Anyone Anytime for Anything: The History of Emergency Medicine in Missouri.

The history of Emergency Medicine (EM) in Missouri reflects the larger history of EM as a burgeoning specialty throughout the United States, but with some important and unique contributions that may not be generally appreciated. We discuss historical events and important leaders of EM, but there are many we could not mention. Much of the information comes from personal interviews with the physicians who "were in the room where it happened.". We hope the article will illuminate the progress made in caring for critical illness and injury through the development of a new specialty focused on that goal. We recognize there are many emergency physicians not mentioned that have played a large role in maintaining and growing the academic programs, improving the delivery of care through administrative and legislative actions, and navigating the specialty through enormously challenging times.

Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial.

STUDY OBJECTIVE: We compare the safety and efficacy of ecallantide with placebo in subjects undergoing assessment for acute angiotensin-converting enzyme inhibitor-induced angioedema (ACEIA) in an emergency department (ED). METHODS: This was a multicenter, phase 2, double-blind study with subjects randomized to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo plus physician-directed conventional therapy. The primary endpoint was defined as meeting predetermined discharge eligibility criteria within 6 hours of study drug administration. Discharge criteria included improvement of edema, stable vital signs, absence of stridor, absence of dyspnea or use of accessory muscles during respiration, absence of drooling, and ability to drink without difficulty. RESULTS: An interim analysis showed that a high percentage of subjects met the primary endpoint, and the study was halted. Overall, 79 subjects were randomized and 76 had data for analysis. Most had mild (45%) or moderate (42%) ACEIA. The discharge eligibility endpoint was met by 72% of the placebo group and 85%, 89%, and 89% of the ecallantide 10-, 30-, and 60-mg groups, respectively. This difference in meeting discharge eligibility endpoint criteria between treatment groups was not statistically significant. The incidence of treatment-emergent adverse events was similar between placebo and active-treatment groups. CONCLUSION: The addition of ecallantide to standard therapy does not appear to improve angioedema compared with placebo in ED patients with ACEIA. Our data suggest that most ED patients presenting with mild to moderate ACEIA are likely to meet our discharge eligibility criteria within 6 hours of treatment, regardless of intervention. Further studies to assess the utility of ecallantide in patients with more severe angioedema may be useful. No new safety signals related to ecallantide administration were identified.

ChatGPT provides inconsistent risk-stratification of patients with atraumatic chest pain.

BACKGROUND: ChatGPT-4 is a large language model with promising healthcare applications. However, its ability to analyze complex clinical data and provide consistent results is poorly known. Compared to validated tools, this study evaluated ChatGPT-4's risk stratification of simulated patients with acute nontraumatic chest pain. METHODS: Three datasets of simulated case studies were created: one based on the TIMI score variables, another on HEART score variables, and a third comprising 44 randomized variables related to non-traumatic chest pain presentations. ChatGPT-4 independently scored each dataset five times. Its risk scores were compared to calculated TIMI and HEART scores. A model trained on 44 clinical variables was evaluated for consistency. RESULTS: ChatGPT-4 showed a high correlation with TIMI and HEART scores (r = 0.898 and 0.928, respectively), but the distribution of individual risk assessments was broad. ChatGPT-4 gave a different risk 45-48% of the time for a fixed TIMI or HEART score. On the 44-variable model, a majority of the five ChatGPT-4 models agreed on a diagnosis category only 56% of the time, and risk scores were poorly correlated (r = 0.605). CONCLUSION: While ChatGPT-4 correlates closely with established risk stratification tools regarding mean scores, its inconsistency when presented with identical patient data on separate occasions raises concerns about its reliability. The findings suggest that while large language models like ChatGPT-4 hold promise for healthcare applications, further refinement and customization are necessary, particularly in the clinical risk assessment of atraumatic chest pain patients.

Angioedema: etiology, pathophysiology, current and emerging therapies.

BACKGROUND: Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%. OBJECTIVE: This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), which is responsible for 30%-40% of all AE seen in United States emergency departments. DISCUSSION: Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE. CONCLUSIONS: New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE.

Racial disparity in emergency department triage.

BACKGROUND: Previous reports of lower triage acuity scores and longer Emergency Department (ED) wait times for African Americans compared to Caucasians had insufficient information to determine if this was due to bias or appropriately based on medical history and clinical presentation. OBJECTIVE: (1) Determine if African Americans are assigned lower triage acuity scores (TAS) after adjusting for a number of demographic and clinical variables likely to affect triage scores. (2) Determine if lower TAS translate into clinically significant longer wait times to assignment to a treatment area. METHODS: This was a retrospective matched cohort design analysis of de-identified data extracted from the ED electronic medical record system, which included demographic and clinical information, as well as TAS, and ED process times. Triage scores were assigned using a 5-point scale (ESI), with 1 being most urgent and 5 being least urgent. Mean TAS and wait times to a treatment area for specific chief complaints were compared by race; after adjusting for age, gender, insurance status, time of day, day of week, presence of co-morbidities, and abnormal vital signs using a 1:1 matched case analysis. RESULTS: The overall mean TAS for African Americans was 2.97 vs. 2.81 for Caucasians (difference of 0.18; p<0.001), translating to a lower acuity rating. African Americans had a significantly longer wait time to a treatment area compared to case-matched Caucasians (10.9min; p<0.001), with much larger differences in wait times noted within certain specific chief complaint categories. CONCLUSION: Our current study supports the hypothesis that racial bias may influence the triage process.

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention.

STUDY OBJECTIVE: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS: Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION: GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.

Patterns and factors associated with intensive use of ED services: implications for allocating resources.

AIM: This study aims to better understand the patterns and factors associated with the use of emergency department (ED) services on high-volume and intensive (defined by high volume and high-patient severity) days to improve resource allocation and reduce ED overcrowding. METHODS: This study created a new index of "intensive use" based on the volume and severity of illness and a 3-part categorization (normal volume, high volume, intensive use) to measure stress in the ED environment. This retrospective, cross-sectional study collected data from hospital clinical and financial records of all patients seen in 2001 at an urban academic hospital ED. RESULTS: Multiple logistic regression models identified factors associated with high volume and intensive use. Factors associated with intensive days included being in a motor vehicle crash; having a gun or stab wound; arriving during the months of January, April, May, or August; and arriving during the days of Monday, Tuesday, or Wednesday. Factors associated with high-volume days included falling from 0 to 10 ft; being in a motor vehicle crash; arriving during the months of January, April, May, or August; and arriving during the days of Monday, Tuesday, or Wednesday. CONCLUSION: These findings offer inputs for reallocating resources and altering staffing models to more efficiently provide high-quality ED services and prevent overcrowding.

Sonographic assessment of jugular venous distension and B-type natriuretic peptide levels in patients with dyspnoea.

BACKGROUND: Sonographic assessment of jugular venous distension (US-JVD) has been described as a sensitive test for pulmonary oedema on chest x-ray in patients with dyspnoea, but chest x-ray may not detect all patients with raised B-type natriuretic peptide (BNP) levels. OBJECTIVE: To compare US-JVD and initial BNP levels in patients with dyspnoea. METHODS: This was a secondary analysis of a previously collected dataset from a prospective study of US-JVD in patients with dyspnoea due to suspected congestive cardiac failure. Initial BNP levels were obtained for each patient. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and likelihood ratios (LR) of US-JVD ≥8 cm H(2)O for BNP ≥500 pg/ml were calculated. The product moment correlation coefficient between US-JVD and BNP was also calculated. RESULTS: 119 patients were included in the initial study. US-JVD ≥8 cm H(2)O had a sensitivity of 100% (95% CI 92% to 100%), specificity of 43% (95% CI 31% to 56%), PPV of 61% (95% CI 50% to 71%), NPV of 100% (95% CI 84% to 100%), LR+=1.75 (95% CI 1.41 to 2.17), and LR-=0 for a BNP ≥ 500 pg/ml. The Pearson correlation coefficient between US-JVD and BNP was 0.35 (95% CI 0.18 to 0.50) and the Spearman correlation coefficient was 0.73 (95% CI 0.63 to 0.80), suggesting a monotonic, but non-linear relationship between US-JVD and BNP. CONCLUSION: US-JVD correlates with initial BNP levels and is a sensitive test for raised BNP levels in patients with dyspnoea due to suspected congestive cardiac failure.

Incidence of Emergency Department Visits for Electric Rental Scooters Using Detailed Ridership Data.

INTRODUCTION: Electric scooter (e-scooter) rental usage has increased exponentially around the country, expanding to more than 120 cities by the end of 2018. Early attempts to capture the safety effects of widespread adoption of this technology have been hampered by lack of accurate ridership data. Here we describe a 17-month evolution of ridership characteristics in St. Louis, Missouri, and the frequency of e-scooter rental-related injuries serious enough to require an emergency department (ED) visit over this time frame; we also provide estimates of incidence rates of injuries based on company ridership data. METHODS: We performed a combination retrospective chart review and prospective questionnaire-based analysis of adult e-scooter rental-related ED visits in both downtown St. Louis Level 1 trauma centers during the first 17 months of e-scooter rental usage (August 2018-December 2019). The retrospective portion focused on demographics, alcohol use, helmet use, disposition, operative repair, and temporal and severity markers. The prospective portion focused on more detailed crash and rider data. Finally, we used ridership data from both e-scooter rental companies in St. Louis to estimate incidence and temporal trends. RESULTS: A total of 221 patients had e-scooter rental-related ED visits. The median age of our population was 31 years with 58.8% male and 53.8% White. There were no deaths. Ninety-two patients were found to have fractures with 38% requiring surgery. Of the 21 patients diagnosed with head injury, five had an intracranial bleed. Overall incidence of ED visits related to e-scooters was 2.1 per 10,000 trips and 2.2 per 10,000 miles with the number of ED visits by month closely correlated with the number of rides per month (Pearson correlation coefficient = 0.95). CONCLUSION: The number of e-scooter rental-related injuries seen in St. Louis trauma centers was relatively low and correlated closely with overall number of rides. The number of injuries decreased and were less severe from 2018 to 2019 with infrequent intracranial injuries and a large percentage of fractures requiring operative repair.

Jugular venous distension on ultrasound: sensitivity and specificity for heart failure in patients with dyspnea.

BACKGROUND: Accurately diagnosing congestive heart failure (CHF) in patients with dyspnea can be difficult because clinical history and physical examination are often nondiagnostic and may be inaccurate, especially when patients have complicated comorbid conditions. OBJECTIVE: To prospectively assess jugular venous distension on ultrasound (JVD-US) performed by emergency physicians for identifying CHF on echocardiography by the department of cardiology (C-ECHO) in patients with dyspnea. MEASUREMENTS: This was a secondary analysis of a previously collected data set from a prospective study of JVD-US in ED patients with dyspnea due to suspected CHF. C-ECHO results were obtained and used as the criterion standard. RESULTS: Jugular venous distension on ultrasound had a sensitivity of 99% (95% confidence interval [CI], 92.2%-100%), specificity of 59% (95% CI, 40.9%-74.4%), positive likelihood ratio of 2.4 (95% CI, 1.6-3.6), and negative likelihood ratio of 0.01 (95% CI, 0.0007-0.20) for identifying CHF on C-ECHO in patients with dyspnea. CONCLUSION: This initial study suggests that JVD-US by emergency physicians is predictive of CHF using echocardiography performed by the department of cardiology as the criterion standard.

Biomarkers May Predict Unfavorable Neurological Outcome after Mild Traumatic Brain Injury.

The objective of this study was to determine if initial or repeat measurements of serum concentrations of glial fibrillary acidic protein (GFAP) or ubiquitin C-terminal hydrolase L1 (UCH-L1) are predictive of an acute unfavorable neurological outcome in patients who present to the emergency department (ED) with brain injury and an initial Glasgow Coma Scale Score (GCS) of 14-15. This multi-center observational trial included brain-injured adults presenting to the ED, receiving a head computed tomography (CT) and venipuncture for biomarker concentration measurements within 6 h of injury. Subjects had repeat serum sampling and GCS scores every 4 h for the first 24 h, if available for assessment. We analyzed blood samples using an enzyme-linked immunosorbent assay approved by the Food and Drug Administration (FDA). Wilcoxin two-sample test was used to compare initial and repeat serum concentrations for both biomarkers between CT-positive patients who did not have an acute unfavorable neurological outcome and those patients who did. A total of 145 enrolled subjects had adequate data for analysis; 69 were CT-positive, 74 were CT-negative, and 2 were CT-inconclusive. Five subjects developed an acute unfavorable neurological outcome, defined as need for intracranial pressure monitoring, craniotomy, persistent neurological deficits, or death resulting from brain injury. Initial median serum concentrations of GFAP and UCH-L1 (obtained <6 h from injury) were significantly greater in CT-positive patients who had an acute unfavorable neurological outcome than in CT-positive patients who did not (GFAP: 5237 pg/mL [IQR 4511, 8180] versus 283.5 pg/mL [IQR 107, 1123]; p = 0.026; UCH-L1: 3329 pg/mL [QR 1423, 5010] versus 679.5 pg/mL [IQR 363, 1100] p = 0.014). Repeat serum testing (6- < 12 h from injury) showed that UCH-L1 serum concentration, but not GFAP, was also significantly greater in the acute unfavorable neurological outcome group than in those without an unfavorable outcome: 1088 pg/mL versus 374 pg/mL; p = 0.041.

Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study.

OBJECTIVES: To evaluate the ability of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) to detect concussion in children and adult trauma patients with a normal mental status and assess biomarker concentrations over time as gradients of injury in concussive and non-concussive head and body trauma. DESIGN: Large prospective cohort study. SETTING: Three level I trauma centres in the USA. PARTICIPANTS: Paediatric and adult trauma patients of all ages, with and without head trauma, presenting with a normal mental status (Glasgow Coma Scale score of 15) within 4 hours of injury. Rigorous screening for concussive symptoms was conducted. Of 3462 trauma patients screened, 751 were enrolled and 712 had biomarker data. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours postinjury in adults. MAIN OUTCOMES: Detection of concussion and gradients of injury in children versus adults by comparing three groups of patients: (1) those with concussion; (2) those with head trauma without overt signs of concussion (non-concussive head trauma controls) and (3) those with peripheral (body) trauma without head trauma or concussion (non-concussive body trauma controls). RESULTS: A total of 1904 samples from 712 trauma patients were analysed. Within 4 hours of injury, there were incremental increases in levels of both GFAP and UCH-L1 from non-concussive body trauma (lowest), to mild elevations in non-concussive head trauma, to highest levels in patients with concussion. In concussion patients, GFAP concentrations were significantly higher compared with body trauma controls (p<0.001) and with head trauma controls (p<0.001) in both children and adults, after controlling for multiple comparisons. However, for UCH-L1, there were no significant differences between concussion patients and head trauma controls (p=0.894) and between body trauma and head trauma controls in children. The AUC for initial GFAP levels to detect concussion was 0.80 (0.73-0.87) in children and 0.76 (0.71-0.80) in adults. This differed significantly from UCH-L1 with AUCs of 0.62 (0.53-0.72) in children and 0.69 (0.64-0.74) in adults. CONCLUSIONS: In a cohort of trauma patients with normal mental status, GFAP outperformed UCH-L1 in detecting concussion in both children and adults. Blood levels of GFAP and UCH-L1 showed incremental elevations across three injury groups: from non-concussive body trauma, to non-concussive head trauma, to concussion. However, UCH-L1 was expressed at much higher levels than GFAP in those with non-concussive trauma, particularly in children. Elevations in both biomarkers in patients with non-concussive head trauma may be reflective of a subconcussive brain injury. This will require further study.

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.

BACKGROUND: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI. METHODS: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT. FINDINGS: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative. INTERPRETATION: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted. FUNDING: Banyan Biomarkers and US Army Medical Research and Materiel Command.

Quantifying the usefulness of CT in evaluating seniors with abdominal pain.

OBJECTIVES: (1) Determine if older patients with abdominal pain who receive emergency department (ED) abdominal CT have changes in diagnosis and/or disposition more often than similar patients without CT; (2) compare physician confidence in diagnosis and disposition for patients with versus without CT; (3) document factors that most influence physician's decision to order abdominal CT in this population. METHODS: ED patients 60 years of age or older, with acute non-traumatic abdominal pain were enrolled over a 6-week period. Physicians documented a preliminary and final ED diagnosis and disposition, along with pre- and post-evaluation confidence levels. Decision to order CT, along with clinical information most influencing that decision, was noted. Physician confidence levels and percent change in diagnosis and disposition were compared for patients with versus without CT. RESULTS: One hundred and twenty-six patients comprised study sample. Abdominal CT rate was 59% (95%CI, 50-67%). CT was associated with an increased change in diagnosis (46%; 95%CI, 4-58% versus 29%; 95%CI, 16-42%), but no change in disposition between patients with versus without CT. Preliminary diagnostic confidence was lower for EPs who ordered a CT than for those who did not (p<0.001). Patient history most influenced ordering CT, whereas prior lab/imaging results most influenced not ordering CT. CONCLUSION: Patients with CT had a change in diagnosis more often than those without. Preliminary diagnostic confidence was lower in CT group. Percent change in disposition did not differ between groups. Physicians most often ordered CT based on history and did not order CT when other diagnostic evaluation supported a specific diagnosis.

Identifying high-risk patients for triage and resource allocation in the ED.

Five-point triage assessment scales currently used in many emergency departments (EDs) across the country have been shown to be accurate and reliable. We have found the system to be highly predictive of outcome (hospital admission, intensive care unit/operating room admission, or death) at either extreme of the scale but much less predictive in the middle triage group. This is problematic because the middle triage acuity group is the largest, in our experience comprising almost half of all patients. Patients triaged to the 2 highest acuity categories (A and B) have admission/ED death rates of 76% and 43%, respectively. In contrast, the 2 lowest acuity categories (D and E) have admission/ED death rates of 1% or less. The middle category (C), however, has an overall admission/ED death rate of 10%, too high to be comfortable with prolonged delays in the ED evaluation of these patients. We studied this group to determine if easily obtainable clinical factors could identify higher-risk patients in this heterogeneous category. Data were obtained from a retrospective, cross-sectional study of all patients seen in 2001 at an urban academic hospital ED. The main outcome measure for multivariate logistic regression models was hospital admission among patients triaged as acuity C. Acuity C patients who were 65 years or older, presenting with weakness or dizziness, shortness of breath, abdominal pain, or a final diagnosis related group diagnosis of psychosis, were more likely to be admitted than patients originally triaged in category B. These findings suggest that a few easily obtainable clinical factors may significantly improve the accuracy of triage and resource allocation among patients assigned with a middle-acuity score.

Utility of Serum Biomarkers in the Diagnosis and Stratification of Mild Traumatic Brain Injury.

OBJECTIVE: The objective was to compare test characteristics of a single serum concentration of glial fibrillary acidic protein (GFAP), S-100ß, and ubiquitin carboxyl terminal hydrolase L1 (UCH-L1), obtained within 6 hours of head injury, to diagnose mild traumatic brain injury (mTBI) in head-injured subjects. METHODS: Adults aged 18 to 80 years who presented to one of seven EDs with a blunt closed head injury underwent head CT within 4 hours of injury and had blood drawn for biomarker analysis within 6 hours of injury were eligible. Subjects were considered to have mTBI if they had an initial Glasgow Coma Scale (GCS) > 13 and met one or more of the following criteria: loss of consciousness (LOC), posttraumatic amnesia, or confusion. Subjects with mTBI and an abnormal head computed tomography (CT) scan were categorized as complicated mTBI; those with a normal head CT were categorized as uncomplicated mTBI; and subjects with a GCS = 15, no LOC, no posttraumatic amnesia, and no confusion were considered to not have a mTBI. Biomarker concentration measurements for GFAP and UCH-L1 were performed using an enzyme-linked immunosorbent assay. S-100ß concentration was determined using an electrochemiluminescence immunoassay. Median biomarker concentration for each group was compared using the Kruskal-Wallis test. Logistic regression was used to determine area under the receiver operating curve (AUC) for each of the three biomarkers. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and negative and positive likelihood ratios (LRs) for the three biomarkers to differentiate between complicated mTBI, uncomplicated mTBI, and no mTBI were calculated. RESULTS: A total of 247 subjects were enrolled and had adequate clinical and biomarker information for analysis. A total of 188 met criteria for mTBI, with 34 (18.1%) having an acute abnormality on CT (complicated mTBI). The mean (±SD) age of the study population was 45.8 (±17.3) years, and 59.9% were male. Median serum concentrations for all biomarkers were significantly different between groups, lowest in the no mTBI group, and progressively increasing in the uncomplicated and complicated mTBI groups (p < 0.0001). All three biomarkers were significant classifiers of mTBI versus no mTBI, with the following AUCs: GFAP, 0.70; S-100ß, 0.69; and UCH-L1, 0.65 (p = 0.17). Sensitivity for mTBI was highest for S-100ß (96.5%). NPVs ranged from 31% for UCH-L1 to 35% for GFAP. PPVs ranged from 75.5% for S-100ß to 96.5% for GFAP. Negative LR ranged from 0.59 for GFAP to 0.71 for UCH-L1, with positive LR ranging from 1.0 for both UCH-L1 and S-100ß to 8.7 for GFAP. CONCLUSION: A single serum concentration of GFAP, UCH-L1, or S-100ß within 6 hours of head injury may be useful in identifying and stratifying the severity of brain injury in emergency department patients with head trauma, but cannot reliably exclude a diagnosis of concussion. A positive GFAP was associated with the presence of concussion.

Modeling the Kinetics of Serum Glial Fibrillary Acidic Protein, Ubiquitin Carboxyl-Terminal Hydrolase-L1, and S100B Concentrations in Patients with Traumatic Brain Injury.

Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and S100B have been shown to be predictive of patients with brain injury. Kinetics of these biomarkers in injured humans have not been extensively examined. This prospective multi-center study included patients with mild-to-moderate traumatic brain injury. Blood samples obtained at enrollment and every 6 h up to 24 h post-injury were assayed for GFAP, UCH-L1, and S100B. Random effects models examined changes in the biomarkers' level over time. A total of 167 patients were enrolled; mean age was 46.0 ± 17.8, 61.1% were male, 143 (85.6%) had a Glasgow Coma Scale score of 15, and 33 (19.8%) had a positive head computed tomography (CT) scan. Baseline median biomarker concentrations for all three were higher among CT-positive patients (p < 0.0001) but GFAP was the only biomarker that significantly increased over time among CT-positive patients relative to CT-negative patients (log transformed values 0.037; 95% confidence interval 0.02, 0.05; p < 0.001), indicating a 3.7% per hour rise in GFAP concentration. There was no significant increase in either UCH-L1 or S100B in CT-positive patients (p = 0.15 and p = 0.47, respectively). GFAP concentrations increased 3.7% per hour among CT-positive patients whereas neither UCH-L1 nor S100B increased, compared with CT-negative patients. The kinetics and temporal profile of GFAP suggest it may be a more robust biomarker to detect patients with positive CT findings, particularly at later post-injury times. Further study is needed to determine if GFAP is a useful test to follow throughout a patient's clinical course.