Pub Date : 2024-04-01DOI: 10.14309/ctg.0000000000000698
Y. Hernandez-Barco, J. McNabb-Baltar
{"title":"Chronic Pancreatitis and Pregnancy: Genetics Matter","authors":"Y. Hernandez-Barco, J. McNabb-Baltar","doi":"10.14309/ctg.0000000000000698","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000698","url":null,"abstract":"","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140764114","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000681
Miguel Mascarenhas Saraiva, Lucas Spindler, Nadia Fathallah, Hélene Beaussier, Célia Mamma, Tiago Ribeiro, João Afonso, Mariana Carvalho, Rita Moura, Pedro Cardoso, Francisco Mendes, Miguel Martins, Julien Adam, João Ferreira, Guilherme Macedo, Vincent de Parades
Introduction: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation).
Methods: A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated.
Results: The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00.
Discussion: The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.
简介:高分辨率肛门镜检查(HRA)是检测肛门鳞状细胞癌(ASCC)前兆的黄金标准。关于将人工智能(AI)模型应用于该模式的初步研究显示了良好的结果。然而,染色技术和肛门操作对这些算法有效性的影响尚未得到评估。我们旨在开发一种深度学习系统,用于自动区分不同亚组患者(未染色、醋酸、鲁戈尔和操作后)HRA 图像中的高级别(HSIL)与低级别(LSIL)鳞状上皮内病变:方法:根据 88 名患者 103 次 HRA 检查的 27,770 张图像,开发了一种卷积神经网络 (CNN),用于检测和区分高级别和低级别肛门鳞状上皮内病变。我们还进行了子分析,以评估算法在无染色、醋酸、鲁戈尔和肛管操作后的图像子集中的性能。计算了灵敏度、特异性、准确性、阳性和阴性预测值以及曲线下面积(AUC):结果:CNN 的总体准确率为 98.3%。该算法的灵敏度和特异度分别为 97.4% 和 99.2%。该算法区分 HSIL 和 LSIL 的准确率介于 91.5%(操作后)和 100%(鲁戈)之间。AUC介于0.95和1.00之间:将人工智能引入 HRA 可以准确检测和区分 ASCC 前体。我们的算法在不同的染色设置下都表现出卓越的性能。这一点极为重要,因为 HRA 检查中的实时人工智能模型有助于指导局部治疗或检测复发疾病。
{"title":"Deep Learning in High-Resolution Anoscopy: Assessing the Impact of Staining and Therapeutic Manipulation on Automated Detection of Anal Cancer Precursors.","authors":"Miguel Mascarenhas Saraiva, Lucas Spindler, Nadia Fathallah, Hélene Beaussier, Célia Mamma, Tiago Ribeiro, João Afonso, Mariana Carvalho, Rita Moura, Pedro Cardoso, Francisco Mendes, Miguel Martins, Julien Adam, João Ferreira, Guilherme Macedo, Vincent de Parades","doi":"10.14309/ctg.0000000000000681","DOIUrl":"10.14309/ctg.0000000000000681","url":null,"abstract":"<p><strong>Introduction: </strong>High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation).</p><p><strong>Methods: </strong>A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated.</p><p><strong>Results: </strong>The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00.</p><p><strong>Discussion: </strong>The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545873","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000688
Freddy Caldera, Stacey Rolak, Francis A Farraye, Brian M Necela, Davitte Cogen, Emily E Zona, Trevor L Schell, Oscar Ramirez Ramirez, Mazen Almasry, Kelly Chun, Mary S Hayney, Keith L Knutson
Introduction: Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine.
Methods: This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t 1 ) after dose 2, 28-65 days (t 2 ) (n = 183) and 6 months (±45 days) (t 3 ) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t 4 ) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t 2 ) and (t 3 ). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t 4 ).
Results: All patients had measurable CMIR at all time points. CMIR increased at t 2 compared with that at t 1 (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t 2 vs t 3 or significant boosting at t 4 . Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t 2 (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t 3 (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t 2 ( P < 0.001) and t 3 ( P < 0.001) and confirmed in a multivariable model ( P < 0.001).
Discussion: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.
{"title":"Higher and Sustained Cell-Mediated Immune Responses After 3 Doses of mRNA COVID-19 Vaccine in Patients With Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy.","authors":"Freddy Caldera, Stacey Rolak, Francis A Farraye, Brian M Necela, Davitte Cogen, Emily E Zona, Trevor L Schell, Oscar Ramirez Ramirez, Mazen Almasry, Kelly Chun, Mary S Hayney, Keith L Knutson","doi":"10.14309/ctg.0000000000000688","DOIUrl":"10.14309/ctg.0000000000000688","url":null,"abstract":"<p><strong>Introduction: </strong>Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine.</p><p><strong>Methods: </strong>This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t 1 ) after dose 2, 28-65 days (t 2 ) (n = 183) and 6 months (±45 days) (t 3 ) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t 4 ) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t 2 ) and (t 3 ). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t 4 ).</p><p><strong>Results: </strong>All patients had measurable CMIR at all time points. CMIR increased at t 2 compared with that at t 1 (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t 2 vs t 3 or significant boosting at t 4 . Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t 2 (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t 3 (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t 2 ( P < 0.001) and t 3 ( P < 0.001) and confirmed in a multivariable model ( P < 0.001).</p><p><strong>Discussion: </strong>A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721851","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000686
Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate
Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.
Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight.
Results: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471).
Discussion: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.
{"title":"Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study.","authors":"Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate","doi":"10.14309/ctg.0000000000000686","DOIUrl":"10.14309/ctg.0000000000000686","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.</p><p><strong>Methods: </strong>NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight.</p><p><strong>Results: </strong>Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471).</p><p><strong>Discussion: </strong>Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570022","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000690
Pei-Dong Miao, Ying Li, Yu-Dong Jiang
Abstract: Hepatocellular carcinoma (HCC) remains a formidable oncological challenge, calling for innovative therapeutic strategies to improve patient outcomes. MicroRNAs have emerged as key regulators in cancer, and miR-3682-3p shows potential as a diagnostic and prognostic biomarker in HCC. We conducted a comprehensive study to uncover its role in HCC biology, revealing dysregulation and clinical associations. Target gene analysis provided insights into potential molecular mechanisms. Moreover, we explored its impact on the tumor microenvironment, immune cell infiltration, and therapy responses. Our findings highlight miR-3682-3p as a promising candidate for further investigations and potential therapeutic strategies in HCC management.
{"title":"Celestial Insights: Unraveling the Role of miR-3682-3p in Hepatocellular Carcinoma.","authors":"Pei-Dong Miao, Ying Li, Yu-Dong Jiang","doi":"10.14309/ctg.0000000000000690","DOIUrl":"10.14309/ctg.0000000000000690","url":null,"abstract":"<p><strong>Abstract: </strong>Hepatocellular carcinoma (HCC) remains a formidable oncological challenge, calling for innovative therapeutic strategies to improve patient outcomes. MicroRNAs have emerged as key regulators in cancer, and miR-3682-3p shows potential as a diagnostic and prognostic biomarker in HCC. We conducted a comprehensive study to uncover its role in HCC biology, revealing dysregulation and clinical associations. Target gene analysis provided insights into potential molecular mechanisms. Moreover, we explored its impact on the tumor microenvironment, immune cell infiltration, and therapy responses. Our findings highlight miR-3682-3p as a promising candidate for further investigations and potential therapeutic strategies in HCC management.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706276","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000657
Rebecca Kristine Kappel, Tania Hviid Bisgaard, Gry Poulsen, Tine Jess
Introduction: Inflammatory bowel disease (IBD) is associated with depression and anxiety in adults, but data are scarce on risk of psychiatric diseases in children with IBD. We aimed to estimate the risk of anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD) in patients with pediatric-onset IBD.
Methods: We performed a nationwide, register-based cohort study including all patients with pediatric-onset IBD diagnosed in Denmark during 1998-2018, resulting in 3,559 patients matched 1:5 on age, sex, municipality of residence, and time period, resulting in 17,795 reference individuals. We used Cox regression to calculate hazard ratios for each outcome after a diagnosis with IBD.
Results: Patients with pediatric-onset IBD had an increased risk of depression (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.26-1.80) and of using antidepressants (HR, 1.54; 95% CI, 1.39-1.71) and, surprisingly, a reduced risk of using methylphenidate (HR, 0.75; 95% CI, 0.58-0.98). Patients with both IBD subtypes (Crohn's disease and ulcerative colitis) had an increased risk of using antidepressants and developing depression, which was particularly high in patients with Crohn's disease (HR, 1.73; 95% CI, 1.35-2.22). Patients with ulcerative colitis had reduced risk of using methylphenidate (HR, 0.63; 95% CI, 0.43-0.93) and a reduced-although not statistically significant-risk of being diagnosed with ADHD compared with the background population.
Discussion: Patients with pediatric-onset IBD have a 50% increased risk of developing depression, which is important for healthcare providers to be aware of and manage. Remarkably, we found a reduced risk of receiving methylphenidate and being diagnosed with ADHD, which merits further investigation.
{"title":"Risk of Anxiety, Depression, and Attention-Deficit/Hyperactivity Disorder in Pediatric Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study.","authors":"Rebecca Kristine Kappel, Tania Hviid Bisgaard, Gry Poulsen, Tine Jess","doi":"10.14309/ctg.0000000000000657","DOIUrl":"10.14309/ctg.0000000000000657","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD) is associated with depression and anxiety in adults, but data are scarce on risk of psychiatric diseases in children with IBD. We aimed to estimate the risk of anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD) in patients with pediatric-onset IBD.</p><p><strong>Methods: </strong>We performed a nationwide, register-based cohort study including all patients with pediatric-onset IBD diagnosed in Denmark during 1998-2018, resulting in 3,559 patients matched 1:5 on age, sex, municipality of residence, and time period, resulting in 17,795 reference individuals. We used Cox regression to calculate hazard ratios for each outcome after a diagnosis with IBD.</p><p><strong>Results: </strong>Patients with pediatric-onset IBD had an increased risk of depression (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.26-1.80) and of using antidepressants (HR, 1.54; 95% CI, 1.39-1.71) and, surprisingly, a reduced risk of using methylphenidate (HR, 0.75; 95% CI, 0.58-0.98). Patients with both IBD subtypes (Crohn's disease and ulcerative colitis) had an increased risk of using antidepressants and developing depression, which was particularly high in patients with Crohn's disease (HR, 1.73; 95% CI, 1.35-2.22). Patients with ulcerative colitis had reduced risk of using methylphenidate (HR, 0.63; 95% CI, 0.43-0.93) and a reduced-although not statistically significant-risk of being diagnosed with ADHD compared with the background population.</p><p><strong>Discussion: </strong>Patients with pediatric-onset IBD have a 50% increased risk of developing depression, which is important for healthcare providers to be aware of and manage. Remarkably, we found a reduced risk of receiving methylphenidate and being diagnosed with ADHD, which merits further investigation.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478711","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000685
Marko Damm, Katharina George, Jonas Rosendahl, Robin Greinert
Introduction: This study explores how chronic pancreatitis (CP) relates to subclinical cognitive impairment (SCI) and its prevalence, characteristics, risk factors, and effects on patients' quality of life (QoL) and physical performance.
Methods: Patients with fulfilled CP criteria in imaging were prospectively enrolled. Overt encephalopathy, neurodegenerative disorders, decompensated cirrhosis, and sepsis were exclusion criteria. All patients underwent psychometric testing and assessment of health-related QoL, such as mobility and strength. SCI was diagnosed when at least 1 test of the psychometric test battery was pathological.
Results: Seventy-one patients were enrolled. The etiology was toxic (alcohol/smoking) in most (49%) of the cases. SCI was prevalent in 41% of the patients while 25% had only 1 and 16% had 2 or more pathological tests. Patients with SCI exhibited diminished overall QoL scores ( P = 0.048), primarily affecting physical functionality ( P < 0.001). This was reaffirmed in mobility tests, where patients with SCI were slower in the timed up-and-go test ( P = 0.008) and showed increased prevalence of abnormal chair rising tests ( P = 0.004). Among all variables analyzed, only alcohol abuse was an independent risk factor of SCI (odds ratio 3.46; P = 0.02) in a multivariable regression model together with the variables age, sex, education, and compensated cirrhosis. Despite SCI affecting global QoL, sleep disturbance seemed to be the strongest variable independently associated with impaired QoL (odds ratio 9.9; P = 0.001).
Discussion: The largest study to the subject to date shows that SCI is common in patients with CP and is linked to significant morbidity. These findings suggest the need for addressing modifiable risk factors in patients with CP to improve outcomes.
研究目的本研究探讨慢性胰腺炎(CP)与亚临床认知障碍(SCI)的关系、其发病率、特征、风险因素、对患者生活质量(QoL)和身体表现的影响:方法:前瞻性地纳入了影像学检查符合 CP 标准的患者。排除标准包括:显性脑病、神经退行性疾病、失代偿性肝硬化或败血症。所有患者都接受了心理测试和健康相关的 QoL 评估,如活动能力和力量。如果心理测试中至少有一项测试出现病理变化,则可诊断为 SCI:共有 71 名患者入选。大多数病例(49%)的病因是中毒性(酗酒/吸烟)。41%的患者患有 SCI,25%的患者只有一项病理测试,16%的患者有两项或两项以上病理测试。SCI 患者的总体 QoL 评分降低(p=0.048),主要影响身体功能(p 结论:这是迄今为止关于该主题的最大规模研究:这项迄今为止规模最大的研究表明,SCI 在 CP 患者中很常见,并与严重的发病率有关。这些研究结果表明,有必要解决 CP 患者中可改变的风险因素,以改善预后。
{"title":"Subclinical Cognitive Impairment in Chronic Pancreatitis Is Associated With Reduced Mobility and Quality of Life.","authors":"Marko Damm, Katharina George, Jonas Rosendahl, Robin Greinert","doi":"10.14309/ctg.0000000000000685","DOIUrl":"10.14309/ctg.0000000000000685","url":null,"abstract":"<p><strong>Introduction: </strong>This study explores how chronic pancreatitis (CP) relates to subclinical cognitive impairment (SCI) and its prevalence, characteristics, risk factors, and effects on patients' quality of life (QoL) and physical performance.</p><p><strong>Methods: </strong>Patients with fulfilled CP criteria in imaging were prospectively enrolled. Overt encephalopathy, neurodegenerative disorders, decompensated cirrhosis, and sepsis were exclusion criteria. All patients underwent psychometric testing and assessment of health-related QoL, such as mobility and strength. SCI was diagnosed when at least 1 test of the psychometric test battery was pathological.</p><p><strong>Results: </strong>Seventy-one patients were enrolled. The etiology was toxic (alcohol/smoking) in most (49%) of the cases. SCI was prevalent in 41% of the patients while 25% had only 1 and 16% had 2 or more pathological tests. Patients with SCI exhibited diminished overall QoL scores ( P = 0.048), primarily affecting physical functionality ( P < 0.001). This was reaffirmed in mobility tests, where patients with SCI were slower in the timed up-and-go test ( P = 0.008) and showed increased prevalence of abnormal chair rising tests ( P = 0.004). Among all variables analyzed, only alcohol abuse was an independent risk factor of SCI (odds ratio 3.46; P = 0.02) in a multivariable regression model together with the variables age, sex, education, and compensated cirrhosis. Despite SCI affecting global QoL, sleep disturbance seemed to be the strongest variable independently associated with impaired QoL (odds ratio 9.9; P = 0.001).</p><p><strong>Discussion: </strong>The largest study to the subject to date shows that SCI is common in patients with CP and is linked to significant morbidity. These findings suggest the need for addressing modifiable risk factors in patients with CP to improve outcomes.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650354","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}
Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.
Methods: A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS.
Results: After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001).
Discussion: PNI had the best performance in predicting the OS for patients with very early-stage HCC.
导言:与肿瘤因素相比,现场因素在预测早期肝细胞癌(HCC)患者的预后方面发挥着更重要的作用。然而,肝纤维化和肝功能储备的非侵入性血清标志物评分对极早期 HCC 的预后能力尚未确定。我们旨在研究这些血清标志物评分在预测极早期 HCC 患者预后方面的表现:方法:回顾性纳入2012年至2022年期间的446例极早期HCC患者。血清生物标志物和决定总生存期(OS)的预后评分通过Cox比例危险模型进行分析。我们比较了预后营养指数(PNI)、谷草转氨酶与血小板比值指数(APRI)、白蛋白-胆红素(ALBI)评分、EZ(easy)-ALBI评分、改良ALBI评分、纤维化(FIB)-4评分和淋巴细胞与单核细胞比值(LMR)之间的阿凯克信息标准(AIC),以确定对OS的预测能力:中位随访时间为41.0个月(四分位数间距IQR为36.9-45.1个月),81名患者死亡,5年OS率为71.0%。在非侵入性血清标志物评分中,与其他评分相比,PNI在预测OS方面表现最佳,AIC(846.407)最低。此外,我们还将患者分为高风险组(PNI=45)。结果显示,PNI 低风险组和高风险组的 5 年 OS 率分别为 83.4% 和 60.8%(P 结论:PNI 在预测癌症 OS 方面表现最佳:PNI在预测极早期HCC患者的OS方面表现最佳。
{"title":"Prognostic Nutritional Index as a Prognostic Factor for Very Early-Stage Hepatocellular Carcinoma.","authors":"Chun-Ting Ho, Elise Chia-Hui Tan, Pei-Chang Lee, Chi-Jen Chu, Yi-Hsiang Huang, Teh-Ia Huo, Ming-Chih Hou, Jaw-Ching Wu, Chien-Wei Su","doi":"10.14309/ctg.0000000000000678","DOIUrl":"10.14309/ctg.0000000000000678","url":null,"abstract":"<p><strong>Introduction: </strong>Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.</p><p><strong>Methods: </strong>A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS.</p><p><strong>Results: </strong>After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001).</p><p><strong>Discussion: </strong>PNI had the best performance in predicting the OS for patients with very early-stage HCC.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490705","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000664
Thomas Greuter, Alex Straumann, Yuniel Fernandez-Marrero, Nina Germic, Aref Hosseini, Apinya Chanwangpong, Shida Yousefi, Dagmar Simon, Margaret H Collins, Christian Bussmann, Mirna Chehade, Evan S Dellon, Glenn T Furuta, Nirmala Gonsalves, Ikuo Hirano, Fouad J Moawad, Luc Biedermann, Ekaterina Safroneeva, Alain M Schoepfer, Hans-Uwe Simon
Introduction: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined.
Methods: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls.
Results: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months).
Discussion: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.
{"title":"A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time.","authors":"Thomas Greuter, Alex Straumann, Yuniel Fernandez-Marrero, Nina Germic, Aref Hosseini, Apinya Chanwangpong, Shida Yousefi, Dagmar Simon, Margaret H Collins, Christian Bussmann, Mirna Chehade, Evan S Dellon, Glenn T Furuta, Nirmala Gonsalves, Ikuo Hirano, Fouad J Moawad, Luc Biedermann, Ekaterina Safroneeva, Alain M Schoepfer, Hans-Uwe Simon","doi":"10.14309/ctg.0000000000000664","DOIUrl":"10.14309/ctg.0000000000000664","url":null,"abstract":"<p><strong>Introduction: </strong>Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined.</p><p><strong>Methods: </strong>Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls.</p><p><strong>Results: </strong>We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months).</p><p><strong>Discussion: </strong>Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691364","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 : 2024-04-01DOI: 10.14309/ctg.0000000000000691
Di Wu, Nan Ru, Yuan-Chen Wang, Guo-Xiu Ma, Tian-Yu Shi, Si-Huai Xiong, Ai-Jun You, Lei Wang, Liang-Hao Hu, Zhao-Shen Li, Wen-Bin Zou, Zhuan Liao
Introduction: The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients.
Methods: This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes.
Results: Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes.
Discussion: Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).
{"title":"Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis.","authors":"Di Wu, Nan Ru, Yuan-Chen Wang, Guo-Xiu Ma, Tian-Yu Shi, Si-Huai Xiong, Ai-Jun You, Lei Wang, Liang-Hao Hu, Zhao-Shen Li, Wen-Bin Zou, Zhuan Liao","doi":"10.14309/ctg.0000000000000691","DOIUrl":"10.14309/ctg.0000000000000691","url":null,"abstract":"<p><strong>Introduction: </strong>The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients.</p><p><strong>Methods: </strong>This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes.</p><p><strong>Results: </strong>Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes.</p><p><strong>Discussion: </strong>Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11042769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706277","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}