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Sabadell, Spain

Millares L.,Fundacio Parc Tauli | Millares L.,CIBER ISCIII | Millares L.,Autonomous University of Barcelona | Serra M.,Autonomous University of Barcelona | And 19 more authors.
Clinical and Experimental Metastasis | Year: 2015

Hypermethylation of the promoter region of tumor suppressor genes is associated with carcinogenesis in lung cancer (LC). Endobronchial ultrasound with needle aspiration (EBUS-NA) is a semi-invasive method for obtaining cell blocks from lymph nodes, which can be used for epigenetic analyses. To establish the relationship between methylation status of p16, DAPK, RASSF1a, APC and CDH13 genes in lymph nodes sampled by EBUS-NA, tumor staging and prognosis. Methylation status of DAPK, p16, RASSF1a, APC and CDH13 genes was assessed in EBUS-NA cell blocks from LC patients and related to stage and survival. Eighty-five consecutive patients [mean age 67 (SD 8)] were included. Methylation of ≥1 gene was found in 43 malignant nodes (67 %). A higher prevalence of RASSF1a methylation was observed in small cell lung cancer patients [9/10 (90 %) vs. 15/53 (28 %); p < 0.001 χ2 test]. Methylation of APC and/or p16 was related to advanced staging in non-small cell lung cancer (NSCLC) [15/29 (52 %) vs. 6/24 (25 %), p = 0.048, χ2 test]. Patients with NSCLC showing methylation of APC and/or p16 had also lower 6-month survival (p = 0.019, log rank test), which persisted after adjustment for age and subtyping (HR = 6, 95 % CI [1.8–19.5], p = 0.003, Cox regression). Epigenetic analyses are feasible in EBUS-NA cell blocks and may identify methylation patterns associated with worse prognosis. Methylation of p16 and APC genes in NSCLC patients was associated with advanced staging and lower 6-month survival. © 2015, Springer Science+Business Media Dordrecht. Source

A growing body of evidence suggests outcome improvement in Intensive Care Unit (ICU) patients by means of telemedicine. At present a highly interoperable, manufacturer-independent telemedicine-platform for detection of ICU-patients at increased risk is missing. Encouraging results in other eHealth-projects influenced the decision to use pre-commercial procurement (PCP), in order to provide best possible solution for THALEA.\n\nClearly identified demand and strategy detected by international ICU experts, consented by multidisciplinary stakeholders (IT-experts, excellence cluster eHealth, insurance companies and ministries) during pre-consortium meeting ensures a perfect match of demand, strategy and funding instrument in an early phase of the project. Besides inacceptable high mortality in ICU patients, telemedicine has the ability to mitigate problematic pan-European challenges, like demographic changes, shortage of ICU professionals, and scarcity of financial resources.\n\nBringing market participant and stakeholders (procurers, ICU-specialist, IT-specialist) in close collaboration, PCP within THALEA will create an appropriate common solution fulfilling demands of a telemedical research framework. Focus on interoperability and scalability will lay foundations for future follow-up projects in telemedicine. Compliance with Directive 95/46/EC is granted by limiting access to sensitive data to health professionals with obligation of professional secrecy and data transfer bound to provision of care in a tele-ICU service.\n\nTHALEA will help to close a knowledge-gap in Europe as well as to close up to research superiority projects in the US. By PCP, dissemination of this promising technology will be spread in Europe thus helping doctors to save more lives and as a result enable more patients living at home independently. An eHealth PCP-pilot for tele-ICU enhances dissemination of PCP as funding instrument beyond the innovative field of ICU-telemedicine.

Milares L.,Fundacio Parc Tauli | Milares L.,Autonomous University of Barcelona | Rosel A.,CIBER ISCIII | Rosel A.,Hospital Universitari Bellvitge | And 11 more authors.
Oncology Reports | Year: 2014

Assessment of the methylation status of genes related to the development of lung cancer (LC) in bronchial secretions has been proposed as a biomarker for early detection. Several techniques are available to detect gene methylation, and the method chosen may have an effect on the results. A cross-sectional study was conducted in which the methylation status of DAPK, CDKN2A (p16) and RASSF1A genes in sputum and bronchial washing (BW) from subjects at risk for LC was analyzed. The methylation results of both samples were compared, considering BW as the reference. Results obtained by methylation-sensitive PCR (MSP) were validated by methylation-sensitive high-resolution melting (MS-HRM). The methylation results obtained in sputum and BW samples did not show statistically significant differences for any of the three genes analyzed in 65 subjects (McNemar test >0.05). Concordant results between sputum and BW were found in 40 patients for DAPK (61%), in 52 patients for p16 (80%) and in 63 patients for RASSF1 (97%). More methylated samples were found in BW, however, and sputum sensitivities and specificities for the identification of methylation status were 44 and 72% for DAPK gene, 21 and 94% for p16 and 100 and 98% for RASSF1A, respectively. When MSP results were validated by MS-HRM, DAPK and p16 gene samples methylated by MSP appeared to be unmethylated by MS-HRM. One sample showing methylation of RASSF1A gene also showed methylation when tested following MS-HRM procedure. Sputum and BW samples may be considered equally valid for the identification of methylated genes in bronchial secretions. The low sensitivity of sputum for the assessment of the methylation status of DAPK and p16 genes, however, suggests that the analysis of two or more sputum samples, or of a BW obtained semi-invasively, would be needed to attain higher reliability, together with the use of confirmatory techniques for positive results. Source

Millares L.,Fundacio Parc Tauli | Millares L.,CIBER ISCIII | Millares L.,Autonomous University of Barcelona | Millares L.,Fundacio Institute DInvestigacio Germans Trias i Pujol | And 20 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014

The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined. Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation. COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa. Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing. Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa. Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p=0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p=0.699; Chao1, 124 (77-159) vs 140 (115-163), p=0.364). In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations. An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples. These increases were not identified by culture in 5 out of 13 participants (38.5 %). Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions. Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa. © 2014 The Author(s). Source

Lopez-Aguilar J.,Fundacio Parc Tauli | Lopez-Aguilar J.,Autonomous University of Barcelona | Lopez-Aguilar J.,Critical Care Center | Lopez-Aguilar J.,CIBER ISCIII | And 14 more authors.
Respiratory Physiology and Neurobiology | Year: 2015

We determined whether the combination of low dose partial liquid ventilation (PLV) with perfluorocarbons (PFC) and prone positioning improved lung function while inducing minimal stress. Eighteen pigs with acute lung injury were assigned to conventional mechanical ventilation (CMV) or PLV (5 or 10. ml/kg of PFC). Positive end-expiratory pressure (PEEP) trials in supine and prone positions were performed. Data were analyzed by a multivariate polynomial regression model. The interplay between PLV and position depended on the PEEP level. In supine PLV dampened the stress induced by increased PEEP during the trial. The PFC dose of 5. ml/kg was more effective than the dose 10. ml/kg. This effect was not observed in prone. Oxygenation was significantly higher in prone than in supine position mainly at lower levels of PEEP. In conclusion, MV settings should take both gas exchange and stress/strain into account. When protective CMV fails, rescue strategies combining prone positioning and PLV with optimal PEEP should improve gas exchange with minimal stress. © 2015 Elsevier B.V. Source

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