Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

GOALS: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. BACKGROUND: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. STUDY: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. RESULTS: Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. CONCLUSIONS: In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Role of mitochondrial complex III/IV in the activation of transcription factor Rst2 in Schizosaccharomyces pombe.

Mitochondria play essential roles in eukaryotic cells for glucose metabolism to produce ATP. In Schizosaccharomyces pombe, transcription factor Rst2 can be activated upon glucose deprivation. However, the link between Rst2 and mitochondrial function remains elusive. Here, we monitored Rst2 transcriptional activity in living cells using a Renilla luciferase reporter system, and found that inhibition of mitochondrial complex III/IV caused cells to produce reactive oxygen species (ROS) and nitric oxide (NO), which in turn activated Rst2. Furthermore, Rst2-GFP was observed to translocate from cytoplasm to nucleus upon mitochondrial complex III/IV inhibitors treatment, and deletion of genes associated with complex III/IV resulted in delayed process of Rst2-GFP nuclear exportation under glucose-rich condition. In particular, we found that Rst2 was phosphorylated following the treatment of complex III/IV inhibitors or SNAP. Altogether, our findings suggest that mitochondrial complex III/IV participates in the activation of Rst2 through ROS and NO generation in Schizosaccharomyces pombe.

Clinical value of the HATCH score for predicting adverse outcomes in patients with heart failure.

The HATCH score is employed as a risk assessment tool for atrial fibrillation (AF) development. However, the impact of the HATCH score on the long-term adverse outcomes in patients with acute heart failure (AHF) remains unknown. We investigated the clinical value of the HATCH score in patients with AHF. From a multicenter AHF registry, we retrospectively evaluated 1543 consecutive patients who required hospitalization owing to AHF (median age, 78 [69-85] years; 42.3% women) from January 2012 to December 2019. These patients were divided into five risk groups based on their HATCH score at admission (scores 0, 1, 2, 3, and 4-7). The correlation between the HATCH score and the composite outcome, including all-cause mortality and re-hospitalization due to HF, was analyzed using Kaplan-Meier and Cox proportional-hazard analyses. The median HATCH score was 2 [1-3], and the median age was 78 years (69-85 years). During the follow-up period (median, 16.8 months), the composite endpoint occurred in 691 patients (44.8%), including 416 (27%) patients who died (with 65 [4.2%] in-hospitalization deaths) and 455 (29.5%) patients requiring re-hospitalizations due to HF. The Kaplan-Meier analysis showed a significant increase in the composite endpoint with an increasing HATCH score (log-rank, p < 0.001). The multivariate Cox regression model revealed that the HATCH score was an independent predictor of the composite endpoint (hazard ratio [HR] 1.181; 95% confidence interval [CI]: 1.111-1.255; p < 0.001) with all-cause mortality (HR 1.153, 95% CI 1.065-1.249; p < 0.001) and re-hospitalizations due to HF (HR 1.21; 95% CI 1.124-1.303; p < 0.001) in patients with AHF, regardless of the presence or absence of AF, ejection fraction, and etiology. The HATCH score is an independent predictor of adverse outcomes in patients with AHF.

Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.

Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer's ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer's ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93-365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan-Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer's ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.

Relationship between Low Pretreatment Geriatric Nutritional Risk Index and Poor Tolerability of Azacitidine in Patients with Myelodysplastic Syndromes.

BACKGROUND: Predicting tolerability and treatment-related risks associated with azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) before the initiation of therapy is required for appropriate treatment. Thus, in this study, the nutritional status of patients with MDS prior to AZA treatment was evaluated using the geriatric nutritional risk index (GNRI). Tolerability and overall survival (OS) after AZA initiation were also investigated. METHODS: This was a single-center retrospective observational study. A total of 59 patients with MDS treated with AZA were assessed using GNRI, and a comparison of undernourished (GNRI <92, n = 27) and non-undernourished (GNRI ≥92, n = 32) patients was performed. RESULTS: The undernourished group had a significant reduction in the number of patients that successfully completed 4 cycles of AZA treatment compared with the non-undernourished group (undernourished group, 11/27 patients, 40.7% vs. non-undernourished group, 24/32 patients, 75.0%; p = 0.009). Factors associated with the difference included karyotype and GNRI. There was also a significant increase in the rate of infectious complications in the undernourished group compared with the non-undernourished group (undernourished group, 33/60 cycles, 55.0% vs. non-undernourished group, 31/92 cycles, 33.7%; p = 0.012). Lastly, a significant reduction in OS was observed in the undernourished group compared with the non-undernourished group (undernourished group, 11.5 months; 95% CI, 5.2-16.7 vs. non-undernourished group, 21.9 months; 95% CI, 13.8-24.0; p = 0.026). Factors associated with OS included both the revised International Prognostic Scoring System (IPSS-R) and GNRI. CONCLUSIONS: These results indicate that predicting treatment completion and adverse events in patients with MDS prior to AZA treatment is important. This study suggests GNRI may be a valuable nutritional assessment tool for determining tolerability and OS of AZA treatment.

Amikacin Pharmacokinetics in Terminal Stage of Hematological Malignancy.

BACKGROUND: The influence of cancer cachexia on the pharmacokinetics of and kidney injury caused by amikacin remains unclear. This study investigated whether the pharmacokinetics of amikacin and the risk of kidney injury are altered with the progression of cancer cachexia. METHODS: A retrospective analysis was conducted using therapeutic drug monitoring data obtained from 52 cancer patients who received amikacin intravenously for infection(s). The patients were classified into 2 groups based on the status of cachexia using a consensus definition: noncachexia group (n = 31) and cachexia group (n = 21). Differences in amikacin pharmacokinetics and occurrence of kidney injury were compared between the 2 groups. Amikacin pharmacokinetics was calculated based on a 1-compartment model using peak and trough concentrations measured clinically for therapeutic drug monitoring. In addition, intrapatient analysis was conducted based on patients who received amikacin treatments more than once during the study period to examine the alteration in amikacin pharmacokinetics with the progression of cancer cachexia. RESULTS: Systemic clearance of amikacin [median (range)] was significantly (P < 0.05) lower in the cachexia group [37.3 (11.2-87.3) (mL/min)] than in the noncachexia group [52.0 (19.1-133.4) (mL/min)]. In contrast, volume of distribution was significantly (P < 0.05) increased in the cachexia group [0.47 (0.20-1.45) L/kg] compared with the noncachexia group [0.32 (0.21-1.00) L/kg]. There was no difference in the occurrence of kidney injuries between the 2 groups. In an intrapatient analysis of the longitudinal alteration of amikacin pharmacokinetics, an approximately 50% reduction in clearance and 30% increase in volume of distribution were observed as cancer cachexia progressed. CONCLUSIONS: The present study suggests that progression of cancer cachexia may reduce amikacin clearance and increase the volume of distribution, but cancer cachexia does not increase amikacin-induced kidney injury.

Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration.

BACKGROUND: Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection. METHODS: A retrospective analysis was conducted on the medical data obtained from 18 patients who received chronic subcutaneous or intramuscular injections of phenobarbital for the prevention of convulsions and underwent plasma concentration monitoring of the drug. Patients whose concomitant medications were altered during the observation periods were excluded from the analysis. Comparisons were performed for concentration/dose (C/D) ratios obtained from patients with induration at injection or infusion sites (induration group, n = 6) and those without induration (noninduration group, n = 12). P < 0.05 was considered statistically significant. RESULTS: The induration group showed significantly reduced C/D ratio compared with the noninduration group [median (range): 0.131 (0.114-0.334) versus 0.219 (0.180-0.322) d/L, P < 0.05). Assuming that systemic clearance was constant in our patients, changes in the C/D ratio would have contributed to 40% (median) reduction in bioavailability of the drug from the injection or infusion site. CONCLUSIONS: Our data suggest that absolute bioavailability of phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection.

Storage of volume-reduced washed platelets in M-sol additive solution for 7 days.

BACKGROUND: Volume-reduced washed platelets (VR-wPLTs), which are prepared by concentrating platelets (PLTs) into a smaller volume of additive solution (AS), may prevent not only circulatory overload, but also adverse reactions caused by plasma components. Although VR-wPLTs may be quickly degraded due to high PLT concentrations, few studies have examined the effects of storage on VR-wPLTs. We examined here the in vitro properties of VR-wPLTs prepared with M-sol AS during their storage for 7 days. STUDY DESIGN AND METHODS: Platelet concentrates (PCs) were divided into two equal aliquots (control group and test group). After the centrifugation of both aliquots and removal of as much supernatant as possible, the pellet of the control group was resuspended in 160 mL of M-sol while that of the test group was resuspended in 80 or 40 mL of M-sol. The wPLTs of both groups were stored in polyolefin bags with agitation at 20 to 24°C for 7 days. RESULTS: The pH values of both groups were maintained at higher than 7.0 during the 7-day storage. Differences in %disk, CD62P, annexin V, percent hypotonic shock response, and aggregation values between the test group and control group were small for at least 2 days after washing. CONCLUSIONS: The in vitro properties of VR-wPLTs were not markedly degraded for at least 2 days. Therefore, the storage properties of PLTs may be maintained in VR-wPLTs prepared at blood centers until they are administered to patients in hospitals.

Coexistence of a Classical Nodoventricular Accessory Pathway With a Left-Sided Mahaim Accessory Pathway.

The coexistence of 2 Mahaim pathways represents a diagnostic challenge. We present a case in which the SH/HA intervals were useful for identifying concealed nodoventricular or His-ventricular pathways.

Nanoscrolls of Janus Monolayer Transition Metal Dichalcogenides.

Tubular structures of transition metal dichalcogenides (TMDCs) have attracted attention in recent years due to their emergent physical properties, such as the giant bulk photovoltaic effect and chirality-dependent superconductivity. To understand and control these properties, it is highly desirable to develop a sophisticated method to fabricate TMDC tubular structures with smaller diameters and a more uniform crystalline orientation. For this purpose, the rolling up of TMDC monolayers into nanoscrolls is an attractive approach to fabricating such a tubular structure. However, the symmetric atomic arrangement of a monolayer TMDC generally makes its tubular structure energetically unstable due to considerable lattice strain in curved monolayers. Here, we report the fabrication of narrow nanoscrolls by using Janus TMDC monolayers, which have an out-of-plane asymmetric structure. Janus WSSe and MoSSe monolayers were prepared by the plasma-assisted surface atom substitution of WSe2 and MoSe2 monolayers, respectively, and then were rolled by solution treatment. The multilayer tubular structures of Janus nanoscrolls were revealed by scanning transmission electron microscopy observations. Atomic resolution elemental analysis confirmed that the Janus monolayers were rolled up with the Se-side surface on the outside. We found that the present nanoscrolls have the smallest diameter of about 5 nm, which is almost the same as the value predicted by the DFT calculation. The difference in work functions between the S- and Se-side surfaces was measured by Kelvin probe force microscopy, which is in good agreement with the theoretical prediction. Strong interlayer interactions and anisotropic optical responses of the Janus nanoscrolls were also revealed by Raman and photoluminescence spectroscopy.

A measurable activation of the bZIP transcription factor Atf1 in a fission yeast strain devoid of stress-activated and cell integrity mitogen-activated protein kinase (MAPK) activities.

In Schizosaccharomyces pombe, the stress-activated Sty1 MAPK pathway is essential for cell survival under stress conditions. The Sty1 MAPK regulates Atf1 transcription factor to elicit stress responses in extreme conditions of osmolarity and reactive oxygen species-generating agents such as hydrogen peroxide, heat, low glucose, and heavy metal. Herein, using a newly developed Renilla luciferase reporter assay with enhanced detection sensitivity and accuracy, we show that distinct signaling pathways respond to cadmium and other reactive oxygen species-generating agents for the activation of Atf1. Also, surprisingly, a measurable activation of Atf1 transcription factor was still observed devoid of Sty1 MAPK activity. Further genetic and biological analyses revealed that the residual activation is caused by the activation of the cell wall integrity Pmk1 MAPK pathway and a redox-mediated activation of Atf1.

Genetic screening for regulators of Prz1, a transcriptional factor acting downstream of calcineurin in fission yeast.

Calcineurin phosphatase plays crucial roles in a wide variety of cell types and organisms. Dephosphorylation of the nuclear factor of activated T-cell (NFAT) family of transcriptional factors by calcineurin is essential for activating immune-responsive genes in mammals. NFAT activity is also regulated by diverse signaling pathways, which affect NFAT kinases and nuclear partner proteins. In fission yeast, calcineurin dephosphorylates and activates Prz1, a C2H2-type zinc finger transcriptional factor. Calcineurin-Prz1 signaling regulates the expression of the Pmc1 Ca(2+) pump. Prz1-overexpressing cells showed extremely slow growth and high transcriptional activity of Prz1 in the absence of stimulation. Here, we isolated seven genes as dosage-dependent suppressors of this slow growth phenotype. These seven genes encode Rad24, Rad25, Pka1, Msn5 (SPAC328.01c), Pac1, Ape2, and Tfs1. All of them decreased the high transcriptional activity caused by Prz1 overexpression. Overexpression of Pka1, Rad24, and Rad25 also repressed the Ca(2+)-induced transcriptional activity in cells with Prz1 expressed at wild-type levels. Knock-out of rad24 or rad25 significantly enhanced the transcriptional activity of Prz1, whereas knock-out or mutation of other genes did not enhance the activity. The 14-3-3 proteins, Rad24 and Rad25, bound Prz1 and the Rad24-binding site located at residues 421-426 of Prz1. In msn5 deletion mutants, GFP-Prz1 localized at nucleus in the absence of Ca(2+) stimulation, suggesting that Msn5 functions as an exportin for Prz1. In summary, our data suggest that Rad24 and Rad25 negatively regulate Prz1 and that Pka1, Msn5, Pac1, Tfs1, and Ape2 also regulate Prz1.

Impact of chemiluminescent enzyme immunoassay screening for human parvovirus B19 antigen in Japanese blood donors.

BACKGROUND: To reduce the risk of human parvovirus B19 (B19V) transmission through contaminated blood for transfusion and plasma-derived products, the Japanese Red Cross (JRC) Blood Centers introduced B19V antigen screening by chemiluminescent enzyme immunoassay (CLEIA-B19V) in 2008. STUDY DESIGN AND METHODS: Donor samples that were positive by CLEIA-B19V screening were tested for B19V DNA. The sensitivity of CLEIA-B19V was tested using samples of all three genotypes and B19V DNA-positive donations. B19V DNA-positive donations and pooled plasma were quantitatively assayed for B19V DNA. B19V DNA-positive donations were phylogenetically analyzed by polymerase chain reaction direct sequencing. RESULTS: The sensitivity of CLEIA-B19V was inferred to be approximately 6.3 log IU/mL with the genotype samples and 6.4 log IU/mL with B19V DNA-positive donor samples. Of 417 CLEIA-B19V-positive samples from 1,035,560 donations in Hokkaido, Japan, 101 were positive for B19V DNA. The 198 strains of B19V DNA-positive donations in Hokkaido over the past 15 years clustered exclusively with Genotype 1. After introduction of CLEIA-B19V, the viral load for B19V DNA in all 772 pooled plasma for fractionation from donors in nationwide Japan did not exceed 4 log IU/mL. CONCLUSION: CLEIA-B19V can detect all three genotypes of B19V (viral load >6.3 log IU/mL) and limit the viral load (<4 log IU/mL) in pooled plasma, and thus such screening has further reduced the risk of transfusion-transmitted B19V infection. These results show that CLEIA-B19V screening at the JRC Blood Centers can be an alternative approach to comply with recommendations regarding B19V in the United States and Europe.

Lycopene inhibits ischemia/reperfusion-induced neuronal apoptosis in gerbil hippocampal tissue.

Plant lycopene exhibits antioxidant activity in animal tissues. Transient cerebral ischemia/reperfusion in Mongolian gerbils resulted in delayed neuronal death in hippocampal regions. We examined the antioxidant effects of lycopene because we expected lycopene to attenuate ischemia-related neuronal damage by controlling apoptosis at the gene level. The gerbils were divided into two groups: the normal feeding (control) group that received normal market food (MF) and the lycopene group that received MF containing lycopene (5 mg in 100 g MF food). After 1.5-2.0 months (when body weight were 60-65 g), the lycopene level was 38.2 ± 17.6 ng/ml in serum and 11.9 ± 4.0 µg/g-wet weight tissue in the liver. Levels of B cell leukemia-2, an apoptosis-suppressing protein, decreased in control animal brains 1, 3, and 7 days after surgery, whereas the levels increased in lycopene-treated animal brains. Moreover, cysteinyl aspartate-specific protease-3 activity increased gradually after ischemia, but was suppressed in the lycopene-treated animal brains 7 days after surgery. Finally, hippocampal superoxide dismutase (SOD) activity decreased in the control group 3 h after ischemia and, gradually increased thereafter, whereas it was significantly elevated in the lycopene group. Thus, orally administered lycopene is accumulated in the body, and provided protections against ischemia/reperfusion-induced brain injury by inducing an increase in SOD activity and inhibiting apoptosis.

Is higher lymphocyte count a potential strategy for preventing chronic kidney disease in patients receiving long-term dasatinib treatment?

BACKGROUND: Dasatinib, which is used to treat treating chronic myeloid leukemia, induces increases in blood lymphocytes during the treatment. In addition, neutrophil-lymphocyte count ratio (NLR) is associated with the related to development of chronic kidney disease (CKD). However, it has not been reported whether development of CKD during long-term dasatinib treatment is related to lymphocyte count or NLR. This study aimed to reveal the relationship between CKD and lymphocyte count or NLR during long-term dasatinib treatment. METHODS: A retrospective study was conducted in patients treated with dasatinib for 6 months or longer. Risk factors for CKD development were explored using multivariate analysis. Changes in maximal lymphocyte count and NLR over time were examined separately. RESULTS: A total of 33 patients in CKD group (n = 8) and No CKD group (n = 25) who received dasatinib were enrolled. In univariate analysis, significant differences between the groups were observed in maximal lymphocyte count, lymphocytosis, age, and estimated glomerular filtration rate at baseline. As the factor independently associated with the development of CKD, maximal lymphocyte count (odds ratio 0.999, 95% confidence interval: 0.999-1.000, p = 0.033) was identified. In this analysis, age had borderline significance (odds ratio 1.073, 95% CI: 0.999-1.153, p = 0.054)]. After 6 months of dasatinib therapy, lymphocyte count was significantly lower in CKD group [median (range), 2184 (878‒3444)/µL] than in the No CKD group [3501 (966‒7888)/µL] (p = 0.020). However, no significant difference in lymphocyte count was observed between the groups at the last follow-up. During the study period, the median NLR in the No CKD group fluctuated between 1.11 and 1.42, and median NLR in CKD group was increased from 1.13 to 2.24 between after 6 months of dasatinib therapy and the last follow-up. CONCLUSIONS: The development of CKD during dasatinib therapy was associated with lower maximal lymphocyte counts. In contrast, the higher levels of lymphocytes induced during dasatinib treatment may prevent CKD progression.

pCO2 decrement through alkalinity enhancement and biological production in a shallow-water ecosystem constructed using steelmaking slag.

Ocean-based carbon dioxide removal has gained immense attention as a countermeasure against climate change. The enhancement of ocean alkalinity and the creation of new blue carbon ecosystems are considered effective approaches for this. To evaluate the function of steelmaking slag from the viewpoints of CO2 reduction and creation of new blue carbon ecosystems, we conducted a comparative experiment using two mesocosms that replicated tidal-flats and shallow-water ecosystems. Initially, approximately 20 seagrasses (Zostera marina) were transplanted into the shallow-water area in the mesocosm tanks. The use of steelmaking slag is expected to increase the pH by releasing calcium and mitigate turbidity by solidifying dredged soil. In the experimental tank, where dredged soil and steelmaking slag were utilized as bed materials, the pH remained higher throughout the experimental period compared with the control tank, which utilized only dredged soil. As a result, pCO2 remained consistently lower in the experimental tank due to mainly its alkaline effect (March 2019: -10 ± 6 µatm, September 2019: -130 ± 47 µatm). The light environment in the control tank deteriorated due to high turbidity, whereas the turbidity in the experimental tank remained low throughout the year. The number of seagrass shoots in the experimental tank was consistently approximately 20, which was higher than that in the control tank. Additionally, more seaweed and benthic algae were observed in the experimental tank, indicating that it was more conducive to the growth of primary producers. In conclusion, tidal-flat and shallow-water ecosystems constructed using dredged soil and steelmaking slag are expected to enhance CO2 uptake and provide a habitat for primary producers that is superior to those constructed using dredged soil only.

Abrupt increased serum creatinine in a hyperferritinemia patient treated with deferoxamine after cord blood transplantation: a case report with literature review.

BACKGROUND: Erythrocyte transfusion is an indispensable component of supportive care after hematopoietic stem cell transplantation (HSCT). However, HSCT recipients are susceptible to the development of acute kidney injury (AKI) with multifactorial causes. We report a case of a rapid elevation in serum creatinine associated with deferoxamine after cord blood transplantation (CBT). CASE PRESENTATION: A 36-year-old Japanese male diagnosed with relapsed Philadelphia-positive acute lymphoblastic leukemia received CBT. At day 88 post-CBT, multidrug-resistant Pseudomonas aeruginosa (MDRP) was isolated from urine culture. Subsequently, colistin 200 mg/day was administered parenterally for treatment of epididymitis from day 91 to 117 post-CBT. Despite concomitant administration of potential nephrotoxic agents such as piperacillin-tazobactam, acyclovir, and liposomal amphotericin B, no development of AKI was observed during this period. At day 127 post-CBT, MDRP was detected in blood and urine cultures, and colistin 200 mg/day was re-started parenterally. Due to extremely higher ferritin level, deferoxamine was administered intravenously at day 133 post-CBT. While serum creatinine was 1.03 mg/dL before starting deferoxamine, the level increased to 1.36 mg/dL one day after commencing deferoxamine (day 134 post-CBT), and further increased to 2.11 mg/dL at day 141. Even though colistin was discontinued at day 141 post-CBT, serum creatinine continued to increase. Deferoxamine was withdrawn at day 145 post-CBT, when serum creatinine peaked at 2.70 mg/dL. In addition, no cylinduria is observed during the period of development of AKI. In adverse drug reaction (ADR) assessment using Naranjo probability score, the scores of 3 in deferoxamine and 2 in colistin, respectively, indicated "possible" ADR. However, while colistin-associated AKI manifested early onset, recovery time within 2 weeks after discontinuation and development of cylinduria, this case was discordant with the properties. Furthermore, in the literature review, development of AKI within 1 day, including sudden increase in serum creatinine or abrupt reduction in urine volume, was reported in 3 identified cases. CONCLUSIONS: We considered the rapid creatinine elevation to be the result of deferoxamine rather than ADR caused by colistin. Therefore, careful monitoring of kidney function is required in recipients of HSCT treated with deferoxamine.

Structural Diversity of Single-Walled Transition Metal Dichalcogenide Nanotubes Grown via Template Reaction.

Monolayers of transition metal dichalcogenides (TMDs) are an ideal 2D platform for studying a wide variety of electronic properties and potential applications due to their chemical diversity. Similarly, single-walled TMD nanotubes (SW-TMDNTs)-seamless cylinders of rolled-up TMD monolayers-are 1D materials that can exhibit tunable electronic properties depending on both their chirality and composition. However, much less has been explored about their geometrical structures and chemical variations due to their instability under ambient conditions. Here, the structural diversity of SW-TMDNTs templated by boron nitride nanotubes (BNNTs) is reported. The outer surfaces and inner cavities of the BNNTs promote and stabilize the coaxial growth of SW-TMDNTs with various diameters, including few-nanometers-wide species. The chiral indices (n,m) of individual SW-MoS2 NTs are assigned by high-resolution transmission electron microscopy, and statistical analyses reveals a broad chirality distribution ranging from zigzag to armchair configurations. Furthermore, this methodology can be applied to the synthesis of various TMDNTs, such as selenides and alloyed Mo1- x Wx S2 . Comprehensive microscopic and spectroscopic analyses also suggest the partial formation of Janus MoS2(1- x ) Se2 x nanotubes. The BNNT-templated reaction provides a universal platform to characterize the chirality-dependent properties of 1D nanotubes with various electronic structures.