Publications by authors named "Hong Koh"

99 Publications

Quantitative MRI Assessment of Pancreatic Steatosis Using Proton Density Fat Fraction in Pediatric Obesity.

Korean J Radiol 2021 Jul 14. Epub 2021 Jul 14.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.

Objective: To assess the feasibility of quantitatively assessing pancreatic steatosis using magnetic resonance imaging (MRI) and its correlation with obesity and metabolic risk factors in pediatric patients.

Materials And Methods: Pediatric patients (≤ 18 years) who underwent liver fat quantification MRI between January 2016 and June 2019 were retrospectively included and divided into the obesity and control groups. Pancreatic proton density fat fraction (P-PDFF) was measured as the average value for three circular regions of interest (ROIs) drawn in the pancreatic head, body, and tail. Age, weight, laboratory results, and mean liver MRI values including liver PDFF (L-PDFF), stiffness on MR elastography, and T2 values were assessed for their correlation with P-PDFF using linear regression analysis. The associations between P-PDFF and metabolic risk factors, including obesity, hypertension, diabetes mellitus (DM), and dyslipidemia, were assessed using logistic regression analysis.

Results: A total of 172 patients (male:female = 125:47; mean ± standard deviation [SD], 13.2 ± 3.1 years) were included. The mean P-PDFF was significantly higher in the obesity group than in the control group (mean ± SD, 4.2 ± 2.5% vs. 3.4 ± 2.4%; = 0.037). L-PDFF and liver stiffness values showed no significant correlation with P-PDFF ( = 0.235 and = 0.567, respectively). P-PDFF was significantly associated with obesity (odds ratio 1.146, 95% confidence interval 1.006-1.307, = 0.041), but there was no significant association with hypertension, DM, and dyslipidemia.

Conclusion: MRI can be used to quantitatively measure pancreatic steatosis in children. P-PDFF is significantly associated with obesity in pediatric patients.
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http://dx.doi.org/10.3348/kjr.2020.1343DOI Listing
July 2021

Effect of different driver power amplitudes on liver stiffness measurement in pediatric liver MR elastography.

Abdom Radiol (NY) 2021 Jul 3. Epub 2021 Jul 3.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: To assess how different driver power amplitudes affect the measurement of liver stiffness in pediatric liver magnetic resonance elastography (MRE).

Methods: From January 2018 to May 2018, pediatric patients (≤ 18 years) who underwent liver MRE with 20% and 56% driver power amplitudes were included in this retrospective study. Region-of-interests (ROIs) were drawn on four stiffness maps to include the largest area of the liver parenchyma. Intraclass correlation coefficients (ICCs) were used to assess agreements for the area, mean, maximum, minimum and standard deviation of liver stiffness between the driver power amplitudes.

Results: 128 MRE stiffness maps from 16 patients (M:F = 10:6, median 12.5 years old) were included. On MRE, median ROI areas of liver were 83.1 cm (range, 46.9-144.1 cm) and 63.0 cm (range, 5.4-123.4 cm) for the driver power amplitudes of 20% and 56%, respectively. Median liver stiffness values were 2.3 kPa (range, 1.7-8.0 kPa) and 2.8 kPa (range, 1.7-8.5 kPa). Maximum and minimum liver stiffness values were 5.3 kPa and 1.0 kPa for 20% and 7.8 kPa and 1.1 kPa for 56%. Standard deviation was 0.6 kPa for 20% and 1.0 kPa for 56%. ICC values between the two power amplitudes were 0.33-0.51 for the ROI area and the maximum, minimum and standard deviation values of liver stiffness. The ICC value for liver stiffness was 0.857 (95% confidence interval, 0.760-0.915).

Conclusion: Liver stiffness with two driver power amplitudes on MRE showed good reliability in pediatric patients. Driver power amplitudes need to be optimized according to the pediatric liver size.
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http://dx.doi.org/10.1007/s00261-021-03197-3DOI Listing
July 2021

Development of a Multidisciplinary Aerodigestive Program: An Institutional Experience.

Children (Basel) 2021 Jun 23;8(7). Epub 2021 Jun 23.

Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.

We share our experience on the implementation of a multidisciplinary aerodigestive program comprising an aerodigestive team (ADT) so as to evaluate its feasibility. We performed a retrospective chart review of the patients discussed at the monthly ADT meetings and analyzed the data. A total of 98 children were referred to the ADT during the study period. The number of cases increased steadily from 3.5 cases per month in 2019 to 8.5 cases per month in 2020. The median age of patients was 34.5 months, and 55% were male. Among the chronic comorbidities, neurologic disease was the most common (85%), followed by respiratory (36%) and cardiac (13%) disorders. The common reasons for consultation were suspected aspiration (56%), respiratory difficulty (44%), drooling/stertor (30%), regurgitation/vomiting (18%), and feeding/swallowing difficulty (17%). Following discussions, 58 patients received active interventions, including fundoplication, gastrostomy, laryngomicrosurgery, tracheostomy, and primary dilatation of the airway. According to the questionnaire of the caregiver, the majority agreed that the main symptoms and quality of life of patients had improved (88%), reducing the burden on caregivers (77%). Aerodigestive programs may provide comprehensive and multidisciplinary management for children with complex airway and digestive tract disorders.
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http://dx.doi.org/10.3390/children8070535DOI Listing
June 2021

KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease.

Clin Mol Hepatol 2021 Jul 22;27(3):363-401. Epub 2021 Jun 22.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3350/cmh.2021.0178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273632PMC
July 2021

High Prevalence of Non-alcoholic Fatty Liver Disease among Adolescents and Young Adults with Hypopituitarism via Growth Hormone Deficiency.

Endocr Pract 2021 Jun 11. Epub 2021 Jun 11.

Department of Pediatrics, Division of Pediatric Endocrinology, Severance Children's Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address:

Objective: To investigate the prevalence of NAFLD in adolescents and young adults with hypopituitarism, and to examine associations for GH deficiency with occurrence of NAFLD.

Methods: A cross-sectional study for determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescents and young adults with hypopituitarism and in the age- and BMI-matched controls. Among the patients with hypopituitarism, anthropometric, clinical, and biochemical assessments on transient elastography and MRI were conducted. Logistic regression was applied to identify the factors associated with NAFLD.

Results: Adolescents and young adults with hypopituitarism exhibited a higher prevalence of NAFLD compared to the age- and BMI-matched controls. Among hypopituitary patients, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS), and IGF-I/IGF binding protein-3 (IGFBP-3) molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was associated with lower IGF-I SDS and IGF-I/IGFBP-3 molar ratios, whereas liver fibrosis was associated with lower IGF-I SDS.

Conclusions: Our results suggest that GH deficiency may contribute to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Since NAFLD occurs early in patients with hypopituitarism, the surveillance, weigh control, and timely replacement of deficit hormones, including GH, are essential.
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http://dx.doi.org/10.1016/j.eprac.2021.06.003DOI Listing
June 2021

Association between Fecal Calprotectin and Mucosal Healing in Pediatric Patients with Crohn's Disease Who Have Achieved Sustained Clinical Remission with Anti-Tumor Necrosis Factor Agents.

Gut Liver 2021 Apr 9. Epub 2021 Apr 9.

Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

Background/aims: : Although mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn's disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents.

Methods: This multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy.

Results: A total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p<0.001). According to the multivariate logistic regression analysis, FC was the only factor associated with MH (odds ratio, 0.62; 95% confidence interval [CI], 0.52 to 0.73; p<0.001). According to the receiver operating characteristic curve analysis, the optimal cutoff value for FC for the association with MH was <140 mg/kg (area under the curve 0.890, 95% CI 0.829 to 0.951, sensitivity 78.2%, specificity 88.6%, p<0.001).

Conclusions: FC was associated with MH in pediatric patients with CD who had achieved a sustained CR for at least 6 months with anti-TNF agents. In these patients, FC can be used to stratify patients and guide decisions regarding ileocolonoscopy in the treat-to-target era.
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http://dx.doi.org/10.5009/gnl20300DOI Listing
April 2021

Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.

Front Med Technol 2020 Aug 7;2. Epub 2020 Aug 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.

Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.
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http://dx.doi.org/10.3389/fmedt.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849371PMC
August 2020

Key imaging features for differentiating cystic biliary atresia from choledochal cyst: prenatal ultrasonography and postnatal ultrasonography and MRI.

Ultrasonography 2021 Apr 31;40(2):301-311. Epub 2020 Jul 31.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Seoul, Korea.

Purpose: This study compared clinical and radiologic differences between cystic biliary atresia (cBA) and choledochal cyst (CC) type Ia/b.

Methods: Infants (≤12 months old) who were diagnosed with cBA or CC type Ia/b from 2005 to 2019 were retrospectively reviewed. Imaging features on preoperative ultrasonography (US) and magnetic resonance imaging (MRI) were compared between the cBA and CC groups. Logistic regression and area under the receiver operating characteristic curve (AUC) analyses were performed for the diagnosis of cBA. Changes in cyst size were also evaluated when prenatal US exams were available.

Results: Ten patients (5.5% of biliary atresia cases) with cBA (median age, 48 days) and 11 infants with CC type Ia/b (Ia:Ib=10:1; median age, 20 days) were included. Triangular cord thickness on US (cutoff, 4 mm) showed 100% sensitivity and 90.9% specificity (AUC, 0.964; 95% confidence interval [CI], 0.779 to 1.000) and cyst size on MRI (cutoff, 2.2 cm) had 70% sensitivity and 100% specificity (AUC, 0.900; 95% CI, 0.690 to 0.987) for diagnosing cBA. Gallbladder mucosal irregularity on US and an invisible distal common bile duct on MRI were only seen in the cBA group (10 of 10). Only the CC group showed prenatal cysts exceeding 1 cm with postnatal enlargement.

Conclusion: Small cyst size (<1 cm) on prenatal US, triangular cord thickening (≥4 mm) and gallbladder mucosal irregularity on postnatal US, and small cyst size (≤2.2 cm) and an invisible distal common bile duct on MRI can discriminate cBA from CC type Ia/b in infancy.
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http://dx.doi.org/10.14366/usg.20061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994739PMC
April 2021

Association between Dietary Patterns and Handgrip Strength: Analysis of the Korean National Health and Nutrition Examination Survey Data Between 2014 and 2017.

Nutrients 2020 Oct 5;12(10). Epub 2020 Oct 5.

Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul 03722, Korea.

Non-invasive anthropometric measurement methods such as those for measuring height and weight are crucial in pediatric patients. However, research focusing on the association between the type of dietary pattern and handgrip strength and handgrip-to-weight ratio in adolescents has not been carried out yet. This cross-sectional analysis of the 2014-2017 Korean National Health and Nutrition Examination Survey assessed 2327 adolescents (aged 10-18 years) who had their handgrip strength measured and analyzed its association with dietary pattern. The clusters were examined for nutritional values, and the , and clusters were ultimately generated. Overall, 85.6% of the participants were assigned to a dietary pattern, 9.3% to a dietary pattern, and 5.1% to a dietary pattern. Compared with the participants following a dietary pattern, those following a dietary pattern were shown to have a significantly lower handgrip strength and handgrip-to-weight ratio. Decreased handgrip strength and handgrip-to-weight ratio values in participants following dietary patterns indicate a diffuse problem in adolescents' health and possibly imply an association between reduced muscle quality and dietary pattern. Therefore, the overall environmental factors potentially inducing such unhealthy dietary preferences should be investigated, and appropriate lifestyle changes in Korean adolescents should be encouraged.
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http://dx.doi.org/10.3390/nu12103048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601920PMC
October 2020

Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.

J Infect 2020 11 11;81(5):719-725. Epub 2020 Sep 11.

Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Objectives: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization.

Methods: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed.

Results: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance.

Conclusion: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.
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http://dx.doi.org/10.1016/j.jinf.2020.09.003DOI Listing
November 2020

Diffusion-Weighted Imaging for Differentiation of Biliary Atresia and Grading of Hepatic Fibrosis in Infants with Cholestasis.

Korean J Radiol 2021 02 28;22(2):253-262. Epub 2020 Aug 28.

Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.

Objective: To determine whether the values of hepatic apparent diffusion coefficient (ADC) can differentiate biliary atresia (BA) from non-BA or be correlated with the grade of hepatic fibrosis in infants with cholestasis.

Materials And Methods: This retrospective cohort study included infants who received liver MRI examinations to evaluate cholestasis from July 2009 to October 2017. Liver ADC, ADC ratio of liver/spleen, aspartate aminotransferase to platelet ratio index (APRI), and spleen size were compared between the BA and non-BA groups. The diagnostic performances of all parameters for significant fibrosis (F3-4) were obtained by receiver-operating characteristics (ROCs) curve analysis.

Results: Altogether, 227 infants (98 males and 129 females, mean age = 57.2 ± 36.3 days) including 125 BA patients were analyzed. The absolute ADC difference between two reviewers was 0.10 mm²/s for both liver and spleen. Liver ADC value was specific (80.4%) and ADC ratio was sensitive (88.0%) for the diagnosis of BA with comparable performance. There were 33 patients with F0, 15 with F1, 71 with F2, 35 with F3, and 11 with F4. All four parameters of APRI (τ= 0.296), spleen size (τ= 0.312), liver ADC (τ= -0.206), and ADC ratio (τ= -0.288) showed significant correlation with fibrosis grade (all, < 0.001). The cutoff values for significant fibrosis (F3-4) were 0.783 for APRI (area under the ROC curve [AUC], 0.721), 5.9 cm for spleen size (AUC, 0.719), 1.044 × 10 mm²/s for liver ADC (AUC, 0.673), and 1.22 for ADC ratio (AUC, 0.651).

Conclusion: Liver ADC values and ADC ratio of liver/spleen showed limited additional diagnostic performance for differentiating BA from non-BA and predicting significant hepatic fibrosis in infants with cholestasis.
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http://dx.doi.org/10.3348/kjr.2020.0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817632PMC
February 2021

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.

Micromachines (Basel) 2020 Jul 7;11(7). Epub 2020 Jul 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.
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http://dx.doi.org/10.3390/mi11070663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408321PMC
July 2020

Trends in measures of handgrip strength from 2014 to 2017 among Korean adolescents using the Korean National Health and Nutrition Examination Survey Data.

BMC Res Notes 2020 Jun 30;13(1):307. Epub 2020 Jun 30.

Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Object: Measuring handgrip strength is a useful method to evaluate sarcopenia. No study has shown the trends of handgrip strength to weight ratio among Korean adolescents by year. This study aimed to determine the trends of handgrip strength among Korean adolescents using data from the Korea National Health and Nutrition Examination Survey (KNHANES). Data of 2304 adolescents who participated in the KNHANES between 2014 and 2017 were obtained. The handgrip-to-weight ratios were categorized by age, sex, and year.

Results: Handgrip strength in adolescents decreased from 28.67 kg in 2014 to 27 kg in 2017 (P for trend < 0.05). The handgrip-to-weight ratio also decreased from 51.48 in 2014 to 48.18 in 2017 (P for trend < 0.05). The handgrip strength and handgrip-to-weight ratio also decreased among boys and girls over the years 2014-2017 (P for trend < 0.05). The results of the present study indicate that the handgrip-to-weight ratio decreased in Korean adolescents from the years 2014 to 2017, and a declining overall ratio indicates a decrease in the health status among Korean adolescents. Hence, there is a need to review the health status of Korean adolescents.
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http://dx.doi.org/10.1186/s13104-020-05112-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329499PMC
June 2020

Periportal thickening on magnetic resonance imaging for hepatic fibrosis in infantile cholestasis.

World J Gastroenterol 2020 Jun;26(21):2821-2830

Department of Radiology, Severance Hospital, Severance Pediatric Liver Disease Research Group, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul 03722, South Korea.

Background: Untreated neonatal cholestasis can progress to liver cirrhosis and end stage liver disease in infancy due to prolonged hepatocyte and biliary tree injury and may require liver transplantation. Therefore, non-invasive evaluation of hepatic fibrosis is important in infants with cholestasis.

Aim: To investigate the usefulness of periportal thickening (PT) measured on liver magnetic resonance imaging (MRI) for the assessment of hepatic fibrosis in infants with cholestasis including biliary atresia (BA).

Methods: This retrospective study included infants less than 6 mo who underwent liver MRI and biopsy for the evaluation of infantile cholestasis. PT and spleen size were measured on MRI. Serologic assessment was based on aspartate transaminase to platelet ratio index (APRI). The grade of histopathologic fibrosis was assessed by the METAVIR grading system. Correlation and diagnostic performance of PT, normalized spleen size ratio (SR, using the upper normal size limit), and APRI for diagnosing hepatic fibrosis were obtained by receiver-operating characteristic (ROC) curve analysis.

Results: A total of 155 patients were included, 110 of which were diagnosed with BA. Mean age at the time of MRI was 57.6 ± 34.4 d. There were positive correlations between fibrosis grade and PT and SR, even after adjusting age (all, < 0.001). For the diagnosis of significant fibrosis (METAVIR grade F2-F4), the area under the ROC curve was 0.899 (95%CI: 0.840-0.941) for PT (cutoff, 4.2 mm), which was higher than 0.741 (95%CI: 0.664-0.808) for SR and 0.712 (95%CI: 0.634-0.782) for APRI (both, < 0.001). For the diagnosis of cirrhosis (F4), the area under the ROC curve was the highest with SR as 0.790 (95%CI: 0.718-0.852).

Conclusion: Liver MRI findings of PT and SR are useful to assess clinically significant hepatic fibrosis (F2 and higher) in infants with cholestasis including BA.
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http://dx.doi.org/10.3748/wjg.v26.i21.2821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284183PMC
June 2020

Draft Genome Sequences of Two Strains of Bifidobacterium dentium Isolated from a Crude Fecal Extract Used for Fecal Microbiota Transplantation in the Republic of Korea.

Microbiol Resour Announc 2020 Jun 4;9(23). Epub 2020 Jun 4.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA

We present the draft genome sequences of two strains isolated from a fecal extract for fecal microbiota transplantation at a hospital in the Republic of Korea. Phylogenetic and functional analyses were performed to understand the physiological characteristics and functions of spp. in the human intestine.
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http://dx.doi.org/10.1128/MRA.00197-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272543PMC
June 2020

Bone marrow fat change in pediatric patients with non-alcoholic fatty liver disease.

PLoS One 2020 2;15(6):e0234096. Epub 2020 Jun 2.

Department of Radiology, Severance Hospital, Severance Pediatric Liver Disease Research Group, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: To investigate changes of fat in bone marrow (BM) and paraspinal muscle (PSM) associated with the degree of fatty liver in pediatric patients with non-alcoholic fatty liver disease (NAFLD) in consideration of age and body mass index (BMI).

Methods: Hepatic fat, BM fat, and PSM fat from proton density fat fraction of liver MRI between June 2015 and April 2019 were quantitatively evaluated on axial images of the fat map at the mid-level of T11-L2 vertebral bodies for BM fat and at the mid-level of L2 for PSM fat. Age, height, and weight at the time of MRI were recorded and BMI was calculated. Correlation analysis was performed.

Results: A total of 147 patients (114 male) were included with a mean age of 13.3 ± 2.9 years (range 7-18 years). The mean fat fractions were 24.3 ± 13.0% (2-53%) in liver, 37.4 ± 8.6% (17.3-56%) in vertebral BM, and 2.7 ± 1.1% (1.0-6.9%) in PSM. Age, height, weight, and BMI were not correlated with liver fat or BM fat. However, weight (ρ = 0.174, p = 0.035) and BMI (ρ = 0.247, p = 0.003) were positively correlated with PSM fat. Liver fat showed positive correlation with BM fat when adjusting age and BMI (ρ = 0.309, p<0.001), but not with PSM fat.

Conclusions: BM fat positively correlates with liver fat, but not with age or BMI in pediatric NAFLD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234096PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266329PMC
August 2020

Validating the BAVENO VI criteria to identify low risk biliary atresia patients without endoscopy for esophageal varix.

Clin Res Hepatol Gastroenterol 2021 Jan 13;45(1):101437. Epub 2020 May 13.

Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Pediatric Liver Disease Research Group, Seoul, Republic of Korea. Electronic address:

Background And Aims: Portoenterostomy is the initial surgical treatment for biliary atresia (BA); however, no curative therapy exists for BA. Varix bleeding is a major complication of end-stage liver disease and must be determined in patients with BA, necessitating routine surveillance using esophagogastroduodenoscopy (EGD). We attempted to validate criteria to identify BA patients requiring EGD.

Methods: From January 2007 to December 2017, we selected BA patients who underwent Kasai surgery, transient elastography (TE), and EGD at Severance hospital. In total, 190 cases were included; laboratory tests and EGDs were carried out from 3 months before TE to 3 months after TE.

Results: Based on the cut-off value (<10) of the liver stiffness measurement (LSM), 35 (81.4%) patients with low-risk varix (LRV) and 8 (18.6%) with high-risk varix (HRV) were identified. Based on platelet counts (>150,000), 87 (77.68%) patients with LRV and 25 (22.32%) with HRV were identified. Based on this, the BAVENO VI criteria, which identify patients who can safely avoid screening EGD, missed 9/68 (13.24%) of HRV patients. The expanded BAVENO VI criteria missed 21/68 (30.88%) of HRV patients. However, the criteria using LSM <10 and platelet count >150,000 missed identifying only 4/68 (5.88%) HRV patients.

Conclusions: The BAVENO criteria may be as useful in children with BA as in adults with liver cirrhosis. Regular laboratory tests, imaging studies, and EGD may avoid missing diagnoses of varices in BA patients. However, LSM<10 and platelet count>150,000 may provide more accurate criteria and help identify patients who does not need endoscopy.
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http://dx.doi.org/10.1016/j.clinre.2020.04.007DOI Listing
January 2021

In Situ Profiling of the Three Dominant Phyla Within the Human Gut Using TaqMan PCR for Pre-Hospital Diagnosis of Gut Dysbiosis.

Int J Mol Sci 2020 Mar 11;21(6). Epub 2020 Mar 11.

School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Korea.

A microbial imbalance called dysbiosis leads to inflammatory bowel disease (IBD), which can include ulcerative colitis (UC). Fecal microbiota transplantation (FMT), a novel therapy, has recently been successful in treating gut dysbiosis in UC patients. For the FMT technique to be successful, the gut microbiota of both the healthy donors and UC patients must be characterized. For decades, next-generation sequencing (NGS) has been used to analyze gut microbiota. Despite the popularity of NGS, the cost and time constraints make it difficult to use in emergency services and activities related to the periodic monitoring of microbiota profile alterations. Hence, in this study, we developed a multiplex TaqMan qPCR assay (MTq-PCR) with novel probes to simultaneously determine the relative proportions of the three dominant microbial phyla in the human gut: Bacteroidetes, Firmicutes, and Proteobacteria. The relative proportions of the three phyla in fecal samples of either healthy volunteers or UC patients were similar when assessed NGS and the MTq-PCR. Thus, our MTq-PCR assay could be a practical microbiota profiling alternative for diagnosing and monitoring gut dysbiosis in UC patients during emergency situations, and it could have a role in screening stool from potential FMT donors.
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http://dx.doi.org/10.3390/ijms21061916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139488PMC
March 2020

Induction of SIRT1 by melatonin improves alcohol-mediated oxidative liver injury by disrupting the CRBN-YY1-CYP2E1 signaling pathway.

J Pineal Res 2020 Apr 28;68(3):e12638. Epub 2020 Feb 28.

School of Applied Biosciences, Kyungpook National University, Daegu, Korea.

Alcoholic liver disease is the most prevalent chronic liver disease. Melatonin is known to control many vital processes. Here, we explored a novel molecular mechanism by which melatonin-induced SIRT1 signaling protects against alcohol-mediated oxidative stress and liver injury. Gene expression profiles and metabolic changes were measured in liver specimens of mice and human subjects. Expression levels of Cb1r, Crbn, Btg2, Yy1, pro-inflammatory cytokines, and Cyp2e1 were significantly enhanced in chronic alcohol-challenged mice and human subjects. Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic CYP2E1 protein, and reactive oxygen species (ROS) were elevated in alcohol-fed WT mice but not in Cb1r antagonist-treated, Crbn null, or Yy1-silenced mice. Importantly, alcohol-induced Yy1 and Cyp2e1 expression, ROS amount, and liver injury were markedly diminished by melatonin treatment and the transduction of Sirt1 in mice, whereas this phenomenon was prominently ablated by silencing of Sirt1. Notably, SIRT1 physically interacted with YY1 and attenuated YY1 occupancy on the Cyp2e1 gene promoter. Melatonin-SIRT1 signaling ameliorates alcohol-induced oxidative liver injury by disrupting the CRBN-YY1-CYP2E1 signaling pathway. The manipulation of CRBN-YY1-CYP2E1 signaling network by the melatonin-SIRT1 pathway highlights a novel entry point for treating alcoholic liver disease.
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http://dx.doi.org/10.1111/jpi.12638DOI Listing
April 2020

Hepatic subcapsular or capsular flow in biliary atresia: is it useful imaging feature after the Kasai operation?

Eur Radiol 2020 Jun 11;30(6):3161-3167. Epub 2020 Feb 11.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.

Objectives: To evaluate the implications of hepatic subcapsular and capsular flows using ultrasonography (US) in children after Kasai operation.

Methods: Children who underwent liver US including color Doppler US and microvascular imaging (MVI) from May 2017 to October 2017 were retrospectively included. Children who underwent the Kasai operation for biliary atresia were included in the Kasai group and children with normal liver were included in the control group. Using US results, the number of intrahepatic biliary cysts and the maximum diameter of the spleen were evaluated in the Kasai group. Liver stiffness values were included when patients in the Kasai group had transient elastography (TE) or shear wave elastography (SWE) results. Hepatic subcapsular and capsular flows on color Doppler US and MVI were compared between the two groups using the following scores: 0, no flow reaching the hepatic capsule; 1, any flow reaching the hepatic capsule; and 2, contiguous hepatic capsular flow. The logistic regression test was used to identify associations between age, intrahepatic biliary cysts, spleen size, SWV, TE results, and flow scores measured on Doppler US and MVI in the Kasai group using the odds ratio (OR) and 95% confidence interval (CI).

Result: A total of 65 children (mean 7.6 ± 5.3 years), 44 in the Kasai group and 21 in the control group, were included. In the control group, one child had score 1 on MVI and others had score 0 on both Doppler US and MVI. Among the Kasai group, 28 children (63.6%) had score 1, while others had score 0 using Doppler US. Using MVI, 24 children (54.5%) had score 2, 18 children had score 1, and one child had score 0. In the Kasai group, increased liver stiffness on TE was the only factor significantly associated with the presence of subcapsular flow on color Doppler US (OR 1.225, 95% CI 1.020-1.470) and increased spleen size was the only factor significantly associated with increased flow scores on MVI (OR 1.397, 95% CI 1.002-2.724).

Conclusion: Detection of hepatic subcapsular, capsular flows on US would be meaningful for children after receiving the Kasai operation.

Key Points: • Hepatic subcapsular or capsular flows can be useful not only for the diagnosis but also for the postoperative follow-up in patients with biliary atresia. • Increased liver stiffness and splenomegaly after the Kasai operation were associated with presence of subcapsular or capsular flow on ultrasonography. • Evaluation of hepatic subcapsular and capsular flows could be needed to assess disease progression after receiving the Kasai operation.
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http://dx.doi.org/10.1007/s00330-020-06656-5DOI Listing
June 2020

Increasing incidence of inflammatory bowel disease in children and adolescents: significance of environmental factors.

Clin Exp Pediatr 2020 Sep 6;63(9):337-344. Epub 2019 Dec 6.

Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Pediatric IBD Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.

Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is reportedly lower in Asia than in Western countries, the rapid increase in the incidence of IBD has drawn attention to its etiology, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to immune dysregulation in IBD. Changes in diet or alterations in the composition of the intestinal microbiota may be associated with the increasing incidence of IBD in Asia. Here, we aim to review recent studies on the role of diet and intestinal microbiota in IBD pathogenesis and the results of the investigations performed to modulate these factors.
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http://dx.doi.org/10.3345/cep.2019.00500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462828PMC
September 2020

Korean Children and Adolescents with Crohn's Disease Are More Likely to Present with Perianal Fistulizing Disease at Diagnosis Compared to Their European Counterparts.

Pediatr Gastroenterol Hepatol Nutr 2020 Jan 9;23(1):49-62. Epub 2020 Jan 9.

Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

Purpose: We aimed to investigate the disease phenotype of Korean pediatric Crohn's disease (CD) patients at diagnosis according to the Paris classification by comparison with patients from the European multicenter 5-years recruitment of children with newly developed IBD (EUROKIDS registry).

Methods: Korean children and adolescents who had been newly diagnosed with CD at the age of <18 years during 2013-2016 were included in this multicenter retrospective study. Disease phenotype at diagnosis was classified according to the Paris classification, and compared with the published data from the EUROKIDS study.

Results: A total of 255 patients were included. The median diagnosis age was 14.7 years (range, 0.8-17.9 years). No significant difference was observed in male-to-female ratio with EUROKIDS (1.9:1 vs. 1.45:1, =0.062). The proportion of children aged <10 years was significantly lower in Koreans (7.1% vs. 19.6%, <0.001). Colonic disease was less prominent (10.0% vs. 27.3%, <0.001), while upper GI involvement was more prominent in Korean children (59.3% vs. 46.2%, <0.001). The proportion with perianal fistulizing disease at diagnosis was significantly higher in Korean patients (44.8% vs. 8.2%, <0.001). A separate analysis of Korean patients revealed that perianal fistulizing disease at diagnosis was positively associated with male sex and body mass index z-score (odds ratio [OR]=2.12, 95% confidence interval [CI]=1.20-3.76, =0.010; and OR=1.29, 95% CI=1.05-1.58, =0.015, respectively).

Conclusion: Approximately half of pediatric CD patients in Korea present with perianal fistulas and/or abscesses at diagnosis, which is a distinct feature of CD in Korean children and adolescents compared to their European counterparts. An underlying genetic difference between ethnicities may play a role in this expression of different phenotypes in pediatric CD.
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http://dx.doi.org/10.5223/pghn.2020.23.1.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966217PMC
January 2020

The Epidemiology and Etiology of Cholangitis After Kasai Portoenterostomy in Patients With Biliary Atresia.

J Pediatr Gastroenterol Nutr 2020 02;70(2):171-177

Department of Pediatrics.

Objectives: We investigated the incidence and characteristics of cholangitis after Kasai portoenterostomy (KPE) in patients with biliary atresia. We also examined the distribution and antimicrobial susceptibility patterns of the causative pathogens, which were isolated in sterile specimens, such as blood and ascites.

Methods: A retrospective chart review was performed in patients with biliary atresia who underwent KPE at Severance Children's Hospital in Korea from 2006 to 2015. The Kaplan-Meier method was used to assess the cumulative incidence of cholangitis.

Results: Among the 160 included patients, there were 494 episodes of cholangitis in 126 patients (78.8%) during the study period. The cumulative incidence of cholangitis at 1 and 5 years after KPE was 75.5% and 84.2%, respectively, and cholangitis recurred in most cases (76.2%). The cumulative incidence of culture-proven cholangitis at 1 and 5 years after KPE was 22.1% and 23.9%, respectively. Enterococcus faecium (27.7%) was the most prevalent pathogen, followed by Escherichia coli (14.9%), Enterobacter cloacae (10.6%), and Klebsiella pneumoniae (8.5%). Gram-positive isolates (n = 19) showed low susceptibility to ampicillin (42.1%) and gentamicin (66.7%), and only 38.1% of Gram-negative isolates (n = 21) were susceptible to cefotaxime.

Conclusions: The present study is the largest to show the high incidence and characteristics of cholangitis after KPE in patients with biliary atresia. Enterococcus is a common pathogen of cholangitis after KPE and should be considered when choosing empiric antimicrobial therapy.
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http://dx.doi.org/10.1097/MPG.0000000000002555DOI Listing
February 2020

Clinical utility of mono-exponential model diffusion weighted imaging using two b-values compared to the bi- or stretched exponential model for the diagnosis of biliary atresia in infant liver MRI.

PLoS One 2019 18;14(12):e0226627. Epub 2019 Dec 18.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.

Purpose: To investigate the clinical utility of mono-exponential model diffusion weighted imaging (DWI) using two b-values compared to the bi- or stretched exponential model to differentiate biliary atresia (BA) from non-BA in pediatric liver magnetic resonance imaging (MRI).

Methods: Patients who underwent liver MRI with DWI for suspected BA from November 2017 to September 2018 were retrospectively included and divided into BA and non-BA groups. Laboratory results including γ-glutamyl transferase (γGT) were compared between the two groups using the Mann-Whitney U test and Fisher's exact test. The hepatic apparent diffusion coefficient (ADC) 10 using ten b-values and ADC 2 using two b-values were obtained from the mono-exponential model. The slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion fraction (f) were obtained from the bi-exponential model. The distributed diffusion coefficient (DDC) and heterogeneity index (α) were measured from the stretched exponential model. Parameters were compared between the two groups using a linear mixed model and diagnostic performance was assessed using the area under the curve (AUC) analysis.

Results: For 12 patients in the BA and five patients in the non-BA group, the ADC 10 (median 0.985 ×10-3 mm2/s vs. 1.332 ×10-3 mm2/s, p = 0.008), ADC 2 (median 0.987 ×10-3 mm2/s vs. 1.335 ×10-3 mm2/s, p = 0.017), D* (median 33.2 ×10-3 mm2/s vs. 55.3 ×10-3 mm2/s, p = 0.021), f (median 13.4%, vs. 22.1%, p = 0.009), and DDC (median 0.889 ×10-3 mm2/s vs. 1.323 ×10-3 mm2/s, p = 0.009) values were lower and the γGT (median 368.0 IU/L vs. 93.5 IU/L, p = 0.02) and α (median 0.699 vs. 0.556, p = 0.023) values were higher in the BA group. The AUC values for γGT (AUC 0.867 95% confidence interval [CI] 0.616-0.984), ADC 10 (AUC 0.963, 95% CI 0.834-0.998), ADC 2 (AUC 0.925, 95% CI 0.781-0.987), f (AUC 0.850, 95% CI 0.686-0.949), and DDC (AUC 0.925, 95% CI 0.781-0.987) were not significantly different, except for the D* and α values.

Conclusion: Patients with BA had lower ADC 10, ADC 2, D*, f, and DDC values and higher γGT and α values than those in the non-BA group. The diagnostic performance of ADC 2 using only two b-values showed excellent diagnostic performance and was not significantly different from that of γGT, ADC 10, f, and DDC for diagnosing BA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226627PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920030PMC
April 2020

Combining faecal calprotectin and sigmoidoscopy can predict mucosal healing in paediatric ulcerative colitis.

Eur J Gastroenterol Hepatol 2020 01;32(1):17-21

Pediatric Gastroenterology, Hepatology and Nutrition, Yonsei University College of Medicine, Severance Pediatric IBD Research Group, Severance Children's Hospital, Seoul.

Objectives: Mucosal healing is the endoscopic treatment target in inflammatory bowel disease. The treat-to-target strategy, emphasizing proactive assessment and optimizing treatment, is commonly applied in the clinical setting. Although colonoscopies are essential for this strategy to be successful, bowel preparation and sedative drugs are required for paediatric patients. We attempted to verify the usefulness of sigmoidoscopy, which is less invasive than colonoscopy, combined with faecal calprotectin, to assess mucosal healing.

Methods: A total of 58 paediatric patients diagnosed with ulcerative colitis and followed up at Severance Children's Hospital from March 2015 to May 2018 were enrolled. Clinical data and laboratory findings (including faecal calprotectin and endoscopic data) were collected from medical records. The predictive power of mucosal healing of sigmoid colon and rectum (s-MH) combined with faecal calprotectin to predict mucosal healing throughout the colon was analysed.

Results: Among 58 patients (mean age 16.13 ± 2.88 years), 18 (31.0%) were in mucosal healing status. The median faecal calprotectin level was 486.5 μg/g. The faecal calprotectin cutoff value for predicting mucosal healing, identified using receiver-operating characteristic analyses, was 148 μg/g (area under the curve, 0.81). Sensitivity, specificity, positive predictive value, and negative predictive value of s-MH in predicting mucosal healing were 1.0, 0.82, 0.72, and 1.0, respectively. When we combined s-MH with faecal calprotectin less than the cutoff value, the sensitivity, specificity, positive predictive value, and negative predictive value were 0.56, 1.0, 1.0, and 0.83, respectively.

Conclusion: For patients with a low faecal calprotectin level, sigmoidoscopy might be sufficient to assess mucosal healing.
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http://dx.doi.org/10.1097/MEG.0000000000001550DOI Listing
January 2020

Predicting variceal bleeding in patients with biliary atresia.

Scand J Gastroenterol 2019 Nov 24;54(11):1385-1390. Epub 2019 Oct 24.

Pediatric Gastroenterology, Hepatology and Nutrition, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.

Variceal bleeding is the main cause of morbidity and mortality in children with portal hypertension and biliary atresia. The aim of this study is to predict high-risk varices by analyzing various clinical factors, thus improve prognosis of patients with biliary atresia. A total of 157 patients with biliary atresia who underwent Kasai portoentrostomy were enrolled in a single center. Clinical data including laboratory values, endoscopic findings and values of transient elastography (FibroScan) were analyzed retrospectively. The bleeding group and the non-bleeding group showed statistically significant differences in several variables; The FibroScan value (HR 1.05, 95% CI (1.03-1.07),   <  .01) was higher in the bleeding group. The bleeding group had values of lower albumin after 3 months of operation (HR 0.28, 95% CI (0.11-0.73),   =  .01), higher bilirubin after 3 months of operation (total bilirubin: HR 1.18, 95% CI (1.04-1.33),   =  .01), (direct bilirubin: HR 1.21, 95% CI (1.05-1.41),   =  .01). Gastric varix (HR 4.10, 95% CI (1.62-10.36),   <  .01) was more frequent in the bleeding group. And the presence of red sign was also predictive of bleeding. The FibroScan cut-off value with the predictive power of bleeding was 31.5 kPa (HR 7.7, 95% CI (3.36-17.73),   <  .01). Several clinical factors including high value of transient elastography (FibroScan), gastric varix or red sign of endoscopy, and low albumin or high bilirubin values after 3 months of Kasai operation can be useful in predicting variceal bleeding in patients with biliary atresia.
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http://dx.doi.org/10.1080/00365521.2019.1683225DOI Listing
November 2019

Association of Vitamin D with Inflammatory Bowel Disease Activity in Pediatric Patients.

J Korean Med Sci 2019 Aug 19;34(32):e204. Epub 2019 Aug 19.

Pediatric Gastroenterology, Hepatology and Nutrition, Severance Pediatric IBD Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: It has been known that vitamin D level (serum 25[OH]D) has correlation with inflammatory bowel disease (IBD). The purpose of this study is to investigate changes of serum 25[OH]D in pediatric IBD patients according to the disease activity.

Methods: A total of 96 children and adolescent with IBD were enrolled in this retrospective study. Serologic inflammatory markers and clinical disease activity scores of the patients were collected, and their correlations with serum 25[OH]D were analyzed. Seasonal variations of serum 25[OH]D were also investigated both in active disease state and remission state.

Results: Of the 96 patients, 41 (43%) were women and patients with a vitamin D deficiency (< 20 ng/mL) at diagnosis were 77 (80.2%). There was no significant difference between Crohn's disease and ulcerative colitis for serum 25[OH]D. Serum 25[OH]D was higher in remission group than in active disease group (12.4 [8.8-29] ng/mL vs. 17.9 [12.3-34.4] ng/mL; < 0.001) and the difference was more significant than other micronutrients. There was no significant difference in serum 25[OH]D concentration between patients with ileal involvement and patients without ileal involvement. There were seasonal variations in the active phase, but there was no significant difference by season in the remission phase.

Conclusion: Serum 25[OH]D is inversely correlated with disease activity in IBD. Monitoring and supplementation is required especially for active disease status and in winter and spring season.
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http://dx.doi.org/10.3346/jkms.2019.34.e204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698452PMC
August 2019

Risk factors and diagnostic markers of bacteremia in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cohort study of 176 patients.

J Am Acad Dermatol 2019 Sep 10;81(3):686-693. Epub 2019 Jun 10.

Department of Dermatology, Singapore General Hospital, Singapore. Electronic address:

Background: Sepsis is the main cause of death in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Objectives: Our aim was to identify admission risk factors predictive of bacteremia and the accompanying clinical or biochemical markers associated with positive blood cultures.

Methods: A retrospective cohort study over a 14-year period (2003-2016) was performed.

Results: The study included 176 patients with SJS (n = 59), SJS-TEN overlap (n = 51), and TEN (n = 66). During hospitalization, bacteremia developed in 52 patients (29.5%), who experienced poorer outcomes, including higher intensive care unit admission (P < .0005), longer length of stay (P < .0005), and higher mortality (P < .0005). There were 112 episodes of bacteremia, and isolates included Acinetobacter baumannii (27.7%, n = 31) and Staphylococcus aureus (21.4%, n = 24). On multivariate analysis, clinical factors present at admission that were predictive of bacteremia included hemoglobin ≤10 g/dL (odds ratio [OR] 2.4, confidence interval [CI] 2.2-2.6), existing cardiovascular disease (OR 2.10, CI 2.0-2.3), and body surface area involvement ≥10% (OR 14.3, CI 13.4-15.2). The Bacteremia Risk Score was constructed with good calibration. Hypothermia (P = .03) and procalcitonin ≥1 μg/L (P = .02) concurrent with blood culture sampling were predictive of blood culture positivity.

Limitations: This is a retrospective study performed in a reference center.

Conclusion: Hemoglobin ≤10 g/dL, cardiovascular disease, and body surface area involvement ≥10% on admission were risk factors for bacteremia. Hypothermia and elevated procalcitonin are useful markers for the timely detection of bacteremia.
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http://dx.doi.org/10.1016/j.jaad.2019.05.096DOI Listing
September 2019

Self-destructing Salmonella via temperature induced gene E of phage PhiX174 improves influenza HA DNA vaccine immune protection against H1N1 infection in mice model.

J Immunol Methods 2019 09 6;472:7-15. Epub 2019 Jun 6.

College of Veterinary Medicine, Chonbuk National University, Iksan Campus, 54596, Republic of Korea. Electronic address:

The delivery of DNA vaccines is the principle impediment for implementation of DNA vaccination on a mass scale. In this study, we report a temperature induced conditionally expressed phage PhiX174 gene E mediated lysis of Salmonella under in vivo conditions that can increase the immunogenicity of a DNA vaccine delivered via Salmonella carrier system. We electroporated gene E encoding lysis plasmid pJHL187 along with the pcDNA-HA plasmid encoding H1N1 HA into attenuated Salmonella Typhimurium, strain JOL1893. Using C57BL/6 mice as the model, we showed that the mice intragastrically vaccinated with JOL1893 induced significant production of HA-specific humoral and cell mediated immune responses compared to the JOL1837, which carry pcDNA-HA plasmid alone. Furthermore, mice vaccinated with JOL1893 vaccine were fully protected against the lethal H1N1 challenge compared to the JOL1837 strain, which showed 90% protection only. However, none of the animals survived treated with either the PBS or the Salmonella carrying empty vector. Taken together, our results indicate that mucosal immunization with conditional lysis enabled live attenuated S. Typhimurium as a DNA vaccine carrier can induce efficient systemic and mucosal immune responses, and improves immune protection against a highly pathogenic H1N1 infection in mice model.
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http://dx.doi.org/10.1016/j.jim.2019.06.008DOI Listing
September 2019

Quick assessment with controlled attenuation parameter for hepatic steatosis in children based on MRI-PDFF as the gold standard.

BMC Pediatr 2019 04 15;19(1):112. Epub 2019 Apr 15.

Department of Radiology and Research Institute of Radiological Science, Severance Children's Hospital, Yonsei University College of Medicine, 50-1Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Background: Controlled attenuation parameter (CAP) is a recently introduced, non-invasive and quantitative method to evaluate hepatic steatosis demonstrated in adults, but limited in obesity and not well evaluated in children. The aim of this study was to investigate the diagnostic performance for assessing hepatic steatosis grades using CAP in children based on MR proton density fat fraction (PDFF).

Methods: Children evaluated for non-alcoholic fatty liver disease (NAFLD) who were assessed for PDFF and CAP were enrolled retrospectively. Hepatic steatosis grades 0-3 were classified according to PDFF using cutoff values of 6, 17.5, and 23.3%. Subgroup analyses were performed in non-obese and obese groups using the 95th percentile body mass index (BMI) as a cutoff and BMI30 group when BMI > 30 kg/m. Pearson's correlations between variables were also analyzed.

Results: In a total of 86 children, there were 53 in the obese group including 17 of the BMI30 group. CAP demonstrated 98.7% sensitivity and 80% specificity for diagnosing grades 1-3 vs. grade 0 using a cutoff value of 241 dB/m (area under the curve = 0.941, p < 0.001). The diagnostic performance for higher steatosis grades was suboptimal. CAP correlated with abdominal wall thickness in both obese (r = 0.549, p = 0.001) and non-obese (r = 0.386, p = 0.004) groups and did not correlate with PDFF in BMI30 group.

Conclusion: In children with NAFLD, CAP showed excellent diagnostic performance for differentiating presence and absence of hepatic steatosis using a cutoff value of 241 dB/m. However, CAP was limited in evaluating grades of steatosis, especially in children with BMI > 30 kg/m.
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http://dx.doi.org/10.1186/s12887-019-1485-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463656PMC
April 2019