Pinocchio: éternelle source d'inspiration?

Pinocchio, célèbre marionnette née de l’imagination de l’écrivain toscan Carlo Collodi, a fait sa première apparition publique il y a cent trente-huit ans déjà. En ce laps de temps, l’humanité de ce pantin est parvenue à attendrir le coeur denombreux lecteurs et lectrices, ainsi que celui des spectatrices et spectateurs des films et des pièces de théâtre qui l’ont mis en scène. Au cours de ce siècle, il a connu bien des aventures et revêtu nombre de casquettes, mais il a surtout franchi des frontières et atteint de nouveaux pays. De la Toscane, sa terre natale, Pinocchio a traversé l'Europe et n’a pas hésité à jeter l’ancre sur d'autres continents. Par quel moyen a-t-il connu un tel succès? C'est simple, grâce à la traduction

Long-term safety of bilateral targeted lung denervation in patients with COPD

Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation. The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure. Patients and methods: This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators. The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year. Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life. Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up. Results: A total of 15 patients (47% male, age 63.2 +/- 4.0 years) underwent TLD with a total procedure time of 89 +/- 16 min, and the total fluoroscopy time was 2.5 +/- 2.7 min. Primary safety end point of freedom from worsening of COPD was 100%. There were no procedural complications reported. Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD. Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy. Conclusion: TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years

Identification of morphological and functional MRI markers predictive of low-grade glioma's growth : Development of an automatic algorithm for segmentation and prediction of malignant transformation

Les gliomes représentent 50% des tumeurs cérébrales primitives. Leur forme la moins agressive, les gliomes diffus de bas grade, classés grade 1 et 2 par l'Organisation mondiale de la santé (OMS), se caractérisent par une croissance lente et continue, préférentiellement le long des trajets de la substance blanche cérébrale. Les gliomes de bas grade évoluent toujours vers un grade agressif, le gliome de haut grade. Avec la volonté de réaliser des traitements et des chirurgies de plus en plus tôt, il devient primordial de pouvoir prévoir la progression de la tumeur et son passage d'un état bénin à plus sévère. L'IRM est une technique non invasive, non irradiante qui possède une sensibilité supérieure aux autres imageries en ce qui concerne le diagnostic de gliomes cérébraux. L'IRM est capable d'évaluer des aspects anatomiques et d'explorer divers aspects fonctionnels au sein d'une tumeur. On peut notamment citer l'imagerie de perfusion capable de quantifier les volumes et les débits sanguins cérébraux. Un manque de standardisation dans les méthodes de diagnostic a été mis en évidence, ce qui entraine des variations dans la prise en charge des patients et donc une hétérogénéité dans les pronostics de la croissance tumorale. Des études ont montré que la transition d'un gliome de bas grade en gliome de haut grade peut être prédite pour une vitesse de croissance du diamètre moyen supérieure à 8 mm/an. Il a aussi été établi que le volume sanguin au niveau de la tumeur pouvait être un indice de la croissance tumorale et de sa prochaine transformation. En effet, un développement tumoral est toujours couplé à un développement chaotique des vaisseaux en son sein et donc à une augmentation anormale du volume sanguin cérébral au niveau de la lésion. Ce développement vasculaire peut aboutir à une rupture de la barrière hémato-encéphalique et une prise de contraste est observable sur l'imagerie IRM pondérée T1 (apparition d'un hypersignal). Cette apparition de contraste est un des signes de la transformation de la tumeur de bas grade en un gliome de haut grade, transformation dite anaplasique, mais n'est pas spécifique du moment de cette transformation. L'approche multimodale en IRM (évaluation morphologique et fonctionnelle) apporte de nombreuses informations diagnostiques. Leur exploitation doit s'appuyer sur un ensemble d'informations qui peuvent être obtenues par le biais du développement de nouvelles techniques automatiques de traitement d'image IRM. Il s'agit, dans l'avenir, de pouvoir définir des métriques multimodales (combinant hypersignal IRM, perfusion, diamètre, volume...) afin de standardiser les diagnostics. L'évaluation longitudinale est particulièrement importante, puisqu'il s'agit d'être capable de prédire la croissance tumorale.L’objectif final de ce travail de thèse est d’être capable de prédire la transformation anaplasique ou, à minima, l’évolution péjorative du gliome cérébral diffus de bas grade au cours de son évolution.Pour parvenir à cet objectif, la première étape a été de mettre en place une segmentation automatique du volume tumoral. Un algorithme de type réseau de neurones convolutifs a été entrainé sur une grande base de données de gliomes de bas grade. Cette base de données a été colligée au sein du service de neuroradiologie du CHU Gui de Chauliac et les zones tumorales ont été tracées manuellement sur chaque examen par des neuroradiologues. L’entrainement de cet algorithme s’est fait exclusivement sur des suivis longitudinaux de gliomes de bas grades car il s’agissait d’être capable de segmenter les lésions sur des examens de routine clinique (gliome opérés, différentes machines IRM d’acquisition…).Pour prédire l’évolution de la tumeur, il a fallu la caractériser au cours de son suivi longitudinal. Cette caractérisation a été possible par le calcul de paramètres quantitatifs morphologiques (volume, diamètre moyen de la tumeur …)Gliomas represent 50% of primary brain tumors. Their least aggressive form, diffuse low-grade gliomas, classified as grade 1 and 2 by the World Health Organization (WHO), are characterized by a slow and continuous growth, preferentially along the tracts of the cerebral white matter. Low-grade gliomas always progress to an aggressive form, the high-grade glioma. With the desire to perform treatments and surgeries earlier and earlier, it becomes essential to be able to predict the progression of the tumor and its passage from a benign to a more severe state. MRI is a non-invasive, non-irradiating technique that has a higher sensitivity than other imaging techniques for the diagnosis of cerebral gliomas. MRI can assess anatomical aspects and exploring various functional parameters within a tumor. These include perfusion imaging which is capable of quantify cerebral blood volumes and flow rates. A lack of standardization in diagnostic methods has been identified, leading to variations in patient management and thus heterogeneity in prognosis of tumor growth. Studies have shown that the transition from low-grade to high-grade glioma can be predicted for a mean diameter growth rate greater than 8 mm/year. It has also been established that the cerebral blood volume at the tumor level can be an indicator of tumor growth and its next transformation. Indeed, a tumor development is always coupled to a chaotic development of vessels within it and thus to an abnormal increase of the cerebral blood volume at the level of the lesion. This vascular development can lead to a rupture of the blood-brain barrier and contrast is observed on T1-weighted MRI (hypersignal). This contrast enhancement is a sign of the low-grade tumor’s transformation to a high-grade glioma, it is called the anaplastic transformation. The observation of the T1 contrast enhancement is not specific of the moment of the malignant transformation. The multimodal approach in MRI (morphological and functional evaluation) provides a lot of diagnosis information. Their exploitation must be based on a set of information that can be obtained through the development of new automatic techniques for the processing of MRI datas. In the future, it will be necessary to define multimodal metrics (combining MRI hypersignal, perfusion, diameter, volume, etc.) in order to standardize diagnoses. Longitudinal evaluation is particularly important, since it is necessary in order to predict tumor growth.The final objective of this work is to be able to predict the anaplastic transformation or, at least, the negative evolution of diffuse low-grade glioma during its evolution.To achieve this goal, the first step was to set up an automatic segmentation of the tumor volume. A convolutional neural network algorithm was trained on a large database of low-grade gliomas. This database was collected in the neuroradiology department of the CHU Gui de Chauliac and the tumor areas were manually traced on each examination by neuroradiologists. The training of this algorithm was done exclusively on longitudinal follow-ups of low-grade gliomas because it was necessary to be able to segment the lesions on clinical routine (glioma with surgical interventions, different MRI acquisition machines...).To predict the evolution, it was necessary to characterize the tumor lesion during its longitudinal follow-up. This characterization was possible by calculating quantitative morphological parameters (volume, average diameter of the tumor ...

Identification de marqueurs IRM morphologiques et fonctionnels prédictifs de la croissance des gliomes de bas grade : Développement d’un algorithme automatique de segmentation et de prédiction de la transformation

Gliomas represent 50% of primary brain tumors. Their least aggressive form, diffuse low-grade gliomas, classified as grade 1 and 2 by the World Health Organization (WHO), are characterized by a slow and continuous growth, preferentially along the tracts of the cerebral white matter. Low-grade gliomas always progress to an aggressive form, the high-grade glioma. With the desire to perform treatments and surgeries earlier and earlier, it becomes essential to be able to predict the progression of the tumor and its passage from a benign to a more severe state. MRI is a non-invasive, non-irradiating technique that has a higher sensitivity than other imaging techniques for the diagnosis of cerebral gliomas. MRI can assess anatomical aspects and exploring various functional parameters within a tumor. These include perfusion imaging which is capable of quantify cerebral blood volumes and flow rates. A lack of standardization in diagnostic methods has been identified, leading to variations in patient management and thus heterogeneity in prognosis of tumor growth. Studies have shown that the transition from low-grade to high-grade glioma can be predicted for a mean diameter growth rate greater than 8 mm/year. It has also been established that the cerebral blood volume at the tumor level can be an indicator of tumor growth and its next transformation. Indeed, a tumor development is always coupled to a chaotic development of vessels within it and thus to an abnormal increase of the cerebral blood volume at the level of the lesion. This vascular development can lead to a rupture of the blood-brain barrier and contrast is observed on T1-weighted MRI (hypersignal). This contrast enhancement is a sign of the low-grade tumor’s transformation to a high-grade glioma, it is called the anaplastic transformation. The observation of the T1 contrast enhancement is not specific of the moment of the malignant transformation. The multimodal approach in MRI (morphological and functional evaluation) provides a lot of diagnosis information. Their exploitation must be based on a set of information that can be obtained through the development of new automatic techniques for the processing of MRI datas. In the future, it will be necessary to define multimodal metrics (combining MRI hypersignal, perfusion, diameter, volume, etc.) in order to standardize diagnoses. Longitudinal evaluation is particularly important, since it is necessary in order to predict tumor growth.The final objective of this work is to be able to predict the anaplastic transformation or, at least, the negative evolution of diffuse low-grade glioma during its evolution.To achieve this goal, the first step was to set up an automatic segmentation of the tumor volume. A convolutional neural network algorithm was trained on a large database of low-grade gliomas. This database was collected in the neuroradiology department of the CHU Gui de Chauliac and the tumor areas were manually traced on each examination by neuroradiologists. The training of this algorithm was done exclusively on longitudinal follow-ups of low-grade gliomas because it was necessary to be able to segment the lesions on clinical routine (glioma with surgical interventions, different MRI acquisition machines...).To predict the evolution, it was necessary to characterize the tumor lesion during its longitudinal follow-up. This characterization was possible by calculating quantitative morphological parameters (volume, average diameter of the tumor ...)Les gliomes représentent 50% des tumeurs cérébrales primitives. Leur forme la moins agressive, les gliomes diffus de bas grade, classés grade 1 et 2 par l'Organisation mondiale de la santé (OMS), se caractérisent par une croissance lente et continue, préférentiellement le long des trajets de la substance blanche cérébrale. Les gliomes de bas grade évoluent toujours vers un grade agressif, le gliome de haut grade. Avec la volonté de réaliser des traitements et des chirurgies de plus en plus tôt, il devient primordial de pouvoir prévoir la progression de la tumeur et son passage d'un état bénin à plus sévère. L'IRM est une technique non invasive, non irradiante qui possède une sensibilité supérieure aux autres imageries en ce qui concerne le diagnostic de gliomes cérébraux. L'IRM est capable d'évaluer des aspects anatomiques et d'explorer divers aspects fonctionnels au sein d'une tumeur. On peut notamment citer l'imagerie de perfusion capable de quantifier les volumes et les débits sanguins cérébraux. Un manque de standardisation dans les méthodes de diagnostic a été mis en évidence, ce qui entraine des variations dans la prise en charge des patients et donc une hétérogénéité dans les pronostics de la croissance tumorale. Des études ont montré que la transition d'un gliome de bas grade en gliome de haut grade peut être prédite pour une vitesse de croissance du diamètre moyen supérieure à 8 mm/an. Il a aussi été établi que le volume sanguin au niveau de la tumeur pouvait être un indice de la croissance tumorale et de sa prochaine transformation. En effet, un développement tumoral est toujours couplé à un développement chaotique des vaisseaux en son sein et donc à une augmentation anormale du volume sanguin cérébral au niveau de la lésion. Ce développement vasculaire peut aboutir à une rupture de la barrière hémato-encéphalique et une prise de contraste est observable sur l'imagerie IRM pondérée T1 (apparition d'un hypersignal). Cette apparition de contraste est un des signes de la transformation de la tumeur de bas grade en un gliome de haut grade, transformation dite anaplasique, mais n'est pas spécifique du moment de cette transformation. L'approche multimodale en IRM (évaluation morphologique et fonctionnelle) apporte de nombreuses informations diagnostiques. Leur exploitation doit s'appuyer sur un ensemble d'informations qui peuvent être obtenues par le biais du développement de nouvelles techniques automatiques de traitement d'image IRM. Il s'agit, dans l'avenir, de pouvoir définir des métriques multimodales (combinant hypersignal IRM, perfusion, diamètre, volume...) afin de standardiser les diagnostics. L'évaluation longitudinale est particulièrement importante, puisqu'il s'agit d'être capable de prédire la croissance tumorale.L’objectif final de ce travail de thèse est d’être capable de prédire la transformation anaplasique ou, à minima, l’évolution péjorative du gliome cérébral diffus de bas grade au cours de son évolution.Pour parvenir à cet objectif, la première étape a été de mettre en place une segmentation automatique du volume tumoral. Un algorithme de type réseau de neurones convolutifs a été entrainé sur une grande base de données de gliomes de bas grade. Cette base de données a été colligée au sein du service de neuroradiologie du CHU Gui de Chauliac et les zones tumorales ont été tracées manuellement sur chaque examen par des neuroradiologues. L’entrainement de cet algorithme s’est fait exclusivement sur des suivis longitudinaux de gliomes de bas grades car il s’agissait d’être capable de segmenter les lésions sur des examens de routine clinique (gliome opérés, différentes machines IRM d’acquisition…).Pour prédire l’évolution de la tumeur, il a fallu la caractériser au cours de son suivi longitudinal. Cette caractérisation a été possible par le calcul de paramètres quantitatifs morphologiques (volume, diamètre moyen de la tumeur …

Les traducteurs : une espèce en voie d'extinction ? : Evolution du profil et du travail des traducteurs Etude de cas réalisée au Parlement européen

Après avoir retracé l'histoire de la traduction de l'Antiquité aux temps modernes, ce mémoire porte sur les menaces qui planent actuellement sur la profession. Sur la base d'une enquête menée au sein de la Direction générale de la traduction du Parlement européen, nous tenterons d'esquisser le destin de la profession. Following a summary of the evolution of translation from antiquity to modern times, this paper identifies threats to the profession. Based on a case study carried out in the European Parliament's Directorate General for Translation, we will attempt to unveil the mysteries of what fate has in store for translators

Impact of Pre-Existing History of Heart Failure on Patient Profile, Therapeutic Management, and Prognosis in Cardiogenic Shock: Insights from the FRENSHOCK Registry

International audienceThere is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking. We aimed to compare CS patients with new-onset HF to those with worsening CHF in the multicenter FRENSHOCK registry. Altogether, 772 CS patients were prospectively included: 433 with a previous history of CHF and 339 without. Worsening CHF patients were older (68 +/− 13.4 vs. 62.7 +/− 16.2, p < 0.001) and had a greater burden of extra-cardiac comorbidities. At admission, acute myocardial infarction was predominantly observed in the new-onset HF group (49.9% vs. 25.6%, p < 0.001). When focusing on hemodynamic parameters, worsening CHF patients showed more congestion and higher ventricular filling pressures. Worsening CHF patients experienced higher in-hospital all-cause mortality (31.3% vs. 24.2%, p = 0.029). Our results emphasize the great heterogeneity of the patients presenting with CS. Worsening CHF patients had higher risk profiles, and this translated to a 30% increase in in-hospital all-cause mortality. The heterogeneity of this population prompts us to better determine the phenotype of CS patients to adapt their management

Safety and Dose Study of Targeted Lung Denervation in Moderate/Severe COPD Patients

RATIONALE: Targeted lung denervation (TLD) is a novel bronchoscopic treatment for the disruption of parasympathetic innervation of the lungs. OBJECTIVES: To assess safety, feasibility, and dosing of TLD in patients with moderate to severe COPD using a novel device design. METHODS: Thirty patients with COPD (forced expiratory volume in 1 s 30-60%) were 1:1 randomized in a double-blinded fashion to receive TLD with either 29 or 32 W. Primary endpoint was the rate of TLD-associated adverse airway effects that required treatment through 3 months. Assessments of lung function, quality of life, dyspnea, and exercise capacity were performed at baseline and 1-year follow-up. An additional 16 patients were enrolled in an open-label confirmation phase study to confirm safety improvements after procedural enhancements following gastrointestinal adverse events during the randomized part of the trial. RESULTS: Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group, p = 0.6. Five patients early in the randomized phase experienced serious gastric events. The study was stopped and procedural changes made that reduced both gastrointestinal and airway events in the subsequent phase of the randomized trial and follow-up confirmation study. Improvements in lung function and quality of life were observed compared to baseline values for both doses but were not statistically different. CONCLUSIONS: The results demonstrate acceptable safety and feasibility of TLD in patients with COPD, with improvements in adverse event rates after procedural enhancements.status: publishe

Amantadine use in the French prospective NS-Park cohort

International audienceObjective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs