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Quenot J.-P.,University of Burgundy | Quenot J.-P.,French Institute of Health and Medical Research | Binquet C.,French Institute of Health and Medical Research | Kara F.,Center Hospitalier | And 15 more authors.
Critical Care | Year: 2013

Introduction: To provide up-to-date information on the prognostic factors associated with 28-day mortality in a cohort of septic shock patients in intensive care units (ICUs). Methods: Prospective, multicenter, observational cohort study in ICUs from 14 French general (non-academic) and university teaching hospitals. All consecutive patients with septic shock admitted between November 2009 and March 2011 were eligible for inclusion. We prospectively recorded data regarding patient characteristics, infection, severity of illness, life support therapy, and discharge. Results: Among 10,941 patients admitted to participating ICUs between October 2009 and September 2011, 1,495 (13.7%) patients presented inclusion criteria for septic shock and were included. Invasive mechanical ventilation was needed in 83.9% (n = 1248), inotropes in 27.7% (n = 412), continuous renal replacement therapy in 32.5% (n = 484), and hemodialysis in 19.6% (n = 291). Mortality at 28 days was 42% (n = 625). Variables associated with time to mortality, right-censored at day 28: age (for each additional 10 years) (hazard ratio (HR) = 1.29; 95% confidence interval (CI): 1.20-1.38), immunosuppression (HR = 1.63; 95%CI: 1.37-1.96), Knaus class C/D score versus class A/B score (HR = 1.36; 95%CI:1.14-1.62) and Sepsis-related Organ Failure Assessment (SOFA) score (HR = 1.24 for each additional point; 95%CI: 1.21-1.27). Patients with septic shock and renal/urinary tract infection had a significantly longer time to mortality (HR = 0.56; 95%CI: 0.42-0.75). Conclusion: Our observational data of consecutive patients from real-life practice confirm that septic shock is common and carries high mortality in general ICU populations. Our results are in contrast with the clinical trial setting, and could be useful for healthcare planning and clinical study design. © 2013 Quenot et al.; licensee BioMed Central Ltd.


Ray-Coquard I.,Center Leon Berard | Morere J.-F.,Hopital Avicenne | Scotte F.,Hopital Europeen Georges Pompidou | Cals L.,Center Hospitalier University Jean Minjoz | Antoine E.-C.,Clinique Hartmann
Advances in Therapy | Year: 2012

Introduction: The purpose of this French survey was to evaluate the adherence to the guidelines (European Organisation for Research and Treatment of Cancer [EORTC]; American Society of Clinical Oncology [ASCO]; French Standards, Options, and Recommendations [SOR]; European Society of Medical Oncology [ESMO]; Food and Drug Administration [FDA]; and National Comprehensive Cancer Network [NCCN]) for the use of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy-induced anemia for patients with advanced breast and lung cancers. Methods: Two-hundred patients were recruited for each malignancy. The collected items were characteristics of ESA initiation, treatment, adjustment, and discontinuation. Metastatic breast cancer and stage IIIb/IV lung cancer patients who had received chemotherapy were eligible. The endpoint was to compare French daily practices with national and international guidelines. Results: From November 2010 to December 2010, 185 breast cancer and 227 lung cancer files were collected. The main reason of ESA initiation was the correction of anemia (49% and 44%, respectively). The median baseline value of hemoglobin was 9.5 g/dL, and the median target value was 12 g/dL. The mean duration of treatment was 12 and 14 weeks, respectively. The mean gain of hemoglobin was 2.3 g/dL and 1.9 g/dL, respectively. In the breast cancer population, two patients (1%) developed a thromboembolic event, which is lower than what has been described in the literature. An iron supplement was prescribed in 55% of patients with breast cancer and 49% of those with lung cancer, with about one-third administered intravenous iron. The interruption of ESA and chemotherapy was synchronous in about 20% of cases, and was earlier in lung cancer patients than in breast cancer patients. Conclusion: The quality and the rigor of the sampling represent one of the key points of this survey. The French and international guidelines for the use of ESA were well respected by the physicians. Overall, the management of chemotherapy-induced anemia was improved compared with what was described in the historical surveys (European Cancer Anaemia Survey [ECAS], French Anaemia Cancer Treatment [F-ACT]). © 2012 Springer Healthcare.


Valmary S.,French Institute of Health and Medical Research | Valmary S.,Center Hospitalier University Jean Minjoz | Dorfmuller P.,French Institute of Health and Medical Research | Dorfmuller P.,Center National Of Reference Of Lhypertension Pulmonaire Severe | And 11 more authors.
Chest | Year: 2011

Background: In susceptible individuals, multiple events may trigger pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). Human herpesvirus-8 (HHV-8), a γ-herpesvirus homologous with Epstein-Barr virus (EBV), was suggested to act as a "second hit" in the development of PAH in susceptible patients. Although there is indirect evidence from in vitro and animal studies in favor of a link between γ-herpesviruses and the pathophysiology of PAH, results remain controversial. Therefore, we investigated the presence of EBV and HHV-8 in the lungs of patients with PAH. Methods: Thirty-four lungs explanted from French patients with end-stage PAH (mean age, 38 ± 14 years; 19 women) were studied. Tissue samples were incorporated into tissue microarrays. Normal lung tissues served as negative controls. Kaposi sarcoma tissue served as a positive control for HHV-8, and EBV-associated lymphoma served as a positive control for EBV. The presence of HHV-8 was investigated with immunohistochemistry and polymerase chain reaction. The presence of EBV was investigated with immunohistochemistry and in situ hybridization. Results: For HHV-8, none of PAH lung samples showed a "stippling" nuclear pattern classically observed in HHV-8-positive Kaposi sarcoma lesions. When studied by polymerase chain reaction, all cases remained negative. For EBV, none of the PAH lung samples showed positive staining, whatever the technique applied. Conclusions: HHV-8 and EBV cannot be detected in the lungs of patients with end-stage PAH. The role of these γ-herpesviruses in the pathophysiology of PAH is, therefore, unlikely. © 2011 American College of Chest Physicians.


Gerfaud-Valentin M.,University Claude Bernard Lyon 1 | Reboux G.,Center Hospitalier University Jean Minjoz | Traclet J.,University Claude Bernard Lyon 1 | Thivolet-Bejui F.,University Claude Bernard Lyon 1 | And 2 more authors.
Chest | Year: 2014

Bakers are exposed daily to flour and may be susceptible to immunologic occupational diseases. A 30-yearold, nonsmoking, female baker was referred for progressive dyspnea on exertion, basal crackles on auscultation, restrictive lung function, decreased diffusing capacity of the lung for carbon monoxide, ground glass hyperdensities with a mosaic pattern on high-resolution CT scan, 25% lymphocytosis by BAL, and cellular chronic bronchiolitis with peribronchiolar interstitial inflammation by lung biopsy specimen. Cultures from flours isolated nine species, including Aspergillus fumigatus . Twenty-six antigens were tested. Serum-specific precipitins were found against A fumigatus , the flour mite Acarus siro, and total extracts from maize and oat. Outcome was favorable with cessation of occupational exposure to flours and transient therapy with prednisone and immunosuppressive agents. To our knowledge, this report is the first of a welldocumented case of hypersensitivity pneumonitis due to sensitization to fungi- and mite-contaminated flours. Hypersensitivity pneumonitis-and not only asthma and allergic rhinitis-should be suspected in bakers with respiratory symptoms. © 2014 American College of Chest Physicians.


Laresche C.,Center Hospitalier University Jean Minjoz | Pelletier F.,Center Hospitalier University Jean Minjoz | Pelletier F.,University of Franche Comte | Garnache-Ottou F.,University of Franche Comte | And 9 more authors.
Journal of Investigative Dermatology | Year: 2014

Microparticles (MPs) are known to be increased in various malignancies and are involved in tumor invasion, angiogenesis, coagulation, and metastasis. We investigated the plasma levels of annexin-V MPs (AV+ MPs), platelet-derived MPs (PMPs), and endothelial-derived MPs (EMPs) in patients with melanoma (n=129) and in healthy controls (n=49). A functional coagulation test STA Procoag-PPL measuring the clotting time was performed on samples containing MPs to evaluate their procoagulant potential. The plasma levels of PMPs, EMPs, and AV+ MPs were significantly higher, and the clotting time-PPL was significantly lower in melanoma patients than in healthy controls. The plasma levels of PMPs, EMPs, and AV+ MPs were higher in stage IV than in the other stages of melanoma, but with no significant difference. In addition, we observed an inverse correlation between PMPs, AV+ MPs, and clotting times. Our data suggest that MPs are involved in the progression of melanoma and may be associated to melanoma-associated thrombogenesis. © 2014 The Society for Investigative Dermatology.


Lablanche S.,Joseph Fourier University | Borot S.,Center Hospitalier University Jean Minjoz | Wojtusciszyn A.,Center Hospitalier Of Montpellier | Bayle F.,Joseph Fourier University | And 13 more authors.
Diabetes Care | Year: 2015

OBJECTIVE To describe the 5-year outcomes of islet transplantation within the Swiss-French GRAGIL Network. RESEARCH DESIGN AND METHODS Retrospective analysis of all subjects enrolled in the GRAGIL-1c and GRAGIL-2 islet transplantation trials. Parameters related to metabolic control, graft function, and safety outcomes were studied. RESULTS Forty-four patients received islet transplantation (islet transplantation alone [ITA] 24 patients [54.5%], islet after kidney [IAK] transplantation 20 patients [45.5%]) between September 2003 and April 2010. Recipients received a total islet mass of 9,715.75 ± 3,444.40 IEQ/kg. Thirty-four patients completed a 5-year follow-up, and 10 patients completed a 4-year follow-up. At 1, 4, and 5 years after islet transplantation, respectively, 83%, 67%, and 58% of the ITA recipients and 80%, 70%, and 60% of the IAK transplant recipients reached HbA1c under 7% (53mmol/mol) and were free of severe hypoglycemia, while none of the ITA recipients and only 10% of the IAK transplant recipients met this composite criterion at the preinfusion stage. Thirty-three of 44 patients (75%) experienced insulin independence during the entire follow-up period, with a median duration of insulin independence of 19.25 months (interquartile range 2-58). Twenty-nine of 44 recipients (66%) exhibited at least one adverse event; 18 of 55 adverse events (33%) were possibly related to immunosuppression; and complications related to the islet infusion (n = 84) occurred in 10 recipients (11.9%). CONCLUSIONS In a large cohortwith a 5-year follow-up and in amulticenter network setting, islet transplantation was safe and efficient in restoring good and lasting glycemic control and preventing severe hypoglycemia in patients with type 1 diabetes. ©2015 by the American Diabetes Association.


Etienne-Grimaldi M.-C.,Center Antoine Lacassagne | Formento P.,Center Antoine Lacassagne | Degeorges A.,University Pierre and Marie Curie | Pierga J.-Y.,University Pierre and Marie Curie | And 10 more authors.
British Journal of Clinical Pharmacology | Year: 2011

AIMS: To test prospectively the impact of VEGF-A gene polymorphisms on the pharmacodynamics of bevacizumab-chemotherapy in breast cancer patients. METHODS: As part of the single-arm MO19391 trial, 137 women with locally recurrent or metastatic breast cancer receiving first-line bevacizumab-containing therapy were analysed. Patients received bevacizumab associated (76%) or not (24%) with taxane-based chemotherapy. Clinical evaluation included clinical response, time to progression (TTP) and a toxicity score corresponding to the sum of each maximum observed toxicity grade (hypertension, haemorrhage, arterial and venous thrombo-embolism). Functional VEGF-A polymorphisms at position -2578 C > A, -1498 T > C, -1154 G > A, -634 G > C and 936 C > T were analysed by PCR-RFLP (blood DNA). RESULTS: Overall response rate (complete response (CR) + partial response (PR)) was 61%. Median TTP was 11 months. None of the VEGF-A polymorphisms was significantly linked to clinical response. Analysis of the 936C > T polymorphism revealed that the 96 patients homozygous for the 936C allele exhibited a marked tendency for a shorter TTP (median 9.7 months) than the 32 patients bearing the 936T allele (median 11.5 months, P= 0.022) of which 30 were CT and two were homozygous TT. Other polymorphisms did not influence TTP. VEGF-A-634 G > C was significantly related to the toxicity score with 39%, 49% and 81% of patients with score >1 in GG, GC and CC patients, respectively (P= 0.01). CONCLUSIONS: The role for VEGF-A 936C > T polymorphism as a potential marker of TTP in breast cancer patients receiving bevacizumab-containing therapy concords with the known impact of VEGF-A 936C > T polymorphism on VEGF-A expression. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.


Bidard F.-C.,University Pierre and Marie Curie | Mathiot C.,University Pierre and Marie Curie | Degeorges A.,University Pierre and Marie Curie | Etienne-Grimaldi M.-C.,Center Antoine Lacassagne | And 8 more authors.
Annals of Oncology | Year: 2010

Background: We investigated whether circulating tumor cells (CTCs) and circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy combined with bevacizumab in metastatic breast cancer patients. Patients and methods: In a French substudy of the MO19391 trial, CTC and CEC counts (CellSearch system) at baseline and changes after two cycles of treatment were correlated with time to progression (TtP). Results: CTC and CEC levels were not correlated in the 67 patients included. At baseline, CTC positivity was a significant prognostic marker for TtP at a threshold of 3 CTC/7.5 ml (P < 0.05) but not at 5 CTC/7.5 ml (P = 0.09). Baseline CEC levels (median 17 CEC/4 ml, range 1-769) were associated with age ≥45 years (P = 0.01), elevated lactate dehydrogenase (P < 0.01) and not with TtP at any threshold. Changes of CTC count during treatment were not a surrogate of TtP, with any of the model tested (threshold based or relative decrease in percent). However, increase in CEC count was associated with improved TtP, at the threshold of 20 CEC/4 ml (P < 0.01). Conclusion: Bevacizumab combined with first-line chemotherapy may modify the predictive value of CTC during treatment possibly due to impaired tumor cells intravasation through vessels endothelium. Variations in CEC levels appear to be a promising early surrogate marker of TtP under antiangiogenic treatment. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


PubMed | Center hospitalier University Jean Minjoz
Type: Journal Article | Journal: Journal francais d'ophtalmologie | Year: 2013

To investigate the association of thrombophilic and fibrinolytic factors with central retinal vein occlusion (CRVO) in patients under 60 years of age.A prospective, observational study of 21 patients with CRVO compared with an age- and sex-matched control group of 23 volunteers was performed. All participants were tested for: cholesterol, hypertension, factors VIII, IX, and XI, homocysteine, antiphospholipid antibodies, antithrombin III, proteins C and S, protein Z and protein Z antibodies, resistance to activated protein C, factor V Leiden mutation, prothrombin mutation, MTHFR genotypes, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) polymorphisms.There was a significantly higher rate of hyperhomocysteinemia (23.8% versus 0%, P=0.018) in CRVO patients. Increased level of factor VIII was more common in the CRVO group at diagnosis (23.8% versus 0%, P=0.018) but no significant difference was observed after one month (P=0.1). Hypercholesterolemia was more common in the CRVO group (42.8% versus 17.4%, P=0.09). Thirty-eight percent of patients with CRVO were hypertensive. Frequencies of other hypercoagulable states were rare. No significant differences were observed for hereditary fibrinolytic abnormalities.Among the coagulopathies studied, hyperhomocysteinemia appears to be a risk factor for central retinal vein occlusion in patients under 60 years of age. Conversely, polymorphisms of fibrinolytic factors do not appear to play a role in this population.


PubMed | Hospices Civils de Lyon, University of Lyon, Joseph Fourier University, Center Hospitalier University Jean Minjoz and 6 more.
Type: Clinical Trial | Journal: Diabetes care | Year: 2015

To describe the 5-year outcomes of islet transplantation within the Swiss-French GRAGIL Network.Retrospective analysis of all subjects enrolled in the GRAGIL-1c and GRAGIL-2 islet transplantation trials. Parameters related to metabolic control, graft function, and safety outcomes were studied.Forty-four patients received islet transplantation (islet transplantation alone [ITA] 24 patients [54.5%], islet after kidney [IAK] transplantation 20 patients [45.5%]) between September 2003 and April 2010. Recipients received a total islet mass of 9,715.75 3,444.40 IEQ/kg. Thirty-four patients completed a 5-year follow-up, and 10 patients completed a 4-year follow-up. At 1, 4, and 5 years after islet transplantation, respectively, 83%, 67%, and 58% of the ITA recipients and 80%, 70%, and 60% of the IAK transplant recipients reached HbA1c under 7% (53 mmol/mol) and were free of severe hypoglycemia, while none of the ITA recipients and only 10% of the IAK transplant recipients met this composite criterion at the preinfusion stage. Thirty-three of 44 patients (75%) experienced insulin independence during the entire follow-up period, with a median duration of insulin independence of 19.25 months (interquartile range 2-58). Twenty-nine of 44 recipients (66%) exhibited at least one adverse event; 18 of 55 adverse events (33%) were possibly related to immunosuppression; and complications related to the islet infusion (n = 84) occurred in 10 recipients (11.9%).In a large cohort with a 5-year follow-up and in a multicenter network setting, islet transplantation was safe and efficient in restoring good and lasting glycemic control and preventing severe hypoglycemia in patients with type 1 diabetes.

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