Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P \u3c .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society of Clinical Oncolog

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS

IF 12.015International audienceProne position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO2/FiO(2) ratio < 150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS. We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed. Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO2 change was found according to oxygenation response or lung morphology. In ARDS patients with a PaO2/FiO(2) ratio aecurrency sign150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP

Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study

International audienc

Experts’ guidelines of intubation and extubation of the ICU patient of French Society of Anaesthesia and Intensive Care Medicine (SFAR) and French-speaking Intensive Care Society (SRLF)

International audienceBackground: Intubation and extubation of ventilated patients are not risk-free procedures in the intensive care unit (ICU) and can be associated with morbidity and mortality. Intubation in the ICU is frequently required in emergency situations for patients with an unstable cardiovascular or respiratory system. Under these circumstances, it is a high-risk procedure with life-threatening complications (20–50%). Moreover, technical problems can also give rise to complications and several new techniques, such as videolaryngoscopy, have been developed recently. Another risk period is extubation, which fails in approximately 10% of cases and is associated with a poor prognosis. A better understanding of the cause of failure is essential to improve success procedure.Results and conclusion: In constructing these guidelines, the SFAR/SRLF experts have made use of new data on intubation and extubation in the ICU from the last decade to update existing procedures, incorporate more recent advances and propose algorithm

Integration and verification testing of the LSST camera

International audienceThe Integration and Verification Testing of the Large Synoptic Survey Telescope (LSST) Camera is described. The LSST Camera will be the largest astronomical camera ever constructed, featuring a 3.2 giga-pixel focal plane mosaic of 189 CCDs with in-vacuum controllers and readout, dedicated guider and wavefront CCDs, a three element corrector with a 1.6-meter diameter initial optic, six optical filters covering wavelengths from 320 to 1000 nm with a novel filter exchange mechanism, and camera-control and data acquisition capable of digitizing each image in two seconds. In this paper, we describe the integration processes under way to assemble the Camera and the associated verification testing program. The Camera assembly proceeds along two parallel paths: one for the focal plane and cryostat and the other for the Camera structure itself. A range of verification tests will be performed interspersed with assembly to verify design requirements with a test-as-you-build methodology. Ultimately, the cryostat will be installed into the Camera structure as the two assembly paths merge, and a suite of final Camera system tests performed. The LSST Camera is scheduled for completion and delivery to the LSST observatory in 2020