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For patients with chronic limb-threatening ischemia and limited revascularization options, alternate means for therapeutic angiogenesis and limb salvage are needed. E-selectin is a cell adhesion molecule that is critical for inflammation and neovascularization in areas of wound healing and ischemia. Here, we tested the efficacy of modifying ischemic limb tissue by intramuscular administration of E-selectin/AAV2/2 (adeno-associated virus serotype 2/2) to modulate angiogenic and inflammatory responses in a murine hindlimb gangrene model. Limb appearance, reperfusion, and functional recovery were assessed for 3 weeks after induction of ischemia. Mice receiving E-selectin/AAV2/2 gene therapy had reduced gangrene severity, increased limb and footpad perfusion, enhanced recruitment of endothelial progenitor cells, and improved performance on treadmill testing compared to control group. Histologically, E-selectin/AAV2/2 gene therapy was associated with increased vascularity and preserved myofiber integrity. E-selectin/AAV2/2 gene therapy also upregulated a panel of pro-angiogenic genes yet downregulated another group of genes associated with the inflammatory response. This novel gene therapy did not induce adverse effects on coagulability, or hematologic, hepatic, and renal function. Our findings highlight the potential of E-selectin/AAV2/2 gene therapy for improving limb perfusion and function in patients with chronic limb-threatening ischemia.

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Small bowel perforation is an uncommon but severe event in the natural history of Crohn’s disease with fewer than 100 cases reported. We review Crohn’s disease cases with necrotizing enteritis and share a case of a 26-year-old female who presented with a recurrent episode of small intestinal perforation. A PubMed literature review of case reports and series was conducted using keywords and combinations of “Crohn’s disease,” “small intestine perforation,” “small bowel perforation,” “free perforation,” “regional enteritis,” and “necrotizing enteritis.” Data extracted included demographic data, pre- or postoperative steroid administration, medical or surgical management, and case fatality. Nineteen reports from 1935 to 2021 qualified for inclusion. There were 43 patients: 20 males and 23 females with a mean age of 36 ± 15 years old. 75 total perforations were described: 56 ileal (74.6%), 15 jejunal (20.0%), 2 cecal (2.7%), and 1 small intestine non-specified (2.7%). 38 of 43 patients were managed surgically by primary repair (11), ostomy creation (21), or an anastomosis (11). Of 11 case fatalities, medical management alone was associated with higher mortality (5/5; 100% mortality) compared to those treated surgically (6/38; 15.8% mortality; P < .001). Patient sex, disease history, acute abdomen, and pre- or postoperative steroid use did not significantly correlate with mortality. Jejunal perforation was significantly ( P = .028) associated with event mortality while ileal was not ( P = .45). Although uncommon, necrotizing enteritis should be considered in Crohn’s patients who present with small intestinal perforation. These cases often require urgent surgical intervention and may progress to fulminant sepsis and fatality if not adequately treated.

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