No abstract

Background. In advanced cutaneous melanoma, new systemic therapies include immunotherapy by checkpoint inhibition and targeted inhibition of the mitogen-activated protein kinase pathway; these are becoming increasingly well established. We describe the clinical presentation of uveitis in three patients with concomitant systemic melanoma treatment. History and Signs. Three patients with metastatic melanoma receiving systemic therapy (ipilimumab, vemurafenib) presented at our institution with a short history of ocular symptoms. Clinical findings included anterior uveitis, intermediate uveitis, disc swelling, inflammatory choroidal lesions and retinal vasculitis. Therapy and Outcome. All three patients responded well to local and/or systemic steroid treatment. In one case, the systemic anti-cancer drug was discontinued after the onset of uveitis. Conclusions. Ocular inflammation may occur in the setting of systemic melanoma therapy. Presentations of uveitis include Vogt-Koyanagi-Harada-like syndromes. Ocular inflammation can usually be controlled by topical and sometimes systemic corticosteroid therapy. However, treatment guidelines are not established and management of these patients demands close cooperation with the oncologist.

Cardiovascular implants must resist infection and thrombosis. A nanocomposite polymeric material [polyhedral-oligomeric-silsesquioxane-poly(carbonate-urea)urethane; POSS-PCU] demonstrates ideal properties for cardiovascular applications. Silver nanoparticles or nanosilver (NS) are recognized for efficient antibacterial properties. This study aims to determine the influence of NS integrated POSS-PCU on thrombogenicity. Silver nitrate was reduced with dimethylformamide and stabilized by the inclusion of fumed silica nanoparticles to prevent aggregation of NS and were incorporated into POSS-PCU to form a range of POSS-PCU-NS concentrations (by weight); 0.20% (NS16), 0.40% (NS32), 0.75% (NS64), and 1.50% (NS128). Surface wettability was determined with sessile-drop water contact angles. Platelets were introduced onto test samples and Alamar Blue (AB), mitochondrial-activity assay, quantified the degree of platelet adhesion whilst platelet-factor-4 (PF4) ELISA quantified the degree of platelet activation. Thromboelastography (TEG) determined the profiles of whole blood kinetics while hemolysis assay demonstrated the degree of blood compatibility. Increasing levels of NS induced greater hydrophilicity. A concentration dependant decrease in platelet adhesion and activation was observed with AB and PF4 readings, respectively. TEG demonstrated that the antithrombogenic properties of POSS-PCU were retained with POSS-PCU-NS16, and enhanced with POSS-PCU-NS32, but was reduced with POSS-PCU-NS64 and POSS-PCU-NS128. POSS-PCU-NS64 and POSS-PCU-NS128 demonstrated a hemolytic tendency, but no hemolysis was observed with POSS-PCU-NS16 and POSS-PCU-NS32. Overall, POSS-PCU-NS32 rendered potent antithrombogenic properties.