Genome-Wide Profile of Pleural Mesothelioma versus Parietal and Visceral Pleura: The Emerging Gene Portrait of the Mesothelioma Phenotype

Malignant pleural mesothelioma is considered an almost incurable tumour with increasing incidence worldwide. It usually develops in the parietal pleura, from mesothelial lining or submesothelial cells, subsequently invading the visceral pleura. Chromosomal and genomic aberrations of mesothelioma are diverse and heterogenous. Genome-wide profiling of mesothelioma versus parietal and visceral normal pleural tissue could thus reveal novel genes and pathways explaining its aggressive phenotype.Well-characterised tissue from five mesothelioma patients and normal parietal and visceral pleural samples from six non-cancer patients were profiled by Affymetrix oligoarray of 38 500 genes. The lists of differentially expressed genes tested for overrepresentation in KEGG PATHWAYS (Kyoto Encyclopedia of Genes and Genomes) and GO (gene ontology) terms revealed large differences of expression between visceral and parietal pleura, and both tissues differed from mesothelioma. Cell growth and intrinsic resistance in tumour versus parietal pleura was reflected in highly overexpressed cell cycle, mitosis, replication, DNA repair and anti-apoptosis genes. Several genes of the “salvage pathway” that recycle nucleobases were overexpressed, among them TYMS, encoding thymidylate synthase, the main target of the antifolate drug pemetrexed that is active in mesothelioma. Circadian rhythm genes were expressed in favour of tumour growth. The local invasive, non-metastatic phenotype of mesothelioma, could partly be due to overexpression of the known metastasis suppressors NME1 and NME2. Down-regulation of several tumour suppressor genes could contribute to mesothelioma progression. Genes involved in cell communication were down-regulated, indicating that mesothelioma may shield itself from the immune system. Similarly, in non-cancer parietal versus visceral pleura signal transduction, soluble transporter and adhesion genes were down-regulated. This could represent a genetical platform of the parietal pleura propensity to develop mesothelioma.Genome-wide microarray approach using complex human tissue samples revealed novel expression patterns, reflecting some important features of mesothelioma biology that should be further explored

Glutamine randomized studies in early life: The unsolved riddle of experimental and clinical studies

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of glutamine-heat shock proteins-stress response in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness. © 2012 Efrossini Briassouli and George Briassoulis

Educational polymorphisms of basic life support algorithms

Background A systematic review of the pooled effect of articles presenting current basic life support (BLS) algorithms for the treatment of cardiac arrest has never been carried. Aims We aimed to record and classify potential inherent factors influencing simplicity negatively in teaching, learning and retention of cardiopulmonary resuscitation (CPR) delivered by health care providers or lay persons. Methods We performed a search of the relevant literature exploring MEDLINE, COCHRANE LIBRARY and SCOPUS databases. Potential inhibitory factors in the structure of available algorithms influencing simplicity in teaching, learning and retention of BLS were recorded and stratified accordingly. In a second phase of this study, we tested the hypothesis that different options of a BLS algorithm might influence CPR retention negatively, by asking 348 health care provider participants of our CPR seminars to describe their predicted response in an emergency to: (1) a real-time model implicating the various victims and rescuers; and (2) a hypothetical challenging 'all-in-one' BLS algorithm model. Results Fifteen articles presenting current BLS algorithms evidenced 163 suggestions that produced 23 different CPR options: five contrasting algorithms (21.8%); three two-option models (13%); six vague technical or scientific suggestions (26%); and nine multiple choices of action (39.1%). Identified references contributed differently in the development of educationally polymorphic BLS options in each of the four categories (P < 0.0001) and were all brought about by variants of victims and rescuers. Participants of CPR seminars answered that in an emergency they could remember the hypothetical BLS model (90%, P = 0.007) rather than a current BLS algorithm for adults (42.2%) or children (36%). Conclusions Educational polymorphisms of BLS algorithms could build unpredictable barriers between rescuers and cardiac arrest victims and might seriously limit instructors' educational effectiveness. These findings might support an alternative trial hypothesis of a simple 'all-in-one algorithm' educational approach in future. © 2010 Blackwell Publishing Ltd

Evaluation of the M-COVX metabolic monitor in mechanically ventilated adult patients

Background & aims: Indirect calorimetry is commonly used for energy expenditure studies. However, older metabolic carts can be cumbersome and difficult to use. This study was aimed at validating the new M-COVX indirect calorimeter. Methods: This prospective study was performed in all ventilated critically ill adults, with a Fractional Inspired Oxygen <60%, respiratory rate below 35 breaths-per-minute and endotracheal tube leak <10%. Patients were studied in steady-state only. Repeated, sequential measurements were performed comparing Deltatrac II NMN-200 to the new M-COVX. For each instrument, 5 consecutive, 1 min measurements of volume of oxygen and carbon dioxide, respiratory quotient and energy expenditure were recorded. Results: Of the 20 patients enrolled in the study, the data of 11 patients was used for analysis. Bland Altman plots indicated clinically significant differences between the 2 indirect calorimeters for volume of oxygen (19.2%) and carbon dioxide (17.6%) and energy expenditure (15.3%). Conclusion: The results show that the M-COVX metabolic monitor might not provide measurement within a clinically accepted range in certain ventilation modes and in non-sedated patients. Further research has to be performed to confirm our findings. © 2008 European Society for Clinical Nutrition and Metabolism