Anti-Clogging Effect of Continuous Hemodiafiltration With Blood Recirculation.

Pediatric dialysis requires low flow from the body, but greater flow is needed to prevent clogging. As a solution, we developed a new continuous hemodiafiltration system with blood recirculation (CHDF-R), which enables separate settings for blood flow from the body and to the hemofilter. We compared CHDF-R with conventional continuous hemodiafiltration (CHDF) of bovine plasma and blood by monitoring the transmembrane pressure (TMP) and observing the hemofilter membrane surface. When using bovine plasma, the postdialysis TMP with CHDF-R was significantly lower than with CHDF (median CHDF, 23.7; median CHDF-R, 18.1; p = 0.029). Likewise, when using bovine blood, the postdialysis TMP was also significantly lower with CHDF-R than with CHDF (median CHDF, 150; median CHDF-R, 100; p = 0.029). Moreover, the area of clogged membrane was significantly smaller with CHDF-R than with CHDF, and the inner membrane surface showed less material deposition with CHDF-R than CHDF. CHDF-R thus appears to suppress accumulation of clogging substances by producing higher shear stress within hollow fiber membranes.

Factors influencing glomerular filtration rate as estimated using preoperative creatinine and cystatin C levels.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) using serum creatinine (Cr) is commonly used to evaluate renal function. However, it can be influenced by other factors, which can risk the overestimation of the true GFR. Impaired renal function prior to cardiovascular surgery reportedly increases mortality and the incidence of postoperative complications. Thus, overestimation of renal function may affect the assessment of postoperative complication risks. Therefore, we aimed to compare the eGFR calculated from serum Cr and cystatin C (Cys-C) levels to assess preoperative renal function and to investigate factors affecting renal function overestimation. MATERIALS AND METHODS: 88 patients admitted for cardiovascular surgery who had preoperative serum Cr and Cys-C measurements were included in the study. Correlations between factors associated with eGFR calculated from serum Cr (eGFRcre) and Cys-C (eGFRcys) and their ratio (eGFRcre/eGFRcys) were examined using multiple regression analysis. RESULTS: Multiple regression analysis revealed that eGFRcre/eGFRcys was significantly negatively correlated with the Short Physical Performance Battery score (SPPB). A clinically significant difference in renal function overestimation was defined as GFRcre/eGFRcys > 1.2, with a cutoff value of 9 points for the SPPB score. The chair stand test, a component of the SPPB, had the same discriminative power as the SPPB for identification of renal function overestimation. CONCLUSION: The SPPB can be used to identify likely GFR overestimation in patients. Additionally, the chair stand test may be used as an alternative to the SPPB for the identification of renal function overestimation when the SPPB is difficult to perform.

Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

OBJECTIVES: Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. MATERIALS AND METHODS: This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. RESULTS: Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. CONCLUSION: Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Dyeable Hydrophilic Surface Modification for PTFE Substrates by Surface Fluorination.

Polytetrafluoroethylene (PTFE) is the most widely used fluoropolymer that has various functionalities such as heat resistance, chemical resistance, abrasion resistance, and non-adhesiveness. However, PTFE is difficult to dye because of its high water repellency. In this study, the PTFE surface was modified by a combination of gold sputtering and surface fluorination to improve dyeability. X-ray photoelectron spectroscopy indicated that, compared with the untreated sample, the gold-sputtered and acid-washed surface of PTFE had a negligible number of C-F terminals. Furthermore, the intensity of the C-C peak increased drastically. The polar groups (C=O and C-Fx) increased after surface fluorination, which enhanced the electronegativity of the surface according to the zeta potential results. Dyeing tests with methylene blue basic dye showed that the dye staining intensity on the surface of fluorinated PTFE samples was superior to other samples. It is due to the increased surface roughness and the negatively charged surface of fluorinated PTFE samples. The modified PTFE substrates may find broad applicability for dyeing, hydrophilic membrane filters, and other adsorption needs.

Comparison between the Effects of Loxoprofen and Acetaminophen on Postoperative Pain Following Radical Prostatectomy: A Propensity Score Matching Analysis.

Non-steroidal anti-inflammatory medications are associated with renal impairment. However, there is little information on whether these medications affect postoperative renal function compared with acetaminophen. The objective of this study was to compare the effects of acetaminophen and loxoprofen, used as postoperative analgesic, effect on postoperative analgesia using propensity score matching analysis. We retrospectively enrolled 328 patients treated with loxoprofen or acetaminophen after open radical prostatectomy between October 2017 and February 2020. We analyzed postoperative pain intensity, the incidence rate of acute kidney injury, drug-induced liver injury, and rate of elevation in serum creatinine after open radical prostatectomy. Eighty-one matched pairs of patients treated with loxoprofen or acetaminophen were selected using propensity score matching analysis. The postoperative numerical rating scale was significantly higher in the acetaminophen group than in the loxoprofen group on postoperative day 5. The use of patient-controlled anesthesia and rescue analgesics was significantly higher in the acetaminophen group than in the loxoprofen group. The loxoprofen group had a significantly higher postoperative increase in serum creatinine than the acetaminophen group on postoperative days 5 and 8. The incidence of acute kidney injury was 4.9% in the loxoprofen group and 0% in the acetaminophen group, while the incidence of drug-induced liver injury was 0% in both groups. Acetaminophen appears to be safer than loxoprofen in terms of effects on renal function. Nevertheless, the number of acetaminophen doses and the dose per dose may need to be increased for patients with significant postoperative pain.

Evaluation of renal function using cystatin C-based estimated glomerular filtration rate in patients with urothelial carcinoma treated with gemcitabine and cisplatin chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Cisplatin-based chemotherapy is a first-line treatment for advanced or metastatic urinary tract urothelial carcinoma (UC). Accurate assessment of renal function is indispensable for determining cisplatin dosing to enhance the safety and effectiveness of cisplatin. The objective of this study was to assess serum cystatin C (sCys C) levels in patients with urothelial carcinoma and to explore its clinical value as a serum marker of glomerular filtration rate (GFR). METHODS: This study retrospectively enrolled 18 UC patients treated with a combination of gemcitabine and cisplatin between April 2018 and November 2020. We calculated the estimated GFR (eGFR) based on serum creatinine (sCr) or sCys C and estimated Cr clearance (eCCr) based on sCr. The correlation, bias, accuracy and creatinine height index between eGFR or eCCr and measured GFR (mGFR) based on Cr clearance were calculated from urinary Cr and sCr. RESULTS AND DISCUSSION: Estimated GFR based on sCys C correlated most strongly with mGFR. Moreover, the bias, mean error, mean absolute error and root mean square error were significantly lower in eGFRs based on sCyc C than in eGFRs based on sCr and eCCr. The correlation between eGFR based on sCys C/mGFR and creatinine height index was weaker than that between eGFR based on sCr/mGFR and creatinine height index, suggesting that sCys C was less affected by muscle mass. WHAT IS NEW AND CONCLUSION: In UC patients, eGFR based on sCys C reflected renal function more accurately than eGFR based on sCr, suggesting that sCys C may be useful for assessing renal function in clinical practice.

Recovery of palladium, cesium, and selenium from heavy metal alkali borosilicate glass by combination of heat treatment and leaching processes.

Reductive heat-treatment and leaching process were applied to a simulated lead or bismuth soda-potash-borosilicate glass with palladium, cesium, and selenium to separate these elements. In the reductive heat treatment, palladium is extracted in liquid heavy metal phase generated by the reduction of the heavy metal oxides, whereas cesium and selenium are concentrated in phase separated Na-K-rich materials on the glass surface. From the materials, cesium and selenium can be extracted in water, and the selenium extraction was higher in the treatment of the bismuth containing glass. The chemical forms of palladium in the glass affected the extraction efficiencies of cesium and selenium. Among the examined conditions, in the bismuth glass treatment, the cesium and selenium extraction efficiencies in water were over 80%, and that of palladium in liquid bismuth was over 80%.

Phase separation of cesium from lead borosilicate glass by heat treatment under a reducing atmosphere.

A phase-separation technique for removing sodium from glass using a heat-treatment method under a reducing atmosphere was previously developed for sodium recovery from waste glass. In this study, this technique was applied to cesium-containing lead borosilicate glass to concentrate the cesium in phase-separated sodium-rich materials for efficient cesium extraction. The theoretical phase-separation temperature of the sodium-rich phase was simulated by thermodynamic equilibrium calculations and was predicted to occur below 700°C for lead borosilicate glass. Experimentally, a simulated lead borosilicate glass was melted at 1000°C and subsequently annealed below 700°C under a CO-containing reducing atmosphere. The phase separation of cesium was found to occur with sodium enrichment on the glass surface that was in contact with the gas phase, promoting cesium extraction from the treated glass using water. The cesium extraction efficiency was affected by the surface area of the treated glass that was in contact with water, and under the examined conditions, the cesium extraction efficiency was up to 66%. Phase separation using reductive heat treatment, combined with a water leaching technique, is suggested to be effective for extracting cesium incorporated in borosilicate glass waste.

Removal of lead from cathode ray tube funnel glass by combined thermal treatment and leaching processes.

The reduction melting process is useful to recover toxic lead from cathode ray tube funnel glass; however, this process generates SiO2-containing residues that are disposed in landfill sites. To reduce the volume of landfill waste, it is desirable to recycle the SiO2-containing residues. In this study, SiO2 powder was recovered from the residue generated by reduction melting. The funnel glass was treated by a process combining reduction melting at 1000°C and annealing at 700°C to recover a large quantity of lead from the glass. The oxide phase generated by the thermal treatment was subjected to water leaching and acid leaching with 1M hydrochloric acid to wash out unwanted non-SiO2 elements for SiO2 purification. In the water washing, the oxide phase was microparticulated, and porous structures formed on the oxide surfaces. This increased the surface area of the oxide phase, and the unwanted elements were effectively washed out during the subsequent acid leaching. By controlling the acid leaching time and the amount of added acid, porous and amorphous SiO2 (purity >95 wt%) was recovered. In the obtained SiO2-concentrated product, unrecovered lead remained at concentrations of 0.25-0.79 wt%. When the Na2CO3 dosage in the thermal treatment was increased, the lead removal by acid leaching was enhanced, and the lead concentration in the obtained product decreased to 0.016 wt%.

Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.

Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels.

No effect of co-administered antiepileptic drugs on in-vivo protein binding parameters of valproic acid in patients with epilepsy.

OBJECTIVES: The aim of this study was to establish the population protein binding parameters of valproic acid (VPA) in patients with epilepsy receiving VPA monotherapy and those receiving VPA combined with other antiepileptic drugs. METHODS: One hundred and thirty nine data sets from 63 Japanese patients with epilepsy were analysed. These patients were separated into two groups: VPA monotherapy and VPA combined with other binding-sensitive antiepileptic drugs, including phenytoin, clonazepam, clobazam, carbamazepine and phenobarbital (VPA polytherapy). The population protein-binding parameters of VPA were obtained by non-linear least-squares method in each group. KEY FINDINGS: The mean (95% confidence interval) dissociation constants were 38.9 µm (33.2-44.6 µm) and 36.9 µm (26.7-47.1 µm), and the numbers of binding sites were 1.36 (1.27-1.44) and 1.33 (1.19-1.47) in the monotherapy and polytherapy groups, respectively. No significant differences in the binding parameters of VPA to serum albumin were observed between the two groups. CONCLUSIONS: The steady-state serum albumin binding of VPA in Japanese patients with epilepsy is not affected by co-administration of other antiepileptic drugs. These findings suggest that serum VPA concentration is stable at the steady state with regard to interaction by protein binding, even when other antiepileptic drugs with moderate-to-high binding properties are co-administered.

Synthesis of prostaglandin E(1) phosphate derivatives and their encapsulation in biodegradable nanoparticles.

PURPOSE: Prostaglandin E(1) (PGE(1)) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE(1) in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients. METHODS: In order to encapsulate PGE(1) in nanoparticles prepared with a poly(lactide) homopolymer (PLA) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA), we synthesized a series of PGE(1) phosphate derivatives and tested their efficacy. RESULTS: Among them, PGE(1) 2-(phosphonooxy)ethyl ester sodium salt (C2) showed the most efficient hydrolysis to yield PGE(1) in human serum. An in vitro platelet aggregation assay showed that C2 inhibited aggregation only after pre-incubation in serum, suggesting that C2 is a prodrug of PGE(1). In vivo, intravenous administration of C2 caused increase in cutaneous blood flow. In the presence of zinc ions, all of the synthesized PGE(1) phosphate derivatives could be encapsulated in PLA-nanoparticles. Use of L-PLA instead of D,L-PLA, and high molecular weight PLA resulted in a slower release of C2 from the nanoparticles. CONCLUSIONS: We consider that C2-encapsulated nanoparticles prepared with L-PLA and PEG-D,L-PLA have good sustained-release profile of PGE(1), which is useful clinically.