Gastro hep advances最新文献_第5页

Soluble Triggering Receptor Expressed on Myeloid Cells 2 is a Biomarker but Not a Mediator of Fibrosing Steatohepatitis 骨髓细胞表达的可溶性触发受体2是纤维化性脂肪性肝炎的生物标志物，但不是中介

Gastro hep advances

Pub Date : 2025-10-10 DOI: 10.1016/j.gastha.2025.100828

Joseph L. Dempsey , Christopher Savard , Vishal Kothari , Jingjing Tang , Sum P. Lee , Karin E. Bornfeldt , Rotonya M. Carr , George N. Ioannou

Background and Aims

Triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane, lipid-sensing protein expressed by Kupffer cells, is thought to play a role in metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH). Plasma levels of the TREM2 cleavage product, soluble TREM2 (sTREM2), are strongly associated with MASLD severity. We investigated the role of TREM2 in MASH pathogenesis and whether sTREM2 acts both as biomarker and mediator of MASH.

Methods

Adult C57BL/6J mice were assigned to normal, high-fat, or high-fat and high-cholesterol (HFHC) diets for 15, 30, 90, and 180 days. Plasma sTREM2 levels, liver pathology, and hepatic RNA expression were assessed. To test whether sTREM2 is a mediator of MASH, C57BL/6J mice were injected retro-orbitally with a liver-targeted adeno-associated virus, TBG-AAV8-sTrem2, resulting in secretion of sTREM2 by hepatocytes, or empty TBG-AAV8-control, and subsequently fed HFHC diet for 15, 90, or 180 days.

Results

HFHC-fed mice developed fibrosing steatohepatitis at 180 days together with a 15-fold increase in plasma sTREM2 levels. In the livers of HFHC-fed mice, crown-like structures consisting of TREM2⁺ macrophages surrounded necrotic, steatotic hepatocytes and their remnant lipid droplets, which contained prominent crystals containing cholesterol. TBG-AAV8-sTrem2-injected mice had higher levels of plasma sTREM2 than TBG-AAV8-control-injected mice, but there were no differences in liver weight, body weight, hepatic fibrosis, hepatic inflammation, hepatic cholesterol crystals, or plasma cholesterol levels.

Conclusion

TREM2⁺ macrophages characterize the crown-like structures that surround necrotic hepatocytes and their remnant lipid droplets and cholesterol crystals in fibrosing steatohepatitis-MASH. Plasma sTREM2 is a biomarker, but not a causal mediator, of MASH.

骨髓细胞2 （TREM2）上表达的触发受体是一种由库普弗细胞表达的跨膜脂感蛋白，被认为在代谢功能障碍相关的脂肪性肝病（MASLD）和代谢功能障碍相关的脂肪性肝炎（MASH）中发挥作用。血浆中TREM2裂解产物可溶性TREM2 （sTREM2）的水平与MASLD的严重程度密切相关。我们研究了TREM2在MASH发病机制中的作用，以及TREM2是否同时作为MASH的生物标志物和中介。方法成年C57BL/6J小鼠分别饲喂正常、高脂、高脂高胆固醇（HFHC）饮食15、30、90和180天。评估血浆strem - 2水平、肝脏病理和肝脏RNA表达。为了检验sTREM2是否为MASH的介质，C57BL/6J小鼠被眶后注射肝靶向腺相关病毒TBG-AAV8-sTrem2，导致肝细胞分泌sTREM2，或空白tbg - aav8 -对照，随后饲喂HFHC饲料15、90或180天。结果fhc喂养的小鼠在180天发生纤维化性脂肪性肝炎，血浆strem - 2水平增加15倍。在hfhc喂养小鼠的肝脏中，由TREM2+巨噬细胞组成的冠状结构包围了坏死的脂肪变性肝细胞及其残余脂滴，脂滴中含有显著的含胆固醇晶体。注射tbg - aav8 - strem - 2的小鼠血浆strem - 2水平高于注射tbg - aav8 -对照的小鼠，但在肝脏重量、体重、肝纤维化、肝脏炎症、肝脏胆固醇结晶或血浆胆固醇水平方面没有差异。结论在纤维化性脂肪性肝炎- mash中，trem2 +巨噬细胞表现为围绕坏死肝细胞及其残余脂滴和胆固醇晶体的冠状结构。血浆sTREM2是MASH的生物标志物，但不是因果介质。

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引用次数: 0

Risk of Clostridioides difficile Infection After Helicobacter pylori Treatment in a Large Population in the United States 美国幽门螺杆菌治疗后艰难梭菌感染的风险

Gastro hep advances

Pub Date : 2025-10-08 DOI: 10.1016/j.gastha.2025.100832

Lawrence J. Leung , Sophie A. Merchant , Jessica M. Badalov , Douglas A. Corley , Dan Li

Background and Aims

Adverse outcomes associated with the treatment of Helicobacter pylori remain poorly understood. We investigated whether H pylori treatment was associated with an increased risk of Clostridioides difficile infection (CDI).

Methods

This retrospective cohort study included all adult members who tested positive for H pylori between January 1, 2000, and December 31, 2020, at Kaiser Permanente Northern California. We measured the incidence of CDI after H pylori treatment and evaluated the predictors of CDI using multivariable logistic regression.

Results

Of 139,226 individuals who tested positive for H pylori, the incidence of CDI was 5.9/10,000 within 3 months (P = .02) and 7.0/10,000 (P = .003) within 6 months after H pylori treatment, compared with 2.7/10,000 among untreated individuals. The adjusted odds ratio (aOR) (95% confidence interval) for CDI within 3 months after H pylori treatment was 2.00 (1.02–3.90) overall, 3.15 (1.14–8.70) for concomitant therapy, and 6.34 (2.75–14.59) for bismuth quadruple therapy. Inflammatory bowel disease (IBD) (aOR, 7.89 [2.38–26.21]) and history of CDI (aOR, 8.27 [1.92–35.62]) had the strongest association with CDI, while Asians/Pacific Islanders (aOR, 0.22 [0.09–0.55] and non-English language preference (aOR, 0.30 [0.12–0.72]) were associated with a lower risk.

Conclusion

In a large, diverse, community-based population, treatment of H pylori was associated with an increased risk of CDI, although the overall incidence was very low. History of IBD and prior CDI were the strongest predictors of CDI. These findings support the safety of H pylori treatment, although caution should be exercised when treating H pylori among individuals with IBD or a prior history of CDI.

背景和目的与幽门螺杆菌治疗相关的不良后果尚不清楚。我们调查了幽门螺杆菌治疗是否与艰难梭菌感染（CDI）风险增加有关。方法本回顾性队列研究纳入了2000年1月1日至2020年12月31日期间在北加州凯撒医疗机构幽门螺杆菌检测呈阳性的所有成年成员。我们测量了幽门螺杆菌治疗后CDI的发生率，并使用多变量logistic回归评估了CDI的预测因素。结果在139226例幽门螺杆菌检测呈阳性的患者中，幽门螺杆菌治疗后3个月内CDI发生率为5.9/10,000 (P = 0.02)， 6个月内CDI发生率为7.0/10,000 (P = 0.003)，而未治疗组为2.7/10,000。幽门螺杆菌治疗后3个月内CDI的调整优势比（aOR）（95%可信区间）为总体2.00(1.02-3.90)，联合治疗为3.15(1.14-8.70)，铋四联治疗为6.34（2.75-14.59）。炎症性肠病（IBD）（aOR, 7.89[2.38-26.21]）和CDI史（aOR, 8.27[1.92-35.62]）与CDI的相关性最强，而亚洲/太平洋岛民(aOR, 0.22[0.09-0.55]和非英语语言偏好（aOR, 0.30[0.12-0.72]）与CDI的相关性较低。结论在一个大的、多样化的、以社区为基础的人群中，幽门螺杆菌的治疗与CDI的风险增加有关，尽管总体发病率非常低。IBD病史和既往CDI是CDI的最强预测因子。这些发现支持幽门螺杆菌治疗的安全性，尽管在IBD患者或有CDI病史的患者中治疗幽门螺杆菌时应谨慎。

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引用次数: 0

Follicular Cholecystitis: A Case Report Highlighting the Diagnostic Challenges and Management Implications 滤泡性胆囊炎：一个病例报告强调诊断挑战和管理意义

Gastro hep advances

Pub Date : 2025-10-08 DOI: 10.1016/j.gastha.2025.100833

Ativitch Asavachaisuvikom , Burana Khiankaew , Narongsak Rungsakulkij

Follicular cholecystitis (FC), a rare benign entity, represents <2% of cholecystectomies. We present imaging findings and immunohistochemistry used for diagnosis in an 82-year-old Thai female presenting with persistent colicky biliary pain. Upper abdomen magnetic resonance imaging revealed a gallstone and mild asymmetric gallbladder wall thickening. Diagnosed with symptomatic gallstones, she underwent laparoscopic cholecystectomy. Gross pathology indicated multiple nodules (0.1–0.5 cm) at the gallbladder fundus. Histopathological examination revealed transmural nodular lymphoid proliferation, suggesting a lymphoproliferative disorder or lymphoma. Subsequent immunohistochemistry led to a FC diagnosis. FC presents a significant diagnostic challenge and requires accurate pathological diagnosis to avoid unnecessary cancer treatments.

滤泡性胆囊炎（FC）是一种罕见的良性实体，占胆囊切除术的2%。我们提出影像学结果和免疫组织化学用于诊断一位82岁的泰国女性表现为持续性绞痛性胆道疼痛。上腹部磁共振成像显示胆囊结石和轻度不对称胆囊壁增厚。诊断为症状性胆结石，她接受了腹腔镜胆囊切除术。大体病理示胆囊底多发结节（0.1 ~ 0.5 cm）。组织病理学检查显示经壁结节性淋巴样增生，提示淋巴增生性疾病或淋巴瘤。随后的免疫组织化学诊断为FC。FC提出了重大的诊断挑战，需要准确的病理诊断以避免不必要的癌症治疗。

引用次数: 0

Risk Factors, Clinical Features and Diagnostic Workup of Sclerosing Mesenteritis: a Single-Center Study of 219 Patients 硬化性肠系膜炎的危险因素、临床特征及诊断：219例患者的单中心研究

Gastro hep advances

Pub Date : 2025-10-07 DOI: 10.1016/j.gastha.2025.100826

Bibek Saha , Anjali Rajagopal , June Tome , Darrell S. Pardi , Xiao Jing Wang

引用次数: 0

Protein Aggregates in Heterozygous Alpha-1 Antitrypsin Phenotype Is a Marker for Progressive Disease 杂合子α -1抗胰蛋白酶表型中的蛋白聚集是疾病进展的标志

Gastro hep advances

Pub Date : 2025-10-07 DOI: 10.1016/j.gastha.2025.100822

George W. Marek, Harmeet Malhi

Background and aims

Alpha 1 antitrypsin deficiency (AATD) is a genetic disease caused by mutations in the SERPINA1 gene, leading to liver disease. This study investigates the role of heterozygous Pi∗Z (MZ) alleles and their histopathologic features in liver disease progression.

Methods

We extracted data from the Mayo Data Explorer, including noninvasive elastography and diagnostic pathology reports from patients with known AATD phenotypes. We analyzed clinical indices, histopathological features, and transplant-free survival in MZ individuals across Mayo Clinic sites in MN, WI, AZ, and FL.

Results

Out of 30,869 individuals with defined phenotypes, 2259 had elastography data. MZ individuals (n = 132) showed higher median liver stiffness (7 kPa) compared to MM individuals (6 kPa, P = .026) and a higher proportion had advanced fibrosis (37% vs 28.4%, P = .035). In biopsies from 409 MZ individuals, periodic acid-Schiff positive diastase resistant (PAS-D) globules were present in 28%, correlating with advanced fibrosis and reduced transplant-free survival (617 vs 1289 days, P < .001). Multivariable analysis identified PAS-D globules, age, and advanced fibrosis as independent predictors of decreased transplant-free survival.

Conclusion

MZ individuals exhibit higher baseline liver stiffness and advanced fibrosis. The presence of PAS-D globules in liver biopsies is associated with more advanced disease and shorter transplant-free survival, highlighting the potential need for targeted therapies in this population.

背景与目的salpha 1 antitrypsin deficiency （AATD）是一种由SERPINA1基因突变引起的遗传性疾病，可导致肝脏疾病。本研究探讨杂合Pi * Z （MZ）等位基因在肝脏疾病进展中的作用及其组织病理学特征。方法我们从Mayo数据浏览器中提取数据，包括已知AATD表型患者的无创弹性成像和诊断病理报告。我们分析了梅奥诊所在MN、WI、AZ和fl的MZ患者的临床指标、组织病理学特征和无移植生存率。结果在30,869例具有明确表型的患者中，2259例有弹性成像数据。与MM患者（6 kPa, P = 0.026）相比，MZ患者（n = 132）表现出更高的中位肝脏硬度（7 kPa），并且更高比例的患者有晚期纤维化（37% vs 28.4%, P = 0.035）。在409名MZ患者的活检中，28%的患者存在周期性的酸-希夫阳性淀化酶耐药（PAS-D）小球，这与晚期纤维化和减少的无移植生存期相关（617天vs 1289天，P < 001）。多变量分析确定PAS-D小球、年龄和晚期纤维化是减少无移植生存的独立预测因素。结论mz个体表现出较高的基线肝硬度和晚期纤维化。肝活检中PAS-D小球的存在与更晚期的疾病和更短的无移植生存期相关，这突出了这类人群对靶向治疗的潜在需求。

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引用次数: 0

Management of Ileal Pouch Cancer in Patients With Inflammatory Bowel Disease 炎性肠病患者回肠袋癌的治疗

Gastro hep advances

Pub Date : 2025-10-01 DOI: 10.1016/j.gastha.2025.100824

Shanshan Wang , Huaibin Mabel Ko , Dana J. Lukin , Ellen Scherl , Ravi Kiran , Bo Shen

Background and aims

Ileal pouch cancer in patients with inflammatory bowel disease, though rare, represents a significant concern due to the high mortality. While prior studies emphasized incidence and risk factors, this study evaluates the current management and prognosis of pouch cancer following ileal pouch-anal anastomosis.

Methods

Consecutive patients with pouch cancer were identified from a prospectively maintained database (2019–2025). Patients with familial adenomatous polyposis and precancerous conditions were excluded. Demographic, clinical, endoscopic, and histologic data were collected. Primary outcomes were disease recurrence/progression and oncological survival.

Results

Of 699 patients, 10 developed pouch cancer (incidence: 0.5 per 100 person-years). Lesions were located at the cuff (n = 3), anal transition zone (n = 3), pouch body (n = 2), prepouch ileum (n = 1), and both anal transition zone and pouch body (n = 1). Two patients presented with distant metastases without endoscopically visible lesions in the pouch. The histological types were adenocarcinoma (n = 5), squamous cell carcinoma (n = 3), non-Hodgkin lymphoma (n = 1), and neuroendocrine tumor (n = 1). The diagnosis was established through endoscopic biopsies (n = 2), surgical resection (n = 6; three with prior endoscopically diagnosed dysplasia), and cross-sectional imaging (n = 2). Seven patients had localized disease, allowing curative treatment. Treatments included surgery (n = 5), chemoradiotherapy (n = 6), and lanreotide for neuroendocrine tumor. Over a median follow-up of 2.8 years (interquartile range: 1.5–5.2), recurrence or disease progression occurred in three patients (30%), and one patient (10%) died from pouch cancer, with a 5-year cumulative survival of 88.9%.

Conclusion

Adenocarcinoma remains the most common histological type; however, nonadenocarcinoma, especially the squamous cell carcinoma, has been increasingly recognized. Endoscopic surveillance was helpful in detecting precancerous lesions.

背景和目的炎性肠病患者的膀胱袋癌虽然罕见，但由于其高死亡率，引起了人们的高度关注。先前的研究强调发生率和危险因素，本研究评估回肠袋-肛门吻合术后袋癌的目前处理和预后。方法从前瞻性维护的数据库（2019-2025）中确定连续的眼袋癌患者。排除家族性腺瘤性息肉病和癌前病变的患者。收集了人口统计学、临床、内镜和组织学数据。主要结局是疾病复发/进展和肿瘤生存。结果699例患者中，10例发生眼袋癌（发病率：0.5 / 100人年）。病变位于袖带（n = 3）、肛门过渡区（n = 3）、袋体（n = 2）、回肠前（n = 1）、肛门过渡区和袋体（n = 1）。2例患者表现为远处转移，在内窥镜下没有可见的眼袋病变。组织学类型为腺癌（n = 5）、鳞状细胞癌（n = 3）、非霍奇金淋巴瘤（n = 1）、神经内分泌肿瘤（n = 1）。通过内镜活检（n = 2）、手术切除（n = 6，其中3例既往内镜诊断为发育不良）和横断面成像（n = 2）确定诊断。7例患者有局限性疾病，可以根治。治疗方法包括手术（n = 5）、放化疗（n = 6）和神经内分泌肿瘤的lanreotide。中位随访2.8年（四分位数范围：1.5-5.2），3例（30%）患者复发或疾病进展，1例（10%）患者死于眼袋癌，5年累计生存率为88.9%。结论腺癌仍是最常见的组织学类型；然而，非腺癌，尤其是鳞状细胞癌，已被越来越多的认识。内镜监测有助于发现癌前病变。

{"title":"Management of Ileal Pouch Cancer in Patients With Inflammatory Bowel Disease","authors":"Shanshan Wang , Huaibin Mabel Ko , Dana J. Lukin , Ellen Scherl , Ravi Kiran , Bo Shen","doi":"10.1016/j.gastha.2025.100824","DOIUrl":"10.1016/j.gastha.2025.100824","url":null,"abstract":"<div><h3>Background and aims</h3><div>Ileal pouch cancer in patients with inflammatory bowel disease, though rare, represents a significant concern due to the high mortality. While prior studies emphasized incidence and risk factors, this study evaluates the current management and prognosis of pouch cancer following ileal pouch-anal anastomosis.</div></div><div><h3>Methods</h3><div>Consecutive patients with pouch cancer were identified from a prospectively maintained database (2019–2025). Patients with familial adenomatous polyposis and precancerous conditions were excluded. Demographic, clinical, endoscopic, and histologic data were collected. Primary outcomes were disease recurrence/progression and oncological survival.</div></div><div><h3>Results</h3><div>Of 699 patients, 10 developed pouch cancer (incidence: 0.5 per 100 person-years). Lesions were located at the cuff (n = 3), anal transition zone (n = 3), pouch body (n = 2), prepouch ileum (n = 1), and both anal transition zone and pouch body (n = 1). Two patients presented with distant metastases without endoscopically visible lesions in the pouch. The histological types were adenocarcinoma (n = 5), squamous cell carcinoma (n = 3), non-Hodgkin lymphoma (n = 1), and neuroendocrine tumor (n = 1). The diagnosis was established through endoscopic biopsies (n = 2), surgical resection (n = 6; three with prior endoscopically diagnosed dysplasia), and cross-sectional imaging (n = 2). Seven patients had localized disease, allowing curative treatment. Treatments included surgery (n = 5), chemoradiotherapy (n = 6), and lanreotide for neuroendocrine tumor. Over a median follow-up of 2.8 years (interquartile range: 1.5–5.2), recurrence or disease progression occurred in three patients (30%), and one patient (10%) died from pouch cancer, with a 5-year cumulative survival of 88.9%.</div></div><div><h3>Conclusion</h3><div>Adenocarcinoma remains the most common histological type; however, nonadenocarcinoma, especially the squamous cell carcinoma, has been increasingly recognized. Endoscopic surveillance was helpful in detecting precancerous lesions.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100824"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555499","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}

引用次数: 0

Care Coordination for Patients Admitted With Alcohol-Associated Liver Disease: An Assessment of Appropriate Follow-up and Treatment at Time of Discharge 酒精相关性肝病住院患者的护理协调：出院时适当随访和治疗的评估

Gastro hep advances

Pub Date : 2025-09-30 DOI: 10.1016/j.gastha.2025.100823

Isabelle S. Byers , Bharathi Selvan , Jacqueline B. Henson , Donna Niedzwiecki , Andrew J. Muir , Stephanie Garbarino

Background and Aims

The prevalence of alcohol-associated liver disease (ALD) is on the rise in the United States, and effective management requires multidisciplinary care and coordination of services across specialties. The aim of this study is to assess whether patients hospitalized with alcohol use disorder (AUD) and ALD have access to appropriate provider follow-up and treatment at time of discharge as well as to identify factors that enable care coordination.

Methods

Hospital admissions for adults with ALD and AUD between January 1, 2022, and December 31, 2022, at our institution were identified. Medical records were reviewed to identify clinical characteristics as well as attendance at a hepatology appointment within 90 days of discharge (primary endpoint), referral to substance use services at discharge, and prescription of medication for AUD at discharge (secondary endpoints). Logistic regression modeling with repeated admissions within patient was performed to identify independent associations with each outcome.

Results

Among the hospital admissions, 417 met the inclusion criteria. Following 16% of admissions, patients attended a hepatology appointment, 4% of patients were referred to substance use services, and 14% of patients were prescribed medication for AUD. Among modifiable factors, hepatology and social work evaluation during hospitalization were associated with successful care coordination.

Conclusion

In our population, rates of specialist follow-up and treatment for AUD and ALD after a hospital admission were overall low. This study not only highlights a significant gap in care delivery for patients with ALD, but it also identifies a critical need to establish quality measures for the inpatient management and long-term follow-up for patients ALD.

背景和目的酒精相关性肝病（ALD）的患病率在美国呈上升趋势，有效的管理需要多学科的护理和跨专业的协调服务。本研究的目的是评估住院的酒精使用障碍（AUD）和ALD患者是否在出院时获得适当的提供者随访和治疗，并确定使护理协调的因素。方法对2022年1月1日至2022年12月31日期间我院收治的成人ALD和AUD患者进行统计。对医疗记录进行审查，以确定临床特征以及出院后90天内肝病预约的出席情况（主要终点），出院时转诊到药物使用服务，以及出院时AUD的药物处方（次要终点）。对重复入院的患者进行逻辑回归建模，以确定与每个结果的独立关联。结果417例住院患者符合纳入标准。在16%的患者入院后，患者参加了肝病预约，4%的患者被转介到药物使用服务，14%的患者因AUD服用处方药。在可调整的因素中，住院期间的肝病学和社会工作评估与成功的护理协调有关。结论：在我们的人群中，住院后AUD和ALD的专科随访和治疗率总体较低。这项研究不仅强调了ALD患者在护理服务方面的重大差距，而且还确定了建立住院管理和ALD患者长期随访的质量措施的迫切需要。

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引用次数: 0

Drug Discontinuation and Persistent Symptoms Among Initiators of Bio-Originator and Biosimilar anti–Tumor Necrosis Factor Drugs in Inflammatory Bowel Disease: Real-World Contemporary Data From the CAnadian Network for Advanced Interdisciplinary Methods/CIRC Registry 炎症性肠病生物源性和生物类似药抗肿瘤坏死因子药物起始者的停药和持续症状：来自加拿大先进跨学科方法网络/CIRC注册的真实世界当代数据

Gastro hep advances

Pub Date : 2025-09-30 DOI: 10.1016/j.gastha.2025.100821

Banke Oketola , Sasha Bernatsky , Luck Lukusa , Cristiano S. Moura , Autumn Neville , Yvette Leung , Neeraj Narula , Waqqas Afif , Marina G. Birck , Petros Zezos , Harminder Singh , Canadian IBD Research Consortium

Background and aims

Biosimilars and their originator anti–tumor necrosis factor drugs remain important in inflammatory bowel diseases (IBDs). We assessed drug discontinuation, IBD symptoms, and quality of life (QoL) in adults after initiating infliximab and adalimumab bio-originators or biosimilars.

Methods

Six Canadian IBD sites enrolled initiators of these drugs, between January 2019 and February 2024. We determined drug discontinuation, concomitant medications, and symptoms and QoL (using the Short Inflammatory Bowel Disease Questionnaire and 5-level EuroQol-5D) at 12 months after initiating therapy, and assessed differences between bio-originator and biosimilar users.

Results

We evaluated 205 initiators of infliximab (N = 151) or adalimumab (N = 54) who had completed at least 12 months of follow-up. Within this time, 21.5% (n = 44) discontinued drug use. There were significant reductions in corticosteroid use, abdominal pain and bowel urgency among both bio-originator and biosimilar users. Significant reduction in overall pain/discomfort and fatigue was detected among biosimilar users only. There was a significant improvement in QoL on the Short Inflammatory Bowel Disease Questionnaire both in the bio-originator (mean difference 9.0, 95% confidence interval: 4.0–15.0) and biosimilar (9.0, 95% confidence interval: 6.0–12.0) groups.

Conclusion

About 80% of individuals initiating infliximab or adalimumab for IBD were still on these drugs at 12 months. Benefits (including less corticosteroid use, abdominal pain, bowel urgency, and improved QoL) were seen in individuals initiating both biosimilar and bio-originators.

背景和目的生物仿制药及其前身抗肿瘤坏死因子药物在炎症性肠病（IBDs）中仍然很重要。我们评估了开始使用英夫利昔单抗和阿达木单抗生物原药或生物仿制药后的成人停药、IBD症状和生活质量（QoL）。方法在2019年1月至2024年2月期间，六个加拿大IBD站点招募了这些药物的起始者。我们在开始治疗后12个月确定药物停药、伴随药物、症状和生活质量（使用短炎症性肠病问卷和5级EuroQol-5D），并评估生物原药和生物仿制药使用者之间的差异。我们评估了205例完成至少12个月随访的英夫利昔单抗（N = 151）或阿达木单抗（N = 54）启动者。在此期间，21.5% （n = 44）停止使用药物。在生物起源者和生物仿制药使用者中，皮质类固醇的使用、腹痛和肠道急症都有显著减少。仅在生物仿制药使用者中检测到总体疼痛/不适和疲劳的显着减少。生物起源组（平均差值9.0,95%可信区间：4.0-15.0）和生物仿制药组（平均差值9.0,95%可信区间：6.0-12.0）在短炎症性肠病问卷上的生活质量均有显著改善。结论：约80%开始使用英夫利昔单抗或阿达木单抗治疗IBD的患者在12个月时仍在使用这些药物。在使用生物仿制药和生物原药的个体中可以看到益处（包括减少皮质类固醇的使用、腹痛、肠道急症和改善的生活质量）。

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引用次数: 0

Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease 粘膜t细胞流式细胞术诊断肠道移植物抗宿主病的可行性及应用

Gastro hep advances

Pub Date : 2025-09-29 DOI: 10.1016/j.gastha.2025.100820

Masaya Iwamuro , Takumi Kondo , Daisuke Ennishi , Nobuharu Fujii , Mai Hiramatsu , Araki Hirabata , Takahide Takahashi , Takehiro Tanaka , Yoshinobu Maeda , Motoyuki Otsuka

Background and Aims

Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.

Methods

We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.

Results

Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56⁺:CD3⁺ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).

Conclusion

Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56⁺:CD3⁺ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions.

背景和目的及时诊断造血干细胞移植（HSCT）后的肠道并发症，包括移植物抗宿主病（GVHD）、移植相关血栓性微血管病和巨细胞病毒感染，对于适当的治疗至关重要。本研究评估了内镜活检的粘膜t细胞谱是否可以支持这些移植后疾病的诊断。方法前瞻性分析21例hsct术后58例肠道活检标本。在上镜检查时从胃和十二指肠获得配对样本，在结肠镜检查时从回肠和大肠获得配对样本。从每个标本中分离淋巴细胞并用流式细胞术进行分析。这些数据与先前收集的队列（35例患者，51个样本）的数据相结合，在组织学定义的组中进行比较免疫表型分析。结果十二指肠活检比胃活检产生更多淋巴细胞（平均±标准差：532±823 vs 233±392；P = 0.070），回肠和结肠的淋巴细胞数量相当。在41例可评估的病例中，GVHD患者的CD56+:CD3+比值（5.5±2.2%）显著低于非特异性或无炎症的患者（28.4±16.3%;P = 0.006）。截断值为11%，诊断GVHD的敏感性为85.7%，特异性为83.3%（曲线下面积= 0.91）。结论内镜下活检粘膜t细胞谱分析是可行的，有助于HSCT术后GVHD的诊断。CD56+:CD3+比值降低是区分GVHD与其他移植后肠道疾病的一个有希望的标志物。

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引用次数: 0

Blockade of Interleukin-6 Trans-signaling in the Presence of Certain Gut Microbiota Induces Mature-onset Obesity in Mice 在某些肠道微生物群存在下，阻断白细胞介素-6反式信号传导可诱导小鼠成熟型肥胖

Gastro hep advances

Pub Date : 2025-09-29 DOI: 10.1016/j.gastha.2025.100819

Tali Lanton , Dana Eidelshtein , Jacob Rachmilewitz , Rinat Abramovitch , Orit Pappo , Shiran Udi , Saja Baraghithy , Joseph Tam , Sharon Perles , Evan Williams , Sharona Elgavish , Shmuel Ruppo , Hadar Benyamini , Uria Mor , Eran Elinav , Dirk Schmidt-Arras , Ateequr Rehman , Philip Rosenstiel , Anastasios Giannou , Samuel Huber , Jonathan H. Axelrod

Background and Aims

Interleukin-6 (IL-6) performs multiple roles in regulating metabolic pathways in both mice and man. Here, we examined the age-dependent metabolic phenotype of SGP mice—mice overexpressing sgp130, a factor that specifically blocks IL-6 trans-signaling—that were housed in distant vivaria.

Methods

Transgenic SGP mice engineered to block IL-6 trans-signaling and wild-type littermates were raised in a Jerusalem animal facility to up to 14 months of age and assessed for weight gain, body composition, and metabolic determinants of energy expenditure in young versus aged mice. Proteomic and RNA-seq analyses were performed on liver samples as a function of age and genotype.

Results

At ∼6 months of age, weight gain, body fat accumulation, hepatosteatosis, hyperglycemia, and macrophage recruitment to adipose tissue emerged and progressed with age in SGP mice maintained in the Jerusalem animal facility, but not in 3 other vivaria. IL-6/sIL-6R blockade strongly reduced signal transducer and activator of transcription 3 phosphorylation in the liver, and hepatocyte-targeted ablation of signal transducer and activator of transcription 3 recapitulated the IL-6 trans-signaling blockade phenotype. Multiomics analyses of mouse livers revealed age- and genotype-related changes in gene expression profiles attributable to bacterial byproducts. Depletion of the gut microbiota by antibiotic treatment from the age of 6 months reversed the obese phenotype in transgenic mice, confirming the crucial role of the microbiome in the phenotype. Accordingly, the microbiome of mice from the Jerusalem animal facility differed significantly from that of mice from animal facilities in Kiel and Hamburg, Germany, where the same mice did not develop a metabolic phenotype.

Conclusion

These findings reveal the crucial functions of IL-6 trans-signaling in preventing mature-onset body fat accumulation induced by certain intestinal microbiota.

背景和目的白细胞介素-6 （IL-6）在调节小鼠和人的代谢途径中发挥多种作用。在这里，我们检查了SGP小鼠的年龄依赖性代谢表型-过度表达sgp130的小鼠，sgp130是一种特异性阻断IL-6反式信号传导的因子-被安置在远处的小鼠体内。方法将阻断IL-6反式信号传导的转基因SGP小鼠和野生型小鼠在耶路撒冷动物设施中饲养至14个月大，并评估幼龄和老年小鼠的体重增加、身体组成和能量消耗的代谢决定因素。对肝脏样本进行蛋白质组学和RNA-seq分析，作为年龄和基因型的函数。结果在耶路撒冷动物设施中维持的SGP小鼠中，在6个月大的时候，体重增加、体脂积累、肝纤维化、高血糖和巨噬细胞向脂肪组织募集出现并随着年龄的增长而进展，但在其他3个体内没有出现这种情况。IL-6/sIL-6R阻断强烈地降低了肝脏中信号换能器和转录激活子3的磷酸化，肝细胞靶向消融信号换能器和转录激活子3再现了IL-6反式信号阻断表型。小鼠肝脏的多组学分析揭示了细菌副产物与年龄和基因型相关的基因表达谱变化。从6个月大开始通过抗生素治疗肠道微生物群的消耗逆转了转基因小鼠的肥胖表型，证实了微生物群在表型中的关键作用。因此，来自耶路撒冷动物设施的小鼠的微生物组与来自德国基尔和汉堡动物设施的小鼠明显不同，在那里相同的小鼠没有产生代谢表型。结论这些发现揭示了IL-6反式信号在预防某些肠道菌群诱导的成熟期体脂积累中的重要作用。

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