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Lascarrou J.B.,Roche Holding AG | Boisrame-Helms J.,Hopitaux Universitaires Of Strasbourg | Boisrame-Helms J.,University of Strasbourg | Bailly A.,Roche Holding AG | And 66 more authors.
JAMA - Journal of the American Medical Association | Year: 2017

IMPORTANCE In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopymay decrease this risk by improving glottis visualization. OBJECTIVE To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up. INTERVENTIONS Intubation using a video laryngoscope (n = 186) or direct laryngoscopy (n = 185). All patients received general anesthesia. MAIN OUTCOMES AND MEASURES The primary outcomewas the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications. RESULTS Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7%vs 70.3%; absolute difference, -2.5%[95%CI, -11.9%to 6.9%]; P = .60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n = 290) did not differ between the groups (84.4%with video laryngoscopy vs 83.2%with direct laryngoscopy; absolute difference 1.2%[95%CI, -6.3%to 8.6%]; P = .76). The median time to successful intubationwas 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95%CI, 0 to 0]; P = .95). Video laryngoscopywas not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95%CI, -2.7%to 10.4%]; P = .25). In post hoc analysis, video laryngoscopywas associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7%[95%CI, 1.8%to 11.6%]; P = .01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, -2.3%[95%CI, -7.4%to 2.8%]; P = .37). CONCLUSIONS AND RELEVANCE Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels.


Garcin B.,APHP Hopital Lariboisiere | Houdart E.,APHP Hopital Lariboisiere | Houdart E.,University Paris Diderot | Porcher R.,APHP Hopital Saint Louis | And 6 more authors.
Neurology | Year: 2012

Objectives: Brain arteriovenous malformations (AVMs) often present with epileptic seizures, but prospective data on the risk of seizures with respect to morphologic AVM characteristics are scarce. Methods: We studied 155 consecutive patients with AVMs from a prospective, single-center database using demographic and morphologic factors based on prospectively coded MRI and digital subtraction angiography (DSA) data. Univariate analysis and multivariate logistic regression models were used to test the effect of demographic (age and sex) and morphologic characteristics (AVM size, anatomic and arterial location, and venous drainage pattern) on seizures as initial presentation in patients with unruptured brain AVMs. Results: Overall, 45 patients with AVMs initially presented with seizures (29%). By univariate comparison, male sex (p = 0.02), increasing AVM size (p < 0,006), frontal lobe localization (p < 0.0001), arterial borderzone location (p < 0.0006), superficial venous drainage (p = 0.0002), and presence of venous ectasia (p = 0.003) were statistically associated with seizures. The multivariate analysis confirmed an independent effect of male sex, frontal lobe AVMs, and arterial borderzone location on seizure occurrence. All patients with seizures showed the presence of a superficial venous drainage component. Conclusions: Our study suggests that seizures mainly occur in AVMs with superficial drainage. Other predisposing factors include male sex, increasing AVM size, and frontal lobe and arterial borderzone location. Whether or not interventional treatment has an effect on the long-term risk of epilepsy remains to be determined. Copyright © 2012 by AAN Enterprises, Inc.


Valent P.,Medical University of Vienna | Bonnet D.,Cancer Research UK Research Institute | Wohrer S.,Bone Marrow Transplantation Unit | Andreeff M.,University of Texas M. D. Anderson Cancer Center | And 5 more authors.
Cancer Research | Year: 2013

Accumulating evidence suggests that human cancers develop through a step-wise, but nonlinear process of cellular diversification and evolution. Recent mutational analyses indicate that this process is more complex and diverse than anticipated before whole-genome sequencing methods were readily available. Examples are also emerging now of genetically abnormal clones of cells that have acquired mutations with known oncogenic potential but, nevertheless, may show no manifestations of malignant change for many years. To accommodate these diverse realities, we suggest the term neoplastic refer to clones of cells that have any type of somatic aberrancy associated with an increased propensity to become malignant, and the derivative term neoplastic stem cell be adopted to identify the cells responsible for the long-term maintenance of such clones. Neoplastic clones would thus include those that never evolve further, as well as those that eventually give rise to fully malignant populations, and all stages in between. The term cancer stem cells would then be more appropriately restricted to cells generating subclones that have established malignant properties. More precise molecular understanding of the different stem cell states thus distinguished should contribute to the development of more effective prognostic and therapeutic tools for cancer diagnosis and treatment. © 2012 American Association for Cancer Research.


PubMed | University of Paris Pantheon Sorbonne, Cochin University Hospital Center, Roche Holding AG, University of Strasbourg and 4 more.
Type: | Journal: JAMA | Year: 2017

In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopy may decrease this risk by improving glottis visualization.To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients.Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up.Intubation using a video laryngoscope (n=186) or direct laryngoscopy (n=185). All patients received general anesthesia.The primary outcome was the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications.Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7% vs 70.3%; absolute difference, -2.5% [95% CI, -11.9% to 6.9%]; P=.60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n=290) did not differ between the groups (84.4% with video laryngoscopy vs 83.2% with direct laryngoscopy; absolute difference 1.2% [95% CI, -6.3% to 8.6%]; P=.76). The median time to successful intubation was 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95% CI, 0 to 0]; P=.95). Video laryngoscopy was not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95% CI, -2.7% to 10.4%]; P=.25). In post hoc analysis, video laryngoscopy was associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7% [95% CI, 1.8% to 11.6%]; P=.01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, -2.3% [95% CI, -7.4% to 2.8%]; P=.37).Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels.clinicaltrials.gov Identifier: NCT02413723.


Garand R.,Nantes University Hospital Center | Beldjord K.,APHP Hopital Saint Louis | Cave H.,APHP Ho Pital Robert Debre | Fossat C.,Ho Pital de la Timone | And 22 more authors.
Leukemia | Year: 2013

Minimal residual disease (MRD) quantification is widely used for therapeutic stratification in pediatric acute lymphoblastic leukemia (ALL). A robust, reproducible, sensitivity of at least 0.01% has been achieved for IG/TCR clonal rearrangements using allele-specific quantitative PCR (IG/TCR-QPCR) within the EuroMRD consortium. Whether multiparameter flow cytometry (MFC) can reach such inter-center performance in ALL MRD monitoring remains unclear. In a multicenter study, MRD was measured prospectively on 598 follow-up bone marrow samples from 102 high-risk children and 136 adult ALL patients, using IG/TCR-QPCR and 4/5 color MFC. At diagnosis, all 238 patients (100%) had at least one suitable MRD marker with 0.01% sensitivity, including 205/238 samples (86%) by using IG/TCR-QPCR and 223/238 samples (94%) by using MFC. QPCR and MFC were evaluable in 495/598 (83%) samples. Qualitative results (<0.01% or ≥0.01%) concurred in 96% of samples and overall positivity (including <0.01% and nonquantifiable positivity) was concurrent in 84%. MRD values ≥0.01% correlated highly (r 2 =0.87) and 69% clustered within half-a-log 10. QPCR and MFC can therefore be comparable if properly standardized, and are highly complementary. MFC strategies will benefit from a concerted approach, as does molecular MRD monitoring, and will contribute significantly to the achievement of 100% MRD informativity in adult and pediatric ALL. © 2013 Macmillan Publishers Limited All rights reserved.


Fossat C.,Hematology Laboratory | Roussel M.,Rennes University Hospital Center | Arnoux I.,Hematology Laboratory | Asnafi V.,APHP Hopital Necker | And 13 more authors.
Cytometry Part B - Clinical Cytometry | Year: 2015

Methods: MRD was assessed by MFC in 1030 follow-up samples from 265 pediatric and adult patients with de novo ALL treated in the FRALLE, EORTC, or GRALL clinical trials. MRD assessment as applied by the eight participating MFC laboratories is described in detail regarding cell preparation, leukemia-associated immunophenotype (LAIP) markers and data analysis. Samples were obtained from bone marrow (BM) and peripheral blood (PB). Immunostaining was performed after erythrocyte lysis or Ficoll enrichment.Results: This study confirms the applicability of MFC-based MRD assessment in 97% of patients with ALL at the 10-4 cut-off. MRD values after Ficoll enrichment and erythrocyte lysis were found comparable. Higher MRD values were obtained in BM than in PB, especially for B-lineage ALL.Background: Minimal residual disease (MRD) assessment provides a powerful prognostic factor for therapeutic stratification in acute lymphoblastic leukemia (ALL). Multiparameter flow cytometry (MFC) has the potential for a rapid and sensitive identification of high risk patients. Our group has previously published that MRD levels analyzed by clone specific Ig/TcR-QPCR and MFC were concordant at a sensitivity of 10-4. Here we report the MFC methodological aspects from this multi-center experience.Conclusions: Measurement of MRD by MFC at the 10-4 cut-off is applicable within a few hours for almost all patients and using a comparable analytical strategy allows for multicenter collaborative studies. The method can be introduced in a strategy aimed at defining the risk of failure of patients with childhood or adult ALL. © 2014 International Clinical Cytometry Society.

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