bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Therapies in Thrombotic Syndromes
Authors: Nguyen T.C. , Stegmayr B.G. , Busund R. , Bunchman T.E. , Carcillo J.A.
Published: January 2018

Background

Plasma therapies are being applied to thombotic syndromes, but there are limited controlled studies.

Objective

To review the evidence and the current practices for plasma therapies in thrombotic syndromes.

Methods

Expert-enhanced evidence-based analysis. Evidence obtained as of Dec 31, 2002 using Pub Med electronic reference library and expert-obtained library for a total of > 3,000 references obtained using the terms plasma therapy or plasma exchange or plasmapheresis or plasmafiltration or sorbents each combined with the words thrombotic syndrome or sepsis or septic shock. The authors screened the abstracts, reviewed the agreed set of papers, and compiled the recommendations.

Results

Plasma therapies, which alter the plasma components in patients, have been applied in thrombotic syndromes worldwide. In these patients, there is a biologic plausibility for plasma therapies since they have molecules that are prothrombotic and/or antifibrinolytic which would put them at risk for microvascular thrombosis and end-organ damage. There are respectively one randomized controlled trial (RCT) in primary thrombotic syndrome, and secondary thrombotic syndrome, which showed an improvement in mortality in applying plasma therapies (plasma exchange by centrifugation). However, there are numerous non-randomized and case series. Plasma exchange is accepted as the standard therapy for primary thrombotic syndrome as in thrombotic thrombocytopenic purpura (TTP). However, no consensus has been reached for plasma exchange in secondary thrombotic syndromes such as in sepsis, hemolytic uremic syndrome (HUS), thrombocytopenia associated multiple organ failure, TTP/HUS, s/p bone marrow or solid organ transplant, HELLP syndrome, immunologic disorders, drug exposure, or pancreatitis.

Conclusions

As we understand more about the pathophysiology of thrombotic syndromes, specific plasma therapies can be applied for the specific need of a particular patient population. There are sufficient preliminary data to recommend a definitive RCT to evaluate the efficacy of the different types of plasma therapies in secondary thrombotic syndromes.
Extracorporeal Ultrafiltration for Acute Exacerbations of Chronic Heart Failure: Report from the Acute Dialysis Quality Initiative
Authors: Clark W.R. , Paganini E. , Weinstein D , Bartlett R. , Sheinfeld G. , Ronco C.
Published: January 2018

This report from a work group affiliated with the Acute Dialysis Quality Initiative is a critical assessment of the use of extracorporeal ultrafiltration (UF) in the management of acutely decompensated heart failure (HF). In addition to assessing UF in this setting, the report also provides background information on HF, including classification, pathophysiology, and the importance of concomitant renal failure. A summary of important results from clinical trials in this area is provided, along with a discussion of technical considerations. Finally, specific recommendations for future clinical evaluations are given.
Characterization of Platelet Adhesion under Flow using Microscopic Image Sequence Analysis
Authors: Machin M. , Santomaso A. , Cozzi M.R. , Battiston M. , Mazzucato M. , De Marco L. , Canu P.
Published: January 2018

A method for quantitative analysis of platelet deposition under flow is discussed here. The model system is based upon perfusion of blood platelets over an adhesive substrate immobilized on a glass coverslip acting as the lower surface of a rectangular flow chamber. The perfusion apparatus is mounted onto an inverted microscope equipped with epifluorescent illumination and intensified CCD video camera. Characterization is based on information obtained from a specific image analysis method applied to continuous sequences of microscopical images. Platelet recognition across the sequence of images is based on a time-dependent, bidimensional, gaussian-like pdf. Once a platelet is located, the variation of its position and shape as a function of time (i.e., the platelet history) can be determined. Analyzing the history we can establish if the platelet is moving on the surface, the frequency of this movement and the distance traveled before its resumes the velocity of a non-interacting cell. Therefore, we can determine how long the adhesion would last which is correlated to the resistance of the platelet-substrate bond. This algorithm enables the dynamic quantification of trajectories, as well as residence times, arrest and release frequencies for a high numbers of platelets at the same time. Statistically significant conclusions on platelet-surface interactions can then be obtained. An image analysis tool of this kind can dramatically help the investigation and characterization of the thrombogenic properties of artificial surfaces such as those used in artificial organs and biomedical devices.
New Generation Ceramic Membranes have the Potential of Removing Endotoxins from Dialysis Water and Dialysate
Authors: Czermak P. , Ebrahimi M. , Catapano G.
Published: January 2018

Poor water properties, use of concentrated bicarbonate, and biofilm growth in pipes and storage tanks often cause dialysis water and dialysate contamination with bacteria and endotoxins. High-flux dialysis with bicarbonate may favor endotoxin transfer from the dialysate into the blood exposing patients to serious short - and long-term side effects. Ultrafiltration across hydrophobic synthetic membranes effectively removes endotoxins from dialysis water by combined filtration and adsorption. However, repeated sterilization worsens the membrane separation properties, and limits their use. Ceramic membranes are generally more resistant to harsh operating conditions than polymeric membranes, and may represent an alternative for endotoxin removal. Previously, we proved that the ceramic membranes commercially available at that time were not retentive enough to ensure production of endotoxin-free dialysis water.

In this paper, we investigated the endotoxin removal capacity of new generation commercial ceramic membranes with nominal molecular weight cut-off down to 1,000. In dead-end filtration, all investigated membranes produced water meeting, the European standards, or close to, when challenged with low endotoxin concentrations, but only one membrane type succeeded at high endotoxin concentrations. In cross-flow filtration, none produced water meeting the European standard. Moreover, sterilization and rinsing procedures altered the separation properties of two out of three membrane types.
New Methods for Hemoglobin Detection in a Microparticle-Plasma Suspension
Authors: Brandl M. , Hartmann J. , Falkenhagen D.
Published: January 2018

In the extracorporeal adsorption system, MDS (Microspheres based Detoxification System), micro-adsorbent particles measuring 1–25 micrometers circulate in a filtrate circuit for highly specific blood purification/adsorption. The MDS circuit containing the adsorbent microparticles is linked to the patient's blood line by a hollow fiber plasma filter. When the transmembrane pressure or the shear forces due to the red blood cells in the hollow fiber filter are too high, they can be damaged and hemoglobin will be released.

In order to detect free hemoglobin (fHb) by optical means, we have designed a new flow-dynamic filter system, placed in the microadsorbent circuit for continuous separation of microparticles from the filtrate. In the flow dynamic filter, we use a high velocity liquid vortex to remove sedimentation and particle plugs on the filter membrane. In our investigations, 3 and 8 μm cellulose nitrate filter membranes for particle separation are used. The obtained particle free bypass filtrate flow rates are typically 0.5 and 0.8 ml/min respectively. The typical sensitivity for fHb detection by the applied noninvasive optical method is 0.15 g/dL.

Medical safety regulations require a fail-safe mechanism for fHb detection which monitors the bypass filtrate flow in the flowdynamic filter and shuts down the system in case of membrane occlusion. The bypass filtrate flow is monitored by periodically occluding and releasing the bypass line by means of a clamp. The resulting back pressure profile gives information about the actual filtration rate. This safety principle was proven by statistical analysis and shows its clear functionality. (Int J Artif Organs 2006; 29: 1092–100)
CFD Simulation of a Novel Bileaflet Mechanical Heart Valve Prosthesis - An Estimation of the Venturi Passage Formed by the Leaflets
Authors: Yokoyama Y. , Medart D. , Hormes M. , Schmitz C. , Hamilton K. , Kwant P.B. , Takatani S. , Schmitz-Rode T. , Steinseifer U.
Published: January 2018

The aim of this study was to validate the flow characteristics of the novel Helmholtz-Institute Aachen Bileaflet (HIA-BL) heart valve prosthesis. The curved leaflets of the HIA-BL valve form a Venturi passage between the leaflets at peak systole. By narrowing the cross section the flow accelerates and the static pressure at the central passage decreases according to the Venturi effect. The low-pressure zone between the leaflets is expected to stabilize the leaflets in fully open position at peak systole.

To investigate the Venturi passage, the flow fields of two valve geometries were investigated by CFD (Computational Fluid Dynamics): one geometry exhibits curved leaflets resulting in a Venturi passage; the other geometry features straight leaflets. The flow profiles, pressure distribution and resulting torque of both passages were compared and investigated.

Although flow profiles downstream of both valves were similar, the flow passages between the leaflets were different for the investigated leaflet geometries. The straight leaflet passage showed a large boundary layer separation zone near the leaflets and the lowest pressure at the leading edge of the leaflet. The Venturi passage showed a reduction of the boundary layer separation zones and the lowest pressure between the leaflets could be found in the narrowest flow cross section of the Venturi passage. Additionally, the resulting torque showed that the Venturi passage produced an opening momentum. The results demonstrate that the Venturi passage stabilizes the leaflets in open position at peak systole.
Promotion of Angiogenesis in Tissue Engineering: Developing Multicellular Matrices with Multiple Capacities
Authors: Suuronen E.J. , Muzakare L. , Doillon C.J. , Kapila V. , Li F. , Ruel M. , Griffith M.
Published: January 2018

One of the aims of tissue engineering is to be able to develop multi-tissue organs in the future. This requires the optimization of conditions for the differentiation of multiple cell types and maintenance of the differentiated phenotype within complex engineered tissues. The goal of this study was to develop prototype tissue engineered matrices to support the simultaneous growth of different cell types with a particular focus on the angiogenic process. We examined two different matrix compositions for the promotion of blood vessel and tube formation. A fibrin-based matrix with the addition of a combination of growth factors supported vascular growth and the invasion of inflammatory cells. Using this fibrin matrix, in combination with a collagen-based hydrogel, a simple in vitro model of the cornea with adjacent sclera was developed that was complete with innervation and vascular structures. In addition, we showed that collagen-based matrices were effective in delivering mononuclear endothelial progenitor cells to ischemic tissue in vivo, and allowing these cells to incorporate into vascular structures. It is anticipated that with further development, these matrices have potential for use as delivery matrices for cell transplantation and for in vitro study purposes of multiple cell types.
A Pilot Study of High-Adsorption Hemofiltration in Human Septic Shock
Authors: Haase M. , Silvester W. , Uchino S. , Goldsmith D. , Davenport P. , Tipping P. , Boyce N. , Bellomo R.
Published: January 2018

Background

To compare the hemodynamic and biological effects of high-adsorption continuous veno-venous hemofiltration (CVVH) with standard CVVH in septic shock. Methods: In a randomized cross-over clinical trial twelve patients with septic shock and multiple organ failure were enrolled at a tertiary intensive care unit. Patients were allocated to either 9 hours of high-adsorption hemofiltration (CVVH with 3 hourly filter change using AN69 hemofilters - 3F-CVVH) or 9 hours of standard hemofiltration (CVVH without filter change - 1F-CVVH).

Results

Changes in hemodynamic variables, dose of noradrenaline required to maintain a mean arterial pressure greater than 75 mmHg and plasma concentrations of cytokines (IL-6, IL-8, IL-10 and IL-18) were measured. A 9-hour period of 3F-CVVH was associated with greater reduction in noradrenaline dose than a similar period of 1F-CVVH (median reduction: 16 vs. 3.5 μg/min, p=0.036; median percentage reduction: 48.1% vs. 17.5%, p=0.028). Unlike 1F-CVVH, 3F-CVVH was associated with a reduction in the plasma concentration of IL-6, IL-10 and IL-18 at 9 hours and a significant decrease 30 minutes after additional filter changes (IL-6: p<0.01, p<0.01; IL-10: p=0.03, p=0.016 and IL-18: p=0.016, p<0.01, respectively). Both, 3F-CVVH and 1F-CVVH were associated with decreased plasma concentrations of IL-8 at 9 hours (p<0.01, p<0.01, respectively). In a confirmatory ex-vivo experiment IL-6 concentrations substantially decreased during 3F-CVVH (at baseline 511pg/mL and at end: 21pg/mL) whereas IL-6 concentrations increased in control blood (at baseline 511pg/mL and at end: 932pg/mL).

Conclusions

High-adsorption CVVH appears more effective than standard CVVH in decreasing noradrenaline requirements and plasma concentrations of cytokines in septic shock patients.
Sandblasted Titanium Osteointegration in Young, Aged and Ovariectomized Sheep
Authors: Borsari V. , Fini M. , Giavaresi G. , Rimondini L. , Chiesa R. , Chiusoli L. , Giardino R.
Published: January 2018

To evaluate how aging and estrogen deficiency influence the success rate of Sandblasted Titanium (Ti/SA) implants, the osteointegration of Ti/SA rods was studied in the cortical and trabecular bone of 5 young, 5 aged and 5 ovariectomized (OVX) sheep.

The characterization of the host bone by transiliac biopsies of the iliac crest showed a progressive rarefaction of trabecular bone in aged and OVX animals when compared to young ones. A significant reduction, both in cortical and trabecular bone, of the osteointegration rate of Ti/SA rods in the presence of estrogen deficiency compared to young animals was observed, while only a minor reduction was observed in aged animals. These results were confirmed by the pushout test in cortical bone.

Bone quality affected the biological response of bone to Ti/SA implants in both trabecular and cortical bone; consequently, strategies to maximize the bone osteogenic properties of osteoporotic patients should be adopted.
Continuous Veno-Venous Hemofiltration in the Treatment of Acute Severe Hyponatremia: A Report of 11 Cases
Authors: Ji D.X. , Gong D.H. , Xu B. , Tao J. , Ren B. , Zhang Y.D. , Liu Y. , Hu W.X. , Wang M.M. , Li L.S.
Published: January 2018

Objectives

To evaluate the treatment effect of continuous veno-venous hemofiltration (CVVH) in patients with acute severe hyponatremia.

Methods

Eleven patients with severe acute hyponatremia, including 6 males and 5 females, aged 25–61 years (mean age 48.36), were treated with CVVH. Hyponatremia occurred 38–48 hours prior to the initiation of CVVH.

Results

All patients tolerated CVVH well, with an average treatment duration of 57.19 (45.6–86) hours. During CVVH, the serum sodium concentration increased significantly from 100.9±3.99 mmol/L at initiation of CVVH to 140.3±1.6 mmol/L after 48 hours of treatment (P<0.01). The serum osmolarity increased concurrently, from 216.7±7.4 mOsm/kgH2O to 295.0±4.2 mOsm/kgH2O (P<0.01). The Glasgow scores and APACHE II scores in these patients improved significantly during treatment.

Conclusions

CVVH is a safe and effective option for the treatment of patients with severe acute hyponatremia due to its slow and continuous nature.
In Vitro Comparison of Two Bioartificial Liver Support Systems: MELS CellModule and AMC-BAL
Authors: Poyck P.P.C. , Pless G. , Hoekstra R. , Roth S. , Van Wijk A.C.W.A. , Schwartländer R. , Van Gulik T.M. , Sauer I.M. , Chamuleau R.A.F.M.
Published: January 2018

Clinically applied bioartificial liver (BAL) support systems are difficult to compare with regard to overall hepatocyte-specific function and clinical outcome. We compared two clinically applied BAL systems, the Modular Extracorporeal Liver Support (MELS) CellModule and the AMC-bioartificial liver (AMC-BAL) in an in vitro set-up. Both BAL systems were loaded with 10 billion freshly isolated porcine hepatocytes, cultured for 7 days and tested on days 1, 2, 4 and 7. Average decrease in hepatocyte-specific functions over 7 days was 9.7%. Three parameters differed between both bioreactors: lidocaine elimination at days 1 and 2 was significantly higher in the AMC-BAL, ammonia elimination showed a significantly higher trend for the AMC-BAL over 7 days and LDH release was significantly lower at day 7 for the MELS CellModule. In conclusion, this first in vitro comparison of two clinically applied BAL systems shows comparable functional capacity over a period of 7 days.
Improving Outcomes from Acute Kidney Injury (AKI): Report on an Initiative
Authors: Ronco C. , Levin A. , Warnock D.G. , Mehta R.L. , Kellum J.A. , Shah S. , Molitoris B.A. ,   The Akin Working Group, Bagga Arvind , Bakkaloglu Aysin , Bonventre Joseph V , Burdmann Emmanuel A , Chen Yipu , Devarajan Prasad , D'Intini Vince , Dobb Geoff , Durbin Charles G , Eckardt Kai-Uwe , Guerin Claude , Herget-Rosenthal Stefan , Hoste Eric , Joannidis Michael , Kellum John A , Kirpalani Ashok , Lassnigg Andrea , Le Gall Jean-Roger , Levin Adeera , Lombardi Raul , Macias William , Manthous Constantine , Mehta Ravindra L , Molitoris Bruce A , Ronco Claudio , Schetz Miet , Schortgen Frederique , Shah Sudhir V , Tan Patrick SK , Wang Haiyan , Warnock David G , Webb Steve
Published: January 2018

Acute Kidney Injury (AKI) is a complex disorder for which currently there is no accepted definition. We describe an initiative to develop uniform standards for defining and classifying AKI and establish a forum for multidisciplinary interaction to improve care for patients with, or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a 2-day conference in Amsterdam in September 2005 to draft consensus recommendations for diagnosing and staging AKI. This report describes the proposed diagnostic and staging criteria for AKI and the formation of a multidisciplinary collaborative network (Acute Kidney Injury Network (AKIN) focused on improving outcomes from AKI.
Changing Emphasis in Modern Hemodialysis Therapies: Cost-Effectiveness of Delivering Higher Doses of Dialysis
Authors: Kult J. , Stapf E.
Published: January 2018

This paper describes the clinical experience of a therapy concept involving advanced functions of a new dialysis machine system (5008 Therapy System, Fresenius Medical Care, Bad Homburg Germany) that is able to provide adequate Kt/V for patients, while consuming lower amounts of dialysate, water and energy during the treatment. The novel “AutoFlow” function of this therapy system adjusts automatically the dialysate flow rate according to the effective blood flow rate of the individual patient without compromising the dose of dialysis the patient receives. The new therapy system of Fresenius Medical Care enables a more widespread application of advanced convective treatment modalities in a more affordable manner. (Int J Artif Organs 2007; 30: 577–82)
Endotoxin Removal from Albumin and Saline Solutions
Authors: Bell C.-M. , Guo K. , Wendel H. P.
Published: January 2018

Microporous membranes have been developed which can remove endotoxins selectively from electrolyte and albumin solutions by regioselective adsorption in the membrane matrix and outside surface of the membrane. The membranes were prepared in the form of hollow fibre membranes in a continuous process. By varying the membrane preparation parameters, different pore sizes and adsorption capacities could be realized, thus broadening applications for biological purification. Dynamic adsorption capacities for endotoxin from albumin and saline solution were determined and were found to be in the range of 0.2 and 0.1 μg endotoxin/g membrane, respectively, suggesting different adsorption mechanisms. (Int J Artif Organs 2007; 30: 589–93)
Differentiation of a Fibrin Gel Encapsulated Chondrogenic Cell Line
Authors: Dare E. V. , Vascotto S. G. , Carlsson D. J. , Hincke M. T. , Griffith M.
Published: January 2018

Hyaline cartilage has very limited regenerative capacity following damage. Therefore engineered tissue substitutes have been the focus of much research. Our objective was to develop a fibrin-based scaffold as a cell delivery vehicle and template for hyaline cartilage regeneration, and compare its cellular properties against monolayer and pellet culture for chondrogenic cells. The chondrogenic precursor cell line, RCJ 3.1C5.18 (C5.18), was chosen as a test system for evaluating the effect of various culture conditions, including cell encapsulation, on articular chondrogenic cell differentiation. The C5.18 cells in monolayer showed elevated expression of collagen II, an articular chondrogenic marker, but also markers for fibrocartilage differentiation (collagen I and versican) when cultured with chondrogenic medium as compared to basic maintenance medium. Pellets of C5.18 cells cultured in chondrogenic medium were histologically more organized in structure than pellets cultured in control maintenance medium. The chondrogenic medium cultured pellets also secreted an extracellular matrix that was comprised of type II with very little type I collagen, indicating a trend towards a more hyaline-like cartilage. Moreover, when cultured in chondrogenic medium, fibrin-encapsulated C5.18 cells elaborated an extracellular matrix containing type II collagen, as well as aggrecan, which are both components of hyaline cartilage. This indicated a more articular-like chondrogenic differentiation for fibrin encapsulated C5.18 cells. The results of these experiments provide evidence that the C5.18 cell line can be used as a tool to evaluate potential scaffolds for articular cartilage tissue engineering. (Int J Artif Organs 2007; 30: 619–27)
Biomaterial Strategies to Reduce Implant-Associated Infections
Authors: Qiu Y. , Zhang N. , An Y. H. , Wen X.
Published: January 2018

Although the prophylaxis in controlling sterility within the operating room environment has been greatly improved, implant-associated infection is still one of the most serious complications in implant surgeries due to the existence of immune depression in the peri-implant area. The antibacterial ability of materials themselves logically becomes an important factor in preventing implant-associated infections. With the understanding of the pathogenesis of implant-associated infections, many approaches have been developed through providing an anti-adhesive surface, delivering antibacterial agents to disrupt cell-cell communication and preventing bacteria aggregation or biofilm formation, or killing bacteria directly (lysing the cell membrane). In this article, we review the current strategies in improving the antibacterial ability of materials to prevent implant infection and further present promising tactics in materials design and applications.
Clinical Effects of Direct Hemoperfusion Using a Polymyxin-B Immobilized Column in Solid Organ Transplanted Patients with Signs of Severe Sepsis and Septic Shock. a Pilot Study
Authors: Ruberto F. , Pugliese F. , D'alio A. , Martelli S. , Bruno K. , Marcellino V. , Summonti D. , Celli P. , Perrella S. , Cappannoli A. , Pietropaoli C. , Tosi A. , Diana B. , Novelli G. , Rossi M. , Corradini S. Ginanni , Ferretti G. , Berloco P. B. , Pietropaoli P.
Published: January 2018

Background

Polymyxin B (PMX-B) is a polycationic antibiotic, known to bind the lipid A portion of endotoxin, a cell wall component found exclusively in gram negative bacteria (GNB). An extracorporeal hemoperfusion device (TORAYMYXIN) has been developed: PMX is covalently bound on the surface of an insoluble carrier material so that the endotoxin can be inactivated in the blood without exerting its toxicity on the brain and kidney The aim of this study was to clarify the efficacy, safety and clinical effects of direct hemoperfusion with an immobilized polymyxin-B fiber column (DHP-PMX) in solid organ transplanted patients with severe sepsis or septic shock.

Methods

From June 2004 to May 2005, 15 patients (10 men and 5 women), mean age 55 years old (46–65 range), underwent kidney or liver transplantation and developed severe sepsis or septic shock, as defined by the Consensus Conference of American College Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. GNB were detected in all the patients receiving conventional treatments including antibiotic therapy, vasopressive or inotropic agents, and ventilation support. The DHP-PMX treatment was performed three times in each patient. Hemodynamic and respiratory parameters, dosage of vasopressor/inotropic drugs were assessed at baseline and after each treatment.

Results

No adverse events occurred. From baseline to 3rd treatment, mean arterial pressure (MAP) was increased (from 63±5 to 83±4 mmHg), while the dosage of dobutamine (from 7.5±3 to 3±2 mcg/kg/min) and noradrenaline (from 1.3±0.45 to 0.05±0.02 mcg/kg/min) were reduced. The PaO2/FiO2 ratio increased (from 234±38.47 to 290±107.48 mmHg).

Conclusion

The use of DHP-PMX in association with conventional therapy may be an important aid in patients with sepsis.
Membranes for Dialysis: Can We do without them?
Authors: Hoenich N.A.
Published: January 2018

Over the past five decades, membranes used for the treatment of chronic kidney disease have continuously evolved. In the course of this evolution, the use of classical non-modified cellulose membranes has declined in favor of cellulose-based membranes in which the basic structure has been modified to improve the biocompatibility profile of the material as well as membranes based on synthetic polymers. In addition to providing improved biocompatibility, manufacturing methods have been innovatively adapted to produce membranes with optimized pore size and pore size distribution. This has led to the more effective removal of molecules involved in the development of complications associated with dialysis treatment.

More recently, the approach has been move membranes beyond being just selective barriers with a high performance and to incorporate biological function.

Despite these advances, membranes in current clinical use represent a compromise: while efficient in their removal of water soluble compounds, they are non-selective, retain some bioreactivity and differ in their ability to adsorb endotoxins or bacterial fragments that may be present in the dialysis fluid. In this paper, an overview of the membranes used in current clinical practice and their limitations are discussed, together with approaches to solute transport in which no membranes are used.
Hyperlipidemia in Chronic Kidney Disease
Authors: Kaysen G. A.
Published: January 2018

The risk of cardiovascular events and mortality increases as renal function declines. The standard Framingham risk factors contributing to the relative risk of mortality (RRM) are altered or re-placed. While obesity predicts loss of renal function, among dialysis patients obesity predicts survival rather than mortality. Among dialysis patients, Low Density Lipoprotein cholesterol (LDL) does not predict mortality; however other risk factors, such as low High Density Lipoprotein cholesterol (HDL) and increased intermediate density lipoproteins (IDL), remain cardiovascular risk factors. While HDL levels are decreased as a result of an increased fractional catabolic rate (FCR) both among obese patients with normal renal function and among dialysis patients, the mechanisms responsible for increased HDL FCR may differ. In patients with advanced kidney disease, HDL fails to mature normally as a result of decreased lecithin cholesterol ester transfer protein (LCAT), leaving cholesterol ester-poor, triglyceride (TG)-rich HDL3 and pre-β-HDL. Chronic kidney disease (CKD) is associated with insulin resistance, providing another potential mechanistic link to low HDL levels. Increased TG levels are found in an expanded Intermediate Density Lipoprotein (IDL) pool and are associated with mortality risk. Lipoprotein (a) (LP(a)) levels are increased. In patients without renal disease, the concentration of Lp(a) is inversely associated with the size of the apo (a) isoform inherited; Lp (a) levels are increased in patients with kidney disease as consequence of increased concentrations, primarily of the high molecular weight isoform resulting from decreased clearance. Lp (a) levels are also associated with cardiovascular outcome among dialysis patients.
A Mathematical Model Comparing Solute Kinetics in Low- and High-BMI Hemodialysis Patients
Authors: Cronin-Fine D. , Gotch F. , Levin N. W. , Kotanko P. , Lysaght M.
Published: January 2018

Background

Patients with low Body Mass Index (BMI) on maintenance hemodialysis have a higher mortality risk than patients with elevated BMI. We investigated the use of kinetic modeling to test different hypotheses which have been advanced to explain this relationship.

Methods

Equations from a three-pool urea-kinetic mathematical model (hepatic mass, extracellular fluid, muscle mass and adipose tissue) were solved to yield predictive profiles of solute and putative toxin concentrations versus time for patients of different body weights.

Results

For the interdialytic interval, our mathematic model suggests that extracellular solute/toxin concentration increases more rapidly in small patients. Additionally, time average concentration (TAC) is higher for this cohort. A lower value of the muscle mass and adipose tissue mass-transfer coefficient (KMMAT), which determines the rate of solute release into the extracellular fluid, exacerbates this difference.

Conclusion

These results suggest that higher mortality for smaller dialysis patients may be mediated by higher time average toxin concentration, especially for solutes with a low mass-transfer coefficient value.
Patient Empowerment in the Management of Hyperphosphatemia
Authors: Kuhlmann M. K , Hoechst S. , Landthaler I.
Published: January 2018

Despite advances in dialysis technology and an increasing variety of effective phosphate binders (PB) target phosphate levels are achieved in only a minority of ESRD patients. This is only partly explained by insufficient weekly phosphate elimination (2400 - 3000 mg) with traditional 3× 4–5 h dialysis, which is significantly lower than the total amount of phosphorus (iP) accrued from dietary consumption during the same period (about 5000 g). In addition, meal-to-meal and day-to-day variability of dietary iP intake in conjunction with inadequate phosphate binder dosing in relation to meal iP content also may contribute to hyperphosphatemia. It was hypothesized that self-adjusting of PB dose to meal iP content by the patient himself will improve management of hyperphosphatemia. A specific Phosphate-Education-Program (PEP) was developed to train patients to eye-estimate meal iP content by “Phosphate Units” (PU), which categorize food components according to iP content (100 mg iP per serving size = 1 PU). To allow self-adjustment of PB dose to meal iP content, a new prescription concept for PB was required. Phosphate binders are no longer prescribed using a fixed dosing regimen but only in strict relation to meal iP content (#PB per PU). In close collaboration with the patient the PB/PU ratio is then adapted to individual patient needs until serum phosphate targets are met. This new management concept for hyperphosphatemia is the first to establish a direct link between dietary phosphorus intake and PB dose and to empower patients to self-adjust PB dose according to dietary phosphorus intake. Clinical studies are under way to establish the practical value of this new concept for CKD and ESRD patients.
Newer Strategies for Anemia Prevention in Hemodialysis
Authors: Handelman G. J.
Published: January 2018

Anemia prevention for hemodialysis relies primarily on supplemental erythropoietin (EPO) and intravenous iron (IV-iron). The doses of EPO utilized are somewhat higher than normal endogenous rates of EPO production in healthy subjects, and the amount of IV-iron used to boost red blood cell (RBC) production may be greater than the amounts used for erythropoiesis. EPO and IV-iron might be used more efficiently if two fundamental problems were solved in the management of dialysis patients: better vitamin C status, and avoidance of chronic inflammation. The low levels of plasma vitamin C commonly observed in dialysis patients restrict mobilization of stored iron from the reticuloendothelial system (RES), and inflammation has a very similar effect. The impact of low vitamin C levels and concurrent inflammation causes a large amount of iron to be stored, with relatively inefficient utilization for erythropoiesis.

Vitamin C intake for dialysis patients is often restricted because of avoidance of vitamin C-rich foods, and because of concerns about oxalosis. Inflammation is a chronic feature of renal disease, which is compounded by infections from use of catheters. Research strategies to improve vitamin C status and to decrease inflammation would lead to better utilization of iron and EPO, and could have parallel benefits for the long-term health of patients on hemodialysis.
Anti-Inflammatory Drugs and the Kidney
Authors: House A. A. , Oliveira S. Silva , Ronco C.
Published: January 2018

Non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) enjoy widespread use in clinical practice, leading to a remarkable frequency of unwanted renal side effects. In most cases, NSAID-induced acute renal failure or acute kidney injury is hemodynamically mediated. Clinical syndromes associated with NSAID use include acute renal failure, acute interstitial nephritis, worsening of chronic kidney disease (CKD), salt and water retention and hypertension. Careful monitoring of renal function is advisable in patients at increased risk such as elderly individuals with compromised cardiac reserve, and diabetics.
Computer and Physical Modeling of Blood Circulation Pump Support for a New Field of Application in Palliative Surgery
Authors: MaƗota Z. , Nawrat Z. , Kostka P.
Published: January 2018

Objectives

One of the most popular palliative procedures performed to increase pulmonary blood flow in children with congenital heart defects is a shunt operation (Blalock-Taussig graft or Glenn procedure), which creates the new blood channel to the pulmonary artery. The main problem with this kind of surgery is poor shunt effectiveness and the lack of possibility to regulate the flow. The aim of this work is to use advanced computer simulation methods to study the effectiveness of a new idea to introduce a small axial blood pump into a Blalock-Taussig (B-T) or Glenn shunt in order to control the blood flow and prevent any increase in the graft stenosis.

Methods

Physical and computer 3-D simulation based on a finite element mesh (FEM) model was applied. Studies for optimization of the shunt and hybrid shunt with pump were performed for different stages of the disease.

Results and Conclusion

The graft with the axial pump creates good conditions for the vascular system and pulmonary artery blood flow as well as regulating blood pressure under variable conditions caused by palliative procedures. Its use permits the afterload of the left heart ventricle to be decreased. A palliative procedure is only a temporary solution. When a child grows, while the graft size is fixed, the blood flow through this graft may be not sufficient under changing hemodynamic conditions. The use of an axial pump for regulating the blood flow volume, during palliative procedures, allows to obtain the optimal flow conditions in pulmonary artery and safely wait on the final cardiac surgery correction later. However, the use of a pump mounted inside the graft increased hemodynamic resistance, which caused the flow to decrease up to 70% in the graft when the axial pump was not working.
Comparison of Icodextrin- and Glucose-Based Peritoneal Dialysis Fluids in Their Acute and Chronic Effects on Human Peritoneal Mesothelial Cells
Authors: Bender T. O. , Witowski J. , KsąŻEk K. , Jörres A.
Published: January 2018

Background

Icodextrin-based peritoneal dialysis fluids (PDFs) display several features that may potentially improve their biocompatibility compared to conventional glucose-containing solutions. So far, however, the studies assessing the biocompatibility profile of icodextrin toward human peritoneal mesothelial cells (HPMC) has produced mixed results. The present study was performed to examine the acute and chronic impact of icodextrin on HPMC in vitro in comparison with standard glucose-based PDF.

Methods

Omentum-derived HPMC were either acutely pre-exposed to or incubated chronically (for up to 10 days) in the presence of icodextrin-PDF. Parallel cultures were treated with conventional PDFs containing either 1.5% or 4.25% glucose. All fluids were tested at neutral pH. HPMC were assessed for viability, proliferation, IL-6 secretion and generation of reactive oxygen species (ROS).

Results

Incubation in the presence of icodextrin-PDF significantly reduced HPMC proliferation in a manner similar to that of 1.5% glucose-PDF In addition, exposure to icodextrin-PDF impaired viability and IL-6 release from HPMC. This effect occurred both after the short pre-treatment with neat icodextrin-PDF for 1–4 hours and after prolonged incubation (up to 10 days) in media supplemented with icodextrin-PDF (1:1). The dysfunction of icodextrin-treated HPMC was of the magnitude that was between the effects exerted by 1.5%- and 4.25%-glucose PDF. Furthermore, exposure of HPMC to icodextrin-PDF induced a dose-dependent increase in ROS generation which was comparable to that produced by 1.5%-glucose PDF.

Conclusion

Exposure to icodextrin-PDF may impair viability and function of HPMC. The detrimental effects of icodextrin-PDF are at least as serious as those produced by conventional heat-sterilized low glucose-based PDF.
High Doses of Water Increase the Purifying Capacity of the Kidneys
Authors: Di Paolo N. , Nicolai G.A. , Lombardi M. , Maccari F. , Garosi G.
Published: January 2018

Background

In previous studies we were successful in demonstrating that the administration of water over a short period of time increases the transport capacity in the excretory tract of rabbit ureters by increasing urinary volume in the ureter from 0.3 ml/min to 10 ml/min. This phenomenon may explain the effect of water therapy performed in thermal spas, where the administration of 1–2 liters of mineral water is performed in 30–60 minutes.

Objectives

The aim of the present study is to investigate if this increased transport capacity can act also in the renal tubular apparatus to modify the excretion of some endogenous substances.

Materials and Methods

We evaluated daily renal clearances in ten subjects under basal conditions during supplemental administration of 25 ml/kg of mineral water over a 24-hour period and during the administration of the same amount of water over a 30-minute period.

Results

Subjects who drank a water load of 25 ml/Kg over 30 minutes showed a higher diuresis than that observed in those who drank the same amount over a 24-hour period. Creatinine and urea clearance at 24 hours were significantly higher in subjects who drank the water load over 30 minutes. Serum magnesium levels and folic acid levels were also significantly higher in subjects who drank the water load over 30 minutes.

Conclusions

Water administration over a short period of time seems to modify the daily excretion of some endogenous metabolites.
Hepatitis C Infection in Patients with Chronic Kidney Disease
Authors: Mangia A. , Burra P. , Ciancio A. , Fagiuoli S. , Guido M. , Picciotto A. , Fabrizi F.
Published: January 2018

The management of hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) is complex and represents a particular concern since numerous issues, such as antiviral therapy in dialysis patients and post renal transplant, and prevention of HCV spread within dialysis units, remain unresolved. An enormous body of literature has been published on HCV in the CKD population; however, clinical evidence on important issues is mostly based on uncontrolled clinical trials or retrospective surveys. The aim of this paper is to provide a systematic review of the literature. Responses to the critical issues have been developed by a consensus of experts, endorsed by the Italian Association for the Study of the Liver (AISF) and some clinical recommendations have been added.
Fluid and Volume Monitoring
Authors: Pinsky M.R. , Brophy P. , Padilla J. , Paganini E. , Pannu N.
Published: January 2018

Background

Fluid resuscitation is not only used to prevent acute kidney injury (AKI) but fluid management is also a cornerstone of treatment for patients with established AKI and renal failure. Ultrafiltration removes volume initially from the intravascular compartment inducing a relative degree of hypovolemia. Normal reflex mechanisms attempt to sustain blood pressure constant despite marked changes in blood volume and cardiac output. Thus, compensated shock with a normal blood pressure is a major cause of AKI or exacerbations of AKI during ultrafiltration.

Methods

We undertook a systematic review of the literature using MEDLINE, Google Scholar and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated clinical practice recommendations and/or directions for future research.

Results

We defined three aspects of fluid monitoring: i) normal and pathophysiological cardiovascular mechanisms; ii) measures of volume responsiveness and impending cardiovascular collapse during volume removal, and; iii) measured indices of each using non-invasive and minimally invasive continuous and intermittent monitoring techniques. The evidence documents that AKI can occur in the setting of normotensive hypovolemia and that under-resuscitation represents a major cause of both AKI and mortality ion critically ill patients. Traditional measures of intravascular volume and ventricular filling do not predict volume responsiveness whereas dynamic functional hemodynamic markers, such as pulse pressure or stroke volume variation during positive pressure breathing or mean flow changes with passive leg raising are highly predictive of volume responsiveness. Numerous commercially-available devices exist that can acquire these signals.

Conclusions

Prospective clinical trials using functional hemodynamic markers in the diagnosis and management of AKI and volume status during ultrafiltration need to be performed. More traditional measure of preload be abandoned as marked of volume responsiveness though still useful to assess overall volume status.
Embryonic Stem Cell Sphere: A Controlled Method for Production of Mouse Embryonic Stem Cell Aggregates for Differentiation
Authors: Rohani L. , Karbalaie K. , Vahdati A. , Hatami M. , Nasr-Esfahani M.H. , Baharvand H.
Published: January 2018

Objectives

Embryonic stem cells (ESCs) are of significant interest as a renewable source of nonproliferating cells. Differentiation of ESCs is initiated by the formation of embryoid bodies (EBs). Standard methods of EB formation are limited in their production capacity, in any variations in EB size and formation of EBs through frequent passages. Here we have reported the utility of a microencapsulation technique for overcoming these limitations by mass production of mouse ESCs in alginate beads called ESC spheres.

Methods

The mouse ESCs were encapsulated in 1.2% alginate solution and cocultured on a feeder layer. The cells were evaluated by flow cytometry, in vitro differentiation, immunofluorescence, and reverse transcriptase polymerase chain reaction (RT-PCR).

Results

Analysis of encapsulated ESC spheres by flow cytometry showed similar percentages of Oct-4 and stage-specific embryonic antigen-1 (SSEA-1) expression in comparison with routine culture of ESCs. Moreover, the ESC spheres maintained a pluripotency potential which was comparable with ESCs cultured on feeder cells directly, as demonstrated by immunofluorescence and RT-PCR.

Conclusions

The results demonstrated that alginate encapsulation as a simple bioreactor, provides a scalable system for mass undifferentiated ESC sphere production with similar sizes and without the need for frequent passages for differentiation and clinical and pharmaceutical applications.
Hemodialysis Dialyzers Contribute to Contamination of Air Microemboli that Bypass the Alarm System in the Air Trap
Authors: Stegmayr C. , Jonsson P. , Forsberg U. , Stegmayr B.
Published: January 2018

Background

Previous studies have shown that micrometer-sized air bubbles are introduced into the patient during hemodialysis. The aim of this study was to investigate, in vitro, the influence of dialysis filters on the generation of air bubbles.

Methods

Three different kind of dialyzers were tested: one high-flux FX80 dry filter (Fresenius Medical Care AG&Co. KGaA, Bad Homburg, Germany), one low-flux F8HPS dry filter (Fresenius Medical Care AG&Co. KGaA, Bad Homburg, Germany) and a wet-stored APS-18u filter (Asahi Kasei Medical, Tokyo, Japan). The F8HPS was tested with pump flow ranging between 100 to 400 ml/min. The three filters were compared using a constant pump flow of 300 ml/min. Measurements were performed using an ultrasound Doppler instrument.

Results

In 90% of the series, bubbles were measured after the outlet line of the air trap without triggering an alarm. There were significantly more bubbles downstream than upstream of the filters F8HPS and FX80, while there was a significant reduction using the APS-18u. There was no reduction in the number of bubbles after passage through the air trap versus before the air trap (after the dialyzer). Increased priming volume reduced the extent of bubbles in the system.

Conclusions

Data indicate that the air trap does not prevent air microemboli from entering the venous outlet part of the dialysis tubing (entry to the patient). More extended priming of the dialysis circuit may reduce the extent of microemboli that originate from dialysis filters. A wet filter may be favorable instead of dry-steam sterilized filters.