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author:("Kim, Hye took")
1.  The use of everolimus to target carcinogenic pathways in a patient with renal cell carcinoma and tuberous sclerosis complex: a case report 
Introduction
An increased understanding of the genetic pathways involved in renal cell carcinoma has resulted in the development of various drugs that target relevant signaling cascades for the specific treatment of this disease. However, no validated predictive markers have been identified to guide the decision whether patients should receive vascular endothelial growth factor–targeted therapy or mammalian target of rapamycin–targeted therapy. We present what is, to the best of our knowledge, the first case of renal cell carcinoma in a patient with tuberous sclerosis complex who was successfully treated with everolimus.
Case presentation
The patient was a 49-year-old Korean woman with tuberous sclerosis complex and recurrent renal cell carcinoma. The patient was treated with the tyrosine kinase inhibitor sunitinib followed by the mammalian target of rapamycin inhibitor everolimus. This treatment resulted in a prolonged response and significant clinical benefit. Notably, everolimus ameliorated the symptoms related not only to renal cell carcinoma but also to tuberous sclerosis complex.
Conclusion
This case provides a rationale for the use of everolimus as first-line treatment for this specific patient population in order to target the correct pathway involved in carcinogenesis.
doi:10.1186/1752-1947-8-95
PMCID: PMC3976165  PMID: 24612911
Everolimus; Mammalian target of rapamycin inhibitor; Renal cell carcinoma; Tuberous sclerosis complex
2.  Predictive Efficacy of Low Burden EGFR Mutation Detected by Next-Generation Sequencing on Response to EGFR Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Carcinoma 
PLoS ONE  2013;8(12):e81975.
Direct sequencing remains the most widely used method for the detection of epidermal growth factor receptor (EGFR) mutations in lung cancer; however, its relatively low sensitivity limits its clinical use. The objective of this study was to investigate the sensitivity of detecting an epidermal growth factor receptor (EGFR) mutation from peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp and Ion Torrent Personal Genome Machine (PGM) techniques compared to that by direct sequencing. Furthermore, the predictive efficacy of EGFR mutations detected by PNA-LNA PCR clamp was evaluated. EGFR mutational status was assessed by direct sequencing, PNA-LNA PCR clamp, and Ion Torrent PGM in 57 patients with non-small cell lung cancer (NSCLC). We evaluated the predictive efficacy of PNA-LNA PCR clamp on the EGFR-TKI treatment in 36 patients with advanced NSCLC retrospectively. Compared to direct sequencing (16/57, 28.1%), PNA-LNA PCR clamp (27/57, 47.4%) and Ion Torrent PGM (26/57, 45.6%) detected more EGFR mutations. EGFR mutant patients had significantly longer progressive free survival (14.31 vs. 21.61 months, P = 0.003) than that of EGFR wild patients when tested with PNA-LNA PCR clamp. However, no difference in response rate to EGFR TKIs (75.0% vs. 82.4%, P = 0.195) or overall survival (34.39 vs. 44.10 months, P = 0.422) was observed between the EGFR mutations by direct sequencing or PNA-LNA PCR clamp. Our results demonstrate firstly that patients with EGFR mutations were detected more frequently by PNA-LNA PCR clamp and Ion Torrent PGM than those by direct sequencing. EGFR mutations detected by PNA-LNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC.
doi:10.1371/journal.pone.0081975
PMCID: PMC3869671  PMID: 24376508
3.  Correction: New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication 
PLoS ONE  2013;8(9):10.1371/annotation/6e1f1f8f-c421-4def-aaf1-4ce7f4915d87.
doi:10.1371/annotation/6e1f1f8f-c421-4def-aaf1-4ce7f4915d87
PMCID: PMC3792148  PMID: 24116247
4.  New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication 
PLoS ONE  2013;8(8):e72519.
Background
Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed.
Methodology/Principal Findings
Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.
Conclusions/Significance
We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.
doi:10.1371/journal.pone.0072519
PMCID: PMC3758303  PMID: 24023620
5.  Successful treatment of disseminated interdigitating dendritic cell sarcoma with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy 
The Korean Journal of Hematology  2012;47(2):150-153.
Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the basis of immunohistochemical findings of a biopsy specimen of the inferior nasal concha. Immunohistochemical staining showed a positive reaction for CD68, leukocyte common antigen, and S-100 protein, but a negative reaction for CD34, CD1a, and CD21. Imaging studies showed cervical and axillary lymphadenopathies, subcutaneous nodules, and a soft tissue lesion in the nasal cavity. Treatment with the ABVD regimen resulted in complete remission after 8 cycles of chemotherapy.
doi:10.5045/kjh.2012.47.2.150
PMCID: PMC3389066  PMID: 22783364
IDCS; ABVD chemotherapy; Complete remission
6.  Optimal time for repeating the IgM anti-hepatitis A virus antibody test in acute hepatitis A patients with a negative initial test 
Background/Aims
The nonspecific clinical presentation of acute hepatitis A (AHA) mandates the detection of anti-hepatitis A virus IgM antibodies (IgM anti-HAV) in the serum for obtaining a definitive diagnosis. However, IgM anti-HAV might not be present during the early phase of the disease. The aim of this study was to determine the optimal time for repeating the IgM anti-HAV test (HAV test) in AHA patients with a negative initial test.
Methods
In total, 261 patients hospitalized with AHA were enrolled for this retrospective study. AHA was diagnosed when the test for IgM anti-HAV was positive and the serum alanine aminotransferase (ALT) level was ≥400 IU/L. Repeat HAV test was conducted after 1-2 weeks if the initial HAV test was negative but AHA was still clinically suspected.
Results
The results of the initial HAV test were negative in 28 (10.7%) patients. The intervals from symptom onset to the initial-HAV-test day and from the peak-ALT day to the initial-HAV-test day were significantly shorter in the negative-initial-HAV-test group, but on multivariate analysis only the latter was significantly associated with negative results for the initial HAV test (β=-0.978; odds ratio [95% confidence interval]=0.376 [0.189-0.747]; P=0.005). The HAV test was positive in all patients when it was performed at least 2 days after the peak-ALT day.
Conclusions
The results of HAV tests were significantly associated with the interval from the peak-ALT day to the HAV-test day. The optimal time for repeating the HAV test in clinically suspicious AHA patients with a negative initial HAV test appears to be at least 2 days after the peak-ALT day.
doi:10.3350/kjhep.2012.18.1.56
PMCID: PMC3326997  PMID: 22511904
Acute hepatitis A; IgM anti-HAV; Alanine aminotransferase
7.  Comparison on the Efficacy of Disinfectants Used in Automated Endoscope Reprocessors: PHMB-DBAC versus Orthophthalaldehyde 
Clinical Endoscopy  2011;44(2):109-115.
Background/Aims
Since endoscopes are reusable apparatus classified as semicritical item, thorough reprocessing to achieve high-level disinfection is of utmost importance to prevent spread of infection. To improve disinfection efficacy and safety, disinfectants and endoscope reprocessors are continuously evolving. This study aimed to compare the efficacy of the combination of polyhexamethylenebiguanide hydrochloride-alkyldimethylbenzylammonium chloride (PHMB-DBAC) and orthophthalaldehyde (OPA) used respectively in ultrasonographic cleaning incorporated automated endoscope reprocessors: COOLENDO (APEX Korea) or OER-A (Olympus Optical).
Methods
A total of 86 flexible upper endoscopes were randomly reprocessed with either COOLENDO/PHMB-DBAC or OER-A/OPA. Culture samplings were done at two sites (endoscope tip and working channel) which were later incubated on blood agar plate. Bacterial colonies were counted and identified.
Results
The culture-positive rate at the endoscope tip and working channel was 0% and 2.33% for COOLENDO/PHMB-DBAC and 4.65% and 0% for OER-A/OPA. Staphylococcus hominis was cultured from one endoscope reprocessed with COOLENDO/PHMB-DBAC and Pseudomonas putida was isolated from two endoscopes reprocessed with OER-A/OPA.
Conclusions
The reprocessing efficacy of COOLENDO/PHMB-DBAC was non-inferior to that of OER-A/OPA (p=0.032; confidence interval, -0.042 to 0.042). During the study period, significant side effect of PHMB-DBAC was not observed.
doi:10.5946/ce.2011.44.2.109
PMCID: PMC3363059  PMID: 22741121
Endoscope reprocessing; Disinfectants; High-level disinfection
8.  New Integrated Information System for Pusan National University Hospital 
Objectives
This study presents the information system for Pusan National University Hospital (PNUH), evaluates its performance qualitatively, and conducts economic analysis.
Methods
Information system for PNUH was designed by component-based development and developed by internet technologies. Order Communication System, Electronic Medical Record, and Clinical Decision Support System were newly developed. The performance of the hospital information system was qualitatively evaluated based on the performance reference model in order to identify problem areas for the old system. The Information Economics approach was used to analyze the economic feasibility of hospital information system in order to account for the intangible benefits.
Results
Average performance scores were 3.16 for input layer, 3.35 for process layer, and 3.57 for business layer. In addition, the cumulative benefit to cost ratio was 0.50 in 2011, 1.73 in 2012, 1.76 in 2013, 1.71 in 2014, and 1.71 in 2015. The B/C ratios steadily increase as value items are added.
Conclusions
While overall performance scores were reasonably high, doctors were less satisfied with the system, perhaps due to the weak clinical function in the systems. The information economics analysis demonstrated the economic profitability of the information systems if all intangible benefits were included. The second qualitative evaluation survey and economic analysis were proposed to evaluate the changes in performance of the new system.
doi:10.4258/hir.2011.17.1.67
PMCID: PMC3092996  PMID: 21818459
Hospital Information System; Evaluation; Cost-Benefit Analysis
9.  Impacts of Individual Innovativeness on the Acceptance of IT-based Innovations in Health Care Fields 
Healthcare Informatics Research  2010;16(4):290-298.
Objectives
The purpose of this study is to identify the role of individual innovation to demographic variables for determining IT adoption behaviors. This study also examines the effect of individual innovation on IT adoption behaviors across IT types.
Methods
To verify the invariant effect of individual innovativeness, two groups of persons working in the health care field were surveyed. The first study subject group was radiologists and their adoption of e-purchasing the second group was emergency rescue crews and their adoption of GPS.
Results
Adopter categories in innovations (ACI) as the measurement of individual innovation were a significant variable in both studies. Innovative adopters were more likely to use new IT tools than the majority of early adopters, and the early majority was more likely to adopt IT than the laggards. After merging the two data sets into one for testing the role of IT types as a moderator, the significance of ACI did not change, compared to the two separate analyses. In the merged data set, innovative adopters were 2.34 times more likely to be adopters than the early majority. The early majority was 2.32 times more likely to be adopters than laggards. Moreover, there were no moderating effects of IT types. Thus, there were no reversed adoption rates according to levels of ACI and demographic variables.
Conclusions
ACI has invariant effects on IT adoption behaviors regardless of IT types and demographic differences. To implement a new innovation, understanding individual innovativeness will provide more sophisticated implementation strategies for health care organizations and appropriate education programs for their employees.
doi:10.4258/hir.2010.16.4.290
PMCID: PMC3092138  PMID: 21818448
IT Adoption Behaviors; Adopter Categories; Innovation Diffusion; Individual Innovativeness; Moderator
10.  Liver Abscess and Empyema due to Lactococcus lactis cremoris 
Journal of Korean Medical Science  2010;25(11):1669-1671.
Lactococcus lactis cremoris infections are very rare in humans. We experienced liver abscess and empyema due to L. lactis cremoris in an immunocompetent adult. A 42-yr-old man was admitted with fever and abdominal pain. Abdominal computed tomography (CT) revealed a liver abscess and chest CT showed loculated pleural effusion consistent with empyema. L. lactis cremoris was isolated from culture of the abscess material and blood. The patient was treated with pus drainage from liver abscess, video-assisted thoracoscopic decortications for empyema, and antibiotics including cefotaxime and levofloxacin. The patient was completely recovered with the treatment. To our knowledge, this is the first report of a L. lactis cremoris infection in Korea.
doi:10.3346/jkms.2010.25.11.1669
PMCID: PMC2967008  PMID: 21060760
Lactococcus lactis; Liver Abscess; Empyema
11.  Phylogeny and Virulence of Naturally Occurring Type III Secretion System-Deficient Pectobacterium Strains▿  
Applied and Environmental Microbiology  2009;75(13):4539-4549.
Pectobacterium species are enterobacterial plant-pathogenic bacteria that cause soft rot disease in diverse plant species. Previous epidemiological studies of Pectobacterium species have suffered from an inability to identify most isolates to the species or subspecies level. We used three previously described DNA-based methods, 16S-23S intergenic transcribed spacer PCR-restriction fragment length polymorphism analysis, multilocus sequence analysis (MLSA), and pulsed-field gel electrophoresis, to examine isolates from diseased stems and tubers and found that MLSA provided the most reliable classification of isolates. We found that strains belonging to at least two Pectobacterium clades were present in each field examined, although representatives of only three of five Pectobacterium clades were isolated. Hypersensitive response and DNA hybridization assays revealed that strains of both Pectobacterium carotovorum and Pectobacterium wasabiae lack a type III secretion system (T3SS). Two of the T3SS-deficient strains assayed lack genes adjacent to the T3SS gene cluster, suggesting that multiple deletions occurred in Pectobacterium strains in this locus, and all strains appear to have only six rRNA operons instead of the seven operons typically found in Pectobacterium strains. The virulence of most of the T3SS-deficient strains was similar to that of T3SS-encoding strains in stems and tubers.
doi:10.1128/AEM.01336-08
PMCID: PMC2704834  PMID: 19411432
12.  The cutoff values of visceral fat area and waist circumference for identifying subjects at risk for metabolic syndrome in elderly Korean: Ansan Geriatric (AGE) cohort study 
BMC Public Health  2009;9:443.
Background
In Korea, the cutoff values of waist circumference (WC) for the identification of metabolic syndrome (MetS) were suggested to be 90 cm for men and 85 cm for women based on the analysis mainly in middle-aged adults. As aging is associated with increased fat, especially abdominal visceral fat, the cutoff value of WC may differ according to age. In addition, the usefulness of visceral abdominal fat area (VFA) to predict MetS in the elderly has not been studied yet. We aimed to suggest WC and VFA criteria and to compare the predictability of WC and VFA to identify people at risk for MetS.
Methods
A total of 689 elderly subjects aged ≥63 years (308 men, 381 women) were chosen in this cross-sectional study from an ongoing, prospective, population-based study, the Ansan Geriatric (AGE) cohort study. VFA was measured by single slice abdominal computed tomography scanning. The metabolic risk factors except WC (plasma glucose, blood pressure, serum triglycerides and HDL cholesterol levels) were defined using modified NCEP-ATP III criteria. We estimated the accuracy of VFA and WC for identifying at least two of these factors by receiver operating characteristic (ROC) curve analysis.
Results
Two hundred three of 308 men and 280 of 381 women had ≥2 metabolic risk factors. The area under the ROC curve (AUC) value for VFA to predict the presence of ≥2 metabolic risk factors was not significantly different from that for WC (men, 0.735 and 0.750; women, 0.715 and 0.682; AUC values for VFA and WC, respectively). The optimal cutoff points for VFA and WC for predicting the presence of ≥2 metabolic risk factors were 92.6 cm2 and 86.5 cm for men and 88.9 cm2 and 86.5 cm for women.
Conclusion
WC had comparable power with VFA to identify elderly people who are at risk for MetS. Elderly Korean men and women had very similar cutoff points for both VFA and WC measurements for estimating the risk of MetS. Age-specific cutoff point for WC might be considered to identify subjects at risk for MetS.
doi:10.1186/1471-2458-9-443
PMCID: PMC2797519  PMID: 19951442

Results 1-12 (12)