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In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014.

Aim:We evaluated two treatment sequences, transarterial radioembolization followed by transarterial chemoembolization and possibly sorafenib (TTS) versus transarterial radioembolization followed by sorafenib alone (TS), to identify the most cost-effective pathway to treat intermediate-stage hepatocellular carcinoma from the Italian healthcare system perspective. Materials & methods:A Markov model was developed to project costs and health outcomes for TTS and TS over a lifetime horizon. Data available at three hospitals in Italy were collected. Healthcare resource utilization was derived from standard clinical protocols. Costs were obtained from official regional tariffs. Results & Conclusion:Taking into consideration 16 patients for TTS and 22 patients for TS pathways, the TTS sequence provided a dominant strategy in comparison to TS. Further evidence is desirable to confirm these results.

Introduction The epidemiology of lung cancer is changing worldwide, with smoking being the key driver of lung cancer incidence and mortality. Our aim is to analyze the incidence, survival and mortality trends in Italy in the framework of the 2017 survey on smoking behavior in Italy.Methods AIRTUM 2017 reports on cancer survival and incidence; 2017 survey on smoking behavior in Italy.Results Men achieved progress in lung cancer control characterized by a decrease in incidence and mortality and an increase in survival. The decreasing use of tobacco in men (from 60% in the 1960s to 24% in 2017) was most likely responsible for the decreasing incidence and mortality. Women showed no progress: although survival improved slightly, the incidence and mortality were both on the rise. This was most likely due to the increasing smoking rates in women in the 1970s and 80s. Of major concern is the accelerated rise in the number of smoking women from 4.6 million in 2016 to 5.7 million in 2017 compared to the decrease observed in men (from 6.9 to 6 million).Conclusions The incidence and mortality trends in males clearly demonstrate that primary prevention is the most effective way to reduce lung cancer mortality. By contrast, a 24% increase in the prevalence of smoking among women in just 1 year is extremely worrying for the future, and calls for immediate action by targeted strategies to reduce tobacco consumption in women and avert the dreadful prospect of a lung cancer epidemic in Italy.

B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although in the epidermis Blimp1 is important for keratinocyte and sebocyte differentiation, its role in dermal fibroblasts is unclear. Here we show that Blimp1 is dynamically regulated in dermal papilla cells during hair follicle (HF) morphogenesis and the postnatal hair cycle, preceding dermal Wnt/β-catenin activation. Blimp1 ablation in E12.5 mouse dermal fibroblasts delayed HF morphogenesis and growth and prevented new HF formation after wounding. By combining targeted quantitative PCR screens with bioinformatic analysis and experimental validation we demonstrated that Blimp1 is both a target and a mediator of key dermal papilla inductive signaling pathways including transforming growth factor-β and Wnt/β-catenin. Epidermal overexpression of stabilized β-catenin was able to override the HF defects in Blimp1 mutant mice, underlining the close reciprocal relationship between the dermal papilla and adjacent HF epithelial cells. Overall, our study reveals the functional role of Blimp1 in promoting the dermal papilla inductive signaling cascade that initiates HF growth.

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6+cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue. Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane. This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

Systemic light chain (AL) amyloidosis is caused by the clonal production of an unstable immunoglobulin light chain (LC), which affects organ function systemically. Although pathogenic LCs have been characterized biochemically, little is known about the biology of amyloidogenic plasma cells (PCs). Intrigued by the unique response rates of AL amyloidosis patients to the first-in-class proteasome inhibitor (PI) bortezomib, we purified and investigated patient-derived AL PCs, in comparison with primary multiple myeloma (MM) PCs, the prototypical PI-responsive cells. Functional, biochemical, and morphological characterization revealed an unprecedented intrinsic sensitivity of AL PCs to PIs, even higher than that of MM PCs, associated with distinctive organellar features and expression patterns indicative of cellular stress. These consisted of expanded endoplasmic reticulum (ER), perinuclear mitochondria, and a higher abundance of stress-related transcripts, and were consistent with reduced autophagic control of organelle homeostasis. To test whether PI sensitivity stems from AL LC production, we engineered PC lines that can be induced to express amyloidogenic and nonamyloidogenic LCs, and found that AL LC expression alters cell growth and proteostasis and confers PI sensitivity. Our study discloses amyloidogenic LC production as an intrinsic PC stressor, and identifies stress-responsive pathways as novel potential therapeutic targets. Moreover, we contribute a cellular disease model to dissect the biology of AL PCs.

Introduction: Atherothrombosis and coronary artery disease affect more than 13 million individuals only in the United States, about 8 millions in Europe and are the major causes of death worldwide. In particular chronic stable angina impairs patient quality of life, is associated with an important health spending and increased patient mortality; it is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. A key role in pathophysiology of cardiovascular acute events is played by activated platelets. Aspirin and adenosine diphosphate antagonist in addition to it is recommended for 1 year for reduction of cardiovascular events in patients with prior myocardial infarction with a weak recommendation to continue thereafter. P2Y12 receptor antagonists, in addition to aspirin, have been shown in the last years, to reduce ischemic events in patients with acute coronary syndrome but their role in secondary prevention is still new and unclear. The aim of our paper is to review the long-term effect of therapy with ticagrelor on the basis of recent evidence based data. Methods: We performed an online search on the major search engines. All the randomized controlled trials were summarized in the table. Results: We included in our paper six randomized controlled trials and we mentioned about ten post – hoc analysis, sub studies and registries. All studies included the type the therapy and a mid or long term clinical follow up. Conclusions: The studies reported in our paper and in particular PEGASUS – TIMI 54 study showed the merit to placing attention of prevention secondary ischemic events after acute coronary syndrome in the context of treatment with dual anti – platelet therapy; it proved a clinical benefit in patients treated with ticagrelor (60 mg x 2) for 3 years. Nevertheless, the effectiveness of these results cannot be generalized to patients with higher bleeding risk or low ischemic risk. In fact prolonged therapy with ticagrelor 60 mg in combination with aspirin could be considered valuable in patients with repeated acute ischemic events or with several coronary revascularizations over time (especially in patients with lower bleeding risk).

Recent reports have shown an increase in the rate of Gram-negative bacteremia in several settings, including catheter-related bloodstream infections (CRBSI). To analyze if the epidemiology of CRBSI is also changing in hemodialysis patients, we revisited the etiology of CRBSIs in our renal unit over 8 years. During the observed periods, 149 episodes of CRBSIs were reported and the CRBSI incidence rate, ranged between 0.67 and 0.82 episodes/1000 tCVC days. Of these 149 episodes, 84 (56.3%) were due to Gram-positive bacteria, 62 (41.6%) to Gram-negative bacteria, and 3 (2.1%) to polymicrobial flora, no episodes of fungi were found. There was a trend, but not statistically significative, increase over time in the number of Gram-negative CRBSIs among the total CRBSIs, rising from 37.8% in the first period to 41.2% in the second period and to 44.3% in the last period, with a parallel decrease in the percentage of Gram-positive CRBSIs (from 59.5% to 56.9% and subsequently to 54.1%). Between Gram-negative, we reported an intensification of CRBSI due to Enterobacterales, particularly Escherichia coli. Among the Gram-negative, we have isolated germs rarely reported in the literature, such as Burkholderia cepacia, Pantoea agglomerans, and Rhizobium radiobacter. Regarding Gram-positive bacteria, a triplicate incidence of Staphylococcus aureus was reported with MRSA accounting for 42% in the third period. Among the Gram-positive bacteria, we reported two episodes of Kocuria kristinae and two of Bacillus spp.Our data demonstrated that the epidemiology of CRBSI in the same center, will change over time and Gram-negative strains are an increasing cause of CRBSI. The limitation of the present report is that statistical significance has not been reached, probably due to the limited number of CRBSI. New bacteria, both Gram-negative and Gram-positive, are emerging. Collaboration with the Microbiology Department appears essential to an appropriate diagnosis.

The treatment of bifurcation lesions remains a challenge with poor immediate results and higher restenosis rate than in nonbifurcated lesions. Drug-eluting stents improve the outcome after coronary stenting, but are associated with a small but statistically significant increase in late and very late stent thrombosis. Thus, aim of the present study was to evaluate the angiographic and clinical results of a new type of stent (coated with murine monoclonal antihuman CD34 antibodies designed to attract circulating endothelial progenitor cells to rapidly establish a functional endothelial layer and promote healing stent implantation) in a cohort of consecutive patients with coronary bifurcation lesions.

Levosimendan is one of the documented pharmacological agents used in the management and treatment of acute and chronic heart failure; it is a novel inodilator agent which enhanced myocardial performance without changes in oxygen consumption. The combination of positive inotropic and vasodilator effects of levosimendan relates to its Ca2+- sensitizing and K+ channels opening effects. Levosimendan has been proposed, in the recent past, to be non-inferior and may have some advantages to standard inotropes; further possible indications for levosimendan have been described, in some observational studies, such as a perioperative use, cardioprotection, cardiogenic shock, sepsis and right ventricular dysfunction. The ability of levosimendan to improve myocardial function without substantially increasing oxygen consumption may appear paradoxical but is possible via improved efficacy not only with regard to the effects on the contractile apparatus of the cardiomyocytes. The aim of this review is to describe the pharmacological characteristics of levosimendan and its clinical applications. The patent review data regarding the use of Levosimendan are also discussed in this review article.

The no — reflow phenomenon occurs in one third of the patients treated with primary percutanous intervention for acute ST segment elevation myocardial infarction. In addition of the effect of prolonged ischaemia, also reperfusion injury contributes significantly to the microvascular damage in the perfusion territory of the infarct — related coronary artery. In the recent years there has been an increasing interest in the concept of adjunctive mechanical thrombectomy to improve outcomes in primary percutaneous coronary intervention. In the literature randomized trials of thrombectomy have provided conflicting results with no definitive evidence for efficacy. The recently published Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (the largest randomized study of a thrombectomy device) demonstrates that adjunctive treatment with aspiration and manual thrombectomy improves clinical end — point. The aim of the report is to review the evidence to our date on the role of mechanical thrombectomy during primary percutaneous intervention in the setting of acute myocardial infarction.

Ivabradine (a compound of the benzocyclobutane) is a highly selective If current inhibitor acting directly on the sino-atrial node, induces a rapid, sustained and dose-dependent reduction of heart rate at rest and during exercise without a significant effect on atrio-ventricular conduction, left ventricular contraction/relaxation or vascular tissues. These properties associated with an improvement in left ventricular loading related to bradycardia resulted in an increase in stroke volume and preservation in cardiac output even during exercise. Various experimental and clinical studies showed the efficacy of ivabradine in patients with chronic stable angina, on heart rate reduction, on ventricular remodelling after acute myocardial infarction and on coronary blood flow. The safety of ivabradine has been documented in several studies and clinical trials, in contrast to beta-blockers, no significant side effects were expressed in the literature. The aim of our review is to describe ivabradine and its cardiovascular effects and outline some recent patents and the results of the most important trials.

Background: Intracoronary bolus administration may provide high local bivalirudin concentration without changing the global dose, potentially offering a more favorable antithrombotic effect in the infarct related artery (IRA).Objectives: The purpose of this study was to investigate the feasibility and safety of intracoronary bolus administration of bivalirudin followed by the standard intravenous infusion in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).Methods: In 245 consecutive patients treated with primary PCI, bivalirudin bolus was given directly in the IRA, followed by a standard intravenous infusion. Clinical reperfusion markers, postprocedural coronary flow indexes, and bleeding events of the intracoronary group were compared with a propensity score-matched cohort of primary PCI patients (n=245) treated with the standard bivalirudin protocol of intravenous bolus and infusion.Results: Higher rates of ?70% ST-segment resolution (72.7% vs 60.0%, p=0.004), lower postprocedural peak CK-MB levels (188.3±148.7 vs 242.1±208.1 IU/dl, p=0.025) and better Thrombolysis in Myocardial Infarction (TIMI) frame count values (14.7 vs 17.9, p=0.001) were observed in the IC bolus group compared with the standard intravenous bolus group. Rates of bleeding were similar between groups. Only three cases of acute stent thrombosis were observed, all in the intravenous bolus group (p=0.25).Conclusions: Intracoronary bivalirudin bolus administration during primary PCI is safe and improves ST-segment resolution, postprocedural coronary flow and enzymatic infarct size compared with the standard intravenous route.

Hematopoietic stem cells (HSCs) generate highly dividing hematopoietic progenitor cells (HPCs), which produce all blood cell lineages. HSCs are usually quiescent, retained by integrins in specific niches, and become activated when the pools of HPCs decrease. We report that Kindlin-3–mediated integrin activation controls homing of HSCs to the bone marrow (BM) and the retention of activated HSCs and HPCs but not of quiescent HSCs in their BM niches. Consequently, Kindlin-3–deficient HSCs enter quiescence and remain in the BM when cotransplanted with wild-type hematopoietic stem and progenitor cells (HSPCs), whereas they are hyperactivated and lost in the circulation when wild-type HSPCs are absent, leading to their exhaustion and reduced survival of recipients. The accumulation of HSPCs in the circulation of leukocyte adhesion deficiency type III patients, who lack Kindlin-3, underlines the conserved functions of Kindlin-3 in man and the importance of our findings for human disease.

Since the first human catheterization performed by Forssman in 1929 angioplasty equipment and medical therapies have undergone considerable evolution and technical improvement allowing interventionalists to perform more complex procedures and solving most of the percutaneous limitations. While percutaneous coronary intervention (PCI) has dramatically changed the outcome in the Acute Coronary Syndrome (ACS) setting, its role in the treatment of chronic stable angina is still debated. Stable coronary artery disease (SCAD) is a major public health issue and its prevalence is still increasing in the industrialized world. The correct treatment sees a multi-strategy approach aimed to a relief of symptoms, prevention of future cardiac events and survival improvement. In so forth, treatment strategies include optimal medical therapy (OMT) alone or combined with percutaneous or surgical coronary revascularization. Despite this, angina remains poorly controlled in the vast majority of CAD patients. Traditional agents such Beta-blockers or Calcium channel blockers or short and long acting nitrates have been used as first-line anti-anginal therapy for several years. Nowadays newer and more effective drugs usually used on top of older medical treatment have become available.

Heart rate is a fundamental determinant of cardiac oxygen consumption and plays a pivotal role in the pathophysiology of chronic stable angina (CSA). Ivabradine selectively and specifically inhibits the sino-atrial If current, slowing selectively heart rate without other significant haemodynamic effects. The consequent clinical effects are a sinus rate reduction similar to that obtained with beta-blockers, but without the related haemodynamic side effects. Ivabradine clinical benefits have been demonstrated both in patients with stable coronary artery disease (CAD) with associated systolic left ventricular dysfunction or in patients with congestive heart failure (HF). In this review we focused on the pharmacology and clinical research about ivabradine in the context of anti-ischemic therapy for CAD patients. Actually most guidelines suggest ivabradine therapy as last resort antianginal drugs in patients with uncontrolled symptoms or excessive heart rate despite maximum tolerated beta-blockade. However, the peculiar pharmacologic effects of the drug suggest that most patients with CAD might benefit from adding ivabradine to their therapeutic schemata. In fact, even if the recently released main analysis of the SIGNIFY study seems not to support an employ of ivabradine in primary prevention, it is easy to imagine a future wider use of this drug in elderly patients with incomplete myocardial revascularization and in patients with total chronic coronary occlusions and failure or unacceptable risk for percutaneous or surgical coronary revascularization.

Chronic angina represents a condition that impairs quality of life and is associated with decreased life expectancy in the industrialized countries. Current therapies that reduce angina frequency include old drugs such as nitrates, β -blockers and calcium antagonists. Several new investigational drugs are being tested for the treatment of chronic angina. This review will focus on ranolazine, a drug approved by the US Food and Drug Administration (FDA) in 2006 for patients with chronic angina who continue to be symptomatic despite optimized therapies. The main molecular mechanism underlying ranolazine-mediated beneficial effects has been identified as inhibition of the late Na+ current during the action potential, which potentially improves oxygen consumption, diastolic dysfunction and coronary blood flow. The aim of this review is to update the evidence for ranolazine treatment in chronic angina and discuss its therapeutic perspectives based on the most recent clinical and experimental studies.

Cardiovascular diseases and in particular coronary atherosclerotic disease are the leading cause of mortality and morbidity in the industrialized countries. Coronary atherosclerosis has been recognized for over a century and it was the subject of various studies. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis; during the last decades the basic research has focused on the study of the instability of atherosclerotic plaque. Plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes including ST – segment elevation myocardial infarction and non ST – segment elevation myocardial infarction. This is a brief review of the pathophysiology of atherosclerotic plaque development.

Many clinically important differences exist between beta blockers. B1-selectivity is of clinical interest because at clinically used doses, b1- selective agents block cardiac b-receptors while having minor effects on bronchial and vascular b-receptors. Beta-adrenergic blocking agents significantly decrease the frequency and duration of angina pectoris, instead the prognostic benefit of beta-blockers in stable angina has been extrapolated from studies of post myocardial infarction but has not yet been documented without left ventricular disfunction or previous myocardial infarction. Organic nitrates are among the oldest drugs, but they still remain a widely used adjuvant in the treatment of symptomatic coronary artery disease. While their efficacy in relieving angina pectoris symptoms in acute settings and in preventing angina before physical or emotional stress is undisputed, the chronic use of nitrates has been associated with potentially important side effects such as tolerance and endothelial dysfunction. B-blockers are the firstline anti-anginal therapy in stable stable angina patients without contraindications, while nitrates are the secondline anti-anginal therapy. Despite 150 years of clinical practice, they remain fascinating drugs, which in a chronic setting still deserve investigation. This review evaluated pharmacotherapy and indications of Beta-blockers and nitrates in stable angina.

Poor prognosis and limited therapeutic options characterize immunoglobulin light-chain (AL) amyloidosis with major heart involvement. Reliable experimental models are needed to study light-chain (LC)/heart interactions and to explore strategies for prevention of cardiac damage. We have exploited the nematode Caenorhabditis elegansas a novel tool, because its pharynx is evolutionarily related to the vertebrate heart. Our data demonstrate that the pharyngeal pumping of C elegansis significantly and selectively reduced by LCs from AL patients suffering from cardiomyopathy, but not by amyloid LCs with different organ tropism or nonamyloidogenic LCs from multiple myeloma. This functional alteration is dependent on the LC concentration and results in persistent pharyngeal dysfunction and in a significant reduction of the worms’ lifespan. These manifestations are paralleled by an increase of mitochondrial reactive oxygen species and can be prevented by treatment with antioxidant agents. In conclusion, these data indicate that this nematode-based assay is a promising surrogate model for investigating the heart-specific toxicity of amyloidogenic LCs and for a rapid screening of new therapeutic strategies.

Coronary obstruction by thrombus, triggered by rupture-prone atherosclerotic plaques, is the leading cause of myocardial infarction and accounts for millions of deaths and invasive coronary revascularization procedures. Coronary plaques become vulnerable far before any hemodynamic effect, thus conventional diagnostic techniques based on the angiographic assessment of the coronary vessels or the induction of myocardial perfusion defects or ischemia fail to identify lesions with an adverse clinical evolution. In this review we report about the currently available imaging methods used to investigate atherosclerotic plaques. Different coronary vessel imaging modalities such as coronary angiography, coronary ultrasound, nuclear imaging, magnetic resonance (MRI), computed tomography and other novel currently investigated methods are discussed in our systematic revision. Virtual histology IVUS, elastography and palpography are ultrasound-based methods used to characterize functions of different tissues their harmonic properties or their deformabilities. Optical coherence tomography, near infrared spectroscopy and fluorescence use infrared light to obtain high definition images of the vessel wall or tissue characterization. Intravascular MRI is a promising tool coupling high tissue-specificity imaging of MRI and high definition of intravascular techniques. Moreover recent advances in plaque-specific contrast media for magnetic resonance and positron emission tomography are described, highlighting their strength, pitfalls and future direction of the Research in the field. This article presents the current status in the technical background of intravascular ultrasound and nuclear tomographic imaging in the areas of clinical practice, and focuses on future developments of related patent forms.

Several cardiac diseases, like supra-ventricular arrhythmias, myocardial infarction, left ventricular remodelling with aneurysms and heart valve diseases like mitral valve stenosis, infective endocarditis and prosthetic heart valves predispose to intracavitary thrombus generation, which is the main source for peripheral embolism. Often the main unifying risk factor for cardio-embolism is atrial fibrillation (AF) and many of these cardio-embolic complications are transient ischemic cerebrovascular attacks or strokes with various levels of residual compromise. Cardiac imaging with different techniques and modalities has the potential to effectively stratify thrombo-embolic risk in patients with AF and other cardiac comorbidities. In this review we tried to characterize the current clinical role of different cardiac imaging methods, specifically echocardiography, cardiac computed tomography and cardiovascular magnetic resonance, in identifying cardio-embolic risk factors and guiding antithrombotic therapy, with a particular attention to novel patents and future developments of these techniques.

Computed tomography (CT) is important for the management of many medical illnesses, including coronary artery disease (CAD). However this technique is not free from disadvantages like the exposure to ionizing radiations and to iodinated contrast agents. To overcome these problems, imaging technologies are changing rapidly. New- generation computed tomography scanners (NGCCT) may bring substantial advantages over traditional CT and other currently used imaging methods. These novel tools employ dedicated protocols to shorten imaging times and reduce radiation doses without affecting accuracy. Current CT scanners can very accurately identify severe CAD requiring intervention in most patients, but NGCCT may further benefit imaging for some “difficult” patients like obese patients, patients with high or irregular heart rates, and patients who have high coronary calcium burden or previous stents or bypass grafts. In fact in these patients traditional CT studies often produce suboptimal quality images. Our review presents the current status in the technical background of coronary nuclear tomographic imaging in the areas of clinical practice, and focuses on future developments of related patent forms.

Angiography has been the cornerstone tool to assess coronary anatomy, leading to a rapid development of percutaneous revascularization techniques. Despite the widespread dissemination and high reproducibility, angiography alone can only provide a limited analysis of the lumen profile, without the possibility to disclose vessel wall characteristics and the composition of coronary lesions. Intracoronary imaging techniques have been developed to overcome these limitations. Intravascular ultrasound (IVUS) was the first intracoronary imaging modality introduced two decades before, followed more than a decade after by optical coherence tomography (OCT), a light based technology. This article presents the current status in the technical background of OCT imaging in the areas of research development and clinical practice, focusing on future developments of related patent forms.

Despite the great innovations of non-invasive coronary imaging, coronary angiography still remains the gold standard for the assessment of coronary artery disease (CAD), even if with several limitations. In fact visual assessment of coronary stenosis is convenient and rapid, but often associated with large inter and intra-observer variability, above all in the setting of unstable CAD with complex lesions. ; Coronary intravascular ultrasound (IVUS) allows accurate tomographic assessment of the coronary lumen and wall. IVUS has several diagnostic applications and is useful for choosing the most appropriate interventional strategy as well as for optimizing percutaneous coronary interventions (PCI) results. The present review focuses on: (1) the role of IVUS to guide therapeutic strategies in complex lesions requiring PCI, (2) IVUS capacity to interrogate borderline coronary stenoses, (3) new perspectives and recent patents for the future of IVUS technology.

Cardiovascular disease and in particular, acute coronary syndromes are one of the principle causes of death in the industrialized countries. In the setting of acute coronary syndromes (both ST – segment or non ST - segment elevation myocardial infarction), platelets aggregation plays a key and central role in their development. Platelets are the mediators of hemostasis at sites of vascular injury, but they also mediate pathologic thrombosis; activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion promoting atherothrombotic disease. Recent patent relates to the methods and devices for treating atherosclerosis and to prevent in-stent restenosis or thrombosis. Because of the importance of platelets involvement in the initiation and propagation of thrombosis, antiplatelet drugs have a source of research; in the recent past, new antiplatelet drugs (such as ticagrelor) have been studied and placed in the routine therapy. The aim of this paper is to summarize the pharmacological properties and the clinical characteristics of ticagrelor.

BackgroundBiodegradable polymer drug eluting stents (BP-DES) have been developed to overcome the limitations of first generation durable polymer DES (DP-DES) but the clinical results of different BP-DES are not consistent. We performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the treatment of coronary artery disease (CAD).Methods and resultsOnline databases including MEDLINE were searched for studies comparing BP-DES and DP-DES for obstructive CAD that reported rates for overall mortality, myocardial infarction (MI), late stent thrombosis (LST), target lesion revascularization (TLR) and late lumen loss (LLL) with a follow-up of ≥6 months. Ten studies (5834 patients) with a 1-year median follow-up were included in the meta-analysis. When comparing patients treated with DP-DES and BP-DES those treated with BP-DES had lower LLL (in-stent: weighted mean difference (WMD) −0.10 mm, 95% CI = −0.17 to −0.03 mm, p = 0.004; in-segment: WMD −0.06 mm, 95% CI = −0.10 to −0.01 mm, p = 0.01) with lower TLR rates (OR 0.67, 95% CI = 0.47 to 0.98, p = 0.04). However, BP-DES did not improve mortality (OR 0.97, 95% CI = 0.73 to 1.29, p = 0.83), MI (OR 1.13, 95% CI = 0.87 to 1.46, p = 0.36) or LST rates (OR 0.64, 95% CI = 0.36 to 1.16, p = 0.14). A pre-specified subgroup analysis of Biolimus BP-DES confirmed significant LLL reduction without differences in other clinical endpoints. Meta-regression analysis demonstrated a strong significant inverse correlation between LLL and reference coronary diameter (p < 0.001).ConclusionsOur present meta-analysis showed that BP-DES when compared with DP-DES significantly reduced LLL and TVR but without clear benefits on mortality, MI and LST rates. (Clinicaltrials.gov identifier: NCT01466634).

Coronary artery disease is the major cause of mortality and morbidity in the industrialized countries; in the United States of America and in Europe, it is responsible for one of every six deaths per year. In the setting of ischemic heart disease, angina pectoris and chest pain, in particular, are the major causes of emergency department accesses. Angina pectoris is a clinical syndrome characterized by discomfort typically in the chest, neck, chin and left arm induced by physical exertion, emotional stress and cold and is relieved by rest or by taking of nitrates. The main targets of treatment of angina pectoris are to improve quality of life by reducing the frequency and the severity of symptoms, to increase functional capacity and to improve prognosis. Ranolazine is a recent antianginal drug with unique methods of action. It was approved by the US Food and Drug Administration in 2006 as add-on therapy in patients symptomatic for stable angina. With the inhibition of the late sodium current, Ranolazine protects against ion deregulation, prevents cellular calcium overload and the subsequent increase in diastolic tension without impacting heart rate and blood pressure. Short term clinical trials and patent research show that add on therapy with Ranolazine in patients with chronic stable angina significantly improves exercise duration, exercise time to angina and reduces the use of nitro glycerine. Long term clinical trials showed no significant differences in the rate of cardiovascular death and myocardial infarction in patients with non-ST segment elevation acute coronary syndromes but a reduction in terms of recurrent ischemia. Ranolazine is generally well tolerated and even if it increases the duration of QTc interval it is not associated with atrial and ventricular arrhythmias. Therefore Ranolazine represents a good therapeutic approach in patients with chronic stable angina still symptomatic, while on optimal anti-ischemic therapy, or intolerant to traditional anti-ischemic drugs.

Intracoronary thrombi are a common finding in the setting of acute coronary syndromes and correlate with intraprocedural complications, adverse prognosis and unpredictable response to standard pharmacological and interventional treatment. Interventional cardiologists have learned to fear the so-called hostile thrombus, with its aggressive and unstable behavior often leading to abrupt and refractory vessel closure. Here we report a case series of intracoronary bivalirudin administration to treat massive intracoronary thrombi, leading to rapid clot disappearance and coronary blood flow restoration. Interventional cardiologists might consider intracoronary bivalirudin administration as a bailout strategy during unusual critical situations.

During the last years an increasing number of patients with high perioperative risk and decreased left ventricular function are referred to cardiac and non-cardiac surgery. In this subgroup of patients, heart failure is the major cause of perioperative morbidity and mortality. In order to prevent and treat this type of complications several therapeutic attempts have been tried involving intra aortic balloon pump and inotropic agents infusion (such as beta-adrenergic agonists and phosphodiesterase inhibitors) Levosimendan is new inotropic agent; it is a calcium-sensitising inotropic agent and a vasodilator used in the treatment of heart failure. In the last ten years several reports have been published on levosimendan. The inotropic efficacy of levosimendan is dose-dependent and equal or even superior to any of the other commercially available inotropic agents. The aim of the present review is to describe experimental and clinical effects of perioperative treatment with levosimendan.

Coronary artery diseases continue to be the most common causes of mortality and morbidity in the industrialized world, especially in the setting of acute myocardial infarction. Anticoagulation during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) has traditionally been supported by anticoagulant unfractionated heparin (UFH). Recently, alternative anticoagulants such as low molecular weight heparin (LMWH) were included in the management of STEMI. The aim of the present review is to compare efficacy and safety outcomes among patients receiving low molecular weight heparins (LMWH) or unfractionated heparin (UFH) while undergoing PCI for STEMI.

The direct thrombin inhibitor bivalirudin has gained popularity in cardiovascular medicine over the past decade because, in comparison with unfractionated heparin, it guarantees a predictable dose-related degree of anticoagulation with a low immunogenic profile and, possibly, with reduced rates of major bleeding complications. In the past bivalirudin has been frequently employed in the management of patients with heparin-induced thrombocytopenia. The REPLACE-2, ACUITY and ISAR-REACT4 studies demonstrated bivalirudin non-inferiority in comparison with unfractionated heparin in terms of ischemic end-points with a reduction of the bleeding rate also in patients acute coronary syndrome without ST elevation. Finally the results of the HORIZONS-AMI study positioned this drug as a first choice anticoagulant during percutaneous coronary interventions in patients with ST-elevation myocardial infarction. In fact the bivalirudin alone regimen, compared to unfractionated heparin plus GP2b3a inhibitors, decreased inhospital bleeding rates and short and long term mortality. Given the body of clinical evidence, bivalirudin is likely to contend to GP2b3a inhibitors the leading place among the proposed anticoagulation strategies in the setting of acute coronary syndromes. The duration of the bivalirudin infusion after PCI and the optimal oral antiplatelet regimen associated to bivalirudin are important issues to be solved in future randomized controlled studies.