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Kanellakos G.W.,Queen Elizabeth Health Science Center
Anesthesiology Clinics | Year: 2012

This article describes the perioperative risks of pregnant patients with anterior mediastinal masses, and demonstrates the importance of a multidisciplinary approach for the management of high-risk patients. Mediastinal mass syndrome is defined as immediate right heart failure secondary to vascular compression when positive pressure ventilation is initiated. Greater emphasis on the potential for cardiovascular collapse (versus respiratory collapse) challenges the conventional teaching of risks associated with mediastinal masses in the adult population. © 2012 Elsevier Inc. Source

Herman C.R.,Queen Elizabeth Health Science Center
Journal of cardiothoracic surgery | Year: 2013

Quality improvement initiatives in cardiac surgery largely rely on risk prediction models. Most often, these models include isolated populations and describe isolated end-points. However, with the changing clinical profile of the cardiac surgical patients, mixed populations models are required to accurately represent the majority of the surgical population. Also, composite model end-points of morbidity and mortality, better reflect outcomes experienced by patients. The model development cohort included 4,270 patients who underwent aortic or mitral valve replacement, or mitral valve repair with/without coronary artery bypass grafting, or isolated coronary artery bypass grafting. A composite end-point of infection, stroke, acute renal failure, or death was evaluated. Age, sex, surgical priority, and procedure were forced, a priori, into the model and then stepwise selection of candidate variables was utilized. Model performance was evaluated by concordance statistic, Hosmer-Lemeshow Goodness of Fit, and calibration plots. Bootstrap technique was employed to validate the model. The model included 16 variables. Several variables were significant such as, emergent surgical priority (OR 4.3; 95% CI 2.9-7.4), CABG + Valve procedure (OR 2.3; 95% CI 1.8-3.0), and frailty (OR 1.7; 95% CI 1.2-2.5), among others. The concordance statistic for the major adverse cardiac events model in a mixed population was 0.764 (95% CL; 0.75-0.79) and had excellent calibration. Development of predictive models with composite end-points and mixed procedure population can yield robust statistical and clinical validity. As they more accurately reflect current cardiac surgical profile, models such as this, are an essential tool in quality improvement efforts. Source

Wood L.,Queen Elizabeth Health Science Center
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: Over the past decade, a greater understanding into the molecular pathogenesis of renal cell carcinoma (RCC) has led to major advances in treatment options. Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI) that targets a number of receptors, including vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR). Sunitinib was one of the first targeted agents studied in metastatic RCC (mRCC) and is currently used worldwide in the management of mRCC. Areas covered: This drug evaluation addresses the preclinical and clinical development of sunitinib. It provides an in-depth discussion of the Phase II data that led to its approval in mRCC and the subsequent Phase III clinical trial comparing sunitinib to interferon-α. More recent data from the large international expanded access trial, in non-clear cell carcinoma patients, different dosing schedule studies and safety issues are also discussed. Finally, areas for the future use of sunitinib, including in the adjuvant setting, are reviewed. Expert opinion: Since the FDA approved sunitinib for advanced RCC in January 2006, much more has been learned about its efficacy and tolerability. Over the past decade of its clinical use, it has become clear that expertise is required when prescribing sunitinib, in terms of maximizing dose, anticipating and managing side effects, and assessing responses. In the future, a better understanding of sunitinib's role compared with other VEGF TKIs and mTOR inhibitors, and in other roles such as the adjuvant setting or in non-clear cell pathology, will become evident. © 2012 Informa UK, Ltd. Source

Burns A.M.,Dalhousie University | Green P.J.,Dalhousie University | Pasternak S.,Queen Elizabeth Health Science Center
Journal of Cutaneous Pathology | Year: 2012

A 59-year-old female with rheumatoid arthritis on etanercept therapy presented with a 7-cm-large subcutaneous forearm mass. Multiple smaller nodules subsequently developed on the upper and lower extremities. Except for a new cough, the patient was systemically well. Biopsy of the mass showed sarcoidal type granulomatous inflammation with nodular aggregations of non-necrotizing epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept was discontinued, and the patient was started on adalimumab for rheumatoid arthritis control. The cutaneous nodules fully resolved in 6 months with no additional treatment. A 4-month follow-up CT scan showed significant regression of mediastinal adenopathy. The patient has since been maintained on adalimumab therapy for 2 years with no recurrence of sarcoid-like manifestations. Biologic response modifiers targeting tumor necrosis factor alpha (TNFα) are effective treatments of chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. TNFα represents a major cytokine in granuloma formation, and TNFα inhibitors are sometimes efficacious in the treatment of sarcoidosis. Paradoxically, there is a small volume of literature implicating TNFα inhibitors in the development of sarcoid-like disease. We present this case to promote the recognition of TNFα inhibitor-induced sarcoidosis and to illustrate the wide clinicopathologic differential of sarcoidal type granulomas. Copyright © 2012 John Wiley & Sons A/S. Source

Khaperskyy D.A.,Dalhousie University | Hatchette T.F.,Dalhousie University | Hatchette T.F.,Queen Elizabeth Health Science Center | McCormick C.,Dalhousie University | McCormick C.,Beatrice Hunter Cancer Research Institute
FASEB Journal | Year: 2012

An important component of the mammalian stress response is the reprogramming of translation. A variety of stresses trigger abrupt polysome disassembly and the accumulation of stalled translation preinitiation complexes. These complexes nucleate cytoplasmic stress granules (SGs), sites of mRNA triage in which mRNAs from disassembling polysomes are sorted and the fates of individual transcripts are determined. Here, we demonstrate that influenza A virus (IAV) actively suppresses SG formation during infection, thereby allowing translation of viral mRNAs. Complete inhibition of SG formation is dependent on the function of the viral nonstructural protein 1 (NS1); at late times postinfection, cells infected with NS1-mutant viruses formed SGs in a double-stranded RNA-activated protein kinase (PKR)-dependent fashion. In these cells, SG formation correlated with inhibited viral protein synthesis. Together, these experiments demonstrate the antiviral potential of SGs and reveal a viral countermeasure that limits SG formation. © FASEB. Source

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