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Communication failures in the pre-hospital/hospital interface have been identified as a major preventable cause of patient harm. This interface has not adequately been studied in Italy. In this study, we: (1) evaluated the communication of pre-hospital and hospital providers during handover through the analysis of simulation sessions; (2) identified the critical information that should be routinely communicated during handover with a survey administered to emergency triage nurses; (3) measured communication within this interface through the adaptation of an existing tool from a multidisciplinary focus group; (4) validated the adapted tool with the inter-rater agreement of physicians who reviewed video recordings from multidisciplinary simulations sessions; and (5) developed a handover training for pre-hospital providers and evaluated the communication improvement between pre- and post-training. In our simulations we found an absence of standardization of the handover communication process, marked variability in information communicated, and a lack of formal transfer of responsibility of patient care. We adapted existing handover communication tools for local use and developed a checklist for the evaluation of handover communication that had good inter-rater reliability. Lectures coupled with high-fidelity simulation exercises on handover did result in a statistically significant improvement in handover communication.

An increase of endothelial progenitor cells (EPCs) among acute myocardial infarction (AMI) patients participating in a cardiac rehabilitation (CR) program has been reported, but no data on the impact of adherence to lifestyle recommendations provided during a CR program on EPCs are available. It was our aim to investigate the effect of adherence to lifestyle recommendations on EPCs, inflammatory and functional parameters after six months of a CR program in AMI patients. In 110 AMI patients (90 male/20 female; mean age 57.9 ± 9.4 years) EPCs, high sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels, and cardiopulmonary testings were determined at the end of the CR (T1) and at a six-month follow-up (T2). At T2 we administered a questionnaire assessing dietary habits and physical activity. At T2, we observed a decrease of EPCs (p<0.05), of hsCRP (p=0.009) and of NT-ProBNP (p<0.0001). Patient population was divided into three categories by Healthy Lifestyle (HL) score (none/low, moderate and high adherence to lifestyle recommendations). We observed a significant association between adherence to lifestyle recommendations, increase in EPCs and exercise capacity between T1 and T2 (Δ EPCs p for trend <0.05; ΔWatt max p for trend=0.004). In a multivariate logistic regression analyses, being in the highest tertile of HL score affected the likelihood of an increase of EPC levels at T2 [OR (95% confidence interval): 3.36 (1.0-10.72) p=0.04]. In conclusion, adherence to lifestyle recommendations provided during a CR program positively influences EPC levels and exercise capacity.

Background: Because of their lower cost, healthcare systems recommend physicians to prefer generic products, rather than brand-name medicaments. There is then considerable interest and debate concerning safety and effectiveness of generic products. Few studies have compared patients treated with brand-name and generic drugs for adherence to treatment, with somewhat inconsistent results. The primary objective of this study was to compare the risk of discontinuing antihypertensive drug therapy in patients treated with generic or brand-name agents., Methods: The 101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years or older who were newly treated on monotherapy with antihypertensive generic or brand-name drugs during 2008, were followed until the earliest date among those of the occurrence of treatment discontinuation to whatever antihypertensive drug therapy (outcome), or censoring (death, emigration, 12 months after treatment initiation). Hazard ratios of discontinuation associated with starting on generic or brand-name products (intention-to-treat analysis), and incidence rate ratio of discontinuation during periods on generic and brand-name products (as-treated analysis) were respectively estimated from a cohort and self-controlled case series analyses., Results: Patients who started on generics did not experience a different risk of discontinuation compared with those starting on brand-name agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation did not occur with different rates during periods covered by generics or brand-name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11) within the same individuals. A number of sensitivity and subgroup analyses confirmed the robustness of these findings., Conclusion: Generic products are not responsible for the high rate of discontinuation from antihypertensive drug therapy. Assuming therapeutic equivalence, clinical implication is of prescribing generic drug therapies.

Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.

This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm(2) and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (-1.92 ± 1.21, -2.94 ± 1.60, and -3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50 % RPL068 vs. -1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment.

Objectives: Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection., Design: The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment., Setting and Participants: Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond., Primary Outcome: weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials., Results: Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001)., Conclusions: Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe.

NSAIDs are largely used for the treatment of a huge variety of clinical conditions in order to relieve symptoms related to inflammation.The use of NSAIDs is associated with a potential increased risk of gastrointestinal and cardiovascular complications.The cardiovascular risk related to NSAIDs administration is often underestimated and it is frequently believed to be less important than the gastrointestinal risk. Adverse effects of NSAIDs are specifically related to their underlying mechanisms of action.The most plausible mechanism underlying the cardiovascular risk of NSAIDs has been identified in the profound inhibition of COX-2-dependent PGI2 in the presence of incomplete and intermittent inhibition of platelet COX-1. Nevertheless, the cardiovascular risk related to the use of NSAIDs is not only due to the COX-2 selectivity. An important determinant of the clinical effects of NSAIDs depends on the pharmacokinetic features of the different drugs such as half-life, and type of formulations, which can influence the extent and duration of patient exposure to COXisozyme inhibition. The aim of this review is to analyse the mechanisms behind the cardiovascular risk of different NSAIDs.

Reticulated platelets (RP) are newly-formed platelets with a greater mass, a residual amount of RNA and an increased prothrombotic potential. No studies investigating the association between RP and the risk of cardiovascular death in acute coronary syndrome (ACS) patients are available. In the frame of the AMI-Florence 2 study, we investigated RP in 229 (154 M/ 75 F) ACS patients (125 ST-elevation myocardial infarction [STEMI]; 104 Non-STEMI/Unstable Angina). RP were measured by using the Sysmex XE-2100 haematology analyzer and were expressed as the percentage of RP out of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (H-IPF). At one-year follow-up, 22 out of 229 patients (9.6%) died from cardiovascular causes. Higher values of IPF (p=0.05) and H-IPF (p=0.006) were detected in dead compared to alive patients. A receiver operating characteristics curve analysis identified IPF ≥3.3% and H-IPF ≥0.9% as optimal cut-off values to predict cardiovascular death. At the multivariate model adjusted for the Global Registry of Acute Coronary Events (GRACE) risk score, the association between RP and cardiovascular death remained significant for both IPF [OR (95%CI) : 4.15 (1.24-13.91) p=0.02] and H-IPF [OR (95%CI): H-IPF 5.03 (1.38-18.38) p=0.01]. In conclusion, RP are independent predictors of cardiovascular death and may be useful in improving risk stratification for ACS patients. Future prospective studies to evaluate the role of RP in determining cardiovascular events are warranted.

Background: Early prediction of neurological outcome for patients resuscitated from cardiac arrest (CA) is a challenging task. Therapeutic hypothermia (TH) has been shown to improve neurological outcome after CA. Two recent studies indicated that somatosensory evoked potentials (SEP) recorded during TH retains high prediction value for poor neurological outcome. It remains unclear whether TH can influence the recovery of bilaterally absent (BA) N20 after re-warming. The primary endpoint of the present study was to evaluate if patients with BA SEPs during TH can recover cortical responses after re-warming. The secondary endpoint was to evaluate whether BA SEPs recorded during TH retains its prediction value for poor neurological outcome as in normothermic patients., Methods: A single centre prospective cohort study including comatose adults resuscitated from in/out-of-hospital CA treated with TH. SEPs were recorded during TH (6-24 hours after CA) and after re-warming in those patients who remained comatose. Neurological outcome was assessed 6 months after CA using the Glasgow Outcome Scale., Results: Sixty patients were included. In patients with preserved SEP, no significant differences were found between N20 mean amplitude during TH and after re-warming. During TH, 24 patients showed bilaterally absent N20 but none of these recovered cortical responses after re-warming. All patients with absent SEPs during TH did not recover consciousness., Conclusions: In a single centre cohort of comatose CA patients, our results showed that all patients with absent SEPs during early recording (6-24 hours) during TH showed bilaterally absent SEPs after re-warming. As a secondary result we confirmed previous data that BA SEPs during TH retains its prognostic value for poor neurological outcome, as in normothermic patients.

Background and Aim: No data are so far available on the impact of age and obesity in ST-elevation myocardial infarction (STEMI) submitted to percutaneous coronary intervention (PCI)., Methods and Results: We assessed the impact of age on the prognostic value of body mass index (BMI) in 1268 consecutive STEMI patients admitted to our Intensive Cardiac Care Unit (ICCU). BMI categories were as follows: 37 "lean" patients (37/1268, 2.9%), 403 "normal" patients (403/1268, 31.8%), 656 "overweight" patients (656/1268, 51.7%), 172 "obese" patients (172/1268, 13.6%). Among patients aged <75 years, as BMI increased, the number of males and diabetic patients significantly increased (p < 0.001 and p = 0.004, respectively). Among STEMI patients aged ≥75 years, lean patients showed a higher in-ICCU mortality in respect to the other BMI categories but this did not reach statistical significance. BMI was an independent predictor of In-ICCU mortality in the whole population (lean vs. "normal": OR 3.47, 95%CI 1.08-11.14, p = 0.036) and it was associated with long term mortality only in patients <75 years since lean and overweight patients showed lower survival rate (lean vs. "normal": HR 9.25, 95%CI 3.09-27.63, p < 0.001; overweight vs. "normal": OR 2.10; 95%CI 1.04-4.23, p = 0.039)., Conclusions: In our series, underweight is associated with the highest mortality across all age subgroups, while only in patients <75 years, overweight patients showed increased in-hospital mortality rate and a poorer long term survival rate. According to our data, the "so called obesity paradox" should be probably age-contextualized., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to evaluate resistin levels in patients with coronary artery disease (CAD) with or without chronic heart failure, in order to define its independent predictor., Methods: One hundred and seven outpatients with CAD were enrolled in the study and divided into three groups: CAD without left-ventricular systolic dysfunction (group 1); CAD with left-ventricular dysfunction without heart failure symptoms (group 2); CAD with overt heart failure (group 3). Plasma resistin was determined by ELISA., Results: Resistin progressively increased from group 1 (10.7±5.0 ng/ml) to groups 2 (11.8±5.8 ng/ml) and 3 (17.0±6.8 ng/ml), with the difference reaching statistical significance in group 3 versus groups 1 and 2 (P=0.001). A multivariable model of analysis demonstrated that the best predictor of plasma resistin level was the estimated glomerular filtration rate (P<0.001), indicating that reduction of kidney function was the main cause of the adipokine increase observed in patients with CAD and overt heart failure., Conclusions: Our data confirm the rise of resistin plasma levels previously described in patients affected by chronic heart failure; however, in our study, this relationship seemed to be mediated mainly by the level of kidney function, and only partially by the severity of ventricular dysfunction.

Objectives: At present, limited experience exists on the treatment of atrial fibrillation (AF) in patients undergoing mitral valve repair (MVR) for Barlow disease. The aim of this investigation was to prospectively evaluate the radiofrequency ablation of AF in patients undergoing MVR for severe regurgitation due to Barlow disease., Methods: From January 1, 2007 to December 31, 2010, out of 85 consecutive patients with Barlow disease, 27 with AF underwent RF ablation associated with MVR. They were examined every 4 months in the first year after surgery and thereafter twice yearly., Results: At follow-up, AF was observed in 4/25 (16.0%). NYHA (New York Heart Association) functional class improved significantly, with no patients in class III or IV (before surgery, 81.5% had been). Otherwise, among 58 patients in sinus rhythm, 6 (11%) developed AF during follow-up. No clinical or echocardiographic predictive factor was found in this subgroup., Conclusions: Results from our investigation suggest that radiofrequency ablation of AF in patients with Barlow disease undergoing MVR for severe regurgitation is effective and should be considered in every patient with Barlow disease and AF undergoing valve surgical repair., (Copyright © 2013 S. Karger AG, Basel.)

The aim of this document is to protect public health through the diffusion on the national territory of appropriate pain treatment guidelines and the definition of a practical, diagnostic and therapeutic tool, which contributes to the diffusion of Law no. 38/2010, particularly through information and health professionals training. The lack of systematic pain evaluation and of an appropriate diagnostic-therapeutic approach are the main issues that make patients treatment remains very poor and inadequate. The 41% of patients with chronic pain states they have not received adequate pain control. The pain incidence in the Italian population is 21.7%, which corresponds to approximately 13 million inhabitants. Consequently, becomes significant identifying the tools and methods to help health professionals to recognize the pain nature, providing a global intervention, which includes the evaluation of patient and of the pathology's clinical characteristics, in order to guarantee an adequate therapeutic choice and a minimization of risks associated with therapy. International guidelines for pain management recommend pain evaluation according to its characteristics, in order to recognize the pain nature (nociceptive pain - inflammatory pain and structural mechanical pain -, neuropathic pain) and an adequate therapy, taking into account pain intensity (analgesics or their associations for management of non-inflammatory pain; for management of inflammatory pain, NSAIDs which may be associated with a central analgesic; drugs with action on ion channels and on neurotransmitters reuptake for management of neuropathic pain). The inadequate management of "pain's suffering patient" underlined the need for health professionals to dispose of a practical and effective tool, a "methods-guide". This tool wishes to become a valuable support for pain examination, from first diagnostic approach to appropriate prescription's dispensing. Authors hope to guide health professionals in the right direction to achieve the cultural change awaited from the application of Law no. 38/2010.

Objectives: To identify factors that were predictive of improved pain status among older adults with chronic back pain participating in the Adaptive Physical Activity (APA) program and to identify factors that were predictive of adherence to APA., Methods: An observational cohort study of 392 older adults (ages 50 to 88) with chronic back pain participating in APA for 12 months. APA was a community-based group exercise program given for 1-hour, twice weekly, in local gyms. Primary outcome measures were improved pain based on a global rating of change evaluation and adherence to the APA program (defined as participation in >75% of exercise sessions). Potential predictor variables were entered into multivariate logistic regression models to determine the most accurate set of variables for predicting improved pain and adherence., Results: Presence of depressive symptoms, poor self-rated health and adherence to APA were the best predictors of improved pain status, with adherence being the strongest predictor [odds ratio: 13.88 (95% confidence interval: 8.17, 23.59)]. Better physical function, longer pain duration, and positive rating of the trainer were all positively associated with adherence to APA; whereas poor self-rated health and further distance from the gym were inversely associated., Conclusions: Given that adherence to APA is the key predictor of improved back pain, future efforts should focus on strategies to improve adherence. Our data suggest that enhanced training of exercise trainers, development of separate classes for people with different functional levels, and use of psychosocial interventions to reduce health pessimism and depression may be potential targets for improving adherence.

Background: Short- and medium-term mortality after acute stroke is related to the severity of the index event and the patient's age. However, recent studies have reassessed the prognostic value of the systemic atherothrombotic burden in these patients, not only in the long term. This post hoc analysis of the findings of the SIRIO trial (Stroke in Italy and Related Impact on Outcome) examined the prognostic impact of systemic atherothrombosis., Methods: SIRIO was a multicenter observational study enrolling patients during the acute phase of stroke of both ischemic and hemorrhagic origin. The present analysis, however, only covered patients with ischemic stroke. At baseline, the main personal and clinical details were recorded and patients were classified as having either polyvascular disease or single arterial disease on the basis of whether they had symptomatic atherothrombotic disease in other sites besides the cerebrovascular location. For all patients we calculated the Essen Stroke Risk Score (ESRS), dividing them into groups with scores of less than 3 or 3 and more. We recorded total mortality and nonfatal vascular events 12 months after enrolment. Multivariate logistic regression analysis was used to select predictors of medium-term mortality and nonfatal cardiovascular events. There were 2,561 patients with ischemic stroke, 823 of them classified as having polyvascular disease; 940 (out of 2,485) had an ESRS of less than 3 and 1,545 had a score of 3 or more., Results: The combined endpoint 'death (all causes) and nonfatal cardiovascular events within 12 months of hospital discharge' was significantly dependent on the following factors: ESRS, Rankin scale and National Institutes of Health Stroke Scale scores, and polyvascular disease. Polyvascular disease status significantly affected mortality and nonfatal cardio- and cerebrovascular events after discharge (OR = 1.44, 95% CI = 1.10-1.88). Age was also confirmed as a significant predictor of the combined endpoint., Conclusions: Besides age and the clinical severity of the index event, symptomatic involvement of several vascular districts was also an important predictor of mortality and nonfatal cardiovascular events in the medium term in patients with ischemic stroke., (Copyright © 2012 S. Karger AG, Basel.)

Background: Back pain is a significant problem due to the high healthcare utilization, rising costs of care and low effectiveness of many current treatments., Aim: Aim of this study was to determine the effects of a community-based Adapted Physical Activity (APA) program focused on chronic, non-specific back pain., Design: Open-label intervention study., Setting: Community., Population: All patients admitted to Empoli Rehabilitation Department for non-specific back pain for at least three months, were considered for APA. Exclusion criteria were: "red flags", difficulty/disability in basic daily living activities, severe/acute medical conditions, acute pain, psychiatric disease or cognitive impairment, severe visuoauditory deficit. Overall, 650 persons were enrolled., Methods: The APA program, including strength and flexibility training and exercises for improving posture was delivered for 12 months, with 1-hour group classes three times per week., Results: Overall 261 (40.2%) subjects completed the 12-month APA program and were compared to the 310 (47.7%) who were screened but failed to initiate or complete the study. There were no significant differences in baseline demographic and clinical characteristics between groups. Patients who followed the APA program reported significantly improved health status and significant back pain improvement, compared with those who did not adhere to the program. In the logistic regression analysis adjusted for age and gender, a distance from home to gymnasium greater than the median for the study population (2.6 km) was the only baseline characteristic significantly associated with an increased risk of non-adherence (OR 1.44, 95%CI 1.01-2.13; P=0.04)., Conclusion: This study suggests that a community-based APA program can improve back pain and health status in persons with chronic, non-specific low back pain. CLINICA REHABILITATION IMPACT: These findings highlight the potential for new approaches to manage chronic disease and disability by facilitating a healthy lifestyle and promoting physical activity through implementation of community-based exercise programs.

Several polymorphisms in genes that encode platelet components (receptors or enzymes), or cytochrome P450 enzyme isoforms, involved in clopidogrel metabolism, have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been focused on the loss-of-function CYP2C19(*)2 (or 681 G > A) polymorphism. We performed a meta-analysis of all the prospective studies that have been published, which analyze the role of such a polymorphism in recurrent cardiovascular events in patients with coronary artery disease (CAD) being treated with clopidogrel. Studies were searched in MedLine, Embase, Web of Science, The Cochrane Systematic Review Database, Google Scholar and bibliographies of retrieved articles up to January 2010. The principal underlying hypothesis was that the presence of the (*)2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Data were available for a total of 8043 patients from seven cohort prospective studies, who were followed for a period of time ranging from 6 months to 8.3 years. The summary risk ratios (RRs) for the prospective cohort studies included showed a significant association between the CYP2C19(*)2 polymorphism and an increased risk of major adverse cardiovascular events in the follow-up (RR: 1.96 (1.14-3.37); P = 0.02). When studies evaluating stent thrombosis (n = 4) for a total of 4975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis (RR: 3.82 (2.23-6.54); P = 0.0001). The current meta-analysis, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19(*)2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis.

Background: Since the first outbreak of a respiratory illness caused by H1N1 virus in Mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ECMO) assistance in young and often healthy patients. Here we describe our experience in H1N1-induced ARDS using both ventilation strategy and ECMO assistance., Methods: Following Italian Ministry of Health instructions, an Emergency Service was established at the Careggi Teaching Hospital (Florence, Italy) for the novel pandemic influenza. From Sept 09 to Jan 10, all patients admitted to our Intensive Care Unit (ICU) of the Emergency Department with ARDS due to H1N1 infection were studied. All ECMO treatments were veno-venous. H1N1 infection was confirmed by PCR assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage. Lung pathology was evaluated daily by lung ultrasound (LUS) examination., Results: A total of 12 patients were studied: 7 underwent ECMO treatment, and 5 responded to protective mechanical ventilation. Two patients had co-infection by Legionella Pneumophila. One woman was pregnant. In our series, PCR from bronchoalveolar lavage had a 100% sensitivity compared to 75% from pharyngeal swab samples. The routine use of LUS limited the number of chest X-ray examinations and decreased transportation to radiology for CT-scan, increasing patient safety and avoiding the transitory disconnection from ventilator. No major complications occurred during ECMO treatments. In three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. Overall mortality rate was 8.3%., Conclusions: In our experience, early ECMO assistance resulted safe and feasible, considering the life threatening condition, in H1N1-induced ARDS. Lung ultrasound is an effective mean for daily assessment of ARDS patients.

Background and Aim: Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n=247) or absence (n=883) of type 2 diabetes in ACS patients., Methods and Results: We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p=0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [β (SE)=0.17 (0.07), p=0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not -786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the -786C/894G/4a and -786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus., Conclusions: Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients., (Copyright © 2009 Elsevier B.V. All rights reserved.)

The Fibrillin-1 gene (FBN1; chromosome 15q21.1) encodes a major glycoprotein component of the extracellular matrix. Mutations in FBN1, TGFBR1, TGFBR2 are known to cause Marfan syndrome (MIM 154700), a pleiotropic disorder. In the present study, we describe five novel missense FBN1 mutations in five Marfan patients that have the peculiarity to activate two contemporary mutational mechanisms: a missense mutation and exon skipping., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background: Elevated C-reactive protein (CRP) concentration is a risk factor for cardiovascular events that may add prognostic information. Statin treatment is associated with significant reductions in CRP concentrations, which appear to be unrelated to the magnitude of LDL-cholesterol reduction. We investigated the effect of atorvastatin, across its dose range, on high sensitivity (hs)CRP in subjects at high cardiovascular risk., Methods: ACTFAST was a 12 week, prospective, multicenter, open-label trial in which high-risk subjects were assigned a starting dose of atorvastatin (10, 20, 40 or 80 mg/d) based on LDL-C and status of statin use at screening (1345 statin-free [SF] and 772 previously statin-treated [ST])., Results: At baseline, ST subjects had significantly lower hsCRP levels than SF subjects (ST group 2.31, 95% CI 2.15, 2.48 mg/L vs. SF group 3.16, 95% CI 2.98, 3.34 mg/L, p<0.05). In the SF group, atorvastatin 10 to 80 mg significantly (p<0.01) reduced hsCRP levels in a dose dependent-manner. In ST group, additional hsCRP reductions were observed over the statin used at baseline, which were not dose-dependent. Atorvastatin significantly decreased hsCRP concentrations in subjects with or without diabetes or the metabolic syndrome., Conclusions: Atorvastatin treatment at different doses, particularly 80 mg, significantly reduced hsCRP serum concentrations. This reduction was observed in both SF and ST groups and was independent of the presence of metabolic syndrome and/or diabetes. The beneficial effect of atorvastatin was evident at 6 weeks, supporting the practice of early introduction of higher doses of atorvastatin in high-risk patients., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Importance of the Field: The present review is aimed at going over the pharmacological profile (and the clinical impact) of the emerging drugs involved in the management of patients with ST-elevation myocardial infarction (STEMI) in order to provide the cardiologists who deal with these patients in the early phase with the most recent evidence on this topic., Areas Covered in This Review: Anticoagulant and antiplatelet drugs are the main cornerstones of therapy in the treatment of STEMI patients undergoing primary percutaneous coronary intervention (PCI). The main issues that clinicians have to deal with are represented by balancing thrombotic and bleeding risks. In tailoring therapy, variables such as age, sex and previous disease should be taken into account, as well as ongoing complications (such as acute renal failure) that could affect hemostasis. Despite the well-established clinical benefits of antiplatelet agents, questions remain, mainly surrounding potential for variable platelet response, which are strictly related to non-genetic (i.e., diet, drug-drug interaction, clinical factors such as obesity, diabetes mellitus, and inflammation) and genetic determinants., What the Reader Will Gain: In their daily practice, cardiologists cannot abstract from the knowledge and updating on the ongoing research fields as well as the newly developed drugs, which they should frame in the very patient in the attempt to the develop a personalized medical strategy. These include also the pharmacological option(s) in the treatment of the reperfusion injury, the metabolic aspects and the stem cell therapy. TAKE HOME MASSAGE: In our opinion, the goal of ongoing research on the pharmacological approach to STEMI patients is a personalized medical strategy that relies on critical clinicians who merge newly developed acquisitions on this topic and a more complete, systemic and critical approach to the patient.

Background and Aim: Some studies recently reported a favourable effect for cis-9, trans-11 conjugated linoleic acid (CLA) on plasma lipoprotein profile of healthy subjects. Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep's milk naturally rich in CLA on several atherosclerotic biomarkers, in comparison with a commercially available cheese., Methods and Results: Ten subjects (6 F; 4 M) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA (intervention period) and for the same period a diet containing a commercially available cheese of the same quantity (placebo period). Consumption of the dairy product naturally rich in cis-9, trans-11 CLA determined a significant (p<0.05) reduction in inflammatory parameters such as interleukin-6 (pre: 8.08+/-1.57 vs. post: 4.58+/-0.94 pg/mL), interleukin-8 (pre: 45.02+/-5.82 vs. post: 28.59+/-2.64 pg/mL), and tumour necrosis factor-alpha (pre: 53.58+/-25.67 vs. post: 32.09+/-17.42 pg/mL) whereas no significant differences in the placebo period were observed. With regard to haemorheological parameters, the test period significantly ameliorated erythrocytes' filtration rate (pre: 7.61+/-0.71% vs. post: 9.12+/-0.97%; p=0.03) with respect to the placebo period. Moreover, a reduction in the extent of platelet aggregation, induced by arachidonic acid [pre: 87.8+/-1.76% vs. post: 77.7+/-3.56%; p=0.04] was observed during the test period in comparison with the placebo period., Conclusions: Dietary short-term intake of the tested dairy product naturally rich in cis-9, trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers., (Copyright 2009 Elsevier B.V. All rights reserved.)

The concept of risk in medicine varies according to different health settings and different times. At present, risk is considered, in the cardiovascular area, the probability of developing a clinical event through time computed on the basis of the quantification of the presence and of the interaction of different diseases and/or risk factors. The definition of risk factors in the biomedical field is here documented through time to show how recent clinical-epidemiological elements have been achieved. In the twentieth century many epistemological and methodological objectives have been attained with regard to the theoretical idea of risk and to the practical tools useful to modify it, and the example of the management of diabetes is furnished as documentation of this progress. Nonetheless, correct risk evaluation continues to remain a formidable challenge in the health scenario.

Introduction: Procalcitonin concentrations are considered as a component of the inflammatory response and as an acute-phase marker, after shock or tissue injury (i.e. burn, trauma, surgery) or infections and sepsis. No data are so far available on the dynamics of procalcitonin levels in patients with cardiogenic shock following ST-elevation myocardial infarction, with no clinical or laboratory sign of infection., Methods: We evaluated procalcitonin values every day during intensive cardiac care staying in ten cardiogenic shock patients admitted to our intensive cardiac care unit. NT-pro Brain Natriuretic Peptide, C Reactive Protein and APACHE II score were also assessed., Results: Six patients survived, whereas 4 patients died. A progressive reduction in procalcitonin values was observed in cardiogenic shock patients who survived, whereas the lack of changes in procalcitonin concentrations was documented in cardiogenic shock patients who died (survivors: slope = -3.76; dead: slope = -0.81, p=0.004). Furthermore, higher values of glycemia, NT-pro Brain Natriuretic Peptide and C Reactive Protein (as well as higher APACHE II scores) were detectable in dead patients in respect to survivors., Conclusions: In our preliminary study we observed that in patients with cardiogenic shock and no sign of infections a reduction of procalcitonin levels was detectable only in survivors. Moreover, higher values of NT- Brain Natriuretic Peptide, a marked systemic inflammation (higher values of C Reactive Protein) and higher severity score (as depicted by APACHE II) are associated with an ominous prognosis in cardiogenic shock patients.

Background: Deep vein thrombosis (DVT) is a major complication in intensive care units (ICU) but dedicated guidelines on its management are still lacking., Objectives and Methods: This study investigated the effect of a 1-year educational program for the implementation of DVT prophylaxis on the incidence of inferior limb DVT in a mixed-bed ICU that admits high-risk surgical and trauma patients, investigated during a first retrospective phase [126 patients, SAPS II score 42 (28-54)] and a following prospective phase [264 patients, SAPS II score II 41 (27-55)]. The role of baseline and time-dependent DVT risk factors in DVT occurrence was also investigated during the prospective phase., Results: The educational program on implementation of DVT prophylaxis was associated with a significant decrease in DVT incidence from 11.9% to 4.5% (P < 0.01) and in the mean length of ICU stay (P < 0.01). Combined with pharmacological prophylaxis, the use of elastic compressive stockings significantly also increased in the prospective phase (P < 0.01). The duration of mechanical ventilation, vasopressor administration and neuromuscular block were significantly different between DVT-positive and DVT-negative patients (P < 0.01). Multivariate analysis identified neuromuscular block as the strongest independent predictor for DVT incidence., Conclusion: One-year ICU-based educational programs on implementation of DVT prophylaxis were associated with a significant decrease in the incidence of DVT and also in the length of stay in ICU.

Background: Despite the importance of hand hygiene in reducing infection, healthcare worker compliance with hand hygiene recommendations remains low. In a previous study, we found a generally low level of compliance at baseline, with substantial differences between doctors and nurses and between hospital units. We describe here the results of our multimodal intervention intended to improve levels of healthcare worker hand hygiene., Methods: A 6-month, before-and-after, multimodal interventional study in five hospital units in Florence, Italy. We used direct observation to assess hand hygiene rates for doctors and nurses, focusing on hygiene before touching the patient. We explored reasons for unit variability via interviews of doctor and nurse leaders on the units., Results: Overall healthcare worker hand hygiene increased from 31.5% to 47.4% (p<0.001). Hand hygiene adherence among nurses increased from 33.7% to 47.9% (p<0.001); adherence among doctors increased from 27.5% to 46.6% (p<0.001). Improvement was statistically significant in three out of five units, and units differed in the magnitude of their improvement. Based on the interviews, variability appeared related to the "champion" on each unit, as well as the level of motivation each physician leader exhibited when the preintervention results were provided., Conclusions: Although overall healthcare worker adherence with hand hygiene procedures before patient contact substantially increased after the multimodal intervention, considerable variability-for both nurses and doctors and across the 5 units-was seen. Although adherence substantially increased, overall hand hygiene in these units could still be greatly improved.

Procalcitonin (PCT) is known to be a biological diagnostic marker for severe sepsis, or septic shock in critically ill patients. There are still contrasting data about a role of procalcitonin in patients with acute myocardial infarction or cardiogenic shock, and in those with acute coronary syndromes, that is, non-ST-elevation myocardial infarction or unstable angina. We evaluated plasma levels of procalcitonin and C-reactive protein (CRP) in 52 patients admitted to our intensive cardiac care unit (ICCU): 14 patients with cardiogenic shock (CS) following ST-elevation myocardial infarction (STEMI), 15 patients with uncomplicated ST-elevation myocardial infarction (STEMI), and 24 with non-ST-elevation myocardial infarction or unstable angina (NSTEMI/UA). In all patients, infective processes were excluded. Procalcitonin values were significantly higher in CS patients with respect to the other two subgroups (P < 0.001, P < 0.001) while CRP levels were higher than NSTEMI/UA patients (P < 0.001) but not with respect to STEMI patients (P = 0.063). No correlations were found in cardiogenic shock patients between CRP and PCT values (R = 0.02; P = 0.762, ns). Procalcitonin levels measured on ICCU admission are significantly higher in patients with cardiogenic shock following the acute myocardial infarction, and they are not correlated with those of CRP. The degree of myocardial ischemia (clinically indicated by the whole spectrum of ACS, from unstable angina to cardiogenic shock ST-elevation following myocardial infarction) and the related inflammatory-induced response are better reflected by CRP (which was positive in most acute cardiac care patients of all our subgroups), than by PCT which seems more reflective of a higher degree of inflammatory activation, being positive only in all CS patients.

Background: Postoperative organ dysfunction in conventional surgery for abdominal aortic aneurysm (AAA) is associated with a complex inflammatory reaction, with activation of coagulation and fibrinolysis. A prospective,observational study was performed to define the complex plasma proteomic changes after AAA repair and to identify factor(s) that may affect myocardial function in uncomplicated procedures., Methods: Ten patients undergoing infrarenal AAA repair were investigated. Eight subjects subjected to major abdominal surgery served as controls. Hemodynamic changes were continuously monitored by using the pressure recording analytical method technique. The time course of plasma proteins was investigated after induction of anesthesia and at different times after surgery (6 h, 12 h, 24 h, 36 h) by using two-dimensional difference gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and Western blot. The effects of plasma on the functional properties of isolated rat ventricular myocytes were also investigated., Results: In AAA patients alone, 18 spots were found to change more than two-fold in expression level, spot identification revealing an increased thrombin generation 6 h after surgery. At the same time cardiac cycle efficiency significantly reduced versus baseline (-0.5 +/- 0.9 vs. 0.18 +/- 0.3 in AAA patients, P < 0.01; 0.4 +/- 0.1 vs. 0.2 +/- 0.3 in control surgery, not significant; P < 0.01 group x time interaction at ANOVA). Plasma obtained 6 h after AAA surgery dose-dependently inhibited contractile function of control rat myocytes (percent shortening fell by 51% with 10% of AAA plasma and was abolished with 20% of AAA plasma, P < 0.001 for both). The inhibitory response was abolished by thrombin antagonism., Conclusions: These findings show for the first time the possible role of thrombin generation within the complex activation of inflammatory response in causing hemodynamic instability in the early postoperative period after AAA surgery.

Background: Single-pill amlodipine/atorvastatin targets the two most common modifiable cardiovascular risk factors, hypertension and dyslipidaemia. We evaluated the clinical utility of this single pill to help patients across Europe and Canada achieve country-specific targets for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C)., Design: Two 16-week, open-label studies conducted in 122 study centres across the United Kingdom and Canada (JEWEL 1) and 113 centres across 11 European countries (JEWEL 2)., Methods: Patients with uncontrolled BP and controlled/uncontrolled LDL-C qualifying for treatment according to local governing guidelines were administered single-pill amlodipine/atorvastatin with appropriate lifestyle modification. Eight dosages of amlodipine/atorvastatin (5/10-10/80 mg) were titrated to achieve country-specific BP and LDL-C targets. The primary outcome was the percentage of patients reaching country-specific BP and LDL-C targets in 16 weeks., Results: Among 2245 patients enrolled in the studies (JEWEL 1, n = 1138; JEWEL 2, n = 1107), 62.9% in JEWEL 1 and 50.6% in JEWEL 2 achieved both country-specific BP and LDL-C goals. BP was reduced by 20.4/10.7 and 21.8/12.6 mmHg in JEWEL 1 and JEWEL 2, respectively, and reductions in LDL-C were 0.90 mmol/l (34.8 mg/dl) and 1.09 mmol/l (42.2 mg/dl), respectively. The most common adverse events were peripheral oedema (11.0%), joint swelling (2.9%) and headache (2.9%), of which, only oedema was linked to study treatment., Conclusion: Single-pill amlodipine/atorvastatin is an effective and well-tolerated treatment, which in a real-world setting helped more than half of the patients achieve both BP and LDL-C targets as recommended by local guidelines. Although fewer patients met their goals in JEWEL 2 than JEWEL 1, reductions in BP and LDL-C were slightly greater in JEWEL 2, suggesting that the observed differences are likely because of more stringent targets in Europe than in the UK/Canada.

Background: PPARgamma (PPARg) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two PPARg common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to PPARg coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS)., Methods: We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations., Results: We identified 7 new and 2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls., Conclusions: The protective role of 93695C>T polymorphism in PPARg promoter in ACS suggests that PPARg genetic variants may affect the susceptibility to atherosclerotic diseases.

Summary Introduction: Protein Z is a vitamin K-dependent protein that serves as a cofactor for the inhibition of activated factor X by the serpin protein Z-dependent protease inhibitor (ZPI). Protein Z plasma levels have been shown to be reduced in patients with peripheral arterial disease (PAD), but ZPI levels have not yet been reported. The aim of this study was to more fully assess the protein Z-ZPI system in individuals with atherosclerosis selected by the presence of symptomatic PAD., Materials and Methods: Protein Z and ZPI levels were determined in 95 PAD patients (73 males; 22 females) [median age: 73 years (range, 50-86 years)] and in 190 controls comparable for age and gender. Protein Z was measured using a commercial immunoassay, and ZPI was measured with a homemade immunoassay and a functional assay., Results: Protein Z antigen, ZPI antigen and ZPI function were found to be significantly lower in PAD patients with respect to controls [protein Z, median 72.5% (range: 3.4-123.7%) vs. 90.7% (range: 32.1-203.2%), P < 0.0001; ZPI antigen, 86.1% (range: 25.1-149.5%) vs. 93.2% (range: 48.9-171.3%), P = 0.004; ZPI function, 83.5% (range: 21.1-135.2%) vs. 97.2% (range: 50.5-175.5%), P < 0.0001]. The lowest tertiles of protein Z antigen [odds ratio (OR) 5.4, 95% confidence interval (CI) 2.2-13.5, P < 0.0001] and ZPI function (OR 2.4, 95% CI 1.1-5.5, P = 0.03) were associated with PAD on multivariate analysis after adjustment for age, gender, and traditional cardiovascular risk factors. A significant inverse relationship was also observed between protein Z and ZPI levels and the number of traditional cardiovascular risk factors and the clinical severity of disease (Fontaine stage)., Conclusions: Low levels of protein Z antigen and protein Z activity are significantly associated with the occurrence and severity of atherosclerotic PAD.

This multidisciplinary guideline provides an overview of the current evidence on the benefits obtained by endoarterectomy and stenting for the surgical treatment of patients with symptomatic and asymptomatic carotid stenosis. A hundred forty-six authors, 37 Italian scientific societies and two Italian patients' associations participated in drafting the Stroke Prevention and Educational Awareness Diffusion (SPREAD) document, which has become the national guideline for the prevention and treatment of stroke in Italy. For the surgical therapy section of this document, the main trials on carotid endoarterectomy and stenting were critically reviewed following The Scottish Intercollegiate Guideline Network Oxford Centre for Evidence-Based Medicine methodology in order to formulate recommendations and syntheses for these procedures. The final document was peer reviewed and approved by all the participants. Recommendations and syntheses are presented for the referral of patients to either carotid endoarterectomy or stenting on the basis of whether carotid stenosis is symptomatic or asymptomatic, on the presence of various risk factors such as degree of arterial narrowing, and on concomitant pathology (cardiopathy and acute stroke).

Background: Pericardial pathology still has challenging diagnostic and treating issues. To reduce surgical trauma and pain for the patient, the authors developed a totally endoscopic echo-guided approach for both diagnostic and operative pericardioscopy., Methods: Three steps moved from animal model (8 pigs) through concomitant open-chest interventions (7 patients) to closed-chest interventions for 10 patients with a diagnosis of severe pericardial effusion., Results: A lesion of the right ventricle in one patient (10%) due to imperfect preoperative pericardial visualization needed sternotomy for repair. All the patients, except the aforementioned one, underwent surgery with local anesthesia or mild sedation. No method-related mortality was reported., Conclusion: The closed-chest nonintrapleural approach to the pericardium may represent an evolution, with a positive impact on the treatment of this pathology. Therapeutic maneuvers with rigid instruments in nonintubated patients are possible. Accurate patient selection and technical refinement should increase the safety and effectiveness of the method.

Background: Percutaneous coronary intervention (PCI) is considered to be the optimal type of revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the long-term effectiveness of this procedure can be reduced by restenosis. This investigation was aimed at a prospective evaluation, in a group of STEMI patients of "the real world" (not involved in randomised trials), of the angiographic restenosis rate at a 6-month follow-up, and at identifying the relationship between restenosis and the patients' characteristics., Materials and Methods: Our study population consisted of 123 patients with STEMI submitted to primary PCI to then undergo stress echocardiography 3 months after PCI and an angiographic evaluation at a 6-month follow-up., Results: a) In real life the restenosis rate is quite high (42.3%); b) no correlation was found between patients' clinical characteristics and restenosis; c) restenosis rate was higher in patients with bare metal stents than in those with drug-eluting stents (55.8% vs. 11.1%; p<0.001); in patients with longer stents (21.6+/-8.62 vs 18.1+/-6.34 mm, p=0.015) and when more than one stent was implanted. Moreover, a consistent number of patients showed restenosis though asymptomatic., Conclusions: Our data suggest that primary PCI is associated with a high incidence of angiographic restenosis. No correlation was found between patients' clinical characteristics and restenosis. The length and the number of implanted stents seem to be associated with a more probable restenosis at six-month angiographic evaluation. Drug-eluting stent implantation seems to be associated with a lower incidence of restenosis even in STEMI patients.

Background: Residual platelet reactivity (RPR) on antiplatelet therapy in ischemic heart disease patients is associated with adverse events. Clinical, cellular and pharmacogenetic factors may account for the variable response to antiplatelet treatment., Objective: We sought to explore the interplay of multiple pro-inflammatory and anti-inflammatory cytokines with platelet function in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy., Methods: In 208 ACS patients undergoing PCI on dual antiplatelet therapy we measured platelet function by platelet aggregation with two agonists [1mM arachidonic acid (AA) and 10muM ADP]. IL-1beta, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, TNF-alpha, and VEGF levels were determined by using the Bio-Plex cytokine assay (Bio-Rad Laboratories Inc., Hercules, CA, USA). We defined patients with RPR those with platelet aggregation by AA >or=20% and/or ADP (10micromol) >or=70%., Results: We documented a significant association between IP-10, IFN-gamma, IL-4 and RPR by both AA- and ADP-induced platelet aggregation after adjustment for age, sex, cardiovascular risk factors, ejection fraction, BMI, vWF and CRP. Patients with pro-inflammatory cytokines not compensated by anti-inflammatory cytokines had higher risk of RPR by both AA and ADP (AA: OR=3.85, 95% CI 1.52-9.74; ADP: OR=2.49, 95% CI 1.33-4.68) with respect to patients with balanced anti-/pro-inflammatory cytokines. Patients with anti-inflammatory response overwhelming pro-inflammatory response have lower risk of RPR (AA: OR=0.55, 95% CI 0.28-1.06; ADP: OR=0.47, 95% CI 0.26-0.87)., Conclusion: Our study provides new insights into the interplay of anti-/pro-inflammatory cytokines with platelet hyper-reactivity in high-risk patients.

Purpose: To investigate whether using an algorithm to select the starting dose of a statin according to baseline and target LDL-cholesterol (LDL-C) values would facilitate achieving lipid targets in patients with diabetes or the metabolic syndrome., Methods: Two 12-week, prospective, open-label trials enrolled 2717 high-risk subjects, of whom 1024 had diabetes and 1251 had metabolic syndrome. Subjects with LDL-C between 100 and 220 mg/dL (2.6-5.7 mmol/L) were assigned a starting dose of atorvastatin (10, 20, 40, or 80 mg/d) based on LDL-C level and status of statin use at baseline (statin-free [SF] or statin-treated [ST]), with a single uptitration at 6 weeks, if required., Results: Among patients with diabetes, 81% of SF subjects (82%, 84%, 82%, and 76% with 10, 20, 40, and 80 mg, respectively) and 60% of ST subjects (61%, 68%, and 47% with 20, 40, and 80 mg, respectively) achieved LDL-C target. Among patients with metabolic syndrome, 78% of SF subjects (81%, 84%, 82%, and 66% with 10, 20, 40, and 80 mg, respectively) and 57% of ST subjects (58%, 70%, and 47% with 20, 40, and 80 mg, respectively) achieved LDL-C target. Among ST subjects, we observed reductions in LDL-C with atorvastatin beyond those achieved with other statins used at baseline in patients with diabetes and patients with metabolic syndrome. Atorvastatin was well tolerated., Conclusions: The ACTFAST studies confirm that a targeted starting dose of atorvastatin allows most patients with type 2 diabetes or the metabolic syndrome to achieve their LDL-C target safely with the initial dose or just a single titration. This therapeutic strategy may help overcome the treatment gap still observed in the treatment of lipids in diabetes.

Doctor-patient communication is an issue that is attracting more and more attention within the international scientific community, stimulating an interest involving many different health contexts, from academic to medico-legal ones. In the academic setting, the insertion of health communication courses into the curriculum has been a recent renovation, given that in the past such training was not considered a necessary formative step. In the medico-legal scenario, among the main causes of legal action is an incorrect, incomplete or non-existent transmission of information. Doctor-patient communication is therefore an extremely up-to-date topic, the problematic of which may already be discerned in Western medicine in the so-called Hippocratic Oath. In this paper the historical roots and the evolution through time of doctor-patient communication are discussed, together with the description of the predominant models of communication of the past (the physician-centred and the disease-centred approaches) and of the present (the patient-centred and the person-centred paradigms). Nowadays complete, correct and comprehensible communication is a primary exigency for the physician, for the patient/person and for all the organizational levels of the sanitary system. Every physician and, more in general, every health operator, must therefore learn to communicate effectively in the course of his/her medical training, and must continually refine this capacity during his/her professional career.

Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

Italy lacks standardized specialty training in emergency medicine. There is no system of national or regional accreditation of the knowledge base or skill set of physicians working in regional emergency departments (ED), which results in variability of emergency medical care delivery not only between hospital EDs but also within individual EDs. To address this need, the Tuscan Minister of Health chose to develop a partnership with emergency medicine specialists from the United States to help expedite the growth of the specialty in Tuscany. The collaboration called the Tuscan Emergency Medicine Initiative consists of the regional health care service, the Tuscan university system, Harvard Medical International, and the Beth Israel Deaconess Medical Center Department of Emergency Medicine. We describe that effort and process, with an expectation of more than 625 physicians completing the program by June 2008.

Adiponectin is known to play a role in fatty acid and glucose metabolism through a change in insulin sensitivity and activation of fuel oxidation by AMP-activated protein kinase. Adiponectin can be considered an important factor able to modulate the adipovascular axis which, through genomic and environmental influences, affects the cardiovascular risk milieu, from the pre-metabolic syndrome-- through the metabolic syndrome--to the overt atherosclerotic process and its clinical manifestations. Hypoadiponectinaemia can be viewed as an early sign of a complex cardiovascular risk factor predisposing to the atherosclerosis process as well as a contributing factor accelerating the progress of the atherosclerotic plaque. In addition, adiponectin per se holds a protective role thanks to its anti-inflammatory and antiatherogenic properties. The early identification of patients "at cardiovascular risk" means in the current practice to search for indexes of metabolic derangements and pro-inflammatory status (adiponectin) from adolescence and childhood.

Background: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients., Objectives and Methods: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5'-diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 micromol L(-1) ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients., Results: Cut-off values for identifying RPR were: > or = 54% and > or = 66% for LTA induced by 2 and 10 micromol L(-1) ADP respectively, and > or = 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was > or = 68 s. RPR was detected in 25.1% of patients by 2 mumol L(-1) ADP-induced LTA (ADP-LTA), in 23.2% by 10 micromol L(-1) ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 micromol L(-1) ADP. The correlation was similar but the agreement was better between VerifyNow and 10 micromol L(-1) ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays., Conclusions: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.