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  • Viewpoint: Personalizing Statin Therapy

    Cardiovascular disease (CVD), associated with vascular atherosclerosis, is the major cause of death in Western societies. Current risk estimation tools, such as Framingham Risk Score (FRS), based on evaluation of multiple standard risk factors, are limited in assessment of individual risk. The majority (about 70%) of the general population is classified as low FRS where the individual risk for CVD is often underestimated but, on the other hand, cholesterol lowering with statin is often excessively administered. Adverse effects of statin therapy, such as muscle pain, affect a large proportion of the treated patients and have a significant influence on their quality of life. Coronary artery calcification (CAC), as assessed by computed tomography, carotid artery intima-media thickness (CIMT), and especially presence of plaques as assessed by B-mode ultrasound are directly correlated with increased risk for cardiovascular events and provide accurate and relevant information for individual risk assessment. Absence of vascular pathology as assessed by these imaging methods has a very high negative predictive value and therefore could be used as a method to reduce significantly the number of subjects who, in our opinion, would not benefit from statins and only suffer from their side-effects. In summary, we suggest that in very-low-risk subjects, with the exception of subjects with low FRS with a family history of coronary artery disease (CAD) at young age, if vascular imaging shows no CAC or normal CIMT without plaques, statin treatment need not be administered.
  • Rembrandt’s Jewish Physician—Dr Ephraim Bueno (1599–1665): A Brief Medical History

    Medicine in the Middle Ages was, and ever since remained, one of the main preoccupations of the professionally restricted Jews. One of the medical dynasties on the Iberian peninsula was the Bueno (Bonus) family. Following the expulsion of the Jews from Spain and their spread in Europe, these Iberian physicians became successful everywhere—just as the Buenos were in the Netherlands.
  • New Technologies and Hybrid Surgery for Atrial Fibrillation

    The Cox maze III and Cox maze IV procedures are surgical solutions for the treatment of symptomatic stand-alone atrial fibrillation. Despite their proven efficacy, these procedures have not gained widespread acceptance because of the invasiveness, complexity, and technical difficulty. Endocardial pulmonary vein isolation is the cornerstone of percutaneous catheter ablation for atrial fibrillation. It is currently accepted as an invasive therapy, if rhythm control has failed using antiarrhythmic drugs or electrical cardioversions. Pulmonary vein isolation is reported to be effective in 60%–85% of patients with paroxysmal atrial fibrillation and in 30%–50% of patients with persistent atrial fibrillation. A second or third ablation is often necessary to achieve these results, and complications may occur in up to 6% of patients. Surgical treatment of atrial fibrillation has seen important improvements in the last decade. New technologies have simplified creation of transmural lesions on the beating heart through a less-invasive, thoracoscopic procedure. This allows for pulmonary vein isolation, isolation of the posterior wall, and left atrial appendage exclusion—usually combined with ganglionic plexi evaluation and destruction. Nonethe¬less, it is still uncertain whether these procedures are effective in restoring permanent sinus rhythm since transmurality of a lesion set cannot be guaranteed with current ablation catheters on the beating heart. In an attempt to limit the shortcomings of an endo- or an epicardial technique, a hybrid approach has recently been introduced. This approach is based on a close collaboration between the surgeon and the electrophysiologist, employing a patient-tailored procedure which is adapted to the origin of the patient’s atrial fibrillation and takes into consideration triggers and substrate. Using a mono- or bilateral energy source, a thoracoscopic epicardial approach is combined with a percutaneous endocardial ablation in a single-step or in a sequential-step procedure. This article provides our experience and an overview of the current knowledge in the hybrid treatment of stand-alone atrial fibrillation.
  • New Technologies in Coronary Artery Surgery

    Coronary artery disease remains the leading cause of death in developed countries. Major recent studies such as SYNTAX and FREEDOM have confirmed that coronary artery bypass grafting (CABG) remains the gold standard treatment in terms of survival and freedom from myocardial infarction and the need for repeat revascularization. The current review explores the use of new technologies and future directions in coronary artery surgery, through 1) stressing the importance of multiple arterial conduits and especially the use of bilateral mammary artery; 2) discussing the advantages and disadvantages of off-pump coronary artery bypass; 3) presenting additional techniques, e.g. minimally invasive direct coronary artery bypass grafting, hybrid, and robotic-assisted CABG; and, finally, 4) debating a novel external stenting technique for saphenous vein grafts
  • New Technologies for Surgery of the Congenital Cardiac Defect

    The surgical repair of complex congenital heart defects frequently requires additional tissue in various forms, such as patches, conduits, and valves. These devices often require replacement over a patient’s lifetime because of degeneration, calcification, or lack of growth. The main new technologies in congenital cardiac surgery aim at, on the one hand, avoiding such reoperations and, on the other hand, improving long-term outcomes of devices used to repair or replace diseased structural malformations. These technologies are: 1) new patches: CorMatrix® patches made of decellularized porcine small intestinal submucosa extracellular matrix; 2) new devices: the Melody® valve (for percutaneous pulmonary valve implantation) and tissue-engineered valved conduits (either decellularized scaffolds or polymeric scaffolds); and 3) new emerging fields, such as antenatal corrective cardiac surgery or robotically assisted congenital cardiac surgical procedures. These new technologies for structural malformation surgery are still in their infancy but certainly present great promise for the future. But the translation of these emerging technologies to routine health care and public health policy will also largely depend on economic considerations, value judgments, and political factors.
  • Technological Solutions for Cardiac Surgery in the Elderly

    The current review addresses contemporary technological answers toadvances in cardiac surgery performed on octogenarian patients, namely off-pump coronary artery bypass grafting (CABG), proximal anastomosis device, routine use of intraoperative epiaortic ultrasound, proximal anastomosis without clamping, transcatheter aortic valve implantation (TAVI), and brain protection during cardiac surgery.
  • Signal, Transduction, and the Hematopoietic Stem Cell

    The hematopoietic stem cell (HSC) is a unique cell positioned highest in the hematopoietic hierarchical system. The HSC has the ability to stay in quiescence, to self-renew, or to differentiate and generate all lineages of blood cells. The path to be actualized is influenced by signals that derive from the cell’s microenvironment, which activate molecular pathways inside the cell. Signaling pathways are commonly organized through inducible protein–protein interactions, mediated by adaptor proteins that link activated receptors to cytoplasmic effectors. This review will focus on the signaling molecules and how they work in concert to determine the HSC’s fate.
  • Brain Neoplasms and Coagulation—Lessons from Heterogeneity

    The coagulation system constitutes an important facet of the unique vascular microenvironment in which primary and metastatic brain tumors evolve and progress. While brain tumor cells express tissue factor (TF) and other effectors of the coagulation system (coagulome), their propensity to induce local and peripheral thrombosis is highly diverse, most dramatic in the case of glioblastoma multiforme (GBM), and less obvious in pediatric tumors. While the immediate medical needs often frame the discussion on current clinical challenges, the coagulation pathway may contribute to brain tumor progression through subtle, context-dependent, and non-coagulant effects such as induction of inflammation, angiogenesis, or by responding to iatrogenic insults (e.g. surgery). In this regard, the emerging molecular diversity of brain tumor suptypes (e.g. in glioma and medulloblastoma) highlights the link between oncogenic pathways and the tumor repertoire of coagulation system regulators (coagulome). This relationship may influence the mechanisms of spontaneous and therapeutically provoked tumor cell interactions with the coagulation system as a whole. Indeed, oncogenes (EGFR, MET) and tumor suppressors (PTEN, TP53) may alter the expression, activity, and vesicular release of tissue factor (TF), and cause other changes. Conversely, the coagulant microenvironment may also influence the molecular evolution of brain tumor cells through selective and instructive cues. We suggest that effective targeting of the coagulation system in brain tumors should be explored through molecular stratification, stage-specific analysis, and more personalized approaches including thromboprophylaxis and adjuvant treatment aimed at improvement of patient survival.
  • Implementing Thrombosis Guidelines in Cancer Patients: A Review

    Venous thromboembolism is a frequent and serious complication in patients with cancer. It is an independent prognostic factor of death in cancer patients and the second leading cause of death, but physicians often underestimate its importance, as well as the need for adequate prevention and treatment. Management of venous thromboembolism in patients with cancer requires the coordinated efforts of a wide range of clinicians, highlighting the importance of a multidisciplinary approach. However, a lack of consensus among various national and international clinical practice guidelines has contributed to knowledge and practice gaps among practitioners, and inconsistent approaches to venous thrombo-embolism. The 2013 international guidelines for thrombosis in cancer have sought to address these gaps by critically re-evaluating the evidence coming from clinical trials and synthesizing a number of guidelines documents. An individualized approach to prophylaxis is recommended for all patients.
  • Minimal Residual Disease Surveillance in Chronic Lymphocytic Leukemia by Fluorescence-Activated Cell Sorting

    Achievement of complete response (CR) to therapy in chronic lymphocytic leukemia (CLL) has become a feasible goal, directly correlating with prolonged survival. It has been established that the classic definition of CR actually encompasses a variety of disease loads, and more sensitive multiparameter flow cytometry and polymerase chain reaction methods can detect the disease burden with a much higher sensitivity. Detection of malignant cells with a sensitivity of 1 tumor cell in 10,000 cells (10–4), using the above-mentioned sophisticated techniques, is the current cutoff for minimal residual disease (MRD). Tumor burdens lower than 10–4 are defined as MRD-negative. Several studies in CLL have determined the achievement of MRD negativity as an independent favorable prognostic factor, leading to prolonged disease-free and overall survival, regardless of the treatment protocol or the presence of other pre-existing prognostic indicators. Minimal residual disease evaluation using flow cytometry is a sensitive and applicable approach which is expected to become an integral part of future prospective trials in CLL designed to assess the role of MRD surveillance in treatment tailoring.