Ensuring sample quality for biomarker discovery studies - Use of ict tools to trace biosample life-cycle

The growing demand of personalized medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological material and its accompanying data are collected, handled and stored in accordance with standard operating procedures (SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life-cycle can be recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research facilities and will represent the starting point of all future personalized medicine-based clinical trials

Association between serum carcinoembryonic antigen and endothelial cell adhesion molecules in colorectal cancer

OBJECTIVES: To analyse the behaviour of pre-surgical serum levels of soluble (s)E-selectin and vascular cell adhesion molecule (sVCAM) in patients with colorectal cancer, and to evaluate their possible correlation with carcinoembryonic antigen (CEA), pro-inflammatory cytokines and clinicopathological features with respect to their prognostic value in predicting metastatic disease. METHODS: Pre-surgical serum levels of sE-selectin, sVCAM, interleukin-6 (IL-6), IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and CEA were measured in 194 patients with colorectal adenocarcinoma, 40 patients with benign colorectal diseases and 59 healthy subjects. RESULTS: sE-selectin, sVCAM, TNF-alpha and IL-6 levels were significantly higher in patients with colorectal cancer compared to either healthy subjects or patients with benign disease. Positive rates of sE-selectin, sVCAM and TNF-alpha levels were significantly associated with Dukes' stage D colorectal cancer, and all three variables were independently associated to the presence of distant metastases. Positive sE-selectin, sVCAM and TNF-alpha levels were significantly associated to CEA. TNF-alpha and CEA levels were independently related to the presence of positive levels of sE-selectin and/or sVCAM. CONCLUSIONS: Our findings suggest that the host inflammatory response to cancer cells, and/or their released products (i.e. CEA), might be responsible (via cytokine release) for the elevation in circulating adhesion molecules in patients with colorectal cancer

Clinical utility of plasma KRAS, NRAS and BRAF mutational analysis with real time PCR in metastatic colorectal cancer patients -The importance of tissue/plasma discordant cases

Background: Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity. Methods: mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were enrolled in the present prospective study. PL mutations were assessed within 2 weeks before chemotherapy start with real time PCR and correlated with T status and Progression free survival (PFS). Clinical and biochemical variables including also total number of tumor lesions (TNL) and the sum of maximum diameter (SMD) of all lesions were assessed as potential predictors of T/PL discordance. RESULTS: Among 45 enrolled patients, all BRAF mutations were concordant between T and PL and there were 20% of patients RAS discordant: 9% wild type in T and mutated in PL and 11% mutated in T and wild type in PL. T mutations were significantly associated to median PFS (mPFS of 4.5, 8.3 and 22.9 months for T-BRAF mutated, T-RAS mutated, and T-wild type patients, respectively, p for trend 0.00014). PL mutations further refined prognosis: RAS wild type in T and mutated in PL had significantly shorter PFS than concordant RAS wild type in T and PL: mPFS 9.6 vs. 23.3 months, respectively, p = 0.02. Patients RAS mutated in T and wild type in PL had longer PFS than concordant RAS mutated in T and PL: 24.4 vs. 7.8 months, respectively, p = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, p = 0.0008). At multivariate logistic regression analysis TNL and SMD were significant predictors of discordant cases. Conclusions: PL mutational analysis allows a better prognostication than T analysis alone and could help in mCRC treatment management

Clinical care pathway program versus open-access system: a study on appropriateness, quality, and efficiency in the delivery of colonoscopy in the colorectal cancer

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed

Position Paper of the Italian Association of Medical Oncology on Early Palliative Care in Oncology Practice (Simultaneous Care)

n/

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies

Cooperative Student Assessment Method: an Evaluation Study

Training through the Internet poses a series of technical problems and pedagogical issues. Traditional training is not indiscriminate but takes on different forms according to the needs of the subject being trained and the context where such training occurs. In order to make the systems adaptable in this way, a model of the studentâ??s characteristics - the student model - has to be set up, maintained and updated. However, there are many difficulties involved in obtaining sufficient information to create an accurate student model. One way to solve this problem is to involve students in the student modeling process, stimulating them to provide the necessary information by means of a dialog in which the student and system build the student model according to a collaborative process. The present work describes a cooperative student modeling method (Cooperative Student Assessment - CSA) which builds a joint system-student assessment of studentâ??s activities on the basis of the studentâ??s self-assessment ability estimation and a prototype system for children, addressing the learning of fractions, in which CSA is implemented. The article also reports the result of an experimentation carried out with learners attending primary school aiming at evaluating the effectiveness of involving students in the assessment process by comparing two versions of the same system: one using cooperative student modeling and the other the traditional overlay model

Riuso e valorizzazione dei resti monastici dell'XI-XII secolo nei territori dell'Alta Irpinia e del Vulture: verso un'idea generale di itinerari turistico-culturali per le aree interne della Campania e della Basilicata.

Monasticism was one of the most authoritative civilizing forces in Europe since from the fourth and fifth centuries; coming from the east, it promulgated to our continent and it has been subjected - and, at the same time, inducing - deep changings. The order of the Benedictines remained for a long time the principal, and Charlemagne relianced to it the role of stability factor for a significant part of the territory subjugated to his government. The form and structure of Romanesque churches are the result of a man's impulse to translate his spiritual life into architecture in a search for: • solidity and robustness • simplicity • geometric rigor. The Abbey of Goleto, near Sant'Angelo dei Lombardi (AV), the Cathedral and Bell tower of Melfi (PZ, the Badia di San Lorenzo at Tufara in Pescopagano (PZ) are some examples of this important cultural heritage of our territory. In this contribution we propose to consider some of these sites and to investigate their architectural typology, outlining hypothesis of enhancement in the framework of a new system of touristic itineraries, conceived as an intangible infrastructure for a new vision of enhancement of the territory and it cultural heritage in a broad sense (religion, history, architecture, eno-gastronomy, agriculture, crafts)

The abandoned villages of the Irpinia: a forgotten heritage

Italy’s cultural and landscape heritage is very complex, characterized for the most part by historical centres of large cities, small towns and ancient villages, where the original structures are not challenged by times. In these settlements, memories of local identity and culture coexist, representing a real priceless resource for the territory. However most of them, e.g. the rural villages, have been completely abandoned, due to a housing problem, a need to improve the standard of living and transportation or due to natural disasters (earthquakes and landslides). So the depopulation of wide territorial areas has occurred and affected especially the South of Italy. The article aims to rediscover and analyse the uniqueness of some of the most significant villages of Irpinia, referring particularly to the Avellino’s territory: Carbonara (well known as Aquilonia Vecchia), Melito Irpino, Conza della Campania, Senerchia, in order to retrace unique strengths that can turn forgotten places into an economic and territorial development