Caillot D.,Dijon University Hospital Center |
Latrabe V.,Bordeaux University Hospital Center |
Thiebaut A.,Lyon University Hospital Center |
Herbrecht R.,University of Strasbourg |
And 6 more authors.
European Journal of Radiology
Background and objective: The exact timing of the evolution of lesion volumes of invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the management of hematological patients but has never been evaluated in a prospective study. We analyzed the CT scan data from the prospective Combistrat trial. Design and methods: Volumes of aspergillosis lesions from 30 patients (including 24 acute myeloid leukaemia) with probable (n = 26) or proven (n = 4) IPA according to the EORTC-MSG modified criteria, were measured prospectively on the thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of treatment (EOT). Results: For the overall population, the volume of pulmonary aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p = 0.003). Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with p = 0.003 for D14 vs. D7, but with p = 0.56 for D14 vs. D0). At EOT (= D17, median value), the volume of lesions was significantly lower than D14 (0.76 fold the initial volume; p < 0.001) but it was not significantly different when compared to D0 (p = 0.11). Conclusions: The results of this prospective study suggest that the sequential analysis of CT scan in neutropenic patients with IPA depicts more precisely the evolution of lesion volumes than comparison to baseline images. Moreover, the systematic use of chest CT appears to be a useful tool for diagnosis and outcome evaluation of IPA in clinical trials. © 2009 Elsevier Ireland Ltd. All rights reserved. Source
Pilliod J.,University of Bordeaux 1 |
Moutton S.,University of Bordeaux 1 |
Moutton S.,Bordeaux University Hospital Center |
Lavie J.,University of Bordeaux 1 |
And 50 more authors.
Annals of Neurology
Objective Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in the SACS gene. SACS encodes sacsin, a protein whose function remains unknown, despite the description of numerous protein domains and the recent focus on its potential role in the regulation of mitochondrial physiology. This study aimed to identify new mutations in a large population of ataxic patients and to functionally analyze their cellular effects in the mitochondrial compartment. Methods A total of 321 index patients with spastic ataxia selected from the SPATAX network were analyzed by direct sequencing of the SACS gene, and 156 patients from the ATAXIC project presenting with congenital ataxia were investigated either by targeted or whole exome sequencing. For functional analyses, primary cultures of fibroblasts were obtained from 11 patients carrying either mono- or biallelic variants, including 1 case harboring a large deletion encompassing the entire SACS gene. Results We identified biallelic SACS variants in 33 patients from SPATAX, and in 5 nonprogressive ataxia patients from ATAXIC. Moreover, a drastic and recurrent alteration of the mitochondrial network was observed in 10 of the 11 patients tested. Interpretation Our results permit extension of the clinical and mutational spectrum of ARSACS patients. Moreover, we suggest that the observed mitochondrial network anomalies could be used as a trait biomarker for the diagnosis of ARSACS when SACS molecular results are difficult to interpret (ie, missense variants and heterozygous truncating variant). Based on our findings, we propose new diagnostic definitions for ARSACS using clinical, genetic, and cellular criteria. © 2015 The Authors. Source