Publications

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.

INTRODUCTION: Evidence-based medicine (EBM) skills are fundamental to lifelong learning. These can be tracked the same way that procedural skills are tracked-via residency program logs. Review of the logs can inform faculty on the EBM activity of their trainees. An understanding of the topics residents query while on shift can provide insight into where they need further knowledge to provide optimal patient care. Our objective in this project was to categorize the relationship of the clinical questions posed by emergency medicine (EM) residents while working in the emergency department to the American Board of Emergency Medicine (ABEM) Model of Clinical Practice.

METHODS: We conducted this institutional review board-approved study (deemed exempt research) in a postgraduate year (PGY) 1-4 EM residency. A toxicology rotation and fellowship were established during the study period. Residents were required to submit three to five descriptions of EBM activity per 28-day EM rotation block into the program's management software. We analyzed each complete log submitted from June 2013-May 2020 using the 2019 ABEM Model of Clinical Practice. The clinical questions posed were mapped to the ABEM Model for content, including sub-categories and acuity level. Demographic information in the logs allowed for analysis for ABEM's pediatric and geriatric modifiers. The primary outcome measure was the number of clinical questions mapped to each section of the Model.

RESULTS: From June 2013-May 2020, 10,444 discrete completed logs were completed by 137 residents. "Procedures and Skills" (n = 1,110, 10.63%) and "Cardiovascular Disorders" (n = 991, 9.49%) were the most prevalent ABEM content areas. "Trauma" (n = 812, 7.77%) and "Drugs and Chemical Classes" (n = 749, 7.17%) were the most prevalent ABEM sub-categories. "Emergent" (n = 7,770, 74.3%) was the most commonly searched ABEM acuity, followed by "lower acuity" (n = 5,341, 51.1%) and "critical" (n = 5,192, 49.7%). Of note, not all conditions have ABEM acuity codes, and some have multiple. Clinical questions addressed issues regarding pediatric patients in 10.16% (n = 1,061) and geriatric patients in 8.05% (n = 841) of logs.

CONCLUSION: In this single-site cohort, "Procedures and Skills" was the most common source of on-shift questions for EM residents, perhaps representing just-in-time training. "Trauma" was the most common sub-category, potentially the result of a large footprint in the ABEM Model of Clinical Practice. The residency program's toxicology rotation and fellowship may have influenced the types of conditions treated by residents and the subsequent content of their logs. Furthermore, completing logs on shift may have impacted the mapping to ABEM acuity levels. Programmatic understanding of residents' on-shift, evidence-based medicine questions could serve to identify educational gaps and opportunities.

Anorexia nervosa is a severe psychiatric disorder characterized by persistent food restriction and often excessive physical activity, implicating dysfunction in neural circuits governing motivation, reward, and behavioral persistence. The nucleus accumbens (NAc) is a central component of these circuits, yet synaptic and cellular adaptations within this region during anorexia-like states remain poorly defined. Using the activity-based anorexia (ABA) paradigm in adult female mice, we examined glutamatergic transmission and intrinsic neuronal properties in the NAc shell. ABA exposure produced rapid weight loss, reduced food intake, and progressively increased running-wheel activity. Biochemical analyses of NAc shell tissue revealed elevated membrane-associated GluA2 AMPA receptor protein. Consistent with this finding, whole-cell patch-clamp recordings from medium spiny neurons showed increased amplitude of spontaneous excitatory postsynaptic currents. ABA also enhanced intrinsic neuronal excitability, reflected by greater firing in response to depolarizing current injections. Together, these convergent biochemical and electrophysiological results demonstrate that ABA induces coordinated postsynaptic strengthening and increased intrinsic excitability in NAc shell medium spiny neurons. These adaptations suggest a sustained increase in accumbal output that may bias motivational circuit function and contribute to excessive activity and suppressed feeding during anorexia-like conditions, paralleling glutamatergic plasticity observed in other compulsive disorders, including substance use disorder.