Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting

Significant bleeding from Meckel’s diverticulum after blunt abdominal trauma: a case report

Abstract Background Meckel’s diverticulum, with an incidence of 2%, is the most common congenital anomaly in the gastrointestinal tract. Its main complications are perforation, obstruction, and bleeding. A few studies have reported that blunt abdominal trauma may result in perforation or obstruction to Meckel’s diverticulum. However, reports of significant major intestinal bleeding from Meckel’s diverticulum as a complication of blunt abdominal trauma is rare. This paper present what we believe to be the first reported case of significant intestinal bleeding from a Meckel’s diverticulum following blunt abdominal trauma. Case presentation A 12-year-old Saudi boy of Arab ethnicity presented to the King Saud Medical City emergency department with bleeding per rectum and mild abdominal pain following blunt trauma to his abdomen. On examination, his abdomen was slightly tender, bowel sounds were present, and he was hemodynamically stable. During admission, rectal bleeding was ongoing. On day 3 he deteriorated with decreasing blood pressure and hemoglobin, and increasing pulse rate with fever. After resuscitation and stabilization, he was urgently taken to the operating room for further diagnostic management and treatment. His nasogastric tube revealed bile without blood, and an intraoperative colonoscopy revealed altered blood within his whole colon and terminal ileum without a definite bleeding site. A laparotomy was performed, and an injured branch of the mesenteric artery supplying the Meckel’s diverticulum was identified as the source of the significant arterial bleeding. Suture ligation controlled the bleeding, and the Meckel’s diverticulum was resected. The patient remained stable after that until discharge without any further intestinal bleeding. Conclusion Identifying bleeding as a complicated Meckel’s diverticulum following blunt trauma to the abdomen can be challenging due to its low incidence and difficulties while making the diagnosis