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Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the "IL-6-Sieve", wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve. Evaluations focused on the: (a) safety of Filter and Magnet placed in an extracorporeal circuit in sheep; (b) safety of Anti-IL-6 Beads-directly infused intravenously as worst case scenario of misuse; or injected into an extracorporeal circuit using the Bead Adapter, Filter, and Magnet as intended-in sheep; (c) biodistribution of Anti-IL-6 Beads intravenously infused in mice; and (d) safety of Filter and Magnet placed in an extracorporeal circuit in healthy volunteers. No serious adverse events or significant changes in vital signs or routine laboratory parameters occurred in any of the animals or humans. Although safety of the IL-6-Sieve requires further study, these initial evaluations represent a promising start for the translation of this new blood purification modality into clinical use., (© 2024. The Author(s).)

Acute decompensated heart failure and fluid overload are the most common causes of hospitalization in heart failure patients, and often, they contribute to disease progression. Initial treatment encompasses intravenous diuretics although there might be a percentual of patients refractory to this pharmacological approach. New technologies have been developed to perform extracorporeal ultrafiltration in fluid overloaded patients. Current equipment allows to perform ultrafiltration in most hospital and acute care settings. Extracorporeal ultrafiltration is then prescribed and conducted by specialized teams, and fluid removal is planned to restore a status of hydration close to normal. Recent clinical trials and European and North American practice guidelines suggest that ultrafiltration is indicated for patients with refractory congestion not responding to medical therapy. Close interaction between nephrologists and cardiologists may be the key to a collaborative therapeutic effort in heart failure patients. Further studies are today suggesting that wearable technologies might become available soon to treat patients in ambulatory and de-hospitalized settings. These new technologies may help to cope with the increasing demand for the care of chronic heart failure patients. Herein, we provide a state-of-the-art review on extracorporeal ultrafiltration and describe the steps in the development of a new miniaturized system for ultrafiltration, called AD1 (Artificial Diuresis)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aim: Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock., Materials and Methods: The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy., Results: Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05)., Conclusion: The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest., (© TÜBİTAK.)

Background: The use of left ventricular assist devices (LVAD) in patients with advance heart failure is still associated with an important risk of immune dysregulation and infections. The aim of this study was to determine whether extracorporeal blood purification using the CytoSorb device benefits patients after LVAD implantation in terms of complications and overall survival., Materials and Methods: Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation, of whom 72 underwent CytoSorb therapy and 135 did not. Overall survival, major adverse events, and laboratory parameters were compared between 112 propensity score-matched patients (CytoSorb: 72 patients; non-CytoSorb: 40 patients)., Results: WBC (p = .033), CRP (p = .001), and IL-6 (p < .001), significantly increased with LVAD implantation, while CytoSorb did not influence this response. In-hospital mortality and overall survival during follow-up were similar with CytoSorb. However, patients treated with CytoSorb were more likely to develop respiratory failure (54.2% vs. 30.0%, p = .024), need mechanical ventilation for longer than 6 days post-implant (50.0% vs. 27.5%, p = .035), and require tracheostomy during hospitalization (31.9% vs. 12.5%, p = .040). No other significant differences were observed with regard to major adverse events during follow-up., Conclusions: Overall, our results showed that CytoSorb might not convey a significant morbidity or mortality benefit for patients undergoing LVAD implantation., (© 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Facile methods for accurate fluid-mechanical characterization of haemofilters (HF) are indispensable for haemofiltration process improvements, equipment design/optimization, and reliable module specifications. Currently employed methods, implemented through specific experimental in vitro protocols, are assessed herein in detail, considering the conditions prevailing during haemofiltration. Minimum number of key parameters required to fully describe the common countercurrent flow field, in the HF active section, include membrane permeance K and friction coefficients in lumen and shell side (f f and f s ). It is shown that the countercurrent flow mode itself is incapable of yielding these parameters, based on externally measured flow rates and pressures. Similarly, the relevant ISO protocol is deficient as it can only provide rough underpredictions of permeance K. The causes of such inherent deficiencies of current standards and practices are analyzed. In contrast, a recently developed methodology, accounting for the (heretofore ignored) pressure drop in module headers and combining a mechanistic theoretical model with experimental data from 2 special haemofilter operating modes, yields an accurate determination of the key parameters (K, f f , f s ). Additionally, it permits a full description of flow field for Newtonian liquids, for both constant and axially varying viscosity in fiber-lumen due to the transmembrane flux. Development of new reliable standards is suggested, facilitated by the insights gained in this work., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

The high mobility group box 1 protein (HMGB1) is recognized as a prototypical endogenous danger cytokine in sepsis. We previously reported that a polyacrylonitrile (AN69ST) membrane rapidly adsorbed HMGB1. Herein, an in vitro hemofiltration system was designed to assess the HMGB1 adsorption capacity, adsorption sites, and adsorption mechanism of the AN69ST membrane. HMGB1 was repeatedly added seven times during hemofiltration. A rapid decrease in circulating HMGB1 was observed after every addition with no sign of saturation. Presence of HMGB1 on the filter membrane was observed on both membrane surfaces and within the bulk layer using a high concentration of HMGB1 by immunoelectron microscopy. We hypothesized that the addition of heparin to the membrane surface or filtration rate would contribute to the adsorption mechanism. We could not measure the influence of heparin and filtration. Although the membrane was too large to saturate under the μg/mL HMGB1 conditions, our results show that the AN69ST membrane has a robust absorption capacity that could be used to treat sepsis., (© 2020 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Excessive pro-inflammatory and anti-inflammatory cytokines are mediators for haemodynamic alterations, metabolic acidosis, and multi-organ failure in sepsis. Recently, oXiris ® haemofilter (Baxter, IL, USA) has been introduced as a novel haemofilter to mitigate inflammatory response during sepsis-associated acute kidney injury requiring renal replacement therapy. In the present case series, the researchers retrospectively reviewed critically ill patients with septic shock with the use of at least one oXiris haemofilter during continuous renal replacement therapy between June 2015 and December 2017. The timing for oXiris initiation was at the nephrologists' discretion. The impact of oXiris haemofilter was evaluated on mean arterial pressure, vasopressor dosage, Sequential Organ Failure Assessment score, lactate and base excess during 72 h after treatment. Thirty-five patients were enrolled in the study. An improvement of haemodynamic status was found, shown by increased mean arterial pressure by 6.1% ( p  = 0.35), decreased norepinephrine dose by 45.9% ( p  = 0.02), inotropic score by 26.4% ( p  = 0.02) and vasopressor dependency index by 40.5% ( p  = 0.01). Cardiovascular Sequential Organ Failure Assessment scores significantly decreased over 72 h ( p  = 0.02). Blood lactate levels and base excess also showed statistically significant improvements. The median filter lifetime was 23 (interquartile range = 14-36) hours. The intensive care unit mortality was 82.9%. Treatment with oXiris was safe and well-tolerated with no device-related adverse events. In conclusion, continuous renal replacement therapy with oXiris haemofilter is safe and may improve haemodynamic parameters in septic patients with severe renal dysfunction. Nonetheless, these findings were drawn from a retrospective analysis without a control group, and therefore cannot be generalised. Randomised controlled trials are warranted to confirm these findings.

Introduction: Continuous renal replacement therapies (CRRTs) are essential in the treatment of critically ill patients with acute kidney injury and are also discussed as a supporting sepsis therapy. CRRT can affect antibiotics plasma concentrations., Objective: The effect of continuous venovenous hemofiltration (CVVH) with an asymmetric triacetate (ATA) membrane hemofilter on concentrations of antibiotics with low (meropenem), medium (vancomycin), and high (daptomycin) protein binding (PB) was investigated., Methods: 1 L human whole blood supplemented with antibiotics was recirculated and filtrated for 6 h in vitro. Clearances and sieving coefficients (SC) were determined from antibiotics concentrations measured at filter inlet, outlet, and filtrate side. Reservoir concentration data were fitted using a first-order kinetic model., Results: Meropenem and vancomycin concentrations decreased to 5-10% of the initial plasma level, while only 50% of daptomycin were removed. Clearances and SCs were (10.8 [10.8-17.4] mL/min, SC = 0.72 [0.72-1.16]) for meropenem, (13.4 [12.3-13.7] mL/min, 0.89 [0.82-0.92]) for vancomycin, and (2.1 [1.8-2.1] mL/min, 0.14 [0.12-0.14]) for daptomycin. Removal by adsorption was negligible., Conclusions: The clearances and SCs presented are comparable with findings of other authors. Meropenem and vancomycin, which exhibit low and medium PB, respectively, were strongly removed, while considerably less daptomycin was removed because of its high PB. Our results suggest that in clinical use of the tested antibiotics during CRRT with the ATA hemofilter, the same factors have to be considered for determining the dosing strategy as with filters with other commonly applied membrane materials., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck., (© 2020 S. Karger AG, Basel.)

Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30 min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10 min and 30 min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10 min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6 mL/min, 23 ± 7 mL/min, and 78 ± 3 mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76 mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design.

Convection-based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion-based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD-HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD-HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady-state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Introduction: Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane., Objective: The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem)., Methods: We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters., Results: The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group., Conclusions: Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability., (The Author(s). Published by S. Karger AG, Basel.)

Objective: To evaluate the efficacy and safety of oXiris hemofilter for septic shock patients., Methods: Clinical data of septic shock patients receiving continuous renal replacement therapy (CRRT) with oXiris hemofilter in department of surgical intensive care unit (SICU) of the First Affiliated Hospital of Xi'an Jiaotong University from March 1st, 2018 to July 20th, 2019 were retrospectively analyzed. The heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO 2 /FiO 2 ), lactate (Lac), platelet count (PLT), serum procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), noradrenaline (NE) dosage, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA) were compared before and after oXiris treatment and the prognosis were also analyzed., Results: Six patients with septic shock were included [5 males, the average age was (56.3±11.8) years old]. A total of 13 oXiris hemofilter sets were performed during treatment. Compared with before treatment, the HR, IL-6 and CRP levels were significantly decreased after treatment [HR (bpm): 93.8±9.7 vs. 133.5±18.3, IL-6 (ng/L): 509.2±169.6 vs. 3 739.8±618.2, CRP (mg/L): 169.1±148.3 vs. 277.8±68.7, all P < 0.05], MAP, PaO 2 /FiO 2 and PLT were significantly increased [MAP (mmHg, 1 mmHg = 0.133 kPa): 73.3±2.2 vs. 63.3±1.6, PaO 2 /FiO 2 (mmHg): 166.8±40.4 vs. 95.1±56.2, PLT (×10 9 /L): 73.3±27.5 vs. 41.2±21.4, all P < 0.05]; meanwhile, NE dosage, APACHE II and SOFA scores were significantly decreased [NE (μg×kg -1 ×min -1 ): 0.4±0.3 vs. 1.2±0.7, APACHE II: 18.8±6.9 vs. 30.0±7.3, SOFA: 11.7±4.2 vs. 17.3±2.1, all P < 0.05]. Although Lac and PCT decreased after treatment, there was no significant difference [Lac (mmol/L): 3.5±2.1 vs. 6.1±3.2, PCT (μg/L): 37.7±48.3 vs. 85.1±32.8, both P > 0.05]. At the end, 3 of the 6 patients survived and the others were discharged again medical advice. The length of SICU stay was 3 to 23 days, with an average of (13.0±8.5) days. No adverse events occurred during the treatment., Conclusions: oXiris hemofilter can effectively remove inflammatory mediators in circulation, significantly improve hemodynamic status and severity, and may be considered as a safe and reliable treatment modality for septic shock patients.

Background and Objectives: Provision of kidney replacement therapy (KRT) to manage kidney injury and volume overload in critically ill neonates and small children is technically challenging. The use of machines designed for adult-sized patients, necessitates large catheters, a high extracorporeal volume relative to patient size, and need for blood priming. The Aquadex FlexFlow System (CHF Solutions Inc., Eden Prairie, MN) is an ultrafiltration device designed for fluid removal in adults with diuretic resistant heart failure. It has an extracorporeal volume of 33 ml, which can potentially mitigate some complications seen at onset of KRT in smaller infants., Design, Setting, Participants, & Measurements: In this multicenter, retrospective case series of children who received KRT with an ultrafiltration device ( n =119 admissions, 884 circuits), we report demographics, circuit characteristics, complications, and short- and long-term outcomes. Patients were grouped according to weight (<10, 10-20, and >20 kg), and received one of three modalities: slow continuous ultrafiltration, continuous venovenous hemofiltration (CVVH), or prolonged intermittent KRT. Our primary outcome was survival to end of KRT., Results: Treatment patterns and outcomes varied between the groups. In patients who weighed <10 kg, the primary indication was AKI in 40%, volume overload in 46%, and ESKD in 14%. These patients primarily received CVVH (66%, n =48) and prolonged intermittent KRT (21%, n =15). In the group weighing >20 kg, volume overload was the primary indication in 91% and slow continuous ultrafiltration was the most common modality. Patients <10 kg had lower KRT survival than those >20 kg (60% versus 97%), more volume overload at onset, and received KRT for a longer duration. Cardiovascular complications at initiation were seen in 3% of treatments and none were severe. Complications during therapy were seen in 15% treatments and most were vascular access-related., Conclusions: We report the first pediatric experience using an ultrafiltration device to provide a range of therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultrafiltration. We were able to initiate KRT with minimal complications, particularly in critically ill neonates. There is an unmet need for devices specifically designed for younger patients. Having size-appropriate machines will improve the care of smaller children who require kidney support., (Copyright © 2019 by the American Society of Nephrology.)

Background and Aims: Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy (CRRT) showed promising results in case reports. However, there are no clinical trials investigating outcomes., Methods: In this investigator-initiated retrospective study, patients with septic shock were treated with CRRT + CytoSorb (n = 67) or CRRT alone (n = 49). The primary outcome was the 28-day all-cause mortality rate. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics., Results: At the start of therapy, CytoSorb-treated patients had higher lactate levels (p < 0.001), lower mean arterial pressure (p = 0.007) and higher levels of noradrenaline (p < 0.001) compared to the CRRT group. For CytoSorb, the mean predicted mortality rate based on a SOFA of 13.8 (n = 67) was 75% (95%CI 71-79%), while the actual 28-day mortality rate was 48% (mean difference - 27%, 95%CI - 38 to - 15%, p < 0.001). For CRRT, based on a SOFA of 12.8 (n = 49), the mean predicted versus observed mortality was 68% versus 51% (mean difference - 16.9% [95%CI - 32.6 to - 1.2%, p = 0.035]). By sIPTW analysis, patients treated with CytoSorb had a significantly lower 28-day mortality rate compared to CRRT alone (53% vs. 72%, respectively, p = 0.038). Independent predictors of 28-day mortality in the CytoSorb group were the presence of pneumosepsis (adjusted odds ratio [aOR] 5.47, p = 0.029), higher levels of lactate at the start of CytoSorb (aOR 1.15, p = 0.031) and older age (aOR per 10 years 1.67, p = 0.034)., Conclusions: CytoSorb was associated with a decreased observed versus expected 28-day all-cause mortality. By IPTW analysis, intervention with CytoSorb may be associated with a decreased all-cause mortality at 28 days compared to CRRT alone.

Purpose: For the first time in Kazakhstan, we have used a combined extracorporeal support, by including the CytoSorb system in a continuous veno-venous hemofiltration system in an 8-month-old patient with a body weight of 5600 g., Results: The CytoSorb therapy session resulted in a reduction of inflammation markers IL-6, S100, procalcitonin, and C-reactive protein. Simultaneously, the level of transaminases, creatine kinase, and troponin were normalized, by the end of the session patient hemodynamics were stable and there was no need for vasopressors, acid-base balance was maintained, and the patient was weaned from mechanical ventilation to spontaneous breathing., Conclusion: Treatment using the CytoSorb device was safe and well-tolerated in a pediatric patient and has proven its practical value as an adjuvant therapy for sepsis in pediatric patient populations.

Background: Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery., Methods: We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors' activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII)., Results: Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors' adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes., Conclusions: CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts., Trial Registration: ClinicalTrials.gov NCT02775123 . Registered 17 May 2016.

Cytokines and high mobility group box chromosomal protein-1 (HMGB-1) play key roles in inflammatory conditions. While hemofiltration has been shown to remove cytokines, removal of cytokines and HMGB-1 by hemofiltration using a polyethersulfone membrane has not been reported. This study aimed to test the hypothesis that the polyethersulfone membrane will achieve higher removal performance for substances including inflammatory cytokines compared to other hemofilters, while retaining low albumin removal capacity. Subjects were eight healthy volunteers. We collected 400 mL each of blood samples into containers with heparin and added 30 mg of lipopolysaccharide to spike cytokines and HMGB-1. After incubation at 39ºC for 12 h, each blood sample was circulated through a hemofiltration circuit with a polyethersulfone hemofilter (2.1 m 2 or 1.1 m 2 ) at a filtration flow rate of 2 L/h. Measurement samples were collected from arterial, venous, and ultrafiltrate sampling points. Concentrations of cytokines (IL-1ß, IL-4, IL-6, IL-8, IL- 10, and tumor necrosis factor [TNF-a]), HMGB-1, and albumin were determined at each time point (1, 4, 8, 12, and 24h). High sieving coefficients (SCs) above 0.8 were obtained for all cytokines except for TNF-a as well as HMGB-1, whereas the SC for albumin was less than 0.04 with both hemofilters. The hemofilter with a larger membrane area achieved significantly higher clearances for TNF-a and HMGB-1, and slower decreases in SCs over time for IL-1ß, IL-6, IL-8, TNF-a, and albumin. Continuous hemofiltration with a polyethersulfone membrane achieved high efficiency removal of cytokines and HMGB-1, without excessive removal of albumin., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Objective:: Extracorporeal circulation devices are coated with a biocompatible polymer coating agent (BPCA) that has a hydrophilic blood-contacting layer, but hemofilters are not. We aimed to investigate the antithrombotic properties of a BPCA-coated hemofilter., Methods:: Four experiments using BPCA-coated circuits and non-coated hemofilters and four experiments using BPCA-coated circuits and BPCA-coated hemofilters were performed with whole human blood and compared by measuring the circuit pressure every 5 min, antithrombin activity every 40 min, and thrombin-antithrombin complex every 40 min, for a total of 240 min of recirculation., Results:: The mean time required for the pressure at the inlet of the hemofilter to increase sharply was longer in BPCA-coated than in non-coated hemofilters (66 ± 11 min vs 25 ± 9 min, p < 0.01). The mean antithrombin activity value at 200 and 240 min of recirculation was significantly higher in the experiments with BPCA-coated versus non-coated hemofilters (43.3 ± 2.87 vs 33.3 ± 5.74, p = 0.04; 42.8 ± 3.59 vs 31.0 ± 5.35, p = 0.01, respectively); the antithrombin activity values at the other time points were not significantly different. Furthermore, all thrombin-antithrombin complex values in experiments with the BPCA-coated hemofilters achieved overrange at 80 min of recirculation, whereas those with the non-coated hemofilter achieved overrange at 40 min., Conclusion:: This study suggests that BPCA-coated hemofilters can inhibit antithrombin consumption, contributing to antithrombotic effects in extracorporeal circulation circuits.

Background: oXiris is a blood purification product that has been launched recently in China. In addition to renal function support and fluid management capabilities, it can also adsorb cytokines and endotoxins. This may complement standard treatment for septic acute kidney injury (AKI) patients to control the amplitude of systemic inflammatory response responsible for acute tissue and organ damage. Objectives of our study are to elucidate characteristics of septic AKI patients who respond to treatment with oXiris and to describe the performance of oXiris through patient cases in the absence of large randomized trials on clinical use of oXiris for septic AKI patients in China., Summary: Here, we present 4 cases managed in intensive care units of major hospitals in China. Key practical aspects from an expert meeting discussing these cases have been included as guidance for the use of oXiris in septic AKI patients. Key Messages: Based on the experience gathered from 4 cases, oXiris should be used early in the treatment of septic AKI patients as an adjuvant therapy with good infection source control. It should not be used to delay or replace infection source control. These cases also demonstrated that patients with high risk of bleeding can use oXiris without additional anticoagulation for up to 36 h without implications on serum protein levels and platelet count. Short of definitive biomarkers to gauge the ideal blood purification initiation and discontinuation time for septic AKI patients, clinical judgment is key to determining optimal use of oXiris in septic AKI patients., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Background: Sepsis is a dysregulated host response to an infection and can result in organ dysfunctions and death. Extracorporeal blood purification techniques aim to improve the prognosis of these patients by modulating the unbalanced immune response. This study reports our experience with the use of the oXiris® membrane for septic shock patients requiring continuous renal replacement therapy (CRRT)., Summary: Thirty-one patients were diagnosed with septic shock and underwent CRRT with the oXiris® membrane between 2014 and 2019. We compared the observed hospital mortality with that predicted by the Simplified Acute Physiology Score II (SAPS II). Change in the Sequential Organ Failure Assessment (SOFA) score and of the main clinical and biological parameters over time were analyzed. Hospital mortality was lower than predicted for the most severe patients (60 vs. 91% for the [74-87] SAPS II quartile and 70 vs. 98% for the [87-163] SAPS II quartile, p < 0.02). There was no significant improvement in the SOFA score from 0h to 48 h. An 88% relative decrease in norepinephrine infusion was observed (median at 0 h was 1.69 [0.52-2.45] µg/kg/min; at 48 h it was 0.20 [0.09-1.14] µg/kg/min, p = 0.002). Lactataemia and pH were significantly improved over time. Patients with intra-abdominal sepsis as well as those with Gram-negative bacilli (GNB) infections seemed to benefit the most from the therapy. Key Messages: CRRT with the oXiris® haemofilter resulted in higher observed survival than predicted by a severity score (SAPS II) for the most severe patients. Haemodynamic status and lactataemia appeared to improve, especially in intra-abdominal sepsis and GNB infections., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Background: Recent innovations in biomaterials technology have led to the development of innovative sorbents adopted as adsorbing devices in the field of extracorporeal blood purification therapies. As removal mechanism, adsorption allows to remove specific molecules, selectively binding them to sorbent materials. In addition to the material properties, a quintessential aspect influencing device properties is blood flow distribution within the sorbent particles., Objectives: In order to adequately characterize the potential adsorbing properties for an effective blood purification therapy, an in vitro study assessing the fluid dynamics inside 3 new cartridges, HA130, HA230 and HA330 (Jafron, Zhuhai City, -China) was conducted through CT imaging technique. -Methods: The cartridges were placed in vertical position in the CT -gantry. Dye solution was circulated through the cartridges at 250 mL/min, longitudinal sections, 0.5 cm thick, were recorded for 60 s. Furthermore, an in vitro test was conducted to build pressure drop profiles. Blood was circulated at a different flow rate, 100-400 mL/min, step 50 mL/min. Pre and post cartridges pressures were acquired and pressure drop calculated., Results: Sequential images demonstrated an excellent distribution of the flow inside the cartridges. Average flow velocity was 0.37 cm/s for the 3 cartridges. HA130 had a homogeneous flow profile along the entire length of the device; HA230 and HA330 showed minimal differences between central and peripheral regions. Pressure drop profiles resulted linear, increasing proportionally with blood flow rate and packing density., Conclusions: We may conclude that the structural and functional design of the studied cartridges is adequate for haemoperfusion with no channelling phenomena. This ensures maximum and optimal utilization of the sorbent contained in the devices., (© 2019 S. Karger AG, Basel.)

Background: Septic shock is a leading cause of acute kidney injury (AKI). Endotoxins and cytokine levels are associated with the occurrence and severity of AKI, and different blood purification devices are available to remove them from circulation. One such device, oXiris, is a hollow-fibre purification filter that clears both endotoxins and cytokines. Due to limited evidence, clinical use of this device is not currently advocated in guidelines. However, clinics do regularly use this device, and there is a critical need for guidance on the application of it in sepsis with and without AKI., Method: A modified Delphi-based method was used to collate -European experts' views on the indication(s), initiation and discontinuation criteria and success measures for oXiris., Results: A panel of 14 participants was selected based on known clinical expertise in the areas of critical care and sepsis management, as well as their experience of using the oXiris blood purification device. The participants used different criteria to initiate treatment with oXiris in sepsis patients with and without AKI. Septic shock with AKI was the priority patient population, with oXiris used to rapidly improve haemodynamic parameters. Achieving haemodynamic stability within 72 h was a key factor for determining treatment success., Conclusion: In the absence of established guidelines, users of hollow-fibre purification devices such as oXiris may benefit from standardised approaches to selecting patients and initiating and terminating treatment, as well as measuring success. Further evidence in the form of randomised clinical trials is urgently required., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Adsorption is an extracorporeal technique utilized for blood purification. It complements convection and diffusion (the main modalities of solute removal). It involves the passage of blood (or plasma) through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridges, with improved characteristics have been developed. Furthermore, the therapeutic applications of adsorption have expanded. These now involve the treatment of inflammatory conditions, chronic uremic symptoms, and autoimmune disease, in addition to intoxication, which was once considered the classical indication for adsorption therapy. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. There has been sufficient body of evidence to support their effectiveness and safety. In this review, we aim to highlight their main clinical applications., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: Lipopolysaccharide (endotoxin) from the outer Gram-negative bacterial wall can induce a harmful immunologic response, involving hemodynamic deprivation, and is one important motor driving the septic cascade. The positively charged poly-imine ethylene layer on the oXiris membrane is capable of adsorbing negatively charged endotoxin molecules and removing them from the blood compartment. Endotoxin is detrimental and should be removed from blood., Summary: The adsorbable endotoxin fraction in blood arises from a tight balance between seeding from an infectious focus and removal by an overwhelmed immune system. The net sum of remaining endotoxin in blood is available for an adsorption process in the oXiris filter. Endotoxin data from 2 patients with severe Gram-negative septic shock and endotoxemia in this case series, speaks for a considerable share of the adsorption of the oXiris filter in the endotoxin net removal over time. Key Messages: Analysis of combined in vitro and in vivo data speaks for an effect of the oXiris filter in lowering endotoxin., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Hemofilters applied in continuous renal replacement therapies (CRRTs) for the treatment of acute kidney injury must meet high standards in biocompatibility and permeability for middle and large molecules over extended treatment times. In general, cellulose-based membranes exhibit good biocompatibility and low fouling, and thus appear to be beneficial for CRRT. In this in vitro study, we compared a novel asymmetric cellulose triacetate (ATA) membrane with three synthetic membranes [polysulfone (PS), polyethersulfone (PES), and polyethylenimine-treated acrylonitrile/sodium methallyl sulfonate copolymer (AN69 ST)] regarding thrombogenicity and cytokine removal. For thrombogenicity assessment, we analyzed the thrombin-antithrombin complex (TAT) generation in human whole blood during 5 h recirculation and filtration. Sieving coefficients of interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were determined using human plasma as test fluid. ATA and AN69 ST membrane permeability were determined also during long-term experiments (48.5 h). ATA exhibited the lowest TAT generation (6.3 µg/L at 5 h), while AN69 ST induced a pronounced concentration increase (152.1 µg/L) and filter clogging during 4 out of 5 experiments. ATA (IL-8: 1.053; IL-6: 1.079; IL-10: 0.898; TNF-α: 0.493) and PES (0.973; 0.846; 0.468; 0.303) had the highest sieving coefficients, while PS (0.697; 0.100; 0.014; 0.012) and AN69 ST (N/A; 0.717; 0; 0.063) exhibited lower permeability. Long-term experiments revealed stronger fouling of the AN69 ST compared to the ATA membrane. We observed the highest permeability for the tested cytokines, the lowest thrombogenicity, and the lowest fouling with the ATA membrane. In CRRT, these factors may lead to increased therapy efficacy and lower incidence of coagulation-associated events.

Purpose of Review: This review aims to summarize the most recent advances on different membranes and cartridges used for extracorporeal blood purification in critically ill patients with sepsis or septic shock., Recent Findings: Despite positive signals from experimental, cases and small clinical studies, blood purification showed no distinct morbidity and mortality benefit in large clinical trials., Summary: None of the discussed specific membranes or cartridges can currently be recommended as sole adjunctive treatment in sepsis and septic shock. Any available technique should be timely initiated and adapted to the patient's status. Sickest patients seem to benefit more from blood purification. Patient selection is thus of crucial importance and may be optimized by focusing on disease severity and degree of organ failure. Measurement of endotoxin activity and plasma procalcitonin levels can support the selection process but ideal cutoff values need to be defined. Well-designed prospective randomized clinical trials assessing or comparing the various available membranes and cartridges are eagerly awaited.

Background: The possibility of clearing Cell-free Plasma Hemoglobin (CPH) from human plasma may appear attractive, especially when considering the noxious effects that CPH has on the immune function and the renal damage caused by its filtration. The existence of the so-called High Cut-Off (HCO) filters, possessing pores as big as 60 kDa, could potentially allow the clearance of the αβ dimers (31.3 kDa), the form in which the α2β2 hemoglobin tetramers (62.6 kDa) physiologically dissociate in plasma. We present herein the first reported case in which such an attempt was made., Case Presentation: The patient was a 51-year-old man with hemolytic crisis due to glucose-6-phosphate dehydrogenase deficiency, further complicated by pigment-induced nephropathy. He underwent a 48-h CVVHD session, in which a HCO filter was used. The Sieving Coefficient (SC) for CPH was initially 0.08 and decreased to 0.02 after 24 h. This unexpected low SC was due to the initial high concentration of CPH (4.24 g/L). At such concentrations, the α2β2 tetramer poorly dissociates into the αβ dimer; but increases exponentially at concentrations lower than 1 g/L., Conclusions: Clearance of CPH through a HCO filter is technically feasible but its performance markedly relies on the initial concentration of CPH. Critically ill patients with smoldering hemolysis, as it happens during septic shock or ECMO treatment, may benefit the most from the use of this membrane in order to clear CPH.

Modified ultrafiltration (MUF) is used in neonates and infants to reduce volume overload and increase oxygen-carrying capacity post cardiopulmonary bypass (CPB). In addition, it decreases edema, attenuates complementation activation and immunogenic response to CPB. Hemodilution in the pediatric patient has always been a challenge, countered in part by miniaturization of CPB circuits. We describe a case in which we maintained an acceptable hematocrit level greater than 24%, considered the nadir below which the adverse effects of hemodilution can become evident. We performed this by the novel use of an intravenous warming device (enFlow, Vyaire Medical, Mettawa, IL) to reduce the prime volume of our MUF circuit by more than 50%. We present the case and discuss the advantages and disadvantages of using a low-prime MUF circuit. We were able to conduct "bloodless" CPB, with the use of acute normovolemic hemodilution, miniaturization of the CPB and MUF circuits.

The purpose of the present study was to establish a continuous hemofiltration model using porcine blood to compare filter life. Continuous hemofiltration (CHF) experiments were performed using an in vitro hemofilter evaluation system utilizing porcine blood containing trisodium citrate in addition to nafamostat mesilate as anticoagulants. The lifetime of the hemofilter was evaluated using the transmembrane pressure and the pressure drop across the hemofilter at varying trisodium citrate concentrations. The porcine blood used in this experiment was considered to be in a slightly hypercoagulable state because of the continuous contact with non-biological materials and calcium inflow from substitution fluid. Blood containing 7 or 8 mM of trisodium citrate and nafamostat mesilate could be effectively used to compare the lifetimes of hemofilters utilized under the same conditions. In this CHF model using porcine blood, the plugging of the hollow fibers occurred shortly after the plugging of the membrane pores. In conclusion, a CHF model using porcine blood can be established by adjusting the concentration of trisodium citrate added to the blood.

Objective Continuous renal replacement therapy (CRRT) is well suited for treating metabolic abnormalities and renal insufficiency associated with tumour lysis syndrome (TLS). However, there is controversy regarding the choice of time for CRRT, the selection of CRRT models, and methods of decreasing complications of CRRT. This study aimed to evaluate the efficacy and outcomes of daytime continuous veno-venous haemofiltration (CVVH) for treating paediatric TLS. Methods The clinical features, technique-related complications, and prognosis were prospectively analysed in eight paediatric patients with TLS who were supported by daytime CVVH in West China Second University Hospital, Sichuan University from January 2007 to July 2016. Results Seven patients were boys and one was a girl. All of the patients had hyperphosphataemia, and there were four cases of hyperkalaemia, four cases of hyperuricaemia, and two cases of hypocalcaemia. All of the patients received one to 10 CVVH treatments. Urine output, renal function, serum uric acid levels, and potassium, phosphate, and calcium levels returned to normal in all of the patients, but recovery of renal function was relatively slow. No significant adverse reactions were observed. All of the patients recovered and were discharged. Conclusion Daytime CVVH is a safe and effective treatment for paediatric TLS.

The objective of this study was to evaluate the hemodynamic performance and gaseous microemboli (GME) handling ability of a simulated neonatal extracorporeal life support (ECLS) circuit with an in-line continuous renal replacement therapy (CRRT) device. The circuit consisted of a Maquet RotaFlow centrifugal pump or HL20 roller pump, Quadrox-iD Pediatric diffusion membrane oxygenator, 8-Fr arterial cannula, 10-Fr venous cannula, and Better-Bladder (BB) with "Y" connector. A second Quadrox-I Adult oxygenator was added postarterial cannula for GME experiments. The circuit and pseudo-patient were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 40%). All hemodynamic trials were conducted at ECLS flow rates ranging from 200 to 600 mL/min and CRRT flow rate of 75 mL/min at 36°C. Real-time pressure and flow data were recorded with a data acquisition system and GME were detected and characterized using the Emboli Detection and Classification Quantifier System. CRRT was added at distinct locations such that blood entered CRRT between the pump and oxygenator (A), recirculated through the pump (B), or bypassed the pump (C). With the centrifugal pump, all CRRT positions had similar flow rates, mean arterial pressure (MAP), and total hemodynamic energy (THE) loss. With the roller pump, C demonstrated increased flow rates (293.2-686.4 mL/min) and increased MAP (59.4-75.5 mm Hg) (P < 0.01); B had decreased flow rates (129.7-529.7 mL/min), and MAP (34.2-45.0 mm Hg) (P < 0.01); A maintained the same when compared to without CRRT. At 600 mL/min C lost more THE (81.4%) (P < 0.01) with a larger pressure drop across the oxygenator (95.6 mm Hg) (P < 0.01) than without CRRT (78.3%; 49.1 mm Hg) (P < 0.01). C also demonstrated a poorer GME handling ability using the roller pump, with 87.1% volume and 17.8% count reduction across the circuit, compared to A and B with 99.9% volume and 65.8-72.3% count reduction. These findings suggest that, in contrast to A and B, adding CRRT at position C is unsafe and not advised for clinical use., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

A major challenge in developing blood-contacting medical devices is mitigating thrombogenicity of an intravascular device. Thrombi may interfere with device function or embolize from the device to occlude distant vascular beds with catastrophic consequences. Chemical interactions between plasma proteins and bioengineered surface occur at the nanometer scale; however, continuum models of blood predict local shear stresses that lead to platelet activation or aggregation and thrombosis. Here, an iterative approach to blood flow path design incorporating in silico, in vitro, and in vivo experiments predicted the occurrence and location of thrombi in an implantable hemofilter. Low wall shear stress (WSS) regions identified by computational fluid dynamics (CFD) predicted clot formation in vivo. Revised designs based on CFD demonstrated superior performance, illustrating the importance of a multipronged approach for a successful design process.

Overseas contingency operations which occur in areas lacking medical infrastructure pose challenges to the stabilization and transportation of critically ill patients. In particular, metabolic derangements resulting from acute kidney injury (AKI) make long-distance aeromedical evacuation risky. Here, we report the first modern use of in-flight continuous veno-venous hemofiltration (CVVH) for intercontinental aeromedical evacuation. Hospital and transport records were reviewed for a 31-yr-old male active duty service member who sustained 40% total body surface area full thickness burns after high-voltage electrical exposure in the southern Philippines. He was evacuated to the Burns Centre at Singapore General Hospital, where CVVH was initiated for anuric AKI secondary to rhabdomyolysis. The United States Army Institute of Surgical Research (USAISR) Burn Flight Team transported the patient to the USAISR Burn Center at Fort Sam Houston, TX, USA. CVVH was performed in-flight for 15 h out of 19.5 h of total flight time. CVVH settings were maintained as follows: blood flow 250 mL/min; replacement fluid rate 3,500 mL/h; and no ultra-filtrate removal. Unfractionated heparin at 500 units/h was utilized for regional anticoagulation. No filter clotting was encountered; a planned filter change was performed during a midway refueling stop. Pre-flight hyperkalemia was managed with low-potassium replacement fluid. No fluid was removed in the setting of large wound insensible losses. The patient remained hemodynamically stable and required no vasoactive medications. Continuous veno-venous hemofiltration can be used safely during high-altitude flight to evacuate casualties with AKI from distant contingency operations. The use of portable hemodialysis equipment in this case also proves the feasibility of deploying renal replacement therapies to more forward facilities than previously considered.

Background: Polymyxin B-immobilized fiber (PMX-F) columns are used as therapeutic interventions for septic shock. The clinical efficacy has been reported for 2-h applications, but their ability to adsorb endotoxin over longer treatments has not been fully elucidated. We hypothesized that PMX-F columns are capable of endotoxin removal for more than 2 h., Method: We designed closed circuits incorporating either a PMX-F column with an 8.5-mL priming volume (PMX-01R) or a sham-control column, and used inactivated fetal bovine serum as the circulating perfusate. Endotoxin was continuously injected at a fixed rate for 24 h, and perfusate endotoxin concentrations were measured at fixed time points. PMX-01R endotoxin adsorption was calculated from the difference in the endotoxin concentrations., Results: PMX-01R endotoxin adsorption increased continuously in a virtually linear manner., Conclusions: The PMX-01R column showed sustained endotoxin adsorption for at least 24 h. This indicated that PMX-F columns would be capable of clinical endotoxin removal for 24 h., (The Author(s). Published by S. Karger AG, Basel.)

This study describes a non-dilutive high-gradient magnetic separation (HGMS) device intended to continuously remove malaria-infected red blood cells (iRBCs) from the circulation. A mesoscale prototype device with disposable photo-etched ferromagnetic grid and reusable permanent magnet was designed with a computationally-optimized magnetic force. The prototype device was evaluated in vitro using a non-pathogenic analog for malaria-infected blood, comprised of 24% healthy RBCs, 6% human methemoglobin RBCs (metRBCs), and 70% phosphate buffer solution (PBS). The device provided a 27.0 ± 2.2% reduction of metRBCs in a single pass at a flow rate of 77 μL min -1 . This represents a clearance rate over 380 times greater throughput than microfluidic devices reported previously. These positive results encourage development of a clinical scale system that would economize time and donor blood for treating severe malaria.

Purpose To evaluate the immediate and long-term safety as well as thrombus-capturing efficacy for 5 weeks after implantation of an absorbable inferior vena cava (IVC) filter in a swine model. Materials and Methods This study was approved by the institutional animal care and use committee. Eleven absorbable IVC filters made from polydioxanone suture were deployed via a catheter in the IVC of 11 swine. Filters remained in situ for 2 weeks (n = 2), 5 weeks (n = 2), 12 weeks (n = 2), 24 weeks (n = 2), and 32 weeks (n = 3). Autologous thrombus was administered from below the filter in seven swine from 0 to 35 days after filter placement. Fluoroscopy and computed tomography follow-up was performed after filter deployment from weeks 1-6 (weekly), weeks 7-20 (biweekly), and weeks 21-32 (monthly). The infrarenal IVC, lungs, heart, liver, kidneys, and spleen were harvested at necropsy. Continuous variables were evaluated with a Student t test. Results There was no evidence of IVC thrombosis, device migration, caval penetration, or pulmonary embolism. Gross pathologic analysis showed gradual device resorption until 32 weeks after deployment. Histologic assessment demonstrated neointimal hyperplasia around the IVC filter within 2 weeks after IVC filter deployment with residual microscopic fragments of polydioxanone suture within the caval wall at 32 weeks. Each iatrogenic-administered thrombus was successfully captured by the filter until resorbed (range, 1-4 weeks). Conclusion An absorbable IVC filter can be safely deployed in swine and resorbs gradually over the 32-week testing period. The device is effective for the prevention of pulmonary embolism for at least 5 weeks after placement in swine. © RSNA, 2017.

Recently, intensive care physicians have focused on continuous hemodiafiltration with a cytokine-adsorbing hemofilter in the treatment of sepsis. We aimed to establish extracorporeal circulation in a rat sepsis model to evaluate the cytokine removal properties of mini-modules using two types of membrane materials. Rats were divided into polyester polymer alloy (PEPA) and cellulose triacetate (CTA) groups as membrane materials of mini-modules. One hour after 0.1 mg/kg of lipopolysaccharide administration, continuous hemofiltration (CHF) was started in each group. Plasma interleukin-6 (IL-6), an important mediator of sepsis, was measured over time during hemofiltration. The peak IL-6 concentration in PEPA group was approximately 13,000 pg/mL, in comparison to approximately 31,000 pg/mL in CTA group. IL-6 clearance in PEPA group was much more than CTA group. Since IL-6 was not detected in the filtrate in PEPA group, it was considered that IL-6 was adsorbed to the membrane. In conclusion, our results suggest that CHF with PEPA hemofilter can be suitable for removing IL-6 from the blood stream efficiently.

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Purpose: The aim of this study was to investigate the filtration efficacy of a 38-µm 1-layer screen filter based on Doppler registrations and video recordings of gaseous microbubbles (GME) observed in a microscope., Methods: The relative filtration efficacy (RFE) was calculated from 20 (n = 20) sequential bursts of air introduced into the Plasmodex® primed test circuit., Results: The main findings indicate that the RFE decreased (p = 0.00), with increasing flow rates (100-300 mL/min) through the filter screen. This reaction was most accentuated for GME below the size of 100 µm, where counts of GME paradoxically increased after filtration, indicating GME fragmentation. For GME sized between 100-250 µm, the RFE was constantly >60%, independently of the flow rate level. The video recording documenting the GME interactions with the screen filter confirmed the experimental findings., Conclusions: The 38-µm 1-layer screen filter investigated in this experimental setup was unable to trap gaseous microbubbles effectively, especially for GME below 100 µm in size and in conjunction with high flow rates.

Invasive candidiasis is common and often fatal in patients supported with extracorporeal membrane oxygenation (ECMO), and treatment relies on optimal antifungal dosing. The ECMO circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit. Fluconazole and micafungin were studied separately in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood, and flow was set to 1 L/min. Drug was dosed to achieve therapeutic concentrations. Each antifungal was added to a separate tube of blood to serve as a control. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point: (C t /C i )*100, with C t and C i the concentrations at time = t and 1 minute, respectively. After 24 hours of recirculation, mean recovery of fluconazole in the ECMO circuit (95-98%) and controls (101%) was high. In contrast, mean recovery of micafungin was dependent on the time and circuit configuration. Recovery at 4 hours was only 46% when a hemofilter was in-line but was much higher when the hemofilter was removed (91%). By 24 hours, however, micafungin recovery was low in all circuit configurations (26-43%), regardless of the presence of a hemofilter, as well as in the controls (57%). In conclusion, these results suggest that micafungin is extracted by the ECMO circuit, which may result in decreased drug exposure in vivo.

Introduction: Percutaneous hepatic perfusion (PHP) with melphalan is an effective treatment for patients with hepatic metastases, but associated with high rates of bone marrow depression. To reduce systemic toxicity, improvements have been made to the filtration system. In pre-clinical studies, the Delcath System's GEN2 filter was superior to the first-generation filters. In this clinical study, we analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter., Methods and Materials: Starting February 2014, two prospective phase II studies were initiated in patients with hepatic metastases from ocular melanoma or colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled patients, blood samples were obtained to determine filter efficiency and systemic drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg. Complications were assessed according to CTCAE v4.03. Response was assessed according to RECIST 1.1., Results: Pharmacokinetic analysis of blood samples showed an overall filter efficiency of 86% (range 71.1-95.5%). The mean filter efficiency decreased from 95.4% 10 min after the start of melphalan infusion to 77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen after up to 80.0% of 10 procedures, but was self-limiting and mostly asymptomatic. No hypotension-related complications or procedure-related mortality occurred., Conclusion: The GEN2 filter has a higher melphalan filter efficiency compared to the first-generation filters and a more consistent performance. PHP with the GEN2 filter appears to have an acceptable safety profile, but this needs further validation in larger studies.