Head injury serum markers for assessing response to trauma: Design of the HeadSMART study

Peters, Matthew E.; Rao, Vani; Bechtold, Kathleen T.; Roy, Durga; Sair, Haris I.; Leoutsakos, Jeannie Marie S.; Stevens, Robert; Batty, D. Scott; Falk, Hayley; Fernandez, Christopher; Ofoche, Uju; Vassila, Alexandra; Hall, Anna J.; Anderson, Braden; Bessman, Edward S.; Eyk, Jennifer E. Van; Korley, Frederick K.

doi:10.1080/02699052.2016.1231344

Cited by 21 publications

(9 citation statements)

References 46 publications

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“…Demographics, clinical features, and mean biomarker levels for healthy and mTBI cohorts are reported in Table 1 . The clinical and demographic data for HeadSMART mTBI patients resemble those reported for other published cohorts ( 37 ).…”

Section: Resultssupporting

confidence: 64%

“…To be included, subjects had to have no known prior or active diagnosed psychiatric or neurologic disease, no history of kidney failure, stroke, brain tumor, or intracranial surgery, no known active medical conditions other than diabetes, hypertension and high cholesterol, no recent blood transfusion, not pregnant, no recreational drug use within 2 weeks of blood draw, and only included non-smokers with a blood pressure below 140/80. Further details about the design of HeadSMART have been published elsewhere ( 37 ).…”

Section: Methodsmentioning

confidence: 99%

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Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

Peacock

Meter²,

Mirshahi³

et al. 2017

Front. Neurol.

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BackgroundNearly 5 million emergency department (ED) visits for head injury occur each year in the United States, of which <10% of patients show abnormal computed tomography (CT) findings. CT negative patients frequently suffer protracted somatic, behavioral, and neurocognitive dysfunction. Our goal was to evaluate biomarkers to identify mild TBI (mTBI) in patients with suspected head injury.MethodsAn observational ED study of head-injured and control patients was conducted at Johns Hopkins University (HeadSMART). Head CT was obtained (ACEP criteria) in patients with Glasgow Coma Scale scores of 13–15 and aged 18–80. Three candidate biomarker proteins, neurogranin (NRGN), neuron-specific enolase (NSE), and metallothionein 3 (MT3), were evaluated by immunoassay (samples <24 h from injury). American Congress of Rehabilitation Medicine (ACRM) criteria were used for diagnosis of mTBI patients for model building. Univariate analysis, logistic regression, and random forest (RF) algorithms were used for data analysis in R. Overall, 662 patients were studied. Statistical models were built using 328 healthy controls and 179 mTBI patients.ResultsMedian time from injury was 5.9 h (IQR, 4.0; range 0.8–24 h). mTBI patients had elevated NSE, but decreased MT3 versus controls (p < 0.01 for each). NRGN was also elevated but within 2–6 h after injury. In the derivation set, the best model to distinguish mTBI from healthy controls used three markers, age, and sex as covariates (C-statistic = 0.91, sensitivity 98%, specificity 72%). Panel test accuracy was validated with the 155 remaining ACRM+ mTBI patients. Applying the RF model to the ACRM+ mTBI validation set resulted in 78% correctly classified as mTBI (119/153). CT positive and CT negative validation subsets were 91% and 75% correctly classified. In samples taken <2 h from injury, 100% (10/10) samples classified correctly, indicating that hyperacute testing is possible with these biomarker assays. The model accuracy varied from 72–100% overall, and had greater accuracy with increasing severity, as shown by comparing CT+ with CT− (91% versus 75%), and Injury Severity Score ≥16 versus <16 (88% versus 72%, respectively). Objective blood tests, detecting NRGN, NSE, and MT3, can be used to identify mTBI, irrespective of neuroimaging findings.

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Section: Resultssupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

Peacock

Meter²,

Mirshahi³

et al. 2017

Front. Neurol.

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“…We performed an analysis of subjects enrolled in the Head Injury Serum Markers for Assessing Response to Trauma (HeadSMART) study. Details of the HeadSMART study design and methods have been previously published [41]. This study was approved by the Johns Hopkins Institutional Review Board.…”

Section: Participants and Proceduresmentioning

confidence: 99%

Poor sleep is linked to impeded recovery from traumatic brain injury

Kalmbach

Conroy

Falk

et al. 2018

Sleep

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“…We'll also consider new potentially diagnostic biomarkers of TBI and TVI such as microRNA (miRNA) [15] and GFAP or/and S100β [16] with the clinical trials. A newly reported design, The Head Injury Serum Markers for Assessing Response to Trauma (HeadSMART), seems to be a worthy trial to examine bloodbased biomarkers for determination of the diagnosis and prognosis of TBI [17].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Vascular Integrity in Traumatic Brain Injury and Correlation with Cerebrovascular Reactivity

Gong¹,

Amyot²,

Qu³

et al. 2017

Biomark J

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Head injury serum markers for assessing response to trauma: Design of the HeadSMART study

Abstract: With systematic phenotyping, HeadSMART will facilitate diagnosis and risk-stratification of the heterogeneous group of individuals currently diagnosed with TBI.

Cited by 21 publications

References 46 publications

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

Poor sleep is linked to impeded recovery from traumatic brain injury

Biomarkers of Vascular Integrity in Traumatic Brain Injury and Correlation with Cerebrovascular Reactivity

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