Implementation of a self-administered questionnaire to detect lung carcinogens.

BACKGROUND: Between 10 and 20% of lung cancers are of occupational origin. Screening for occupational risk factors is part of the diagnostic workup. A self-administered questionnaire to detect lung carcinogens of occupational origin, the RECAP questionnaire, was drawn up and validated with a view to limiting under-declaration of lung cancer as an occupational disease (OD). AIMS: Optimal administration conditions were investigated, to facilitate systematic use in the management of patients admitted to hospital with lung cancer. METHODS: The various care pathways of lung cancer patients were first studied in two centres, to identify the health-care professionals involved in medical management, the various care sites and the stages of treatment. A focus group of health-care professionals was set up, and semi-directive interviews were conducted with 24 patients. RESULTS: Caregivers tended to suggest that a physician or nurse should present the RECAP questionnaire, whereas patients rather chose non-caregiver staff, seeing the undertaking as being 'administrative' in nature. Some caregivers and patients thought the questionnaire should not be administered at the outset of treatment, due to the psychological trauma entailed by diagnosis. Administration during chemotherapy was recommended by patients, as they are more freely available at that time, and by caregivers, who thought patients better able to pay attention then. CONCLUSIONS: The study highlighted patients' lack of information on how lung cancer can be recognized as an OD. Implementing the RECAP questionnaire should facilitate patients' claims for insurance cover for lung cancer as an OD.

[Congenital heart disease: from childhood to adulthood]. / Cardiopathie congénitale: de l'enfance à l'âge adulte.

With the improvement of congenital heart surgery, most children with congenital heart disease will survive into adulthood with a good quality of life. Regular cardiac follow-up is recommended for all patients. The adolescent period coincides often with medium and long term consequences and complications and repeat surgery or catheter interventions might be needed. It is therefore of prime importance to begin the transition process early and to pursue it well into adulthood. We have elaborated a formal transition program adapted to youngsters with congenital heart disease.

Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer's Disease.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

[Management of EGFR mutated non-small cell lung carcinoma patients]. / Analyse de la prise en charge des cancers bronchiques avec mutation du gène de l'EGFR.

INTRODUCTION: Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small-cell lung cancer (NSCLC). Over the past decade, the management of NSCLC-carrying EGFR mutation has evolved considerably with the use of tyrosine kinase inhibitors (TKIs). The main objective of this retrospective study was to analyze the evolution of therapeutic strategies in a cohort of patients with metastatic or locally advanced EGFR- mutated NSCLC. METHODS: Data on patients with EGFR-mutated NSCLC, eligible for TKIs, and treated between 2010 to 2019 were collected. The main therapeutic strategies adopted following progression under TKIs and the prognostic factors for survival were analyzed. RESULTS: The median age of the 177 patients was included in the cohort was 70years. The majority of patients (77.4%) received TKIs as first-line treatment, while 16.4% received chemotherapy. Osimertinib initiation as second-line treatment was a factor for better prognosis (OR=0.5). Finally, change of chemotherapy line was the main therapeutic strategy adopted for 41.3% of the patients having relapsed under TKIs. DISCUSSION: Therapeutic management of EGFR-mutated NSCLC patients was in accordance with regional, national and international recommendations. The characterization of progression under TKI therapy has become systematic, allowing better adaption of therapeutic strategies.

Complex aortic coarctation, regurgitant bicuspid aortic valve with VSD and ventricular non-compaction: a challenging combination.

Left ventricular non-compaction is a myocardial disorder characterized by excessive trabeculations and deep recesses that communicate with the ventricular cavity, which is thought to result from a failure of the trabecular regression that occurs during normal embryonic development. It carries a high mortality from heart failure or sudden cardiac death. A 15-year-old female patient was referred to our institution for moderate symptoms of heart failure. Echocardiography and MRI showed a bicuspid aortic valve with severe regurgitation, subaortic VSD, dilated left ventricle and left ventricular non-compaction with a moderately decreased ejection fraction, as well as isthmic coarctation and transverse arch hypoplasia. We elected to perform transaortic VSD closure and aortic valve replacement using a mechanical prosthetic valve on an arrested heart, and to address aortic coarctation and transverse arch hypoplasia using an extra-anatomic ascending-to-descending aorta bypass. Aortic cross-clamping was limited to 41 minutes. The postoperative recovery was rapid and the girl was discharged in NYHA class I with an estimated LVEF of 39%. Although management must be individualized, extra-anatomic bypass is a good single-stage approach for patients with complex coarctation and concomitant cardiovascular or myocardial disorders, reducing ischemic time and offering a better chance of successful weaning from cardiopulmonary bypass.

How central and connected am I in my family? Family-based social capital of individuals with intellectual disability.

Using social network methods, this article explores the ways in which individuals with intellectual disability (ID) perceive their family contexts and the social capital that they provide. Based on a subsample of 24 individuals with ID, a subsample of 24 individuals with ID and psychiatric disorders, and a control sample of 24 pre-graduate and postgraduate students matched to the clinical respondents for age and sex, we found that family networks of clinical individuals are distinct both in terms of composition and in terms of social capital made available to them by their family ties. Individuals with ID perceive themselves as less central in their own family; their family networks are perceived as less dense, less centralized, and more disconnected. Individuals with intellectual disabilities and psychiatric disorders have less family-based social capital than individuals with intellectual disabilities only. The composition of their family is also distinct as spouses or partners and children are missing. We discuss the importance of those findings for research on family relationships of individuals with ID.

Protein regulation: tag wrestling with relatives of ubiquitin.

Ubiquitin modification is a well established way of regulating protein levels and activities. Modification by related ubiquitin-like proteins is turning out to have a diverse range of interesting cellular functions.

Reasons for and functional results of repeated hip arthroscopy: A continuous prospective study of 17 revisions out of 295 primary hip arthroscopies at mean 28months' follow-up.

INTRODUCTION: The rate of iterative arthroscopy has been increasing over the last decade as the technique has grown. The results of and reasons for these revision procedures, however, are not exactly known. We therefore conducted a prospective study to shed light on: 1) functional results and patient satisfaction following repeated arthroscopy, and 2) the relevant indications. HYPOTHESIS: Functional scores and patient satisfaction increase following repeated arthroscopy. MATERIALS AND METHOD: A single-center continuous prospective study without control group included patients undergoing repeated hip arthroscopy between September 2010 and September 2014, with a mean 28months' follow-up (median, 23.3months; range, 12-62months). Preoperative and follow-up functional assessment used the modified Harris hip, WOMAC and Christensen (NHAS) questionnaires, and a satisfaction scale. On etiological analysis, repeated arthroscopy was indicated if a cause of recurrent or persistent pain accessible to arthroscopic treatment was identified. RESULTS: Seventeen patients were included out of 295 primary arthroscopies (5.7%): 9 male, 8 female; median age, 29.6years (range, 16-48years). Indications for primary arthroscopy comprised 13 cases of femoroacetabular impingement, 3 labrum lesions with instability, 1 chondromatosis and 1 case of osteoarthritis. Eleven of the 17 primary lesions showed persistence, including 9 of the 13 cases of femoroacetabular impingement. There were 3 failures in 17 repeated arthroscopies. All functional scores improved, with a gain of 7 points (P<0.06) on modified Harris hip score, 25 points (P<0.0006) on WOMAC score, and 27 points (P<0.001) on NHAS score. Ten of the 17 patients were satisfied or very satisfied with the repeated arthroscopy (59%). CONCLUSION: Although less good than on primary arthroscopy, functional results on repeated hip arthroscopy were satisfactory in the short term. The main reason for repeated arthroscopy was persistence of initial abnormality due to insufficient treatment.

[Free circulating DNA as a tool for lung cancer patients management]. / Intérêts de l'ADN circulant pour la prise en charge du cancer broncho-pulmonaire.

Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. These genomic fragments are mainly constitutional (nucleated blood cell DNA), but in patients with cancer, a fraction comes from tumor cells. Although poorly known in the field of thoracic oncology, quantitative and qualitative analysis of the cDNA is nevertheless of great interest. Total cfDNA concentration appears to be an independent prognostic factor in lung cancer. Although changes in total cfDNA concentration is not informative to assess the effectiveness of chemotherapy, following-up the fraction of mutated genes such as EGFR during therapy with tyrosine kinase inhibitors appears to be particularly promising for the early detection of disease progression. The use of cfDNA as liquid biopsy is also very promising for the non-invasive somatic molecular profile either at baseline either for sampling at follow-up. Thus, cfDNA is a very promising tool in thoracic oncology and its translation into practice should be developed quickly.

Both human alpha/beta and gamma interferons upregulate the expression of CD48 cell surface molecules.

We have established a cDNA library from interferon (IFN)-treated human lymphoblastoid Daudi cells and made use of differential screening to search for yet unidentified IFN-regulated genes. In the course of these studies, we have isolated a human cDNA coding for the glycosyl-phosphatidylinositol-linked (GPI) membrane glycoprotein CD48 (TCT-1, Blast-1). Various studies demonstrated that the murine CD48 is the predominant counterreceptor for the mouse CD2 and is involved in the regulation of T cell activation. Since the murine CD48 is functionally homologous to the human CD2 ligand LFA-3 (CD48), the function of the human CD48 remains unknown. In this report, we show that both Hu-IFN-alpha/beta and Hu-IFN-gamma increase the level of CD48 mRNA and upregulate the expression of CD48 proteins at the surface of various cultured human cell lines. However, the IFN have no effect on the expression of LFA-3. In addition, we show that IFN increase CD48 expression on peripheral blood mononuclear CD3+, CD14+, and CD19+ subpopulations. These data suggest that in addition to modulation of the conventional MHC class I and class II-restricted interactions, the IFN might promote MHC-unrestricted interactions of target cells with the immune cells by inducing the expression of the cell surface CD48 molecule.

The interferon-inducible Staf50 gene is downregulated during T cell costimulation by CD2 and CD28.

It is well established that interferons (IFN) exert potent regulatory effects on the immune system. We have recently isolated a new IFN-induced human cDNA coding for a member of the Ring finger B-box/B30.2 subfamily that localizes to the chromosome band 11p15. We have named it Staf50. We show in this report that Staf50 is expressed in resting T cells in the absence of exogenous IFN treatment and is strongly repressed during T cell activation by anti-CD28 and anti-CD2 monoclonal antibodies (mAb) at both messenger and protein levels. In addition, we show that several members of the Ring finger B-box/B30.2 subfamily, including the 52-kDa SSA/Ro autoantigen, localize to the same chromosome band, 11p15, and are upregulated by IFN. These data led us to define a family of IFN-induced genes clustered on chromosome 11p15 that may be involved in T cell regulatory processes.

Red cell antibody screening, red cell antibody identification and compatibility testing with the Column Agglutination Technology (CAT). The Bio Vue system.

A new system for irregular antibody screening was described in 1993 by Reis K.J. This test is performed in a microcolumn prefilled with glass microbeads in suspension in a neutral or Anti Human Globulin isotonic solution. When the red cells are sensitized they are trapped by the microbead suspension during column centrifugation. 21365 irregular antibody screenings were performed with this Column Agglutination Technology (CAT) and the results were compared to those obtained with conventional manual tests. The CAT was more efficient than the manual tests. The number of positive samples containing specific antibodies was higher with CAT tests (924 samples) than with manual tests (802 samples). The CAT is easy to perform and the elimination of washing steps decreases the overall test time. It allows the use of this test for pre-transfusion compatibility testing particularly in emergency transfusion cases. The red cell age and more generally the red cell storage conditions seem to be an influential parameter on the percentage of unspecific reactions. In this study the unspecific reaction rate was low but we used only reagent red cells prepared every day. This new technology may be considered as an alternative technology to the Gel Test in Blood Transfusion security.

[Introduction of health education in Vaud schools]. / L'introduction de l'éducation pour la santé dans les écoles vaudoises.

The traditional activities of screening are the prerogative of the school health professionals. Nonetheless health education should be approached in an interdisciplinary fashion and involve the form teachers as well as the specialized area teachers. This article describes a program of health education which is about to be organized in the canton of Vaud. This programs plans for the introduction of health education in the general curriculum and not limit it to a specific period or course. The themes are graded to the age of the pupils. Documents are being worked out by an ad hoc committee and will be available to teachers who desire them. The article also reviews the present activities in health education both at primary and secondary levels and reports on a number of experiences to make teachers aware of health problems. The article concludes on the advantages and difficulties that are linked, on the one hand, to the introduction of education for health in the basic curriculum and, on the other hand, to the use of teachers as promoters of health awareness.

[Haemodialysis, L-carnitine therapy and valproic acid overdose]. / Epuration extrarénale, supplémentation en L-carnitine et intoxication à l'acide valproïque.

We report the case of a severe valproic acid poisoning in a 36-year-old man. In front of a high serum concentration of valproic acid at the admission, haemodialysis was initiated to decrease serum valproic acid concentration. A L-carnitine therapy (50 mg/kg per day) was also started. A cerebral oedema appeared at the third day, but the patient recovered without any sequela.

Extracting recurrent scenarios from narrative texts using a Bayesian network: application to serious occupational accidents with movement disturbance.

A probabilistic approach has been developed to extract recurrent serious Occupational Accident with Movement Disturbance (OAMD) scenarios from narrative texts within a prevention framework. Relevant data extracted from 143 accounts was initially coded as logical combinations of generic accident factors. A Bayesian Network (BN)-based model was then built for OAMDs using these data and expert knowledge. A data clustering process was subsequently performed to group the OAMDs into similar classes from generic factor occurrence and pattern standpoints. Finally, the Most Probable Explanation (MPE) was evaluated and identified as the associated recurrent scenario for each class. Using this approach, 8 scenarios were extracted to describe 143 OAMDs in the construction and metallurgy sectors. Their recurrent nature is discussed. Probable generic factor combinations provide a fair representation of particularly serious OAMDs, as described in narrative texts. This work represents a real contribution to raising company awareness of the variety of circumstances, in which these accidents occur, to progressing in the prevention of such accidents and to developing an analysis framework dedicated to this kind of accident.

IRF4 and BATF are critical for CD8⁺ T-cell function following infection with LCMV.

CD8(+) T-cell functions are critical for preventing chronic viral infections by eliminating infected cells. For healthy immune responses, beneficial destruction of infected cells must be balanced against immunopathology resulting from collateral damage to tissues. These processes are regulated by factors controlling CD8(+) T-cell function, which are still incompletely understood. Here, we show that the interferon regulatory factor 4 (IRF4) and its cooperating binding partner B-cell-activating transcription factor (BATF) are necessary for sustained CD8(+) T-cell effector function. Although Irf4(-/-) CD8(+) T cells were initially capable of proliferation, IRF4 deficiency resulted in limited CD8(+) T-cell responses after infection with the lymphocytic choriomeningitis virus. Consequently, Irf4(-/-) mice established chronic infections, but were protected from fatal immunopathology. Absence of BATF also resulted in reduced CD8(+) T-cell function, limited immunopathology, and promotion of viral persistence. These data identify the transcription factors IRF4 and BATF as major regulators of antiviral cytotoxic T-cell immunity.

Successful use of a new Amplatzer Vascular plug for percutaneous closure of a large aortopulmonary collateral artery in a pulmonary atresia with ventricular septal defect prior to complete repair.

We report the case of a 14 year-old girl with a pulmonary atresia with VSD and multiple aortopulmonary collaterals who underwent a successful complementary occlusion of a large collateral vessel using an Amplatzer vascular plug after a previously failed attempt of occlusion with a coil. The percutaneous procedure, performed from the femoral artery before the complete surgical repair, provided an immediate closure of the vessel. This new device is safe and effective for the occlusion of aortopulmonary collaterals, specifically if of large dimensions.

Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression.

Transcriptional induction of genes is an essential part of the cellular response to interferons. To isolate yet unidentified IFN-regulated genes we have performed a differential screening on a cDNA library prepared from human lymphoblastoid Daudi cells treated for 16 h with human alpha/beta interferon (Hu-alpha/beta IFN). In the course of these studies we have isolated a human cDNA which codes for a protein sharing homology with the mouse Rpt-1 gene; it will be referred as Staf-50 for Stimulated Trans-Acting Factor of 50 kDa. Amino acid sequence analysis revealed that Staf-50 is a member of the Ring finger family and contains all the features of a transcriptional regulator able to initiate a second cascade of gene induction (secondary response). Staf-50 is induced by both type I and type II IFN in various cell lines and down-regulates the transcription directed by the long terminal repeat promoter region of human immunodeficiency virus type 1 in transfected cells. These data are consistent with a role of Staf-50 in the mechanism of transduction of the IFN antiviral action.