关键词： colitis   Hermansky-Pudlak syndrome   inflammatory bowel disease   infliximab   tumor necrosis factor alpha  

摘要： Background. Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective. To expand the understanding of IBD in patients with HPS. Methods. Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results. IBD affected 37 (14.2%;12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years;range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30% or 22%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73% and 35% of patients with HPS IBD, respectively;7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions. IBD resembling Crohn's disease affects some patients with HPS;genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.

关键词： anti-tumour necrosis factor   clinical remission   combination immunotherapy   paediatric inflammatory bowel disease   thiopurines   withdrawal  

摘要： Objectives: To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process. Methods: A web-based, 43-question survey. Results: Surveys were completed by 70 paediatric gastroenterologists (PGs) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients [interquartile range (IQR) 130-300] per centre). Routine use of co-immunosuppression was significantly higher with infliximab (IFX) versus adalimumab (ADL) ([61/70, 87.1%] compared with [23/70, 32.9%];P < 0.01). Thiopurines (azathioprine [AZA] or 6-mercaptopurine) were the preferred option overall for co-immunosuppression. They were favoured with either IFX or ADL (76% and 77%, respectively) and in both ulcerative colitis (UC) and Crohn disease (CD) (84% and 69%) compared with methotrexate (MTX). Immunomodulators were the preferred choice as the initial drug to be withdrawn from the combination therapy rather than anti-tumour necrosis factor-alpha (anti-TNF alpha) therapy (59/67, 88% [P < 0.01]). The most common withdrawal time was after 6-12 months, with this decision usually based on clinical assessment rather than a scheduled withdrawal time (51/67, 76% vs 16/67, 24%). Indicators of mucosal healing and therapeutic drug monitoring results tended to be the most important "clinical factors" in the withdrawal decision (P = 0.05). Conclusion: Most PG's favour initial withdrawal of immunomodulator (usually thiopurines) rather than biologic therapy in the step-down process, usually after 6-12 months based on sustained clinical remission. This survey precedes an in-depth, multicentre study of clinical outcomes of withdrawal of co-immunosuppression in PIBD.

关键词： Crohn's disease   inflammatory bowel disease   ulcerative colitis   vedolizumab  

摘要： Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169;ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone > 1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease;corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

摘要： This article is linked to Rhudy et al paper. To view this article, visit https://***/10.1111/apt.16269

关键词： Inflammatory bowel disease   Infliximab   Response predictors  

摘要： Infliximab/adalimumab (IFX/ADA) and vedolizumab (VDZ) are the most widely used biologics in inflammatory bowel diseases. Current models used to predict their efficacies are restricted to either Crohn's disease or ulcerative colitis or to only one type of biologic, which makes them limited in external validation. We therefore designed a comprehensive comparison among these models to identify the most meaningful predictors for patient responses. Several biomarkers and models were compared for their abilities to predict both IFX/ADA and VDZ responses by receiver operating characteristic curves. Least absolute shrinkage and selection operator regression was adopted to determine a simplified gene signature. Verification was performed in biopsy samples by immunohistochemical staining. The GIMATS module (based on counts of IgG plasma cells, inflammatory monocytes, activated T cells, and stromal cells) had the best overall performance for response prediction in both biologics (IFX/ADA, AUC = 0.720-0.853;VDZ, AUC = 0.661-0.728). Based on this module, patients were equally divided into 3 groups: M type (GIMATS-low, metabolism), with a preference for IFX/ADA;I type (GIMATS-high, immune), with a preference for VDZ;and N type (GIMATS-medium, normal), with no preference for either treatment. Furthermore, to improve clinical utility, a simplified 6-gene model, MIN score, was established to determine the baseline expression of G0S2, S100A9, SELE, CHI3L1, MMP1 and CXCL13 and function as a substitute for GIMATS module. Our study suggested that the classification of metabolic or immune type by MIN score was valuable for IBD diagnosis to assist with selection of IFX/ADA and VDZ.

摘要： Objective To collect and evaluate the diagnostic approach of inflammatory bowel disease (IBD) guidelines and provide useful feedback for guideline developers and evidence-based clinical information to help physicians make decisions. Methods Diagnostic guidelines for IBD were retrieved by performing systemic and manual searches. Qualified clinical practice guidelines (CPGs) were included and then evaluated by four well-trained evaluators using the AGREE II instrument. To reduce the bias generated in this process, we used the Measurement Scale of Rate of Agreement (MSRA) tool to interpret the results. Guidelines with good recommendation distributions among the diagnostic field were further reclassified and evaluated. Results Fifteen diagnostic CPGs for IBD were identified and evaluated, and 70.3% (11/15) of the CPGs were above the recommended level. We observed heterogeneity among the diagnostic CPGs for IBD and discrepancies among different domains in one specific guideline. Potential improvements were identified in the fields of stakeholder involvement, rigour of development and applicability. By further analysing the heterogeneity of the recommendations and evidence in 5 UC-CPGs, we found the following issues: no discussion of diagnosing severe complications of UC, disputed significance of serologic and genetic diagnoses of UC, insufficient attention towards medical histories/physical examinations/differential diagnoses and discrepancy in classification criteria. Conclusion The included diagnostic CPGs for IBD were generally of good quality, but heterogeneity was identified. Addressing these issues will provide useful feedback for the guideline updating process, and it will also benefit current clinical practice and eventually patient outcome.

摘要： Introduction. Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. Result. Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively (Chi-square test=3.87, p<0.05). Conclusion. Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels

关键词： 肛瘘   挂线疗法   肛管的静压   肛管最大收缩压   复发  

摘要： 探讨不同的挂线疗法对肛肠疾病患者临床疗效、肛门直肠动力学指标及复发的影响。方法:回顾性分析我院2019年04月至2019年11月收治的120例肛瘘患者的临床资料。根据治疗方法的不同,将其分为对照组68例和观察组52例。对照组采用常规手术方法治疗,观察组采用挂线方法治疗。比较两组术后伤口表面的大小,伤口愈合时间,临床疗效,最大肛门收缩压(AMCP),最大肛门收缩时间(ALCT),直肠静息压(RRP)和肛门静息压(ARP)手术。术后1年内水平和复发率。结果:观察组术后伤口面积大于观察组,伤口愈合时间明显长于对照组(P<0.01);两组总有效率无显着性差异(P>0.05)。与术前相比,两组治疗后RRP和ARP水平均明显降低,观察组低于对照组(P<0.05)。观察组总复发率明显低于对照组(P<0.05)。结论:两种疗法各有千秋。临床效果显著,不影响排便功能。挂线疗法在降低术后复发率方面具有较为明显的优势。

关键词： 幽门螺杆菌   消化内科   感染   危险因素   耐药性  

摘要： 分析消化内科幽门螺杆菌(Hp)感染的相关因素及耐药特征,为合理的门诊药物干预提供参考。方法:选择2018年11月至2020年1月在医院门诊肠胃科首次确诊的62例Hp感染患者并纳入观察组,同时对62例在医院接受身体检查的健康人进行检查,期间被纳入对照组。两组人的Hp感染检测和药敏试验结果,分析Hp感染患者的常见危险因素和耐药特性。结果:观察组14C-CO2结果均为阳性,Hp感染率为100.00%。对照组的Hp感染率为12.90%,消化系统疾病史,高中及以下文化程度,吸烟和饮酒史,不健康的饮食习惯,血脂升高是Hp感染的独立危险因素,Hp对常见的抗菌药(例如甲硝唑,阿莫西林,克拉霉素和左氧氟沙星)具有较高的耐药率。结论:胃肠病患者Hp感染的发生受多种因素影响,Hp对各种常见的抗菌药物具有不同程度的耐药性。诊断和治疗必须明确患者的危险因素并改善药物敏感性试验,采用个体化抗菌药物联合干预,以提高根除Hp的效果。

关键词： 消化内科   幽门螺杆菌   胃肠道疾病  

摘要： 分析消化内科患者幽门螺杆菌感染现状及其对胃肠疾病的相关性。方法:选取自2018年6月~2020年6月于本院接收治疗的消化内科患者100例作为研究对象,对所有患者的临床资料进行分析,分析目前临床中幽门螺杆菌感染现状及其与胃肠疾病之间的相关性。结果:研究结果表示,男性患者感染率略多于女性患者,年龄超过50岁以上的患者感染率略高于49岁以下患者,存在长期饮酒史的患者感染率高于不饮酒患者,对比统计学差异明显(P<0.01);幽门螺杆菌感染下,患者胃肠疾病包括复合型溃疡、反流性食管炎、萎缩性胃炎、十二指肠溃疡、非萎缩性溃疡、胃息肉、胃癌;十二指肠溃疡感染率略高于其他疾病患者,其次为复合型溃疡患者。结论:年龄、性别等因素均是影响患者幽门螺杆菌感染的高危因素,此外,幽门螺杆菌长时间感染下容易导致患者出现十二指肠溃疡等胃肠疾病,临床需根据对患者的具体情况进行筛查,防止幽门螺杆菌感染。