{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:15:35Z","timestamp":1790673335768,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dig Dis Sci"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1007\/s10620-024-08581-9","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T15:02:00Z","timestamp":1723042920000},"page":"3932-3941","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Absence of Paneth Cell Metaplasia to Predict Clinical Relapse in Ulcerative Colitis with Endoscopically Quiescent Mucosa"],"prefix":"10.1007","volume":"69","author":[{"given":"Kazuki","family":"Horiuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Higashiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Yoshidome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Ayaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tomioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Narimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Komoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Hokari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"8581_CR1","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1002\/cbin.11764","volume":"46","author":"EBL Barreto","year":"2022","unstructured":"Barreto EBL, Rattes IC, da Costa AV et al. Paneth cells and their multiple functions. Cell Biol Int. 2022;46:701\u2013710.","journal-title":"Cell Biol Int."},{"key":"8581_CR2","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1046\/j.1440-1746.2001.02629.x","volume":"16","author":"M Tanaka","year":"2001","unstructured":"Tanaka M, Saito H, Kusumi T et al. Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease. J Gastroenterol Hepatol. 2001;16:1353\u20131359.","journal-title":"J Gastroenterol Hepatol."},{"key":"8581_CR3","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1097\/PAP.0000000000000325","volume":"29","author":"B K\u0151v\u00e1ri","year":"2022","unstructured":"K\u0151v\u00e1ri B, B\u00e1thori \u00c1, Friedman MS et al. Histologic diagnosis of inflammatory bowel diseases. Adv Anat Pathol. 2022;29:48\u201361.","journal-title":"Adv Anat Pathol."},{"key":"8581_CR4","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1136\/gut.2003.032805","volume":"53","author":"J Wehkamp","year":"2004","unstructured":"Wehkamp J, Harder J, Weichenthal M et al. NOD2 (CARD15) mutations in Crohn\u2019s disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004;53:1658\u20131664.","journal-title":"Gut."},{"key":"8581_CR5","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nature10400","volume":"477","author":"C G\u00fcnther","year":"2011","unstructured":"G\u00fcnther C, Martini E, Wittkopf N et al. Caspase-8 regulates TNF-\u03b1-induced epithelial necroptosis and terminal ileitis. Nature. 2011;477:335\u2013339.","journal-title":"Nature."},{"key":"8581_CR6","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1053\/j.gastro.2007.05.051","volume":"133","author":"KF Fr\u00f8slie","year":"2007","unstructured":"Fr\u00f8slie KF, Jahnsen J, Moum BA et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412\u2013422.","journal-title":"Gastroenterology."},{"key":"8581_CR7","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.crohns.2011.11.001","volume":"6","author":"W Reinisch","year":"2012","unstructured":"Reinisch W, Van Assche G, Befrits R et al. Recommendations for the treatment of ulcerative colitis with infliximab: a gastroenterology expert group consensus. J Crohns Colitis. 2012;6:248\u2013258.","journal-title":"J Crohns Colitis."},{"key":"8581_CR8","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/j.1365-2036.2011.04701.x","volume":"34","author":"SP Travis","year":"2011","unstructured":"Travis SP, Higgins PD, Orchard T, Panaccione R, Bitton A et al. Review article: defining remission in ulcerative colitis. Aliment Pharmacol Ther. 2011;34:113\u2013124.","journal-title":"Aliment Pharmacol Ther."},{"key":"8581_CR9","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1097\/MIB.0000000000000816","volume":"22","author":"AR Reinink","year":"2016","unstructured":"Reinink AR, Lee TC, Higgins PD. Endoscopic mucosal healing predicts favorable clinical outcomes in inflammatory bowel disease: a meta-analysis. Inflamm Bowel Dis. 2016;22:1859\u20131869.","journal-title":"Inflamm Bowel Dis."},{"key":"8581_CR10","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1053\/j.gastro.2015.03.001","volume":"148","author":"B Bressler","year":"2015","unstructured":"Bressler B, Marshall JK, Bernstein CN et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology. 2015;148:1035\u201358.e3.","journal-title":"Gastroenterology."},{"key":"8581_CR11","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.cgh.2013.07.022","volume":"12","author":"L Peyrin-Biroulet","year":"2014","unstructured":"Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? Clin Gastroenterol Hepatol. 2014;12:929\u201334.e2.","journal-title":"Clin Gastroenterol Hepatol."},{"key":"8581_CR12","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s40265-016-0676-y","volume":"77","author":"P Boal Carvalho","year":"2017","unstructured":"Boal Carvalho P, Cotter J. Mucosal healing in ulcerative colitis: a comprehensive review. Drugs. 2017;77:159\u2013173.","journal-title":"Drugs."},{"key":"8581_CR13","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1080\/14712598.2020.1701652","volume":"20","author":"A Dal Buono","year":"2020","unstructured":"Dal Buono A, Roda G, Argollo M et al. Histological healing: should it be considered as a new outcome for ulcerative colitis? Expert Opin Biol Ther. 2020;20:407\u2013412.","journal-title":"Expert Opin Biol Ther."},{"key":"8581_CR14","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1053\/j.gastro.2021.02.035","volume":"160","author":"C Ma","year":"2021","unstructured":"Ma C, Sedano R, Almradi A et al. An international consensus to standardize integration of histopathology in ulcerative colitis clinical trials. Gastroenterology. 2021;160:2291\u20132302.","journal-title":"Gastroenterology."},{"key":"8581_CR15","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/ecco-jcc\/jjy114","volume":"13","author":"S Andreas","year":"2019","unstructured":"Andreas S, Christian M, Emma C et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 2: IBD scores and general principles and technical aspects. J Crohns Colitis. 2019;13:273\u2013284.","journal-title":"J Crohns Colitis."},{"key":"8581_CR16","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1111\/apt.16147","volume":"52","author":"N Neeraj","year":"2020","unstructured":"Neeraj N, Achuthan A, Abdul-Aziz A et al. Histologic remission does not offer additional benefit for ulcerative colitis patients in endoscopic remission. Aliment Pharmacol Ther. 2020;52:1676\u20131682.","journal-title":"Aliment Pharmacol Ther."},{"key":"8581_CR17","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1177\/2050640617752207","volume":"6","author":"L Triana","year":"2018","unstructured":"Triana L, Talat B, Alexandra R et al. Prognostic value of histological activity in patients with ulcerative colitis in deep remission: a prospective multicenter study. United European Gastroenterol J. 2018;6:765\u2013772.","journal-title":"United European Gastroenterol J."},{"key":"8581_CR18","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1038\/ajg.2016.418","volume":"111","author":"S Park","year":"2016","unstructured":"Park S, Abdi T, Gentry M et al. Histological disease activity as a predictor of clinical relapse among patients with ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2016;111:1692\u20131701.","journal-title":"Am J Gastroenterol."},{"key":"8581_CR19","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1111\/apt.16147","volume":"52","author":"N Narula","year":"2020","unstructured":"Narula N, Aruljothy A, Alshahrani AA et al. Histologic remission does not offer additional benefit for ulcerative colitis patients in endoscopic remission. Aliment Pharmacol Ther. 2020;52:1676\u20131682.","journal-title":"Aliment Pharmacol Ther."},{"key":"8581_CR20","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature05698","volume":"446","author":"A Nenci","year":"2007","unstructured":"Nenci A, Becker C, Wullaert A et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature. 2007;446:557\u2013561.","journal-title":"Nature."},{"key":"8581_CR21","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1093\/ecco-jcc\/jjy092","volume":"12","author":"R Ozaki","year":"2018","unstructured":"Ozaki R, Kobayashi T, Okabayashi S et al. Histological risk factors to predict clinical relapse in ulcerative colitis with endoscopically normal mucosa. J Crohns Colitis. 2018;12:1288\u20131294.","journal-title":"J Crohns Colitis."},{"key":"8581_CR22","doi-asserted-by":"publisher","first-page":"e38965","DOI":"10.1371\/journal.pone.0038965","volume":"7","author":"S Roth","year":"2012","unstructured":"Roth S, Franken P, Sacchetti A et al. Paneth cells in intestinal homeostasis and tissue injury. PLoS One. 2012;7:e38965.","journal-title":"PLoS One."},{"key":"8581_CR23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1053\/gast.2001.20912","volume":"120","author":"A Bitton","year":"2001","unstructured":"Bitton A, Peppercorn MA, Antonioli DA et al. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology. 2001;120:13\u201320.","journal-title":"Gastroenterology."},{"key":"8581_CR24","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1136\/gutjnl-2015-309598","volume":"65","author":"RV Bryant","year":"2016","unstructured":"Bryant RV, Burger DC, Delo J et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016;65:408\u2013414.","journal-title":"Gut."},{"key":"8581_CR25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1471-230X-14-93","volume":"14","author":"N Simmonds","year":"2014","unstructured":"Simmonds N, Furman M, Karanika E et al. Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children. BMC Gastroenterol. 2014;14:93.","journal-title":"BMC Gastroenterol."},{"key":"8581_CR26","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1136\/gut.32.2.174","volume":"32","author":"SA Riley","year":"1991","unstructured":"Riley SA, Mani V, Goodman MJ et al. Microscopic activity in ulcerative colitis: what does it mean? Gut. 1991;32:174\u2013178.","journal-title":"Gut."},{"key":"8581_CR27","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.crohns.2013.06.001","volume":"7","author":"F Magro","year":"2013","unstructured":"Magro F, Langner C, Driessen A et al. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7:827\u2013851.","journal-title":"J Crohns Colitis."},{"key":"8581_CR28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/ecco-jcc\/jjv158","volume":"10","author":"M Barreiro-de Acosta","year":"2016","unstructured":"Barreiro-de Acosta M, Vallejo N, de la Iglesia D et al. Evaluation of the risk of relapse in ulcerative colitis according to the degree of mucosal healing (Mayo 0 vs 1): a longitudinal cohort study. J Crohns Colitis. 2016;10:13\u201319.","journal-title":"J Crohns Colitis."},{"key":"8581_CR29","doi-asserted-by":"publisher","first-page":"57","DOI":"10.12938\/bmfh.2015-019","volume":"35","author":"K Nakamura","year":"2016","unstructured":"Nakamura K, Sakuragi N, Takakuwa A et al. Paneth cell \u03b1-defensins and enteric microbiota in health and disease. Biosci Microbiota Food Health. 2016;35:57\u201367.","journal-title":"Biosci Microbiota Food Health."},{"key":"8581_CR30","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature09637","volume":"469","author":"T Sato","year":"2011","unstructured":"Sato T, van Es JH, Snippert HJ et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469:415\u2013418.","journal-title":"Nature."},{"key":"8581_CR31","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1097\/MIB.0000000000000069","volume":"20","author":"A Jauregui-Amezaga","year":"2014","unstructured":"Jauregui-Amezaga A, L\u00f3pez-Cer\u00f3n M, Aceituno M et al. Accuracy of advanced endoscopy and fecal calprotectin for prediction of relapse in ulcerative colitis: a prospective study. Inflamm Bowel Dis. 2014;20:1187\u20131193.","journal-title":"Inflamm Bowel Dis."},{"key":"8581_CR32","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1016\/j.cgh.2017.02.016","volume":"15","author":"B Christensen","year":"2017","unstructured":"Christensen B, Hanauer SB, Erlich J et al. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol. 2017;15:1557\u201364.e1.","journal-title":"Clin Gastroenterol Hepatol."},{"key":"8581_CR33","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1038\/ajg.2012.301","volume":"107","author":"T Bessissow","year":"2012","unstructured":"Bessissow T, Lemmens B, Ferrante M et al. Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am J Gastroenterol. 2012;107:1684\u20131692.","journal-title":"Am J Gastroenterol."},{"key":"8581_CR34","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/00365529950172844","volume":"34","author":"M Tanaka","year":"1999","unstructured":"Tanaka M, Riddell RH, Saito H et al. Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn\u2019s disease from ulcerative colitis. Scand J Gastroenterol. 1999;34:55\u201367.","journal-title":"Scand J Gastroenterol."},{"key":"8581_CR35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115230119","author":"M Kamioka","year":"2022","unstructured":"Kamioka M, Goto Y, Nakamura K et al. Intestinal commensal microbiota and cytokines regulate Fut2(+) Paneth cells for gut defense. Proc Natl Acad Sci USA. 2022. https:\/\/doi.org\/10.1073\/pnas.2115230119.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8581_CR36","first-page":"1448","volume":"12","author":"X Gui","year":"2018","unstructured":"Gui X, Li J, Ueno A et al. Histopathological features of inflammatory bowel disease are associated with different CD4+ T cell subsets in colonic mucosal lamina propria. J Crohns Colitis. 2018;12:1448\u20131458.","journal-title":"J Crohns Colitis."}],"container-title":["Digestive Diseases and Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-024-08581-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10620-024-08581-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-024-08581-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T18:05:11Z","timestamp":1729274711000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10620-024-08581-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["8581"],"URL":"https:\/\/doi.org\/10.1007\/s10620-024-08581-9","relation":{},"ISSN":["0163-2116","1573-2568"],"issn-type":[{"value":"0163-2116","type":"print"},{"value":"1573-2568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,7]]},"assertion":[{"value":"26 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no conflict of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the Research Ethics Committee of the National Defense Medical College (no.4715). Patients and the general population were excluded from this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}