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Frat J.-P.,University of Poitiers | Thille A.W.,University of Poitiers | Mercat A.,Center Hospitalier Regional dOrleans | Girault C.,University of Rouen | And 30 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS: We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS: A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P = 0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P = 0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P = 0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P = 0.006). CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.) Copyright © 2015 Massachusetts Medical Society. All rights reserved.


PubMed | Center Francois Baclesse, Hopital Jean Minjoz, Icl Institute Of Cancerologie Of Lorraine, Institute Bergonie and 15 more.
Type: | Journal: British journal of cancer | Year: 2017

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma.This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety.A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100mg and to continue the clinical trial with a lower dose of 60mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade 3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity.The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.British Journal of Cancer advance online publication 10 January 2017; doi:10.1038/bjc.2016.430 www.bjcancer.com.


Saez-Cirion A.,Institute Pasteur Paris | Bacchus C.,University Pierre and Marie Curie | Hocqueloux L.,Center Hospitalier Regional dOrleans | Avettand-Fenoel V.,Laboratoire Of Virologie | And 23 more authors.
PLoS Pathogens | Year: 2013

Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure. © 2013 Saez-Cirion et al.


Kervarrec T.,Center Hospitalier Regional dOrleans | Binois R.,Center Hospitalier Regional dOrleans | Blechet C.,Center Hospitalier Regional dOrleans | Esteve E.,Center Hospitalier Regional dOrleans
Annales de Dermatologie et de Venereologie | Year: 2015

Background Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare disease involving urticarial cutaneous vasculitis, hypocomplementaemia and systemic manifestations. Pericardial involvement occurs in very rare cases. We report a case of HUVS associated with specific pericarditis and bullous lesions. Patients and methods A 63-year-old woman consulted for chronic urticaria that had appeared ten months earlier. Her skin lesions were associated with weight loss of 10 kg, deterioration of respiratory function and abdominal pain. Leukocytoclastic vasculitis was seen in the skin biopsy sample. Hypocomplementaemia and anti C1q antibodies were present and a diagnosis of HUVS was made. During hospitalisation, extensive compressive pericardial effusion was identified, and histological examination of the biopsy revealed specific pericardial lymphocytic vasculitis. During follow-up, four episodes of infectious pneumonitis were noted. Bullous skin lesions were also observed. Discussion HUVS is a disease caused by an antibody against C1q complement responsible for urticarial lesions and vasculitis antibodies. To our knowledge, there have been only five reports in the literature of pericardial injury associated with HUVS. In our case, histological examination of the pericardium demonstrated lymphocytic vasculitis. © 2014 Elsevier Masson SAS.


Bijek J.H.,Center Hospitalier Regional dOrleans | Ehnart N.,Center Hospitalier Regional dOrleans | Mathevet P.,Center Hospitalier Regional dOrleans
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2011

Epithelial carcinomas represent 80% of cancers. Dissemination of ovarian epithelial cancers is usually peritoneal and rarely hematogenous. The case at hand concerns the hematogenous transmission of an ovarian epithelial cancer with cystic rectal metastasis. The cytology test shows no evidence of peritoneal carcinomatosis. The immunohistochemistry test confirms the primary ovarian cancer with rectal metastasis and the presence of vascular emboli. This clinical study describes one of the rare forms of dissemination of epithelial cancers. Hematogenous transmission should not be confused with dissemination through accessory lymphatic routes. © 2011 Elsevier Masson SAS. Tousdroits réservés.


Bretagnol A.,Center Hospitalier Regional Dorleans | Barbier F.,Center Hospitalier Regional Dorleans
Reanimation | Year: 2015

Renal failure is common in human immunodeficiency virus (HIV)-infected patients admitted to the intensive care unit (ICU). Improved life expectancy in patients receiving combination antiretroviral therapy (cART) is associated with an increasing prevalence of chronic kidney diseases (CKD) in this population, as a result of extended exposure to comorbidities that may impair renal function (including hepatic and cardiovascular diseases) and late nephrotoxic effects of certain cART regimen. Meanwhile, a decreasing trend is observed in the incidence of HIV-associated nephropathy (HIVAN) and other kidney diseases directly related to HIV infection or the acquired immunodeficiency syndrome. Acute renal failure (ARF) is present upon admission or occurs during the ICU stay in one to two-thirds of patients, and significantly increases the risk of ICU death and subsequent progression to CKD. Sepsis and exposure to nephrotoxic drugs are the main causes of ARF in this context. Renal biopsy should be discussed in each ARF episode when noninvasive methods failed to identify the underlying nephropathy. Lastly, since published data are dramatically lacking, the management of cART remains challenging in critically ill patients with altered renal function. This crucial aspect of intensive care in HIV-infected patients should be the focus of further prospective works. © 2015, Société de réanimation de langue française (SRLF) and Springer-Verlag France.


Alouini S.,Center Hospitalier Regional dOrleans | Coly S.,Center Hospitalier Regional dOrleans | Megier P.,Center Hospitalier Regional dOrleans | Lemaire B.,Center Hospitalier Regional dOrleans | And 2 more authors.
American Journal of Obstetrics and Gynecology | Year: 2011

OBJECTIVE: The purpose of this study was to evaluate the efficiency and morbidity of multiple square sutures in severe postpartum hemorrhage. STUDY DESIGN: A retrospective study encompassed 30 multiple square sutures that were performed for severe postpartum hemorrhage in 26,605 deliveries in a tertiary maternity center. The main outcome measures were the ability to stop hemorrhage and the assessment of the uterine cavity by hysteroscopy at 3 months. RESULTS: Multiple square sutures stopped postpartum hemorrhage in 28 of 30 cases (93%). Twenty women underwent hysteroscopy after multiple square sutures. Eight women (40%) did not have intrauterine adhesions. Nine women (45%) had thin and localized intrauterine adhesions that were removed easily by the tip of the hysteroscope; 2 women had moderate intrauterine adhesions that were resected. One patient had endometritis followed by severe intrauterine adhesions. CONCLUSION: Multiple square sutures are effective and safe for the control of severe postpartum hemorrhage and for uterine conservation in most cases. Although some patients had moderate or severe adhesions, a normal uterine cavity or minimal intrauterine adhesions that were removed easily were the most frequent findings at hysteroscopy. A prospective study may be helpful to compare the safety and efficiency of square and brace sutures. © 2011 Mosby, Inc. All rights reserved.


Vandenhende M.-A.,University of Bordeaux 1 | Buret J.,Center Hospitalier Regional dOrleans | Camou F.,University of Bordeaux 1 | Morlat P.,University of Bordeaux 1 | Bonnet F.,University of Bordeaux 1
Diagnostic Microbiology and Infectious Disease | Year: 2014

There are no data on how to manage implantable intra-arterial catheter (IAC) infections. We report the case of a patient with liver metastases of colon cancer treated by regional intra-arterial chemotherapy who presented a suspected IAC-related infection, in whom daptomycin systemic treatment and lock therapy allowed to cure the IAC infection. © 2014 Elsevier Inc.


Patent
French National Center for Scientific Research, University of Orléans and Center Hospitalier Regional Dorleans | Date: 2012-06-19

The present invention relates to a composition comprising a maxi-K potassium channel opener the use in the treatment of fragile X syndrome. More specifically the present invention relates to a composition comprising a fluoro-oxindole or a chloro-oxindole for use in the treatment of fragile X syndrome.


Antela A.,Hospital Clinico Universitario | Clumeck N.,Center Hospitalier University Saint Pierre | Duiculescu D.,Dr Victor Babes Infectious And Tropical Diseases Hospital | Eberhard A.,Medizinisches Versorgungszentrum Karlsplatz Research and Clinical Care Center | And 9 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. METHODS: We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. RESULTS: A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P = 0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. CONCLUSIONS: Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. Copyright © 2013 Massachusetts Medical Society.

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