Apparent Efficacy of Low-Dose Constant-Infusion Crotalidae Antivenom for Control of Defibrinogenation Recurrence Syndrome Following Envenomation by the Eastern Diamondback Rattlesnake (Crotalus adamanteus)

Background: Eastern Diamondback rattlesnake bites produce coagulopathy in the bite victims. The syndrome is treated with antivenom called Crotalidae Polyvalent Immune Fab. However following resolution of coagulopathy with the antidote, and sometimes days later, fibrinogen drops to very low levels. Rare bleeding may occur due to this recurrent defibrinogenation syndrome. No guidelines exist at this time of how these patients should be treated. However, many centers repeat the initial treatment protocol using another 6-18 vials of antidote acquiring significant treatment costs. Methods: We analyzed all cases treated at the University of Florida between 2013 and 2014 for the rattlesnake bites.  All cases were treated with Crotalidae Polyvalent Immune Fab as recommended per manufacturer recommendations upon initial presentation.  However, upon the recurrence of defibrinogenation, we administered the antivenom 1 vial diluted in 250 ml of normal saline and administered by continuous IV infusion over 2 to 12 hours tapered over 2 to 3 days. The patients and their coagulation labs were monitored at least daily during the recurrence of the defibrinogenation. Results: We identified 5 cases treated for Eastern Diamondback snake bites. All cases had recurrent defibrinogenation syndrome and treated as described above. All patients had normalization in their fibrinogen levels with the reinstitution of the antidote. Additionally, none of them had any further bleeding. No chills, fevers or cloudiness of solution reported during the continuous antidote administration

Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis

Mesenchymal stem cell (MSC) therapy is an emerging field of regenerative medicine; however, it is often unclear how these cells mediate repair. Here, we investigated the use of MSCs in the treatment of intestinal disease and modeled abnormal repair by creating focal wounds in the colonic mucosa of prostaglandin-deficient mice. These wounds developed into ulcers that infiltrated the outer intestinal wall. We determined that penetrating ulcer formation in this model resulted from increased hypoxia and smooth muscle wall necrosis. Prostaglandin I(2) (PGI(2)) stimulated VEGF-dependent angiogenesis to prevent penetrating ulcers. Treatment of mucosally injured WT mice with a VEGFR inhibitor resulted in the development of penetrating ulcers, further demonstrating that VEGF is critical for mucosal repair. We next used this model to address the role of transplanted colonic MSCs (cMSCs) in intestinal repair. Compared with intravenously injected cMSCs, mucosally injected cMSCs more effectively prevented the development of penetrating ulcers, as they were more efficiently recruited to colonic wounds. Importantly, mucosally injected cMSCs stimulated angiogenesis in a VEGF-dependent manner. Together, our results reveal that penetrating ulcer formation results from a reduction of local angiogenesis and targeted injection of MSCs can optimize transplantation therapy. Moreover, local MSC injection has potential for treating diseases with features of abnormal angiogenesis and repair