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Background: In the municipalities of Sannazzaro de’ Burgondi and Ferrer Erbognone (District of Lomellina, Pavia, Lombardy, Italy), an oil refinery is operating since 1963. In 2008, the company running the plant (eni S.p.A.) asked the competent bodies the permission for building a new facility (“EST”). The present work is aimed at evaluating the ante-operam health impacts of the existing facility refinery. Methods: A case-control study design was implemented. Cases were subjects admitted to hospital in 2002-2014 due to acute respiratory, cardiovascular or gastrointestinal conditions. Controls were selected among those who had not been hospitalised in that timespan. Cases and controls had to be alive at enrolment, aged 20-64 years, and were frequency-matched by age, gender and municipality. Data were extracted from the health insurance registry and from Hospital Discharge Records (ATS Pavia). Enrolled subjects were asked to complete a mailed survey. Environmental exposure was the fallout of refinery emissions (PM10) at participants’ homes, as predicted by an AERMOD model. Results: 541 respondents (125 cases, 416 controls) were included in the analyses. Response bias was excluded. Individual PM10 exposure was not significantly different between cases and controls, while it was significantly associated with municipality (being higher in Sannazzaro). The crude effect estimate of PM10 over case/control status indicated a not-significant excess of hospitalisation with the increase in PM10 exposure. Multivariate analyses confirmed those results. Conclusion: Findings indicate a possible excess of hospitalisation risk in most exposed people, but the effect is not statistically significant and may be affected by bias.

The Italian National Health Service (I-NHS) was established in 1978 to guarantee universal access to healthcare. Prominent in international reports, the I-NHS has reached a satisfactory level of efficiency and excellent standards of care in many regions, in forty years. Along the years, I-NHS has developed a structural public-private partnership in health services delivery that in some regions contributes to the achievement of very high standards of healthcare quality. However, the I-NHS is currently facing some major challenges: (a) Italy is experiencing a remarkable aging of its population with increasing health needs; (b) the recent and constant cuts to public expenditures are reducing the budget for welfare. It is of utmost importance to ensure that on-going efforts to contain health system costs do not subsume health care quality. In addition, monitoring of the essential levels of care (Livelli Essenziali di Assistenza, LEA) highlights significant differences in healthcare delivery among Italian regions that, in turns, contribute to the burdensome migration of patients to best-performing regions. Therefore, a more consolidated and ambitious approach to quality monitoring and healthcare improvement at a system level is needed to guarantee its sustainability in the future.

This paper outlines the characteristics of scientific leadership and the role of Scientific Associations with their specific activities. The recent activities of the Lombard Academy of Public Health are subsequently described, including the creation, in 2019, of the Academy of young leaders in public health. Comparing to other sectors, scientific leadership dynamics take into consideration different aspects. Besides awards (Nobel Prize or several other) and prestigious affiliations, eventual indicators might be academic roles, fundraising abilities, relevant positions among scientific associations, editors of prestigious journals or editorial series and, more recently, high bibliometric indicators. The peculiar topics of public health encompass interactions with institutions, authorities, politicians, involved in different levels in health policies. Recently, in Italy, the Ministry of Health has identified parameters to be accreditated as a scientific and technical association. The role of SItI (Italian Society of Hygiene), EUPHA, ASPHER, and WFPHA appears relevant in PH, in national and international contexts, with Italian praiseworthy members constantly achieving leading roles. Considering that few training opportunities aimed to improve research and leadership skills are available, Accademia Lombarda di Sanità Pubblica (ALSP) designed the AYLPH (Academy of Young Leaders in Public Health) program. AYLPH program is a 1-year training to shape leadership skills among young professionals. A set of didactic, theoretical and practical methods was offered and evaluated.

Aims To present the results of a novel technique of aortic valve decalcification (AVD) in a consecutive population of elderly patients with severe aortic valve stenosis (AVS) and small aortic annulus. Methods Between January 2008 and December 2012, a consecutive series of 34 patients (mean age 80 ± 13 years) with severe AVS were operated on using AVD. They were compared with a matched population of 68 patients (mean age 82 ± 7 years) submitted to aortic valve replacement (AVR) with bioprosthesis. The two groups were comparable for cardiac risk factors and admission symptoms. Preoperatively, all patients presented with severe AVS, small aortic annulus (19 mm) and preserved left ventricular function. Results Thirty-day mortality was 8.8 vs. 7.5% in the AVD and AVR groups, respectively (P = 0.88). Actuarial 2 and 5-year survival rates were 80 vs. 82% and 64 vs. 78% in the AVD and AVR groups, respectively (P = 0.27). Long-term valve-related events incidence was significantly higher in the AVD group (12%) compared with that in the AVR group (4%; P = 0.01). However, in the AVD group, patients with no or mild residual AR experienced 2 and 5 years of freedom from valve-related events, which is not significantly different from the patients submitted to the AVR group (P = 0.76). After AVD, a significant increase in the aortic valve area (from 0.8 to 1.9 cm) and a parallel reduction in the mean gradient (from 40 to 12 mmHg) was observed in all patients (P = 0.01). Postoperative aortic valve area (1.9 vs. 1.26 cm), as well as mean gradient (12 vs. 21 mmHg), were significantly better in the AVD group compared with that in the AVR group (P = 0.01). Conclusion In this preliminary experience, AVD seems a good therapeutic option for elderly patients with severe AVS. Further studies with longer follow-up are needed in order to confirm these preliminary results and to ascertain the valve durability over time.

Objective To evaluate whether a school-based multicomponent educational program could improve adiposity measures in middle-school adolescents. Methods A non-randomized controlled pilot study was conducted in six state middle schools (487 adolescents, 11-15 years) in townships in an urban area around Milan, three schools (n = 262 adolescents) being assigned to the intervention group and three schools (n = 225 adolescents) to the control group. The two-school-year intervention included changes in the school environment (alternative healthy vending machines, educational posters) and individual reinforcement tools (school lessons, textbook, text messages, pedometers, re-usable water bottles). The main outcome measure was change in BMI z-score. The secondary outcomes were changes in waist-to-height ratio (WHtR) and behavioral habits. Results The intervention was associated with a significant difference in BMI z-score (−0.18 ± 0.03, P

Healthcare Associated Infections (HAI) are a global concern, further threatened by the increasing drug resistance of HAI-associated pathogens. On the other hand, persistent contamination of hospital surfaces contributes to HAI transmission, and it is not efficiently controlled by conventional cleaning, which does not prevent recontamination, has a high environmental impact and can favour selection of drug-resistant microbial strains. In the search for effective approaches, an eco-sustainable probiotic-based cleaning system (Probiotic Cleaning Hygiene System, PCHS) was recently shown to stably abate surface pathogens, without selecting antibiotic-resistant species. The aim of this study was to determine whether PCHS application could impact on HAI incidence. A multicentre, pre-post interventional study was performed for 18 months in the Internal Medicine wards of six Italian public hospitals (January 1st 2016-June 30th 2017). The intervention consisted of the substitution of conventional sanitation with PCHS, maintaining unaltered any other procedure influencing HAI control. HAI incidence in the pre and post-intervention period was the main outcome measure. Surface bioburden was also analyzed in parallel. Globally, 11,842 patients and 24,875 environmental samples were surveyed. PCHS was associated with a significant decrease of HAI cumulative incidence from a global 4.8% (284 patients with HAI over 5,930 total patients) to 2.3% (128 patients with HAI over 5,531 total patients) (OR = 0.44, CI 95% 0.35-0.54) (P

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined timepoints before during and after surgery. In all CHD children, S100B levels showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P

Perinatal asphyxia (PA) still constitutes a common complication involving a large number of infants with or without congenital heart diseases (CHD). PA affects 0.2-0.6% of full-term neonates, 20% of which suffer mortal hypoxic-ischemic encephalopathy, and among survivors 25% exhibit permanent consequences at neuropsychological level. Each year, about one third of 1000 live births underwent to surgical intervention in early infancy and/or are at risk for ominous outcome. Advances in brain monitoring, in anesthetic and cardiothoracic surgical techniques, including selective or total body cooling, cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest, have essentially reduced mortality expanding the possibility to address functional neurologic and cardiac outcomes in long-term survivors. However, open-heart surgery constitutes a time-frame of planned ischemia-reperfusion injury, which is a price to pay in the treatment or palliation of CHD. Infants who underwent heart surgery and non-CHD infants complicated by PA share similarities in their neurodevelopmental profile and a common form of brain damage due to hypoxic-ischemic injury. The purpose of the present review was to evaluate different mechanisms implicated in brain injury following CPB and PA and how it is possible to monitor such injury by means of available biomarkers (S100B protein, Activin A, Adrenomedullin).

Patients with chronic fatigue syndrome (CFS) commonly exhibit orthostatic intolerance. Abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli was previously described in numerous studies. The aim of the current study was to describe cardiological and clinical characteristics of Italian patients with CFS. All of the patients were of Caucasian ethnicity and had been referred to our center, the Cardiology Department of the University Hospital of Pavia (Pavia, Italy) with suspected CFS. A total of 44 patients with suspected CFS were included in the present study and the diagnosis was confirmed in 19 patients according to recent clinical guidelines. The characteristics at baseline of the population confirm findings from various previous reports regarding the prevalence in females with a female to male ratio of 4:1, the age of onset of the pathology and the presence of previous infection by the Epstein-Barr virus, cytomegalovirus and other human herpesviruses. Despite the current data indicating that the majority of the cardiological parameters investigated are not significantly different in patients with and without CFS, a significant association between the disease and low levels of blood pressure was identified. Other pilot studies revealed a higher prevalence of hypotension and orthostatic intolerance in patients with CFS. Furthermore, many of the CFS symptoms, including fatigue, vertigo, decreased concentration, tremors and nausea, may be explained by hypotension.

Introduction: Excessive hemodilution during cardiopulmonary bypass (CPB) is associated with an increased rate of red blood cell (RBC) transfusion and acute kidney injury (AKI). Minimization of the oxygenator priming volume is a measure to contain hemodilution. In this study, we evaluated the new oxygenator, Sorin Inspire 6™, with respect to its ability to limit hemodilution, RBC transfusion rate and postoperative AKI rate. Methods: A retrospective study on a consecutive series of 1,724 adult patients receiving heart surgery with CPB. Patients treated with the Inspire 6™ were assigned to the low priming volume oxygenator (LPVO) group (N=383) and patients treated with conventional oxygenators to the conventional group (N=1,341). Dynamic priming volume, time course of the hematocrit, RBC transfusions and AKI rate were compared between the groups. Results: Priming volume was significantly (p=0.001) lower in the LPVO group (624±113 mL) vs. the conventional group (775±150 mL), with higher values of hematocrit during and after CPB. After correction for other confounders, patients in the LPVO group had a significantly lower RBC transfusion rate (odds ratio 0.68, 95% confidence interval 0.52-0.90, p=0.006) and AKI rate (odds ratio 0.55, 95% confidence interval 0.32-0.93, p=0.032). Conclusion: The Inspire 6™ oxygenator allows a significant containment of hemodilution during CPB, reducing the risk of RBC transfusions and postoperative AKI.

OBJECTIVE Transcutaneous oxygen tension (TcPO2) measures tissue perfusion and is important in the management of peripheral artery disease (PAD). Ankle brachial index (ABI) is used for the diagnosis of PAD and represents a predictor of major adverse cardiovascular events (MACE), even if in diabetes its diagnostic and predictive value seems to be reduced. No study has evaluated TcPO2 as a predictor of cardiovascular events. Aim of this longitudinal study was to assess whether TcPO2 is better than ABI at predicting MACE in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Among 361 consecutive patients with apparently uncomplicated diabetes, 67 MACE occurred during a follow-up period of 45.8 ± 23.2 months. RESULTS The percentage of both subjects with low ABI (≤0.9) and subjects with low TcPO2 (≤46 mmHg as measured by a receiver operating characteristic curve) was significantly ( 0.0001) were associated with a higher rate of MACEs. Cox regression analysis showed that low TcPO2 (hazard ratio 1.78 [95% CI 1.44–2.23]; P < 0.001) was a significant predictor of MACE, while ABI did not enter the model. CONCLUSIONS This longitudinal study showed that TcPO2 may be a potential predictor of MACE among patients with uncomplicated type 2 diabetes and that its predictive value seems to be greater than that of ABI.

ObjectivesPurified antithrombin supplementation in cardiac surgery has been suggested for the treatment of heparin resistance and the prevention of thromboembolic complications. This study is a randomized controlled trial of preoperative purified antithrombin supplementation, with the primary end point of avoiding low (

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE-RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF)

Background. Healthcare professionals have an important role to play both as advisers—influencing smoking cessation—and as role models. However, many of them continue to smoke. The aims of this study were to examine smoking prevalence, knowledge, attitudes, and behaviours among four cohorts physicians specializing in public health, according to the Global Health Profession Students Survey (GHPSS) approach.Materials and Methods. A multicentre cross-sectional study was carried out in 24 Italian schools of public health. The survey was conducted between January and April 2012 and it was carried out a census of students in the selected schools for each years of course (from first to fourth year of attendance), therefore among four cohorts of physicians specializing in Public Health (for a total of n. 459 medical doctors). The GHPSS questionnaires were self-administered via a special website which is created ad hoc for the survey. Logistic regression model was used to identify possible associations with tobacco smoking status. Hosmer-Lemeshow test was performed. The level of significance wasP≤0.05.Results. A total of 388 answered the questionnaire on the website (85%), of which 81 (20.9%) declared to be smokers, 309 (79.6%) considered health professionals as behavioural models for patients, and 375 (96.6%) affirmed that health professionals have a role in giving advice or information about smoking cessation. Although 388 (89.7%) heard about smoking related issues during undergraduate courses, only 17% received specific smoking cessation training during specialization.Conclusions. The present study highlights the importance of focusing attention on smoking cessation training, given the high prevalence of smokers among physicians specializing in public health, their key role both as advisers and behavioural models, and the limited tobacco training offered in public health schools.

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P < 0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. © 2014 Landes Bioscience.

About 40% of diabetic patients with asymptomatic coronary artery disease (CAD) are missed on the basis of the current screening guidelines. Erectile Dysfunction (ED) is a powerful marker of asymptomatic CAD. Aim of the study is to evaluate whether ED can improve the effectiveness of the current guidelines for the screening of CAD in diabetes. From among 299 consecutive men with newly diagnosed type 2 diabetes without any apparent vascular complication, 293 (mean age 56.6 ± 5.9 years) were enrolled. Among them, 219 did not have myocardial ischemia (NO CAD group) and 74 men had a coronary stenosis angiographically proven (CAD group). Five risk factors (RFs) of the current screening guidelines (hypertension, dyslipidemia, family history for CAD, smoking e micro/macroalbuminuria) and ED were assessed. ED was significantly more prevalent in the CAD than in the NO CAD group (37.8 versus 15.1%; P

Background: The percutaneous closure of single atrial septal defect (ASD) is a valid alternative to surgery. Objectives: To assess the feasibility of percutaneous treatment of multiple ASDs. Methods: Between 1998 and 2007, 165 out of 1280 consecutive patients undergoing ASD percutaneous closure at our institution showed multiple defects that were classified in four categories: double atrial septal defects (d-ASD), multifenestrated atrial septal defects (f-ASD), multifenestrated defects with no signs of right heart overload (f-PFO), and complex cases (c-ASD). The following end points were taken into consideration: (1) immediate procedural success; (2) long term safety and efficacy. In this study, up to 81% of multiple ASDs were suitable for percutaneous closure. Results: Multiple device implantations were required in 47% of cases, especially in patients with d-ASD and c-ASD. Complication rate, residual shunt, and long term outcome were comparable among the four different categories. In particular, at long term follow-up (6 ± 2 years) no patient required further surgical or percutaneous treatment and complete closure was confirmed in 99% of cases. Conclusions: Percutaneous closure of multiple ASDs is feasible and associated with a good outcome. A thorough identification and analysis of morphological aspects are mandatory in order to select the appropriate device and the optimal strategy. © 2010 Wiley-Liss, Inc.

Subclinical hypothyroidism and hyperthyroidism have been recognized as clinical entities with negative effects on the cardiovascular system. Moreover, the effect of treated thyroid dysfunction on parameters associated with the cardiovascular control system has been poorly investigated. In the present study we analyzed time-domain heart rate variability in coronary artery disease (CAD) patients with known thyroid diseases. Twenty-four hour ECG monitoring was performed in 344 patients with coronary artery disease (174 with thyroid dysfunction and 170 without thyroid dysfunction used as a control group), using a 3-channel tape recorder. Time domain parameters of heart rate variability (HRV) were definitely lower both in patients with subclinical hypothyroidism and subclinical hyperthyroidism than in the control group, with statistically significant differences in SDNN, RMSSD, TINN, and mean RR for both subgroups. Furthermore, patients on L-thyroxine treatment and restored euthyroidism had generally higher HRV values than patients with subclinical hypothyroidism, nevertheless SDNN, RMSSD, SDNN index, TINN, and mean RR were significantly lower when compared to those of the control group. Significant differences in HRV were also found between hyperthyroid patients under treatment and control group subjects with respect to RMSSD, TINN, and mean RR values. In conclusion, patients with cardiac disease and known thyroid disease, even when the disease is in the subclinical range or despite treatment, should be regarded as patients at additional risk conveyed by thyroid hormone disturbances.

Objective: Cardiovascular Disease (CVD) is the leading cause of death and disability worldwide. sDyregulation of the autonomic nervous system associated with various pathological conditions often occurs in presence of cardiovascular risk factors. Heart Rate Variability (HRV) may be used to assess autonomic imbalances. The aim of our study is to evaluate the correlation between HRV and the main cardiovascular risk factors in subject who underwent digital ambulatory 24 hours Holter ECG monitoring for clinical investigations. Methods: We evaluated time domain parameters of HRV by Holter ECG monitoring in a large population categorized based on the presence or absence of the major cardiovascular risk factors. Results: We found significant differences in time domain parameters of HRV in patients with and without common risk factor for CVD such as diabetes, family history for Coronary Artery Disease and dyslipidemia. We also analyzed our study population based on age and we found a positive correlation with the standard deviation of all NN intervals (SDNN), square root of the mean of the sum of the square of the differences between adjacent NN intervals (RMSSD), mean R-R intervals and by the number of adjacent NN intervals differing by more than 50 ms divided by the total number of all NN intervals (pNN50) and an inverse correlation for the others parameters. Conclusion: Non-modifiable risk factors (age, gender, family history) along with dyslipidemia and diabetes, are related to a change in HRV, while modifiable risk factors (smoking, hypertension, overweight, hyperhomocysteinemia) showed no correlation. This would seem to indicate that the genetic components more than lifestyle habits and behavior act on the nervous control of the heart. Our study shows the possibility to find interesting clinical-prognostic data, analyzing simple parameters obtained from instrumental methods of investigation performed for other clinical reasons.

Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

The population of adults with congenital heart disease is increasing due to advancements in cardiology and cardiac surgery. Many patients face medical complications and psychosocial difficulties; however, it is not yet clear whether there is a direct relationship between medical status and the psychological functioning of these patients. This systematic review of the relevant literature is an attempt to: provide a comparison between the population of adults with congenital heart disease, the healthy reference population and similar cardiac populations when it comes to psychological functioning; explore the relationship between medical status/cardiac condition and psychological functioning; and identify the predictors of psychological distress in this population.

Postoperative bleeding is common after cardiac surgery. Major bleeding (MB) is a determinant of red blood cell (RBC) transfusion, especially in patients with preoperative anemia. Preoperative anemia and RBC transfusions are recognized risk factors for operative mortality. The present study investigates the role of MB as an independent determinant of operative mortality in cardiac surgery.A single-center retrospective study based on the institutional database of cardiac surgery in the period 2000-2012 was conducted. Sixteen thousand one hundred fifty-four (16,154) consecutive adult patients undergoing cardiac surgery were analyzed. The impact of postoperative bleeding and MB on operative (30 days) mortality was analyzed univariately and after correction for preoperative anemia, RBC transfusions, and other confounders.Postoperative bleeding was significantly (p0.001) associated with operative mortality, both in univariate and multivariable models. The main complications associated with MB were thromboembolic complications, infections, and surgical reexploration. In a multivariable model, MB remained an independent predictor of operative mortality (odds ratio, 3.45; 95% confidence interval, 2.78 to 4.28). Preoperative anemia and RBC transfusions coexist in the model, acting with a multiplying effect when associated with MB.Major bleeding is per se a risk factor for operative mortality. However, its deleterious effects are strongly enhanced by RBC transfusions and, to a lesser extent, preoperative anemia. Major bleeding is a partially modifiable risk factor, and adequate preemptive and treatment strategies should be applied to limit this event.

Objective: The mechanisms by which migraine is linked to ischemic vascular disease remain uncertain and are likely to be complex. The aim of this study was to investigate the correlation between silent myocardial ischemia (SMI) and a history of documented primary headache in a large population of patients with exercise-induced myocardial ischemia. Methods: The study involved 1,427 consecutive patients (918 symptomatic and 509 asymptomatic patients) with exercise-induced myocardial ischemia and documented coronary artery disease (CAD). Results: Patients with anginal symptoms during exercise-induced myocardial ischemia had a significantly higher prevalence of primary headache than those without (41 vs. 30%, p < 0.001). Patients with angina pectoris in daily life also had greater prevalence of primary headache than those without anginal symptoms (37 vs. 20%; p < 0.0001). Symptomatic patients during percutaneous transluminal coronary angiography or myocardial infarction had a greater prevalence of primary headache than asymptomatic patients (p < 0.001 and p = 0.005, respectively). Conclusions: Our data suggest that a history of headache in CAD population is correlated to a high probability of anginal symptoms and a decreased probability of SMI. The anamnestic absence of headache requires a close monitoring for patients with risk factors for CAD, because this population seems to have a lower susceptibility to pain and the risk of developing SMI might be increased.

The Receptor for Advanced Glycation End-products (RAGE), a multi-ligand member of the immunoglobulin superfamily, is a ubiquitous receptor present on epithelial, neuronal, vascular and inflammatory cells. AGEs have been implicated in vascular and myocardial dysfunction and in development of atherosclerosis but little are known about the role of the AGE-RAGE system in heart failure. The main objective of the study was to assess sRAGE plasma levels in patients with Chronic Heart Failure (CHF) focusing on patients with severe reduction of left ventricle function. We measured sRAGE plasma levels in 389 patients with CHF and 319 stable patients with Coronary Artery Disease (CAD). Patients with CHF had significantly lower values of soluble RAGE in respect to stable CAD population. The linear regression analysis showed that LVEF (Left Ventricularv Ejection Fraction) significantly correlated with sRAGE plasma concentrations; sRAGE plasma levels were significantly lower in patients with severe left ventricular systolic dysfunction compared with those with ejection Fraction ≥ 30%. Our data support a positive correlation between soluble RAGE plasma levels and left ventricular ejection fraction in the CHF population; we demonstrated that in subjects with CHF and severe left ventricular systolic dysfunction, soluble RAGE plasma concentrations were significantly lower in comparison with patients with moderate left ventricular dysfunction. This study suggests the possibility that soluble RAGE can be considered a new element to be used in prognostic stratification in patients affected by CHF.

Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand receptor ubiquitous present on epithelial, neuronal, vascular and inflammatory cells, usually expressed at low levels in homeostasis and to increased degrees at sites of stress or injury. The aim of the present study was to evaluate sRAGE plasma levels in patients with Acute Coronary Syndrome (ACS) and to assess its diagnostic efficacy in identification of patients with acute events. Plasma levels of sRAGE were determined in 860 patients with Coronary Artery Disease (CAD): 530 patients presented stable angina and 330 were observed during acute ischemic event (147 with unstable angina and 183 with myocardial infarction). sRAGE plasma levels were significantly lower in patients with ACS than in patients with stable angina: [median 584 pg/mL (IQR: 266–851 pg/mL) in MI patients, median 769 pg/mL (IQR: 394–987 pg/mL) in patients with unstable angina, median 834 pg/mL (IQR 630–1005 pg/mL) in patients with stable angina;P<0.001]. sRAGE levels did not differ among ACS patients stratified by the extent of coronary artery disease. In conclusion, this study confirm the role of sRAGE in activation and progression of inflammatory process and suggests the possibility that sRAGE can be considered an indicator of destabilization of vulnerable plaque.

OBJECTIVES: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) has been used for many years since its introduction in 1999. Recently, a new EuroSCORE (EuroSCORE II) has been developed to update the previous version. The EuroSCORE II includes some different predictors and/or introduces a new classification of the already existing predictors. This study presents a validation series for the EuroSCORE II compared with the previous additive and the logistic EuroSCORE and with the Age, Creatinine and Ejection Fraction (ACEF) score. METHODS: A total of 1090 consecutive adult patients operated on at our institution from September 2010 to October 2011 were admitted to this retrospective study. All the patients received a risk stratification based on the EuroSCORE II and the other scores considered. Accuracy, calibration and clinical performance of the various risk models were assessed. RESULTS: The accuracy of the EuroSCORE II was good (c-statistic 0.81) but not significantly higher than the other scores (range 0.78– 0.8). Calibration at the Hosmer–Lemeshow statistic was good for all the scores; the difference between observed (3.75%) and predicted mortality in the overall population was not significant for the EuroSCORE II (3.1%) and the ACEF score (3.4%), whereas the additive EuroSCORE (5.8%) and the logistic EuroSCORE (7.3%) significantly overestimated the risk. In patients at low, mild moderate and high mortality risk, the EuroSCORE II provided a risk prediction not significantly different from the observed mortality rate, whereas in very high-risk patients (observed mortality rate 11%), it significantly underestimated (6.5%) the mortality risk. The accuracy of the EuroSCORE II was acceptable in isolated coronary surgery, and good or excellent in the other operations. CONCLUSIONS: The EuroSCORE II represents a useful update of the previous EuroSCORE version, with a much better clinical performance and the same good level of accuracy. It is possible that for the risk stratification of very high-risk patients, other factors (rare but associated with a mortality rate >50%) should be included in the future models.

The recent advent of an entirely subcutaneous implantable defibrillator (ICD) has provided a relevant contribution to the debate concerning the use of ICD therapy in patients at high risk for death. Although conventional transvenous ICDs have proven very effective during the past 23 years, they still appear to be limited by nontrivial acute and long-term complications. This study delineates some of the historical and current issues characterizing the advent of the subcutaneous ICD system in daily clinical practice. Subcutaneous ICDs have proven effective in more than 1100 patients worldwide and appear to be competitive with transvenous ICD in all clinical conditions not requiring antibradycardia, antitachycardia, or cardiac resynchronization pacing.

Preoperative anemia is not considered an operative mortality risk factor by the majority of the risk stratification tools used in cardiac surgery. However, retrospective studies have found associations between preoperative anemia and morbidity and mortality in cardiac operations. The present study compares the postoperative outcome of a group of moderate-to-severe anemic patients with a propensity-matched group of nonanemic patients undergoing cardiac operations.This is a retrospective study based on 17,056 consecutive patients included in our Institutional Database. A total of 13,843 adult patients with preoperative hematocrit value available were selected for this study; 401 patients had a severe anemia (hematocrit30%). From the remaining patients, a control group of 401 non-severely anemic patients was selected with a propensity-based matching. Postoperative morbidity and mortality were compared between the 2 groups.The 2 groups were comparable for preoperative comorbidities and operative details. Anemic patients had a significantly (p=0.045) higher rate of stroke (1% vs 0%), major morbidity (27.4% vs 17.5%, p=0.001), and a significantly higher (0.014) operative mortality rate (12.7% vs 7.5%). An additional analysis, inclusive of patients with moderate preoperative anemia, confirmed these results.Moderate-to-severe preoperative anemia is a risk factor for major morbidity and operative mortality in adult cardiac operations. This finding is confirmative of the role of preoperative anemia in determining adverse events in major noncardiac operations. The exclusion of preoperative anemia from the existing risk scores is probably a statistical consequence of the associated comorbid conditions that confound the specific role of anemia as a risk factor.

Neuropathy and peripheral artery disease represent the main pathophysiological conditions underlying diabetic foot. Several studies showed that Lipoprotein(a)-Lp(a)-and homocysteine (Hcy) can be associated with diabetic complications, but their relationship with diabetic foot is unclear. Aim of this study was to investigate whether Lp(a) and Hcy were associated with diabetic foot ulcerations, classified according to the presence of peripheral artery disease (PAD) or neuropathy. From among consecutive type 2 diabetic attending at the Diabetic Foot Clinic 27 subjects with vascular diabetic foot (VDF), 43 with neuropathic diabetic foot (NDF) and 52 controls without foot ulceration, neuropathy, and PAD were enrolled. Both Lp(a) (26.1 ± 22.7 vs. 14.9 ± 19.5 mg/dl; P = 0.003) and Hcy levels (15.4 ± 5.7 vs. 12.2 ± 5.1 μmol/l; P = 0.022) were significantly greater in the VDF group than in controls. Lp(a) levels were significantly lower in the NDF group than in controls (6.9 ± 8.1 versus 14.9 ± 19.5 mg/dl; P = 0.009), while no difference in Hcy levels was found. Multiple logistic regression analysis showed that Hcy was associated with VDF (OR: 1.11; 95% CI: 1.07-14.1; P = 0.048). Lp(a) did not enter the model, but its P-value was very near to the significant level (OR: 1.09; 95% CI: 0.99-12.05; P = 0.059). Moreover, low Lp(a) levels were associated with NDF (OR: 0.84; 95% CI: 0.21-0.96; P = 0.039). Our study has shown for the first time that high Lp(a) and Hcy levels are associated with the development of VDF, while low Lp(a) levels appear to be associated with delayed wound healing in patients with neuropathic foot ulcerations.

Apelin is an endogenous peptide that increases cardiac inotropism through its APJ receptor. Certain findings indicate that the apelinergic system may have a pathophysiological role in cardiovascular disease and there is evidence showing the role of the apelinergic system in blood pressure regulation in vitro and in animal models. The role of the apelin-APJ system in cardiovascular physiology and its interaction with other neuroendocrine pathways has not been fully elucidated. However, the small number of reported studies indicates that apelin signaling may be involved in the regulation of blood pressure, cardiac contractile function, fluid balance, angiogenesis and inhibition of apoptosis. We evaluated the possible relationship between the G212A and A445C APJ polymorphisms and coronary artery disease (CAD) in Italian patients and in healthy controls by RFLP-PCR. We analyzed the allelic and genotypic frequencies of APJ polymorphisms in 664 patients (378 with hypertension) and 143 controls. There were no differences between allelic and genotypic frequencies in patients in respect to the controls for both polymorphisms analyzed. In the CAD population, there was an increased frequency of the G212 allele in patients with hypertension in respect to patients without hypertension. No differences were present in the two subgroups for the A445C polymorphism. Although the functional role of the G212A polymorphism has not yet been identified, it is possible to hypothesize that the presence of the A allele may cause a gain in function of the apelin/APJ system associated with a lower risk of hypertension.

To summarise data from studies comparing surgical (SC) versus percutaneous closure (PC) of atrial septal defects (ASDs).Electronic databases, journals and major international conference proceedings were systematically searched for pertinent clinical studies comparing the two methods of closure (percutaneous and surgical) published up to December 2008, including only those reporting on more than 20 patients. Primary endpoints: occurrence of death and of total and major early complications. Thirteen original studies (3,082 patients) were included. All studies were non-randomised. One death was reported in the surgical group (0.08%; 95% C.I. 0-0.23%). Analysis of postprocedural complications showed a 31% rate (95% CI 21-41%) in SC patients and a 6.6% rate (95% CI 3.9-9.2%) in PC subjects. The adjusted OR for SC vs. PC total complications was 5.4 (95% CI 2.96-9.84; p0.0001), significantly in favour of PC. The postprocedural major complication rate was 6.8% (95% CI 4-9.5%) in SC patients and 1.9% (95% CI 0.9-2.9%) in PC patients. The adjusted OR for SC vs. PC major complications was 3.81 (95% CI 2.7-5.36; p=0.006), again favouring PC.The largest cohort to date of patients with secundum ASD shows that treatment by a percutaneous approach has a significantly lower rate of either total or major early postprocedural complications compared to surgery.

Background Patients with ventilator dependency after cardiac operations may require a tracheostomy. This study determined the hospital and postdischarge outcome in a series of patients who underwent a tracheostomy due to ventilator dependency after cardiac operations. Methods Medical records of cardiac surgical patients were retrospectively reviewed for preoperative, intraoperative, and postoperative variables, and also prospective follow-up for all-cause mortality. All adult patients treated with tracheostomy due to postoperative ventilator dependency between January 1, 2004, and December 31, 2009, were admitted to the study. Statistical methods included a multivariable logistic regression analysis for hospital mortality and a Kaplan-Meier analysis with multivariable Cox regression model for postdischarge mortality. Results The study group included 131 patients. The hospital mortality rate was 49%. The only independent predictor for hospital mortality was the number of fresh frozen plasma units transfused during the hospital stay (6% mortality risk increase per each unit transfused). Survival rate for patients discharged from the hospital was 61% at 1 year, 49% at 2 years, 45% at 3 years, and 34% at 5 years. Factors affecting death after discharge were concomitant postoperative heart failure (hazard ratio, 2.6) and the length of ventilator dependency. Conclusions Patients with a respiratory failure without associated heart failure or neurologic dysfunction have a significantly better long-term outcome. Caution should be applied in the use of fresh frozen plasma in patients with postoperative respiratory failure and ventilator dependency requiring a tracheostomy.

We thank Dr Lown et al and Dr Miceli et al for their comments about our article.1 They raise several different and interesting points. It is of course possible that the selection of a limited number of variables for the risk model may better benefit from other more sophisticated statistical approaches. However, even if our model is apparently simplistic, it seems to work better than other complex models. We agree that an area under curve value of 0.744 is probably inadequate for clinical purposes, but this is the value reached by the widely used EuroSCORE in many clinical settings.2 Actually, in the validation series, the area under curve value of the ACEF score (age, creatinine, ejection fraction) was higher than 0.8.2 As stated in our article, it is a matter of terminology. We could say that the ACEF and the EuroSCORE are equally good or equally bad …

Background: The European system for cardiac operative risk evaluation (EuroSCORE) is currently used in many institutions and is considered a reference tool in many countries. We hypothesised that too many variables were included in the EuroSCORE using limited patient series. We tested different models using a limited number of variables. Methods: A total of 11 150 adult patients undergoing cardiac operations at our institution (2001—2007) were retrospectively analysed. The 17 risk factors composing the EuroSCORE were separately analysed and ranked for accuracy of prediction of hospital mortality. Seventeen models were created by progressively including one factor at a time. The models were comparedfor accuracywith a receiveroperatingcharacteristics (ROC)analysisandareaunder thecurve(AUC)evaluation. Calibration wastested with Hosmer—Lemeshow statistics. Clinical performance was assessed by comparing the predicted with the observed mortality rates. Results: The best accuracy (AUC 0.76) was obtained using a model including only age, left ventricular ejection fraction, serum creatinine, emergency operation and non-isolated coronary operation. The EuroSCORE AUC (0.75) was not significantly different. Calibration and clinical performance were better in the five-factor model than in the EuroSCORE. Only in high-risk patients were 12 factors needed to achieve a good performance. Conclusions: Including many factors in multivariable logistic models increases the risk for overfitting, multicollinearity and human error. A fivefactor model offers the same level of accuracy but demonstrated better calibration and clinical performance. Models with a limited number of factors may work better than complex models when applied to a limited number of patients. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background— Several mortality risk scores exist in cardiac surgery. All include a considerable number of independent risk factors. In elective cardiac surgery patients, the operative mortality is low, the number of events recorded per year is limited, and the risk model may be overfitted. The present study aims to develop and validate an operative mortality risk score for elective patients based on a limited number of factors. Methods and Results— The development series included 4557 adult patients who had undergone an elective cardiac operation at our institution from 2001 to 2003; the validation series includes the 4091 patients who subsequently underwent an operation. Three independent factors were included in the mortality risk model: age, creatinine, and left ventricular ejection fraction (ACEF). The ACEF score was computed as follows: age (years)/ejection fraction (%)+1 (if serum creatinine value was >2 mg/dL). The ACEF score was compared with 5 other risk scores in the validation series. Discriminatory power (accuracy) was defined with a receiver-operating characteristics analysis. The best accuracy was achieved by the Cleveland Clinic score (0.812), with ACEF score just below it (0.808). In coronary operations, the 2 scores performed equally well (0.815 versus 0.813), and in isolated coronary operations, the best accuracy was achieved by ACEF (0.826), with the Cleveland Clinic score at 0.806. Conclusion— A risk model limited to 3 independent predictors has similar or better accuracy and calibration compared with more complex risk scores if applied to elective cardiac operations.

Background Preoperative anemia and the lowest registered hematocrit value on cardiopulmonary bypass are recognized risk factors for morbidity and mortality after coronary operations. A low hematocrit often results in blood transfusions with all of the associated possible complications. The relative contribution of these three factors to long-term outcome is still not well established. This study aimed to identify the role of preoperative anemia and hemodilution during cardiopulmonary bypass as determinants of morbidity and mortality after coronary operations. Methods A consecutive series of 3,003 patients was analyzed. They had all undergone isolated coronary operations without receiving blood transfusions during their hospital stay. The preoperative hematocrit and the lowest hematocrit on cardiopulmonary bypass were analyzed in a multivariable model as predictors of major morbidity and operative mortality. Results After adjustment for the other explanatory variables, both the preoperative hematocrit and the lowest hematocrit on cardiopulmonary bypass were found to be independent risk factors for major morbidity, but not for operative mortality. However, low values of preoperative hematocrit were not associated with an increased morbidity, provided that the lowest hematocrit on cardiopulmonary bypass was maintained above 28%. Median values of the lowest hematocrit on cardiopulmonary bypass below 25% were associated with an increased major morbidity rate. Conclusions Excessive hemodilution during cardiopulmonary bypass is a risk factor for major morbidity even in the absence of blood transfusions. Techniques that aim to reduce the fall in hematocrit during cardiopulmonary bypass, including blood cardioplegia, may be useful, especially in patients with a low preoperative hematocrit.

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27–39.09) vs 6.48 ng/ml (4.88–8.83), p