133 results on '"Umeno J"'
Search Results
2. P325 Combination therapy with adalimumab and immunomodulators decreases incidence of intestinal resection in Crohnʼs disease patients previously treated with infliximab: a large, multicentre cohort study
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Tanaka, H., Kamata, N., Yamada, A., Fujii, T., Endo, K., Yoshino, T., Sugaya, T., Kawaguchi, T., Bamba, S., Ishii, M., Shinzaki, S., Toya, Y., Yanai, Y., Yokoyama, Y., Umeno, J., Okada, T., Kobayashi, T., Nojima, M., and Hibi, T.
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- 2017
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3. P215 Clinical features of chronic enteropathy associated with SLCO2A1 gene (CEAS)
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Umeno, J., Esaki, M., Hirano, A., Hisamatsu, T., Watanabe, K., Hirai, F., Matsui, T., Hibi, T., Kitazono, T., and Matsumoto, T.
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- 2017
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4. DOP24 Japan prospective multicenter study for optimization of COVID-19 vaccinations based on the immune response and safety profile in Inflammatory Bowel Disease patients: Interim analyses of the J-COMBAT trial
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Watanabe, K, primary, Hisamatsu, T, additional, Nakase, H, additional, Nagase, K, additional, Matsuura, M, additional, Aoyama, N, additional, Kobayashi, T, additional, Sakuraba, H, additional, Yokoyama, K, additional, Nishishita, M, additional, Esaki, M, additional, Hirai, F, additional, Nagahori, M, additional, Nanjo, S, additional, Omori, T, additional, Tanida, S, additional, Yokoyama, Y, additional, Moriya, K, additional, Maemoto, A, additional, Handa, O, additional, Ohmiya, N, additional, Shinzaki, S, additional, Kato, S, additional, Tanaka, H, additional, Uraoka, T, additional, Takatsu, N, additional, Suzuki, H, additional, Takahashi, K, additional, Umeno, J, additional, Mishima, Y, additional, Tsuchida, K, additional, Fujiya, M, additional, Hiraoka, S, additional, Yamamoto, S, additional, Saruta, M, additional, Nojima, M, additional, and Andoh, A, additional
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- 2022
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5. Associations of HLA class I alleles in Japanese patients with Crohn’s disease
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Oryoji, D, Hisamatsu, T, Tsuchiya, K, Umeno, J, Ueda, S, Yamamoto, K, Matsumoto, T, Watanabe, M, Hibi, T, and Sasazuki, T
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- 2015
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6. Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations
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Degenhardt, F, Mayr, G, Wendorff, M, Boucher, G, Ellinghaus, E, Ellinghaus, D, ElAbd, H, Rosati, E, Huebenthal, M, Juzenas, S, Abedian, S, Vahedi, H, Thelma, BK, Yang, S-K, Ye, BD, Cheon, JH, Datta, LW, Daryani, NE, Ellul, P, Esaki, M, Fuyuno, Y, McGovern, DPB, Haritunians, T, Hong, M, Juyal, G, Jung, ES, Kubo, M, Kugathasan, S, Lenz, TL, Leslie, S, Malekzadeh, R, Midha, V, Motyer, A, Ng, SC, Okou, DT, Raychaudhuri, S, Schembri, J, Schreiber, S, Song, K, Sood, A, Takahashi, A, Torres, EA, Umeno, J, Alizadeh, BZ, Weersma, RK, Wong, SH, Yamazaki, K, Karlsen, TH, Rioux, JD, Brant, SR, Franke, A, Degenhardt, F, Mayr, G, Wendorff, M, Boucher, G, Ellinghaus, E, Ellinghaus, D, ElAbd, H, Rosati, E, Huebenthal, M, Juzenas, S, Abedian, S, Vahedi, H, Thelma, BK, Yang, S-K, Ye, BD, Cheon, JH, Datta, LW, Daryani, NE, Ellul, P, Esaki, M, Fuyuno, Y, McGovern, DPB, Haritunians, T, Hong, M, Juyal, G, Jung, ES, Kubo, M, Kugathasan, S, Lenz, TL, Leslie, S, Malekzadeh, R, Midha, V, Motyer, A, Ng, SC, Okou, DT, Raychaudhuri, S, Schembri, J, Schreiber, S, Song, K, Sood, A, Takahashi, A, Torres, EA, Umeno, J, Alizadeh, BZ, Weersma, RK, Wong, SH, Yamazaki, K, Karlsen, TH, Rioux, JD, Brant, SR, and Franke, A
- Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
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- 2021
7. Letter: lansoprazole consumption is more common in Japanese patients with collagenous colitis
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Umeno, J., Esaki, M., Nuki, Y., Kim, H., Kitazono, T., and Matsumoto, T.
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- 2013
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8. P822 Genetic analysis of ulcerative colitis in Japanese individuals using population-specific SNP array
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Okamoto, D, primary, Kakuta, Y, additional, Takeo, N, additional, Moroi, R, additional, Kuroha, M, additional, Kanazawa, Y, additional, Hisashi, S, additional, Fuyuno, Y, additional, Umeno, J, additional, Hirano, A, additional, Torisu, T, additional, Nakamura, M, additional, Esaki, M, additional, Matsumoto, T, additional, Kinouchi, Y, additional, and Masamune, A, additional
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- 2020
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9. P752 A nationwide survey of chronic enteropathy associated with SLCO2A1 gene in Japan
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Umeno, J, primary, Fuyuno, Y, additional, Torisu, T, additional, Hirano, A, additional, Esaki, M, additional, Yanai, S, additional, Ohmiya, N, additional, Hisamatsu, T, additional, Watanabe, K, additional, Hosoe, N, additional, Ogata, H, additional, Hirai, F, additional, Hisabe, T, additional, Matsui, T, additional, Yao, T, additional, Kitazono, T, additional, and Matsumoto, T, additional
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- 2020
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10. P732 The clinical efficacy and safety of indigo naturalis in induction & maintenance therapy for moderate-to-severe ulcerative colitis: A single-centre prospective uncontrolled open-label study
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Matsuno, Y, primary, Hirano, A, additional, Torisu, T, additional, Fuyuno, Y, additional, Okamoto, Y, additional, Shin, F, additional, Tomohiko, M, additional, Umeno, J, additional, Hirakawa, Y, additional, Esaki, M, additional, and Kitazono, T, additional
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- 2020
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11. P838 Characteristics of mucosal microbial composition of patients with inflammatory bowel disease susceptibility HLA genotype
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Hirano, A, primary, Umeno, J, additional, and Torisu, T, additional
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- 2020
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12. P230 Prediction of loss of response to anti-TNF therapy using SES-CD in patients with Crohn’s disease
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Fuyuno, Y, primary, Torisu, T, additional, Hirano, A, additional, Fujioka, S, additional, Umeno, J, additional, Moriyama, T, additional, Kitazono, T, additional, and Esaki, M, additional
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- 2019
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13. P395 Postoperative immunosuppressive therapies decrease the risk of second intestinal surgery in patients with Crohn’s disease: a retrospective cohort study
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Nagata, Y, primary, Esaki, M, additional, Fuyuno, Y, additional, Okamoto, Y, additional, Fujioka, S, additional, Hirano, A, additional, Umeno, J, additional, Torisu, T, additional, Moriyama, T, additional, Nakamura, S, additional, and Kitazono, T, additional
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- 2019
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14. Gastrointestinal: Multiple venous malformations and polyps of the small intestine in Cowden syndrome
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Harada, A, primary, Umeno, J, additional, and Esaki, M, additional
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- 2018
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15. P324 Inter- and intra-observer variation of capsule endoscopic findings for the diagnosis of Crohn’s disease: A case–control study
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Esaki, M, primary, Washio, E, additional, Morishita, T, additional, Sakamoto, K, additional, Fuyuno, Y, additional, Hirano, A, additional, Umeno, J, additional, Kitazono, T, additional, Matsumoto, T, additional, and Suzuki, Y, additional
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- 2018
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16. Gastrointestinal: Peutz–Jeghers syndrome with a novel frameshift mutation in STK 11 gene observed by magnifying narrowband imaging endoscopy.
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Kawasaki, K, Kawatoko, S, Nagasue, T, Umeno, J, and Torisu, T
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PEUTZ-Jeghers syndrome ,FRAMESHIFT mutation ,ENDOSCOPY ,CERVICAL intraepithelial neoplasia - Abstract
This article discusses a case of Peutz-Jeghers syndrome (PJS) in a 62-year-old woman who presented with intermittent melena. The patient had multiple polyps in the stomach, as well as polyps in the small and large bowels. The largest gastric polyp had a reddish color and a lobular surface structure, which was observed using magnifying endoscopy with narrowband imaging (M-NBI). Genetic analysis revealed a frameshift mutation in the STK 11 gene. The article suggests that M-NBI findings, in combination with Helicobacter pylori infection status, may be useful for diagnosing Peutz-Jeghers polyps, and the novel mutation in the STK 11 gene may contribute to delayed-onset PJS. [Extracted from the article]
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- 2024
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17. The influence of CYP2C19 polymorphisms on exacerbating effect of rabeprazole in celecoxib‐induced small bowel injury
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Nuki, Y., primary, Umeno, J., additional, Washio, E., additional, Maehata, Y., additional, Hirano, A., additional, Miyazaki, M., additional, Kobayashi, H., additional, Kitazono, T., additional, Matsumoto, T., additional, and Esaki, M., additional
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- 2017
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18. Associations of HLA class I alleles in Japanese patients with Crohn’s disease
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Oryoji, D, primary, Hisamatsu, T, additional, Tsuchiya, K, additional, Umeno, J, additional, Ueda, S, additional, Yamamoto, K, additional, Matsumoto, T, additional, Watanabe, M, additional, Hibi, T, additional, and Sasazuki, T, additional
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- 2014
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19. P442 Replication of susceptibility loci identified by genome-wide association studies for ulcerative colitis in Japanese population
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Matsumoto, T., primary, Umeno, J., additional, Asano, K., additional, Matsui, T., additional, Kubo, M., additional, Kiyohara, Y., additional, Iida, M., additional, and Kitazono, T., additional
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- 2012
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20. Endoscopic features of intestinal follicular lymphoma: the value of double-balloon enteroscopy
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Nakamura, S., primary, Matsumoto, T., additional, Umeno, J., additional, Yanai, S., additional, Shono, Y., additional, Suekane, H., additional, Hirahashi, M., additional, Yao, T., additional, and Iida, M., additional
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- 2007
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21. Gastric MALT lymphoma with t(14;18)(q32;q21) involving IGH and BCL2 genes that responded to Helicobacter pylori eradication
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Nakamura, S., primary, Ye, H., additional, Bacon, C. M, additional, Liu, H., additional, Goatly, A., additional, Matsumoto, T., additional, Koga, H., additional, Umeno, J., additional, Ohji, Y., additional, Yao, T., additional, Nakahara, T., additional, Iida, M., additional, and Du, M.-Q., additional
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- 2007
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22. Risk factors for local recurrence of superficial esophageal cancer after treatment by endoscopic mucosal resection
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Esaki, M., primary, Matsumoto, T., additional, Hirakawa, K., additional, Nakamura, S., additional, Umeno, J., additional, Koga, H., additional, Yao, T., additional, and Iida, M., additional
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- 2007
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23. Arginase 2 attenuates ulcerative colitis by antioxidant effects of spermidine.
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Imazu N, Torisu T, Yokote A, Umeno J, Kawasaki K, Fujioka S, Matsuno Y, Nagasue T, Kawatoko S, Moriyama T, Nitahata T, Uchida Y, Aihara S, Taniguchi Y, Oda Y, and Kitazono T
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- Animals, Humans, Mice, Male, Intestinal Mucosa metabolism, Intestinal Mucosa drug effects, Mice, Knockout, Disease Models, Animal, Female, Colon metabolism, Colon pathology, Colon drug effects, Middle Aged, Adult, Colitis, Ulcerative drug therapy, Colitis, Ulcerative metabolism, Spermidine pharmacology, Spermidine metabolism, Antioxidants pharmacology, Arginase metabolism, Oxidative Stress drug effects, Mice, Inbred C57BL, Dextran Sulfate
- Abstract
Background: Spermidine suppress oxidative stress and is involved in various disease pathogenesis including ulcerative colitis (UC). Arginase 2 (ARG2) plays a central role in the synthesis of spermidine. This study aimed to clarify the effect of endogenously produced spermidine on colitis., Methods: The physiological role of ARG2 and spermidine was investigated using Arg2-deficient mice with reduced spermidine. Immunohistochemical staining of the rectum was used to analyze ARG2 expression and spermidine levels in healthy controls and UC patients., Results: In mice with dextran sulfate sodium-induced colitis, ARG2 and spermidine levels were increased in the rectal epithelium. Spermidine protects colonic epithelial cells from oxidative stress and Arg2 knockdown cells reduced antioxidant activity. Organoids cultured from the small intestine and colon of Arg2-deficient mice both were more susceptible to oxidative stress. Colitis was exacerbated in Arg2-deficient mice compared to wild-type mice. Supplementation with spermidine result in comparable severity of colitis in both wild-type and Arg2-deficient mice. In the active phase of UC, rectal ARG2 expression and spermidine accumulation were increased compared to remission. ARG2 and spermidine levels were similar in healthy controls and UC remission patients., Conclusions: ARG2 produces spermidine endogenously in the intestinal epithelium and has a palliative effect on ulcerative colitis. ARG2 and spermidine are potential novel therapeutic targets for UC., (© 2024. Japanese Society of Gastroenterology.)
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- 2024
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24. Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis.
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Naito T, Osaka R, Kakuta Y, Kawai Y, Khor SS, Umeno J, Tokunaga K, Nagai H, Shimoyama Y, Moroi R, Shiga H, Nagasaki M, Kinouchi Y, and Masamune A
- Abstract
Background: It is crucial to pinpoint the metabolites that cause Crohn's disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC., Methods: As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance-weighted method, while stability of the findings was evaluated through sensitivity analyses., Results: After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10-3; and OR, 0.64; P = 1.90 × 10-2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10-4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10-2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10-2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10-2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites., Conclusions: In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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25. Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.
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Makuuchi M, Kakuta Y, Umeno J, Fujii T, Takagawa T, Ibuka T, Miura M, Sasaki Y, Takahashi S, Nakase H, Kiyohara H, Tominaga K, Shimodaira Y, Hiraoka S, Ueno N, Yanai S, Yoshihara T, Kakimoto K, Matsuoka K, Hayashi R, Nanjo S, Iwama I, Ishiguro Y, Chiba H, Endo K, Kagaya T, Fukuda T, Sakata Y, Kudo T, Takagi T, Takahashi K, Naganuma M, Shinozaki M, Ogata N, Tanaka H, Narimatsu K, Miyazaki H, Ishige T, Onodera M, Hashimoto Y, Nagai H, Shimoyama Y, Naito T, Moroi R, Shiga H, Kinouchi Y, Andoh A, Hisamatsu T, and Masamune A
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- Humans, Female, Male, Retrospective Studies, Adult, Middle Aged, Japan, Young Adult, Aged, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents adverse effects, Adolescent, Risk Factors, Codon, Nudix Hydrolases, Pyrophosphatases genetics, Mercaptopurine therapeutic use, Mercaptopurine adverse effects, Genotype, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases genetics, Azathioprine adverse effects, Azathioprine therapeutic use
- Abstract
Background: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies., Methods: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status., Results: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users., Conclusions: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach., (© 2024. The Author(s).)
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- 2024
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26. Duodenal microbiome in chronic kidney disease.
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Kondo M, Torisu T, Nagasue T, Shibata H, Umeno J, Kawasaki K, Fujioka S, Matsuno Y, Moriyama T, and Kitazono T
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- Humans, RNA, Ribosomal, 16S genetics, Duodenum, Intestine, Small, Feces, Renal Insufficiency, Chronic, Gastrointestinal Microbiome
- Abstract
Background: The intestinal microbiome is involved in the pathogenesis of chronic kidney disease (CKD). Despite its importance, the microbiome of the small intestinal mucosa has been little studied due to sampling difficulties, and previous studies have mainly focused on fecal sources for microbiome studies. We aimed to characterize the small intestinal microbiome of CKD patients by studying the microbiome collected from duodenal and fecal samples of CKD patients and healthy controls., Methods: Overall, 28 stage 5 CKD patients and 21 healthy participants were enrolled. Mucosal samples were collected from the deep duodenum during esophagogastroduodenoscopy and fecal samples were also collected. The 16S ribosomal RNA gene sequencing using Qiime2 was used to investigate and compare the microbial structure and metagenomic function of the duodenal and fecal microbiomes., Results: The duodenal flora of CKD patients had decreased alpha diversity compared with the control group. On the basis of taxonomic composition, Veillonella and Prevotella were significantly reduced in the duodenal flora of CKD patients. The tyrosine and tryptophan metabolic pathways were enhanced in the urea toxin-related metabolic pathways based on the Kyoto Encyclopedia of Genes and Genomes database., Conclusion: The small intestinal microbiome in CKD patients is significantly altered, indicating that increased intestinal permeability and production of uremic toxin may occur in the upper small intestine of CKD patients., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)
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- 2024
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27. Ustekinumab Decreases Circulating Th17 Cells in Ulcerative Colitis.
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Imazu N, Torisu T, Ihara Y, Umeno J, Kawasaki K, Fujioka S, Fuyuno Y, Matsuno Y, Moriyama T, and Kitazono T
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- Humans, Th17 Cells metabolism, Ustekinumab pharmacology, Ustekinumab therapeutic use, CD4-Positive T-Lymphocytes metabolism, Th1 Cells metabolism, Colitis, Ulcerative drug therapy
- Abstract
Objective T helper (Th) cells play a central role in the pathogenesis of ulcerative colitis (UC). The present study analyzed the changes in circulating T cells by administration of ustekinumab (UST), an interleukin-12/23p40 antibody. Methods CD4 T cells were isolated from peripheral blood at 0 and 8 weeks after UST treatment, and we analyzed the proportion of CD4 T cells by flow cytometry. Clinical information and laboratory data were obtained at 0, 8, and 16 weeks. Patients We evaluated 13 patients with UC who received UST for the induction of remission between July 2020 and August 2021. Results The median partial Mayo score improved from 4 (1-7) to 0 (0-6) (p<0.001) with UST. Among serological parameters, albumin concentrations, C-reactive protein concentrations, the sedimentation rate, and leucine-rich alpha 2 glycoprotein concentrations showed significant improvement with UST. A flow cytometric analysis of circulating CD4 T cells showed that the percentage of Th17 cells was significantly decreased by UST treatment in all patients (1.85% to 0.98%, p<0.0001). Th1 cells were significantly increased by UST treatment (9.52% to 10.4%, p<0.05), but Th2 and regulatory T cells were not significantly different. The high-Th17 subgroup had a significantly better partial Mayo score than the low-Th17 subgroup at 16 weeks after UST treatment (0 vs. 1, p=0.028). Conclusion Treatment with UST decreases circulating Th17 cells, suggesting that this change may be related to the anti-inflammatory effect of UC.
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- 2024
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28. [Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].
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Saiki T, Harada A, Umeno J, Iwatake S, Kajiya Y, Taniguchi Y, Morisaki S, Nagasue T, Suekane H, and Torisu T
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- Humans, Male, Aged, Neoplasms, Second Primary pathology, Neoplasms, Multiple Primary, Adenocarcinoma diagnosis, Hamartoma Syndrome, Multiple complications
- Abstract
A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.
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- 2024
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29. Reply to "Ferroptosis in the colon epithelial cells as a therapeutic target for ulcerative colitis".
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Yokote A, Imazu N, Umeno J, Kawasaki K, Fujioka S, Fuyuno Y, Matsuno Y, Moriyama T, Miyawaki K, Akashi K, Kitazono T, and Torisu T
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- Humans, Colon, Epithelial Cells, Colitis, Ulcerative drug therapy, Ferroptosis
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- 2024
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30. Immunomodulators after the discontinuation of anti-tumor necrosis factor-alpha antibody treatment and relapse in ulcerative colitis: A multicenter cohort study.
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Asonuma K, Ozeki K, Yamazaki H, Okabayashi S, Okano S, Ozaki R, Nishimata N, Kiyohara H, Ichinari N, Kobayashi T, Yamada M, Matsubayashi M, Yokoyama Y, Arimitsu S, Umeno J, Munetomo Y, Andoh A, and Shinzaki S
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- Humans, Tumor Necrosis Factor-alpha, Infliximab therapeutic use, Cohort Studies, Retrospective Studies, Tumor Necrosis Factor Inhibitors therapeutic use, Immunologic Factors adverse effects, Remission Induction, Recurrence, Necrosis, Colitis, Ulcerative drug therapy
- Abstract
Background and Aim: Strategies to reduce relapse using immunomodulators (IMs) after discontinuing anti-tumor necrosis factor-alpha (TNF-α) antibody treatment are controversial in patients with ulcerative colitis (UC). In this study, we assessed the association between IMs after discontinuing anti-TNF-α antibody treatment and relapse in patients with UC., Methods: This retrospective, multicenter cohort study included 257 patients with UC in clinical remission. These patients discontinued anti-TNF-α antibody treatment between June 2010 and March 2019 and were followed up until March 2020. We evaluated the differences in relapse rates between patients with IMs (IM group) and those without IMs (non-IM group) after discontinuing the treatment. Relapse was defined as further undergoing an induction treatment or colectomy. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for relapse. Exploratory analyses were performed to identify other factors that could predict relapse., Results: During the median follow-up period of 22 months (interquartile range: 10-41), 114 relapses occurred: 42/100 (42.0%) in the IM group and 72/157 (45.9%) in the non-IM group. In the multivariable analysis, IMs were not associated with relapse (HR, 0.95 [95% CI, 0.64-1.41]). In the exploratory analyses, discontinuation due to side effects (HR, 1.83 [95% CI, 1.18-2.82]) and younger age (HR, 0.99 [95% CI, 0.98-1.00]) predicted relapse., Conclusion: Immunomodulators were not associated with relapse after discontinuing anti-TNF-α antibody treatment in patients with UC. Careful patient follow-up is needed when discontinuing due to side effects or when the patient is of a younger age at the time of discontinuation., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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31. White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study.
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Kiyohara H, Yamazaki H, Moriya K, Akimoto N, Kawai S, Takenaka K, Fukuda T, Tominaga K, Umeno J, Shinzaki S, Honzawa Y, Takagi T, Ichikawa H, Endo T, Ozaki R, Andoh A, Matsuoka K, Hibi T, and Kobayashi T
- Abstract
Introduction: Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study., Methods: This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for 3 years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts <3,000/µL ( N = 31), 3,000-4,000/µL ( N = 167), 4,000-5,000/µL ( N = 241), and ≥5,000/µL ( N = 284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse., Results: During a median follow-up period of 1,095 (interquartile range, 1,032-1,119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) (95% confidence interval [CI]) were 1.50 (0.74-3.06), 1.02 (0.66-1.59), and 0.67 (0.43-1.05) in WBC <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively (WBC ≥5,000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs (95% CI) were 1.21 (0.59-2.49), 1.08 (0.69-1.69), and 0.69 (0.44-1.07), in <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse., Discussion/conclusion: WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy., Competing Interests: Hiroki Kiyohara and Tomohiro Fukuda received a research grant from Mitsubishi Tanabe Pharma. Shinichiro Shinzaki served as a speaker, a consultant, or an advisory role for Janssen Pharmaceuticals and Mitsubishi Tanabe Pharma. Tomohisa Takagi received lecture fees from Janssen Pharmaceuticals, Mitsubishi Tanabe Pharma, Towa Pharmaceutical, and Mochida Pharmaceutical, and received a research grant from Fujifilm Medical. Katsuyoshi Matsuoka served as a speaker, a consultant, or an advisory role for Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Janssen Pharmaceuticals, AbbVie, EA Pharma, Pfizer, and Mochida Pharmaceutical, and received research grants from Janssen Pharmaceuticals, Mitsubishi Tanabe Pharma, AbbVie, EA Pharma, Mochida Pharmaceutical, and Nippon Kayaku Pharmaceutical. Kaoru Yokoyama served as a speaker, a consultant, or an advisory role for Takeda Pharmaceutical and Mochida Pharmaceutical. Akira Andoh served as a speaker, a consultant, or an advisory role for Takeda Pharmaceutical, Janssen Pharmaceuticals, Miyarisan Pharmaceutical, and AbbVie, and received research grant from AbbVie. Toshifumi Hibi served as a speaker, a consultant, or an advisory role for AbbVie GK, Mitsubishi Tanabe Pharma, Sandoz, Takeda Pharmaceutical, Pfizer, and Janssen Pharmaceuticals, received research grants from AbbVie GK, Activaid, Alfresa Pharma, JMDC, Gilead Sciences, Nippon Kayaku, Eli Lilly Japan, Mochida Pharmaceutical, Janssen Pharmaceuticals, Pfizer Japan, Takeda Pharmaceutical, Bristol Myers Squibb, Google Asia Pacific Pte. Ltd., Mitsubishi Tanabe Pharma, Zeria, and received endowed chairs from Otsuka Holdings, EA Pharma, JIMRO, AbbVie, Zeria, Kyorin, and Mochida Pharmaceutical. Taku Kobayashi served as a speaker, a consultant, or an advisory role for AbbVie, Janssen Pharmaceuticals, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, and Pfizer, received research grants from AbbVie GK, Activaid, Alfresa Pharma, JMDC, Gilead Sciences, Nippon Kayaku, Eli Lilly Japan, Mochida Pharmaceutical, Janssen Pharmaceuticals, Pfizer Japan, Takeda Pharmaceutical, Bristol Myers Squibb, Google Asia Pacific Pte. Ltd., Mitsubishi Tanabe Pharma, Zeria, and received endowed chairs from Otsuka Holdings, EA Pharma, JIMRO, AbbVie, Zeria, Kyorin, and Mochida Pharmaceutical., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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32. Disease Flares Following COVID-19 Vaccination in Patients with Inflammatory Bowel Disease.
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Yoshida Y, Fujioka S, Moriyama T, Umeno J, Kawasaki K, Fuyuno Y, Matsuno Y, Ihara Y, Torisu T, and Kitazono T
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- Humans, Symptom Flare Up, Vaccination adverse effects, Colitis, Ulcerative drug therapy, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Crohn Disease drug therapy, Inflammatory Bowel Diseases complications
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Objective Flares of inflammatory bowel disease (IBD) can occur infrequently after vaccination for coronavirus disease 2019 (COVID-19), although the details of this phenomenon are poorly understood. To clarify the possibility of an unfavorable response in patients with IBD, we investigated IBD-related symptoms during the COVID-19 vaccination. Methods Between October 2021 and February 2022, we obtained the COVID-19 vaccination status of 411 IBD patients who were being treated at our institution. The disease course of IBD after vaccination was investigated in 188 patients with ulcerative colitis (UC) and 119 patients with Crohn's disease (CD) who had received at least one dose of the vaccine during the clinical remission phase. The baseline characteristics before vaccination were compared between the patients with UC with or without disease flares. Results During the 30-day follow-up period, eight patients with UC (4.3%) and one patient with CD (0.8%) experienced disease flares following vaccination. Disease flares occurred after the first vaccination in six patients and after the second vaccination in three patients. As for the timing of onset of disease flares, eight events (88.9%) occurred within one week of vaccination. Two patients required hospitalization, and one patient with CD required surgery for an intra-abdominal abscess. The baseline characteristics did not significantly differ between patients with UC who experienced flares and those who did not. Conclusion IBD flares following COVID-19 vaccination are rare and vaccination should therefore be recommended for patients with IBD. However, the possibility of disease flares should be considered for approximately one week after each vaccination, especially in patients with UC.
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- 2023
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33. Clinical Features of Gastroduodenal Ulcers in Kidney Transplant Patients.
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Kondo M, Torisu T, Ihara Y, Kawasaki K, Umeno J, Kawatoko S, Tsuchimoto A, Nakano T, Okabe Y, and Kitazono T
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- Humans, Aged, Ulcer complications, Retrospective Studies, Immunosuppressive Agents adverse effects, Kidney Transplantation adverse effects, Helicobacter Infections complications, Helicobacter Infections epidemiology, Helicobacter pylori, Peptic Ulcer complications, Peptic Ulcer epidemiology, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic epidemiology
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Objective The risk of developing peptic ulcers and gastrointestinal bleeding is high in patients with chronic kidney disease (CKD). Whether or not kidney transplant patients, who are treated with multiple medications, including immunosuppressive drugs, are at an increased risk of developing peptic ulcers is unclear. Methods In this retrospective study, we compared the clinical and endoscopic features of gastroduodenal ulcers between kidney transplant patients and CKD patients. The subjects underwent upper gastrointestinal endoscopy between January 2015 and March 2021. Results Gastroduodenal ulcers were observed more frequently (6.5%) in kidney transplant patients than in CKD patients (2.1%) (p=0.026). Due in part to the lower median age in the kidney transplant ulcer group than in the CKD ulcer group (59 vs. 70 years old, p=0.016), the rates of atrophic gastritis and Helicobacter pylori infection were also lower in the kidney transplant ulcer group than in the CKD ulcer group. Significantly more kidney transplant patients were treated with acid secretion inhibitors than CKD ulcer patients (100% vs. 34.8%, p=0.0005). Peptic ulcers were observed frequently in kidney transplant patients, even though common risk factors for gastroduodenal ulcers other than immunosuppressive drugs were few. All kidney transplant patients were taking immunosuppressive medications, and tacrolimus, mycophenolate mofetil, and methylprednisolone were taken more frequently than others. Conclusion Kidney transplant patients have a high risk of developing gastroduodenal ulcers. All kidney transplant patients take immunosuppressive medications, so there may be an association between immunosuppressive medications and gastroduodenal ulcer development.
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- 2023
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34. Importance of Magnifying Endoscopy in the Diagnosis and Management of Gastric Juvenile Polyposis Syndrome.
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Umeno J and Torisu T
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- Humans, Stomach, Endoscopy, Gastrointestinal, Neoplastic Syndromes, Hereditary diagnosis, Neoplastic Syndromes, Hereditary genetics, Intestinal Polyposis diagnosis, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms therapy
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- 2023
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35. Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT.
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Watanabe K, Nojima M, Nakase H, Sato T, Matsuura M, Aoyama N, Kobayashi T, Sakuraba H, Nishishita M, Yokoyama K, Esaki M, Hirai F, Nagahori M, Nanjo S, Omori T, Tanida S, Yokoyama Y, Moriya K, Maemoto A, Handa O, Ohmiya N, Tsuchiya K, Shinzaki S, Kato S, Uraoka T, Tanaka H, Takatsu N, Nishida A, Umeno J, Nakamura M, Mishima Y, Fujiya M, Tsuchida K, Hiraoka S, Okabe M, Toyonaga T, Matsuoka K, Andoh A, Hirota Y, and Hisamatsu T
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- Humans, COVID-19 Vaccines administration & dosage, Prospective Studies, Vaccination, COVID-19 prevention & control, Inflammatory Bowel Diseases drug therapy
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Background: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown., Methods: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls., Results: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001)., Conclusions: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders., (© 2023. Japanese Society of Gastroenterology.)
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- 2023
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36. Ferroptosis in the colon epithelial cells as a therapeutic target for ulcerative colitis.
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Yokote A, Imazu N, Umeno J, Kawasaki K, Fujioka S, Fuyuno Y, Matsuno Y, Moriyama T, Miyawaki K, Akashi K, Kitazono T, and Torisu T
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- Humans, Indigo Carmine pharmacology, Caco-2 Cells, Antioxidants, Epithelial Cells, Colitis, Ulcerative drug therapy, Colitis, Ulcerative genetics, Ferroptosis
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Background: Ferroptosis, a type of programmed cell death triggered by oxidative stress, was suspected to play a role in ulcerative colitis. Indigo naturalis is highly effective against ulcerative colitis, but its mechanism is unclear. This study found that indigo naturalis treatment suppressed ferroptosis., Methods: We analyzed 770 mRNA expressions of patients with ulcerative colitis. Suppression of ferroptosis by indigo naturalis treatment was shown using a cell death assay. Malondialdehyde levels and reactive oxygen species were analyzed in CaCo-2 cells treated with indigo naturalis. Glutathione metabolism was shown by metabolomic analysis. Extraction of the ingredients indigo naturalis from the rectal mucosa was performed using liquid chromatograph-mass spectrometry., Results: Gene expression profiling showed that indigo naturalis treatment increased antioxidant genes in the mucosa of patients with ulcerative colitis. In vitro analysis showed that nuclear factor erythroid-2-related factor 2-related antioxidant gene expression was upregulated by indigo naturalis. Indigo naturalis treatment rendered cells resistant to ferroptosis. Metabolomic analysis suggested that an increase in reduced glutathione by indigo naturalis. The protein expression of CYP1A1 and GPX4 was increased in the rectum by treatment with indigo naturalis. The main ingredients of indigo naturalis, indirubin and indigo inhibited ferroptosis. Indirubin was detected in the rectal mucosa of patients with ulcerative colitis who were treated with indigo naturalis., Conclusions: Suppression of ferroptosis by indigo naturalis in the intestinal epithelium could be therapeutic target for ulcerative colitis. The main active ingredient of indigo naturalis may be indirubin., (© 2023. Japanese Society of Gastroenterology.)
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- 2023
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37. Usefulness of Serum Leucine-Rich Alpha-2 Glycoprotein as a Surrogate Marker of Small Bowel Mucosal Injury in Crohn's Disease.
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Saiki T, Torisu T, Harada A, Kajiya Y, Taniguchi Y, Morisaki S, Umeno J, Suekane H, and Kitazono T
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Introduction: Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel., Methods: We retrospectively analyzed the clinical data of 30 patients with Crohn's disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn's Disease Activity Index [CECDAI], and Crohn's Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE., Results: LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) ( p < 0.05 , Spearman's rank correlation coefficient). The degree of correlation was greater for LRG than for CRP., Conclusions: LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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38. Small bowel capsule endoscopy examination and open access database with artificial intelligence: The SEE-artificial intelligence project.
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Yokote A, Umeno J, Kawasaki K, Fujioka S, Fuyuno Y, Matsuno Y, Yoshida Y, Imazu N, Miyazono S, Moriyama T, Kitazono T, and Torisu T
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Objectives: Artificial intelligence (AI) may be practical for image classification of small bowel capsule endoscopy (CE). However, creating a functional AI model is challenging. We attempted to create a dataset and an object detection CE AI model to explore modeling problems to assist in reading small bowel CE., Methods: We extracted 18,481 images from 523 small bowel CE procedures performed at Kyushu University Hospital from September 2014 to June 2021. We annotated 12,320 images with 23,033 disease lesions, combined them with 6161 normal images as the dataset, and examined the characteristics. Based on the dataset, we created an object detection AI model using YOLO v5 and we tested validation., Results: We annotated the dataset with 12 types of annotations, and multiple annotation types were observed in the same image. We test validated our AI model with 1396 images, and sensitivity for all 12 types of annotations was about 91%, with 1375 true positives, 659 false positives, and 120 false negatives detected. The highest sensitivity for individual annotations was 97%, and the highest area under the receiver operating characteristic curve was 0.98, but the quality of detection varied depending on the specific annotation., Conclusions: Object detection AI model in small bowel CE using YOLO v5 may provide effective and easy-to-understand reading assistance. In this SEE-AI project, we open our dataset, the weights of the AI model, and a demonstration to experience our AI. We look forward to further improving the AI model in the future., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2023
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39. Continuous use of antithrombotic medications during peri-endoscopic submucosal dissection period for colorectal lesions: A propensity score matched study.
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Kawasaki K, Torisu T, Esaki M, Eizuka M, Kawatoko S, Kumei T, Hirai M, Kondo M, Fujioka S, Fuyuno Y, Matsuno Y, Umeno J, Moriyama T, Kitazono T, Sugai T, and Matsumoto T
- Subjects
- Humans, Fibrinolytic Agents adverse effects, Postoperative Hemorrhage chemically induced, Postoperative Hemorrhage prevention & control, Propensity Score, Risk Factors, Retrospective Studies, Endoscopic Mucosal Resection adverse effects, Colorectal Neoplasms drug therapy, Stomach Neoplasms etiology
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Background and Aim: The aim of this study was to elucidate the continuous use of antithrombotic medications during the peri-colorectal endoscopic submucosal dissection (ESD) period., Methods: This study included 468 patients with colorectal epithelial neoplasms treated by ESD, consisting of 82 under antithrombotic medications and 386 patients without the medications. Among patients taking antithrombotic medications, antithrombotic agents were continued during the peri-ESD period. Clinical characteristics and adverse events were compared after propensity score matching., Results: Before and after propensity score matching, post-colorectal ESD bleeding rate was higher in patients continuing antithrombotic medications (19.5% and 21.6%, respectively) than in those not taking antithrombotic medications (2.9% and 5.4%, respectively). In the Cox regression analysis, continuation of antithrombotic medications was associated with post-ESD bleeding risk (hazard ratio, 3.73; 95% confidence interval, 1.2-11.6; P < 0.05) compared with patients without antithrombotic therapy. All patients who experienced post-ESD bleeding were successfully treated by endoscopic hemostasis procedure or conservative therapy., Conclusions: Continuation of antithrombotic medications during the peri-colorectal ESD period increases the risk of bleeding. However, the continuation may be acceptable under careful monitoring for post-ESD bleeding., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2023
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40. Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.
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Liu Z, Liu R, Gao H, Jung S, Gao X, Sun R, Liu X, Kim Y, Lee HS, Kawai Y, Nagasaki M, Umeno J, Tokunaga K, Kinouchi Y, Masamune A, Shi W, Shen C, Guo Z, Yuan K, Zhu S, Li D, Liu J, Ge T, Cho J, Daly MJ, McGovern DPB, Ye BD, Song K, Kakuta Y, Li M, and Huang H
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- Humans, East Asian People, European People, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics, Tumor Necrosis Factor Ligand Superfamily Member 15 genetics, Colitis, Ulcerative genetics, Crohn Disease genetics, Inflammatory Bowel Diseases genetics
- Abstract
Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with ~370,000 EUR individuals (~30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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41. Clinical Guidelines for Diagnosis and Management of Juvenile Polyposis Syndrome in Children and Adults-Secondary Publication.
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Matsumoto T, Umeno J, Jimbo K, Arai M, Iwama I, Kashida H, Kudo T, Koizumi K, Sato Y, Sekine S, Tanaka S, Tanakaya K, Tamura K, Hirata K, Fukahori S, Esaki M, Ishikawa H, Iwama T, Okazaki Y, Saito Y, Matsuura N, Mutoh M, Tomita N, Akiyama T, Yamamoto T, Ishida H, and Nakayama Y
- Abstract
Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps within the gastrointestinal tract. SMAD4 or BMPR1A is known as a causative gene of JPS. Approximately 75% of newly diagnosed cases have an autosomal-dominantly inherited condition, whereas 25% are sporadic without previous history of polyposis in the family pedigree. Some patients with JPS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood. JPS is classified into three categories according to phenotypic features of polyp distributions, including generalized juvenile polyposis, juvenile polyposis coli, and juvenile polyposis of the stomach. Juvenile polyposis of the stomach is caused by germline pathogenic variants of SMAD4 with a high risk leading to gastric cancer. Pathogenic variants of SMAD4 are also associated with hereditary hemorrhagic telangiectasia-JPS complex, inducing regular cardiovascular survey. Despite growing concerns regarding the managing JPS in Japan, there are no practical guidelines. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labor and Welfare involving specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of JPS with three clinical questions and corresponding recommendations based on a careful review of the evidence and involve incorporating the concept of the Grading of Recommendations, Assessment, Development, and Evaluation system. Herein, we present the clinical practice guidelines of JPS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with JPS., Competing Interests: Conflicts of Interest Prior to the preparation of these clinical guidelines, all members of the Guidelines Committee declare any conflict of interest. T.M. received payment for lectures from Mitsubishi Tanabe Pharma Co.; EA Pharma Co., Ltd.; Janssen Pharmaceutical K.K.; AbbVie GK. and KYORIN Pharmaceutical Co., Ltd.; grants from Mitsubishi Tanabe Pharma Co. and NIPPON KAYAKU CO., LTD. M.A. received payment for lectures from AstraZeneca Co., Ltd. N.T. has received grants from Taiho Pharmaceutical Co., Ltd. H.I. has received grants from Taiho Pharmaceutical Co., Ltd. and Yakult Honsha Co., Ltd. The other authors declare no conflict of interest., (Copyright © 2023 The Japan Society of Coloproctology.)
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- 2023
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42. Predictive factors of the clinical efficacy of ustekinumab in patients with refractory Crohn's disease: tertiary centers experience in Japan.
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Esaki M, Ihara Y, Tominaga N, Takedomi H, Tsuruoka N, Akutagawa T, Yukimoto T, Kawasaki K, Umeno J, Torisu T, and Sakata Y
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- Humans, Japan, Retrospective Studies, Serum Albumin, Treatment Outcome, Crohn Disease drug therapy, Ustekinumab therapeutic use
- Abstract
Purpose: Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab., Methods: We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index < 150 and CRP < 0.3 mg/dL, and factors predictive of the induction and maintenance of dual remission were investigated. The cumulative continuation rates and safety of ustekinumab were assessed., Results: The dual remission rates at weeks 8, 26, 52, and 104 were 31.9%, 37.9%, 47.5%, and 42.6%, respectively. A short disease duration (≤ 2 years) and higher baseline serum albumin levels (≥ 3.1 g/dL) were positively associated with dual remission at weeks 8 and 52. Meanwhile, higher serum CRP levels (≥ 1.19 mg/dL) were negatively associated with dual remission at week 8. The cumulative ustekinumab continuation rate was favorable, and no severe adverse events were found., Conclusion: A short disease duration and higher baseline serum albumin levels might be predictive of favorable therapeutic efficacy of ustekinumab in refractory CD. Induction efficacy appears to be lower in patients with higher serum CRP levels., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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43. A rare case of an enterochromaffin-like neuroendocrine tumor associated with parietal cell dysfunction treated using endoscopic submucosal dissection.
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Shiroma S, Higuchi K, Ota H, Umeno J, Ishioka M, Hirasawa T, Kuba H, Ono T, Uchima R, and Nagamura R
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- Female, Humans, Middle Aged, Hyperplasia pathology, Gastric Mucosa surgery, Gastric Mucosa pathology, Endoscopic Mucosal Resection methods, Neuroendocrine Tumors surgery, Neuroendocrine Tumors pathology, Stomach Neoplasms surgery, Stomach Neoplasms pathology
- Abstract
Most gastric neuroendocrine tumors (NETs) develop from enterochromaffin-like (ECL) cells. ECL-cell NETs are classically categorized into three types according to their etiology. A 50-year-old woman presented with submucosal tumor-like lesions in the stomach, which were identified via esophagogastroduodenoscopy. Although esophagogastroduodenoscopy and pathological findings of biopsy specimens showed an absence of mucosal atrophy in the body of the stomach, sticky, adherent, dense mucus was observed. All lesions were diagnosed as ECL-cell NETs based on histological examination findings; however, ECL-cell NETs did not apply to any of the classic types I-III categorization based on laboratory, computed tomography, and 24-h intragastric pH monitoring test findings. Endoscopic submucosal dissection of the tumor was performed. Pathological findings of the excised specimen indicated that parietal cell hyperplasia with a protrusion, dilated fundic glands, and endocrine cell hyperplasia in the background mucosa, and parietal cells were not immunostained for the α-subunits of H
+ /K+ -ATPase. Genetic analysis identified mutation in the ATP4A gene. The patient opted for additional gastric resection due to the risk of lymph node metastasis with deeper submucosal invasion and vascular infiltration. This report describes the first case of ECL-cell NETs caused by parietal cell dysfunction, which was treated via endoscopic submucosal dissection., (© 2022. Japanese Society of Gastroenterology.)- Published
- 2022
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44. Crohn's Disease and Early Exposure to Thiopurines are Independent Risk Factors for Mosaic Chromosomal Alterations in Patients with Inflammatory Bowel Diseases.
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Kakuta Y, Iwaki H, Umeno J, Kawai Y, Kawahara M, Takagawa T, Shimoyama Y, Naito T, Moroi R, Kuroha M, Shiga H, Watanabe K, Nakamura S, Nakase H, Sasaki M, Hanai H, Fuyuno Y, Hirano A, Matsumoto T, Kudo H, Minegishi N, Nakamura M, Hisamatsu T, Andoh A, Nagasaki M, Tokunaga K, Kinouchi Y, and Masamune A
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- Genome-Wide Association Study, Humans, Immunologic Factors, Risk Factors, Colitis, Ulcerative complications, Colitis, Ulcerative drug therapy, Colitis, Ulcerative genetics, Crohn Disease complications, Crohn Disease drug therapy, Crohn Disease genetics, Hematologic Neoplasms, Inflammatory Bowel Diseases complications
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Background and Aims: Mosaic chromosomal alterations [mCAs] increase the risk for haematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases [IBDs], including Crohn's disease [CD] and ulcerative colitis [UC], are associated with mCAs, and patients may be at risk for haematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs., Methods: We analysed mCAs in peripheral blood from 3339 patients with IBD and investigated the clinical and genetic risk factors for mCAs., Results: CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs [odds ratio = 2.15 and 5.68, p = 1.17e-2 and 1.60e-3, respectively]. In contrast, there were no significant associations of disease duration, anti-tumour necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD [p = 1.56e-8, 1.65e-8, and 4.92e-8, respectively]., Conclusions: The difference in mCAs between patients with CD and UC supports the higher incidence of haematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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45. One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study.
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Matsuno Y, Torisu T, Umeno J, Shibata H, Hirano A, Fuyuno Y, Okamoto Y, Fujioka S, Kawasaki K, Moriyama T, Nagasue T, Zeze K, Hirakawa Y, Kawatoko S, Koga Y, Oda Y, Esaki M, and Kitazono T
- Abstract
Background/aims: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC., Methods: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences., Results: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment., Conclusions: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.
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- 2022
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46. Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method.
- Author
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Sakaue S, Hosomichi K, Hirata J, Nakaoka H, Yamazaki K, Yawata M, Yawata N, Naito T, Umeno J, Kawaguchi T, Matsui T, Motoya S, Suzuki Y, Inoko H, Tajima A, Morisaki T, Matsuda K, Kamatani Y, Yamamoto K, Inoue I, and Okada Y
- Abstract
The killer cell immunoglobulin-like receptor (KIR) recognizes human leukocyte antigen (HLA) class I molecules and modulates the function of natural killer cells. Despite its role in immunity, the complex genomic structure has limited a deep understanding of the KIR genomic landscape. Here we conduct deep sequencing of 16 KIR genes in 1,173 individuals. We devise a bioinformatics pipeline incorporating copy number estimation and insertion or deletion (indel) calling for high-resolution KIR genotyping. We define 118 alleles in 13 genes and demonstrate a linkage disequilibrium structure within and across KIR centromeric and telomeric regions. We construct a KIR imputation reference panel (n
reference = 689, imputation accuracy = 99.7%), apply it to biobank genotype (ntotal = 169,907), and perform phenome-wide association studies of 85 traits. We observe a dearth of genome-wide significant associations, even in immune traits implicated previously to be associated with KIR (the smallest p = 1.5 × 10-4 ). Our pipeline presents a broadly applicable framework to evaluate innate immunity in large-scale datasets., Competing Interests: H.I. is a founder of GenoDive Pharma. Inc. J.H. is an employee of Teijin Pharma Limited., (© 2022 The Author(s).)- Published
- 2022
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47. [A case of chronic enteropathy associated with SLCO2A1 gene diagnosed by capsule endoscopy and successfully treated by ferric carboxymaltose].
- Author
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Harada A, Umeno J, Morisaki S, Saiki T, Taniguchi Y, Suzuki T, Matsuno Y, Fuyuno Y, Torisu T, and Suekane H
- Subjects
- Female, Ferric Compounds, Humans, Iron therapeutic use, Maltose analogs & derivatives, Middle Aged, Ulcer drug therapy, Ulcer genetics, Anemia, Anemia, Iron-Deficiency drug therapy, Anemia, Iron-Deficiency genetics, Capsule Endoscopy, Inflammatory Bowel Diseases, Organic Anion Transporters genetics
- Abstract
Chronic non-specific multiple ulcers of the small intestine is a disease condition postulated in Japan. It is an uncommon gastrointestinal disease that causes chronic anemia and hypoalbuminemia by causing numerous ulcers without any histopathologically identifiable features. In recent years, it has been revealed that the mutations of SLCO2A1, which codes the prostaglandin transporter protein, are the cause of this disease;it is called the new name "chronic enteropathy associated with SLCO2A1 gene." The ileum, except the terminal ileum, is the most common place making it difficult to identify major lesions. Other than conservative treatments, such as nutrition therapy and iron supplements, no effective treatment has been identified so far. We present a case of chronic non-specific multiple ulcers of the small intestine diagnosed by capsule endoscopy and effectively treated by ferric carboxymaltose. A 48-year-old female had chronic iron deficiency anemia since around the age of 15. Because of severe anemia, the patient had upper and lower endoscopy at the age of 47 to find the source of the bleeding, but it was not detected. Except for the terminal ileum, the capsule endoscopy revealed ring-like ulcers, tape-like ulcers, and oblique ulcer scars in the ileum. Genetic analysis showed a homozygous mutation in intron 7, c.940+1G>A, indicating a definitive diagnosis of non-specific multiple ulcers of the small intestine. Anemia and anemia-related symptoms such as general malaise persisted despite continuous oral administration of iron drugs. Three intravenous injections of ferric carboxymaltose increased hemoglobin and enhanced the symptoms.
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- 2022
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48. [Chronic enteropathy associated with SLCO2A1 gene (CEAS)].
- Author
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Umeno J, Uchida K, and Matsumoto T
- Subjects
- Humans, Inflammatory Bowel Diseases, Organic Anion Transporters genetics
- Published
- 2022
- Full Text
- View/download PDF
49. The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted Enteroscopy.
- Author
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Nagasue T, Hirano A, Torisu T, Umeno J, Shibata H, Moriyama T, Kawasaki K, Fujioka S, Fuyuno Y, Matsuno Y, Esaki M, and Kitazono T
- Subjects
- Feces, Humans, Intestine, Small, RNA, Ribosomal, 16S genetics, Gastrointestinal Microbiome genetics, Microbiota
- Abstract
Introduction: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites., Methods: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing., Results: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p < 0.001). Jejunal and duodenal microbiotas formed similar clusters. Wide clusters spanning the upper and lower GI tracts were observed with the ileal microbiota, which differed significantly from the jejunal microbiota (p < 0.001). Veillonella and Streptococcus were abundant in the jejunum but less so in the lower GI tract and feces. The metagenomic functions associated with nutrient metabolism differed significantly between the small intestine and the feces., Conclusions: The fact that the compositional structures of small intestinal microbiota differed from those of fecal and other GI microbiotas reveals that analyzing the small intestinal microbiota is necessary for association studies on metabolic diseases and gut microbiota., (© 2022 S. Karger AG, Basel.)
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- 2022
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50. Role of barium enema examination for the diagnosis of submucosal invasion depth in T1 colorectal cancers.
- Author
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Kawasaki K, Torisu T, Nagahata T, Esaki M, Kurahara K, Eizuka M, Tanaka Y, Fujiwara M, Kawatoko S, Oshiro Y, Yamada S, Ikegami K, Fujioka S, Fuyuno Y, Matsuno Y, Umeno J, Moriyama T, Kitazono T, Sugai T, and Matsumoto T
- Subjects
- Humans, Neoplasm Invasiveness, ROC Curve, Barium Enema, Colorectal Neoplasms diagnostic imaging
- Abstract
Background: The indication for endoscopic resection for submucosally invasive colorectal cancer (T1-CRC) depends on the preoperative diagnosis of invasion depth. The aim of this investigation was to evaluate the association between barium enema examination (BE) profile views and depth of submucosal (SM) invasion in CRCs., Methods: We reviewed the radiographic and endoscopic findings of 145 T1-CRCs diagnosed from 2008 to 2019. We measured the widths of horizontal and vertical rigidity under a BE profile view corresponding to CRC and compared the values with SM invasion depth. Horizontal rigidity was defined as the horizontal length and vertical rigidity as the vertical width of the barium defect corresponding to each target lesion. The most appropriate cut-off values for predicting SM invasion ≥1.8 mm were calculated by receiver operating characteristic curve analysis., Results: Values of horizontal rigidity (r = 0.626, P < 0.05) and vertical rigidity (r = 0.482, P < 0.05) correlated significantly with SM invasion depth. The most appropriate cut-off values for the prediction of SM invasion depth ≥ 1.8 mm were 4.5 mm for horizontal rigidity, with an accuracy of 80.7%; and 0.7 mm for vertical rigidity, with an accuracy of 77.9%. The prevalence of lympho-vascular invasion was significantly different when those cut-off values were applied (43.2% vs. 17.5% for horizontal rigidity, P < 0.005)., Conclusions: In T1-CRC, values of horizontal and vertical rigidities under a BE profile view were correlated with SM invasion depth. While the accuracy of the rigidities for the prediction of SM invasion depth ≥ 1.8 mm was not high, horizontal rigidity may be predictive of lympho-vascular invasion, thus aiding in therapeutic decision-making., (© 2021. The Author(s).)
- Published
- 2021
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