Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

BackgroundIn the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.MethodsA FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.ResultsSamples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].ConclusionsThis study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials

[Diagnosis and care of postembolic pulmonary hypertension: the role of the pneumologist].

International audienceThe prognosis of postembolic pulmonary hypertension, a rare and serious disease, has been transformed with the curative intervention of pulmonary endarteriectomy. The screening is based on two key non invasive examinations, the cardiac ultrasound and ventilation-perfusion scintigraphy. The confirmation of the diagnosis and the determination of the best therapeutic options then relies on the expertise of the national reference centre, based on the haemodynamics and the morphological data provided by pulmonary angiography and spiral computerised tomography. Although the technique of endarteriectomy is fully validated, a drug approach is in the assessment process, both in the inoperable forms or when confronted with persistent postsurgical pulmonary hypertension

Approche quantitative de l'érosion des versants dans le Massif Central : étude comparée de la sédimentation des lacs de Guéry (1 244 m a.s.l.) et de Montcineyre (1 182 m a.s.l.)

National audienc

Fenfluramine-like cardiovascular side-effects of benfluorex.

International audienceSince 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects. The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2-49 kg x m(-2). No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted

Association between Rheumatoid Arthritis and Pulmonary Hypertension: Data from the French Pulmonary Hypertension Registry

International audienceBackground: Precapillary pulmonary hypertension (PH), and particularly pulmonary arterial hypertension (PAH), is a life-threatening complication of connective tissue diseases (systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease). The relationship between PH and rheumatoid arthritis (RA) has not been clearly established.Objectives: The aim of the study was to evaluate the relationship between precapillary PH and RA.Methods: We identified patients with PH and suspected RA included in the French PH Registry between 1 May 2004 and 31 December 2012 and evaluated the prevalence of confirmed RA in this population. RA phenotypes, clinical, functional, and hemodynamic data, and patient outcomes were recorded.Results: RA was confirmed in 20 patients (70% female; mean age 52 years) with precapillary PH, including 10 patients with PAH, 6 with severe PH due to lung disease, and 4 with chronic thromboembolic PH. The prevalence of RA was 0.35% (95% CI: 0.23-0.54) in the French PH Registry and 0.58% (95% CI: 0.30-1.11) in idiopathic PAH, comparable to that in the general population. The RA phenotype was characterized by the presence of specific RA autoantibodies and joint erosions in 75% of the patients. The outcomes of PH in the RA patients were unremarkable compared to those in other patients from the registry, and RA therapies had no major impact on the cardiopulmonary parameters.Conclusion: When precapillary PH occurs in RA patients, all PH subsets may be identified. The RA prevalence in the French PH Registry is similar to that in the general population, which does not support a specific association or an indication for PH screening in RA patients

Comparison of hydrosedimentary signatures of catchments from the French Critical Zone network

International audienceSoil erosion and sediment transport understanding has important implications for the management of soil and water resources in the critical zone. Water erosion is considered the main threat to soils, causing irreversible losses. The transfer of suspended sediments (SS) downstream poses problems of degradation of the quality of rivers by clogging the bottom and is also a privileged vector for the transport of nutrients, contaminants or pathogens. Particulate transfers arealso very sensitive to changes in land use and in the occurrence and severity of rainfall.Most studies that have sought to synthesise measurements made in different contexts focused on the spatial variability of erosion rates on hillslopes (Cerdan et al., 2010) or on the comparison of integrative variables such as sediment fluxes in different hydrosystems (Milliman and Syvitski, 1992; De Vente et al. 2011; Vanmaercke et al., 2011). However, very few studies have been interested in comparing the relationships between the variables that allow to establish the fluxes (i.e. iquid discharge, turbidity, SS concentrations) whereas their analysis can shed light on hydrosedimentary processes, particularly by exploring their temporal variability (Vercruysse et al., 2017). Within the OZCAR and RZA French networks, many observatories carry out measurements of discharges, turbidities and/or point measurements of SS concentrations at catchment outlets. These datasets are used to address the following questions: i) Are there similar temporal hydrosedimentary signatures at some sites, ii) Is it possible to identify control factors responsible for these signatures? Results show a large diversity of the temporal hydrosedimentary behaviours of the 22 studied catchments as illustrated by some striking features. Indeed, 90% of the SS are transported during less than 0.1% of the time for some sites and during 40% for others. Half of the SS are transported at SS concentrations exceeding 34 g/l for some sites and less than 0.1 g/l for others.First attempts have shown that some of these indicators of temporal variability of SS fluxes can be predicted by site (e.g. area, slope, pedo-geo-morphology, soil use, meteorological forcing) or hydrological characteristics

(ob šestdesetletnici)

none56siPulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. The composition of the guidelines task force reflects themultidisciplinary nature of PH, including members of different medical societies, associations and working groups. The current document follows the two previous ESC and ERS Guidelines, published in 2004 and 2009, focusing on clinical management of PH. A systematic literature review was performed from MEDLINEw to identify new studies published since 2009 concerning the topic of PH. Task force members selected studies based on relevance and appropriateness.noneGaliè, Nazzareno; Humbert, Marc; Vachiery, Jean-Luc; Gibbs, Simon; Lang, Irene; Torbicki, Adam; Simonneau, Gérald; Peacock, Andrew; Vonk Noordegraaf, Anton; Beghetti, Maurice; Ghofrani, Ardeschir; Gomez Sanchez, Miguel Angel; Hansmann, Georg; Klepetko, Walter; Lancellotti, Patrizio; Matucci, Marco; Mcdonagh, Theresa; Pierard, Luc A; Trindade, Pedro T; Zompatori, Maurizio; Hoeper, Marius; Aboyans, Victor; Vaz Carneiro, Antonio; Achenbach, Stephan; Agewall, Stefan; Allanore, Yannick; Asteggiano, Riccardo; Paolo Badano, Luigi; Albert Barberà, Joan; Bouvaist, Hélène; Bueno, Héctor; Byrne, Robert A; Carerj, Scipione; Castro, Graça; Erol, Çetin; Falk, Volkmar; Funck-Brentano, Christian; Gorenflo, Matthias; Granton, John; Iung, Bernard; Kiely, David G; Kirchhof, Paulus; Kjellstrom, Barbro; Landmesser, Ulf; Lekakis, John; Lionis, Christos; Lip, Gregory Y H; Orfanos, Stylianos E; Park, Myung H; Piepoli, Massimo F; Ponikowski, Piotr; Revel, Marie-Pierre; Rigau, David; Rosenkranz, Stephan; Völler, Heinz; Luis Zamorano, JoseGaliè, Nazzareno; Humbert, Marc; Vachiery, Jean-Luc; Gibbs, Simon; Lang, Irene; Torbicki, Adam; Simonneau, Gérald; Peacock, Andrew; Vonk Noordegraaf, Anton; Beghetti, Maurice; Ghofrani, Ardeschir; Gomez Sanchez, Miguel Angel; Hansmann, Georg; Klepetko, Walter; Lancellotti, Patrizio; Matucci, Marco; Mcdonagh, Theresa; Pierard, Luc A; Trindade, Pedro T; Zompatori, Maurizio; Hoeper, Marius; Aboyans, Victor; Vaz Carneiro, Antonio; Achenbach, Stephan; Agewall, Stefan; Allanore, Yannick; Asteggiano, Riccardo; Paolo Badano, Luigi; Albert Barberà, Joan; Bouvaist, Hélène; Bueno, Héctor; Byrne, Robert A; Carerj, Scipione; Castro, Graça; Erol, Çetin; Falk, Volkmar; Funck-Brentano, Christian; Gorenflo, Matthias; Granton, John; Iung, Bernard; Kiely, David G; Kirchhof, Paulus; Kjellstrom, Barbro; Landmesser, Ulf; Lekakis, John; Lionis, Christos; Lip, Gregory Y H; Orfanos, Stylianos E; Park, Myung H; Piepoli, Massimo F; Ponikowski, Piotr; Revel, Marie-Pierre; Rigau, David; Rosenkranz, Stephan; Völler, Heinz; Luis Zamorano, Jos