소아기 기능성 복통

Functional abdominal pain (FAP) is one of the most common pain syndromes in childhood and is a functional gastrointestinal disorder (FGID). Recurrent abdominal pain (RAP) is characterized by three or more episodes of abdominal pain that occurover at least 3 months and are severe enough to interfere with activities. It may be caused by many conditions, including inflammatory bowel disease, peptic ulcer, pancreatitis or, functional abdominal pain. The most common clinical manifestation is periumbilical pain related to autonomic and functional symptoms like nausea, vomiting, pallor and other painful conditions like headache and limb pains. RAP requires accurate diagnostic tests to rule out organic causes of pain based on 'red flag' sign. Furthermore, to diagnose and classify functional abdominal pain, Rome III criteria were published and updated with multiple discussions of FGIDs. Conventional interventions for RAP include reassurance and general advice, symptom-based pharmacological therapies, and psychological and behavioral treatments. But further research should be conducted to advance our understanding of the multiple factors involved in the pathogenesis of this group of conditions and to provide evidence for its therapeutic benefit.ope

Clinical Practice Guideline for the Diagnosis and Treatment of Pediatric Obesity: Recommendations from the Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology Hepatology and Nutrition

The Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition newly developed the first Korean Guideline on the Diagnosis and Treatment of Obesity in Children and Adolescents to deliver an evidence-based systematic approach to childhood obesity in South Korea. The following areas were systematically reviewed, especially on the basis of all available references published in South Korea and worldwide, and new guidelines were established in each area with the strength of recommendations based on the levels of evidence: 1) definition and diagnosis of overweight and obesity in children and adolescents; 2) principles of treatment of pediatric obesity; 3) behavioral interventions for children and adolescents with obesity, including diet, exercise, lifestyle, and mental health; 4) pharmacotherapy; and 5) bariatric surgery.ope

Micronutrients Are Not Deficient in Children with Nonorganic Failure to Thrive

Purpose: Inadequate calorie intake is one of the most important causes of nonorganic failure to thrive (NOFTT) and is thought to lead to multiple micronutrient deficiencies. However, there have been few studies on NOFTT and micronutrients. The aim of this study was to evaluate the micronutrient status of children with NOFTT. Methods: We conducted a retrospective cohort study in 161 children (106 with NOFTT and 55 health controls) at a single institution. Data on weight for age, height for age, body mass index, and biochemical parameters, indicating the children's nutritional and micronutrient status were reviewed via electronic medical records, and the two groups were compared. Results: Except inorganic phosphate levels, no statistically significant differences were seen in the laboratory findings indicating the children's nutritional and micronutrient status; notably, the inorganic phosphate levels were within the normal range in both groups. We then compared the severe NOFTT (weight for age below the first percentile) and control groups; however, no statistically significant differences were seen for any of the measured parameters. Conclusion: Most children with NOFTT in this study had normal micronutrient levels and other laboratory findings. Therefore, element deficiencies should not be considered a natural consequence of NOFTT or in healthy children. Close monitoring and additional evaluations are needed.ope

A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip

The majority of human gut microbiome is comprised of obligate anaerobic bacteria that exert essential metabolic functions in the human colon. These anaerobic gut bacteria constantly crosstalk with the colonic epithelium in a mucosal anoxic-oxic interface (AOI). However, in vitro recreation of the metabolically mismatched colonic AOI has been technically challenging. Furthermore, stable co-culture of the obligate anaerobic commensal microbiome and epithelial cells in a mechanically dynamic condition is essential for demonstrating the host-gut microbiome crosstalk. Here, we developed an anoxic-oxic interface-on-a-chip (AOI Chip) by leveraging a modified human gut-on-a-chip to demonstrate a controlled oxygen gradient in the lumen-capillary transepithelial interface by flowing anoxic and oxic culture medium at various physiological milieus. Computational simulation and experimental results revealed that the presence of the epithelial cell layer and the flow-dependent conditioning in the lumen microchannel is necessary and sufficient to create the steady-state vertical oxygen gradient in the AOI Chip. We confirmed that the created AOI does not compromise the viability, barrier function, mucin production, and the expression and localization of tight junction proteins in the 3D intestinal epithelial layer. Two obligate anaerobic commensal gut microbiome, Bifidobacterium adolescentis and Eubacterium hallii, that exert metabolic cross-feeding in vivo, were independently co-cultured with epithelial cells in the AOI Chip for up to a week without compromising any cell viability. Our new protocol for creating an AOI in a microfluidic gut-on-a-chip may enable to demonstrate the key physiological interactions of obligate anaerobic gut microbiome with the host cells associated with intestinal metabolism, homeostasis, and immune regulation.ope

Diet-Induced Host-Microbe Interactions: Personalized Diet Strategies for Improving Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease. Environmental sanitization, modern lifestyles, advanced medicines, ethnic origins, host genetics and immune systems, mucosal barrier function, and the gut microbiota have been delineated to explain how they cause mucosal inflammation. However, the pathogenesis of IBD and its therapeutic targets remain elusive. Recent studies have highlighted the importance of the human gut microbiota in health and disease, suggesting that the pathogenesis of IBD is highly associated with imbalances of the gut microbiota or alterations of epithelial barrier function in the gastrointestinal (GI) tract. Moreover, diet-induced alterations of the gut microbiota in the GI tract modulate immune responses and perturb metabolic homeostasis. This review summarizes recent findings on IBD and its association with diet-induced changes in the gut microbiota; furthermore, it discusses how diets can modulate host gut microbes and immune systems, potentiating the impact of personalized diets on therapeutic targets for IBD.ope

Association between Fecal Calprotectin and Mucosal Healing in Pediatric Patients with Crohn's Disease Who Have Achieved Sustained Clinical Remission with Anti-Tumor Necrosis Factor Agents

Background/aims: : Although mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn's disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents. Methods: This multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy. Results: A total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p<0.001). According to the multivariate logistic regression analysis, FC was the only factor associated with MH (odds ratio, 0.62; 95% confidence interval [CI], 0.52 to 0.73; p<0.001). According to the receiver operating characteristic curve analysis, the optimal cutoff value for FC for the association with MH was <140 mg/kg (area under the curve 0.890, 95% CI 0.829 to 0.951, sensitivity 78.2%, specificity 88.6%, p<0.001). Conclusions: FC was associated with MH in pediatric patients with CD who had achieved a sustained CR for at least 6 months with anti-TNF agents. In these patients, FC can be used to stratify patients and guide decisions regarding ileocolonoscopy in the treat-to-target era.ope

Two cases of chronic pancreatitis associated with anomalous pancreaticobiliary ductal union and SPINK1 mutation

Chronic pancreatitis is a progressive inflammatory disease resulting from repeated episodes of acute pancreatitis that impair exocrine function and eventually produce endocrine insufficiency. Some causes of chronic pancreatitis appear to be associated with alterations in the serine-protease inhibitor, Kazal type 1 (SPINK1), cationic trypsinogen (PRSS1), and cystic fibrosis-transmembrane conductance regulator (CFTR) genes, or with structural disorders in the pancreaticobiliary ductal system, such as pancreatic divisum or anomalous pancreaticobiliary ductal union (APBDU). However, it is unusual to observe both genetic alteration and structural anomaly. Here, we report 2 cases with both APBDU and a mutation in the SPINK1 genes, and we discuss the implications of these findings in clinical practice.ope

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.ope

Prevalence and Complications of Glycogen Storage Disease in South Korea: A Nationwide Population-Based Study, 2007-2018

Glycogen storage disease (GSD) is a rare disease that can cause life-threatening problems owing to metabolic errors in storing or using glycogen. The disease course of GSD remains unknown, despite medical technology advances. We determined the prevalence and complications of GSD using data from the National Health Insurance Service database. Data were collected and analyzed for the entire South Korean population with GSD during 2007-2018. GSD was defined as a combination of disease code E74.0 and rare incurable disease insurance code V117, a unique disease code combination for GSD in South Korea. Overall, 23,055 patients had the E74 disease code; 404 had an additional V117 insurance code. Most GSD patients were aged <10 years. Many complications were identified, the most common being hepatomegaly, hyperuricemia, and elevated liver enzyme levels. The most prescribed drug was α-glucosidase, followed by allopurinol. Seventy-two percent of patients were treated in pediatrics. Twenty-five patients underwent liver transplantation, and 14 died after GSD diagnosis. In South Korea, more patients than expected had GSD diagnosis and were managed accordingly. GSD causes many complications and hospitalizations, resulting in high medical expenses. Serious complications can result in liver transplantation and, eventually, death in some cases. Although the patients' condition was identified only by the disease code, this is the first study to present the current situation of GSD patients in South Korea. Because GSD patients can have dangerous medical conditions, they should be managed consistently while minimizing various complications that may occur with optimal metabolic control.ope

Rotavirus Vaccines

Rotavirus infection is the leading cause of severe diarrhea disease in infants and young children worldwide. Rotavirus infects every child at least once by her/his 5th birthday. It has been known that single episode of rotavirus infection can protect or alleviate subsequent illness caused by both homotypic and heterotypic rotaviruses. There are two currently licensed rotavirus vaccines. One is human-bovine rotavirus reassortant pentavalent vaccine (RotaTeqTM), which contains five reassortant rotavirus (expressing protein G1, G2, G3, G4 and P[8]) and was licensed in Korea for use among infants in 2007. Another is live-attenuated human rotavirus vaccine (RotarixTM) derived from 89-12 strain which represents the most common of the human rotavirus VP7(G1) and VP4(P[8]) antigens. RotarixTM was licensed in Korea in 2008. Both live oral rotavirus vaccines are efficacious in preventing severe rotavirus gastroenteritisope