A Shortened Diagnostic Interval and Its Associated Clinical Factors and Related Outcomes in Inflammatory Bowel Disease Patients from a Cohort Study in China.

Aim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined. Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval. Results: A total of 516 and 848 patients were confirmed to have Crohn's disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P<0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51-60 years and 12.5 months in UC patients at the age of 41-50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay. Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.

Colonic interleukin-22 protects intestinal mucosal barrier and microbiota abundance in severe acute pancreatitis.

Intestinal barrier dysfunction plays a critical role in the pathophysiology of many diseases including severe acute pancreatitis (SAP). Interleukin-22 (IL-22) is a critical regulator of intestinal epithelial homeostasis. However, the mechanism, origin site, and characteristics of IL-22 in the intestinal barrier dysfunction remains elusive. Studies were conducted in patients with SAP and SAP mice model. SAP mice model was induced by intraductal infusion of 5% taurocholic acid. The level and source of IL-22 were analyzed by flow cytometry. The effect of IL-22 in SAP-associated intestinal injury were examined through knockout of IL-22 (IL-22-/- ) or administration of recombinant IL-22 (rIL-22). IL-22 increased in the early phase of SAP but declined more quickly than that of proinflammatory cytokines, such as IL-6 and TNF-α. CD177+ neutrophils contributed to IL-22 expression in SAP. IL-22 was activated in the colon rather than the small intestine during SAP. Deletion of IL-22 worse the severity of colonic injury, whereas administration of rIL-22 reduced colonic injury. Mechanistically, IL-22 ameliorates the intestinal barrier dysfunction in SAP through decreasing colonic mucosal permeability, upregulation of E-cadherin and ZO-1 expression, activation of pSTAT3/Reg3 pathway and restoration of fecal microbiota abundance. This study revealing that early decreased colonic IL-22 aggravates intestinal mucosal barrier dysfunction and microbiota dysbiosis in SAP. Colonic IL-22 is likely a promising treating target in the early phase of SAP management. Research in context Evidence before this study Intestinal barrier dysfunction plays a critical role in the pathophysiology of severe acute pancreatitis (SAP). Interleukin-22 (IL-22) is a critical regulator of intestinal epithelial homeostasis. However, the mechanism, origin site and characteristics of IL-22 in the intestinal barrier dysfunction remains elusive. Added value of this study Firstly, we determined the dynamic expression profile of IL-22 in SAP and found that IL-22 was mostly activated in the pancreas and colon and decreased earlier than proinflammatory cytokines. CD177+ neutrophils contributed to IL-22 expression in SAP. Furthermore, we found that IL-22 ameliorates intestinal barrier dysfunction in SAP through decreasing colonic mucosal permeability, upregulation of E-cadherin and ZO-1 expression, activation of pSTAT3/Reg3 pathway and restoration of fecal microbiota abundance. Implications of all the available evidence This study highlights the role of colonic injury and colonic IL-22 in SAP. IL-22 is likely a promising treating target in the early phase of SAP management.

Increasing newly diagnosed inflammatory bowel disease and improving prognosis in China: a 30-year retrospective study from a single centre.

BACKGROUND: We aimed to characterize the trends of prognosis in ulcerative colitis (UC) and Crohn's disease (CD) in a Chinese tertiary hospital. METHODS: A 30-year retrospective cohort analysis was conducted at Peking Union Medical College Hospital. Consecutive patients newly diagnosed with UC or CD from 1985 to 2014 were included. The primary outcome was in-hospital mortality. The secondary outcomes included surgery and length of stay in hospital. The Pearson correlation coefficient was applied to determine the relationship between time and prognosis. Multivariable logistic regression analysis was performed to determine the risk factors for in-hospital mortality and surgery. RESULTS: In total, 1467 patients were included in this study (898 cases with UC and 569 cases with CD). Annual admissions for UC and CD have increased significantly over the last 30 years (UC, r = 0.918, P < 0.05; CD, r = 0.898, P < 0.05). Decreased in-hospital mortality was observed both in patients with UC and CD (UC, from 2.44 to 0.27%, r = - 0.827, P < 0.05; CD, from 12.50 to 0.00%, r = - 0.978, P < 0.05). A decreasing surgery rate was observed in patients with CD (r = - 0.847, P < 0.05), while an increasing surgery rate was observed in patients with UC (r = 0.956, P < 0.05). Shortened average lengths of hospital stay were observed in both UC and CD patients (UC, from 47.83 ± 34.35 to 23.58 ± 20.05 days, r = - 0.970, P < 0.05; CD, from 65.50 ± 50.57 to 26.41 ± 18.43 days, r = - 0.913, P < 0.05). Toxic megacolon and septic shock were independent risk factors for in-hospital mortality in patients with UC. Intestinal fistula and intestinal perforation were independent risk factors for in-hospital mortality in patients with CD. CONCLUSIONS: In this cohort, the admissions of patients with UC and CD were increased, with significantly improved prognoses during the past 30 years.

Corrigendum to: Association between matrix Gla protein and ulcerative colitis according to DNA microarray data.

[This corrects the article DOI: 10.1093/gastro/goz038.][This corrects the article DOI: 10.1093/gastro/goz038.].

Association between matrix Gla protein and ulcerative colitis according to DNA microarray data.

BACKGROUND: Matrix Gla protein (MGP) is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells. Microarray profiling found a significantly higher expression level of the extracellular matrix gene MGP in patients with ulcerative colitis (UC). However, little is known about the role of MGP in UC and its upstream signaling regulation. This study aimed to identify the expression of MGP in UC and its upstream regulator mechanism. METHODS: Colonic mucosa biopsies were obtained from patients with UC and healthy controls. DNA microarray profiling was used to explore underlying genes correlating with UC development. Mice were fed with water containing different concentrations of dextran sodium sulfate (DSS) to induce an experimental colitis model. Colonic tissues were collected and evaluated using immunohistochemistry, immunoblot, real-time polymerase chain reaction, and chromatin immunoprecipitation assay. Bioinformatics analysis was performed to identify candidate MGP gene-promoter sequence and transcription-initiation sites. Luciferase-reporter gene assay was conducted to examine the potential transcription factor of MGP gene expression. RESULTS: The expression of MGP was significantly increased in colonic tissues from UC patients and DSS-induced colitis models, and was positively correlated with disease severity. Bioinformatics analysis showed a conserved binding site for Egr-1 in the upstream region of human MGP gene. The significantly higher level of Egr-1 gene expression was found in UC patients than in healthy controls. The activity of luciferase was significantly enhanced in the Egr-1 expression plasmid co-transfected group than in the control group and was further inhibited when co-transfected with the Egr-1 binding-site mutated MGP promoter. CONCLUSIONS: Up-regulated expression of MGP was found in UC patients and DSS-induced colitis. The expression of MGP can be regulated by Egr-1.