Resuscitative endovascular balloon occlusion of the aorta for non-traumatic intra-abdominal hemorrhage.

BACKGROUND: Hemorrhagic shock is the second leading cause of death in blunt trauma and a significant cause of mortality in non-trauma patients. The increased use of resuscitative endovascular balloon occlusion of the aorta (REBOA) as a bridge to definitive control for massive hemorrhage has provided promising results in the trauma population. We describe an extension of this procedure to our hemodynamically unstable non-trauma patients. METHODS: This is a retrospective review of patients requiring REBOA for end stage non-traumatic abdominal hemorrhage from our tertiary care facility. After excluding patients with trauma, supradiaphragmatic bleed and thoracic/abdominal aortic aneurysms, demographics, etiology of bleed, REBOA placement specifics, complications and outcomes were reviewed. RESULTS: From August 2013 to August 2016, 11 patients were identified requiring REBOA placement for hemodynamic instability from non-traumatic abdominal hemorrhage. Average patient age was 54.9 (SD 15.2). Sixty-four percent suffered cardiac arrest prior to REBOA, with mean shock index of 1.29. Average time from diagnosis of shock (MAP ≤ 65) or signs of bleeding to placement of REBOA was 177 min. The leading etiologies of hemorrhage were ruptured visceral aneurysm and massive upper gastrointestinal bleed. REBOA was placed by both acute care and vascular surgeons. The procedure was mainly completed in the operating room in 82% of the patients and at the bedside in 18%. One patient expired before operative repair. Definitive surgical control of the source of bleeding was obtained by open surgical approach (n = 6) and combined surgical and endovascular approach (n = 4). In-hospital survival was 64%. There were no local complications related to REBOA placement. CONCLUSION: Similar to the trauma population, REBOA is an adjunctive technique for proximal control of bleeding as well as resuscitation in end stage non-traumatic intra-abdominal hemorrhage. We propose an algorithmic approach to REBOA use in this population and a larger prospective review is necessary to determine both the timing of REBOA placement and which non-traumatic patients may benefit from this technique. LEVEL OF EVIDENCE: V. STUDY TYPE: Brief report.

Posttranscriptional regulation of 14-3-3ζ by RNA-binding protein HuR modulating intestinal epithelial restitution after wounding.

The 14-3-3ζ is a member of the family of 14-3-3 proteins and participates in many aspects of cellular processes, but its regulation and involvement in gut mucosal homeostasis remain unknown. Here, we report that 14-3-3ζ expression is tightly regulated at the posttranscription level by RNA-binding protein HuR and plays an important role in early intestinal epithelial restitution after wounding. The 14-3-3ζ was highly expressed in the mucosa of gastrointestinal tract and in cultured intestinal epithelial cells (IECs). The 3' untranslated region (UTR) of the 14-3-3ζ mRNA was bound to HuR, and this association enhanced 14-3-3ζ translation without effect on its mRNA content. Conditional target deletion of HuR in IECs decreased the level of 14-3-3ζ protein in the intestinal mucosa. Silencing 14-3-3ζ by transfection with specific siRNA targeting the 14-3-3ζ mRNA suppressed intestinal epithelial restitution as indicated by a decrease in IEC migration after wounding, whereas ectopic overexpression of the wild-type 14-3-3ζ promoted cell migration. These results indicate that HuR induces 14-3-3ζ translation via interaction with its 3' UTR and that 14-3-3ζ is necessary for stimulation of IEC migration after wounding.

miR-195 competes with HuR to modulate stim1 mRNA stability and regulate cell migration.

Stromal interaction molecule 1 (Stim1) functions as a sensor of Ca2+ within stores and plays an essential role in the activation of store-operated Ca2+ entry (SOCE). Although lowering Stim1 levels reduces store-operated Ca2+ entry and inhibits intestinal epithelial repair after wounding, the mechanisms that control Stim1 expression remain unknown. Here, we show that cellular Stim1 abundance is controlled posttranscriptionally via factors that associate with 3'-untranslated region (3'-UTR) of stim1 mRNA. MicroRNA-195 (miR-195) and the RNA-binding protein HuR competed for association with the stim1 3'-UTR and regulated stim1 mRNA decay in opposite directions. Interaction of miR-195 with the stim1 3'-UTR destabilized stim1 mRNA, whereas the stability of stim1 mRNA increased with HuR association. Interestingly, ectopic miR-195 overexpression enhanced stim1 mRNA association with argonaute-containing complexes and increased the colocalization of tagged stim1 RNA with processing bodies (P-bodies); the translocation of stim1 mRNA was abolished by HuR overexpression. Moreover, decreased levels of Stim1 by miR-195 overexpression inhibited cell migration over the denuded area after wounding but was rescued by increasing HuR levels. In sum, Stim1 expression is controlled by two factors competing for influence on stim1 mRNA stability: the mRNA-stabilizing protein HuR and the decay-promoting miR-195.