Non-pegylated liposomal doxorubicin plus cyclophosphamide as first-line therapy in elderly women with HER2 negative metastatic breast cancer.

Background: The use of anthracyclines in metastatic breast cancer (MBC) is limited by cumulative dose-dependent cardiotoxicity mostly in elderly women with comorbidities. The aim of this observational retrospective study was to evaluate the efficacy of non-pegylated liposomal doxorubicin (Myocet®) and cyclophosphamide in elderly women as HER2 negative first-line MBC treatment. Methods: 84 elderly women >70 years of age (median age 78 years) with MBC HER2 negative were enrolled. Performance Status in 58 patients was ECOG-0 and in 26 patients was ECOG-1. Results: The drug was well tolerated, with overall response rates were >40%, median overall survival was 16.2 months (95%CI:14.6-18.8) and median progression free survival was 5.8 months (95%CI:4.4-8.6). Hematologic toxicity with neutropenia was the most frequent adverse event, but the treatment was well tolerated maintained a manageable cardiotoxicity. Conclusion: Non-pegylated liposomal doxorubicin may represent a valid therapeutic option in first-line for elderly patients with HER/2 negative MBC improving survival, anti-tumor response rate and de-creases cardiotoxicity.

Trans-limb embolization for treatment of Type 2 endoleak post EVAR: Case report.

INTRODUCTION: Type 2 endoleaks (T2EL) occur after 10%-25% of endovascular abdominal aortic aneurysm repairs and increase the risk factor of endograft repair failure and rupture. Herein we report a case of endovascular treatment of T2EL where we performed a trans-limb embolization. PRESENTATION OF CASE: A 63-years-old male previously treated for AAA with endovascular aortic aneurysms repair (EVAR), showed an angio-CT scan followup with a type 2 endoleak fed from inferior mesenteric artery (AMI) with growth of AAA greater of 1 cm than preoperative CT-scan and increase of chronic lumbar pain. Due to high risk of rupture was performed a trans-limb embolization with complete sealing. The 6 months CT-angiography showed complete type 2 endoleak exclusion without changes of AAA. DISCUSSION: The risk of aneurysm rupture in the presence of an isolated T2EL is exceptionally low. However, when a persistent T2EL is associated with a significant sac size increase, commonly considered as at least 5 mm over 6 months, should be treated. Detachable coils are repositionable, allowing an extremely precise deployment and subsequent embolization of different targets. CONCLUSION: In this experience trans-limb embolization was feasible and this tool should be taken in account especially when no other surgical options exists.

Transcervical approach for carotid artery stenting with transitory reversal flow: Case report.

INTRODUCTION: Carotid artery stenting (CAS) has been indicated as an alternative to carotid endarterectomy in high risk patients. Sometimes, an aortic arch can be anatomically unfavourable for CAS. Herein we report our experience in a case of CAS with transcervical approach. PRESENTATION OF CASE: A 77-year-old male was referred to our hospital for severe subtotal occlusion of the left internal carotid artery. He had a past medical history of radiation to the head and neck for laryngeal cancer. Previous CT-angiography had shown a type III aortic with bovine arch. CAS via transcervical approach was performed with transitory reversal flow during the placement of RX Spider Filter 6 Fr (Medtronic, Minneapolis, MN). After release of 7 × 30 mm RX Xact carotid stent (Abbott Vascular, Chicago, IL) and ballooning with a 5.5 × 30 mm Rx Submarine balloon catheter (Medtronic Minneapolis, MN), angiography check showed a good result. DISCUSSION: The transcervical approach is an innovative technique where usually a shunt is created, either between the common carotid artery and the internal jugular vein or between the common carotid artery and the common femoral vein. This flow reversal reduces the risk of periprocedural embolic events. In our experience a short proximal clamping with transitory reversal flow, reduces the invasiveness of procedure with good outcomes. CONCLUSION: Transcervical carotid access with transitory reversal flow is a valid alternative in complicated patient with anatomy unfit for CAS.

Penetrating aortic ulcer post migration of thoracic aortic endoprosthesis: Case report.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) is the first treatment option for many thoracic aortic pathologies. Especially after aortic dissections, it is possible to have progression during follow-up with appearance of new lesions on arterial wall. Herein, we report a case of Penetrating Aortic Ulcer (PAU) post release of Thoracic endoprosthesis. PRESENTATION OF CASE: A 67-years-old male with hypertension and diabetes mellitus was followed at our hospital after an emergency procedure for Type B aortic dissection (TBAD) complicated by symptomatic large infrarenal AAA and treated with a proximal TEVAR plus chimney for left subclavian artery and PETTICOAT with EVAR for abdominal aortic disease. Follow up at 15 months showed a deep PAU with partial crush of stent in Left Subclavian Artery. Thus, we performed a left carotid-subclavian bypass and subsequently a TEVAR procedure with release of Bolton Relay endoprosthesis (Terumo Aortic, Sunrise, Florida, United States). DISCUSSION: In literature there are few studeis that focus on migration after TEVAR during follow-up. Elongation, changes of tortuosity on thoracic aorta after TEVAR, can help to determine a migration of prosthesis. In this case Bolton Relay endoprosthesis (Terumo Aortic, Sunrise, Florida, United States) has permitted to improve precision and quality of procedure. CONCLUSION: In literature there are few studies reporting complications of TEVAR post prosthesis migration. In this case, Bolton Relay endoprosthesis was useful and safe.

Comparison of coronary artery flow impairment in diabetic and hypertensive patients with stable microvascular angina.

OBJECTIVE: Stable microvascular angina (SMVA) describes patients with angina, findings compatible with myocardial ischemia and normal coronary angiograms. The aim of this study was to evaluate the impact of diabetes on the coronary microcirculation troughs angiography indexes (TIMI Frame Count, Myocardial Blush Grade, Total Myocardial Blush Score) and a new index: Total TIMI Frame Count (TTFC). PATIENTS AND METHODS: The study population included 310 patients with SMVA that we split into two populations: diabetic-non hypertensive (164 patients) and non-diabetic-hypertensive (146 patients). We calculated, on angiographic images of each patient, TIMI Frame Count (TFC), Myocardial Blush Grade (MBG) and Total Myocardial Blush Score (TMBS) using the protocol described by Gibson and Yusuf. On the basis of Yusuf's experience we imagined a new index: TTFC like sum of the three coronary TFC. RESULTS: We found a worse coronary microcirculation in diabetic-non hypertensive patients with lower values of TFC, MBG and TMBS (p = 0.02), compared with non-diabetic hypertensive. New index TTFC is usually higher in diabetics-non hypertensive than non-diabetic hypertensive patients. Patients with positive scintigraphy had a worse TMBS than patients with a negative one, with a high statistical significance (p = 0.003). CONCLUSIONS: Analysis of diabetic non hypertensive and non-diabetic and hypertensive patients with cardiac syndrome X has led to asses that the diabetic population has a greater involvement of microcirculation. Also the new index, TTFC, proved to be a good marker, in agreement with results of other indexes.

Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study.

BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, considered as emerging and promoting atherosclerosis. This study aimed at the evaluation of the influence of MetS on the prediction of cerebro and cardiovascular events during a 20 years follow-up period in an asymptomatic population of middle-aged subjects. METHODS: We evaluated 529 asymptomatic persons through a prospective study. Study population was divided into two subgroups: patients with and without MetS. Echo-color-Doppler was used in order to assess the presence of subclinical atherosclerosis. A 20 years follow-up study was carried out in order to estimate the incidence of cerebro and cardiovascular, fatal and non fatal, events (AMI, stroke, abdominal aortic aneurysm, TIA, angina pectoris). RESULTS: 242 cerebro and cardiovascular events were registered, 43 fatal (24 in MetS and 19 in controls) and 199 non fatal (120 with MetS and 79 without it, p < 0.0001). Free-events survival was lower in patients suffering from MetS (p < 0.0012; HR 0.6847; C.I.95%: 0.5274-0.8889). Ultrasound showed a higher prevalence of subclinical atherosclerosis in patients with MetS than in the unaffected ones (68.12% vs. 57.5% p < 0.01; OR = 1.58 with C.I.95% = 1.10-2.28, p < 0.01). CONCLUSIONS: Patients with MetS have a higher cardiovascular risk that can be explained by atherosclerotic changes: the components of MetS interact to affect vascular thickness synergistically and promote the development of subclinical atherosclerosis. So we recommend to prevent the development of MetS abnormalities and to investigate the presence of subclinical atherosclerosis by echo-color-Doppler in order to stratify more accurately the global CV risk.

Insulin resistance and acute coronary syndrome.

BACKGROUND: Insulin resistance (IR), which can be quantified by HOMA index (fasting glucose X fasting insulin/22.5), is considered the "primum movens" for the development of Metabolic Syndrome. Many authors have suggested that insulin resistance could raise both incidence and mortality of coronary heart disease (CHD). IR is also associated with important predictors of cardiovascular disease, as increased concentration of LDL or triglyceride, decreased concentration of HDL, high systolic blood pressure, visceral obesity. There is accumulating evidence that chronic sub-clinical inflammation, as measured by inflammatory markers as C-reactive protein (CRP) and fibrinogen, is related with insulin resistance. AIM OF THE STUDY: To clarify if insulin resistance would predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidemia, by focusing our attention on the relation between Acute Coronary Syndrome (ACS) and high HOMA index. METHODS: We evaluated glucose and insulin levels at baseline and post-prandial phase, in order to estimate HOMA index in both the conditions; we related the data obtained with the incidence of cardiovascular events, also investigating traditional cardiovascular risk factors. The cohort included 118 patients with a clinical diagnosis of ACS and excluded those with type 1 diabetes, acute inflammatory diseases, hepatic or renal failure, disreactive disorders, autoimmunity and cancer. SUBJECTS: Subjects were followed-up for a period of 1 year, being subdivided in three groups: (1) subjects at elevated HOMA (HOMA > or = 6); (2) subjects at intermediate HOMA (HOMA <6 and > or = 2); (3) subjects at low HOMA (HOMA < or = 2). We considered as end points new cardiovascular events, cerebrovascular events (both TIA and stroke), procedures of revascularization with angioplasty or surgery, cardiovascular death, sudden death. RESULTS: Patients with elevated HOMA have a higher incidence of previous cardio- and cerebrovascular events (p=0.03), myocardial infarction without ST elevation (p=0.005), unstable angina (p=0.01), asymptomatic carotid plaques (p=0.05), depressed systolic function (p=0.05); we found, also, a significant statistic correlation between HOMA index and high levels of CRP, fibrinogen, serum creatinine and TnI. Cardiovascular and cerebrovascular events were registered in 61% of patients with elevated HOMA during the follow up, despite of 25% registered in the control group: so we could consider HOMA index as a negative prognostic variable, also in virtue by the statistic correlation with the inflammatory markers, whose power of prediction is already known. CONCLUSIONS: Beyond traditional cardiovascular risk factors, insulin resistance quantified by HOMA index seems to significantly have an important prognostic role, both in primary and secondary prevention in patients with Acute Coronary Syndrome.

Carotid intimal-media thickness and endothelial function in young patients with history of myocardial infarction.

AIM: The aim of the study was to evaluate the prevalence of carotid atherosclerosis and endothelial dysfunction in 45 young patients (38 mens and 7 females) with myocardial infarction (MI), age 29-45, mean age 42+/-3 years, to verify its possible role as a marker of coronary atherosclerosis. METHODS: Vascular echography was performed to verify the presence of carotid atherosclerosis and/or endothelial dysfunction in 45 young patients with MI and in 45 healthy control subjects well matched for age and sex. RESULTS: We observed a normal intima media thickness (IMT) only in 30% of patients with juvenile myocardial infarction (JMI) compared with 66% in the control group (P<0.0001) and 34% of patients showed an increased IMT compared with 24% of healthy subjects (P<0.0001). Compared with control subjects, patients with JMI had lower flow-mediated reactivity of the brachial arteries (P<0.05). There was a negative linear relationship between flow-mediated dilation and IMT (P<0.001). The severity of coronary artery disease (CAD) was correlated with increased IMT and with a lower flow-mediated dilation. Finally, multiple regression analysis, demonstrated that both brachial-artery reactivity and carotid IMT were significantly and independently correlated with severity of CAD. CONCLUSIONS: Structural (carotid atherosclerosis) and functional changes (endothelial dysfunction) were present at an early age in the arteries of persons with history of JMI.

Short term prognostic role of NT-proBNP in patients after myocardial infarction.

AIM: The clinical and prognostic role of cardiac natriuretic peptides (CNP) in patients with heart failure is well known; recently, several studies have evaluated the possibility of using CNP to evaluate their potential prognostic role in patients with acute coronary syndromes (ACS). The aim of this study was to evaluate the short term prognostic value of NT-proBNP in 70 patients admitted for ACS. METHODS: The authors studied 70 patients with ACS, evaluating, at admission, clinical-anamnestic, instrumental and laboratory characteristics including NT-proBNP plasma levels. Patients were monitored in a 6-month-follow-up to record adverse fatal events and their possible correlation with baseline characteristics. RESULTS: The incidence of adverse events during the follow-up period was 28% (10 patients). In patients with adverse events, the authors observed lower left ventricle ejection fraction (P=0.01), higher prevalence of ST elevation myocardial infarction (P=0.03) and higher NT-proBNP levels (P=0.03), compared to those without adverse events. Moreover, the logistic regression analysis underlined how ST elevation myocardial infarction (P=0.05) and higher NT-proBNP levels (P=0.05) were the only predictive variables for adverse events during the follow up period. CONCLUSIONS: This study demonstrates the short term prognostic role of NT-pro BNP in patients admitted for ACS.

Prognostic role of endothelial dysfunction and carotid intima-media thickness in patients undergoing coronary stent implantation.

AIM: Impaired endothelial function and increased carotid intima-media thickness are key events in the atherosclerotic process and predict future cardiovascular events in subjects with and without coronary artery disease. The purpose of this study was to investigate whether the vasodilator response to increased flow in the brachial artery and the presence of carotid lesions may have a prognostic significance for in-stent restenosis in patients undergoing coronary angioplasty. METHODS: The study population included 58 patients undergoing percutaneous coronary intervention (PCI) with stenting and at least 10 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI. Flow mediated dilatation (FMD) was investigated after 5 minutes of occlusion of the artery and nitroglycerin mediated dilation (NMD) was investigated after administration of sublingual nitrates. Vascular echography was performed to measure intima media thickness (IMT) of carotid arteries. At baseline we evaluated all the established traditional cardiovascular risk factors. We also subdivided our study cohort according to values of FMD in patients with FMD above and patients below the median value. RESULTS: Patients with FMD above the median value showed higher prevalence of hypertension (P=0.002), diabetes (P=0.02) and carotid IMT (P=0.006) than those below the median. Brachial FMD was inversely correlated (P=0.001) to carotid IMT. At the end of follow-up clinical events occurred in nine patients. In a multivariate analysis, including all the variables evaluated at baseline, carotid IMT (P=0.02), level of glycemia (P=0.001), a lower FMD (P=0.005) and presence of carotid plaque remained the only variables predictive of restenosis. CONCLUSIONS: Evaluation of FMD and carotid IMT may provide important prognostic information in patients undergoing PCI.

Role of ARBs in the blood hypertension therapy and prevention of cardiovascular events.

Hypertension has a worldwide high incidence in the general population and undoubtedly it is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries. In this Review we investigated the role of angiotensin II receptor antagonists (ARBs) therapy in the treatment of essential hypertension. We selected in the PubMed and in a list of selected sources the most significant clinical trials and meta-analysis carried out from 1999 to now, to assess, in adult patients populations, ARBs' efficacy, safety and tolerability profile, in comparison with the efficacy of the other common antihypertensive drugs, with particular regard to both the prevention of disabling consequences of hypertension (like cerebrovascular events, coronary events and heart failure) and the influence of an adequate antihypertensive therapy on comorbidities which strongly influence the outcome of hypertensive patients (like atherosclerosis, kidney damage, type II diabetes mellitus and arrhythmias). We also evaluated, in a detailed pharmacological and pharmaco-economic analysis, the basilar differences between ACE-inhibitors and ARBs in the control of the RAA system, and we assessed the possible benefits of their associated use, according to the new evidences concerning the treatment of arterial hypertension.

Extracoronary atherosclerosis in patients with chronic ischemic heart disease: relationship with risk factors and the severity of coronary artery disease.

AIM: The aim of the present study was to investigate the prevalence of carotid and/or peripheral atherosclerotic lesions in patients with chronic ischemic heart disease (previous acute myocardial infarction [AMI] or stable angina). METHODS: We studied 248 patients (168 male and 80 female), mean age 63+/-10 years, which were investigated for traditional risk factors. Systolic blood pressure, body mass index, lipid profile, fasting glucose and plasma fibrinogen were also measured. We assessed the prevalence of atherosclerotic lesions in carotid and lower limb arteries, by ultrasound duplex scanning (UDS). RESULTS: Angina was present in 33% of the patients, a previous AMI in 67%, a previous transient ischemic attack in 4% and a previous ischemic stroke in 6% of patients. A total of 195 patients underwent coronary angiography: 1 vessel was involved in 48% of patients, 2 vessels in 33%, and 3 vessels in 19%. Detecting peripheral atherosclerotic lesions by UDS, increased intima-media thickness (IMT) or plaques in carotid arteries were found in 232 patients (94%) and carotid stenosis >70% in 13 patients (5%). In lower limb arteries, IMT or plaques were present in 202 patients (82%) and a stenosis >70% in 18 patients (7%). Severity of coronary artery disease (CAD) was correlated to extracoronary atherosclerosis: carotid and lower limb arterial atherosclerosis was detected in 73% of patients with 1 vessel, in 83% of patients with 2 vessel, in 87% of those with 3 vessel CAD. CONCLUSION: Our study suggests that in patients with CAD, it is useful to screen the peripheral circulation by non-invasive tests, such as UDS. Patients with the diagnosis of ischemic heart disease and combined extracoronary atherosclerosis need a careful follow-up and a more aggressive therapy for secondary prevention.

Comprehensive cardiovascular ECG-gated MDCT as a standard diagnostic tool in patients with acute chest pain.

Acute myocardial infarction, pulmonary embolism, and aortic dissection are diseases associated with acute chest pain and may lead to severe morbidity and mortality. These diseases may not be trivial to diagnose in the settings of emergency room. ECG-gated multi-detector computed tomography (MDCT), already established for the assessment of pulmonary embolism and aortic dissection, provides reliable information regarding the triage of patients with acute coronary syndrome in the emergency room. MDCT recently appeared to be logistically feasible and a promising comprehensive method for the evaluation of cardiac and non-cardiac chest pain in emergency department patients. The possibility to scan the entire thorax visualizing the thoracic aorta, the pulmonary arteries, and the coronary arteries could provide a new approach to the triage of acute chest pain. The inherent advantage of MDCT with cardiac state-of-the-art capabilities is the rapid investigation of the main sources of acute chest pain with a high negative predictive value. Recent studies also reports an advantage in terms of costs. With current evidence, the selection of patients with acute chest pain candidates to MDCT should remain restricted to avoid unjustified risk of ionizing radiation.

Carotid and peripheral atherosclerosis in patients who underwent primary percutaneous coronary intervention and outcome associated with multifocal atherosclerosis.

AIM: The aim of our study was to determine if patients with multifocal atherosclerosis have a worse prognosis than patients with atherosclerosis only in the coronary bed. METHODS: We studied 45 subjects admitted to intensive coronary care unit of the Division of Cardiology with the diagnosis of acute myocardial infarction (AMI). Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of plasma lipids, glycemia, fibrinogen and high-sensitivity-C-reactive protein (hs-CRP). Each patient underwent coronary-angiography as well as carotid and peripheral arterial ultrasound examination. A follow-up of 13+/-2 months was performed. RESULTS: We found that the severity of coronary atherosclerosis is significantly associated with the presence of carotid (P<0.05) and peripheral atherosclerosis (P<0.005). Markers of inflammation, hs-CRP (P<0.005) and fibrinogen (P<0.05), were significantly associated with multifocal atherosclerosis. We have shown that an increased number of coronary vessels with atherosclerotic stenosis is associated with a higher value of carotid (P<0.0001) and peripheral intima media thickness (P<0.0001). During 13 months of follow-up the incidence of fatal or non fatal events was 18%. The multivariate analysis showed that the variables independently associated with fatal and non fatal events were: male sex (P<0.001), family history of cardiovascular disease (P<0.005), hypertension (P<0.01), diabetes mellitus (P<0.05), higher levels of total cholesterol (P<0.05), smoking habit (P<0.05), and multifocal atherosclerosis (P<0.05). CONCLUSIONS: The ultrasound examination of carotid and peripheral atherosclerotic lesions may be useful in placing patients with AMI in a category of higher risk of cerebrovascular and cardiovascular events. Moreover, the precocious identification of patients at risk can suggest a more aggressive pharmacological treatment and a more accurate follow-up in order to avoid future events.

Expression of a chimeric CaMV 35S Bacillus thuringiensis insecticidal protein gene in transgenic tobacco.

Insecticidal transgenic tobacco plants containing a truncated Bacillus thuringiensis cryIA(b) crystal protein (ICP) gene expressed from the CaMV 35S promoter were analyzed for ICP gene expression under field and greenhouse conditions over the course of a growing season. We present new information on temporal and tissue-specific expression of a CaMV 35S/cryIA(b) gene. Levels of cryIA(b) protein and mRNA were compared in both homozygous and hemizygous lines throughout plant development. Levels of ICP mRNA and protein increased during plant development with a pronounced rise in expression at the time of flowering. Homozygous ICP lines produced higher levels of ICP than the corresponding hemizygous lines. ELISA analysis of different tissues in the tobacco plant showed ICP gene expression in most tissues with a predominance of ICP in older tissue. All transgenic ICP tobacco lines which were studied in the field and greenhouse contained 400 ng to 1 microgram ICP per gram fresh weight in leaves from the mid-section of the plant at flowering. The amounts of ICP produced by field lines were directly comparable to levels observed in greenhouse-grown plants.