VA-ECMO appears to be an effective tool to optimize end-organ function as a bridge to recovery or intervention, with excellent outcomes. This approach may allow clinicians to better triage patients with massive pulmonary embolism to the appropriate therapy on the basis of recovery of RV function, residual thrombus burden, operative risk, and neurologic status.

In this single institution experience, surgical pulmonary embolectomy is a safe and effective therapy to treat patients with a submassive or massive pulmonary embolism. Although survival in this study is higher than previously reported for patients treated with medical therapy alone, a prospective trial comparing surgical therapy with medical therapy is necessary to further elucidate the role of surgical pulmonary embolectomy in the treatment of pulmonary embolism.

A protocolized strategy involving the aggressive institution of VA-ECMO appears to be an effective method to triage and optimize patients with massive PE to recovery or intervention. Implementation of this strategy rather than an aggressive surgical approach may reduce the mortality associated with massive PE.

Background Specific blockade of T cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. The goal of this study is to compare results associated with 3 monoclonal antibodies directed against the CD40/CD154 T cell costimulation pathway. Methods Cynomolgus monkey heterotopic cardiac allograft recipients were treated with either IDEC-131 (humanized αCD154, n=9), 5C8H1 (mouse-human chimeric αCD154, n=5), or 2C10R4 (mouse-rhesus chimericαCD40, n=6) monotherapy using a consistent, comparable dosing regimen for 3 months after transplant. Results Relative to the previously reported IDEC-131 treated allografts, median survival time (MST 35±31 days) was significantly prolonged in both 5C8H1 (142±26, p<0.002) and 2C10R4 (124±37, p<0.020) treated allografts. IDEC-131 treated grafts had higher CAV severity scores during treatment relative to either 5C8H1 (p=0.008) or 2C10R4 (p=0.0002). Both 5C8H1(5 of 5 animals, p=0.02) and 2C10R4 (6/6, p=0.007), but not IDEC-131 (2/9), completely attenuated IgM antidonor alloAb production during treatment;5C8H1 (5/5) more consistently attenuated IgG alloAb production compared to 2C10R4 (4/6) and IDEC-131 (0/9). All evaluable explanted grafts experienced antibody-mediated rejection. Only 2C10R4 treated animals exhibited a modest, transient drop in CD20+ lymphocytes from baseline at d14 after transplant (-457±152 cells/μL) compared to 5C8H1 treated animals (16±25, p=0.037), and the resurgent B cells were primarily of a naïve phenotype. Conclusion In this model, CD154/CD40 axis blockade using IDEC-131 is an inferior immunomodulatory treatment than 5C8H1 or 2C10R4, which have similar efficacy to prolong graft survival and to delay CAV development and antidonor alloAb production during treatment.

Induction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants.