Emerging therapeutic options in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.     

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

翁连解毒汤治疗浊毒内蕴型溃疡性结肠炎的疗效观察

目的：探究翁连解毒汤治疗浊毒内蕴型溃疡性结肠炎（Ulcerative Colitis，UC）临床疗效及可能的作用机制。方法：选取2016年2月至2018年12月在攀枝花学院附属医院收治的浊毒内蕴型UC患者130例作为研究对象，按照入院先后顺序分为对照组和观察组，每组65例。对照组常规西医治疗，观察组加用翁连解毒汤，观察2组治疗前、完成治疗后T细胞、NK细胞、炎性反应因子、凝血功能、生命质量变化，完成治疗后总结疗效。结果：观察组患者在NK细胞、T淋巴细胞组成、CR、TNF-α、IL-1 β、ESR、内毒素、IL-10、FIB、PLT、APTT改善方面的效果较对照组更优，组间差异有统计学意义（P<0.05）。观察组患者完成治疗后的生命质量量表各维度评分及总评分改善效果优于对照组患者（P<0.05），且临床总有效率和组织病理学疗效率均高于对照组患者（P<0.05）。结论：翁连解毒汤能抑制浊毒内蕴型UC炎性反应，改善高凝状态，提高机体免疫功能，从而提高疗效和生命质量。     

Diet and nutrition against inflammatory bowel disease: Trick or treat(ment)?

Even if the relationships between nutrition and inflammatory bowel disease (IBD) remain underexplored, the current literature is providing, day by day, much more evidence on the effects of various diets in both prevention and treatment of such illnesses. Wrong dietary habits, together with other environmental factors such as pollution, breastfeeding, smoke, and/or antibiotics, are among the theoretical pathogenetic causes of IBD, whose multifactorial aetiology has been already confirmed. While some of these risk factors are potentially reversible, some others cannot be avoided, and efficient treatments become necessary to prevent IBD spread or recurrence. Furthermore, the drugs currently available for treatment of such disease provide low-to-no effect against the symptoms, making the illnesses still strongly disabling. Whether nutrition and specific diets will prove to effectively interrupt the course of IBD has still to be clarified and, in this sense, further research concerning the applications of such dietary interventions is still needed.     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

The management of emergency hospital visits for inflammatory bowel diseases: A French national expert consensus report

BackgroundManagement of inflammatory bowel diseases (IBD) in the emergency department is often suboptimal.AimsTo develop a national consensus checklist of indicators to facilitate decision-making in emergency departments concerning hospitalisation and referral for abdominopelvic computed tomography (CT).MethodsA Delphi survey was used to obtain consensus on a checklist of clinical and biological variables. 119 healthcare professionals experienced in treating IBD were invited to participate. Panellists were provided with a literature survey and invited to agree or disagree with items on a prototype checklist. Two successive rounds of voting were organised.ResultsThe prototype checklist included fifteen clinical or laboratory indicators for hospitalisation or CT. Four indicators were not retained in the Delphi process and four additional indicators added. The final indicators retained were: abdominal signs/symptoms of disease exacerbation, intravenous morphine titration, fever, vomiting, dehydration, recent intestinal surgery, ano-perineal abscess, bowel obstruction, haemodynamic instability, anaemia, acute kidney failure and elevated C-reactive protein. Consensus for the retained indicators was >88%.ConclusionsUse of this consensus checklist for the management of IBD in the emergency department may help improve standards of care and thus reduce the burden of these diseases.     

化浊清解愈溃煎对溃疡性结肠炎大鼠p38MAPK、TNF-α、IL-4的影响

目的观察化浊清解愈溃煎对溃疡性结肠炎(UC)大鼠血清及结肠组织p38MAPK、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)含量的影响。方法清洁级Wistar雄性大鼠50只按随机数字表法分为两组,空白组8只,其余大鼠均为造模组。采用TNBS/乙醇联合造模法构建UC大鼠模型。造模成功后按照随机数字表法将模型大鼠分为模型组、西药组(予美沙拉嗪肠溶片混悬液0.42 g/kg)及中药高、中、低剂量组。中药高、中、低剂量组予化浊清解愈溃煎中药混悬液,剂量分别为22、11、5.5 g/(kg·d),每日灌胃1次,疗程14 d。采用免疫组化法检测各组大鼠结肠组织内p38MAPK的蛋白表达量。ELISA法检测各组大鼠血清内TNF-α、IL-4含量。结果与空白组比较,模型组一般情况较差,血清中TNF-α含量显著升高(P<0.05),IL-4含量则明显降低(P<0.05),结肠组织中p38MAPK水平明显升高(P<0.05)。与模型组比较,西药组、中药各剂量组大鼠一般生存状况改善明显,血清中TNF-α含量下降,IL-4含量明显升高,尤以中药高剂量组和西药组疗效显著(P<0.05)。结论化浊清解愈溃煎高、中剂量可改善UC大鼠一般生存状况,并通过调节血清中IL-4含量,下调TNF-α表达水平和结肠组织中p38MAPK蛋白表达水平而达到保护结肠黏膜和治疗UC的作用。     

溃疡性结肠炎患者外周血中性粒细胞凋亡与粘附分子水平的关系及意义

目的　探讨溃疡性结肠炎 (U C)患者外周血中性粒细胞 (PMN)凋亡机制。方法　采用流式细胞术检测 32例 UC患者外周血 PMN凋亡 ,EL ISA法检测 P-选择素 (P- sel)和细胞间粘附分子 - 1(ICAM- 1)的水平。结果　活动期 UC患者 PMN凋亡率明显低于对照组和缓解期 UC患者 (P<0 .0 1)。不同病情活动期 U C患者 PMN凋亡有显著性差异 (P<0 .0 1)。活动期 UC患者外周血中 P- sel和 ICAM- 1水平均高于对照组和缓解期 U C患者(P<0 .0 1或 (P<0 .0 5 ) ,且与 PMN凋亡呈负相关 (r值分别为 - 0 .72 38和 - 0 .5 2 13,P均 <0 .0 1) ,与病情呈正相关。结论　各种免疫细胞粘附分子表达上调可能是导致 UC患者 PMN凋亡延迟的重要机制