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1.  Clinical significance of glycated hemoglobin in the acute phase of ST elevation myocardial infarction 
World Journal of Cardiology  2014;6(4):140-147.
In population-based studies, including diabetic and nondiabetic cohorts, glycated hemoglobin A1c (HbA1c) has been reported as an independent predictor of all-cause and cardiovascular disease mortality. Data on the prognostic role of HbA1c in patients with acute myocardial infarction (MI) are not univocal since they stem from studies which mainly differ in patients’ selection criteria, therapy (thrombolysis vs mechanical revascularization) and number consistency. The present review is focused on available evidence on the prognostic significance of HbA1c measured in the acute phase in patients with ST-elevation myocardial infarction (STEMI) submitted to primary percutaneous coronary intervention (PCI). We furthermore highlighted the role of HbA1c as a screening tool for glucose intolerance in patients with STEMI. According to available evidence, in contemporary cohorts of STEMI patients submitted to mechanical revascularization, HbA1c does not seem to be associated with short and long term mortality rates. However, HbA1c may represent a screening tool for glucose intolerance from the early phase on in STEMI patients. On a pragmatic ground, an HbA1c test has several advantages over fasting plasma glucose or an oral glucose tolerance test in an acute setting. The test can be performed in the non-fasting state and reflects average glucose concentration over the preceding 2-3 mo. We therefore proposed an algorithm based on pragmatic grounds which could be applied in STEMI patients without known diabetes in order to detect glucose intolerance abnormalities from the early phase. The main advantage of this algorithm is that it may help in tailoring the follow-up program, by helping in identifying patients at risk for the development of glucose intolerance after MI. Further validation of this algorithm in prospective studies may be required in the contemporary STEMI population to resolve some of these uncertainties around HbA1c screening cutoff points.
doi:10.4330/wjc.v6.i4.140
PMCID: PMC3999334  PMID: 24772254
Glycated hemoglobin; ST-elevation myocardial infarction; Prognosis; Hyperglycemia; Glucose intolerance
2.  Non invasive continuous hemodynamic evaluation of cirrhotic patients after postural challenge 
World Journal of Hepatology  2012;4(4):149-153.
AIM: To assess whether Most Care is able to detect the cardiovascular alterations in response to physiological stress (posture).
METHODS: Non invasive hemodynamic was assessed in 26 cirrhotic patients compared to healthy subjects, both in the supine and standing positions.
RESULTS: In baseline conditions, when compared to healthy subjects, cirrhotic patients showed significantly lower values of dicrotic and diastolic pressures and systemic vascular resistance. While in the standing position, cirrhotic patients showed higher values of cardiac index, stroke volume index and cardiac cycle efficiency. When returning to the supine position, cirrhotic patients exhibited lower values of dicrotic and diastolic pressures and systemic vascular resistance in the presence of higher values of cardiac index, stroke volume index and cardiac cycle efficiency.
CONCLUSION: Most Care proved to be able to detect cardiovascular abnormalities bedside in the resting state and after postural challenge in cirrhotic patients.
doi:10.4254/wjh.v4.i4.149
PMCID: PMC3345539  PMID: 22567187
Liver cirrhosis; Non-invasive hemodynamic; Pressure recording analytical method; Posture
3.  Environmental Temperature and Thermal Indices: What Is the Most Effective Predictor of Heat-Related Mortality in Different Geographical Contexts? 
The Scientific World Journal  2014;2014:961750.
The aim of this study is to identify the most effective thermal predictor of heat-related very-elderly mortality in two cities located in different geographical contexts of central Italy. We tested the hypothesis that use of the state-of-the-art rational thermal indices, the Universal Thermal Climate Index (UTCI), might provide an improvement in predicting heat-related mortality with respect to other predictors. Data regarding very elderly people (≥75 years) who died in inland and coastal cities from 2006 to 2008 (May–October) and meteorological and air pollution were obtained from the regional mortality and environmental archives. Rational (UTCI) and direct thermal indices represented by a set of bivariate/multivariate apparent temperature indices were assessed. Correlation analyses and generalized additive models were applied. The Akaike weights were used for the best model selection. Direct multivariate indices showed the highest correlations with UTCI and were also selected as the best thermal predictors of heat-related mortality for both inland and coastal cities. Conversely, the UTCI was never identified as the best thermal predictor. The use of direct multivariate indices, which also account for the extra effect of wind speed and/or solar radiation, revealed the best fitting with all-cause, very-elderly mortality attributable to heat stress.
doi:10.1155/2014/961750
PMCID: PMC3910390  PMID: 24523657
4.  A meta-analysis of potential risks of low levels of protein Z for diseases related to vascular thrombosis 
Thrombosis and haemostasis  2010;103(4):749-756.
Summary
The relationship between protein Z levels and thrombosis is controversial. We performed a systematic review and meta-analysis of the available studies to assess the association between protein Z and vascular thrombotic diseases. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library, bibliographies of retrieved articles and abstracts of congresses up to October, 2009. Studies were included if they analysed protein Z levels in patients with vascular thrombotic diseases. After the review process, 28 case-control studies (33 patient cohorts), including 4,218 patients with thrombotic diseases and 4,778 controls, were selected for analysis. The overall analysis using a random-effects model showed that low protein Z levels were associated with an increased risk of thrombosis (odds ratio [OR] 2.90, 95% confidence interval [CI] 2.05–4.12; p<0.00001). On subgroup analysis, a significant association was found between low protein Z levels and arterial vascular diseases (OR 2.67, 95%CI 1.60–4.48; p=0.0002), pregnancy complications (OR 4.17, 95%CI 2.31–7.52; p<0.00001), and venous thromboembolic diseases (OR 2.18, 95%CI 1.19–4.00; p=0.01). The results of this meta-analysis are consistent with a role for protein Z deficiency in thrombotic diseases, including arterial thrombosis, pregnancy complications and venous thromboembolism.
doi:10.1160/TH09-09-0645
PMCID: PMC3692349  PMID: 20076855
Protein Z; thrombosis; coagulation; meta-analysis
5.  Minimally invasive thoracoscopic hybrid treatment of lone atrial fibrillation: early results of monopolar versus bipolar radiofrequency source 
We compare results of a hybrid monopolar vs. a hybrid bipolar thoracoscopic approach employing radiofrequency (RF) sources for the surgical treatment of lone atrial fibrillation (LAF). From January 2008 to June 2010, 19 patients (35.1%) underwent RF monopolar/monolateral RF ablation, whereas 35 (64.9%) had RF bipolar/bilateral thoracoscopic ablation. One-year time-related prevalence of postoperative AF was 13.3 (11.0–17.4) and 5.2% (4.2–6.7), in monopolar and bipolar groups, respectively (P < 0.001). It was 21.1 (17.6–24.9) vs. 8.2% (5.1–11.6) in long standing persistent (P < 0.001), 13.2 (10.6–17.8) vs. 3.8% (1.4–6.9) in persistent (P < 0.001) and 5.6 (2.8–8.3) vs. 3.2% (1.0–6.5) in paroxysmal AF (P = 0.64). At 12 months, estimated prevalence of anti-arrhythmic drugs was 26 (22.4–30.1) and 18.0% (15.5–21.7, P = 0.04), whereas prevalence of Warfarin use was 48.2 (44.2–52.2) and 29.0% (26.2–33.1, P < 0.001) in the monopolar and bipolar groups, respectively. Left atrial (LA) reverse remodelling occurred in 47.3% of monopolar patients (n = 9) and in 77.1% of bipolar patients (P = 0.03). The hybrid bilateral approach with a bipolar device for the treatment of LAF showed a good 1-year success rate independently of the AF type and seems to be the better choice for longstanding persistent and persistent LAF.
doi:10.1093/icvts/ivr142
PMCID: PMC3309825  PMID: 22228287
Atrial fibrillation; Ablation; Minimally invasive; Catheter ablation; Surgical ablation
6.  Minimally Invasive Mitral Valve Surgery: A Systematic Review 
Minimally Invasive Surgery  2013;2013:179569.
In the recent years minimally invasive mitral valve surgery (MIMVS) has become a well-established and increasingly used option for managing patients with a mitral valve pathology. Nonetheless, whether the purported benefits of MIMVS translate into clinically important outcomes remains controversial. Therefore, in this paper we provide an overview of MIMVS and discuss results, morbidity, mortality, and quality of life following mitral minimally invasive procedures. MIMVS has been proven to be a feasible alternative to the conventional full sternotomy approach with low perioperative morbidity and short-term mortality. Reported benefits of MIMVS include also decreased postoperative pain, improved postoperative respiratory function, reduced surgical trauma, and greater patient satisfaction. Finally, compared to standard surgery, MIMVS demonstrated comparable efficacy across a range of long-term efficacy measures such as freedom from reoperation and long-term survival.
doi:10.1155/2013/179569
PMCID: PMC3625540  PMID: 23606959
7.  Early Hemodynamic and Biochemical Changes in Overloaded Swine Ventricle 
Texas Heart Institute Journal  2013;40(3):235-245.
The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload.
In 54 study-group pigs, weighing 40 ± 5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr).
All indices of left ventricular function declined significantly, with a peak at 6 hr and a return to baseline at 168 hr. At each observational time, SERCA2a activity, Ca2+ uptake, and acylphosphatase activity rose significantly, with a maximum increase at 6 hr. These changes indicated a higher expression of these proteins; conversely, phospholamban did not show significant changes in its concentration or in its phosphorylation status. Nuclear proto-oncogene c-fos expression rose at 6 hr. A strong inverse correlation was found when Ca2+-ATPase activity, Ca2+-ATPase expression, Ca2+ uptake, and acylphosphatase were compared with indices of systolic function.
In our model of induced pressure overload, an initial phase of depressed myocardial contractility was accompanied by an increased sarcoplasmic reticulum function and by higher Ca2+-ATPase and Ca2+ uptake activities mediated by acylphosphatase. This new finding of Ca2+ homeostasis might indicate a compensatory mechanism for mechanical stress. Further studies are needed to confirm our findings.
PMCID: PMC3709230  PMID: 23914011
Aortic valve stenosis/pathology; calcium; calcium-transporting ATP-ases; disease models, animal; hemodynamics; myocardial contraction/physiology; sarcoplasmic reticulum/physiology; sarcoplasmic reticulum calcium-transporting ATPases; swine
8.  Impact of one or two visits strategy on hypertension burden estimation in HYDY, a population-based cross-sectional study: implications for healthcare resource allocation decision making 
BMJ Open  2012;2(4):e001062.
Context
The prevalence of hypertension in developing countries is coming closer to values found in developed countries. However, surveys usually rely on readings taken at a single visit, the option to implement the diagnosis on readings taken at multiple visits, being limited by costs.
Objective
To estimate more accurately the magnitude and extent of the resource that should be allocated to the prevention of hypertension.
Design
Population-based cross-sectional survey with triplicate blood pressure (BP) readings taken on two separate home-visits.
Setting
Rural and urban locations in three areas of Yemen (capital, inland and coast).
Participants
A nationally representative sample of the Yemen population aged 15–69 years (5063 men and 5179 women), with an overall response rate of 92% in urban and 94% in rural locations.
Main outcome measure
Hypertension diagnosed as systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or self-reported use of antihypertensive drugs.
Results
Hypertension prevalence (age-standardised to the WHO world population 2001) based on fulfilling the same criteria on both visits (11.3%; 95% Cl 10.7% to 11.9%), was 35% lower than estimation based on the first visit (17.3%; 16.5% to 18.0%). Advanced age, blood glucose ≥7 mmol/l or proteinuria ≥1+ at dipstick test at visit one were significant predictors of confirmation at visit 2. The 959 participants found to be hypertensive at visit 1 or at visit 2 only and thus excluded from the final diagnosis had a rate of proteinuria (5.0%; 3.8% to 6.5%) comparable to rates of the general population (6.1%; 5.6% to 6.6%), and of subjects normotensive at both visits (5.6%; 5.1% to 6.2%). Only 1.9% of Yemen population classified at high or very high cardiovascular (CV) risk at visit 1 moved to average, low or moderate CV risk categories after two visits.
Conclusions
Hypertension prevalence based on readings obtained after two visits is 35% lower than estimation based on the first visit, subjects were excluded from final diagnosis belonging to low CV risk classes.
doi:10.1136/bmjopen-2012-001062
PMCID: PMC3425947  PMID: 22874627
Cardiology; Hypertension; Epidemiology; Preventive Medicine; Public Health; Internal Medicine; Diabetes & endocrinology; Internal Medicine; Cardiology
9.  Lactate and lactate clearance in acute cardiac care patients 
Hyperlactataemia is commonly used as a diagnostic and prognostic tool in intensive care settings. Recent studies documented that serial lactate measurements over time (or lactate clearance), may be clinically more reliable than lactate absolute value for risk stratification in different pathological conditions. While the negative prognostic role of hyperlactataemia in several critical ill diseases (such as sepsis and trauma) is well established, data in patients with acute cardiac conditions (i.e. acute coronary syndromes) are scarce and controversial. The present paper provides an overview of the current available evidence on the clinical role of lactic acid levels and lactate clearance in acute cardiac settings (acute coronary syndromes, cardiogenic shock, cardiac surgery), focusing on its prognostic role.
doi:10.1177/2048872612451168
PMCID: PMC3760525  PMID: 24062898
Acute cardiac setting; lactate; lactate clearance
10.  Effect of prior medical treatments on ischemic stroke severity and outcome  
Functional Neurology  2011;26(3): 133 - 139 .
Summary
Antiplatelets, antihypertensives, and statins might reduce the severity of the event or improve outcome in patients who, despite prior medical treatment, have a stroke.
We evaluated, in patients who had an ischemic stroke, the effect, on stroke severity and outcome, of prior treatment with antiplatelets, antihypertensives, and statins, used either alone or in a three-drug combination.
Stroke in Italy and Related Impact on Outcome (SIRIO) was a prospective, nationwide, multicenter, hospital-based, observational study that included patients aged ≥18 years with acute ischemic stroke.
We studied 2,529 acute ischemic stroke patients from the SIRIO population: 887 were antiplatelet users, 1,497 antihypertensive users, 231 statin users, and 138 three-drug combination users prior to the index event. The adjusted logistic regression analysis showed an association between prior treatment with statins and good functional outcome at discharge, while prior treatment with antiplatelets, antihypertensives or the three-drug combination did not influence severity or outcome. The absolute probability of a good functional outcome was 46.3% (95% CI: 40.3%–53.2%) in statin users and 36.7% (95% CI: 34.7%–38.7%) in non-users of statins; the absolute risk difference was 9.6% (95% CI: 2.9%–16.4%; p=0.004).
Prior treatment with antiplatelets, antihypertensives, or the three-drug combination did not influence stroke severity or outcome, while prior treatment with statins did not influence stroke severity but was associated with a better functional outcome.
PMCID: PMC3814556  PMID: 22152434
antihypertensives ;  antiplatelets ;  statins ;  stroke
11.  The Impact of Hypertension on Patients with Acute Coronary Syndromes 
Arterial chronic hypertension (HTN) is a well-known cardiovascular risk factor for development of atherosclerosis. In order to explain the relation between HTN and acute coronary syndromes the following factors should be considered: (1) risk factors are shared by the diseases, such as genetic risk, insulin resistance, sympathetic hyperactivity, and vasoactive substances (i.e., angiotensin II); (2) hypertension is associated with the development of atherosclerosis (which in turn contributes to progression of myocardial infarction). From all the registries and the data available up to now, hypertensive patients with ACS are more likely to be older, female, of nonwhite ethnicity, and having a higher prevalence of comorbidities. Data on the prognostic role of a preexisting hypertensive state in ACS patients are so far contrasting. The aim of the present paper is to focus on hypertensive patients with ACS, in order to better elucidate whether these patients are at higher risk and deserve a tailored approach for management and followup.
doi:10.4061/2011/563657
PMCID: PMC3124673  PMID: 21747979
12.  Surgical Treatment in Active Infective Endocarditis: Results of a Four-Year Experience 
ISRN Cardiology  2011;2011:492543.
Background. Aim of present investigation was to analyze survival and recurrence rate in patients with active endocarditis referred to our centre for surgical treatment. Methods. 80 consecutive patients with active infective endocarditis (52 males, 28 females, mean age 59.2 years) were referred to our institution for surgical treatment. 78 patients underwent surgery, and 2 patients died before intervention. Results. Fifty patients had native valve endocarditis, 30 prosthetic valve involvement. Hospital mortality has been 10.2%. Three discharged patients (4.9%) died at an average 18-month followup. Endocarditis recurred in 4 (2 being S. aureus prosthetic tricuspid endocarditis in drug addicts). All patients who underwent valve repair or homograft implant were alive and free of recurrence. Conclusions. Our results suggest that with proper surgical treatment patients with active endocarditis discharged alive from hospital have a survival >90% at 18 months with a low recurrence rate.
doi:10.5402/2011/492543
PMCID: PMC3262504  PMID: 22347645
13.  Pharmacological Management of Atrial Fibrillation: One, None, One Hundred Thousand 
Abstract atrial fibrillation (AF) is associated with a significant burden of morbidity and increased risk of mortality. Antiarrhythmic drug therapy remains a cornerstone to restore and maintain sinus rhythm for patients with paroxysmal and persistent AF based on current guidelines. However, conventional drugs have limited efficacy, present problematic risks of proarrhythmia and cause significant noncardiac organ toxicity. Thus, inadequacies in current therapies for atrial fibrillation have made new drug development crucial. New antiarrhythmic drugs and new anticoagulant agents have changed the current management of AF. This paper summarizes the available evidence regarding the efficacy of medications used for acute management of AF, rhythm and ventricular rate control, and stroke prevention in patients with atrial fibrillation and focuses on the current pharmacological agents.
doi:10.4061/2011/874802
PMCID: PMC3090750  PMID: 21577272
14.  Cardiorenal Syndrome Caused by Heart Failure with Preserved Ejection Fraction 
Since cardiorenal dysfunction is usually secondary to multiple factors acting in concert (and not only reduced cardiac output) in the present paper we are going to focus on the interrelationship between heart failure with normal ejection fraction and the development of cardiorenal syndrome. The coexistence of renal impairment in heart failure with preserved ejection fraction (CRS type 2 and 4) is common especially in older females with hypertension and/or diabetes. It can be hypothesized that the incidence of this disease association is growing, while clinical trials enrolling these patients are still lacking. The main mechanisms thought to be involved in the pathophysiology of this condition are represented by the increase of intra-abdominal and central venous pressure and the activation of the renin-angiotensin system. Differently from CRS in heart failure with reduced ejection fraction, the involvement of the kidney may be under-diagnosed in patients with heart failure and preserved ejection fraction and the optimal therapeutic strategy in this condition, though challenging, is far to be completely elucidated. Further studies are needed to assess the best therapeutic regimen in patients with renal dysfunction (and worsening) and heart failure and preserved ejection fraction.
doi:10.4061/2011/634903
PMCID: PMC3038429  PMID: 21331316
15.  Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes 
Background
Treatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended when it is not possible to attain LDL-C targets with statin monotherapy. Understanding which treatment or patient-related factors are associated with attaining a target may be clinically relevant.
Methods
Data were pooled from two multicenter, randomized, double-blind studies. After stabilization on simvastatin 20 mg, patients with coronary heart disease (CHD) alone and/or type 2 diabetes mellitus (T2DM) were randomized to ezetimibe 10 mg/simvastatin 20 mg (EZ/Simva) or simvastatin 40 mg. The change from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides, and the proportion of patients achieving LDL-C < 2.6 mmol/L (100 mg/dL) after 6 weeks of treatment were assessed, and factors significantly correlated with the probability of achieving LDL-C < 2.6 mmol/L in a population of high cardiovascular risk Italian patients were identified. A stepwise logistic regression model was conducted with LDL-C < 2.6 mmol/L at endpoint as the dependent variable and study, treatment, gender, age (≥65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable).
Results
EZ/Simva treatment (N = 93) resulted in significantly greater reductions in LDL-C, TC, and TC/HDL-C ratio and higher attainment of LDL-C < 2.6 mmol/L vs doubling the simvastatin dose to 40 mg (N = 106). Study [including diabetic patients (OR = 2.9, p = 0.003)], EZ/Simva treatment (OR = 6.1, p < 0.001), and lower baseline LDL-C (OR = 0.9, p = 0.001) were significant positive predictors of LDL-C target achievement. When baseline LDL-C was expressed as a discrete variable, the odds of achieving LDL-C < 2.6 mmol/L was 4.8 in favor of EZ/Simva compared with Simva 40 mg (p < 0.001), regardless of baseline LDL-C level.
Conclusion
EZ/Simva is an effective therapeutic option for patients who have not achieved recommended LDL-C treatment targets with simvastatin 20 mg monotherapy.
Trial Registration
Clinical trial registration numbers: NCT00423488 and NCT00423579
doi:10.1186/1476-511X-9-80
PMCID: PMC2918617  PMID: 20663203
16.  Predictors of Vitamin B6 and Folate Concentrations in Older Persons: The InCHIANTI Study 
Clinical chemistry  2006;52(7):1318-1324.
Background
Low dietary intake and low serum concentrations of vitamin B6 and/or folate are associated with increased risk of vascular events, possibly because of their association with inflammation, which plays a crucial role in the pathogenesis of cardiovascular diseases.
Methods
Using data from 1320 participants in the population-based InCHIANTI study (586 men and 734 women; median age, 69 years; range, 21–102 years) for whom complete data on folate, vitamin B6, inflammatory markers, 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T sequence variant, and important covariates were available, we evaluated the association of inflammatory markers with circulating concentrations of vitamin B6 and folate, independently of dietary vitamin intake, circulating vitamin concentrations, and MTHFR C677T sequence variant.
Results
According to multiple linear regression analysis, C-reactive protein and interleukin-6 receptor were strongly and negatively associated with circulating vitamin B6 but not with folate concentrations, independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, dietary nutrient intake, and circulating homocysteine and vitamin concentrations. Serum folate concentrations were related to MTHFR 677 TT genotype in persons with folate intake in the lowest tertile (<221.2 μg/day). Vitamin C and retinol intakes were strongly and positively associated with serum folate concentrations independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, homocysteine plasma concentrations, dietary nutrient intakes, serum vitamin B6 and vitamin B12 concentrations, and MTHFR C677T sequence variant.
Conclusions
Low serum vitamin B6, but not serum folate, concentrations are independent correlates of the proinflammatory state, and both are influenced by antioxidant reserves.
doi:10.1373/clinchem.2005.066217
PMCID: PMC2645619  PMID: 16690736
17.  Adherence to Mediterranean diet and health status: meta-analysis 
Objective To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention setting.
Design Meta-analysis of prospective cohort studies.
Data sources English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008.
Studies reviewed Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574 299 subjects followed for a time ranging from three to 18 years were included.
Results The cumulative analysis among eight cohorts (514 816 subjects and 33 576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson’s disease and Alzheimer’s disease (0.87, 0.80 to 0.96).
Conclusions Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson’s disease and Alzheimer’s disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.
doi:10.1136/bmj.a1344
PMCID: PMC2533524  PMID: 18786971
18.  Cardiovascular evaluation, including resting and exercise electrocardiography, before participation in competitive sports: cross sectional study 
BMJ : British Medical Journal  2008;337(7661):88-92.
Objective To evaluate the clinical usefulness of complete preparticipation cardiovascular screening in a large cohort of sports participants.
Design Cross sectional study of data over a five year period.
Setting Institute of Sports Medicine in Florence, Italy.
Participants 30 065 (23 570 men) people seeking to obtain clinical eligibility for competitive sports.
Main outcome measures Results of resting and exercise 12 lead electrocardiography.
Results Resting 12 lead ECG patterns showed abnormalities in 1812 (6%) participants, with the most common abnormalities (>80%) concerning innocent ECG changes. Exercise ECG showed an abnormal pattern in 1459 (4.9%) participants. Exercise ECG showed cardiac anomalies in 1227 athletes with normal findings on resting ECG. At the end of screening, 196 (0.6%) participants were considered ineligible for competitive sports. Among the 159 participants who were disqualified at the end of the screening for cardiac reasons, a consistent proportion (n=126, 79.2%) had shown innocent or negative findings on resting 12 lead ECG but clear pathological alterations during the exercise test. After adjustment for possible confounders, logistic regression analysis showed that age >30 years was significantly associated with an increased risk of being disqualified for cardiac findings during exercise testing.
Conclusions Among people seeking to take part in competitive sports, exercise ECG can identify those with cardiac abnormalities. Follow-up studies would show if disqualification of such people would reduce the incidence of CV events among athletes.
doi:10.1136/bmj.a346
PMCID: PMC2453296  PMID: 18599474
19.  Cardiovascular evaluation, including resting and exercise electrocardiography, before participation in competitive sports: cross sectional study 
Objective To evaluate the clinical usefulness of complete preparticipation cardiovascular screening in a large cohort of sports participants.
Design Cross sectional study of data over a five year period.
Setting Institute of Sports Medicine in Florence, Italy.
Participants 30 065 (23 570 men) people seeking to obtain clinical eligibility for competitive sports.
Main outcome measures Results of resting and exercise 12 lead electrocardiography.
Results Resting 12 lead ECG patterns showed abnormalities in 1812 (6%) participants, with the most common abnormalities (>80%) concerning innocent ECG changes. Exercise ECG showed an abnormal pattern in 1459 (4.9%) participants. Exercise ECG showed cardiac anomalies in 1227 athletes with normal findings on resting ECG. At the end of screening, 196 (0.6%) participants were considered ineligible for competitive sports. Among the 159 participants who were disqualified at the end of the screening for cardiac reasons, a consistent proportion (n=126, 79.2%) had shown innocent or negative findings on resting 12 lead ECG but clear pathological alterations during the exercise test. After adjustment for possible confounders, logistic regression analysis showed that age >30 years was significantly associated with an increased risk of being disqualified for cardiac findings during exercise testing.
Conclusions Among people seeking to take part in competitive sports, exercise ECG can identify those with cardiac abnormalities. Follow-up studies would show if disqualification of such people would reduce the incidence of CV events among athletes.
doi:10.1136/bmj.a346
PMCID: PMC2453296  PMID: 18599474
20.  Timing, setting and incidence of cardiovascular complications in patients with acute myocardial infarction submitted to primary percutaneous coronary intervention 
The Canadian Journal of Cardiology  2006;22(12):1047-1052.
BACKGROUND
At the Istituto di Clinica Medica Generale e Cardiologia (Florence, Italy), the widespread use of percutaneous coronary intervention (PCI) has markedly changed the hospital course of patients with acute myocardial infarction (AMI). These patients are typically transferred to the coronary care unit (CCU) only after primary PCI, whereas during the thrombolytic era, patients were first admitted to CCU before reperfusion.
OBJECTIVES AND METHODS
The incidence, timing and setting of complications from symptom onset to hospital discharge in 689 consecutive AMI patients undergoing PCI were evaluated.
RESULTS
Ventricular fibrillation occurred in 11% of patients, and most episodes (94.7%) occurred before or during PCI. Of all patients, 6.3% developed complete atrioventricular block (CAVB), and in 86.3% of these cases, the CAVB occurred before or during PCI; in 94.5%, a CAVB resolution occurred in the catheterization laboratory (CL). Thirty-one patients (4.5%) had impending shock on admission to the CL. Cardiogenic shock developed in 29 patients (4.2%), mostly in the prehospital phase or in the CL. Only four patients (less than 1%) developed cardiogenic shock later during their hospital course. Similarly, circulatory and ventilatory support, as well as temporary pacing and cardiac defibrillation, were used mostly in the prehospital phase or in the CL. During the CCU stay, 45 patients (6.5%) had hemorrhagic or vascular complications, and the incidence of post-PCI ischemia and early reocclusion of the culprit vessel were low (2.1% and 0.6%, respectively). Thus, cardiac complications usually associated with AMI were observed mainly before hospital admission or in the CL during the reopening of the target vessel. These complications were rarely observed after a successful PCI.
CONCLUSIONS
For AMI patients, the CL is not only the site of PCI, it is also where most life-threatening cardiac complications are observed and treated.
PMCID: PMC2568965  PMID: 17036099
Angioplasty; Complications; Myocardial infarction
21.  Academic Education in Complementary Medicine: a Tuscan Methodological Perspective 
The implementation of complementary medicine (CM) involves a large number of persons in Italy, and in the nineties, the percentage of Italian citizens adopting the most frequent and relevant practices of CM almost doubled. Appropriate academic education in CM is an important and fascinating challenge for current didactic systems in the Italian University. Already in 2004, the Joint Italian Conference of the Deans of the Faculties of Medicine and of the Presidents of Medical Degree Courses released an official statement regarding the relationship between CM and health area degree courses. The main teaching objectives embedded in the institutional framework proposed by the Joint Italian Conference are now finding specific implementation modalities in the University of Florence. For many years, the Florence Medical School has had strong and fruitful contacts with institutional bodies in Tuscany and, together with these institutions, has established a continuous dialogue with the world of CM. This exchange has given rise to various teaching activities within the academic setting. With specific reference to the undergraduate curriculum in Medicine and Surgery, a methodological course regarding CM has been designed and conducted, with selective attention being given to the CM practices having an enhanced rate of supportive scientific evidence, such as herbal medicine and acupuncture. With regard to the postgraduate curriculum, a Master degree in Acupuncture and Traditional Chinese Medicine and a Master in Clinical Phytotherapy are already active in the University of Florence and are having a remarkable success among the attending health professionals. This high degree of satisfaction well documents the importance, need and feasibility of structured academic education in CM and, in particular, of a methodological didactics such as those currently implemented in the Florence Medical School.
doi:10.1093/ecam/nem105
PMCID: PMC2206245  PMID: 18227930
complementary medicine; evidence based medicine; clinical methodology; medical education; history of medicine
22.  Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome 
BMC Medical Genetics  2014;15:23.
Background
Bicuspid aortic valve (BAV) is the most frequent congenital heart disease with frequent involvement in thoracic aortic dilatation, aneurysm and dissection. Although BAV and Marfan syndrome (MFS) share some clinical features, and some MFS patients with BAV display mutations in FBN1, the gene encoding fibrillin-1, the genetic background of isolated BAV is poorly defined.
Methods
Ten consecutive BAV patients [8 men, age range 24–42 years] without MFS were clinically characterized. BAV phenotype and function, together with evaluation of aortic morphology, were comprehensively assessed by Doppler echocardiography. Direct sequencing of each FBN1 exon with flanking intron sequences was performed on eight patients.
Results
We detected three FBN1 mutations in two patients (aged 24 and 25 years) displaying aortic root aneurysm ≥50 mm and moderate aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp and p.Arg636Gly) one of which has been previously associated with variable Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported to be associated with an incomplete MFS phenotype.
Conclusions
The present findings enlarge the clinical spectrum of isolated BAV to include patients with BAV without MFS who have involvement of FBN1 gene. These results underscore the importance of accurate phenotyping of BAV aortopathy and of clinical characterization of BAV patients, including investigation of systemic connective tissue manifestations and genetic testing.
doi:10.1186/1471-2350-15-23
PMCID: PMC3937520  PMID: 24564502
Bicuspid aortic valve; Aortic disease; Aneurysm; Marfan syndrome; Fibrillin-1
23.  EXCAVATOR: detecting copy number variants from whole-exome sequencing data 
Genome Biology  2013;14(10):R120.
We developed a novel software tool, EXCAVATOR, for the detection of copy number variants (CNVs) from whole-exome sequencing data. EXCAVATOR combines a three-step normalization procedure with a novel heterogeneous hidden Markov model algorithm and a calling method that classifies genomic regions into five copy number states. We validate EXCAVATOR on three datasets and compare the results with three other methods. These analyses show that EXCAVATOR outperforms the other methods and is therefore a valuable tool for the investigation of CNVs in largescale projects, as well as in clinical research and diagnostics. EXCAVATOR is freely available at http://sourceforge.net/projects/excavatortool/.
doi:10.1186/gb-2013-14-10-r120
PMCID: PMC4053953  PMID: 24172663
24.  The hybrid approach for the surgical treatment of lone atrial fibrillation: One-year results employing a monopolar radiofrequency source 
Background
The hybrid technique combines a mono or bilateral epicardial approach with a percutaneous endocardial ablation in a single-step procedure. We present our early results with this technique employing a monopolar radiofrequency source through a right thoracoscopy in patients with lone atrial fibrillation (LAF).
Methods
Between June 2009 and December 2010 nineteen consecutive patients (mean 60.8 ± 8.6 years, 84.2% male) underwent right unilateral minimally invasive hybrid procedure for LAF at our Institution. Ten patients (52.6.6%) had long-standing persistent AF while four (21.1%) had persistent and five (26.3%) paroxysmal AF. All patients were followed-up according the Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society (HRS/EHRA/ECA) and Society of Thoracic Surgeon (STS) guidelines.
Results
There were neither early nor late deaths. It was possible to complete all the procedures as planned without any conversion to cardiopulmonary bypass. No patient died during the follow up. At one year, 7/19 (36.8%) patients were in sinus rhythm with no episode of AF and off antiarrhythmic drugs (AAD). Time-related prevalence of postoperative AF peaked at 44.4% (41.3–47.4) at two weeks, was 30.4% (27.3–34.9) at three months, fell to 14.2% (11.6–18.1) by 6 months and was 13.3% (11.0–17.4) at 12 months Among patients with long-standing persistent (LSP) AF, 20% (2/10) were in Sinus rythm and off AAD. One-year success rates were 50% (2/4) in persistent and 60% (3/5) in paroxysmal AF. At 12 months estimated prevalence of antyarrhythmic drugs and Warfarin use were 26% (22.4–33.1) and 48% (37.2–53.2), respectively.
Conclusions
One year results combining the percutaneous endocardial with the right thoracoscopic epicardial technique were, in our experience, not satisfactory, particularly in patients with LSP and persistent AF. Our findings need to be confirmed by larger studies.
doi:10.1186/1749-8090-7-71
PMCID: PMC3432010  PMID: 22812613
Atrial fibrillation; Lone atrial fibrillation; Ablation; Minimally invasive
25.  Assessment of a continuous blood gas monitoring system in animals during circulatory stress 
BMC Anesthesiology  2011;11:1.
Background
The study was aimed to determine the measurement accuracy of The CDI™ blood parameter monitoring system 500 (Terumo Cardiovascular Systems Corporation, Ann Arbor MI) in the real-time continuous measurement of arterial blood gases under different cardiocirculatory stress conditions
Methods
Inotropic stimulation (Dobutamine 2.5 and 5 μg/kg/min), vasoconstriction (Arginine-vasopressin 4, 8 and 16 IU/h), hemorrhage (-10%, -20%, -35%, and -50% of the theoretical volemia), and volume resuscitation were induced in ten swine (57.4 ± 10.7 Kg).Intermittent blood gas assessments were carried out using a routine gas analyzer at any experimental phase and compared with values obtained at the same time settings during continuous monitoring with CDI™ 500 system. The Bland-Altman analysis was employed.
Results
Bias and precision for pO2 were - 0.06 kPa and 0.22 kPa, respectively (r2 = 0.96); pCO2 - 0.02 kPa and 0.15 kPa, respectively; pH -0.001 and 0.01 units, respectively ( r2 = 0.96). The analysis showed very good agreement for SO2 (bias 0.04,precision 0.33, r2 = 0.95), Base excess (bias 0.04,precision 0.28, r2 = 0.98), HCO3 (bias 0.05,precision 0.62, r2 = 0.92),hemoglobin (bias 0.02,precision 0.23, r2 = 0.96) and K+ (bias 0.02, precision 0.27, r2 = 0.93). The sensor was reliable throughout the experiment during hemodynamic variations.
Conclusions
Continuous blood gas analysis with the CDI™ 500 system was reliable and it might represent a new useful tool to accurately and timely monitor gas exchange in critically ill patients. Nonetheless, our findings need to be confirmed by larger studies to prove its reliability in the clinical setting.
doi:10.1186/1471-2253-11-1
PMCID: PMC3027108  PMID: 21223536

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