Bouche O.,Center Hospitalier University Of Reims |
Beretta G.D.,U.O. Oncologia Medica |
Alfonso P.G.,Hospital Gregorio Maranon |
Geissler M.,Municipal Hospital Esslingen
Cancer Treatment Reviews | Year: 2010
Despite the introduction of newer chemotherapeutic agents such as irinotecan, capecitabine and oxaliplatin, patients with metastatic colorectal cancer (mCRC) still have a poor prognosis. More effective and better-tolerated treatment strategies are needed to improve patient outcomes, particularly in subsequent lines of treatment following chemotherapy failure. The favourable efficacy and acceptable safety profiles of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have led to the approval of panitumumab and cetuximab monotherapy for the treatment of patients with EGFR-expressing mCRC whose tumours express non-mutated (wildtype) KRAS, after failure of standard chemotherapy. Cetuximab is also approved in combination with chemotherapy for the treatment of mCRC in this patient population. In phase III monotherapy studies, panitumumab and cetuximab demonstrated significant improvements in progression-free survival when administered with best supportive care (BSC) vs. BSC alone in chemotherapy-refractory mCRC patients. A planned retrospective analysis of the panitumumab monotherapy trial was the first large-scale clinical demonstration that efficacy was confined to patients with tumours expressing wild-type KRAS. It is now recognised that anti-EGFR mAb therapy should only be used in patients whose tumours express wild-type KRAS. While generally well tolerated, anti-EGFR mAb monotherapy is associated with skin toxicity, and severity of the skin rash has been proposed as an early marker of response to treatment. BRAF, PTEN, and PI3K are also emerging as future potential predictive markers of response; however, further clinical studies are warranted to define the role of these biomarkers. © 2010 Elsevier Ltd. All rights reserved.
Robert C.,French Institute of Health and Medical Research |
Karaszewska B.,Przychodnia Lekarska Komed |
Schachter J.,Medical University of Gdańsk |
Rutkowski P.,Center of Oncology of Poland |
And 25 more authors.
New England Journal of Medicine | Year: 2015
Background The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining dabrafenib and the MEK inhibitor trametinib, as compared with dabrafenib alone, enhanced antitumor activity in this population of patients. Methods In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. Results At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combinationtherapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P<0.001). The objective response rate was 64% in the combinationtherapy group and 51% in the vemurafenib group (P<0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group. Conclusions Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity. © 2015 Massachusetts Medical Society.
Potheegadoo J.,French Institute of Health and Medical Research |
Potheegadoo J.,University of Strasbourg |
Berna F.,French Institute of Health and Medical Research |
Berna F.,University of Strasbourg |
And 4 more authors.
Schizophrenia Research | Year: 2013
There is growing interest in clinical research regarding the visual perspective adopted during memory retrieval, because it reflects individuals' self-attitude towards their memories of past personal events. Several autobiographical memory deficits, including low specificity of personal memories, have been identified in schizophrenia, but visual perspective during autobiographical memory retrieval has not yet been investigated in patients. The aim of this study was therefore to investigate the visual perspective with which patients visualize themselves when recalling autobiographical memories and to assess the specificity of their memories which is a major determinant of visual perspective. Thirty patients with schizophrenia and 30 matched controls recalled personal events from 4 life periods. After each recall, they were asked to report their visual perspective (Field or Observer) associated with the event. The specificity of their memories was assessed by independent raters. Our results showed that patients reported significantly fewer Field perspectives than comparison participants. Patients' memories, whether recalled with Field or Observer perspectives, were less specific and less detailed. Our results indicate that patients with schizophrenia adopt Field perspectives less frequently than comparison participants, and that this may contribute to a weakened sense of the individual of being an actor of his past events, and hence to a reduced sense of self. They suggest that this may be related to low specificity of memories and that all the important aspects involved in re-experiencing autobiographical events are impaired in patients with schizophrenia. © 2013 Elsevier B.V.
Long A.,Center Hospitalier University Of Reims |
Rouet L.,Philips |
Lindholt J.S.,Viborg Hospital |
Allaire E.,Center Hospitalier University Henri Mondor |
Allaire E.,University Paris Est Creteil
European Journal of Vascular and Endovascular Surgery | Year: 2012
Objectives: Maximum diameter is a determinant parameter for the clinical management of asymptomatic abdominal aortic aneurysm (AAA). However, its measurement is not standardised. We review the different methods used to measure AAA maximum diameter, with ultrasound (US) or computed tomography (CT). Methods: A review of maximum diameter measurement methods with US and CT was performed, focussing on screening, surveillance before repair and decision for intervention. Diameter measurement methodology was described according to four parameters: plane of acquisition, axis of measurement, position of callipers and selected diameter. A quality score to evaluate methodology descriptions was defined (plane, axis, callipers placement and selected diameter), ranging from 0 (worst) to 4 (best). Results: Review showed a wide range of definitions and practices. The mean value of the quality score was 2.52 in screening studies, 1.66 in guidelines for screening, 2.81 in follow-up studies and 1.63 in studies describing decision for intervention. Conclusion: To improve the efficiency of AAA management (in screening programmes, follow-up and decision for intervention), and enable comparison between future studies, a standardised methodology for AAA maximum diameter measurement is necessary. Until such a consensus is reached, publications should at least clearly report the method of measurement. © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Tran A.,University of Western Brittany |
Talmud D.,Center Hospitalier University Of Reims |
Lejeune B.,University of Western Brittany |
Jovenin N.,Center Hospitalier University Of Reims Et Center Godinot Of Lutte Contre Le Cancer |
And 4 more authors.
Journal of Clinical Microbiology | Year: 2010
From January to December 2007, 973 stool specimens were prospectively collected from children hospitalized for gastroenteritis signs or from neonates and premature cases who were born in two French hospital settings in the north of France. They were tested by rapid enzyme immunoassay (EIA) analyses for rotavirus and adenovirus and by two commercially available ELISA tests for the detection of norovirus and astrovirus. The overall rates of prevalence for rotavirus, norovirus, adenovirus, and astrovirus were 21, 13, 5, and 1.8%, respectively, and they did not significantly differ between the two hospital settings (P = 0.12). Mixed virus infections were detected in 32 (3.3%) of the 973 study children and were associated with norovirus in 21 (66%) infants, including 5 premature cases. From fall to spring, norovirus infections accounted for 52% of documented gastroenteritidis viral infections at a time when rotavirus was epidemic, resulting in mixed norovirus and rotavirus gastrointestinal tract infections. Of the 367 documented viral gastroenteritis cases, 15 (4.1%) were identified as nosocomial infections, 5 of which occurred in premature cases. These findings highlight the need to implement norovirus and astrovirus ELISA detection assays in association with rapid EIA rotavirus and adenovirus detection assays for the clinical diagnosis and the nosocomial prevention of gastroenteritis viral infections in pediatric departments. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Renois F.,Center Hospitalier University Of Reims |
Talmud D.,Center Hospitalier University Of Reims |
Talmud D.,Reims University Hospital Center |
Huguenin A.,Center Hospitalier University Of Reims |
And 5 more authors.
Journal of Clinical Microbiology | Year: 2010
We prospectively tested 95 nasal swabs or nasopharyngeal aspirates taken from 56 adults and 39 children visiting the Reims University Medical Centre (northern France) for influenza-like illnesses (ILI) during the early stage of the French influenza A/H1N1v pandemic (October 2009). Respiratory samples were tested using a combination of two commercially available reverse transcription-PCR (RT-PCR) DNA microarray systems allowing rapid detection of influenza A virus strains, including the new A/H1N1v strain as well as 20 other common or newly discovered respiratory viruses. Concomitantly, a generic and classical real-time RT-PCR assay was performed to detect all circulating influenza A virus strains in the same samples. Of the 95 respiratory samples tested, 30 (31%) were positive for the detection of influenza A/H1N1v virus infection by both RT-PCR DNA microarray and classical real-time RT-PCR detection assays. Among the infections, 25 (83%) were monoinfections, whereas 5 (17%) were multiple infections associating influenza A/H1N1v virus with coronavirus (CoV), human bocavirus (HBoV), respiratory syncytial virus (RSV), or human rhinoviruses (HRVs). Of the 95 respiratory samples tested, 35 (37%) were positive for respiratory viruses other than influenza A/H1N1v virus. Among these infections, we observed 30 monoinfections (HRVs [63%], parainfluenza viruses [PIVs] [20%]), influenza A/H3N2 virus [6%], coronavirus [4%], and HBoV [4%]) and 5 multiple infections, in which HRVs and PIVs were the most frequently detected viruses. No specific single or mixed viral infections appeared to be associated significantly with secondary hospitalization in infectious disease or intensive care departments during the study period (P > 0.5). The use of RT-PCR DNA microarray systems in clinical virology practice allows the rapid and accurate detection of conventional and newly discovered viral respiratory pathogens in patients suffering from ILI and therefore could be of major interest for development of new epidemiological survey systems for respiratory viral infections. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Bredahl K.,Copenhagen University |
Long A.,Center Hospitalier University Of Reims |
Taudorf M.,Copenhagen University |
Lonn L.,Copenhagen University |
And 4 more authors.
European Journal of Vascular and Endovascular Surgery | Year: 2013
Objectives: Volume estimation is more sensitive than diameter measurement for detection of aneurysm growth after endovascular aneurysm repair (EVAR), but this has only been confirmed on three-dimensional, reconstructed computer tomography (3-D CT). The potential of 3-D ultrasound (3-D US) for volume estimation in EVAR surveillance is unknown. Design: Prospective validation study comparing 3-D US with 3-D CT, using 3-D CT as the gold standard. Materials and methods: From August 2011 to March 2012, 93 consecutive EVAR patients were enrolled and examined with both 3-D US and CT angiography (CTA). Image data were analysed in a mutual blinded setup using a 3-D interactive segmentation technique. Results: The technical success rate of 3D-US was 98% (91/93). In 91 EVAR patients (F/M; 10/81) eligible for further analysis, the mean maximum volume (SD) was 126 (58) ml using 3-D US and 128 (58) ml using 3-D CT. The mean difference was 1 ml (0.4%) and the limits of agreement were -14 to 16 ml (-11; 12%). Conclusion: Volume estimation of the aortic sac after EVAR using 3-D US is a feasible and accurate method using 3-D CT as the gold standard. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Reguiai Z.,Center Hospitalier University Of Reims |
Tabary T.,Center Hospitalier University Of Reims |
Maizieres M.,Center Hospitalier University Of Reims |
Bernard P.,Center Hospitalier University Of Reims
Journal of the American Academy of Dermatology | Year: 2012
Background: Rituximab (RTX) has been shown to be effective and safe for short-term treatment of severe pemphigus. Its long-term results remain unknown. Objective: We sought to evaluate long-term RTX efficacy and safety in comparison with classic immunosuppressants for the treatment of severe pemphigus. Methods: This retrospective study included, from 1997 to 2010, 24 consecutive patients with severe pemphigus, treated with RTX (n = 13) or systemic corticosteroids alone or combined with immunosuppressants (n = 11 control subjects). Anti-desmoglein antibodies were titered by enzyme-linked immunosorbent assay, every 3 months the first year, then at least annually. Results: Among the 13 patients treated with RTX, 9 achieved complete remission 3 months after a first RTX cycle. Thereafter, 7 patients (4 with maintenance therapy) relapsed within a mean of 18 months after the last RTX cycle and received 1 or 2 additional RTX cycles. With mean follow-up at 41 months after the first RTX cycle and 28 months after the last one, all 13 patients remained in complete remission (5 patients off therapy). No severe RTX side effects occurred. Anti-desmoglein-3 autoantibodies remained positive in 7 patients, despite long-term complete remission. Long-term remission rates and immunologic profiles did not differ between patients with pemphigus according to RTX status. Limitations: This was a single-center, retrospective study. Conclusions: RTX appeared to be an effective and well-tolerated treatment for severe pemphigus at long term. However, the long-term remission rate without maintenance therapy did not differ significantly from that of control subjects. Anti-desmoglein-1 autoantibody titers were more reliable than anti-desmoglein-3 titers for long-term follow-up.
Gomis P.,Center Hospitalier University Of Reims |
Graftieaux J.P.,Center Hospitalier University Of Reims |
Sercombe R.,University Paris Diderot |
Hettler D.,Center Hospitalier University Of Reims |
And 2 more authors.
Journal of Neurosurgery | Year: 2010
Object. The object of this study was to determine the efficacy of methylprednisolone in reducing symptomatic vasospasm and poor outcomes after subarachnoid hemorrhage (SAH). Methods. Ninety-five patients with proven SAH were recruited into a double-blind, placebo-controlled, randomized trial. Starting within 6 hours after angiographic diagnosis of aneurysm rupture, placebo or methylprednisolone, 16 mg/kg, was administered intravenously every day for 3 days to 46 and 49 patients, respectively. Deterioration, defined as development of a focal sign or decrease of more than 1 point on the Glasgow Coma Scale for more than 6 hours, was investigated by using clinical criteria and transcranial Doppler ultrasonography, cerebral angiography, or CT when appropriate. The end points were incidence of symptomatic vasospasm (delayed ischemic neurological deficits associated with angiographic arterial narrowing or accelerated flow on Doppler ultrasonography, or both) and outcome 1 year after entry into the study according to a simplified Rankin scale (Functional Outcome Scale [FOS]) in living patients and the Glasgow Outcome Scale in all patients included. Results. All episodes of deterioration and all living patients with a 1-year outcome were assessed by a review committee. In patients treated with methylprednisolone, the incidence of symptomatic vasospasm was 26.5% compared with 26.0% in those given placebo. Poor outcomes according to FOS were significantly reduced in the Methylprednisolone Group at 1 year of follow-up; the risk difference was 19.3% (95% CI 0.5-37.9%). The outcome was poor in 15% (6/40) of patients in the Methylprednisolone Group versus 34% (13/38) in the Placebo Group. Conclusions. A safe and simple treatment with methylprednisolone did not reduce the incidence of symptomatic vasospasm but improved ability and functional outcome at 1 year after SAH.
Pathophysiology, epidemiology, clinical presentation, diagnosis and treatment options for autosomal dominant polycystic kidney disease [Pathophysiologie, épidémiologie, présentation clinique, diagnostic et options thérapeutiques dans la polykystose rénale autosomique dominante]
Noel N.,Center Hospitalier University Of Reims |
Rieu P.,Center Hospitalier University Of Reims
Nephrologie et Therapeutique | Year: 2015
Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end-stage renal disease (ESRD) worldwide. Its prevalence is evaluated according to studies and population between 1/1000 and 1/4000 live births and it accounts for 6 to 8% of incident ESRD patients in developed countries. ADPKD is characterized by numerous cysts in both kidneys and various extrarenal manifestations that are detailed in this review. Clinico-radiological and genetic diagnosis are also discussed. Mutations in the PKD1 and PKD2 codifying for polycystin-1 (PC-1) and polycystin-2 (PC-2) are responsible for the 85 and 15% of ADPKD cases, respectively. In primary cilia of normal kidney epithelial cells, PC-1 and PC-2 interact forming a complex involved in flow- and cilia-dependant signalling pathways where intracellular calcium and cAMP play a central role. Alteration of these multiple signal transduction pathways leads to cystogenesis accompanied by dysregulated planar cell polarity, excessive cell proliferation and fluid secretion, and pathogenic interactions of epithelial cells with an abnormal extracellular matrix. The mass effect of expanding cyst is responsible for the decline in glomerular filtration rate that occurs late in the course of the disease. For many decades, the treatment for ADPKD aims to lessen the condition's symptoms, limit kidney damage, and prevent complications. Recently, the development of promising specific treatment raises the hope to slow the growth of cysts and delay the disease. Treatment strategies targeting cAMP signalling such as vasopressin receptor antagonists or somatostatin analogs have been tested successfully in clinical trials with relative safety. Newer treatments supported by preclinical trials will become available in the next future. Recognizing early markers of renal progression (clinical, imaging, and genetic markers) to identify high-risk patients and multidrug approaches with synergistic effects may provide new opportunities for the treatment of ADPKD. © 2015 Published by Elsevier Masson SAS on behalf of the Association Société de néphrologie.