Publications

Transfusion is intended to correct anemia when it is believed to either impair adequate oxygen (O2) delivery or when the resulting compensatory cardiovascular workload poses clinical risk. Dosing is typically based on hemoglobin (Hb) levels, without consideration of differences in red blood cell (RBC) or Hb-based blood substitute O2 delivery potential. Such consideration requires quantified assessment of O2 delivery potency, for which there is no accepted metric. We developed an in vitro metric to predict the O2 delivery potency for various "Hb formulations" (fresh and stored whole blood [sWB]), stored RBC concentrate (sRBCc), and artificial WB analogs (WBAs) composed with different Hb-based O2 carriers. O2 uptake and delivery were modeled across physiologic O2 gradients by integrating data from matched O2 association (high pH; ie, in the lungs) and dissociation curves (low pH; ie, in tissues). These data were used to compute a novel O2 delivery potency metric, lung-to-tissue O2 flux (L-TOF). Using L-TOF, we quantified O2 delivery potency of sRBCc (additive solution 1) and determined that equipotent transfusion at day 0 and day 42 would require an increase in "dose" of 158% (476 ± 21.6 mL of day 42 sRBCc was equipotent to 300 ± 0.0 mL of fresh RBCs). Employing a novel in vitro model of massive transfusion, L-TOF was used to quantify transfusion effectiveness by examining change in recipient blood L-TOF after receipt of either crystalloid (normal saline), sWB (citrate phosphate dextrose adenine-1), or WBAs. L-TOF enables direct comparison of O2 delivery potency between different blood products, offering a predictive readout of transfusion quality.

OBJECTIVES: 
Prehospital transfusion using Rhesus D antigen (RhD)-positive low-titer group O whole blood (LTOWB) or red blood cells is increasingly common when RhD-negative blood products are not available. However, concerns remain regarding D-alloimmunization in RhD-negative females of childbearing potential (FCPs), which could lead to future hemolytic disease of the fetus and newborn (HDFN). The magnitude of these risks, and their policy implications, have been the subject of recent investigation. To summarize the biological and epidemiological impacts and post-exposure management of RhD-positive transfusion in FCPs in hemorrhagic shock.

METHODS: 
This narrative review synthesizes the literature on the rate of D-alloimmunization, describes the results of modeling studies on the risk of HDFN following RhD-positive transfusion to FCPs, and examines epidemiologic studies estimating the HDFN risk at local, regional, and national levels. The D-alloimmunization risk mitigation strategies and current clinical guidelines are also reviewed.

RESULTS: 
Several factors, including the low prevalence of RhD-negative individuals, the low rate of D-alloimmunization itself, potentially reduced pregnancy rates post-trauma, and advances in modern perinatal care decrease the overall risk of HDFN following the transfusion of RhD-positive blood products to FCPs in trauma. Some modeling studies estimated that fetal death due to anti-D-mediated HDFN would occur in fewer than 0.1% of FCPs exposed to RhD-positive blood products. Timely prehospital transfusion has demonstrated survival benefits for injured adults and children. National and regional epidemiological studies support the safety and utility of RhD-positive blood product use in emergency settings. Risk mitigation strategies include Rh immune globulin (RhIg) administration and structured post-exposure follow-up to detect alloimmunization and reduce potential future pregnancy harm.

CONCLUSIONS: 
RhD-positive transfusion in FCPs during hemorrhagic shock when RhD-negative products are not available is supported by current evidence and ethical considerations. The risk of future HDFN is low and favorable perinatal outcomes can be achieved when the woman has access to modern prenatal health care. Risk may be further mitigated through post-exposure protocols. Prehospital transfusion policies should reflect this risk-benefit balance by enabling access to RhD-positive blood products for all trauma patients, including FCPs, if RhD-negative blood products are not available.

Arterial thrombosis is a leading cause of death and disability worldwide. Administration of tissue plasminogen activator (tPA) remains the current noninvasive clinical gold standard but is ineffective for many patients. Von Willebrand factor (VWF) is mechanistically critical in arterial thrombosis and has been studied as an alternative target for thrombolytic therapy. This study utilizes a microfluidic system of arterial thrombosis to evaluate VWF-A1 domain inhibitor aptamer (BB-031), aiming to understand VWF-mediated recanalization (vessel reopening) and compare efficacy of BB-031 to Alteplase and Tenecteplase. Thrombotic occlusion is simulated in a microfluidic device, and thrombi are allowed to retract and remodel for up to 6 hr. During a subsequent 2 h treatment reperfusion period (not disruptive to the original thrombus), thrombus morphology, composition, and channel patency (openness) are analyzed. Thrombi substantially remodel post-occlusion. BB-031 treatment results in an inability to maintain thrombus and significantly improves microfluidic patency compared to vehicle and tPA. Acute ischemic stroke patient samples demonstrate improved microfluidic patency with BB-031 compared to vehicle. Here we establish an in vitro/ex vivo platform to study arterial occlusion, clot retraction, drug delivery, and recanalization/patency, and implement this platform to demonstrate BB-031 could be a safe and efficacious therapeutic alternative to tPA.

INTRODUCTION: To support the development of the National Trauma Research Repository (NTRR), a multidisciplinary workgroup focused on prehospital trauma care used a consensus-driven approach to review established data elements and recommend basic common data elements (CDEs) for inclusion in the NTRR data dictionary.

METHODS: A 13-member workgroup of military and civilian trauma researchers and data scientists located and reviewed databases, codebooks, data collection forms, and published articles for data elements relevant to prehospital trauma care. Identified data elements were reviewed in a three-round Delphi survey and during monthly workgroup meetings. Consensus during the Delphi survey was determined with an 80% agreement threshold.

RESULTS: Twenty-one sources were reviewed for prehospital data elements. Following three rounds and workgroup discussions, 52 elements (84%) reached consensus for inclusion, two elements (3%) were excluded, and eight elements (13%) did not reach consensus.

DISCUSSION: The Delphi process proved effective in achieving expert consensus on basic CDEs for prehospital trauma care research. The resulting standardized basic CDEs will improve data harmonization and support consistent data collection in the NTRR. These CDEs represent an initial framework and serve as a foundational starting point for prehospital data collection within the NTRR. As researchers use the NTRR, the list of CDEs will grow and evolve to meet the needs of the trauma research community.

Major trauma dysregulates the immune system, leaving injured patients at increased risk of infection. Despite extensive research to define the effect of trauma of the immune system, there are no effective interventions to restore immune function in injured patients. We previously used single cell phosphoproteomics to identify pathways for immunomodulation in COVID-19 induced critical illness. We hypothesized that trauma would also be associated with definable changes in leukocyte signaling, providing therapeutic targets. To test this hypothesis, we used a mass cytometry to assess signaling phosphoproteins and associated surface makers at single cell resolution in a cohort of critically injured patients. We find that injury causes an acute increase in STAT3 signaling across leukocyte populations, followed by a shift from STAT3 to STAT5 predominance in T cells over the first 72 hours after injury. We used computational clustering to identify subpopulations of T cells and found that injury causes an increase in activated CD4 memory T cells. We assessed the relationship between phosphoproteins levels and clinical outcomes and identified significant correlations between early phospho-STAT3 levels in T cells, monocytes and neutrophils and clinical outcomes including ICU and hospital length of stay. These data demonstrate that severe injury is associated with cell-type specific changes in signaling phosphoproteome in circulating leukocytes which may underlie clinical outcomes from injury.

Relatively little is known about social workers in interprofessional primary healthcare (PHC) teams, despite social work being one of the largest health and social service professions. Understanding the experiences of social workers in PHC teams will help strengthen the integration of social workers in these settings. The research question guiding this study was: "What are the experiences of social workers working in interprofessional PHC teams in Ontario, Canada?" This was a descriptive qualitative study and the authors conducted focus groups with social workers embedded in PHC. Fifty-seven social workers participated in 10 focus groups that were recorded and transcribed verbatim. Thematic analysis guided an inductive analysis of the data. Seven themes in the data were identified: (1) social work is valued by the team, (2) social work enhances the team, (3) the pandemic disrupted team relationships, (4) team collaboration requires intention and opportunity, (5) lack of physical space, (6) limited influence on decision making, and (7) clinical supervision mitigates isolation. While social workers feel valued by their team members, opportunities to contribute to organizational decision making remain limited. Addressing the tacit hierarchies that facilitate these challenges through shared leadership practices or adoption of collaborative competency frameworks is recommended.