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The prevalence of obesity among children and adolescents with autism spectrum disorder (ASD) is higher than that among typically developing children and adolescents. However, very few studies have explored the genetic factors associated with obesity in children and adolescents with ASD. Thus, the aim of this study was to examine the associations between 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene polymorphisms and obesity among children and adolescents with ASD. The study participants consisted of 33 children and adolescents with ASD and 271 age- and sex-matched typically developing controls. We compared the metabolic traits (body mass index, blood pressure, triglyceride, high-density lipoprotein, and fasting glucose levels) between the ASD and control group. Furthermore, we assessed the genotypes of rs12654264 in the HMGCR gene within the participants with ASD, and compared metabolic traits among the different allele subgroups. The mean body mass index (BMI) and triglyceride level of the ASD group were significantly higher than those of the control group. Within the ASD group, the triglyceride level of participants with rs12654264-T alleles was significantly higher than that of participants with A-alleles. A pattern of increasing values in the BMI and fasting glucose was also observed in participants with T allele. This is the first study to show that obesity in children and adolescents with ASD is associated with the cholesterol synthesis pathway. Future studies are needed to further clarify the molecular mechanisms by which the HMGCR gene influences metabolic traits.

Purpose Seoul National University College of Medicine operates a faculty development program for clinical teachers at multiple affiliated teaching hospitals. In 2020, the program was moved online due to coronavirus disease 2019. The purpose of this study was to determine whether it is feasible and effective to provide faculty development programs online in terms of clinical teachers' participation and satisfaction in comparison with offline programs. Methods Clinical teachers participated in the clinical teaching methods programs offline in 2019 and online in 2020. We analyzed participation rate and satisfaction level. All surveys items were rated on a 5-point Likert scale. We also interviewed instructors about the advantages and drawbacks of the online program. Results The participation rate of the online program (89.5%) was significantly higher than that of the offline program (67.8%). The overall satisfaction level for the online program (4.37) was similar to that for the offline program (4.50). Conclusion Faculty development programs online are feasible and effective in medical education. We need to design training content that fits online programs, consider various online training methods to reinforce the strengths of online programs, and support participants to make good use of these programs.

Pancreaticopleural fistula (PPF) a fistulous connection between the pancreas and pleural space due to prolonged chronic pancreatitis (CP). PPF is a very rare complication which presents in 0.4% of chronic pancreatitis cases, especially among children. We report a case involving a 3-year-old boy who presented with pleural effusion caused by a PPF, a complication of hereditary pancreatitis, which was, for the first time in Korea, successfully managed with endoscopic treatment. Chest radiography and computed tomography showed massive pleural effusion. Percutaneous catheter drainage was performed. High amylase levels were observed in the pleural fluid and serum, suggesting PPF. The patient was managed with bowel rest and octreotide infusion. Endoscopic retrograde cholangiopancreatography revealed CP, and pleural effusion was successfully managed with stent placement. PRSS1 genetic screening revealed R122H mutation.

Purpose Vitamin D deficiency is a condition widespread throughout the world. Recent studies have suggested that vitamin D deficiency was associated with obesity and metabolic syndrome. The purpose of the study was to examine the relationship between vitamin D deficiency and nonalcoholic fatty liver disease (NAFLD) in adolescents. Methods The data were obtained from the Korean National Health and Nutrition Examination Survey from 2008–2014. A total of 3,878 adolescents were included in the study. Vitamin D deficiency was defined as a 25-hydroxyvitamin D concentration 30 U/L. Results Vitamin D deficiency was noted in 78.9% of the studied population. Age, body mass index, waist circumference, and blood pressure, glucose, cholesterol, and triglyceride levels were significantly higher in adolescents with suspected NAFLD than in adolescents without suspected NAFLD, while the mean vitamin D level was significantly lower in adolescents with suspected NAFLD. The multivariate-adjusted odds of suspected NAFLD were higher with increased age, male gender, obesity, and metabolic syndrome. Individuals with vitamin D deficiency were at higher risk of suspected NAFLD (odds ratio, 1.77; 95% confidence interval, 1.07–2.95) after adjusting for age, gender, obesity, and metabolic syndrome. Conclusion Vitamin D deficiency was associated with suspected NAFLD, independent of obesity and metabolic syndrome, in adolescents.

Objectives Inflammatory bowel disease (IBD) is characterised by dysregulated mucosal immune responses associated with genetic, environmental and microbial factors. Recent therapies targeting key inflammatory mediators such as tumor necrosis factor (TNF)‐α emphasise the importance of innate immunity in the development of IBD. Methods We examined the distribution of innate immune cells such as innate lymphoid cells (ILCs) and myeloid cells in the intestinal epithelium from children diagnosed as IBD and murine models of colitis induced by dextran sulphate sodium (DSS) or an anti‐CD40 antibodies. Results We found an increased number of type 3 ILCs (ILC3s) that do not express the natural cytotoxicity receptor (NCR) and neutrophils, in both human IBD patients and colitis‐induced mice. A co‐culture experiment of neutrophils with NCR‐ ILC3s revealed that NCR‐ ILC3s stimulate neutrophils by producing granulocyte–macrophage colony‐stimulating factor (GM‐CSF). Furthermore, a blockade of GM‐CSF could inhibit the development of IBD by inhibiting neutrophil activity. Conclusion The NCR‐ ILC3: GM‐CSF: neutrophil axis could contribute to the development of IBD., We showed type 3 innate lymphoid cells (ILC3s) that do not express natural cytotoxicity receptor (NCR), and neutrophils, are increased in the inflamed colons from both humans and mice. NCR‐ ILC3s produce granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and, in turn, stimulate neutrophils. This NCR‐ ILC3s: GM‐CSF: neutrophil axis may be a critical innate aspect of inflammatory bowel disease.

Background Longitudinal integrated clerkships (LICs) have been adopted by medical schools to overcome the limitations of traditional block clerkship rotations and to promote continuity of care. In 2018, Seoul National University College of Medicine introduced a patient-centered LIC program as part of a new curriculum in parallel with traditional block rotation clerkships. The purpose of this study was to present the patient-centered LIC program and to investigate its educational effects. Methods In 2018 and 2019, a total of 298 third-year medical students participated in the LIC program. We divided the students into groups of eight, which were organized into corresponding discussion classes. Throughout the academic year, students followed up patients by interviewing them at the hospital or reviewing their electric medical records. Discussion classes on set topics were held seven times per year with facilitators and clinical faculites. Students completed a course evaluation questionnaire at the end of the academic year. The questionnaire included 22 items measured on a 5-point scale and two open-ended questions asking about the benefits and limitations of the program. The items covered three domains: student experience, satisfaction, and self-assessment. Final reflective essays were collected as both student assessments and data for qualitative analysis. Results During the study period, the overall experience of the students improved. We increased the number of faculty members and patients and decreased the number of students in each discussion class. We also provided additional feedback through an e-portfolio. Students' satisfaction changed positively. Compared to the rotational clerkship, students answered that the LIC provided additional help in learning the two core competencies. During the first 2 years of the program, the percentage of students who answered that the program was more helpful than the rotational clerkship increased from 23.7% to 46.4% for continuity of care (P < 0.001), and from 20.5% to 50.7% for patient-centered care (P < 0.001). Conclusion Our patient-centered LIC, in parallel with traditional block rotation clerkships, had a positive effect on students' experience of continuity of care and patient-centered care., Graphical Abstract

Objectives This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). Methods We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF: total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. Results Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). Conclusion A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.

Background Due to the outbreak of coronavirus disease 2019 (COVID-19), school openings were postponed worldwide as a way to stop its spread. Most classes are moving online, and this includes medical school classes. The authors present their experience of running such online classes with offline clinical clerkship under pandemic conditions, and also present data on student satisfaction, academic performance, and preference. Methods The medical school changed every first-year to fourth-year course to an online format except the clinical clerkship, clinical skills training, and basic laboratory classes such as anatomy lab sessions. Online courses were pre-recorded video lectures or live-streamed using video communication software. At the end of each course, students and professors were asked to report their satisfaction with the online course and comment on it. The authors also compared students’ academic performance before and after the introduction of online courses. Results A total of 69.7% (318/456) of students and 35.2% (44/125) of professors answered the questionnaire. Students were generally satisfied with the online course and 62.2% of them preferred the online course to the offline course. The majority (84.3%) of the students wanted to maintain the online course after the end of COVID-19. In contrast, just 13.6% of professors preferred online lectures and half (52.3%) wanted to go back to the offline course. With the introduction of online classes, students' academic achievement did not change significantly in four subjects, but decreased in two subjects. Conclusions The inevitable transformation of medical education caused by COVID-19 is still ongoing. As the safety of students and the training of competent physicians are the responsibilities of medical schools, further research into how future physicians will be educated is needed.

Patients with lysosomal acid lipase (LAL) deficiency and glycogen storage disease (GSD) demonstrated hepatomegaly and dyslipidemia. In our case, a 6-year-old boy presented with hepatosplenomegaly. At 3 years of age, GSD had been diagnosed by liver biopsy at another hospital. He showed elevated serum liver enzymes and dyslipidemia. Liver biopsy revealed diffuse microvesicular fatty changes in hepatocytes, septal fibrosis and foamy macrophages. Ultrastructural examination demonstrated numerous lysosomes that contained lipid material and intracytoplasmic cholesterol clefts. A dried blood spot test revealed markedly decreased activity of LAL. LIPA gene sequencing identified the presence of a novel homozygous mutation (p.Thr177Ile). The patient's elevated liver enzymes and dyslipidemia improved with enzyme replacement therapy. This is the first report of a Korean child with LAL deficiency, and our findings suggest that this condition should be considered in the differential diagnosis of children with hepatosplenomegaly and dyslipidemia.

Background It is critical to develop remedial education for underperforming medical students, but little is known about how to create an effective remediation program. Deliberate practice (DP) is a structured and reflective activity that is designed to optimize performance. Here we applied the concept of DP to create remedial education to improve the clinical practices of medical students. We also analyzed the effectiveness of the remediation program. Methods Based on the expert performance approach of DP, we designed a 4-week remedial program for clinical performance that included feedback and reflection. There were 74 student participants in this program from 2014 to 2017. Their clinical performance was re-evaluated after completion, and changes in their clinical performance scores were analyzed. Results Students who completed the remediation program showed significant improvements in clinical performance scores (P < 0.001). Most students found the program to be instructive and helpful for improving their clinical performance. They reported that role play with peers was the most helpful for improving their skills. Conclusion The DP-based remediation program improved the clinical performance of failing medical students. This remediation program should continue to be offered to underperforming students to ensure that medical school graduates are competent., Graphical Abstract

Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine. Physical examination showed generalized icterus and splenomegaly. The laboratory findings suggested warm-type AHA with cholestatic hepatitis. Liver biopsy revealed giant cell transformation of hepatocytes and moderate lobular inflammation. The patient was successfully treated with four doses of rituximab. Early relapse of hemolytic anemia and hepatitis was observed, which prompted the use of an additional salvage dose of rituximab. He is currently in clinical remission.

Purpose Pediatric Crohn's disease (CD) is directly related to growth and has a high probability of requiring surgical intervention(s); therefore, more active treatment for CD is required for children. This study investigated the impact of biologics on growth and disease course associated with surgery. Methods This was a retrospective cohort study involving patients diagnosed with CD at the Seoul National University Children's Hospital (Seoul, Korea) between January 2006 and October 2017. The aim was to determine the characteristics of pediatric patients with CD and whether biologics affected growth and the surgical disease course. Results Among patients who underwent surgery for CD, the mean number of operations per patient was 1.89. The mean time from initial diagnosis to surgery was 19.3 months. The most common procedure was fistulectomy (34%), followed by incision and drainage (25%). In all patients, the use of biologics increased the height (p=0.002) and body mass index (BMI) (p=0.005). Among patients who underwent surgery, height (p=0.004) and BMI (p=0.048) were increased in the group using biologics. Patients who used biologics exhibited a low operation rate only within 2 years after diagnosis, with no differences thereafter (p=0.027). Conclusion Although biologics could not mitigate the operation rate in pediatric patients who underwent surgery for CD, biological therapy delayed disease progression within 2 years of disease onset. Additionally, biologics conferred growth and BMI benefits in this window period. Therefore, it may be helpful to use biologics for optimal growth in pediatric patients with a high probability of undergoing future surgery.

Biliary atresia (BA) is the major cause of cholestasis and the leading indication for liver transplantation (LT). However, the incidence of BA in Korea has not been reported. The aim of this study was to investigate the incidence and clinical outcomes of BA in Korea. We used the Korean universal health insurance database and extracted data regarding BA patients younger than 18 years of age admitted between 2011 and 2015. The incidence of BA was calculated by dividing the number of BA patients by the number of live births. Two hundred forty infants were newly diagnosed with BA. A total of 963 BA patients younger than 18 years of age were followed up for 5 years. The overall incidence of BA was 1.06 cases per 10,000 live births. The incidence of BA was 1.4 times higher for female patients than for male patients. Additionally, significant seasonal variation was observed; in particular, the incidence of BA was 2 times higher from June through August than from December through February. Congenital anomalies were found in 38 of 240 patients (15.8%). Congenital heart diseases were major associated congenital anomalies (6.3%). Several complications developed during the study period, including cholangitis (24.0%), varix (6.2%), and gastrointestinal bleeding (4.4%). Three hundred and one of the 963 BA patients under 18 years of age (31.3%) received LT for BA. The incidence of BA is higher in Korea than that in Western countries. We also report significant gender-associated differences and seasonal variation with respect to the incidence of BA., Graphical Abstract

Purpose Vitamin D deficiency is common in Crohn disease (CD). The aim of the study was to examine the prevalence of vitamin D deficiency and evaluate the association between vitamin D status and growth outcome in Korean pediatric CD patients. Methods In this retrospective study, 17 children younger than 18 years old diagnosed with CD were enrolled and their serum 25-hydroxy vitamin D (25[OH]D) was checked between 2011 and 2015. We categorized the patients into two groups, Group 1 and Group 2. Group 1 included patients with serum 25(OH)D levels below 10 ng/mL, and Group 2 was for patients with a 25(OH)D serum levels between 10 ng/mL and 30 ng/mL. The z-scores for height (Htz), weight (Wtz), and body mass index (BMIz) were measured at baseline, 6 months, and 12 months. Results The mean serum 25(OH)D levels of the total 65 CD patients and 17 enrolled patients were 15.64±6.9 ng/mL and 13.1±5.1 ng/mL, respectively. There was no correlation at the beginning of the study between vitamin D level and growth parameters (Htz, Wtz, BMIz) or other variables including laboratory data and Pediatric Crohn Disease Activity Index. The Htz, Wtz, and BMIz in Group 1 showed no significant improvement at 6 months and 12 months follow-up. In Group 2, Wtz and BMIz showed significant improvements sustained until 12 months of follow-up. Htz showed no significant improvement at 6 months but there was significant improvement at 12 months. Conclusion It seems that baseline vitamin D status affects growth outcome in pediatric CD.