A new prescription model for regional citrate anticoagulation in therapeutic plasma exchanges.

Regional citrate anticoagulation (RCA) is proposed for various extracorporeal purification techniques to overcome the risk of bleeding that might result from systemic anticoagulation. Yet, no individualized treatment protocol has been proposed for therapeutic plasma exchange (TPE) so far. The objective of this study was to assess the determinants of blood citrate concentration needed and to develop an individualized RCA protocol useful for clinical practice. The study population included 14 patients who underwent a total of 47 TPE sessions. Citrate was infused pre-plasmafilter. Post-plasmafilter and systemic plasma ionized calcium concentrations were measured at standardized time intervals. An algorithm was proposed for the supplementation of calcium. During the discovery phase, citrate was infused at a fixed starting rate, and adapted accordingly to obtained post-plasmafilter ionized calcium levels. Using a mathematical approach, an algorithm was thereafter developed for individualized prescriptions of citrate. Pre-treatment values of hematocrit and plasma ionized calcium were the main determinants of the required rate of citrate infusion. These can be integrated into a final equation enabling to individualize the prescription. A prefilter ionized calcium concentration between 0.24 and 0.33 mmol/l prevented coagulation of the extracorporeal circuit. Significant hypocalcemia occurred in 8.5% of treatments. There were no significant acid-base disturbances. We propose a new protocol, which enables for the first time to individualize the prescription of regional citrate anticoagulation during TPE, in an efficient manner. The immediately obtained regional anticoagulation protects against both the risk of coagulation of the membrane and the exposure to an excess of citrate

Erratum to: A new prescription model for regional citrate anticoagulation in therapeutic plasma exchanges.

BACKGROUND: Regional citrate anticoagulation (RCA) is proposed for various extracorporeal purification techniques to overcome the risk of bleeding that might result from systemic anticoagulation. Yet, no individualized treatment protocol has been proposed for therapeutic plasma exchange (TPE) so far. The objective of this study was to assess the determinants of blood citrate concentration needed and to develop an individualized RCA protocol useful for clinical practice. METHODS: The study population included 14 patients who underwent a total of 47 TPE sessions. Citrate was infused pre-plasmafilter. Post-plasmafilter and systemic plasma ionized calcium concentrations were measured at standardized time intervals. An algorithm was proposed for the supplementation of calcium. During the discovery phase, citrate was infused at a fixed starting rate, and adapted accordingly to obtained post-plasmafilter ionized calcium levels. Using a mathematical approach, an algorithm was thereafter developed for individualized prescriptions of citrate. RESULTS: Pre-treatment values of hematocrit and plasma ionized calcium were the main determinants of the required rate of citrate infusion. These can be integrated into a final equation enabling to individualize the prescription. A prefilter ionized calcium concentration between 0.24 and 0.33 mmol/l prevented coagulation of the extracorporeal circuit. Significant hypocalcemia occurred in 8.5% of treatments. There were no significant acid–base disturbances. CONCLUSION: We propose a new protocol, which enables for the first time to individualize the prescription of regional citrate anticoagulation during TPE, in an efficient manner. The immediately obtained regional anticoagulation protects against both the risk of coagulation of the membrane and the exposure to an excess of citrate. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-017-0494-9) contains supplementary material, which is available to authorized users

Validation des procédures de maillage pour l'étude des écoulements sanguins dans une fistule artério-veineuse réelle

Une fistule artério-veineuse permet chez les insuffisants rénaux d'accéder à un débit sanguin suffisant lors des séances d'hémodialyse. Nous avons établi, à partir d'images d'angio-scanner, un protocole d'investigation pour simuler l'écoulement sanguin dans ce vaisseau atypique. Dans cette étude, nous nous focalisons sur la fiabilité des simulations pour des réseaux réels et complexes. Nous avons comparé et optimisé plusieurs types de maillage (hexaédrique, hybride), en tenant compte de différents critères (qualité des mailles, profil de vitesse, cisaillement) sur une géométrie simplifiée. Nous appliquons ensuite le protocole de maillage hybride au cas réel pour relier les paramètres mécaniques obtenus par les simulations aux caractéristiques physiopathologiques issues de l'imagerie

Regulation of Epithelial Cell Morphology and Functions Approaching To More In Vivo-Like by Modifying Polyethylene Glycol on Polysulfone Membranes

Cytocompatibility is critically important in design of biomaterials for application in tissue engineering. However, the currently well-accepted “cytocompatible" biomaterials are those which promote cells to sustain good attachment/spreading. The cells on such materials usually lack the self-assembled cell morphology and high cell functions as in vivo. In our view, biomaterials that can promote the ability of cells to self-assemble and demonstrate cell-specific functions would be cytocompatible. This paper examined the interaction of polyethylene glycol (PEG) modified polysulfone (PSf) membranes with four epithelial cell types (primary liver cells, a liver tumor cell line, and two renal tubular cell lines). Our results show that PSf membranes modified with proper PEG promoted the aggregation of both liver and renal cells, but the liver cells more easily formed aggregates than the renal tubular cells. The culture on PEG-modified PSf membranes also enhanced cell-specific functions. In particular, the cells cultured on F127 membranes with the proper PEG content mimicked the in vivo ultrastructure of liver cells or renal tubules cells and displayed the highest cell functions. Gene expression data for adhesion proteins suggest that the PEG modification impaired cell-membrane interactions and increased cell-cell interactions, thus facilitating cell self-assembly. In conclusion, PEG-modified membrane could be a cytocompatible material which regulates the morphology and functions of epithelial cells in mimicking cell performance in vivo

Integrated Proteomic and Transcriptomic Investigation of the Acetaminophen Toxicity in Liver Microfluidic Biochip

Microfluidic bioartificial organs allow the reproduction of in vivo-like properties such as cell culture in a 3D dynamical micro environment. In this work, we established a method and a protocol for performing a toxicogenomic analysis of HepG2/C3A cultivated in a microfluidic biochip. Transcriptomic and proteomic analyses have shown the induction of the NRF2 pathway and the related drug metabolism pathways when the HepG2/C3A cells were cultivated in the biochip. The induction of those pathways in the biochip enhanced the metabolism of the N-acetyl-p-aminophenol drug (acetaminophen-APAP) when compared to Petri cultures. Thus, we observed 50% growth inhibition of cell proliferation at 1 mM in the biochip, which appeared similar to human plasmatic toxic concentrations reported at 2 mM. The metabolic signature of APAP toxicity in the biochip showed similar biomarkers as those reported in vivo, such as the calcium homeostasis, lipid metabolism and reorganization of the cytoskeleton, at the transcriptome and proteome levels (which was not the case in Petri dishes). These results demonstrate a specific molecular signature for acetaminophen at transcriptomic and proteomic levels closed to situations found in vivo. Interestingly, a common component of the signature of the APAP molecule was identified in Petri and biochip cultures via the perturbations of the DNA replication and cell cycle. These findings provide an important insight into the use of microfluidic biochips as new tools in biomarker research in pharmaceutical drug studies and predictive toxicity investigations

Bioartificial livers (BAL): current technological aspects and future developments

International audienc

Depyrogenation of snake antivenom serum solutions by hollow fiber-based pseudobioaffinity filtration

The affinity filtration technique using histidine as the pseudobiospecific ligand immobilized on poly(ethylene vinyl alcohol) hollow fiber membranes (Histidine-PEVA) was used to remove endotoxin (ET) from snake antivenom serum solutions. Immobilized histidine bound to horse antibodies (F(ab')(2) fragments) and ET. The effects of solution conditions on the efficiency of ET removal and protein recovery were studied. The lowest antibody adsorption capacity was obtained with acetate pH 6.0 and phosphate pH 6.5 buffers. Under both conditions, ET was removed but the highest efficiency was found for the acetate buffer. This buffer was used to determine the optimal combination of ET concentration and Q(F)/Q(i) (filtrate flow rate/inlet flow rate) ratio for achieving a high rate of ET removal without a significant loss of antibodies. Removal of 93% of the ET and recuperation of 95% of the antibodies were obtained at a Q(F)/Q(i) ratio equal to 0.68 and an initial ET concentration of 675 EU/ml, A high clearance rate of 99% was obtained with initial concentrations of 65 and 351 EU/ml for lachesis-bothrops and bothrops antivenom sera, respectively, and an almost complete depyrogenation of bothrops antivenom serum was achieved, since the final ET content in solution was 0.8 EU/mL. (C) 2000 Elsevier Science B.V. All rights reserved.173223524

Mass Transfers in a Fluidized Bed Bioreactor using Alginate Beads for a Future Bioartificial Liver

International audienc