SCGN deficiency results in colitis susceptibility.

Inflammatory bowel disease (IBD) affects 1.5-3.0 million people in the United States. IBD is genetically determined and many common risk alleles have been identified. Yet, a large proportion of genetic predisposition remains unexplained. In this study, we report the identification of an ultr arare missense variant (NM_006998.3:c.230G > A;p.Arg77His) in the SCGN gene causing Mendelian early-onset ulcerative colitis. SCGN encodes a calcium sensor that is exclusively expressed in neuroendocrine lineages, including enteroendocrine cells and gut neurons. SCGN interacts with the SNARE complex, which is required for vesicle fusion with the plasma membrane. We show that the SCGN mutation identified impacted the localization of the SNARE complex partner, SNAP25, leading to impaired hormone release. Finally, we show that mouse models of Scgn deficiency recapitulate impaired hormone release and susceptibility to DSS-induced colitis. Altogether, these studies demonstrate that functional deficiency in SCGN can result in intestinal inflammation and implicates the neuroendocrine cellular compartment in IBD.

Massive and recurrent diverticular hemorrhage, risk factors and treatment.

AIM: Diverticular hemorrhage may be massive or recurrent, requiring surgical management. The aim of our study is to define risk factors that predict rebleeding or need for urgent operation in patients with diverticular hemorrhage. METHODS: Retrospective study was conducted on patients who were admitted for diverticular hemorrhage. Data pertaining to patient and bleeding characteristics, method of diagnosis, blood transfusion and type of operation were collected. Multivariate analysis model compared patients who experienced single bleeding episode with those with recurrent episodes, and patients who underwent surgery with those who did not. RESULTS: One hundred and four patients met the inclusion criteria. Thirty four patients experienced more than one bleeding episode. Ten patients needed surgery for recurrent bleeding. Five patients presented with hemodynamic instability, none of them required surgical treatment. Neither patients' comorbidity nor anticoagulant and antiaggregant treatments were associated with increased risk for recurrent hemorrhage. Diabetes mellitus was correlated with decreased risk for recurrent hemorrhage, OR = 0.21, (CI 95% (0.06-0.73)); p = 0.014. Independent risk factor for massive recurrent diverticular hemorrhage requiring surgery was right sided diverticulosis, OR = 4.6(CI 95% (2.1-19)); p = 0.006. CONCLUSIONS: Right colon diverticulosis rather than patient characteristics and medical treatment should prompt for aggressive management with lower threshold for surgical intervention.