Digestive Diseases and Sciences最新文献

{"title":"The Impact of Concomitant Hypothyroid Disease on the Course of Inflammatory Bowel Disease.","authors":"Maaz Ahsan, Jahnavi Udaikumar, Simon Hong, Adam S Faye, Seymour Katz, Olivia Delau, Jordan Axelrad","doi":"10.1007/s10620-025-08956-6","DOIUrl":"10.1007/s10620-025-08956-6","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. In IBD, systemic inflammation and immune dysregulation may also impact extraintestinal organs, such as the thyroid gland. Despite this, little is known about the influence of concomitant hypothyroidism on the clinical course of IBD.</p><p><strong>Methods: </strong>A retrospective analysis was conducted among adult patients with IBD and at least one thyroid stimulating hormone (TSH) measurement within a large healthcare network. Patient charts were reviewed, and baseline demographics, disease characteristics, biomarkers, healthcare utilization, medication use, and other comorbidities were extracted. Patients were stratified by those with IBD only and those with concomitant IBD and hypothyroidism. Multivariable logistic regression was used to identify factors associated with concomitant hypothyroidism. Concomitant disease as an independent predictor for lab abnormalities and increased healthcare utilization was also assessed using multivariable logistic and negative binomial regression.</p><p><strong>Results: </strong>We identified 287 adult patients with IBD, including 146 (50.9%) with Crohn's disease (CD) and 141 (49.1%) with ulcerative colitis (UC). Among this sample, 178 (62.0%) patients had concomitant hypothyroidism. Concomitant disease was associated with older age (_adjOR 1.04, 95% CI 1.02, 1.06), female sex (_adjOR 1.78, 95% CI 1.01, 3.16), and the presence of other extraintestinal manifestations (_adjOR 2.30, 95% CI 1.06, 5.00). Concomitant disease was also found to be a significant predictor for increased healthcare utilization, specifically, higher number of radiation-based abdominal imaging (RBAI) studies (_adjIRR: 1.89, 95% CI 1.08, 3.32).</p><p><strong>Conclusion: </strong>Patients with both IBD and hypothyroidism have an increased likelihood of other extraintestinal manifestations compared to individuals who have IBD without hypothyroidism. Furthermore, patients with concomitant disease exhibited greater healthcare utilization, specifically, increased rates of RBAI studies. The presence of concomitant hypothyroidism may be associated with a more severe course of IBD.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1854-1863"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NFAT2 Induces Tumor Cell Proliferation and Metastasis by Acting as a Transcriptional Co-activator of the TGF-β1/SMAD Signaling Pathway and Inducing the Epithelial-Mesenchymal Transition in Liver Cancer.","authors":"Yuqi Liu, Wenhui Mo, Weijie Sun, Jianqing Chen, Jiaojiao Chen, Yueyue Li, Dengyu Han, Weiqi Dai, Ruling Zhang","doi":"10.1007/s10620-025-08890-7","DOIUrl":"10.1007/s10620-025-08890-7","url":null,"abstract":"<p><strong>Background: </strong>The role of NFAT2 in liver cancer is conflicting, with evidence suggesting both oncogenic and tumor-suppressive effects. A clear understanding of its expression, function, regulation, and mechanism of action in liver cancer remains critical.</p><p><strong>Objectives: </strong>To examine the expression levels, biological functions, regulatory mechanisms, and downstream pathways of NFAT2 in liver cancer and its metastasis.</p><p><strong>Methods: </strong>The expression of NFAT2 was analyzed in liver cancer patients and correlated with clinical outcomes. Functional assays, including proliferation, migration, invasion, and xenograft models, were employed to assess the effects of NFAT2 upregulation and downregulation. Molecular analyses were conducted to identify key pathways and protein interactions underpinning NFAT2's effects. The therapeutic potential of NFAT2 inhibition in combination with sorafenib was also evaluated.</p><p><strong>Results: </strong>NFAT2 overexpression was associated with poor prognosis and shorter disease-free survival in liver cancer patients. Upregulation of NFAT2 promoted hepatoma cell proliferation, migration, and invasion, while its downregulation impaired these pro-oncogenic effects. Mechanistically, NFAT2 enhanced the epithelial-to-mesenchymal transition (EMT) by increasing mesenchymal marker expression (N-cadherin, vimentin, MMP9) and decreasing invasion inhibitors (E-cadherin, ZO-1). It physically interacted with SMAD3 and p300, thereby activating the TGF-β1/SMAD pathway to drive tumor progression. NFAT2 knockdown or inhibition re-sensitized tumor cells to sorafenib, indicating its promising therapeutic potential.</p><p><strong>Conclusion: </strong>NFAT2 acts as a transcriptional co-activator of the TGF-β1/SMAD signaling pathway, promoting liver cancer progression and metastasis. Its inhibition could serve as a novel therapeutic strategy for the treatment of advanced liver cancer, particularly in combination with sorafenib.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1799-1812"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Prior Anti-TNF Exposure and Colectomy in Acute Severe Ulcerative Colitis.","authors":"Cong Dai, Xin-Yi Su","doi":"10.1007/s10620-025-08891-6","DOIUrl":"10.1007/s10620-025-08891-6","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1915-1916"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pressure Mounts: Predictive Power of Intra-abdominal Hypertension in Patients with Severe Acute Pancreatitis.","authors":"Sukhraj Pal Singh, Bipadabhanjan Mallick, Preetam Nath","doi":"10.1007/s10620-025-08931-1","DOIUrl":"10.1007/s10620-025-08931-1","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1738-1739"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous Hepatoduodenal Fistula Due to Ruptured Amoebic Liver Abscess.","authors":"Sanjeev Sachdeva, Venkatesh Vaithiyam, Aarushi Ahuja, Ravi Teja Reddy","doi":"10.1007/s10620-025-08924-0","DOIUrl":"10.1007/s10620-025-08924-0","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1736-1737"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholestatic Phenotype in Autoimmune Hepatitis: A Rare Presentation.","authors":"Vutukuri Bhargava Sai Srinath, Fatima Shahid, Muhammad Nabeel Saddique, Hassan Mumtaz, Javed Iqbal","doi":"10.1007/s10620-025-08927-x","DOIUrl":"10.1007/s10620-025-08927-x","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1733-1735"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are Non-invasive Multi-cancer Early Cancer Detection Tests the Future?","authors":"William M Grady","doi":"10.1007/s10620-024-08839-2","DOIUrl":"10.1007/s10620-024-08839-2","url":null,"abstract":"<p><p>Current cancer screening methods are effective for detecting early stage cancers and even preventing some cancers, but their effectiveness has only been demonstrated for a handful of cancers, and for many cancers, there are no screening tests clinically available. In addition, the majority of the screening methods are not ideal, resulting in suboptimal compliance and the occurrence of preventable cancers. A screening test that is convenient, safe, accurate and that can screen for multiple cancers is an ideal screening test that would address many of the shortcomings of the current tests. Multi-cancer detection tests (MCD) have the potential to meet these challenges and have engendered substantial enthusiasm in light of this. Using advances in DNA sequencing technology, cancer epigenetics and artificial intelligence, they are able to detect a large number of cancers predominantly via the patterns of methylated DNA alterations, DNA sequence alterations, and DNA fragment patterns of cell free DNA in the plasma and can accurately distinguish the cancer site of origin. Of note, some of the tests also combine circulating free DNA (cfDNA) with protein-based markers. However, for the majority of early stage cancers, the sensitivity is modest and below that of most of the current standard of care cancer screening tests. Furthermore, the clinical utility of screening for many of the cancers detectable by MCD tests remains to be proven. Here we describe the features of MCD tests, review the current data supporting their potential to be used in the clinic for cancer screening, and discuss the knowledge gaps surrounding understanding their clinical utility, with a focus on GI cancer screening.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1694-1702"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Guidance and Key Requirements for Invitro Diagnostic Test Development Phases.","authors":"Gerard J Davis","doi":"10.1007/s10620-024-08837-4","DOIUrl":"10.1007/s10620-024-08837-4","url":null,"abstract":"<p><p>Biomarker development phases require progressively greater test maturity to meet critical alignment for use at the downstream development phases. During discovery phase, many biomarkers may be candidates for addressing a clinical indication. Well-controlled early assay prototypes may be sufficient to identify which markers are promising test candidates to evaluate further. Advancing biomarker candidates require subsequent clinical evidence expansion consisting of smaller research level clinical studies. An analytically robust prototype is needed to assure that results are reproducible across all research study conditions. This requires vigilant QC utilization to support results validity across many research studies. With supportive clinical evidence, advancing candidates in clinical translation phase requires development of highly robust and reproducible assay formats that are analytically reliable across an extensive range of testing variables such as numerous laboratories, laboratory conditions, and manufactured test lots. Regulators and best practices require extensive processes development, kit stability establishment, extensive analytical verifications and clinical validation to support submissions, and test suitability for the clinical intended use. Rigorous analytical verifications by standardized methods are required to establish that the test's analytical attributes achieve the product requirements. Structured clinical validation requires final test/instrumentation/software configurations with final manufacturing formulas. Clinical validation requires appropriately planned clinical cohorts that align with the test's proposed clinical intended use. Formal analytical verification and clinical validation studies support regulatory submissions, and if approved support the labeling claims of the test in the package inserts of the diagnostic test.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1723-1727"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling and the Use of Surrogate Endpoints: Is This a Valid Approach?","authors":"Uri Ladabaum, Luuk A van Duuren, Elizabeth E Half, Zohar Levi, Barbara Silverman, Iris Lansdorp-Vogelaar","doi":"10.1007/s10620-024-08725-x","DOIUrl":"10.1007/s10620-024-08725-x","url":null,"abstract":"<p><strong>Background: </strong>Development of novel colorectal cancer (CRC) screening tests is a dynamic field. Decision analytic modeling based on inputs derived from rigorous prospective studies informs CRC screening guidelines. Exploratory modeling may have a place in early phases of test development.</p><p><strong>Methods: </strong>We explored whether (1) surrogate endpoints for long-term, programmatic effectiveness, and cost-effectiveness could be potentially informative in early stages of test development and (2) whether rapid exploratory modeling with a web-based tool would be feasible.</p><p><strong>Results: </strong>First, based on comparisons with published estimates for reductions in CRC mortality with various screening tests in four established decision analytic models of CRC screening, the surrogate endpoint of the number needed to colonoscope to detect one CRC or advanced precancerous lesion (APL) in round 1 of screening appears to hold promise as a measure of clinical effectiveness. Similarly, based on comparisons with published estimates for cost/quality-adjusted life-year gained with screening in the four models, the surrogate endpoint of cost to detect one CRC or APL in round 1 of screening appears to hold promise as a measure of cost-effectiveness. Second, exploration of the impact of lowering the screening initiation age in Israel from age 50 to 45 with the web-based EU-TOPIA tool, compared with the results of a recently published comprehensive modeling study, suggests that exploratory modeling of programmatic screening may be feasible with relatively low time demand vs. that required for typical full-length modeling publications.</p><p><strong>Conclusion: </strong>Further validation in other models and with a broader set of test performance characteristics is prudent before surrogate endpoints or rapid modeling are incorporated into the novel test development process.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1711-1722"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Colonoscopy as a First Screening Test Still Make Sense?-Counterpoint.","authors":"Mark Pi-Chun Chuang, Han-Mo Chiu","doi":"10.1007/s10620-024-08695-0","DOIUrl":"10.1007/s10620-024-08695-0","url":null,"abstract":"<p><p>Colonoscopy has been widely regarded as the gold standard for its high diagnostic accuracy and preventive potential. However, its invasive nature, high cost, and suboptimal participation rates limit its utility at the population level. Non-invasive screening tests, notably the fecal immunochemical test (FIT) and multitarget stool DNA tests, present promising alternatives that may improve screening participation and reduce barriers to participation. Among these, FIT has demonstrated a consistent advantage in enhancing participation, which subsequently contributes to better long-term outcomes in CRC prevention. FIT-based two-step screening offers several practical advantages, including cost-effectiveness, non-invasiveness, and greater flexibility. Moreover, the quantitative nature of FIT allows for adjustable sensitivity thresholds and the ability of risk stratification, making it adaptable across diverse populations and scenarios. Through serial testing, FIT can increase cumulative detection rates over time. This approach facilitates the identification of high-risk individuals, allowing for more judicious use of colonoscopy resources and reducing unnecessary invasive procedures, especially among low-risk populations. Notably, evidence indicates that participation to FIT-based screening is consistently higher than to colonoscopy, which enhances the detection of early-stage cancers and advanced adenomas in the long run. Given the constraints of limited endoscopic capacity, the aging population, and the recent lowering of the recommended screening age due to the rising incidence of early-onset CRC, FIT emerges as a practical, flexible solution. The role of two-step FIT screening in improving participation and enabling risk-stratified, personalized approaches to CRC prevention is pivotal, advocating for its expanded integration into future screening paradigms.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":" ","pages":"1606-1615"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}