A functional magnetic resonance imaging study of pathophysiological changes responsible for mirror movements in Parkinson's disease.

Mirror movements correspond to involuntary movements observed in the limb contralateral to the one performing voluntary movement. They can be observed in Parkinson's disease (PD) but their pathophysiology remains unclear. The present study aims at identifying their neural correlates in PD using functional magnetic resonance imaging. Ten control subjects and 14-off drug patients with asymmetrical right-sided PD were included (8 with left-sided mirror movements during right-hand movements, and 6 without mirror movements). Between-group comparisons of BOLD signal were performed during right-hand movements and at rest (p<0.005 uncorrected). The comparison between PD patients with and without mirror movements showed that mirror movements were associated with an overactivation of the insula, precuneus/posterior cingulate cortex bilaterally and of the left inferior frontal cortex and with a deactivation of the right dorsolateral prefrontal cortex, medial prefrontal cortex, and pre-supplementary motor area and occipital cortex. These data suggest that mirror movements in Parkinson's disease are promoted by: 1- a deactivation of the non-mirroring inhibitory network (dorsolateral prefrontal cortex, pre-supplementary motor area); 2- an overactivation of prokinetic areas (notably the insula). The concomitant overactivation of a proactive inhibitory network (including the posterior cingulate cortex and precuneus) could reflect a compensatory inhibition of mirror movements

Efficacy and safety of programmed cell-death-protein-1 and its ligand inhibitors in pretreated patients with epidermal growth-factor receptor-mutated or anaplastic lymphoma kinase-translocated lung adenocarcinoma

Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting. In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK-or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation. Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5-3.2) months for the entire cohort, 2.2 (95% CI, 1.4-3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1-not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1-19.2) months for the entire population and 13.9 (95% CI, 8.8-20.0) and 19.2 (95% CI, 13.1-not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3. In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed. Abbreviations: ALK = anaplastic lymphoma kinase, ECOG PS = the Eastern Cooperative Oncology Group performance status, EGFR = epidermal growth-factor receptor, GFPC = French Lung Cancer Group, HR = hazard ratio, ICI = immune-checkpoint inhibitor, NSCLC = non-small-cell lung cancer, OS = overall survival, PFS = progression-free survival, ROS-1 = c-ros oncogene 1, TKIs = tyrosine-kinase inhibitors

BOLD signal changes related to Mirror Movements.

<p><b>A:</b> Reduction of activation during MM (PD+MM B: Increase of activation during MM (PD+MM >PD-MM). Graphs show the regionally averaged beta weights across patients from each group. Error bars indicate inter-patient standard error of the mean (SEM). L = left; R = right.</p

Changes of BOLD signal related to Mirror Movements.

<p>Abbreviations : L : left, R : right, BA : Brodmann’s Area</p

Changes of BOLD signal related to Parkinson’s disease.

<p>Abbreviations : L = left; R = right; BA = Brodmann’s area</p

Clinical characteristics of PD patients and controls.

<p>Levodopa Eq = levodopa equivalent: 100 mg L-dopa = 10 mg Bromocriptine = 5mg Ropinirole = 1 mg Pergolide = 50 mg Piribedil = 1 mg Pramipexole <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066910#pone.0066910-Thobois2" target="_blank">[20]</a>; SD: Standard Deviation;</p>*<p>p<0.05.</p

First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score ≥ 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study)

International audienceFew real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation

First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score ≥ 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study)

International audienceFew real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation

Driving Innovation in Anglo-Saxon Economies: Comparative Perspectives

A l’heure de l’avènement de la société de la connaissance, le thème de l’innovation apparaît comme central dans la réflexion sur la croissance et le développement des économies. De ce point de vue, les deux principales économies du monde anglo-saxon présentent un bilan contrasté. Si, depuis leur constitution, les États-Unis se sont attachés à stimuler l’innovation, au point de développer un système dont la performance en a fait, au XXe siècle, un modèle, l’économie britannique, berceau de la révolution industrielle, apparaît aujourd’hui, au même titre que les autres économies européennes, impuissante à rivaliser avec la puissance américaine. Ce contraste, replacé dans le cadre de la stratégie de Lisbonne1, souligne la fascination qu’exerce le modèle américain pour l’Europe et trouve une traduction dans les efforts déployés au tournant du XXIe siècle, tant au Royaume-Uni qu’en Irlande, pour y stimuler l’innovation. Pour le CERVEPAS, qui place au cœur de son projet de recherche la mise en lumière de la dynamique propre aux économies anglo-saxonnes, une réflexion sur ce thème semblait incontournable, dans la continuité des recherches déjà menées sur le rôle de l’entrepreneur dans l’économie britannique et américaine

PD-L1-expression patterns in large-cell neuroendocrine carcinoma of the lung: potential implications for use of immunotherapy in these patients: the GFPC 03-2017 “EPNEC” study

Background: Few data are available on programmed cell-death-protein-1-ligand-1 (PD-L1) expression on large-cell neuroendocrine carcinomas of the lung (LCNECs). We analyzed PD-L1 expression on tumor (TCs) and inflammatory cells (ICs) from LCNEC patients to assess relationships between this expression, clinical characteristics, and disease outcomes. Methods: PD-L1 expression was determined by immunohistochemistry with monoclonal antibody 22C3 in consecutive LCNEC patients managed in 17 French centers between January 2014 and December 2016. Results: After centralized review, only 68 out of 105 (64%) patients had confirmed LCNEC diagnoses. Median overall survival (OS) (95% CI) was 11 (7-16) months for all patients, 7 (5-10), 21 (10-not reached) and not reached months for metastatic, stage III and localized forms (p = 0.0001). Respectively, 11% and 75% of the tumor samples were TC+ and IC+, and 66% had a TC-/IC+ profile. Comparing IC+ versus IC-metastatic LCNEC, the former had significantly longer progression-free survival [9 (4-13) versus 4 (1-8) months; p = 0.03], with a trend towards better median OS [12 (7-18) versus 9.5 (4-14) months; p = 0.21]. Compared to patients with TCtumors, those with TC+ LCNECs tended to have non-significantly shorter median OS [4 (1-6.2) versus 11 (8-18) months, respectively]. Median OS was significantly shorter for patients with TC+/IC-metastatic LCNECs than those with TC-IC+ lesions (2 versus 8 months, respectively; p = 0.04). Conclusion: TC-/IC+ was the most frequent PD-L1-expression profile for LCNECs, a pattern quite specific compared with non-small-cell lung cancer and small-cell lung cancer. IC PD-L1 expression seems to have a prognostic role