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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. 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. 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). 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.

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. 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. 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. 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. Banyan Biomarkers and US Army Medical Research and Materiel Command.

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.

The Institute of Medicine found that unnecessary healthcare services total $210 billion annually7 Although fee-for-service and the drive to increase profits might not be the dominant factor for unnecessary testing, both serve as disincentives to clinical initiatives to reduce wasteful practices, some of which result in harm to patients.8 On the macro-economic level, the growth of our healthcare sector to 20% of our GDP basically starves out the ability to fund many potential goods and services. Burnout is an increasing problem in healthcare, even before COVID-19, affecting nearly half the physician workforce in a 2017 survey9 Most recently, burnout is affecting over half of physicians surveyed, and almost two-thirds of emergency physicians.10 The bureaucratic tasks associated with the ever-increasing pressure to increase throughput and documentation, whether medically necessary or not, along with the lack of support to provide the necessary resources to ease these pressures has been identified as the dominant factor in physician burnout.10 Now, besides these pressures, which often directly conflict with providing thoughtful and careful patient care, the increasing threat of job insecurity looms due to financial demands on hospital systems and private equity firms to replace physicians with less expensive and less trained personnel. [...]we want to acknowledge the important contributions of APPs, including nurse practitioners and physician assistants, to the delivery of emergency care.11 We believe that APPs are best utilized as members of a physician-led team and should not be utilized as replacements for emergency physicians. For all the above reasons, we support ACEPs guidelines that APPs \"should not perform indirect unsupervised care in the ED... regardless of state law or hospital regulation.\"

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.

Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70–0.88) for GFAP, 0.80 (0.71–0.89) for UCH-L1, and 0.75 (0.65–0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.

ObjectivesTo 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.DesignLarge prospective cohort study.SettingThree level I trauma centres in the USA.ParticipantsPaediatric 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 outcomesDetection 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).ResultsA 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.ConclusionsIn 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.

Current standard therapy for patients with acute proximal deep vein thrombosis (DVT) consists of anticoagulant therapy and graduated elastic compression stockings. Despite use of this strategy, the postthrombotic syndrome (PTS) develops frequently, causes substantial patient disability, and impairs quality of life. Pharmacomechanical catheter-directed thrombolysis (PCDT), which rapidly removes acute venous thrombus, may reduce the frequency of PTS. However, this hypothesis has not been tested in a large multicenter randomized trial. The ATTRACT Study is an ongoing National Institutes of Health–sponsored, Phase III, multicenter, randomized, open-label, assessor-blinded, parallel two-arm, controlled clinical trial. Approximately 692 patients with acute proximal DVT involving the femoral, common femoral, and/or iliac vein are being randomized to receive PCDT + standard therapy versus standard therapy alone. The primary study hypothesis is that PCDT will reduce the proportion of patients who develop PTS within 2 years by one-third, assessed using the Villalta Scale. Secondary outcomes include safety, general and venous disease-specific quality of life, relief of early pain and swelling, and cost-effectiveness. ATTRACT will determine if PCDT should be routinely used to prevent PTS in patients with symptomatic proximal DVT above the popliteal vein.