Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung

This study investigated the relation between positive thyroid transcription factor 1 (TTF1) staining and survival of patients affected by primary adenocarcinoma (ADC) of the lung. Pathological tissue from consecutive ADC patients was collected from 2002 to 2004. The anti-TTF1 antibody (8G7G3/1, dilution of 1/200) was used. Thyroid transcription factor 1 staining was assessed for each tumour as positive or negative. Probability of survival was estimated by Kaplan–Meier and difference tested by log-rank test. A Cox's regression multivariate analysis was carried out. In all, 106 patients were studied (66% male, 69% PS0–1, 83% with stage III or IV). Tumours expressed positive TTF1 staining in 66% of cases. Multivariate analysis demonstrated an independent lower risk of death for patients whose tumour expresses positive TTF1 staining (HR=0.51, 95% CI 0.30–0.85; P=0.01) and higher grade of differentiation (HR=0.40, 95% CI 0.24–0.68; P=0.001). In conclusion, positive TTF1 staining strongly and independently correlates with survival of patients with primary ADC of the lung

Rare copy number variants contribute to congenital left-sided heart disease

Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology

TIA-1 Cytotoxic Granule-Associated RNA Binding Protein Improves the Prognostic Performance of CD8 in Mismatch Repair-Proficient Colorectal Cancer

Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed

Complications rythmiques de la chirurgie des cardiopathies congénitales

RésuméAu cours des cinquante dernières années, la chirurgie cardiaque a révolutionné l’histoire naturelle des cardiopathies congénitales, de sorte qu’une proportion importante des enfants nés porteurs d’une cardiopathie congénitale atteindra l’âge adulte. Les arythmies postopératoires précoces ou tardives représentent cependant une cause importante de morbidité et de mortalité. En postopératoire immédiat, le bloc auriculo-ventriculaire complique encore de 1 à 3 % des chirurgies et nécessite un cardiostimulateur s’il persiste au-delà de 10 jours. La dysfonction sinusale complique principalement les chirurgies palliatives pour cœurs univentriculaires. Les tachycardies sont plus fréquentes que les bradycardies et se manifestent autant en postopératoire immédiat que plusieurs années plus tard. La tachycardie jonctionnelle ectopique est fréquente, potentiellement mortelle, mais peut être bien contrôlée si reconnue et traitée agressivement. L’amiodarone en perfusion est la pierre angulaire du traitement.Les tachycardies auriculaires et ventriculaires tardives peuvent venir perturber de façon significative la qualité de vie et même la survie du patient atteint. La tachycardie par réentrée intra-auriculaire affecte une forte proportion des patients opérés pour la transposition des gros vaisseaux par atrioseptopexie ou pour toute forme de cœur univentriculaire. L’ablation par radiofréquence en utilisant les nouvelles technologies de cartographie tridimensionnelle et les cathéters irrigués offre une alternative efficace au traitement médical et repousse à plus tard les reprises chirurgicales complexes et risquées. La tachycardie ventriculaire est la cause principale de mort subite du patient adulte porteur d’une tétralogie de Fallot opérée.SummaryOver the past 50 years, cardiac surgery has dramatically modified the natural history of congenital heart defects in such a way that a high proportion of babies born with a heart defect will survive to adulthood. Early and late postoperative arrhythmias, however, are a major cause of morbidity and mortality in this growing population. In the immediate postoperative period, heart block still complicates 1–3 % of surgeries and a pacemaker is required if the block persists beyond 10 days. Sinus node dysfunction is not uncommon in palliated univentricular hearts. Tachycardias are even more common than bradycardias and may occur early or late after a cardiac repair. Junctional ectopic tachycardia is common and potentially fatal but may well be controlled and treated if recognised early and treated aggressively (amiodarone is the cornerstone of therapy). Late atrial and ventricular tachycardias may modify significantly the patient's quality and duration of life. Intra-atrial re-entrant tachycardia affects a high proportion of patients operated on for transposition of the great arteries at the atrial level or for any palliation of univentricular hearts. Radiofrequency catheter ablation using new three-dimensional mapping and irrigated catheter technologies offers an interesting alternative to medical therapy and diminishes needs for complex surgical reinterventions. Ventricular tachycardia is the main cause of sudden death in adults with operated tetralogy of Fallot

Using rule-based machine learning for candidate disease gene prioritization and sample classification of cancer gene expression data

Microarray data analysis has been shown to provide an effective tool for studying cancer and genetic diseases. Although classical machine learning techniques have successfully been applied to find informative genes and to predict class labels for new samples, common restrictions of microarray analysis such as small sample sizes, a large attribute space and high noise levels still limit its scientific and clinical applications. Increasing the interpretability of prediction models while retaining a high accuracy would help to exploit the information content in microarray data more effectively. For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. A comparison with other benchmark microarray sample classifiers based on three diverse feature selection algorithms suggests that these evolutionary learning techniques can compete with state-of-the-art methods like support vector machines. The obtained models reach accuracies above 90% in two-level external cross-validation, with the added value of facilitating interpretation by using only combinations of simple if-then-else rules. As a further benefit, a literature mining analysis reveals that prioritizations of informative genes extracted from BioHEL's classification rule sets can outperform gene rankings obtained from a conventional ensemble feature selection in terms of the pointwise mutual information between relevant disease terms and the standardized names of top-ranked genes

Outcome of acute fulminant myocarditis in children

OBJECTIVES: To highlight clinical features and outcome of acute fulminant myocarditis (AFM) in children. METHODS: Diagnostic criteria were (1) the presence of severe and acute heart failure; (2) left ventricular dysfunction on echocardiography; (3) recent history of viral illness; and (4) no history of cardiomyopathy. RESULTS: Eleven children were included between 1998 and 2003, at a median age of 1 (0 to 9) year. Their mean left ventricular ejection fraction (LVEF) was 22 (SD 9)% at presentation. A virus was identified in five patients: human parvovirus B19 (n  =  2), Epstein–Barr (n  =  1), varicella zoster (n  =  1), and coxsackie (n = 1). The median intensive care unit course was 13 (2–34) days. Intravenous inotropic support was required by nine patients and eight were mechanically ventilated. All patients received corticosteroid, associated with intravenous immunoglobulin in seven. Five patients experienced cardiocirculatory arrest that was successfully resuscitated in four. At a median follow up of 58.7 (33.8–83.1) months, the 10 survivors are asymptomatic with normalised LVEF. CONCLUSION: Despite a severe presentation, the outcome of AFM is favourable. Aggressive symptomatic management is warranted and heart transplantation should be considered only when maximal supportive therapy does not lead to improvement