Introduction: Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation to 20 mg daily is generally recommended. This study aims to clarify the proper timing and predictors for dose escalation of VPZ therapy in patients with refractory GERD treated with the maintenance dose.
Methods: This retrospective observational study included 257 patients with symptomatic GERD. Data from medical records, including endoscopic findings and Izumo scale scores, were analyzed.
Results: The mean follow-up period was 3.3 years. Throughout the follow-up period, VPZ dose escalation (from 10 to 20 mg daily) was required in 56 of 257 patients (22%). Kaplan-Meier analysis showed cumulative dose-escalation-free rates at 6 months, 1 year, and 2 years were 87%, 81%, and 78%, respectively. Predictive factors for VPZ dose escalation were analyzed using a Cox proportional-hazards regression model. Multivariate analysis revealed that pre-existing epigastric pain was a significant positive predictor for dose escalation, whereas pre-existing constipation was identified as a significant negative predictor. Kaplan-Meier analysis indicated that the 1-year dose-escalation-free rates were 69% in patients with epigastric pain compared to 88% in those without (p = 0.001). GERD symptom scores showed a significant improvement 1 month after dose escalation.
Conclusion: The incidence of refractory GERD requiring VPZ dose escalation is relatively low. Epigastric pain prior to VPZ initiation independently predicts the need for dose escalation. VPZ dose escalation effectively improves GERD symptoms.
{"title":"Timing and Predictors for Vonoprazan Dose Escalation in Refractory Gastroesophageal Reflux Disease: A Long-Term Observational Study.","authors":"Satoshi Shinozaki, Hirotsugu Sakamoto, Hiroyuki Osawa, Tomonori Yano, Nikolaos Lazaridis, Hironori Yamamoto","doi":"10.1159/000546992","DOIUrl":"10.1159/000546992","url":null,"abstract":"<p><strong>Introduction: </strong>Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation to 20 mg daily is generally recommended. This study aims to clarify the proper timing and predictors for dose escalation of VPZ therapy in patients with refractory GERD treated with the maintenance dose.</p><p><strong>Methods: </strong>This retrospective observational study included 257 patients with symptomatic GERD. Data from medical records, including endoscopic findings and Izumo scale scores, were analyzed.</p><p><strong>Results: </strong>The mean follow-up period was 3.3 years. Throughout the follow-up period, VPZ dose escalation (from 10 to 20 mg daily) was required in 56 of 257 patients (22%). Kaplan-Meier analysis showed cumulative dose-escalation-free rates at 6 months, 1 year, and 2 years were 87%, 81%, and 78%, respectively. Predictive factors for VPZ dose escalation were analyzed using a Cox proportional-hazards regression model. Multivariate analysis revealed that pre-existing epigastric pain was a significant positive predictor for dose escalation, whereas pre-existing constipation was identified as a significant negative predictor. Kaplan-Meier analysis indicated that the 1-year dose-escalation-free rates were 69% in patients with epigastric pain compared to 88% in those without (p = 0.001). GERD symptom scores showed a significant improvement 1 month after dose escalation.</p><p><strong>Conclusion: </strong>The incidence of refractory GERD requiring VPZ dose escalation is relatively low. Epigastric pain prior to VPZ initiation independently predicts the need for dose escalation. VPZ dose escalation effectively improves GERD symptoms.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Oesophageal cancer is a leading global health issue, with increasing prevalence of oesophageal adenocarcinoma and its precursor lesion, Barrett's oesophagus (BE). Despite the opportunity to treat dysplasia prior to adenocarcinoma development, rates of missed advanced dysplasia at BE surveillance remain high. This pilot study aimed to assess whether Texture and Colour Enhancement Imaging (TXI), a new advanced mucosal imaging modality, improves dysplasia detection during BE surveillance compared to white light endoscopy (WLE).
Methods: Patients undergoing endoscopy for BE assessment or surveillance at a single centre were included for analysis. Patients were randomized in a 1:1 ratio to examination with WLE then TXI or vice versa, followed by narrow-band imaging (NBI). Targeted biopsies were taken from any suspicious areas and 4-quadrant surveillance biopsies were taken at 1 cm intervals in the entire BE segment.
Results: A total of 50 patients were included in the study, with 27 suspicious lesions seen in 22 patients. A total 93.3% (n = 14/15) of high-grade dysplasia or early adenocarcinoma was detected as endoscopically visible lesions on TXI and NBI. However, 4 such lesions were not detected on WLE. On per-patient analysis, the sensitivity and NPV of TXI in combination with magnified NBI were both 100% with specificity of 84.6%, surpassing all PIVI thresholds for dysplasia diagnosis in BE.
Conclusion: This pilot study demonstrates the feasibility of TXI as a potential addition to the armamentarium of advanced mucosal imaging available to proceduralists surveilling BE. Further large multi-centre studies would be required to make statistical comparisons with existing imaging modalities.
{"title":"Texture and Colour Enhancement Imaging versus White Light Endoscopy for Detection of Dysplasia within Barrett's Oesophagus: A Pilot Study.","authors":"Edward Young, Hamish Philpott, Rajvinder Singh","doi":"10.1159/000546637","DOIUrl":"10.1159/000546637","url":null,"abstract":"<p><strong>Introduction: </strong>Oesophageal cancer is a leading global health issue, with increasing prevalence of oesophageal adenocarcinoma and its precursor lesion, Barrett's oesophagus (BE). Despite the opportunity to treat dysplasia prior to adenocarcinoma development, rates of missed advanced dysplasia at BE surveillance remain high. This pilot study aimed to assess whether Texture and Colour Enhancement Imaging (TXI), a new advanced mucosal imaging modality, improves dysplasia detection during BE surveillance compared to white light endoscopy (WLE).</p><p><strong>Methods: </strong>Patients undergoing endoscopy for BE assessment or surveillance at a single centre were included for analysis. Patients were randomized in a 1:1 ratio to examination with WLE then TXI or vice versa, followed by narrow-band imaging (NBI). Targeted biopsies were taken from any suspicious areas and 4-quadrant surveillance biopsies were taken at 1 cm intervals in the entire BE segment.</p><p><strong>Results: </strong>A total of 50 patients were included in the study, with 27 suspicious lesions seen in 22 patients. A total 93.3% (n = 14/15) of high-grade dysplasia or early adenocarcinoma was detected as endoscopically visible lesions on TXI and NBI. However, 4 such lesions were not detected on WLE. On per-patient analysis, the sensitivity and NPV of TXI in combination with magnified NBI were both 100% with specificity of 84.6%, surpassing all PIVI thresholds for dysplasia diagnosis in BE.</p><p><strong>Conclusion: </strong>This pilot study demonstrates the feasibility of TXI as a potential addition to the armamentarium of advanced mucosal imaging available to proceduralists surveilling BE. Further large multi-centre studies would be required to make statistical comparisons with existing imaging modalities.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noriyuki Kawami, Yoshimasa Hoshikawa, Eri Momma, Shintaro Hoshino, Katsuhiko Iwakiri
Background: Esophagogastroduodenoscopy is often performed as an initial examination in patients with symptoms such as dysphagia or chest pain, which may suggest esophageal motility disorders. However, its current role is largely limited to ruling out organic diseases.
Summary: High-resolution manometry (the gold standard for diagnosing primary esophageal motility disorders such as achalasia) along with esophagography is extremely useful for diagnosis. In recent years, however, several new endoscopic findings - esophageal rosette, gingko leaf sign, champagne glass sign, corona appearance, and pinstripe pattern - have been reported, making it increasingly possible to strongly suspect achalasia through endoscopy. Additionally, the presence of multiple annular contractions, spiral (corkscrew) contractions, or narrowing (poor distensibility) in the esophageal body during endoscopy may suggest abnormal motility of the esophageal body.
Key messages: When performing endoscopic examinations in patients with symptoms such as dysphagia or chest pain, it is important to consider the possibility of esophageal motility disorders. Careful endoscopic observation may allow for the suspicion of such disorders during the examination itself.
{"title":"Role of Endoscopy in Achalasia.","authors":"Noriyuki Kawami, Yoshimasa Hoshikawa, Eri Momma, Shintaro Hoshino, Katsuhiko Iwakiri","doi":"10.1159/000546952","DOIUrl":"10.1159/000546952","url":null,"abstract":"<p><strong>Background: </strong>Esophagogastroduodenoscopy is often performed as an initial examination in patients with symptoms such as dysphagia or chest pain, which may suggest esophageal motility disorders. However, its current role is largely limited to ruling out organic diseases.</p><p><strong>Summary: </strong>High-resolution manometry (the gold standard for diagnosing primary esophageal motility disorders such as achalasia) along with esophagography is extremely useful for diagnosis. In recent years, however, several new endoscopic findings - esophageal rosette, gingko leaf sign, champagne glass sign, corona appearance, and pinstripe pattern - have been reported, making it increasingly possible to strongly suspect achalasia through endoscopy. Additionally, the presence of multiple annular contractions, spiral (corkscrew) contractions, or narrowing (poor distensibility) in the esophageal body during endoscopy may suggest abnormal motility of the esophageal body.</p><p><strong>Key messages: </strong>When performing endoscopic examinations in patients with symptoms such as dysphagia or chest pain, it is important to consider the possibility of esophageal motility disorders. Careful endoscopic observation may allow for the suspicion of such disorders during the examination itself.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Systemic sclerosis (SSc) causes esophageal motility disorders. However, esophageal symptom severity often does not correlate with the physiological findings of high-resolution manometry (HRM) in patients with SSc. Esophageal hypervigilance and visceral anxiety play a relevant role in symptom perception in patients with gastroesophageal reflux disease and esophageal motility disorders. Therefore, the present study examined the effects of anxiety and hypervigilance, along with HRM findings, on esophageal symptom severity in patients with SSc.
Methods: We reviewed the clinical data of consecutive patients with SSc who underwent HRM and were assessed using the esophageal hypervigilance and anxiety scale (EHAS) at our hospital between January 2022 and February 2025. Predictors for the Eckardt symptom score (ESS) and gastroesophageal reflux disease questionnaire (GerdQ) were investigated.
Results: This study included 51 patients with SSc. Significant differences were observed in EHAS scores between patients with ESS >3 and those with ESS ≤3 (34.0 [24.0-42.0] vs. 13.0 [1.0-24.0], p = 0.003), but not in HRM findings. The EHAS score accounted for 38.2% of the variance in the ESS score. Significant differences were also observed in the EHAS score between patients with GerdQ ≥8 and those with GerdQ <8 (26.0 [14.3-32.5] vs. 13.0 [0-22.0], p = 0.011). The combined factors of the EHAS score and absent contractility accounted for 17.3% of the variance in the GerdQ score.
Conclusion: Esophageal hypervigilance and anxiety may be involved in esophageal symptom severity, particularly dysphagia severity, in patients with SSc. Further studies involving interventions targeting these conditions, such as cognitive behavioral therapy, are warranted.
{"title":"Esophageal Hypervigilance and Visceral Anxiety Are Involved in Esophageal Symptom Perception in Patients with Systemic Sclerosis.","authors":"Yoshimasa Hoshikawa, Mikito Suzuki, Eri Momma, Shintaro Hoshino, Noriyuki Kawami, Masataka Kuwana, Katsuhiko Iwakiri, Masanori Atsukawa","doi":"10.1159/000546892","DOIUrl":"10.1159/000546892","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic sclerosis (SSc) causes esophageal motility disorders. However, esophageal symptom severity often does not correlate with the physiological findings of high-resolution manometry (HRM) in patients with SSc. Esophageal hypervigilance and visceral anxiety play a relevant role in symptom perception in patients with gastroesophageal reflux disease and esophageal motility disorders. Therefore, the present study examined the effects of anxiety and hypervigilance, along with HRM findings, on esophageal symptom severity in patients with SSc.</p><p><strong>Methods: </strong>We reviewed the clinical data of consecutive patients with SSc who underwent HRM and were assessed using the esophageal hypervigilance and anxiety scale (EHAS) at our hospital between January 2022 and February 2025. Predictors for the Eckardt symptom score (ESS) and gastroesophageal reflux disease questionnaire (GerdQ) were investigated.</p><p><strong>Results: </strong>This study included 51 patients with SSc. Significant differences were observed in EHAS scores between patients with ESS >3 and those with ESS ≤3 (34.0 [24.0-42.0] vs. 13.0 [1.0-24.0], p = 0.003), but not in HRM findings. The EHAS score accounted for 38.2% of the variance in the ESS score. Significant differences were also observed in the EHAS score between patients with GerdQ ≥8 and those with GerdQ <8 (26.0 [14.3-32.5] vs. 13.0 [0-22.0], p = 0.011). The combined factors of the EHAS score and absent contractility accounted for 17.3% of the variance in the GerdQ score.</p><p><strong>Conclusion: </strong>Esophageal hypervigilance and anxiety may be involved in esophageal symptom severity, particularly dysphagia severity, in patients with SSc. Further studies involving interventions targeting these conditions, such as cognitive behavioral therapy, are warranted.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Esophageal squamous cell carcinoma (ESCC) is a highly fatal cancer with unclear molecular underpinnings. This study utilized bioinformatics to uncover key genes and pathways associated with ESCC and to identify prognostic markers.
Methods: We identified the differentially expressed genes (DEGs) using three datasets (GSE53625, GSE67269, and GSE23400-GPL96). Meanwhile, weighted gene co-expression network analysis (WGCNA) constructed gene co-expression networks based on the GSE23400-GLP97 dataset. Machine-learning algorithms further identified the most critical genes. Additionally, we validated the expression and diagnostic potential of the hub genes using the GSE161533 and GSE38129 datasets. Survival analysis and Gene Set Enrichment Analysis (GSEA) revealed the prognostic value and potential functions of the hub genes, respectively.
Results: The study identified 240 DGEs (103 upregulated and 137 downregulated). Concurrently, WGCNA pinpointed 209 genes associated with ESCC. Subsequently, machine-learning algorithms identify four hub genes, including KIF14, GALNT12, MGLL, and EMP1. Moreover, their expression differences and potential as diagnostic biomarkers for ESCC were validated. Survival analysis indicated that elevated GALNT12 expression was associated with a poor prognosis for ESCC patients. GSEA delineated the involvement of GALNT12 in critical biological pathways.
Conclusion: Our results identified GALNT12 as a novel potential diagnostic and prognostic marker for ESCC.
{"title":"Identification of <italic>GALNT12</italic> as a Novel Potential Diagnostic and Prognostic Marker for Esophageal Squamous Cell Carcinoma by Integrated Bioinformatics Analysis.","authors":"Zhaowei Chen, Lili Kang, Zhenze Yang, Yaoqing Cai, Shuyong Yu, Ping Li, Jian Song","doi":"10.1159/000546092","DOIUrl":"10.1159/000546092","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal squamous cell carcinoma (ESCC) is a highly fatal cancer with unclear molecular underpinnings. This study utilized bioinformatics to uncover key genes and pathways associated with ESCC and to identify prognostic markers.</p><p><strong>Methods: </strong>We identified the differentially expressed genes (DEGs) using three datasets (GSE53625, GSE67269, and GSE23400-GPL96). Meanwhile, weighted gene co-expression network analysis (WGCNA) constructed gene co-expression networks based on the GSE23400-GLP97 dataset. Machine-learning algorithms further identified the most critical genes. Additionally, we validated the expression and diagnostic potential of the hub genes using the GSE161533 and GSE38129 datasets. Survival analysis and Gene Set Enrichment Analysis (GSEA) revealed the prognostic value and potential functions of the hub genes, respectively.</p><p><strong>Results: </strong>The study identified 240 DGEs (103 upregulated and 137 downregulated). Concurrently, WGCNA pinpointed 209 genes associated with ESCC. Subsequently, machine-learning algorithms identify four hub genes, including KIF14, GALNT12, MGLL, and EMP1. Moreover, their expression differences and potential as diagnostic biomarkers for ESCC were validated. Survival analysis indicated that elevated GALNT12 expression was associated with a poor prognosis for ESCC patients. GSEA delineated the involvement of GALNT12 in critical biological pathways.</p><p><strong>Conclusion: </strong>Our results identified GALNT12 as a novel potential diagnostic and prognostic marker for ESCC.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-08-23DOI: 10.1159/000540939
Siyuan Dong, Yu Zhang, Lingna Ye, Qian Cao
<p><strong>Introduction: </strong>Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.</p><p><strong>Methods: </strong>Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correction" and "Robust rank aggregation" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by "AddModuleScore" and "AUCell."</p><p><strong>Results: </strong>Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001).</p><p><strong>Conclusion: </strong>This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.</p><p><strong>Introduction: </strong>Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.</p><p><strong>Methods: </strong>Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the "Batch correctio
{"title":"Identification of a Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis.","authors":"Siyuan Dong, Yu Zhang, Lingna Ye, Qian Cao","doi":"10.1159/000540939","DOIUrl":"10.1159/000540939","url":null,"abstract":"<p><strong>Introduction: </strong>Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.</p><p><strong>Methods: </strong>Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the \"Batch correction\" and \"Robust rank aggregation\" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by \"AddModuleScore\" and \"AUCell.\"</p><p><strong>Results: </strong>Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001).</p><p><strong>Conclusion: </strong>This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.</p><p><strong>Introduction: </strong>Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.</p><p><strong>Methods: </strong>Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the \"Batch correctio","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-22"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-02-12DOI: 10.1159/000543921
Takahisa Matsuda, Ai Fujimoto, Yoshinori Igarashi
Background: Colorectal cancer (CRC) is a significant global health issue, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Countries with a high Human Development Index (HDI) report the highest incidence rates, driven by dietary and lifestyle factors. In contrast, low-to-middle HDI countries are experiencing rising CRC rates due to urbanization and westernization. Japan exemplifies this shift, with increasing CRC incidence linked to the adoption of westernized diets. Despite advances in screening and treatment, CRC-related mortality remains substantial, with 53,088 deaths reported in Japan.
Summary: This review examines global and regional CRC trends, focusing on incidence, mortality, and risk factors such as genetic predispositions, diet, and lifestyle influences. The review highlights the growing burden of CRC in Japan and other regions where dietary changes and urbanization are prevalent. Key findings include the significant impact of processed foods, sugary beverages, obesity, alcohol, and smoking on CRC risk, as well as the protective effects of vitamin D, calcium, and fermented foods. The role of inflammatory bowel disease and diabetes in CRC risk is also discussed. Furthermore, the review emphasizes the importance of public health initiatives, including organized screening programs, in mitigating the CRC burden.
Key messages: Understanding the interplay between genetic, lifestyle, and environmental factors is crucial for developing effective prevention strategies. Enhancing CRC screening, early detection, and public health interventions can significantly reduce CRC-related mortality. Continued research and collaboration are essential for advancing CRC prevention and improving global health outcomes.
{"title":"Colorectal Cancer: Epidemiology, Risk Factors, and Public Health Strategies.","authors":"Takahisa Matsuda, Ai Fujimoto, Yoshinori Igarashi","doi":"10.1159/000543921","DOIUrl":"10.1159/000543921","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a significant global health issue, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Countries with a high Human Development Index (HDI) report the highest incidence rates, driven by dietary and lifestyle factors. In contrast, low-to-middle HDI countries are experiencing rising CRC rates due to urbanization and westernization. Japan exemplifies this shift, with increasing CRC incidence linked to the adoption of westernized diets. Despite advances in screening and treatment, CRC-related mortality remains substantial, with 53,088 deaths reported in Japan.</p><p><strong>Summary: </strong>This review examines global and regional CRC trends, focusing on incidence, mortality, and risk factors such as genetic predispositions, diet, and lifestyle influences. The review highlights the growing burden of CRC in Japan and other regions where dietary changes and urbanization are prevalent. Key findings include the significant impact of processed foods, sugary beverages, obesity, alcohol, and smoking on CRC risk, as well as the protective effects of vitamin D, calcium, and fermented foods. The role of inflammatory bowel disease and diabetes in CRC risk is also discussed. Furthermore, the review emphasizes the importance of public health initiatives, including organized screening programs, in mitigating the CRC burden.</p><p><strong>Key messages: </strong>Understanding the interplay between genetic, lifestyle, and environmental factors is crucial for developing effective prevention strategies. Enhancing CRC screening, early detection, and public health interventions can significantly reduce CRC-related mortality. Continued research and collaboration are essential for advancing CRC prevention and improving global health outcomes.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"91-99"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 h of arrival) or other clinical outcomes of CDB.
Methods: We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (<30 days) and late (<1 year) rebleeding, length of hospital stay, and transfusion requirements.
Results: In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], -7.9 to 12.3; p = 0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, -9.4 to 10.4; p = 1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay, and transfusion requirements.
Conclusion: The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN registry number, UMIN000026865).
{"title":"Urgent Contrast-Enhanced Computed Tomography before Early Colonoscopy in the Management of Colonic Diverticular Bleeding: A Multicenter Randomized Controlled Trial.","authors":"Yuichiro Hirai, Toshio Uraoka, Michiko Wada, Hideki Mori, Ai Fujimoto, Yuko Sakakibara, Tatsuya Toyokawa, Takashi Kagaya, Yoshihiro Sasaki, Tomohiko Mannami, Toshio Kuwai, Noriko Watanabe, Hiroshige Hamada, Naoki Esaka, Toshihisa Kimura, Hiroyuki Fujii, Yasuo Hosoda, Masaaki Shimada, Hideharu Miyabayashi, Shinichi Somada, Katsuhiro Mabe, Shuji Inoue, Hiroki Saito, Kensuke Furuya, Norio Kawamura, Tomohiro Kudo, Keisuke Hori, Naoto Sakamoto, Mototsugu Kato, Nobuya Higuchi, Naohiko Harada","doi":"10.1159/000541942","DOIUrl":"10.1159/000541942","url":null,"abstract":"<p><strong>Introduction: </strong>Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 h of arrival) or other clinical outcomes of CDB.</p><p><strong>Methods: </strong>We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (<30 days) and late (<1 year) rebleeding, length of hospital stay, and transfusion requirements.</p><p><strong>Results: </strong>In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], -7.9 to 12.3; p = 0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, -9.4 to 10.4; p = 1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay, and transfusion requirements.</p><p><strong>Conclusion: </strong>The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN registry number, UMIN000026865).</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"176-188"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Potassium-competitive acid blockers are effective against proton pump inhibitor-refractory gastroesophageal reflux disease; however, their long-term use is associated with economic disadvantages. Endoscopic procedures may reduce potassium-competitive acid blocker use. This study aimed to determine the optimal treatment strategy for patients with proton pump inhibitor-refractory gastroesophageal reflux disease from a cost-effectiveness perspective.
Methods: Using a Markov state transition model to simulate symptom changes in patients with proton pump inhibitor-refractory gastroesophageal reflux disease, the cost-effectiveness of two strategies was compared: endoscopic treatment (anti-reflux mucosectomy or endoscopic submucosal dissection for gastroesophageal reflux disease) followed by potassium-competitive acid blocker versus medication with high-dose potassium-competitive acid blocker. In both strategies, potassium-competitive acid blocker maintained symptoms at the lowest controllable dose. The time horizon varied from 10 to 50 years. The quality-adjusted life year and incremental cost-effectiveness ratio were calculated. Willingness to pay was set at 5,000,000 Japanese yen.
Results: The quality-adjusted life years gained were 0.90 and 0.95 for the endoscopic treatment and medication strategies, respectively. The incremental cost-effectiveness ratio varied with the follow-up period after the initial treatment, with the endoscopic treatment strategy being more cost-effective than the medication strategy at ≥50 years of follow-up. A dose reduction success rate of <84.1% for high-dose potassium-competitive acid blocker and an endoscopic treatment success rate of >66.8% were required to determine the superiority of the endoscopic treatment strategy at the 50-year follow-up after treatment.
Conclusions: The endoscopic treatment strategy is not cost-effective unless the patient is followed up for >50 years after the initial treatment.
{"title":"Cost-Effectiveness Analysis of Endoscopic Treatment versus Medication Strategy for Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease.","authors":"Fumiaki Ishibashi, Sho Suzuki, Kentaro Mochida, Takao Tonishi, Yuichi Ishibashi","doi":"10.1159/000543365","DOIUrl":"10.1159/000543365","url":null,"abstract":"<p><strong>Introduction: </strong>Potassium-competitive acid blockers are effective against proton pump inhibitor-refractory gastroesophageal reflux disease; however, their long-term use is associated with economic disadvantages. Endoscopic procedures may reduce potassium-competitive acid blocker use. This study aimed to determine the optimal treatment strategy for patients with proton pump inhibitor-refractory gastroesophageal reflux disease from a cost-effectiveness perspective.</p><p><strong>Methods: </strong>Using a Markov state transition model to simulate symptom changes in patients with proton pump inhibitor-refractory gastroesophageal reflux disease, the cost-effectiveness of two strategies was compared: endoscopic treatment (anti-reflux mucosectomy or endoscopic submucosal dissection for gastroesophageal reflux disease) followed by potassium-competitive acid blocker versus medication with high-dose potassium-competitive acid blocker. In both strategies, potassium-competitive acid blocker maintained symptoms at the lowest controllable dose. The time horizon varied from 10 to 50 years. The quality-adjusted life year and incremental cost-effectiveness ratio were calculated. Willingness to pay was set at 5,000,000 Japanese yen.</p><p><strong>Results: </strong>The quality-adjusted life years gained were 0.90 and 0.95 for the endoscopic treatment and medication strategies, respectively. The incremental cost-effectiveness ratio varied with the follow-up period after the initial treatment, with the endoscopic treatment strategy being more cost-effective than the medication strategy at ≥50 years of follow-up. A dose reduction success rate of <84.1% for high-dose potassium-competitive acid blocker and an endoscopic treatment success rate of >66.8% were required to determine the superiority of the endoscopic treatment strategy at the 50-year follow-up after treatment.</p><p><strong>Conclusions: </strong>The endoscopic treatment strategy is not cost-effective unless the patient is followed up for >50 years after the initial treatment.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"277-286"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-04-29DOI: 10.1159/000545483
Majid Komijani, Ez Sadoon Mahdi, Majid Komijani, Anita Alaghmand
Introduction: Autism is a neurological disability that often appears after the age of three in children, also known as an autism spectrum disorder (ASD). Several studies have examined the influence of some environmental factors, and many parameters related to the behavior of autistic patients have been measured in order to find ways to reduce ASD. This study investigates the relationship between ASD and serum levels of vitamin D3, B12, folic acid, and the gut microbiome.
Methods: The serum levels of vitamin D3, B12, and folic acid in ASD patients were measured by the ELISA method and compared to healthy groups. DNA was extracted from stool samples of ASD patients and the control group, and then the gut microbiome was investigated via a metagenomics approach. Metagenomics sequencing was performed to analyze the 16S rRNA gene sequencing for phylum and sub phylum level microbiome.
Result: The result showed no significant change in the VitD3 and folate levels of ASD patients compared to the control group (p = 0.157 and p = 0.0505, respectively). There was a significant difference in the VitB12 level between control healthy individuals and ASD patients, in which the serum VitB12 concentration was significantly lower than the control group (p = 0.0001). Our results regarding gut metagenomics showed that the abundance of the Actinobacteria by the phylum level was significantly higher in the ASD patients compared to the control group (p = 0.0013). The abundance of the Firmicutes by the phylum level was significantly lower in the ASD patients compared to the control group (p = 0.0016). The abundance of Bifidobacteriaceae, and Ruminococcaceae by the family level was significantly higher in the ASD patients compared to the control group (p = 0.0004 and p = 0.0489, respectively). Our results indicated less species richness in the ASD patients compared to the control group.
Conclusion: Patients with ASD have lower serum levels of vitamin B12 and different gut microbiome compared to healthy controls. Low vitamin B12 levels and altered gut microbiome are significantly associated with ASD in this study. However, further research is needed to determine whether these factors could serve as predictors of severe outcomes in ASD.
{"title":"Metagenomics Study Suggests the Role of Vitamins and Gut Microbiome in Autism Spectrum Disorder.","authors":"Majid Komijani, Ez Sadoon Mahdi, Majid Komijani, Anita Alaghmand","doi":"10.1159/000545483","DOIUrl":"10.1159/000545483","url":null,"abstract":"<p><strong>Introduction: </strong>Autism is a neurological disability that often appears after the age of three in children, also known as an autism spectrum disorder (ASD). Several studies have examined the influence of some environmental factors, and many parameters related to the behavior of autistic patients have been measured in order to find ways to reduce ASD. This study investigates the relationship between ASD and serum levels of vitamin D3, B12, folic acid, and the gut microbiome.</p><p><strong>Methods: </strong>The serum levels of vitamin D3, B12, and folic acid in ASD patients were measured by the ELISA method and compared to healthy groups. DNA was extracted from stool samples of ASD patients and the control group, and then the gut microbiome was investigated via a metagenomics approach. Metagenomics sequencing was performed to analyze the 16S rRNA gene sequencing for phylum and sub phylum level microbiome.</p><p><strong>Result: </strong>The result showed no significant change in the VitD3 and folate levels of ASD patients compared to the control group (p = 0.157 and p = 0.0505, respectively). There was a significant difference in the VitB12 level between control healthy individuals and ASD patients, in which the serum VitB12 concentration was significantly lower than the control group (p = 0.0001). Our results regarding gut metagenomics showed that the abundance of the Actinobacteria by the phylum level was significantly higher in the ASD patients compared to the control group (p = 0.0013). The abundance of the Firmicutes by the phylum level was significantly lower in the ASD patients compared to the control group (p = 0.0016). The abundance of Bifidobacteriaceae, and Ruminococcaceae by the family level was significantly higher in the ASD patients compared to the control group (p = 0.0004 and p = 0.0489, respectively). Our results indicated less species richness in the ASD patients compared to the control group.</p><p><strong>Conclusion: </strong>Patients with ASD have lower serum levels of vitamin B12 and different gut microbiome compared to healthy controls. Low vitamin B12 levels and altered gut microbiome are significantly associated with ASD in this study. However, further research is needed to determine whether these factors could serve as predictors of severe outcomes in ASD.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"515-529"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}