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Background-Pharmacological blockade of ␤ 3 -integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, ␤ 3 -integrin-deficient (␤ 3 Ϫ/Ϫ ) mice are not protected from neointimal lesion formation after arterial injury. We investigated this discrepancy in ␤ 3 Ϫ/Ϫ and wild-type (␤ 3 ϩ/ϩ ) mice using different models of injury. Methods and Results-After disruption of the carotid with a transluminal probe, there was no significant difference in neointimal thickening between ␤ 3 Ϫ/Ϫ and ␤ 3 ϩ/ϩ mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in ␤ 3 Ϫ/Ϫ mice compared with ␤ 3 ϩ/ϩ mice at intervals up to 3 months. Lesion reduction in ␤ 3 Ϫ/Ϫ mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with ␤ 3 ϩ/ϩ mice, consistent with reduced SMC migration from the media into the intima of ␤ 3 Ϫ/Ϫ mice. Moreover, combined eccentric medial disruption and ligation of the carotid in ␤ 3 Ϫ/Ϫ mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from ␤ 3 ϩ/ϩ mice into irradiated ␤ 3 Ϫ/Ϫ mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of ␣ v ␤ 3 and not ␣ IIb ␤ 3 in the attenuated response. Conclusions-The ␣ v ␤ 3 -integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation.

Background: Budd-Chiari syndrome (BCS) is a rare but fatal disease caused by obstruction in the hepatic venous outflow tract. Aim: To provide an update of the pathophysiology, aetiology, diagnosis, management and follow-up of BCS. Methods: Analysis of recent literature by using Medline, PubMed and EMBASE databases. Results: Primary BCS is usually caused by thrombosis and is further classified into "classical BCS" type where obstruction occurs within the hepatic vein and "hepatic vena cava BCS" which involves thrombosis of the intra/suprahepatic portion of the inferior vena cava (IVC). BCS patients often have a combination of prothrombotic risk factors. Aetiology and presentation differ between Western and certain Asian countries. Myeloproliferative neoplasms are present in 35%-50% of European patients and are usually associated with the JAK2-V617F mutation. Clinical presentation is diverse and BCS should be excluded in any patient with acute or chronic liver disease. Non-invasive imaging (Doppler ultrasound, computed tomography, or magnetic resonance imaging) usually provides the diagnosis. Liver biopsy should be obtained if small vessel BCS is suspected. Stepwise management strategy includes anticoagulation, treatment of identified prothrombotic risk factors, percutaneous revascularisation and transjugular intrahepatic portosystemic stent shunt to re-establish hepatic venous drainage, and liver transplantation in unresponsive patients. This strategy provides a 5-year survival rate of nearly 90%. Long-term outcome is influenced by any underlying haematological condition and development of hepatocellular carcinoma. Conclusions: With the advent of newer treatment strategies and improved understanding of BCS, outcomes in this rare disease have improved over the last three decades. An underlying haematological disorder can be the major determinant of outcome. Primary BCS is considered a multifactorial disease and multicentre data found a combination of several prothrombotic conditions in 25% to 46% of the patients with BCS, 11,19-21 several times greater than expected in the general population. The discovery of one causal factor should not discourage further investigation to identify other prothrombotic conditions. Multifactorial causes may explain the rarity of BCS. 2 The prothrombotic conditions found in BCS, in particular the classical type, include: Factor V Leiden mutation, prothrombin (PT) gene mutation, protein C deficiency, protein S deficiency, antithrombin deficiency, antiphospholipid syndrome, hyperhomocysteinemia and paroxysmal nocturnal haemoglobinuria. 22 BCS is also associated with systemic inflammatory diseases, such as Behçet's disease, sarcoidosis, vasculitis and other connective tissue diseases. 22 A detailed description of the frequency of inherited/acquired thrombophilias and risk factors found in patients with BCS compared to those with portal vein thrombosis is summarised by Poisson and colleagues. 23

Objectives The Coronavirus disease 2019 (COVID‐19) pandemic is straining healthcare resources. Molecular testing turnaround time precludes having results at the point‐of‐care (POC) thereby exposing COVID‐19/Non‐COVID‐19 patients while awaiting diagnosis. We evaluated the utility of a triage strategy including FebriDx, a 10‐minute POC finger‐stick blood test that differentiates viral from bacterial acute respiratory infection through detection of Myxovirus‐resistance protein A (MxA) and C‐reactive protein (CRP), to rapidly isolate viral cases requiring confirmatory testing. Methods This observational, prospective, single‐center study enrolled patients presenting to/within an acute care hospital in England with suspected COVID‐19 between March and April 2020. Immunocompetent patients ≥16 years requiring hospitalisation with pneumonia or acute respiratory distress syndrome or influenza‐like illness (fever and ≥1 respiratory symptom within 7 days of enrolment, or inpatients with new respiratory symptoms, fever of unknown cause or pre‐existing respiratory condition worsening). The primary endpoint was diagnostic performance of FebriDx to identify COVID‐19 as a viral infection; secondary endpoint was SARS‐CoV‐2 molecular test diagnostic performance compared with the reference standard COVID‐19 Case Definition (molecular or antibody detection of SARS‐CoV‐2). Results Valid results were available for 47 patients. By reference standard, 35 had viral infections (34/35 COVID‐19; 1/35 non‐COVID‐19; overall FebriDx viral sensitivity 97.1% (95%CI 83.3‐99.9)). Of the COVID‐19 cases, 34/34 were FebriDx viral positive (sensitivity 100%; 95%CI 87.4‐100); 29/34 had an initial SARS‐CoV‐2 positive molecular test (sensitivity 85.3%; 95%CI 68.2‐94.5). FebriDx was viral negative when the diagnosis was not COVID‐19 and SARS‐Cov‐2 molecular test was negative (negative predictive value (NPV) 100% (13/13; 95%CI 71.7‐100)) exceeding initial SARS‐CoV‐2 molecular test NPV 72.2% (13/19; 95%CI 46.4‐89.3). The diagnostic specificity of FebriDx and initial SARS‐CoV‐2 molecular test was 100% (13/13; 95%CI 70‐100 and 13/13; 95%CI 85.4‐100, respectively). Conclusions FebriDx could be deployed as part of a reliable triage strategy for identifying symptomatic cases as possible COVID‐19 in the pandemic.

Objective-Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E (apoE)-deficient (apoE Ϫ/Ϫ ) MMP-9 -deficient (MMP-9 Ϫ/Ϫ ) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation. Methods and Results-Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE Ϫ/Ϫ MMP-9 Ϫ/Ϫ mice had a significant reduction in intimal plaque length and volume compared with apoEMMP-9 ϩ/ϩ mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow-derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE Ϫ/Ϫ MMP-9 ϩ/ϩ and apoE Ϫ/Ϫ MMP-9mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development. Key Words: atherosclerosis Ⅲ MMP-9 Ⅲ bone marrow Ⅲ mouse Ⅲ compartmentalization S everal matrix metalloproteinases (MMPs), namely MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-11, and MMP-14, are present in human atherosclerotic lesions, leading to the speculation that overexpression of these enzymes is linked to atherogenesis. [1][2][3][4][5][6] However, experimental models of atherosclerosis demonstrated that mice deficient in apolipoprotein E (apoE) and MMP-3 had larger atherosclerotic plaque, whereas apoE-deficient (apoE Ϫ/Ϫ ) mice overexpressing human MMP-1 had a reduction in plaque size. 1,7 Moreover, inactivation of tissue inhibitor of metalloproteinase 1, which can inhibit MMP-1, MMP-3, MMP-9, and MMP-11 activity and is overexpressed in human atherosclerotic lesions, reduced the plaque size in apoE Ϫ/Ϫ mice. 1 Thus, it is likely that some MMPs are involved in atherogenic processes, whereas others function to inhibit plaque formation. Conclusions-MMP-9 is derived from resident arterial cells and isMMP-9 (gelatinase B) is expressed in late atherosclerotic lesions in humans and has been suggested to mediate plaque instability, a leading cause of acute coronary syndrome and stroke. 2,3 Studies in humans have revealed that polymorphisms in the MMP-9 promoter, which enhance expression, correlate with the development and progression of coronary atherosclerosis. 8,9 Studies with apoE Ϫ/Ϫ MMP-9 Ϫ/Ϫ mice have demonstrated that MMP-9 is critical to intimal plaque size. 10,11 To determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation, we also cross-bred apoE Ϫ/Ϫ mice with MMP-9 Ϫ/Ϫ mice. We demonstrate that although MMP-9 expression is derived mostly from bone marrow cells, MMP-9 derived from resident arterial cells dictates the overall plaque composition. Therefore, MMP-9 activity associated with the resident cells (compartmental...