Journal of internal medicine
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Patients with coronary artery disease who have prognostically significant lesions or symptoms despite optimum medical therapy require mechanical revascularization with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or both. In this review, we will evaluate the evidence-based use of the two revascularization approaches in treating patients with coronary artery disease. CABG has been the predominant mode of revascularization for more than half a century and is the preferred strategy for patients with multivessel disease, especially those with diabetes mellitus, left ventricular systolic dysfunction or complex lesions. ⋯ Improvements in both CABG (including total arterial revascularization, off-pump CABG and 'no-touch' graft harvesting) and PCI (including newer-generation stents, adjunctive pharmacotherapy and intracoronary imaging) mean that they will continue to challenge each other in the future. A 'heart team' approach is strongly recommended to select an evidence-based, yet individualized, revascularization strategy for all patients with complex coronary artery disease. Finally, optimal medical therapy is important for all patients with coronary artery disease, regardless of the mode of revascularization.
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The aim of this study was to combine clinical criteria and next-generation sequencing (pyrosequencing) to establish a diagnosis of familial hypercholesterolaemia (FH). ⋯ Using a combination of clinical criteria and targeted next-generation sequencing, we have achieved FH diagnosis with a high success rate. Furthermore, we identified a new splicing-site mutation in the LDLR gene.
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Xanthomatosis associated with monoclonal gammopathy includes hyperlipidaemic xanthoma (HX), normolipidaemic xanthoma (NX) and necrobiotic xanthogranuloma (NXG). All three pathologies are characterized by skin or visceral lesions related to cholesterol accumulation, monoclonal immunoglobulin (MIg) and hypocomplementemia. The pathophysiology underlying NXG remains unknown although the involvement of MIg is suspected. ⋯ This study revealed that NXG is characterized by impaired macrophage lipid homeostasis associated with a systemic inflammatory profile that may result from the interaction of MIg and lipoproteins.
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Observational and genetic studies have shown that lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] isoform size are both associated with coronary heart disease (CHD) risk, but the relative independence of these risk factors remains unclear. Clarification of this uncertainty is relevant to the potential of future Lp(a)-lowering therapies for the prevention of CHD. ⋯ The effect of KIV repeats on CHD risk is mediated through their impact on Lp(a) levels, suggesting that absolute levels of Lp(a), rather than apo(a) isoform size, are the main determinant of CHD risk.
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Review
Tumour-induced immune suppression: role of inflammatory mediators released by myelomonocytic cells.
Tumour-induced immune dysfunction is a serious challenge to immunotherapy for cancer, and intact adaptive and innate cellular immunity is key to its success. Myelomonocytic cells have a central role in this immune suppression, and tumour-associated macrophages, eosinophils, neutrophils and myeloid-derived suppressor cells have all been shown to be of major importance. These myelomonocytic cells secrete a broad repertoire of inflammatory mediators providing them with powerful tools to inhibit tumour-reactive T cells and natural killer cells; free oxygen radicals including reactive oxygen species and NO, arginase, indoleamine 2,3-dioxygenase, prostaglandins, the pro-inflammatory heterodimer S100A8/9 and cytokines, such as granulocyte-macrophage colony-stimulating factor and transforming growth factor-β, have proven particularly potent in suppressing antitumour cellular immunity. Determining which of these factors prevail in individual cancer patients and designing methods aimed at neutralization or inhibition of their effects on target tissues have the potential to greatly enhance the clinical efficacy of immunotherapy.