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Boulogne-Billancourt, France

Paoletti X.,Institute National du Cancer | Oba K.,Kyoto University | Burzykowski T.,Hasselt University | Michiels S.,Institute Gustave Roussy | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking. Objectives: To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments. Data Sources: Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer. We searched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings. Study Selection: All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified. Data Extraction: As of 2010, individual patient data were available from 17 trials (3838 patients representing 60% of the targeted data) with a median follow-up exceeding 7 years. Results: There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P<.001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P<.001). There was no significant heterogeneity for overall survival across RCTs (P=.52) or the 4 regimen groups (P=.13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy. Conclusion: Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone. ©2010 American Medical Association. All rights reserved.

Repesse X.,University Hospital Ambroise Pare | Charron C.,University Hospital Ambroise Pare | Fink J.,University Hospital Ambroise Pare | Beauchet A.,University Hospital Ambroise Pare | And 6 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2015

Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any. We performed a prospective study in 202 patients who died in the ICU with a central venous and/or arterial catheter. One minute after the heart stopped beating, intravascular pressures were recorded in the supine position after ventilator disconnection. Parameters at admission, during the ICU stay, and at the time of death were prospectively collected. One-minute Pmsf was 12.8 ± 5.6 mmHg. It did not differ according to gender, severity score, diagnosis at admission, fluid balance, need for and duration of mechanical ventilation, or length of stay. Nor was there any difference according to suspected cause of death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock, although a large variability of values was observed. The presence of norepinephrine at the time of death (102 patients) was associated with a higher 1-min Pmsf (14 ± 6 vs. 11.4 ± 4.5 mmHg), whereas the decision to forgo life-sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 ± 3.8 vs. 13.1 ± 5.3 mmHg). In a multiple-regression analysis, norepinephrine (β= 2.67, P = 0.0004) and age (β= –0.061, P = 0.022) were associated with 1-min Pmsf. One-minute Pmsf appeared highly variable without any difference according to the kind of shock and fluid balance, but was higher with norepinephrine. © 2015 the American Physiological Society.

Charron C.,University Hospital Ambroise Pare | Templier F.,University Hospital Raymond Poincare | Goddet N.S.,University Hospital Raymond Poincare | Baer M.,University Hospital Raymond Poincare | And 2 more authors.
European Journal of Emergency Medicine | Year: 2015

OBJECTIVE: Pocket ultrasound devices (PUDs) increase the scope of transthoracic echocardiography. We assessed the ability of emergency physicians (EPs) to obtain and interpret views using PUDs in prehospital emergencies.MATERIALS AND METHODS: Nine EPs underwent a 2-day training program focused on acquisition of four views and on evaluation of left ventricular function, right ventricular size, the inferior vena cava, and detection of pericardial effusion. Then, EPs used a PUD to perform transthoracic echocardiography in patients with shock or acute respiratory failure. The quality and interpretation of views were graded by an expert as not obtained/inadequate, adequate, or optimal. Agreement between the expert and the physicians was evaluated using Cohen's κ test.RESULTS: One hundred consecutive exams were evaluated in patients with shock or acute respiratory failure. Parasternal long-axis and short-axis views, and a subcostal view were not obtained or inadequate in 56, 54, and 54 patients, respectively. An apical four-chamber view was not obtained or inadequate in 33 patients. One, two, or three views were graded as adequate or optimal in 86, 65, and 35 patients. Agreement between physicians and experts for left ventricular systolic function, right ventricular size, and pericardial effusion was weak [κ 0.37 (0.17; 0.59), 0.27 (0.023; 0.53), and 0.33 (-0.008; 0.67)]. Agreement for inferior vena cava evaluation was very weak [0.13 (-0.17; 0.43)].CONCLUSION: After a very short training program, echocardiography using a PUD in prehospital emergencies was feasible in half of patients. Acquisition of technical skills is reasonable, but accurate evaluation of cardiac function may require more extensive training. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Perrin J.,French Institute of Health and Medical Research | Charron C.,University Hospital Ambroise Pare | Francois J.-H.,University Hospital Ambroise Pare | Cramer-Borde E.,University Hospital Ambroise Pare | And 6 more authors.
Shock | Year: 2015

Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis. © 2014 by the Shock Society.

Repesse X.,University Hospital Ambroise Pare | Charron C.,University Hospital Ambroise Pare | Vieillard-Baron A.,University Hospital Ambroise Pare | Vieillard-Baron A.,University of Versailles | Vieillard-Baron A.,French Institute of Health and Medical Research
Current Opinion in Critical Care | Year: 2016

Purpose of review The right ventricle (RV) plays a pivotal role during respiratory failure because of its high sensitivity to small loading changes during inspiration. Both RVs, preload and afterload, are altered during inspiration, either in spontaneous breathing or during mechanical ventilation. Some clinical situations especially affect RV load during inspiration, for example acute asthma and acute respiratory distress syndrome. The aim of this review is to explain and to summarize the different mechanisms leading to RV failure in these situations. Recent findings Research has recently reemphasized the importance to well known physiology of the venous return which is a contributor of RV preload. Authors recently focused on the mean systemic filling pressure which is one of the determinants of venous return. Venous return may change in opposite direction according to the type of ventilation (spontaneous or assisted). Recent works have also demonstrated the crucial impact of lung inflation and driving pressure on RV afterload, and have confirmed the deleterious effect of severe RV failure, described as acute cor pulmonale. In most situations of RV overload induced by inspiration, significant pulse pressure variations are observed, either called 'pulsus paradoxus' in spontaneously breathing patients or 'reverse pulsus paradoxus' in mechanically ventilated patients. Summary RV is very sensitive to abnormal inspiration, which is always responsible for an increase in its afterload. Pulse pressure variations, central venous pressure and especially echocardiography may monitor RV function in abnormal clinical situations. The pulmonary artery catheter was also proposed although now less used. © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

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