Background: Hypercoagulability and endothelial dysfunction are hallmarks of coronavirus disease 2019 (COVID-19) and appear to predict disease severity. A high incidence of thrombosis despite thromboprophylaxis is reported in patients with moderate to severe COVID-19. Recent randomized clinical trials suggest that therapeutic-intensity heparin confers a survival benefit in moderate-severity COVID-19 compared to standard-intensity heparin, potentially by harnessing heparin-mediated endothelialstabilizing and anti-inflammatory effects. Objective: We hypothesized that patients with moderate-severity COVID-19 exhibit enhanced hypercoagulability despite standard-intensity thromboprophylaxis with low molecular weight heparin (LMWH) compared to non-COVID-19 hospitalized patients. Methods: Patients with moderate COVID-19 and a control group (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]-negative hospitalized patients) receiving LMWH thromboprophylaxis were recruited. Markers of endothelial damage and plasma thrombin generation parameters were assessed. Results: Tissue plasminogen activator levels were significantly increased in the COVID-19 group (8.3 ± 4.4 vs. 4.9 ± 2.4 ng/ml; P = .02) compared to non-COVID-19-hospitalized patients. Despite thromboprophylaxis, mean endogenous thrombin potential was significantly increased among COVID-19 patients (1929 ± 448 vs. 1528 ± 460.8 nM*min; P = .04) but lag time to thrombin generation was significantly | 1009 KELLIHER Et aL.

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BCP crystals can activate a number of inflammatory pathways which in turn may lead to cartilage degradation and osteoarthritis. Understanding of these pathways may ultimately yield targeted therapies for osteoarthritis, for which none currently exists.

Myocarditis is a rare but life-threatening complication of systemic sclerosis (SSc). Here we present the case of a 38-year-old man who presented with rapidly progressive diffuse cutaneous systemic sclerosis (dcSS) with skin, gastrointestinal, lung, and cardiac involvement in the form of myocarditis. His myocarditis has been successfully controlled with pulsed intravenous (IV) cyclophosphamide and methylprednisolone. Serial cardiac magnetic resonance imaging (MRI) scans have demonstrated disease stability in the interim.The 38-year-old male, a landscape gardener, presented with a 6-month history of arthritis affecting the small joints of his hand, Raynaud's disease, and sclerodactyly. Blood pressure and urinanalysis were normal. Antinuclear antibody (ANA) and anti-Scl-70 antibody tests were positive. Rheumatoid screen was negative. The clinical impression was that of early dcSS and the patient was commenced on a calcium channel blocker and prednisolone 20 mg once daily.The patient's disease progressed rapidly, with skin tightness developing over the face, chest wall, back, forearms, and hands. Suspected oesophageal dysmotility was confirmed by oesophageal manometry. Renal indices remained normal.In September 2008 the patient developed exertional dyspnoea. Pulmonary function tests, echocardiogram, and right heart catheterization were normal. High-resolution computed tomography (CT) of the thorax showed no evidence of pulmonary fibrosis but did reveal extensive mediastinal lymphadenopathy. Lymph node and lung biopsy were obtained by video-assisted thorascopic surgery (VATS). Histology revealed reactive lymphadenopathy and desquamative interstitial pneumonitis indicating early pulmonary involvement of SSc.Shortly after the VATS procedure the patient developed chest pain at rest, elevated cardiac enzymes (creatine kinase 494 U/L), troponin leakage (troponin T 0.39 μg/L), and intermittent atrio-ventricular re-entrant tachycardia. Coronary angiogram was normal. A cardiac MRI was obtained that demonstrated normal ventricular function and no obvious abnormal subendocardial enhancement (Figure 1).Although symptoms initially settled they recurred over the following 6 weeks with further chest pain at rest, recurrent dysrhythmias, persistently raised cardiac enzymes, and troponin leakage that proved refractory to treatment with oral steroids and anti-arrhythmic agents. A repeat cardiac MRI 6 weeks after the previous MRI showed a deterioration of ventricular function with a right ventricular ejection fraction of 25% and a left ventricular ejection fraction of 39%. In addition, abnormal subendocardial enhancement was noted in the left ventricular papillary muscle and the right ventricular trabeculum septum marginale (Figure 1). The MRI findings confirmed the clinical impression of an acute myocarditis secondary to SSc and the patient was commenced on pulsed IV cyclophosphamide (10 mg/kg monthly).Unfortunately, cardiac enzymes remained persistently elevated 3 days following the start of treatment indicating ongoing myocarditis. ...

ObjectivesAnti-citrullinated protein antibodies (ACPA) have been shown to cause platelet activation in vitro, through the low-affinity immunoglobulin G (IgG) receptor (FcγRIIa) on platelets. Platelet activation via engagement of FcγRIIa results in proteolytic cleavage and shedding of platelet specific glycoprotein VI (GPVI) which can be detected in the plasma as soluble GPVI (sGPVI). We hypothesized that plasma levels of sGPVI would be increased among patients with seropositive RA as a consequence of antibody-induced platelet activation and GPVI shedding.MethodsSamples from 84 patients with RA (65 seropositive and 19 seronegative) and 67 healthy controls were collected prospectively and analysed for sGPVI using a standardised ELISA.ResultsPatients with seropositive RA had significantly higher levels of sGPVI compared to seronegative RA and controls. Median (IQR) sGPVI levels were 4.2 ng/ml (3.2, 8.0) in seropositve RA, 2.2 ng/ml (1.5, 3.5) in seronegative RA and 2.2 ng/ml (1.6, 3.4) in controls (p<0.0001). sGPVI levels correlated with ACPA titres (r = 0.32, p = 0.0026) and with RF titres (r = 0.48, p<0.0001).ConclusionPlasma sGPVI, a specific marker of platelet activation is increased among patients with seropositive RA.

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ObjectiveCalcium 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.MethodsSupported 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.ResultsAmong 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).ConclusionThe 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

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