Pub Date : 2024-11-21DOI: 10.14309/ctg.0000000000000794
Sooyoung Jang, JaeYong Yu, Sowon Park, Hyeji Lim, Hong Koh, Yu Rang Park
Introduction: Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).
Methods: This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.
Results: Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.
Discussion: We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.
导言:与成人克罗恩病(CD)相比,小儿克罗恩病(CD)很容易进展为活动性疾病,因此预测并尽量减少 CD 复发非常重要。然而,对小儿克罗恩病不同时间点(TPs)的复发预测研究仍然不足。我们的目的是开发一个实时汇总模型,以预测小儿 CD 在不同时间点和时间窗 (TW) 的复发:这项回顾性研究针对2015年至2022年期间在塞弗兰医院确诊为CD的儿童。从确诊后 3 个月开始收集实验室检查结果和人口统计学数据,并以 1 个月为间隔,使用 6 个不同 TP 的数据组成队列。预测复发定义为小儿 CD 活动指数≥30 点,TW 为 3-7 个月,间隔为 1 个月。结果:结果:来自 180 名患者的数据被用于构建与 TPs 相对应的队列。我们确定了能可靠预测小儿 CD 复发的最佳 TP 和 TW,当以 3 个月的 TW 预测 3 个月的 TP 时,接收者操作特征曲线下面积得分为 0.89。C反应蛋白水平和淋巴细胞比例等变量被认为是重要因素:讨论:我们建立了一个时间聚合模型来预测小儿 CD 在多个 TP 和 TW 中的复发。该模型确定了预测小儿 CD 复发的重要变量,以支持实时临床决策。
{"title":"Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.","authors":"Sooyoung Jang, JaeYong Yu, Sowon Park, Hyeji Lim, Hong Koh, Yu Rang Park","doi":"10.14309/ctg.0000000000000794","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000794","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).</p><p><strong>Methods: </strong>This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.</p><p><strong>Results: </strong>Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.</p><p><strong>Discussion: </strong>We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680896","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 : 2024-11-06DOI: 10.14309/ctg.0000000000000787
Maya Mahmoud, Hassan Kawtharany, Mohamed Awali, Nadine Mahmoud, Islam Mohamed, Wing-Kin Syn
Background: Sex steroids modulate metabolic-dysfunction associated steatotic liver disease (MASLD) pathobiology. We hypothesized that testosterone therapy (TT) modulates progression of MASLD, and performed a systematic review to evaluate the efficacy of TT on liver steatosis and fibrosis.
Methods: We searched PubMed and Embase from inception until November 2023. We screened 1489 studies and identified 9 eligible studies. We assessed risk of bias for randomized trials using RoB-2 "Cochrane risk of bias tool for randomized trials", non-randomized studies using ROBINS-I tool "Risk of Bias in Non-randomized Studies-of Interventions", and Murad's Tool for single-arm studies. We pooled estimates using RevMan 5.
Results: 3 randomized controlled trials (RCTs), 4 non-randomized studies, and 2 single-arm studies were identified. The population of interest comprised men with MASLD. TT was administered at varying doses, routes, and frequencies, with follow-up ranging 12-weeks to 8-years. Liver fibrosis and steatosis were assessed using liver biopsy in 3 studies, CT/MRI in 5, and serum scores in 2. All studies provided evidence of reduction in liver steatosis with TT compared to no TT. In addition, the LiFT (RCT) trial demonstrated a resolution of MASLD / MASH and a regression in liver fibrosis. TT led to decrease in liver enzymes. Studies were heterogenous in terms of population characteristics, treatment modalities, endpoints, and follow-up. Adverse events were comparable between the 2 groups.
Conclusion: TT is a promising treatment option for men with MASLD and low testosterone. It may improve liver steatosis and reduce liver fibrosis. Large, double-blinded randomized placebo-controlled trials are needed.
{"title":"The Effects of Testosterone Replacement Therapy in Adult Men with Metabolic Dysfunction associated Steatotic Liver Disease: A Systematic Review and Meta-analysis.","authors":"Maya Mahmoud, Hassan Kawtharany, Mohamed Awali, Nadine Mahmoud, Islam Mohamed, Wing-Kin Syn","doi":"10.14309/ctg.0000000000000787","DOIUrl":"10.14309/ctg.0000000000000787","url":null,"abstract":"<p><strong>Background: </strong>Sex steroids modulate metabolic-dysfunction associated steatotic liver disease (MASLD) pathobiology. We hypothesized that testosterone therapy (TT) modulates progression of MASLD, and performed a systematic review to evaluate the efficacy of TT on liver steatosis and fibrosis.</p><p><strong>Methods: </strong>We searched PubMed and Embase from inception until November 2023. We screened 1489 studies and identified 9 eligible studies. We assessed risk of bias for randomized trials using RoB-2 \"Cochrane risk of bias tool for randomized trials\", non-randomized studies using ROBINS-I tool \"Risk of Bias in Non-randomized Studies-of Interventions\", and Murad's Tool for single-arm studies. We pooled estimates using RevMan 5.</p><p><strong>Results: </strong>3 randomized controlled trials (RCTs), 4 non-randomized studies, and 2 single-arm studies were identified. The population of interest comprised men with MASLD. TT was administered at varying doses, routes, and frequencies, with follow-up ranging 12-weeks to 8-years. Liver fibrosis and steatosis were assessed using liver biopsy in 3 studies, CT/MRI in 5, and serum scores in 2. All studies provided evidence of reduction in liver steatosis with TT compared to no TT. In addition, the LiFT (RCT) trial demonstrated a resolution of MASLD / MASH and a regression in liver fibrosis. TT led to decrease in liver enzymes. Studies were heterogenous in terms of population characteristics, treatment modalities, endpoints, and follow-up. Adverse events were comparable between the 2 groups.</p><p><strong>Conclusion: </strong>TT is a promising treatment option for men with MASLD and low testosterone. It may improve liver steatosis and reduce liver fibrosis. Large, double-blinded randomized placebo-controlled trials are needed.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582199","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 : 2024-11-05DOI: 10.14309/ctg.0000000000000789
Brent Hiramoto, Bryn E Falahee, Mayssan Muftah, Ryan Flanagan, Eric D Shah, Walter W Chan
Background: The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.
Methods: This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry (DXA) were included.
Results: On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared to the third (OR:2.05, CI:1.18-3.56, p=0.014) and fourth (OR:1.94, CI:1.02-3.70, p=0.045) quartiles. Sex-stratified analyses found similar association among female patients only.
Conclusion: Small pelvic area on DXA is a potential risk factor for FI.
背景:骨盆骨骼结构对大便失禁(FI)的影响尚不明确。我们评估了体重调整后骨盆面积与 FI 之间的关系:这是一项基于 2005-2006 年全国健康与营养调查的人群分析。方法:这是一项基于 2005-2006 年全国健康与营养调查的人群分析,纳入了完成肠道健康调查和双能 X 射线吸收测定(DXA)的参与者:对 2,772 名参与者进行多变量分析后发现,骨盆面积最低的四分位数与第三(OR:2.05,CI:1.18-3.56,p=0.014)和第四(OR:1.94,CI:1.02-3.70,p=0.045)个四分位数相比,预示着 FI 的增加。性别分层分析仅在女性患者中发现了类似的关联:结论:DXA显示骨盆面积小是FI的潜在风险因素。
{"title":"Size of Pelvic Outlet as a Potential Risk Factor for Fecal Incontinence: A Population-Based Exploratory Analysis.","authors":"Brent Hiramoto, Bryn E Falahee, Mayssan Muftah, Ryan Flanagan, Eric D Shah, Walter W Chan","doi":"10.14309/ctg.0000000000000789","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000789","url":null,"abstract":"<p><strong>Background: </strong>The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.</p><p><strong>Methods: </strong>This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry (DXA) were included.</p><p><strong>Results: </strong>On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared to the third (OR:2.05, CI:1.18-3.56, p=0.014) and fourth (OR:1.94, CI:1.02-3.70, p=0.045) quartiles. Sex-stratified analyses found similar association among female patients only.</p><p><strong>Conclusion: </strong>Small pelvic area on DXA is a potential risk factor for FI.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582196","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 : 2024-10-25DOI: 10.14309/ctg.0000000000000718
Adjoa Anyane-Yeboa, Kevin Casey, Andrea L Roberts, Emily Lopes, Kristin Burke, Ashwin Ananthakrishnan, James Richter, Yvette C Cozier, Karenstan C Koenen, Andrew T Chan, Hamed Khalili
Introduction: A link between inflammatory bowel disease (IBD), stressful life events and psychological factors has previously been reported. Our objective was to examine the relationship between childhood emotional, physical, and sexual abuse and risk of IBD using a large cohort of female health professionals.
Methods: We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by two physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates.
Results: Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared to women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% CI 0.67 - 2.02) for mild, 1.58 (95% CI 0.92 - 2.69) for moderate, and 1.95 (95% CI 1.22 - 3.10) for severe abuse (Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC.
Conclusions: Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.
简介以前曾有报道称炎症性肠病(IBD)、生活压力事件和心理因素之间存在联系。我们的目的是通过一个大型女性卫生专业人员队列来研究童年情感、身体和性虐待与 IBD 风险之间的关系:我们的研究对象包括 2001 年参加护士健康研究 II 并填写了童年创伤问卷中的身体和情感虐待分量表以及亲子冲突策略量表中的性虐待量表的人员。IBD 诊断通过自我报告确定,并由两名医生通过查看病历独立确认。我们使用 Cox 比例危险模型来估算克罗恩病(CD)和溃疡性结肠炎(UC)的发病风险,同时调整协变量:从1989年到2017年,在68 167名女性中,有146例CD和215例UC病例。与无虐待史的女性相比,轻度虐待的CD调整危险比为1.16(95% CI 0.67 - 2.02),中度虐待的CD调整危险比为1.58(95% CI 0.92 - 2.69),重度虐待的CD调整危险比为1.95(95% CI 1.22 - 3.10)(Ptrend = 0.002)。我们没有观察到童年虐待与 UC 风险之间的关联:结论:报告早期遭受严重虐待的女性罹患 CD 的风险更高。这些数据为越来越多的证据增添了新的内容,这些证据表明早期生活中的压力因素对 CD 的发展起着至关重要的作用。
{"title":"Association of Childhood Abuse with Incident Inflammatory Bowel Disease.","authors":"Adjoa Anyane-Yeboa, Kevin Casey, Andrea L Roberts, Emily Lopes, Kristin Burke, Ashwin Ananthakrishnan, James Richter, Yvette C Cozier, Karenstan C Koenen, Andrew T Chan, Hamed Khalili","doi":"10.14309/ctg.0000000000000718","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000718","url":null,"abstract":"<p><strong>Introduction: </strong>A link between inflammatory bowel disease (IBD), stressful life events and psychological factors has previously been reported. Our objective was to examine the relationship between childhood emotional, physical, and sexual abuse and risk of IBD using a large cohort of female health professionals.</p><p><strong>Methods: </strong>We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by two physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates.</p><p><strong>Results: </strong>Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared to women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% CI 0.67 - 2.02) for mild, 1.58 (95% CI 0.92 - 2.69) for moderate, and 1.95 (95% CI 1.22 - 3.10) for severe abuse (Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC.</p><p><strong>Conclusions: </strong>Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496189","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}
Background: While Helicobacter pylori (H. pylori) infection is common in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, there are still individuals who test negative for it. The proportion and characteristics of these patients remain unclear.
Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane Library databases for relevant articles. Using a random effects model, we performed a meta-analysis to assess the pooled proportion of gastric MALT lymphoma patients with negative H. pylori tests. Additionally, we compared characteristics between gastric MALT lymphoma patients with and without H. pylori infection to examine clinical features in H. pylori-negative cases.
Results: A total of 50 studies involving 6033 patients were included. The overall proportion of gastric MALT lymphoma patients with negative H. pylori tests was 20.5% (95% confidence interval: 17.0%-24.6%). This rate exhibited an increasing trend over the years, particularly in non-Asian countries and in studies published after 2013, as well as in cases with sample sizes exceeding 100 participants, in male individuals, and among those with proximal or multiple lesions, non-superficial type morphology, submucosal invasion, and advanced clinical staging. Compared to H. pylori-positive patients, those who tested negative were more likely to be male, have proximal lesions, exhibit submucosal invasion, and present with an advanced clinical stage.
Conclusions: This study provides comprehensive information on the proportion and characteristics of H. pylori-negative gastric MALT lymphoma cases, highlighting the need for future clinical attention to treatment and surveillance in this patient population.
{"title":"Proportion and characteristics of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: A systematic review and meta-analysis.","authors":"Xiu-He Lv, Qing Lu, Jia-Huan Liu, Bi-Han Xia, Zi-Jing Wang, Zhu Wang, Jin-Lin Yang","doi":"10.14309/ctg.0000000000000781","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000781","url":null,"abstract":"<p><strong>Background: </strong>While Helicobacter pylori (H. pylori) infection is common in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, there are still individuals who test negative for it. The proportion and characteristics of these patients remain unclear.</p><p><strong>Methods: </strong>We conducted a systematic search of the PubMed, Embase, and Cochrane Library databases for relevant articles. Using a random effects model, we performed a meta-analysis to assess the pooled proportion of gastric MALT lymphoma patients with negative H. pylori tests. Additionally, we compared characteristics between gastric MALT lymphoma patients with and without H. pylori infection to examine clinical features in H. pylori-negative cases.</p><p><strong>Results: </strong>A total of 50 studies involving 6033 patients were included. The overall proportion of gastric MALT lymphoma patients with negative H. pylori tests was 20.5% (95% confidence interval: 17.0%-24.6%). This rate exhibited an increasing trend over the years, particularly in non-Asian countries and in studies published after 2013, as well as in cases with sample sizes exceeding 100 participants, in male individuals, and among those with proximal or multiple lesions, non-superficial type morphology, submucosal invasion, and advanced clinical staging. Compared to H. pylori-positive patients, those who tested negative were more likely to be male, have proximal lesions, exhibit submucosal invasion, and present with an advanced clinical stage.</p><p><strong>Conclusions: </strong>This study provides comprehensive information on the proportion and characteristics of H. pylori-negative gastric MALT lymphoma cases, highlighting the need for future clinical attention to treatment and surveillance in this patient population.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496190","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 : 2024-10-17DOI: 10.14309/ctg.0000000000000778
Matthew D Coates, Vonn Walter, August Stuart, Jeffrey Small, Shannon Dalessio, Nurgul Carkaci-Salli, Ann Ouyang, Kofi Clarke, Andrew Tinsley, Emmanuelle D Williams, Piotr Janicki, Victor Ruiz-Velasco, Kent E Vrana
Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970,A1073V;1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question.
Methods: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension(RBD).
Results: We analyzed 416 IBD patients (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients and healthy controls. Hypoalgesic CD (30%vs.12%,p=0.004) and hypoalgesic UC (32%vs.15%,p=0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals(n=50), rs6795970 homozygotes(n=11) also demonstrated reduced abdominal discomfort to RBD.
Discussion: These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.
{"title":"Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.","authors":"Matthew D Coates, Vonn Walter, August Stuart, Jeffrey Small, Shannon Dalessio, Nurgul Carkaci-Salli, Ann Ouyang, Kofi Clarke, Andrew Tinsley, Emmanuelle D Williams, Piotr Janicki, Victor Ruiz-Velasco, Kent E Vrana","doi":"10.14309/ctg.0000000000000778","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000778","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970,A1073V;1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question.</p><p><strong>Methods: </strong>Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension(RBD).</p><p><strong>Results: </strong>We analyzed 416 IBD patients (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients and healthy controls. Hypoalgesic CD (30%vs.12%,p=0.004) and hypoalgesic UC (32%vs.15%,p=0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals(n=50), rs6795970 homozygotes(n=11) also demonstrated reduced abdominal discomfort to RBD.</p><p><strong>Discussion: </strong>These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521164","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 : 2024-10-17DOI: 10.14309/ctg.0000000000000780
Jincheng Wang, Lihua Cao, Fang Liu, Chunhui Li, Peng Zhao, Zhaoyi Li, Xiaojie Lu, Xiaohang Ye, Jianfeng Bao
Introduction: Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI).
Methods: Texture features were extracted from ultrasound images. Spearman correlation and logistics regression selected independent variables for significant (F ≥ 2) and advanced (F ≥ 3) fibrosis. We compared the diagnostic performance of transient elastography (TE), ultrasound image biomarker, conventional serum indices (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, gamma-glutamyl transpeptidase-to-platelet ratio), and NSI in 365 patients with chronic hepatitis B.
Results: Among patients, 52.1% had significant fibrosis and 24.2% had advanced fibrosis. PLT, gamma-glutamyl transferase, prealbumin, and globulin were incorporated into NSI. In the validation group, TE achieved the best performance (area under the curve [AUC]: 0.765 [0.690-0.849] for significant fibrosis; 0.812 [0.745-0.878] for advanced fibrosis), followed by ultrasound image biomarker (AUC: 0.712 [0.629-0.795]; 0.678 [0.595-0.763]) and NSI (AUC: 0.630 [0.534-0.725]; 0.659 [0.572-0.745]), outperforming conventional indices.
Discussion: Texture analysis enhances ultrasound's diagnostic utility, but TE remains superior. When TE is unavailable, ultrasound image analysis and NSI, incorporating prealbumin, can serve as alternative tools for fibrosis staging.
{"title":"A Multi-Institutional Study on Ultrasound Image Analysis for Staging HBV-Derived Liver Fibrosis: A Potential Noninvasive Alternative to Liver Stiffness Measurement.","authors":"Jincheng Wang, Lihua Cao, Fang Liu, Chunhui Li, Peng Zhao, Zhaoyi Li, Xiaojie Lu, Xiaohang Ye, Jianfeng Bao","doi":"10.14309/ctg.0000000000000780","DOIUrl":"10.14309/ctg.0000000000000780","url":null,"abstract":"<p><strong>Introduction: </strong>Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI).</p><p><strong>Methods: </strong>Texture features were extracted from ultrasound images. Spearman correlation and logistics regression selected independent variables for significant (F ≥ 2) and advanced (F ≥ 3) fibrosis. We compared the diagnostic performance of transient elastography (TE), ultrasound image biomarker, conventional serum indices (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, gamma-glutamyl transpeptidase-to-platelet ratio), and NSI in 365 patients with chronic hepatitis B.</p><p><strong>Results: </strong>Among patients, 52.1% had significant fibrosis and 24.2% had advanced fibrosis. PLT, gamma-glutamyl transferase, prealbumin, and globulin were incorporated into NSI. In the validation group, TE achieved the best performance (area under the curve [AUC]: 0.765 [0.690-0.849] for significant fibrosis; 0.812 [0.745-0.878] for advanced fibrosis), followed by ultrasound image biomarker (AUC: 0.712 [0.629-0.795]; 0.678 [0.595-0.763]) and NSI (AUC: 0.630 [0.534-0.725]; 0.659 [0.572-0.745]), outperforming conventional indices.</p><p><strong>Discussion: </strong>Texture analysis enhances ultrasound's diagnostic utility, but TE remains superior. When TE is unavailable, ultrasound image analysis and NSI, incorporating prealbumin, can serve as alternative tools for fibrosis staging.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521163","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}
Background: A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. The present study investigated whether serum autotaxin (ATX) could predict liver-related events (LRE) in PBC patients.
Methods: This retrospective multicenter investigation included 190 biopsy-proven untreated PBC patients. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation to ATX levels at the time of liver biopsy.
Results: During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥ 1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs. 3.6%, p < 0.00001). Notably, the predictive capability of ATX for LRE in PBC patients surpassed that of FIB-4, ALBI, APRI, and M2BPGi. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, p = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, p < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32).
Conclusion: Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.
{"title":"Serum Autotaxin Levels Predict Liver-Related Events in Primary Biliary Cholangitis Patients: A Long-term Multicenter Observational Study: Autotaxin predict liver-related events in PBC.","authors":"Takanobu Iwadare, Takefumi Kimura, Yuki Yamashita, Taiki Okumura, Shun-Ichi Wakabayashi, Hiroyuki Kobayashi, Ayumi Sugiura, Tomoo Yamazaki, Satoshi Shimamoto, Koji Igarashi, Satoru Joshita, Takeji Umemura","doi":"10.14309/ctg.0000000000000779","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000779","url":null,"abstract":"<p><strong>Background: </strong>A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. The present study investigated whether serum autotaxin (ATX) could predict liver-related events (LRE) in PBC patients.</p><p><strong>Methods: </strong>This retrospective multicenter investigation included 190 biopsy-proven untreated PBC patients. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation to ATX levels at the time of liver biopsy.</p><p><strong>Results: </strong>During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥ 1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs. 3.6%, p < 0.00001). Notably, the predictive capability of ATX for LRE in PBC patients surpassed that of FIB-4, ALBI, APRI, and M2BPGi. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, p = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, p < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32).</p><p><strong>Conclusion: </strong>Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521165","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 : 2024-10-16DOI: 10.14309/ctg.0000000000000777
Jihane Meziani, Jedidja G Y de Jong, Gwenny M Fuhler, Brechtje D M Koopmann, Iris J M Levink, Paul Fockens, Frank P Vleggaar, Marco J Bruno, Djuna L Cahen
Introduction: Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance.
Methods: Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates.
Results: Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development.
Discussion: In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.
{"title":"Assessment of Glucose and HbA1c Monitoring in a Pancreatic Cancer Surveillance Program for High-Risk Individuals.","authors":"Jihane Meziani, Jedidja G Y de Jong, Gwenny M Fuhler, Brechtje D M Koopmann, Iris J M Levink, Paul Fockens, Frank P Vleggaar, Marco J Bruno, Djuna L Cahen","doi":"10.14309/ctg.0000000000000777","DOIUrl":"10.14309/ctg.0000000000000777","url":null,"abstract":"<p><strong>Introduction: </strong>Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance.</p><p><strong>Methods: </strong>Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates.</p><p><strong>Results: </strong>Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development.</p><p><strong>Discussion: </strong>In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459441","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}