- 作者列表："Vale Rodrigues R","Sladek M","Katsanos K","van der Woude CJ","Wei J","Vavricka SR","Teich N","Ellul P","Savarino E","Chaparro M","Beaton D","Oliveira AM","Fragaki M","Shitrit AB","Ramos L","Karmiris K","ECCO CONFER investigators .
BACKGROUND AND AIMS:Crohn's disease [CD] can involve any part of the gastrointestinal tract. We aimed to characterize the clinical, endoscopic and histological features and treatment outcomes of CD patients with oesophageal involvement. METHODS:We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS:A total of 40 patients were reported (22 males, mean [±SD, range] age at oesophageal CD diagnosis: 25 [±13.3, 10-71] years and mean time of follow-up: 67 [±68.1, 3-240] months). Oesophageal involvement was established at CD diagnosis in 26 patients [65%] and during follow-up in 14. CD was exclusively located in the oesophagus in two patients. Thirteen patients [32.2%] were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in five patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors [PPIs] were administered in 37 patients [92.5%]. Three patients underwent endoscopic dilatation for symptomatic strictures but none underwent oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients [82.5%] after a mean time of 7 [±5.6, 1-18] months. Follow-up endoscopy was performed in 29/40 patients and 26/29 [89.7%] achieved mucosal healing. CONCLUSION:In this case series the endoscopic and histological characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing inflammatory bowel disease-related therapy occurring in two-thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.
背景和目的: 克罗恩病 [CD] 可累及胃肠道的任何部位。我们旨在描述食管受累的 CD 患者的临床、内镜和组织学特征以及治疗结果。 方法: 我们通过回顾性多中心欧洲克罗恩病和结肠炎组织 convention [异常罕见病例报告协作网络] 项目收集病例。临床资料以标准化病例报告表记录。 结果: 共报告 40 例患者 (22 例男性，平均 [± SD，范围] 食管 CD 诊断时的年龄: 25 [± 13.3, 10-71] 年和平均随访时间: 67 [± 68.1，3-240] 个月)。26 例 CD 诊断时确定食管受累 [65%]，14 例随访时确定食管受累。2 例患者 CD 仅位于食管。13 例患者 [32.2%] 在食管疾病诊断时无症状。5 例有食管狭窄，1 例有瘘管性食管病变。8 例患者活检显示肉芽肿。质子泵抑制剂 [PPIs] 用于 37 例患者 [92.5%]。3 例患者因症状性狭窄行内镜下扩张术，但均未行食管相关手术。预先建立的 CD 中的诊断导致 9/14 例患者的治疗修改。在平均 7 [± 33/40，1-18] 个月后，82.5% 例患者 [5.6] 食管疾病临床缓解。随访内镜检查 29/40 例患者，26/29 [89.7%] 达到黏膜愈合。 结论: 在本系列病例中，孤立性食管 CD 的内镜和组织学特征与其他受累部位报道的相似。治疗主要是保守治疗，大多数患者给予 ppi，其中 3分之2 的患者发生预先存在的炎症性肠病相关治疗的修改。超过 80% 的患者获得临床和内镜缓解。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.