Preconditioning-Induced Facilitation of Lactate Release from Astrocytes Is Essential for Brain Ischemic Tolerance.

A sublethal ischemic episode [termed preconditioning (PC)] protects neurons in the brain against a subsequent severe ischemic injury. This phenomenon is known as brain ischemic tolerance and has received much attention from researchers because of its robust neuroprotective effects. We have previously reported that PC activates astrocytes and subsequently upregulates P2X7 receptors, thereby leading to ischemic tolerance. However, the downstream signals of P2X7 receptors that are responsible for PC-induced ischemic tolerance remain unknown. Here, we show that PC-induced P2X7 receptor-mediated lactate release from astrocytes has an indispensable role in this event. Using a transient focal cerebral ischemia model caused by middle cerebral artery occlusion, extracellular lactate levels during severe ischemia were significantly increased in mice who experienced PC; this increase was dependent on P2X7 receptors. In addition, the intracerebroventricular injection of lactate protected against cerebral ischemic injury. In in vitro experiments, although stimulation of astrocytes with the P2X7 receptor agonist BzATP had no effect on the protein levels of monocarboxylate transporter (MCT) 1 and MCT4 (which are responsible for lactate release from astrocytes), BzATP induced the plasma membrane translocation of these MCTs via their chaperone CD147. Importantly, CD147 was increased in activated astrocytes after PC, and CD147-blocking antibody abolished the PC-induced facilitation of astrocytic lactate release and ischemic tolerance. Taken together, our findings suggest that astrocytes induce ischemic tolerance via P2X7 receptor-mediated lactate release.

Analysis of patients' thoughts and background factors influencing attitudes toward Deprescribing: interviews to obtain hints for highly satisfying and valid prescriptions.

BACKGROUND: Prescribing with high levels of medical appropriateness and patient satisfaction improves adherence. However, its appropriateness does not always match patient preference. Deprescription is important for ensuring the safety of medication therapy, but is not straightforward. Although successful deprescribing requires knowledge of patients' thoughts on their prescriptions and factors that influence their acceptance of deprescribing, few comprehensive studies have been conducted on this topic. The aim of this study was to identify factors that influence patients' attitudes toward deprescribing and obtain hints on how to achieve higher patient satisfaction and prescribing adequacy. METHODS: A questionnaire was administered to hospitalized patients and a logistic regression analysis was conducted to examine factors that influence their attitude toward deprescribing. Individual factors affecting patients' thoughts and wishes regarding prescribing were extracted and analysed in detail. RESULTS: The analysis included 106 patients, of whom 40 (37.7%) wished deprescribing. Logistic regression analysis showed that "Age", "Wish to reduce the number and types of medications", "Satisfaction", "Concerns about side effects", and "Wish not to have certain medications changed" were factors influencing attitudes toward deprescribing. The results suggested that the factors were influenced by patients' perceptions and individual patient backgrounds. There was a gap between willingness to reduce medication and to change their medications. Seventy-eight percent of all respondents indicated that they would like to reduce the number and type of pills they take if possible. However, only 44.6% of these patients indicated that they would actually like to change their medication. CONCLUSIONS: This study is the only one to comprehensively investigate prescription content, patient background, and patients' thoughts on factors influencing attitudes toward deprescribing. This study revealed five factors that can influence inclination toward deprescribing. In addition, the results suggest that patients want to be able to feel well with fewer medications if possible. This information may be useful in determining prescriptions that have high validity and patient satisfaction. Further research is needed on the gap between willingness to reduce medications and to change medications.

Reversible suspension culture of human vascular smooth muscle cells using the functional biopolymer FP003.

Human vascular smooth muscle cells (SMCs) are adherent cells, and they cannot survive without scaffolds in suspension culture. Here, we aimed to establish a suspension culture of SMCs using the functional biopolymer FP003 and to investigate the proliferation status of the cells. When SMCs were suspension cultured with FP003, their proliferation was inhibited with a viability of 75% until day 15. When SMCs were re-plated on plastic plates after suspension culture with FP003 for 48 h, the SMCs proliferated as in a normal plate culture. The SMCs cultured in suspension with FP003 showed a relatively low phosphorylation of retinoblastoma protein, low expression of cyclin D1, high proportion of G0/G1 phase cells, low proportion of S phase cells, and no obvious signs of apoptosis, indicating that this culture system inhibited progression from the G1 to S phase. This growth arrest was a reversible property that showed no significant changes in the expressions of the marker proteins α-smooth muscle actin and smooth muscle myosin heavy chain. These results suggest that human SMCs can be stably cultured in suspension with FP003 without losing their characteristics when they are cultured on plastic plates again.

Development of an Alcohol Dilution-Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability.

The lipid nanoparticle (LNP) is one of the promising nanotechnologies for the delivery of RNA molecules, such as small interfering RNA (siRNA) and messenger RNA (mRNA). A series of LNPs that contain an mRNA encoding the antigen protein of SARS-CoV-2 were already approved as RNA vaccines against this infectious disease. Since LNP formulations are generally metastable, their physicochemical properties are expected to shift toward a more stable state during the long-time storage of suspensions. The current mRNA vaccines are supplied in the form of frozen formulations with a cryoprotectant for preventing deterioration. They must be stored in a freezer at temperatures from -80 °C to -15 °C. It is thought that therapeutic applications of this mRNA-LNP technology could be accelerated if a new formulation that permits mRNA-LNPs to be stored under milder conditions were available. We previously reported on a one-pot method for producing siRNA-encapsulated LNPs by combining freeze-drying technology with the conventional alcohol dilution method (referred to herein as the "alcohol dilution-lyophilization method"). In this study, this method was applied to the preparation of mRNA-LNPs to provide a freeze-dried formulation of mRNA LNPs. The resulting formulation can be stored at 4 °C for at least 4 months.

A novel method for predicting the unbound valproic acid concentration.

In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07-0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [µM] - 2 × SA [µM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPA values, the constructed formula showed a weak trend with CtVPA or SA. The formula based on (CtVPA [µM] - 2 × SA [µM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.

Pharmacokinetics of vancomycin and meropenem during continuous online hemodiafiltration: A case report.

OBJECTIVES: The pharmacokinetics of vancomycin and meropenem in patients treated with continuous online hemodiafiltration (OL-HDF) are not well understood. CASE: We evaluated dialytic clearance and serum concentrations of vancomycin and meropenem by OL-HDF in a critically ill patient with soft tissue infection. The mean clearance of OL-HDF and mean serum concentrations during continuous OL-HDF were 155.2 mL/min and 23.1 µg/mL for vancomycin and 145.6 mL/min and 22.7 µg/mL for meropenem. CONCLUSION: Vancomycin and meropenem showed high clearance rates during continuous OL-HDF. However, continuous infusion of these agents at high doses maintained therapeutic serum concentrations.

A search for acrolein scavengers among food components.

Brain stroke is a major cause of being bedridden for elderly people, and preventing stroke is important for maintaining quality of life (QOL). Acrolein is a highly reactive aldehyde and causes tissue damage during stroke. Decreasing acrolein toxicity ameliorates tissue injury during brain stroke. In this study, we tried to identify food components which decrease acrolein toxicity. We found that 2-furanmethanethiol, cysteine methyl and ethyl esters, alliin, lysine and taurine decreased acrolein toxicity. These compounds neutralized acrolein by direct interaction. However, the interaction between acrolein and taurine was not so strong. Approximately 30 mM taurine was necessary to interact with 10 µM acrolein, and 2 g/kg taurine was necessary to decrease the size of mouse brain infarction. Taurine also slightly increased polyamine contents, which are involved in decrease in the acrolein toxicity. Mitochondrial potential damage by acrolein was also protected by taurine. Our results indicate that daily intake of foods containing 2-furanmethanethiol, cysteine methyl and ethyl esters, alliin, lysine and taurine may prevent severe injury in brain stroke and improve the quality of life for elderly people.

Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

OBJECTIVES: A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. METHODS: Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. RESULTS: Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. CONCLUSIONS: PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

In vitro analysis of factors affecting the continuous hemodiafiltration clearance of teicoplanin.

BACKGROUND: In the treatment of sepsis, continuous hemodiafiltration (CHDF) and the administration of antibiotics such as teicoplanin (TEIC) are frequently performed in parallel. We aimed to clarify the factors influencing the CHDF clearance (CLCHDF ) of TEIC using a polymethylmethacrylate (PMMA) membrane or a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST). We also investigated whether the adsorption of TEIC onto the hemofilters inhibits the adsorption of interleukin (IL)-6 onto the membranes. METHODS: TEIC, human serum albumin (HSA), and IL-6 were incubated with pieces of hemofilter membranes and adsorption rates were calculated. The CLCHDF , diafiltration rate, and adsorption rate of TEIC were calculated using an in vitro CHDF circuit model. RESULTS: The adsorption rates of TEIC onto the pieces of PMMA and AN69ST membranes ranged from 15.0% to 100% and from -10% to 5%, respectively. The adsorption rate of IL-6 was similar with or without TEIC. The CLCHDF and adsorption rate of TEIC under PMMA-CHDF depended on HSA, but not on effluent flow rate (Qe). The CLCHDF under AN69ST-CHDF depended on HSA and Qe. The observed CLCHDF under AN69ST-CHDF was similar to the predicted value (the product of Qe and the plasma unbound fraction). The observed CLCHDF under PMMA-CHDF was 2.0-7.8 times greater than the predicted value. CONCLUSIONS: Adsorption mainly contributes to the CLCHDF of TEIC using PMMA membranes, whereas diafiltration mainly contributes to the CLCHDF of TEIC using AN69ST membranes. TEIC adsorption might not affect the adsorption of IL-6 onto PMMA membrane.

[Report on a Psychiatric Clinical Practicum in Which Pharmacy Students Perform a Pharmaceutical Intervention].

Neuropsychiatric disorders are among the most represented disorders in the 2013 revision of the Model Core Curriculum for Pharmaceutical Education in Japan. However, it is reported that many pharmacy students have a negative impression of neuropsychiatric disorders because they do not know how to interact with psychiatric patients. To deepen students' understanding of pharmacotherapy for psychiatric disorders, Chiba University Hospital provides a one-day psychiatric clinical practicum in which pharmacy students perform a pharmaceutical intervention. In this practicum, students first had a group discussion about the case, assessed the pharmaceutical problem, and considered pharmacotherapy solutions to the problem on their own. Then, the students interviewed the patients directly to collect pharmaceutical-related information. Finally, the students participated in a conference and presented their own pharmacotherapy solutions to the problem. In this study, we conducted a questionnaire survey and assessed the students' reports in order to investigate their satisfaction with the practicum, changes in their impression of psychiatric disorders or patients with psychiatric disorders, and the level of knowledge they attained. The results showed that almost all students were satisfied with the practicum. The students' impression of psychiatric disorders or patients with psychiatric disorders changed in a positive direction. It seems that students came to realize the role and responsibility of the pharmacist in medical teams. These findings suggest that the practicum led to a positive change in the students' impression of psychiatric patients through conversations with the patients, assessment of pharmacotherapy from a pharmaceutical point of view, and proposing prescriptions.

Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study.

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.

[Compliance with Vaccination against SARS-CoV-2; Information Transmission Based on Scientific Evidence and Its Difficulty].

The fight against coronavirus disease 2019 (COVID-19) in Japan began after January 2020. In order for the country to resume an active social life as a society, it is necessary to prevent an increase in the number of newly infected people with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), and to prevent aggravation and/or death after infection. Although several therapeutic agents have been developed to treat COVID-19 after infection, vaccination with SARS-CoV-2 is the most effective in controlling or even ending the COVID-19 pandemic in Japan. The Ministry of Health, Labour and Welfare has convened a council to publish the collected data on COVID-19 and to proceed with discussions for promoting safe and effective vaccination. However, no matter how we release to the public the scientific basis of our findings and proposed methods of prevention and treatment, there remain cases where false opinions have spread, and vaccinations are refused accordingly. This paper traces the course of the work of this council, and considers current challenges in communicating COVID-19 information to the public based on scientific evidence.

Nelarabine-induced rhabdomyolysis in a patient with T-cell acute lymphoblastic leukemia: a case report.

BACKGROUND: Nelarabine is an antineoplastic purine analog used for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL). The most prominent side effect of nelarabine are neurotoxicity and hematologic disorder, which are considered dose-limiting factors. Although clinical studies have reported myopathy due to nelarabine, actual detailed outcomes were not well-known initial approval. The incidence of nelarabine induced rhabdomyolysis has been reported at 2% in study in children. Cases of rhabdomyolysis have been reported in adults from medical facilities in the United Sates with renal dysfunction or severe muscle symptoms after administration of multiple courses of nelarabine. In this report, we discuss a case of rhabdomyolysis diagnosed after a single course of nelarabine. In this case, creatine kinase (CK) level was elevated in grade 4, without renal dysfunction and severe muscle symptoms. CASE PRESENTATION: A 46-year-old man from Japan was diagnosed with T-ALL and received a hematopoietic stem cell transplantation in first remission. However, the disease relapsed 6 months after transplantation. Nelarabine was selected as the next-line chemotherapeutic agent. The patient received 1500 mg/m2 of nelarabine on day 1 followed by a dose on days 3 and 5. CK levels, which were baseline before treatment, increased to grade 4 (18,620 IU/L) on the 8th day of treatment. He was diagnosed as rhabdomyolysis due to nelarabine with little possibility of other factors. He complained only of mild pain in his upper extremities and no other symptoms were noticed. The patient was managed with hydration. The pain lasted approximately 7 days, but there were no sequelae secondary to the rhabdomyolysis. Because of the elevation of CK in grade 4, we avoided re-administration. CONCLUSION: In the patient administrated nelarabine, CK level was elevated in grade 4, without other symptoms of rhabdomyolysis. The results suggest that CK may be elevated at the onset of rhabdomyolysis caused by nelarabine, even in the absence of other symptoms. Therefore, it was suggested that monitoring CK during nelarabine administration is important for detecting rhabdomyolysis before it becomes severe. We consider that CK should be monitored even in absence of symptoms.

Oral antibiotics and a low-residue diet reduce the incidence of anastomotic leakage after left-sided colorectal surgery: a retrospective cohort study.

PURPOSE: Anastomotic leakage is a potential complication after colorectal surgery. We investigated the effects of oral antibiotics and a low-residue diet on the incidence of anastomotic leakage after left-sided colorectal surgery. METHODS: Outcomes were retrospectively compared between 64 patients who underwent mechanical bowel preparation alone (group A) and 183 patients who underwent mechanical bowel preparation with addition of oral kanamycin and metronidazole (group B) on the day before left-sided colorectal surgery. After surgery, patients in group A received a normal diet containing dietary fiber and those in group B received a low-residue diet. The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were rates of other postoperative complications, length of postoperative hospital stay, and laboratory data. RESULTS: Anastomotic leakage, surgical site infection, and diarrhea were less common in group B than in group A (4.9% vs 18.8%, 6.6% vs 23.4%, and 25.7% vs 43.8%, respectively). Postoperative C-reactive protein levels were significantly lower in group B. The median postoperative hospital stay was significantly shorter in group B than in group A (8 days vs 9 days, P = 0.010). Adaptive double least absolute shrinkage and selection operator regression revealed that use of preoperative oral antibiotics and a postoperative low-residue diet were associated with lower incidence of anastomotic leakage (odds ratio 0.163, 95% confidence interval 0.062-0.430; P < 0.001). CONCLUSION: Oral antibiotics and a low-residue diet reduced the incidence of anastomotic leakage and shortened the postoperative hospital stay by 1 day.

Effective situation-based delirium simulation training using flipped classroom approach to improve interprofessional collaborative practice competency: a mixed-methods study.

BACKGROUND: Interprofessional collaborative practice competency (ICPC) is key to providing safe, high-quality, accessible, patient-centred care. Effective delirium management, particularly, requires a multi-component intervention, including the use of interprofessional teams at care point. This research aims to investigate the effectiveness of the flipped classroom approach for improving ICPC in simulation-based delirium case management. METHOD: An embedded mixed-methods study was designed to investigate the effects of the flipped classroom approach on health professionals' performance in delirium management. The study population comprised nine health professionals (three physicians, nurses, and pharmacists each). They used pre-class study materials about delirium management via a digital learning platform before a simulation case training session. A readiness assurance process test was conducted on key concepts, covered in the pre-class study material. Participants were randomly assigned to three teams, each of which included health professionals. Each team participated in a simulation case scenario. For the quantitative outcome measures, the Chiba Interprofessional Competency Scale (CICS29), a validated scale for measuring competencies of interprofessional practice, was used before, after, and three months after the educational intervention. The qualitative component consisted of a post-training questionnaire and semi-structured focused group interviews about the impact of the flipped classroom approach. RESULT: The CICS29 measured after the intervention and three months after was noted to be significantly higher than before the intervention. Three semi-structured focused group interviews were conducted (n=9), which, upon analysis revealed that the flipped classroom approach effected on four stages of Bloom's taxonomy level. A total of nine categories and 17 subcategories were identified corresponding to four levels of the revised Bloom's taxonomy: remember (1), understand (12), apply (23), and analyse (3). CONCLUSION: The simulation-based skill training using flipped classroom approach can be an effective method for improving ICPC for health professionals. In this approach, an elevated level of cognitive activity is practiced in the Bloom's taxonomy, and the participants worked on an application-based case simulation that promoted higher level learning and engagement in interprofessional collaborative practice. This approach also established a basic common language of delirium assessment and management, thus facilitating communication among health professionals and improving ICPC.

Cost-effectiveness of managing HBV reactivation in patients with resolved HBV infection treated with anti-CD20 antibody for B-cell non-Hodgkin lymphoma.

There is no universal recommendation for managing the reactivation of HBV in patients with resolved HBV infection treated with anti-CD20 monoclonal antibodies for B-cell non-Hodgkin lymphoma. This study compared the cost-effectiveness of two commonly used strategies: prophylactic anti-HBV nucleos(t)ide analog therapy (Pro NAT), and HBV DNA monitoring followed by on-demand antiviral therapy (HBV DNA monitoring). Using a decision tree model, the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. The threshold for cost-effectiveness was set at 5,000,000 JPY, equivalent to 45,662 USD. In a base-case analysis, HBV DNA monitoring was found to be more cost-effective based on the calculation of ICER as 132,048 USD per QALY, a value that far exceeds 45,662 USD. The same results were consistently obtained by a one-way deterministic sensitivity analysis, even after changing each parameter value within the predetermined range. A probabilistic sensitivity analysis with 10,000 simulations also revealed that HBV DNA monitoring is more cost-effective than Pro NAT in 96.8% of cases. Therefore, this study suggests that HBV DNA monitoring is an appropriate managing measure in Japan from a cost-effectiveness perspective.

Adverse effect investigation using application software after vaccination against SARS-CoV-2 for healthcare workers.

INTRODUCTION: The usefulness of smartphone-based application software as a way to manage adverse events (AEs) after vaccination is well known. The purpose of this study is to clarify the usefulness and precautions of employing a smartphone application for collecting AEs after the administration of Comirnaty®ï¸. METHODS: Healthcare workers (HCWs) who were vaccinated with Comirnaty®ï¸ were asked to register for the application software and to report AEs for 14 days after vaccination. AEs were self-reported according to severity. The software was set to output an alert in case of fever. RESULTS: The number of HCWs who received the first dose was 2,551, and 2,406 (94.3%) reported their vaccinations. 2,547 received the second dose, and 2,347 (92.1%) reported their vaccinations. With the first dose, the reporting rate stayed above 83.3% until the final day. On the other hand, that of the second dose decreased rapidly after 6 days. The most frequent symptom was "pain at injection site" (more than 70%). Severe AEs were 6.6% after the second dose, with 0.6% visiting a clinic. Many AEs peaked on the day after administration and disappeared within 1 week. There were few reports of fever. CONCLUSION: Smartphone applications can be used to collect information on AEs after vaccination. Application settings and dissemination are necessary to maintain the reporting rate of HCWs.

Decrease of voriconazole trough levels during therapy with enteral nutrition: a case report.

BACKGROUND: Voriconazole (VRCZ) is the first-line therapy for chronic pulmonary aspergillosis and is available in both intravenous and oral formulations. The bioavailability of the oral form is estimated to be over 90% in healthy volunteers. Some drugs are reported to interact with enteral nutrition (EN), but there are few reports about the trough levels of VRCZ during EN therapy. Here, we describe changes in the VRCZ trough levels in a patient receiving continuous EN therapy. CASE PRESENTATION: The patient was a 58-year-old man with esophageal cancer and a history of partial pulmonary resection due to aspergilloma. He was taking oral VRCZ tablets and his VRCZ trough level was about 2 µg/mL before esophageal cancer surgery. Following esophagectomy, VRCZ was restarted on postoperative day 16. Crushed VRCZ tablets were administered via a jejunostomy tube because of swallowing difficulty. He was also receiving EN, which was interrupted only during the administration of VRCZ. When we checked his VRCZ level 5 days after restarting VRCZ, the trough level was 0.80 µg/mL. After increasing the VRCZ dose, reducing EN, and changing the administration route from jejunostomy tube to oral, his trough level increased to 1.87 µg/mL. CONCLUSIONS: A decrease in the VRCZ trough level was observed when VRCZ was administered via a jejunostomy tube while the patient was receiving continuous EN. Careful monitoring of VRCZ levels is needed in such cases.

Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate.

BACKGROUND: The blood concentration of cyclosporine (CyA) is frequently elevated following the transfusion of red blood cell concentrate (RCC) to patients after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to identify the variable factors affecting changes in the blood concentration of CyA before and after transfusion of RCC. METHODS: We enrolled 105 patients (age, 5-66 years) who received both CyA and transfusion after HSCT. The ratio of the measurement after transfusion to the measurement before transfusion was calculated for the hematocrit and blood concentration/dose ratio of CyA (termed the HCT ratio and the CyA ratio, respectively). RESULTS: The blood concentration/dose ratio of CyA was increased after transfusion compared with before transfusion (P < 0.001). The HCT ratio was significantly correlated with the CyA ratio (P = 0.23, P < 0.001). The HCT ratio, concomitant medication that could elevate CyA concentration after RCC transfusion, and difference in the alkaline phosphatase level between before and after transfusion (ΔALP) were explanatory variables associated with the variation in the CyA ratio. There was no correlation between the CyA concentration after transfusion and the change in the estimated glomerular filtration rate. CONCLUSIONS: A change in the blood concentration/dose ratio of CyA was found to be associated with a change in the HCT, concomitant medication that could elevate CyA concentration after RCC transfusion, and ALP levels. If the HCT level rises significantly after RCC transfusion, clinicians and pharmacists should pay attention to changes in the blood CyA concentration.

Contribution of diafiltration and adsorption to vancomycin clearance in a continuous hemodiafiltration circuit model in vitro.

BACKGROUND: Vancomycin (VCM) is eliminated mainly by diafiltration under continuous hemodiafiltration (CHDF), but the contribution of adsorption to CHDF clearance (CLCHDF ) of VCM using a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST) or a polymethylmethacrylate (PMMA) membrane is unknown. This study sought to investigate the contribution of diafiltration and adsorption to the CLCHDF of VCM using AN69ST and PMMA membranes in vitro. METHODS: An in vitro CHDF circuit model was developed. The initial concentration of VCM was 50 µg/mL and human serum albumin (HSA) was prepared at a concentration of 0, 2.5, or 5.0 g/dL. The effluent flow rate (Qe) was set at 800, 1500, or 3000 mL/h. The CLCHDF , diafiltration rate, and adsorption rate of VCM were calculated. RESULTS: Total CLCHDF of VCM using the AN69ST membrane increased and decreased with increasing Qe and HSA concentration, respectively. Diafiltration and adsorption rates were 82.1 ± 9.8% and 12.1 ± 6.1% under all conditions, respectively. Total CLCHDF using the PMMA membrane increased with increasing Qe. Diafiltration and adsorption rates were 89.2 ± 20.4% and 4.6 ± 17.0% under all conditions, respectively. The observed CLCHDF values significantly correlated with the predicted CLCHDF , calculated according to a previous study as the product of Qe and the plasma unbound fraction. CONCLUSIONS: Diafiltration predominantly contributed to CLCHDF of VCM using AN69ST and PMMA membranes. When diafiltration rather than adsorption mainly contributes to the CLCHDF of VCM, the CLCHDF could be predicted from the Qe and HSA concentration, at least in vitro.