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Cinotti R.,Nantes University Hospital Center | Roquilly A.,Nantes University Hospital Center | Roquilly A.,University of Nantes | Mahe P.J.,Nantes University Hospital Center | And 9 more authors.
Journal of Critical Care | Year: 2014

Purpose: Preload responsiveness parameters could be useful in the hemodynamic management of septic shock. Methods: A multicentric prospective echocardiographic observational study was conducted from March 2009 to August 2011. Clinically brain-dead subjects were included. Pulse pressure variations (δPPs) were recorded. Cardiac index, variation of the maximum flow velocity of aortic systolic blood flow, and right ventricular function parameters were evaluated via transthoracic echocardiography. Fluid responsiveness was defined by at least 15% cardiac index increase, 30 minutes after a 500-mL colloid solution infusion. The number of organs harvested was recorded. Results: Twenty-five subjects were included. Pulse pressure variation could not discriminate responders (n = 15) from nonresponders (n = 10). The best δPP threshold (20%) could discriminate responders with a sensitivity of 100% and a specificity of 40%. Variation of the maximum flow velocity of aortic systolic blood flow, tricuspid annular plane systolic excursion, and right ventricle dilation could not discriminate responders from nonresponders. Eighteen subjects underwent organ harvesting. The number of organs harvested was higher in responders (3.5 [3-5]) than in nonresponders (2.5 [2-3]; P = .03). Conclusions: A δPP threshold of 13% is insufficient to guide volume expansion in donors. The best threshold is 20%. Fluid responsiveness monitoring could enhance organ harvesting. © 2014 Elsevier Inc.

Zemb P.,Cabinet de Gynecologie Obstetrique | Bellec J.-Y.,Center Hospitalier Of Bretagne Sud
Reproduction Humaine et Hormones | Year: 2010

Usual antepartum semiology (short-term variability of fetal heart rate, amount of amniotic fluid, etc.) can indicate the fetal homeostatic status, and thus the placental efficiency. A clinical study concerning the predictability of fetal tolerance to labor using this antepartum semiology leads us to conclude the following dominant factual chronology: after several weeks of complex fluctuations, an appearance of placental efficiency decrease is likely to precede parturition by an average of 6 to 72 hours. We interpret the suspected chronology as relying on two phenomena: 1) an effective oscillation of the placental efficiency, involving an intermittent hypoxic stimulation 2) a paradoxical sedative effect of the fetal cortisol pulsatile crescendo initiator of parturition (simulating some of the low placental efficiency semiology). The unstable equilibrium generated by the balance (hypoxic stimulation/trophoblastic and fetal reactivity) could be effective since early in the pregnancy, influencing especially the setting of the corticotrophin-releasing hormone placental clock. By else, the high nuchal translucency thickness could be due to a fetal hypercortisolism. Finally, postnatal, the sudden infant death syndrome could be due to the resurgence of the prenatal sedative effect exerted by an hypoxic stimulation. © Editions ESKA 2010.

Patients receiving palliative care experience extreme vulnerability reminding them of the fragility of their human condition. How are they to trust nurses bearing bad news in these crucial moments? Trust is built on team coherence and rigorous support. © 2013 Published by Elsevier Masson SAS.

Barlesi F.,Aix - Marseille University | Mazieres J.,University Paul Sabatier | Merlio J.-P.,University of Bordeaux 1 | Debieuvre D.,Hopital Emile Muller | And 30 more authors.
The Lancet | Year: 2016

Background The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. Methods This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. Findings 18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18-98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7-16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8-25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7-38·2] for presence of a genetic alteration vs 33% [29·5-35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0-18·8] vs 9% [6·7-11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2-10·7] vs 7·1 months [6·1-7·9]; p<0·0001) and overall survival (16·5 months [15·0-18·3] vs 11·8 months [10·1-13·5]; p<0·0001) compared with absence of a genetic alteration. Interpretation Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit. Funding French National Cancer Institute (INCa). © 2016 Elsevier Ltd.

Corre R.,University of Rennes 2 - Upper Brittany | Greillier L.,University Of Medecine | Le Caer H.,Center Hospitalier Of Draguignan | Audigier-Valette C.,Center Hospitalier Intercommunal Of Toulon | And 18 more authors.
Journal of Clinical Oncology | Year: 2016

Purpose Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non - small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. Patients and Methods In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. Results Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P =.015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P =.007). Conclusion In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity. © 2016 by American Society of Clinical Oncology.

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