Publications

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.

BACKGROUND: Blood transfusion before arrival at a hospital reduces mortality from traumatic hemorrhage and shock. Whether transfusion with whole blood is more beneficial than transfusion with blood components is uncertain, as are the effects of the length of time that blood products are in storage between donation and transfusion.

METHODS: In this pragmatic, multicenter, phase 3, cluster-randomized trial, we assigned 44 air medical bases in a 2:1 ratio to the use of up to 2 units of whole blood or as-indicated blood components (plasma, red cells, or both) for prehospital transfusion in trauma patients during 1-month blocks. The primary outcome was death from any cause within 30 days after randomization. An observational substudy assessed outcomes according to the storage age of whole blood.

RESULTS: Of 1020 eligible patients transported to hospitals by the air bases, 715 were assigned to receive whole blood and 305 to receive blood components; 695 and 298, respectively, were included in the primary analysis. Mortality at 30 days was 25.9% in the whole-blood group and 20.5% in the component group (adjusted odds ratio, 1.24; 95% confidence interval [CI], 0.87 to 1.76; P = 0.24). No substantial between-group differences in adverse events were observed. In the observational substudy, 30-day mortality was 27.1% among 210 patients who received whole blood with a storage age of 15 to 21 days and 26.4% among 443 patients who received whole blood with a storage age of 1 to 14 days (adjusted odds ratio, 0.99; 95% CI, 0.74 to 1.32).

CONCLUSIONS: In injured patients with hemorrhagic shock, the use of whole blood for prehospital transfusion did not result in lower 30-day mortality than the use of blood components. (Funded by the Congressionally Directed Medical Research Programs and the U.S. Army Medical Research Acquisition Activity; TOWAR ClinicalTrials.gov number, NCT04684719.).

BACKGROUND: COVID-19 and other respiratory viral infections can cause cardiovascular complications. SARS-CoV-2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID-19 and enrolled in the ACTIV-4a (Accelerating COVID-19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy.

METHODS: We quantified SARS-CoV-2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine-Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death.

RESULTS: In 93 patients, SARS-CoV-2 RNA and N-antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90-day death (hazard ratio [HR], 1.31 [95% CI, 1.17-1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24-1.47]). Viral RNA more effectively predicted survivorship than N-antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%-32.3%; P=0.048) after adjustment for age and sex of the relationship between viral RNA and the 90-day mortality rate.

CONCLUSIONS: Elevated plasma SARS-CoV-2 RNA levels are associated with death in ACTIV-4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung-blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04505774.

BACKGROUND: Air medical transport (AMT) has demonstrated a survival benefit for select patients. The Air Medical Prehospital Triage (AMPT) score identifies patients with a survival benefit from AMT. Patients with positive AMPT score may be heterogenous with different levels of benefit. Our objective was to identify phenotypes of injured patients with a positive AMPT score with differential benefits of AMT compared with ground emergency medical services.

METHODS: Patients 16 years or above transported by AMT or ground emergency medical services from the scene (>3 and <40 miles) and met AMPT score criteria in the Pennsylvania Trauma Outcomes Study 2000-2017 were included. Patients were clustered using latent class analysis (LCA) and k-modes clustering. From the two class memberships, we then assessed the association between in-hospital survival and actual transport mode using multilevel generalized linear models, adjusting for demographics, injury characteristics, vital signs, and in-hospital variables. To validate our membership assignments, the same analysis was performed on separately on NTDB data.

RESULTS: In total, 22,569 patients were included from the Pennsylvania Trauma Outcomes Study, with 7,607 (35%) actually undergoing AMT. LCA resulted in five phenotype classes. Among these, Class 2, composed of patients with physiological plus anatomic triage criteria and Glasgow Coma Scale (GCS)≤13, and Class 5, composed of a GCS≤13 plus abnormal respiratory rate, demonstrated profound survival benefit [aOR, 1.83 (1.41, 2.36) and 2.23 (1.76, 2.81)]. K-modes also resulted in five classes. Among these, Classes 2, 4, and 5 also composed of patients with physiological plus anatomic criteria, GCS≤13 and/or abnormal respiratory rate. These groups also demonstrated profound survival benefit [aOR, 1.85 (1.33, 2.59), 2.02 (1.49, 2.73) and 2.5 (1.97, 3.17)]. Replication in NTDB illustrated similar results.

CONCLUSIONS: These findings suggest that patients with GCS≤13 and abnormal respiratory rate or physiological plus anatomic triage criteria should be prioritized in AMT use. (J Trauma Acute Care Surg. 2026;00: 00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.).

LEVEL OF EVIDENCE: Prognostic; Level IV.

BACKGROUND: Thrombotic and thromboembolic events are a common and potentially preventable complication in multitrauma patients, and substantial quality improvement efforts are directed at prevention. The results of several randomized controlled trials (RCTs) related to the association between tranexamic acid (TXA) and thrombotic/thromboembolic events have demonstrated conflicting results. We aimed to address this by examining whether prehospital TXA was associated with higher rates of thrombotic/thromboembolic events in a harmonized data set from three large multicenter RCTs.

METHODS: We analyzed data using a harmonized data set from three RCTs examining the effects of prehospital TXA: The Pre-Hospital Anti-fibrinolytics for Traumatic Coagulopathy and Hemorrhage Study (PATCH trial), Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial (STAAMP trial) and the Prehospital TXA for TBI trial, part of the Resuscitation Outcomes Consortium (ROC trial). Outcomes included deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, stroke, combined venous thrombotic/thromboembolic events (VTE), and combined arterial thrombotic/thromboembolic events. Multivariable regression was used to adjust for TXA administration, sex, age, injury severity score, Glasgow Coma Scale, shock index, and 24-hour red cell transfusion.

RESULTS: There were no differences in myocardial infarction, stroke, arterial thrombotic/thromboembolic events, DVT, PE, or VTE in patients who were randomized to TXA compared with those who were not. On univariate analysis, rates of PE, DVT and VTE were significantly higher in the PATCH cohort compared with STAAMP and ROC cohorts, but patients in PATCH had significantly higher injury severity scores and chest trauma when compared with those in ROC and STAAMP.

CONCLUSION: This multicenter database combining three large RCTs showed that randomization to TXA was not associated with higher rates of arterial and VTE. The higher rates of thrombotic/thromboembolic events observed in the PATCH trial may be explained by higher injury severity as well as protocolized screening. (J Trauma Acute Care Surg. 2026;00: 000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.).

LEVEL OF EVIDENCE: Sub-analysis of randomized controlled trials; Level II.

Platelet transfusions to treat bleeding complications use donor-derived platelets stored at room-temperature, that have a shelf-life of only 5-7 days due to bacterial contamination risks. Cold-stored and freeze-dried platelets are being investigated for extending shelf-life, but these still have the inherent challenge of donor-dependency. To address this, we developed a liposome-based synthetic platelet (SP) nanoconstruct that mimics the primary hemostatic mechanisms of platelets, and have previously reported its efficacy. However, a logistical limitation of SP is its susceptibility to environment-induced physico-chemical instabilities that reduces shelf-life when stored as aqueous suspension, impacting its availability and bioactivity. Lyophilization of liposomal nanotherapeutics utilizing anhydrobiosis-inspired lyoprotectants can enhance shelf-life, but this has not been explored for synthetic platelets. With these considerations, we report advancing SP into a lyophilized product (Lyo-SP) that can be rapidly aqueous-reconstituted for on-demand use. Lyo-SP retained morphology, size, and charge in long-term storage at various temperatures, and conserved platelet-mimetic functions in multiparametric assays with human plasma and blood. Lyo-SP demonstrated biosafety in its effect analysis on endothelial cells, neutrophils, RBCs and complement C3. Lyo-SP significantly reduced bleeding in a tail-clip model in thrombocytopenic mice. These studies establish the potential of Lyo-SP as a shelf-stable platelet surrogate for treating bleeding complications.

BACKGROUND: Substituting group A whole blood (GAWB) might relieve some of the burden on the low titer group O whole blood (LTOWB) inventory. This simulation examined the effect of implementing GAWB at a large trauma hospital.

STUDY DESIGN AND METHODS: A civilian trauma center with LTOWB and GAWB par levels set to 22 and 10 units, respectively, was modeled as the baseline. The average daily number of WB recipients was 0.5 who received an average of four WB units per patient. LTOWB was issued in packages of five and all had to be consumed before a group A patient could be switched to GAWB. Several variations on the baseline simulation were also modeled.

RESULTS: In the baseline simulation, there was a median (interquartile range, IQR) of 1 (0-2) GAWB and 16 (13-19) LTOWB recipients per month. The median (IQR) GAWB and LTOWB units transfused per month was 2 (0-9) and 56 (42-72), respectively. Fourteen percent of group A patients received any quantity of GAWB. The variations that had the most impact on GAWB usage included increasing the number of WB recipients to 2.5 per day where the median (IQR) monthly number of GAWB recipients and units transfused increased to 4 (3-5) recipients and 21 (12-29) units, respectively, and when the average WB requirements increased to eight units per patient resulting in transfusing a median (IQR) of 10 (5-15) GAWB units per month to 3 (1-4) recipients.

DISCUSSION: Under routine civilian hospital circumstances, implementing GAWB will have a modest impact on LTOWB inventory.