A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Geranylgeranyl pyrophosphate amplifies Treg differentiation via increased IL-2 expression to ameliorate DSS-induced colitis.

Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin-induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4+ T cell, which can be observed on the complete deletion of HMG-CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T-cell homeostasis. Following dextran sulfate sodium (DSS)-induced colitis, simvastatin increased the severity of disease, while cotreatment with GGPP, but not with cholesterol, reversed the disease magnitude. GGPP ameliorated DSS-induced colitis by increasing Treg cells. GGPP amplified Treg differentiation through increased IL-2/STAT 5 signaling. GGPP prenylated Ras protein, a prerequisite for extracellular signal-regulated kinase (ERK) pathway activation, leading to increased IL-2 production. Higher simvastatin dose increased the severity of colitis. GGPP ameliorated simvastatin-increased colitis by increasing Treg cells. Treg cells, which have the capacity to suppress inflammatory T cells and were generated through IL-2/STAT5 signaling, increased IL-2 production through prenylation and activation of the Ras/ERK pathway.

Comparison of Ustekinumab Trough Concentrations Measured by 2 ELISA Kits and Evaluation of Clinical Response in Crohn's Disease.

BACKGROUND: Ustekinumab is a recently introduced biological agent for the treatment of Crohn's disease. The clinical use of the trough concentration of ustekinumab is not as standardized as that of infliximab. The authors aimed to introduce a measurement method and the results of trough concentrations of ustekinumab in clinical applications. METHODS: Thirty-two blood samples from 10 young adult patients diagnosed with Crohn's disease were analyzed. During the maintenance treatment, injection intervals were shortened from 12 weeks to 8 weeks in 4 patients who exhibited a loss of response. Ustekinumab trough concentrations were measured using 2 commercial ELISA kits, kit A and kit B. RESULTS: The median trough concentrations measured with kits A and B were 0.26 and 0.38 mcg/mL, respectively. In the case of kit A, low trough concentrations were undetected on many occasions and measured as zero, whereas kit B displayed their relative values even at low concentrations. Poor clinical parameters, elevated erythrocyte sedimentation rate, C-reactive protein, and calprotectin levels were significantly correlated with lower trough concentrations ( P < 0.05). The area under the receiver operating characteristics curve of kit B (0.921) was greater than that of kit A (0.744). The optimal cutoff values for prediction clinical responses were 0.17 and 0.41 mcg/mL for kit A and kit B, respectively. CONCLUSIONS: The trough concentration of ustekinumab measured by the 2 ELISA kits correlated with laboratory results that indicated the activity of Crohn's disease. Furthermore, kit B detected even minute changes in trough concentrations.

Nationwide Survey for Pediatric Gastrostomy Tube Placement in Korea.

BACKGROUND: Various methods have been implemented for pediatric gastrostomy tube placement. We aimed to investigate the performance status of pediatric gastrostomy in South Korea and to present indications and appropriate methods for domestic situations. METHODS: A survey was conducted among pediatric endoscopists who performed upper gastrointestinal endoscopy in Korea. The questionnaire consisted of 16 questions on gastrostomy performance status. RESULTS: Among the 48 institutions where the survey was applied, 36 (75%) responded. Of the 36 institutions, gastrostomy was performed in 31 (86.1%). The departments in which gastrostomy was performed were pediatrics at 26 institutions (81.3%), surgery at 24 institutions (75.0%), internal medicine at 9 institutions (28.1%), and radiology at 7 institutions (21.9%). There were 18 institutions (66.7%) using the pull method for percutaneous endoscopic gastrostomy (PEG) and nine institutions (33.3%) using the push method. When performing gastrostomies, fundoplication procedures were performed in 19 institutions (61.3%), if deemed necessary. However, 12 institutions (38.7%) answered that gastrostomy was always implemented alone. Complications after gastrostomy included buried bumper syndrome, wound infection, leakage, tube migration, and incorrect opening site in the stomach, but the number of cases with complications was very small. CONCLUSION: In Korea, a pediatric gastrostomy is implemented in various ways depending on the institution. Clinicians are concerned about choosing the most effective methods with fewer complications after the procedure. In our study, we reported only a few complications. Korea has good accessibility for pediatric gastrointestinal endoscopy, and this survey showed that it is a safe procedure that can be considered initially in pediatric gastrostomy. This study is expected to help to create optimal pediatric PEG guidelines in Korea.

Vedolizumab Is Safe and Efficacious for the Treatment of Pediatric-Onset Inflammatory Bowel Disease Patients Who Fail a Primary Biologic Agent.

BACKGROUND: Vedolizumab (VDZ) is currently licensed for use in adults for the treatment of inflammatory bowel disease (IBD). We aimed to investigate the clinical course of pediatric-onset IBD following treatment with VDZ as more than a secondary biologic agent. We also evaluated factors associated with secondary loss of response (LOR) and durability of VDZ treatment. METHODS: Pediatric-onset IBD patients diagnosed at an age younger than 18 years who had received VDZ as more than a secondary biologic agent were included in this retrospective observational study conducted at the Department of Pediatrics of two centers in Korea. Comparative analysis was conducted between groups divided according to the development of secondary LOR during VDZ treatment. RESULTS: A total of 24 patients comprising 10 patients with Crohn's disease and 14 with ulcerative colitis were included. Of these, 19 were male and 5 were female. The mean age at diagnosis was 14.6 ± 2.5 years. The mean age at initiation of VDZ was 20.5 ± 2.8 years. Nine patients (37.5%) had received two or more biologic agents before starting VDZ. During a median of 0.9 years follow-up from VDZ initiation, 9 patients (37.5%) experienced LOR requiring interval shortening and 4 patients (16.7%) were changed to a different biologic agent. According to multivariate Cox proportional hazard regression analysis, administration of two or more biologic agents before VDZ treatment was the only factor positively associated with LOR (hazard ratio [HR], 5.6; 95% confidence interval [CI], 1.026-30.56; P = 0.047), while LOR was the only factor negatively associated with VDZ durability (HR, 0.003; 95% CI, 0.00-0.08; P = 0.010). No adverse events were observed during treatment with VDZ. CONCLUSION: VDZ is safe and efficacious for the treatment of pediatric-onset IBD patients failing a primary biologic agent. The durability of VDZ may be enhanced by introducing VDZ earlier in the disease course. Further prospective studies in children are required in the future to validate these findings.

Potential Utility of Fecal Calprotectin in Discriminating Colorectal Polyps From Other Major Etiologies in Children Presenting With Isolated Hematochezia.

BACKGROUND: Colorectal polyps are the most common cause of isolated hematochezia in children, which requires a colonoscopy for diagnosis. We aimed to investigate the potential utility of fecal calprotectin (FC) in assessing colorectal polyps detected by colonoscopy among children presenting with isolated hematochezia. METHODS: Pediatric patients of the age of < 18 years who had undergone both colonoscopy and FC tests for isolated hematochezia from June 2016 to May 2020 were included in the present multicenter, retrospective, cross-sectional study. Comparative analysis was conducted between major causes of isolated hematochezia and FC cut-offs for discriminating colorectal polyps were explored. RESULTS: A total 127 patients were included. Thirty-five patients (27.6%) had colorectal polyps, followed by anal fissure (14.2%), ulcerative colitis (UC; 12.6%), and others. A significant difference in FC levels was observed between patients with colorectal polyps (median, 278.7 mg/kg), anal fissures (median, 42.2 mg/kg), and UC (median, 981 mg/kg) (P < 0.001). According to receiver operating characteristic curve analysis, among patients diagnosed with colorectal polyp or anal fissure, the most accurate FC cut-off for discriminating colorectal polyps from anal fissures on colonoscopy was 225 mg/kg (sensitivity, 59.4%; specificity, 94.4%; positive predictive value [PPV], 95.0%; negative predictive value [NPV], 56.7%; area under the curve [AUC], 0.8; 95% confidence interval [CI], 0.678-0.923; P < 0.001), while among patients diagnosed with colorectal polyp or UC, the most accurate FC cut-off for discriminating colorectal polyps from UC on colonoscopy was 879 mg/kg (sensitivity, 81.2%; specificity, 56.2%; PPV, 78.8%; NPV, 60.0%; AUC, 0.687; 95% CI, 0.521-0.852; P < 0.001). CONCLUSION: FC may assist in assessing the cause of lower gastrointestinal tract bleeding in children who present with isolated hematochezia.

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era.

BACKGROUND: Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19). METHODS: This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021. RESULTS: A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn's disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn's disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020). CONCLUSION: Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.

AMPK Amplifies IL2-STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice.

AMP-activated protein kinase (AMPK), an important regulator of the aging process, is expressed in various immune cells. However, its role in regulatory T cell (Treg) stability during aging is poorly understood. Here, we addressed the role of AMPK in Treg function and stability during aging by generating Treg-specific AMPKα1 knockout mice. In this study, we found that AMPKα1-deficient Tregs failed to control inflammation as effectively as normal Tregs did during aging. AMPK knockout from Tregs reduces STAT5 phosphorylation in response to interleukin (IL)-2 stimulation, thereby destabilizing Tregs by decreasing CD25 expression. Thus, our study addressed the role of AMPK in Tregs in sensing IL-2 signaling to amplify STAT5 phosphorylation, which, in turn, supports Treg stability by maintaining CD25 expression and controlling inflamm-aging.

The Changes in Trends of Lower Gastrointestinal Endoscopy Conducted in Children and Adolescents after the COVID-19 Outbreak in Korea.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected medical practice in diverse ways. We aimed to investigate the change in trends of lower gastrointestinal (LGI) endoscopy conducted in children and adolescents after the COVID-19 outbreak in Korea. Material and Methods: This was a multicenter, retrospective study conducted in Korea. We included children and adolescents aged <19 years who had undergone their first LGI endoscopy between 2016 and 2020. We compared clinicodemographic and endoscopic factors between groups divided according to the pre- and postCOVID-19 era in Korea. Results: We included 1307 patients in this study. Colonoscopies, instead of sigmoidoscopies, were conducted in most patients in the postCOVID-19 era compared to those in the preCOVID-19 era (86.9% vs. 78.5%, p = 0.007). The diagnosis of inflammatory bowel disease (IBD) was also significantly higher in the postCOVID-19 era compared to the preCOVID-19 era (47.2% vs. 28.5%, p < 0.001). According to multivariate logistic regression analysis, age at LGI endoscopy, LGI bleeding indication, and IBD diagnosis were independently associated with the use of a colonoscopy over a sigmoidoscopy (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.12−1.27, p < 0.001; OR 0.56, 95% CI 0.37−0.83, p = 0.005; OR 1.80, 95% CI 1.20−2.77, p = 0.006, respectively). Conclusions: The COVID-19 pandemic has changed LGI endoscopy practice trends of pediatric gastroenterologists in Korea, who tended to perform lesser LGI endoscopies compared to previous years while conducting significantly more colonoscopies than sigmoidoscopies in the postCOVID-19 era. Furthermore, these colonoscopies were significantly associated with the diagnosis of IBD, as well as a significant increase in IBD diagnosis in the postCOVID-19 era.

AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway.

BACKGROUND: AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined. METHODS: AMPKα1fl/flFoxp3YFP-Cre, Foxp3YFP-Cre, Rag1-/-, and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation. RESULTS: The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3ß (GSK-3ß), inhibiting the expression of PD-1 in Tregs. CONCLUSION: Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3ß signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.

Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients With Crohn Disease.

OBJECTIVES: We investigated the therapeutic drug monitoring of adalimumab (ADL) on clinical remission (CR) and mucosal healing (MH) rates in paediatric patients with Crohn disease (CD). Furthermore, long-term treatment efficacy of ADL in paediatric CD was evaluated through 3-year follow-up. METHODS: We conducted a prospective study of 31 patients with CD who received ADL maintenance therapy and underwent endoscopic evaluation of MH and pharmacokinetic analysis. Patients in CR were identified based on Paediatric Crohn Disease Activity Index (PCDAI) scores less than 10. Patients with MH were identified based on Simple Endoscopic Scores for Crohn Disease (SES-CD) of less than 2. RESULTS: At 4 months and 1 year of ADL treatment, 28 and 26 patients, respectively, were under CR; 13 and 17 patients, respectively, achieved MH. The median trough levels (TLs) of ADL were higher in patients in CR (7.6 ±â€Š3.5 µg/mL) than in patients with active disease (5.1 ±â€Š2.2 µg/mL). ADL TLs were significantly higher in patients who achieved MH than in those who did not (14.2 ±â€Š7.6 vs 7.8 ±â€Š5.2 µg/mL). The optimal cut-point for predicting MH at 1 year of ADL treatment was 8.18 µg/mL. During long-term follow-up, ADL TLs were stably maintained over 10 µg/mL; not only CR and MH but also histologic remission was obtained at a high rate. ADL administration maintained a positive effect on growth during the maintenance period. CONCLUSIONS: ADL TLs were significantly higher in paediatric patients with CD who achieved CR or MH. ADL treatment showed long-term stable efficacy and positive effects on growth indicators.

Severe Disease Activity Based on the Paris Classification Is Associated with the Development of Extraintestinal Manifestations in Korean Children and Adolescents with Ulcerative Colitis.

BACKGROUND: There are limited data regarding the extraintestinal manifestations (EIMs) associated with pediatric inflammatory bowel disease (IBD) in Korea. We aimed to investigate the clinical features and factors associated with the development of EIMs in Korean children and adolescents with IBD. METHODS: This multicenter, retrospective study was conducted from 2010 to 2017. Baseline clinicodemographic, laboratory findings, disease activity, disease phenotypes, and EIMs were investigated. RESULTS: A total of 172 patients were included. One-hundred thirty-seven (79.7%) had Crohn's disease (CD), and 35 (20.3%) had ulcerative colitis (UC). EIMs occurred in 42 patients (24.4%). EIMs developed in 34/137 diagnosed with CD (24.8%), and in 8/35 diagnosed with UC (22.9%), during a median follow-up duration of 3.2 (interquartile range, 1.9-5.4) years for CD and 3.0 (1.0-4.0) years for UC, respectively. Arthritis/arthralgia was most commonly observed (n = 15, 35.7%), followed by stomatitis/oral ulcer (n = 10, 23.8%), hepatitis (n = 5, 11.9%), nephritis (n = 4, 9.5%), pancreatitis (n = 2, 4.8%), erythema nodosum (n = 2, 4.8%), pyoderma gangrenosum (n = 1, 2.4%), primary sclerosing cholangitis (n = 1, 2.4%), uveitis (n = 1, 2.4%), and ankylosing spondylitis (n = 1, 2.4%). A significant difference in disease severity based on the Paris classification (P = 0.011) and ESR at diagnosis (P = 0.043) was observed between the EIM positive and negative group in patients with UC. According to logistic regression analyses, S1 disease severity based on the Paris classification was the only factor that was significantly associated with the development of EIMs (odds ratio, 16.57; 95% confidence interval, 2.18-287.39; P = 0.017). CONCLUSION: Severe disease activity based on the Paris classification in pediatric patients with UC was significantly associated with EIM development. As disease severity in the Paris classification is a dynamic parameter, treatment should be focused on disease control to minimize the occurrence of EIMs in Korean children and adolescents with UC.

Severe Phenotype of Non-alcoholic Fatty Liver Disease in Pediatric Patients with Subclinical Hypothyroidism: a Retrospective Multicenter Study from Korea.

BACKGROUND: It is uncertain whether non-alcoholic fatty liver disease (NAFLD) is associated with subclinical hypothyroidism (SH) in pediatric patients. The purpose of this study was to investigated the prevalence and related factors of SH in pediatric patients with NAFLD. We also evaluate the association between liver fibrosis and SH. METHODS: We retrospectively reviewed medical records for patients aged 4 to 18 years who were diagnosed with NAFLD and tested for thyroid function from January 2015 to December 2019 at 10 hospitals in Korea. RESULTS: The study included 428 patients with NAFLD. The prevalence of SH in pediatric NAFLD patients was 13.6%. In multivariate logistic regression, higher levels of steatosis on ultrasound and higher aspartate aminotransferase to platelet count ratio index (APRI) score were associated with increased risk of SH. Using receiver operating characteristic curves, the optimal cutoff value of the APRI score for predicting SH was 0.6012 (area under the curve, 0.67; P < 0.001; sensitivity 72.4%, specificity 61.9%, positive predictive value 23%, and negative predictive value 93.5%). CONCLUSION: SH was often observed in patients with NAFLD, more frequently in patients with more severe liver damage. Thyroid function tests should be performed on pediatric NAFLD patients, especially those with higher grades of liver steatosis and fibrosis.

Procedural Sedation for Pediatric Upper Gastrointestinal Endoscopy in Korea.

BACKGROUND: Sedative upper endoscopy is similar in pediatrics and adults, but it is characteristically more likely to lead to respiratory failure. Although recommended guidelines for pediatric procedural sedation are available within South Korea and internationally, Korean pediatric endoscopists use different drugs, either alone or in combination, in practice. Efforts are being made to minimize the risk of sedation while avoiding procedural challenges. The purpose of this study was to collect and analyze data on the sedation methods used by Korean pediatric endoscopists to help physicians perform pediatric sedative upper endoscopy (PSUE). METHODS: The PSUE procedures performed in 15 Korean pediatric gastrointestinal endoscopic units within a year were analyzed. Drugs used for sedation were grouped according to the method of use, and the depth of sedation was evaluated based on the Ramsay scores. The procedures and their complications were also assessed. RESULTS: In total, 734 patients who underwent PSUE were included. Sedation and monitoring were performed by an anesthesiologist at one of the institutions. The sedative procedures were performed by a pediatric endoscopist at the other 14 institutions. Regarding the number of assistants present during the procedures, 36.6% of procedures had one assistant, 38.8% had 2 assistants, and 24.5% had 3 assistants. The average age of the patients was 11.6 years old. Of the patients, 19.8% had underlying diseases, 10.0% were taking medications such as epilepsy drugs, and 1.0% had snoring or sleep apnea history. The average duration of the procedures was 5.2 minutes. The subjects were divided into 5 groups as follows: 1) midazolam + propofol + ketamine (M + P + K): n = 18, average dose of 0.03 + 2.4 + 0.5 mg/kg; 2) M + P: n = 206, average dose of 0.06 + 2.1 mg/kg; 3) M + K: n = 267, average dose of 0.09 + 0.69 mg/kg; 4) continuous P infusion for 20 minutes: n = 15, average dose of 6.6 mg/kg; 5) M: n = 228, average dose of 0.11 mg/kg. The average Ramsay score for the five groups was 3.7, with significant differences between the groups (P < 0.001). Regarding the adverse effects, desaturation and increased oxygen supply were most prevalent in the M + K group. Decreases and increases in blood pressure were most prevalent in the M + P + K group, and bag-mask ventilation was most used in the M + K group. There were no reported incidents of intubation or cardiopulmonary resuscitation. A decrease in oxygen saturation was observed in 37 of 734 patients, and it significantly increased in young patients (P = 0.001) and when ketamine was used (P = 0.014). Oxygen saturation was also correlated with dosage (P = 0.037). The use of ketamine (P < 0.001) and propofol (P < 0.001) were identified as factors affecting the Ramsay score in the logistic regression analysis. CONCLUSION: Although the drug use by Korean pediatric endoscopists followed the recommended guidelines to an extent, it was apparent that they combined the drugs or reduced the doses depending on the patient characteristics to reduce the likelihood of respiratory failure. Inducing deep sedation facilitates comfort during the procedure, but it also leads to a higher risk of complications.

Development and Validation of the Mucosal Inflammation Noninvasive Index For Pediatric Crohn's Disease.

BACKGROUND & AIMS: Mucosal healing (MH) has become a goal of therapy for Crohn's disease (CD), but frequent endoscopies are not feasible. We aimed to develop and validate a non-invasive index to assess mucosal inflammation in children with CD. METHODS: We collected data from the multi-center prospective ImageKids study, in which children with CD underwent ileocolonoscopy with magnetic resonance enterography. We investigated the association of pediatric CD activity index (PCDAI) items and laboratory test results with the simple endoscopic score for CD (SESCD). We used these data in a blended mathematical judgmental clinimetric approach to develop a weighted categorized index to identify children with CD who have MH, which we called the MINI index. We validated the index using data from 3 independent patient cohorts. The derivation and validation cohorts included 154 and 168 children, respectively (age 14.1 ± 2.5 years and 14.2 ± 3.9 years), of whom 16% and 36% had MH (defined as SESCD<3). RESULTS: In multivariable models, the stooling item of the PCDAI, erythrocyte sedimentation rate, and level of fecal calprotectin were associated with SESCD (all P < .05). We added data on level of C-reactive protein to develop the MINI index. MINI scores below 8 identified children with MH with 88% sensitivity and 85% specificity in the derivation cohort and with 84% sensitivity and 87% specificity in the validation cohorts. Ninety percent of the patients in the validation cohort with scores of 8 or more had active mucosal inflammation, yet 78% of patients with scores below 8 had MH. Scores below 6 increase the positive predictive value to 86%. CONCLUSIONS: We developed an index to non-invasively assess mucosal inflammation in children with CD. This index, identifies children with MH with high sensitivity and specificity. The added benefit of MINI over measurement of fecal calprotectin was small but significant, especially for patients with concentrations of fecal calprotectin from 100 to 599 µg/g. ClinicalTrials.gov no: NCT01881490.

Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition.

INTRODUCTION: With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19. METHODS: An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members. RESULTS: Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD. Among the Porto group members, face-to-face appointments were often replaced by remote consultations but almost all did not change current IBD treatment. Ten guidance points for clinicians caring for PIBD patients in epidemic areas have been endorsed with consensus rate of 92% to 100%. CONCLUSIONS: Preliminary data for PIBD patients during COVID-19 outbreak are reassuring. Standard IBD treatments including biologics should continue at present through the pandemic, especially in children who generally have more severe IBD course on one hand, and milder SARS-CoV-2 infection on the other.

Fecal calprotectin as a marker of gastrointestinal involvement in pediatric Henoch-Schönlein purpura patients: a retrospective analysis.

BACKGROUND: Henoch-Schönlein purpura is a type of systemic vasculitis found in children. Its prognosis is usually good; however, recurrence is relatively common. If the intestines are affected, severe complications could arise. Here, we investigated the value of fecal calprotectin in the early screening of Henoch-Schönlein purpura and as a useful factor for predicting gastrointestinal manifestations. METHODS: We retrospectively reviewed the medical records of pediatric patients who were diagnosed with Henoch-Schönlein purpura and underwent fecal calprotectin testing during the acute phase. The patients were categorized into gastrointestinal involvement and non-gastrointestinal involvement groups based on their clinical symptoms. Moreover, gastrointestinal involvement was categorized as follows: upper gastrointestinal tract involvement (up to the duodenum) and lower gastrointestinal tract involvement (from the terminal ileum). RESULTS: A total of 69 patients were diagnosed with Henoch-Schönlein purpura and underwent fecal calprotectin testing. Among them, 40 patients (58.0%) showed signs of gastrointestinal involvement. The gastrointestinal involvement group had higher fecal calprotectin levels (379.9 ± 399.8 vs. 77.4 ± 97.6 mg/kg, P = 0.000). There were no significant differences in the recurrence of Henoch-Schönlein purpura symptoms or gastrointestinal symptoms. The cut-off value to identify gastrointestinal involvement was 69.10 mg/kg (P < 0.01). Patients with fecal calprotectin levels of > 50 mg/kg showed more frequent gastrointestinal involvement (77.8% vs. 20.8%, P = 0.000) and more severe gastrointestinal symptoms. Significant differences in abdominal pain duration, Henoch-Schönlein purpura clinical score, and abdominal pain severity were observed (P = 0.002, P = 0.000, and P = 0.000, respectively). Additionally, fecal calprotectin levels were significantly higher in patients with lower gastrointestinal tract involvement (214.67 ± 150.5 vs. 581.8 ± 510.1 mg/kg, P = 0.008), and the cut-off value was 277.5 mg/kg (P < 0.01). CONCLUSION: Fecal calprotectin testing is useful for identifying gastrointestinal involvement in pediatric Henoch-Schönlein purpura patients.

Potential Utility of Therapeutic Drug Monitoring of Adalimumab in Predicting Short-Term Mucosal Healing and Histologic Remission in Pediatric Crohn's Disease Patients.

BACKGROUND: Limited data exist regarding mucosal healing (MH) and therapeutic drug monitoring (TDM) in pediatric Crohn's disease (CD) patients treated with adalimumab (ADL). We aimed to investigate the associations between ADL trough levels (TLs) and MH, and between ADL TLs and histologic remission (HR) at 16 weeks from ADL treatment in pediatric CD patients. METHODS: This was a prospective study on moderate-to-severe luminal pediatric CD patients receiving ADL. Ileocolonoscopies and biopsies, as well as clinical activity assessments, laboratory examinations, including tests for ADL TLs and antibody to ADL, were performed 16 weeks after ADL initiation. MH was defined as a Simple Endoscopic Score for CD of 0. HR was defined as the complete absence of microscopic inflammation. RESULTS: Seventeen subjects (13 males, 4 females) were included. At 16 weeks from ADL initiation, 14 (82.4%), 8 (47.1%), and 4 (23.5%) patients achieved clinical remission, MH, and HR, respectively. ADL TLs were significantly higher in patients who achieved MH compared to those who did not (13.0 ± 6.5 vs. 6.2 ± 2.6 µ/mL, respectively; P = 0.023) and also significantly higher in patients who achieved HR compared to those who did not (17.9 ± 5.3 vs. 6.8 ± 2.5 µ/mL, respectively; P = 0.02). The optimal TL for predicting MH was 8.76 µ/mL. CONCLUSION: Serum ADL TLs at 16 weeks were significantly higher in pediatric patients with CD who achieved MH and HR, respectively. TDM may guide in optimizing treatment efficacy and better target MH in the era of treat-to-target.

Can We Estimate Quality of Life in Pediatric Inflammatory Bowel Disease Patients? An Asian Multicenter Study.

OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic lifelong condition and is related to poor quality of life (QoL). The aim of this study was to evaluate the QoL of Asian pediatric patients with IBD and to determine the clinical factors that can influence QoL. METHODS: Children and adolescents aged 9 to 18 years diagnosed with IBD were enrolled from 7 hospitals. The patients completed the IMPACT-III questionnaire, and clinical data were collected. The results of the questionnaire and the correlation with clinical data were analyzed. RESULTS: A total of 208 patients (Crohn disease: n = 166; ulcerative colitis: n = 42) were enrolled. There was no definite QoL difference according to the Paris classification. Female sex (-5.92 ±â€Š2.97, P = 0.0347) and active disease status (-10.79 ±â€Š3.11, P = 0.0006) were significantly associated with poor QoL. Extreme body weight z score and older age at diagnosis were also associated with worse QoL. CONCLUSIONS: Various clinical factors may affect the QoL in patients with IBD, but determining the overall QoL of patients using only these clinical factors is difficult. Therefore, regular direct measurements of QoL are necessary to better understand patients with IBD.

Propionic Acidemia with Novel Mutation Presenting as Recurrent Pancreatitis in a Child.

Propionic acidemia (PA) is a rare organic acidemia resulting from a deficiency of the mitochondrial enzyme propionyl-coenzyme A carboxylase. Most cases are diagnosed after the detection of metabolic abnormalities-such as hyperammonemia, metabolic acidosis, and ketosis-associated with complaints of vomiting, feeding difficulties, and hypotonia during the neonatal period. However, in rare late-onset cases, mild or vague symptoms make the diagnosis more challenging. Even though acute pancreatitis is relatively uncommon in children, it can occur in association with PA. We present the case of a 4-year-old child who was admitted owing to the complaint of recurrent pancreatitis and had not previously been diagnosed with having metabolic disease. During inpatient treatment for acute pancreatitis, convulsions occurred with concomitant hyperammonemia, metabolic acidosis, coagulopathy, and shock 1 week after the administration of total parenteral nutrition. He was diagnosed to have PA after a metabolic work-up and confirmed to have novel mutation by molecular genetic analysis. Because children with PA may have acute pancreatitis, although rare, vomiting and abdominal pain should raise a suspicion of acute pancreatitis. On the contrary, even among children who have never been diagnosed with a metabolic disease, if a child has recurrent pancreatitis, metabolic pancreatitis caused by organic acidemia should be considered.