Implementation of a management guideline aimed at minimizing the severity of primary graft dysfunction after lung transplant

Objective
Primary graft dysfunction, a severe form of lung injury that occurs in the first 72 hours after lung transplant, is associated with morbidity and mortality. We sought to assess the impact of an evidence-based guideline as a protocol for respiratory and hemodynamic management.

Methods
Preoperative and postoperative data for patients treated per the guideline (n = 56) were compared with those of a historical control group (n = 53). Patient data such as ratio of arterial Po2 to inspired oxygen fraction, central venous pressure, cumulative fluid balance, vasopressor dose, and serum urea and creatinine were measured and documented at specific times. Primary outcome was severity of primary graft dysfunction within the first 72 hours.

Results
Primary graft dysfunction grade was progressively lower in patients treated after introduction of the guideline (P = .01). Lower postoperative fluid balances (P = .01) and vasopressor doses (P = .007) were seen, with no associated renal dysfunction. There were no differences in duration of mechanical ventilation or mortality. Nonadherence to the guideline occurred in 10 cases (18%).

Conclusions
Implementation of an evidence-based guideline for managing respiratory and hemodynamic status is feasible and safe and was associated with reduction in severity of primary graft dysfunction. Further studies are required to determine whether such a guideline would lead to a consistent reduction in severity of primary graft dysfunction at other institutions. Creation of a protocol for postoperative care provides a template for further studies of novel therapies or management strategies for primary graft dysfunction.

Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.

We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)- specific CD8þ T cells compared with systemic immunization, and interleukin (IL)-13 is detrimental to the functional avidity of these T cells. We have now constructed two unique recombinant HIV-1 vaccines that co-express soluble or membrane-bound forms of the IL-13 receptor a2 (IL-13Ra2), which can ‘‘transiently’’ block IL-13 activity at the vaccination site causing wild-type animals to behave similar to an IL-13 KO animal. Following intranasal/intramuscular prime-boost immunization, these IL-13Ra2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8þ Tcells with higher functional avidity, with broader cytokine/chemokine profiles and greater protective immunity using a surrogate mucosal HIV-1 challenge, and also (ii) excellent multifunctional mucosal CD8þ T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer’s patch (PP). Data revealed that intranasal delivery of these IL-13Ra2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8þ Tcells. We believe our novel IL-13R cytokine trap vaccine strategy offers great promise for not only HIV-1, but also as a platform technology against range of chronic infections that require strong sustained high-avidity mucosal/systemic immunity for protection.