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Le Touquet – Paris-Plage, France

Gheorghiade M.,Northwestern University | Follath F.,University of Zurich | Ponikowski P.,Military Hospital | Barsuk J.H.,Northwestern University | And 22 more authors.
European Journal of Heart Failure | Year: 2010

Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion priorto discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present. © The Author 2010. Source

Jacobs M.,French Institute of Health and Medical Research | Jacobs M.,University of Poitiers | Gregoire N.,French Institute of Health and Medical Research | Gregoire N.,University of Poitiers | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2016

Colistin is increasingly used as a last option for the treatment of severe infections due to Gram-negative bacteria in critically ill patients requiring intermittent hemodialysis (HD) for acute renal failure. Our objective was to characterize the pharmacokinetics (PK) of colistin and its prodrug colistin methanesulfonate (CMS) in this population and to suggest dosing regimen recommendations. Eight intensive care unit (ICU) patients who were under intermittent HD and who were treated by CMS (Colimycine) were included. Blood samples were collected between two consecutive HD sessions. CMS and colistin concentrations were measured by a specific chromatographic assay and were analyzed using a PK population approach (Monolix software). Monte Carlo simulations were conducted to predict the probability of target attainment (PTA). CMS nonrenal clearance was increased in ICU-HD patients. Compared with that of ICU patients included in the same clinical trial but with preserved renal function, colistin exposure was increased by 3-fold in ICU-HD patients. This is probably because a greater fraction of the CMS converted into colistin. To maintain colistin plasma concentrations high enough (>3 mg/liter) for high PTA values (area under the concentration- time curve for the free, unbound fraction of a drug [fAUC]/MIC of>10 and fAUC/MIC of>50 for systemic and lung infections, respectively), at least for MICs lower than 1.5 mg/liter (nonpulmonary infection) or 0.5 mg/liter (pulmonary infection), the dosing regimen of CMS should be 1.5 million international units (MIU) twice daily on non-HD days. HD should be conducted at the end of a dosing interval, and a supplemental dose of 1.5 MIU should be administered after the HD session (i.e., total of 4.5 MIU for HD days). This study has confirmed and complemented previously published data and suggests an a priori clear and easy to follow dosing strategy for CMS in ICU-HD patients. Copyright © 2016, American Society for Microbiology. All Rights Reserved. Source

Schievink W.I.,Cedars Sinai Medical Center | Dodick D.W.,Mayo Medical School | Mokri B.,Mayo Medical School | Silberstein S.,Thomas Jefferson University | And 2 more authors.
Headache | Year: 2011

The clinical and radiographic manifestations of spontaneous intracranial hypotension are highly variable and many patients do not satisfy the 2004 International Classification of Headache Disorders criteria. We developed new diagnostic criteria for spontaneous intracranial hypotension based on cases we have seen reflecting the variable manifestations of the disorder. These criteria provide a basis for change when the classification criteria are next revised. The diagnostic criteria consist of A, orthostatic headache; B, the presence of at least one of the following: low opening pressure (≤60 mm H;bsubesub&O), sustained improvement of symptoms after epidural blood patching, demonstration of an active spinal cerebrospinal fluid leak, cranial magnetic resonance imaging changes of intracranial hypotension (eg, brain sagging or pachymeningeal enhancement); C, no recent history of dural puncture; and D, not attributable to another disorder. © © 2011 American Headache Society. Source

Poulsen C.B.,Aarhus University Hospital | Al-Mashhadi A.L.,Aarhus University Hospital | Von Wachenfeldt K.,Truly Translational | Bentzon J.F.,Aarhus University Hospital | And 15 more authors.
International Journal of Cardiology | Year: 2016

Background Immunization with oxidized LDL (oxLDL) reduces atherosclerosis in rodents. We tested the hypothesis that treatment with a human recombinant monoclonal antibody against oxLDL will reduce the burden or composition of atherosclerotic lesions in hypercholesterolemic minipigs. Methods and results Thirty-eight hypercholesterolemic minipigs with defective LDL receptors were injected with an oxLDL antibody or placebo weekly for 12 weeks. An 18F-fluorodeoxyglucose positron emission tomography (FDG PET) scan (n = 9) was performed before inclusion and after 3 months of treatment. Blood samples were obtained prior to each injection. Following the last injection all animals were sacrificed, and the heart, aorta, and iliac arteries were removed. The left anterior descending coronary artery was sectioned at 5 mm intervals for quantitative and qualitative assessments of atherosclerosis, including immunohistochemical phenotyping of macrophages using a pan-macrophage marker (CD68) and markers for putative pro-atherogenic (cathepsin S) and atheroprotective (CD163) macrophages. Aorta, right coronary artery, and left iliac artery were stained en face with Sudan IV and the amount of atherosclerosis quantified. There was no effect of treatment on plasma lipid profile, vascular FDG-PET signal or the amount of atherosclerosis in any of the examined arteries. However, immunostaining of coronary lesions revealed reduced cathepsin S positivity in the treated group compared with placebo (4.8% versus 8.2% of intima area, p = 0.03) with no difference in CD68 or CD163 positivity. Conclusions In hypercholesterolemic minipigs, treatment with a human recombinant monoclonal antibody against oxLDL reduced cathepsin S in coronary lesions without any effect on the burden of atherosclerosis or aortic FDG-PET signal. © 2016 Published by Elsevier Ireland Ltd. Source

Prada-Villaverde A.,Deaprtment of General Surgery | Esquivel J.,Cancer Treatment Centers of America | Lowy A.M.,University of California at San Diego | Markman M.,Cancer Treatment Centers of America | And 24 more authors.
Journal of Surgical Oncology | Year: 2014

Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery. Methods The American Society of Peritoneal Surface Malignancies (ASPSM) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C (MMC), stratifying them by the Peritoneal Surface Disease Severity Score (PSDSS). Results Median overall survival (OS) of 539 patients with complete cytoreduction was 32.6 months, 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group (P=0.925). However, when stratified by PSDSS, median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin (P=0.012), whereas in PSDSS III/IV patients, median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin (P=0.427). Conclusion These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC, favorable histologies and low burden of disease (PSDSS I/II) undergoing complete cytoreduction. Propsective studies are warranted, which stratify patients by their PSDSS and randomize them to HIPEC with MMC vs. Oxaliplatin. J. Surg. Oncol. 2014 110:779-785. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc. Source

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