Purpose: Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity. Materials and Methods: We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs. Results: The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg. Conclusion The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.

BACKGROUND: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. METHODS: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant antifungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. RESULTS: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: CL (L/h) = 5.9 × (BSA / 1.2)0.9, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, ka (h-1) = 0.000377. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. CONCLUSION: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

OBJECTIVE: This article examined the psychometric properties of the Korean version of the Infant-Toddler Social and Emotional Assessment (K-ITSEA). METHODS: Translation and back-translation of the K-ITSEA were conducted after obtaining a permission. Two thousand two hundred thirty six Korean community infants (1,199 boys and 1,037 girls) between the ages of 12 and 36 months (M=34.23, SD=3.80) and 90 clinical infant samples (60 boys and 30 girls) between the ages of 12 and 36 months (M=26.84, SD=6.24) participated in the present study. RESULTS: Confirmatory factor analyses supported the Internalizing, Externalizing, Dysregulation, and Competence domains as well as the 17 individual scales that comprise the K-ITSEA. Young children's sex and age differences emerged for some problem and most competence scales. All domains showed adequate intrascale reliability and test-retest reliability. Scale intracorrelation analyses and associations between the K-ITSEA and Korean version of PSI, Korean version of CBCL1.5-5 supported the validity of the assessment. Comparisons of the K-ITSEA scores for the Autism Spectrum Disorder, Psychiatric Disorders and Matched control groups supported the discriminant validity of the K-ITSEA. CONCLUSION: This preliminary results indicate that the K-ITSEA would be a useful assessment for detecting the early childhood's behavior problems and competences in Korean population.
Autism Spectrum Disorder ; Humans ; Infant ; Mental Competency ; Psychometrics ; Reproducibility of Results* ; Weights and Measures

PURPOSE: This study aimed to examine the development of socializing and emotional expressions through vocalizations and joint attention (JA) behaviors in Korean-speaking children with autism spectrum disorder (ASD), compared to those with developmental delay (DD). MATERIALS AND METHODS: Video samples were collected from 28 toddlers with ASD and 18 age-matched toddlers with DD, and vocalizations were each coded in detail for the purpose of this retrospective research. In addition to some statistical analysis, Computerized Language Analysis was conducted to obtain the final results. RESULTS: Although they produced a higher number of vocalizations than the DD group, the ASD group did not engage in emotional or social interactions with their caretakers, whereas the DD group did. The children with ASD used more atypical vocalizations and socially unengaged vocalizations than the children with DD did. JA using vocalizations in the ASD group, in particular, was largely dyadic, with triadic types occurring at a significantly lower frequency than those in the DD group. CONCLUSION: Results from this study indicate the importance of assessing early vocalizations in toddlers with ASD, suggesting that some common symptoms of ASD, such as lack of typical, emotional, and social functions in early vocalizations, could be used to develop screening and intervention programs related to ASD.
Autism Spectrum Disorder* ; Autistic Disorder* ; Child ; Child Behavior ; Communication Disorders ; Developmental Disabilities ; Humans ; Interpersonal Relations ; Joints ; Mass Screening ; Mother-Child Relations ; Retrospective Studies

Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD⁺) metabolism. However, the functional role of NAD⁺ metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD⁺ levels affect the characteristics of glioma-driven SSEA1⁺ TICs, including clonogenic growth potential. An increase in the mitochondrial NAD⁺ levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD⁺ levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.
Glioblastoma* ; Lactic Acid ; Metabolism ; Mitochondria ; NAD ; NADP Transhydrogenases ; Phenotype ; Tics ; Up-Regulation*

Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients. We used nonintegrating oriP/EBNA-1-based episomal vectors to reprogram dermal fibroblasts from patients with AIDs such as ankylosing spondylitis (AS), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The pluripotency and multilineage differentiation capacity of each patient-specific iPSC line was validated. The safety of these iPSCs for use in stem cell transplantation is indicated by the fact that all AID-specific iPSCs are integrated transgene free. Finally, all AID-specific iPSCs derived in this study could be differentiated into cells of hematopoietic and mesenchymal lineages in vitro as shown by flow cytometric analysis and induction of terminal differentiation potential. Our results demonstrate the successful generation of integration-free iPSCs from patients with AS, SS and SLE. These findings support the possibility of using iPSC technology in autologous and allogeneic cell replacement therapy for various AIDs, including AS, SS and SLE.
Autoimmune Diseases* ; Fibroblasts ; Humans ; In Vitro Techniques ; Induced Pluripotent Stem Cells* ; Lupus Erythematosus, Systemic ; Pluripotent Stem Cells ; Spondylitis, Ankylosing ; Stem Cell Transplantation ; Stem Cells ; Transgenes

BACKGROUND: In this report, we present the annual data of the intensive care unit (ICU) module of the Korean Nosocomial Infections Surveillance System (KONIS) from July 2013 through June 2014. METHODS: We performed a prospective surveillance of nosocomial urinary tract infections (UTIs), bloodstream infections (BSIs), and pneumonia (PNEU) in 166 ICUs of 94 hospitals using the KONIS. Nosocomial infection (NI) rate was defined as the number of infections per 1,000 patient-days or device-days. RESULTS: A total of 2,843 NIs were found during the study period: 861 UTIs (846 were urinary catheter-associated), 1,173 BSIs (1,021 were central line-associated), and 809 PNEUs (498 were ventilator-associated). The rate of urinary catheter-associated UTIs was 1.21 per 1,000 device-days (95% confidence interval [CI]=1.13-1.29), and the urinary catheter utilization ratio was 0.84 (95% CI=0.839-0.841). The rate of central line-associated BSIs was 2.33 per 1,000 device-days (95% CI=2.20-2.48), and the utilization ratio was 0.53 (95% CI=0.529-0.531). The rate of ventilatorassociated PNEUs (VAPs) was 1.46 per 1,000 device-days (95% CI=1.34-1.60), and the utilization ratio was 0.41 (95% CI=0.409-0.411). In hospitals with more than 900 beds, although the ventilator utilization ratio was highest, the rate of VAPs was lower than in hospitals with 300-699 or 700-899 beds. CONCLUSION: BSIs were the most commonly reported nosocomial infections. Although device utilization ratios had increased, nosocomial infection rates did not differ significantly from those during the previous period (July 2012 through June 2013).
Cross Infection* ; Intensive Care Units* ; Critical Care* ; Pneumonia ; Prospective Studies ; Urinary Catheters ; Urinary Tract Infections ; Ventilators, Mechanical

The National Evidence-based Collaborating Agency (NECA) holds the NECA Round-table Conference that not only disseminates objective and systematic information on topics of social concern in public health care but also organizes discussions on core issues under dispute in the literature through panels composed of multidisciplinary experts. Accordingly, the Round-table Conference was composed of multidisciplinary experts including medical specialists in the areas of psychiatry and preventive medicine, psychiatric and mental health nursing, psychologists, social welfare experts, consultation experts, religious leaders, and government officials from the Ministry of Education, Science and Technology, and Ministry of Health and Welfare. The Round-table Conference, tasked with analysis of the actual status and causes of, and search for solutions for suicide in adolescents, has reached consensus on the current status, trend, risk factors and prevention factors, problems and issues in prevention and coping strategies, effective prevention and coping strategies and areas of research needed for the future. The Round-table Conference commented on the actual status and gravity of suicides in adolescents, and came to the agreement that mental health issues including stress from interpersonal relationships and depression are the key risk factors of suicide. It was further agreed that problems in the measures being implemented for each of the areas include lack of manpower and funding, and inadequate organic association and cooperation among relevant institutions. They also agreed that development of a government-initiated suicide prevention program for adolescents, association among relevant experts, and development, and management of practical guidelines that are of broad and practical use are important. Furthermore, the panels were in agreement that the mass media must comply with the recommended level of coverage in reporting of suicide as adolescents are greatly influenced by provocative mass media reports due to their strong impulsive dispositions.
Adenosine-5'-(N-ethylcarboxamide) ; Adolescent ; Cause of Death ; Consensus ; Depression ; Dissent and Disputes ; Financial Management ; Gravitation ; Humans ; Mass Media ; Mental Health ; Occupational Groups ; Porphyrins ; Preventive Medicine ; Public Health ; Risk Factors ; Social Welfare ; Specialization ; Suicide

OBJECTIVES: The aim of this study was to investigate the effect of the clinical and demographic variables such as body weight, dosage, family history of attention-deficit hyperactivity disorder (ADHD), and psychiatric co-morbidity on the side-effects of OROS-Methylphenidate (OROS-MPH), and to evaluate the relationship between drug response and side effect severity. METHODS: A total of 144 children (ages 6-18) with diagnosed ADHD were treated with OROS-MPH. Children were examined at baseline and after 1, 3, 6, 9, and 12 weeks of each treatment condition. The stimulant drug side effect rating scale (SERS), pulse rate, systolic blood pressure, diastolic blood pressure, and electrocardiogram (ECG) were evaluated to assess side effect profiles. Changes in these parameters from baseline were examined and analyzed. RESULTS: Anorexia (30.95%) and insomnia (13.10%) were the most commonly reported side effects during this study. Insomnia and loss of appetite score increased at one week follow-up, but was sustained or decreased as treatment progressed. Small but significant increases in pulse rate and diastolic blood pressure were observed during treatment; however, no clinically meaningful changes in ECG parameters were noted during the study. Low body weight, high dosage of OROS-MPH, and family history of ADHD were associated with cardiovascular side effect. In contrast, there was no significant relationship between OROS-MPH treatment response and the severity of side effect and no difference resulted between the responder and non-responder groups with respect to OROS-MPH dosage in the 12 weeks of follow-up. CONCLUSION: To the best of our knowledge, this study is the first Korean study to investigate comprehensive side effect profiles and their correlates in OROS-MPH treatment for ADHD children. OROS-MPH was well tolerated with no clinically significant side effects during the treatment period. In conclusion, low body weight, high dosage of OROS-MPH, and family history of ADHD could be used as predictive factors in increasing pulse rate and blood pressure.
Adolescent ; Anorexia ; Appetite ; Blood Pressure ; Body Weight ; Child ; Electrocardiography ; Follow-Up Studies ; Heart Rate ; Humans ; Sleep Initiation and Maintenance Disorders

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (> or =500/microL) and platelets (> or =20,000/microL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cytarabine/*therapeutic use/toxicity ; Disease-Free Survival ; Female ; Granulocyte Colony-Stimulating Factor/*therapeutic use/toxicity ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Vidarabine/*analogs & derivatives/therapeutic use/toxicity