Predictors of Massive Transfusion Protocol Initiation Among Trauma Patients Transported From the Scene Via Flight Emergency Management Services.

OBJECTIVE: Early identification of the subset of trauma patients with acute hemorrhage who require resuscitation via massive transfusion protocol (MTP) initiation is vital because such identification can ensure the availability of resuscitation products immediately upon hospital arrival and result in improved clinical outcomes, including reduced mortality. However, there are currently few studies on the predictors of MTP in the unique setting of flight transport. METHODS: This was a retrospective study of adult trauma patients transported from the scene via flight to 6 trauma centers between March 1, 2019, and January 21, 2021. Patients were included if they had emergency medical service vitals documented. The variables collected included demographics, comorbidities, cause of injury, body regions injured, in-flight treatments, and transport vitals. The primary outcome was MTP initiated by the receiving hospital. RESULTS: A total of 212 patients were included, of whom 16 (8%) had MTP initiated. During flight transport, 24 (11%) received whole blood, 9 (4%) received packed red blood cells, 11 (5%) had a tourniquet placed, and 5 (2%) received tranexamic acid. In adjusted analyses, receiving whole blood during transport (odds ratio [OR] = 8.52, P < .01), systolic blood pressure ≤ 90 mm Hg (OR = 8.07, P < .01), and a Glasgow Coma Scale score < 13 (OR = 8.38, P < .01) were independently associated with MTP. CONCLUSIONS: This retrospective cohort study showed that 3 factors readily available in the flight setting-receipt of whole blood, systolic blood pressure, and Glasgow Coma Scale score-are strong predictors of MTP at the receiving facility, particularly when considered in aggregate.

Associations of Neutrophil-Lymphocyte Ratios with Reperfusion and Functional Outcomes in Ischemic Stroke after Endovascular Therapy.

OBJECTIVES: Treatment of ischemic stroke with endovascular thrombectomy (EVT) leads to improved outcomes compared to IV tPA. The neutrophil-lymphocyte ratio (NLR), a marker of inflammation, has been proposed to predict outcomes in ischemic stroke patients and may be used to identify patients at risk for poor outcomes after EVT. MATERIALS AND METHODS: This was a retrospective study of adult ischemic stroke patients undergoing EVT between 1/1/2018 and 12/31/2020. Outcomes were successful reperfusion (TICI score ≥2B), favorable discharge NIHSS (≤4), favorable discharge and 3-month mRS (≤2), and symptomatic intracranial hemorrhage (sICH). The primary exposure was NLR, measured pre- and post-EVT. Other variables collected included demographics and timing of stroke onset, arrival, groin puncture, tPA, and recanalization. RESULTS: A total of 592 patients were included. The most common vessel involved was the middle cerebral artery (73%). Lower admission NLR was associated with favorable discharge NIHSS and favorable discharge and 3-month mRS (all P < 0.01). NLRs measured after EVT were associated with all the primary outcomes. Improvements in NLR after EVT were associated with favorable discharge (P = 0.02) and 3-month mRS (P = 0.02) and lower incidence of sICH (P = 0.01). CONCLUSIONS: Because of the long-term functional deficits that can persist after ischemic stroke, it is vital to identify patients with higher probability for these outcomes. The results from this study showed that favorable NLR measures, as well as favorable trends in NLR over time, are associated with improved outcomes, indicating that NLR is a useful marker to identify patients at risk for poor functional outcomes.

Recalibrating the Glasgow Coma Score as an Age-Adjusted Risk Metric for Neurosurgical Intervention.

BACKGROUND: The Glasgow Coma Scale (GCS) score is the most frequently used neurologic assessment in traumatic brain injury (TBI). The risk for neurosurgical intervention based on GCS is heavily modified by age. The objective is to create a recalibrated Glasgow Coma Scale (GCS) score that accounts for an interaction by age and determine the predictive performance of the recalibrated GCS (rGCS) compared to the standard GCS for predicting neurosurgical intervention. METHODS: This retrospective cohort study utilized the National Trauma Data Bank and included all patients admitted from 2010-2015 with TBI (ICD9 diagnosis code 850-854.19). The study population was divided into 2 subsets: a model development dataset (75% of patients) and a model validation dataset (remaining 25%). In the development dataset, logistic regression models were used to calculate conditional probabilities of having a neurosurgical intervention for each combination of age and GCS score, to develop a point-based risk score termed the rGCS. Model performance was examined in the validation dataset using area under the receiver operating characteristic (AUROC) curves and calibration plots. RESULTS: There were 472,824 patients with TBI. The rGCS ranged from 1-15, where rGCS 15 denotes the baseline risk for neurosurgical intervention (4.4%) and rGCS 1 represents the greatest risk (62.6%). In the validation dataset there was a statistically significant improvement in predictive performance for neurosurgical intervention for the rGCS compared to the standard GCS (AUROC: 0.71 versus 0.67, difference, -0.04, P<0.001), overall and by trauma level designation. The rGCS was better calibrated than the standard GCS score. CONCLUSIONS: The relationship between GCS score and neurosurgical intervention is significantly modified by age. A revision to the GCS that incorporates age, the rGCS, provides risk of neurosurgical intervention that has better predictive performance than the standard ED GCS score.

Is preexisting mental illness associated with lower patient satisfaction for older trauma patients? A cross-sectional descriptive study.

BACKGROUND: The purpose of this study was to examine if satisfaction with care differs among older trauma patients with and without preexisting mental illness (PMI+/PMI-). METHODS: Data from two level I trauma centers were examined from 11/2016 through 12/2017. Trauma patients ≥55 years were included and satisfaction of those who had a diagnosis of mental illness prior to the trauma admission (PMI+) to those without a diagnosis (PMI-) (n = 299; 62 PMI+ and 237 PMI-) were compared. Enrolled patients completed the Family Satisfaction with Advanced Care Cancer Scale Patient Survey (FAMCARE-P13) prior to discharge. Associations between mental illness status and patient baseline characteristics, overall mean satisfaction, and mean satisfaction by question were compared. Generalized linear models adjusted for differences in patient satisfaction by mental illness status. Analyses were stratified by hospital to account for the interaction between hospital and mental illness status. RESULTS: Compared to PMI- patients, PMI+ patients were more likely to be younger, female, have multiple comorbidities, and to report lower overall satisfaction with care. Among PMI+ patients, the most common diagnoses were depression and anxiety. After adjustment, PMI+ was associated with lower patient satisfaction at hospital 1; after examining individual questions lower satisfaction was associated with information provided on procedures and questions surrounding "Physical care." Conversely, PMI+ did not affect satisfaction at hospital 2 after adjustment. CONCLUSIONS: At hospital 1, room for improvement was identified in providing information about prognosis and procedures, symptom management, and continuity of care. Reexamining practices for older PMI+ trauma patients is warranted.

Examining emergency medical services' prehospital transport times for trauma patients during COVID-19.

INTRODUCTION: Longer prehospital times were associated with increased odds for survival in trauma patients. The purpose of this study was to determine how the COVID-19 pandemic affected emergency medical services (EMS) prehospital times for trauma patients. METHODS: This retrospective cohort study compared trauma patients transported via EMS to six US level I trauma centers admitted 1/1/19-12/31/19 (2019) and 3/16/20-6/30/20 (COVID-19). Outcomes included: total EMS pre-hospital time (dispatch to hospital arrival), injury to dispatch time, response time (dispatch to scene arrival), on-scene time (scene arrival to scene departure), and transportation time (scene departure to hospital arrival). Fisher's exact, chi-squared, or Kruskal-Wallis tests were used, alpha = 0.05. All times are presented as median (IQR) minutes. RESULTS: There were 9400 trauma patients transported by EMS: 79% in 2019 and 21% during the COVID-19 pandemic. Patients were similar in demographics and transportation mode. Emergency room deaths were also similar between 2019 and COVID-19 [0.6% vs. 0.9%, p = 0.13].There were no differences between 2019 and during COVID-19 for total EMS prehospital time [44 (33, 63) vs. 43 (33, 62), p = 0.12], time from injury to dispatch [16 (6, 55) vs. 16 (7, 77), p = 0.41], response time [7 (5, 12) for both groups, p = 0.27], or on-scene time [16 (12-22) vs. 17 (12,22), p = 0.31]. Compared to 2019, transportation time was significantly shorter during COVID-19 [18 (13, 28) vs. 17 (12, 26), p = 0.01]. CONCLUSION: The median transportation time for trauma patients was marginally significantly shorter during COVID-19; otherwise, EMS prehospital times were not significantly affected by the COVID-19 pandemic.

LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC.

BACKGROUND: Dysregulation of transcription and cytokine expression has been implicated in the pathogenesis of a variety inflammatory diseases. The resulting imbalance between inflammatory and resolving transcriptional programs can cause an overabundance of pro-inflammatory, classically activated macrophage type 1 (M1) and/or helper T cell type 1 (Th1) products, such as IFNγ, TNFα, IL1-ß, and IL12, that prevent immune switching to resolution and healing. The low molecular weight fraction of human serum albumin (LMWF5A) is a novel biologic drug that is currently under clinical investigation for the treatment of osteoarthritis and the hyper-inflammatory response associated with COVID-19. This study aims to elucidate transcriptional mechanisms of action involved with the ability of LMWF5A to reduce pro-inflammatory cytokine release. METHODS: ELISA arrays were used to identify cytokines and chemokines influenced by LMWF5A treatment of LPS-stimulated peripheral blood mononuclear cells (PBMC). The resulting profiles were analyzed by gene enrichment to gain mechanistic insight into the biologic processes and transcription factors (TFs) underlying the identified differentially expressed cytokines. DNA-binding ELISAs, luciferase reporter assays, and TNFα or IL-1ß relative potency were then employed to confirm the involvement of enriched pathways and TFs. RESULTS: LMWF5A was found to significantly inhibit a distinct set of pro-inflammatory cytokines (TNFα, IL-1ß, IL-12, CXCL9, CXCL10, and CXCL11) associated with pro-inflammatory M1/Th1 immune profiles. Gene enrichment analysis also suggests these cytokines are, in part, regulated by NF-κB and STAT transcription factors. Data from DNA-binding and reporter assays support this with LMWF5A inhibition of STAT1α DNA-binding activity as well as a reduction in overall NF-κB-driven luciferase expression. Experiments using antagonists specific for the immunomodulatory and NF-κB/STAT-repressing transcription factors, peroxisome proliferator-activated receptor (PPAR)γ and aryl hydrocarbon receptor (AhR), indicate these pathways are involved in the LMWF5A mechanisms of action by reducing LMWF5A drug potency as measured by TNFα and IL-1ß release. CONCLUSION: In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARγ and AhR. In addition, our data indicate that LMWF5A suppresses NF-κB and STAT1α pro-inflammatory pathways. This suggests that LMWF5A acts through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production.

Long-term mortality and causes of death among patients with mild traumatic brain injury: a 5-year multicenter study.

Objective: Undergoing mild traumatic brain injury (mTBI) increases mortality risk, but it is unclear what drives this finding. This study explored associations with mortality in patients with mTBI.Methods: This was a retrospective study of patients with mTBI and controls admitted to six level 1 trauma centers in 1/1/2009-12/31/2013. Mortality data were from the CDC National Death Index. Patients with mTBI were identified by ICD-9 code, Glasgow Coma Scale 13-15, Injury Severity Score (ISS) <16, and loss of consciousness ≤1 hour. Controls had hospital length of stay ≤24 hours, ISS<16, and no head injury.Results: This study included 964 patients with mTBI and 5,567 controls. mTBI was associated with a 47% increased 5-year mortality risk (HR = 1.47, 95% CL 1.08-2.01). Patients with mTBI were more likely to die of a neurodegenerative disease (17% vs 11%, P = .119). Cardiovascular (HR = 1.80, 95% CL 1.17-2.77), neurological (HR = 3.33, 95% CL 2.07-5.38), and respiratory (HR = 1.70, 95% CL 1.01-2.86) comorbidities were associated with mortality in patients with mTBI.Conclusions: Patients with mTBI are at increased mortality risk in the 5 years post-injury. Mortality in patients with mTBI was most influenced by preexisting conditions.

Associations of Antithrombotic Timing and Regimen with Ischemic Stroke and Bleeding Complications in Blunt Cerebrovascular Injury.

BACKGROUND: Blunt cerebrovascular injuries (BCVIs) are associated with long-term neurological effects. The first-line treatment for BCVIs is antithrombotics, but consensus on the optimal choice and timing of treatment is lacking. METHODS: This was a retrospective study on patients aged at least 18 years admitted to 6 level 1 trauma centers between 1/1/2014 and 12/31/2017 with grade 1-4 BCVI and treated with antithrombotics. Differences in treatment practices were examined across the 6 centers. The primary outcome was ischemic stroke, and secondary outcomes were related to bleeding complications: blood transfusion and intracranial hemorrhage (ICH). Treatment characteristics examined were time to diagnosis and first computerized tomography angiography, time of total treatment course, time on each antithrombotic (anticoagulants, antiplatelets, combination), time from hospital arrival to antithrombotic initiation, and treatment interruption, i.e., treatment halted for a surgical procedure and restarted postoperatively. Chi-square, Fisher exact, Spearman's rank-order correlation, Wilcoxon rank-sum, Kruskal-Wallis, and Cox proportional hazards models with time-varying covariates were used to evaluate associations with the outcomes. RESULTS: A total of 189 patients with BCVI were included. The median (IQR) time from arrival to antithrombotic initiation was 27 (8-61) hours, and 28% of patients had treatment interrupted. The ischemic stroke rate was 7.5% (n = 14), with most strokes (64%, n = 9) occurring between arrival and treatment initiation. Treatment interruption was associated with ischemic stroke (75% of patients with stroke had an interruption versus 24% of patients with no stroke; P < .01). Time on anticoagulants was not associated with ischemic stroke (P = .78), transfusion (P = .43), or ICH (P = .96). Similarly, time on antiplatelets (P = .54, P = .65, P = .60) and time on combination therapy (P = .96, P = .38, P = .57) were not associated with these outcomes. CONCLUSIONS: The timing and consistency of antithrombotic administration are critical in preventing adverse outcomes in patients with BCVI. Most ischemic strokes in this study population occurred between arrival and antithrombotic initiation, representing events that may potentially be intervened upon by earlier treatment. Future studies should examine the safety of continuing treatment through surgical procedures.

Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis.

Objective: A few studies report comparable analgesic efficacy between low-dose ketamine and opioids such as morphine or fentanyl; however, limited research has explored the safety and effectiveness of intravenous low-dose ketamine as a primary analgesic in a civilian prehospital setting. The objective of this study is to compare pain control between low-dose ketamine and fentanyl when administered intravenously (IV) for the indication of severe pain. Methods: This was a retrospective, observational review of prehospital adult patients (≥18 years) who presented with severe pain (numeric rating scale, 7-10) and were treated solely with either low-dose ketamine IV or fentanyl IV between January 1, 2014 and December 31, 2016. Propensity matched analysis was performed adjusting for all baseline variables with p ≤ 0.10 and for baseline pain score to match ketamine and fentanyl patients on a one-to-one ratio. The primary outcome was change in pain score from baseline to after treatment and evaluated with a paired t-test. Secondary outcomes were changes in vital signs and Glasgow coma scale (GCS) from baseline to after treatment, as well as incidence of clinically significant adverse events (AEs); AEs were followed from scene arrival through emergency department discharge. Results: Propensity matched analysis produced 79 matched pairs. Ketamine IV patients, receiving a mean (SD) dose of 0.3 (0.1) mg/kg, showed a significantly larger mean decrease in pain after treatment, compared to the fentanyl IV patients (-5.5 (3.1) vs. -2.5 (2.4), p < 0.001). A significantly greater proportion of patients receiving ketamine IV achieved at least a 50% reduction in pain compared to those receiving fentanyl IV (67% vs. 19%, p < 0.001), marking 52 ketamine IV patients as responders to treatment. Vital signs demonstrated a nonsignificant decrease in blood pressure, respiratory rate, heart rate, and GCS. No clinically significant AEs were reported for patients receiving ketamine IV. Conclusion: The significant reduction in pain, significantly high proportion of ketamine responders, and the lack of clinically significant AEs characterizing patients receiving low-dose ketamine IV compared to fentanyl IV, all provide further support for its use as an effective prehospital analgesic. Level of Evidence: Level III, therapeutic.

Comparing Outcomes of Patients With Idiopathic Subarachnoid Hemorrhage by Stratifying Perimesencephalic Bleeding Patterns.

BACKGROUND: To determine the clinical outcomes of perimesencephalic subarachnoid hemorrhages based on the computed tomography (CT) bleeding patterns. METHODS: This retrospective cohort study included: (1) patients (≥18 years) admitted to a comprehensive stroke center (January 2015-May 2018), (2) with angiography-negative, nontraumatic subarachnoid hemorrhage in a perimesencephalic or diffuse bleeding pattern, and (3) had CT imaging performed in ≤ 72 hours of symptom onset. Patients were stratified by location of bleeding on CT: Peri-1: focal prepontine hemorrhage; Peri-2: prepontine with suprasellar cistern +/- intraventricular extension; and diffuse. RESULTS: Of the 39 patients included, 13 were Peri-1, 11 were Peri-2, and 15 were diffuse. The majority were male (n = 26), with a mean (standard deviation) age of 55.3 (11.3) years, who often presented with headache (n = 37) and nausea (n = 28). Overall, patients in Peri-1 were significantly less likely to have hydrocephalus compared to Peri-2 and dSAH (P= .003), and 4 patients required an external ventricular drain. Five patients developed symptomatic vasospasm. Patients in Peri-1, compared to Peri-2 and diffuse, had a significantly shorter median neuro critical care unit length of stay (LOS) and hospital LOS. Most patients (n = 35) had a discharge modified Rankin Score between 0 and 2 with no significant differences found between groups. CONCLUSION: These data suggest that patients with the best clinical course were those in Peri-1, followed by Peri-2, and then diffuse. Because these patients often present with similar clinical signs, stratifying by hemorrhage pattern may help clinicians predict which patients with perimesencephalic subarachnoid hemorrhage develop complications.