Clinical Assessment of Continuous Hemodialysis with the Medium Cutoff EMiC®2 Membrane in Patients with Septic Shock.

INTRODUCTION: At the time of renal replacement therapy, approximately 20% of critically ill patients have septic shock. In this study, medium cutoff (MCO) continuous venovenous hemodialysis (CVVHD) was compared to high-flux membrane continuous venovenous hemodiafiltration (CVVHDF) in terms of hemodynamic improvement, efficiency, middle molecule removal, and inflammatory system activation. METHODS: This is a monocenter crossover randomized study. Between December 31, 2017, and December 31, 2019, 20 patients with septic shock and stage 3 acute kidney injury (AKI) admitted to 2 Italian ICUs were enrolled. All patients underwent CVVHD with Ultraflux® EMiC®2 and CVVHDF with AV1000S® without washout. Each treatment lasted 24 h. RESULTS: Compared to AV1000S®-CVVHDF, EMIC®2-CVVHD normalized cardiac index (ß = -0.64; p = 0.02) and heart rate (ß = 5.72; p = 0.01). Interleukin-8 and myeloperoxidase removal were greater with AV1000S®-CVVHDF than with EMiC®2-CVVHD (ß = 0.35; p < 0.001; ß = 0.43; p = 0.03, respectively). Leukocytosis improved over 24 h in EMiC®2-CVVHD-treated patients (ß = 4.13; p = 0.03), whereas procalcitonin levels decreased regardless of the modality (ß = 0.89; p = 0.01) over a 48-h treatment period. Reduction rates, instantaneous plasmatic clearance of urea, creatinine, and ß2-microglobulin were similar across modalities. ß2-Microglobulin removal efficacy was greater in the EMiC®2 group (ß = 0-2.88; p = 0.002), while albumin levels did not differ. Albumin was undetectable in the effluent in both treatments. DISCUSSION: In patients with septic shock and severe AKI, the efficacy of uremic toxin removal was comparable between MCO-CVVHD and CVVHDF. Further, MCO-CVVHD was associated with improved hemodynamics. Fraction of filtration and transmembrane pressure reduction and the maintenance of equal efficacy might be the key features of CVVHD with MCO membranes in critically ill patients.

Effects of cement addition and briquetting of rock wool on its geomechanical stability in landfills.

Landfilling of mineral wool waste in big bags at separate landfill compartments is required in Austria. This results in enormous differences in the Young's moduli between common construction and demolition (C&D) waste compartments and mineral wool compartments, which causes severe accidents in terms of overturned vehicles due to sudden subsidence of the subsurface. Conditioning of mineral wool waste might be applied to adjust its geomechanical behaviour to that of common C&D waste but has never been investigated scientifically before. In this study we compare three scenarios for the conditioning of rock wool for landfilling: (A) loosely packing, (B) cutting comminution + cement addition and (C) cutting comminution + cement-supported briquetting. The performance of the different sample bodies under landfill conditions was simulated at the lab scale by cyclic loading (1223-3112 N, up to 160 cycles) using a 'Wille Geotechnik UL 300' press. The deformation was monitored during the experiment and Young's modulus was derived graphically, whereas the test execution was piston controlled. The Young's modulus increased during the experiments from 0.2 MPa to 4.6 MPa for scenario (A), from 0.6 MPa to 20.5 MPa for scenario (B) and from 7.5 MPa to 111.0 MPa for scenario (C). These results show that a combination of comminution and cement-supported briquetting significantly increases the geotechnical performance of mineral wool waste with respect to landfilling, which is still three orders of magnitude below that of common C&D waste, which is in the range of 30,000 MPa.

Kinetics of Linezolid in Continuous Renal Replacement Therapy: An In Vitro Study.

BACKGROUND: Continuous veno-venous hemofiltration (CVVH) could affect the pharmacokinetic profile of linezolid (LZD). The aim of this study was to evaluate the LZD extracorporeal clearance using an in vitro CVVH model. METHODS: A sham miniaturized CVVH circuit (CARPEDIEM; Bellco, Mirandola, Italy) was set up with a polysulfone hemofilter (0.25 m; cutoff 50,000 Da) for 240 minutes using normal saline solution (0.9% wt/vol NaCl) and blood (n = 6) spiked with LZD. Drug solution samples were collected during CVVH at 10, 30, 60, 120, and 240 minutes. LZD levels were measured by high-performance liquid chromatography. RESULTS: Results were used to estimate pharmacokinetic parameters. The LZD baseline level decreased from 17.24 ± 0.54 to 9.73 ± 4.85 mg/L and from 11.75 ± 0.08 to 5.01 ± 0.67 mg/L in the first 10 minutes, and then increased to 13.2 ± 3.10 and 7.4 ± 0.71 mg/L in normal saline solution and blood, respectively. Mass balance analysis reported a rapid adsorption of LZD onto a polysulfone membrane followed by its release: a rebound phenomenon occurred. CONCLUSIONS: Although further studies are necessary to clarify this phenomenon, LZD level variations observed in our study should be considered to avoid antimicrobial underexposure. Several strategies are available for adjusting the dosage regimen of LZD, but therapeutic drug monitoring is highly recommended when it is used.

Optimizing a kidney stress test to evaluate renal functional reserve.

BACKGROUND: Renal function reserve (RFR) describes the capacity of the kidney to increase glomerular filtration rate (GFR) in response to physiological or pathological stimuli. The scope of our study was to evaluate the optimal level of stimulation using different doses of protein load (PL) for a standard renal stress test (RST). METHODS: 18 young healthy individuals were given sessions of PL with 1 and 2 g/kg body weight. Endogenous creatinine clearance was calculated. Baseline GFR (bGFR) and stress GFR (sGFR) (post-PL) were obtained; RFR is the difference between stress and baseline GFR. A p-value < 0.05 was considered statistically significant. RESULTS: Mean bGFR was 107.97 ± 12.33 mL/min/1.73m2. sGFR with 1 and 2 g PL were significantly higher than bGFR in all subjects. The sGFR after 2 g PL (141.75 ± 19.90 mL/min/1.73m2) was not statistically different from the sGFR after 1 g PL (142.37 ± 22.35 mL/min/1.73m2). sGFR and therefore RFR were independent from the value of bGFR. CONCLUSIONS: We found no difference between 1 and 2 g/kg body weight PL to elicit sGFR. RST may be useful to predict susceptibility and risk of developing acute kidney injury and/or progression to chronic kidney disease. RST uncovers the possible loss of renal functional mass when this condition is not manifested clinically. Further studies are needed to set this hypothesis.

Fabry's disease: an example of cardiorenal syndrome type 5.

Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry's disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors-and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

Pumps in wearable ultrafiltration devices: pumps in wuf devices.

The wearable artificial kidney (WAK) is a device that is supposed to operate like a real kidney, which permits prolonged, frequent, and continuous dialysis treatments for patients with end-stage renal disease (ESRD). Its functioning is mainly related to its pumping system, as well as to its dialysate-generating and alarm/shutoff ones. A pump is defined as a device that moves fluids by mechanical action. In such a context, blood pumps pull blood from the access side of the dialysis catheter and return the blood at the same rate of flow. The main aim of this paper is to review the current literature on blood pumps, describing the way they have been functioning thus far and how they are being engineered, giving details about the most important parameters that define their quality, thus allowing the production of a radar comparative graph, and listing ideal pumps' features.

Cerebral fat embolism after traumatic bone fractures: a structured literature review and analysis of published case reports.

BACKGROUND: The incidence of cerebral fat embolism (CFE) ranges from 0.9-11%, with a mean mortality rate of around 10%. Although no univocal explanation has been identified for the resulting fat embolism syndrome (FES), two hypotheses are widely thought: the 'mechanical theory', and the 'chemical theory'. The present article provides a systematic review of published case reports of FES following a bone fracture. METHODS: We searched MEDLINE, Web of Science and Scopus to find any article related to FES. Inclusion criteria were: trauma patients; age ≥ 18 years; and the clinical diagnosis of CFE or FES. Studies were excluded if the bone fracture site was not specified. RESULTS: One hundred and seventy studies were included (268 cases). The male gender was most prominent (81.6% vs. 18.4%). The average age was 33 years (±18). The mean age for males (29 ± 14) was significantly lower than for females (51 ± 26) (p < 0.001). The femur was the most common fracture site (71% of cases). PFO was found in 12% of all cases. Univariate and multivariate regression analyses showed the male gender to be a risk factor for FES: RR 1.87 and 1.41, respectively (95%CI 1.27-2.48, p < 0.001; 95%CI 0.48-2.34, p < 0.001). CONCLUSIONS: FES is most frequent in young men in the third decades of life following multiple leg fractures. FES may be more frequent after a burst fracture. The presence of PFO may be responsible for the acute presentation of cerebral embolisms, whereas FES is mostly delayed by 48-72 h.

Validation of a simple and economic HPLC-UV method for the simultaneous determination of vancomycin, meropenem, piperacillin and tazobactam in plasma samples.

Critically ill patients are often affected by several pathophysiological conditions requiring antibiotic administration and, frequently, extracorporeal therapy that significantly alter the normal pharmacokinetics of drugs. Therapeutic drug monitoring (TDM) may assist to establish the correct antibiotic dosage, but a TDM service is usually available only for some aminoglycosides and glycopeptides. The aim of this study is the validation of an HPLC-UV method for the simultaneous quantification of meropenem, vancomycin, piperacillin and tazobactam in human plasma samples. The analytes were extracted from 250 µL of human plasma by the addition of acetonitrile for protein precipitation. After evaporation to dryness of the solvent, samples were reconstituted with 250 µL of mobile phase, and 100 µL were injected in HPLC. Chromatographic analysis was performed using a Kinetex C18 column and an UV/Vis detector set at 220 and 298 nm. The mobile phase was a mixture of phosphate buffer 0.1 M pH 3.15 and methanol in gradient, delivered at 1 mL/min. The method was validated over clinical concentration ranges. For all the analytes, the lower limit of quantification was 1 µg/mL, and the calibration curves were linear between 1 and 100 µg/mL, with coefficients of determination ≥ 0.999. Intra-day precision was < 4%, while inter-day precision was < 7% for each analyte. The applicability of the method has been evaluated by analysing plasma samples collected from 4 critically ill patients undergoing continuous renal replacement therapy. Moreover, the analysis of vancomycin with VANC Flex® confirmed a good correlation between the results of HPLC-UV and commercially available kits usually used by TDM service. The method we developed only requires a small volume of plasma and uses the same sample preparation protocol, stationary phase and elution conditions for all analytes. This method offers the additional advantages of simple and rather inexpensive sample preparation and instrumentation, features that make this method an easy implementation for a general TDM laboratory.

Modeling of Internal Filtration in Theranova Hemodialyzers.

High retention onset (HRO) is the designation for a new class of hemodialysis membranes. A unique characteristic of this class is the highly selective and controlled porosity resulting in sieving properties that provide a clinically desirable balance between middle/large molecular weight solute removal and albumin loss. Another defining feature of this membrane class is the relatively small fiber diameter, which produces high convective volumes in the form of internal filtration. The aim of the present study was to estimate, by semi-empirical methods, convective volumes for 2 new HRO dialyzers: Theranova 400 and Theranova 500 (Baxter International Inc., Deerfield, IL, USA). Axial blood and dialysate compartment pressure drop along with transmembrane pressure, measured in vitro with blood (Qb = 300 or 400 mL/min; Qd = 500 mL/min; net ultrafiltration rate = 0), served as input parameters for 3 different models: linear, geometric, and (non-linear) mathematical. Based on the most rigorous mathematical model, the estimated convective volumes were 1,661 mL/h (Qb = 300 mL/min) and 1,911 mL/h (Qb = 400 mL/min) for Theranova 400 and 1,864 mL/h (Qb = 300 mL/min) and 1,978 mL/h (Qb = 400 mL/min) for Theranova 500. These results suggest that the unique fiber characteristics of this new class of membranes provide substantial convective volumes without the need for exogenous substitution fluid. As such, HRO membranes are a major end-stage renal disease treatment advance in the quest to enhance the removal of larger-sized uremic toxins.

Prospective, Randomized, Multicenter, Controlled Trial (TRIATHRON 1) on a New Antithrombogenic Hydrophilic Dialysis Membrane.

INTRODUCTION: Hemodialysis treatment requires anticoagulation to prevent thrombosis of the dialyzer. The Hydrolink® (NV series; Toray) has been designed to reduce thrombotic complications by increasing membrane hydrophilic properties. Previous studies have confirmed reduced platelet activation, improved removal of ß2-microglobulin and excellent small-solute removal. METHODS: We designed a prospective, multi-centered, randomized clinical study to compare the antithrombogenic effects (platelet count) of NV dialyzers versus conventional treatment. To compare the possibility of performing heparin-free dialysis, we carried out progressive heparin reduction tests. Patients with an average platelet count lower than 170,000 cells/mm3 using standard high flux membranes in the 6 months prior to the study were enrolled and randomized. Patients were either dialyzed for 6 months without changing the previous membrane (control group) or treated with the Hydrolink® membrane (NV group). After the third week, the heparin reduction test was conducted for 5 weeks in order to assess the minimum amount of anticoagulant needed to safely perform a 4-hour dialysis treatment. Performance and safety were evaluated measuring platelet count and activation, middle-molecule removal rate and nutritional status. RESULTS: We found no significant difference in platelet count, platelet activation factors ß-thromboglobulin and platelet factor 4 (PF-4), between the groups. More patients in the study group reached heparin-free dialysis without clotting events during the heparin reduction test. The NV dialyzers displayed anti-thrombogenic effects as compared to conventional dialyzers. CONCLUSIONS: The NV dialyzer series is safe with no adverse events reported. Further studies are required to understand the mechanisms of anti-thrombogenic effects.

Pharmacokinetic analysis of antibiotic adsorption (vancomycin and teicoplanin) by the Lixelle extracorporeal unit.

PURPOSE: The pharmacokinetic properties of vancomycin (VAN) and teicoplanin (TEC) may be affected by adsorption during hemofiltration as well as hemoperfusion therapies. The aim of this in vitro study was to investigate VAN and TEC removal adsorption kinetics with mass balance analysis by direct hemoperfusion (DHP) with the Lixelle S-35 cartridge (Lixelle, Kaneka Corporation, Tokyo). METHODS: Mock DHP was performed for 120 min using VAN and TEC solutions (46.08 ± 0.81 and 74.79 ± 1.24 mg/l per N = 6). Clinical plasma antibiotic concentrations were circulated in a closed circuit simulating DHP using an adsorption column (Lixelle S-35) at flow rate of 250 ml/min. Samples were collected at 10, 60, and 120 min through both arterial and venous ports; drug levels were measured with particle enhanced turbidimetric inhibition immunoassay and fluorescence polarization immunoassay. All tests were performed in triplicate. RESULTS: Results subsequent to DHP at the primary assessment interval for VAN mass was 49.06 ± 1.47 mg, indicating a significant reduction of the starting mass (94.74 ± 1.63 mg). The observed reduction of TEC levels greatly exceeded that of VAN at the first interval (10 min). At 120 min of DHP, the estimated mass adsorption of VAN was 45.68 ± 2.26 mg, while the mesured total TEC mass adsorbed was 126.86 ± 0.91 mg. CONCLUSIONS: A VAN adsorption plateau indicating the VAN loading dose may be required in patients receiving DHP with the Lixelle S-35. The total TEC mass was adsorbed subsequent to 60 min of circulation, so the loading dose should be closely considered. In addition, the Lixelle S-35 may represent an option as a rescue therapy in accidental overdose of TEC.

New option for the treatment of hyperbilirubinemia: in vitro direct hemoperfusion with the Lixelle S-35.

PURPOSE: Limited options are available to treat critically ill patients with acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF), therefore we set up an in vitro study in order to test the bilirubin adsorption capacity of the Lixelle S-35 cartridge by direct hemoperfusion (DHP). METHODS: Mock DHP was performed for 120 min using hyperbilirubinic human plasma and blood obtained from a plasmapheresis and exchange transfusion, respectively. The total bilirubin (TBIL) and direct bilirubin (DBIL) baseline concentrations were 17.57 ± 0.53, 12.57 ± 0.23 mg/dl for plasma and 23.10 ± 0.47, 15.37 ± 0.24 mg/dl for blood. Plasma and blood were separately circulated in a closed circuit simulating DHP using an adsorption column (Lixelle S-35) at flow rate of 100 ml/min. TBIL and DBIL levels were measured at 10, 30, 60, and 120 min from arterial and venous ports and assessed with the Jendrassik-Grof method. All tests were performed in triplicate. RESULTS: The total removal subsequent to DHP (120 min) was seen as TBIL in plasma 55.60%, TBIL in blood 62.16%, DBIL plasma 58.87%, DBIL in blood 64.41%, respectively. The estimated mass adsorption of TBIL in plasma 958.20 ± 5.72 mg, TBIL in blood 1233.60 ± 10.22 mg, DBIL in plasma 680.70 ± 10.68, DBIL in blood 818.10 ± 4.68, respectively. CONCLUSIONS: The bilirubin adsorption rates after DHP were very promising for both hyperbilirubinic plasma and blood. Although further in vitro investigations are required, including comparisons with other techniques, these findings have shown that the Lexille S-35 should represent an option for the management of hyperbilirubinemia in ALF or AoCLF.

Quality evaluation of JAMA Patient Pages on diabetes using the Ensuring Quality Information for Patient (EQIP) tool.

CONTEXT: Many medical journals provide patient information leaflets on the correct use of medicines and/or appropriate lifestyles. Only a few studies have assessed the quality of this patient-specific literature. OBJECTIVE: The purpose of this study was to evaluate the quality of JAMA Patient Pages on diabetes using the Ensuring Quality Information for Patient (EQIP) tool. METHOD: A multidisciplinary group of 10 medical doctors analyzed all diabetes-related Patient Pages published by JAMA from 1998 to 2010 using the EQIP tool. Inter-rater reliability was assessed using the percentage of observed total agreement (p(o)). A quality score between 0 and 1 (the higher score indicating higher quality) was calculated for each item on every page as a function of raters' answers to the EQIP checklist. A mean score per item and a mean score per page were then calculated. DATA SUMMARY: We found 8 Patient Pages on diabetes on the JAMA web site. The overall quality score of the documents ranged between 0.55 (Managing Diabetes and Diabetes) and 0.67 (weight and diabetes). p(o) was at least moderate (>50%) for 15 of the 20 EQIP items. Despite generally favorable quality scores, some items received low scores. The worst scores were for the item assessing provision of an empty space to customize information for individual patients (score=0.01, p(o)=95%) and patients involvement in document drafting (score=0.11, p(o)=79%). CONCLUSIONS: The Patient Pages on diabetes published by JAMA were found to present weak points that limit their overall quality and may jeopardize their efficacy. We therefore recommend that authors and publishers of written patient information comply with published quality criteria. Further research is needed to evaluate the quality and efficacy of existing written health care information.

Formulação de leite em pó enriquecido com ferro / Formulation of iron-enriched powdered milk

Este trabalho objetivou estudar o enriquecimento de leite em pó com duas fontes diferentes de ferro: sulfato ferroso e ferro aminoácido quelato. As fontes de ferro foram adicionadas antes e após a secagem do leite. Foram estadadas a reconstituição, a estabilidade oxidativa e a biodisponibilidade das fontes de ferro. Quanto à forma de enriquecimento não houve diferença entre as características estudadas. Ambos os processos tecnológicos mostraram-se simples e de fácil execução em laboratório. A estabilidade oxidativa do leite enriquecido foi maior quando se utilizou ferro aminoácido quelato e ambas as fontes apresentou mior biodisponibilidade in vitro (31,81 por cento) que o sulfato ferroso (17,41 por cento). A biodisponibilidade in vivo, deduzida, foi de 15,45 por cento para o ferro aminoácido quelato e de 8,66 por cento para o sulfato ferroso. O ferro aminoácido quelato mostrou melhor estabilidade oxidativa e melhor biodisponibilidade comparado com o sulfato ferroso, constituindo boa fonte para o enriquecimento do leite em pó.