Whole blood versus balanced resuscitation in massive hemorrhage: six of one or half dozen of the other?

INTRODUCTION: Whole blood (WB) resuscitation is increasingly used at trauma centers. Prior studies investigating outcomes in WB versus component-only (CO) resuscitation have been limited by small cohorts, low volumes of WB resuscitation, and unbalanced CO resuscitation. This study aimed to address these limitations using data from a high-volume Level I trauma center, which adopted a WB-first resuscitation paradigm in 2018. We hypothesized that the resuscitation method, WB or balanced CO, would have no impact on patient mortality. METHODS: A single-center, retrospective cohort study of adults presenting as a trauma activation from July 2016 through July 2021 was performed. Receipt of 3 or more units of WB or packed red blood cells (RBC) within the first hour of resuscitation was required for inclusion. Patients were grouped into WB versus CO resuscitation and important clinical outcomes were compared. Mortality was evaluated with Kaplan-Meier analysis, log-rank testing, and multivariable Cox proportional hazards modeling. RESULTS: There were 180 patients in the WB group and 170 patients in the CO group. Of the 180 WB patients, 110 (61%) received only WB during the first 24 hours. The WB group received a median of 5.0 units (IQR 4.0-8.0) of WB and CO group received a median of 6.0 units (IQR 4.0-11.8) of RBCs during the first 24 hours of resuscitation. In the CO group, median RBC/plasma and RBC/platelet ratios approximated 1:1:1. Groups were similar in clinicopathologic characteristics including age, injury severity score, mechanism of injury, and requirement for hemorrhage control interventions (WB 55% vs CO 59%, p = 0.60). Unadjusted survival was equivalent at 24 hours (p = 0.52) and 30 days (p = 0.70) between both groups on Kaplan-Meier analysis with log-rank testing. On multivariable Cox regression, WB resuscitation was not independently associated with improved survival after accounting for age, ISS, mechanism of injury, and receipt of hemorrhage control procedure (HR 0.85, 95% CI 0.61-1.19, p = 0.34). CONCLUSIONS: Balanced CO resuscitation is associated with similar mortality outcomes to that of WB based resuscitation. LEVEL OF EVIDENCE: Level IV; Therapeutic/Care Management.

Fusion proteins of Arabidopsis cap-binding proteins: Cautionary "tails" of woe.

The use of fluorescent proteins fused to other proteins has been very useful in revealing the location and function of many proteins. However, it is very important to show that the fusion of these reporter proteins does not impact the function of the protein of interest. Plants have 2 forms of the cap-binding protein that function in initiation of translation, eIF4E and a plant specific form, eIFiso4E. In an attempt to determine the cellular localization of eIFiso4E, fusions to GFP were made, but were found to not be competent to rescue the lethal phenotype of plants lacking eIF4E and eIFiso4E. This suggested that the GFP fusions at either the N- or C-terminus of eIFiso4E were not functional. Biochemical analysis of the fusions revealed that eIFiso4E•GFP fusions were not able to bind to m7GTP Sepharose indicating that they were not functional as cap-binding proteins. Analysis of eIF4E•GFP fusions, both in yeast and in vitro, showed that the N-terminal fusion may be functional, whereas the C-terminal fusion bound m7GTP Sepharose very poorly and functioned poorly in yeast. These results highlight the importance of verification both biochemically and in vivo that reporter fusions of proteins maintain activity and are stable in order to prevent observations that may result in artifacts.