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1.  Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study 
Clinical and molecular hepatology  2013;19(2):165-172.
Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.
130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.
Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment.
ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
PMCID: PMC3701849  PMID: 23837141
Hepatitis B; Carnitine; Entecavir
2.  Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data 
While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.
The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.
The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).
The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.
PMCID: PMC3622854  PMID: 23593608
Gastric variceal bleeding; Rebleeding; Mortality; Cirrhosis
4.  Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data 
This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.
Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.
Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality.
A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.
PMCID: PMC3992326  PMID: 24757655
Liver cirrhosis; Transjugular intrahepatic portosystemic shunt; Portal hypertension
5.  Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001) 
Journal of Gastric Cancer  2013;13(3):164-171.
Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer.
Materials and Methods
Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation.
Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).
PMCID: PMC3804675  PMID: 24156036
Gastrectomy; Stomach neoplasms; Lymph node excision
6.  Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with liver cirrhosis: a retrospective multicenter study 
Clinical and molecular hepatology  2012;18(4):368-374.
This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC).
We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010.
Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047).
BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO.
PMCID: PMC3540373  PMID: 23323252
Balloon-occluded retrograde transvenous obliteration; Esophageal varices; Gastric varices; Liver cirrhosis; Variceal hemorrhage
7.  A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study 
Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.
To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.
In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).
This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.
PMCID: PMC3446390  PMID: 22452962
8.  Current Trends in the Epidemiological and Pathological Characteristics of Gastrointestinal Stromal Tumors in Korea, 2003-2004 
Journal of Korean Medical Science  2010;25(6):853-862.
Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.
PMCID: PMC2877229  PMID: 20514305
Gastrointestinal Stromal Tumors; Epidemiology; Pathology; Prognosis
9.  Targeted exon sequencing fails to identify rare coding variants with large effect in rheumatoid arthritis 
Although it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea.
We analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n = 1,217) and controls (n = 717). We conducted a single-marker association test and a gene-based analysis of rare variants. For meta-analysis or enrichment tests, we also used ethnically matched independent samples of Korean genome-wide association studies (GWAS) (n = 4,799) or immunochip data (n = 4,722).
After stringent quality control, we analyzed 10,588 variants of 398 genes from 1,934 Korean RA case controls. We identified 13 nonsynonymous variants with nominal association in single-variant association tests. In a meta-analysis, we did not find any novel variant with genome-wide significance for RA risk. Using a gene-based approach, we identified 17 genes with nominal burden signals. Among them, VSTM1 showed the greatest association with RA (P = 7.80 × 10−4). In the enrichment test using Korean GWAS, although the significant signal appeared to be driven by total genic variants, we found no evidence for enriched association of coding variants only with RA.
We were unable to identify rare coding variants with large effect to explain the missing heritability for RA in the current targeted resequencing study. Our study raises skepticism about exon sequencing of targeted genes for complex diseases like RA.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0447-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4203956  PMID: 25267259
10.  Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture 
Journal of medical genetics  2013;50(4):212-219.
Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population.
Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study.
In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10−8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis.
Our findings provide new insights into the genetic architecture underlying OF in East Asians.
PMCID: PMC4169276  PMID: 23349225
11.  Comparison of Methicillin-Resistant Staphylococcus aureus Community-Acquired and Healthcare-Associated Pneumonia 
Yonsei Medical Journal  2014;55(4):967-974.
Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of not only healthcare-associated pneumonia (HCAP) but also community-acquired pneumonia (CAP). We determined the impact of MRSA on differences in clinical characteristics, courses, and outcomes between CAP and HCAP.
Materials and Methods
We conducted a retrospective observational study on 78 adult patients admitted with MRSA pneumonia at a university-affiliated tertiary hospital between January 2008 and December 2011. We compared baseline characteristics, chest radiographs, treatment outcomes, and drug resistance patterns between the CAP and HCAP groups.
Of the 78 patients with MRSA pneumonia, 57 (73.1%) were HCAP and 21 (26.9%) were CAP. MRSA infection history in the previous year (29.8% vs. 14.3%, p=0.244) tended to be more common in HCAP than in CAP. Despite similar Pneumonia Severity Index scores (151 in CAP vs. 142 in HCAP), intubation rates (38.1% vs. 17.5%; p=0.072) and intensive care unit admission (42.9% vs. 22.8%; p=0.095) tended to be higher in the CAP group, while 28-day mortality was higher in the HCAP group (14.3% vs. 26.3%; p=0.368), although without statistical significance. All patients showed sensitivity to vancomycin and linezolid; meanwhile, HCAP patients showed greater resistance to gentamicin than CAP patients (58.3% vs. 16.6%; p=0.037). The median total hospital charges were 6899 American dollars for CAP and 5715 American dollars for HCAP (p=0.161).
MRSA pneumonia showed significantly differences in baseline characteristics, chest radiographs, treatment outcomes, and medical expenses between HCAP and CAP groups.
PMCID: PMC4075401  PMID: 24954325
Pneumonia; methicillin-resistant Staphylococcus aureus; community-acquired pneumonia; healthcare-associated pneumonia
12.  Variation block-based genomics method for crop plants 
BMC Genomics  2014;15:477.
In contrast with wild species, cultivated crop genomes consist of reshuffled recombination blocks, which occurred by crossing and selection processes. Accordingly, recombination block-based genomics analysis can be an effective approach for the screening of target loci for agricultural traits.
We propose the variation block method, which is a three-step process for recombination block detection and comparison. The first step is to detect variations by comparing the short-read DNA sequences of the cultivar to the reference genome of the target crop. Next, sequence blocks with variation patterns are examined and defined. The boundaries between the variation-containing sequence blocks are regarded as recombination sites. All the assumed recombination sites in the cultivar set are used to split the genomes, and the resulting sequence regions are termed variation blocks. Finally, the genomes are compared using the variation blocks. The variation block method identified recurring recombination blocks accurately and successfully represented block-level diversities in the publicly available genomes of 31 soybean and 23 rice accessions. The practicality of this approach was demonstrated by the identification of a putative locus determining soybean hilum color.
We suggest that the variation block method is an efficient genomics method for the recombination block-level comparison of crop genomes. We expect that this method will facilitate the development of crop genomics by bringing genomics technologies to the field of crop breeding.
PMCID: PMC4229737  PMID: 24929792
Comparative genomics; Recombination; Whole-genome sequencing; Soybean; Crop plants
13.  Discordance between Perceived and Actual Cancer Stage among Cancer Patients in Korea: A Nationwide Survey 
PLoS ONE  2014;9(5):e90483.
We assessed the accuracy of communication between doctors and patients by evaluating the consistency between patient perception of cancer stage and the medical records, and analyzed the most influential factors of incongruence among cancer patients at 10 cancer centers across Korea.
Information was gathered from cancer patients at the National Cancer Center and nine regional cancer centers located in every province of Korea between 1 July 2008 and 31 August 2008. Data were analyzed using Pearson's χ2 test and multivariate logistic regression analysis.
The stages of cancer reported by the 1,854 patients showed a low degree of congruence with the stages given in medical records (k = 0.35, P<0.001). Only 57.1% of the patients had accurate knowledge of their cancer stage. In total, 18.5% underestimated their stage of disease, and the more advanced the cancer stage, the more likely they were to underestimate it, in order of local (14.2%), regional (23.7%), and distant (51.6%). Logistic regression analysis showed that congruence was lower in patients with cervical cancer (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.30–0.87), recurrence (OR = 0.64, 95% CI = 0.50–0.83), and treatment at the National Cancer Center (OR = 0.53, 95% CI = 0.39–0.72).
There are knowledge gaps between patients' perceived and actual stage of cancer. Patients with cervical cancer, recurrence, and who received treatment at a regional cancer center showed less understanding of their cancer stage.
PMCID: PMC4015901  PMID: 24817193
14.  Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barré Syndrome in Korea: A Nationwide Multicenter Study 
Background and Purpose
No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barré syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance.
Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody.
Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study.
Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.
PMCID: PMC4017025  PMID: 24829594
Guillain-Barré syndrome; ganglioside; antibodies; Korea; acute motor axonal neuropathy
15.  A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene 
Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man who was employed as a lead welder at a computer repair center. He was installing the capacitors on computer chip boards and had been wiped down with TCE. He was admitted to our hospital with complaints of dry coughs, night sweats, and weight losses for the past two months. HP due to TCE exposure was being suspected due to his occupational history, and the results of a video-associated thoracoscopic biopsy confirmed the suspicions. Symptoms have resolved after the steroid pulse therapy and his occupational change. TCE should be taken into consideration as a potential trigger of HP. Early recognition and avoidance of the TCE exposure in the future is important for the treatment of TCE induced HP.
PMCID: PMC3948855  PMID: 24624216
Alveolitis, Extrinsic Allergic; Trichloroethylene; Occupational Exposure; Lung Diseases
16.  Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA) 
Korean Journal of Pediatrics  2013;56(10):439-445.
Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort.
The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia.
The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004).
The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.
PMCID: PMC3827492  PMID: 24244212
Cohort studies; Infant; Respiratory tract infections; Umbilical cord blood; Vitamin D
17.  Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions 
The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data.
PMCID: PMC3622850  PMID: 23593604
Guidelines; Contrast enhanced Ultrasonography (CEUS); Focal liver lesions (FLLs)
18.  Tinea Incognito in Korea and Its Risk Factors: Nine-Year Multicenter Survey 
Journal of Korean Medical Science  2013;28(1):145-151.
Tinea incognito (TI) is a dermatophytic infection which has lost its typical clinical appearance because of improper use of steroids or calcineurin inhibitors. The incidence of TI is increasing nowadays. We conducted retrospective review on 283 patients with TI from 25 dermatology training hospitals in Korea from 2002-2010 to investigate the demographical, clinical, and mycological characteristics of TI, and to determine the associated risk factors. More than half (59.3%) patients were previously treated by non-dermatologists or self-treated. The mean duration of TI was 15.0 ± 25.3 months. The most common clinical manifestations were eczema-like lesion, psoriasis-like, and lupus erythematosus-like lesion. The trunk and face were frequently involved, and 91 patients (32.2%) also had coexisting fungal infections. Among 67 isolated strains, Trichophyton rubrum was the most frequently detected (73.1%). This is the largest study of TI reported to date and the first investigational report concerning TI in Korea. We suggest that doctors should consider TI when a patient has intractable eczema-like lesions accompanied by tinea pedis/unguium. Furthermore, there should be a policy change, which would make over-the-counter high-potency topical steroids less accessible in some countries, including Korea.
PMCID: PMC3546093  PMID: 23341725
Calcineurin Inhibitor; Dermatophytoses; Korea; Steroid; Tinea; Tinea Incognito
19.  Trends in the Incidence of Hospitalized Acute Myocardial Infarction and Stroke in Korea, 2006-2010 
This study attempted to calculate and investigate the incidence of hospitalized acute myocardial infarction (AMI) and stroke in Korea. Using the National Health Insurance claim data, we investigated patients whose main diagnostic codes included AMI or stroke during 2006 to 2010. As a result, we found out that the number of AMI hospitalized patients had decreased since 2006 and amounted to 15,893 in 2010; and that the number of those with stroke had decreased since 2006 and amounted to 73,501 in 2010. The age-standardized incidence rate of hospitalized AMI, after adjustment for readmission, was 41.6 cases per 100,000-population in 2006, and had decreased to 29.4 cases in 2010 (for trend P < 0.001). In the case of stroke was estimated at 172.8 cases per 100,000-population in 2006, and had decreased to 135.1 cases in 2010 (for trend P < 0.001). In conclusion, the age-standardized incidence rates of both hospitalized AMI and stroke in Korea had decreased continuously during 2006 to 2010. We consider this decreasing trend due to the active use of pharmaceuticals, early vascular intervention, and the national cardio-cerebrovascular disease care project as the primary and secondary prevention efforts.
PMCID: PMC3546096  PMID: 23341707
Epidemiology; Acute Myocardial Infarction; Stroke; Patient Readmission
20.  Mutation Screening of the γ-Aminobutyric Acid Type-A Receptor Subunit γ2 Gene in Korean Patients with Childhood Absence Epilepsy 
Background and Purpose
Since the γ-aminobutyric acid type-A receptor subunit γ2 gene (GABRG2) mutation was discovered in an Australian family with childhood absence epilepsy (CAE) and febrile convulsions, a few screening studies for the GABRG2 mutation have been conducted in sporadic individuals with CAE from other ethnic groups. The aim of this study was to determine whether or not the previously reported genetic mutations and single-nucleotide polymorphisms (SNPs) of GABRG2 can be reproduced in sporadic Korean individuals with CAE, compared to healthy Korean individuals.
Thirty-five children with CAE in Chonnam National University Hospital and healthy controls (n=207) were enrolled, and the medical records of patients with CAE were reviewed. CAE was diagnosed according to the Classification and Terminology of the International League Against Epilepsy. All nine exons of GABRG2 were directly sequenced. In addition, the two SNPs found in our CAE patients were analyzed: C315T in exon 3 (E3) and C588T in exon 5 (E5). The frequencies of the two SNPs in the CAE patients were compared with data from healthy controls (for E3 and E5) and from previously reported Korean population data (only for E3).
No mutation of GABRG2 was found in our CAE patients. In addition, the allele and genotype frequencies of the two polymorphisms did not differ significantly between CAE patients, healthy controls, and the Korean general population (p>0.05).
Our study of sporadic Korean individuals with CAE found no evidence that GABRG2 contributes to the genetic basis of CAE.
PMCID: PMC3540286  PMID: 23323135
GABAA receptor gamma subunit; absence epilepsy; child
21.  Bispectral index monitoring as an adjunct to nurse-administered combined sedation during endoscopic retrograde cholangiopancreatography 
AIM: To determine whether bispectral index (BIS) monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: Fifty-nine consecutive patients with a variety of reasons for ERCP who underwent the procedure at least twice between 1 July 2010 and 30 November 2010. This was a randomized cross-over study, in which each patient underwent ERCP twice, once with BIS monitoring and once with control monitoring. Whether BIS monitoring was done during the first or second ERCP procedure was random. Patients were intermittently administered a mixed regimen including midazolam, pethidine, and propofol by trained nurses. The nurse used a routine practice to monitor sedation using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale or the BIS monitoring. The total amount of midazolam and propofol used and serious side effects were compared between the BIS and control groups.
RESULTS: The mean total propofol dose administered was 53.1 ± 32.2 mg in the BIS group and 54.9 ± 30.8 mg in the control group (P = 0.673). The individual propofol dose received per minute during the ERCP procedure was 2.90 ± 1.83 mg/min in the BIS group and 3.44 ± 2.04 mg in the control group (P = 0.103). The median value of the MOAA/S score during the maintenance phase of sedation was comparable for the two groups. The mean BIS values throughout the procedure (from insertion to removal of the endoscope) were 76.5 ± 8.7 for all 59 patients in using the BIS monitor. No significant differences in the frequency of < 80% oxygen saturation, hypotension (< 80 mmHg), or bradycardia (< 50 beats/min) were observed between the two study groups. Four cases of poor cooperation occurred, in which the procedure should be stopped to add the propofol dose. After adding the propofol, the procedure could be conducted successfully (one case in the BIS group, three cases in the control group). The endoscopist rated patient sedation as excellent for all patients in both groups. All patients in both groups rated their level of satisfaction as high (no discomfort). During the post-procedural follow-up in the recovery area, no cases of clinically significant hypoxic episodes were recorded in either group. No other postoperative side effects related to sedation were observed in either group.
CONCLUSION: BIS monitoring trend to slighlty reduce the mean propofol dose. Nurse-administered propofol sedation under the supervision of a gastroenterologist may be considered an alternative under anesthesiologist.
PMCID: PMC3501778  PMID: 23180950
Conscious sedation; Bispectral index monitors; Pancreatic neoplasm; Endoscopic retrograde cholangiopancreatography
22.  Clinical Characteristics of Idiopathic Pulmonary Fibrosis Patients with Diabetes Mellitus: the National Survey in Korea from 2003 to 2007 
Journal of Korean Medical Science  2012;27(7):756-760.
Evidence suggests that diabetes mellitus (DM) is associated with idiopathic pulmonary fibrosis (IPF). According to the new IPF guidelines, high-resolution computed tomography (HRCT) is an essential means of diagnosing IPF. We investigated the relationship between IPF and DM in patients treated between 2003 and 2007. Newly diagnosed IPF patients in large university teaching hospitals in Korea were enrolled from January 2003 to December 2007. We retrospectively analyzed 1,685 patients using the interstitial lung disease (ILD) registry. In total, 299 IPF patients (17.8%) also had DM. The mean age of our subjects was 68.0 ± 9.4 yr. HRCT showed significantly more reticular and honeycomb patterns in IPF patients with DM than in IPF patients without DM (P = 0.014, P = 0.028, respectively). Furthermore, significantly higher incidences of hypertension, cardiovascular diseases, and other malignancies (except lung cancer) were found in IPF patients with DM than in IPF patients without DM. In conclusion, IPF patients with DM are more likely to have the usual interstitial pneumonia (UIP) pattern, including reticular and honeycomb patterns, on HRCT than are those without DM.
PMCID: PMC3390723  PMID: 22787370
Idiopathic Pulmonary Fibrosis; Diabetes Mellitus; High Resolution Computed Tomography
23.  The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis 
Clinical and molecular hepatology  2012;18(2):213-218.
Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH.
The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2±12.8 years (mean±SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively.
Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase levels were 662.2±574.8 U/L, 905.4±794.9 U/L, 12.9±10.8 mg/dL, 195.8±123.3 U/L, and 255.3±280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1±519.1 vs. 1043.3±600.5 U/L), globulin levels (2.7±0.4 vs. 3.3±0.5 g/dL), and prothrombin time (12.9±2.4 vs. 15.2±3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7±0.9 in the DILI group and 6.5±0.9 in the AIH group (P<0.001).
Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.
PMCID: PMC3415876  PMID: 22893872
Drug-induced liver injury; Autoimmune hepatitis; Diagnosis
24.  Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients 
The Korean Journal of Hepatology  2011;17(3):206-212.
We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease.
Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR.
Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity.
Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.
PMCID: PMC3304657  PMID: 22102387
Occult infection; Hepatitis B virus; Hepatitis C virus; HBV DNA
25.  A case of hemocholecyst associated with hemobilia following radiofrequency ablation therapy for hepatocellular carcinoma 
The Korean Journal of Hepatology  2011;17(2):148-151.
Radiofrequency ablation (RFA) is performed as an alternative to surgical resection for primary or secondary liver malignancies. Although RFA can be performed safely in most patients, early and late complications related to mechanical or thermal damage occur in 8-9.5% cases. Hemocholecyst, which refers to hemorrhage of the gallbladder, has been reported with primary gallbladder disease or as a secondary event associated with hemobilia. Hemobilia, defined as hemorrhage in the biliary tract and most commonly associated with accidental or iatrogenic trauma, is a rare complication of RFA. Here we report a case of hemocholecyst associated with hemobilia after RFA for hepatocellular carcinoma that was successfully managed by laparoscopic cholecystectomy.
PMCID: PMC3304637  PMID: 21757986
Hemobilia; Hemocholecyst; Radiofrequency ablation; Complication

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