Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment.

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways.

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.

Heavy Environmental Pressure in Campania and Other Italian Regions: A Short Review of Available Evidence.

The area of Naples and Campania region, in Italy, are experiencing the dramatic consequences of diffuse and illegal waste dumping, resulting in possible threats to human health. This area has been referred to as the "Land of Fires" because of the common practice of waste burning. International interest in the Campania "waste emergency" has triggered several epidemiological studies. This article is aimed at highlighting the body of evidence available concerning human and environmental contamination in the Campania region, and considers the possible lack of comparable knowledge about the situation in other areas suffering from high environmental pollution. We analyzed the results of studies addressing environmental pollution and population health in the Campania region, starting from the most recent reviews on this topic, and compared their findings with those concerning other regions. We reviewed 18 studies of epidemiological/cancer surveillance and human or animal biomonitoring. These studies show worrying results, which could be considered comparable to those available for other Italian areas impacted by heavy industrial activities. The release of environmental contaminants associated with waste incineration and waste disposal in landfills poses a risk to public health, as shown by a number of studies (although not conclusively). The current knowledge available for the Campania region is better than that available for other areas which are facing similar problems due to anthropic activities, including illegal waste trafficking. Thus, Naples and Campania could represent a valuable setting to develop general models for studies of environmental and human contamination.

Illegal Dumping of Toxic Waste and Its Effect on Human Health in Campania, Italy.

The region of Campania (particularly Naples and Caserta) has experienced an emergency in the waste management cycle during past years. Although the most critical phase has been overcome after the construction of the incineration plant in Acerra (an old-fashioned technology built up over a few months, whose impact on environment and health has not yet been assessed), most of the underlying problems have not been resolved. The illegal burning of wheels, plastics, textiles, and other industrial residuals, along with the detection of two thousand toxic substance dumping sites, still represents major concerns of environmental pollution and population health. This review summarizes the most relevant studies, which analyzed chemical contamination (primarily dioxins and polychlorinated biphenyls (PCBs)) of the air, soil, water, animals, and humans in Campania. In addition, we reviewed information on population health (i.e., mortality data, congenital malformations, and cancer incidence). Moving from a detailed mapping of (mostly illegal) waste dumping sites in Campania, we have focused on recent studies which have found: (a) high concentrations of dioxins (≥5.0 pg TEQ/g fat) in milk samples from sheep, cows, and river buffaloes; (b) remarkable contamination of dioxin and PCBs in human milk samples from those living in the Naples and Caserta areas (PCDDs+PCDFs and dioxin-like-PCBs (dl-PCBs) assessed at 16.6 pg TEQ/g of fat; range: 7.5-43 pg/g of fat); (c) potential age-adjusted standardized mortality rates associated with some specific cancer types; (d) a statistically significant association between exposure to illegal toxic waste dumping sites and cancer mortality, even after adjustment by socio-economic factors and other environmental indicators.

The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records.

BACKGROUND: Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy. METHODS: We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented. RESULTS: The overall number of mastectomies decreased, with an AAPC of -2.1% (-2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (-3.0%, -3.4 -3.6 and -3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5-4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6). CONCLUSIONS: In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.

Wasting lives: the effects of toxic waste exposure on health. The case of Campania, Southern Italy.

Three decades of illegal practices of waste dumping and consequent environmental abuse have made the Campania region of Southern Italy a unique case in the context of waste-related health outcomes. Scientific evidence is mounting in support of a significant increase in cancer mortality and malformation occurrence in specific areas of the Campania region, where improper waste management and illegal waste trafficking have been repeatedly documented. However, the currently available evidence suffers from limitations mainly due to study design, lack of consideration of confounders and quality of the exposure data. Recent economic studies have shown the economic benefits of reclaiming toxic waste sites in Campania. Future perspectives include the adoption of different study designs, use of biomarkers and a molecular approach. Current knowledge, both scientific and economic, might be of help in orienting the short and long term governmental policy on waste related health outcomes at a regional level.

Pulmonary arterial hypertension: the key role of echocardiography.

Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.

Reduced serum homocysteine levels in type 2 diabetes.

OBJECTIVE: To assess the contribution of fasting blood glucose and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism on fasting serum homocysteine (tHcy) levels in patients with uncomplicated type 2 diabetes compared with healthy subjects. METHODS AND RESULTS: We studied 105 type 2 diabetic patients without cardiovascular complications or diabetic nephropathy (55 males, 50 females, mean age 53+/-10 years, mean duration of diabetes 11.4+/-8 years) and 120 age- and sex-matched control subjects (65 males, 55 females, mean age 52+/-8 years). tHcy and other biochemical variables were measured. The C677T MTHFR gene polymorphism was determined by analysis of HinfI restriction fragment length polymorphism tHcy levels were significantly lower in diabetic patients compared with control subjects (7.7 +/- 2.2 vs. 11.8 +/- 4.5 micromol/l, P < 0.0001). In both patients and control subjects, homocysteinemia was higher in men than in women (8.4+/-2.6 vs. 7.3+/-2.0 micromol/l, P < 0.03, and 13.0+/-5.3 vs. 10.4+/-2.6 micromol/l, P < 0.0001, respectively). Levels were slightly higher in subjects with the mutated Val/Val genotype compared with the Ala/Val plus Ala/Ala genotypes in both diabetic patients (P < 0.02) and control subjects (P < 0.003). On simple regression analysis, tHcy was inversely related with blood glucose levels (P < 0.02) and directly with sex (P < 0.04) in diabetic patients, and with sex (P < 0.0001), age (P < 0.02), BMI (P < 0.03), systolic and diastolic blood pressure (P < 0.0004 and P < 0.0002), uric acid and creatinine (P < 0.0001 and P < 0.0003) in control subjects. On multiple regression, tHcy levels were associated with sex (P < 0.03) and glucose levels (P < 0.04) in diabetic patients, and with uric acid (P < 0.002) and MTHFR genotype (P < 0.03) in control subjects. CONCLUSION: In type 2 diabetic patients without nephropathy, basal levels of tHcy were 35% lower compared with healthy controls. Chronic hyperglycemia may control tHcy by affecting its renal excretion, or accelerate hepatic trans-sulfuration secondary to insulin disorders.

[Homocysteine and cardiovascular risk]. / Omocisteina e rischio cardiovascolare.

Many studies have shown that raised serum/plasma levels of total homocysteine (tHcy) increase the risk of coronary, cerebral, and peripheral artery disease. The risk associated with hyperhomocysteinemia appears to be concentration-dependent and not attributable to traditional risk factors. tHcy are increased as a result of age, male gender, impaired renal function, low vitamin B and folate intake, and genetically-determined defects of the enzymes involved in homocysteine metabolism. Conflicting results have been reported in genetic, observational and experimental studies on relationship between tHcy and these atherothrombotic disease. In facts in individuals with tHcy concentrations are increased for genetic origin there is no clear evidence fore causal role of tHcy in the pathogenesis of atherosclerosis disease and positive association between tHcy and cardiovascular disease observed in many, but not all clinical-epidemiologic studies does not prove causality. Despite increasing recognition of hyperhomocysteinemia as a risk factor for arterial thrombosis disease, irrefutable proof that mild hyperhomocysteinemia contributes directly to the pathogenesis of atherothrombosis will come if interventions to lower total homocysteine reduce cardiovascular events.

Electrocardiographic features in critical pulmonary embolism. Results from baseline and continuous electrocardiographic monitoring.

BACKGROUND: Pulmonary embolism (PE) afflicts millions of individuals worldwide. Electrocardiography along with chest X-ray and arterial blood gas analysis represent the basic examinations to reinforce the clinical suspicion of PE. We describe the electrocardiographic (ECG) features in a series of patients with PE and a critical clinical presentation. METHODS: We report the ECG findings registered at baseline, 48 hours after admission and on continuous ECG monitoring in 51 patients with PE and critical clinical conditions. RESULTS: At admission, the following parameters were recorded: an S1Q3 pattern in 34 patients, a "septal embolic pattern" in 27, anterior lead T-wave inversion in 8, and a new right bundle branch block in 7. At 48 hours after admission a trend toward a regression of the S1Q3 and "septal embolic" patterns was noted together with evident T-wave inversion in the anterior leads. During continuous ECG monitoring no major arrhythmias were recorded, even in case of cardiopulmonary arrest. CONCLUSIONS: Critical PE induces transient ECG abnormalities reflecting right ventricular overload and/or strain. The patient's clinical status is usually not complicated by major ventricular arrhythmias, not even in case of cardiopulmonary arrest.

[Role of matrix metalloproteinases in aneurysmatic aortic disease]. / Ruolo delle metalloproteinasi nella patologia aneurismatica dell'aorta.

The aorta is involved in a large variety of diseases and the atherosclerotic aneurysms represent the most common type of these. Recent reports have attempted to clarify the mechanisms, that cause the formation and the progression of the atherosclerotic aneurysms, caused not only by the atherosclerosis. One of the features of this disease is the extensive proteolytic destruction of structural matrix proteins in the aortic wall realized by the matrix metalloproteinases. The atherosclerotic aneurysm can be considered a disease caused by an imbalance between connective tissue destruction and its repair. Knowledge of the role played by matrix metalloproteinases in the formation process of the aneurysms has made the inhibition of these proteins a logical therapeutic strategy. Once completed the aneurysm treatment, surgical or endovascular, the endothelial damage must disappear; the persistence of this damage, after endovascular procedure, is the cause of the formation of the endoleaks. The preoperative matrix metalloproteinases plasmatic levels are related to the aneurysm diameter and after endovascular treatment these values come back normal, except in the case of presence of an endoleak, that don't make possible the reduction of these values. In spite of that, obscure points still remain, above all about the dosage of these proteins and their inhibition through drugs with clear metalloproteinases-inhibiting properties. The aim of this study is to clarify further on the mechanisms of the formation of the aneurysms with particular care to the matrix metalloproteinases, their dosage and their drug inhibition.

[Lack of association between Chlamydia pneumoniae seropositivity and common carotid intima-media thickness in type 2 diabetic patients]. / Mancanza di associazione tra sieropositività alia Chlamydia pneumoniae ed ispessimento medio-intimale della carotide comune in pazienti con diabete tipo 2.

BACKGROUND: The current body of evidence suggests that Chlamydia Pneumoniae (CP) infections may play a role in the development and maintenance of atherosclerosis process and related clinical complications. METHODS: In our study we assess the association between seropositivity of CP antibody IgG to common carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus (DM). One hundred thirty DM patients (mean age 53 +/- 10 years, 70 female) were enrolled for study. Serum CP IgG antibody were detected by microimmunofluorescent technique; IMT and plaques or stenosis in the common carotid were assessed by ultrasonography. RESULTS: In univariate analysis common carotid IMT was significantly associated with age (P>0.00001), body mass index [(BMI) P>0.0003], acid uric (P>0.004), systolic blood pressure (P>0.03), glycemia (P>0.03) and total cholesterol (P>0.04). No significant correlation was found between CP antibody IgG titer and IMT. In multiple regression analysis only age (P>0.0001), uric acid (P>0.03), glycemia and BMI (P>0.05) were independently associated with IMT. CONCLUSION: Lack of association was found between CP seropositivity and common carotid IMT in patients with DM.