In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts.

The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR.The amount of proteins characteristic for cardiac cells (alpha-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively) inclines toward an increase in both alpha-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart

A Systematic Review of Meta-Analyses on Gene Polymorphisms and Gastric Cancer Risk

BACKGROUND: Individual variations in gastric cancer risk have been associated in the last decade with specific variant alleles of different genes that are present in a significant proportion of the population. Polymorphisms may modify the effects of environmental exposures, and these gene-environment interactions could partly explain the high variation of gastric cancer incidence around the world. The aim of this report is to carry out a systematic review of the published meta-analyses of studies investigating the association between gene polymorphisms and gastric cancer risk, and describe their impact at population level. Priorities on the design of further primary studies are then provided. METHODS: A structured bibliographic search on Medline and EMBASE databases has been performed to identify meta-analyses on genetic susceptibility to gastric cancer, without restriction criteria. We report the main results of the meta-analyses and we describe the subgroup analyses performed, focusing on the detection of statistical heterogeneity. We investigated publication bias by pooling the primary studies included in the meta-analyses, and we computed the population attributable risk (PAR) for each polymorphism. RESULTS: Twelve meta-analyses and one pooled-analysis of community based genetic association studies were included, focusing on nine genes involved in inflammation (IL-1beta, IL-1RN, IL-8), detoxification of carcinogens (GSTs, CYP2E1), folate metabolism (MTHFR), intercellular adhesion (E-cadherin) and cell cycle regulation (p53). According to their random-Odds Ratios, individuals carrying one of the IL-1RN *2, IL-1beta -511T variant alleles or homozygotes for MTHFR 677T are significantly at higher risk of gastric cancer than those with the wild type homozygote genotypes, showing high PARs. The main sources of heterogeneity in the meta-analyses were ethnicity, quality of the primary study, and selected environmental co-exposures. Effect modification by Helicobacter pylori infection for subjects carrying the unfavourable variant of IL-1 polymorphisms and by low folate intake for individuals homozygotes for MTHFR 677T allele has been reported, while genes involved in the detoxification of carcinogens show synergistic interactions. Publication bias was observed (Egger test, p = 0.03). DISCUSSION: The published meta-analyses included in our systematic review focused on polymorphisms having a small effect in increasing gastric cancer risk per se. Nevertheless, the risk increase by interacting with environmental exposures and in combination with additional unfavourable polymorphisms. Unfortunately meta-analyses are underpowered for many subgroup analyses, so additional primary studies performed on larger population and collecting data on environmental and genetic co-exposures are demanded

A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to analyze the combined effects of selected <it>p</it>53 and <it>p</it>73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.</p> <p>Methods</p> <p>Two hundred and eighty-three cases and 295 hospital controls were genotyped for <it>p</it>53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and <it>p</it>73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the <it>p</it>53 polymorphisms, and a gene-gene interaction analysis for the combined effects of <it>p</it>73 G4C14-to-A4T14 and <it>p</it>53 polymorphisms.</p> <p>Results</p> <p>We found a significant increased risk of SCCHN among individuals with combined <it>p</it>73 exon 2 G4A and <it>p</it>53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the <it>p</it>53 exon 4-<it>p</it>53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying <it>p</it>73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among <it>p</it>53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).</p> <p>Conclusion</p> <p>Our study provides for the first time evidence that individuals carrying <it>p</it>53 exon 4 and <it>p</it>53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of <it>p</it>73 exon 2 G4C14-to-A4T14 and <it>p</it>53 intron 3 variant allele. Larger studies are required to confirm these findings.</p

ISYDE-2008 Study presentation The Italian Survey on cardiac rehabilitation: a snapshot of current cardiac rehabilitation programmes and provides in Italy

The Italian Society of Cardiac Rehabilitation and Prevention (GICR) has developed the ISYDE-2008 survey with the purpose to take a detailed snapshot in terms of number, distribution, facilities, staffing levels, organization, and programme details of CR units in Italy and to compare actual provision with the recommendation of National GL for CR and secondary prevention.The study will be carried out with a web-based questionnaire running on the GICR website in 2 weeks from Jan. 28 to Feb. 10, 2008. The first part of the questionnaire is designed to collect information on the institutional organization of the CR unit, on its location and functional relationships within the hospital, on the number of beds for inpatient CR units and hours of activity for outpatient and home–based services, on the composition of the core and multidisciplinary teams, and finally on the components of CR programmes.In the second part of the survey, CR directors will be requested to report for each patient discharged during the 2 weeks of the study, indications for admission to CR, time of enrolment, comorbidity, complications, risk profile, diagnostic procedures, exercise and educational programme, discharge modalities, treatment at discharge and follow-up schedule.More than 2300 pts are expected to enter in the survey, whose results depicting the status of CR in Italy will be available within April 2008

The Italian Survey on Cardiac Rehabilitation - 2008 (ISYDE-2008). Part 3. National availability and organization of cardiac rehabilitation facilities. Official report of the Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiolog

From January 28th to February 10th 2008, the Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiology (IACPR-GICR) conducted the ISYDE- 2008 study, the primary aim of which was to take a detailed snapshot of cardiac rehabilitation (CR) provision in Italy – in terms of number and distribution of facilities, staffing levels, organization and setting – and compare the actual CR provision with the recommendations of national guidelines for CR and secondary prevention. The secondary aim was to describe the patient population currently being referred to CR and the components of the programs offered. Out of 190 cardiac rehabilitation centers existing in Italy in 2008, 165 (87%) took part in the study. On a national basis, there is one CR unit every 299,977 inhabitants: in northern Italy there is one CR unit every 263,578 inhabitants, while in central and southern Italy there is one every 384,034 and 434,170 inhabitants, respectively. The majority of CR units are located in public hospitals (59%), the remainder in privately owned health care organizations (41%). Fifty-nine percent are located in hospitals providing both acute and rehabilitation care, 32% are in specifically dedicated rehabilitation structures, while 8% operate in the context of residential long term care for chronic conditions. Almost three-quarters of CR units currently operating are linked to dedicated cardiology divisions (74%), 5% are linked to physical medicine and rehabilitation divisions, 2% to internal medicine, and 19% to cardiac surgery and other divisions. Inhospital care is provided by 62.4% of the centers; outpatient care is provided on a day-hospital basis by 10.9% of facilities and on an ambulatory basis by 20%. The CR units are led in 86% of cases by a cardiologist and in only 14% of cases by specialists in internal medicine, geriatrics, physical medicine and rehabilitation, pneumology or other disciplines. In terms of staffing, each cardiac rehabilitation unit has 4.0±2.7 dedicated physicians (range 1-16, mode 2), 10.1±8.0 nurses, 3.3±2.5 physiotherapists (range 0 – 20; 16% of services have no physiotherapist in the rehabilitation team), 1.5±0.8 psychologists, and a dietitian (present in 62% of CR units). Phase II CR programs are available in 67.9% of cases in residential (inpatient) and in 30.9% of cases in outpatient (day-hospital and ambulatory) settings. Phase III programs are offered by 56.4% of the centers in ambulatory outpatient regime, and on an at home basis by 4.8% with telecare supervision, 7.3% without. Long term secondary prevention follow up programs are provided by 42.4% of CR services

Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment

Psoriasis is a type I interferon-driven T cell–mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15+ neutrophils and CD123+/BDCA-2+/ChemR23+ pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development

ICAROS (Italian survey on CardiAc RehabilitatiOn and Secondary prevention after cardiac revascularization): temporary report of the first prospective, longitudinal registry of the cardiac rehabilitation network GICR/IACPR

The Italian survey on CardiAc RehabilitatiOn and Secondary prevention after cardiac revascularization (ICAROS) was a multicenter, prospective, longitudinal survey carried out by the Italian Association on Cardiovascular Prevention and Rehabilitation (GICR/IACPR) in patients on completion of a CR program after coronary artery by pass grafting (CABG) and percutaneous coronary intervention (PCI). The aim was to evaluate in the short and medium term: i) the cardioprotective drug prescription, modification and adherence; ii) the achievement and maintenance of recommended lifestyle targets and risk factor control and their association with cardiovascular events; iii) the predictors of non-adherence to therapy and lifestyle recommendations. The ICAROS results offers a portrait of the “real world” of clinical practice concerning patients after CABG and PCI, and stresses the need to improve secondary prevention care after the index event: many patients after revascularization leave the acute wards without an optimal prescription of preventive medication but the prescription of cardiopreventive drugs and risk factors control is excellent after completion of a CR program. Following CR, the maintenance of evidence-based drugs and lifestyle adherence at one year is fairly good as far as the target goals of secondary prevention are concerned, but to investigate the influence of CR on long term outcome longer term studies are required. Last, but not least, ICAROS shows that some characteristics (PCI as index event, living alone, poor eating habits or smoking in young age, and old age, in particular with comorbidities) may identify patients with poor behavioral modification in the medium term follow-up and in these patients further support may be warranted. In conclusion, participation in CR results in excellent treatment after revascularization, as well as a good lifestyle and medication adherence at 1 year and provides further confirmation of the the benefit of secondary prevention

After ACC/AHA and ESC Guidelines Pre-operative cardiological evaluation in non-cardiac surgery: certainties, controversial areas and opportunities for a team approach

A standardized and evidence-based approach to the cardiological management of patients undergoing noncardiac surgery has been recently defined by Task Forces of the American Heart Association (AHA), American College of Cardiology (ACC) and the European Society of Cardiology (ESC) that published their guidelines in 2007 and 2009, respectively. Both the recommendations moved from risk indices to a practical, stepwise approach of the patient, which integrates clinical risk factors and test results with the estimated stress of the planned surgical procedure. In the present paper the main topics of the guidelines are discussed, and moreover, emphasis is placed on four controversial issues such as the use of prophylactic coronary revascularization in patients with myocardial ischemia, the perioperative management of patients with congestive heart failure, the routine use of betablockers and statins, and, finally, the management of antiplatelet therapies in patients with coronary stents. In addition to promoting an improvement of immediate perioperative care, the preoperative cardiological evaluation should be a challenge for identifying subjects with enhanced risk of cardiovascular events, who should be treated and monitored during a long-term follow-up

The Italian Network for Heart Failure five years after the publication of the Italian “Consensus conference on the management of heart failure”

In the year 2006 the Italian Association of Hospital Cardiologists (ANMCO) promoted a Consensus Conference among professional Scientific Societies in order to redefine the role and core responsibilities of each health professionals involved in heart failure management in a novel integrated network. Five years later, a questionnaire has been proposed to each Italian Regional President of the Association, in order to assess the implementation of the proposed management strategies in the different clinical scenarios of the Italian Regions. Although the Document utilization is not homogeneous through Italy, it is still considered a valuable tool of work