Journal of Gastroenterology最新文献

{"title":"Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: a final report of safety and effectiveness data.","authors":"Katsuyoshi Matsuoka, Satoshi Motoya, Takayuki Yamamoto, Minoru Matsuura, Toshimitsu Fujii, Shinichiro Shinzaki, Yohei Mikami, Shoko Arai, Junichi Oshima, Yutaka Endo, Hirotoshi Yuasa, Masato Hoshi, Keiko Sato, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02249-5","DOIUrl":"10.1007/s00535-025-02249-5","url":null,"abstract":"<p><strong>Background: </strong>We present the final analysis of a tofacitinib post-marketing surveillance (PMS) study in Japanese patients with ulcerative colitis (UC).</p><p><strong>Methods: </strong>Safety/effectiveness data were evaluated (through Sept/30/2022). All patients with UC in Japan receiving tofacitinib were registered (60-week observation period). Adverse events (AEs) were recorded. Per protocol, several AEs were identified as clinically important/potential risks; all treatment-period data were used to calculate incidence rates (IRs; unique patients with events/100 patient-years [PY] of exposure). Effectiveness was assessed (partial/total Mayo score), with last observation carried forward for imputation of missing data.</p><p><strong>Results: </strong>Overall, 2043 patients were enrolled (safety analysis set: n = 1982/effectiveness analysis set: n = 1969). Data were excluded for 13 patients from two hospitals from which consent was not obtained for publication and which, therefore, were not permitted for publication. AEs and serious AEs were observed in 33.4% and 5.2% of patients, respectively; one death occurred (intestinal abscess). Herpes zoster (HZ; non-serious and serious) was the most reported infection (n = 92 [IR 5.93/100 PY, 95% confidence interval 4.78, 7.27]). Serious infection, malignancy, cardiovascular and venous thromboembolic events IRs were 1.51/100 PY, 0.62/100 PY, 0.13/100 PY, and 0.31/100 PY, respectively. Overall, 52.4% of patients discontinued treatment, mostly due to inadequate clinical response (48.9%). At Week 60, 1151/1969 patients (58.5%) achieved partial Mayo score remission.</p><p><strong>Conclusion: </strong>The overall safety profile was generally comparable with tofacitinib data from PMS reports from Japan, worldwide and the tofacitinib UC clinical program. However, HZ IR was higher than in the tofacitinib UC clinical program. Tofacitinib effectiveness was consistent with data from the tofacitinib UC clinical program.</p><p><strong>Clinicaltrials: </strong>GOV: NCT03643211.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"979-989"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status and trends in ERCP and post-ERCP pancreatitis in Japan: a nationwide observational study.","authors":"Tomoo Manaka, Tetsuya Takikawa, Kunio Tarasawa, Kazuhiro Kikuta, Ryotaro Matsumoto, Yu Tanaka, Takanori Sano, Shin Hamada, Shin Miura, Kiyoshi Kume, Kenji Fujimori, Kiyohide Fushimi, Atsushi Masamune","doi":"10.1007/s00535-025-02254-8","DOIUrl":"10.1007/s00535-025-02254-8","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic retrograde cholangiopancreatography (ERCP) is indispensable for the management of biliary and pancreatic diseases but carries a high risk of post-ERCP pancreatitis (PEP). This study aimed to clarify the current status and temporal trends of ERCP and PEP in Japan, including preventive measures.</p><p><strong>Methods: </strong>We conducted a retrospective, population-based cohort study using the Diagnosis Procedure Combination database from April 1, 2016, to March 31, 2023. Trend analyses were performed for ERCP, PEP, nonsteroidal anti-inflammatory drugs (NSAIDs), and protease inhibitors. Additionally, factors associated with PEP and severe PEP were evaluated.</p><p><strong>Results: </strong>Among the 1,073,513 ERCP cases, PEP and severe PEP incidences were 85,212 (7.9%) and 4841 cases (0.5%), respectively. The mortality rate was 0.5% for severe PEP and 0.2% for non-severe cases. The number of ERCP procedures and the proportion of therapeutic ERCP increased over time. The incidence of PEP declined from 9.1% in the fiscal year 2016-2017 to 6.4% in the fiscal year 2022, while the incidence of severe PEP decreased from 0.5 to 0.33% over the same period. The usage rate of rectal NSAIDs increased from 16.4 to 27.6%, whereas that of protease inhibitors decreased from 70.5 to 53.5%. The administration of rectal NSAIDs at doses of 20-25 mg and 50 mg was associated with a reduced risk of severe PEP.</p><p><strong>Conclusions: </strong>The number of ERCP procedures and the proportion of therapeutic ERCP have increased, whereas the incidences of PEP and severe PEP have decreased. Rectal NSAIDs may prevent the progression of PEP to severe disease.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1036-1046"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of neuropilin-1 and hepatocyte growth factor/C-Met pathway in liver fibrosis progression in hepatocyte-specific NRP-1 knockout mice.","authors":"Han Ding, Huanran Lv, Minghao Sui, Xinyu Wang, Yanning Sun, Miaomiao Tian, Shujun Ma, Yuchan Xue, Miao Zhang, Xin Wang, Jianni Qi, Le Wang, Qiang Zhu","doi":"10.1007/s00535-025-02262-8","DOIUrl":"10.1007/s00535-025-02262-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatocyte growth factor (HGF)/c-Met signaling critically influences liver fibrosis, but its interaction with neuropilin-1 (NRP-1) in hepatocytes remains unclear. We investigated the role of hepatocyte-specific NRP-1 deletion in liver fibrosis progression and its relationship with the HGF/c-Met pathway.</p><p><strong>Methods: </strong>Hepatocyte-specific NRP-1 knockout mice were generated using the Cre-lox system, and liver fibrosis was induced by carbon tetrachloride injections or a methionine- and choline-deficient diet. Fibrosis severity, hepatocyte injury, and cytokine secretion were evaluated via histology, biochemical assays, and molecular analyses in isolated hepatocytes. In vitro experiments were conducted in primary hepatocytes and Huh7 cells using lentiviral overexpression and knockdown of NRP-1. Chromatin immunoprecipitation and dual-luciferase reporter assays were performed to analyze transcription factor binding to the NRP-1 promoter.</p><p><strong>Results: </strong>Hepatocyte NRP-1 expression increased significantly during liver fibrosis and was positively correlated with HGF/c-Met expression and fibrosis severity. In vivo, NRP-1 inhibition reduced extracellular matrix accumulation and abnormal angiogenesis in Alb-Cre NRP-1^f/f mice. In vitro, NRP-1 blockade inhibited c-Met activation and reduced transforming growth factor-beta and vascular endothelial growth factor secretion in hepatocytes. NRP-1 functioned as a co-receptor for HGF/c-Met, with HGF upregulating NRP-1 expression at transcript and protein levels. NRP-1 promoted fibrosis through the Met/extracellular signal-regulated kinase pathway. Furthermore, HGF increased retinoic acid receptor alpha expression, promoting NRP-1 transcription.</p><p><strong>Conclusions: </strong>HGF-induced upregulation of hepatocyte NRP-1, mediated by RARA binding to its promoter, drives liver fibrosis through c-Met pathway activation, highlighting NRP-1 as a potential therapeutic target for liver fibrosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1000-1013"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide epidemiological survey of acute pancreatitis in Japan, 2021: the impact of the COVID-19 pandemic and revised clinical guidelines.","authors":"Yuichi Tanaka, Atsushi Masamune, Ryotaro Matsumoto, Tetsuya Takikawa, Yu Tanaka, Shin Hamada, Shin Miura, Kiyoshi Kume, Yoshifumi Takeyama, Kazuhiro Kikuta","doi":"10.1007/s00535-025-02284-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02284-2","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to clarify the current clinico-epidemiological characteristics of acute pancreatitis (AP) in Japan.</p><p><strong>Methods: </strong>We conducted a two-stage nationwide survey of patients with AP treated at selected hospitals in 2021, during the COVID-19 pandemic. The first stage estimated the total number of AP patients, while the second collected detailed clinical data.</p><p><strong>Results: </strong>The estimated number of AP patients requiring hospitalization was 61,080, with an overall incidence rate of 49 per 100,000 persons, decreasing from 78,450 in 2016. Detailed clinical data were obtained for 4,375 patients, including 1,362 (31.1%) classified as severe. The male-to-female ratio was 2.0, with mean ages at onset of 60.1 years for males and 65.4 years for females. The three major causes were alcohol (31.2%), gallstones (22.5%), and idiopathic etiology (22.1%). The AP-associated in-hospital mortality rate was 2.1% in all AP and 5.3% in severe cases, down from 6.1% in the 2016 survey. Antibiotics were administered to 61.2% of mild cases, a significant reduction from 94.5% in 2016. Enteral nutrition was provided to 56.9% of severe cases, up from 31.8% in 2016. Among 124 patients undergoing interventional drainage for walled-off necrosis, 57 were treated using a step-up approach. Notably, no patients underwent upfront surgery as the initial treatment.</p><p><strong>Conclusions: </strong>During the pandemic, the estimated number of AP cases requiring hospitalization declined for the first time in nearly four decades. Mortality in severe cases improved, and adherence to clinical guidelines on prophylactic antibiotics and enteral nutrition also improved, indicating enhanced management of AP in Japan.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pivotal role of SFRP2 in promoting glycolysis and progression in the high-risk group based on the glycometabolism prognostic model for colorectal cancer.","authors":"Feng Du, Xu Ji, Jiayi Su, Chuntao Liu, Junxiong Wang, Tingting Ning, Nan Zhang, Junxuan Xu, Si-An Xie, Si Liu, Li Min, Jing Wu, Shutian Zhang, Shuilong Guo, Shengtao Zhu, Peng Li","doi":"10.1007/s00535-025-02281-5","DOIUrl":"https://doi.org/10.1007/s00535-025-02281-5","url":null,"abstract":"<p><strong>Background: </strong>Reprogramming glucose metabolism is a hallmark of human cancer during its occurrence and development. However, the comprehensive glycometabolism signature and underlying mechanism in CRC prognosis and immune response remind to be elucidated.</p><p><strong>Methods: </strong>A prognostic model derived from 297 glycometabolism-related genes (GRGs) was developed using LASSO-Cox and nomogram algorithms. Immune dysfunction between high-risk (Risk^H) and low-risk (Risk^L) groups was compared using CIBERSORT, TIMER, and TIDE analyses. The expression and function of key genes, including secreted frizzled-related protein 2 (SFRP2), were validated using PCR, western blotting, immunohistochemistry, transwell assays, and metastatic model in mice. Luciferase reporter and chromatin immunoprecipitation were used to determine the transcription regulation of ENO2 by TCF4.</p><p><strong>Results: </strong>More than half of the GRGs (152 out of 297) showed differential expression, mainly those associated with glycolysis and biosynthesis. The GRG-risk score outperformed other clinical indicators (AUC = 0.810) and served as an independent risk predictor (P < 0.001, HR = 3.180). The Risk^H group showed increased infiltration of immune cells and higher immune checkpoint expression. Mechanistically, SFRP2, a key gene in Risk^H, promoted CRC glycolysis and metastasis via enolase 2 (ENO2) activation through the TCF4/β-catenin axis. Inhibiting ENO2 reversed SFRP2-induced metastasis. Coexpression of SFRP2 and ENO2 correlated with poorer survival and higher recurrence.</p><p><strong>Conclusion: </strong>The Risk^H group is characterized by glycolysis overactivation and immune exclusion. SFRP2 and ENO2 have emerged as promising treatment targets for high-risk CRC patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating tumor-infiltrating lymphocytes as predictors of lymph node metastasis in deep submucosal invasive esophageal squamous cell carcinoma: a retrospective cross-sectional study.","authors":"Hirona Konishi, Yuji Urabe, Yoshiki Hatsushika, Satoshi Masuda, Takeo Nakamura, Kazuki Ishibashi, Junichi Mizuno, Takeshi Takasago, Hidenori Tanaka, Akiyoshi Tsuboi, Ken Yamashita, Yuichi Hiyama, Yoshihiro Kishida, Hidehiko Takigawa, Akira Ishikawa, Toshio Kuwai, Yoichi Hamai, Yuji Murakami, Shiro Oka","doi":"10.1007/s00535-025-02286-0","DOIUrl":"https://doi.org/10.1007/s00535-025-02286-0","url":null,"abstract":"<p><strong>Background: </strong>Various subtypes of tumor-infiltrating lymphocytes (TILs) are associated with prognosis in various cancer types. In esophageal squamous cell carcinoma (ESCC), TILs have been associated with prognosis in advanced stages of the disease. However, their significance in superficial esophageal squamous cell carcinoma (SESCC) remains unknown. In this study, we investigated the role of TILs in SESCC.</p><p><strong>Methods: </strong>First, we included 212 SESCC lesions with a diameter of 10-20 mm (65 pT1a-EP, 74 pT1a-LPM,40 pT1a-MM, and 33 pT1b-SM lesions) that were resected at our hospital from November 2007 to December 2019. We then examined changes in TILs related to tumor invasion. We evaluated the phenotype and number of TILs using triple immunofluorescence staining for CD4, CD8, and FoxP3. In addition, we selected 97 consecutive pT1b-SM lesions treated during the same period. These specimens were used to examine the association between TILs and lymph node metastasis (LNM) in pT1b-SM cases.</p><p><strong>Results: </strong>The number of CD4 + , CD8 + , and FoxP3 + TILs infiltrating the tumor increased significantly with increasing invasion depth. In pT1b-SM lesions, CD4 + , CD8 + , and FoxP3 + TIL counts were significantly higher in the invasive front (IF) than in the tumor center (CT). Moreover, in patients undergoing surgical resection or endoscopic submucosal dissection (regardless of additional chemoradiotherapy), the number and ratio of FoxP3 + TILs in IF were significantly higher in patients with LNM than in those without, suggesting their potential utility as predictive biomarkers.</p><p><strong>Conclusions: </strong>The number and ratio of FoxP3 + TILs in the IF may be an indicator of LNM risk in SESCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PNPLA3 I148M variant is associated with immune cell infiltration and advanced fibrosis in MASLD: a prospective genotype-phenotype study.","authors":"Jaejun Lee, Jung Hoon Cha, Hee Sun Cho, Keungmo Yang, Hyun Yang, Heechul Nam, Mi Young Byun, Seok Keun Cho, Jinsung Park, Hyuk Wan Ko, Seong Wook Yang, Pil Soo Sung, Si Hyun Bae","doi":"10.1007/s00535-025-02285-1","DOIUrl":"https://doi.org/10.1007/s00535-025-02285-1","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence reveals that immune cells significantly contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been linked to hepatic inflammation and fibrosis; however, its role in immune cell infiltration and activation within the liver remains unclear.</p><p><strong>Methods: </strong>Seventy patients with MASLD were prospectively enrolled. Genomic DNA was extracted from buccal swabs or liver biopsy samples, followed by single nucleotide polymorphism genotyping to determine the rs738409 SNP genotype at codon 148 of PNPLA3. Immunohistochemistry was conducted using CD3 and CD68 antibodies to quantify T cell and macrophage infiltration, respectively. Total RNA extracted from biopsy specimens was used for quantitative reverse transcription polymerase chain reaction to assess the expression of specific markers associated with immune cell activation.</p><p><strong>Results: </strong>Among the 70 patients with MASLD, 34 had the GG genotype, whereas 21 and 15 had the GC and CC genotypes, respectively. The GG genotype group showed a higher proportion of advanced fibrosis (F3 or F4) than the GC + CC group (P = 0.051). GG genotype carriers exhibited significantly higher CD3⁺ and CD68⁺ cell counts in the periportal region than the GC/CC carriers (P < 0.05). The transcriptomic analysis revealed elevated expression of markers associated with chronic antigen stimulation and immune cell activation (CD8A, GZMB, CCL2, and TIMP1) in GG carriers compared with those of GC and CC (P < 0.05). Furthermore, correlations among various markers, including inflammatory, steatosis-associated, and fibrosis-associated markers, exhibited consistent positive correlations.</p><p><strong>Conclusions: </strong>Our findings revealed that the PNPLA3 I148M variant and increased immune cell infiltration and activation were significantly correlated within the MASLD liver. Further studies are needed to elucidate the mechanistic links between this genetic variant and liver inflammation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of sarcopenia and changes in skeletal muscle mass on prognosis of patients with pancreatic ductal adenocarcinoma receiving chemotherapy with first-line gemcitabine and nab-paclitaxel: a prospective study.","authors":"Tomoya Emori, Masahiro Itonaga, Reiko Ashida, Tomokazu Ishihara, Akiya Nakahata, Yuki Kawaji, Takashi Tamura, Yasunobu Yamashita, Kazuhiro Fukatsu, Masayuki Kitano","doi":"10.1007/s00535-025-02283-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02283-3","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is an important prognostic factor for cancer patients. Here, we prospectively examined the effects of sarcopenia on progression-free survival (PFS) and overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC) treated with first-line gemcitabine and nab-paclitaxel (GnP).</p><p><strong>Methods: </strong>This single-center prospective study enrolled patients with unresectable PDAC treated with first-line GnP between May 2020 and January 2024. The skeletal muscle index (SMI) was used as an index of sarcopenia. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 diagnostic algorithm. PFS and OS of patients with/without sarcopenia were compared. The univariate and multivariate analyses were performed to identify variables significantly associated with prognosis. Changes in skeletal muscle mass (SMM) were also compared with patient prognosis.</p><p><strong>Results: </strong>Of the 66 patients who received first-line GnP, 21 had sarcopenia. The median PFS of those with or without sarcopenia was 3.7 and 6.9 months, respectively (p = 0.045); the median OS was 8.4 and 15.1 months, respectively (p = 0.006). Multivariate analysis identified sarcopenia as an independent prognostic factor for PFS and OS (p = 0.009, p = 0.005, respectively). The rates of major grade 3 or 4 adverse events were significantly higher in the sarcopenia group (p = 0.008). In the sarcopenia group, an early increase in SMM was an independent good prognostic factor (p = 0.041).</p><p><strong>Conclusions: </strong>Sarcopenia is an independent indicator of poor prognosis in patients with PDAC treated with first-line GnP. Increasing SMM in patients with sarcopenia may prolong PFS.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing age at diagnosis raises malignancy risk and aminosalicylate intolerance influences therapeutic strategies in ulcerative colitis: a multicenter I‑BRITE cohort study.","authors":"Shintaro Akiyama, Yuka Ito, Mamiko Shiroyama, Satoshi Suzuki, Masanori Ochi, Toshiro Kamoshida, Hiroshi Kashimura, Junichi Iwamoto, Rie Saito, Tsuyoshi Kaneko, Kazuto Ikezawa, Yoshinori Hiroshima, Junji Hattori, Takashi Mamiya, Satoshi Fukuda, Kazuho Ikeda, Hiroyuki Ariga, Junya Kashimura, Masaaki Nishi, Masaomi Nagase, Kiichiro Tsuchiya","doi":"10.1007/s00535-025-02279-z","DOIUrl":"https://doi.org/10.1007/s00535-025-02279-z","url":null,"abstract":"<p><strong>Background: </strong>The management and characteristics of ulcerative colitis (UC) have evolved over time. We aimed to clarify how changing clinical profiles and treatment options affect patient outcomes.</p><p><strong>Methods: </strong>This retrospective multicenter study of 13 hospitals divided diagnostic era into six periods: Era 1 (before June 30, 1998) and five subsequent 5-year intervals, with Era 6 (July 1, 2018-June 30, 2023) representing the most recent period. We compared therapeutic trends and outcomes across diagnostic eras, including the risk of first systemic steroid, advanced therapy (ADT) use, colectomy, UC-associated neoplasia (UCAN), and extracolonic malignancies.</p><p><strong>Results: </strong>We included 1,867 UC patients. The proportion of elderly onset cases was significantly higher in Eras 5-6 (13%) compared to Eras 1-4 (0%-8.1%). Aminosalicylate intolerance was significantly more frequent in Era 6 (10%) and was significantly associated with earlier systemic steroid and ADT use, though not with colectomy or UCAN. While prescribing patterns of conventional therapies remained unchanged, the preferred first-line ADT shifted from infliximab to vedolizumab in recent diagnostic years. The cumulative risk of colectomy and UCAN did not significantly differ between eras. However, the cumulative risk of extracolonic malignancy was significantly higher in recent diagnostic years and significantly associated with older age at diagnosis.</p><p><strong>Conclusions: </strong>In the recent diagnostic era, the increase in elderly onset UC has been accompanied by a higher malignancy risk, favoring vedolizumab as first-line ADT, especially in elderly patients. Increased aminosalicylate intolerance has led to earlier initiation of systemic steroids and ADTs, which may contribute to improved outcomes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New potential biomarkers of ulcerative colitis and disease course - integrated metagenomic and metabolomic analysis among Polish patients.","authors":"Oliwia Zakerska-Banaszak, Karolina Ladziak, Dariusz Kruszka, Kacper Maciejewski, Lukasz Wolko, Iwona Krela-Kazmierczak, Agnieszka Zawada, Marie Vibeke Vestergaard, Agnieszka Dobrowolska, Marzena Skrzypczak-Zielinska","doi":"10.1007/s00535-025-02280-6","DOIUrl":"10.1007/s00535-025-02280-6","url":null,"abstract":"<p><strong>Background & aim: </strong>The course of ulcerative colitis (UC) involves successive periods of remission and exacerbation but is difficult to predict. Gut dysbiosis in UC has already been intensively investigated. However, are periods of exacerbation and remission associated with specific disturbances in the composition of the intestinal microbiota and its metabolome? Our goal was to answer this question and to identify bacteria and metabolites necessary to maintain the remission.</p><p><strong>Methods: </strong>We enrolled 65 individuals, including 20 UC patients in remission, 15 in exacerbation, and 30 healthy controls. Metagenomic profiling of the gut microbial composition was performed based on 16S rRNA V1-V9 sequencing. Stool and serum metabolic profiles were studied by chromatography combined with mass spectrometry.</p><p><strong>Results: </strong>We revealed significant differences in the gut bacterial and metabolic composition between patients in active UC and those in remission, as well as in healthy controls. As associated with UC remission we have identified following bacteria: Akkermansia, Agathobacter, Anaerostipes, Enterorhabdus, Coprostanoligenes, Colinsella, Ruminococcus, Subdoligranulum, Lachnoclostridium, Coriobacteriales, Erysipelotrichaceae, and Family XII, and compounds - 1-hexadecanol, phytanic acid, squalene, adipic acid, cis-gondoic acid, nicotinic acid, tocopherol gamma, ergosterol and lithocholic acid. Whereas, in the serum lithocholic acid, indole and xanthine were found as potential candidates for biomarkers of UC remission.</p><p><strong>Conclusion: </strong>We have demonstrated that specific bacteria, metabolites, and their correlations could be crucial in the remission of UC among Polish patients. Our results provide valuable insights and a significant source for developing new hypotheses on host-microbiome interactions in diagnosis and course of UC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}