关键词： Pediatric inflammatory bowel disease   6-thioguanine   6-methyl-mercaptopurine   thiopurine toxicity   activity index  

摘要： Background Azathioprine is widely used for the maintenance of remission in children with inflammatory bowel disease (IBD). Measuring thiopurine metabolites 6-thioguanine (6-TGN) and 6-methyl-mercaptopurine (6-MMP) can aid in optimizing treatment and preventing toxicity. We report a proactive approach combining early metabolite measurements with IBD activity index to achieve optimal azathioprine dosing. Methods The reporting of azathioprine dosing, IBD activity indexes and thiopurine metabolites was evaluated retrospectively in 40 children with IBD. Additional treatments and the effect of azathioprine on blood counts were also examined. Results Forty children (40% female) with IBD (26 Crohn's disease, 12 ulcerative colitis, and 2 unclassified IBD), mean age 12.2 +/- 3.4 years, were included in the study. The mean azathioprine dose was 1.3 +/- 0.4 mg/kg;mean 6-TGN level was 280 +/- 151 pmol/8 x 10(8) red blood cells (RBC) and mean 6-MMP level 1022 +/- 1007 pmol/8 x 10(8) RBC. Disease activity index (Crohn's and ulcerative colitis, pediatric specific) at the time of metabolite measurement was 6.5 +/- 8. Twenty-eight children did not require azathioprine dose adjustment, while it was increased in 12. Data from children with azathioprine monotherapy were analyzed separately and the results were similar. Conclusion Timely measurement of thiopurine metabolites and clinical assessment can provide a powerful tool to optimize azathioprine dosing and reduce serious adverse effects in children with IBD.

关键词： Biosimilar   CT-P13   Crohn's disease   infliximab   ulcerative colitis  

摘要： Background The purpose of this study was to assess the efficacy and safety of biosimilar infliximab (IFX) CT-P13 in treating outpatients with inflammatory bowel disease (IBD) in Italian primary gastroenterology centers. Methods Consecutive IBD outpatients who completed the induction treatment were evaluated retrospectively. Clinical activity was scored according to the Mayo score for ulcerative colitis (UC) and to the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD). The primary endpoint was the achievement of clinical remission (Mayo score <= 2 in UC and HBI <= 5 in CD). Secondary endpoints were clinical response to treatment, achievement of mucosal healing, and safety. Results One hundred forty-one patients (96 UC and 45 CD) were enrolled. Previous treatment with anti-tumor necrosis factor (TNF)alpha had been provided to 26% of UC patients and 28.9% of CD patients. Remission was achieved in 57.3% UC patients and in 75.6% CD patients during a median (interquartile range) follow up of 24 (6-24) months. Clinical response and mucosal healing were achieved in 87.5% and 75.0% of UC patients and in 84.4% and 84.2% of CD patients, respectively. By both univariate and multivariate analysis, age >40 years, presence of comorbidities, and naivety to anti-TNF were significantly related to remission. Only one (0.7%) adverse event was reported in the CD group. Surgery was performed in 2.1% of UC patients and 6.7% of CD patients. Switching from IFX originator to bioshnilar did not influence the maintenance of the clinical remission. Conclusion This study confirmed the long-term efficacy and safety of CT-P13 therapy in IBD, in both naive patients and those switching from IFX originator.

关键词： Fecal calprotectin   potential clinical application   non-inflammatory bowel disease  

摘要： Fecal calprotectin (FC) is an inflammatory marker released mainly from gastrointestinal granulocytes measured in stool samples. FC is noninvasive, economical, simple, and acceptable for patients. Levels of FC have proven reliable for intestinal inflammation, with good clinical sensitivity, and are useful in screening and monitoring inflammatory bowel disease (1111)), as well as in the differential diagnosis between IBD and irritable bowel syndrome (IBS). Given its advantages, FC represents an attractive biomarker that could be utilized in various gastrointestinal (GI) diseases apart from IBD, and is currently being studied extensively by many research groups with significant amounts of data emerging. In this current review we aim to provide an outline of the utility of FC in distinguishing between IBS and I BD, as well as an up-to-date summary of the available clinical experience concerning FC in various common conditions of the GI tract commonly encountered by gastroenterology practitioners, such as IBS, microscopic colitis, acute gastroenteritis, Clostridium difficile infection, colorectal cancer, diverticular disease, coeliac disease, and other GI conditions.

关键词： inflammatory bowel disease   allergy   children  

摘要： Introduction: There are many similarities between inflammatory bowel disease (IBD) and allergic diseases, including similar epidemiological data, pathomechanism, clinical course and even treatment methods. So far, many studies of IBD comorbidity with other diseases, including allergy, but mainly in adults, have been conducted. Aim: To analyse the prevalence of allergic diseases, i.e. food allergy (FA), cow's milk allergy (CMA), atopic dermatitis (AD), allergic rhinitis (AR) and asthma in children with IBD. Material and methods: The study included 105 IBD patients from the Department of Paediatrics, Allergology and Gastroenterology of Collegium Medicum in Bydgoszcz and 100 children without IBD from the Outpatient Clinics. The authors applied the validated questionnaire as a study method. Results: At least one allergic disease was found in 26 (43%) IBD children. The allergological diagnosis was made in IBD children more frequently than in the control group (p = 0.04). The difference was more noticeable with regards to skin prick tests (p = 0.02). FA was the most common disease;it was noted in 19 (32%) IBD children;followed by: AD - in 13 (22%), CMA - in 12 (20%), AR - in 10 (17%) and asthma - in 6 (10%) children. The prevalence of allergic diseases in the control and study groups was comparable (p > 0.05). There was no correlation between age of IBD children and allergy (p > 0.05). Asthma was significantly more common in children undergoing biological treatment (p = 0.01). Conclusions: Children with IBD should be constantly monitored by medical professionals, not only due to the under-lying disease but also due to a possible concomitant allergic disease.

关键词： Correction  

摘要： [This corrects the article DOI: 10.1371/***.0194036.].

关键词： Continued attenuation parameter   Inflammatory bowel disease   Non-alcoholic fatty liver disease  

摘要： Objective: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disorder of the gastrointestinal tract which has an unknown etiology. In this study, we aimed to investigate the fatty liver disease frequency in IBD patients using transient elastography (TE) which is a non-invasive and accurate method for the diagnosis of liver fibrosis. Material and Methods: The data were collected from registered patients retrospectively. On the basis of previous studies, a cut-off value of 238 dB/m for controlled attenuation parameter (CAP) was used for the diagnosis of hepatic steatosis. In this study we have also settled CAP value above 238 dB/m as fatty liver. Results: A total of 99 patients were enrolled in the study. Mean age was 45.59 +/- 11.72 years and 41 (41.4%) patients were female. Fifty-eight patients (58.6%) had Crohn's disease, 39 (39.4%) had ulcerative colitis and 2 (2.0%) had indeterminate colitis. In 8 (8.1%) patients extra-large probe and in 91 (91.9%) patients medium probe was used to detect liver steatosis. Fatty liver disease was detected in 44 (44.4%) patients with IBD. Conclusion: Despite the nutrition disorders in IBD, fatty liver disease was seen in 44.4% of patients in our cohort. However, fatty liver disease may be seen without any aminotransferase elevation in IBD patients. Therefore, liver steatosis should always be kept in mind and careful attention should be paid during follow-up of patients with IBD in our daily practice.

关键词： IBD   EpCAM   连接分子   肝发育   双氢青蒿素  

摘要： 研究背景:炎症性肠病(IBD)被认为是一种遗传与环境相互作用的慢性肠道炎症性疾病,主要包括克罗恩病(CD)和溃疡性结肠炎(UC),临床上表现为严重腹泻、腹痛,甚至可能出现血便。IBD发生时,肠上皮组织完整性受损。肠道上皮组织的完整性是由上皮细胞间的细胞连接维持的,包括紧密连接、粘附连接、间隙连接、桥粒连接等连接结构。肠道是机体最大的粘膜免疫场所,天然免疫作为第一道防线,在肠道稳态平衡中起着重要的作用。深入了解肠道的完整性及其稳态平衡机理对于人类健康的发展很有必要。有研究表明,小鼠结肠中敲低EpCAM后更容易形成葡聚糖硫酸钠(DSS)诱导的IBD小鼠模型,但具体分子机制仍不完全明确。肝脏和肠道上皮在胚胎发育期来源于同一胚胎层,是肠的一种附属腺体。在胚胎发育阶段,肝细胞中有大量的EpCAM基因表达。当小鼠出生后,肝细胞中EpCAM基因表达降低,甚至消失,而在肝细胞发生癌变时EpCAM基因表达会又升高,但是EpCAM基因在肝脏发育及癌变过程中的功能仍不是很清楚。因此,探讨EpCAM基因缺失对肝脏发育的影响十分重要。由于IBD发病率高、治愈难,因此寻找治疗IBD的药物已经成为当前迫切的任务。而双氢青蒿素作为一种抗疟疾药青蒿素的衍生物,在临床上能够迅速控制疟疾发作及症状。除了抗疟疾作用,还有治疗红斑狼疮、抑制血管生成、神经保护、抗炎等特性,因此有必要探讨其在其它疾病防治方面的扩大应用。研究目的:1.本研究通过分析EpCAM基因打靶小鼠模型,探讨EpCAM基因对肠道及肝脏发育的调控机制;2.通过分析EpCAM基因打靶小鼠模型,探讨EpCAM基因缺失与IBD的关系;3.通过建立葡聚糖硫酸钠(DSS)诱导的IBD模型,探讨双氢青蒿素对IBD的改善作用及分子机制。研究方法:1.以借助CRISPR-Cas9技术建立的EpCAM基因打靶小鼠为模型,探究上皮细胞连接分子(EpCAM)功能缺失与IBD的关系;2.探究上皮细胞连接分子(EpCAM)功能缺失,对小鼠肠道上皮细胞连接结构的影响;3.探究上皮细胞连接分子(EpCAM)功能缺失,对小鼠肝脏表观遗传学产生影响;4.以借助RNA干涉技术敲低EpCAM基因的Caco-2细胞为模型,验证体内外结果是否一致,从而确认体内的变化是否为细胞自主性调控。5.C57/BL雄性小鼠经葡聚糖硫酸钠(DSS)诱导成IBD模型小鼠,自由分成正常组、DSS模型组、双氢青蒿素给药组。为了诱导IBD模型的建立(主要是结肠炎模型),给予硫酸葡聚糖钠(DSS)组、双氢青蒿素剂量组自由饮用一周硫酸葡聚糖钠(DSS)后,换成自由饮用纯水5天后,再次用DSS刺激小鼠肠道6天,同时给予双氢青蒿素剂量组小鼠灌胃双氢青蒿素治疗。研究结果:***基因缺失引起肠道炎症发生,而IBD鼠中EpCAM基因表达量减少,由此推测EpCAM基因缺失可视为IBD的一种遗传因素;***基因缺失导致肠上皮细胞紧密连接分子发生改变;***基因缺失,肝糖原变化可能通过调节肝脏糖原代谢、肝脏circRNA,从而对肝发育产生影响;4.与DSS模型组小鼠相比,DHA可以缓解IBD的炎症以及改善IBD对连接分子的影响研究结论:EpCAM基因缺失对细胞连接分子尤其是紧密连接分子产生影响;同时可能通过调节肝脏糖原代谢、肝脏circRNA,从而对肝发育产生影响;DHA可以缓解IBD产生的炎症及对连接分子产生的影响。

关键词： Epstein-Barr virus   Infection   Intestinal mucosa   Inflammatory bowel disease   Chinese  

摘要： Aims: This cross-sectional study is to investigate the presence of Epstein-Barr virus (EBV) in colonic mucosa of inflammatory bowel disease (IBD) patients and its correlation with the clinical disease activities and therapeutic regimens. Methods: Subjects undergoing colonoscopy for screening of polyps were recruited as control. EBV DNA load was analyzed by means of quantitative real-time polymerase chain reaction and EBV-encoded RNAs were tested by in situ hybridization in intestinal mucosa of IBD patients. EBV infection was defined as positive with either method. Clinical disease activity was assessed using the Mayo Clinic Score for ulcerative colitis and Crohn's disease activity index for CD. Results: EBV was detectable in 33 out of 99 IBD patients (33.3%). In controls, EBV prevalence was 7.5% (3/40). We found a significant correlation between EBV prevalence and clinical disease activities (mild [10.71%, 3/28] versus moderate [32.73%, 18/55], severe [75.00%, n = 12/16], p < 0.001). However, no significant difference was found in EBV preva-lence between patients who received immunosuppressive therapy and those who did not. Conclusions: EBV infection is common in colonic mucosa of IBD patients. There is a significant correlation between EBV infection and clinical disease activities of IBD. However, prospective studies are still needed to explore the exact role of EBV in IBD. (C) 2018 S. Karger AG, Basel

关键词： Hepatic steatosis   inflammatory bowel disease   non-alcoholic fatty liver disease   antitumor necrosis factor  

摘要： Background Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). This study evaluated the prevalence of NAFLD and the associated risk factors among IBD patients who received anti-tumor necrosis factor (TNF) therapy. Methods Adult IBD patients receiving anti-TNF therapy (infliximab, adalimumab, certolizumab, golimumab) were enrolled. Hepatic steatosis was assessed by abdominal ultrasound. Patients with a history of excessive alcohol or recent steroid use were excluded. Univariate and multivariate analysis were performed. Results Eighty patients, 55% male, mean age 42 +/- 15 years, were enrolled. The sonographic prevalence of NAFLD was 54% (43/80), significantly higher than the general prevalence in the US adult population (30%) (P<0.0001). NAFLD patients had a significantly higher proportion of males, as well as greater body weight and body mass index, compared to non-NAFLD. The Crohns disease activity index (CDAI) was significantly higher among patients with NAFLD. Multivariate analysis demonstrated that a higher CDAI was independently associated with NAFLD, with an odds ratio of 1.6 (95% confidence interval 1.05-2.44;P=0.03). Conclusions The presence of IBD is strongly associated with NAFLD. We identified a high prevalence of NAFLD among IBD patients receiving anti-TNF. CDAI was independently associated with hepatic steatosis. Further studies arc still needed to evaluate the pathophysiology of NAFLD development and disease progression among IBI) populations.

关键词： 结直肠疾病   流行病学   肠镜检查  

摘要： 目的:1.通过对12160例肠镜资料的分析，探究当地市民结直肠疾病的构成情况及流行病学特点，掌握结直肠疾病的发生、发展规律。2.通过对结直肠疾病分布特征和影响结直肠疾病检出率因素的分析，为当地结直肠疾病的筛查提供研究数据，为当地卫生主管部门制定结直肠疾病特别是结直肠癌的防治措施提供理论依据。3.总结苏北人民医院近些年肠镜水平快速提高的经验，为其它医院提供参考。　　方法:采用横断面研究、回顾性分析苏北人民医院内镜中心2015.1.1至2016.12.31共12160例患者的结肠镜检查资料。1.用Excell表格对收录的受检者肠镜检查资料，按结直肠癌（再按患者性别、患者年龄、肠段部位分组），结直肠息肉（再按患者性别、患者年龄、肠段部位、息肉数量、息肉大小、息肉病理类型分组）及其它常见结直肠疾病（再按患者性别、患者年龄分组）分组建立数据库。2.计算每种肠道疾病的检出率（或占比或构成比）并分别绘制直方图。3.应用spss25.0软件进行统计分析，根据数据特征采用2×2或R×C列联表卡方检验。进行组内及组间比较其差异，总结结直肠疾病分布特征。　　结果:本研究中当地市民常见的结直肠疾病有11种，三大主要疾病是:肠息肉、肠炎和结直肠癌，它们的检出率分别为25.00％、7.64％、5.00％，三者占结直肠疾病总数的82.78％;不同结直肠疾病的检出率男性和女性之间存在显著差异，肠息肉、结直肠癌、肠憩室、肠血吸虫病的检出率男性大于女性，肠炎、溃疡性结肠炎、缺血性肠病的检出率女性大于男性，差异均有统计学意义(P＜0.05)。肠息肉主要分布在50～79岁年龄段;肠炎在18～29岁年龄段高发;溃疡性结肠炎、糜烂性病变、克罗恩病在18-29岁年龄段多发;结直肠黑变病、缺血性肠病在70-79岁年龄段多发;肠憩室在大于80岁年龄段多发。结直肠癌、肠息肉、肠憩室、缺血性肠病、肠血吸虫病检出率随年龄的增加而升高;肠炎、溃疡性结肠炎随年龄增加检出率降低。结直肠癌总的检出率为5.00％，其中直肠癌占结直肠癌的比例最高(42.77％);从肠道的远端到近端部位，检出率呈递减趋势。左侧肠癌的检出率远高于右侧。不同部位结直肠癌的检出率男性均高于女性。　　结直肠息肉总的检出率为25.00％。青年组、中年组、老年组肠息肉检出率分别为9.91％、23.90％、32.79％，呈递增趋势。各年龄组男性结直肠息肉的检出率均高于女性，差异有统计学意义(P＜0.05)。不同肠段息肉的检出率不同，其中乙状结肠检出率最高(26.69％)，其次分别为直肠(21.13％)、降结肠(17.31％)、横结肠(16.43％)、升结肠(12.87％)、回盲部(5.58％)。腺瘤性息肉在所有结直肠息肉中占比最高，从青年组、中年组到老年组呈递增趋势;炎性息肉在所有结直肠息肉中占比随着年龄的增加而减少，三个年龄组分别为48.95％、36.53％、32.61％。在腺瘤性息肉中，管状腺瘤检出率最高，绒毛状腺瘤检出率最低。青年组的非腺瘤性息肉检出率高于腺瘤性息肉，中年组和老年组的腺瘤性息肉检出率高于非腺瘤性息肉，随着年龄的增长，非腺瘤性息肉的比例逐渐减少，腺瘤性息肉的比例逐渐增加，组间比较差异有统计学意义(P＜0.05)。在检出结直肠息肉的3040例患者中，单发息肉1637例，多发息肉1403例。青年组和中年组单发息肉检出率均高于多发息肉，而老年组多发息肉检出率高于单发息肉，这些差异均有统计学意义（P＜0.05）。将结直肠息肉根据大小分为4个组，其中5-9mm的息肉所占比例最高(47.22％)，其次是小于5mm组，大于20mm组的息肉比例最低(7.58％)。结直肠息肉的大小与患者年龄、患者性别、肠段部位之间没有明显相关性。随着结直肠息肉直径的增大，非腺瘤性息肉的检出率逐渐降低，腺瘤性息肉的检出率逐渐增加。将本院近7年肠镜资料做纵向对比发现，每年做镜总人数在不断增加，肠息肉的检出率逐年上升，而肠癌的检出率逐年下降。　　结论:肠息肉、肠炎、结直肠癌是当地市民的三大主要肠道疾病;肠道恶性疾病发病率与年龄正相关，肠炎发病率与年龄负相关;左半结肠癌及左半结肠腺瘤性息肉检出率均大于右半结肠，符合腺瘤-癌序列;从肠道近端到远端，结直肠癌的检出率逐渐升高;腺瘤性息肉较非腺瘤性息肉多，其中腺瘤性息肉中，管状腺瘤检出率最高，绒毛状腺瘤检出率最低;当地肠息肉的检出率逐年升高，结直肠癌检出率呈下降趋势。男性医师、高年资医师以及无痛肠镜检查方式表现出更高的息肉检出率。多因素回归分析得出，患者年龄及性别、检查医师的性别及职称、是否使用无痛检查手段等是肠息肉检出率的独立影响因素。