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Leukemia and Crohn’s disease are both diseases that can be influenced by genetic factors. Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurogenetic disorder caused by genetic mutation. This report presents a pediatric case of concomitant development of leukemia, Crohn’s disease, and TSC. We aimed to study the pathogenesis of each disease and report this case to provide data for future reports and research on correlation of these three diseases.

Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic granulomatous inflammation of any part of the body, primarily the gastrointestinal (GI) tract, and is increasing in incidence worldwide. As CD is a systemic disease, the features of CD typically manifest in the GI tract; however, a variety of extra-intestinal manifestations, such as the involvement of joints, skin, and eyes may also occur. Although pyogenic liver abscess itself is rare in the general population (approximately 3–5 per 100,000 hospital admissions), it is also an unusual and rare presentation in pediatric CD patients. In this report, we present a case of pyogenic liver abscess in a 7-year-old female CD patient and discuss the clinical features, laboratory findings, imaging studies, and pathologic report of liver biopsy.

ObjectiveBiliary atresia (BA) patients develop chronic liver disease after the Kasai operation and are eventually indicated for liver transplantation (LT). The purposes of this study were to analyze long-term outcomes after LT and risk factors that affect complications to reduce graft failure.Study designOverall, 145 pediatric patients who underwent LT between June 1996 and June 2020 after a diagnosis of BA were included. We performed a retrospective analysis of medical records and evaluated patient and graft survival, cumulative incidence of complications, risk factors, and the results of policy changes.ResultsPatient and graft survival rates in over 20 years were 95.8% and 91.0%, respectively. Post-transplantation lymphoproliferative disease was frequently observed in the early period of immunosuppression within the first 1–2 years after LT. The incidence of cholangitis and rejection steadily increased over time. Weight-to-portal vein size was evaluated as a risk factor for cholangitis and bile duct strictures (OR = 12.82, p = 0.006 and OR = 16.54, p = 0.015, respectively). When evaluated using 2013 as a reference point, the split graft indication was expanded and the group that received LT after 2013 had a significantly lower survival over time compared with that of the group that received LT before 2013 (p = 0.006).ConclusionThis study revealed time differences in prevalence of complications. The evaluation of weight-to-duct or vessel size is a more important factor in considering complications than the graft-to-recipient weight ratio. Survival outcomes may have been altered by a policy change that affects the donor type ratio in transplantation.

IntroductionAcute gastrointestinal graft-versus-host disease (GVHD) is a common life-threatening complication after hematopoietic stem cell transplantation (HCT). We aimed to investigate outcomes according to the clinical, endoscopic, and histologic severity of gastrointestinal GVHD in pediatric patients treated with allogeneic HCT.MethodsThis retrospective cohort study included pediatric patients who underwent sufficient endoscopic and histopathologic evaluation for clinically suspected acute gastrointestinal GVHD between 2010 and 2020.ResultsFifty-one patients were included (male proportion, 68.6% [35/51]; median age at HCT, 6.4 years). When the patients were classified according to the histologic severity of gastrointestinal GVHD, the severe group had an earlier onset of GVHD symptoms and a higher proportion of patients with severe clinical gastrointestinal GVHD than the mild-to-moderate and “absent” groups. In Cox proportional hazards regression analysis, the groups with more severe clinical and histologic gastrointestinal GVHD showed a higher risk of non-relapse mortality (NRM). The 5-year overall survival (OS) rates were 58.3 and 36.4% in the mild-to-moderate and histologic gastrointestinal GVHD groups, respectively (p = 0.0384). Patients with higher clinical and histologic grades of gastrointestinal GVHD showed higher cumulative incidence of NRM.DiscussionOur results demonstrated that histologic severity of gastrointestinal GVHD is a relevant factor affecting OS and NRM, and patients with mild-to-moderate or severe histologic gastrointestinal GVHD have worse outcomes than patients without histologic GVHD. These findings support the importance of assessing the histologic grade in the diagnostic evaluation of patients with clinical gastrointestinal GVHD.

Background/Aims: We aimed to compare the differences in pediatric Crohn’s disease (CD) and ulcerative colitis (UC) at diagnosis in Korea. Methods: This was a multicenter, registry-based, inception cohort study conducted at five centers in Korea between 2013 and 2017. Baseline demographics, clinical characteristics, and results from laboratory, endoscopic, radiologic examinations were compared between pediatric CD and UC patients who were

Background: Immunogenicity to antitumor necrosis factor alpha agents, such as infliximab (IFX), may lead to therapeutic failure. Objectives: This study evaluated the relationship between free and total antibodies-to-infliximab (ATIs), trough levels (TLs) of IFX, and the response to dose intensification. Design: We performed a prospective, observational study including pediatric patients with Crohn’s disease (CD) receiving IFX maintenance therapy without dose intensification. Methods: We compared clinical and laboratory outcomes according to the presence of free and total ATIs. Factors associated with response to IFX dose intensification were investigated by analyzing IFX TLs and free and total ATIs. Results: Of the 98 patients, 9 patients had detectable free ATIs and 38 patients had total ATIs. Patients with free ATIs had significantly lower TLs (0.7 versus 5.1 µg/mL, p

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

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

Abstract Few studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn’s disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression and statistical internal validation identified three factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P = 0.0081), IFX TLs during maintenance therapy (HR 0.581, P = 0.003), 6-thioguanine nucleotide (6-TGN) level (HR 0.978, P

Monocytes are involved in the upstream inflammatory process in the immune reaction in inflammatory bowel disease (IBD). Patients with IBD who discontinued biologics have been found to relapse, even after checking for deep remission. This study investigated whether monocytes could act as a predictor of relapse in patients who experienced relapse after the discontinuation of biologics. To this end, pediatric patients (

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.

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

It is necessary to reflect on the question, “How to prepare for medical education after coronavirus disease 2019 (COVID-19)?” Although we are preparing for the era of Education 4.0 in line with the 4th industrial revolution of artificial intelligence and big data, most measures are focused on the methodologies of transferring knowledge; essential innovation is not being addressed. What is fundamentally needed in medicine is insightful intelligence that can see the invisible. We should not create doctors who only prescribe antispasmodics for abdominal pain, or antiemetic drugs for vomiting. Good clinical reasoning is not based on knowledge alone. Insightology in medicine is based on experience through Bayesian reasoning and imagination through the theory of mind. This refers to diagnosis of the whole, greater than the sum of its parts, by looking at the invisible using the Gestalt strategy. Identifying the missing process that links symptoms is essential. This missing process can be described in one word: context. An accurate diagnosis is possible only by understanding context, which can be done by standing in someone else’s shoes. From the viewpoint of medicine, Education 4.0 is worrisome because people are still clinging to methodology. The subject we should focus on is “human”, not “artificial” intelligence. We should first advance the “insightology in medicine” as a new paradigm, which is the “essence” that will never change even when rare “phenomena” such as the COVID-19 outbreak occur. For this reason, we should focus on teaching insightology in medicine, rather than teaching medical knowledge.

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.

BackgroundUlcerative colitis (UC) is a systemic inflammatory disease with a gut predominance, which may involve other organs. The presence of extraintestinal manifestation (EIM) is an important symptom for clinicians as it alters the treatment decisions. In this study, we aimed to evaluate the initial clinical presentation and disease severity of pediatric UC patients with EIMs.MethodsOne hundred forty-two patients under the age of 18 years who were diagnosed with UC from January 2003 to November 2021 were included in this study. Forty-seven patients with confirmed EIMs and 95 patients without EIMs were divided into two groups and their differences were analyzed.ResultsThe most common EIM was peripheral arthritis. The disease extent at the time of diagnosis shows a higher rate of pancolitis in the EIM-positive group (65.9%) than that of the EIM-negative group (33.7%) (p < 0.001). More than 90% of EIM-positive patients had moderate to severe disease activity on the Mayo endoscopic subscore. In the EIM-positive group, the cumulative use of systemic steroids, immunosuppressants, and biological agents from diagnosis to 1 year follow-up were significantly higher than those of the EIM-negative group (p = 0.009, 0.001, and < 0.001, respectively). About 80% of patients in the EIM-negative group reached remission, but only about 50% of the EIM-positive patients reached remission (p = 0.005). The relapse occurred more frequently in the EIM-positive group than in the EIM-negative group with statistical significance (p < 0.001).ConclusionPediatric UC with EIMs had higher disease severity and often manifested upper gastrointestinal tract involvement. Despite EIMs treatment, the occurrence of new EIMs was observed repeatedly. Cumulative drug demand (steroids, immunosuppressants, and biological agents) for the treatment increased steadily over time, and frequent relapses occurred despite the combinatory use of therapeutic drugs.

BackgroundThe spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis to fibrosis. We aimed to introduce useful biomarkers released during liver inflammation and fibrogenesis that are easy to use in outpatient clinic and adjust to children to evaluate each NAFLD stage without biopsy.MethodsThis prospective study included 60 patients aged under 19 years whose alanine aminotransferase (ALT) levels were elevated from March 2021. All patients were proven to have NAFLD by ultrasonography and laboratory work-up to exclude other causes of hepatitis. Fibroscan and additional laboratory tests for biomarkers [procollagen type1 amino-terminal propeptide (P1NP), osteocalcin, interleukin-6 (IL-6), and Mac-2 binding protein glycosylated isomer (M2BPGi)] were performed. Fibroscan-AST (FAST) score was used for the comparison of steatohepatitis and liver stiffness measurement (kPa) was used for the comparison of advanced fibrosis.ResultsThe biomarker that showed a significant difference between the FAST-positive and negative groups was the P1NP/osteocalcin ratio with a p-value of 0.008. The area under receiver operating characteristic (AUROC) of P1NP/osteocalcin ratio*ALT values (values obtained through multivariate analysis) was 0.939 with the cut-off value of 305.38. The biomarkers that showed a significant difference between the LSM-positive and negative groups were IL-6 and M2BPGi with a p-values of 0.005 and

Abstract 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

Abstract 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.

In children and adolescents, acute pancreatitis is a rare cause of abdominal pain. The causes of pancreatitis in children are various including infection and drugs, but the overall cause of this condition in a pediatric patient is sometimes unknown. We describe a case of Burkitt lymphoma which showed acute pancreatitis findings as an initial presentation. In this case, a 16-year-old boy presented with abdominal pain in the left upper quadrant that had been present for one month. Pancreatitis was suspected due to high amylase and lipase and the computed tomography findings in the patient, which showed swelling and adjacent infiltration of the pancreas. However, initial treatments did not improve the patient's symptoms. The following imaging studies showed mass-like lesions involving the pancreas, distal duodenum and jejunum associated with mesenteric lymphadenopathy that suggested a lymphoma in this case. In the final analysis, the patient was diagnosed with Burkitt lymphoma which was seen on bone marrow biopsies and also found on the small bowel tissue biopsies.

There has been a growing need to utilize the concept of “precision medicine” in the treatment of inflammatory bowel disease (IBD). In practice, precision medicine for IBD comprises prediction and personalizing therapies. Prediction is divided into two subcategories: pre-treatment investigation and monitoring response to therapy. Pre-treatment prediction includes clinical outcome assessment, investigation of factors for poor outcome, magnetic resonance enterography, and measurement of TPMT, NUDT15, and other biologic markers. Mucosal healing or transmural healing is considered the “treat-to-target” approach in IBD. To achieve “treat-to-target,” the “top-down strategy” is recommended in patients with pediatric Crohn’s disease, because the therapeutic window of opportunity may be shorter than that generally believed. We are unable to state that we are truly utilizing biologics in a perfect manner until both “treat-to-target” and “top-down strategy” are supported by “therapeutic drug monitoring (TDM),” a key component of personalizing therapy for IBD. Proactive TDM, or more precisely, model-based proactive dosing with point-of-care assay will soon emerge as the new standard for IBD treatment. It is speculated that “treat-to-target,” “top-down strategy,” and “TDM” may aid personalized therapy to achieve outstanding improvement in patients with pediatric IBD.

Background/AimsInfliximab (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%).Conclusion : sCutoff values are considered a prerequisite for further investigating the clinical usefulness of measurements of IFX in patients maintained with IFX treatment.

The gastrointestinal (GI) tract is frequently affected by inborn errors of immunity (IEI), and GI manifestations can be present in IEI patients before a diagnosis is confirmed. We aimed to investigate clinical features, endoscopic and histopathologic findings in IEI patients. This was a retrospective cohort study conducted from 1995 to 2020. Eligible patients were diagnosed with IEI and had GI manifestations that were enough to require endoscopies. IEI was classified according to the International Union of Immunological Societies classification. Of 165 patients with IEI, 55 (33.3%) had GI manifestations, and 19 (11.5%) underwent endoscopy. Among those 19 patients, nine (47.4%) initially presented with GI manifestations. Thirteen patients (68.4%) were male, and the mean age of patients 11.5 ± 7.9 years (range, 0.6 – 26.6) when they were consulted and evaluated with endoscopy. The most common type of IEI with severe GI symptoms was “Disease of immune dysregulation” (31.6%) followed by “Phagocyte defects” (26.3%), according to the International Union of Immunological Societies classification criteria. Patients had variable GI symptoms such as chronic diarrhea (68.4%), hematochezia (36.8%), abdominal pain (31.6%), perianal disease (10.5%), and recurrent oral ulcers (10.5%). During the follow-up period, three patients developed GI tract neoplasms (early gastric carcinoma, mucosa associated lymphoid tissue lymphoma of colon, and colonic tubular adenoma, 15.8%), and 12 patients (63.2%) were diagnosed with inflammatory bowel disease (IBD)-like colitis. Investigating immunodeficiency in patients with atypical GI symptoms can provide an opportunity for correct diagnosis and appropriate disease-specific therapy. Gastroenterologists and immunologists should consider endoscopy when atypical GI manifestations appear in IEI patients to determine if IBD-like colitis or neoplasms including premalignant and malignant lesions have developed. Also, if physicians in various fields are better educated about IEI-specific complications, early diagnosis and disease-specific treatment for IEI will be made possible.

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.

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

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, n = 64) or via Cesarean section (CS, n = 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 (p < 0.015). Bacterial structures of infants from both groups separated at day 7 (p < 0.001) and day 14 (p < 0.01). The bacterial structure of VD infants gradually changed over time (day 3 vs. day 7, p < 0.012; day 3 vs. day 14, p < 0.001). Day 14 samples of CS infants differed from day 3 and 7 samples (day 3 vs. day 14, p < 0.001). VD infant relative abundance of Bifidobacterium (days 7, 14), Bacteroides (days 7, 14), and Lachnospiraceae (day 7) significantly increased compared to CS infants, with a lower abundance of Enterobacteriaceae (found in all periods of the CS group) (LDA > 3.0). Relative abundances of Bifidobacterium, Lactobacillus, and Staphylococcus 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.

Background/AimsInformation regarding the efficacy of early infliximab treatment in pediatric patients with Crohn’s disease (CD) is limited. We aimed to evaluate the impact of early combined immunosuppression on linear growth in pediatric patients with CD by performing step-up comparisons.Methods : This retrospective study included pediatric patients with moderate-to-severe CD, who received a combination therapy with infliximab and azathioprine for at least 3 years and sustained corticosteroid-free remission without loss of response. The z-scores of the growth indicators obtained at the time of diagnosis and annually for 3 years thereafter were compared between the two groups.Results : The early combined immunosuppression group displayed significantly increased linear growth 3 years after diagnosis (p=0.026). A significant difference was also observed in the linear growth 3 years after diagnosis between subgroups of Tanner stages 1–2 (p=0.016).Conclusion : sThe early introduction of biologics should be considered to improve linear growth in pediatric patients with CD.

Background/AimsTens 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.MethodsA total of 378 DNA samples extracted from 164 infants and 214 adults were analyzed using quantitative real-time polymerase chain reaction.ResultsAnalysis 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.ConclusionsTo 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.

Alagille syndrome (AGS) is a complex multisystem disorder that involves mainly the liver, heart, eyes, face, and skeleton. The main associated clinical features are chronic cholestasis due to a paucity of intrahepatic bile ducts, congenital heart disease primarily affecting pulmonary arteries, vertebral abnormalities, ocular embryotoxon, and peculiar facies. The manifestations generally become evident at a pediatric age. AGS is caused by defects in the Notch signaling pathway due to mutations in JAG1 or NOTCH2. It is inherited in an autosomal dominant pattern with a high degree of penetrance, but variable expressivity results in a wide range of clinical features. Here we report on a 31-year-old male patient who presented with elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase, and was diagnosed with AGS associated with the JAG1 mutation after a comprehensive workup.

Background/AimsThe clinical use of measuring infliximab (IFX) trough levels (TLs) and antibodies against IFX (ATIs) in patients with pediatric inflammatory bowel disease (IBD) remains unclear. We propose measuring these variables to create individual IFX treatment strategies for patients with pediatric IBD.Methods : This retrospective study was conducted in pediatric patients with IBD who received IFX from July 2009 to June 2014.Results : Samples were available from 39 patients with pediatric IBD. A significant difference was observed in IFX TLs in 16 patients who were in clinical remission (group A) after IFX therapy (median, 3.99 μg/mL; interquartile range [IQR], 0.30 to 21.96) compared to 23 patients who had a poor response to treatment (group B) (median, 0.88 μg/mL; IQR, 0.00 to 6.80, p=0.002). In group B, 21 patients underwent empiric intensification of IFX treatment. After dose intensification, 17 patients had an improved response to treatment. Four patients still had no response to dose intensification. Therefore, these patients were switched to other biologics.Conclusion : sPatients who had poor responses and subtherapeutic IFX TLs had an improved response to dose intensification. Patients who had ATIs were likely to continue to have no response after dose intensification. Therefore, tailoring individual IFX treatments based on IFX TLs, ATIs, and the clinical response should be considered.

Purpose: In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. The purpose of this report is to share SKKUSOM’s experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. Methods: Through a process of reflection-on-action, we examined SKKUSOM’s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. Results: The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. Conclusion: Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology.

We report a case of a 5-year-old girl who developed left hemiparesis and left facial palsy, 6 days after the initiation of fever and respiratory symptoms due to pneumonia. Chest radiography, conducted upon admission, showed pneumonic infiltration and pleural effusion in the left lung field. Brain magnetic resonance imaging showed acute ischemic infarction in the right middle cerebral artery territory. Brain magnetic resonance angiography and transfemoral cerebral angiography revealed complete occlusion of the right middle cerebral artery. Mycoplasma pneumoniae infection was identified by a 4-fold increase in IgG antibodies to M. pneumoniae between acute and convalescent sera by enzyme-linked immunosorbent assay. Fibrinogen and D-dimer levels were elevated, while laboratory exams in order to identify other predisposing factors of pediatric stroke were all negative. This is the first reported pediatric case in English literature of a M. pneumoniae-associated cerebral infarction involving complete occlusion of the right middle cerebral artery.

Here we present the case of an 11-year-old female patient diagnosed with Caroli syndrome, who had refractory esophageal varices. The patient had a history of recurrent bleeding from esophageal varices, which was treated with endoscopic variceal ligation thrice over a period of 2 years. However, the bleeding was not controlled. When the patient finally visited the Emergency Department, the hemoglobin level was 4.4 g/dL. Transhepatic intrajugular portosystemic shunt was unsuccessful. Subsequently, the patient underwent percutaneous transhepatic variceal obliteration. Twenty hours after this procedure, the patient complained of aphasia, dizziness, headache, and general weakness. Six hours later, the patient became drowsy and unresponsive to painful stimuli. Lipiodol particles used to embolize the coronary and posterior gastric veins might have passed into the systemic arterial circulation, and they were found to be lodged in the brain, kidney, lung, and stomach. There was no abnormality of the portal vein on portal venography, and blood flow to the azygos vein through the paravertebral and hemiazygos systems was found to drain to the systemic circulation on coronary venography. Contrast echocardiography showed no pulmonary arteriovenous fistula. Symptoms improved with conservative management, and the esophageal varices were found to have improved on esophagogastroduodenoscopy.

Children have a natural tendency to explore objects with their mouths; this can result in the swallowing of foreign objects. Most ingested foreign bodies pass uneventfully through the gastrointestinal tract. However, some foreign bodies cause obstruction or perforation of the gastrointestinal tract, requiring surgical intervention. Perforation of the gastrointestinal tract may be associated with considerable morbidity and mortality. The most common sites of intestinal foreign body perforation are the ileocecal and rectosigmoid regions. Foreign body perforation of the duodenum is relatively uncommon. We report the first Korean case of duodenal perforation by an ingested 8-cm lollipop stick. Lollipops are popular with the children and fairly accessible to them, as most parents are not aware of their potential harm. Pediatric clinicians should be aware of the risks associated with lollipop stick ingestion. Our report also describes the feasibility and safety of laparoscopic diagnosis and management of pediatric patients with peritonitis induced by the ingestion of foreign bodies.

PURPOSE:To compare preoperative CT findings before liver transplantation between patients with Alagille syndrome (AGS) and those with end-stage biliary atresia (BA). MATERIALS AND METHODS:The institutional review board approved this retrospective study. Eleven children with AGS (median age, 19.0 ± 13.0 months; male to female ratio, 3:8) and 109 children with end-stage BA (median age, 17.9 ± 25.8 months; male to female ratio, 37:72) who underwent abdomen CT as candidates for liver transplant were included. CT images were reviewed focusing on hepatic parenchymal changes, vascular changes, presence of focal lesions, and signs of portal hypertension. RESULTS:Hepatic parenchymal changes were present in 27% (3/11) of AGS patients and 100% (109/109) of end-stage BA patients (P < .001). The hepatic artery diameter was significantly smaller (1.9 mm versus 3.6 mm, P = 008), whereas portal vein diameter was larger (6.8 mm versus 5.0 mm, P < .001) in patients with AGS compared with patients with end-stage BA. No focal lesion was seen in patients with AGS, whereas 44% (48/109) of patients with end-stage BA had intrahepatic biliary cysts (39%, 43/109) and hepatic tumors (8%, 9/109) (P = .008). Splenomegaly was commonly seen in both groups (P = .082), and ascites (9% [1/11] versus 50% [54/109], P = .010) and gastroesophageal varix (0% [0/11] versus 80% [87/109], P < .001) were less common in patients with AGS than in patients with end-stage BA. CONCLUSION:Fibrotic or cirrhotic changes of the liver, presence of focal lesions, and relevant portal hypertension were less common in patients with AGS than in patients with end-stage BA.

To evaluate the incremental value of a combination of magnetic resonance cholangiopancreatography (MRCP) and ultrasonography (US), compared to US alone, for diagnosing biliary atresia (BA) in neonates and young infants with cholestasis.The institutional review board approved this retrospective study. The US and MRCP studies were both performed on 64 neonates and young infants with BA (n = 41) or without BA (non-BA) (n = 23). Two observers reviewed independently the US alone set and the combined US and MRCP set, and graded them using a five-point scale. Diagnostic performance was compared using pairwise comparison of the receiver operating characteristics (ROC) curve. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value were assessed.The diagnostic performance (the area under the ROC curve [Az]) for diagnosing BA improved significantly after additional review of MRCP images; Az improved from 0.688 to 0.901 (P = .015) for observer 1 and from 0.676 to 0.901 (P = .011) for observer 2. The accuracy of MRCP combined with US (observer 1, 95% [61/64]; observer 2 92% [59/64]) and PPV (observer 1, 95% [40/42]; observer 2 91% [40/44]) were significantly higher than those of US alone for both observers (accuracy: observer 1, 73% [47/64], P = 0.003; observer 2, 72% [46/64], P = 0.004; PPV: observer 1, 76% [35/46], P = 0.016; observer 2, 76% [34/45], P = 0.013). Interobserver agreement of confidence levels was good for US alone (ĸ = 0.658, P < .001) and was excellent for the combined set of US and MRCP (ĸ = 0.929, P < .001).Better diagnostic performance was achieved with the combination of US and MRCP than with US alone for the evaluation of BA in neonates and young infants with cholestasis.

Crohn's disease is characterized by chronic inflammation involving any portion of the gastrointestinal tract. Treating Crohn's disease is a major challenge for clinicians, as no curative therapy currently exists. Pediatric Crohn's disease is characterized by frequent relapses, a wide extent of disease, a high prevalence of extraintestinal manifestations, and a severe clinical course. The classic therapeutic approach is known as the 'step-up' strategy, and follows a progressive course of treatment intensification as disease severity increases. Although this approach is usually effective for symptom control, many patients become either resistant to or dependent on corticosteroids. The efficacy of infliximab suggests that, rather than a progressive course of treatment, early intense induction may reduce complications associated with conventional treatment and improve quality of life. Intensive early therapy with infliximab is known as the 'top-down' strategy. Such therapy offers the potential for altering the natural history of Crohn's disease, and is changing treatment paradigms. However, the relatively new concept of an early aggressive or 'top-down' treatment approach is not yet widely accepted, especially in pediatric patients. The results of our current study demonstrate that early and intensive treatment of pediatric Crohn's disease patients with infliximab, at initial diagnosis, was more effective for maintaining remission and reducing flares.

Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia, caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib, caused by a deficiency of glucose-6-phosphate transporter (G6PT). We report that a substantial improvement was achieved following several infusions of hepatocytes in a patient with GSD-Ib. Hepatocytes were isolated from the unused cadaveric whole livers of two donors. At the first transplantation, approximately 2 × 109 cells (2% of the estimated recipient's total hepatocytes) were infused. Seven days later 1 × 109 (1% of liver mass) cryopreserved hepatocytes from the same donor were infused, and an additional 3 × 109 (3% of liver mass) cells from the second donor were infused 1 month after the second transplantation. After the hepatocyte transplantation, the patient showed no hypoglycemic symptoms despite the discontinuation of cornstarch meals. Liver biopsies on posttransplantation days 20 and 250 showed a normal level of glucose-6-phosphatase activity in presolubilization assay that was very low before transplantation. This was the first and successful clinical hepatocyte transplantation in Korea. In this study, hepatocyte transplantation allowed a normal diet in a patient with GSD-Ib, with substantial improvement in their quality of life. Hepatocyte transplantation might be an alternative to liver transplantation and dietary therapy in GSD-Ib.