Treat-to-target approach in the management of inflammatory Bowel disease

With the advent of biologic and small molecule therapies, there has been a substantial change in the treatment of inflammatory bowel disease. These advances have had a great impact in preventing disease progression, intestinal damage and, therefore, have contributed to a better quality of life. Discordance between symptom control and mucosal healing has been demonstrated. This has led to the search for new disease control targets. The treat to target strategy, based on expert recommendations and now a randomized controlled trial, has determined that clinical and endoscopic remission should be the goal of therapy. Biomarkers (fecal calprotectin) can be a surrogate target. Although histological healing has shown benefits, there is inadequate evidence and inadequate therapy for that to be a fixed goal at this time.This review will focus on therapeutic goals, according to the evidence currently available, and evaluate strategies to achieve them.     

Validity and reliability of the health-related questionnaire IBDQ-32 in Mexican patients with inflammatory bowel disease

BackgroundInflammatory bowel disease comprises two conditions: ulcerative colitis and Crohn's disease. Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) is a specific questionnaire which has been translated from English into Spanish and validated. In the Spanish-speaking countries of America it has not been validated. The aim was to determine the psychometric properties, validity and reliability of the Mexican version of the IBDQ-32 questionnaire.MethodsA total of 316 patients with inflammatory bowel disease and 100 healthy controls participated in the study. The questionnaires IBDQ-32 and SF-36 were issued on two occasions (separated by 15 days). The psychometric properties of the Mexican version of the IBDQ-32 questionnaire were determined.ResultsPatients with inflammatory bowel disease had an impaired quality of life compared to healthy controls. There were no differences between ulcerative colitis and Crohn's disease in the total scores of IBDQ-32 and its domains. The internal consistency reliability was good. The intraclass coefficient showed good reliability (repeated measurement) for total scale and all four subscales. Factor analysis explained variance is higher than 50% therefore is considered adequate/acceptable. The correlation between IBDQ-32 and SF-36 showed a satisfactory association. The social domain is the only one that presented a ceiling effect.ConclusionsThe Mexican version of the IBDQ-32 quality of life questionnaire is valid and reliable. This sample included the entire spectrum of inflammatory disease (remission and activity) and was comparable when assessing quality of life with the SF-36 generic questionnaire.     

Risk stratification and geographical mapping of Brazilian inflammatory bowel disease patients during the COVID-19 outbreak: Results from a nationwide survey

BACKGROUNDCoronavirus disease 2019 (COVID-19) pandemic is still evolving globally, and Brazil is currently one of the most affected countries. It is still debated whether patients with inflammatory bowel disease (IBD) are at a higher risk for developing COVID-19 or its complications.AIMTo assess geographical distribution of IBD patients at the highest risk and correlate these data with COVID-19 mortality rates in Brazil.METHODSThe Brazilian IBD Study Group (Grupo de Estudos da Doença Inflamatória Intestinal do Brasil) developed a web-based survey adapted from the British Society of Gastroenterology guidelines. The included categories were demographic data and inquiries related to risk factors for complications from COVID-19. Patients were categorized as highest, moderate or lowest individual risk. The Spearman correlation test was used to identify any association between highest risk and mortality rates for each state of the country.RESULTSA total of 3568 patients (65.3% females) were included. Most participants were from the southeastern and southern regions of Brazil, and 84.1% were using immunomodulators and/or biologics. Most patients (55.1%) were at moderate risk, 23.4% were at highest risk and 21.5% were at lowest risk of COVID-19 complications. No association between the proportion of IBD patients at highest risk for COVID-19 complications and higher mortality rates was identified in different Brazilian states (r = 0.146, P = 0.467).CONCLUSIONThis study indicates a distinct geographical distribution of IBD patients at highest risk for COVID-19 complications in different states of the country, which may reflect contrasting socioeconomic, educational and healthcare aspects. No association between high risk of IBD and COVID-related mortality rates was identified.     

Management of acute severe ulcerative colitis in children

The incidence of pediatric-onset ulcerative colitis (UC) is rising. Children often present with a more severe disease phenotype as compared to adults with over a third requiring hospitalization for the management of acute severe ulcerative colitis (ASUC). Further, in pediatric patients presenting with inflammatory bowel disease (IBD) limited to the colon, a definitive diagnosis of UC vs. Crohn’s disease is often unclear. Here, we review the unique aspects of pediatric ASUC including the epidemiology, diagnosis, medical, and surgical management of this disease.     

深在性囊性结肠炎并发肠梗阻1例报告和文献复习

报告１例少见病：深在性囊性结肠炎,患者因反复腹痛,腹泻低热,贫血,消瘦２年余入院,因并发不完全性小肠梗阻,持续１个月不缓解,而行剖腹探查。行右半结肠和部分小肠切除术,明确诊断,术后病情缓解。本病的组织病理特征为多发性囊肿性病变位于肠壁的粘膜下层,囊肿壁内衬以细胞无异常的单层柱状,立方或扁平上皮,病变周围有慢性炎细胞浸润。结合文献复习,对本病的病因、临床特点、诊断、鉴别诊断和治疗进行了讨论。     

参苓白术散对脾虚湿困型溃疡性结肠炎大鼠结肠组织ERK、p38 MAPK蛋白表达的影响

目的：探讨脾虚湿困型溃疡性结肠炎（Ulcerative Colitis,UC）大鼠结肠组织中ERK、p38MAPK蛋白表达的变化及参苓白术散的干预作用。方法40只Wistar大鼠随机分为正常对照组、模型对照组、柳氮磺吡啶组、参苓白术散组,每组10只。采用环境与饮食干预结合TNBS/乙醇灌肠法复制脾虚湿困型UC大鼠模型,应用免疫组织化学法检测各组大鼠结肠组织中ERK、p38MAPK蛋白表达情况。结果模型对照组大鼠结肠组织ERK、p38MAPK表达明显增多,与正常对照组比较具有显著性差异（P〈0.05）。柳氮磺嘧啶组和参苓白术散组大鼠结肠组织ERK、p38MAPK的表达与模型对照组比较差异有统计学意义（P〈0.05）。参苓白术散组大鼠结肠组织ERK、p38MAPK的表达与柳氮磺嘧啶组比较差异亦有统计学意义（P〈0.05或P〈0.01）。结论脾虚湿困型UC大鼠结肠组织ERK、p38MAPK表达明显增强,参苓白术散治疗可显著降低其ERK、p38MAPK的表达水平。     

感染后肠易激综合征与溃疡性结肠炎缓解期病人直肠黏膜细胞因子的表达

目的探讨感染后肠易激综合征（PI-IBS）与溃疡性结肠炎（ UC）缓解期病人肠黏膜细胞因子的表达,从神经-免疫机制分析肠易激综合征（IBS）与炎症性肠病（IBD）的相关性。方法 PI-IBS组病人20例,UC组病人45例,正常对照组30例,结肠镜下取直肠黏膜标本,采用免疫组化方法检测其肠黏膜细胞因子的表达情况。结果PI-IBS病人直肠IFN-γ、IL-2阳性表达高于对照组（χ^2=14.012、13.931,P〈0 .01） ,而与UC病人比较差异无统计学意义（χ^2=2.290、2.323,P〉0 .05）。PI-IBS病人直肠黏膜P物质（SP）强度均值高于对照组（t=3.722,P〈0 .01） ,而与UC病人比较差异无统计学意义（t=1.643,P〉0 .05）。直肠黏膜IFN-γ、IL-2阳性表达的PI-IBS病人SP强度均值高于对照组（t=2.301、2.252,P〈0 .05） ,与UC病人比较差异无统计学意义（t=1.574,1.676,P〉0 .05）。结论 PI-IBS与IBD之间可能存在某种相关性。     

活动期溃疡性结肠炎发病机制的免疫学探讨

目的 :目前研究认为溃疡性结肠炎发病机制与免疫因素有关 ,已有研究表明溃疡性结肠炎与白细胞介素6 (IL - 6 )、白细胞介素 8(IL - 8)密切相关。另有报导认为一氧化氮合酶 (NOS)与溃疡性结肠炎有关 ,但是IL- 6、IL - 8与NOS关系的报导并不多见。为了揭示活动期溃疡性结肠炎结肠粘膜细胞因子 (白细胞介素 6、白细胞介素 8)的表达 ,以及与诱导型一氧化氮合酶 (iNOS)的关系 ,进一步探讨溃疡性结肠炎免疫学发病机制 ,设计本研究。方法 :对 34例活动期溃疡性结肠炎粘膜标本及 10例正常结肠粘膜标本进行iNOS的免疫组织化学分析及IL - 6mRNA ,IL - 8mRNA的原位杂交技术检测分析。结果 :34例活动期溃疡性结肠炎粘膜标本IL - 6mRNA有 2 8例阳性 (83% ) ,较对照组明显增高 (P <0 .0 1) ,IL - 8mRNA有 2 7例阳性 (79% ) ,与对照组相比明显增高 (P <0 .0 1) ,iNOS阳性 30例 (88% ) ,与对照组比较增高 (P <0 .0 5 )。结论 :细胞因子 (IL- 6 ,IL - 8)及诱导型一氧化氮合酶 (iNOS)在活动期溃疡性结肠炎免疫学发病机制中起重要作用 ,细胞因子是iNOS活性增加的重要原因。     

粪菌移植对不同溃疡性结肠炎小鼠的疗效及其中药性味研究

背景 溃疡性结肠炎被世界卫生组织列为现代难治性疾病之一。目前治疗技术均有相应的不足之处,粪菌移植（FMT）治疗溃疡性结肠炎的有效性已被证实,但疗效参差不齐。 目的 比较FMT治疗小鼠普通型溃疡性结肠炎模型（CUCM）与湿热型溃疡性结肠炎模型（DUCM）的效果及FMT（新金汁）的中药性味。 方法 于2019年12月9—28日,将35只雄性SPF级C57BL/6小鼠分为7组,分别为正常对照组（Control组）、CUCM组、CUCM+FMT组、CUCM+5-氨基水杨酸（5-ASA）组、DUCM组、DUCM+FMT组、DUCM+5-ASA组,每组各5只小鼠。Control组不做任何干预处理;CUCM组和DUCM组根据造模需求分别制备模型;CUCM+FMT组和DUCM+FMT组于造模成功后,给予制备的粪菌液0.2 ml对小鼠进行灌肠;CUCM+5-ASA组和DUCM+5-ASA组于造模成功后,给予0.019 5 g/ml 5-ASA对小鼠进行灌肠。通过HE染色观察各组肠组织的变化,透射电镜观察组织的超微结构变化,流式细胞检测辅助性T细胞1（Th1）、Th2细胞含量,血常规检测血液中白细胞计数（WBC）、红细胞计数（RBC）、血小板计数（PLT）和血红蛋白（HGB）,尼莫地平法评估干预前后疗效指数,16S rRNA高通量测序技术检测肠内容物中的菌群分布。 结果 各组小鼠均造模成功。肠组织HE染色显示：CUCM组与DUCM组肠黏膜表面出现不同程度的缺损或脱落坏死;CUCM+FMT组、CUCM+5-ASA组、DUCM+FMT组、DUCM+5-ASA组肠黏膜基本完整;并且DUCM+FMT组与CUCM+FMT组相比,前者腺体较后者排列整齐并紧密。肠组织透射电镜超微结构显示：CUCM组与DUCM组上皮细胞表面微绒毛稀疏,杯状细胞减少;CUCM+FMT组、CUCM+5-ASA组、DUCM+FMT组、DUCM+5-ASA组微绒毛较为致密,杯状细胞数目较多;并且DUCM+FMT组与CUCM+FMT组相比,前者微绒毛较后者紧密,杯状细胞也较后者多。各组小鼠Th1、Th2细胞含量、WBC、RBC、PLT、HGB比较,差异均有统计学意义（P<0.001）。CUCM+5-ASA组、DUCM+FMT组、DUCM+5-ASA组疗效指数高于CUCM+FMT组（P<0.05）。菌群分析显示CUCM组与DUCM组中丰度显著降低的属是Ruminococcus,显著升高的属是Akkermansia,经过FMT治疗后,CUCM+FMT组、DUCM+FMT组有逐步向Control组靠拢的趋势,表明肠道菌群正在改善。 结论 FMT可治疗溃疡性结肠炎模型小鼠,且针对DUCM疗效更佳,FMT（新金汁）的中药性味苦寒,推测其发挥功效的途径可能是通过调节肠道菌群进而改善Th1/Th2细胞平衡,达到治疗的目的。