Coadministration of Voriconazole and Rifabutin Can Increase the Risk of Adverse Drug Reactions in Patients with Multiple Infections.

BACKGROUND: Coinfection of tuberculosis or nontuberculous mycobacteria and Aspergillus presents a challenge in medication selection because of the pharmacokinetic interactions between rifampin and voriconazole. Some researchers have suggested the use of rifabutin as an alternative to rifampin because of its lower hepatic cytochrome P450 enzyme induction potency despite its contraindication to drug labels. This study presents clinical cases of voriconazole and rifabutin coadministration and their potential risks. METHODS: This retrospective study was conducted using clinical data from patients who met the following criteria: (1) admitted to Seoul National University Hospital between July 2014 and August 2023 and (2) concurrently administered rifabutin and voriconazole for more than 5 days. RESULTS: Among the 6 patients analyzed, 4 experienced adverse drug reactions (ADRs). Three patients experienced visual and auditory hallucinations, lower extremity numbness, or delirious behavior. Two patients had prolonged the time from the start of the Q wave to the end of the T wave intervals, and 1 had elevated aspartate aminotransferase and alanine aminotransferase levels. In addition, 2 patients experienced severe nausea, poor oral intake, and weight loss. Despite receiving 1.81-fold the recommended voriconazole dosage, a therapeutic concentration (1.0-5.5 mg/L) was not achieved because of cytochrome P450 induction by rifabutin. However, during septic shock, the voriconazole concentration increased by 13.7- to 36-fold. CONCLUSIONS: Concurrent use of rifabutin and voriconazole was associated with ADRs, including the time from the start of the Q wave to the end of the T wave prolongation, hallucinations, and severe nausea. Moreover, initially, there was a significant decrease in voriconazole concentrations; however, these concentrations substantially increased during septic shock. Therefore, it is essential to monitor drug concentrations and ADRs during concurrent use of voriconazole and rifabutin.

Identification of Potential Biomarkers for Diagnosis of Patients with Methamphetamine Use Disorder.

The current method for diagnosing methamphetamine use disorder (MUD) relies on self-reports and interviews with psychiatrists, which lack scientific rigor. This highlights the need for novel biomarkers to accurately diagnose MUD. In this study, we identified transcriptome biomarkers using hair follicles and proposed a diagnostic model for monitoring the MUD treatment process. We performed RNA sequencing analysis on hair follicle cells from healthy controls and former and current MUD patients who had been detained in the past for illegal use of methamphetamine (MA). We selected candidate genes for monitoring MUD patients by performing multivariate analysis methods, such as PCA and PLS-DA, and PPI network analysis. We developed a two-stage diagnostic model using multivariate ROC analysis based on the PLS-DA method. We constructed a two-step prediction model for MUD diagnosis using multivariate ROC analysis, including 10 biomarkers. The first step model, which distinguishes non-recovered patients from others, showed very high accuracy (prediction accuracy, 98.7%). The second step model, which distinguishes almost-recovered patients from healthy controls, showed high accuracy (prediction accuracy, 81.3%). This study is the first report to use hair follicles of MUD patients and to develop a MUD prediction model based on transcriptomic biomarkers, which offers a potential solution to improve the accuracy of MUD diagnosis and may lead to the development of better pharmacological treatments for the disorder in the future.

Performance evaluation of immunoassay for infectious diseases on the Alinity i system.

BACKGROUND: Although a diagnosis of infectious diseases is essential for timely treatment, the performance of diagnostic tests has been hardly evaluated due to variable results that are influenced by multiple factors in different conditions. In the present study, the performance of the Alinity i system, which is a newly developed immunoassay to diagnose infectious diseases, was evaluated. METHODS: We evaluated the precision, linearity, correlation, and carryover of 16 analytes (HAV Ab IgG, HBsAg, HBeAg, anti-HBc, anti-HBe, anti-HBs, anti-HCV, HIV Ag/Ab, EBV VCA IgM, EBV VCA IgG, EBV EBNA IgG, CMV IgM, CMV IgG, Toxoplasma IgG, Rubella IgG, and Syphilis TP) of Alinity i by comparison with ARCHITECT i2000SR system following the rationale of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: For quantitative tests, the coefficients of variation (CV) % of repeatability and intermediate precision were between 0% and 4.18%. The coefficients of the linearity (r2 ) over a widely tested analytical range were ≥ 0.990 and the correlation between Alinity i and the ARCHITECT i2000SR system was strong (r ≥ 0.994). For qualitative tests, the agreement between Alinity i and the ARCHITECT i2000SR system was excellent (kappa coefficient 1) with 100% sensitivity and specificity. Carryover rates for all analytes were less than 1.0% (-0.11% ~ 0.21%). CONCLUSION: The Alinity i system showed good analytical performance and favorable comparability with the ARCHITECT i2000SR. It could be suitable as a routine immunoassay analyzer for screening and diagnosis of infectious disease.

Analytical performance evaluation of the Norudia HbA1c assay.

BACKGROUND: Hemoglobin A1c (HbA1c) is arguably the most important biomarker used in the diagnosis and treatment monitoring of diabetes mellitus. We evaluated the analytical performance of the Norudia HbA1c assay (Sekisui Medical Co., LTD), which uses an enzymatic method incorporated into a fully automated, high-throughput system. METHODS: The precision, linearity, and carryover of the Norudia HbA1c assay were evaluated. Using 60 patient samples, comparative analysis of HbA1c measurements with two commonly used HbA1c assays, the D100 (Bio-Rad Laboratories, Inc) and HLC-723 G11 (Tosoh), was undergone. Thirteen commutable samples with known HbA1c concentrations measured using an IFCC reference measurement procedure were used to compare accuracy between methods. Interference of HbA1c measurement by Hb variants was evaluated using 16 known Hb variant samples. RESULTS: Repeatability (% CV) for low and high concentrations ranged from 1.12%-1.50% and 0.66%-0.75%, respectively, and within-laboratory precision for low and high concentrations ranged from 1.73%-2.89% and 0.98%-1.64%, respectively. For linearity, the coefficient of determination was 0.9987. No significant carryover was observed. When compared to the D100 and HLC-723 G11 assays, the Norudia HbA1c assay showed the best accuracy with the lowest mean bias (-1.72%). Furthermore, the Norudia was least affected by Hb variants and gave the most reliable HbA1c measurements. CONCLUSION: The Norudia HbA1c showed excellent analytical performance with good precision and linearity, and minimal carryover. When compared to other routine HbA1c methods, the Norudia HbA1c assay showed the highest accuracy and was least affected by Hb variants.

A Case of Breakthrough COVID-19 during Hydroxychloroquine Maintenance.

There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 µg/L and 4,890 µg/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.

Best ultrasound parameter for prediction of adverse renal function outcome after pyeloplasty.

OBJECTIVE: To evaluate the clinical value of preoperative ultrasound parameters for post-pyeloplasty outcomes in pediatric patients with ureteropelvic junction obstruction. METHODS: The medical records of 187 pediatric and adolescent patients who underwent pyeloplasty as a result of ureteropelvic junction obstruction between 2010 and 2016 were retrospectively reviewed. The severity of hydronephrosis was measured by the Society for Fetal Urology grade, anteroposterior pelvic diameter, urinary tract dilation, hydronephrosis index, and the hydronephrosis area to renal parenchyma ratio at 3, 6 and 12 months. Adverse renal function outcome was defined as ≥10% decrease in postoperative differential renal function compared with preoperative values. RESULTS: Of the 187 patients, preoperative hydronephrosis was categorized as Society for Fetal Urology grade 3 in 26 patients (13.9%) and grade 4 in 161 patients (86.1%). No surgical failures, defined as requirement of repeat surgery or deterioration of hydronephrosis grade, were noted. The mean changes in Society for Fetal Urology grade, anteroposterior pelvic diameter, urinary tract dilation and hydronephrosis area to renal parenchyma ratio showed similar trends of recovery during the follow-up period. In total, 19 patients (10.2%) showed >10% decrease in differential renal function during follow up (mean 42 months). Multivariate logistic regression analysis showed that the hydronephrosis area-to-renal parenchyma ratio was the only significant prognostic factor for adverse renal function outcome (hazard ratio 1.806, 95% confidence interval 1.210-2.859, P = 0.005). Receiver operating characteristic analysis showed that the hydronephrosis area-to-renal parenchyma ratio was the most significant predictive value (area under the curve 0.711, 95% confidence interval 0.618-0.804, P = 0.006). CONCLUSIONS: Pediatric patients with high hydronephrosis area-to-renal parenchyma ratio values before surgery are more likely to show renal function decline after pyeloplasty.

Transcriptional Profiling of Whisker Follicles and of the Striatum in Methamphetamine Self-Administered Rats.

Methamphetamine (MA) use disorder is a chronic neuropsychiatric disease characterized by recurrent binge episodes, intervals of abstinence, and relapses to MA use. Therefore, identification of the key genes and pathways involved is important for improving the diagnosis and treatment of this disorder. In this study, high-throughput RNA sequencing was performed to find the key genes and examine the comparability of gene expression between whisker follicles and the striatum of rats following MA self-administration. A total of 253 and 87 differentially expressed genes (DEGs) were identified in whisker follicles and the striatum, respectively. Multivariate and network analyses were performed on these DEGs to find hub genes and key pathways within the constructed network. A total of 129 and 49 genes were finally selected from the DEG sets of whisker follicles and of the striatum. Statistically significant DEGs were found to belong to the classes of genes involved in nicotine addiction, cocaine addiction, and amphetamine addiction in the striatum as well as in Parkinson's, Huntington's, and Alzheimer's diseases in whisker follicles. Of note, several genes and pathways including retrograde endocannabinoid signaling and the synaptic vesicle cycle pathway were common between the two tissues. Therefore, this study provides the first data on gene expression levels in whisker follicles and in the striatum in relation to MA reward and thereby may accelerate the research on the whisker follicle as an alternative source of biomarkers for the diagnosis of MA use disorder.

Plasma-based protein biomarkers can predict the risk of acute graft-versus-host disease and non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation.

Predictive biomarkers for acute graft-versus-host disease (aGVHD) is currently lacking. In this study, we employed an unbiased proteome profiling method to prospectively collected plasma samples from allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients to identify protein biomarkers that predict the risk of aGVHD and non-relapse mortality (NRM). In the discovery set, including five aGVHD patients and five controls, we identified seven candidate proteins. Patients with high levels of these proteins tended to exhibit a higher risk of aGVHD and NRM compared to patients with low levels in post-engraftment plasma samples from an independent validation set (n = 89). Tissue inhibitor of metalloproteinase 1, plastin-2, and regenerating islet-derived protein 3-α were selected as the most-predictive biomarkers via an exhaustive variable screening algorithm and were collectively used to develop a biomarker panel score ranging from 0 to 3. The biomarker panel score correlated significantly with aGVHD and NRM risk in univariable and multivariable Cox models. Furthermore, using the biomarker panel score in conjunction with clinical predictors significantly improved the discriminatory performance of the Cox model in predicting aGVHD and NRM risk. Our findings suggest that plasma-derived protein biomarkers can be used to predict aGVHD and NRM before the onset of clinical manifestations.

Quantification of Thiopurine Nucleotides in Erythrocytes and Clinical Application to Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Concentrations of 6-thioguanine (6TG) nucleotides and 6-methylmercaptopurine (6MMP) nucleotides in RBCs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay was validated for clinical use and was applied to blood samples from patients taking mercaptopurine (6MP). METHODS: RBCs were hemolyzed and deproteinized using perchloric acid, followed by heating for the hydrolysis of nucleotides, and the resultant base was measured using LC-MS/MS. Precision, recovery, linearity, matrix effect, and limit of quantification was validated for clinical application. Our results were compared with another institution's established LC-MS/MS assay. We measured the concentrations of 6TG and 6MMP in RBCs of pediatric patients with acute lymphoblastic leukemia (ALL), and the clinical impact of those metabolites was investigated. RESULTS: The imprecision coefficient of variations of 6TG and 6MMP were 5.7%-8.1%, and the bias was within 5%. Lower limits of quantification were set at 54 ng/mL for 6TG and 1036 ng/mL for 6MMP. Correlation coefficients for 6TG and 6MMP were 0.997 and 1.0 in a comparison study. For clinical proof-of-concept, 74 blood samples were collected from 37 pediatric ALL patients receiving maintenance therapy. Concentration of 6TG ranged from 16.1 to 880 pmol/8 × 10 RBCs and that of 6MMP from 55 to 20,937 pmol/8 × 10 RBCs. The 6MP metabolites were not correlated with WBC or absolute neutrophil count. On the other hand, the higher 6MMP level was associated with elevated alanine aminotransferase and aspartate aminotransferase. CONCLUSIONS: In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients.

Mirabegron as a treatment for overactive bladder symptoms in men (MIRACLE study): Efficacy and safety results from a multicenter, randomized, double-blind, placebo-controlled, parallel comparison phase IV study.

AIMS: To evaluate the efficacy and safety of mirabegron in males with overactive bladder (OAB) symptoms. METHODS: In total, 464 males with OAB symptoms were enrolled from 14 institutes and were sorted into either the mirabegron 50 mg (n = 310) or placebo (n = 154) groups. The change in (i) the mean number of 24-h micturition episodes; (ii) OAB Symptom Scale (OABSS); and (iii) International Prostate Symptom Score (IPSS) from baseline to 12 weeks of treatment were compared between the two groups. Safety assessments included treatment-emergent adverse events, blood pressure, pulse rate, postvoid residual volume, and maximum urinary flow rate. After 12 weeks, the study was extended for 14 additional weeks by administering mirabegron 50 mg to both groups. RESULTS: The reduction in the mean number of 24-h micturition episodes from baseline to 12 weeks of treatment was similar between the two groups. However, significantly greater changes from baseline to 12 weeks were observed in total OABSS, OABSS urgency incontinence score (Q4), IPSS storage subscore (Q2 + Q4 + Q7), and IPSS urgency score (Q4) in the mirabegron group (P = 0.01 for all). According to the extended study, the changes of all efficacy variables from baseline to 26 weeks were similar between both groups. The safety assessment results were also similar between the two groups at 12 and 26 weeks. CONCLUSION: A daily 50 mg dose of mirabegron for 12 weeks reduced OAB symptoms in men, and no significant adverse events compared to the placebo group were noted.

Favorable Outcome of Post-Transplantation Cyclophosphamide Haploidentical Peripheral Blood Stem Cell Transplantation with Targeted Busulfan-Based Myeloablative Conditioning Using Intensive Pharmacokinetic Monitoring in Pediatric Patients.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PTCy) was performed previously in adults using a nonmyeloablative conditioning regimen and bone marrow as a graft source. In an effort to reduce relapse rates, myeloablative conditioning regimens with higher intensities are now used. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing in children for effective myeloablation and to reduce toxicity. Here, we report the retrospective results of 34 patients (median age 11.1 years) who underwent haplo-HSCT with PTCy using a targeted busulfan-based myeloablative conditioning regimen and peripheral blood as a stem cell source. The donor-type neutrophil engraftment rate was 97.1%, and the cumulative incidence rates of grade II to IV and grade III to IV acute and extensive chronic graft-versus-host disease were 38.2%, 5.9%, and 9.1%, respectively. The overall survival and event-free survival rates, and treatment-related mortality were 85.0%, 79.4%, and 2.9%, respectively. Based on the subgroup analysis of patients with malignancies (n = 23), the relapse incidence rate was 21.7%. Haplo-HSCT using PTCy with targeted busulfan-based myeloablative conditioning and peripheral blood as a stem cell source was a safe and promising therapeutic option for children.

The Genetic Polymorphism UGT1A4*3 Is Associated with Low Posaconazole Plasma Concentrations in Hematological Malignancy Patients Receiving the Oral Suspension.

The metabolism of posaconazole is mediated mainly by uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, especially UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the posaconazole plasma concentration (PPC). This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome treated with posaconazole oral suspension (200 mg) three times daily for fungal prophylaxis. The patients were examined for the multidrug resistance gene 1 3435C>T and 2677G>T/A variations and the UGT1A4*3 allele by direct sequencing of DNA from peripheral whole-blood samples. We defined poor absorbers to be those with PPCs of <200 ng/ml and the optimal PPC to be ≥700 ng/ml on day 8. The associations between genetic polymorphisms and the PPC were evaluated using multivariate logistic regression analysis including clinical variables. During the study period, 132 patients were enrolled. Six patients (4.5%) were defined as poor absorbers, and 49 patients (37.1%) did not reach the optimal PPC on day 8. In multivariate analysis, the independent risk factors for a poor absorber were at least one UGT1A4*3 allele (adjusted odds ratio [aOR], 18.81; 95% confidence interval [CI], 1.09 to 324.44; P = 0.043) and poor oral food intake (aOR per -100 kcal, 1.44; 95% CI, 1.04 to 1.99; P = 0.029). There was no statistically significant association between the genetic polymorphisms and achievement of the optimal PPC on day 8. The UGT1A4*3 polymorphism is an independent risk factor for being a poor absorber of posaconazole oral suspension in patients with hematological malignancies.

Early Therapeutic Drug Monitoring of Posaconazole Oral Suspension in Patients With Hematologic Malignancies.

BACKGROUND: Therapeutic drug monitoring (TDM) of posaconazole is usually performed 1 week after starting the drug because of its long half-life. However, previous studies showed that measuring the posaconazole plasma concentration (PPC) on day 3 is effective for predicting steady-state levels. The purpose of this study was to evaluate the relevance of early TDM (day 3) of posaconazole for achieving an optimal PPC. METHODS: This prospective study was conducted from September 2014 to August 2016. A total of 148 patients with acute myeloid leukemia or myelodysplastic syndromes received a 200 mg posaconazole oral suspension 3 times daily for fungal prophylaxis. During the period from September 2014 to December 2015 (control group), no dose adjustment was performed on day 3. During the period from January 2016 to Aug 2016 (early TDM group), the frequency of posaconazole 200-mg administration was increased to 4 times daily in patients whose PPC on day 3 was <400 ng/mL. The cutoff value for optimal PPC on day 8 was defined as 500 ng/mL. RESULTS: In 21 of 107 patients (20%) in the control group, PPC was <400 ng/mL on day 3. In 15 (71%) of these 21 patients, the PPC was suboptimal on day 8. In the early TDM group, the PPC was <400 ng/mL on day 3 in 4 of 41 patients (10%). After increasing the posaconazole administration frequency in these 4 patients, PPC was suboptimal on day 8 in 1 patient (25%). In both groups, 104 patients had a PPC of ≥500 ng/mL on day 3, but 7% (7/104) of these had a suboptimal level on day 8. CONCLUSIONS: Early TDM on day 3 for posaconazole suspension may help more patients achieve optimal drug levels on day 8, although TDM on day 8 is needed even in patients with optimal levels on day 3.

Antenatal Prediction of Neonatal Survival in Sacrococcygeal Teratoma.

OBJECTIVES: In sacrococcygeal teratoma, the presence of high-output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. METHODS: The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3 ). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N-terminal pro-B-type natriuretic peptide [NT-pro-BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. RESULTS: The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT-pro-BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3 /cm, elevated NT-pro-BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. CONCLUSIONS: The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

Clinicopathological Characteristics of Urinary Bladder Tumors in Korean Patients 20 Years or Younger.

BACKGROUND: To investigate the clinicopathological characteristics of urinary bladder tumors, a rare malignancy, in patients 20 years or younger. METHODS: Using a retrospective chart review among patients who received bladder surgery at 2 institutions between July 1996 and January 2013, we analyzed the clinicopathological characteristics of urinary bladder tumors in 21 pediatric patients (male:female = 4.25:1.00; mean age, 12.1 years). RESULTS: Pathology revealed 9 urothelial tumors, 6 rhabdomyosarcomas, 1 low-grade leiomyosarcoma, 1 large cell neuroendocrine carcinoma, 1 inflammatory myofibroblastic tumor, and 3 cases of chronic inflammation without tumors (including 1 xanthogranulomatous inflammation). Urothelial tumors (mean patient age, 16.0 years) were benign or low-grade; and only transurethral resection of the bladder tumor was necessary for treatment. Patients with rhabdomyosarcomas (mean age, 5 years) underwent radiotherapy (if unresectable) or transurethral resection of the bladder tumor (if resectable), after chemotherapy. Of these patients, 2 underwent radical cystectomy, with the remaining patients not receiving a cystectomy. With the exception of one patient, all patients are currently alive and recurrence-free. CONCLUSION: Urothelial tumors were the most commonly found pediatric bladder tumor, with embryonal rhabdomyosarcoma being the second most common. Urothelial tumors are common in relatively older age. Since urothelial tumors in children typically have a good prognosis and rarely recur, transurethral resection of the bladder tumor is the treatment of choice. Rhabdomyosarcomas are common in younger patients. Since rhabdomyosarcoma is generally chemosensitive, chemotherapy and radiotherapy are the treatment of choice for bladder preservation in these patients.

Long-term Outcomes of Endoscopic Anti-reflux Surgery in Pediatric Patients with Vesicoureteral Reflux: Urinary Tract Infection, Renal Scarring, and Predictive Factors for Success.

BACKGROUND: To report the long-term outcomes of endoscopic surgery (ES) in pediatric patients with vesicoureteral reflux in terms of success rate, urinary tract infection, and renal function. METHODS: We retrospectively reviewed the records of 73 pediatric patients (110 ureters) who underwent ES for vesicoureteral reflux. Ultrasonography was performed 1, 3, and 12 months postoperatively. Voiding cystourethrography was performed 3 months postoperatively and repeated after 1 year if vesicoureteral reflux persisted. Success was defined as the absence of reflux at the first voiding cystourethrography. Renal scans were performed at least 12 months postoperatively. Renal function deterioration was defined as a new scar or a greater than 5% decrease in function. RESULTS: The median follow-up duration was 24 (12-118) months. The overall success was 65.6%, while it was 78.9%, 87.0%, 62.5%, 37.5%, 66.7% for grades I, II, III, IV, and V, respectively. In multivariate analyses, significant predictive factors for success were vesicoureteral reflux grade (odds ratio [OR], 0.28; P < 0.001) and mound detection at the first postoperative ultrasonography (OR, 13.53; P < 0.001). Renal function deterioration was found in 8 (15.3%) ureters and was less common in those with successful surgeries than in those with failures (9.5% vs. 40.0%; P = 0.035). No significant predictive factor for renal function deterioration or urinary tract infection was found. CONCLUSION: Successful short-term outcomes of ES are expected in low-grade vesicoureteral reflux, especially when a mound is detected by postoperative ultrasonography. However, unpredictable long-term renal deterioration warrants continued follow-up.

Pediatric patients undergoing hematopoietic stem cell transplantation can greatly benefit from a novel once-daily intravenous busulfan dosing nomogram.

Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2183 busulfan concentrations in 137 pediatric patients (age: 0.6-22.2 years), who received IV busulfan once-daily for 4 days before undergoing HSCT. Based on the final population PK model, an optimal once-daily IV busulfan dosing nomogram was derived. The percentage of simulated patients achieving the daily target area under the concentration-time curve (AUC) by the new nomogram was compared with that by other busulfan dosing regimens including the FDA regimen, the EMA regimen, and the empirical once-daily regimen without therapeutic drug monitoring (TDM). A one-compartment open linear PK model incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as a significant covariate adequately described the concentration-time profiles of busulfan. An optimal dosing nomogram based on the PK model performed significantly better than the other dosing regimens, resulting in >60% of patients achieving the target AUC while the percentage of patients exceeding the toxic AUC level was kept <25% during the entire treatment period. A novel once-daily busulfan dosing nomogram for pediatric patients undergoing HSCT is useful for clinicians, particularly in a setting where TDM service is not readily available or to optimize the dose on day 1.

Hb variants in Korea: effect on HbA1c using five routine methods.

BACKGROUND: Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). METHODS: Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. RESULTS: Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb ß-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. CONCLUSIONS: HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

Ileal Augmentation Cystoplasty Combined with Ileal Ureter Replacement After Radical Treatment for Cervical Cancer.

BACKGROUND: This study reviewed the outcomes for patients who underwent simultaneous bladder and ureter reconstructive surgery using the ileum after radical treatment for cervical cancer. METHODS: The medical records of seven patients who underwent augmentation ileocystoplasty with ileal ureter replacement between September 2006 and May 2013 were reviewed. Data on indications for surgery, underlying urologic comorbidities, type of ureteral replacement, postoperative complications, and changes in renal function were obtained. RESULTS: The median age of the patients was 56 years. The primary tumor was cervical cancer in all the patients, and the majority of the patients (4/7, 57.1 %) were previously treated with radical hysterectomy plus radiotherapy. Ileal ureter replacement was performed on 11 renal units, and bilateral ileal ureter substitution was performed for four patients, with the largest ureteral defect being 15 cm. The median length of the ileum used for augmentation and ureter substitution was 30 cm (range 15-40 cm), and the median hospital stay was 23 days (range 18-47 days). The overall rate of major complications (grade ≥3) was 57.1 % (4 of 7 patients). The median preoperative and immediate postoperative serum creatinine levels were respectively 1.2 mg/dL and 0.9 mg/dL. During a mean follow-up duration of 38 months, none of the patients experienced deterioration of renal function after surgery. CONCLUSION: Ileal ureter substitution combined with augmentation ileocystoplasty is a useful surgical technique for bridging long ureteral defects caused by ureteric stenosis from surgery, radiotherapy, or both for pelvic tumors in contracted low-compliance bladders.

Prenatal prediction of neonatal death in single ventricle congenital heart disease.

OBJECTIVE: The objective of this study was to determine whether prenatal ultrasound findings and cord blood N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac troponin T (cTnT) can predict neonatal mortality in single ventricle congenital heart disease. METHODS: The association between neonatal mortality and prenatal ultrasound findings/cord blood biomarkers was evaluated in neonates delivered with a diagnosis of single ventricle congenital heart disease. The presence of prenatal ultrasound findings suggesting systemic outflow obstruction (ascending aorta < 2.5 percentile) or ventricular dysfunction (the presence of cardiomegaly or hydrops) was evaluated, and the total number of abnormal findings was converted to a numeric score called the 'single ventricle score'. In addition, NT pro-BNP and cTnT were measured in cord blood taken at the time of delivery. RESULTS: A total of 48 cases of single ventricle congenital heart disease were included. The rate of neonatal mortality was 31% (15/48). The presence of either abnormal ultrasound findings (single ventricle score ≥ 2) or elevated concentrations of NT pro-BNP or cTnT was associated with increased risk of neonatal death. CONCLUSION: The presence of either abnormal prenatal ultrasound findings or increased cord blood NT pro-BNP and cTnT concentrations was associated with the risk of neonatal death in single ventricle congenital heart disease.