70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.)

Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI

Background: Fibrosis, which is characterized by the pathological accumulation of collagen, is recognized as an important feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methods for the early diagnosis and follow-up of fibrosis in various disorders. Collagen targeting molecules are therefore of interest for potential in vivo imaging of fibrosis. In this study, we developed a collagen-specific probe using a new approach that takes advantage of the inherent specificity of Glycoprotein VI (GPVI), the main platelet receptor for collagens I and III. Methodology/Principal: Findings An anti-GPVI antibody that neutralizes collagen-binding was used to screen a bacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin) was synthesized. Solid-phase binding assays and histochemical analysis showed that collagelin specifically bound to collagen (Kd 10−7 M) in vitro, and labelled collagen fibers ex vivo on sections of rat aorta and rat tail. Collagelin is therefore a new specific probe for collagen. The suitability of collagelin as an in vivo probe was tested in a rat model of healed myocardial infarctions (MI). Injecting Tc-99m-labelled collagelin and scintigraphic imaging showed that uptake of the probe occurred in the cardiac area of rats with MI, but not in controls. Post mortem autoradiography and histological analysis of heart sections showed that the labeled areas coincided with fibrosis. Scintigraphic molecular imaging with collagelin provides high resolution, and good contrast between the fibrotic scars and healthy tissues. The capacity of collagelin to image fibrosis in vivo was confirmed in a mouse model of lung fibrosis. Conclusion/Significance: Collagelin is a new collagen-targeting agent which may be useful for non-invasive detection of fibrosis in a broad spectrum of diseases.Psycholog

Hémorragies sous anticoagulants oraux en gériatrie : résultats d’une étude observationnelle.

Over recent years, new oral anticoagulant agents (NOAC) have been commercialized as a new treatment in order to prevent or treat thromboembolic events. Although the use of NOACs is easier than for vitamin K antagonists (VKA), their risk-benefit balance still raises concerns, especially in the elderly. To evaluate bleeding complications with anticoagulants agents (NOAC and VKA) among a geriatric population. A retrospective study performed in the four units of the acute geriatric department of CHU Charleroi (116 beds). All the patients who received at least one dose of oral anticoagulant (NOAC or VKA) during their hospitalization between January 1st2013 and May 31th 2014 were enrolled. Medical files of 242 patients were analyzed, and the type and severity of bleeding were recorded. Mean age was 84 ± 5.4 years old. Seventy-three percent were prescribed VKA. Rivaroxaban was the most prescribed NOAC among this population. Atrial fibrillation was the primary indication of oral anticoagulation in 73% with VKA and 94% with NOAC. Fourty-six patients presented a bleeding (38 patients (22% of patients with VKA) with VKA and 8 patients with NOAC (12% of patients with NOAC)). We found 13 major bleedings with VKA and only one with NOAC. The results of this study are encouraging concerning the utilization of NOACs in the geriatric population. However, larger studies are needed to confirm this.info:eu-repo/semantics/publishe

Newcastle disease virus f glycoprotein expressed from a recombinant vaccinia virus vector protects chickens against live-virus challenge

Chickens were immunised using a vaccinia recombinant virus (vaccinia-Italien-F), expressing the F protein of Newcastle disease virus (NDV). Immunisation was successful using either TK cells infected with the vaccinia-Italien-F virus, the recombinant virus grown in tk cells and inoculated intra-cerebrally in one-day-old chickens or the recombinant virus given by wing-web to adult chickens after adaptation by alternate passage in chick embryo fibroblasts and chickens. The use of recombinant viruses expressing the F protein of NDV as vaccines would allow joint application of vaccination and eradication programmes for NDV. Therefore, recombinant viruses obtained in chickens virus vectors are needed. © 1988, Taylor & Francis Group, LLC. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of the use of monoclonal antibodies to hemagglutinin and fusion glycoproteins of Newcastle disease virus for virus identification and strain differentiation purposes

Monoclonal antibodies detect evident antigenic variations in NDV HN and F protein. However, the A/PMV-1 viruses can be identified by HI test using a preparation made of the combination of two different monoclonals. A primary evaluation of the pathogenicity of the isolated viruses can be made by HI test using monoclonal antibodies but needs always confirmation using conventional pathogenicity tests. © 1987 Springer-Verlag.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Antigenic and biological characterization of avian paramyxovirus type 1 isolates from pigeons

21 A/PMV-1 viruses were isolated from pigeons and characterized using polyclonal and monoclonal antisera in hemagglutination inhibition, sero-neutralization and immunoprecipitation studies. Polyclonal and monoclonal antibodies directed against the HN and F proteins of Italien virus reacted with all pigeon isolates showing a close relationship between chicken velogenic and pigeon viruses. Differences in the M.W. of F0, P and M proteins were however observed between pigeon and chicken Italien virus. Marked differences in virulence were recorded among pigeon isolates; these were reflected by great variation in the IVPI of the different strains. © 1986 Springer-Verlag.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Protective Effects Of Hn And F Glycoprotein-Specific Monoclonal Antibodies On Experimental Newcastle Disease

Monoclonal antibodies directed against two different epitopes of HN protein of NDV Italien neutralised this virus in both in vitro and in vivo tests. Moreover, the combination of these two HN monoclonal antibodies neutralised the Italien virus synergistically. Five monoclonal antibodies directed against the F protein of NDV had variable neutralising activity against NDV Italien. Passive protection afforded by some anti F monoclonal antibodies was higher than that observed with the combination of the two HN monoclonal antibodies and even equivalent or better than that obtained with rabbit polyclonal antiserum. The importance of the F protein in the immune response against NDV is demonstrated. © 1986, Taylor & Francis Group, LLC. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Survey of non-invasive ventilation for acute exacerbation of chronic obstructive pulmonary disease patients in emergency departments in Belgium.

A study was undertaken to assess the availability and use of non-invasive ventilation (NIV) for the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) in emergency departments in Belgium. A questionnaire was sent to the head physicians of 145 emergency departments (EDs) found in the list of the Belgian College of Emergency Physicians (BeCEP). Ninety eight questionnaires were analysed (representing 68% of the questionnaires sent). NIV was used in 49% of the EDs. In the hospitals where NIV was not used, the most important reasons given were no available equipment in 71%, lack of experience with this form of treatment in 32.7%, and more time consuming for physicians and nursing staff in 22.8%. Only 3.8% of the physicians doubted the benefit of NIV treatment. In the hospitals where NIV was used, the patient was watched during the first hour by one nurse only in 19.6%, by one physician in 8.6% and by a nurse and a physician in 54.5%. NIV was used for more than 4 h in 33% of EDs. Pressure-controlled ventilation (with home respirators) was used more often than volume-controlled ventilation.Journal Articleinfo:eu-repo/semantics/publishe

A systematic encounter with a psycho-oncologist: Longitudinal study in women with breast cancer

Introduction: Cancer patients usually will not ask for psychological support. To increase the proportion of patients who may benefit from psychological support, an encounter was implemented in our hospital, within days following the announcement of a breast cancer diagnosis. In the current study the interest and the efficiency of such an intervention on the distress across the stages of the oncological treatment was assessed. Methods: A longitudinal design with an intervention group and a control group that did not receive the visit of the psychologist was performed. Sociodemographic and disease information, distress, coping, and patients’ needs were assessed on three occasions (diagnosis, treatment and end of treatment). Results: A significant decrease in depression (p < .05), in needs of medical information (p < .05) and a mobilization of distractive coping (p < .05) was found only in the encounter group. Conclusion: Current research indicates that an encounter with the psychologist can be helpful to cope with cancer. It also highlights the importance of coping from cancer patients. Hence, although the intervention of a psycho-oncologist is not always necessary, a systematic encounter is an adequate time where a possible psychological consultation is proposed

Comprehensive RNA and protein functional assessments contribute to the clinical interpretation of MSH2 variants causing in-frame splicing alterations

International audienceBackground Spliceogenic variants in disease-causing genes are often presumed pathogenic since most induce frameshifts resulting in loss of function. However, it was recently shown in cancer predisposition genes that some may trigger in-frame anomalies that preserve function. Here, we addressed this question by using MSH2 , a DNA mismatch repair gene implicated in Lynch syndrome, as a model system. Methods Eighteen MSH2 variants, mostly localised within canonical splice sites, were analysed by using minigene splicing assays. The impact of the resulting protein alterations was assessed in a methylation tolerance-based assay. Clinicopathological characteristics of variant carriers were collected. Results Three in-frame RNA biotypes were identified based on variant-induced spliceogenic outcomes: exon skipping (E3, E4, E5 and E12), segmental exonic deletions (E7 and E15) and intronic retentions (I3, I6, I12 and I13). The 10 corresponding protein isoforms exhibit either large deletions (49–93 amino acids (aa)), small deletions (12 or 16 aa) or insertions (3–10 aa) within different functional domains. We showed that all these modifications abrogate MSH2 function, in agreement with the clinicopathological features of variant carriers. Conclusion Altogether, these data demonstrate that MSH2 function is intolerant to in-frame indels caused by the spliceogenic variants analysed in this study, supporting their pathogenic nature. This work stresses the importance of combining complementary RNA and protein approaches to ensure accurate clinical interpretation of in-frame spliceogenic variants