Introduction: Altered gut microbiota may play a role in slow-transit constipation (STC). We conducted a study of gut microbiota composition and functionality in STC using metagenomic analyses.
Methods: We assembled a clinical cohort of 24 patients with STC physiology age- and sex-matched to 24 controls. We performed shotgun metagenomic sequencing followed by prediction of metabolite composition from functional profiles.
Results: In a middle-aged (mean 55.3 years), predominantly female cohort, there were no significant differences in α-diversity indices, but permutational multivariate analysis of variance analysis showed significant between-group differences (R 2 = 0.050, P < 0.001) between STC patients and controls. Gordonibacter pamelaeae , Bifidobacterium longum , Firmicutes bacterium co-abundance gene group 94, and Anaerotruncus colihominis were more abundant in STC, whereas Coprococcus comes and Roseburia intestinalis were more abundant in controls. Gut-derived metabolites varying in STC relative to controls were related to bile acid and cholesterol metabolism.
Discussion: We found a unique metagenomic and metabolomic signature of STC.
{"title":"Metagenomics Analysis Reveals Unique Gut Microbiota Signature of Slow-Transit Constipation.","authors":"Kyungsun Han, Braden Kuo, Hamed Khalili, Kyle Staller","doi":"10.14309/ctg.0000000000000766","DOIUrl":"10.14309/ctg.0000000000000766","url":null,"abstract":"<p><strong>Introduction: </strong>Altered gut microbiota may play a role in slow-transit constipation (STC). We conducted a study of gut microbiota composition and functionality in STC using metagenomic analyses.</p><p><strong>Methods: </strong>We assembled a clinical cohort of 24 patients with STC physiology age- and sex-matched to 24 controls. We performed shotgun metagenomic sequencing followed by prediction of metabolite composition from functional profiles.</p><p><strong>Results: </strong>In a middle-aged (mean 55.3 years), predominantly female cohort, there were no significant differences in α-diversity indices, but permutational multivariate analysis of variance analysis showed significant between-group differences (R 2 = 0.050, P < 0.001) between STC patients and controls. Gordonibacter pamelaeae , Bifidobacterium longum , Firmicutes bacterium co-abundance gene group 94, and Anaerotruncus colihominis were more abundant in STC, whereas Coprococcus comes and Roseburia intestinalis were more abundant in controls. Gut-derived metabolites varying in STC relative to controls were related to bile acid and cholesterol metabolism.</p><p><strong>Discussion: </strong>We found a unique metagenomic and metabolomic signature of STC.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e1"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119130","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 : 2024-10-01DOI: 10.14309/ctg.0000000000000733
Helena Ekoff, Niclas Rydell, Per M Hellström, Robert Movérare
Introduction: Neutrophilic calprotectin (CP) and myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and eosinophil-derived neurotoxin (EDN) are suggested proxy markers for gut inflammation. However, there are insufficient supporting data for MPO, NGAL, and EDN.
Methods: In a cross-sectional investigation including adult patients, we studied the ability of CP, MPO, NGAL, and EDN, measured in fecal and serum samples, to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and to predict disease activity.
Results: Fifty-nine patients had ulcerative colitis (UC), 38 had Crohn's disease, and 100 patients had IBS. The protein concentrations were higher in patients with IBD in the fecal samples ( P < 0.001) and the serum samples ( P < 0.01), and they correlated weakly (r s ≤0.38) between the sample sources. Fecal EDN was higher in patients with Crohn's disease compared with UC (1.79 vs 0.50 mg/kg, P = 0.016). The neutrophilic proteins were superior to EDN in the fecal samples for differentiating between patients with IBD and IBS. Fecal MPO (cutoff: 0.86 mg/kg) had the highest sensitivity (74.7%) and specificity (84.6%). Combining fecal CP and MPO increased the sensitivity to 82.3% (specificity: 73.6%). NGAL (cutoff: 196.9 μg/L) showed the best discriminating performance in serum (sensitivity: 62.9%; specificity: 68.0%). Serum NGAL (cutoff: 272.4 μg/L) predicted active disease in UC (Partial Mayo Score ≥2) with a sensitivity and specificity of 57.1% and 83.3%, respectively.
Discussion: Fecal MPO and serum NGAL are promising novel biomarkers, in addition to fecal CP, for differentiating between IBD and IBS. Serum NGAL may also predict disease activity in patients with UC.
{"title":"Fecal and Serum Granulocyte Protein Levels in Inflammatory Bowel Disease and Irritable Bowel Syndrome and Their Relation to Disease Activity.","authors":"Helena Ekoff, Niclas Rydell, Per M Hellström, Robert Movérare","doi":"10.14309/ctg.0000000000000733","DOIUrl":"10.14309/ctg.0000000000000733","url":null,"abstract":"<p><strong>Introduction: </strong>Neutrophilic calprotectin (CP) and myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and eosinophil-derived neurotoxin (EDN) are suggested proxy markers for gut inflammation. However, there are insufficient supporting data for MPO, NGAL, and EDN.</p><p><strong>Methods: </strong>In a cross-sectional investigation including adult patients, we studied the ability of CP, MPO, NGAL, and EDN, measured in fecal and serum samples, to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and to predict disease activity.</p><p><strong>Results: </strong>Fifty-nine patients had ulcerative colitis (UC), 38 had Crohn's disease, and 100 patients had IBS. The protein concentrations were higher in patients with IBD in the fecal samples ( P < 0.001) and the serum samples ( P < 0.01), and they correlated weakly (r s ≤0.38) between the sample sources. Fecal EDN was higher in patients with Crohn's disease compared with UC (1.79 vs 0.50 mg/kg, P = 0.016). The neutrophilic proteins were superior to EDN in the fecal samples for differentiating between patients with IBD and IBS. Fecal MPO (cutoff: 0.86 mg/kg) had the highest sensitivity (74.7%) and specificity (84.6%). Combining fecal CP and MPO increased the sensitivity to 82.3% (specificity: 73.6%). NGAL (cutoff: 196.9 μg/L) showed the best discriminating performance in serum (sensitivity: 62.9%; specificity: 68.0%). Serum NGAL (cutoff: 272.4 μg/L) predicted active disease in UC (Partial Mayo Score ≥2) with a sensitivity and specificity of 57.1% and 83.3%, respectively.</p><p><strong>Discussion: </strong>Fecal MPO and serum NGAL are promising novel biomarkers, in addition to fecal CP, for differentiating between IBD and IBS. Serum NGAL may also predict disease activity in patients with UC.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e1"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449858","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 : 2024-10-01DOI: 10.14309/ctg.0000000000000699
Han-Ning Liu, Rui Wang, Yan Cao, Feng Xian, Xian-Jin Bi, Ding-Jian Wu, Bin Wang, Xing-Wei Wang, Chun-Hui Lan
Introduction: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period.
Methods: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multicenter, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed.
Results: The intention-to-treat analysis revealed that H. pylori eradication rates were 83.9% (95% confidence interval 78.2%-91.3%) and 81.4% (95% confidence interval 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them ( P = 0.606). The per-protocol analysis revealed that the H. pylori eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively ( P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs 89.0%, P = 0.020).
Discussion: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.
简介替戈普拉赞(Tegoprazan,TPZ)是一种钾竞争性酸阻滞剂,具有很强的抑酸作用,而且起效迅速。然而,有关 TPZ-阿莫西林(TA)双重治疗的研究还很有限。在此,我们比较了TPZ-阿莫西林双重治疗与TPZ、枸橼酸铋钾、阿莫西林和克拉霉素(TBAC)四联疗法在新诊断的幽门螺杆菌感染患者中14天治疗期的安全性和有效性:这项多中心、前瞻性、开放标签和随机对照研究共招募了 236 名新确诊的幽门螺杆菌感染患者。患者随机接受 TA 双联疗法或 TBAC 四联疗法。研究记录并分析了不良反应发生率和治疗依从性:意向治疗分析显示,TA组和TBAC组的幽门螺杆菌根除率分别为83.9%(95%置信区间[CI] 78.2%-91.3%)和81.4%(95%置信区间[CI] 74.2%-88.5%),差异无统计学意义(P = 0.606)。按协议分析显示,TA组和TBAC组的幽门螺杆菌根除率分别为88.3%和84.8%(P = 0.447)。TA组的不良反应发生率明显低于TBAC组(4.2% vs. 15.3%,P = 0.004)。此外,TA组的治疗依从性大大高于TBAC组(94.1% vs. 89.0%,P = 0.020):TA双重疗法成功根除了幽门螺杆菌,根除率高,不良反应发生率低。因此,建议将该疗法作为新诊断幽门螺杆菌感染患者的替代疗法。
{"title":"Comparison of the Efficacy Between the Dual Therapy of Tegoprazan and the Quadruple Therapy of Tegoprazan: A Randomized Controlled Multicenter Study.","authors":"Han-Ning Liu, Rui Wang, Yan Cao, Feng Xian, Xian-Jin Bi, Ding-Jian Wu, Bin Wang, Xing-Wei Wang, Chun-Hui Lan","doi":"10.14309/ctg.0000000000000699","DOIUrl":"10.14309/ctg.0000000000000699","url":null,"abstract":"<p><strong>Introduction: </strong>Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period.</p><p><strong>Methods: </strong>A total of 236 patients newly diagnosed with H. pylori were enrolled in this multicenter, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed.</p><p><strong>Results: </strong>The intention-to-treat analysis revealed that H. pylori eradication rates were 83.9% (95% confidence interval 78.2%-91.3%) and 81.4% (95% confidence interval 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them ( P = 0.606). The per-protocol analysis revealed that the H. pylori eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively ( P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs 89.0%, P = 0.020).</p><p><strong>Discussion: </strong>The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e1"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334906","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 : 2024-09-26DOI: 10.14309/ctg.0000000000000771
Miguel Mascarenhas Saraiva, Mariano González-Haba, Jessica Widmer, Francisco Mendes, Tamas Gonda, Belen Agudo, Tiago Ribeiro, António Costa, Yousef Fazel, Marcos Eduardo Lera, Eduardo Horneaux de Moura, Matheus Ferreira de Carvalho, Alexandre Bestetti, João Afonso, Miguel Martins, Maria João Almeida, Filipe Vilas-Boas, Pedro Moutinho-Ribeiro, Susana Lopes, Joana Fernandes, João Ferreira, Guilherme Macedo
Introduction: Endoscopic ultrasound (EUS) allows for characterization and biopsy of pancreatic lesions. Pancreatic cystic neoplasms (PCN) include mucinous (M-PCN) and nonmucinous lesions (NM-PCN). Pancreatic ductal adenocarcinoma (P-DAC) is the commonest pancreatic solid lesion (PSL), followed by pancreatic neuroendocrine tumor (P-NET). Although EUS is preferred for pancreatic lesion evaluation, its diagnostic accuracy is suboptimal. This multicentric study aims to develop a convolutional neural network (CNN) for detecting and distinguishing PCN (namely M-PCN and NM-PCN) and PSL (particularly P-DAC and P-NET).
Methods: A CNN was developed with 378 EUS examinations from 4 international reference centers (Centro Hospitalar Universitário São João, Hospital Universitario Puerta de Hierro Majadahonda, New York University Hospitals, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo). About 126.000 images were obtained-19.528 M-PCN, 8.175 NM-PCN, 64.286 P-DAC, 29.153 P-NET, and 4.858 normal pancreas images. A trinary CNN differentiated normal pancreas tissue from M-PCN and NM-PCN. A binary CNN distinguished P-DAC from P-NET. The total data set was divided into a training and testing data set (used for model's evaluation) in a 90/10% ratio. The model was evaluated through its sensitivity, specificity, positive and negative predictive values, and accuracy.
Results: The CNN had 99.1% accuracy for identifying normal pancreatic tissue, 99.0% and 99.8% for M-PCN and NM-PCN, respectively. P-DAC and P-NET were distinguished with 94.0% accuracy.
Discussion: Our group developed the first worldwide CNN capable of detecting and differentiating the commonest PCN and PSL in EUS images, using examinations from 4 centers in 2 continents, minimizing the impact of the demographic bias. Larger multicentric studies are needed for technology implementation.
{"title":"Deep Learning and Automatic Differentiation of Pancreatic Lesions in Endoscopic Ultrasound: A Transatlantic Study.","authors":"Miguel Mascarenhas Saraiva, Mariano González-Haba, Jessica Widmer, Francisco Mendes, Tamas Gonda, Belen Agudo, Tiago Ribeiro, António Costa, Yousef Fazel, Marcos Eduardo Lera, Eduardo Horneaux de Moura, Matheus Ferreira de Carvalho, Alexandre Bestetti, João Afonso, Miguel Martins, Maria João Almeida, Filipe Vilas-Boas, Pedro Moutinho-Ribeiro, Susana Lopes, Joana Fernandes, João Ferreira, Guilherme Macedo","doi":"10.14309/ctg.0000000000000771","DOIUrl":"10.14309/ctg.0000000000000771","url":null,"abstract":"<p><strong>Introduction: </strong>Endoscopic ultrasound (EUS) allows for characterization and biopsy of pancreatic lesions. Pancreatic cystic neoplasms (PCN) include mucinous (M-PCN) and nonmucinous lesions (NM-PCN). Pancreatic ductal adenocarcinoma (P-DAC) is the commonest pancreatic solid lesion (PSL), followed by pancreatic neuroendocrine tumor (P-NET). Although EUS is preferred for pancreatic lesion evaluation, its diagnostic accuracy is suboptimal. This multicentric study aims to develop a convolutional neural network (CNN) for detecting and distinguishing PCN (namely M-PCN and NM-PCN) and PSL (particularly P-DAC and P-NET).</p><p><strong>Methods: </strong>A CNN was developed with 378 EUS examinations from 4 international reference centers (Centro Hospitalar Universitário São João, Hospital Universitario Puerta de Hierro Majadahonda, New York University Hospitals, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo). About 126.000 images were obtained-19.528 M-PCN, 8.175 NM-PCN, 64.286 P-DAC, 29.153 P-NET, and 4.858 normal pancreas images. A trinary CNN differentiated normal pancreas tissue from M-PCN and NM-PCN. A binary CNN distinguished P-DAC from P-NET. The total data set was divided into a training and testing data set (used for model's evaluation) in a 90/10% ratio. The model was evaluated through its sensitivity, specificity, positive and negative predictive values, and accuracy.</p><p><strong>Results: </strong>The CNN had 99.1% accuracy for identifying normal pancreatic tissue, 99.0% and 99.8% for M-PCN and NM-PCN, respectively. P-DAC and P-NET were distinguished with 94.0% accuracy.</p><p><strong>Discussion: </strong>Our group developed the first worldwide CNN capable of detecting and differentiating the commonest PCN and PSL in EUS images, using examinations from 4 centers in 2 continents, minimizing the impact of the demographic bias. Larger multicentric studies are needed for technology implementation.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342738","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 : 2024-09-23DOI: 10.14309/ctg.0000000000000770
Mian B Khalid, Hanna L Blaney, Anusha Vittal, Alexander H Yang, Bilal A Asif, Natasha Kamal, Elizabeth C Wright, Chris Koh, David George, David Goldman, Yvonne Horneffer, Nancy Diazgranados, Theo Heller
Introduction: Splenic stiffness (SS) measurement (SSM) is an evolving noninvasive assessment to evaluate portal hypertension. Studies with respect to SSM in patients with alcohol use disorder are limited.
Methods: We studied patients seeking treatment for alcohol use disorder in an inpatient treatment protocol at the National Institutes of Health and parsed SSM into 3 groups based on degree of change.
Results: The improved SS group had statistically higher initial SSM and a nonstatistically increased liver stiffness measurement compared with others.
Discussion: SS is dynamic in a subset of patients immediately after alcohol cessation, and improved SS is associated with a normalization of platelet count.
{"title":"Dynamics of Splenic Transient Elastography in Patients With Alcohol Use Disorder.","authors":"Mian B Khalid, Hanna L Blaney, Anusha Vittal, Alexander H Yang, Bilal A Asif, Natasha Kamal, Elizabeth C Wright, Chris Koh, David George, David Goldman, Yvonne Horneffer, Nancy Diazgranados, Theo Heller","doi":"10.14309/ctg.0000000000000770","DOIUrl":"10.14309/ctg.0000000000000770","url":null,"abstract":"<p><strong>Introduction: </strong>Splenic stiffness (SS) measurement (SSM) is an evolving noninvasive assessment to evaluate portal hypertension. Studies with respect to SSM in patients with alcohol use disorder are limited.</p><p><strong>Methods: </strong>We studied patients seeking treatment for alcohol use disorder in an inpatient treatment protocol at the National Institutes of Health and parsed SSM into 3 groups based on degree of change.</p><p><strong>Results: </strong>The improved SS group had statistically higher initial SSM and a nonstatistically increased liver stiffness measurement compared with others.</p><p><strong>Discussion: </strong>SS is dynamic in a subset of patients immediately after alcohol cessation, and improved SS is associated with a normalization of platelet count.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281264","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 : 2024-09-23DOI: 10.14309/ctg.0000000000000772
Anne-Marie Ellegaard, Martin L Kårhus, Lukasz Krych, David P Sonne, Julie L Forman, Svend H Hansen, Lars Ove Dragsted, Dennis S Nielsen, Filip K Knop
Introduction: Both liraglutide and colesevelam improve bile acid diarrhea (BAD) symptoms. Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon whereas the mode of action for liraglutide remains elusive. Here, we examined the impact of colesevelam and liraglutide treatment on the concentrations of bile acids in serum and feces and the fecal microbiota composition to better understand the two drugs' modes of action.
Methods: Bile acid species were analyzed in serum and fecal samples from a randomized, double-blind, double-dummy trial at baseline and after three and six weeks of orally administered colesevelam (1,875 mg twice daily, n = 26) or subcutaneously administered liraglutide (uptitrated by weekly increments of 0.6 mg from 0.6 to 1.8 mg daily, n = 26) in patients with 75selenium-homotaurocholic acid test-verified, idiopathic, or post-cholecystectomy BAD. Fecal microbiota composition was analyzed by 16S rRNA gene amplicon sequencing at the same time points.
Results: Colesevelam increased the fecal concentrations of all bile acid species while it decreased serum concentrations of secondary bile acids. Liraglutide induced a small increase in serum unconjugated bile acid concentrations without affecting fecal bile acid concentrations. No changes in fecal microbiota composition were observed with either treatment.
Conclusion: Colesevelam and liraglutide exhibit distinct effects on serum and fecal bile acid concentrations with colesevelam reducing serum concentrations of secondary bile acids and promoting fecal bile acid excretion while liraglutide enhances serum concentrations of unconjugated bile acids, potentially through deceleration of small intestinal transit time allowing more time for passive absorption of bile acids.
{"title":"Liraglutide and Colesevelam Changes Serum and Fecal Bile Acid Levels in a Randomized Trial with Patients with Bile Acid Diarrhea.","authors":"Anne-Marie Ellegaard, Martin L Kårhus, Lukasz Krych, David P Sonne, Julie L Forman, Svend H Hansen, Lars Ove Dragsted, Dennis S Nielsen, Filip K Knop","doi":"10.14309/ctg.0000000000000772","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000772","url":null,"abstract":"<p><strong>Introduction: </strong>Both liraglutide and colesevelam improve bile acid diarrhea (BAD) symptoms. Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon whereas the mode of action for liraglutide remains elusive. Here, we examined the impact of colesevelam and liraglutide treatment on the concentrations of bile acids in serum and feces and the fecal microbiota composition to better understand the two drugs' modes of action.</p><p><strong>Methods: </strong>Bile acid species were analyzed in serum and fecal samples from a randomized, double-blind, double-dummy trial at baseline and after three and six weeks of orally administered colesevelam (1,875 mg twice daily, n = 26) or subcutaneously administered liraglutide (uptitrated by weekly increments of 0.6 mg from 0.6 to 1.8 mg daily, n = 26) in patients with 75selenium-homotaurocholic acid test-verified, idiopathic, or post-cholecystectomy BAD. Fecal microbiota composition was analyzed by 16S rRNA gene amplicon sequencing at the same time points.</p><p><strong>Results: </strong>Colesevelam increased the fecal concentrations of all bile acid species while it decreased serum concentrations of secondary bile acids. Liraglutide induced a small increase in serum unconjugated bile acid concentrations without affecting fecal bile acid concentrations. No changes in fecal microbiota composition were observed with either treatment.</p><p><strong>Conclusion: </strong>Colesevelam and liraglutide exhibit distinct effects on serum and fecal bile acid concentrations with colesevelam reducing serum concentrations of secondary bile acids and promoting fecal bile acid excretion while liraglutide enhances serum concentrations of unconjugated bile acids, potentially through deceleration of small intestinal transit time allowing more time for passive absorption of bile acids.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307247","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}
BACKGROUNDThe incidence of liver cancer has shown different temporal trends across populations, while the underlying reasons remain unclear.METHODSWe examined temporal trends in the incidence of liver cancer in Hong Kong, Sweden, and the United States since the 1970s through 2021 using joinpoint regression and age-period-cohort analysis.RESULTSThe age-standardized incidence rate of liver cancer in Hong Kong steadily decreased (average annual percentage change [AAPC] -2.2%, 95% confidence interval [CI] -2.8% to -1.7% in men; AAPC -2.1%, 95%CI -3.1% to -1.1% in women) in 1983-2020. The rate in Sweden increased on average by 0.8% (95%CI 0.2% to 1.4%) per year in men and was stable in women (AAPC 0.2%, 95%CI -0.9% to 1.4%) in 1970-2021. The rate in the United States increased by 2.1% (95%CI 1.5% to 2.8%) per year in men and by 2.1% (95%CI 1.6% to 2.5%) in women in 1975-2020, but decreasing trends were noted in 2015-2020 (AAPC -6.6%, 95%CI -8.3% to -4.9% in men; AAPC -4.2%, 95%CI -7.5% to -0.5% in women). Stratified analysis by histological type showed such decrease in recent years was limited to hepatocellular carcinoma, rather than intrahepatic cholangiocarcinoma. We observed distinct changes in trends across age groups and different trends across birth cohorts.CONCLUSIONThe incidence of liver cancer has decreased in Hong Kong but increased in Sweden and the United States since the 1980s, despite decreasing incidence in the United States since 2015. Such disparities may be explained by different etiology and implementation of preventive measures across populations.
{"title":"Different etiological entities of liver cancer across populations: Implications from age-period-cohort analysis on incidence trends.","authors":"Tian-Wen Chen,Yi-Jun Cheng,Yong-Ying Huang,Zhiqiang Liu,Jing-Feng Liu,Shao-Hua Xie","doi":"10.14309/ctg.0000000000000769","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000769","url":null,"abstract":"BACKGROUNDThe incidence of liver cancer has shown different temporal trends across populations, while the underlying reasons remain unclear.METHODSWe examined temporal trends in the incidence of liver cancer in Hong Kong, Sweden, and the United States since the 1970s through 2021 using joinpoint regression and age-period-cohort analysis.RESULTSThe age-standardized incidence rate of liver cancer in Hong Kong steadily decreased (average annual percentage change [AAPC] -2.2%, 95% confidence interval [CI] -2.8% to -1.7% in men; AAPC -2.1%, 95%CI -3.1% to -1.1% in women) in 1983-2020. The rate in Sweden increased on average by 0.8% (95%CI 0.2% to 1.4%) per year in men and was stable in women (AAPC 0.2%, 95%CI -0.9% to 1.4%) in 1970-2021. The rate in the United States increased by 2.1% (95%CI 1.5% to 2.8%) per year in men and by 2.1% (95%CI 1.6% to 2.5%) in women in 1975-2020, but decreasing trends were noted in 2015-2020 (AAPC -6.6%, 95%CI -8.3% to -4.9% in men; AAPC -4.2%, 95%CI -7.5% to -0.5% in women). Stratified analysis by histological type showed such decrease in recent years was limited to hepatocellular carcinoma, rather than intrahepatic cholangiocarcinoma. We observed distinct changes in trends across age groups and different trends across birth cohorts.CONCLUSIONThe incidence of liver cancer has decreased in Hong Kong but increased in Sweden and the United States since the 1980s, despite decreasing incidence in the United States since 2015. Such disparities may be explained by different etiology and implementation of preventive measures across populations.","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":"6 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263898","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 : 2024-09-12DOI: 10.14309/ctg.0000000000000768
Trevor S Barlowe,Shruti Saxena-Beem,Rumey C Ishizawar,Hans Herfarth,Andrew M Moon
OBJECTIVESDescribe immune related adverse events (irAE) affecting multiple organs of the gastrointestinal system in patients who received immune checkpoint inhibitors (ICI).METHODSWithin a 2843-patient retrospective cohort consisting of patients with cancer treated with ICIs, EMERSE (Electronic Medical Record Search Engine), an information retrieval system, was used to search free text in the medical record to identify patients with multiple gastrointestinal irAEs.RESULTS13 patients developed multiple gastrointestinal irAEs (0.46%). The most common patterns of multisystem gastrointestinal irAE were colitis + pancreatitis and colitis + enteritis.CONCLUSIONSMultisystem gastrointestinal irAEs are rare but warrant further characterization and attention.
{"title":"Multiple gastrointestinal immune related adverse events from immune checkpoint inhibitor therapy.","authors":"Trevor S Barlowe,Shruti Saxena-Beem,Rumey C Ishizawar,Hans Herfarth,Andrew M Moon","doi":"10.14309/ctg.0000000000000768","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000768","url":null,"abstract":"OBJECTIVESDescribe immune related adverse events (irAE) affecting multiple organs of the gastrointestinal system in patients who received immune checkpoint inhibitors (ICI).METHODSWithin a 2843-patient retrospective cohort consisting of patients with cancer treated with ICIs, EMERSE (Electronic Medical Record Search Engine), an information retrieval system, was used to search free text in the medical record to identify patients with multiple gastrointestinal irAEs.RESULTS13 patients developed multiple gastrointestinal irAEs (0.46%). The most common patterns of multisystem gastrointestinal irAE were colitis + pancreatitis and colitis + enteritis.CONCLUSIONSMultisystem gastrointestinal irAEs are rare but warrant further characterization and attention.","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":"39 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204852","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 : 2024-09-01DOI: 10.14309/ctg.0000000000000734
Yanqi Kou, Shenshen Du, Mingcheng Zhang, Biao Nie, Weinan Yuan, Kun He, Ling Qin, Shicai Ye, Yuping Yang
Introduction: The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis.
Methods: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values. Cox regression and Kaplan-Meier survival analysis were used to assess the relationships between AG levels and outcomes.
Results: Both cohorts showed strong parameter similarity ( P > 0.05). High AG was associated with significantly lower survival probabilities. Cox models confirmed elevated AG as a risk factor, even after adjusting for covariates (hazard ratio: 1.920, 1.793, and 1.764 for 30-day, 60-day, and hospital mortality, respectively). Subgroup analyses, especially regarding chronic kidney disease, revealed complex interactions. Serum AG displayed predictive power comparable with established scoring systems.
Discussion: Elevated AG at admission is a valuable predictor of poor outcomes and increased mortality risk in critically ill cirrhotic patients. Serum AG can serve as an easily accessible tool for risk assessment and prognosis evaluation in this population.
背景和目的:本研究的主要目的是评估肝硬化重症患者入院时血清阴离子差距(AG)作为全因死亡率的预测指标:本研究的主要目的是评估入院血清阴离子间隙(AG)作为肝硬化重症患者全因死亡率预测指标的作用:共纳入 3,084 名肝硬化患者,并随机分为训练组和验证组(分别为 2,159 人和 925 人)。根据 AG 值将患者分为高 AG 组和正常 AG 组。采用 Cox 回归和 Kaplan-Meier 生存分析评估 AG 水平与预后之间的关系:结果:两组患者的参数具有很强的相似性(P > 0.05)。高AG与明显较低的生存概率相关。Cox 模型证实 AG 升高是一个风险因素,即使在调整协变量后也是如此(30 天、60 天和住院死亡率的 HR 分别为 1.920、1.793 和 1.764)。亚组分析,尤其是有关慢性肾病的亚组分析,显示了复杂的相互作用。血清AG的预测能力与已建立的评分系统相当:结论:入院时 AG 升高是预测肝硬化重症患者不良预后和增加死亡风险的重要指标。血清AG可作为该人群风险评估和预后评价的便捷工具。
{"title":"Serum Anion Gap at Admission Predicts All-Cause Mortality in Critically Ill Patients With Cirrhosis: A Retrospective Cohort Study.","authors":"Yanqi Kou, Shenshen Du, Mingcheng Zhang, Biao Nie, Weinan Yuan, Kun He, Ling Qin, Shicai Ye, Yuping Yang","doi":"10.14309/ctg.0000000000000734","DOIUrl":"10.14309/ctg.0000000000000734","url":null,"abstract":"<p><strong>Introduction: </strong>The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis.</p><p><strong>Methods: </strong>A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values. Cox regression and Kaplan-Meier survival analysis were used to assess the relationships between AG levels and outcomes.</p><p><strong>Results: </strong>Both cohorts showed strong parameter similarity ( P > 0.05). High AG was associated with significantly lower survival probabilities. Cox models confirmed elevated AG as a risk factor, even after adjusting for covariates (hazard ratio: 1.920, 1.793, and 1.764 for 30-day, 60-day, and hospital mortality, respectively). Subgroup analyses, especially regarding chronic kidney disease, revealed complex interactions. Serum AG displayed predictive power comparable with established scoring systems.</p><p><strong>Discussion: </strong>Elevated AG at admission is a valuable predictor of poor outcomes and increased mortality risk in critically ill cirrhotic patients. Serum AG can serve as an easily accessible tool for risk assessment and prognosis evaluation in this population.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e1"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449860","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 : 2024-09-01DOI: 10.14309/ctg.0000000000000724
Camilla Mattiuzzi, Giuseppe Lippi
{"title":"Epidemiological Analysis on the Impact of Early COVID-19 Pandemic on Mortality for Hepatocellular Carcinoma in the United States.","authors":"Camilla Mattiuzzi, Giuseppe Lippi","doi":"10.14309/ctg.0000000000000724","DOIUrl":"10.14309/ctg.0000000000000724","url":null,"abstract":"","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":"e1"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619488","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}