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What Is the Role of the Environment (Exposome) in Inflammatory Bowel Disease? 环境(暴露体)在炎症性肠病中的作用?
Pub Date : 2022-03-17 DOI: 10.33590/emjgastroenterol/22f0317-2
Carlotta Zennaro
OPENING Day 2 of the 17th Congress of European Crohn’s and Colitis Organisation (ECCO), James Lindsay, Professor of Inflammatory Bowel Disease, Barts Health NHS Trust, London, UK, and The London School of Medicine, Queen Mary University of London, UK, discussed the influence of the environment on the risk of developing inflammatory bowel disease (IBD). The presentation discussed the pathways that mediate environmental impact on IBD as well as the limitations of presently available research, giving a valuable insight into what future studies could be conducted to ultimately determine the role of environmental factors in IBD.The present understanding of IBD, an inflammatory disease, which includes Crohn’s disease (CD) and ulcerative colitis (UC), is that the condition arises from an immune response to micro-organisms of the intestinal flora in genetically susceptible individuals. In addition to disease pathogenesis, other important aspects such as progression, extraintestinal manifestations, and immunogenicity to therapies, are yet to be well understood. While the genetics base is clear, it does not account for the discordance of disease in monozygotic twins, the increased incidence in second generation immigrants, or the rapid increase in IBD cases in the last 50 years. In light of these observations, Lindsay expressed the importance of examining the role of the environment, which, he stressed, does not comprise a single factor, but a multitude of factors that are likely to impact disease onset and natural history.
第17届欧洲克罗恩病和结肠炎组织(ECCO)大会开幕第二天,英国伦敦巴特健康NHS信托基金会炎症性肠病教授James Lindsay和英国伦敦玛丽女王大学伦敦医学院讨论了环境对发展炎症性肠病(IBD)风险的影响。该报告讨论了介导环境对IBD影响的途径以及目前可用研究的局限性,为未来的研究提供了有价值的见解,以最终确定环境因素在IBD中的作用。IBD是一种炎症性疾病,包括克罗恩病(CD)和溃疡性结肠炎(UC),目前对IBD的理解是,这种疾病是由遗传易感个体对肠道菌群微生物的免疫反应引起的。除了疾病的发病机制外,其他重要的方面,如进展、肠外表现和对治疗的免疫原性,尚未得到很好的理解。虽然遗传学基础是明确的,但它并不能解释同卵双胞胎的疾病不一致,第二代移民的发病率增加,或者过去50年来IBD病例的快速增加。根据这些观察结果,Lindsay表达了检查环境作用的重要性,他强调,环境不是由单一因素组成的,而是由许多因素组成的,这些因素可能影响疾病的发病和自然历史。
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引用次数: 0
Gastrin-17 Levels in Pre-malignancy Gastritis Lesions 胃泌素-17在恶性前期胃炎病变中的表达
Pub Date : 2022-02-04 DOI: 10.33590/emjgastroenterol/21-00156
S. Halim, Gontar Alamnsyah Siregar
Background: Gastritis is an inflammatory process on the lining of the stomach that could be caused by various factors. Untreated inflammatory processes could lead to ulcers. Gastrin hormone is released by gastrin-secreting enteroendocrine cells (G cells) in the stomach, which influence the secretion of gastric acid and helps the proliferation of gastric epithelial cells. Its abnormal secretion in H. pylori infection, with food-stimulated excessive release of gastrin, is the most prominent abnormality. One concern is the relationship of excess gastrin secretion to the incidence of gastric cancer. This study aimed to show the difference in gastrin levels on patients with gastritis, both with and without pre-malignant lesions.Methods: This research was a cross-sectional study with 40 samples that had met the inclusion and exclusion criteria. Endoscopy was performed to assess the gastric mucosa and tissue biopsy was performed afterward. The data was analysed in univariate and bivariate ways.Results: From this study, 20 people were positive for pre-malignant lesions (50%). Mann–Whitney test analysis was used to analyse the data and showed there was a significant difference between gastrin levels on patients with gastritis with and without pre-malignant lesions, with a p value of 0.01.Conclusion: There is a significant difference between gastrin levels in patients with gastritis with and without pre-malignant lesions, which could be the basis for early detection of patients with gastric cancer.
背景:胃炎是一种发生在胃内壁的炎症过程,可由多种因素引起。未经治疗的炎症过程可能导致溃疡。胃泌素激素由胃内分泌胃泌素的肠内分泌细胞(G细胞)释放,影响胃酸的分泌,帮助胃上皮细胞增殖。其在幽门螺杆菌感染中分泌异常,以食物刺激的胃泌素过度释放为最突出的异常。其中一个问题是胃泌素分泌过量与胃癌发病率的关系。本研究旨在显示胃炎患者胃泌素水平的差异,无论有无恶性前病变。方法:本研究采用横断面研究,选取符合纳入和排除标准的样本40例。胃镜检查评估胃粘膜,然后进行组织活检。数据以单变量和双变量的方式进行分析。结果:在本研究中,20人(50%)的癌前病变呈阳性。采用Mann-Whitney检验分析数据,发现伴有和未伴有癌前病变的胃炎患者胃泌素水平差异有统计学意义,p值为0.01。结论:伴有和不伴有癌前病变的胃炎患者胃泌素水平存在显著差异,可作为早期发现胃癌患者的依据。
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引用次数: 0
Interview: Michael Farthing 采访:Michael Farthing
Pub Date : 2022-01-04 DOI: 10.33590/emjgastroenterol/10179885
Michael Farthing
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引用次数: 0
Jejunojejunal Intussusception as Initial Presentation of Coeliac Disease: A Case Report and Review of Literature 空肠-空肠肠套叠是乳糜泻的最初表现:1例报告及文献复习
Pub Date : 2021-06-14 DOI: 10.33590/EMJGASTROENTEROL/20-00139
M. Saad, F. Ghandour, A. Abdullah, E. Fiani, I. Hajj, E. Saikaly
Intussusception as the initial presentation of coeliac disease has been rarely reported, with an incidence of 1% in all coeliac disease presentations. Furthermore, intussusception requiring surgical reduction as the primary presentation for coeliac disease in adults is even rarer. Presented here is a case of a 37-year-old female Asian patient who presented with abdominal pain and distension; she was diagnosed with small bowel obstruction due to jejunojejunal intussusception and required surgical reduction as the initial presentation of coeliac disease.
肠套叠作为乳糜泻的最初表现很少有报道,在所有乳糜泻表现中发病率为1%。此外,需要手术切除的肠套叠作为成人乳糜泻的主要表现更是罕见。这里有一个37岁的亚洲女性病人,她表现为腹痛和腹胀;她被诊断为空肠肠套叠引起的小肠梗阻,需要手术复位作为乳糜泻的最初表现。
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引用次数: 0
An Overview of Novel and Emerging Therapies for Inflammatory Bowel Disease 炎症性肠病新疗法综述
Pub Date : 2020-12-01 DOI: 10.33590/emjgastroenterol/20-00166
Sumona Bhattacharya Sumona Bhattacharya, Raymond K. Cross Raymond K. Cross
Inflammatory bowel disease, consisting of Crohn’s disease and ulcerative colitis, causes chronic gastrointestinal symptoms and can lead to morbidity and mortality if uncontrolled or untreated. However, for patients with moderate-to-severe disease, currently available therapies do not induce or maintain remission in >50% of patients. This underscores the need for additional therapies. In this review, the authors detail the novel therapies vedolizumab, tofacitinib, and ustekinumab and delve into therapies which may come onto the market within the next 10 years, including JAK-1 inhibitors (filgotinib and upadacitinib), IL-23 inhibitors (guselkumab, mirikizumab, and risankizumab), the anti-β4β7 and anti-βEβ7 integrin monoclonal antibody etrolizumab, the sphingosine-1-phosphate subtypes 1 and 5 modulator ozanimod, and mesenchymal stem cells. Further studies are required before these emerging therapies gain approval.
炎症性肠病,包括克罗恩病和溃疡性结肠炎,引起慢性胃肠道症状,如果不加以控制或治疗,可导致发病率和死亡率。然而,对于患有中度至重度疾病的患者,目前可用的治疗方法不能诱导或维持50%的患者的缓解。这强调了需要额外的治疗方法。在这篇综述中,作者详细介绍了新疗法vedolizumab, tofacitinib和ustekinumab,并深入研究了可能在未来10年内上市的疗法,包括jk -1抑制剂(filgotinib和upadacitinib), IL-23抑制剂(guselkumab, mirikizumab和risankizumab),抗β4β7和抗β e β7整合素单克隆抗体etrolizumab,鞘氨醇-1-磷酸亚型1和5调节剂ozanimod,以及间充质干细胞。在这些新兴疗法获得批准之前,还需要进一步的研究。
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引用次数: 1
The Gene Expression Signature Modulated by Dupilumab is Correlated with Histological Severity and Endoscopic Features of Mucosal Inflammation and Remodelling in Eosinophilic Oesophagitis Dupilumab调节的基因表达特征与嗜酸性食管炎的组织学严重程度和粘膜炎症和重塑的内镜特征相关
Pub Date : 2020-12-01 DOI: 10.33590/emjgastroenterol/201208
M. Collins
Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signalling in multiple Type 2 inflammatory disorders, including eosinophilic oesophagitis (EoE). This article reviews the oral presentation given by Dr Collins at the United European Gastroenterology (UEG) Week Virtual 2020 and describes the results of a post hoc analysis of a Phase II proof-of-concept study of dupilumab in adults with active EoE. The aim of the analysis was to ascertain whether there were any correlations between gene expression and disease severity in patients enrolled in the study.
Dupilumab是一种单克隆抗体,可抑制多种2型炎性疾病(包括嗜酸性粒细胞性食管炎(EoE))中的IL-4和IL-13信号传导。本文回顾了Collins博士在2020年欧洲胃肠病学联合周(UEG)虚拟周上的口头报告,并描述了dupilumab用于成人活动性EoE的II期概念验证研究的事后分析结果。分析的目的是确定参与研究的患者的基因表达和疾病严重程度之间是否存在任何相关性。
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引用次数: 0
Cachexia in Patients with Gastrointestinal Cancers: Contributing Factors, Prevention, and Current Management Approaches 胃肠道癌症患者的恶病质:影响因素、预防和当前的管理方法
Pub Date : 2020-12-01 DOI: 10.33590/emjgastroenterol/20-00181
O. Grundmann, S. L. Yoon, Joseph J. Williams
Cancer cachexia is highly prevalent among patients with the advanced stage of cancers and leads to a higher risk of mortality. Delayed management of cachexia results in suboptimal treatment outcomes and irreversible progression to refractory cachexia. The purpose of this review is to provide the pathophysiology of cancer cachexia, emerging diagnostic criteria with potential biomarkers, prevention strategies, and novel treatment approaches. Cachexia is characterised by the presence of an inflammatory process in conjunction with muscle mass and unintentional body weight loss. Various biomarkers such as leptin, ghrelin, TNFα, essential amino acids, total amino acids, and C-reactive protein are indicative of cachexia. Increased circulating levels of β-dystroglycan, myosin heavy-chain, and dystrophin are indicators of shortened survival time as skeletal muscle tissues break down. Despite muscle wasting being a hallmark of cachexia, recommended cachexia management is limited to nutritional counselling and administration of an appetite stimulant and corticosteroids for a short period, which often fail to reverse cancer cachexia. It is critical to monitor weight loss using the cachexia grading system for early detection, to halt progression to refractory cachexia and improve the survival of patients with cancer cachexia.
癌症恶病质在癌症晚期患者中非常普遍,并导致更高的死亡风险。对恶病质的延迟管理导致治疗结果不理想和不可逆转地发展为难治性恶病质。本文综述的目的是提供癌症恶病质的病理生理学、具有潜在生物标志物的新诊断标准、预防策略和新的治疗方法。恶病质的特点是存在炎症过程,同时伴有肌肉质量和无意的体重减轻。各种生物标志物,如瘦素、胃饥饿素、TNFα、必需氨基酸、总氨基酸和c反应蛋白都是恶病质的指示物。β-肌营养不良聚糖、肌球蛋白重链和肌营养不良蛋白的循环水平升高是骨骼肌组织分解时生存时间缩短的指标。尽管肌肉萎缩是恶病质的标志,但推荐的恶病质管理仅限于营养咨询和短期服用食欲兴奋剂和皮质类固醇,这往往不能逆转癌症恶病质。使用恶病质分级系统监测体重减轻,以早期发现,阻止难治性恶病质的进展,提高癌症恶病质患者的生存率是至关重要的。
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引用次数: 1
Stem Cell Therapies: A Review of Current Therapeutic Approach for Inflammation-Associated Sigmoid Colon Diseases 干细胞治疗:炎症相关乙状结肠疾病的当前治疗方法综述
Pub Date : 2020-12-01 DOI: 10.33590/emjgastroenterol/20-00169
Natalie Menassa, Maria Destouni, P. Katafygiotis
Chronic inflammation is the single major contributor to the pathogenesis of sigmoid colon inflammatory diseases such as segmental colitis associated disease and inflammatory bowel disease (IBD). Existing conventional anti-inflammatory treatments have not proven to be a sufficient long-term solution for management of symptoms due to the immunosuppressive nature of these agents. Stem cell (SC) transplantation is a novel approach to treatment that could improve the prognosis of IBD patients in the long term by preventing inflammation, restoring defective immune balance, and promoting mucosal healing. Multiple studies have shown that bone marrow SC, mesenchymal SC (MSC), and most recently intestinal SC (ISC) have had marked success in improving immune functionality in cases of IBD. Effects of bone marrow SC did not show the kind of longevity that researchers initially anticipated, leading them to instead pursue thorough study of MSC. The tolerogenic effects of MSC have proven them to be a key player in the development of SC therapy; however, their exact mechanism of action has yet to be fully characterised. Due to existing discrepancies in the data detailing the association between MSC and colorectal cancer risk, ISC have since become of interest with the intention of finding a more reliable alternative source of SC. Preliminary studies have shown that ISC may be capable of achieving the same immunomodulatory effects as MSC but with reduced colorectal cancer risk, suggesting them to be the most promising new method of treating inflammatory-based sigmoid colon diseases under study thus far.
慢性炎症是乙状结肠炎症性疾病(如节段性结肠炎相关疾病和炎症性肠病(IBD))发病机制的单一主要因素。由于这些药物的免疫抑制性质,现有的传统抗炎治疗尚未被证明是治疗症状的足够长期解决方案。干细胞(SC)移植是一种新的治疗方法,可以通过预防炎症、恢复免疫平衡缺陷和促进粘膜愈合来改善IBD患者的长期预后。多项研究表明,骨髓SC、间充质SC (MSC)和最近的肠SC (ISC)在改善IBD患者的免疫功能方面取得了显著的成功。骨髓SC的效果并没有显示出研究人员最初预期的那种长寿,这导致他们转而对MSC进行深入研究。骨髓间充质干细胞的耐受性效应已被证明是骨髓间充质干细胞治疗发展的关键因素;然而,它们的确切作用机制尚未完全确定。由于间充质干细胞与结直肠癌风险之间的相关数据存在差异,因此ISC已成为人们关注的焦点,目的是寻找更可靠的SC替代来源。初步研究表明,ISC可能能够实现与MSC相同的免疫调节作用,但降低结直肠癌风险,这表明它们是迄今为止研究中治疗炎症性乙状结肠疾病最有希望的新方法。
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引用次数: 0
Achalasia Cardia: A Comprehensive Review 贲门失弛缓症:综合综述
Pub Date : 2020-12-01 DOI: 10.33590/emjgastroenterol/20-00178
M. Ramchandani, P. Pal
Achalasia cardia is the best characterised oesophageal motility disorder. It is characterised by progressive ganglion cell degeneration in the oesophageal myenteric plexus, which results in impaired lower oesophageal sphincter (LES) relaxation upon swallowing and aperistalsis in the distal smooth muscle segment of the oesophagus. The usual presenting features are dysphagia to both liquids and solids from onset, regurgitation of undigested food, retrosternal pain, heartburn, and weight loss. Initial investigations include upper gastrointestinal (GI) endoscopy and timed barium oesophagogram, whereas high resolution manometry is diagnostic. Therapy in achalasia cardia is directed towards biochemical or mechanical reduction in LES pressures. If candidates are fit for surgery, pneumatic dilatation, peroral endoscopic myotomy, and laparoscopic Heller’s myotomy are the mainstays of therapy that act by mechanical disruption of LES. On the other hand, botulinum toxin and pharmacotherapy (nitrates and calcium channel blockers) act by biochemical reduction of LES and are reserved for surgically unfit patients with limited life expectancy because of their short-lived efficacy. Oesophagectomy is reserved for treating refractory longstanding cases, who have previously failed multiple therapies.
贲门失弛缓症是最典型的食道运动障碍。其特征是食道肌丛神经节细胞进行性变性,导致食道下括约肌(LES)在吞咽和食道远端平滑肌段的胃蠕动时松弛受损。通常表现为一开始就对液体和固体都有吞咽困难,未消化的食物反流,胸骨后疼痛,胃灼热和体重减轻。最初的检查包括上消化道(GI)内窥镜检查和定时钡食管造影,而高分辨率压力测量是诊断。贲门失弛缓症的治疗方向是生化或机械降低LES压力。如果候选人适合手术,气动扩张,经口内窥镜肌切开术和腹腔镜Heller肌切开术是机械破坏LES的主要治疗方法。另一方面,肉毒杆菌毒素和药物治疗(硝酸盐和钙通道阻滞剂)通过生化减少LES起作用,由于其疗效短暂,因此保留给不适合手术且预期寿命有限的患者。食道切除术保留用于治疗难治性长期病例,这些病例以前多次治疗失败。
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引用次数: 2
That Gut Feeling: The Role of Inflammatory Cytokines in Depression Among Patients with Inflammatory Bowel Disease 肠道感觉:炎症细胞因子在炎症性肠病患者抑郁中的作用
Pub Date : 2020-12-01 DOI: 10.33590/emjgastroenterol/20-00180
Brant J. Chapman Brant J. Chapman, Graham B. Jones Graham B. Jones
There is mounting evidence of an associative link between inflammatory bowel disease (IBD) and clinical depression. In the first major treatise on the eponymous disease, Burrill Crohn himself noted that: “The number of cases of ileitis that have been rescued from institutions for the treatment of mental diseases emphasises not the personality but the end results of the drain of the disease upon the psychic constitution of the sufferer.” In the 70 years since that prescient statement, a high incidence of neuropsychiatric symptoms (depression, anxiety, cognitive fatigue, and sleep disorders) in patients with IBD has been frequently observed. Since patients with depression have significantly increased rates of relapse, surgery, hospitalisation, and suicide, recognising and treating depression is of paramount importance. In this narrative review, the authors will trace some of the biochemical connections between intestinal inflammation and neuropsychiatric symptoms and focus on strategies to manage both. Additionally, the authors offer a cautionary reflection on the extant need for widespread screening for depression among patients with IBD.
越来越多的证据表明炎症性肠病(IBD)和临床抑郁症之间存在关联。在关于这种同名疾病的第一篇重要论文中,伯里尔·克罗恩(Burrill Crohn)自己指出:“从精神疾病治疗机构中拯救出来的回肠炎病例的数量强调的不是患者的个性,而是疾病对患者精神体质的最终影响。”在这一有先见之明的声明发表后的70年里,经常观察到IBD患者神经精神症状(抑郁、焦虑、认知疲劳和睡眠障碍)的高发。由于抑郁症患者的复发率、手术率、住院率和自杀率显著增加,认识和治疗抑郁症至关重要。在这篇叙述性综述中,作者将追踪肠道炎症和神经精神症状之间的一些生化联系,并重点讨论管理两者的策略。此外,作者还提出了对IBD患者进行广泛抑郁筛查的必要性的警告性反思。
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引用次数: 2
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EMJ. Gastroenterology
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