The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Optimal energy management of distributed generation in micro-grids using artificial bee colony algorithm.

The use of renewable energy sources in energy distribution networks as distributed generation sources for dispersed and low consumption loads in remote areas such as remote villages and islands with low population can be a proper solution for reducing economic costs, reducing environmental pollutions and increasing energy efficiency. The purpose of this paper is optimal operation management of micro-grids by considering the existing capacities in the electricity market. In fact the microgrid operator, which is responsible for the safe operation of the network, should consider a process for planning in the network that takes into account all benefits of micro-grid's components. In other words, enough reliability for generation resources in these networks should be created in order to reduce costs and environmental pollution from energy production. In this paper, the artificial bee colony (ABC) algorithm has been used to minimize the costs and environmental pollutions by providing the optimal production power of distributed generation.

Validity of Intermittent Infusion Hemodiafiltration.

BACKGROUND: Intermittent infusion hemodiafiltration (I-HDF) has been developed to prevent a rapid drop in blood pressure during a dialysis session and to improve peripheral circulation. In Japan, >10,000 dialysis patients underwent treatment with I-HDF in 2017, and the number of dialysis patients is increasing year by year. I-HDF involves the intermittent infusion of ultrapure dialysis fluid or sterile nonpyrogenic substitution fluid, for example, at a volume of 200 mL and a rate of 150 mL/min by backfiltration every 30 min during treatment. The total infusion volume can therefore be estimated at 200 (mL) × 7 (infusions) or 1.4 L/session. I-HDF may be regarded as online HDF with a very small replacement volume. SUMMARY: Several clinical trials of I-HDF have been conducted in Japan. (1) In a 2007 study, despite there being no differences noted in the volume of water removal between hemodialysis (HD) and I-HDF, a significantly lower rate of reduction in the time-averaged blood volume was seen in I-HDF than in HD, so the plasma refilling rate was greater during I-HDF. (2) In a 2015 study, at 13 weeks after a switch from HD, I-HDF was found to be significantly superior to HD in terms of the incidence of events needing intervention by medical staff. However, significantly lower blood ß2-microglobulin (MG) and α1-MG levels were observed in the predilution online HDF (pre-HDF) group than in the I-HDF group, and the amount of albumin leak was lower in the I-HDF group than in the pre-HDF group. (3) In a 2017 study, compared with HD, I-HDF was associated with a reduced number of interventions for intradialytic hypotension and less severe tachycardia, suggesting less sympathetic stimulation during I-HDF. Key messages: I-HDF is a valid treatment option because it is associated with an increased plasma refilling rate and fewer interventions needed by medical staff.

Relationship between Dose of Bolus Dialysate Infusion and Blood Pressure in Intermittent Infusion Hemodiafiltration.

BACKGROUND: Intermittent infusion hemodiafiltration is a recently developed convective method of renal replacement therapy using cyclic back-filtration infusion. Quick and regular infusion prevents intradialytic hypotension. However, the optimal dose of bolus dialysate infusion required to stabilize blood pressure has not been reported. Here, we investigated the relationship between the dose of bolus dialysate infusion and blood pressure. SUMMARY: A total of 77 patients on maintenance hemodialysis were enrolled in this study. Dialysate was infused rapidly by backward filtration at a rate of 150 mL/min at 30-min intervals using an automated dialysis machine. The effects with two bolus infusion volumes (100 and 200 mL) were compared, each for an observation period of 2 weeks. Systolic blood pressure (SBP) was measured at the start and at the end of each dialysis session, and the highest SBP and lowest SBP measurements were also recorded. Patients were divided according to dry weight into a <52 kg group and a ≥52 kg group, and various parameters were compared between the 100 and 200 mL bolus infusion volumes in each group. Among patients in the <52 kg group, SBP did not vary at any of the time points. However, for patients in the ≥52 kg group, SBP at the end of treatment was significantly lower in the 100-mL group than in the 200-mL group (141 ± 20 vs. 144 ± 21 mm Hg, p = 0.041), and the minimum SBP was also lower in the 100-mL group than in the 200-mL group (127 ± 17 vs. 131 ± 18 mm Hg, p = 0.010). Key Messages: Among patients with a dry weight of ≥52 kg, blood pressure was more stable when a bolus fluid volume of 200 mL was used, compared with a volume of 100 mL. However, for patients with a dry weight of <52 kg, the significance of the difference in bolus fluid volumes disappeared. Thus, the replacement fluid volume might be better determined based on the patient's dry weight. TRIAL REGISTRATION: UMIN 000028145, Registered July 10, 2017.

Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055.

Lactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with multifunctional effects, including the prevention of influenza A virus infection in mice, reduction of adipocyte size in mice, and increased lifespan in C. elegans. We investigated whether LG2055 exhibits antiviral activity against respiratory syncytial virus (RSV), a global pathogen for which a preventive strategy is required. Following oral administration of LG2055 in mice, the RSV titre in the lung was significantly decreased, while body weight was not decreased after virus infection. Additionally, the elevated expression of pro-inflammatory cytokines in the lung upon RSV infection decreased after LG2055 administration. Moreover, interferon and interferon stimulated genes were upregulated by LG2055 treatment. Comparative cellular proteomic analysis revealed that SWI2/SNF2-related CREB-binding protein activator protein (SRCAP) was a candidate for the antiviral activity of LG2055 against RSV. There was a positive correlation between the inhibition of RSV replication and the suppression of SRCAP expression and RSV replication was suppressed by SRCAP silencing. Since SRCAP is a scaffold protein to which viral non-structural proteins bind, the downregulation of SRCAP induced by LG2055 could provide new insights about the inhibition of RSV replication. In summary, our study demonstrated that LG2055 has prophylactic potential against RSV infection.

Intermittent Infusion Hemodiafiltration: The Principle and Its Clinical Application.

The present study aimed to propose a new hemodiafiltration (HDF) method (intermittent infusion HDF) that repeats intermittent infusion during hemodialysis to temporarily enhance peripheral circulation and improves solute removal efficiency through (a) correcting blood distribution (increase in effective vascular surface area), (b) stirring body fluids, and (c) promoting solute removal and examining its clinical effects.

Clinical Effectiveness of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared with Predilution On-Line Hemodiafiltration.

BACKGROUND: In conventional hemodialysis (HD) treatment, excessive water removal sometimes induces a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF) has been developed to improve patients' peripheral circulation by repeated intermittent infusion during HD treatment. SUMMARY: A prospective, multicenter, parallel group comparative trial examined the clinical effectiveness of I-HDF compared with predilution on-line HDF (pre-HDF), the most popular on-line HDF therapy in Japan. Patients were allocated to 2 groups after matching for age (± 5 years), dry weight (± 5 kg), and presence/absence of diabetes. After informed consent was obtained, 36 patients (18 pairs) participated in the trial. The results showed no difference in clinical condition or quality of life (QOL) scores between the 2 therapy groups. The rate of reduction in systolic blood pressure initially showed no difference between the groups, but decreased slightly as the trial proceeded after changing from HD therapy. There was also no difference in the incidence rate of treatments initially, although this significantly decreased in both groups as the trial proceeded. Rates of ß2-microglobulin removal were significantly higher in the pre-HDF group than in the I-HDF group. At the same time, the amount of albumin leakage during treatment was significantly greater in the pre-HDF group. Key Messages: The clinical condition and QOL of patients receiving I-HDF was not inferior to those receiving pre-HDF. Pre-HDF demonstrated a significantly higher removal rate of middle- and larger-molecular-weight solutes and higher albumin leakage compared with I-HDF.

In vitro study of removal of protein-bound toxins.

Protein-bound toxins are not efficiently removed by conventional hemodialysis techniques. In order to improve the removal of protein-bound toxins, we performed an in vitro study to evaluate the effects of dilution and pH change on the dissociation of protein-bound toxins from albumin. Human plasma harvested by therapeutic apheresis treatment was diluted with saline or isotonic NaHCO3 solution, and the amounts of the free fractions of indoxyl sulfate (IS) and homocysteine were determined. The results suggested that IS was dissociated easily from albumin by dilution and pH change; higher dilution was associated with more effective removal and a greater increase of the free fraction of IS. However, these methods did not facilitate dissociation of homocysteine from albumin. Effective removal of some protein-bound toxins may be achieved by applying dilution and pH change methods to blood purification techniques, such as pre-dilution on-line hemodiafiltration.

Development of intermittent infusion hemodiafiltration using ultrapure dialysis fluid with an automated dialysis machine.

To reduce the potential occurrence of hypotension during a dialysis treatment, intermittent infusion hemodiafiltration (I-HDF) using back filtration with an ultrapure dialysis fluid was developed. Under typical I-HDF treatment conditions, some 200-300 ml of ultrapure dialysis fluid was infused into the blood component through the dialyzer at a rate of 100 ml/min, every 30 min. A multicenter clinical trial was carried out to evaluate the clinical effectiveness of I-HDF compared with standard hemodialysis (SHD). The peripheral blood flow rate of each patient as detected with a laser flow meter increased for each I-HDF infusion. A significantly lower value for averaged blood volume reduction was obtained with I-HDF compared with SHD in spite of there being no difference in the total amount of water removal. The amount of normalized solute removal, cleared space for inorganic phosphate and α1-microglobulin (α1-MG) during a treatment were higher with I-HDF. Moderate α1-MG K reduction was found in I-HDF due to the prevention of membrane fouling by intermittent back filtration of the dialysis fluid. I-HDF using an automated dialysis machine was effective for improvement of the peripheral circulation of dialysis patients.

An adhesin-like protein, Lam29, from Lactobacillus mucosae ME-340 binds to histone H3 and blood group antigens in human colonic mucus.

A cell-surface 29-kDa protein (Lam29, cysteine-binding protein of the ABC transporter) from Lactobacillus mucosae ME-340 showed an adhesin-like property for human ABO blood group antigens expressed on the gastrointestinal mucosa. In addition, here we report that Lam29 also bound to an 18-kDa protein on human colonic mucus. By ligand blot assay and N-terminal amino acid sequence of the protein, it was identified as human histone H3. By ligand blot and microplate binding assays with recombinant histone H3, binding between Lam29 and histone H3 was confirmed. The adhesion of ME-340 cells to histone H3 was significantly inhibited by 26% after the addition of 2.5 mg/mL Lam29 as compared to the absence of Lam29 (p<0.01). By GHCl extraction and transcription attenuation of ME-340 cells, binding reduction of ME340 cells against histone H3 was detected at 12% and 13% respectively, as compared to control cells by the BIACORE assay (p<0.01). These data indicate that Lam29 shows multiple binding activities to blood group antigens and histone H3 in human colonic mucus. This is the first report to indicate that lactobacilli expressing Lam29 adhere to histone H3 on gastrointestinal mucosa.

Modification of the leukapheresis procedure for use in rhesus monkeys (Macaca mulata).

One of the most serious problems in applying leukapheresis to human infants is the large extracorporeal blood volume (ECV), resulting in substantial loss of platelets and red blood cells (RBCs). In this study, we developed a safe and effective modified procedure to collect peripheral blood stem cells (PBSCs) from rhesus monkeys (Macaca mulata) using a Baxter CS3000+ Blood Cell Separator (Baxter, Deerfield, IL) with several devices that reduced chamber size and shortened the standard apheresis kit to decrease ECV from 130 to 70 ml. Pump speed was controlled by monitoring hematocrit values and platelet counts during leukapheresis. This system makes it possible to perform safe and effective leukapheresis in rhesus monkeys whose body weight is similar to that of human infants. A total of 12 leukapheresis procedures were performed in nine monkeys and resulted in the collection of sufficient numbers of white blood cells (mean, 1.38 x 10(9) cells/kg), CD34(+) cells (mean, 17.80 x 10(6) cells/kg), mononuclear cells (mean, 3.67 x 10(8) cells/kg), and colony forming units (mean, 75.02 x 10(6) cells/kg) in all cases. In addition, no complications, such as anemia or thrombocytopenia, occurred after leukapheresis. This modified leukapheresis procedure will be useful to test new approaches in gene therapy, perform organ transplantation using nonhuman primates, and collect PBSCs from human infants in a noninvasive manner. Our nonhuman primate model provides an important framework for such future clinical studies.