Pub Date : 2024-03-07DOI: 10.1101/2024.03.05.24303658
Maria de Lourdes Moreno Amador, Maria Gonzalez Rovira, Cristina Martinez Pancorbo, Maria Martin Camean, Ana Maria Najar Moyano, Mercedes Romero Cabezas, Esther de la Hoz, Cristina Lopez Beltran, Encarnacion Mellado Duran, Jose Luis Bartha Rasero, Petter Brodin, Alfonso Rodriguez Herrera, Jose Antonio Sainz Bueno, Carolina Sousa Martin
The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a lifecourse perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant's solid diet after birth. We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. 119 pregnant women with different gluten diets and gestational ages were recruited. GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. The study shows evidence, for the first time, of the fetal exposure to gluten immunogenic peptides, and establish a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a closed-loop circuit entailing fetal swallowing of GIP contained in AF, and its subsequent excretion through the fetal kidneys. The study adds important new information to understanding the coeliac exposome.
{"title":"Fetal-maternal interactions with gluten immunogenic peptides during pregnancy: a new determinant on the coeliac exposome","authors":"Maria de Lourdes Moreno Amador, Maria Gonzalez Rovira, Cristina Martinez Pancorbo, Maria Martin Camean, Ana Maria Najar Moyano, Mercedes Romero Cabezas, Esther de la Hoz, Cristina Lopez Beltran, Encarnacion Mellado Duran, Jose Luis Bartha Rasero, Petter Brodin, Alfonso Rodriguez Herrera, Jose Antonio Sainz Bueno, Carolina Sousa Martin","doi":"10.1101/2024.03.05.24303658","DOIUrl":"https://doi.org/10.1101/2024.03.05.24303658","url":null,"abstract":"The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a lifecourse perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant's solid diet after birth. We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. 119 pregnant women with different gluten diets and gestational ages were recruited. GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. The study shows evidence, for the first time, of the fetal exposure to gluten immunogenic peptides, and establish a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a closed-loop circuit entailing fetal swallowing of GIP contained in AF, and its subsequent excretion through the fetal kidneys. The study adds important new information to understanding the coeliac exposome.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140057673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-06DOI: 10.1101/2024.03.05.24303668
Parakkal Deepak, Scott McHenry, Anastasia Karachalia Sandri, Maiara Brusco De Freitas, Mohammad Zamani, Andres J. Yarur, Tine Jess
Background and Aims Prior studies suggest an increased risk of non-alcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD). We aimed to investigate the risk of cirrhosis in a nationwide cohort of IBD patients compared to a matched non-IBD population. Methods Patients diagnosed with IBD without prior cirrhosis during 1998-2018 were identified in the Danish health registries and were matched 1:10 to persons without IBD. Cox regression was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results Within the study population of 495,220 persons, a total of 2,741 cirrhosis cases were identified during follow-up, with a higher proportion of cases among patients with IBD (0.9%) compared to non-IBD persons (0.5%). Patients with IBD had a significantly higher risk of cirrhosis compared to non-IBD persons (adjusted HR (aHR) (95% CI): 1.84 (1.64-2.04)). The leading etiology of cirrhosis in IBD was NAFLD (51.6%), followed by alcohol (39.0%). The risk of cirrhosis among IBD patients (compared to non-IBD persons) was more pronounced among those diagnosed with IBD ≤ 40 years of age (aHR (95% CI): 3.08 (2.45-3.87); vs. > 40 years of age, 1.63 (1.45-1.84); p-value <0.001) and CD patients (aHR (95% CI): 2.20 (1.80-2.67); vs. 1.72 (1.52-1.95) among UC; p-value 0.04). Conclusion IBD was associated with an increased risk of incident cirrhosis, especially in patients aged ≤ 40 years at IBD diagnosis and in patients with CD. These findings point towards a need for focused screening for cirrhosis among IBD patients, especially in certain groups.
{"title":"Increased Risk of Cirrhosis in Patients with Inflammatory Bowel Disease: A Danish registry-based cohort study (1998-2018)","authors":"Parakkal Deepak, Scott McHenry, Anastasia Karachalia Sandri, Maiara Brusco De Freitas, Mohammad Zamani, Andres J. Yarur, Tine Jess","doi":"10.1101/2024.03.05.24303668","DOIUrl":"https://doi.org/10.1101/2024.03.05.24303668","url":null,"abstract":"Background and Aims\u0000Prior studies suggest an increased risk of non-alcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD). We aimed to investigate the risk of cirrhosis in a nationwide cohort of IBD patients compared to a matched non-IBD population. Methods\u0000Patients diagnosed with IBD without prior cirrhosis during 1998-2018 were identified in the Danish health registries and were matched 1:10 to persons without IBD. Cox regression was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results\u0000Within the study population of 495,220 persons, a total of 2,741 cirrhosis cases were identified during follow-up, with a higher proportion of cases among patients with IBD (0.9%) compared to non-IBD persons (0.5%). Patients with IBD had a significantly higher risk of cirrhosis compared to non-IBD persons (adjusted HR (aHR) (95% CI): 1.84 (1.64-2.04)). The leading etiology of cirrhosis in IBD was NAFLD (51.6%), followed by alcohol (39.0%). The risk of cirrhosis among IBD patients (compared to non-IBD persons) was more pronounced among those diagnosed with IBD ≤ 40 years of age (aHR (95% CI): 3.08 (2.45-3.87); vs. > 40 years of age, 1.63 (1.45-1.84); p-value <0.001) and CD patients (aHR (95% CI): 2.20 (1.80-2.67); vs. 1.72 (1.52-1.95) among UC; p-value 0.04). Conclusion\u0000IBD was associated with an increased risk of incident cirrhosis, especially in patients aged ≤ 40 years at IBD diagnosis and in patients with CD. These findings point towards a need for focused screening for cirrhosis among IBD patients, especially in certain groups.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140044034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-06DOI: 10.1101/2024.03.05.24303786
Ali Nazarizadeh, Touraj Banirostam, Taraneh Biglari, Mohammadreza Kalantarhormozi, Fatemeh Chichagi, Amir Hossein Behnoush, Mohammad Amin Habibi, Ramin Shahidi
Background: Liver fibrosis is important in terms of staging, and liver biopsy is the gold standard diagnostic tool. We aim to design and evaluate an artificial neural network (ANN) method by taking advantage of the Teaching Learning Based Optimization (TLBO) algorithm for the prediction of liver fibrosis stage in blood donors and hepatitis C. Method: We proposed a method based on a selection of machine learning classification methods including Multi Layers Perceptron neural network (MLP), Naive Bayesian (NB), decision tree, and deep learning. Initially, the Synthetic minority oversampling technique (SMOTE) was performed to address the imbalance of the dataset. Afterward, the integration of MLP and TLBO was implemented. Result: We proposed a novel algorithm that reduced the number of required patient features to 7 inputs. The accuracy of MLP using 12 features is 0.903, while the accuracy of the proposed MLP with the TLBO method is 0.891. Besides, the diagnostic accuracy in all methods, except the model designed with the Bayesian Network, increased when the SMOTE balancer was applied. Conclusion: The Decision tree deep learning methods showed the highest levels of accuracy with 12 features. Interestingly, with the use of TLBO and 7 features, the MLP reached a 0.891 accuracy rate which is quite satisfying compared with similar studies. The proposed model provided great diagnostic accuracy by reducing the required properties from the samples without reducing the accuracy. The results of our study showed that the recruited algorithm of our study was more straightforward, with lower required properties and similar accuracy.
{"title":"An Integrated Neural Network and Evolutionary Algorithm Approach for Liver Fibrosis Staging: Can Artificial Intelligence Reduce Patient Costs?","authors":"Ali Nazarizadeh, Touraj Banirostam, Taraneh Biglari, Mohammadreza Kalantarhormozi, Fatemeh Chichagi, Amir Hossein Behnoush, Mohammad Amin Habibi, Ramin Shahidi","doi":"10.1101/2024.03.05.24303786","DOIUrl":"https://doi.org/10.1101/2024.03.05.24303786","url":null,"abstract":"Background: Liver fibrosis is important in terms of staging, and liver biopsy is the gold standard diagnostic tool. We aim to design and evaluate an artificial neural network (ANN) method by taking advantage of the Teaching Learning Based Optimization (TLBO) algorithm for the prediction of liver fibrosis stage in blood donors and hepatitis C.\u0000Method: We proposed a method based on a selection of machine learning classification methods including Multi Layers Perceptron neural network (MLP), Naive Bayesian (NB), decision tree, and deep learning. Initially, the Synthetic minority oversampling technique (SMOTE) was performed to address the imbalance of the dataset. Afterward, the integration of MLP and TLBO was implemented.\u0000Result: We proposed a novel algorithm that reduced the number of required patient features to 7 inputs. The accuracy of MLP using 12 features is 0.903, while the accuracy of the proposed MLP with the TLBO method is 0.891. Besides, the diagnostic accuracy in all methods, except the model designed with the Bayesian Network, increased when the SMOTE balancer was applied.\u0000Conclusion: The Decision tree deep learning methods showed the highest levels of accuracy with 12 features. Interestingly, with the use of TLBO and 7 features, the MLP reached a 0.891 accuracy rate which is quite satisfying compared with similar studies. The proposed model provided great diagnostic accuracy by reducing the required properties from the samples without reducing the accuracy. The results of our study showed that the recruited algorithm of our study was more straightforward, with lower required properties and similar accuracy.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140043938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-04DOI: 10.1101/2024.02.27.24303446
Ankit Chhoda, Marco Noriega, Tamara Kahan, Anabel Liyen-Cartelle, Kelsey Anderson, Shaharyar A. Zuberi, Miriam Olivares, Jill Kelly, Steven D. Freedman, Loren Rabinowitz, Sunil Sheth
BACKGROUND AND AIM: Food access is an important social determinant of health and refers to geographical and infrastructural aspects of food availability. Using publicly available data on food access from the United States Department of Agriculture (USDA), geospatial analyses can identify regions with variable food access, which may impact acute pancreatitis (AP), an acute inflammatory condition characterized by unpredictable outcomes and substantial mortality. This study aimed to investigate the association of clinical outcomes in patients with AP with geospatial food access. METHODS: We examined AP-related hospitalizations at a tertiary center from January 2008 to December 2018. The physical addresses were geocoded through ArcGIS Pro2.7.0 (ESRI, Redlands, CA). USDA Food Access Research Atlas defined low food access as urban areas with 33% or more of the population residing over one mile from the nearest food source. Regression analyses enabled assessment of the association between AP outcomes and food access. RESULTS: The study included 772 unique patients with AP residing in Massachusetts with 931 AP-related hospitalizations. One hundred and ninety-eight (25.6%) patients resided in census tracts with normal urban food access and 574 (74.4%) patients resided in tracts with low food access. AP severity per revised Atlanta classification [OR: 1.88 (95%CI: 1.21-2.92); p=0.005], and 30-day AP-related readmission [OR: 1.78(95%CI: 1.11-2.86); p=0.02] had significant association with food access, despite adjustment for demographics, healthcare behaviors, and comorbidities (Charlson Comorbidity Index). However, food access lacked significant association with AP-related mortality (p=0.40) and length of stay (LOS: p=0.99). CONCLUSION: Low food access had a significant association with 30-day AP-related readmissions and AP severity. However, mortality and LOS lacked significant association with food access. The association between nutrition, lifestyle, and AP outcomes warrants further prospective investigation.
背景和目的：食物获取是健康的一个重要社会决定因素，指的是食物供应的地理和基础设施方面。利用美国农业部（USDA）公开提供的食物可及性数据，地理空间分析可以确定食物可及性存在差异的地区，这可能会对急性胰腺炎（AP）产生影响，而急性胰腺炎是一种急性炎症，其特点是难以预测的结果和高死亡率。本研究旨在调查急性胰腺炎患者的临床结果与地理空间食物获取的关联性。方法：我们调查了一家三级中心 2008 年 1 月至 2018 年 12 月期间与急性胰腺炎相关的住院情况。物理地址通过 ArcGIS Pro2.7.0 （ESRI，加利福尼亚州雷德兰兹）进行地理编码。美国农业部食物获取研究图集将低食物获取率定义为城市地区有 33% 或以上的人口居住在距离最近食物来源一英里以上的地方。回归分析可评估 AP 结果与食物获取之间的关联。结果：该研究包括 772 名居住在马萨诸塞州的 AP 患者，其中有 931 人因 AP 住院。198名患者（25.6%）居住在城市食物供应正常的人口普查区，574名患者（74.4%）居住在食物供应不足的人口普查区。尽管对人口统计学、医疗保健行为和合并症（Charlson 合并症指数）进行了调整，但根据修订后的亚特兰大分类法得出的 AP 严重程度[OR：1.88（95%CI：1.21-2.92）；P=0.005]和 30 天 AP 相关再入院[OR：1.78（95%CI：1.11-2.86）；P=0.02]与食物获取有显著关联。结论：食物可及性低与急性呼吸道感染相关的 30 天再入院率和急性呼吸道感染严重程度有显著关系。结论：食物获取率低与急性呼吸衰竭相关的 30 天再入院率和急性呼吸衰竭严重程度有显著关系，但死亡率和住院时间与食物获取率无显著关系。营养、生活方式和急诊室预后之间的关系值得进一步的前瞻性研究。
{"title":"IMPACT OF GEOSPATIAL FOOD ACCESS ON ACUTE PANCREATITIS OUTCOMES","authors":"Ankit Chhoda, Marco Noriega, Tamara Kahan, Anabel Liyen-Cartelle, Kelsey Anderson, Shaharyar A. Zuberi, Miriam Olivares, Jill Kelly, Steven D. Freedman, Loren Rabinowitz, Sunil Sheth","doi":"10.1101/2024.02.27.24303446","DOIUrl":"https://doi.org/10.1101/2024.02.27.24303446","url":null,"abstract":"BACKGROUND AND AIM: Food access is an important social determinant of health and refers to geographical and infrastructural aspects of food availability. Using publicly available data on food access from the United States Department of Agriculture (USDA), geospatial analyses can identify regions with variable food access, which may impact acute pancreatitis (AP), an acute inflammatory condition characterized by unpredictable outcomes and substantial mortality. This study aimed to investigate the association of clinical outcomes in patients with AP with geospatial food access.\u0000METHODS: We examined AP-related hospitalizations at a tertiary center from January 2008 to December 2018. The physical addresses were geocoded through ArcGIS Pro2.7.0 (ESRI, Redlands, CA). USDA Food Access Research Atlas defined low food access as urban areas with 33% or more of the population residing over one mile from the nearest food source. Regression analyses enabled assessment of the association between AP outcomes and food access.\u0000RESULTS: The study included 772 unique patients with AP residing in Massachusetts with 931 AP-related hospitalizations. One hundred and ninety-eight (25.6%) patients resided in census tracts with normal urban food access and 574 (74.4%) patients resided in tracts with low food access. AP severity per revised Atlanta classification [OR: 1.88 (95%CI: 1.21-2.92); p=0.005], and 30-day AP-related readmission [OR: 1.78(95%CI: 1.11-2.86); p=0.02] had significant association with food access, despite adjustment for demographics, healthcare behaviors, and comorbidities (Charlson Comorbidity Index). However, food access lacked significant association with AP-related mortality (p=0.40) and length of stay (LOS: p=0.99).\u0000CONCLUSION: Low food access had a significant association with 30-day AP-related readmissions and AP severity. However, mortality and LOS lacked significant association with food access. The association between nutrition, lifestyle, and AP outcomes warrants further prospective investigation.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-02DOI: 10.1101/2024.02.29.24303572
Jocelyn J Chang, Subhash Kulkarni, Trisha S Pasricha
Introduction: The gut-first hypothesis of Parkinsons Disease (PD) has gained traction, yet the inciting events triggering PD from gut-related factors remain unclear. While H. pylori infection is linked to peptic injury and is 1.47 times more prevalent in PD individuals, it is unknown how gastrointestinal mucosal damage (MD) may increase the risk of PD. We aimed to study the association between upper endoscopy findings of MD and subsequent PD development. Methods: In our retrospective study of 18,305 adults without prior PD, undergoing upper endoscopy between 2000 and 2005, patients with MD were matched with non-MDs. PD risk in MDs versus non-MDs was assessed using incidence rate ratio (IRR) and multivariate Cox analysis, controlling for covariates. Results: In the matched cohort, MD patients were significantly more likely to develop PD (IRR 3.00, p<0.0001), even after covariate adjustment (HR 2.42, p<0.001). Covariates including constipation, dysphagia, older age, and male sex were also associated with higher PD risk. Among MDs, H. pylori presence (AOR 5.38, p=0.04) and chronic NSAID use (AOR 3.28, p=0.04) increased PD odds, while chronic smoking decreased PD odds (AOR 0.19, p<0.05). Conclusion: MD elevates PD risk, with H. pylori increasing risk only in the presence of MD, suggesting a closer link between PD and gastric mucosa disruption. Furthermore, chronic NSAID use significantly raises PD odds in MD, while chronic smoking reduces PD risk in this context. Increased vigilance among MD patients for future PD risk is warranted, with further studies needed to elucidate precise pathophysiology.
{"title":"GASTROINTESTINAL MUCOSAL DAMAGE AND SUBSEQUENT RISK OF PARKINSONS DISEASE","authors":"Jocelyn J Chang, Subhash Kulkarni, Trisha S Pasricha","doi":"10.1101/2024.02.29.24303572","DOIUrl":"https://doi.org/10.1101/2024.02.29.24303572","url":null,"abstract":"Introduction: The gut-first hypothesis of Parkinsons Disease (PD) has gained traction, yet the inciting events triggering PD from gut-related factors remain unclear. While H. pylori infection is linked to peptic injury and is 1.47 times more prevalent in PD individuals, it is unknown how gastrointestinal mucosal damage (MD) may increase the risk of PD. We aimed to study the association between upper endoscopy findings of MD and subsequent PD development.\u0000Methods: In our retrospective study of 18,305 adults without prior PD, undergoing upper endoscopy between 2000 and 2005, patients with MD were matched with non-MDs. PD risk in MDs versus non-MDs was assessed using incidence rate ratio (IRR) and multivariate Cox analysis, controlling for covariates.\u0000Results: In the matched cohort, MD patients were significantly more likely to develop PD (IRR 3.00, p<0.0001), even after covariate adjustment (HR 2.42, p<0.001). Covariates including constipation, dysphagia, older age, and male sex were also associated with higher PD risk. Among MDs, H. pylori presence (AOR 5.38, p=0.04) and chronic NSAID use (AOR 3.28, p=0.04) increased PD odds, while chronic smoking decreased PD odds (AOR 0.19, p<0.05).\u0000Conclusion: MD elevates PD risk, with H. pylori increasing risk only in the presence of MD, suggesting a closer link between PD and gastric mucosa disruption. Furthermore, chronic NSAID use significantly raises PD odds in MD, while chronic smoking reduces PD risk in this context. Increased vigilance among MD patients for future PD risk is warranted, with further studies needed to elucidate precise pathophysiology.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140017461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction Most cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients. Methods 5-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using Log-Rank test. Multivariate analyses were performed for significant factors from univariate analyses. Results A total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9%, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9% and MST was 15.6 months (p<0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p = 0.014). Conclusion US is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.
导言：由于难以早期诊断，大多数胆管癌（CCA）患者都是晚期，导致 CCA 患者的生存率很低。胆管癌筛查和护理计划显示，超声筛查是发现早期 CCA 的有效工具。本研究旨在评估通过超声筛查（US）确诊的患者与无症状患者的生存结果。方法采用 Log-Rank 检验计算 CCA 的 5 年生存率（5-YSR）和中位生存时间（MST）。结果 共检查了 711 例经组织学证实的 CCA 病例，包括超声筛查组和无症患者组。筛查组的 5-YSR 为 53.9%，MST 为 67.2 个月，而就诊组的 5-YSR 为 21.9%，MST 为 15.6 个月（p<0.001）。此外，多变量分析显示，与步行组相比，筛查项目是预测 CCA 患者良好预后的独立因素（p = 0.014）。实际上，US 应被视为高危人群筛查 CCA 的首选工具。
{"title":"Improvement of Survival Outcomes of Cholangiocarcinoma by Ultrasonography Surveillance: Multicenter Retrospective Cohorts","authors":"Nittaya Chamadol, Vallop Laopaiboon, Apiwat Jareanrat, Vasin Thanasukarn, Tharatip Srisuk, Vor Luvira, Poowanai Sarkhampee, Winai Ungpinitpong, Phummarat Khamvijite, Yutthapong Chumnanua, Nipath Nethuwakul, Passakorn Sodarat, Samrit Thammarit, Anchalee Techasen, Jaruwan Thuanman, Chaiwat Tawarungruang, Bandit Thinkhamrop, Prakasit Sa-Ngiamwibool, Watcharin Loilome, Piya Prajumwongs, Attapol Titapun","doi":"10.1101/2024.02.29.24303543","DOIUrl":"https://doi.org/10.1101/2024.02.29.24303543","url":null,"abstract":"Introduction\u0000Most cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients.\u0000Methods\u00005-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using Log-Rank test. Multivariate analyses were performed for significant factors from univariate analyses.\u0000Results\u0000A total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9%, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9% and MST was 15.6 months (p<0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p = 0.014).\u0000Conclusion\u0000US is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140017911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background & Aims: Iron corrected T1 (cT1) is an MRI derived biomarker of liver disease activity. Emerging data suggest a change in cT1 of >=80 ms reflects histological improvement. We aimed to validate the association between the >=80 ms decline in cT1 and histological improvement, specifically the resolution of MASH. Methods: A retrospective analysis of study participants from three interventional clinical trials with histologically confirmed MASH (n = 150) who underwent multi-parametric MRI to measure cT1 (LiverMultiScan) and biopsies at baseline and end of study. Histological responders were defined using the four criteria: (1) a decrease in NAFLD Activity score (NAS) >= 2 with no worsening in fibrosis, (2) a decrease in fibrosis >=1 stage with no worsening in NAS, (3) both a NAS decrease >=2 and a fibrosis decrease >=1, and (4) MASH resolution with no worsening in fibrosis. Difference in the magnitude of change in cT1 between responders and non-responders was assessed. Results: Significant decreases in cT1 were observed in responders for all the histological criteria. The optimal threshold for separating responders from non-responders was 0.73 for MASH resolution (64ms-73ms for the other criteria), in close agreement with the predefined threshold of 80ms. The largest decrease was observed for those achieving MASH resolution, and was 119ms, compared to 43ms for non-responders. Those achieving an >=80 ms drop in cT1 were substantially more likely to achieve histological response with odds ratios ranging from 2.7 to 6.3. Conclusions: These results demonstrate that a drop in cT1 of >=80 ms was associated with histological response supporting the utility of cT1 to predict clinical improvement in patients undergoing therapeutic intervention.
{"title":"Decreases in liver cT1 accurately reflect histological improvement induced by therapies in MASH: a multi-centre pooled cohort analysis.","authors":"Naim Alkhouri, Cayden Beyer, Elizabeth Shumbayawonda, Anneli Andersson, Kitty Yale, Timothy Rolph, Raymund Chung, Raj Vuppalanchi, Kenneth Cusi, Rohit Loomba, Andrea Dennis, Michele Pansini","doi":"10.1101/2024.02.28.24302571","DOIUrl":"https://doi.org/10.1101/2024.02.28.24302571","url":null,"abstract":"Background & Aims: Iron corrected T1 (cT1) is an MRI derived biomarker of liver disease activity. Emerging data suggest a change in cT1 of >=80 ms reflects histological improvement. We aimed to validate the association between the >=80 ms decline in cT1 and histological improvement, specifically the resolution of MASH. Methods: A retrospective analysis of study participants from three interventional clinical trials with histologically confirmed MASH (n = 150) who underwent multi-parametric MRI to measure cT1 (LiverMultiScan) and biopsies at baseline and end of study. Histological responders were defined using the four criteria: (1) a decrease in NAFLD Activity score (NAS) >= 2 with no worsening in fibrosis, (2) a decrease in fibrosis >=1 stage with no worsening in NAS, (3) both a NAS decrease >=2 and a fibrosis decrease >=1, and (4) MASH resolution with no worsening in fibrosis. Difference in the magnitude of change in cT1 between responders and non-responders was assessed. Results: Significant decreases in cT1 were observed in responders for all the histological criteria. The optimal threshold for separating responders from non-responders was 0.73 for MASH resolution (64ms-73ms for the other criteria), in close agreement with the predefined threshold of 80ms. The largest decrease was observed for those achieving MASH resolution, and was 119ms, compared to 43ms for non-responders. Those achieving an >=80 ms drop in cT1 were substantially more likely to achieve histological response with odds ratios ranging from 2.7 to 6.3. Conclusions: These results demonstrate that a drop in cT1 of >=80 ms was associated with histological response supporting the utility of cT1 to predict clinical improvement in patients undergoing therapeutic intervention.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140006487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-28DOI: 10.1101/2024.02.27.24302719
Ankit Chhoda, Anabel Liyen-Cartelle, Marco Noriega, Tamara Kahan, Kelsey Anderson, Shaharyar A. Zuberi, Alana Sur, Miriam Olivares, Jill R. Kelly, Steven D. Freedman, Steven D. Freedman, Loren Rabinowitz, Sunil Sheth
BACKGROUND AND AIM: Geospatial analyses integrate location-based sociodemographic data, offering a promising approach to investigate the impact of social determinants on acute pancreatitis (AP) outcomes. This study aimed to examine the association of social vulnerability index (SVI) and its constituent 16 attributes in 4 domains: 1) socioeconomic status, 2) household composition and disability, 3) minority status and language, and 4) housing type and transportation, with outcomes of patients with AP. METHODS: This study included AP patients hospitalized between 1/1/2008 and 12/31/2018 and recorded their demographics and clinical outcomes. Physical addresses were geocoded to determine SVI, a composite variable beyond unidimensional demographics, and the SVI were ranked and divided into quartiles (I to IV: IV representing the highest vulnerability). RESULT: In 824 patients [age of 53.0(10) years and 48.2% females], with 993 AP-related hospitalizations, we noted significantly higher prevalence of no/federal/state insurance (P<0.001) and racial minorities (P<0.001) in patients residing in communities with higher SVI. We noted a non-significant trend of higher 30-day admission rate amongst patients from higher SVI regions (III/IV: 27(18.0%)/31(18.9%) vs. I/II: 40(13.8%)/36(16.3%); p=0.49). Significantly higher odds of alcohol withdrawal were observed among patients with AP residing in areas with higher SVI ranks despite adjustment for age, body mass index, and comorbidity burden (OR:1.62[95%CI:1.19-2.22]; p= 0.003). However, we observed no association of SVI ranks with severity of AP (Revised Atlanta Classification), inpatient opioid use, time to feeding, length of stay, and mortality. CONCLUSION: We noted significantly higher alcohol withdrawal in patients residing in areas with higher SVI ranks although AP severity and other outcomes lacked significant association with SVI. Given our findings further investigation of various social determinants of health in AP is warranted in large-sized prospective studies. KEYWORDS: Alcohol Withdrawal, Geospatial Disparity
背景和目的：地理空间分析整合了基于位置的社会人口数据，为研究社会决定因素对急性胰腺炎（AP）预后的影响提供了一种很有前景的方法。本研究旨在考察社会脆弱性指数（SVI）及其组成的 16 个属性在 4 个领域中的关联性：1）社会经济地位；2）家庭组成和残疾；3）少数民族地位和语言；4）住房类型和交通）与急性胰腺炎患者预后的关系。方法：本研究纳入了 2008 年 1 月 1 日至 2018 年 12 月 31 日期间住院的 AP 患者，并记录了他们的人口统计学特征和临床结果。对物理地址进行地理编码以确定 SVI，这是一个超越单维人口统计学的复合变量，SVI 被排序并分为四分位（I 至 IV：IV 代表最高脆弱性）。结果：在 824 名患者（年龄为 53.0(10) 岁，48.2% 为女性）中，有 993 人因急性肾衰竭住院，我们注意到，居住在 SVI 较高社区的患者中，无/联邦/州保险（P<0.001）和少数种族（P<0.001）的患病率明显较高。我们注意到，在 SVI 较高地区的患者中，30 天入院率较高的趋势并不显著（III/IV：27(18.0%)/31(18.9%) vs. I/II：40(13.8%)/36(16.3%)；P=0.49）。尽管对年龄、体重指数和合并症负担进行了调整，但仍观察到居住在 SVI 等级较高地区的 AP 患者发生戒酒的几率明显更高（OR：1.62[95%CI：1.19-2.22]；P= 0.003）。然而，我们没有观察到 SVI 等级与 AP 严重程度（修订的亚特兰大分类）、住院患者阿片类药物使用、进食时间、住院时间和死亡率有任何关联。结论：我们注意到，尽管 AP 严重程度和其他结果与 SVI 没有显著关联，但居住在 SVI 等级较高地区的患者酒精戒断率明显较高。鉴于我们的研究结果，有必要在大型前瞻性研究中进一步调查急性酒精中毒患者健康的各种社会决定因素。
{"title":"Investigation of the Association of Acute Pancreatitis Outcomes with Social Vulnerability Indicators","authors":"Ankit Chhoda, Anabel Liyen-Cartelle, Marco Noriega, Tamara Kahan, Kelsey Anderson, Shaharyar A. Zuberi, Alana Sur, Miriam Olivares, Jill R. Kelly, Steven D. Freedman, Steven D. Freedman, Loren Rabinowitz, Sunil Sheth","doi":"10.1101/2024.02.27.24302719","DOIUrl":"https://doi.org/10.1101/2024.02.27.24302719","url":null,"abstract":"BACKGROUND AND AIM: Geospatial analyses integrate location-based sociodemographic data, offering a promising approach to investigate the impact of social determinants on acute pancreatitis (AP) outcomes. This study aimed to examine the association of social vulnerability index (SVI) and its constituent 16 attributes in 4 domains: 1) socioeconomic status, 2) household composition and disability, 3) minority status and language, and 4) housing type and transportation, with outcomes of patients with AP. METHODS: This study included AP patients hospitalized between 1/1/2008 and 12/31/2018 and recorded their demographics and clinical outcomes. Physical addresses were geocoded to determine SVI, a composite variable beyond unidimensional demographics, and the SVI were ranked and divided into quartiles (I to IV: IV representing the highest vulnerability). RESULT: In 824 patients [age of 53.0(10) years and 48.2% females], with 993 AP-related hospitalizations, we noted significantly higher prevalence of no/federal/state insurance (P<0.001) and racial minorities (P<0.001) in patients residing in communities with higher SVI. We noted a non-significant trend of higher 30-day admission rate amongst patients from higher SVI regions (III/IV: 27(18.0%)/31(18.9%) vs. I/II: 40(13.8%)/36(16.3%); p=0.49). Significantly higher odds of alcohol withdrawal were observed among patients with AP residing in areas with higher SVI ranks despite adjustment for age, body mass index, and comorbidity burden (OR:1.62[95%CI:1.19-2.22]; p= 0.003). However, we observed no association of SVI ranks with severity of AP (Revised Atlanta Classification), inpatient opioid use, time to feeding, length of stay, and mortality. CONCLUSION: We noted significantly higher alcohol withdrawal in patients residing in areas with higher SVI ranks although AP severity and other outcomes lacked significant association with SVI. Given our findings further investigation of various social determinants of health in AP is warranted in large-sized prospective studies.\u0000KEYWORDS: Alcohol Withdrawal, Geospatial Disparity","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140006488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-28DOI: 10.1101/2024.02.26.24303272
Huma Arshad Cheema, Aliaksandr Skrahin, Anjum Saeed, Zafar Fayyaz, Muhammad Arshad Alvi, Muhammad Nadeem Anjum, Nadia Waheed, Khalil Ur Rehman, Ahmad Malik, Arndt Rolfs, Volha Skrahina
This study analyzes 116 Pakistani children with Progressive Familial Intrahepatic Cholestasis (PFIC), diagnosed with whole genome sequencing. PFIC3 was the predominant type (44.8%), followed by PFIC2 (24.1%), PFIC1 (16.4%), PFIC4 (12.9%), and PFIC5 (1.7%). Diverging from prior studies, we found a notable absence of pruritus in a quarter of PFIC1 and PFIC3 patients, and in one-third of those with PFIC2 and PFIC4; diarrhea in 6.7% of PFIC4; hearing loss in 13.3% of PFIC4 and some PFIC3; elevated GGT levels in about half the patients with PFIC1, PFIC2, and PFIC4; anemia in 84.2%-89.3% of cases; no liver tumors observed in PFIC patients even into the second decade. Survival analysis revealed a grim 20-year cumulative survival rate of 20%. However, liver transplantation significantly improved survival to 89%, compared to 9% with standard medical treatment. PFIC3 patients showed a less aggressive disease course and better survival. This study, highlighting the genetic and phenotypic diversity within PFIC and the poor outcomes with conventional treatment, underscores the critical need for revising medical management strategies for PFIC patients.
{"title":"Clinical Diversity and Outcomes of Progressive Familial Intrahepatic Cholestasis Diagnosed by Whole Genome Sequencing in Pakistani Children","authors":"Huma Arshad Cheema, Aliaksandr Skrahin, Anjum Saeed, Zafar Fayyaz, Muhammad Arshad Alvi, Muhammad Nadeem Anjum, Nadia Waheed, Khalil Ur Rehman, Ahmad Malik, Arndt Rolfs, Volha Skrahina","doi":"10.1101/2024.02.26.24303272","DOIUrl":"https://doi.org/10.1101/2024.02.26.24303272","url":null,"abstract":"This study analyzes 116 Pakistani children with Progressive Familial Intrahepatic Cholestasis (PFIC), diagnosed with whole genome sequencing. PFIC3 was the predominant type (44.8%), followed by PFIC2 (24.1%), PFIC1 (16.4%), PFIC4 (12.9%), and PFIC5 (1.7%). Diverging from prior studies, we found a notable absence of pruritus in a quarter of PFIC1 and PFIC3 patients, and in one-third of those with PFIC2 and PFIC4; diarrhea in 6.7% of PFIC4; hearing loss in 13.3% of PFIC4 and some PFIC3; elevated GGT levels in about half the patients with PFIC1, PFIC2, and PFIC4; anemia in 84.2%-89.3% of cases; no liver tumors observed in PFIC patients even into the second decade. Survival analysis revealed a grim 20-year cumulative survival rate of 20%. However, liver transplantation significantly improved survival to 89%, compared to 9% with standard medical treatment. PFIC3 patients showed a less aggressive disease course and better survival. This study, highlighting the genetic and phenotypic diversity within PFIC and the poor outcomes with conventional treatment, underscores the critical need for revising medical management strategies for PFIC patients.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140006490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Primary sclerosing cholangitis (PSC), a progressive cholestatic hepatobiliary disease characterized by inflammation and fibrosis of the bile ducts, has a pathophysiology that is not understood. No effective therapies exist. The only treatment option for PSC is liver transplant. We undertook a pilot randomized trial of diet to investigate the pathophysiology of the disease, the role of diet and to advance potential therapy. We enrolled 20 patients with PSC and randomly assigned them to a Low Protein/low sulfur Diet (LPD, n=10) or the Specific Carbohydrate Diet (SCD, n=10) for 8 weeks. Results showed that low protein intake benefits PSC patients, whereas higher protein levels exacerbate the condition. We further identified gut bacterial markers useful for distinguishing LPD responders (mostly PSC with concomitant ulcerative colitis) from non-responders. Additionally, by integrating multi-omics data, we propose that this diet modifies the intestinal sulfur cycle reducing hydrogen sulfide (H2S) production. Our findings provide an understanding of the beneficial effect of LPD as well as insights into a possible key driver of inflammation in PSC.
{"title":"Demonstrating the Beneficial Effect of Low Protein Diet in Primary Sclerosing Cholangitis through a Randomized Clinical Trial and Multi-omics Data Analysis","authors":"Xiaole Yin, Gila Sasson, Zheng Sun, Shanlin Ke, Demsina Babazadeh, Shaikh Danish Mahmood, Macie Andrews, Shelley Hurwitz, Tinashe Chikowore, Maia Paul, Nadine Javier, Malav Dave, Alexandra Austin, Linda Gray, Francene Steinberg, Elaine Souza, Christopher Bowlus, Yang-Yu Liu, Joshua Korzenik","doi":"10.1101/2024.02.23.24303167","DOIUrl":"https://doi.org/10.1101/2024.02.23.24303167","url":null,"abstract":"Primary sclerosing cholangitis (PSC), a progressive cholestatic hepatobiliary disease characterized by inflammation and fibrosis of the bile ducts, has a pathophysiology that is not understood. No effective therapies exist. The only treatment option for PSC is liver transplant. We undertook a pilot randomized trial of diet to investigate the pathophysiology of the disease, the role of diet and to advance potential therapy. We enrolled 20 patients with PSC and randomly assigned them to a Low Protein/low sulfur Diet (LPD, n=10) or the Specific Carbohydrate Diet (SCD, n=10) for 8 weeks. Results showed that low protein intake benefits PSC patients, whereas higher protein levels exacerbate the condition. We further identified gut bacterial markers useful for distinguishing LPD responders (mostly PSC with concomitant ulcerative colitis) from non-responders. Additionally, by integrating multi-omics data, we propose that this diet modifies the intestinal sulfur cycle reducing hydrogen sulfide (H2S) production. Our findings provide an understanding of the beneficial effect of LPD as well as insights into a possible key driver of inflammation in PSC.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"632 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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