The emergence of mucosal healing as a treatment goal that could modify the natural course of Crohn's disease and the accumulating evidence showing that biologics are most effective in achieving mucosal healing, along with the success of early treatment regimens for rheumatoid arthritis, have led to the identification of early Crohn's disease and development of the concept of catching the therapeutic window during the early disease course. Thus, an increasing number of pediatric gastroenterologists are adopting an early biologic treatment strategy with or without an immunomodulator. Although early biologic treatment is effective, cost and overtreatment are issues that limit its early use. Currently, there are insufficient data on who will benefit most from early biologics, as well as on who will not need early or even any biologics. For now, top-down biologics should be considered for patients with currently known high-risk factors of poor outcomes. For other patients, close, objective monitoring and accelerating the step-up process by means of a treat-to-target approach seems the best way to catch the therapeutic window in early pediatric Crohn's disease. The individual benefits of immunomodulator addition during early biologic treatment should be weighed against its risks and decision on early combination treatment should be made after comprehensive discussion with each patient and guardian.
Arthritis, Rheumatoid ; Biological Products ; Crohn Disease ; Humans ; Medical Overuse ; Pediatrics

Homozygous mutations in NUDT15 R139C are known as the major factor associated with thiopurine-induced early leukopenia, particularly in Asian patients. Therefore, NUDT15 genotyping is currently recommended before thiopurine treatment to identify patients who are NUDT15 poor metabolizers and consider the use of an alternative immunomodulatory therapy. We report a case of a 12-year-old Korean girl with Crohn’s disease (CD), in whom thiopurine-induced leukopenia was prevented by initiation of azathioprine (AZA) therapy at a low dose (0.5 mg/kg/day) and early detection of significant hair loss and white blood cell (WBC) count decrease at 17 days from the start of AZA treatment. The WBC count dropped from 8,970/μL to 3,370/μL in 2 weeks, and AZA treatment was stopped because of concerns of potential leukopenia in the near future. Her WBC count recovered to 5,120/μL after 3 weeks. Gene analysis later revealed that she had a homozygous mutation in NUDT15 R139C, resulting in a poor metabolizing activity of NUDT15. In situations when NUDT15 genotyping is unavailable, initiation of AZA therapy at 0.5 mg/kg/day with close observation of hair loss and WBC counts within 2 weeks may be an alternative way to prevent thiopurine-induced early leukopenia in Asian children with CD.

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1–2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.
Brain ; Brain Neoplasms ; Central Nervous System ; Child ; Chromatin Assembly and Disassembly ; Drug Therapy ; Epigenomics ; Humans ; Phosphotransferases ; Protein-Tyrosine Kinases ; Radiotherapy ; Stem Cells ; Tyrosine

Background/Aims: Anti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients. Methods: Pediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this crosssectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors. Results: A total of 76 patients (Crohn’s disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%). Conclusions IFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.

Background/Aims: Anti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients. Methods: Pediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this crosssectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors. Results: A total of 76 patients (Crohn’s disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%). Conclusions IFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.

Background: Various methods have been implemented for pediatric gastrostomy tube placement. We aimed to investigate the performance status of pediatric gastrostomy in South Korea and to present indications and appropriate methods for domestic situations. Methods: A survey was conducted among pediatric endoscopists who performed upper gastrointestinal endoscopy in Korea. The questionnaire consisted of 16 questions on gastrostomy performance status. Results: Among the 48 institutions where the survey was applied, 36 (75%) responded.Of the 36 institutions, gastrostomy was performed in 31 (86.1%). The departments in which gastrostomy was performed were pediatrics at 26 institutions (81.3%), surgery at 24 institutions (75.0%), internal medicine at 9 institutions (28.1%), and radiology at 7 institutions (21.9%). There were 18 institutions (66.7%) using the pull method for percutaneous endoscopic gastrostomy (PEG) and nine institutions (33.3%) using the push method. When performing gastrostomies, fundoplication procedures were performed in 19 institutions (61.3%), if deemed necessary. However, 12 institutions (38.7%) answered that gastrostomy was always implemented alone. Complications after gastrostomy included buried bumper syndrome, wound infection, leakage, tube migration, and incorrect opening site in the stomach, but the number of cases with complications was very small. Conclusion In Korea, a pediatric gastrostomy is implemented in various ways depending on the institution. Clinicians are concerned about choosing the most effective methods with fewer complications after the procedure. In our study, we reported only a few complications.Korea has good accessibility for pediatric gastrointestinal endoscopy, and this survey showed that it is a safe procedure that can be considered initially in pediatric gastrostomy. This study is expected to help to create optimal pediatric PEG guidelines in 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 Lactobacillus, Bifidobacterium, Bacteroides, and Clostridium. 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 Lactobacillus, Bifidobacterium, Bacteroides, and Clostridium showed that the gut microbiota in infants had higher relative abundances of Bifidobacterium and Lactobacillus than that in adults, which was dominated by Bacteroides and Clostridium. 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.
Adult ; Bacteroides ; Bifidobacterium ; Clostridium ; Diet ; DNA ; Gastrointestinal Microbiome ; Human Body ; Humans ; Infant ; Korea ; Lactobacillus ; Metabolism ; Microbiota* ; Real-Time Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; Sample Size ; Transcutaneous Electric Nerve Stimulation

Background: Vedolizumab (VDZ) is currently licensed for use in adults for the treatment of inflammatory bowel disease (IBD). We aimed to investigate the clinical course of pediatric-onset IBD following treatment with VDZ as more than a secondary biologic agent. We also evaluated factors associated with secondary loss of response (LOR) and durability of VDZ treatment. Methods: Pediatric-onset IBD patients diagnosed at an age younger than 18 years who had received VDZ as more than a secondary biologic agent were included in this retrospective observational study conducted at the Department of Pediatrics of two centers in Korea. Comparative analysis was conducted between groups divided according to the development of secondary LOR during VDZ treatment. Results: A total of 24 patients comprising 10 patients with Crohn’s disease and 14 with ulcerative colitis were included. Of these, 19 were male and 5 were female. The mean age at diagnosis was 14.6 ± 2.5 years. The mean age at initiation of VDZ was 20.5 ± 2.8 years. Nine patients (37.5%) had received two or more biologic agents before starting VDZ. During a median of 0.9 years follow-up from VDZ initiation, 9 patients (37.5%) experienced LOR requiring interval shortening and 4 patients (16.7%) were changed to a different biologic agent. According to multivariate Cox proportional hazard regression analysis, administration of two or more biologic agents before VDZ treatment was the only factor positively associated with LOR (hazard ratio [HR], 5.6; 95% confidence interval [CI], 1.026–30.56; P = 0.047), while LOR was the only factor negatively associated with VDZ durability (HR, 0.003; 95% CI, 0.00–0.08; P = 0.010). No adverse events were observed during treatment with VDZ. Conclusion VDZ is safe and efficacious for the treatment of pediatric-onset IBD patients failing a primary biologic agent. The durability of VDZ may be enhanced by introducing VDZ earlier in the disease course. Further prospective studies in children are required in the future to validate these findings.

PURPOSE: We aimed to investigate the efficacy and safety of adalimumab in pediatric-onset Crohn's disease patients who had failed treatment with infliximab. METHODS: In this retrospective study, patients included were those who had been diagnosed with Crohn's disease before 18 years old, and had received treatment with adalimumab after infliximab failure. The efficacy of adalimumab treatment was investigated at 1 month and 1 year, and adverse events that had occurred during treatment with adalimumab were explored. RESULTS: Ten patients were included in this study. The median duration from diagnosis to adalimumab treatment was 5.5 years (range: 2.4-7.9 years). At 1 month after adalimumab initiation, 80% (8/10) of patients showed clinical response, and 40% (4/10) achieved clinical remission. At 1 year, 71% (5/7) of patients showed clinical response, and 43% (3/7) were under clinical remission. Among the total included patients, 5 patients (50%) showed clinical response at 1 year. Primary non-response to adalimumab was observed in 2 patients (20%), and secondary failure to adalimumab was observed in 3 patients (30%) during 1 year treatment with adalimumab. No serious adverse event had occurred during adalimumab treatment. CONCLUSION: Adalimumab was effective for 1 year without serious adverse events in half of pediatric-onset Crohn's disease patients who had failed treatment with infliximab.
Adalimumab* ; Crohn Disease* ; Diagnosis ; Humans ; Infliximab* ; Retrospective Studies

PURPOSE: The prevalence of reflux esophagitis (RE) has increased recently in Korea. Little is known concerning the prevalence and characteristics of RE in pediatric patients. This study investigated the prevalence and influence of risk factors in endoscopically proven RE in Korea in pediatric patients over a period of 14 years. METHODS: A retrospective chart review of all patients between the ages of 1 month and 20 years who underwent esophagogastroduodenoscopy at Samsung Medical Center between 2001 and 2014 was carried out. Univariate and multivariate analyses were conducted to identify independent risk factors for RE. RESULTS: The prevalence rate of endoscopically proven RE in this study was 28.7% (978/3,413). The prevalence of RE increased from 11.8% from 2001 to 2007 to 37.7% from 2008 to 2014. Multivariate logistic regression analysis revealed that residency in the Greater Gangnam area (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.02-1.44) and age (OR, 1.13; 95% CI, 1.11-1.15) were significant predictive factors for the presence of RE. CONCLUSION: The prevalence rate of endoscopically proven pediatric RE has increased over the past 14 years. Residency and older age are more important independent risk factors for pediatric RE in Korea.
Child* ; Endoscopy ; Endoscopy, Digestive System ; Esophagitis, Peptic* ; Gastroesophageal Reflux ; Humans ; Internship and Residency ; Korea* ; Logistic Models ; Multivariate Analysis ; Pediatrics ; Prevalence* ; Retrospective Studies ; Risk Factors