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Le Kremlin-Bicêtre, France

Voicu S.,Lariboisiere University Hospital | Voicu S.,University Paris Diderot | Deye N.,Lariboisiere University Hospital | Deye N.,University Paris Diderot | And 16 more authors.
Critical Care Medicine | Year: 2014

Objectives: In patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest, two blood gas management strategies are used regarding the PaCO2 target: α-stat or pH-stat. We aimed to compare the effects of these strategies on cerebral blood flow and oxygenation. Design: Prospective observational single-center crossover study. Setting: ICU of University hospital. Patients: Twenty-one therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest more than 18 years old without history of cerebrovascular disease were included. Interventions: Cerebral perfusion and oxygenation variables were compared in α-stat (PaCO 2 measured at 37°C) versus pH-stat (PaCO2 measured at 32-34°C), both strategies maintaining physiological PaCO2 values: 4.8-5.6 kPa (36-42 torr). Measurements and main results: Bilateral transcranial middle cerebral artery flow velocities using Doppler and jugular vein oxygen saturation were measured in both strategies 18 hours (14-23 hr) after the return of spontaneous circulation. Pulsatility and resistance indexes and cerebral oxygen extraction were calculated. Data are expressed as median (interquartile range 25-75) in α-stat versus pH-stat. No differences were found in temperature, arterial blood pressure, and oxygenation between α-stat and pH-stat. Significant differences were found in minute ventilation (p = 0.006), temperature-corrected PaCO2 (4.4 kPa [4.1-4.6 kPa] vs 5.1 kPa [5.0-5.3 kPa], p = 0.0001), and temperature-uncorrected PaCO2 (p = 0.0001). No differences were found in cerebral blood velocities and pulsatility and resistance indexes in the overall population. Significant differences were found in jugular vein oxygen saturation (83.2% [79.2-87.6%] vs 86.7% [83.2-88.2%], p = 0.009) and cerebral oxygen extraction (15% [11-20%] vs 12% [10-16%], p = 0.01), respectively. In survivors, diastolic blood velocities were 25 cm/s (19-30 cm/s) versus 29 cm/s (23-35 cm/s) (p = 0.004), pulsatility index was 1.10 (0.97-1.18) versus 0.94 (0.89-1.05) (p = 0.027), jugular vein oxygen saturation was 79.2 (71.1-81.8) versus 83.3% (76.6-87.8) (p = 0.033), respectively. However, similar results were not found in nonsurvivors. Conclusions: In therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest at physiological PaCO2, α-stat strategy increases jugular vein blood desaturation and cerebral oxygen extraction compared with pH-stat strategy and decreases cerebral blood flow velocities in survivors. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

Sibon D.,Center Hospitalier Lyon Sud | Cannas G.,Center Hospitalier Lyon Sud | Baracco F.,Center Hospitalier Lyon Sud | Prebet T.,Institute Paoli Calmette | And 10 more authors.
British Journal of Haematology | Year: 2012

Lenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis-stimulating agents (ESA) is not known. We report on 31 consecutive lower-risk non-del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion-dependent (RBC-TD) patients, who became transfusion-independent (RBC-TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion-free after 11 +-31 +months. Median response duration was 24months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN+ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC-TI and in patients treated with LEN after primary resistance to ESA. The main toxicity of LEN was cytopenias. We confirm that, in a patient population of lower risk MDS without del 5q clearly resistant to ESA, LEN is an interesting second line therapeutic option. Its combination with ESAs in this context warrants prospective studies. © 2011 Blackwell Publishing Ltd.

Sudarshan S.,University of Alabama at Birmingham | Karam J.A.,University of Houston | Brugarolas J.,University of Texas Southwestern Medical Center | Thompson R.H.,Mayo Medical School | And 6 more authors.
European Urology | Year: 2013

Context: There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer. Objective: This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer. Evidence acquisition: A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL. Evidence synthesis: Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes. Conclusions: Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers. © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Barennes H.,Agence Nationale de Recherche sur le VIH et Hepatite | Pussard E.,CHU Bicetre
American Journal of Tropical Medicine and Hygiene | Year: 2015

Improving the availability of point-of-care (POC) diagnostics for glucose is crucial in resource-constrained settings (RCS). Both hypo and hyperglycemia have an appreciable frequency in the tropics and have been associated with increased risk of deaths in pediatrics units. However, causes of dysglycemia, including hyperglycemia, are numerous and insufficiently documented in RCS. Effective glycemic control with glucose infusion and/or intensive insulin therapy can improve clinical outcomes in western settings. A non-invasive way for insulin administration is not yet available for hyperglycemia. We documented a few causes and developed simple POC treatment of hypoglycemia in RCS. We showed the efficacy of sublingual sugar in two clinical trials. Dextrose gel has been recently tested for neonate mortality. This represents an interesting alternative that should be compared with sublingual sugar in RCS. New studies had to be done to document dysglycemia mechanism, frequency and morbid-mortality, and safe POC treatment in the tropics. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene.

Transanal excision has emerged as an alternative treatment to radical resection for selected patients with early-stage cancer. Transanal excision can be only attempted as the definitive treatment of well or moderate differentiated rectal tumours of less than 4 cm diameter that are mobile, involve less than half the rectal circumference, lift completely after submucosal injection at endoscopy and are classified usT1N0 by endorectal ultrasound. Poor indicated transanal excision can worsen long-term oncologic results. Transanal excision can be combined with radiotherapy as palliative treatment for more locally advanced rectal tumor in high-risk patients who are unsuitable for major surgery. Finally, in the near future, transanal excision could probably be proposed as curative treatment for patients with no or minimal residual disease after neoadjuvant radiochemotherapy. From a technical point of view, transanal endoscopic microsurgery (TEM) might be considered as the transanal technique of reference since it improves R0 resection and decreases in situ recurrence rate. Transanal excision is a safe technique with near zero mortality, a low morbidity and a decreased risk of long term impairment when compared to rectal resection with total mesorectal excision. © Copyright 2016 JLE.

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