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Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls
by
Ankawi, Ghada
,
Zhang, Jingxiao
,
Breglia, Andrea
in
Acute kidney injury
,
Artificial blood circulation
,
Care and treatment
2018
Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.
Journal Article
Renal Replacement Techniques in Septic Shock
by
Järvisalo, Mikko J.
,
Hellman, Tapio
,
Uusalo, Panu
in
Chemokines
,
Cytokine storm
,
Gram-positive bacteria
2021
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.
Journal Article
Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)
by
Hall, Anna
,
Crichton, Siobhan
,
Ostermann, Marlies
in
Acute renal failure
,
Adsorption
,
Care and treatment
2021
Background
The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.
Methods
This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.
Results
Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (
p
< 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period.
Conclusion
EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.
Trial registration
: NCT03231748, registered on 27th July 2017.
Journal Article
Effects of Weak Bedding Plane, Fault, and Extreme Rainfall on the Landslide Event of a High Cut-Slope
2022
High cut-slopes are widespread in engineering constructions and often converted into landslides. Some extreme circumstances facilitate the landslide process, such as the weak bedding plane, rainfall, and faults. Therefore, this paper intends to offer insights into the influence of the weak bedding plane, extreme rainfall as well as faults on the landslide process of the high cut-slope. In this paper, the Anling landslide in Anhui Province, China, is selected as an example. Geological surveys, displacement monitoring, data analysis, as well as numerical simulation are carried out. The entire excavation construction and landslide deformation process are simulated to reveal the formation mechanism of the landslide using the finite difference code, FLAC3D. The effects of the fault on the landslide and the effectiveness of adjusting protection measures by adding piles are investigated on the basis of the finite difference analysis. According to monitoring data and numerical simulation, the weak bedding plane and extreme rainfall are considered the main factors leading to the Anling landslide. Field investigation and numerical experiments indicate that the fault shall facilitate and accelerate the landslide process. The construction of piles in a suitable position for the landslide is a reasonable and economical measure to stabilize the landslide.
Journal Article
Kinetics of Serum-Free Light Chain Removal by High-Cutoff Hemodialysis in Patients with Multiple Myeloma and Acute Renal Failure
by
Weerman, Debora J.
,
Molog, Saskia
,
Diepenbroek, Adry
in
Acute Kidney Injury - blood
,
Acute Kidney Injury - therapy
,
Acute renal failure
2025
Background and objectives: Cast nephropathy is the main cause of acute renal failure in patients with multiple myeloma. There are conflicting data on whether removal of serum free light chains (sFLCs) with a high-cutoff (HCO) dialyzer has a favorable effect on the recovery of renal function. This may in part be explained by differences in the efficacy of sFLC removal by HCO dialysis and treatment responses to anti-plasma cell therapy between studies. We studied the removal of sFLCs during HCO treatment in detail in relation to treatment response. Materials and methods: Pre-dialysis serum and dialysate levels of sFLCs were simultaneously and repeatedly measured during the first two HCO treatments in 10 patients with kappa (κ)- and 5 patients with lambda (λ)-producing myeloma that presented with dialysis-dependent renal failure at our institution between 2009 and 2024. Results: The average change in sFLCs during 6 h treatments was −57 ± 13%, but it varied widely between −29% and −77%. Mean reductions in sFLCs were comparable for κ and λ (−61.4 ± 19.1% and −55 ± 16.7%, respectively; p = 0.78). The average clearance of sFLCs at 15 min after the start of HCO dialysis was 42.1 ± 8.5 and 27.4 ± 15.6 mL/min for κ and λ, respectively (p < 0.01). Clearances decreased to 27.2 ± 11.3 for κ and 13.8 ± 7.9 mL/min for λ after 6 h of HCO treatment (p = 0.042). Renal function recovered in 11 patients (73%). In three of the four patients whose renal function did not recover, sFLC levels were >5 g/L at any time beyond 2 weeks after the start of HCO treatment. Conclusions: Although the clearance of κ was higher compared to λ, reductions in sFLCs were similar for κ and λ. We speculate that this discrepancy is explained by greater adherence of λ to the HCO membrane. Patients whose renal function did not recover had less of a reduction in sFLC levels during HCO treatment, probably due to a suboptimal hematological response to anti-plasma cell therapy.
Journal Article
Improvement of electrochemical performance of LiNi0.5Co0.2Mn0.3O2 by LaF3 coating at high cut-off voltage
by
Zhang, Hailang
,
Yang, Huapeng
,
Zhao, Wentao
in
Batteries
,
Chemistry
,
Chemistry and Materials Science
2023
A simple wet chemical method was used to coat a layer of LaF
3
on the surface of LiNi
0.5
Co
0.2
Mn
0.3
O
2
(NCM523) to improve the electrochemical performance. Through the characterization of X-ray diffractometer (XRD), scanning electron microscope (SEM), X-ray energy dispersive spectrometer (EDS), and X-ray photoelectron spectroscopy (XPS), it can be seen that the LaF
3
coating can be uniformly coated on the surface of the material and will not change the crystal structure and micro-morphology of the material. In this work, the amount of LaF3 coating on the materials is 0.0 wt%, 0.5 wt%, 1.0 wt%, and 2.0 wt%, respectively. Under the condition of the optimum coating amount of 1 wt%, the rate performance and cycle performance of the coated material can be improved obviously. After 100 cycles at a high cut-off voltage of 4.6 V, the capacity retention of the 1 wt% LaF
3
coated material is 88.7%, which is higher than 80.4% of the bare material. And through EIS analysis, the coated material after 50 cycles still has excellent lithium ion diffusion kinetics. This may be due to the fact that an appropriate amount of LaF
3
coating can effectively avoid direct contact between cathode materials and electrolytes, inhibit the generation of oxygen vacancies, and reduce unnecessary side effects. This could provide a new idea for improving the electrochemical performance of LiNi
0.5
Co
0.2
Mn
0.3
O
2
at high cut-off voltage.
Journal Article
Sn-Doping and Li2SnO3 Nano-Coating Layer Co-Modified LiNi0.5Co0.2Mn0.3O2 with Improved Cycle Stability at 4.6 V Cut-off Voltage
by
Yan, Xiaoyan
,
Fan, Zhiqiang
,
Zhu, Huali
in
cathode material
,
high cut-off voltage
,
LiNi0.5Co0.2Mn0.3O2
2020
Nickel-rich layered LiNi1−x−yCoxMnyO2 (LiMO2) is widely investigated as a promising cathode material for advanced lithium-ion batteries used in electric vehicles, and a much higher energy density in higher cut-off voltage is emergent for long driving range. However, during extensive cycling when charged to higher voltage, the battery exhibits severe capacity fading and obvious structural collapse, which leads to poor cycle stability. Herein, Sn-doping and in situ formed Li2SnO3 nano-coating layer co-modified spherical-like LiNi0.5Co0.2Mn0.3O2 samples were successfully prepared using a facile molten salt method and demonstrated excellent cyclic properties and high-rate capabilities. The transition metal site was expected to be substituted by Sn in this study. The original crystal structures of the layered materials were influenced by Sn-doping. Sn not only entered into the crystal lattice of LiNi0.5Co0.2Mn0.3O2, but also formed Li+-conductive Li2SnO3 on the surface. Sn-doping and Li2SnO3 coating layer co-modification are helpful to optimize the ratio of Ni2+ and Ni3+, and to improve the conductivity of the cathode. The reversible capacity and rate capability of the cathode are improved by Sn-modification. The 3 mol% Sn-modified LiNi0.5Co0.2Mn0.3O2 sample maintained the reversible capacity of 146.8 mAh g−1 at 5C, corresponding to 75.8% of its low-rate capacity (0.1C, 193.7mAh g−1) and kept the reversible capacity of 157.3 mAh g−1 with 88.4% capacity retention after 100 charge and discharge cycles at 1C rate between 2.7 and 4.6 V, showing the improved electrochemical property.
Journal Article
High cut-off membranes in patients requiring renal replacement therapy: a systematic review and meta-analysis
2023
Whether high cut-off (HCO) membranes are more effective than high-flux (HF) membranes in patients requiring renal replacement therapy (RRT) remains controversial. The aim of this systematic review was to investigate the efficacy of HCO membranes regarding the clearance of inflammation-related mediators, β2-microglobulin and urea; albumin loss; and all-cause mortality in patients requiring RRT.
We searched all relevant studies on PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure, with no language or publication year restrictions. Two reviewers independently selected studies and extracted data using a prespecified extraction instrument. Only randomized controlled trials (RCTs) were included. Summary estimates of standardized mean differences (SMDs) or weighted mean differences (WMDs) and risk ratios (RRs) were obtained by fixed-effects or random-effects models. Sensitivity analyses and subgroup analyses were performed to determine the source of heterogeneity.
Nineteen RCTs involving 710 participants were included in this systematic review. Compared with HF membranes, HCO membranes were more effective in reducing the plasma level of interleukin-6 (IL-6) (SMD -0.25, 95% confidence interval (CI) -0.48 to -0.01, P = 0.04, I2 = 63.8%); however, no difference was observed in the clearance of tumor necrosis factor-α (TNF-α) (SMD 0.03, 95% CI -0.27 to 0.33, P = 0.84, I2 = 4.3%), IL-10 (SMD 0.22, 95% CI -0.12 to 0.55, P = 0.21, I2 = 0.0%), or urea (WMD -0.27, 95% CI -2.77 to 2.23, P = 0.83, I2 = 19.6%). In addition, a more significant reduction ratio of β 2 -microglobulin (WMD 14.8, 95% CI 3.78 to 25.82, P = 0.01, I2 = 88.3%) and a more obvious loss of albumin (WMD -0.25, 95% CI -0.35 to -0.16, P < 0.01, I2 = 40.8%) could be observed with the treatment of HCO membranes. For all-cause mortality, there was no difference between the two groups (risk ratio [RR] 1.10, 95% CI 0.87 to 1.40, P = 0.43, I2 = 0.0%).
Compared with HF membranes, HCO membranes might have additional benefits on the clearance of IL-6 and β 2-microglobulin but not on TNF-α, IL-10, and urea. Albumin loss is more serious with the treatment of HCO membranes. There was no difference in all-cause mortality between HCO and HF membranes. Further larger high-quality RCTs are needed to strengthen the effects of HCO membranes.
Journal Article
Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review
by
Adembri, Chiara
,
De Gaudio, A. Raffaele
,
Novelli, Andrea
in
Acute Kidney Injury - blood
,
Acute Kidney Injury - therapy
,
Anti-Bacterial Agents - pharmacokinetics
2016
Background
Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT.
Method
Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported.
Results
Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2–2.3 L/h for CVVH, 0.9–2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only.
Conclusions
Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings.
Journal Article
Real world analysis of high-cut-off (HCO) hemodialysis with bortezomib-based backbone therapy in patients with multiple myeloma and acute kidney injury
2021
Background
In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic.
Methods
Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed.
Results
The median number of HCO hemodialysis sessions was 11 (range 1–42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m
2
. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent.
Conclusion
The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.
Journal Article