Comparison of endoscopic healing and durability between infliximab originator and CT-P13 in pediatric patients with inflammatory bowel disease.

Background and aims: Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Methods: Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. Results: We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). Conclusions: The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era.

BACKGROUND: Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19). METHODS: This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021. RESULTS: A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn's disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn's disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020). CONCLUSION: Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.

Epidemiologic Changes in Over 10 Years of Community-Acquired Bacterial Enteritis in Children.

PURPOSE: Community-acquired bacterial enteritis (CABE) is a common problem in developed countries. It is important to understand the epidemiologic changes in bacterial pathogens for prevention and treatment. Therefore, we studied the epidemiologic changes in CABE in Korean children. METHODS: A total of 197 hospitalized pediatric patients aged <19 years that presented with dysentery symptoms and showed positive polymerase chain reaction results for bacterial species in stool samples, were enrolled in this study for 10 years (June 2010 to June 2020). We classified patients in phase I (06, 2010-06, 2015) and phase II (07, 2015-06, 2020) and analyzed their epidemiologic and clinical characteristics. RESULTS: The most common pathogens were Campylobacter species (42.6%) and Salmonella species were the second most common pathogens (23.9%). The abundance of pathogens decreased in the following order: Clostridium difficile (9.6%), Shigella (5.6%), and Clostridium perfringens (5.6%). Escherichia coli O157:H7 was found to be the rarest pathogen (2.0%). Campylobacter species showed an increase in the infection rate from 32.1% in phase I to 49.6% in phase II (p=0.0011). Shigella species showed a decline in the infection rate in phase I from 14.1% to 0.0% in phase II (p<0.001). C. difficile and C. perfringens showed an increase in infection rate in phase II compared to phase I, but the difference was not statistically significant. CONCLUSION: The infection rate of Campylobacter species in CABE has been rising more recently, reaching almost 50%. This study may help establish policies for prevention and treatment of CABE in Korean children.

Interpretation of XIAP Variants of Uncertain Significance in Paediatric Patients with Refractory Crohn's Disease.

BACKGROUND AND AIMS: Mutations in XIAP can lead to the development of treatment-refractory severe paediatric Crohn's disease [CD], for which haematopoietic stem cell transplantation is the primary therapeutic option. The interpretation of variants of uncertain significance [VUSs] in XIAP needs to be scrutinized. METHODS: Targeted next-generation sequencing was performed for 33 male paediatric patients with refractory CD admitted at a tertiary referral hospital. To obtain functional data, biomolecular cell assays and supercomputing molecular dynamics simulations were performed. RESULTS: Nine unrelated male patients harboured hemizygous XIAP variants. Four known pathogenic variants and one novel pathogenic variant [p.Lys168Serfs*12] were identified in five patients, and two novel VUSs [p.Gly205del and p.Pro260Ser] and one known VUS [p.Glu350del] were identified in the remaining four. Among children with VUSs, only the subject with p.Gly205del exhibited defective NOD2 signalling. Using molecular dynamics simulation, we determined that the altered backbone torsional energy of C203 in XIAP of p.G205del was ~2 kcal/mol, suggesting loss of zinc binding in the mutant XIAP protein and poor coordination between the mutant XIAP and RIP2 proteins. Elevated auto-ubiquitination of zinc-depleted p.G205del XIAP protein resulted in XIAP protein deficiency. CONCLUSION: A high prevalence of XIAP deficiency was noted among children with refractory CD. Advanced functional studies decreased the subjectivity in the case-level interpretation of XIAP VUSs and directed consideration of haematopoietic stem cell transplantation.

Nationwide Multicenter Study of Eosinophilic Esophagitis in Korean Children.

PURPOSE: In East Asian countries, there are only a few epidemiologic studies of eosinophilic esophagitis (EoE) and no studies in children. We investigated the incidence and compared the clinical characteristics of EoE and eosinophilic gastroenteritis involving the esophagus (EGEIE) in Korean children. METHODS: A total of 910 children, who had symptoms of esophageal dysfunction, from 10 hospitals in Korea were included. EoE was diagnosed according to diagnostic guidelines and EGEIE was diagnosed when there were >15 eosinophils in the esophagus per high power field (HPF) and >20 eosinophils per HPF deposited in the stomach and duodenum with abnormal endoscopic findings. RESULTS: Of the 910 subjects, 14 (1.5%) were diagnosed with EoE and 12 (1.3%) were diagnosed with EGEIE. Vomiting was the most common symptom in 57.1% and 66.7% of patients with EoE and EGEIE, respectively. Only diarrhea was significantly different between EoE and EGEIE (p=0.033). In total, 61.5% of patients had allergic diseases. Exudates were the most common endoscopic findings in EoE and there were no esophageal strictures in both groups. The median age of patients with normal endoscopic findings was significantly younger at 3.2 years, compared to the median age of 11.1 years in those with abnormal endoscopic findings (p=0.004). CONCLUSION: The incidence of EoE in Korean children was lower than that of Western countries, while the incidence of EGEIE was similar to EoE. There were no clinical differences except for diarrhea and no differences in endoscopic findings between EoE and EGEIE.

A Case of Eosinophilic Esophagitis Associated with Herpes Esophagitis in a Pediatric Patient.

Eosinophilic esophagitis is a rare disease in Asian countries, but its incidence is growing rapidly in Western countries. The main pathophysiology of eosinophilic esophagitis is esophageal epithelial barrier dysfunction; disruption of the esophageal epithelial barrier easily induces antigen sensitization to foods and aeroallergens, which leads to subsequent esophageal inflammation as a result of eosinophil recruitment. Here we report a case of an 11-year-old Korean boy who suffered from fever, odynophagia, dysphagia, and chest pain. His upper endoscopic findings showed longitudinal ulcers with a volcano-like appearance at the distal esophagus. Polymerase chain reaction test results and biopsy specimens were positive for herpes simplex virus type 1. He was treated with acyclovir and a proton pump inhibitor, but his follow-up endoscopy showed typical patterns of eosinophilic esophagitis, and the biopsy specimens were compatible with the diagnostic criteria for eosinophilic esophagitis. Therefore, we report a very rare case of eosinophilic esophagitis after herpes esophagitis in a Korean child with normal immunity.

[Rapunzel Syndrome Removed with Enteroscopy in a Child].

A trichobezoar is a type of bezoar that is composed of hair. In most cases, it is confined to the stomach, but in rare cases, it may extend to the small intestine. This condition is referred to as Rapunzel syndrome. The therapeutic method for bezoar removal depends on its type, location, and size. Generally, the treatment for Rapunzel syndrome involves surgical laparotomy. Endoscopic removal has also been effective in some cases. On the other hand, complications, such as respiratory difficulty and esophageal impaction may be encountered during endoscopic removal. Until now, the successful endoscopic removal of trichobezoars has been limited to the stomach or duodenum. This paper reports the case of a 4-year-old female patient with Rapunzel syndrome whose trichobezoar reached the proximal jejunum. The trichobezoar was removed without complications using an electrosurgical knife and snare through a single-balloon enteroscopy. The trichobezoar can be removed successfully using enteroscopy under general anesthesia without abdominal laparotomy in young children. Therefore, this method of removal can be considered preferentially for children with Rapunzel syndrome.

Eosinophilic Esophagitis Is an Underlying Cause for Gastrointestinal Concerns in Children.

Eosinophilic esophagitis (EoE) is a chronic immune antigen-mediated disorder characterized by symptoms of esophageal dysfunction in combination with dense esophageal eosinophilia. The clinical presentation of EoE can vary depending on children's age and their ability to report symptoms, therefore a high index of suspicion for EoE is required because children and teenagers may develop coping strategies around eating. The development of symptoms measurement tools in EoE assists in not only assessing symptoms, but also coping strategies children may have developed. While the diagnosis of EoE requires endoscopic evaluation with histologic assessment of esophageal mucosal biopsy samples, several emerging methods to assess and survey the esophageal mucosa have been developed. Advances in the field to better understand the natural history, clinical and molecular features of phenotypes in EoE will be important in considering novel therapeutic options and assessing outcomes.

Epidemiological Correlation between Fecal Adenovirus Subgroups and Pediatric Intussusception in Korea.

We investigated the adenoviral etiology and seasonal epidemic trends in intussusception and each adenoviral subgroup. Also we confirmed whether we can use the adenovirus data of Acute Infectious Agents Laboratory Surveillance Report (AIALSR) as an epidemic predictor of intussusception. Patients with intussusception (n = 126), < 5 years old, were enrolled and matched by age and sex with controls suffering acute gastroenteritis without intussusception (n = 106), all recruited at 8 centers. All fecal specimens were assayed for adenovirus, including subgroups A, B, C, E, and F, with reverse transcriptase-polymerase chain reaction (RT-PCR). Adenovirus was detected in 53 cases and 13 controls (P < 0.001). Nonenteric adenoviruses (NEAds) were detected in 51 cases and four controls (P < 0.001). We used Spearman's correlation analysis to analyze the incidence of intussusception and adenoviral epidemic trends, and compared them with fecal and respiratory adenoviral epidemic trends in the AIALSR. The trend of intussusception correlated with total NEAds (r = 0.635; P = 0.011), as did the fecal AIALSR adenovirus trends (r = 0.572; P = 0.026). Among the NEAd subgroups, subgroup C was dominant (P < 0.001), but subgroups B (P = 0.007) and E (P = 0.013) were also significant to intussusception. However, only subgroup C showed a significant epidemic correlation (r = 0.776; P = 0.001) with intussusception. Not respiratory but fecal AIALSR adenovirus trends correlated with the incidence of NEAds and intussusception. We suggest the possibility of using fecal AIALSR adenovirus data as an approximate epidemic predictor of intussusception.

Respiratory effects of the hebei spirit oil spill on children in taean, Korea.

PURPOSE: The oil spill from the Heibei Spirit in December 2007 contaminated the Yellow Coast of South Korea. We evaluated the respiratory effects of that spill on children who lived along the Yellow Coast. METHODS: Of 662 children living in the area exposed to the oil spill, 436 (65.9%) were enrolled as subjects. All subjects completed a modified International Study of Asthma and Allergies in Childhood questionnaire. A health examination, including a skin prick test, pulmonary function test, and methacholine bronchial provocation test (MBPT), was administered. The children were assigned to two groups: those who lived close to the oil spill area and those who lived far from the oil spill area. RESULTS: The children who lived close to the oil spill area showed a significantly lower forced expiratory volume in one second (FEV1), an increased prevalence of 'asthma ever' (based on a questionnaire), and 'airway hyperresponsiveness' (based on the MBPT) than those who lived far from the oil spill area (FEV1; P=0.011, prevalence of 'asthma ever' based on a questionnaire; P=0.005, prevalence of 'airway hyperresponsiveness' based on the MBPT; P=0.001). The onset of wheezing after the oil spill was significantly higher in children who lived close to the oil spill area than in those who lived far from the oil spill area among the 'wheeze ever' group (P=0.002). In a multiple logistic regression analysis, male sex, family history of asthma, and residence near the oil spill area were significant risk factors for asthma (sex [male/female]: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.31-4.91; family history of asthma [No/Yes]: OR, 3.77; 95% CI, 1.83-7.75; exposure group [low/high]; OR, 2.43; 95% CI, 1.27-4.65). CONCLUSIONS: This study suggests that exposure to an oil spill is a risk factor for asthma in children.