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    Boother EJ, Brownlow S, Tighe HC, Bamford KB, Jackson JE, Shovlin CLet al., 2017,

    Cerebral abscess associated with odontogenic bacteremias, hypoxemia, and iron loading in immunocompetent patients with right-to-left shunting through pulmonary arteriovenous malformations.

    , Clin Infect Dis

    Background: Cerebral abscess is a recognised complication of pulmonary arteriovenous malformations (PAVMs) that allow systemic venous blood to bypass the pulmonary capillary bed through anatomic right-to-left shunts. Broader implications and mechanisms remain poorly explored. Methods: Between June 2005 and December 2016, at a single institution, 445 consecutive adult patients with CT-scan confirmed PAVMs (including 403 (90.5%) with hereditary haemorrhagic telangiectasia) were recruited to a prospective series. Multivariate logistic regression, and detailed peri-abscess histories were evaluated to identify potential associations with cerebral abscess. Rates were compared to an earlier non-overlapping series. Results: Thirty-seven (8.3%) of the 445 patients experienced a cerebral abscesses at median age 50 (range 19-76) years. The rate adjusted for ascertainment bias was 27/435 (6.2%). 29/37 (78.4%) abscess patients had no PAVM diagnosis prior to their abscess, a rate unchanged from earlier UK series. 21/37 (56.7%) suffered residual neurological deficits, most commonly memory/cognition impairment; hemiparesis, and visual defects. Isolation of periodontal microbes, and precipitating dental and other interventional events emphasised potential sources of endovascular inoculations. In multivariate logistic regression, cerebral abscess was associated with low oxygen saturation (indicating greater right-to-left shunting); higher transferrin iron saturation index; intravenous iron use for anemia (adjusted odds ratio 5.4 [95% confidence intervals 1.4, 21.1]); male gender; and venous thromboemboli. There were no relationships with anatomic attributes of PAVMs, or red cell indices often increased due to secondary polycythemia. Conclusions: Greater appreciation of the risk of cerebral abscess in undiagnosed PAVMs is required. Lower SaO2 and intravenous iron may be modifiable risk factors.

    Bauer A, Mylroie H, Thornton CC, Calay D, Birdsey GM, Kiprianos AP, Wilson GK, Soares MP, Yin X, Mayr M, Randi AM, Mason JCet al., 2016,

    Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis

    , SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322
    Khamis RY, Hughes AD, Caga-Anan M, Chang CL, Boyle JJ, Kojima C, Welsh P, Sattar N, Johns M, Sever P, Mayet J, Haskard DOet al., 2016,

    High Serum Immunoglobulin G and M Levels Predict Freedom From Adverse Cardiovascular Events in Hypertension: A Nested Case-Control Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

    , EBioMedicine, Vol: 9, Pages: 372-380

    AIMS: We aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination. METHODS AND RESULTS: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p<0.0001; IgM 0.83[0.75,0.93], p=0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p<0.0001, IgM OR 0.81 (0.71,0.93); p=0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index. CONCLUSION: High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.

    Khan E, Ambrose NL, Ahnstroem J, Kiprianos AP, Stanford MR, Eleftheriou D, Brogan PA, Mason JC, Johns M, Laffan MA, Haskard DOet al., 2016,

    A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behcet's Syndrome

    , SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322
    Thornton CC, Al-Rashed F, Calay D, Birdsey GM, Bauer A, Mylroie H, Morley BJ, Randi AM, Haskard DO, Boyle JJ, Mason JCet al., 2016,

    Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation

    , ANNALS OF THE RHEUMATIC DISEASES, Vol: 75, Pages: 439-448, ISSN: 0003-4967
    Mylroie H, Dumont O, Bauer A, Thornton CC, Mackey J, Calay D, Hamdulay SS, Choo JR, Boyle JJ, Samarel AM, Randi AM, Evans PC, Mason JCet al., 2015,

    PKC epsilon-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis

    , CARDIOVASCULAR RESEARCH, Vol: 106, Pages: 509-519, ISSN: 0008-6363
    Shah AV, Birdsey GM, Reynolds LE, Dufton N, Almagro LO, Yang Y, Aspalter IM, Khan ST, Mason JC, Dejana E, Goettgens B, Hodivala-Dilke K, Gerhardt H, Adams RH, Randi AMet al., 2014,

    The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/beta-catenin signaling

    , ANGIOGENESIS, Vol: 17, Pages: 715-715, ISSN: 0969-6970

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