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Guglielmina Pepe,1,2 Betti Giusti,1,2 Elena Sticchi,1,2 Rosanna Abbate,1,2 Gian Franco Gensini,1–3 Stefano Nistri2,4 1Department of Experimental and Clinical Medicine, Section of Critical Medical Care and Medical Specialities, DENOTHE Center, University of Florence, 2Cardiothoracovascular Department, Marfan Syndrome and Related Disorders Regional Referral Center, Careggi Hospital, 3Santa Maria agli Ulivi, Fondazione Don Carlo Gnocchi, Onlus, Institute for Cancer Research and Treatment, Florence, 4Cardiology Service, CMSR Veneto Medica, Altavilla Vicentina, Italy Abstract: Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity. Keywords: Marfan syndrome, thoracic aortic aneurysm, fibrillin 1, cardiovascular manifestations, diagnosis, therapy more...

Giorgio Galanti,1 Laura Stefani,1 Gianfranco Gensini2 1Sports Medicine Center, 2Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Background: Breast and colon tumors are the most common types of cancer in the general population. As a result of improved diagnosis and treatment, more people are now surviving cancer. Lifestyle has been identified as one of the potential risk factors for cancer, and it has been demonstrated recently that physical activity reduces the physiological and psychological symptoms and side effects of chemotherapy. Muscular atrophy, weight changes, decreased aerobic capacity, fatigue, and depression are the most common symptoms in cancer patients. The exact amount of moderate to vigorous physical activity needed to overcome these effects has not yet been established, but an individualized and variable exercise program as prescription therapy could be considered a helpful tool for improving quality of life. This paper proposes a model of lifestyle analysis and dedicated individualized exercise programs for the treatment of cancer patients. The program starts with a preliminary evaluation of the patient’s lifestyle using a questionnaire and accelerometer, which provides information on the amount of daily physical activity and number of steps taken, as well as an assessment of aerobic capacity, cardiovascular response, muscle strength, and resistance. Two different levels of aerobic exercise, ie, low-to-moderate (40% of maximal heart rate) to moderate (60% of maximal heart rate) can be prescribed. This model of exercise prescription in patients with cancer offers a flexible program for assisting in the management of this complex disease. It is projected to ensure easier management of medical problems related to cancer, and to attract a greater number of participants over time. Keywords: physical exercise, therapy, breast cancer, colon cancer, lifestyle more...

BACKGROUND: Novel facilities such as an intensive observation unit and an outpatient clinic could result in improving management of patients presenting with atrial fibrillation (AF). METHODS: This observational study enrolled 3475 patients. Group 1 (1120 patients; years 2004-2005) was managed with standard approach; group 2 (992 patients; years 2006-2007) was managed with additional intensive observation; group 3 (1363 patients; years 2008-2009) was managed with additional intensive observation and outpatient clinic. Primary end point was admission to hospital. Secondary end points included modalities of rhythm conversion and administration of class IC vs class III antiarrhythmic drugs in patients with AF lasting less than 48 hours. RESULTS: Lack of rhythm control, comorbidities, diabetes, and age were independent predictors of hospitalization. Admissions significantly decreased from group 1 (50%) to 2 (38%) and to 3 (24%) (P < .001). Interestingly, more than a quarter of patients in group 3 were referred to the outpatient clinic for short-term follow-up, eventually avoiding admission. Patients with AF lasting less than 48 hours (n = 2189) and without structural heart disease (n = 1685) achieved sinus rhythm in 89% of cases and were discharged. In these patients, early administration of antiarrhythmic drugs of class IC and III gained sinus rhythm in 80% and 20%, respectively (P < .001). Spontaneous conversion occurred in 26%; electrical, 17%; and pharmacological, 57%. CONCLUSIONS: In patients with AF, beyond the standard approach, the novel organization with an additional intensive observation unit for early pharmacological interventions and an outpatient clinic for elective treatment and short-term follow-up significantly reduced admission irrespective of independent predictors of hospitalizations. Patients without structural heart disease treated with antiarrhythmic drugs achieved sinus rhythm in 89% of cases, mostly with class IC drugs. [ABSTRACT FROM AUTHOR] more...

AIM: The aim of this study is to evaluate incidence of adverse cardiac events in patients with chest pain with or without known existing coronary disease presenting normal electrocardiogram (ECG) and initial troponin. METHODS: Prospective, nonrandomized study enrolled low-risk patients with normal ECG and troponin on admission who underwent observation and/or stress testing by unstandardized clinical judgment. Patients who experienced recurrent angina or positive ECGs or positive troponins during observation or patients with positive stress testing were admitted; otherwise, they were discharged. END POINT: The end points are cardiac events at short- and long-term follow-up including cardiovascular death, myocardial infarction, unstable angina, and revascularization. RESULTS: Of 5656 patients considered, 1732 with ischemic ECG were initially admitted and, therefore, excluded from the analysis; 2860 with pleuritic chest pain and normal ECG were discharged; 1064 with visceral chest pain and normal ECG were enrolled. Patients with known coronary disease (45%) were older and likely presented known vascular disease. Patients with known vascular disease, older age, female sex, diabetes mellitus, and lower chest pain score were likely managed with observation. In patients with known coronary disease as compared with patients without, overall cardiac events account for 35% vs 14%, respectively (P < .001), as follows: in-hospital, 23% vs 10%, (P < .001); 1 month, 4% vs 2% (P = .133); and 9.9 ± 4.9 months, 8% vs 2%, respectively (P < .001). CONCLUSIONS: One-third of patients with chest pain with known coronary disease, negative ECG, and biomarkers were subsequently found to have adverse cardiac events. The value of this research for an emergency medicine audience could be extended to all clinicians and general practitioners beyond cardiologists. [ABSTRACT FROM AUTHOR] more...

Coronary stent thrombosis (CST) is a major concern of interventional cardiology. Several risk factors for CST have been identified, but as a whole they do not explain the pathophysiology of CST. This study was designed to investigate whether acute infection-inflammation could facilitate the occurrence of CST. Forty-one patients, aged 66.6 +/- 11 years, consecutively admitted to our catheterization laboratory for acute, subacute or late CST, were retrospectively analysed. Transient acute infection-inflammation on admission for CST was diagnosed by predefined criteria. Prevalence of known risk factors for CST was also investigated. Twenty-one patients (51%) met predefined criteria for the occurrence of acute infection-inflammation. On admission, in these patients, levels of systemic humoral and cellular inflammatory markers were significantly higher than those of patients without recent or ongoing acute infection-inflammation (p < 0.05 for all). 62% of patients with acute infection-inflammation had less than two known risk factors for CST whereas only 37% patients without infection-inflammation showed less than two risk factors (p = 0.03) and showed more frequent interruption of antiplatelet treatment (17 vs. 2.4%, p = 0.02), mean longer stent length (20.5 +/- 4.8 vs. 16.5 +/- 5.1 mm, p = 0.02) and lower left ventricular ejection fraction before CST (42.9 +/- 14 vs. 47.3 +/- 11%, p = 0.02). In conclusion, acute infection-inflammation could play a role in facilitating the occurrence of CST in a subgroup with low risk profile for known risk factors. Our findings, if confirmed, could suggest new opportunities for prevention and treatment of CST. [ABSTRACT FROM AUTHOR] more...

Background: Prolongation of the action potential duration, whose major determinants are the delayed-rectifier potassium currents, is a hallmark of failing ventricular myocardium. Genetic variants in the KCNE1 gene, encoding for the beta-subunit (minK) of a slowly activated cardiac potassium channel (I(ks)), may impair myocardial repolarization. Experimental data demonstrated a higher KCNE1 expression in heart failure (HF).Objective: The purpose of this study was to investigate the association between a KCNE1 S38G single-nucleotide polymorphism (SNP) and HF.Methods: We genotyped 197 out of 323 previously investigated patients and 352 healthy controls comparable for age and sex. This study was replicated in 186 HF patients and in 200 healthy subjects comparable for age and sex and recruited from the Department of Cardiovascular Medicine of the National Research Council, Pisa, Italy.Results: A significant difference in genotype distribution and allele frequency between patients and controls was observed for the KCNE1 S38G SNP (P = .002 and P = .0008, respectively). The KCNE1 38G variant was associated with a significant predisposition to HF under a dominant (odds ratio [OR] = 2.22 [1.23-3.28]; P = .008) and additive (OR = 2.13 [1.09-4.15]; P = .03) model, after adjustment for age, sex, and traditional cardiovascular risk factors. No difference in genotype distribution and allele frequency for the KCNE1 S38G SNP according to functional New York Heart Association class was found (P = .4 and P = .3, respectively). In the HF replication study, the KCNE1 38G allele frequency was significantly higher in comparison with that observed in the control population (38G = 0.59 vs. 0.49; P = .004). The 38G allele was associated with HF predisposition under the recessive (OR [95% confidence interval (CI)] = 2.49 [1.45-4.29]; P = .001) and additive models (OR [95% CI] = 2.63 [1.29-5.35]; P = .008), after adjustment for traditional risk factors.Conclusion: KCNE1 S38G SNP is associated with HF predisposition in two study populations. Nevertheless, further studies performed in larger populations and aimed to better define the role of this locus are required. [ABSTRACT FROM AUTHOR] more...

Purpose: We hypothesized that inducibility of the VT responsible for ICD therapies at the end of RFCA, would also be associated with a differential risk, depending on left ventricular function.Methods: We retrospectively studied 66 patients with previous myocardial infarction and with ICD who also underwent RFCA for recurrent refractory VTs.Results: During the follow-up only 19 patients (29%) showed VTs. Among patients with ejection fraction (EF) 35% and <50%, no recurrent VT was any longer detected in the nine patients in whom the VT was not inducible, while VT recurrences still continued only in the eight patients in whom it was. Finally, all the 24 patients with EF >or=50% did not show any recurrent VT.Conclusions: Our findings confirm the role of RFCA in reducing ICD therapies and also place RFCA in the overall clinical management of recurrent post infarction VTs according to the left ventricular function. [ABSTRACT FROM AUTHOR] more...

BACKGROUND: International authorities recommend that the hand hygiene of health care workers be improved to prevent health care-associated infection. In 2005, Tuscany, a region in central Italy, initiated a campaign to improve hand hygiene that focused on raising awareness and educating health care workers. We assessed hand hygiene rates approximately 3 years after the campaign was initiated in 5 units of 2 hospitals in Florence, Italy, the capital of Tuscany. We also were curious whether variability would exist in the hand hygiene rates despite the close proximity of the units. METHODS: We conducted a 3-month observational study in 2008 to assess hand hygiene adherence of doctors and nurses. Four of the units (ophthalmology, cardiology, geriatrics, and infectious diseases) were within one hospital, and the fifth unit (an emergency department) was in another hospital located less than 1 km away. External observers were used to assess the hand hygiene adherence of doctors and nurses before patient contact. RESULTS: A total of 665 doctor-patient observations and 1147 nurse-patient observations were made. Doctors used some type of hand hygiene before touching the patient in 28% of their patient interactions (soap and water in 16% and alcohol-based handrub in 12%). Nurses used some type of hand hygiene in 34% of their interactions (soap and water in 27% and alcohol-based handrub in 7%). Hand hygiene adherence varied substantially across the units, from a low of 6% to a high of 66% for doctors and from 19% to 56% for nurses. The correlation between nurse adherence and doctor adherence was 0.90. CONCLUSION: The overall rates of hand hygiene adherence observed were similar to those found when Tuscany initiated a hand hygiene campaign 3 years earlier. Focusing on overall rates may be misleading, however, because substantial variability existed between units. Furthermore, these rates come only from the 'first moment' (before touching the patient) and can only be compared with rates from studies using the same approach. [ABSTRACT FROM AUTHOR] more...

OBJECTIVE: To evaluate the role of factor V Leiden, prothrombin G20210A polymorphism, plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism, PAI-1, homocysteine, and lipoprotein (a) (Lp(a)) in the occurrence of major adverse cardiac events (MACE) in patients with acute coronary syndromes who underwent coronary stenting. DESIGN: 520 patients (375 men and 145 women) with acute coronary syndromes and 520 age and sex matched controls were enrolled. MACE were recorded for 109 patients. Heterozygosity for factor V Leiden, prothrombin G20210A polymorphism, and 4G/5G polymorphism did not significantly differ between patients with and without MACE. A significantly higher percentage of patients with increased homocysteine (28% v 19%, p < 0.001) and PAI-1 concentrations (25% v 16%, p < 0.001) had MACE with respect to those who did not. In Kaplan-Meier survival analysis, the overall risk of MACE was significantly higher among patients with increased PAI-1 (p = 0.006) and homocysteine concentrations (p = 0.04). Cox regression analysis adjusted for age, sex, traditional cardiovascular risk factors, renal function, systolic left ventricular function, the number of stenosed vessels, and history of percutaneous coronary intervention or coronary artery bypass grafting showed that homocysteine (odds ratio 7.5, 95% confidence interval (CI) 1.1 to 57.7, p < 0.05) and PAI-1 concentrations (odds ratio 5.3, 95% CI 1.2 to 23.8, p < 0.05) within the fifth quintile (with respect to the first) were significant and independent risk factors for the future occurrence of MACE. CONCLUSIONS: Increased PAI-1 and homocysteine concentrations are independent risk factors for MACE after successful coronary stenting, whereas Lp(a) and thrombophilic polymorphisms are not predictive. [ABSTRACT FROM AUTHOR] more...

BACKGROUND: The mechanism by which high circulating homocysteine concentrations are a risk factor for atherothrombosis is incompletely understood. A proinflammatory state is related to atherosclerosis, and recent studies suggest that acute phase reactants correlate with circulating concentrations of homocysteine. OBJECTIVE: We determined whether high concentrations of inflammatory markers are associated with hyperhomocysteinemia independently of dietary vitamin intakes, vitamin concentrations, and cardiovascular disease risk factors in a large, representative sample of the general population. DESIGN: Five hundred eighty-six men and 734 women were randomly selected from the inhabitants of 2 small towns near Florence, Italy. RESULTS: After adjustment for multiple potential confounders, interleukin 1 receptor antagonist (IL-1ra) and interleukin 6 (IL-6) concentrations were significantly (P < 0.001) associated with plasma homocysteine concentrations in older (>65 y) populations. Compared with participants in the lowest IL-6 tertile, those in the highest tertile had a higher risk of having homocysteine concentrations that were high (>30 micromol/L; odds ratio: 2.6; 95% CI: 1.1, 5.6; P = 0.024) or in the intermediate range 15-30 micromol/L (odds ratio: 1.6; 95% CI: 1.2, 2.2; P = 0.0014). Sedentary state, intakes of vitamin B-6 and folic acid, and serum folate, vitamin B-12, vitamin B-6, and alpha-tocopherol concentrations were significant independent correlates of homocysteine. CONCLUSIONS: High circulating concentrations of IL-1ra and IL-6 are independent correlates of hyperhomocysteinemia and may explain, at least in part, the association between homocysteine and atherosclerosis. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR] more...

Marfan syndrome (MFS) is a multisystemic disease associated with mutations in the fibrillin-1 gene. Most of the reported mutations are missense substitutions mainly affecting the epidermal growth factor (EGF)-like protein domain structure and the calcium-binding (cb) site. The aim of our study was to investigate the correlation between fibrillin-1 frameshift mutations and the clinical phenotype in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic mutation was found. We detected novel mutations causing premature termination codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the skeletal and cardiovascular systems. Interestingly, we noticed that, while mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the mutation in exon 40 (cbEGF #24 domain) is more severe and causes major cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is noteworthy that the degree of the severity in the phenotype of one of our patients and another from the literature carrying a mutation in exon 41 could be explained with alterations in mRNA expression. [ABSTRACT FROM AUTHOR] more...

To characterize the time course of plasma and red blood cell (RBC) changes after n-3 polyunsaturated fatty acid (PUFA) supplementation, 20 healthy male volunteers were randomly assigned to receive either four l-g capsules of n-3 PUFA ethyl esters or four l-g capsules of olive oil (as placebo) for a period of 4 mo, followed by a 3-mo washout period. Fatty acids of plasma and RBC phospholipid fractions were analyzed at 0, 2, and 4 mo of treatment and at 1, 2, and 3 mo of washout. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were marked after 2 mo with differences among different fractions of plasma and RBCs in further accumulation up to 4 mo. During the first and second months of the washout, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 mo of washout, only minor alterations were still detectable with respect to pretreatment values. These data confirm the complex relations among different fatty acid pools after n-3 PUFA supplementation. [ABSTRACT FROM AUTHOR] more...

1. Picotamide has been shown to interfere competitively with the thromboxane A2 (TxA2) platelet receptor. In the present study the effect of in vivo administration of picotamide on TxA2 human platelet receptors was investigated in 10 healthy subjects. 2. Picotamide (300 mg x 3 daily) or placebo were administered in a double-blind, cross- over, placebo controlled study, each treatment lasting 1 week with a 2 week interval period. TxA2 receptors were investigated by a direct radioligand binding assay method employing [125I]-PTA-OH as labelled ligand. Platelet studies were performed on the first day of treatment immediately before and 2, 4 and 8 h after the ingestion of the drug. The effects of chronic administration were assessed on the seventh day. 3. Two and 4 h after the administration of picotamide 300 mg orally platelet TxA2 receptors were significantly reduced from 1366 +/- 237 to 957 +/- 221 (P less than 0.05) and 753 +/- 119 receptors/platelet (mean +/- s.d.) (P less than 0.03). After 8 h platelet receptor population was restored (1362 +/- 324, NS). The same pattern was observed after 7 days of treatment. Thus picotamide seems to induce a short lasting down regulation of platelet TxA2 receptors. [ABSTRACT FROM AUTHOR] more...