Gastro hep advances最新文献

英文中文

Thiamine-Reduced Fatigue in Quiescent Inflammatory Bowel Disease Is Linked to Faecalibacterium prausnitzii Abundance 静止炎性肠病中硫胺素减少的疲劳与prausnitzi粪杆菌的丰度有关

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.012

Sandra Bermúdez-Sánchez , Palle Bager , Jens Frederik Dahlerup , Simon Mark Dahl Baunwall , Tine Rask Licht , Martin Steen Mortensen , Christian Lodberg Hvas

Background and Aims

Chronic fatigue is common in patients with inflammatory bowel disease (IBD). The gut microbiota, specifically, microbial diversity and butyrate-producing bacteria have been linked to the fatigue pathogenesis. High-dose oral thiamine reduces fatigue, potentially through gut microbiota modification. In this study, we investigated how the gut microbiota influences the efficacy of high-dose thiamine in alleviating chronic fatigue in quiescent IBD (qIBD).

Methods

We analyzed the microbiota and short-chain fatty acids concentrations in fecal samples from patients with qIBD, with (n = 40) or without (n = 20) chronic fatigue. The 40 patients with qIBD and fatigue were included in a randomized, placebo-controlled, crossover trial to assess a 4-week high-oral-dose thiamine regimen.

Results

Butyrate and butyrate-producing bacteria were similar in patients with and without fatigue and did not change with high-dose thiamine treatment. Notably, Faecalibacterium prausnitzii was more abundant in thiamine responders compared with nonresponders both pretreatment (P = .019) and post-treatment (P = .038). The relative abundances of Faecalibacterium prausnitzii and Roseburia hominis, both pretreatment and post-treatment, inversely correlated with IBD fatigue score changes for patients with chronic fatigue (PRE; R = −0.48, P = .004, and R = −0.40, P = .018; POST; R = −0.42, P = .012, and R = −0.40, P = .017) respectively.

Conclusion

Faecalibacterium prausnitzii and Roseburia hominis may serve as markers for response to high-dose thiamine in alleviating chronic fatigue in patients with qIBD. The mechanistic role of gut bacteria and butyrate in patients with chronic fatigue and qIBD should be further explored.

背景和目的：慢性疲劳在炎症性肠病（IBD）患者中很常见。肠道微生物群，特别是微生物多样性和产生丁酸盐的细菌与疲劳的发病机制有关。大剂量口服硫胺素可能通过改变肠道菌群来减轻疲劳。在这项研究中，我们研究了肠道微生物群如何影响高剂量硫胺素缓解静止性IBD （qIBD）慢性疲劳的疗效。方法：我们分析了qIBD患者粪便样本中的微生物群和短链脂肪酸浓度，这些患者有（n = 40）或没有（n = 20）慢性疲劳。40名患有qIBD和疲劳的患者被纳入一项随机、安慰剂对照、交叉试验，以评估为期4周的高剂量口服硫胺素方案。结果：有疲劳和无疲劳患者的丁酸盐和产丁酸细菌相似，且大剂量硫胺素治疗后无变化。值得注意的是，在硫胺素治疗前（P = 0.019）和治疗后（P = 0.038），对硫胺素有反应的Faecalibacterium prausnitzii的含量高于无反应的Faecalibacterium。治疗前后，prausnitzii Faecalibacterium和Roseburia hominis的相对丰度与慢性疲劳患者IBD疲劳评分变化呈负相关(PRE；R = -0.48, P = 0.004, R = -0.40, P = 0.018；文章;R = -0.42, P = .012, R = -0.40, P = .017)。结论：prausnitzii粪杆菌和Roseburia hominis可能是大剂量硫胺素缓解qIBD患者慢性疲劳的标志物。肠道细菌和丁酸盐在慢性疲劳和qIBD患者中的作用机制有待进一步探讨。

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引用次数: 0

Early Endoscopic Outcomes After Risankizumab Are Associated With Fewer Hospitalizations and Surgeries in Crohn’s Disease 利桑珠单抗治疗克罗恩病后的早期内镜疗效与较少的住院和手术有关。

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.022

Brian G. Feagan , Jean-Frederic Colombel , Remo Panaccione , Stefan Schreiber , Marc Ferrante , Koji Kamikozuru , Christopher Ma , Wan-Ju Lee , Jenny Griffith , Namita Joshi , Kristina Kligys , Jasmina Kalabic , Si Xuan , Marla Dubinsky

Background and Aims

We evaluated the association between endoscopic outcomes following risankizumab induction and subsequent rates of hospitalization and surgery through 52 weeks of risankizumab (both doses) maintenance therapy in patients with Crohn’s disease (CD).

Methods

Patients with moderately to severely active CD and clinical response to 12-week risankizumab induction were rerandomized to continued therapy or drug withdrawal in the phase 3 FORTIFY maintenance trial. Incidence rates (events/100 person-years) of CD-related hospitalization and surgery, and the composite of both, through 52 weeks of maintenance were compared between patients achieving vs not achieving predefined endoscopic outcomes following induction.

Results

Patients who achieved vs did not achieve endoscopic response or remission, or absence of ulcers (ulcer-free endoscopy) after induction had reduced rates of CD-related hospitalization through 52 weeks of risankizumab maintenance (endoscopic response, 1.7 vs 7.9/100 person-years; endoscopic remission, 1.2 vs 6.9/100 person-years; ulcer-free endoscopy, 1.5 vs 6.4/100 person-years; all P < .05). No CD-related surgeries were observed through 52 weeks of risankizumab maintenance among patients who achieved vs did not achieve endoscopic outcomes following induction (endoscopic response, 0 vs 3.2/100 person-years; endoscopic remission, 0 vs 2.6/100 person-years; ulcer-free endoscopy, 0 vs 2.4/100 person-years; all P = .025). In contrast, patients who received placebo during maintenance had statistically similar rates of CD-related hospitalizations and surgeries regardless of achievement of endoscopic outcomes after induction.

Conclusion

Patients achieving endoscopic outcomes following risankizumab induction experienced less CD-related hospitalizations and surgeries through 52 weeks of maintenance when continuing active therapy. Early treatment success may predict favorable long-term outcomes of disease.

背景和目的：我们评估了克罗恩病（CD）患者在52周的利桑单抗（两种剂量）维持治疗中内窥镜结果与随后住院和手术率之间的关系。方法：在3期FORTIFY维持试验中，对12周利桑单抗诱导有临床反应的中度至重度活动性CD患者被重新随机分配到继续治疗或停药组。通过52周的维持，比较了在诱导后达到与未达到预定内镜结果的患者之间与cd相关的住院和手术发生率（事件/100人年）以及两者的组合。结果：诱导后达到或未达到内窥镜反应或缓解，或没有溃疡（无溃疡内窥镜检查）的患者，通过52周的利桑单抗维持，cd相关住院率降低(内窥镜反应，1.7 vs 7.9/100人年；内镜下缓解，1.2 vs 6.9/100人年；无溃疡内窥镜检查，1.5 vs 6.4/100人年；P < 0.05)。在52周的利桑单抗维持期中，在诱导后达到或未达到内窥镜结果的患者中，没有观察到与cd相关的手术(内窥镜反应，0 vs 3.2/100人年；内镜下缓解，0 vs 2.6/100人年；无溃疡内窥镜检查，0 vs 2.4/100人年；P = 0.025)。相比之下，在维持期间接受安慰剂的患者与cd相关的住院率和手术率在统计上相似，无论诱导后的内窥镜结果如何。结论：在利桑单抗诱导后达到内镜治疗结果的患者，在持续积极治疗的52周维持期内，与cd相关的住院和手术次数减少。早期治疗的成功可能预示着疾病良好的长期预后。临床注册号：ADVANCE (NCT03105128)；MOTIVATE （NCT03104413）和FORTIFY （NCT03105102）。

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引用次数: 0

Gastric Ischemia From Partial Dual-Vessel Occlusion

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.10.013

Fangfang Wang , Amani Elshaer , Vijay P. Singh

引用次数: 0

Short-Term Outcomes of Endoscopic Ultrasound-Guided Pancreatic Cyst Ablation: A Systematic Review and Meta-Analysis

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.100595

Ahmed Al Qady , Kapil Dev Nayar , Fatima Elmustafa , Mohamed Salih , Joseph Emran , Amir Beirat , Sasmith Menakuru , Dana Harris , Dan J. Echols , Baoan Ji , John M. DeWitt , Zhen Wang , Fernando F. Stancampiano , Yan Bi

Background and Aims

Pancreatic cysts (PCs) are increasingly detected through abdominal imaging, prompting exploration of alternatives such as endoscopic ultrasound–guided PC ablation due to the risks and costs associated with surgery. This study conducts a systematic review and meta-analysis of endoscopic ultrasound–guided PC ablation’s short-term efficacy and complications for PC management.

Methods

A systematic review and meta-analysis were carried out on PubMed, Ovid, Cochrane, and TRIP electronic databases. The primary outcome was cyst resolution (partial and complete) and persistence on imaging 12 months after ablation. The secondary outcome was procedure-related adverse events.

Results

Eight studies were eligible for analysis. Complete cyst resolution on imaging 12 months after endoscopic ultrasound ablation was 50% [95% CI 36‒63, I2 = 85.31%]. Partial cyst resolution was 27% [95% CI 15‒41, I2 = 87.07%], and cyst persistence was 17% [95% CI 11‒24, I2 = 62.11%]. The rate of complete resolution varied depending on the treatment agent (for ethanol 29% [95% CI 10‒53]; lauromacrogol 51% [95% Cl 36‒67]; ethanol and paclitaxel 63% [95% CI 48‒76]; paclitaxel and gemcitabine 67% [95% CI 45‒83]; and ethanol, paclitaxel, and gemcitabine 61% [95% CI 39‒80]). Postprocedure adverse events included abdominal pain in 4% [95% CI 0‒11], pancreatitis in 3% [95% CI 1‒5], and fever in 1% [95% CI 0‒3] of all patients.

Conclusion

The treatment of pancreatic cysts with endoscopic ultrasound ablation results in acceptable levels of complete resolution, and low incidence of severe adverse events. The effectiveness of this treatment is further enhanced when chemoablative agents are employed.

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引用次数: 0

Combined MALT Lymphoma and Early Gastric Cancer in a Reconstructed Gastric Tube Successfully Treated With Endoscopic Submucosal Dissection 内镜下粘膜下剥离术成功治疗重建胃管中的 MALT 淋巴瘤和早期胃癌合并症

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.07.009

Kimitoshi Kubo , Issei Ashida , Noriko Kimura

引用次数: 0

Patient Perspective of Use of Artificial Intelligence During Colonoscopy 人工智能在结肠镜检查中的应用。

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.021

Samuel J. Burton , Dennis Shung , Sunny Chung , Harry Aslanian

引用次数: 0

The Role of Myeloid Cells on the Development of Hepatic Metastases in Gastrointestinal Cancer 髓系细胞在胃肠癌肝转移发展中的作用。

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.017

Austin R. Dosch , Mary P. Martos , Samara Singh , Karishma Kodia , Nipun B. Merchant , Nagaraj S. Nagathihalli

The development of hepatic metastases is the leading cause of mortality in gastrointestinal (GI) cancers and substantial research efforts have been focused on elucidating the intricate mechanisms by which tumor cells successfully migrate to, invade, and ultimately colonize the liver parenchyma. Recent evidence has shown that perturbations in myeloid biology occur early in cancer development, characterized by the initial expansion of specific innate immune populations that promote tumor growth and facilitate metastases. This review summarizes the pathophysiology underlying the proliferation of myeloid cells that occurs with incipient neoplasia and explores the role of innate immune-host interactions, specifically granulocytes and neutrophil extracellular traps, in promoting hepatic colonization by tumor cells through the formation of the “premetastatic niche”. We further summarize the role of additional myeloid subpopulations such as monocytes and macrophages, dendritic cells, platelets, and eosinophils on promoting disease metastases in GI cancers. Lastly, we describe burgeoning therapeutic approaches aimed at targeting specific myeloid populations to reduce liver metastases and highlight the inherent challenges that exist in studying the efficacy of these treatments in preclinical models. As the inception and outgrowth of liver metastases are primary drivers of prognosis in GI malignancies; further research into the complex mechanisms involved in this critical process is urgently needed.

肝转移的发展是胃肠道（GI）癌症死亡的主要原因，大量的研究工作集中在阐明肿瘤细胞成功迁移、侵入并最终定植肝实质的复杂机制上。最近的证据表明，骨髓生物学的扰动发生在癌症发展的早期，其特征是促进肿瘤生长和促进转移的特异性先天免疫群体的初始扩张。这篇综述总结了早期肿瘤发生时骨髓细胞增殖的病理生理学，并探讨了先天免疫-宿主相互作用，特别是粒细胞和中性粒细胞胞外陷阱，通过形成“转移前生态位”促进肿瘤细胞在肝脏定植的作用。我们进一步总结了其他髓系亚群如单核细胞和巨噬细胞、树突状细胞、血小板和嗜酸性粒细胞在促进胃肠道癌症转移中的作用。最后，我们描述了针对特定髓系人群的新兴治疗方法，以减少肝转移，并强调了在临床前模型中研究这些治疗方法的有效性所存在的固有挑战。由于肝转移的发生和发展是胃肠道恶性肿瘤预后的主要驱动因素；迫切需要进一步研究涉及这一关键过程的复杂机制。

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引用次数: 0

Activated CD27+PD-1+ CD8 T Cells and CD4 T Regulatory Cells Dominate the Tumor Microenvironment in Refractory Celiac Disease Type II 活化的CD27+PD-1+ CD8 T细胞和CD4 T调节细胞主导难治性乳糜泻II型肿瘤微环境

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.023

Tessa Dieckman , Mette Schreurs , Ciska Lindelauf , Ahmed Mahfouz , Caroline R. Meijer , Louise Pigeaud , Vincent van Unen , Gerd Bouma , Frits Koning

Background and Aims

Refractory celiac disease type II (RCDII) is characterized by a clonally expanded aberrant cell population in the small intestine. The role of other tissue-resident immune subsets in RCDII is unknown. Here, we characterized CD8 and CD4 T cells in RCDII duodenum at the single-cell level and in situ.

Methods

We applied mass cytometry on CD45⁺ duodenal cells derived from intestinal biopsies (n = 23) and blood samples (n = 20) from RCDII patients and controls. Additionally, we analyzed intestinal biopsies from celiac disease (n = 11) and RCDI (n = 2) patients. We performed single-cell RNA-sequencing on CD45⁺ duodenal cells derived from a RCDII patient, immunofluorescence staining for in situ analysis and flow cytometry for phenotyping of RCDII aberrant and CD8 T cells.

Results

Compared to healthy controls, we observed that CD27⁺PD-1⁺ memory CD8αβ cells and CD4 T regulatories (Tregs) were more abundant in RCDII duodenum (CD8 ∗∗0.0029; CD4 ∗∗∗0.0001). The CD27⁺PD-1⁺ memory CD8αβ cells expressed the tissue-resident marker CD69, immunoregulatory markers (TIGIT, HAVCR2, TNFRSF9), NKG2A, were enriched for activated pathways and displayed cytotoxic gene signatures (NKG7, PRF1, GZMA). The absence of CD103 accords with their localization in the lamina propria as determined by in situ analysis. The CD25⁺FoxP3⁺CD27⁺CD127^dim/- CD4 Tregs expressed IL1R2 and IL32 and costimulatory molecules (TNFSRS4, ICOS and TNFRSF18) and resided in the lamina propria as well. Flow cytometry confirmed the presence of the inhibitory receptor NKG2A on expanded duodenal CD8 T cells and HLA-E, the ligand for NKG2A, on expanded aberrant cells.

Conclusion

RCDII is characterized by the simultaneous presence of an activated CD27⁺PD-1⁺ memory CD8αβ T cell subset and CD4 Tregs, suggesting that checkpoint blockade with anti-NKG2A/PD-1 and/or anticytotoxic T lymphocyte antigen 4 may be an attractive treatment option.

背景和目的：难治性乳糜泻II型（RCDII）的特点是小肠中细胞群的克隆扩增。其他组织驻留免疫亚群在RCDII中的作用尚不清楚。在这里，我们在单细胞水平和原位鉴定了RCDII十二指肠中的CD8和CD4 T细胞。方法：我们对来自RCDII患者和对照组的肠道活检（n = 23）和血液样本（n = 20）的CD45+十二指肠细胞进行了大规模细胞计数。此外，我们还分析了乳糜泻（n = 11）和RCDI （n = 2）患者的肠道活检。我们对来自RCDII患者的CD45+十二指肠细胞进行单细胞rna测序，免疫荧光染色进行原位分析，流式细胞术进行RCDII异常细胞和CD8 T细胞的表型分析。结果：与健康对照组相比，我们观察到CD27+PD-1+记忆性CD8αβ细胞和CD4 T调节细胞（Tregs）在RCDII十二指肠中更丰富(CD8∗0.0029；CD4∗∗∗0.0001)。CD27+PD-1+记忆性CD8αβ细胞表达组织驻留标记CD69、免疫调节标记（TIGIT、HAVCR2、TNFRSF9）、NKG2A，激活通路富集，显示细胞毒性基因特征（NKG7、PRF1、GZMA）。CD103的缺失符合原位分析确定的它们在固有层的定位。CD25+FoxP3+CD27+CD127dim/- CD4 treg表达IL1R2、IL32和共刺激分子（TNFSRS4、ICOS和TNFRSF18），也驻留在固有层中。流式细胞术证实抑制受体NKG2A存在于扩大的十二指肠CD8 T细胞上，而NKG2A的配体HLA-E存在于扩大的异常细胞上。结论：RCDII的特点是同时存在活化的CD27+PD-1+记忆CD8αβ T细胞亚群和CD4 Tregs，提示用抗nkg2a /PD-1和/或抗细胞毒性T淋巴细胞抗原4阻断检查点可能是一种有吸引力的治疗选择。

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引用次数: 0

Characterization of Pancreatic Collagen-Expressing Fibroblasts in Mouse Acute Pancreatitis

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.09.012

Amy Qin , Kevin Shi , Rachel R. Tindall , Jiajing Li , Binglu Cheng , Jing Li , Baibing Yang , Qiang Yu , Yinjie Zhang , Bangxing Hong , Balveen Kaur , Mamoun Younes , Qiang Shen , Jennifer M. Bailey-Lundberg , Yanna Cao , Tien C. Ko

Background and Aims

Pancreatic stellate cells (PSCs) are critical mediators in chronic pancreatitis with an undefined role in acute pancreatitis (AP). PSCs consist of a heterogenous group of cells and are considered interchangeable with pancreatic fibroblasts. This study explored the heterogeneous nature of PSCs by characterizing pancreatic collagen-expressing fibroblasts (PCFs) via lineage tracing in mouse normal and AP pancreas and determining the effect of PCF depletion in AP.

Methods

Tandem dimer Tomato (tdTom⁺) PCFs in collagen type 1 (Col1)a2CreER^{tdTomato (Tom)} mice receiving tamoxifen were characterized via fluorescence, Oil Red staining, and flow cytometry. AP was induced by cerulein, AP injury was assessed, and tdTom⁺ PCFs were monitored. The effect of PCF depletion on AP injury was evaluated in Col1a2CreER^{diphtheria toxin A} mice.

Results

Approximately 13% of pancreatic cells in Col1a2CreER^Tom mice were labeled by tdTom (tdTom⁺ PCFs), which surrounded acini, ducts, and blood vessels, and stained with Oil Red, collagen type I, vimentin, and desmin. tdTom⁺ PCFs increased 2-fold during AP, correlating with AP score, amylase, and alpha-smooth muscle actin⁺ and Ki67⁺ staining. PCF depletion in Col1a2CreER^{diphtheria toxin A} mice receiving tamoxifen resulted in enhanced inflammation compared to control.

Conclusion

PCFs may constitute a subset of PSCs and can be activated during AP. PCF depletion aggravates AP, suggesting a protective role for PCFs.

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引用次数: 0

Can Artificial Intelligence and Machine Learning Transform Prediction and Treatment of Post-Transjugular Intrahepatic Portosystemic Shunt (TIPS) Overt Hepatic Encephalopathy?

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.09.015

Eric Kalo, Scott Read, Jacob George, Avik Majumdar, Golo Ahlenstiel

引用次数: 0

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