Contrast-Enhanced Ultrasonography for the Evaluation of Crohn’s Disease in Pediatric Patients

Background@#Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn’s disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn’s disease activity in children with endoscopy as the reference standard.Method: In this prospective study, 30 pediatric patients with Crohn’s disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021.The simple endoscopic score for Crohn’s disease, pediatric Crohn’s disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings. @*Results@#CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn’s disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn’s disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015). @*Conclusion@#CEUS can be a safe and specific diagnostic modality for Crohn’s disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn’s disease.

Significance of Follow-Up Ultrasonography 24 Hours Post-Reduction in Detecting Intussusception Recurrence / 대한소아소화기영양학회지

Purpose@#The objective of this study was to identify the significance of 24-hour postreduction ultrasonography (US) in pediatric patients with intussusception. @*Methods@#A total of 229 patients with intussusception who were treated with saline reduction at Severance Children’s Hospital between January 2014 and September 2020 were retrospectively reviewed. The 229 patients with successful saline reduction were divided into two groups: a recurrence at 24 hours group (R, n=41) and a non-recurrence group (NR, n=188). The full patient sample was divided into two groups: follow-up US (FU) or no followup US (NFU); the recurrence group was divided into follow-up (R-FU) and non-follow-up (R-NFU) subgroups, and stratified analyses were performed. @*Results@#There were no significant differences in age, sex, laboratory findings, symptoms, and sonographic findings between the NR and R groups. In the R group, 24 patients underwent follow-up US, and 17 patients did not. Specific sonographic findings were statistically significant in the R-FU group compared to the R-NFU group (p=0.002). The R-FU group had fewer admissions (p=0.012) and longer mean hospitalization times (p<0.001) than the R-NFU group. The NFU group had a 12.2% recurrence rate, while the R-FU group recurrence rate was 25.8% (p=0.0099), suggesting that the omission of some recurrent events and follow-up US was a significant variable in the recurrence of intussusception. The median time to recurrence was 21 hours which supports the 24-hour follow-up protocol. @*Conclusion@#Twenty-four-hour follow-up US was shown to be valuable for detecting early recurrence of intussusception.

Effectiveness of High-Volume Therapeutic Plasma Exchange for Acute and Acute-on-Chronic Liver Failure in Korean Pediatric Patients / 대한소아소화기영양학회지

Purpose@#Liver transplantation (LT) is the only curative treatment for acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). In high-volume therapeutic plasma exchange (HV-TPE), extracorporeal liver support filters accumulate toxins and improve the coagulation factor by replacing them. In this study, we aimed to evaluate the effectiveness of HV-TPE in pediatric patients with ALF and ACLF. @*Methods@#We reviewed the records of children waiting for LT at Severance Hospital who underwent HV-TPE between 2017 and 2021. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin (TB and DB), gamma-glutamyl transferase (GGT), ammonia, and coagulation parameter-international normalized ratio (INR) were all measured before and after HV-TPE to analyze the liver function. The statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Co., Armonk, NY, USA). @*Results@#Nine patients underwent HV-TPE with standard medical therapy while waiting for LT. One had neonatal hemochromatosis, four had biliary atresia, and the other four had ALF of unknown etiology. Significant decreases in AST, ALT, TB, DB, GGT, and INR were noted after performing HV-TPE (930.38–331.75 IU/L, 282.62–63.00 IU/L, 11.75–5.59 mg/dL, 8.10– 3.66 mg/dL, 205.62–51.75 IU/L, and 3.57–1.50, respectively, p<0.05). All patients underwent LT, and two expired due to acute complications. @*Conclusion@#HV-TPE could remove accumulated toxins and improve coagulation. Therefore, we conclude that HV-TPE can be regarded as a representative bridging therapy before LT.

Initial Abdominal CT and Laboratory Findings Prior to Diagnosis of Crohn’s Disease in Children

Purpose@#To identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn’s disease (CD) in children. @*Materials and Methods@#In this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC). @*Results@#In total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/ dL), lower albumin (≤4 g/dL), and higher platelet (>320×103 /μL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778–2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891–0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD. @*Conclusion@#Multisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.

The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model

Background@#Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy. @*Methods@#Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/ EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology. @*Results@#Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the β-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier. @*Conclusion@#EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.

Micronutrients Are Not Deficient in Children with Nonorganic Failure to Thrive / 대한소아소화기영양학회지

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.

Therapeutic Efficacy of Exclusive Enteral Nutrition with Specific Polymeric Diet in Pediatric Crohn's Disease / 대한소아소화기영양학회지

PURPOSE: The efficacy of exclusive enteral nutrition (EEN) with a polymeric diet has not been confirmed in Korean pediatric patients with Crohn's disease (CD). This study aimed to compare the effectiveness of EEN with a specific polymeric diet (Encover®) and corticosteroids (CSs) for the induction of remission in Korean pediatric CD patients. METHODS: We retrospectively compared data from 51 pediatric CD patients who underwent induction therapy with EEN (n=19) or CSs (n=32) at Severance Children's Hospital or Incheon St. Mary's Hospital in Korea. The primary endpoint of this study was the rate of clinical remission, defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score < 10, after 8 weeks of induction treatment. Clinical, laboratory, and growth data at post-induction as well as their changes from baseline were also compared between groups. RESULTS: After 8 weeks of induction therapy, clinical remission rates were 78.9% (15/19) and 65.6% (21/32) in the EEN and CS groups, respectively (p=0.313). No significant differences in PCDAI scores, laboratory variables, and growth parameters were noted between the two groups at post-induction. However, significant changes in albumin levels at post-induction were observed in the EEN group compared to the CS group (p=0.038). CONCLUSION: Our results suggest that the effectiveness of EEN with a polymeric diet and CSs for induction therapy did not differ in Korean pediatric CD patients. EEN with a polymeric diet is a good first-line treatment option for the induction of remission in these patients.

Association of Vitamin D with Inflammatory Bowel Disease Activity in Pediatric Patients

BACKGROUND: It has been known that vitamin D level (serum 25[OH]D) has correlation with inflammatory bowel disease (IBD). The purpose of this study is to investigate changes of serum 25[OH]D in pediatric IBD patients according to the disease activity. METHODS: A total of 96 children and adolescent with IBD were enrolled in this retrospective study. Serologic inflammatory markers and clinical disease activity scores of the patients were collected, and their correlations with serum 25[OH]D were analyzed. Seasonal variations of serum 25[OH]D were also investigated both in active disease state and remission state. RESULTS: Of the 96 patients, 41 (43%) were women and patients with a vitamin D deficiency (< 20 ng/mL) at diagnosis were 77 (80.2%). There was no significant difference between Crohn's disease and ulcerative colitis for serum 25[OH]D. Serum 25[OH]D was higher in remission group than in active disease group (12.4 [8.8–29] ng/mL vs. 17.9 [12.3–34.4] ng/mL; P < 0.001) and the difference was more significant than other micronutrients. There was no significant difference in serum 25[OH]D concentration between patients with ileal involvement and patients without ileal involvement. There were seasonal variations in the active phase, but there was no significant difference by season in the remission phase. CONCLUSION: Serum 25[OH]D is inversely correlated with disease activity in IBD. Monitoring and supplementation is required especially for active disease status and in winter and spring season.

Correlation between the occurrence of acute gastroenteritis in children and regional temperature at a tertiary hospital emergency department in Korea

PURPOSE: Several studies have investigated the association between acute gastroenteritis (AGE) and regional temperatures. We aimed to investigate the correlation between the occurrence of AGE and regional temperature in Korean children. METHODS: We reviewed the clinical characteristics of children aged 18 years or younger with AGE, defined according to the International Statistical Classification of Diseases, 10th Revision codes, who visited a Korean tertiary hospital emergency department (ED) between 2006 and 2016, and compared the children who were discharged from the ED and those who were hospitalized. Data on temperature in Seoul, Korea during the period were obtained from the Korea Meteorological Administration. Subsequently, we assessed correlations between the monthly mean numbers of the children with AGE and monthly mean temperature using Pearson's correlation analysis.

Estimated Prevalence of Adolescents with Nonalcoholic Fatty Liver Disease in Korea

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become prevalent worldwide in the last decade. However, the recent prevalence of NAFLD in adolescents has not yet been investigated in Korea. METHODS: Data were obtained from 1,416 participants aged 10–18 years from the Korea National Health and Nutrition Examination Survey conducted in 2010 and 2015. Systolic blood pressure (SBP), diastolic blood pressure (DBP), height, weight, waist circumference (WC), body mass index (BMI), fasting glucose, total cholesterol, high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT) level, waist-to-height ratio (WHtR), and pediatric NAFLD fibrosis index (PNFI) were analyzed. RESULTS: SBP, weight, WC, BMI, WHtR, and total cholesterol level were significantly higher in 2015 than in 2010. Prevalence of NAFLD (BMI ≥ 85th percentile plus ALT > 30 U/L for boys and ALT > 19 U/L for girls) were 4.7% in 2010 and 5.9% in 2015 (P = 0.360). Using various cutoffs for the ALT level (> 40, > 30, > 25.8 U/L for boys and >22.1 U/L for girls) NAFLD prevalence rates were 3.0%, 4.1%, and 5.5% in 2010; 2.9%, 5.0%, and 7.1% in 2015, respectively (P = 0.899, 0.469, and 0.289). Boys had a higher SBP, DBP, height, weight, WC, BMI, WHtR, fasting glucose, total cholesterol, ALT, and lower HDL level than girls. The probability of liver fibrosis using the PNFI varies between 21.3% and 24.5% among NAFLD participants (P < 0.001). CONCLUSION: The Korean society needs to quickly control the increasing prevalence of NAFLD in adolescents and reduce its complications.

Alpers-Huttenlocher Syndrome First Presented with Hepatic Failure: Can Liver Transplantation Be Considered as Treatment Option? / 대한소아소화기영양학회지

Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure. The hepatic manifestation usually occurs late in the disease's course, but in some references, hepatitis was reportedly the first manifestation. Liver transplantation was considered contraindicated in Alpers-Huttenlocher syndrome due to its poor prognosis. We acknowledged a patient with the first manifestation of the disease being hepatic failure who eventually underwent liver transplantation, and whose neurological outcome improved after cocktail therapy.

Alpers-Huttenlocher Syndrome First Presented with Hepatic Failure: Can Liver Transplantation Be Considered as Treatment Option? / 대한소아소화기영양학회지

Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure. The hepatic manifestation usually occurs late in the disease's course, but in some references, hepatitis was reportedly the first manifestation. Liver transplantation was considered contraindicated in Alpers-Huttenlocher syndrome due to its poor prognosis. We acknowledged a patient with the first manifestation of the disease being hepatic failure who eventually underwent liver transplantation, and whose neurological outcome improved after cocktail therapy.