Serum Eosinophilic Cationic Protein as a Useful Noninvasive Marker of Eosinophilic Gastrointestinal Disease in Children.

Purpose: Recently, the prevalence of eosinophilic gastrointestinal disease (EGID) has shown an increasing trend worldwide. As the diagnosis of EGID requires invasive endoscopy with biopsy, noninvasive markers for detecting EGID in suspected patients, particularly children, are urgently needed. Therefore, this study aimed to evaluate the diagnostic accuracy of serum eosinophil cationic protein (ECP) beyond peripheral eosinophil counts in pediatric patients with EGID. Methods: Overall, 156 children diagnosed with EGID were enrolled and 150 children with functional abdominal pain disorder (FAPD) were recruited as controls. All participants underwent endoscopic biopsy in each segment of the gastrointestinal (GI) tract and serum ECP measurement, as well as peripheral eosinophil percent and absolute eosinophil count. Results: Comparing EGID (n=156) with FAPD (n=150) patients, serum ECP levels were significantly higher in pediatric patients with EGID than in those with FAPD (25.8±28.6 µg/L vs. 19.5±21.0 µg/L, p=0.007), while there was no significant difference in peripheral eosinophil percent and absolute eosinophil counts between the two groups. Serum ECP levels were correlated with peripheral eosinophil percent (r=0.593, p<0.001) and the absolute eosinophil count (r=0.660, p<0.001). The optimal cutoff value of serum ECP for pediatric EGID was 10.5 µg/mL, with a sensitivity of 69.9% and a specificity of 43.4% with an area under the receiver operating characteristic curve of 0.562. Conclusion: The combination of serum ECP levels and peripheral eosinophil counts, when employed with appropriated thresholds, could serve as a valuable noninvasive biomarker to distinguish between EGID and FAPD in pediatric patients manifesting GI symptoms.

Role of peripheral and tissue eosinophils and eosinophil cationic protein in pediatric inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). METHODS: Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. RESULTS: A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). CONCLUSION: Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.

Sex-specific differences in ectopic fat and metabolic characteristics of paediatric nonalcoholic fatty liver disease.

BACKGROUND/OBJECTIVES: Sex-specific differences in obesity-related metabolic characteristics of non-alcoholic fatty liver disease (NAFLD) have rarely been explored, particularly in children with biopsy-verified NAFLD. The influence of sex hormones on ectopic fat disposition may cause inter-sex differences in various metabolic factors. This study aimed to assess the sex-based differences in ectopic fat and metabolic characteristics in children with NAFLD. SUBJECT/METHODS: We enrolled 63 children with biopsy-verified NAFLD (48 boys; mean age, 12.9 ± 3.2 years; mean body mass index z-score [BMI-z], 2.49 ± 1.21). Ectopic fat in the liver and pancreas was quantified based on magnetic resonance imaging within 2 days of the liver biopsy. Laboratory tests, body composition, blood pressure, and anthropometric measurements were also assessed. RESULTS: Sex-based differences were neither observed in age, BMI-z, or total body fat percentage nor in the proportions of obesity, abdominal obesity, diabetes, dyslipidaemia, hypertension, or metabolic syndrome. Furthermore, liver enzyme levels, lipid profiles, and pancreatic fat did not differ between the sexes. However, boys had significantly higher fasting insulin (median 133.2 vs. 97.8 pmol/L; p = 0.039), fasting plasma glucose (median 5.30 vs. 4.83 mmol/L; p = 0.013), homeostasis model assessment of insulin resistance (median 5.4 vs. 3.6; p = 0.025), serum uric acid (404.1 ± 101.2 vs. 322.4 ± 87.1 µmol/L; p = 0.009), and liver fat (median 26.3% vs. 16.3%; p = 0.014). CONCLUSIONS: Male-predominant hepatic steatosis and insulin resistance caused by sex-specific ectopic fat accumulation may contribute to higher uric acid levels in boys than in girls with NAFLD.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease.

OBJECTIVE: This study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). METHODS: Pediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. RESULTS: In all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. CONCLUSION: Serological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis.

Background: Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022. Methods: We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term "autoimmune hepatitis" in combination with "incidence," "prevalence," or "trend." Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I2 statistic. The study protocol was registered with PROSPERO, CRD42023430138. Findings: A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45°). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970-1999; 9.95 [4.77-15.13], I2 = 95·58% versus 2015-2022; 27.91 [24.86-30.96], I2 = 99·32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias. Interpretation: AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa. Funding: National Research Foundation of Korea.

The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator of Maintenance Therapy in Pediatric Crohn Disease.

OBJECTIVES: Methotrexate (MTX) has been used as maintenance therapy for Crohn disease (CD) in adults and children. However, there are only a few studies on the MTX's effectiveness in thiopurine-naïve CD adult patients and children. This study aimed to evaluate the MTX's effectiveness and safety as first immunomodulator for maintenance therapy in pediatric CD. METHODS: This retrospective cohort study recruited 64 pediatric CD patients treated with MTX as a first-line immunomodulator. Clinical remission (CR) was assessed at weeks 14, 26, and 52. Mucosal healing (MH) was assessed at weeks 26 and 52. RESULTS: Of 64 patients who received MTX, CR was noted in 60.9% at week 14, 29.7% with MH in 68.0% at week 26, and 27.8% with MH in 81.8% at week 52. When comparing age subtypes according to the Paris classification, the CR rate was higher in A1a than in the other subtypes at week 26 (60.0% in A1a, 26.5% in A1b, 0% in A2; P = 0.038). There were no differences in disease location, behavior, or perianal involvement. Adverse effects were noted in 30 of 64 (46.9%) patients, including 1 patient who stopped MTX before 26 weeks owing to side effects; increased liver enzymes in 25 (39.0%) patients, leukopenia in 5 (7.8%), nausea in 5 (7.8%), skin erosion in 1 (1.6%), and headache in 1 (1.6%). CONCLUSION: MTX as a first-line immunomodulator may be an effective and safe maintenance therapy for pediatric CD patients.

Update on eosinophilic gastrointestinal disease beyond eosinophilic esophagitis in children.

Eosinophilic gastrointestinal disease (EGID) is an emerging condition worldwide in both children and adults, although it is considered rare. EGID has been underestimated owing to its underdiagnosis in the past, and its prevalence has recently increased. The diagnosis of EGID is based on histopathologic findings of endoscopic mucosal biopsy in which the total number of infiltrating eosinophils in each segment of the gastrointestinal tract is determined in patients with chronic or recurrent gastrointestinal symptoms despite a lack of consensus or guidelines on the definition of tissue eosinophilia except for eosinophilic esophagitis. Laboratory findings, including peripheral eosinophilia and increased fecal calprotectin levels, may be additional clues for detection of EGID in practice. Individualized treatment strategies, including adequate dietary modification and pharmacological therapy, may improve clinical outcomes of pediatric patients with EGID.

Transperineal ultrasonography for treatment response evaluation in children with perianal Crohn's disease.

PURPOSE: This study assessed the performance of transperineal ultrasonography (TPUS) in evaluating the treatment response in children with perianal Crohn's disease (PACD) compared with pelvic magnetic resonance imaging (MRI). METHODS: This retrospective study was approved by the Institutional Review Board of our institution, which waived the requirement for informed consent. Twenty-nine patients (19 boys and 10 girls; median age, 14 years [range, 8 to 18 years]) with 56 fistulas were examined. Each fistula's thickness and abscess size were measured using both modalities, and treatment response was classified as positive or negative based on each modality. The concordance of the classifications was compared between TPUS and pelvic MRI. A receiver operating characteristic curve (ROC) was used to evaluate the performance of TPUS. RESULTS: TPUS found 80.4% (45/56) of the fistulas. On MRI, 39 fistulas (70%) were classified as having positive treatment responses, and the remaining 17 as having no response. The agreement of the classifications between TPUS and MRI was moderate (κ=0.486; P<0.001; Spearman ρ=0.573; P<0.001). Based on the ROC analysis with the MRI findings as a reference to distinguish positive from negative treatment responses, TPUS exhibited sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 63.3%, 93.3%, 95.0%, 56.0%, and 73.3%, respectively. CONCLUSION: TPUS can be an appropriate adjuvant imaging modality for pelvic MRI to evaluate the treatment response of PACD in children when initial TPUS detects PACD with a location and imaging features comparable to those visualized on MRI.

Pelvic radiography as a non-invasive screening tool for hiatal hernia in children with cerebral palsy.

The diagnosis of hiatal hernia (HH), causing severe gastroesophageal reflux disease and complications in children with cerebral palsy (CP) is cumbersome because invasive investigations are required for diagnosis. Hip displacement, one of the most common complications in children with CP, can be diagnosed with a simple pelvic radiograph. This study aimed to evaluate the association between the severity of hip displacement and HH and the diagnostic accuracy of Reimers' hip migration percentage (MP) on pelvic radiography in assessing the presence of HH. A total of 52 children with CP (27 boys, 25 girls; mean age, 6.3 years; range, 0.6-17.4 years) who underwent esophagogastroduodenoscopy, upper gastrointestinal series and pelvic radiography between March 2013 and February 2020 were recruited. Demographic and clinical characteristics, as well as endoscopic and radiological findings, were evaluated and statistically analyzed. HH was defined as ≥ 2 cm proximal displacement of the gastroesophageal junction identified in esophagogastroduodenoscopy or upper gastrointestinal series, and MP was calculated by evaluating the pelvic radiograph. Of the 52 children enrolled in this study, HH was diagnosed in 18 children (34.6%). When the patients were classified and analyzed according to the MP result, HH was observed in 10%, 26.7%, and 70.6% in MP <33%, MP 33%-39%, and MP > 40% groups, respectively (P < .001). The optimal MP cutoff of 36.5% distinguished pediatric CP patients with HH from those without HH with a sensitivity of 78%, specificity of 68%, a positive predictive value of 56.0%, and a negative predictive value of 85.2%, respectively. The application of MP and the severity of hip displacement, which can be easily measured by simple radiography, may be useful and reliable in screening for detecting HH in children with CP. Retrospectively registered. This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-2007-627-106).

Inflammatory cloacogenic polyps in children: diagnostic yield of rectal retroflexion during colonoscopy.

BACKGROUND AND AIMS: Inflammatory cloacogenic polyps (ICPs) are inflammatory lesions occurring around the anal transitional zone. These are rare in the pediatric population, and most reported cases are found in adults. Therefore, this study aimed to evaluate the usefulness of rectal retroflexion (RR) during colonoscopy in detecting ICPs in children. METHODS: A total of 1837 colonoscopies were performed in 1278 children between September 2003 and August 2020 at the Seoul National University Bundang Hospital. The laboratory test results and colonoscopic and histopathological findings were retrospectively reviewed. ICP was detected using the RR and was diagnosed based on the histologic findings of the polyp. RESULTS: A total of 69 patients were diagnosed with juvenile polyps (n = 62) or ICP (n = 7), with the latter being detected through RR. All children with ICP were diagnosed from 2013 onwards when RR during colonoscopy came to be routinely performed in our medical center. The patients with ICP were older at diagnosis and more associated with a family history of colorectal polyps than JP. Stool occult blood and the polyps' endoscopic characteristics, such as number, location, volume, and shape, significantly varied between the two groups. Additionally, there was a statistically significant difference in the polypectomy method. During the long-term follow-up, there was no recurrence of ICP. CONCLUSIONS: Due to their location at the anorectal junction, ICPs may be overlooked during colonoscopy, leading to misdiagnosis. Therefore, a retroflexion view during colonoscopy may help detect ICPs in pediatric patients, especially those presenting with hematochezia.

Differentiation of food protein-induced enterocolitis syndrome misleading to necrotizing enterocolitis.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-immunoglobulin E-mediated food allergy with necrotizing enterocolitis (NEC)-like symptoms which requires differential diagnosis as treatments differ. OBJECTIVE: To evaluate the clinical, laboratory, and radiologic findings that differentiate FPIES from NEC in preterm and term infants. METHODS: Clinical features, comorbidities, and laboratory and radiologic findings of neonates with presumed NEC were reviewed retrospectively and compared between FPIES and NEC in preterm and term infants who were admitted to the neonatal intensive care unit at Seoul National University Bundang Hospital between May 2003 and February 2020. RESULTS: A total of 10 of 150 (6.7%) preterm and 17 of 38 (44.7%) term infants with presumed NEC were confirmed to have FPIES; the remainder had NEC by modified Bell's criteria. Demographics and comorbidities were similar between these groups. Symptoms such as hematochezia, shock, leukocytosis, peripheral eosinophilia, and feeding of extensively hydrolyzed milk formula or elemental formula after discharge were significantly different between the 2 groups in term infants (P <.05), but not in preterm infants. On abdominal ultrasonography, pneumatosis intestinalis was more common among preterm FPIES (44.4%) than NEC cases (21.6%) (P =.04). Among the preterm infants, 4 FPIES (40%) and 25 NEC (17.9%) cases required surgery (P =.10). CONCLUSION: Differentiating FPIES in neonates suspected of having NEC is important as dietary elimination of the triggering milk protein can be recommended instead of prolonged fasting and antibiotic treatment, which are indicated for NEC, in both term and preterm infants.

Factors associated with hiatal hernia in neurologically impaired children.

BACKGROUND: Hiatal hernia is clinically important because it impairs the protective mechanism that prevents gastroesophageal reflux-induced injury. Diagnosing hiatal hernia is more important in neurologically impaired children because hiatal hernia-induced gastroesophageal reflux often causes severe complications such as aspiration pneumonia or malnutrition. We aimed to evaluate the patient characteristics and early predictors of hiatal hernia in neurologically impaired children. METHODS: We retrospectively investigated 97 neurologically impaired children who underwent esophagogastroduodenoscopy and upper gastrointestinal series between March 2004 and June 2019. Demographic and clinical characteristics, as well as endoscopic and radiological findings, were statistically analyzed. RESULTS: Of the 97 children recruited, 22 (22.7%) had hiatal hernia. When comparing the non-hiatal hernia group with the hiatal hernia group, neurological disease longer than 6 months (odds ratio 10.9, 95% confidence interval 1.2-96.5), wasting (odds ratio 4.6, 95% confidence interval 1.3-16.3), enteral tube feeding (odds ratio 9.2, 95% confidence interval 1.6-53.0), and history of aspiration pneumonia (odds ratio 6.5, 95% confidence interval 1.2-34.5) were identified as early predictors of hiatal hernia. CONCLUSIONS: Timely identification of predictors of developing hiatal hernia in neurologically impaired children is important for early diagnostic confirmation to initiate optimal medical or surgical treatment of hiatal hernia to avoid serious complications such as aspiration pneumonia and malnutrition.

Ectopic pancreatic fat as a risk factor for hypertension in children and adolescents with nonalcoholic fatty liver disease.

Although nonalcoholic fatty liver disease (NAFLD) is known to be a risk factor for cardiovascular diseases, few studies have reported an association between ectopic fat deposition and metabolic complications, including hypertension, in children with NAFLD. The present study evaluated the risk factors for hypertension in children with NAFLD from the aspect of ectopic fat. This cross-sectional retrospective study investigated 65 children with NAFLD (49 boys, mean age 13.0 ± 3.2 years, mean body mass index z-score [BMI-z] 2.5 ± 1.2), who underwent liver biopsy and magnetic resonance imaging-based fat fraction measurement for ectopic hepatic and pancreatic fats, as well as anthropometry, blood pressure, laboratory tests, and body composition analysis. A logistic regression model was used to identify the risk factors for hypertension. Through a simple logistic regression analysis, age (OR 1.392), BMI-z (OR 3.971), waist circumference-to-height ratio (OR 1.136), fat-free mass index (OR 1.444), γ-glutamyl transferase (OR 1.021), quantitative insulin sensitivity check index (OR 0.743), dyslipidemia (OR 5.357), and pancreatic fat fraction (PFF) (OR 1.205) were associated with hypertension. The optimal cut-off of PFF to divide children with NAFLD into two groups with and without hypertension was 4.39% (area under the curve 0.754, p = .001, sensitivity 82.4%, specificity 73.9%). Multiple logistic regression analysis in the fully adjusted model revealed both BMI-z (OR 4.912, 95% CI, 1.463-16.497) and PFF (OR 1.279, 95% CI, 1.007-1.624) were independent risk factors for hypertension. In conclusions, in addition to BMI-z, ectopic pancreatic fat is an important risk factor for hypertension in children with NAFLD.

Relationship Between Histological Features of Non-alcoholic Fatty Liver Disease and Ectopic Fat on Magnetic Resonance Imaging in Children and Adolescents.

Objectives: To investigate the association between ectopic fat content in the liver and pancreas, obesity-related metabolic components, and histological findings of non-alcoholic fatty liver disease (NAFLD) in children. Methods: This cross-sectional study investigated 63 children with biopsy-proven NAFLD who underwent magnetic resonance imaging (MRI), anthropometry, laboratory tests, and body composition analysis. Clinical and metabolic parameters, MRI-measured hepatic fat fraction (HFF) and pancreatic fat fraction (PFF), and histological findings were analyzed. Results: In a total of 63 children (48 boys, median age 12.6 years, median body mass index z-score 2.54), HFF was associated with histological steatosis [10.4, 23.7, and 31.1% in each steatosis grade, P < 0.001; Spearman's rho coefficient (rs) = 0.676; P < 0.001] and NAFLD activity score (rs = 0.470, P < 0.001), but not with lobular inflammation, hepatocyte ballooning, and hepatic fibrosis. PFF was not associated with any histological features of the liver. Waist circumference-to-height ratio and body fat percentage were associated with the steatosis grade (P = 0.006 and P = 0.004, respectively). Alanine aminotransferase was not associated with steatosis but was associated with lobular inflammation (P = 0.008). Lobular inflammation was also associated with high total cholesterol and low-density lipoprotein cholesterol and metabolic syndrome (P = 0.015, P = 0.036, and P = 0.038, respectively). Conclusions: Hepatic steatosis on MRI was only associated with the histological steatosis grade, while elevated serum levels of liver enzymes and lipids were related to the severity of lobular inflammation. Therefore, MRI should be interpreted in conjunction with the anthropometric and laboratory findings in pediatric patients.

Association between ectopic pancreatic and hepatic fat and metabolic risk factors in children with non-alcoholic fatty liver disease.

BACKGROUND: Few studies have reported an association between ectopic pancreatic and hepatic fat and metabolic factors in children with non-alcoholic fatty liver disease (NAFLD). OBJECTIVES: We investigated this association and also the factors associated with pancreatic and hepatic fat deposition in children with NAFLD. METHODS: This cross-sectional study investigated 65 children with NAFLD (49 boys, 13.0 ± 3.2 years, mean body mass index z-score 2.5 ± 1.2), who underwent liver biopsy and magnetic resonance imaging-based proton density fat fraction, as well as anthropometry, laboratory tests, body composition analysis, and hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) measurements. RESULTS: HFF and PFF were 4.2%-49.9% (median 24.3) and 0.4%-26.9% (median 3.8), respectively. HFF was not significantly correlated with PFF. HFF was correlated with total body fat% (r = 0.329, p = 0.010) and γ-glutamyl transpeptidase (GGT) (r = 0.260, p = 0.040), while PFF was correlated with the diastolic blood pressure (r = 0.253, p = 0.045), GGT (r = 0.335, p = 0.007) and fasting plasma glucose (r = 0.417, p = 0.001). Multiple linear regression analysis showed that HFF was significantly associated with sex, age, body fat% and GGT, whereas PFF was associated with hypertension and fasting plasma glucose levels but not insulin resistance. CONCLUSIONS: HFF was associated with sex, age and body fat in children with NAFLD, while PFF was associated with hypertension and increased fasting plasma glucose, which suggests that the pathophysiology of ectopic fat accumulation varies across organs in children with NAFLD.

Nationwide "Pediatric Nutrition Day" survey on the nutritional status of hospitalized children in South Korea.

BACKGROUND/OBJECTIVES: To evaluate the nutritional status and prevalence of malnutrition in hospitalized children at admission and during hospitalization in South Korea. SUBJECTS/METHODS: This first cross-sectional nationwide "Pediatric Nutrition Day (pNday)" survey was conducted among 872 hospitalized children (504 boys, 368 girls; 686 medical, 186 surgical) from 23 hospitals in South Korea. Malnutrition risk was screened using the Pediatric Yorkhill Malnutrition Score (PYMS) and the Screening Tool Risk on Nutritional status and Growth. Nutritional status was assessed by z-scores of weight-for-age for underweight, weight-for-height for wasting, and height-for-age for stunting as well as laboratory tests. RESULTS: At admission, of the 872 hospitalized children, 17.2% were underweight, and the prevalence of wasting and stunting was 20.2% and 17.3%, respectively. During hospitalization till pNday, 10.8% and 19.6% experienced weight loss and decreased oral intake, respectively. During the aforementioned period, fasting was more prevalent in surgical patients (7.5%) than in medical patients (1.6%) (P < 0.001). According to the PYMS, 34.3% and 30% of the children at admission and on pNday, respectively, had a high-risk of malnutrition, requiring consultation with the nutritional support team (NST). However, only 4% were actually referred to the NST during hospitalization. CONCLUSIONS: Malnutrition was prevalent at admission and during hospitalization in pediatric patients, with many children experiencing weight loss and poor oral intake. To improve the nutritional status of hospitalized children, it is important to screen and identify all children at risk of malnutrition and refer malnourished patients to the multidisciplinary NST for proper nutritional interventions.

Usefulness of Endoscopic Hill Grade in Evaluating Children Suspected of Having Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: This study aim to evaluate the relationship between the Hill grade confirmed by esophagogastroduodenoscopy (EGD) and the degree of gastroesophageal reflux (GER) by 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH) in children suspected of having gastroesophageal reflux disease (GERD). METHODS: A retrospective review of 105 children and adolescents who underwent EGD and MII-pH for the evaluation of GERD from March 2013 to July 2019 was performed. Clinical features and results of EGD and 24-hour MII-pH were collected and statistically analyzed. RESULTS: Hill grades 1, 2, 3, and 4 were identified using EGD in 56 (53.3%), 22 (22.0%), 16 (15.2%), and 11 (10.5%) patients, respectively. As the Hill grade increased, the proportion of neurological diseases (P < 0.001) and endoscopic erosive esophagitis (P < 0.001) increased significantly. The acid exposure index, bolus exposure index, number of reflux episodes, and number of GER reaching proximal extent on MII-pH increased significantly as the endoscopic Hill grade increased (all P < 0.001). Linear regression analysis revealed an increase in the Hill grade by 1 increased the acid exposure index by 2.0%, bolus exposure index by 0.7%, number of reflux episodes by 18.9 episodes, and the number of GER reaching the proximal esophagus increased by 10.5 episodes on average (all P < 0.001). CONCLUSIONS: Hill grade on EGD was associated with GER in children. Estimating the degree of GER by applying Hill grade in the retroflexion view may be useful in practice when evaluating children suspected with GERD.

Particulate matter causes skin barrier dysfunction.

The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis/trans-UCA, were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM2.5, to Seoul, an area with high PM2.5 count. Experimentally, PM2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM2.5. We demonstrate that this process was mediated by PM2.5-induced TNF-α and was aryl hydrocarbon receptor dependent. PM2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss, and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM2.5-induced TNF-α caused FLG deficiency in the skin and subsequently induced skin barrier dysfunction. Compromised skin barrier due to PM2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as atopic dermatitis.

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Combination therapy with immunomodulators (IMMs) was proposed as a strategy to prevent the development of loss of response (LOR) to anti-tumor necrosis factor (TNF) for patients with inflammatory bowel disease (IBD). However, the effect is unclear in patients already exposed to IMMs. The aim of this study was to evaluate whether combination therapy with IMMs is superior to monotherapy for prevention of LOR to anti-TNF. METHODS: This was a retrospective study of patients in Seoul National University Bundang Hospital with IBD between January 2009 and October 2018. LOR was defined as clinical deterioration after maintenance of anti-TNF for at least 6 months. We investigated the difference in incidence of LOR to anti-TNF between the monotherapy and combination groups. We additionally assessed factors affecting LOR development to anti-TNF. RESULTS: A total of 116 patients with IBD were included in this study (monotherapy 61 patients; combination 55 patients). Overall, LOR to anti-TNF occurred in 31 patients during the follow-up period. The combination of an anti-TNF agent and IMM showed no significant difference in the incidence of LOR compared to anti-TNF agent monotherapy (hazard ratio [HR], 1.64; 95% confidence interval [CI], 0.786 to 3.148; p = 0.182). Female sex was significantly associated with the development of LOR to anti-TNF (HR, 3.032; 95% CI, 1.467 to 6.268; p = 0.003). CONCLUSION: Anti-TNF and IMM combination therapy did not prove efficacious in preventing the development of LOR in IBD patients. Female sex was associated with the development of LOR to anti-TNF; further studies are required to confirm these results.

Eosinophilic gastroenteritis as a cause of non-Helicobacter pylori, non-gastrotoxic drug ulcers in children.

BACKGROUND: While Helicobacter pylori (H. pylori) ulcers has declined recently, H. pylori-negative and/or gastrotoxic drug-negative peptic ulcers (HNGN-PU) has increased. This study aimed to analyze the etiology of peptic ulcers in children and the differences in clinical, laboratory, endoscopic, and histopathologic findings of peptic ulcers according to etiology, including eosinophilic gastroenteritis (EoGE). METHODS: In total, 255 children (157 boys and 98 girls) with peptic ulcers were recruited. The subjects were categorized into 5 groups according to the etiology of the ulcer: 1) H. pylori infection (n = 51); 2) gastrotoxic drugs (n = 18); 3) idiopathic (n = 144); 4) systemic disease (n = 23); 5) EoGE (n = 19). Clinical data were reviewed and analyzed retrospectively. RESULTS: Age at diagnosis, ulcer recurrence, atopic dermatitis history, white blood cell count, blood eosinophil count, platelet count, serum albumin level, iron level, erythrocyte sedimentation rate, and C-reactive protein level differed significantly among the 5 groups (all p < 0.05). Regarding endoscopic findings, multiple ulcers and gastric mucosal nodularity differed among the 5 groups (all p < 0.05). When comparing the EoGE ulcer group with the others, EoGE group revealed older ages (p = 0.022), higher rates of ulcer recurrence (p = 0.018), atopic dermatitis history (p = 0.001), and both blood and tissue eosinophilia (both p = 0.001). CONCLUSIONS: EoGE ulcers constituted 10.2% of HNGN-PU in pediatric patients. In children with HNGN-PU, peripheral eosinophilia, ulcer recurrence, and atopic dermatitis history might imply EoGE, necessitating thorough investigation of tissue eosinophils during endoscopic biopsy. TRIAL REGISTRATION: A total of 255 children was retrospectively registered between between July 2003 and April 2017.