Publications by authors named "Yon Ho Choe"

123 Publications

Author Correction: COVID-19-related school closing aggravate obesity and glucose intolerance in pediatric patients with obesity.

Sci Rep 2021 Jul 6;11(1):14284. Epub 2021 Jul 6.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1038/s41598-021-93375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258489PMC
July 2021

Infliximab Therapy for Children with Moderate to Severe Ulcerative Colitis: A Step-Up versus a Top-Down Strategy.

Yonsei Med J 2021 Jul;62(7):608-614

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: We aimed to investigate clinical outcomes between top-down (TD) and conventional step-up (SU) therapies in pediatric patients with moderate to severe ulcerative colitis (UC).

Materials And Methods: All patients underwent clinical and endoscopic evaluation at diagnosis and 4 months and 1 year after treatment. Patients who started treatment with corticosteroid were grouped in the SU group, while those that initiated early infliximab (IFX) were grouped in the TD group. Among the SU group, patients who eventually changed to IFX treatment due to steroid resistance or dependency were included in the SU(R) group.

Results: In total, 44 children with moderate to severe UC were included for analysis. Twenty-one patients were included in the SU group, 23 were included in the TD group, and 10 were enrolled in the SU(R) group. Relapse rates were 47.6% (10/21) in the SU group and 17.4% (4/23) in the TD group (=0.033). Among relapsed patients, the durations from remission to relapse were 17.3 months (0.9-46.9) in the SU group and 24.3 months (1.8-44.9) in the TD group. There was no statistically significant difference in the sustained durations of remission after IFX administration between the SU(R) and TD groups [3.9 (1.4-6.3) and 2.3 (0.3-5.2) years, respectively (>0.05)].

Conclusion: According to our study, early use of IFX without corticosteroid treatment for children with moderate to severe UC helps to lower relapse rates. We also found that IFX was a very effective treatment for pediatric UC, with a sustained duration of remission similar between TD and SU(R) groups.
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http://dx.doi.org/10.3349/ymj.2021.62.7.608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236348PMC
July 2021

Albumin-to-Globulin Ratio at 1 Year after Anti-Tumor Necrosis Factor α Therapy Can Serve as a Prognostic Biomarker in Pediatric Crohn's Disease Patients.

Gut Liver 2021 Jun 9. Epub 2021 Jun 9.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: The efficacy of biologics for the treatment of Crohn's disease (CD) is affected by the drug concentrations. We aimed to evaluate the importance of albumin and globulin which are known to be associated with drug concentrations as prognostic biomarkers in CD.

Methods: In total, 121 pediatric patients with CD who had received anti-tumor necrosis factor (TNF)-α therapy were retrospectively examined between January 2010 and February 2019.

Results: Relapse was observed in 48.8% of patients (59/121). The level of calprotectin (odds ratio, 2.13; p=0.03) and the albumin-to-globulin ratio (AGR) at 1 year after anti-TNF-α therapy (odds ratio, 0.0002; p=0.003) were associated with relapse. The AGR at 1 year after anti-TNF-α therapy was the only factor associated with the time-to-relapse (hazard ratio, 0.02; p<0.001). The optimal AGR cutoff value for the prediction of relapse was 1.47 (area under the curve, 0.916; p<0.001). The median infliximab trough level (TL) was lower in patients with AGRs <1.47 than in those with AGRs ≥1.47. Anti-drug antibody (ADA) concentrations were negatively correlated with the AGR at 1 year of anti-TNF-α therapy (r=-0.413, p=0.032).

Conclusions: AGR can be used to predict relapse. Patients with AGRs <1.47 at 1 year after anti-TNF-α therapy are more likely to have low drug TLs and develop ADAs, which increase the possibility of relapse than those with AGRs ≥1.47. Therefore, if the AGR at 1 year after anti-TNF-α therapy is less than 1.47, clinicians should monitor disease activity, assess the TLs of the anti-TNF-α agents, test for ADAs and determine the appropriate therapeutic strategies.
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http://dx.doi.org/10.5009/gnl20322DOI Listing
June 2021

[How Can We Do Transition Successfully from Pediatric to Adult Clinics in Inflammatory Bowel Disease?]

Korean J Gastroenterol 2021 05;77(5):227-230

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

With the increasing incidence of pediatric inflammatory bowel disease (IBD) in children and its impact throughout life, transition care has become an important issue. In Korea, no guidelines have been proposed to support the transition from the pediatric clinic to the adult IBD clinic. This paper reviews the current issues related to IBD patient care during the transition from pediatrics to adults to identify the barriers and critical elements for a successful transition. Thus far, a multi-disciplinary pediatric/adult clinic or alternate visits between pediatric and adult health care providers is the best model for pediatric to adult IBD clinics. Self-reliance and independence of patients with pediatric IBD are also essential for a successful transition. In addition, the timing of the transition from a pediatric clinic to an adult IBD clinic should not be determined because the issue is not the chronological age but rather the individual maturity.
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http://dx.doi.org/10.4166/kjg.2021.065DOI Listing
May 2021

Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients With Crohn Disease.

J Pediatr Gastroenterol Nutr 2021 06;72(6):870-876

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.

Objectives: We investigated the therapeutic drug monitoring of adalimumab (ADL) on clinical remission (CR) and mucosal healing (MH) rates in paediatric patients with Crohn disease (CD). Furthermore, long-term treatment efficacy of ADL in paediatric CD was evaluated through 3-year follow-up.

Methods: We conducted a prospective study of 31 patients with CD who received ADL maintenance therapy and underwent endoscopic evaluation of MH and pharmacokinetic analysis. Patients in CR were identified based on Paediatric Crohn Disease Activity Index (PCDAI) scores less than 10. Patients with MH were identified based on Simple Endoscopic Scores for Crohn Disease (SES-CD) of less than 2.

Results: At 4 months and 1 year of ADL treatment, 28 and 26 patients, respectively, were under CR; 13 and 17 patients, respectively, achieved MH. The median trough levels (TLs) of ADL were higher in patients in CR (7.6 ± 3.5 μg/mL) than in patients with active disease (5.1 ± 2.2 μg/mL). ADL TLs were significantly higher in patients who achieved MH than in those who did not (14.2 ± 7.6 vs 7.8 ± 5.2 μg/mL). The optimal cut-point for predicting MH at 1 year of ADL treatment was 8.18 μg/mL. During long-term follow-up, ADL TLs were stably maintained over 10 μg/mL; not only CR and MH but also histologic remission was obtained at a high rate. ADL administration maintained a positive effect on growth during the maintenance period.

Conclusions: ADL TLs were significantly higher in paediatric patients with CD who achieved CR or MH. ADL treatment showed long-term stable efficacy and positive effects on growth indicators.
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http://dx.doi.org/10.1097/MPG.0000000000003070DOI Listing
June 2021

Therapeutic Lymphatic Embolization in Pediatric Primary Intestinal Lymphangiectasia.

Yonsei Med J 2021 May;62(5):470-473

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Primary intestinal lymphangiectasia (IL) can cause leakage of lymphatic fluids into the gastrointestinal tract, eventually leading to protein-losing enteropathy. A 15-year-old male patient, whose disease began at the age of 8 years, recently felt worsening general weakness. After diagnosing abnormal lymphatic lesions in the duodenum through endoscopy with biopsy and contrast-enhanced magnetic resonance lymphangiography, glue embolization of the leaking duodenal lymphatic channel was successfully performed. This procedure is typically reserved for adult patients, although as shown in this case, it can be properly performed in children. His serum albumin level was initially 1.5 g/dL, but elevated to 5.0 g/dL after two sessions of lymphatic embolization. Accordingly, we suggest that embolization could potentially be considered a first-line treatment for focal lesions of primary intestinal IL.
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http://dx.doi.org/10.3349/ymj.2021.62.5.470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084696PMC
May 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

COVID-19-related school closing aggravate obesity and glucose intolerance in pediatric patients with obesity.

Sci Rep 2021 03 9;11(1):5494. Epub 2021 Mar 9.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

It is important to pay attention to the indirect effects of the social distancing implemented to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic on children and adolescent health. The aim of the present study was to explore impacts of a reduction in physical activity caused by COVID-19 outbreak in pediatric patients diagnosed with obesity. This study conducted between pre-school closing and school closing period and 90 patients aged between 6- and 18-year-old were included. Comparing the variables between pre-school closing period and school closing period in patients suffering from obesity revealed significant differences in variables related to metabolism such as body weight z-score, body mass index z-score, liver enzymes and lipid profile. We further evaluated the metabolic factors related to obesity. When comparing patients with or without nonalcoholic fatty liver disease (NAFLD), only hemoglobin A1c (HbA1c) was the only difference between the two time points (p < 0.05). We found that reduced physical activity due to school closing during COVID-19 pandemic exacerbated obesity among children and adolescents and negatively affects the HbA1C increase in NAFLD patients compared to non-NAFLD patients.
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http://dx.doi.org/10.1038/s41598-021-84766-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943757PMC
March 2021

Individual approach for treatment of primary intestinal lymphangiectasia in children: single-center experience and review of the literature.

BMC Pediatr 2021 01 7;21(1):21. Epub 2021 Jan 7.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

Background: Intestinal lymphangiectasia is a rare disease. Thus, prospective studies are impossible, and therapy is still controversial. Several medicines are suggested for treatment but there are no existing indications for drug choice and treatment guidelines. We aimed to introduce the action mechanism of each drug and treatment overview in a single-center experience and a review of the literature on second-line therapy for primary intestinal lymphangiectasia.

Method: Children under 18 years old diagnosed with intestinal lymphangiectasia from June 2000 to June 2020 were included and retrospectively reviewed in the study. Capsule endoscopy, MR lymphangiography, or whole-body MRI for investigating the extent of abnormal lymphatic vessels in addition to endoscopy and biopsy were conducted. The individual treatment approaches depended upon the lymphangiectasis locations involved.

Results: Only one patient showed a response to dietary therapy. One patient was successfully cured after two therapeutic lymphatic embolization. Octreotide was tried for two patients who had extensive lymphangiectasis. Lymphangiectasis recurred when octreotide was used for 3 months in one patient, and there was no effect in the other patient. Sirolimus was tried for four patients. Two of them had abnormal lymphatic lesions only in the intestine, and the others had extensive lymphangiectasis. The former group showed clinical improvement after 3-4 months of sirolimus treatment, whereas the latter group showed clinical improvement only after 1 month of sirolimus treatment.

Conclusion: Surgery or embolization is a potential therapeutic option for patients with focal abnormal lymphatic lesions. Octreotide is not an optimal choice for patients with extensive lymphangiectasis. Sirolimus is an effective and safe drug and can be the first drug of choice for patients with extensive lymphangiectasis.
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http://dx.doi.org/10.1186/s12887-020-02447-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789338PMC
January 2021

Anti- Antibody in Pediatric Crohn's Disease Patients without Mucosal Healing Is a Useful Marker of Mucosal Damage.

Gut Liver 2020 Dec 30. Epub 2020 Dec 30.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: We evaluated whether anti-Saccharomyces cerevisiae antibody (ASCA) titers are associated with diagnostic findings, disease activity, Paris classification phenotypes, and persistence after infliximab (IFX) treatment in children with Crohn's disease (CD). We also investigated the role of ASCA as a predictor of mucosal healing (MH) and clinical remission (CR).

Methods: This study included 61 CD patients aged 19 years or younger who were diagnosed and treated between September 2010 and January 2019 and followed for at least 1 year. ASCA was regularly measured at the diagnosis of CD and at least 1 year after IFX therapy.

Results: The average follow-up period was 3.8±3.4 years (range, 1.0 to 7.2 years). Regression analysis showed that the ASCA titer was the only factor associated with Simple Endoscopic Score for Crohn's Disease (SES-CD) or CR among all the parameters. In patients who had achieved MH (SES-CD=0), ASCA immunoglobulin G (IgG) was not associated with MH, but in patients without MH, ASCA IgG was associated with SES-CD (p=0.005) and CR (p<0.001). The cutoff value of ASCA IgG in patients with CR was 21.8 units. However, there was no difference in the relapse rate between the ASCA IgG-positive and -negative groups during the follow-up period.

Conclusions: In patients who have not achieved MH, ASCA IgG is closely related to mucosal damage and CR. Unlike western studies, ASCA IgG may be more helpful in predicting prognosis than IgA in Korean patients, but it is not an appropriate indicator to predict the relapse of CD.
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http://dx.doi.org/10.5009/gnl20212DOI Listing
December 2020

The Identification of a Novel Thiopurine S-Methyltransferase Allele, , in Korean Patient with Crohn's Disease.

Pharmgenomics Pers Med 2020 26;13:665-671. Epub 2020 Nov 26.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Pediatric Crohn's disease (CD) carries a higher genetic susceptibility and an increased risk of a more aggressive disease course than adult CD. Treatment of CD is based on immunomodulatory drugs, such as thiopurines. The enzyme mainly involved in drug metabolism is thiopurine S-methyltransferase (TPMT). An increased concentration of drug metabolites can cause adverse drug effects, such as myelosuppression and hepatotoxicity; therefore, assessing the activity of TPMT is essential both before and during treatment. genotyping result is not affected by previous thiopurine dose and currently is the primary component of TPMT activity and disease monitoring. Until now, more than 40 allelic variants of the gene have been reported, with most of them having an uncertain or no enzyme function. In this article, we report the first case of a novel allele, , that was identified in a Korean girl with CD whose findings suggested decreased TPMT activity. This newly observed variant is caused by a single nucleotide polymorphism resulting in nonsense mutation (c.676C>T, p.R226*) and the partial loss of amino acids in the TPMT protein. Initially, the patient began azathioprine at a standard dosage (1.5 mg/kg/day), and her laboratory results, including red blood cell (RBC) TPMT activity (6-methylmercaptopurine 2.68 nmol/mL/h and 6-methylmercaptopurine riboside 4.82 nmol/mL/h) along with thiopurine metabolite levels (6-thioguanine nucleotides 479.3 pmol/8×10 RBC), suggested an enzyme deficiency. The thiopurine dose was reduced to half (0.7 mg/kg/day), and the follow-up metabolite results as well as the associated inflammatory markers were continuously within reference ranges. Along with an improvement in the patient's subjective reports and clinical symptoms, the patient demonstrated a good treatment response to the adjusted dose. The results of our report illustrate the importance of genotyping and pharmacogenetic-based thiopurine dose adjustment. Further research should focus on the functional characterization and impact on this novel allele's treatment effect.
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http://dx.doi.org/10.2147/PGPM.S279446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705256PMC
November 2020

Upper gastrointestinal tract involvement is more prevalent in Korean patients with pediatric Crohn's disease than in European patients.

Sci Rep 2020 11 4;10(1):19032. Epub 2020 Nov 4.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

In pediatric Crohn's disease (CD) patients, it is important to define the disease phenotype at diagnosis for stratifying risk. In this retrospective study, we aimed to assess the disease phenotype compared to EUROKIDS registry and analyze disease outcome of pediatric CD patients according to upper gastrointestinal (GI) tract involvement. A total of 312 patients were included. The median age at diagnosis was 13.7 years and 232 patients (74.4%) were identified to have upper GI involvement at diagnosis. In Korean pediatric CD patients, there were significant differences in male predominance (72.8% vs. 59.2, p < 0.001), proportion of upper GI involvement (74.4% vs. 46.2%, p < 0.001), and perianal disease (62.1% vs. 8.2%, p < 0.001) compared to data in the EUROKIDS registry. Younger age (OR 2.594, p = 0.0139) and ileal involvement (OR 2.293, p = 0.0176) at diagnosis were associated with upper GI involvement. There were no significant differences in disease outcomes between patients with and without upper GI tract involvement. This study revealed that upper GI involvement is more prevalent in Korean patients with pediatric Crohn's disease than in European patients, and the disease outcome did not appear to differ according to upper GI tract involvement.
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http://dx.doi.org/10.1038/s41598-020-75938-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642352PMC
November 2020

Pediatric Crohn's disease with severe morbidity manifested by gastric outlet obstruction: two cases report and review of the literature.

Intest Res 2020 Oct 29. Epub 2020 Oct 29.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Crohn's disease (CD) presenting as gastric outlet obstruction is rare but serious clinical presentation of CD causing severe morbidity. However, there have been few case reports concerning this disorder in East Asian children and adolescents. The current case report describes 2 pediatric patients with CD who had had gastric outlet obstruction as an initial symptom of CD. Two pediatric patients developed postprandial vomiting, bloating, and unintentional weight loss. The upper endoscopy result indicated that there was pyloric obstruction with mucosal edema, inflammation and ulcers. The serologic test and colonoscopy results suggested CD. These patients were treated with infliximab, and endoscopic balloon dilation without surgery and showed remarkable improvement in obstructing symptoms with maintaining clinical and biochemical remission. This case report elucidates the benefits of early intervention using infliximab and endoscopic balloon dilation to improve gastric outlet obstruction and achieve baseline recovery in patients with upper gastrointestinal B2 phenotype of CD.
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http://dx.doi.org/10.5217/ir.2020.00072DOI Listing
October 2020

Delayed Establishment of Gut Microbiota in Infants Delivered by Cesarean Section.

Front Microbiol 2020 11;11:2099. Epub 2020 Sep 11.

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

The maternal vaginal microbiome is an important source for infant gut microbiome development. However, infants delivered by Cesarean section (CS) do not contact the maternal vaginal microbiome and this delivery method may perturb the early establishment and development of the gut microbiome. The aim of this study was to investigate the early gut microbiota of Korean newborns receiving the same postpartum care services for two weeks after birth by delivery mode using fecal samples collected at days 3, 7, and 14. Early gut microbiota development patterns were examined using 16S rRNA gene-based sequencing from 132 infants either born vaginally (VD, = 64) or via Cesarean section (CS, = 68). VD-born neonates showed increased alpha diversity in infant fecal samples collated at days 7 and 14 compared to those from day 3, while those of CS infants did not differ ( < 0.015). Bacterial structures of infants from both groups separated at day 7 ( < 0.001) and day 14 ( < 0.01). The bacterial structure of VD infants gradually changed over time (day 3 vs. day 7, < 0.012; day 3 vs. day 14, < 0.001). Day 14 samples of CS infants differed from day 3 and 7 samples (day 3 vs. day 14, < 0.001). VD infant relative abundance of (days 7, 14), (days 7, 14), and (day 7) significantly increased compared to CS infants, with a lower abundance of (found in all periods of the CS group) (LDA > 3.0). Relative abundances of , , and were significantly increased in both VD and CS groups at day 14 (LDA > 3.0). Predicted functional analysis showed that VD infants had overrepresented starch/sucrose, amino acid and nucleotide metabolism in gut microbiota with depleted lipopolysaccharide biosynthesis until day 14 compared to CS infants. This study confirmed that delivery mode is the major determinant of neonatal intestinal microbiome establishment and provides a profile of microbiota perturbations in CS infants. Our findings provide preliminary insight for establishing recovery methods to supply the specific microbes missing in CS infants.
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http://dx.doi.org/10.3389/fmicb.2020.02099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516058PMC
September 2020

Adjustment of azathioprine dose should be based on a lower 6-TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers.

Aliment Pharmacol Ther 2020 08 29;52(3):459-470. Epub 2020 Jun 29.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The association between NUDT15 polymorphisms and thiopurine-induced leucopenia is well known.

Aim: To investigate the association between NUDT15 polymorphisms and time-to-leucopenia in paediatric patients with inflammatory bowel disease (IBD) receiving azathioprine and to determine the relationship between NUDT15 polymorphisms and 6-thioguanine nucleotide (6-TGN) levels.

Methods: This retrospective observational study included Korean paediatric patients with IBD who were treated with azathioprine and underwent NUDT15 and TPMT genotyping. Azathioprine doses were adjusted by regular thiopurine metabolite monitoring. Factors associated with time-to-leucopenia and the relationship between NUDT15 polymorphisms and 6-TGN levels were analysed.

Results: Among the 167 patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolisers respectively (P < 0.001). NUDT15 polymorphism was significantly associated with time-to-leucopenia (HR = 5.26, 95% CI = 2.74-10.09, P < 0.001). There was a positive association between 6-TGN levels and leucopenia among the NUDT15 intermediate/TPMT normal metabolisers (median 361.3 vs 263.8 pmol/8 × 10 RBC, P = 0.013). The most accurate 6-TGN cut-off level associated with leucopenia was 308.2 pmol/8 × 10 RBC (AUC = 0.742, 95% CI = 0.569-0.915, sensitivity 80.0%, specificity 72.7%, P < 0.001) in this subgroup. When the specificity was set to <15%, the 6-TGN cut-off level was 167.1 pmol/8 × 10 RBC (sensitivity 93.3%, specificity 13.6%).

Conclusions: NUDT15 polymorphisms were associated with time-to-leucopenia during azathioprine treatment in Korean paediatric patients with IBD. In order to reduce the development of thiopurine-induced leucopenia (<15%) in NUDT15 intermediate metabolisers, adjustment of azathioprine doses should be based on a lower 6-TGN target level (<167.1 pmol/8 × 10 RBC).
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http://dx.doi.org/10.1111/apt.15810DOI Listing
August 2020

Myositis as an Initial Presentation of Ulcerative Colitis before Gastrointestinal Symptoms.

Pediatr Gastroenterol Hepatol Nutr 2020 May 8;23(3):297-303. Epub 2020 May 8.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The musculoskeletal system can be involved as an extra-intestinal manifestation of inflammatory bowel disease. Among these, myositis in ulcerative colitis (UC) is very rare. A 14-year-old girl was admitted due to severe shoulder tenderness. She had complained of left jaw pain and swelling for the past 10 days. Inflammatory markers were elevated with no evidence of infectious etiology. Myositis was suspected by shoulder magnetic resonance imaging. Three days after admission, she developed hematochezia. Muscle biopsy and colonoscopy was performed due to worsening left mandibular area pain and persistent hematochezia. Colonoscopy showed consistent findings with UC. She was finally diagnosed with UC with myositis as an extra-intestinal manifestation. She showed a dramatic response to UC treatment. Gastrointestinal symptoms were well-controlled. After 14 months, UC symptoms and muscle pain were aggravated, which were relieved after steroid and cyclosporin treatment. We report a unique case of UC initially presented with myositis, preceding gastrointestinal symptoms.
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http://dx.doi.org/10.5223/pghn.2020.23.3.297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231739PMC
May 2020

Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea.

Yonsei Med J 2020 Jun;61(6):542-546

Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in , which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8-7.5) at a dose of 2.6-3.6 mg/m². Two patients who needed high-dose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332-799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163-346 mg/dL) (<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.
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http://dx.doi.org/10.3349/ymj.2020.61.6.542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256007PMC
June 2020

Potential Utility of Therapeutic Drug Monitoring of Adalimumab in Predicting Short-Term Mucosal Healing and Histologic Remission in Pediatric Crohn's Disease Patients.

J Korean Med Sci 2020 Apr 27;35(16):e114. Epub 2020 Apr 27.

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

Background: Limited data exist regarding mucosal healing (MH) and therapeutic drug monitoring (TDM) in pediatric Crohn's disease (CD) patients treated with adalimumab (ADL). We aimed to investigate the associations between ADL trough levels (TLs) and MH, and between ADL TLs and histologic remission (HR) at 16 weeks from ADL treatment in pediatric CD patients.

Methods: This was a prospective study on moderate-to-severe luminal pediatric CD patients receiving ADL. Ileocolonoscopies and biopsies, as well as clinical activity assessments, laboratory examinations, including tests for ADL TLs and antibody to ADL, were performed 16 weeks after ADL initiation. MH was defined as a Simple Endoscopic Score for CD of 0. HR was defined as the complete absence of microscopic inflammation.

Results: Seventeen subjects (13 males, 4 females) were included. At 16 weeks from ADL initiation, 14 (82.4%), 8 (47.1%), and 4 (23.5%) patients achieved clinical remission, MH, and HR, respectively. ADL TLs were significantly higher in patients who achieved MH compared to those who did not (13.0 ± 6.5 vs. 6.2 ± 2.6 μ/mL, respectively; = 0.023) and also significantly higher in patients who achieved HR compared to those who did not (17.9 ± 5.3 vs. 6.8 ± 2.5 μ/mL, respectively; = 0.02). The optimal TL for predicting MH was 8.76 μ/mL.

Conclusion: Serum ADL TLs at 16 weeks were significantly higher in pediatric patients with CD who achieved MH and HR, respectively. TDM may guide in optimizing treatment efficacy and better target MH in the era of treat-to-target.
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http://dx.doi.org/10.3346/jkms.2020.35.e114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183843PMC
April 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

Correlation of Dickkopf-1 with Inflammation in Crohn Disease.

Indian Pediatr 2019 11;56(11):929-932

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: To explore the potential roles of Dickkopf-1 (DKK-1) and b-catenin in Crohn disease, and to evaluate the effects of a tumor necrosis factor (TNF)-a inhibitor on Wnt signaling in patients with the disease.

Methods: We enrolled 21 patients who received infliximab treatment for one year and achieved clinical remission during the treatment period. Disease activity was graded according to the Pediatric Crohn's Disease Activity Index (PCDAI). Peripheral blood and colonic mucosal specimens were collected from all patients with Crohn disease and from 14 healthy controls. DKK-1 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA). Total RNA for DKK-1 and b-catenin from the frozen colonic tissue were obtained via real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), and albumin were also measured in patients with Crohn disease before and after infliximab therapy.

Results: The serum levels of DKK-1 were significantly higher in patients with Crohn disease than in healthy controls (P=0.003) and were decreased in those treated with infliximab (P=0.026). Serum DKK-1 level was correlated with levels of ESR (r=0.527, P=0.025), CRP (r=0.502, P=0.034), albumin (r=0.363, P=0.021) and PCDAI (r =0.462, P=0.054) in Crohn disease. DKK-1 mRNA expression in the colonic mucosa was higher in patients than in controls and decreased after infliximab treatment. b-catenin expression in the colonic mucosa was lower in patients than in controls and increased after infliximab treatment. However, the differences were not significant (P<0.05).

Conclusions: DKK-1 might be an important mediator of the pathogenesis of Crohn disease, and changes in DKK-1 levels may serve as biomarkers of inflammation in these patients.
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November 2019

Development and Validation of the Mucosal Inflammation Noninvasive Index For Pediatric Crohn's Disease.

Clin Gastroenterol Hepatol 2020 01 10;18(1):133-140.e1. Epub 2019 Apr 10.

Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Israel. Electronic address:

Background & Aims: Mucosal healing (MH) has become a goal of therapy for Crohn's disease (CD), but frequent endoscopies are not feasible. We aimed to develop and validate a non-invasive index to assess mucosal inflammation in children with CD.

Methods: We collected data from the multi-center prospective ImageKids study, in which children with CD underwent ileocolonoscopy with magnetic resonance enterography. We investigated the association of pediatric CD activity index (PCDAI) items and laboratory test results with the simple endoscopic score for CD (SESCD). We used these data in a blended mathematical judgmental clinimetric approach to develop a weighted categorized index to identify children with CD who have MH, which we called the MINI index. We validated the index using data from 3 independent patient cohorts. The derivation and validation cohorts included 154 and 168 children, respectively (age 14.1 ± 2.5 years and 14.2 ± 3.9 years), of whom 16% and 36% had MH (defined as SESCD<3).

Results: In multivariable models, the stooling item of the PCDAI, erythrocyte sedimentation rate, and level of fecal calprotectin were associated with SESCD (all P < .05). We added data on level of C-reactive protein to develop the MINI index. MINI scores below 8 identified children with MH with 88% sensitivity and 85% specificity in the derivation cohort and with 84% sensitivity and 87% specificity in the validation cohorts. Ninety percent of the patients in the validation cohort with scores of 8 or more had active mucosal inflammation, yet 78% of patients with scores below 8 had MH. Scores below 6 increase the positive predictive value to 86%.

Conclusions: We developed an index to non-invasively assess mucosal inflammation in children with CD. This index, identifies children with MH with high sensitivity and specificity. The added benefit of MINI over measurement of fecal calprotectin was small but significant, especially for patients with concentrations of fecal calprotectin from 100 to 599 μg/g. ClinicalTrials.gov no: NCT01881490.
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http://dx.doi.org/10.1016/j.cgh.2019.04.012DOI Listing
January 2020

Serum Infliximab Cutoff trough Level Values for Maintaining Hematological Remission in Pediatric Inflammatory Bowel Disease.

Gut Liver 2019 09;13(5):541-548

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: Infliximab (IFX) often loses its therapeutic effect in initial responders with inflammatory bowel disease (IBD) over time. Low serum IFX trough levels (TLs) are linked to poor clinical response and outcomes. Maintenance of optimal therapeutic IFX concentrations is important for sustaining response and achieving good clinical outcomes. Measurement of serum IFX TLs is helpful for determining a further proper therapeutic plan. However, adequate therapeutic IFX TLs in pediatric IBD is uncertain. We aimed to identify the cutoff values for IFX TLs associated with laboratory response to IFX maintenance therapy.

Methods: Patients with pediatric IBD who had received IFX infusions between December 2008 and March 2015 at Samsung Medical Center were retrospectively investigated. We analyzed 239 blood samples that were collected from 103 pediatric patients. We measured IFX TLs at induction (6 and 14 weeks) and during maintenance therapy (>22 weeks, 8 weeks interval) by fluid-phase radioimmunoassays.

Results: A significant association was found between the erythrocyte sedimentation rate (ESR) and IFX TLs during maintenance (correlation coefficient, -0.11; p=0.0005). A cutoff value of 18 mm/hr for ESR was used to define higher levels. Receiver operating characteristic analysis identified optimal cutoff values: IFX TL >1.58 µg/mL (sensitivity 82% and specificity 73%).

Conclusions: Cutoff values are considered a prerequisite for further investigating the clinical usefulness of measurements of IFX in patients maintained with IFX treatment.
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http://dx.doi.org/10.5009/gnl18129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743797PMC
September 2019

The Characteristics and Outcomes of Abernethy Syndrome in Korean Children: A Single Center Study.

Pediatr Gastroenterol Hepatol Nutr 2019 Jan 10;22(1):80-85. Epub 2019 Jan 10.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Abernethy malformation is a rare condition, which was first described in 1793 as a congenital extrahepatic porto-systemic shunt (CEPS) directing splanchnic blood flow into the inferior vena cava. Eighty cases have been published so far that reported CEPS, while in Korea, very few cases have been reported. Through this study, we present 6 cases of patients diagnosed with CEPS at Samsung Medical Center and compare these with other such cases published in France and China.

Methods: We reviewed clinical, laboratory, and imaging data of 6 children with CEPS in our pediatric clinic between 2004 and 2017.

Results: A total of 6 children with CEPS was included in this study, namely, one with type 1a, two with type 1b, and three with type 2 CEPS. The most common presenting symptom was gastrointestinal bleeding (50.0%). Therapeutic interventions included shunting vessel ligation (16.7%) in type 2 CEPS and liver transplantation (16.7%) in type 2 CEPS patient with suddenly developed hepatic encephalopathy.

Conclusion: There is no consensus guideline for the optimal management of patients with CEPS. Large-sample studies regarding CEPS are needed to evaluate the characteristics of patients with CEPS and determine the treatment guideline for CEPS.
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http://dx.doi.org/10.5223/pghn.2019.22.1.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333588PMC
January 2019

A contact investigation after exposure to a child with disseminated tuberculosis mimicking inflammatory bowel disease.

Korean J Pediatr 2018 Nov 15;61(11):366-370. Epub 2018 Nov 15.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Tuberculosis (TB) is one of the most important diseases that cause significant mortality and morbidity in young children. Data on TB transmission from an infected child are limited. Herein, we report a case of disseminated TB in a child and conducted a contact investigation among exposed individuals.

Methods: A 4-year-old child without Bacille Calmette-Guérin vaccination was diagnosed as having culture-proven disseminated TB. The child initially presented with symptoms of inflammatory bowel disease, and nosocomial and kindergarten exposures were reported. The exposed individuals to the index case were divided into 3 groups, namely household, nosocomial, or kindergarten contacts. Evaluation was performed following the Korean guidelines for TB. Kindergarten contacts were further divided into close or casual contacts. Chest radiography and tuberculin skin test or interferon-gamma-releasing assay were performed for the contacts.

Results: We examined 327 individuals (3 household, 10 nosocomial, and 314 kindergarten contacts), of whom 18 (5.5%), the brother of the index patient, and 17 kindergarten children were diagnosed as having latent TB infection (LTBI). LTBI diagnosis was more frequent in the children who had close kindergarten contact with the index case (17.1% vs. 4.4%, P=0.007). None of the cases had active TB.

Conclusion: This is the first reported case of TB transmission among young children from a pediatric patient with disseminated TB in Korea. TB should be emphasized as a possible cause of chronic diarrhea and failure to thrive in children. A national TB control policy has been actively applied to identify Korean children with LTBI.
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http://dx.doi.org/10.3345/kjp.2018.07206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258968PMC
November 2018

Infliximab Trough Levels Are Associated With Mucosal Healing During Maintenance Treatment With Infliximab in Paediatric Crohn's Disease.

J Crohns Colitis 2019 Feb;13(2):189-197

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background And Aims: Mucosal healing is an important treatment goal in Crohn's disease. We investigated the association between serum infliximab trough levels and mucosal healing, and the infliximab cut-off levels required for mucosal healing in paediatric patients.

Methods: In this multicentre, retrospective, cross-sectional study, medical records and electronic data of paediatric patients with luminal Crohn's disease, who had received infliximab for ≥1 year, were examined. Ileocolonoscopy was performed on the same day as the infliximab infusion, and serum samples for trough levels were collected immediately before infusion. Mucosal healing was defined as a Simple Endoscopic Score for Crohn's Disease of 0. Univariate, multivariate logistic regression, and receiver operating characteristic curve analyses were performed.

Results: Overall, 105 patients [median age 14.8 years] were included, with mucosal healing observed in 48.6%. Median serum infliximab trough levels were higher in patients with mucosal healing [4.5 µg/mL] than without [3.3 µg/mL, p = 0.002]. In the final multivariate model, infliximab trough level ≥4.2 µg/mL [p = 0.002] and ≥1-year duration from diagnosis to infliximab treatment [p = 0.003] were positively and negatively associated with mucosal healing, respectively. The infliximab trough level for achieving mucosal healing with a specificity of 80% was ≥5 µg/mL.

Conclusions: Associations between serum infliximab trough concentrations and mucosal healing were observed in paediatric patients. Identification of the infliximab trough level that positively associates with mucosal healing in most paediatric patients with Crohn's disease [≥5 µg/mL] may guide treatment decisions to optimise therapeutic response in the era of treat-to-target.
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http://dx.doi.org/10.1093/ecco-jcc/jjy155DOI Listing
February 2019

A Case of Glycogen Storage Disease IV with Rare Homozygous Mutations in the Glycogen Branching Enzyme Gene.

Pediatr Gastroenterol Hepatol Nutr 2018 Oct 10;21(4):365-368. Epub 2018 Oct 10.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Glycogen storage disease (GSD) IV is a rare autosomal recessive inherited disorder caused by mutations in the gene coding for glycogen branching enzyme leading to progressive liver disease. GSD IV is associated with mutations in , which encodes the glycogen branching enzyme. We report a case of GSD IV with rare homozygous mutations in the gene (c.791G>A (p.Gly264Glu), which was successfully treated by liver transplantation.
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http://dx.doi.org/10.5223/pghn.2018.21.4.365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182483PMC
October 2018

Renal involvement in children and adolescents with inflammatory bowel disease.

Korean J Pediatr 2018 Oct 12;61(10):327-331. Epub 2018 Sep 12.

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

Purpose: The incidence of inflammatory bowel disease (IBD) is rapidly increasing, and several reports have described the renal complications of IBD. We sought to evaluate the clinical manifestations of renal complications in children with IBD in order to enable early detection and prompt treatment of the complications.

Methods: We retrospectively reviewed the medical records of 456 children and adolescents aged <20 years who had been diagnosed with IBD since 2000. We analyzed patient age, sex, medication use, IBD disease activity, and clinical manifestations of renal symptoms.

Results: Our study comprising 456 children with IBD included 299 boys (65.6%) and 157 girls (34.4%). The study included 346 children with Crohn disease and 110 children with ulcerative colitis. The incidence of kidney-related symptoms was 14.7%, which was significantly higher than that in normal children. We observed 26 children (38.8%) with isolated hematuria, 30 children (44.8%) with isolated proteinuria, and 11 children (16.4%) with hematuria and concomitant proteinuria. A renal biopsy was performed in 7 children. Histopathological examination revealed immunoglobulin A nephropathy in 5 children (71.4%). All children presented with mild disease and well-controlled disease activity of IBD.

Conclusion: Children with IBD are more likely to show kidney-related symptoms than healthy children and adolescents are. Therefore, regular screening of urine and evaluation of renal function in such children are necessary for early detection of renal complications.
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http://dx.doi.org/10.3345/kjp.2018.06485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212711PMC
October 2018

Characterization of the fecal microbiota differs between age groups in Koreans.

Intest Res 2018 Apr 30;16(2):246-254. Epub 2018 Apr 30.

Probioticslab R&D Institute, Bioeleven Co., Seoul, Korea.

Background/aims: Tens of trillions of microorganisms constitute the gut microbiota of the human body. The microbiota plays a critical role in maintaining host immunity and metabolism. Analyses of the gut microbial composition in Korea are limited to a few studies consisting of small sample sizes. To investigate the gut microbial community in a large sample of healthy Koreans, we analyzed the 16S ribosomal RNA of 4 representative bacterial genera , , , and .

Methods: A total of 378 DNA samples extracted from 164 infants and 214 adults were analyzed using quantitative real-time polymerase chain reaction.

Results: Analysis of 16S ribosomal RNA of 4 representative bacterial genera , , , and showed that the gut microbiota in infants had higher relative abundances of and than that in adults, which was dominated by and .

Conclusions: To the best of our knowledge, this was the first study evaluating the distinct characteristics of the microbial community of Korean infants and adults. The differences between the 2 populations suggest that external factors such as age, diet, and the environment are important contributing factors to the change in gut microbial composition during development.
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http://dx.doi.org/10.5217/ir.2018.16.2.246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934597PMC
April 2018

Subtherapeutic Infliximab Trough Levels and Complete Mucosal Healing Are Associated With Sustained Clinical Remission After Infliximab Cessation in Paediatric-onset Crohn's Disease Patients Treated With Combined Immunosuppressive Therapy.

J Crohns Colitis 2018 May;12(6):644-652

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background And Aims: We aimed to investigate the outcome in paediatric-onset Crohn's disease patients who had discontinued infliximab after maintaining clinical remission with combined immunosuppression, and to determine factors associated with clinical relapse.

Methods: We conducted a retrospective observational study of 63 paediatric-onset Crohn's disease patients who had stopped scheduled infliximab during sustained corticosteroid-free clinical remission for at least 1 year with infliximab and azathioprine, and were followed up for at least 1 year thereafter. Cumulative relapse rates and the median time to relapse were estimated statistically. Factors at cessation were also evaluated for their association with clinical relapse.

Results: After a median follow-up period of 4.3 years [range, 1-7.5 years], 60.3% [38/63] of patients had experienced clinical relapse. According to Kaplan-Meier survival analysis, the estimated cumulative relapse rates at 1, 4, and 6 years were 19.0%, 62.2%, and 75.2%, respectively, and the median relapse time was 3.3 years from infliximab cessation. According to multivariate Cox proportional hazard regression analysis, infliximab trough levels of ≥2.5 μg/mL and incomplete mucosal healing were associated with clinical relapse (hazard ratio [HR] = 7.199, 95% confidence interval [CI] = 1.641-31.571, p = 0.009 and HR = 3.628, 95% CI = 1.608-8.185, p = 0.002, respectively). Although re-treatment with infliximab was effective in 90.9% [30/33] of patients, 7.9% [3/38] eventually underwent surgery within 1 year of relapse.

Conclusions: Considering the high cumulative relapse rates in the long term and cases of severe relapse requiring surgery, discontinuing infliximab in paediatric-onset Crohn's disease patients is currently inadvisable. However, there may be a subgroup of patients who are good candidates for infliximab withdrawal.
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http://dx.doi.org/10.1093/ecco-jcc/jjy021DOI Listing
May 2018
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