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Bernard F.,CHU dAngers | Lemee J.-M.,CHU dAngers | Pasco-Papon A.,CHU dAngers | Fournier H.D.,CHU dAngers
Interdisciplinary Neurosurgery: Advanced Techniques and Case Management | Year: 2017

Background The optimal management of skull base DAVFs remains controversial. Some groups advocate endovascular therapy, which is an efficient therapeutic option, but can be limited by inadequate access to the fistula point, non-target embolization, and recanalization risk. We report our experience in microsurgical obliteration after embolization failure, emphasizing the importance of a prompt effective treatment for the long-term clinical status improvement. Patients and methods This is a retrospective review, on 6 patients undergoing surgery for skull base Cognard grade IV DAVF after one or several failed embolization procedures in our institution between January 2006 and July 2016. Patients and treatments characteristics/outcomes are reported. Results In all patients endovascular therapy had failed prior to surgery. The mean modified Rankin scale from diagnosis to preoperative surgical cure increased from 1.8 range to 2.7. After surgical treatment, symptoms improved in 5 (83.3%), stayed the same in 1 (16.7%). In all cases total elimination of arteriovenous shunting was achieved, without hemorrhage and recurrence during the mean follow-up period of 5.4 years. Conclusion Surgical occlusion of skull base Cognard IV DAVFs yields excellent exclusion rate. However, complete occlusion of the shunt may not lead to clinical improvement if symptoms had been progressing for an excessively long period of time before curative treatment was initiated. Hence the patient remains at risk of rebleeding as long as the shunt is open. We do believe that a single stage endovascular attempt can be decided, but a failed procedure should lead to immediate surgery. © 2017 The Authors


Huguet F.,Hopital Purpan | Rousselot P.,Hopital Mignot | Vey N.,Institute Paoli Calmettes | Ifrah N.,CHU dAngers
Leukemia and Lymphoma | Year: 2015

Abstract Clofarabine, a second-generation purine analog displaying potent inhibition of DNA synthesis and favorable pharmacologic profile, is approved for the treatment of acute lymphoblastic leukemia (ALL) after failure of at least two previous regimens in patients up to 21 years of age at diagnosis. Good neurologic tolerance, synergy with alkylating agents, management guidelines defined through pediatric ALL and adult acute myeloid leukemia, have also prompted its administration in more than 100 adults with Philadelphia chromosome-positive and negative B lineage and T lineage ALL, as single agent (40 mg/m2/ day for 5 days), or in combination. In a Group for Research on Adult Acute Lympho- blastic Leukemia (GRAALL) retrospective study of two regimens (clofarabine ± cyclophosphamide + / - etoposide (ENDEVOL) ± mitoxantrone ± asparaginase ± dexamethasone (VANDEVOL)), remission was achieved in 50% of 55 relapsed/refractory patients, and 17-35% could proceed to allogeneic stem cell. Clofarabine warrants further exploration in advanced ALL treatment and bridge-to-transplant. © 2015 Informa UK, Ltd.


Arnaud L.,systemIC | Arnaud L.,French Institute of Health and Medical Research | Hervier B.,systemIC | Hervier B.,University Pierre and Marie Curie | And 28 more authors.
Blood | Year: 2011

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsyproven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality. © 2011 by The American Society of Hematology.


PubMed | APHP Beaujon Hospital, Bordeaux University Hospital Center, Lyon Civil Hospitals, Amiens University Hospital and 16 more.
Type: Journal Article | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2016

To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications).From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted.The median progression-free survival was 10.3 months (95% CI, 10.0-11.0). The median overall survival was 19.7 months (95% CI, 18.5-21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1-9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS.Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival.


PubMed | University of Poitiers, CHI Poissy St Germain, Center Hospitalier Of Versailles, University of Versailles and 11 more.
Type: | Journal: Trials | Year: 2015

Incomplete spontaneous abortions are defined by the intrauterine retention of the products of conception after their incomplete or partial expulsion. This condition may be managed by expectant care, medical treatment or surgery. Vacuum aspiration is currently the standard surgical treatment in most centers. However, operative hysteroscopy has the advantage over vacuum aspiration of allowing the direct visualization of the retained conception product, facilitating its elective removal while limiting surgical complications. Inadequately powered retrospective studies reported subsequent fertility to be higher in patients treated by operative hysteroscopy than in those treated by vacuum aspiration. These data require confirmation in a randomized controlled trial comparing fertility rates between women undergoing hysteroscopy and those undergoing vacuum aspiration for incomplete spontaneous abortion.After providing written informed consent, 572 women with incomplete spontaneous abortion recruited from 15 centers across France will undergo randomization by a centralized computer system for treatment by either vacuum aspiration or operative hysteroscopy. Patients will not be informed of the type of treatment that they receive and will be cared for during their hospital stay in accordance with standard practices at each center. The patients will be monitored for pregnancy or adverse effects by a telephone conversation or questionnaire sent by e-mail or post over a period of two years. In cases of complications, failure of the intervention or diagnosis of uterine cavity disease, patient care will be left to the discretion of the medical center team.If our hypothesis is confirmed, this study will provide evidence that the use of operative hysteroscopy can increase the number of pregnancies continuing beyond 22weeks of gestation in the two-year period following incomplete spontaneous abortion without increasing the incidence of morbidity and peri- and postoperative complications. The standard surgical treatment of this condition would thus be modified. This study would therefore have a large effect on the surgical management of incomplete spontaneous abortion.ClinicalTrials.gov Identifier: NCT02201732 ; registered on 17 July 2014.


Gressin R.,Grenoble University Hospital Center | Gressin R.,French Institute of Health and Medical Research | Caulet-Maugendre S.,Rennes University Hospital Center | Deconinck E.,Besancon University Hospital Center | And 17 more authors.
Haematologica | Year: 2010

Background There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation. Design and Methods Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed. Results The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3-4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3-4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389). © 2010 Ferrata Storti Foundation.


Bachy E.,University of Lyon | Houot R.,University of Rennes 1 | Morschhauser F.,Lille 2 University of Health and Law | Sonet A.,Catholic University of Leuven | And 13 more authors.
Haematologica | Year: 2013

Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy- based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P<0.0001 and P=0.001, respectively). Considering long-term toxicity, the addition of rituximab in the firstline setting was confirmed as safe with regards to development of secondary malignancies. Long-term follow up of patients with follicular lymphoma treated in the FL2000 study confirms the sustained clinical benefit of rituximab without long-term toxicity. This study was registered at ClinicalTrials.gov.


Saleh N.,Groupe Hospitalier Chenevier Mondor | Saleh N.,University Paris Est Creteil | Saleh N.,French Institute of Health and Medical Research | Moutereau S.,Groupe Hospitalier Chenevier Mondor | And 12 more authors.
Neurology | Year: 2010

Objective: The somatotropic axis (growth hormone [GH] and insulinlike growth factor I [IGFI]) play a role in the cognitive deficits seen with aging, GH deficiency, and neurodegenerative disorders such as Alzheimer disease. We recently reported elevations in basal plasma GH and IGFI levels in patients with Huntington disease (HD). Here, our objective was to determine whether somatotropic axis abnormalities predicted cognitive dysfunction in HD. Methods: In this prospective cohort study of 109 patients with genetically documented HD, aged 21 to 85 years, we determined fasting blood levels of total IGFI, GH, and insulinlike factor binding protein 3 at baseline, and we used the cognitive Unified Huntington's Disease Rating Scale to assess cognitive impairment at baseline and for up to 5 years subsequently. Associations were evaluated using mixed linear model analysis. Results: Higher plasma IGFI concentrations were associated with greater cognitive decline (β Stroop Words,-6.01, p = 0.003; β Stroop Color,-4.41, p = 0.01; β Stroop Color/Words,-3.86, p = 0.02; β Symbol Digit Modalities,-3.69, p = 0.03; and β verbal fluency,-5.01, p = 0.03). Higher free IGFI concentrations and higher GH concentrations in men also predicted greater cognitive decline. Conclusions: Our findings in patients with HD suggest that a high IGFI level at baseline may be associated with greater subsequent declines in executive function and attention. © 2010 by AAN Enterprises, Inc.


PubMed | CHU dAngers, Pole de neurosciences and France
Type: Journal Article | Journal: Geriatrie et psychologie neuropsychiatrie du vieillissement | Year: 2013

long-term outcomes of elderly patients after an intensive care unit (ICU) stay are not fully elucidated. The objective of the pre-Seniorea study was to examine the feasibility of comprehensive geriatric assessment (CGA) during and after the ICU stay.inpatients aged 75 years and over admitted to medical and surgical ICUs of Angers University Hospital, France, from june to september 2012, received a SGA (assessment of morbidities, frailty, cognition, anxiety, mood, nutrition, functional abilities, motor function, pain, caregiver burden and quality of life) at ICU admission (through a proxy interview), at the end of the ICU stay, and 3 month later in the place of life.fifty-two patients were included (81 [78; 83] years (median [25(th); 75(th) percentile]); 35 males; SAPSII 47 [38; 56]; 80% ventilation). ICU survival was 73% (n=38), 58% (n=30) after three months, and 54% (n=28) after 12 months. The CGA at ICU admission was performed in all patients and lasted 10 [5; 10] minutes. The CGA at discharge was performed in all survivors and lasted 10 [5; 15] minutes. In all, 26 survivors received CGA in their place of life after 3 months. Travel time by evaluators was 42 minutes, and time on site 45 [45; 60] minutes. At 3 months, 85% of surviving patients were at home and felt happy, 80% had preserved autonomy. The only variable predictive of survival at three months was the SAPSII score.the follow-up of elderly inpatient admitted to ICU with repeated CGAs, including long-term evaluations in the place of life, was feasible and well-accepted. These results set the place for larger multicentric trials.


Gouraud-Tanguy A.,Nantes University Hospital Center | Berlioz-Thibal M.,Nantes University Hospital Center | Brisseau J.-M.,Nantes University Hospital Center | Aoudia V.O.,Nantes University Hospital Center | And 3 more authors.
Geriatrie et Psychologie Neuropsychiatrie du Vieillissement | Year: 2012

Anticholinergic medications are responsible for most frequent adverse drug effects. Two scales have been elaborated as tools for prescribers: the Anticholinergic Drug Scale (ADS) of Carnahan et al., and the Anticholinergic Risk Scale (ARS) of Rudolph et al. The objective of this study was to analyze the diagnostic performance of both scales for predicting signs related to an anticholinergic effect. Method: Medical records of 1379 patients aged 75 years or older hospitalized in a geriatric acute care unit between 2002 and 2005 were studied. The analyze was made retrospectively, but data were collected prospectively. Results: Risk of appearance of total anticholinergic signs (ADS : OR 1,45, CI 95% [1,03-2,03], p=0,037 and ARS : OR 1,98, CI 95% [1,19-3,28] p<0,01) and peripheral signs (ADS: OR 1,66, CI 95% [1,22-2,26], p<0,01 and ARS : OR 1,81, CI 95% [1,19-2,75], p<0,01) increased when score was ≥ 3 with both scales, which wasn't the case for central signs. Conclusion: Both scales permitted to detect an increased risk of appearance of total and peripheral anticholinergic signs, but not the centrals as delirium. Interest of total anticholinergic burden remains to be demonstrated, especially for delirium risk assessment.

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