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.
Tardieu C.,R.A.U.M. |
Bonneau N.,R.A.U.M. |
Hecquet J.,R.A.U.M. |
Boulay C.,Service dOrthopedie |
And 3 more authors.
Journal of Human Evolution | Year: 2013
We compare adult and intact neonatal pelves, using a pelvic sagittal variable, the angle of sacral incidence, which presents significant correlations with vertebral curvature in adults and plays an important role in sagittal balance of the trunk on the lower limbs. Since the lumbar curvature develops in the child in association with gait acquisition, we expect a change in this angle during growth which could contribute to the acquisition of sagittal balance. To understand the mechanisms underlying the sagittal balance in the evolution of human bipedalism, we also measure the angle of incidence of hominid fossils.Fourty-seven landmarks were digitized on 50 adult and 19 intact neonatal pelves. We used a three-dimensional model of the pelvis (DE-VISU program) which calculates the angle of sacral incidence and related functional variables. Cross-sectional data from newborns and adults show that the angle of sacral incidence increases and becomes negatively correlated with the sacro-acetabular distance. During ontogeny the sacrum becomes curved, tends to sink down between the iliac blades as a wedge and moves backward in the sagittal plane relative to the acetabula, thus contributing to the backwards displacement of the center of gravity of the trunk. A chain of correlations links the degree of the sacral slope and of the angle of incidence, which is tightly linked with the lumbar lordosis. We sketch a model showing the coordinated changes occurring in the pelvis and vertebral column during the acquisition of bipedalism in infancy. In the australopithecine pelves, Sts 14 and AL 288-1, and in the Homo erectus Gona pelvis the angle of sacral incidence reaches the mean values of humans. Discussing the incomplete pelves of Ardipithecus ramidus, Australopithecus sediba and the Nariokotome Boy, we suggest how the functional linkage between pelvis and spine, observed in humans, could have emerged during hominid evolution. © 2013 Elsevier Ltd.
Polosukhin V.V.,Vanderbilt University |
Cates J.M.,Vanderbilt University |
Lawson W.E.,Vanderbilt University |
Zaynagetdinov R.,Vanderbilt University |
And 11 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Rationale: Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent inflammation are largely unknown. Objectives: We investigated relationships between bronchial epithelial remodeling, polymeric immunoglobulin receptor (pIgR) expression, secretory IgA (SIgA), airway inflammation, and mural remodeling in COPD. Methods: Lung tissue specimens and bronchoalveolar lavage were obtained from lifetime nonsmokers and former smokers with or without COPD. Epithelial structural changes were quantified by morphometric analysis. Expression of pIgR was determined by immunostaining and real-time polymerase chain reaction. Immunohistochemistry was performed for IgA, CD4 and CD8 lymphocytes, and cytomegalovirus and Epstein-Barr virus antigens. Total IgA and SIgA were measured by ELISA and IgA transcytosis was studied using cultured human bronchial epithelial cells. Measurements and Main Results: Areas of bronchial mucosa covered by normal pseudostratified ciliated epithelium were characterized by pIgR expression with SIgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced pIgR expression, localized SIgA deficiency, and increased CD4+ and CD8+ lymphocyte infiltration. In small airways (<2 mm), these changes were associated with presence of herpesvirus antigens, airway wall remodeling, and airflow limitation in patients with COPD. Patients with COPD had reduced SIgA in bronchoalveolar lavage. Air-liquid interface epithelial cell cultures revealed that complete epithelial differentiation was required for normal pIgR expression and IgA transcytosis. Conclusions: Our findings indicate that epithelial structural abnormalities lead to localized SIgA deficiency in COPD airways. Impaired mucosal immunity may contribute to persistent airway inflammation and progressive airway remodeling in COPD.
Eloy P.,Cliniques Universitaires Of Mont Godinne |
Poirrier A.L.,Cliniques Universitaires Of Mont Godinne |
De Dorlodot C.,Cliniques Universitaires Of Mont Godinne |
Van Zele T.,Ghent University |
And 2 more authors.
Current Allergy and Asthma Reports | Year: 2011
Rhinosinusitis (RS) is a heterogeneous group of diseases. It is a significant and increasing health problem that affects about 15% of the population in Western countries. It has a substantial impact on patients' health-related quality of life and daily functioning and represents a huge financial burden to society and the health care system as a result of the direct and indirect costs. In addition, RS is not well-understood, and little is known about the etiology and pathophysiology. In the past decade, many papers have been published that have changed our understanding of RS. RS is commonly classified into acute and chronic RS based on symptom duration. In acute RS, an inflammatory reaction initiated by a viral infection characterizes most uncomplicated, mild to moderate cases. Therefore, the first line of treatment for these cases are intranasal steroids and not antibiotics. In severe and complicated cases, antibiotics combined with topical steroids remain the treatment of choice. On the other hand, chronic RS is actually subdivided into two distinct entities (chronic rhinosinusitis with and without polyps), as growing evidence indicates that these entities have specific inflammatory pathways and cytokine profiles. The authors review recent data regarding the clinical presentations, cytokine profiles, tissue remodeling, and modalities of treatment for each form of RS. © Springer Science+Business Media, LLC 2011.
De Saint-Hubert M.,Cliniques Universitaires Of Mont Godinne |
Schoevaerdts D.,Cliniques Universitaires Of Mont Godinne |
Cornette P.,Cliniques Universitaires Saint Luc |
D'Hoore W.,Public Health School |
And 2 more authors.
Journal of Nutrition, Health and Aging | Year: 2010
Background: Functional decline frequently occurs following hospitalisation in older people and may be prevented or minimized by specific management. Such care processes needs appropriate early screening of older hospitalized patients. Objective: To identify instruments able to detect on admission older hospitalized patients at risk of functional decline at and after discharge. Methods: Functional decline is defined as loss of independence in activities of daily living (functional decline) or admission in nursing home. The systematic search used Medline 1970-2007, Web of Science 1981-2007 and references list of relevant papers. An independent epidemiologist assessed methodological quality of the retained articles. Results: We found 12 studies developing predictive tools, including 7145 patients. Functional outcomes were assessed at or after discharge. Preadmission functional status, cognition, and social support were major components for prediction of functional evolution. Few instruments are fully validated and data concerning reliability are often lacking. Operational characteristics are moderate (sensitivity 29-87%, negative likelihood ratio 0.2-0.8). Conclusions: Instruments predicting functional adverse outcomes are difficult to compare due to heterogeneity of functional outcomes and hospital settings. The reason why so many tools have been developed is probably because none gives full satisfaction: their general predictive validity and performances are insufficient. Further research is needed to improve the screening of frail older patients admitted to hospital with standardized and validated tools. The Journal of Nutrition, Health & Aging©.
Floris N.,Cliniques Universitaires Of Mont Godinne |
Gabriel L.,Cliniques Universitaires Of Mont Godinne |
Marchandise B.,Cliniques Universitaires Of Mont Godinne
Acta Cardiologica | Year: 2010
We report the discovery at transthoracic echocardiography of a very large, sessile formation in the left atrium in a 77-year-old woman with permanent non-valvular atrial fibrillation who did not receive anticoagulant therapy. After six weeks of anticoagulation by subcutaneous low-molecular-weight heparin, a control echocardiogram demonstrated an almost complete resolution of the mass without systemic embolisation. This case highlights the success, without complications, of a medical anticoagulant therapy for giant left atrial thrombus.
Substitution of 11C-methionine PET by perfusion MRI during the follow-up of treated high-grade gliomas: Preliminary results in clinical practice [Substitution du PET-méthionine par la perfusion IRM lors du suivi thérapeutique des gliomes de haut grade: Résultats préliminaires en pratique clinique]
Dandois V.,Catholic University of Louvain |
Rommel D.,Catholic University of Louvain |
Renard L.,Catholic University of Louvain |
Jamart J.,Cliniques Universitaires Of Mont Godinne |
Cosnard G.,Catholic University of Louvain
Journal of Neuroradiology | Year: 2010
Purpose: Our aim was to compare perfusion magnetic resonance imaging (MRI) and positron emission tomography (PET) using carbon-11 labelled methionine (MET) in gliomas and their value in differentiating tumour recurrence from necrosis. Materials and methods: We retrospectively reviewed 28 patients with a high-grade glioma. A total of 33. MR perfusions and MET-PET were ultimately analysable for comparison between the relative cerebral blood volume (rCBV) and MET-PET examinations. Intra- and interobserver reproducibility was assessed and diagnostic value of rCBV compared to MET-PET and histology was assessed by the area under the receiver operating characteristic (ROC) curve. Results: ROC curve analysis showed that rCBV had at least equal performances in differentiating tumour recurrence and necrosis than MET-PET. Cut-off value of rCBV for differentiating tumour from necrosis was 182% with a sensitivity of 81.5% and a specificity of 100%. Conclusion: In clinical practice, perfusion MRI could replace MET-PET for differentiating necrosis from tumour recurrence. © 2009 Elsevier Masson SAS.
Mouthuy J.,Cliniques Universitaires St Luc |
Mouthuy J.,Catholic University of Louvain |
Detry B.,Catholic University of Louvain |
Sohy C.,Catholic University of Louvain |
And 5 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Rationale: Intrinsic asthma was described by Rackemann as asthma without allergy. Local IgE production has been documented in intrinsic asthma, but antigen specificity of this response remains elusive. Objectives: We investigated (1) the presence of dust mite-specific IgE in sputum of patients with intrinsic asthma, (2) their clinical/immunological relevance, and (3) their functionality. Methods: Specific IgE to Dermatophagoides pteronyssinus (Der p) and to recombinant major allergens (rDer p1 and rDer p2) were assayed by ELISA in sputum samples from patients with intrinsic versus atopic asthma and control subjects. Whole-lung challenge was performed with Der p for clinical and inflammatory readouts. Functionality of local IgE to trigger effector cells was assessed using basophil activation test (surface expression of CD203c). Measurements and Main Results: Both total IgE and Der p-specific IgE levels are increased in patients with intrinsic asthma compared with healthy nonatopic patients. However, no immediate asthmatic responses were observed in patients with intrinsic asthma after Der p exposure. These sputum Der p-specific IgE do, however, recognize major allergens Der p1 and Der p2 and are able to trigger activation of blood basophils from atopic donors. Conclusions: We confirm that IgE production occurs in intrinsic asthma and show that part of this IgE recognizes Der p antigens. However, this IgE reactivity does not translate into clinical responses to Der p exposure, despite specificity to major allergens and functionality to activate effector cells in vitro. We postulate that a second signal that promotes IgE-mediated asthmatic responses through FceRI is lacking in intrinsic asthma.
Full conversion from transfemoral to transradial approach for percutaneous coronary interventions results in a similar success rate and a rapid reduction of in-hospital cardiac and vascular major events
Dangoisse V.,Catholic University of Leuven |
Guedes A.,Catholic University of Leuven |
Guedes A.,Cliniques Universitaires Of Mont Godinne |
Gabriel L.,Catholic University of Leuven |
And 4 more authors.
EuroIntervention | Year: 2013
Aims: The transradial approach (TRA) for percutaneous coronary intervention (PCI) recently emerged as a safer vascular access with a similar rate of MACE but a lower success rate requiring crossover to another approach when compared to the transfemoral approach (TFA). Methods and results: In our hospital the introduction of the TRA in November 2003 resulted in a progressive decline of TFA use. Over the five years of conversion to TRA, from 2002 (100% TFA) to 2007 (98% TRA), major adverse cardiac events (MACE) and all in-hospital vascular and bleeding events, related or not to vascular access, were prospectively collected to assess performances of each approach in the specific setting of PCI (percutaneous coronary interventions). Data of 1,928 TFA and 1,672 TRA for a total of 3,600 consecutive PCI procedures are reported. PCI success rate was unchanged by TRA (96.1% versus 95.3% for TFA, NS). TRA was associated with a reduction in the rate of post-PCI myocardial infarction (2.3% versus 3.6% for TFA, p=0.023) and with a significant reduction of MACE (3.8% versus 5.2% for TFA, p=0.041). TRA use was also associated with a marked reduction of blood transfusion and surgery for post-PCI bleeding (0.2% versus 1.5% for TFA, p<0.001), despite more frequent prescription of downstream glycoprotein IIb/IIIa inhibitors (23.7% versus 7.4% for TFA, p<0.001). Thus, TRA resulted in a rapid and significant reduction of all major in-hospital adverse events, cardiac as well as non-cardiac, pooled in a "Net Adverse Clinical Event (NACE) index" of non-desirable events: death, myocardial infarction, stroke, urgent CABG surgery, surgery for bleeding and vascular events and blood transfusion. Such events occurred in 4.1% of TRA (n=69) as compared to 7% of TFA (n=134) (p<0.001), accounting for a 41% relative reduction of this NACE index by TRA. By multivariate analysis, TRA was related to a better in-hospital outcome (OR 0.64, 95% confidence interval [CI] 0.47-0.87; p=0.005). Conclusions: TRA for PCI provides the same success rate as TFA but significantly reduces post hoc related complications. © Europa Digital and Publishing 2013. All rights reserved.
Kleppe M.,Vlaams Institute for Biotechnology |
Kleppe M.,Catholic University of Leuven |
Lahortiga I.,Vlaams Institute for Biotechnology |
Lahortiga I.,Catholic University of Leuven |
And 19 more authors.
Nature Genetics | Year: 2010
PTPN2 (protein tyrosine phosphatase non-receptor type 2, also known as TC-PTP) is a cytosolic tyrosine phosphatase that functions as a negative regulator of a variety of tyrosine kinases and other signaling proteins 1-3. In agreement with its role in the regulation of the immune system, PTPN2 was identified as a susceptibility locus for autoimmune diseases4,5. In this work, we describe the identification of focal deletions of PTPN2 in human T-cell acute lymphoblastic leukemia (T-ALL). Deletion of PTPN2 was specifically found in T-ALLs with aberrant expression of the TLX1 transcription factor oncogene, including four cases also expressing the NUP214-ABL1 tyrosine kinase. Knockdown of PTPN2 increased the proliferation and cytokine sensitivity of T-ALL cells. In addition, PTPN2 was identified as a negative regulator of NUP214-ABL1 kinase activity. Our study provides genetic and functional evidence for a tumor suppressor role of PTPN2 and suggests that expression of PTPN2 may modulate response to treatment. © 2010 Nature America, Inc. All rights reserved.