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.

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."

Foreign body ingestion trends in children in the Daegu-Kyungpook Province, Korea before and during the COVID-19 period: a repeated cross-sectional study.

Background: During the coronavirus disease 2019 (COVID-19) period, children spent more time at home, which is where most foreign body ingestions (FBIs) in children occur. We compared the rate of FBI in children in the Daegu-Kyungpook Province during COVID-19 to the rate in the 2 years before the COVID-19 period. Methods: The period from January to December in the year 2020 was defined as the COVID-19 period, and the corresponding time period in 2018 and 2019 was defined as the pre-COVID-19 period. Medical records were analyzed retrospectively for pediatric patients aged 0-15 years who visited outpatient and emergency rooms at seven tertiary referral hospitals in Daegu-Kyungpook Province. Results: The annual occurrence rate of FBIs in patients visiting seven tertiary referral hospitals was not different during COVID-19 compared to that in the pre-COVID-19 period and the median age of these patients during the COVID-19 and pre-COVID-19 periods was similar. However, occurrence rates increased in the groups aged 0-3 and 4-6 years but decreased in the group aged 7-15 years during the COVID-19 period. The proportion of male patients as well as inpatients increased significantly during the COVID-19 period (both P=0.01). The proportion of foreign bodies located in the post-pyloric region increased during the COVID-19 period (P=0.02). The most common symptom, foreign body sensation in the neck, was similar in both groups. There was no significant difference in the foreign body removal method between the two groups. The occurrence rates of swallowing of toys, coins, magnets, button batteries, and superabsorbent polymers non-significantly increased; and the food ingestion rate decreased, while the non-food ingestion rate increased in all age groups during the COVID-19 period. Conclusions: The FBI rate in children did not differ during the COVID-19 period compared to that in the pre-COVID-19 period. The occurrence of FBI in boys, the number of foreign bodies located in the post-pyloric region, and the number of hospitalizations due to FBI increased during the COVID-19 period.

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.

Rapid Molecular Tests for Detecting Respiratory Pathogens Reduced the Use of Antibiotics in Children.

Multiplex polymerase chain reaction (mPCR) is increasingly being used to diagnose infections caused by respiratory pathogens in pediatric inpatient facilities. mPCR assays detect a broader array of viruses, with higher specificity and sensitivity and faster turnaround than previous assays. We adapted the FilmArray Respiratory Panel (FA-RP) for diagnosing respiratory infections. FA-RP is an in vitro mPCR assay that simultaneously and rapidly (in about 1 h) detects 20 pathogens directly from respiratory specimens. Here, we studied the clinical efficacy of FA-RP in children who underwent testing for respiratory pathogens at Yeungnam University Hospital from November 2015 to August 2018. From November 2015 to June 2016, routine mPCR testing was performed on nasopharyngeal swabs using the routine mPCR kit. From November 2016 to July 2018, mPCR testing was performed using FA-RP. A total of 321 tests by routine mPCR and 594 tests by FA-RP were included. The positive detection rates for routine mPCR and FA-RP were 71.3% and 83.3%, respectively. FA-RP reduced the lead time, waiting time, turnaround time, intravenous (IV) antibiotic use, and length of hospital stay for pediatric patients. The decreased use of antibiotics is expected to reduce antibiotic resistance in children.

Incidence and Prevalence Trends of Pediatric Inflammatory Bowel Disease in the Daegu-Kyungpook Province From 2017 to 2020.

Background and Aim: There is paucity of data regarding the epidemiology of pediatric IBD in Asia compared to that of Western countries. We aimed to investigate the incidence and prevalence trends of pediatric inflammatory bowel disease (IBD) in the Daegu-Kyungpook province of South Korea from 2017 to 2020. Methods: This study was a multicenter, retrospective study conducted in eight IBD referral centers located in the Daegu-Kyungpook province. Children and adolescents of ≤18 years who were initially diagnosed with IBD between 2017 and 2020 were included. The annual number of children and adolescents newly diagnosed with IBD and the annual resident population of children and adolescents ≤18 years of age in the Daegu-Kyungpook province were investigated to calculate the annual incidence and prevalence in the region. Results: A total 304 children and adolescents that had been diagnosed with IBD were included in this study. Among these patients, 71.4% had been diagnosed with Crohn's disease (CD), and 28.6% with ulcerative colitis (UC). The population based annual incidences of IBD from 2017 to 2020 were each 7.24, 6.82, 10.27, and 13.33 per 100,000, respectively (P for trend <0.001), 4.48, 5.26, 7.39, and 9.8 per 100,000, respectively, for CD (P for trend <0.001), and 2.76, 1.56, 2.88, and 3.53 per 100,000, respectively, for UC (P for trend = 0.174). Conclusion: Pediatric IBD, especially CD has significantly increased recently in the Daegu-Kyungpook province. Epidemiology studies from other regions of Asia are required to better elucidate this trend of increase in Asia.

Characteristics and Incidence Trends for Pediatric Inflammatory Bowel Disease in Daegu-Kyungpook Province in Korea: a Multi-Center Study.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous chronic disease of unknown etiology. Although it is an important disease that shows a rapid increase in pediatric population, there are no pediatric studies that represent a specific region in Korea. Therefore, we studied the epidemiological and phenotypic characteristics of pediatric IBD in Daegu-Kyungpook province, Korea. METHODS: We included 122 children with pediatric IBD initially diagnosed at one of four university hospitals in Daegu-Kyungpook province between July 2010 and June 2016. We investigated the incidence trends, and the clinical characteristics at diagnosis were compared by Paris classification. RESULTS: We included 122 children: 98 with Crohn's disease (CD) and 24 with ulcerative colitis (UC). The average age at diagnosis was 13.6 years for IBD. The incidence shows an increasing trend. CD showed a significant increase, whereas UC appears to be increasing slowly. In CD, there was a significant male predominance. For disease activity sites, the most common location was L3 (77.6%), indicating ileocolonic involvement as the major type. B1 (88.8%) was the most common disease behaviors type. Perianal disease was noted in 43 patients (43.9%) and weight loss in 60 (61.2%). In UC, E4 (58.4%) was the most common disease activity site, indicating pancolonic involvement as the major type. CONCLUSION: We found that the number of pediatric patients with IBD is increasing rapidly in Daegu-Kyungpook province in Korea. Our study also revealed that the characteristics of pediatric IBD in our province differ somewhat from those of pediatric IBD in Western countries.

The association between blood cadmium level, frequency and amount of gejang (marinated crab) intake.

BACKGROUND: Gejang (marinated crab) is a favorite traditional food and a main source of crab intake among Koreans. The present study aimed to identify the possibility of cadmium inflow to the body through gejang; accordingly, the relationship between gejang intake frequency and amount, and blood cadmium concentrations was investigated. METHODS: Using data from the first Korea National Health and Nutrition Examination Survey in the sixth period in 2013, means and standard errors of blood cadmium concentrations in relation to gejang intake frequency and amount, as well as the monthly intake of gejang, were obtained from 1381 participants for whom data regarding blood cadmium concentration measurements was available. RESULTS: After adjustment for confounding factors, a gejang intake frequency of four or fewer times per week and a monthly intake of 200 cm(3) or less had no significant effect on blood cadmium concentrations. However, participants with gejang intake of at least five times per week had a weighted mean cadmium concentration of 2.12 µg/L (p < 0.001), and participants who had a gejang monthly intake of more than 200 cm(3) had a weighted mean cadmium concentration of 1.76 µg/L (p < 0.001). CONCLUSION: These results suggest that to minimize the effect of gejang consumption on blood cadmium level, gejang intake should be limited to four or less times per week and 200 cm(3) or less per month. Weekly intake of at least five times and monthly intake of more than 200 cm(3) may increase blood cadmium levels.

Kikuchi-Fujimoto disease mimicking malignant lymphoma with 2-[(18)F]fluoro-2-deoxy-D-glucose PET/CT in children.

PURPOSE: Kikuchi-Fujimoto disease (KFD) is a benign disease, which is characterized by a cervical lymphadenopathy with fever, and it often mimics malignant lymphoma (ML). 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) is a powerful imaging modality for the diagnosis, staging and monitoring of ML, with the limitations including the nonspecific FDG uptake in infectious or inflammatory processes. This study compared clinical manifestations and PET/CT findings between KFD and ML patients. METHODS: We retrospectively reviewed the medical records of 23 patients with KFD and 33 patients with ML, diagnosed histopathologically, between January 2000 and May 2013 at the Department of Pediatrics, Yeungnam University Medical Center. Among them, we analyzed the clinical manifestations, laboratory findings and characteristics, and the amount of (18)F-FDG uptake between 8 KFD and 9 ML patients who had (18)F-FDG PET/CT. RESULTS: The (18)F-FDG PET/CT maximum standardized uptake values (SUVmax) ranged from 8.3 to 22.5 (mean, 12.0) in KFDs, and from 5.8 to 34.3 (mean, 15.9) in MLs. There were no significant differences in SUVmax between KFDs and MLs. (18)F-FDG PET/CT with ML patients showed hot uptakes in the extranodal organs, such as bone marrow, small bowel, thymus, kidney, orbit and pleura. However, none of the KFD cases showed extranodal uptake (P<0.001). (18)F-FDG PET/CT findings of KFD with nodal involvement only were indistinguishable from those of ML. CONCLUSION: Patients who had extranodal involvement on PET/CT were more likely to have malignancy than KFD.

Clinical characteristics of Kawasaki disease with sterile pyuria.

PURPOSE: Kawasaki disease (KD) is a systemic vasculitis and affects many organ systems. It often presents sterile pyuria, microscopic hematuria, and proteinuria due to renal involvement. The aims of this study were to define clinical characteristics of acute KD patients with pyuria and to analyze meaning of pyuria in KD. METHODS: The medical records and laboratory findings including serum and urine test of 133 patients with KD admitted to Yeungnam University Hospital from March 2006 to December 2010 were reviewed retrospectively. RESULTS: Forty patients had sterile pyuria and their clinical characteristics including age, gender and body weight were not significantly different with those who did not have pyuria. Fever duration after treatment was significantly longer in KD patients with pyuria. Erythrocyte sedimentation rate, C-reactive protein and serum concentration of alanine aminotransferase were significantly higher in patients with pyuria. Hyponatremia and coronary artery lesion were seen more often in patients with pyuria but there was no significant difference. Also serum blood urea nitrogen was significantly higher in KD patients with pyuria. Urine ß(2)-microglobulin was elevated in both patients groups and showed no difference between two groups. CONCLUSION: We found more severe inflammatory reaction in KD patients with pyuria. We also found elevation of some useful parameters like ß(2)-microglobulin that indicate renal involvement of KD through the urine test. Careful management and follow up will need for KD patients with pyuria and it is necessary in the future to study the specific parameters for renal involvement of KD.

Development of a Nutrition Questionnaire and Guidelines for the Korea National Health Screening Program for Infants and Children / 대한소아소화기영양학회지

PURPOSE: A new health policy, referred to as the National Health Screening Program for Infants and Children, was launched in November 2007 by the Ministry of Health and Welfare and National Health Insurance Corporation in Korea. We have developed a nutrition-counseling program that was incorporated into this project. METHODS: We reviewed the nutritional guidelines published by The Korean Pediatric Society and internationally well-known screening programs such as Bright Future in the United States. We also reviewed the recent Korean national surveys on nutritional issues, including the Korea National Health and Nutrition Examination Survey (KNHANES) and the 2005 National Survey of Physical Body and Blood Pressure in Children and Adolescents. The development of questions, pamphlets, computer programs, and manuals for doctors was carried out after several meetings of researchers and governmental officers. RESULTS: We summarized the key nutritional issues according to age, including breastfeeding in infants, healthier complementary feeding, and prevention of iron deficiency anemia, establishment of healthier diets, as well as dietary prevention of overweight children with an emphasis on physical exercise. We have constructed a new Korean nutrition questionnaire and an anticipatory guidance program based on the primary care schedule of visits at 4, 9, 18, 30, and 60 months of age. Five to eight questions were asked at each visit and age-matched pamphlets for parents and guidelines for doctors were provided. CONCLUSION: We developed a nutrition-counseling program based on recent scientific evidence for Korean infants and children. Further research on this national program for screening the nutritional problems in detail and setting the therapeutic approaches may help identify areas of success as well as those that need further attention.

Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance.

To evaluate whether metformin enhances leptin sensitivity, we measured leptin sensitivity after 4 weeks of metformin treatment (300 mg/kg daily) in both standard chow and high-fat-fed obese rats. Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 microg daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat-fed obese rats compared with age-matched standard chow rats. However, these responses to leptin were corrected by metformin treatment in high-fat-fed obese rats. Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat-fed obese rats. The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats. In an acute study, metformin treatment also increased the anorexic effect of leptin (5 microg), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus. These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat-fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.

LY294002 inhibits LPS-induced NO production through a inhibition of NF-kappaB activation: independent mechanism of phosphatidylinositol 3-kinase.

Phosphatidylinositol 3-kinase (PI3K) is critical player in cell proliferation and survival. The effects of LY294002 and wortmannin, inhibitors of PI3K, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipoploysaccharide (LPS)-induced Raw 264.7 cells were investigated. Significant inhibition of LPS-induced protein kinase B (PKB, Akt) phosphorylation occurred at 25 microM LY294002 or 0.5 microM wortmannin. At the same concentrations, LY294002, but not wortmannin, significantly inhibited NO production and iNOS expression. LY303511, an inactive analogue of LY294002, also inhibited NO production and iNOS expression. In addition, LY294002 and LY303511 significantly inhibited the DNA binding activity of NF-kappaB and NF-kappaB dependent reporter gene expression. These results suggest that LY294002 inhibits iNOS expression at least in part via inhibition of NF-kappaB activation, independent of PI3K.

Leptin-like effects of MTII are augmented in MSG-obese rats.

To evaluate whether MTII, a melanocortin receptor 3/4 agonist, is working in hypophagic and hypothermogenic obese model, we measured food intake, body weight, oxygen consumption, and fat mass following intracerebroventricular (i.c.v.) infusion of MTII in monosodium glutamate (MSG)-induced obese rats. MTII, or artificial cerebrospinal fluid (aCSF), was infused into i.c.v. with an osmotic minipump for 1 week. MSG-obese rats were induced by neonatal injection of MSG. Five-month-old MSG rats were characterized by hypophagia, lower oxygen consumption, hyperleptinemia, and obesity compared to age-matched control rats. The infusion of MTII decreased their food intake, visceral fat, and body weight in MSG-obese rats compared with aCSF-infused rats. The oxygen consumption was increased by MTII treatment in MSG-obese rats compared with aCSF as well as pair fed (PF) rats. Interestingly, these leptin-like effects of MTII were greater in MSG-obese rats than in controls, which might be related to the increased expression of melanocortin receptor 4 (MC4R) in the hypothalamus of MSG-obese rats. Our results suggested that both anorexic and thermogenic mechanisms were activated by MTII in the MSG-obese rats and contributed to the decrease in body weight and fat mass. Moreover, there was a sensitization to MTII caused by upregulation of the melanocortin receptor in the MSG-obese rats.

Production of chemokines in Kawasaki disease, Henoch-Schönlein purpura and acute febrile illness.

We compared the production of three chemokines; interferon-gamma-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and growth-related onco-gene-alpha(Gro-alpha) that attracts monocytes or neutrophils, or both, in peripheral blood at acute stage of Kawasaki disease (n=29), Henoch-Schönlein purpura (n=15) and acute febrile illnesses (n=12). The production of the chemokines was assayed by ELISA. The plasma levels of IP-10 were markedly elevated in Kawasaki disease (538.6+/-336.4 pg/mL) and acute febrile illnesses (417.1 +/-262.2 pg/mL) compared with in Henoch-Schönlein purpura (58.7 +/-95.7 pg/mL) (p<0.05). The MCP-1 levels were elevated in Kawasaki disease (443.0 +/-473.1 pg/mL) and acute febrile illnesses (328.6 +/-261.1 pg/mL) compared with in Henoch-Schönlein purpura (82.9 +/-79.0 pg/mL) (p<0.05). The Gro-alpha levels were elevated only in acute febrile illnesses (134.3 +/-153.6 pg/mL) compared with in Kawasaki disease (31.8 +/-22.1 pg/mL) or Henoch-Schönlein purpura (29.4 +/-53.3 pg/mL) (p<0.05). According to these results, monocytes may play an important role in Kawasaki disease. In acute febrile illnesses, both monocytes and neutrophils may play an important role. By contrast, Henoch-Schönlein purpura may not be associated with the role of monocytes and neutrophils. Further studies using a larger number of cases are needed.