Features and Outcomes of Children with Ulcerative Colitis who Undergo a Diagnostic Change: A Single-Center Experience

Ito, Natsuki,Takeuchi, Ichiro,Kyodo, Reiko,Hirano, Yuri,Sato, Takuro,Usami, Masaaki,Shimizu, Hirotaka,Shimizu, Toshiaki,Arai, Katsuhiro The Korean Society of Pediatric Gastroenterology 2021 Pediatric gastroenterology, hepatology & nutrition Vol.24 No.4

Purpose: A change in diagnosis from ulcerative colitis (UC) to Crohn's disease (CD) has been reported in pediatric inflammatory bowel disease; however, only a few clinical characteristics and predictors of this diagnostic change have been reported. We aimed to describe the clinical characteristics of patients with UC who underwent a change in diagnosis to CD and identify variables associated with the change. Methods: The medical records of pediatric patients with UC who were followed up at the National Center for Child Health and Development between 2006 and 2019 were retrospectively reviewed. Clinical data on disease phenotype, laboratory parameters, endoscopic findings, and treatment of patients whose diagnosis changed to CD (cCD) were compared to those of patients whose diagnosis remained UC (rUC). Results: Among the 111 patients initially diagnosed with UC, 11 (9.9%) patients were subsequently diagnosed with CD during follow-up. There was no significant difference between the cCD and rUC groups in terms of sex, age at initial diagnosis, and the extent and severity of disease at initial diagnosis. Albumin and hemoglobin levels were significantly lower in the cCD group than in the rUC group. The proportion of patients who required biologics was significantly higher in the cCD group than in the rUC group (p<0.05). Conclusion: Approximately 10% children initially diagnosed with UC were subsequently diagnosed with CD. Hypoalbuminemia and anemia at initial diagnosis and use of biologics could be predictors of this diagnostic change.

Clinical features of very early-onset inflammatory bowel disease in Japan: a retrospective single-center study

Masaaki Usami,Ichiro Takeuchi,Reiko Kyodo,Yuri Hirano,Kosuke Kashiwagi,Hiroki Fujikawa,Hirotaka Shimizu,Toshinao Kawai,Katsuhiro Arai 대한장연구학회 2022 Intestinal Research Vol.20 No.4

Background/Aims: Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed in patients younger than 6 years, is a challenge for pediatric gastroenterologists. Although there have been reports regarding VEO-IBD in Western countries, those in Asia are still lacking. This study aimed to investigate the clinical features of Japanese VEO-IBD patients.Methods: Patients with VEO-IBD diagnosed between 2006 and 2019 were evaluated retrospectively. The disease phenotypes were classified into ulcerative colitis type (UC-type) and Crohn’s disease type (CD-type), and the clinical features and courses were compared between the phenotypes.Results: Overall, 54 VEO-IBD patients (19 patients with UC-type and 35 patients with CD-type) were evaluated. The median age at onset was 18 months. One patient had severe combined immunodeficiency (SCID), and 9 patients had monogenic IBD. Monogenic IBD was more prevalent in the CD-type patients with perianal disease (CD-type (PD)). The age at onset was significantly lower in the CD-type group (P<0.05). The most common initial symptom was bloody stools (70%), followed by diarrhea (63%), weight loss (24%), fever (20%), and perianal disease (20%). Excluding patients with SCID and monogenic IBD, 23 out of 44 patients (52%) required biologics. The biologics were switched in 11 out of 44 patients (25%), and the majority of these patients (82%) were in the CD-type group. Overall, 9 patients (20%) required intestinal resection or ostomy placement.Conclusions: CD-type tends to occur at an earlier age, and monogenic IBD occurs significantly more frequently in CD-type (PD). Disease severity and treatment should be individualized, owing to the disease heterogeneity.

Side reaction in the hydrogen and carbothermal reductions of BaO and BaCO3: The role of an infinitesimal amount of water

오주현,박지훈,강미정,정성철,Takeuchi Ichiro,정정현,이승훈 한국물리학회 2022 Current Applied Physics Vol.34 No.-

Alkaline earth (AE) metals are irreplaceable ingredients in the synthesis of AE metal-based antiperovskite oxides, and it can be achieved by a chemical reduction of a stable AE metal compound. In this study, hydrogen and carbothermal reduction of BaO and BaCO3 were attempted, and we here report an undesirable side reaction creating barium hydroxide (Ba(OH)2) as the product of the reaction with the small amount of water in ultra-high purity inert gas used in the reduction processes. Such side reaction pathways and products are hardly identifiable in a high-temperature reaction; yet, systematic investigations on phase evolutions using X-ray diffraction, IR spectroscopy, and thermogravimetric analysis enabled the detection of Ba(OH)2⋅xH2O. Unintentional creation of alkaline earth metal oxides in intermediate and subsequent hydration even under a negligible amount of H2O may lead to an unexpected loss of alkaline earth metal element and, consequently, its deficiency in a desired final product.

Long-Term Durability of Infliximab for Pediatric Ulcerative Colitis: A Retrospective Data Review in a Tertiary Children's Hospital in Japan

Shimizu, Hirotaka,Arai, Katsuhiro,Takeuchi, Ichiro,Minowa, Kei,Hosoi, Kenji,Sato, Masamichi,Oka, Itsuhiro,Kaburaki, Yoichiro,Shimizu, Toshiaki The Korean Society of Pediatric Gastroenterology 2021 Pediatric gastroenterology, hepatology & nutrition Vol.24 No.1

Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.

Anxiety, Depression, and Quality of Life in Parents of Adolescents with Inflammatory Bowel Disease: A Longitudinal Study

Satomi Nomura,Yuri Hirano,Ichiro Takeuchi,Hirotaka Shimizu,Katsuhiro Arai 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.5

Purpose: The parents of adolescents with inflammatory bowel disease may experience impaired mental health and quality of life. This longitudinal study aimed to verify whether the mental health and quality of life of the parents of adolescents with inflammatory bowel disease declined when their children had active disease. Methods: Sociodemographic data, parental anxiety, depression, and quality of life were analyzed using validated questionnaires for each variable. After the baseline survey, the second and follow-up surveys were conducted at 3 and 12 months, respectively. The active disease group comprised eight parents whose children had active disease during the baseline and second surveys. The remission group comprised 14 parents whose children remained in remission during both surveys. The improved group comprised nine parents whose children experienced active disease at baseline and remission during the second survey. Parental mental health and quality of life were compared among the groups. Results: Significantly higher levels of anxiety were observed in the active disease group in all surveys (p<0.050). Although depression levels and quality of life did not differ significantly among the three groups, pairing the active disease group with other groups showed some large effect sizes. Conclusion: Parents tended to experience decreased mental health and quality of life when their adolescents experienced active inflammatory bowel disease. Consequently, our hypothesis was partially verified. Therefore, parents need support when their children have active disease; this finding highlights the need for parental support systems.

DEBRIS DISKS AND THE ZODIACAL LIGHT EXPLORED BY THE AKARI MID-INFRARED ALL-SKY SURVEY

DAISUKE ISHIHARA,NAMI TAKEUCHI,TORU KONDO,HIROSHI KOBAYASHI,HIDEHIRO KANEDA,SHU-ICHIRO INUTSUKA,SHINKI OYABU,TAKAHIRO NAGAYAMA,HIDEAKI FUJIWARA,TAKASHI ONAKA 한국천문학회 2017 天文學論叢 Vol.32 No.1

Debris disks are circumstellar dust disks around main-sequence stars. They are important observational clues to understanding the planetary system formation. The zodiacal light is the thermal emission from the dust disk in our Solar system. %For a comprehensive understanding of the nature andthe evolution of dust disks around main-sequence stars,we try a comparative study of debris disks and the zodiacal light. %We search for debris disks using the AKARI mid-infrared all-sky point source catalog. By applying accurate flux estimate of the photospheric emissionbased on the follow-up near-infrared observations with IRSF,we have improved the detection rate of debris disks. %For a detailed study of the structure and grain propertiesin the zodiacal dust cloud,as an example of dust disks around main-sequence stars,we analyze the AKARI mid-infrared all-sky diffuse maps. %As a result of the debris disks search,we found old ($>$1\,Gyr) debris disks which have large excess emissioncompared to their age, which cannot be explained simplyby the conventional steady-state evolution model. %From the zodiacal light analysis, we find the possibilitythat the dust grains trapped in the Earth's resonance orbitshave increased by a factor of $\sim$3 in the past $\sim$20 years. %Combining these results, we discuss the non-steady processes in debris disks and the zodiacal light.

Longitudinal exome-wide association study to identify genetic susceptibility loci for hypertension in a Japanese population

Yoshiki Yasukoch,Jun Sakuma,Ichiro Takeuchi,Kimihiko Kato,Mitsutoshi Oguri,Tetsuo Fujimaki,Hideki Horibe,Yoshiji Yamada 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~ 244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) ‘CAAAA’ comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype ‘TGGGT’. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.

Long-Term Efficacy and Safety of Golimumab for Ulcerative Colitis in a Pediatric Inflammatory Bowel Disease Center in Japan

Kazuhide Tokita,Hirotaka Shimizu,Ichiro Takeuchi,Toshiaki Shimizu,Katsuhiro Arai 대한소아소화기영양학회 2022 Pediatric gastroenterology, hepatology & nutrition Vol.25 No.6

Purpose: Golimumab (GLM) is an anti-tumor necrosis factor (TNF)-α antibody preparation known to be less immunogenic than infliximab (IFX) or adalimumab. Few reports on GLM in pediatric patients with ulcerative colitis (UC) are available. This study aimed to review the long-term durability and safety of GLM in a pediatric center. Methods: The medical records of 17 pediatric patients (eight boys and nine girls) who received GLM at the National Center for Child Health and Development were retrospectively reviewed. Results: The median age at GLM initiation was 13.9 (interquartile range 12.0–16.3) years. Fourteen patients had pancolitis, and 11 had severe disease (pediatric ulcerative colitis activity index ≥65). Ten patients were biologic-naïve, and 50% achieved corticosteroid-free remission at week 54. Two patients discontinued prior anti-TNF-α agents because of adverse events during remission. Both showed responses to GLM without unfavorable events through week 54. However, the efficacy of GLM in patients who showed primary nonresponse or loss of response to IFX was limited. Four of the five patients showed non-response at week 54. Patients with severe disease had significantly lower corticosteroid-free remission rate at week 54 than those without severe disease. No severe adverse events were observed during the study period. Conclusion: GLM appears to be safe and useful for pediatric patients with UC. Patients with mild to moderate disease who responded to but had some adverse events with prior biologics may be good candidates for GLM. Its safety and low immunogenicity profile serve as favorable options for selected children with UC.

Predictors of Small Bowel Transit Time for Capsule Endoscopy in Children with Inflammatory Bowel Disease

Itsuhiro Oka,Rie Funayama,Hirotaka Shimizu,Ichiro Takeuchi,Shuko Nojiri,Toshiaki Shimizu,Katsuhiro Arai 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.4

Purpose: The development of assistive devices has allowed for the performance of capsule endoscopy in children. Anticipating the capsule’s transit time could affect the efficacy of the investigation and potentially minimize the fasting period. This study determined the predictors of small bowel transit time for small-bowel capsule endoscopy in children and adolescents with inflammatory bowel disease. Methods: We retrospectively examined children and adolescents with inflammatory bowel disease who underwent capsule endoscopy by the age 18 at a Japanese tertiary care children’s hospital. Small bowel transit time predictors were analyzed using multiple regression with explanatory variables. Results: Overall, 92 patients, aged 1–17 years, with inflammatory bowel disease (63 Crohn’s disease and 29 ulcerative colitis cases) were examined for factors affecting small bowel transit time. In the simple regression analysis, diagnosis, age, height, weight, serum albumin, general anesthesia, and small intestine lesions were significantly associated with small bowel transit time. In the multiple regression analyses, serum albumin (partial regression coefficient: −58.9, p=0.008), general anesthesia (partial regression coefficient: 127, p<0.001), and small intestine lesions (partial regression coefficient: 30.1, p=0.037) showed significant associations with small bowel transit time. Conclusion: Hypoalbuminemia, the use of general anesthesia for endoscopic delivery of the capsule, and small intestine lesions appeared to be predictors of prolonged small bowel transit time in children and adolescents with inflammatory bowel disease. Expecting the finishing time may improve examination with a fasting period reduction, which benefits both patients and caregivers.

Doping BiFeO₃: approaches and enhanced functionality

Yang, Chan-Ho,Kan, Daisuke,Takeuchi, Ichiro,Nagarajan, Valanoor,Seidel, Jan The Royal Society of Chemistry 2012 Physical chemistry chemical physics Vol.14 No.46

<P>BiFeO<SUB>3</SUB> is one of the most studied multiferroic materials. Both its magnetic and ferroelectric properties can be influenced by doping. A large body of work on the doped material has been presented in the past couple of years. In this paper we provide a perspective on general doping concepts and their impact on the material's functionality.</P> <P>Graphic Abstract</P><P>This paper provides a perspective on general doping concepts of multiferroic BiFeO<SUB>3</SUB> and their impact on the material's functionality. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2cp43082g'> </P>