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Duhamel A.,Unite de Biostatistiques | Robin S.,Service dExplorations Fonctionnelles Respiratoires | Aguilaniu B.,Laboratoire Physiopathologie Of Lexercice
Respiration | Year: 2011

Background: Patients with sarcoidosis frequently exhibit exertional dyspnea. Although the functional limitation might be related to ventilatory problems, some patients exhibited exertional dyspnea without significant abnormalities of pulmonary function tests (PFT). Therefore, the mechanisms responsible for exercise intolerance remain unclear. Objectives: The aim of this retrospective study was to determine the mechanisms responsible for exercise intolerance. Methods: Cardiopulmonary exercise testing (CPET) was performed in 157 dyspneic sarcoid patients (stage I: 29; stage II-III: 95; stage IV: 33) and VO 2 peak was correlated with radiological stage and resting PFT. Results: VO 2 peak was decreased in 73% patients, did not differ according to radiological stage and was correlated with VC, FVC, FEV 1, TLC and DLCO. FVC was the major significant predictor of VO 2 peak explaining 17% of VO 2 variation. Among CPET variables, peak heart rate and VE/VO 2 at ventilatory threshold explained 22% of VO 2 alteration in stage I and stage II-III, and 9% in stage IV. In stage IV, V D/V T peak explained 41% of VO 2 alteration. Conclusion: In conclusion, in the lower stages circulatory impairment and impaired heart rate response to exercise are involved in the exercise capacity limitation, whereas in stage IV the ventilatory and gas exchange impairment may be more important. CPET must be performed to accurately characterize the mechanisms responsible for exercise limitation and help the clinician in the management of the disease. Copyright © 2011 S. Karger AG, Basel.


Leroi A.M.,French Institute of Health and Medical Research | Siproudhis L.,Rennes University Hospital Center | Etienney I.,Service de Proctologie | Damon H.,University of Lyon | And 12 more authors.
American Journal of Gastroenterology | Year: 2012

Objectives: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials.METHODS:In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events.Results: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b).CONCLUSIONS:We failed to demonstrate any benefit of TENS on our primary end-point. © 2012 by the American College of Gastroenterology.


Grosbois J.M.,FormAction Sante | Gicquello A.,Center des Competences des Maladies Pulmonaires Rares | Langlois C.,Unite de Biostatistiques | Le Rouzic O.,Center des Competences des Maladies Pulmonaires Rares | And 4 more authors.
International Journal of COPD | Year: 2015

Introduction: Personalized, global pulmonary rehabilitation (PR) management of patients with COPD is effective, regardless of the place in which this rehabilitation is provided. The objective of this retrospective observational study was to study the long-term outcome of exercise capacity and quality of life during management of patients with COPD treated by home-based PR. Methods: Home-based PR was administered to 211 patients with COPD (mean age, 62.3±11.1 years; mean forced expiratory volume in 1 second, 41.5%±17.7%). Home-based PR was chosen because of the distance of the patient’s home from the PR center and the patient’s preference. Each patient was individually managed by a team member once a week for 8 weeks with unsupervised continuation of physical exercises on the other days of the week according to an individual action plan. Exercise conditioning, therapeutic patient education, and self-management were included in the PR program. The home assessment comprised evaluation of the patient’s exercise capacity by a 6-minute stepper test, Timed Up and Go test, ten times sit-to-stand test, Hospital Anxiety and Depression score, and quality of life (Visual Simplified Respiratory Questionnaire, VQ11, Maugeri Respiratory Failure 28). Results: No incidents or accidents were observed during the course of home-based PR. The 6-minute stepper test was significantly improved after completion of the program, at 6 months and 12 months, whereas the Timed Up and Go and ten times sit-to-stand test were improved after PR and at 6 months but not at 12 months. Hospital Anxiety and Depression and quality of life scores improved after PR, and this improvement persisted at 6 months and 12 months. Conclusion: Home-based PR for unselected patients with COPD is effective in the short term, and this effectiveness is maintained in the medium term (6 months) and long term (12 months). Home-based PR is an alternative to outpatient management provided all activities, such as exercise conditioning, therapeutic education, and self-management are performed. © 2015, Grosbois et al.


Delourme J.,Lille 2 University of Health and Law | Stervinou-Wemeau L.,Lille 2 University of Health and Law | Salieron J.,Unite de Biostatistiques | Grosbois J.M.,Service de Pneumologie | Wallaert B.,Lille 2 University of Health and Law
Sarcoidosis Vasculitis and Diffuse Lung Diseases | Year: 2012

The six-minute stepper test (6MST) is a new test for evaluating exercise tolerance. Unlike the six-minute walk test (6MWT) it can be carried out in a limited space. The aim of this study was to compare the 6MST and the 6MWT in patients with various diffuse interstitial lung disease (ILD). 6MWT and 6MST were performed the same day in 84 patients with various ILD. The covered distance during 6MWT was compared to the number of steps during the 6MST. We also compared heart rate, oxygen saturation, dyspnoea and leg tiredness on a Borg scale. All the patients successfully completed the tests, and tolerance was considered good. The number of steps completed in the 6MST was strongly correlated with the distance walked in the 6MWT (r2=0.5; p<0.0001). Oxygen desaturation was less frequent and less severe (p<0.0001), heart rate was higher (p<0.0001) and dyspnoea and leg tiredness were more marked (p<0.0001) in the 6MST than in the 6MWT. The 6MST is feasible for patients with ILD. It is a simple, safe, mobile test that is cheap and easy to carry out in all structures. © Mattioli 1885.


Robert R.,French Institute of Health and Medical Research | Reignier J.,Roche Holding AG | Tournoux-Facon C.,Unite de Biostatistiques | Boulain T.,Service de Reanimation Polyvalente | And 6 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Rationale: Intensive care unit (ICU) beds are a scarce resource, and patients denied intensive care only because the unit is full may be at increased risk of death. Objective: To compare mortality after first ICU referral in admitted patients and in patients denied admission because the unit was full. Methods: Prospective observational multicenter cohort study of consecutive patients referred for ICU admission during two 45-day periods, conducted in 10 ICUs. Measurements and Main Results: Of 1,762 patients, 430 were excluded from the study, 116 with previously denied admission to another ICU and 270 because they were deemed too sick or too well to benefit from ICU admission. Of the remaining 1,332 patients, 1,139 were admitted,and 193 were denied admission because the unit was full (65 were never admitted, 39 were admitted after bumping of another patient, and 89 were admitted on subsequent referral). Crude Day 28 and Day 60 mortality rates in the nonadmitted and admitted groups were 30.1 versus 24.3% (P = 0.07) and 33.3 versus 27.2% (P = 0.06), respectively. Day 28 mortality adjusted on age, previous disease, Glasgow scale score less than or equal to 8, shock, creatinine level greater than or equal to 250 mmol/L, and prothrombin time greater than or equal to 30 seconds was nonsignificantly higher in patients refused ICU admission only because of a full unit compared with patients admitted immediately. Patients admitted after subsequent referral had higher mortality rates on Day 28 (P =0.05) and Day 60 (P = 0.04) compared with directly admitted patients. Conclusions: Delayed ICU admission due to a full unit at first referral is associated with increased mortality. Copyright © 2012 by the American Thoracic Society.


Leconet W.,French Institute of Health and Medical Research | Larbouret C.,French Institute of Health and Medical Research | Chardes T.,French Institute of Health and Medical Research | Thomas G.,French Institute of Health and Medical Research | And 10 more authors.
Oncogene | Year: 2014

AXL receptor tyrosine kinase (RTK) is implicated in proliferation and invasion of many cancers, particularly in pancreatic ductal adenocarcinoma (PDAC), for which new therapeutic options are urgently required. We investigated whether inhibition of AXL activity by specific monoclonal antibodies (mAbs) is efficient in limiting proliferation and migration of pancreatic cancer cells. Expression of AXL was evaluated by immunohistochemistry in 42 PDAC. The AXL role in oncogenesis was studied using the short hairpin RNA approach in a pancreatic carcinoma cell line. We further generated antihuman AXL mAbs and evaluated their inhibitory effects and the AXL downstream signaling pathways first in vitro, in a panel of pancreatic cancer cell lines and then in vivo, using subcutaneous or orthotopic pancreatic tumor xenografts. AXL receptor was found expressed in 76% (32/42) of PDAC and was predominantly present in invasive cells. The AXL-knockdown Panc-1 cells decreased in vitro cell migration, survival and proliferation, and reduced in vivo tumor growth. Two selected anti-AXL mAbs (D9 and E8), which inhibited phosphorylation of AXL and of its downstream target AKT without affecting growth arrest-specific factor 6 (GAS6) binding, induced downexpression of AXL by internalization, leading to an inhibition of proliferation and migration in the four pancreatic cancer cell lines studied. In vivo, treatment by anti-AXL mAbs significantly reduced growth of both subcutaneous and orthotopic pancreatic tumor xenografts independently of their KRAS mutation status. Our in vitro and preclinical in vivo data demonstrate that anti-human AXL mAbs could represent a new approach to the pancreatic cancer immunotherapy.


Ehlinger M.,Service de chirurgie orthopedique et de traumatologie | Delaunay C.,Clinique de lYvette | Karoubi M.,Royal University | Bonnomet F.,Service de chirurgie orthopedique et de traumatologie | And 2 more authors.
Orthopaedics and Traumatology: Surgery and Research | Year: 2014

Background: Revision total hip arthroplasty (reTHA) for peri-prosthetic fracture (PPF) is increasingly performed but still ranks fourth among reasons for reTHA in registries. In France, no specific registry is available and the frequency of PPF among reasons for THA revision is therefore unknown. Here, our objectives were to determine the relative frequency of PPF as a reason for reTHA, to identify patient-related and primary-THA-related factors associated with reTHA for PPF, to describe reTHA modalities for PPF, and to determine the morbidity and mortality associated with reTHA for PPF. Hypothesis: PPF is the second most common reason for reTHA, after loosening. Methods: Consecutive reTHA procedures performed in 30French centres over a 2-year period were collected prospectively. Repeat revisions and revisions of hemi-arthroplasties were excluded. The epidemiological, clinical, and surgical data needed to answer the questions of the study were collected. Results: PPF was the second leading reason for reTHA (249/2107, 11.8%). Vancouver type B2 fractures were the most common (n= 127 [51.5%]). Compared to patients who underwent reTHA for reasons other than PPF, those with reTHA for PPF were older at primary THA (67.9. years versus 57.7. years) and more often had intra-operative complications (16.9% versus 11.6%); furthermore, the primary THA was more often cementless (62.7% versus 42.7%) with a dual-mobility cup (20.6% versus 11.1%). At reTHA, the patients with PPF were older (77.6. years versus 69.2. years), had worst medical condition (mean ASA score, 2.4 versus 2.1) and less physically active (mean Devane score, 2.1 versus 2.4). The patients with reTHA for PPF had a shorter time to revision (9.8. years versus 11.4. years), a longer operative time (144. minutes versus 128. minutes), and more frequent use of the posterior approach (77% versus 67%) with a cementless dual-mobility cup (78% versus 60%) and a cementless revision femoral stem (72% versus 50%). Morbidity and mortality rates were high (5.9% operative complication rate and 12% of surgical complications with 4.8% mortality within the first 3. months) however, these results were similar to those in the rest of the cohort. Discussion and conclusion: PPF is the second most common reason for reTHA, a result that is at variance with data in national registries. Level of evidence: Level IV, prospective observational cohort study. © 2014 Elsevier Masson SAS.


Pastre J.,Lille 2 University of Health and Law | Prevotat A.,Lille 2 University of Health and Law | Tardif C.,Service de Physiologie Respiratoire | Langlois C.,Unite de Biostatistiques | And 2 more authors.
BMC Pulmonary Medicine | Year: 2014

Background: Adult patients with cystic fibrosis (CF) frequently have reduced exercise tolerance, which is multifactorial but mainly due to bronchial obstruction. The aim of this retrospective analysis was to determine the mechanisms responsible for exercise intolerance in patients with mild-to-moderate or severe disease.Methods: Cardiopulmonary exercise testing with blood gas analysis at peak exercise was performed in 102 patients aged 28 ± 11 years: 48 patients had severe lung disease (FEV1 < 50%, group 1) and 54 had mild-to-moderate lung disease (FEV1 ≥ 50%, group 2). VO2 peak was measured and correlated with clinical, biological, and functional parameters.Results: VO2 peak for all patients was 25 ± 9 mL/kg/min (65 ± 21% of the predicted value) and was < 84% of predicted in 82% of patients (100% of group 1, 65% of group 2). VO2 peak was correlated with body mass index, C-reactive protein, FEV1, FVC, RV, DLCO, VE/VCO2 peak, VD/VT, PaO2, PaCO2, P(A-a)O2, and breathing reserve. In multivariate analysis, FEV1 and overall hyperventilation during exercise were independent determinants of exercise capacity (R2 = 0.67). FEV1 was the major significant predictor of VO2 peak impairment in group 1, accounting for 31% of VO2 peak alteration, whereas excessive overall hyperventilation (reduced or absent breathing reserve and VE/VCO2) accounted for 41% of VO2 alteration in group 2.Conclusion: Exercise limitation in adult patients with CF is largely dependent on FEV1 in patients with severe lung disease and on the magnitude of the ventilatory response to exercise in patients with mild-to-moderate lung disease. © 2014 Pastré et al.; licensee BioMed Central Ltd.


Vieillot S.,CRLC Val dAurelle Paul Lamarque | Azria D.,CRLC Val dAurelle Paul Lamarque | Lemanski C.,CRLC Val dAurelle Paul Lamarque | Moscardo C.L.,CRLC Val dAurelle Paul Lamarque | And 4 more authors.
Radiation Oncology | Year: 2010

Background: To compare volumetric-modulated arc therapy (RapidArc) plans with conventional intensity-modulated radiation therapy (IMRT) plans in anal canal cancers.Methods: Ten patients with anal canal carcinoma previously treated with IMRT in our institution were selected for this study. For each patient, three plans were generated with the planning CT scan: one using a fixed beam IMRT, and two plans using the RapidArc technique: a single (RA1) and a double (RA2) modulated arc therapy. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB) a dose of 59.4 Gy to the planning target volume (PTV2) based on the gross disease in a 1.8 Gy-daily fraction, 5 days a week. At the same time, the subclinical disease (PTV1) was planned to receive 49.5 Gy in a 1.5 Gy-daily fraction. Plans were normalized to 99% of the PTV2 that received 95% of the prescribed dose. Planning objectives were 95% of the PTV1 will receive 95% of the prescribed dose and no more than 2% of the PTV will receive more than 107%. Dose-volume histograms (DVH) for the target volume and the organs at risk (bowel tract, bladder, iliac crests, femoral heads, genitalia/perineum, and healthy tissue) were compared for these different techniques. Monitor units (MU) and delivery treatment time were also reported.Results: All plans achieved fulfilled objectives. Both IMRT and RA2 resulted in superior coverage of PTV than RA1 that was slightly inferior for conformity and homogeneity (p < 0.05).Conformity index (CI95%) for the PTV2 was 1.15 ± 0.15 (RA2), 1.28 ± 0.22 (IMRT), and 1.79 ± 0.5 (RA1). Homogeneity (D5%- D95%) for PTV2 was 3.21 ± 1.16 Gy (RA2), 2.98 ± 0.7 Gy (IMRT), and 4.3 ± 1.3 Gy (RA1). RapidArc showed to be superior to IMRT in terms of organ at risk sparing. For bowel tract, the mean dose was reduced of 4 Gy by RA2 compared to IMRT. Similar trends were observed for bladder, femoral heads, and genitalia. The DVH of iliac crests and healthy tissue resulted in comparable sparing for the low doses (V10 and V20). Compared to IMRT, mean MUs for each fraction was significantly reduced with RapidArc (p = 0.0002) and the treatment time was reduced by a 6-fold extent.Conclusion: For patients suffering from anal canal cancer, RapidArc with 2 arcs was able to deliver equivalent treatment plan to IMRT in terms of PTV coverage. It provided a better organ at risk sparing and significant reductions of MU and treatment time per fraction. © 2010 Vieillot et al; licensee BioMed Central Ltd.


Vieillot S.,CRLC Val dAurelle Paul Lamarque | Fenoglietto P.,CRLC Val dAurelle Paul Lamarque | Lemanski C.,CRLC Val dAurelle Paul Lamarque | Moscardo C.L.,CRLC Val dAurelle Paul Lamarque | And 4 more authors.
Radiation Oncology | Year: 2012

Purpose: To assess outcomes of patients with carcinoma of the anal canal (CAC) treated with intensity-modulated radiation therapy (IMRT).Method and materials: From August 2007 to January 2011, seventy-two patients suffering from CAC were treated with IMRT. Concurrent chemotherapy was added in case of locally advanced tumors. Radiation course consisted in delivering an initial plan to the PTV1 defined as the primary tumor and the risk area including pelvic and inguinal nodes. Forty-five Gy in daily 1.8 Gy-daily fractions were delivered five days a week. A second plan of 14.4-20 Gy to the primary tumor (PTV2) was administered in 1.8-2 Gy-daily fractions, 5 days a week. We present here the results of dosimetry, toxicities, and clinical outcome of the first 39 patients with a median follow-up of 24 months.Results: Thirty-one women and eight men were included in the present analysis. Tumors were classified as stages I, II, III and IV in 2, 7, 27 and 2 patients, respectively. Median age was 59 years (range, 38-85). Radiotherapy alone (RT) or combined with chemotherapy (RCT) were delivered in 6 (15%) and 33 (85%) patients, respectively.Six patients (15%) required a treatment break ≥ 3 days, and median time for treatment break was 8 days (range, 3-14 days). Acute grade 3 gastrointestinal (GI) and genitourinary (GU) toxicities were seen in 10 and 5% of patients, respectively. Grade 4 toxicity was only hematologic and occurred in 12% patients receiving RCT. With a median follow-up of 24 months, no patient experienced any late grade 4 toxicity. The 2-year overall survival rate was 89%, the 2-year local relapse free survival was 77% and the 2-year colostomy-free survival rate was 85%.Conclusion: IMRT is well tolerated with acceptable treatment interruption allowing dose escalation. © 2012 Vieillot et al; licensee BioMed Central Ltd.

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