Expression of angiogenesis related factors in glioblastoma and peritumor tissue

Glioblastoma (GBM) is a lethal brain glial tumor characterized by extensive angiogenesis that is mostly triggered by tumor hypoxia. We previous reported that in GBM and in peritumor areas, endothelial cells expressed CD105, which probably marks newly formed vessels with a quite similar morphology. In this study, with the aim of better understanding the involvement of angiogenesis in tumor progression, we analyzed, by immunohistochemistry, the expression of Hypoxia-inducible factor (HIF) 1α and 2α, VEGF and its receptors (VEGFR-1 and -2) in GBM and in peritumor tissue. Twenty two patients were enrolled in this study. Tissue specimens were derived from enhanced lesion (first area) and white matter at a distance ≤1 mm from the tumor edge (second area). Immunoreactivity for all markers was detected not only in the tumor but also in the peritumor tissue and it was present in neoplastic cells, in endothelium and in apparently normal glial cells. HIF1α and 2α expression was mainly confined in the nuclei. VEGF, localized in the cytoplasm, showed diffuse expression with an intense staining in GBM. VEGFR-1 and 2 immupositivity was localized especially to the cell membrane and also to the cytoplasm, as expected. All molecule staining was evident in a heterogeneous manner and there was no significant difference in the expression marker levels between the first and second area also in relation to the presence or absence of tumor cells in the second area. No significant correlation was found between the above molecule expression and survival time. In conclusion, we demonstrated that HIF1α, HIF2α, VEGF and VEGFR-1 and -2 are present in peritumor area, probably reflecting perturbations of oxygenation emanating from the tumor microenvironment. Since, unfortunately, the response to anti-VEGF therapy is transient and the majority of patients eventually relapse, the gain of a deeper knowledge of the above molecule role, in the peritumor tissue, may lead to consider them as the target for new treatment regimens to counteract angiogenesis. Supported by FIRB “Accordi di Programma” 201

Extra Virgin Olive Oil Extracts Modulate the Inflammatory Ability of Murine Dendritic Cells Based on Their Polyphenols Pattern: Correlation between Chemical Composition and Biological Function

Extra virgin olive oil (EVOO) represents one of the most important health-promoting foods whose antioxidant and anti-inflammatory activities are mainly associated to its polyphenols content. To date, studies exploring the effect of EVOO polyphenols on dendritic cells (DCs), acting as a crosstalk between the innate and the adaptive immune response, are scanty. Therefore, we studied the ability of three EVOO extracts (cv. Coratina, Cima di Mola/Coratina, and Casaliva), characterized by different polyphenols amount, to regulate DCs maturation in resting conditions or after an inflammatory stimulus. Cima di Mola/Coratina and Casaliva extracts were demonstrated to be the most effective in modulating DCs toward an anti-inflammatory profile by reduction of TNF and IL-6 secretion and CD86 expression, along with a down-modulation of Il-1β and iNOS expression. From factorial analysis results, 9 polyphenols were tentatively established to play a synergistic role in modulating DCs inflammatory ability, thus reducing the risk of chronic inflammation

A population-based study on myelodysplastic syndromes in the Lazio Region (Italy), medical miscoding and 11-year mortality follow-up. The Gruppo Romano-Laziale Mielodisplasie experience of retrospective multicentric registry

Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer registries because of the lack of reporting and the use of different classifications of the disease. In the Lazio Region, data from patients with a confirmed diagnosis of MDS, treated by a hematology center, have been collected since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the second MDS registry existing in Italy. This study aimed at evaluating MDS medical miscoding during hospitalizations, and patients' survival. For these purposes, we selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked with two regional health information systems: the Hospital Information System (HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the 442 patients who were hospitalized at least once during the study period, 92% had up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes scored like MDS, code 238.7 of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The rate of death during a median follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML) was the first cause of mortality, interestingly a relevant portion of deaths is due to cerebro-cardiovascular events and second tumors. This study highlights that MDS diagnosis and treatment, which require considerable healthcare resources, tend to be under-documented in the HIS archive. Thus we need to improve the HIS to better identify information on MDS hospitalizations and outcome. Moreover, we underline the importance of comorbidity in MDS patients' survival

Treatment persistence with aripiprazole once monthly: a 4-year follow-up

Objectives: Treatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months. Methods: This was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication. Results: Study subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit. The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM. Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162-0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician's choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues. Conclusions: In subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations

Does Clinical Governance influence the quality of medical records?

Background. Clinical Governance (CG) is a validated framework for continuous quality improvement in health care settings. Quality medical records may reflect the quality of care delivered and are a viable tool to implement CG skills. Aim. Aim of this study is to investigate the correlation between the level of implementation of CG dimensions and the quality of medical records. Material and methods. A cross-sectional study was carried out in an Italian Teaching Hospital. CG implementation levels were quantified through a systematic methodology (OPTIGOV©). The overall quality of medical records was measured through a revised version of a National-validated scale. A multiple linear regression model was used to test the likely influence of all the variables constituting the OPTIGOV evaluation on the quality of medical records. 47 hospital wards and 1458 medical records were assessed. Results. A significant and positive association between the quality of medical records and the accountability score (β = 0.15; p < 0.01) and the clinical audit score (b = 0.11; p = 0.02), was found. Conversely, the risk management score shown a negative and significant correlation (b = -0.17; p < 0.01). This study confirms that CG plays a central role in driving quality improvement and advocates a systematic implementation of such an approach within healthcare organizations.

Association between Vitamin D Receptor Gene Polymorphisms and Periodontal Bacteria: A Clinical Pilot Study

Abstract: Background: Periodontitis is an inflammatory disease caused by microorganisms involving the supporting tissues of the teeth. Gene variants may influence both the composition of the biofilm in the oral cavity and the host response. The objective of the study was to investigate the potential correlations between the disease susceptibility, the presence and the quantity of periodontopathogenic oral bacterial composition and the VDR gene polymorphisms. Methods: Fifty (50) unrelated periodontal patients and forty-one (41) healthy controls were selected for genomic DNA extraction. DNA concentration was measured and analyzed. The periodontopathogenic bacterial species were identified and quantified using a Real Time PCR performed with species-specific primers and probes. Results: Genotype distribution showed a different distribution between the groups for BsmI rs1544410 genotypes (p = 0.0001) with a prevalence of the G(b) allele in periodontal patients (p = 0.0003). Statistical significance was also found for VDR TaqI rs731236 (p ≤ 0.00001) with a prevalence of the T(T) allele in periodontal patients (p ≤ 0.00001). The average bacterial copy count for the periodontitis group was significantly higher than that of control group. Dividing patients into two groups based on high or low bacterial load, FokI rs2228570 T allele (f) was statistically more represented in patients with high bacterial load. Conclusions: The findings of the study suggest the involvement of the VDR gene BsmI and TaqI polymorphisms in periodontal disease, while FokI and BsmI may be involved in determining an increased presence of periodontopathogens

Activated ERK1/2 expression in glioblastoma multiforme and in peritumor tissue

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