later stages of the disease indicative of a regulatory role for CLEC12A in RA.

BackgroundThe coronavirus disease 2019 (COVID-19) global pandemic is a highly stressful event that may contribute to psychological symptoms, particularly in patients with pre-existing chronic conditions. This study examined COVID-19 pandemic related stress experienced by patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) and its association with symptoms of psychological distress.MethodsAn on-line cross-sectional survey study was conducted with 55 SLE (mean age = 54.8, ±13.8) and 42 RA (mean age = 64.2, ±12.2) patients recruited from a tertiary care centre in Quebec City between May 25, 2021 and June 13, 2021. Participants completed the COVID-19 Stressors Questionnaire adapted by our team for inflammatory arthritis. The Impact of Event Scale-Revised (IES-R) assessed post-traumatic stress symptoms (PTSS) caused by the COVID-19 pandemic. The Patient Health Questionnaire-8 (PHQ-8) and the Generalized Anxiety Disorder-7 (GAD-7) measured symptoms of depression and anxiety, respectively.ResultsAmong respondents 3/97 had been diagnosed with COVID-19 since the start of the pandemic (SLE=2, RA=1). Clinically significant PTSS (IES-R score ≥24) due to the COVID-19 pandemic was reported by 13.4% of participants, with no statistically significant difference between both disease groups (SLE = 16.4%; RA=9.5%). The degree of concern related to COVID-19 stressors were similar in both disease groups (SLE: M = 10.0 ±8.2; RA: M = 8.7 ±9.5). As shown in table 1, COVID-19 stressors that were associated with the highest degree of concerns were: having a loved one contract coronavirus (SLE 50.9%; RA 28.6%), the possibility of contracting (SLE 45.5%; RA 35.7%) or getting sick from coronavirus (SLE 40%; RA 21.4%), working in a place with high likelihood of exposure (SLE 30.9%; RA 21.4%), and the possibility of their disease worsening or being poorly managed due to changes in medical care (SLE 27.3%; RA 26.2%). In patients with SLE, a higher level of concern related to COVID-19 stressors was significantly correlated with greater symptoms of PTSS (r = 0.46, p < 0.001), depression (r = 0.46, p < 0.001) and anxiety (r = 0.62, p < 0.001). In patients with RA, a higher level of concerns related to COVID-19 stressors was significantly correlated with greater symptoms of PTSS (r = 0.33, p -0.036), but not with symptoms of depression and anxiety.Abstract 1202 Table 1Degree of Concerns related to COVID-19 Stressors for Patients with SLE or RACOVID-19 Stressors All Participantsn=97n (%) SLEn=55n (%) RAn=42n (%) Having loved ones who contracts coronavirus 40 (41.2) 28 (50.9) 12 (28.6) Possibility of contracting coronavirus 40 (41.2) 25 (45.5) 15 (35.7) Getting sick from exposure to coronavirus 31 (32) 22 (40) 9 (21.4) Working in a place likely to be exposed to the coronavirus. 26 (26.8) 17 (30.9) 9 (21.4) Possibility of condition worsening or being poorly managed due to changes in medical care 26 (26.8) 15 (27.3) 11 (26.2) Postponement or cancellation of diagnostic and disease monitoring tests 19 (19.6) 10 (18.2) 9 (21.4) Increased responsibilities at home 19 (19.6) 11 (20) 8 (19.0) Difficulty obtaining food, medicine and other essentials 16 (16.5) 9 (16.4) 7 (16.7) Changes in treatments due coronavirus pandemic 15 (15.5) 9 (16.4) 6 (14.3) Postponement or cancellation of medical visits 15 (15.5) 9 (16.4) 6 (14.3) Difficulty obtaining help or social support needed 12 (12.4) 8 (14.5) 4 (9.5) Losing a job or experiencing a drop in income related to the coronavirus pandemic 10 (10.3) 5 (9.1) 5 (11.9) Responses rated on a scale of 0 “not at all” to 4 “extremely” concerned or worried. Responses dichotomized such that a threshold of 2 or higher represent greater concern/worry.ConclusionsStressors related to the COVID-19 pandemic are experienced by an important proportion of patients with SLE and RA and are associated with psychological symptoms, particularly for patients with SLE.

During vascular injury, platelets are essential for halting bleeding and recruiting neutrophils to prevent microbial invasion. However, in antibody-mediated autoimmune diseases occurring without vascular damage, neutrophils infiltrate tissues and contribute to pathology. Here, we investigated whether the dependence of neutrophils on platelets is conserved in the context of antibody-driven inflammation. Using human cells from individuals with rheumatoid arthritis and a microfluidic system mimicking physiological shear over IgG-containing immune complexes, we demonstrate that despite expressing Fc receptors, neutrophils required platelets to stably adhere to immune complexes under flow. Platelet Fcγ receptor 2a (FcγRIIA) binding was critical for resisting shear stress, while neutrophils used FcγRIIA and FcγRIIIB for immune complex recognition. Platelet P-selectin binding to neutrophil P-selectin glycoprotein ligand 1 (PSGL-1) was essential for recruitment, whereas macrophage-1 antigen (Mac-1) was dispensable. In a mouse model of autoantibody-mediated arthritis, intravital imaging confirmed that neutrophil recruitment relied on PSGL-1. Importantly, expression of FcγRIIA aggravated arthritis, and blockade of PSGL-1, but not Mac-1, in these mice abrogated both the platelet and neutrophil interactions and disease. These findings identify key molecular interactions in platelet-neutrophil cooperation and reveal that platelets are essential enablers of FcR-mediated neutrophil adhesion in antibody-driven inflammation.

We apply the Markov Game formalism to develop a context-aware approach to valuing player actions, locations, and team performance in ice hockey. The Markov Game formalism uses machine learning and AI techniques to incorporate context and look-ahead. Dynamic programming is applied to learn value functions that quantify the impact of actions on goal scoring. Learning is based on a massive new dataset, from SportLogiq, that contains over 1.3M events in the National Hockey League. The SportLogiq data include the location of an action, which has previously been unavailable in hockey analytics. We give examples showing how the model assigns context and location aware values to a large set of 13 action types. Team performance can be assessed as the aggregate value of actions performed by the team’s players, or the aggregate value of states reached by the team. Model validation shows that the total team action and state value both provide a strong indicator predictor of team success, as measured by the team’s average goal ratio.

Polypharmacy can be associated with poor outcomes in chronic diseases. Our objective is to determine the prevalence of polypharmacy and its association with disease control in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). An observational study was conducted using the SARD database of the CHU de Québec. Participants newly diagnosed with RA or SLE enrolled in the database after 24 months were included. Collected data included number and type of medications, Charlson Comorbidity Index, and medication adherence (proportion of days covered during the first 180 days). Polypharmacy was defined as the simultaneous use ≥5 medications. Multivariable logistic and linear regressions were used to determine the association between polypharmacy and disease control (DAS28CRP, SLEDAI-2 K). The study included 111 participants (RA = 81; SLE = 30). Medication count increased at two years in RA (mean ± SD): 4.6 ± 3.3 to 6.9 ± 3.6; and SLE: 6.5 ± 4.6 to 7.80 ± 4.82. Polypharmacy prevalence increased at two years: RA: from 43 to 74%; SLE: from 47 to 73%. Mean medication adherence exceeded 85%. For RA participants, polypharmacy was associated with a better DAS28CRP score at one year [adjusted odds ratio of achieving a poor outcome: 0.17 (95%CI 0.04–0.71)], but this association was lost at two years [2.88 (0.45–18.29)]. For SLE, polypharmacy was not associated with disease activity based on the SLEDAI-2 K at one year [7.36 (0.26-211.16)] or two years [0.32 (0.05–1.99)]. Overall, polypharmacy is very prevalent in RA and SLE and could be positively associated with the level of disease control in the year after a diagnosis of RA.