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.

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.

A Multicenter Study of Real-world Practice for Management of Abnormal Liver Function Tests in Children with Acute Infectious Diseases.

BACKGROUND: Abnormal liver function tests (LFTs) are commonly seen in pediatric patients with acute infectious diseases. Few studies and no definite clinical guidelines for these conditions are available. The present study aimed to elucidate the causes and factors associated with prolongation of liver enzyme elevation. We also investigated actual real-world practices in Korea. METHODS: A retrospective study was performed on all patients younger than 18 years, who visited six tertiary teaching hospitals around Korea in 2018 for acute infectious diseases and showed alanine aminotransferase (ALT) levels above 60 IU/L without other specific conditions that could cause ALT elevation. We categorized the infections that cause LFT elevation into six groups: respiratory infection, gastrointestinal infection, urinary tract infection, other febrile disease, Epstein-Barr virus infection, and cytomegalovirus infection. We collected data on the medical specialty of the attending physician who followed up the subject, follow-up duration, percentage of follow-up loss, and their investigation. RESULTS: A total of 613 patients were enrolled in this study, half of whom (50.7%) were younger than 12 months. The mean initial aspartate aminotransferase and ALT values were 171.2 ± 274.1 and 194.9 ± 316.1 IU/L (range 23-2,881, 60-2,949 IU/L), respectively; however, other LFTs were within the normal range. Respiratory infection was the most common diagnosis (45.0%), and rhinovirus was the most commonly identified pathogen (9.8%). The follow-up rate was higher with pediatric gastroenterologists (90.5%) and non-gastroenterology pediatricians (76.4%) than with pediatric residents and emergency doctors. Older age was related to better ALT recovery (odds ratio [OR] of age for month = 1.003; 95% confidence interval [CI], 1.001-1.004; P = 0.004), while the number of infection episodes (OR = 0.626; 95% CI, 0.505-0.777; P < 0.001) was associated with poor ALT recovery. Abdominal sonography was the most commonly used diagnostic tool (36.9%), followed by the hepatotropic virus workup. The modalities of hepatitis workup were significantly differently applied by physicians based on their specialties and institutions. CONCLUSION: Abnormal liver function test after a systemic infection was common in respiratory infection and under the age of 1 year. Age, number of infections, and initial results of LFTs were related to ALT recovery time. Inter-physician, inter-institution, and inter-specialty variances were observed in real-world practice.

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.

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.

Baseline Wall Thickness Is Lower in Mucosa-Healed Segments 1 Year After Infliximab in Pediatric Crohn Disease Patients.

OBJECTIVES: We aimed to quantitatively investigate the therapeutic response to combined immunosuppression treatment by magnetic resonance enterography (MRE) in active luminal Crohn disease (CD) in the pediatric population. METHODS: Pediatric patients with moderate-to-severe luminal CD, who received scheduled infliximab and azathioprine, were included in this preliminary study. Ileocolonoscopy and MRE were performed at baseline and at 1 year, and Simple Endoscopic Score for Crohn's Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) scores were calculated. The correlation between SES-CD and MaRIA scores were investigated with analysis per person and per segment. RESULTS: A total of 167 segments from 17 patients were evaluated by both Ileocolonoscopy and MRE. SES-CD and MaRIA scores showed significant correlations on both per-person analysis (ρ = 0.699, P < 0.001) and per-segment analysis (ρ = 0.596, P < 0.001). Analysis according to ileocolonic location of each segment revealed that the correlation strength was strongest in the right colon (ρ = 0.653, P < 0.001), whereas the correlation in the rectum was statistically insignificant (ρ = 0.29, P = 0.096). A comparative analysis of MaRIA components revealed a significantly thinner bowel wall thickness at baseline in endoscopically healed segments (50/65) compared with unhealed segments (15/65) (median 4.3 vs 7.2 mm, P = 0.036). CONCLUSIONS: Therapeutic response to combined immunosuppression at 1 year assessed by MRE correlates with ileocolonoscopy in pediatric patients with CD. Bowel wall thickness of the involved segments at baseline may affect treatment response to combined immunosuppression.

PHKA2 mutation spectrum in Korean patients with glycogen storage disease type IX: prevalence of deletion mutations.

BACKGROUND: Molecular diagnosis of glycogen storage diseases (GSDs) is important to enable accurate diagnoses and make appropriate therapeutic plans. The aim of this study was to evaluate the PHKA2 mutation spectrum in Korean patients with GSD type IX. METHODS: Thirteen Korean patients were tested for PHKA2 mutations using direct sequencing and a multiplex polymerase chain reaction method. A comprehensive review of the literature on previously reported PHKA2 mutations in other ethnic populations was conducted for comparison. RESULTS: Among 13 patients tested, six unrelated male patients with GSD IX aged 2 to 6 years at the first diagnostic work-up for hepatomegaly with elevated aspartate transaminase (AST) and alanine transaminase (ALT) were found to have PHKA2 mutations. These patients had different PHKA2 mutations: five were known mutations (c.537 + 5G > A, c.884G > A [p.Arg295His], c.3210_3212delGAG [p.Arg1072del], exon 8 deletion, and exons 27-33 deletion) and one was a novel mutation (exons 18-33 deletion). Notably, the most common type of mutation was gross deletion, in contrast to other ethnic populations in which the most common mutation type was sequence variant. CONCLUSIONS: This study expands our knowledge of the PHKA2 mutation spectrum of GSD IX. Considering the PHKA2 mutation spectrum in Korean patients with GSD IX, molecular diagnostic methods for deletions should be conducted in conjunction with direct sequence analysis to enable accurate molecular diagnosis of this disease in the Korean population.

Factors Associated with Reaching Mid-Parental Height in Patients Diagnosed with Inflammatory Bowel Disease in Childhood and Adolescent Period.

Background/Aims: The recent update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added normal growth in children as an intermediate target in Crohn's disease and ulcerative colitis. We aimed to investigate factors associated with reaching mid-parental height (MPH) in patients diagnosed with inflammatory bowel disease in childhood and the adolescent period. Methods: This multicenter retrospective observational study included pediatric patients with inflammatory bowel disease that had reached adult height. Factors associated with reaching MPH were investigated by logistic regression analyses. Results: A total of 166 patients were included in this study (128 Crohn's disease and 38 ulcerative colitis). Among them, 54.2% (90/166) had reached their MPH. Multivariable logistic regression analysis revealed that height Z-score at diagnosis and MPH Z-score were independently associated with reaching MPH (odds ratio [OR], 8.45; 95% confidence interval [CI], 4.44 to 17.90; p<0.001 and OR, 0.11; 95% CI, 0.04 to 0.24; p<0.001, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level of "height Z-score at diagnosis minus MPH Z-score" that was associated with reaching MPH was -0.01 with an area under the curve of 0.889 (95% CI [0.835 to 0.944], sensitivity 88.9%, specificity 84.2%, positive predictive value 87.0%, negative predictive value 86.5%, p<0.001). Conclusions: Height Z-score at diagnosis and MPH Z-score were the only factors associated with reaching MPH. Efforts should be made to restore growth in pediatric patients who present with a negative "height Z-score at diagnosis minus MPH Z-score."

Comparison of endoscopic healing and durability between infliximab originator and CT-P13 in pediatric patients with inflammatory bowel disease.

Background and aims: Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Methods: Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. Results: We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). Conclusions: The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.

WavelNet: A novel convolutional neural network architecture for arrhythmia classification from electrocardiograms.

BACKGROUND AND OBJECTIVE: Automated detection of arrhythmias from electrocardiograms (ECGs) can be of considerable assistance to medical professionals in providing efficient treatment for patients with cardiovascular diseases. In recent times, convolutional neural network (CNN)-based arrhythmia classification models have been introduced, but their decision-making processes remain unclear and their performances are not reproducible. This paper proposes an accurate, interpretable, and reproducible end-to-end arrhythmia classification model based on a novel CNN architecture named WavelNet, which is interpretable and optimal for dealing with ECGs. METHODS: Inspired by SincNet, which is capable of band-pass filtering-based spectral analysis, WavelNet was devised to achieve wavelet transform-based spectral analysis. WavelNet was trained using a subject-oriented five-class ECG arrhythmia dataset generated from the MIT-BIH Arrhythmia Database while following a benchmark scheme. By adopting various mother wavelets, multiple WavelNet-based arrhythmia classification models were implemented. To investigate whether our wavelet transform-based approach outperforms original end-to-end and band-pass filtering-based approaches, our proposed models were compared with vanilla CNN- and SincNet-based models. Model implementation and evaluation processes were repeated ten times in a Google Colab Pro+ environment. Furthermore, our most successful model was compared with state-of-the-art arrhythmia classification models for performance evaluation. RESULTS: The proposed WavelNet-based models showed excellent performance on classifying non-ectopic, supraventricular ectopic, and ventricular ectopic beats because of their ability to perform adaptive spectral analysis while preserving temporal ECG information compared with vanilla CNN- and SincNet-based models. In particular, a Symlet 4 wavelet-adopting WavelNet-based model achieved the best performance with nearly 90% overall accuracy as well as the highest levels of sensitivity in classifying each arrhythmia class: 91.4%, 49.3%, and 91.4% for non-ectopic, supraventricular ectopic, and ventricular ectopic beat classifications, respectively. These results were comparable to those of state-of-the-art models. In addition, the results are reproducible, which differentiates our study from previous studies. CONCLUSIONS: Our proposed WavelNet-based arrhythmia classification model achieved remarkable performance based on a reasonable decision-making process, in comparison with other models. As its noteworthy performance is clinically reasonable and reproducible, our proposed model can contribute toward implementing a real-world precision healthcare system for patients with cardiovascular diseases.

Infliximab trough levels are associated with endoscopic healing but not with transmural healing at one year treatment with infliximab in pediatric patients with Crohn's disease.

Introduction: It is well known that infliximab (IFX) trough levels (TLs) are associated with endoscopic healing (EH) in Crohn's disease (CD). We investigated whether IFX TLs are associated with transmural healing (TH) in pediatric patients with CD following 1-year treatment. Methods: Pediatric patients with CD treated with IFX were included in this single-center prospective study. IFX TL tests, magnetic resonance enterography (MRE), and colonoscopies were simultaneously conducted after 1-year IFX treatment. TH was defined as a wall thickness of ≤3 mm without inflammatory signs evaluated using MRE. EH was defined as a Simple Endoscopic Score for Crohn's disease of <3 points on colonoscopy. Results: Fifty-six patients were included. EH and TH were observed in 60.7% (34/56) and 23.2% (13/56) of patients, respectively. IFX TLs were higher in patients with EH (median, 5.6 vs. 3.4 µg/mL, P = 0.002), whereas IFX TLs showed no significant difference in patients with and without TH (median, 5.4 vs. 4.7 µg/mL, P = 0.574). No significant difference was observed in EH and TH between patients whose intervals were shortened or not. Multivariate logistic regression analysis showed that IFX TLs and disease duration to IFX initiation were associated with EH (odds ratio [OR] = 1.82, P = 0.001, and OR = 0.43, P = 0.02, respectively). Discussion: In pediatric patients with CD, IFX TLs were associated with EH but not with TH. Further studies investigating long-term TH and proactive dosing based on therapeutic drug monitoring may clarify whether an association between IFX TLs and TH exists.

Fecal Calprotectin at Postinduction Is Capable of Predicting Persistent Remission and Endoscopic Healing after 1 Year of Treatment with Infliximab in Pediatric Patients with Crohn's Disease.

Background/Aims: : The recent update on Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added a decrease in fecal calprotectin (FC) to an acceptable range as an intermediate target for Crohn's disease (CD). We aimed to investigate whether postinduction FC could predict future persistent remission (PR) and endoscopic healing (EH) after 1 year of treatment with infliximab (IFX) in pediatric patients with CD. Methods: : This multicenter retrospective observational study included pediatric patients with CD who were followed up for at least 1 year after starting IFX. The association of postinduction FC with PR and EH was investigated. Results: : A total of 132 patients were included in this study. PR and EH were observed in 71.2% (94/132) and 73.9% (82/111) of the patients, respectively. In multivariate logistic regression analysis, only the postinduction FC level was associated with PR (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08 to 0.66; p=0.009). The FC levels at initiation of IFX and postinduction were significantly associated with EH (OR, 0.73; 95% CI, 0.53 to 0.99; p=0.044 and OR, 0.20; 95% CI, 0.06 to 0.49; p=0.002, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level for postinduction FC associated with PR was 122 mg/kg, and that associated with EH was 377 mg/kg. Conclusions: : Postinduction FC was associated with PR and EH after 1 year of treatment with IFX in pediatric patients with CD. Our findings emphasize the importance of FC as an intermediate target in the treat-to-target era.

A Nationwide Survey on Gastrointestinal Endoscopy Practice Patterns among Pediatric Endoscopists in South Korea.

Purpose: Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. Methods: Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. Results: The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. Conclusion: While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.

Associations of Polyp Characteristics in Children and Adolescents Presenting with Less Than Five Colorectal Polyps: A Full Colonoscopy Is Still Required.

Background/Aims: A full colonoscopy is currently required in children and adolescents with colorectal polyps, because of their potential of neoplastic transformation and complications such as intussusception. We aimed to analyze the associations of polyp characteristics in children and adolescents with colorectal polyps. Based on these findings, we also aimed to reevaluate the necessity of conducting a full colonoscopy. Methods: Pediatric patients <18 years of age who had undergone a colonoscopic polypectomy and those with <5 colorectal polyps were included in this multicenter, retrospective study. Baseline clinicodemographics, colonoscopic and histologic findings were investigated. Results: A total of 91 patients were included. Multivariate logistic regression analysis showed that polyp size was the only factor associated with the presence of any polyps located proximal to the splenic flexure (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.28 to 4.28; p=0.007). Furthermore, polyp location proximal to the splenic flexure and sessile morphology were associated with the presence of any adenomatous polyp (OR, 8.51; 95% CI, 1.43 to 68.65; p=0.023; OR, 18.41; 95% CI, 3.45 to 173.81; p=0.002, respectively). Conclusions: In children and adolescents presenting with <5 colorectal polyps, polyp size and the presence of any adenomatous polyp were positively associated with polyp location proximal to the splenic flexure. This finding supports the necessity of a full colonoscopic exam in pediatric patients with colorectal polyps for the detection of polyps before the occurrence of complications such as intussusception or neoplastic transformation.

Fecal Calprotectin Levels Significantly Correlate with Polyp Size in Children and Adolescents with Juvenile Colorectal Polyps.

Purpose: We aimed to investigate factors that correlate with fecal calprotectin (FC) levels in children and adolescents with colorectal polyps. Methods: Pediatric patients aged <19 years who underwent colonoscopic polypectomy for a juvenile polyps (JPs) and FC tests were simultaneously conducted in a multicenter, retrospective study. Baseline demographics, colonoscopic and histological findings, and laboratory tests, including FC levels, were investigated. Correlations between the factors were investigated, and linear regression analysis revealed factors that correlated with FC levels. FC levels measured after polypectomies were investigated and the FC levels pre- and post-polypectomies were compared. Results: A total of 33 patients were included in the study. According to Pearson correlation analysis, the polyp size was the only factor that showed a statistically significant correlation with FC levels (r=0.75, p<0.001). Furthermore, according to the multivariate linear regression analysis, polyp size was the only factor that showed a statistically significant correlation with FC levels (adjusted R2 =0.5718, ß=73.62, p<0.001). The median FC level was 400 mg/kg (interquartile range [IQR], 141.6-1,000 mg/kg), and the median polyp size was 14 mm (IQR, 9-20 mm). Nineteen patients underwent post-polypectomy FC tests. FC levels showed a significant decrease after polypectomy from a median of 445.2 mg/kg (IQR, 225-1,000) to 26.5 mg/kg (11.5-51) (p<0.001). Conclusion: FC levels significantly correlated with polyp size in children and adolescents with JPs.

Adalimumab in Pediatric Inflammatory Bowel Disease.

The introduction of biological agents with strong anti-inflammatory action, such as antitumor necrosis factor (TNF) agents, has changed inflammatory bowel disease (IBD) treatment strategy and goals, and has contributed significantly to improve the long-term prognosis of patients. Moreover, several biological agents are being used or researched in pediatric populations. However, only two biological agents, infliximab (IFX) and adalimumab (ADL), are currently approved for children and adolescents. In pediatric IBD, there are limitations and burdens associated with facilitating mucosal healing (MH) when utilizing these two biological agents. ADL is effective in both naïve patients and those with previous experience with biologics. Beyond clinical remission, this drug is also effective for MH and histological remission. The use of therapeutic drug monitoring to further enhance the effectiveness of ADL treatment can be expected to reduce treatment failure of ADL and pave the way for appropriate treatment in the treat-to-target era. This review paper focuses on ADL, examine studies conducted in children, and determine the role this agent plays against pediatric inflammatory bowel disease.

Neutralizing Antibody Response, Safety, and Efficacy of mRNA COVID-19 Vaccines in Pediatric Patients with Inflammatory Bowel Disease: A Prospective Multicenter Case-Control Study.

The vaccination of immunocompromised children against coronavirus disease 2019 is an important public health issue. We evaluated the serological response, safety, and efficacy of the BNT162b2 vaccine in children with and without inflammatory bowel disease (IBD). A prospective, multicenter, case-control study was conducted in a pediatric population, including patients with IBD, aged 12-18 years. Clinical characteristics, safety profile, and serum samples for surrogate virus-neutralizing antibody testing pre- and post-BNT162b2 vaccination were assessed. The breakthrough infection rate during the Omicron outbreak was calculated to evaluate efficacy. Fifteen controls and twenty-three patients with IBD were enrolled. After two vaccine doses, the median level of percentage inhibition was highly increased, without significant differences between the groups (control 96.9 and IBD 96.3). However, it was significantly reduced in IBD patients receiving combination therapy (anti-tumor necrosis factor-α + immunomodulators) relative to those in other therapies and controls. Serious adverse events were not observed. The breakthrough infection rate was 42.1%, without statistical differences between the groups. Immunization with BNT162b2 in patients with IBD was comparable with that in healthy adolescents in terms of immunogenicity and safety. Nevertheless, the efficacy of BNT162b2 in preventing infection caused by the Omicron variant in the pediatric population was insufficient.

Transmural healing evaluated by magnetic resonance enterography in paediatric patients with Crohn's disease receiving maintenance treatment with biologics.

BACKGROUND: The optimal treatment goal in Crohn's disease (CD) is endoscopic healing (EH). However, transmural healing (TH) facilitated by the development and increasing performance of magnetic resonance enterography (MRE) is emerging as a potential treatment goal. AIMS: To assess TH rates after 1 year of treatment by MRE and its relationship with EH in paediatric patients with CD receiving anti-tumour necrosis factor (TNF) agents, and to investigate factors associated with TH after 1 year of treatment. METHODS: This multi-centre, prospective, observational study included Korean paediatric patients with luminal CD diagnosed at age < 19 years who were naïve to anti-TNF treatment. They simultaneously underwent ileocolonoscopy and MRE at baseline and after 1 year of treatment with biologics. RESULTS: We included 116 patients. At 1 year, EH and TH were achieved in 59.5% (69/116) and 38.8% (45/116) of the patients, respectively. Both EH and TH was observed in 35.3% (41/116), EH without TH in 24.1% (28/116), TH without EH in 3.4% (4/116), and neither EH nor TH in 37.1% (43/116). Moreover, 59.4% (41/69) of patients who achieved EH at 1 year exhibited TH, and 91.1% (41/45) of patients who achieved TH exhibited EH. Baseline MaRIA score was associated with TH according to a multivariate analysis (OR 0.97, 95% CI 0.95-0.99, p = 0.023). CONCLUSION: TH is a more stringent goal than EH. Regular follow-up evaluation of transmural status, and efforts to achieve TH, may alter the natural course of CD in the era of treat-to-target.