Predictors of Mortality in Trauma patients Receiving massive Transfusion Protocol.

INTRODUCTION: Massive transfusion protocol (MTP) is often defined as the transfusion of ≥10 units of packed red blood cells (PRBCs) in 24 hours. The purpose of this study is to determine which factors most significantly contribute to mortality in patients receiving MTP after trauma. METHODS: An initial database search followed by retrospective chart review was performed on patients treated at four trauma centers in Southern California. Data were collected on all patients who received MTP, defined as at least 10 units PRBCs within the first 24 hours of admission, between January 2015 and December 2019. Patients with isolated head injuries were excluded. Univariate and multivariate analyses were used to determine which factors most significantly influenced mortality. RESULTS: Of 1278 patients who met our inclusion criteria in the database, 596 (46.6%) survived and 682 (53.4%) died. On univariate analysis initial vitals and labs, except for initial hemoglobin and initial platelet count were significant predictors of mortality. A multivariate regression model showed the strongest predictors of mortality were pRBC transfusions at 4 hours (OR 1.073, CI 1.020-1.128, P = .006) and 24 hours (OR 1.045, CI 1.003-1.088, P = .036), and FFP transfusion at 24 hours (OR 1.049, CI 1.016-1.084, P = .003). CONCLUSION: Our data indicates that several factors may contribute to mortality in patients receiving MTP. In particular age, mechanism, initial GCS, and PRBC transfusions at 4 and 24 hours provided the strongest correlation. Further multicenter trials are indicated to provide further guidance in deciding when to discontinue massive transfusion.

A KDEL-tagged monoclonal antibody is efficiently retained in the endoplasmic reticulum in leaves, but is both partially secreted and sorted to protein storage vacuoles in seeds.

Transgenic plants are attractive biological systems for the large-scale production of pharmaceutical proteins. In particular, seeds offer special advantages, such as ease of handling and long-term stable storage. Nevertheless, most of the studies of the expression of antibodies in plants have been performed in leaves. We report the expression of a secreted (sec-Ab) or KDEL-tagged (Ab-KDEL) mutant of the 14D9 monoclonal antibody in transgenic tobacco leaves and seeds. Although the KDEL sequence has little effect on the accumulation of the antibody in leaves, it leads to a higher antibody yield in seeds. sec-Ab(Leaf) purified from leaf contains complex N-glycans, including Lewis(a) epitopes, as typically found in extracellular glycoproteins. In contrast, Ab-KDEL(Leaf) bears only high-mannose-type oligosaccharides (mostly Man 7 and 8) consistent with an efficient endoplasmic reticulum (ER) retention/cis-Golgi retrieval of the antibody. sec-Ab and Ab-KDEL gamma chains purified from seeds are cleaved by proteases and contain complex N-glycans indicating maturation in the late Golgi compartments. Consistent with glycosylation of the protein, Ab-KDEL(Seed) was partially secreted and sorted to protein storage vacuoles (PSVs) in seeds and not found in the ER. This dual targeting may be due to KDEL-mediated targeting to the PSV and to a partial saturation of the vacuolar sorting machinery. Taken together, our results reveal important differences in the ER retention and vacuolar sorting machinery between leaves and seeds. In addition, we demonstrate that a plant-made antibody with triantennary high-mannose-type N-glycans has similar Fab functionality to its counterpart with biantennary complex N-glycans, but the former antibody interacts with protein A in a stronger manner and is more immunogenic than the latter. Such differences could be related to a variable immunoglobulin G (IgG)-Fc folding that would depend on the size of the N-glycan.