The Experts below are selected from a list of 13362 Experts worldwide ranked by ideXlab platform
Beatrice Beckschimmer - One of the best experts on this subject based on the ideXlab platform.
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magnetic separation based Blood Purification a promising new approach for the removal of disease causing compounds
Journal of Nanobiotechnology, 2015Co-Authors: Inge K Herrmann, Wendelin J Stark, Andrea Schlegel, Rolf Graf, Beatrice BeckschimmerAbstract:Recent studies report promising results regarding extracorporeal magnetic separation-based Blood Purification for the rapid and selective removal of disease-causing compounds from whole Blood. High molecular weight compounds, bacteria and cells can be eliminated from Blood within minutes, hence offering novel treatment strategies for the management of intoxications and Blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based Purification while keeping important safety considerations in mind.
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endotoxin removal by magnetic separation based Blood Purification
Advanced Healthcare Materials, 2013Co-Authors: Inge K Herrmann, Martin Urner, Wendelin J Stark, Samuel Graf, Christoph M Schumacher, Birgit Rothzgraggen, Melanie Hasler, Beatrice BeckschimmerAbstract:This work describes a magnetic separation-based approach using polymyxin B-functionalized metal alloy nanomagnets for the rapid elimination of endotoxins from human Blood in vitro and functional assays to evaluate the biological relevance of the Blood Purification process. Playing a central role in gram-negative sepsis, bacteria-derived endotoxins are attractive therapeutic targets. However, both direct endotoxin detection in and removal from protein-rich fluids remains challenging. We present the synthesis and functionalization of ultra-magnetic cobalt/iron alloy nanoparticles and a magnetic separation-based approach using polymyxin B-functionalized nanomagnets to remove endotoxin from human Blood in vitro. Conventional chromogenic Limulus Amebocyte Lysate assays confirm decreased endotoxin activity in purified compared to untreated samples. Functional assays assessing key steps in host defense against bacteria show an attenuated inflammatory mediator expression from human primary endothelial cells in response to purified Blood samples compared to untreated Blood and less chemotactic activity. Exposing Escherichia coli-positive Blood samples to polymyxin B-functionalized nanomagnets even impairs the ability of gram-negative bacteria to form colony forming units, thus making magnetic separation based Blood Purification a promising new approach for future sepsis treatment.
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device for continuous extracorporeal Blood Purification using target specific metal nanomagnets
Nephrology Dialysis Transplantation, 2011Co-Authors: Inge K Herrmann, Riccardo E Bernabei, Martin Urner, Robert N Grass, Beatrice Beckschimmer, Wendelin J StarkAbstract:Background. The present work illustrates how magnetic separation-based Blood Purification using ultra-strong iron nanomagnets can be implemented into an extracorporeal Blood Purification circuit. By this promising technique, today’s Blood Purification may be extended to specifically filter high-molecular compounds without being limited by filter cut-offs or column surface saturation. Methods. Blood spiked with digoxin (small molecule drug) and interleukin-1b (inflammatory protein) was circulated ex vivo through a device composed of approved Blood transfusion lines. Target-specific nanomagnets were continuously injected and subsequently recovered with the aid of a magnetic separator before recirculating the Blood. Results. Magnetic Blood Purification was successfully carried out under flow conditions: already in single-pass experiments, removal efficiencies reached values of 75 and 40% for digoxin and interleukin-1b, respectively. Circulating 0.5 L of digoxin-intoxicated Blood in a closed loop, digoxin concentration was decreased from initially toxic to therapeutic concentrations within 30 min and Purification extents of 90% were achieved after 1.5 h. Conclusions. Magnetic separation can be successfully implemented into an extracorporeal Blood Purification device. Simultaneous and specific filtering of high-molecular compounds may offer promising new therapeutic tools for the future treatment of complex diseases, such as sepsis and autoimmune disorders.
John A Kellum - One of the best experts on this subject based on the ideXlab platform.
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Blood Purification for sepsis
2019Co-Authors: Vincenzo Cantaluppi, Marita Marengo, Zhi Yong Peng, John A Kellum, Rinaldo Bellomo, Claudio RoncoAbstract:Abstract There is currently a clear biologic rationale for Blood Purification used in sepsis. Immunomodulation and organ support play important roles in the application of Blood Purification. Conventional continuous venovenous hemofiltration and hemodialysis have been shown not to be effective in sepsis in the absence of concomitant acute renal failure. Plasma therapies, high-volume hemofiltration, hemadsorption, or combinations of these therapies appear promising. However many questions still remain unanswered. Current technologies still remain inadequate for the removal of middle-molecular-weight substances, and the current practice worldwide is extremely variable. Moreover, there is lack of large-scale randomized clinical trials. Recently, new developing technologies may enhance the clinical results of current RRT strategies, including high-porosity of membranes to improve middle molecular clearance. Finally, multicenter randomized controlled trials are needed to test these promising Blood Purification technologies.
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in vitro comparison of the adsorption of inflammatory mediators by Blood Purification devices
Intensive Care Medicine Experimental, 2018Co-Authors: Benjamin Malard, Corine Lambert, John A KellumAbstract:Septic shock, a leading cause of acute kidney injury, induces release of pro-/anti-inflammatory mediators, leading to increased mortality and poor renal recovery. This is the first in vitro study directly comparing three single-use Blood Purification devices in terms of removing sepsis-associated mediators and endotoxins. In vitro hemoperfusion was performed using oXiris®, CytoSorb®, and Toraymyxin®. Heparinized human plasma from healthy volunteers was pre-incubated with pathologic quantities of inflammatory mediators and filtered in a closed-loop circulation model for 2 h. For each device, the removal of 27 inflammatory mediators was measured over time. Endotoxin removal mediated by oXiris and Toraymyxin was assessed using hemoperfusion over 6 h. Endotoxin (lipopolysaccharide) removal was most rapid with Toraymyxin; mean adsorptive clearance over the first 30 min was ~ 20 ml/min vs ~ 8 ml/min with oXiris (p < 0.05). There was minimal endotoxin removal with CytoSorb (1 ml/min). At 120 min, there was no significant difference between the endotoxin removal rates using oXiris (mean ± standard deviation, 68.0 ± 4.4%) and Toraymyxin (83.4 ± 3.8%); both were significantly higher vs CytoSorb (− 6.3 ± 4.9%; p < 0.05). Total removal with oXiris was 6.9 μg vs 9.7 μg for Toraymyxin, where the total lipopolysaccharide quantity introduced was approximately 15.8 μg. Removal rates of pro-/anti-inflammatory cytokines and other inflammatory mediators were similar between oXiris and CytoSorb and were higher with CytoSorb and oXiris vs Toraymyxin. Granulocyte colony-stimulating factor was only effectively adsorbed by CytoSorb (99.4%). Differences were detected between the adsorption mechanism of the devices; binding to oXiris was mainly ionic, while CytoSorb was hydrophobic. No specific protein adsorption was found qualitatively with Toraymyxin. Adsorption rate kinetics varied for individual inflammatory mediators using the three Blood Purification devices. Mechanisms of adsorption differed between the devices. oXiris was the only device tested that showed both endotoxin and cytokine removal. oXiris showed similar endotoxin adsorption to Toraymyxin and similar adsorption to CytoSorb for the removal of other inflammatory mediators. Differences in device removal capacities could enable treatment to be more tailored to patients.
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Nomenclature for renal replacement therapy and Blood Purification techniques in critically ill patients: practical applications
Critical Care, 2016Co-Authors: Gianluca Villa, Patrick M Honore, John A Kellum, Rinaldo Bellomo, Mauro Neri, Jorge Cerdá, A. Raffaele De Gaudio, Silvia De Rosa, Francesco Garzotto, Anna LorenzinAbstract:This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and Blood Purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal Blood Purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and Blood Purification in sepsis.
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Blood Purification and mortality in sepsis a meta analysis of randomized trials
Critical Care Medicine, 2013Co-Authors: Feihu Zhou, Zhi Yong Peng, Raghavan Murugan, John A KellumAbstract:Objectives Although Blood Purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various Blood Purification techniques and all-cause mortality in humans with sepsis.
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high volume hemofiltration in the intensive care unit a Blood Purification therapy
Anesthesiology, 2012Co-Authors: Thomas Rimmele, John A KellumAbstract:High-volume hemofiltration is an extracorporeal therapy that has been available in the intensive care unit for more than 10 yr. Recent improvements in technology have made its clinical application easier and safer. However, the definition, indications, and management of this technique are still unclear, and considerable controversy and confusion remain. The aim of this review is to analyze the available data while taking into account the distinction between two very different clinical situations: acute kidney injury requiring renal support, and severe inflammatory states where Blood Purification has been suggested as an adjuvant therapy. For patients with acute kidney injury requiring renal replacement therapy, the two largest multicenter studies performed to date established that high ultrafiltration flow rates are not necessary. Conversely, much experimental and some clinical evidence suggest that high-volume hemofiltration can be beneficial for the subset of critically ill patients with severe inflammatory states such as septic shock.
Inge K Herrmann - One of the best experts on this subject based on the ideXlab platform.
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magnetic separation based Blood Purification a promising new approach for the removal of disease causing compounds
Journal of Nanobiotechnology, 2015Co-Authors: Inge K Herrmann, Wendelin J Stark, Andrea Schlegel, Rolf Graf, Beatrice BeckschimmerAbstract:Recent studies report promising results regarding extracorporeal magnetic separation-based Blood Purification for the rapid and selective removal of disease-causing compounds from whole Blood. High molecular weight compounds, bacteria and cells can be eliminated from Blood within minutes, hence offering novel treatment strategies for the management of intoxications and Blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based Purification while keeping important safety considerations in mind.
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endotoxin removal by magnetic separation based Blood Purification
Advanced Healthcare Materials, 2013Co-Authors: Inge K Herrmann, Martin Urner, Wendelin J Stark, Samuel Graf, Christoph M Schumacher, Birgit Rothzgraggen, Melanie Hasler, Beatrice BeckschimmerAbstract:This work describes a magnetic separation-based approach using polymyxin B-functionalized metal alloy nanomagnets for the rapid elimination of endotoxins from human Blood in vitro and functional assays to evaluate the biological relevance of the Blood Purification process. Playing a central role in gram-negative sepsis, bacteria-derived endotoxins are attractive therapeutic targets. However, both direct endotoxin detection in and removal from protein-rich fluids remains challenging. We present the synthesis and functionalization of ultra-magnetic cobalt/iron alloy nanoparticles and a magnetic separation-based approach using polymyxin B-functionalized nanomagnets to remove endotoxin from human Blood in vitro. Conventional chromogenic Limulus Amebocyte Lysate assays confirm decreased endotoxin activity in purified compared to untreated samples. Functional assays assessing key steps in host defense against bacteria show an attenuated inflammatory mediator expression from human primary endothelial cells in response to purified Blood samples compared to untreated Blood and less chemotactic activity. Exposing Escherichia coli-positive Blood samples to polymyxin B-functionalized nanomagnets even impairs the ability of gram-negative bacteria to form colony forming units, thus making magnetic separation based Blood Purification a promising new approach for future sepsis treatment.
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device for continuous extracorporeal Blood Purification using target specific metal nanomagnets
Nephrology Dialysis Transplantation, 2011Co-Authors: Inge K Herrmann, Riccardo E Bernabei, Martin Urner, Robert N Grass, Beatrice Beckschimmer, Wendelin J StarkAbstract:Background. The present work illustrates how magnetic separation-based Blood Purification using ultra-strong iron nanomagnets can be implemented into an extracorporeal Blood Purification circuit. By this promising technique, today’s Blood Purification may be extended to specifically filter high-molecular compounds without being limited by filter cut-offs or column surface saturation. Methods. Blood spiked with digoxin (small molecule drug) and interleukin-1b (inflammatory protein) was circulated ex vivo through a device composed of approved Blood transfusion lines. Target-specific nanomagnets were continuously injected and subsequently recovered with the aid of a magnetic separator before recirculating the Blood. Results. Magnetic Blood Purification was successfully carried out under flow conditions: already in single-pass experiments, removal efficiencies reached values of 75 and 40% for digoxin and interleukin-1b, respectively. Circulating 0.5 L of digoxin-intoxicated Blood in a closed loop, digoxin concentration was decreased from initially toxic to therapeutic concentrations within 30 min and Purification extents of 90% were achieved after 1.5 h. Conclusions. Magnetic separation can be successfully implemented into an extracorporeal Blood Purification device. Simultaneous and specific filtering of high-molecular compounds may offer promising new therapeutic tools for the future treatment of complex diseases, such as sepsis and autoimmune disorders.
Wendelin J Stark - One of the best experts on this subject based on the ideXlab platform.
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magnetic separation based Blood Purification a promising new approach for the removal of disease causing compounds
Journal of Nanobiotechnology, 2015Co-Authors: Inge K Herrmann, Wendelin J Stark, Andrea Schlegel, Rolf Graf, Beatrice BeckschimmerAbstract:Recent studies report promising results regarding extracorporeal magnetic separation-based Blood Purification for the rapid and selective removal of disease-causing compounds from whole Blood. High molecular weight compounds, bacteria and cells can be eliminated from Blood within minutes, hence offering novel treatment strategies for the management of intoxications and Blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based Purification while keeping important safety considerations in mind.
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endotoxin removal by magnetic separation based Blood Purification
Advanced Healthcare Materials, 2013Co-Authors: Inge K Herrmann, Martin Urner, Wendelin J Stark, Samuel Graf, Christoph M Schumacher, Birgit Rothzgraggen, Melanie Hasler, Beatrice BeckschimmerAbstract:This work describes a magnetic separation-based approach using polymyxin B-functionalized metal alloy nanomagnets for the rapid elimination of endotoxins from human Blood in vitro and functional assays to evaluate the biological relevance of the Blood Purification process. Playing a central role in gram-negative sepsis, bacteria-derived endotoxins are attractive therapeutic targets. However, both direct endotoxin detection in and removal from protein-rich fluids remains challenging. We present the synthesis and functionalization of ultra-magnetic cobalt/iron alloy nanoparticles and a magnetic separation-based approach using polymyxin B-functionalized nanomagnets to remove endotoxin from human Blood in vitro. Conventional chromogenic Limulus Amebocyte Lysate assays confirm decreased endotoxin activity in purified compared to untreated samples. Functional assays assessing key steps in host defense against bacteria show an attenuated inflammatory mediator expression from human primary endothelial cells in response to purified Blood samples compared to untreated Blood and less chemotactic activity. Exposing Escherichia coli-positive Blood samples to polymyxin B-functionalized nanomagnets even impairs the ability of gram-negative bacteria to form colony forming units, thus making magnetic separation based Blood Purification a promising new approach for future sepsis treatment.
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device for continuous extracorporeal Blood Purification using target specific metal nanomagnets
Nephrology Dialysis Transplantation, 2011Co-Authors: Inge K Herrmann, Riccardo E Bernabei, Martin Urner, Robert N Grass, Beatrice Beckschimmer, Wendelin J StarkAbstract:Background. The present work illustrates how magnetic separation-based Blood Purification using ultra-strong iron nanomagnets can be implemented into an extracorporeal Blood Purification circuit. By this promising technique, today’s Blood Purification may be extended to specifically filter high-molecular compounds without being limited by filter cut-offs or column surface saturation. Methods. Blood spiked with digoxin (small molecule drug) and interleukin-1b (inflammatory protein) was circulated ex vivo through a device composed of approved Blood transfusion lines. Target-specific nanomagnets were continuously injected and subsequently recovered with the aid of a magnetic separator before recirculating the Blood. Results. Magnetic Blood Purification was successfully carried out under flow conditions: already in single-pass experiments, removal efficiencies reached values of 75 and 40% for digoxin and interleukin-1b, respectively. Circulating 0.5 L of digoxin-intoxicated Blood in a closed loop, digoxin concentration was decreased from initially toxic to therapeutic concentrations within 30 min and Purification extents of 90% were achieved after 1.5 h. Conclusions. Magnetic separation can be successfully implemented into an extracorporeal Blood Purification device. Simultaneous and specific filtering of high-molecular compounds may offer promising new therapeutic tools for the future treatment of complex diseases, such as sepsis and autoimmune disorders.
Thomas Rimmele - One of the best experts on this subject based on the ideXlab platform.
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Blood Purification Techniques for Sepsis and Septic AKI.
Seminars in nephrology, 2019Co-Authors: Thibaut Girardot, Antoine G. Schneider, Thomas RimmeleAbstract:Sepsis is the primary cause of acute kidney injury in critically ill patients. During the past decades, several extracorporeal Blood Purification techniques have been developed for sepsis and sepsis-induced acute kidney injury management. These therapies could act on both the infectious agent itself and the host immune response. In this article, we review the available literature discussing the different extracorporeal Blood Purification techniques, including high-volume hemofiltration, cascade hemofiltration, hemoperfusion, coupled plasma filtration adsorption, plasma exchange, and specific optimized renal replacement therapy membranes.
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Extracorporeal Blood Purification Therapies for Sepsis
S. Karger AG, 2018Co-Authors: Céline Monard, Thomas Rimmele, Claudio RoncoAbstract:Extracorporeal Blood Purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, which is known to induce organ dysfunctions. Different therapies have been developed to address certain steps of the immune dysregulation. Most of the available Blood Purification devices focus on a single target, such as the endotoxin that triggers the immune cascade, or the cytokine storm that causes organ damages. However, the highly adsorptive membrane named oXiris® is a unique 4-in-1 device that combines cytokine and endotoxin removal properties, renal replacement function, and antithrombogenic properties. More recently, promising treatments that focus on the pathogen itself or the immune cells have been developed and are currently under investigation. In this review, we aim to summarize, according to their target, the different extracorporeal Blood Purification techniques that are already available for use. We will also briefly introduce the most recent techniques that are still under development. Because of its unique ability to remove both endotoxins and cytokines, we will particularly discuss the highly adsorptive preheparinized oXiris® membrane. We will present its properties, advantages, pitfalls, as well as therapeutic perspectives based on experimental and clinical data. Video Journal Club “Cappuccino with Claudio Ronco” at https://www.karger.com/Journal/ArticleNews/223997?sponsor=52
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leukocyte capture and modulation of cell mediated immunity during human sepsis an ex vivo study
Critical Care, 2013Co-Authors: Thomas Rimmele, Zhi Yong Peng, Kai Singbartl, Jeffery V Bishop, Ata Murat Kaynar, Joseph N Mclaughlin, Morgan V Fedorchak, Anan Chuasuwan, Daniel R Frederick, Melinda CarterAbstract:Introduction: Promising preclinical results have been obtained with Blood Purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole Blood taken from patients with sepsis. Methods: We performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal Blood Purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function. Results: Hemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cellmediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function. Conclusions: Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better Blood Purification therapies.
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high volume hemofiltration in the intensive care unit a Blood Purification therapy
Anesthesiology, 2012Co-Authors: Thomas Rimmele, John A KellumAbstract:High-volume hemofiltration is an extracorporeal therapy that has been available in the intensive care unit for more than 10 yr. Recent improvements in technology have made its clinical application easier and safer. However, the definition, indications, and management of this technique are still unclear, and considerable controversy and confusion remain. The aim of this review is to analyze the available data while taking into account the distinction between two very different clinical situations: acute kidney injury requiring renal support, and severe inflammatory states where Blood Purification has been suggested as an adjuvant therapy. For patients with acute kidney injury requiring renal replacement therapy, the two largest multicenter studies performed to date established that high ultrafiltration flow rates are not necessary. Conversely, much experimental and some clinical evidence suggest that high-volume hemofiltration can be beneficial for the subset of critically ill patients with severe inflammatory states such as septic shock.
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acute removal of common sepsis mediators does not explain the effects of extracorporeal Blood Purification in experimental sepsis
Kidney International, 2012Co-Authors: Zhi Yong Peng, Thomas Rimmele, Jeffery V Bishop, Feihu Zhou, Hongzhi Wang, Melinda Carter, Morgan V Dileo, Xiaoyan Wen, Kai SingbartlAbstract:The effect of extracorporeal Blood Purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal Blood Purification that did not result in acute changes in a panel of common cytokines associated with inflammation (TNF-α, IL-1β, IL-6, and IL-10). Pre- and immediate post-treatment levels of these cytokines were unchanged compared to the sham therapy of extracorporeal circulation without Blood purifying sorbent. The overall survival to 7 days, however, was significantly better in animals that received extracorporeal Blood Purification compared to those with a sham procedure. This panel of common plasma cytokines along with alanine aminotransferase and creatinine was significantly lower 72h following extracorporeal Blood Purification compared to sham-treated rats. Thus, the effects of this procedure on organ function and survival do not appear to be due solely to immediate changes in the usual measured circulating cytokines. These results may have important implications for the design and conduct of future trials in sepsis including defining alternative targets for extracorporeal Blood Purification and other therapies.