PubMed | Joseph Fourier University, Center Hospitalier Regional Of La Citadelle, University of Rouen, Lille University Hospital Center and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2017
Reduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments.Dyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (VO2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included VO2 peak as the dependent variable and principal components as covariates.VO2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: pseudorestriction; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of VO2 peak. The 4 principal components were independently associated with VO2 peak (coefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]).Impaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea.
Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): A double-blind, placebo-controlled, phase 3 trial
Herbst R.S.,University of Houston |
Herbst R.S.,Yale Cancer Center |
Ansari R.,Michiana Hematology Oncology |
Bustin F.,Center Hospitalier Regional Of La Citadelle |
And 7 more authors.
The Lancet | Year: 2011
Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles. On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer (NSCLC), we aimed to assess efficacy and safety of this combination in a phase 3 trial. In our double-blind, placebo-controlled, randomised phase 3 trial (BeTa), we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment. Patients were randomly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab (bevacizumab group) or erlotinib plus placebo (control group) according to a computer-generated randomisation sequence by use of an interactive voice response system. The primary endpoint was overall survival in all enrolled patients. Patients, study staff, and investigators were masked to treatment assignment. We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses. This trial is registered with ClinicalTrials.gov, number NCT00130728. Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group (hazard ratio [HR] 0·97, 95 CI 0·80-1·18, p=0·7583). Median overall survival was 9·3 months (IQR 4·1-21·6) for patients in the bevacizumab group compared with 9·2 months (3·8-20·2) for controls. Progression-free survival seemed to be longer in the bevacizumab group (3·4 months [1·4-8·4]) than in the control group (1·7 months [1·3-4·1]; HR 0·62, 95 CI 0·52-0·75) and objective response rate suggested some clinical activity of bevacizumab and erlotinib. However, these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done, to control type I error rate. In the bevacizumab group, 130 (42) of 313 patients with safety data had a serious adverse event, compared with 114 (36) controls. There were 20 (6) grade 5 adverse events, including two arterial thromboembolic events, in the bevacizumab group, and 14 (4) in the control group. Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC. Genentech. © 2011 Elsevier Ltd.
Castren M.,Sodersjukhuset |
Castren M.,Karolinska Institutet |
Nordberg P.,Sodersjukhuset |
Svensson L.,Sodersjukhuset |
And 19 more authors.
Circulation | Year: 2010
Background: Transnasal evaporative cooling has sufficient heat transfer capacity for effective intra-arrest cooling and improves survival in swine. The aim of this study was to determine the safety, feasibility, and cooling efficacy of prehospital transnasal cooling in humans and to explore its effects on neurologically intact survival to hospital discharge. Methods and Results: Witnessed cardiac arrest patients with a treatment interval ≤20 minutes were randomized to intra-arrest cooling with a RhinoChill device (treatment group, n=96) versus standard care (control group, n=104). The final analysis included 93 versus 101 patients, respectively. Both groups were cooled after hospital arrival. The patients had similar demographics, initial rhythms, rates of bystander cardiopulmonary resuscitation, and intervals to cardiopulmonary resuscitation and arrival of advanced life support personnel. Eighteen device-related adverse events (1 periorbital emphysema, 3 epistaxis, 1 perioral bleed, and 13 nasal discolorations) were reported. Time to target temperature of 34°C was shorter in the treatment group for both tympanic (102 versus 282 minutes, P=0.03) and core (155 versus 284 minutes, P=0.13) temperature. There were no significant differences in rates of return of spontaneous circulation between the groups (38% in treated subjects versus 43% in control subjects, P=0.48), in overall survival of those admitted alive (44% versus 31%, respectively, P=0.26), or in neurologically intact survival to discharge (Pittsburgh cerebral performance category scale 1 to 2, 34% versus 21%, P=0.21), although the study was not adequately powered to detect changes in these outcomes. Conclusions-: Prehospital intra-arrest transnasal cooling is safe and feasible and is associated with a significant improvement in the time intervals required to cool patients. © 2010 American Heart Association, Inc.
Pallis A.G.,University of Crete |
Ring A.,Royal Sussex County Hospital |
Fortpied C.,European Organisation for Research and Treatment of Cancer |
Penninckx B.,European Organisation for Research and Treatment of Cancer |
And 11 more authors.
Annals of Oncology | Year: 2011
Background: Due to the aging of the population, the number of older patients diagnosed with a malignant disease is increasing. A multidisciplinary approach to the senior adult cancer patient is mandatory, to assure optimal diagnosis and therapeutic management.Design: European Organisation for Research and Treatment of Cancer (EORTC) has currently defined senior adult oncology as one of its priorities and has established an active Elderly Task Force (ETF). Under the auspices of the EORTC, the ETF organized a workshop on clinical trial methodology in older cancer patients and in this article, we present the conclusions of this workshop. Results: Besides the 'classical' efficacy end points, quality of life, functional status and independence of the patient should be assessed in clinical trials in older patients. The participants of the workshop agreed on the use of a minimum dataset for the assessment of global health and functional status in older cancer patients. The panel also recommended that optimization of collaboration with pharmaceutical industry requires reporting of age-related data (subgroup analyses of clinical trials, age-related pooled analyses and obligatory post-marketing studies in vulnerable and frail older patients). Conclusion: The identification of proper clinical outcomes and the validation of geriatric screening tools are needed for conducting sound and comparable clinical trials. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Lubicz B.,Erasme University Hospital |
Mine B.,Erasme University Hospital |
Collignon L.,Center Hospitalier Regional Of La Citadelle |
Brisbois D.,Erasme University Hospital |
And 2 more authors.
American Journal of Neuroradiology | Year: 2013
BACKGROUND AND PURPOSE: The WEB is an intrasaccular flow disrupter dedicated to EVT of IA. We report our initial experience in a series of patients treated with this device. MATERIALS AND METHODS: This prospective study was approved by the authors' ethical committees. Nineteen patients with 20 unruptured wide-neck bifurcation IAs were treated by WEB placement. Technical issues, immediate posttreatment angiographic findings, and clinical and imaging follow-up at 3, 6, and 12 months were assessed. RESULTS: Failure of WEB placement occurred in 1 case because of unavailability of a suitably sized device. Embolization was successful in 18 patients with 19 IAs, and it required additional stent placement and/or coiling in 3 cases at the acute phase and in 1 case at follow-up. Two patients experienced a symptomatic complication, and 16 patients had normal neurologic examination findings at discharge. Immediate anatomic outcome showed 1 complete occlusion, 13 near-complete occlusions, and 5 incomplete occlusions. At follow-up, 17 patients had normal neurologic examination findings and 1 retained a hemiparesis. Angiographic controls were obtained in all patients (mean, 6 months), and they showed stable or improved results in all except 4 cases, including 2 complete occlusions, 15 near-complete occlusions, and 2 incomplete occlusions. CONCLUSIONS: In this initial series of patients, EVT of wide-neck bifurcation IAa with the WEB was feasible. Further studies are needed to evaluate the indications, safety, and efficacy of this new technique.
Machurot P.Y.,Center Hospitalier Regional Of La Citadelle |
Vergnion M.,Center Hospitalier Regional Of La Citadelle |
Fraipont V.,Center Hospitalier Regional Of La Citadelle |
Bonhomme V.,University of Liège |
Damas F.,University of Liège
Acta Anaesthesiologica Belgica | Year: 2010
Postdural puncture headaches represent one of the main complications of spinal anesthesia. Sometimes, they can reveal the presence of an intracerebral hemorrhage or intracranial subdural hematoma. Atypical postdural puncture headaches or secondary alterations of a typical headache, and particularly the disappearance of its postural character, must prompt to search for another cause. Early diagnosis and careful and rapid management are mandatory. We here report the case of a 53-year-old woman who presented with an intracranial subdural hematoma following spinal anesthesia for hallux valgus surgery performed 48 hours earlier. The implications of such a diagnosis are then discussed, in the light of the existing literature. © Acta Anæsthesiologica Belgica, 2010.
Huang T.-D.,Catholic University of Louvain |
Bogaerts P.,Catholic University of Louvain |
Ghilani E.,Catholic University of Louvain |
Heinrichs A.,Catholic University of Louvain |
And 8 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014
Objectives: The objective of this study was to evaluate in a multicentre survey the analytical performance of the Check-Direct CPE® assay (CDCPE), a multiplex PCR assay for the detection of carbapenemase-producing Enterobacteriaceae (CPE), directly from rectal swabs. Methods: Adult patients admitted to a high-risk unit in four participating centres were prospectively screened for CPE carriage by rectal swabbing. Samples were cultured on chromogenic CPE-selective media in the local laboratories. All growing Enterobacteriaceae strains were transferred for confirmation of carbapenemase production by multiplex PCR, together with the faecal swabs for CDCPE, to the coordinating laboratory. Results: Overall, 38 of the 394 samples analysed (9.6%; range 3%-20% per centre) yielded a positive signal for a carbapenemase gene with CDCPE, including 17 samples (4.3%; range 0%-15% per centre) that grewa total of 25 CPE-confirmed isolates (all OXA-48-like producers, including one isolate that simultaneously harboured a VIMtype carbapenemase). No CPE culture-positive samples were missed by CDCPE. Among the 21 samples that were CPE-positive with CDCPE but negative on culture, five were collected from previously known CPE carriers and 6/9 OXA-48-positive signals were detected at one participating centre that was undergoing a hospital-wide outbreak of OXA-48 CPE. When compared with the selective culture, the sensitivity and specificity of CDCPE were 100% and 94%, respectively. Conclusions: This study showed the value of CDCPE as a tool for screening CPE carriage in an epidemiological setting with a high prevalence of OXA-48 CPE. However, the potential added value for infection control management remains to be demonstrated. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Identification and Validation of the Methylated TWIST1 and NID2 Genes through Real-Time Methylation-Specific Polymerase Chain Reaction Assays for the Noninvasive Detection of Primary Bladder Cancer in Urine Samples
Renard I.,OncoMethylome science SA |
Joniau S.,Catholic University of Leuven |
van Cleynenbreugel B.,Catholic University of Leuven |
Collette C.,OncoMethylome science SA |
And 12 more authors.
European Urology | Year: 2010
Background: Accumulating evidence suggests that DNA methylation markers could serve as sensitive and specific cancer biomarkers. Objective: To determine whether a panel of methylated genes would have the potential to identify primary bladder cancer (BCa) in voided urine samples. Design, setting, and participants: A pharmacologic unmasking reexpression analysis in BCa cell lines was initially undertaken to unveil candidate methylated genes, which were then evaluated in methylation-specific polymerase chain reaction (MSP) assays performed on DNA extracted from noncancerous and cancerous bladder tissues. The most frequently methylated genes in cancerous tissues, with 100% specificity, were retained for subsequent MSP analysis in DNA extracted from urine samples to build and validate a panel of potential methylated gene markers. Urine samples were prospectively collected at three urologic centres from patients with histologically proven BCa and processed for use in real-time MSP and cytologic analysis. Patients with nonmalignant urologic disorders were included as controls. Measurements: A urine sample was classified as valid when ≥10 copies of the gene encoding ß-actin were measured in the urine sediment genomic DNA. Sensitivity, specificity, and predictive values of the MSP and cytology tests were assessed and compared. Results and limitations: MSP assays performed on 466 of the 496 (94%) valid urine samples identified two genes, TWIST1 and NID2, that were frequently methylated in urine samples collected from BCa patients, including those with early-stage and low-grade disease. The sensitivity of this two-gene panel (90%) was significantly better than that of cytology (48%), with comparable specificity (93% and 96%, respectively). The positive predictive value and negative predictive value of the two-gene panel was 86% and 95%, respectively. Conclusions: Detection of the methylated TWIST1 and NID2 genes in urine sediments using MSP provides a highly (≥90%) sensitive and specific, noninvasive approach for detecting primary BCa. Trial registration: BlCa-001 study - EudraCt 2006-003303-40. © 2009 European Association of Urology.
Lapitskaya N.,Hammel Neurorehabilitation and Research Center |
Lapitskaya N.,University of Liège |
Gosseries O.,University of Liège |
De Pasqua V.,University of Liège |
And 6 more authors.
Brain Stimulation | Year: 2013
Background: Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. Objective/hypothesis: It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Methods: Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). Results: On average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). Conclusions: The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction. © 2013 Elsevier Inc. All rights reserved.
Matar V.W.,Center Hospitalier Regional Of La Citadelle |
Betz P.,Center Hospitalier Regional Of La Citadelle
Journal Francais d'Ophtalmologie | Year: 2011
We report a rare case of periorbital necrotizing fasciitis following a dacryocystorhinostomy procedure. We describe the common features of this rare infection of the skin and subcutaneous tissues and discuss the different management strategies as well as the controversial role of anti-inflammatory medication in treating this condition. © 2010 Elsevier Masson SAS.