Inhibition of a triggering receptor expressed on myeloid cells-1 (TREM-1) with an extracellular cold-inducible RNA-binding protein (eCIRP)-derived peptide protects mice from intestinal ischemia-reperfusion injury.

BACKGROUND: Intestinal ischemia-reperfusion injury results in morbidity and mortality from both local injury and systemic inflammation and acute lung injury. Extracellular cold-inducible RNA-binding protein is a damage associated molecular pattern that fuels systemic inflammation and potentiates acute lung injury. We recently discovered a triggering receptor expressed on myeloid cells-1 serves as a novel receptor for extracellular cold-inducible RNA-binding protein. We developed a 7-aa peptide, named M3, derived from the cold-inducible RNA-binding protein, which interferes with cold-inducible RNA-binding protein's binding to a triggering receptor expressed on myeloid cells-1. Here, we hypothesized that M3 protects mice against intestinal ischemia-reperfusion injury. METHODS: Intestinal ischemia was induced in C57BL/6 mice via clamping of the superior mesenteric artery for 60 minutes. At reperfusion, mice were treated intraperitoneally with M3 (10 mg/kg body weight) or normal saline vehicle. Mice were killed 4 hours after reperfusion and blood and lungs were collected for various analysis. A 24-hours survival after intestinal ischemia-reperfusion was assessed. RESULTS: Serum levels of organ injury markers aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and lactate were increased with intestinal ischemia-reperfusion, while treatment with M3 significantly decreased their levels. Serum, intestinal, and lung levels of proinflammatory cytokines and chemokines were also increased by intestinal ischemia-reperfusion, and treatment with M3 significantly reduced these values. Intestinal ischemia-reperfusion caused significant histological intestinal and lung injuries, which were mitigated by M3. Treatment with M3 improved the survival from 40% to 80% after intestinal ischemia-reperfusion. CONCLUSION: Inhibition of triggering receptor expressed on myeloid cells-1 by an extracellular cold-inducible RNA-binding protein-derived small peptide (M3) decreased inflammation, reduced lung injury, and improved survival in intestinal ischemia-reperfusion injury. Thus, blocking the extracellular cold-inducible RNA-binding protein-triggering receptor expressed on myeloid cells-1 interaction is a promising therapeutic avenue for mitigating intestinal ischemia-reperfusion injury.

Outpatient curettage and electrocautery as an alternative to primary surgical closure for pediatric gastrocutaneous fistulae.

BACKGROUND: The development of a gastrocutaneous fistula (GCF) after gastrostomy tube removal is a frequent complication that occurs 5%-45% of the time. Conservative therapy with chemical cauterization is frequently unsuccessful, and surgical GCF repair with open primary layered closure of the gastrotomy is often required. We describe an alternative approach of GCF closure that is an outpatient, less invasive procedure that allows patients to avoid the comorbidities of general endotracheal anesthesia and intraabdominal surgery. METHODS: This is an Institutional Review Board approved retrospective review of all patients who underwent GCF closure from January 2010 to July 2016 at a tertiary care children's hospital. Demographics including age, weight, body mass index, comorbidities, and initial indication for gastrostomy tube were recorded. Operative details such as ASA score, operative duration, type of anesthesia, and airway were noted. Based on surgeon preference, two types of operative closure were used during that time frame: primary layered closure or curettage and cautery (C&C). The latter is a procedure in which the fistula tract is first scraped with a fine curette, and then the fistula opening and tract are cauterized circumferentially. Finally, the presence of a persistent fistula and the need for formal reoperation were determined. RESULTS: Sixty-five unique patients requiring GCF closure were identified. Of those, 44 patients (67.6%) underwent primary closure and 21 patients (32.3%) underwent C&C. The success rate of primary closure was 97% with one patient experiencing wound breakdown with persistent fistula. The overall success rate of C&C was 66.7% (14/21). Among those 14 patients, 11 (52.4%) GCF patients were closed by 1 mo. An additional two patients' gastrocutaneous fistulae were closed by 4 mo (61.9%). One GCF was successfully closed with a second C&C procedure. Seven of the 21 patients (33.3%) required subsequent formal layered surgical closure. C&C had significantly shorter operative times (13.5 ± 14.7 min versus 93.4 ± 61.8, P <0.0001) and significantly shorter times in the postanesthesia care unit (101.8 ± 42.4 min versus 147 ± 86, P <0.0001). Patients were intubated with an endotracheal tube 88.6% of the time for primary closure and 23.8% of the time for C&C.Among patients admitted for an elective procedure, the average length of stay for primary closure was 1.9 d as compared to 0 d for the C&C group. Among patients who underwent C&C with a persistent fistula, there were no significant differences in time since initial creation of gastrostomy, age, body mass index, or ASA score. CONCLUSIONS: Our study verifies that primary closure remains the gold standard for persistent GCF. However, C&C is a safe, outpatient procedure that effectively treats a GCF the majority of the time in children. We suggest that in select patients, it may be an appropriate initial and definitive procedure for GCF closure.