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Saint-Jean O.,Hopital Europeen Georges Pompidou HEGP | Gisselbrecht M.,Hopital Europeen Georges Pompidou HEGP | Cudennec T.,Medical Geriatric Division | Girre V.,University Pierre and Marie Curie
Annals of Oncology | Year: 2011

Background: Pilot Oncogeriatric Coordination Units (UPCOGs) were created by the French National Cancer Institute (INCA) in order to implement routine geriatric assessment of all cancer patients over 75 years of age. This article examines the role of geriatric and oncologic tools in the organization of medical oncogeriatric activities, focusing on the role and place of geriatricians. Methods: We conducted a qualitative sociological survey in the West Paris Oncogeriatric Program (POGOP), one of the Pilot Oncogeriatric Coordination Units (UPCOGs) recently created in France. Various qualitative methods were used including a review of the literature, participative observational surveys, and semidirective interviews with medical staff managing elderly cancer patients. Results: The results show that the way in which geriatric assessment procedures are implemented confirms the role of the geriatrician in the diagnosis and prevention of vulnerabilities and fragility at the time of initial diagnosis and medical decision making. Nevertheless, the articulation of these different working methods gives rise to various organizational configurations. Conclusions: The POGOP has largely contributed to clarifying medical activity in oncogeriatrics: identification of physicians, definition of shared goals, initiation, and structuring of new partnerships. Nevertheless, the geriatrician's tools, expertise, and know-how are often perceived ambiguously. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Le Blanche A.F.,University of Picardie Jules Verne | Le Blanche A.F.,Vascular Imaging | Ricco J.-B.,University of Poitiers | Bonneau M.,French National Institute for Agricultural Research | Reynaud P.,Hopital Europeen Georges Pompidou HEGP
CardioVascular and Interventional Radiology | Year: 2012

Purpose: Retrieval of optional caval filters may be impaired by filter tilting, migration, fracture, or embedding in the IVC wall. The goal of this experimental study was to evaluate a new optional filter, convertible by unlocking and removing the filter head. Methods: Forty-nine Pre-Alp sheep (average weight, 55 kg) were anesthetized. IVC was catheterized via the right femoral vein (n = 46) or via the internal jugular vein (n = 3) with a 12.9-F sheath. VenaTech™ Convertible™ IVC filters were inserted as either permanent filters (n = 14) or as filters to be converted. Conversion was immediately after deployment (n = 19) or delayed after 1, 3, or 6 months (n = 20). Filter delivery, deployment, and conversion with measurement of migration and tilting were evaluated by cavography. Incorporation of the filter's stabilizers and arms in the IVC wall was assessed by gross anatomy. Results: Delivery system insertion, filter release, and immediate conversion were successful in all cases. Delayed conversion was completed in all but one sheep, due to insufficient snare tension. Complimentary balloon-catheter inflation was required in 12 of 20 delayed conversions to achieve filter opening. In all 49 sheep, no thrombosis, migration, or significant tilting occurred. Within 4 weeks of conversion, the filter's stabilizers and arms were incorporated into the IVC wall. Upon removal, the filter head was free of intimal growth. Conclusions: The VenaTech ™ Convertible™ optional IVC filter was successfully implanted in all sheep with no migration or tilting. Conversion at various dates by filter head removal was feasible in all but one case. © 2011 Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).

Petitguillaume A.,Institute for Radiological Protection and Nuclear Safety | Bernardini M.,Hopital Europeen Georges Pompidou HEGP | Hadid L.,Institute for Radiological Protection and Nuclear Safety | De Labriolle-Vaylet C.,University Pierre and Marie Curie | And 2 more authors.
Journal of Nuclear Medicine | Year: 2014

In the last decades, selective internal radiation therapy (SIRT) has become a real alternative in the treatment of unresectable hepatic cancers. In practice, the activity prescription is limited by the irradiation of organs at risk (OAR), such as the lungs and nontumoral liver (NTL). Its clinical implementation is therefore highly dependent on dosimetry. In that context, a 3-dimensional personalized dosimetry technique-personalized Monte Carlo dosimetry (PMCD)- based on patient-specific data and Monte Carlo calculations was developed and evaluated retrospectively on clinical data. Methods: The PMCD method was evaluated with data from technetium human albumin macroaggregates (99mTc-MAA) evaluations of 10 patients treated for hepatic metastases. Region-of-interest outlines were drawn on CT images to create patient-specific voxel phantoms using the OEDIPE software. Normalized 3-dimensional matrices of cumulated activity were generated from 99mTc-SPECT data. Absorbed doses at the voxel scale were then obtained with the MCNPX Monte Carlo code. The maximum-injectable activity (MIA) for tolerance criteria based on either OAR mean absorbed doses (D mean) or OAR dose-volume histograms (DVHs) was determined using OEDIPE. Those MIAs were compared with the one recommended by the partition model (PM) with Dmean tolerance criteria. Finally, OEDIPE was used to evaluate the absorbed doses delivered if those activities were injected to the patient and to generate the corresponding isodose curves and DVHs. Results: The MIA recommended using Dmean tolerance criteria is, in average, 27% higher with the PMCD method than with the PM. If tolerance criteria based on DVHs are used along with the PMCD, an increase of at least 40% of the MIA is conceivable, compared with the PM. For MIAs calculated with the PMCD, D mean delivered to tumoral liver (TL) ranged from 19.5 to 118 Gy for Dmean tolerance criteria whereas they ranged from 26.6 to 918 Gy with DVH tolerance criteria. Thus, using the PMCD method, which accounts for fixation heterogeneities, higher doses can be delivered to TL. Finally, absorbed doses to the lungs are not the limiting criterion for activity prescription. However, Dmean to the lungs can reach 15.0 Gy. Conclusion: Besides its feasibility and applicability in clinical routine, the interest for treatment optimization of a personalized Monte Carlo dosimetry in the context of SIRT was confirmed in this study. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PubMed | Hopital europeen Georges Pompidou HEGP, Laboratory of Biochemistry, HU Necker Enfants malades, University of Paris Descartes and Biological Resources Center and Tumor Bank Platform 0033 00063
Type: Journal Article | Journal: International journal of antimicrobial agents | Year: 2016

The incidence of urinary tract infections caused by extended-spectrum -lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1g intravenous (i.v.) dose of ertapenem 1h (n=10, group A) or 12h (n=9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3mg/L (95% CI 126.5-157.9) in group A and 30.7mg/L (95% CI 22.9-36.4) in group B (P<0.001); median intraprostatic concentrations were 16.6mg/L (95% CI 13.3-31.4mg/L) and 4.2mg/L (95% CI 3.1-4.9mg/L), respectively (P<0.001), which were above the MIC90 values of bacteria, including ESBL-producers, during surgery and for 40% of the dosing interval. The plasma-to-prostate concentration ratio was not significantly different between groups (P=0.97). Single-dose i.v. ertapenem reached satisfactory intraprostatic concentrations, suggesting that it could be a relevant prophylactic strategy for carriers of ESBL-producing bacteria undergoing prostatic procedures, which needs to be confirmed by further prospective trials.

PubMed | Hopital Bichat, Hopital Europeen Georges Pompidou HEGP, University of Paris Pantheon Sorbonne and Hopital Cochin
Type: | Journal: Oncotarget | Year: 2015

STK11 is commonly mutated in lung cancer. In light of recent experimental data showing that specific STK11 mutants could acquire oncogenic activities due to the synthesis of a short STK11 isoform, we investigated whether this new classification of STK11 mutants could help refine its role as a prognostic marker. We conducted a retrospective high-throughput genotyping study in 567 resected non-squamous non-small-cell lung cancer (NSCLC) patients. STK11 exons 1 or 2 mutations (STK11ex1-2) with potential oncogenic activity were analyzed separately from exons 3 to 9 (STK11ex3-9). STK11ex1-2 and STK11ex3-9 mutations occurred in 5% and 14% of NSCLC. STK11 mutated patients were younger (P = .01) and smokers (P< .0001). STK11 mutations were significantly associated with KRAS and inversely with EGFR mutations. After a median follow-up of 7.2 years (95%CI 6.8-.4), patients with STK11ex1-2 mutation had a median OS of 24 months (95%CI 15-57) as compared to 69 months (95%CI 56-93) for wild-type (log-rank, P = .005) and to 91 months (95%CI 57-unreached) for STK11ex3-9 mutations (P = .003). In multivariate analysis, STK11ex1-2 mutations remained associated with a poor prognosis (P = .002). Results were validated in two public datasets. Western blots showed that STK11ex1-2 mutatedtumors expressed short STK11 isoforms. Finally using mRNAseq data from the TCGA cohort, we showed that a stroma-derived poor prognosis signature was enriched in STK11ex1-2 mutated tumors. All together our results show that STK11ex1-2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.

Danchin N.,Hopital Europeen Georges Pompidou HEGP | Marzilli M.,Azienda Ospedaliero | Parkhomenko A.,Strazhesko Md Institute Of Cardiology | Ribeiro J.P.,Hospital Of Clinicas Of Porto Alegre | Ribeiro J.P.,Federal University of Rio Grande do Sul
Cardiology | Year: 2011

Aims: To compare the antianginal efficacy of trimetazidine with that of other agents with no influence on heart rate. Methods and Results: Medline and Embase databases were searched for blinded, randomized, controlled trials assessing the effects of non-heart-rate-lowering antianginal treatments on exercise tolerance and/or clinical criteria in stable angina patients. All relevant trimetazidine trials including the VASCO trial, the results of which are published herein, were included. A Bayesian network meta-analysis on the summary data was performed. Comparator antianginal agents were considered as a group and in agent/class subgroups. Trials involving β-blockers, non-dihydropyridine calcium channel blockers, and ivabradine were excluded. 218 trials totaling 19,028 patients were included in at least 1 network analysis. Effects of trimetazidine were statistically significant compared with placebo for exercise tolerance and clinical criteria. Transposition of results into seconds for clinical interpretation of exercise tolerance parameters showed a mean improvement of +46 s (95% credibility interval: 28; 66) for total exercise duration, +55 s (35; 77) for 1-mm ST segment depression (T1), and +54 s (24; 84) for time to onset of angina, in favor of trimetazidine. Differences between trimetazidine and active comparators were not significant when exercise tolerance and clinical criteria were analyzed, with +7 s (-12; 28) for total exercise duration, -1 s (-23; 22) for T1, +8 s (-22; 40) for time to onset of angina, and -0.28 (-1.17; 0.64) attacks per week for trimetazidine compared with antianginal agents as a group. Conclusions: Trimetazidine efficacy was comparable to that of other non-heart-rate-lowering antianginal treatments in patients with stable angina pectoris. Copyright © 2011 S. Karger AG, Basel.

PubMed | Hopital Europeen Georges Pompidou HEGP, Paris-Sorbonne University and Pharmacogenetics and Molecular Oncology
Type: Journal Article | Journal: PLoS medicine | Year: 2016

Circulating tumor DNA (ctDNA) is an approved noninvasive biomarker to test for the presence of EGFR mutations at diagnosis or recurrence of lung cancer. However, studies evaluating ctDNA as a noninvasive real-time biomarker to provide prognostic and predictive information in treatment monitoring have given inconsistent results, mainly due to methodological differences. We have recently validated a next-generation sequencing (NGS) approach to detect ctDNA. Using this new approach, we evaluated the clinical usefulness of ctDNA monitoring in a prospective observational series of patients with non-small cell lung cancer (NSCLC).We recruited 124 patients with newly diagnosed advanced NSCLC for ctDNA monitoring. The primary objective was to analyze the prognostic value of baseline ctDNA on overall survival. ctDNA was assessed by ultra-deep targeted NGS using our dedicated variant caller algorithm. Common mutations were validated by digital PCR. Out of the 109 patients with at least one follow-up marker mutation, plasma samples were contributive at baseline (n = 105), at first evaluation (n = 85), and at tumor progression (n = 66). We found that the presence of ctDNA at baseline was an independent marker of poor prognosis, with a median overall survival of 13.6 versus 21.5 mo (adjusted hazard ratio [HR] 1.82, 95% CI 1.01-3.55, p = 0.045) and a median progression-free survival of 4.9 versus 10.4 mo (adjusted HR 2.14, 95% CI 1.30-3.67, p = 0.002). It was also related to the presence of bone and liver metastasis. At first evaluation (E1) after treatment initiation, residual ctDNA was an early predictor of treatment benefit as judged by best radiological response and progression-free survival. Finally, negative ctDNA at E1 was associated with overall survival independently of Response Evaluation Criteria in Solid Tumors (RECIST) (HR 3.27, 95% CI 1.66-6.40, p < 0.001). Study population heterogeneity, over-representation of EGFR-mutated patients, and heterogeneous treatment types might limit the conclusions of this study, which require future validation in independent populations.In this study of patients with newly diagnosed NSCLC, we found that ctDNA detection using targeted NGS was associated with poor prognosis. The heterogeneity of lung cancer molecular alterations, particularly at time of progression, impairs the ability of individual gene testing to accurately detect ctDNA in unselected patients. Further investigations are needed to evaluate the clinical impact of earlier evaluation times at 1 or 2 wk. Supporting clinical decisions, such as early treatment switching based on ctDNA positivity at first evaluation, will require dedicated interventional studies.

Carbonnelle E.,HOpital Europeen Georges Pompidou HEGP | Carbonnelle E.,University of Paris Descartes | Grohs P.,HOpital Europeen Georges Pompidou HEGP | Jacquier H.,Hopital Lariboisiere | And 12 more authors.
Journal of Microbiological Methods | Year: 2012

MALDI-TOF-MS systems (Microflex-Bruker Daltonics/BioTyper™ and Axima-Assurance-Shimadzu/SARAMIS-AnagnosTec) were assessed for bacterial identification. Focusing on bacteria difficult to identify routinely, 296 strains were identified by molecular biology techniques as gold standard. MALDI-TOF-MS identification provided correct results at genus and species level for 94.9%, 83.4% and 83.8%, 65.9% with Biotyper and Saramis respectively. © 2012 Elsevier B.V.

PubMed | Hopital Europeen Georges Pompidou HEGP and French Institute of Health and Medical Research
Type: | Journal: Studies in health technology and informatics | Year: 2015

Efficient and adequate coding is essential for all hospitals to optimize funding, follow activity, and perform epidemiological studies.We propose an autocompletion method for optimizing diagnostic coding in acute care hospitals.Using a terminology snowflake model integrating SNOMED 3.5 and ICD-10 codes, autocompletion algorithms generate a list of diagnostic expressions from partial input concepts.A general autocompletion component has been developed and tested on a set of inpatient summary reports. Concepts expressed as strings of three or four characters return a noisy list of diagnostic labels or codes. Concepts expressed as groups of strings return lists that are semantically close to the labels present in hospital reports. The most pertinent information lies in the length of the expressions entered.Autocompletion can be a complementary tool to existing coding support systems.

PubMed | Hopital Europeen Georges Pompidou HEGP and University of Paris Pantheon Sorbonne
Type: Journal Article | Journal: Clinical chemistry | Year: 2016

Detecting single-nucleotide variations and insertions/deletions in circulating tumor DNA is challenging because of their low allele frequency. The clinical use of circulating tumor DNA to characterize tumor genetic alterations requires new methods based on next-generation sequencing.We developed a method based on quantification of error rate of each base position [position error rate (PER)]. To identify mutations, a binomial test was used to compare the minor-allele frequency to the measured PER at each base position. This process was validated in control samples and in 373 plasma samples from patients with lung or pancreatic cancer.Minimal mutated allele frequencies were 0.003 for single-nucleotide variations and 0.001 for insertions/deletions. Independent testing performed by droplet digital PCR (n = 231 plasma samples) showed strong agreement with the base-PER method ( = 0.90).Targeted next-generation sequencing analyzed with the base-PER method represents a robust and low cost method to detect circulating tumor DNA in patients with cancer.

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