Ulcerative Colitis Endoscopic Index of Severity(UCEIS)versus Mayo Endoscopic Score(MES)in guiding the need for colectomy in patients with acute severe colitis

Background:The Ulcerative Colitis Endoscopic Index of Severity(UCEIS)and the Mayo Endoscopic Score(MES)were developed as an objective method of the endoscopic severity in ulcerative colitis(UC);however,it was still unclear whether UCEIS vs MES could guide the need for colectomy in acute severe colitis(ASC).Methods:Consecutive ASC patients between January 2012 and May 2016 were retrospectively evaluated.Demographic data,previous therapy,clinical observations,laboratory parameters,medical therapy and endoscopic assessments were documented.The primary outcome was the need for colectomy during admission and follow-up.Results:Ninety-two patients were enrolled.37(40.2%)needed colectomy.UCEIS score is a predictor of requirement for colectomy inmultivariate analysis(OR,3.25;95%CI,1.77–5.97;P<0.001).Receiver-operator characteristic(ROC)area of UCEIS is 0.85,with a sensitivity of 60.3%and specificity of 85.5%using cut-off value of 7,which outperforms MES with the ROC area of 0.65;When UCEIS score7,80%of patients eventually need colectomy.Conclusion:UCEIS outperformed MES as a predictor for need for colectomy in ASC patients.The high probability of medical treatment failure and benefits of early colectomy should be discussed in patients with baseline UCEIS7.Acute severe colitis;colectomy;Ulcerative Colitis Endoscopic Index of Severity;Mayo Endoscopic Score.

Gut microbiota and its implications in small bowel transplantation

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabofism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation （SBT） is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allografl rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

The response of intestinal stem cells and epithelium after alemtuzumab administration

Qiurong Li1,Qiang Zhang1,Chenyang Wang1,Shaojun Jiang2,Ning Li1,Jieshou Li1 Intestinal stem cells may have important roles in the maintenance of epithelial integrity during tissue repair.Alemtuzumab is a humanized anti-CD52 lymphocytic antibody that is increasingly being used to induce immunosuppression;intestinal barrier function is impaired during treatment with alemtuzumab.We investigated the response of intestinal stem cells to epithelial damage resulting from alemtuzumab treatment.Intestinal epithelial cell loss and abnormal Paneth cell morphology were found following a single dose of alemtuzumab.The animals receiving alemtuzumab exhibited increased apoptosis in the villi 3 days after alemtuzumab treatment and in the crypt on day 9,but apoptosis was scarce on day 35.We assessed expression of Musashi-1-and Lgr5-positive stem cells following alemtuzumab treatment.Increased numbers of cells staining positive for both Musashi-1 and Lgr5 were found in the stem cell zone after alemtuzumab treatment for 3 and 9 days.These data indicated that the epithelial cells were injured following alemtuzumab treatment,with the associated expansion of intestinal stem cells.After alemtuzumab treatment for 35 days,the numbers of intestinal epithelial cells and intestinal stem cells returned to normal.This study suggests that alemtuzumab treatment induced the increase in stem cells,resulting in the availability of more enterocytes for repair.

Damps’role in inflammatory bowel disease:a paradoxical player of mtDNA-STING signaling pathway in gut homeostasis

The inflammatory bowel disease(IBD),including Crohn’s disease(CD)and ulcerative colitis,are chronic,relapsing immune mediated disorders of the gastrointestinal homeostasis and intestinal inflammation[1].Failure to resolve mucosal inflammation and maintain gut barrier are notable shared clinical challenges in IBD,in particular when they activate immune cells within the gut lamia propria.Clinical trials and animal model studies aiming towards DAMPs have demonstrated that they can be effective therapeutic targets in mucosal inflammation of IBD.

Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns.It takes~24 h for tri-gas incubator to achieve steady cell hypoxia,which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion(IR)injury.Inspired from the structure of native intestinal villi,we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on coaxial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold.The chip was featured on:(i)eight times the oxygen exchange efficiency compared with the conventional device,tri-gas incubator,(ii)implantation of intestinal organoid reproducing all types of intestinal epithelial cells,and(iii)bio-responsiveness to hypoxia and reoxygenation(HR)by presenting metabolism disorder,inflammatory reaction,and cell apoptosis.Strikingly,it was found for the first time that Olfactomedin 4(Olfm4)was the most significantly downregulated gene under a rapid HR condition by sequencing the RNA from the organoids.Mechanistically,OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation,thus it could be used as a therapeutic target.Altogether,this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo,and sets an example of next-generation multisysteminteractive organoid chip for finding precise therapeutic targets of IR injury.